ID	title	abstract	authors	journal
221	Randomised trial to assess benefits and safety of vitamin A supplementation linked to immunisation in early infancy. WHO/CHD Immunisation-Linked Vitamin A Supplementation Study Group	BACKGROUND: The benefits and safety of vitamin A supplementation linked to immunisation in infancy need to be assessed before it can be widely recommended. We assessed the safety and benefits of maternal postpartum and infant vitamin A supplementation administered with each of the three diphtheria-tetanus-pertussis (DPT) and poliomyelitis immunisations and with a fourth dose with measles immunisation. METHODS: From January, 1995, we enrolled 9424 mother-infant pairs from Ghana, India, and Peru in this randomised, double-blind, placebo-controlled trial. 4716 mothers of infants in the vitamin A group received 200000 IU vitamin A, and their infants were given 25000 IU vitamin A with each of the first three doses of DPT/poliomyelitis immunisation at 6, 10, and 14 weeks. In the control group, 4708 mothers and their infants received placebo at the same times. At 9 months, with measles immunisation, infants in the vitamin A group were given a further dose of 25000 IU and those in the control group received 100000 IU vitamin A. Infants were followed up to age 12 months. The primary outcome measures were vitamin A status, signs of acute toxic effects, anthropometric indicators, and severe morbidity. Analysis was by intention to treat. FINDINGS: 3933 (93%) of the eligible 4212 infants on vitamin A and 3938 (93%) of the eligible 4227 controls received all four study doses. At the 6-month follow-up, there was a small decrease in vitamin A deficiency in the vitamin A group compared with controls (serum retinol < or =0.70 micromol/L 101 [29.9%] vs 122 [37.1%; 95% CI of the difference -14.3% to -0.2%]). This effect was no longer apparent at 9 and 12 months. There were no significant between-group differences in mortality throughout the study. The rate ratio to compare all deaths up to age 9 months in the two groups was 0.96 (95% CI 0.73 to 1.27). Fewer than 1% of the infants had bulging fontanelle. The intervention had no effect on anthropometric status, or on overall or severe morbidity. INTERPRETATION: The trial confirmed the safety of the intervention, but shows no sustained benefits in terms of vitamin A status beyond age 6 months or infant morbidity.		Lancet
210	Randomized, placebo-controlled trial of inactivated poliovirus vaccine in Cuba	BACKGROUND: After poliomyelitis has been eradicated, access to live polioviruses will be highly restricted and the use of oral poliovirus vaccine (OPV) will probably be discontinued. Countries using OPV must decide whether to switch to inactivated poliovirus vaccine (IPV) or stop polio vaccination. Because data on the immunogenicity of IPV in tropical developing countries are limited, we conducted a randomized, controlled trial of IPV in Cuba. METHODS: The study population consisted of healthy infants born in Havana. A total of 166 infants were randomly assigned to two groups. Group A received a combination of the diphtheria-pertussis-tetanus (DPT) vaccine, the Haemophilus influenzae type b (Hib) vaccine, and IPV (DPT-Hib-IPV) at 6, 10, and 14 weeks of age. Group B, the control group, received a combination of the DPT vaccine and the Hib vaccine at 6, 10, and 14 weeks of age. Another group (group C, 100 infants), which did not undergo randomization at the same time as groups A and B, received the DPT-Hib-IPV combination at 8 and 16 weeks of age. Serum samples were collected before vaccination and at least 4 weeks after the last dose. Stool samples were obtained before and 7 days after challenge with OPV. RESULTS: The seroconversion rates in group A were 94%, 83%, and 100% for types 1, 2, and 3 poliovirus, respectively. There were no seroconversions in group B. The seroconversion rates in group C were 90%, 89%, and 90% for poliovirus types 1, 2, and 3, respectively. For groups A, B, and C, the virus isolation rates after challenge with OPV were 94%, 91%, and 97%, respectively, and the mean log10 viral titers of any serotype were 3.46, 3.89, and 3.37, respectively. There was one major adverse event, an episode of hypotonia. CONCLUSIONS: Vaccination with two or three doses of IPV resulted in a rate of seroconversion of at least 90%, except for seroconversion against type 2. The viral titer of OPV shed in the stool after OPV challenge was reduced in both groups receiving IPV. (ClinicalTrials.gov number, NCT00260312 [ClinicalTrials.gov].).		The New England journal of medicine
177	Differences in female-male mortality after high-titre measles vaccine and association with subsequent vaccination with diphtheria-tetanus-pertussis and inactivated poliovirus: reanalysis of West African studies	BACKGROUND: Females given high-titre measles vaccine (HTMV) have high mortality; diphtheria-tetanus-pertussis (DTP) vaccination might be associated with increased female mortality. We aimed to assess whether DTP or inactivated poliovirus (IPV) administered after HTMV was associated with increased female-male mortality ratio. METHODS: In three trials from West Africa, 2000 children were randomised to HTMV or control vaccine at 4-5 months of age; a second vaccination was given at age 9-10 months (standard measles vaccine). Children in high-titre groups were given IPV or DTP-IPV. Another 944 children received HTMV as routine vaccination in Senegal. FINDINGS: When we compared high-titre and control groups, no difference in mortality between the first and the second vaccination was noted. After the second vaccination, the female-male mortality ratio was 1.84 (95% CI 1.19-2.84) in children in the high-titre groups who received DTP-IPV or IPV, and 0.59 (0.34-1.04) in controls who received standard measles vaccine (p=0.007). Children who received HTMV but no additional DTP-IPV or IPV had a female-male mortality ratio of 0.83 (0.41-1.67). This ratio was 2.22 (1.04-4.71) for children who received DTP-IPV after routine HTMV and 1.00 (0.68-1.47) for those who did not. When we combined the results from all trials, the female-male mortality ratio was 1.93 (1.33-2.81) for those who received DTP or IPV after HTMV, and 0.96 (0.69-1.34) for those who did not (p=0.006). INTERPRETATION: A change in sequence of vaccinations, rather than HTMV itself, may have been the cause of increased female mortality in these trials.	P. Aaby, H. Jensen, B. Samb, B. Cisse, M. Sodemann, M. Jakobsen, A. Poulsen, A. Rodrigues, I. M. Lisse, F. Simondon and H. Whittle	Lancet
452	Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period?	BACKGROUND: Observational studies have suggested that BCG may have nonspecific beneficial effects on survival. Low-birth-weight (LBW) children are not given BCG at birth in Guinea-Bissau; we conducted a randomized trial of BCG at birth (early BCG) vs delayed BCG. METHODS: In the period 2004-2008 we recruited 2320 LBW children in Bissau. The children were visited at home at 2, 6, and 12 months of age. With a pretrial infant mortality of 250 per 1000, we hypothesized a 25% reduction in infant mortality for LBW children. RESULTS: Infant mortality was only 101 per 1000 during the trial. In the primary analysis, infant mortality was reduced insignificantly by 17% (mortality rate ratio [MRR] = .83 [.63-1.08]). In secondary analyses, early BCG vaccine was safe with an MRR of .49 (.21-1.15) after 3 days and .55 (.34-.89) after 4 weeks. The reduction in neonatal mortality was mainly due to fewer cases of neonatal sepsis, respiratory infection, and fever. The impact of early BCG on infant mortality was marked for children weighing <1.5 kg (MRR = .43 [.21-.85]) who had lower coverage for diphtheria-tetanus-pertussis vaccinations. CONCLUSIONS: Though early BCG did not reduce infant mortality significantly, it may have a beneficial effect in the neonatal period. This could be important for public health because BCG is often delayed in low-income countries.	P. Aaby, A. Roth, H. Ravn, B. M. Napirna, A. Rodrigues, I. M. Lisse, L. Stensballe, B. R. Diness, K. R. Lausch, N. Lund, S. Biering-Sørensen, H. Whittle and C. S. Benn	The Journal of infectious diseases
260	The use of a topical refrigerant anesthetic to reduce injection pain in children	Early childhood experiences with painful injections may lead to anxiety and fear. These reactions need not develop if steps are taken to reduce the pain associated with injections. The purpose of this study was to assess the efficacy of a refrigerant topical anesthetic in reducing injection pain in preschool children experiencing routine diphtheria-pertussis-tetanus (DPT) immunizations. This double-blind placebo-controlled study was conducted in community health clinics in conjunction with ongoing immunization programs. Ninety subjects, aged 4-5.5 years, were randomly assigned to one of three groups: (a) refrigerant topical anesthetic; (b) placebo topical spray; and (c) no-spray control. Pain was measured subjectively using a four-point visual analogue scale. Both the refrigerant topical anesthetic spray and the placebo spray significantly reduced injection pain. Age was found to be an important factor influencing pain response in this study. Parental anxiety was not a significant factor influencing pain response. In addition, parents were not good at predicting their child's pain. The results of the study support the use of an intervention, such as refrigerant topical anesthetic, as a practical, simple, and effective treatment strategy for reduction of short-term painful procedures like injections.	K. Abbott and S. Fowler-Kerry	Journal of pain and symptom management
441	Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants	BACKGROUND: The RTS,S/AS malaria vaccine is being developed for delivery through the World Health Organization's Expanded Program on Immunization (EPI). We assessed the feasibility of integrating RTS,S/AS02D into a standard EPI schedule for infants.METHODS: In this phase 2B, single-center, double-blind, controlled trial involving 340 infants in Bagamoyo, Tanzania, we randomly assigned 340 infants to receive three doses of either the RTS,S/AS02D vaccine or the hepatitis B vaccine at 8, 12, and 16 weeks of age. All infants also received a vaccine containing diphtheria and tetanus toxoids, whole-cell pertussis vaccine, and conjugated Haemophilus influenzae type b vaccine (DTPw/Hib). The primary objectives were the occurrence of serious adverse events during a 9-month surveillance period and a demonstration of noninferiority of the responses to the EPI vaccines (DTPw/Hib and hepatitis B surface antigen) with coadministration of the RTS,S/AS02D vaccine, as compared with the hepatitis B vaccine. The detection of antibodies against Plasmodium falciparum circumsporozoite and efficacy against malaria infection were secondary objectives.RESULTS: At least one serious adverse event was reported in 31 of 170 infants who received the RTS,S/AS02D vaccine (18.2%; 95% confidence interval [CI], 12.7 to 24.9) and in 42 of 170 infants who received the hepatitis B vaccine (24.7%; 95% CI, 18.4 to 31.9). The results showed the noninferiority of the RTS,S/AS02D vaccine in terms of antibody responses to EPI antigens. One month after vaccination, 98.6% of infants receiving the RTS,S/AS02D vaccine had seropositive titers for anticircumsporozoite antibodies on enzyme-linked immunosorbent assay (ELISA). During the 6-month period after the third dose of vaccine, the efficacy of the RTS,S/AS02D vaccine against first infection with P. falciparum malaria was 65.2% (95% CI, 20.7 to 84.7; P=0.01).CONCLUSIONS: The use of the RTS,S/AS02D vaccine in infants had a promising safety profile, did not interfere with the immunologic responses to coadministered EPI antigens, and reduced the incidence of malaria infection. (ClinicalTrials.gov number, NCT00289185.)	S. Abdulla, R. Oberholzer, O. Juma, S. Kubhoja, F. Machera, C. Membi, S. Omari, A. Urassa, H. Mshinda, A. Jumanne, N. Salim, M. Shomari, T. Aebi, D. M. Schellenberg, T. Carter, T. Villafana, M. A. Demoitié, M. C. Dubois, A. Leach, M. Lievens, J. Vekemans, J. Cohen, W. R. Ballou and M. Tanner	The New England journal of medicine
204	Randomized, controlled trial of the long term safety, immunogenicity and efficacy of RTS,S/AS02(D) malaria vaccine in infants living in a malaria-endemic region	BACKGROUND: The RTS,S/AS malaria candidate vaccine is being developed with the intent to be delivered, if approved, through the Expanded Programme on Immunization (EPI) of the World Health Organization. Safety, immunogenicity and efficacy of the RTS,S/AS02(D) vaccine candidate when integrated into a standard EPI schedule for infants have been reported over a nine-month surveillance period. This paper describes results following 20 months of follow up. METHODS: This Phase IIb, single-centre, randomized controlled trial enrolled 340 infants in Tanzania to receive three doses of RTS,S/AS02(D) or hepatitis B vaccine at 8, 12, and 16 weeks of age. All infants also received DTPw/Hib (diphtheria and tetanus toxoids, whole-cell pertussis vaccine, conjugated Haemophilus influenzae type b vaccine) at the same timepoints. The study was double-blinded to month 9 and single-blinded from months 9 to 20. RESULTS: From month 0 to 20, at least one SAE was reported in 57/170 infants who received RTS,S/AS02(D) (33.5%; 95% confidence interval [CI]: 26.5, 41.2) and 62/170 infants who received hepatitis B vaccine (36.5%; 95% CI: 29.2, 44.2). The SAE profile was similar in both vaccine groups; none were considered to be related to vaccination. At month 20, 18?months after completion of vaccination, 71.8% of recipients of RTS,S/AS02(D) and 3.8% of recipients of hepatitis B vaccine had seropositive titres for anti-CS antibodies; seroprotective levels of anti-HBs antibodies remained in 100% of recipients of RTS,S/AS02(D) and 97.7% recipients of hepatitis B vaccine. Anti-HBs antibody GMTs were higher in the RTS,S/AS02(D) group at all post-vaccination time points compared to control. According to protocol population, vaccine efficacy against multiple episodes of malaria disease was 50.7% (95% CI: -6.5 to 77.1, p?=?0.072) and 26.7% (95% CI: -33.1 to 59.6, p?=?0.307) over 12 and 18?months post vaccination, respectively. In the Intention to Treat population, over the 20-month follow up, vaccine efficacy against multiple episodes of malaria disease was 14.4% (95% CI: -41.9 to 48.4, p?=?0.545). CONCLUSIONS: The acceptable safety profile and good tolerability of RTS,S/AS02(D) in combination with EPI vaccines previously reported from month 0 to 9 was confirmed over a 20?month surveillance period in this infant population. Antibodies against both CS and HBsAg in the RTS,S/AS02(D) group remained significantly higher compared to control for the study duration. Over 18?months follow up, RTS,S/AS02(D) prevented approximately a quarter of malaria cases in the study population. CLINICAL TRIALS: Gov identifier: NCT00289185.	S. Abdulla, N. Salim, F. Machera, R. Kamata, O. Juma, M. Shomari, S. Kubhoja, A. Mohammed, G. Mwangoka, T. Aebi, H. Mshinda, D. Schellenberg, T. Carter, T. Villafana, M. C. Dubois, A. Leach, M. Lievens, J. Vekemans, J. Cohen, W. R. Ballou and M. Tanner	Malaria journal
240	Haemophilus influenzae type b vaccine in India: need and timing, immunogenecity and tolerance	OBJECTIVE: (i) To assess the natural immunity and susceptibility to Haemophilus influenzae type b (Hib) infections in children in India. (ii) To study the immunogenecity and tolerance of Hib vaccine (ACTHIB) in young infants. DESIGNS: (i) Cross sectional study. (ii) Prospective trial. SETTING: Well baby and immunization clinics. METHODS: (i) PRP antibody titers against Hib estimated in 172 healthy infants and children aged 1 month to 10 years. (ii) Antibody titres estimated before and after ACTHIB vaccine given with primary immunization (age group 6 to 8 weeks) in 50 babies. RESULTS: (i) Naturally protective levels of Hib antibodies found in less than 20% of infants under one year, but in over 80% above 4 years. (ii) Seroconversion after ACTHIB vaccination was 100% with very high protective levels. There were no significant adverse reactions. CONCLUSIONS: ACTHIB vaccine proved to be safe and highly immunogenic. As susceptibility to Hib is highest in the first year of life, the vaccine should be recommended in the primary immunization schedule (combined with DPT). The very high titers achieved suggest the possibility of decreasing the number of doses or the amount of antigen to reduce the prevalent high cost.	D. Acharya, S. Bhave, V. Joshi, A. Bavdekar and A. Pandit	Indian pediatrics
229	Impact of health education on mothers' knowledge of preventive health practices	A prospective community-based intervention study was conducted in a slum area of Karachi, Pakistan, with the objective of evaluating the impact of health education on the knowledge of mothers. One hundred and fifty households were studied in the intervention and the same in the non-intervention group. The post intervention knowledge scores of the mothers showed a significant difference of P < 0.05. Nearly 50.7% mothers in the intervention group knew of at least four diseases against which vaccination is given as compared to the non-intervention group (P < 0.05). Similarly, mothers in the intervention group were more aware about the advantages of breast feeding, signs of dehydration, measures for prevention of measles and tuberculosis as compared to the non-intervention group (P < 0.05). Finally, a comparison was made between the pre- and post-intervention scores between the two groups. The score in the non-intervention group changed from 11.5 to 16.1 (P > 0.05) as compared to the intervention group in which it changed from 10.2 to 32.2 (P < 0.05).	M. Agboatwalla and D. S. Akram	Tropical doctor
201	Evaluation of the safety and immunogenicity of the RTS,S/AS01E malaria candidate vaccine when integrated in the expanded program of immunization	BACKGROUND: The RTS,S/AS01(E) malaria candidate vaccine is being developed for immunization of African infants through the Expanded Program of Immunization (EPI).METHODS: This phase 2, randomized, open, controlled trial conducted in Ghana, Tanzania, and Gabon evaluated the safety and immunogenicity of RTS,S/AS01(E) when coadministered with EPI vaccines. Five hundred eleven infants were randomized to receive RTS,S/AS01(E) at 0, 1, and 2 months (in 3 doses with diphtheria, tetanus, and whole-cell pertussis conjugate [DTPw]; hepatitis B [HepB]; Haemophilus influenzae type b [Hib]; and oral polio vaccine [OPV]), RTS,S/AS01(E) at 0, 1, and 7 months (2 doses with DTPwHepB/Hib+OPV and 1 dose with measles and yellow fever), or EPI vaccines only.RESULTS: The occurrences of serious adverse events were balanced across groups; none were vaccine-related. One child from the control group died. Mild to moderate fever and diaper dermatitis occurred more frequently in the RTS,S/AS01(E) coadministration groups. RTS,S/AS01(E) generated high anti-circumsporozoite protein and anti-hepatitis B surface antigen antibody levels. Regarding EPI vaccine responses upon coadministration when considering both immunization schedules, despite a tendency toward lower geometric mean titers to some EPI antigens, predefined noninferiority criteria were met for all EPI antigens except for polio 3 when EPI vaccines were given with RTS,S/AS01(E) at 0, 1, and 2 months. However, when antibody levels at screening were taken into account, the rates of response to polio 3 antigens were comparable between groups.CONCLUSION: RTS,S/AS01(E) integrated in the EPI showed a favorable safety and immunogenicity evaluation. Trial registration. ClinicalTrials.gov identifier: NCT00436007 . GlaxoSmithKline study ID number: 106369 (Malaria-050).	S. T. Agnandji, K. P. Asante, J. Lyimo, J. Vekemans, S. S. Soulanoudjingar, R. Owusu, M. Shomari, A. Leach, J. Fernandes, D. Dosoo, M. Chikawe, S. Issifou, K. Osei-Kwakye, M. Lievens, M. Paricek, S. Apanga, G. Mwangoka, B. Okissi, E. Kwara, R. Minja, J. Lange, O. Boahen, K. Kayan, G. Adjei, D. Chandramohan, E. Jongert, M. A. Demoitié, M. C. Dubois, T. Carter, P. Vansadia, T. Villafana, M. Sillman, B. Savarese, D. Lapierre, W. R. Ballou, B. Greenwood, M. Tanner, J. Cohen, P. G. Kremsner, B. Lell, S. Owusu-Agyei and S. Abdulla	The Journal of infectious diseases
440	Dose dependency of antibody response in infants and children to pneumococcal polysaccharides conjugated to tetanus toxoid	Three injections of tetravalent pneumococcal polysaccharide-tetanus toxoid conjugate vaccine (PncT) were given to infants at 2, 4 and 6 months of age simultaneously with diphtheria-tetanus-pertussis and Haemophilus influenzae type b-tetanus toxoid conjugate vaccines. Three doses (1, 3 or 10 microg) of polysaccharides were used. Children were boosted with unconjugated polysaccharide vaccine at 14 months of age. No dose dependency was seen after primary immunization. However, booster response to three vaccine serotypes was highest in the group primed with the lowest dose of conjugate vaccine. As the magnitude of the response to booster may be related to the number of polysaccharide-specific memory B cells, we hypothesize that the 10 microg dose of the tetravalent conjugate vaccine is too high for optimal induction of immunologic memory.	H. Ahman, H. Käyhty, A. Vuorela, O. Leroy and J. Eskola	Vaccine
462	Safety, immunogenicity and duration of protection of the RTS,S/ASO2D malaria vaccine: one year follow-up of a randomized controlled phase I/IIb trial	Background: The RTS,S/AS02D vaccine has been shown to have a promising safety profile, to be immunogenic and to confer protection against malaria in children and infants. Methods and Findings: We did a randomized, controlled, phase I/IIb trial of RTS,S/AS02D given at 10, 14 and 18 weeks of age staggered with routine immunization vaccines in 214 Mozambican infants. The study was double-blind until the young child completed 6 months of follow-up over which period vaccine efficacy against new Plasmodium falciparum infections was estimated at 65.9% (95% CI 42.6-79.8, p<0.0001). We now report safety, immunogenicity and estimated efficacy against clinical malaria up to 14 months after study start. Vaccine efficacy was assessed using Cox regression models. The frequency of serious adverse events was 32.7% in the RTS,S/ASO2D and 31.8% in the control group. The geometric mean titers of anti-circumsporozoite antibodies declined from 199.9 to 7.3 EU/mL from one to 12 months post dose three of RTS,S/ASO2D, remaining 15-fold higher than in the control group. Vaccine efficacy against clinical malaria was 33% (95% CI: 24.3-56.9, p = 0.076) over 14 months of follow-up. The hazard rate of disease per 2-fold increase in anti-CS titters was reduced by 84% (95% CI 35.1-88.2, p = 0.003). Conclusion: The RTS,S/ASO2D malaria vaccine administered to young infants has a good safety profile and remains efficacious over 14 months. A strong association between anti-CS antibodies and risk of clinical malaria has been described for the first time. The results also suggest a decrease of both anti-CS antibodies and vaccine efficacy over time. 2010 Aide et al.	P. Aide, J. J. Aponte, M. Renom, T. Nhampossa, J. Sacarlal, I. Mandomando, Q. Bassat, M. N. Manaca, A. Leach, M. Lievens, J. Vekemans, M. C. Dubois, C. Loucq, W. Ripley Ballou, J. Cohen and P. L. Alonso	PLoS ONE
362	Immunogenicity study for Tetra and Penta component vaccines in infants	Objectives: A randomized controlled trial to evaluate the immunogenicity of combined Hemophilus Influenzae type b with DTP+/-injectable polio vaccine and the immunogenicity of giving one injectable polio vaccine combined with the first of 3 doses of oral polio vaccine. Methods: After parental consent, infants were randomized into 4 groups to receive the following vaccines; First group: Single Hemophilus Influenzae type b vaccine (PRP-T, Act-HIB(TM)) in addition to DPT and oral polio vaccine. Second group: Combined (PRP-T+DTP) TETRAct-HIB(TM) and oral polio vaccine. Third group: First dose is combined (PRP-T+DPT+injectable polio vaccine) PENTAct-HIB(TM) and oral polio vaccine. Then, the 2nd and 3rd dose is TETRAct-HIB(TM) and oral polio vaccine. Fourth group: DPT and oral polio vaccine only (Control group). Vaccines were given at 6 weeks, 3 months and 5 months. Blood samples were collected from all children, one month after the 3rd dose at the age of 6 months. Samples were sent for laboratory assay for anti-PRP, Diphtheria anti-toxin, Tetanus anti- toxin, polio antibody type 1, 2 and 3 and pertussis Agglutinins. Results: Single Hemophilus Influenzae type b vaccine produced a higher anti-PRP level (15 ug ml-1) compared to combined Hemophilus Influenzae type b vaccine, (9.5 ug ml-1) in the second group and (11 ug ml-1) in the 3rd group but without significant level. It was found that 90% of non-vaccinated children in our sample are lacking the protective level against Hemophilus Influenzae type b diseases. Giving injectable polio vaccine with oral polio vaccine in the first of 3 doses did not affect the level of polio antibody for the 3 poliovirus types but positivity after the 3 polio doses increased compared to previous studies. In the 4 groups, 100% of the children achieved the protective level against Pertussis, Tetanus and 95% for Diphtheria. No significant negative interaction was found between vaccine antigens used in the study. Conclusions: Combined vaccines are effective methods to include Hemophilus Influenzae type b and injectable polio vaccine in the Extended Program of Immunization without unacceptable decrease in immunogenicity of each component. Number of References 16. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	Y. Y. Al-Mazrou, M. K. Khalil, M. N. Al-Howasi, M. H. Al-Jeffri and S. E. Elgizouli	Saudi Medical Journal
338	Comparison of the therapeutic efficacy of four agents in pertussis		R. G. Ames, S. M. Cohen, A. E. Fischer, J. Kohn, A. Z. McPherson, J. Marlow, J. Rutzky and H. E. Alexander	Pediatrics
164	Immunogenicity and safety of a liquid combination of DTP-PRP-T [corrected] vs lyophilized PRP-T reconstituted with DTP	The immunogenicity and safety of a combined diphtheria, tetanus, pertussis and Haemophilus influenzae type b-tetanus conjugate vaccine (DTP-PRP-T) was compared to the same combination obtained by the reconstitution of H. influenzae type b-tetanus conjugate vaccine lyophilized (PRP-T) with liquid diphtheria-tetanus-pertussis vaccine (DTP). Two hundred and sixty-two healthy infants were randomized to receive a intramuscular injection of 0.5 ml of one of the above combination vaccines at 2, 4 and 6 months of age, and a subgroup of 134 infants received a booster dose at 12 months. Serum antibody levels to each vaccine component were measured at ages 2, 6, 7, 12 and 13 months. Systemic and local reactions were assessed during the first 3 days after each injection by diary cards distributed to the parents. After the third dose and booster administered at 12 months of age, significant equivalence between the groups was observed, and the geometric mean titer of anti H. influenzae type b capsular polysaccharide (Hib-CP) antibodies were 5.9 and 32.6 micrograms ml-1 for the liquid combination group and 5.8 and 19.4 for the lyophilized group, respectively. After the third dose, anti-Hib-PC antibody levels of > or = 1.0 microgram ml-1 and 0.15 microgram ml-1 were seen in 94% and 100%, respectively, of the liquid combination group and 90 and 99%, respectively of the lyophilized group. After the booster dose, levels of > or = 1.0 microgram ml-1 were observed in 100% and 93.5% of the liquid combination group and the lyophilized combination group, respectively. Systemic and local reactions to the vaccination were generally mild and did not differ significantly between the groups. We conclude that the liquid combination of DTP-PRP-T is safe and at least as immunogenic as the lyophilized preparation. This liquid preparation, like other combined vaccines may be helpful for planning vaccination programs with a reduced number of injections.	J. Amir, R. Melamed, J. Bader, C. Ethevenaux, B. Fritzell, J. R. Cartier, F. Arminjon and R. Dagan	Vaccine
142	Acellular pertussis vaccines in infants: evaluation of single component and two-component products	Two acellular pertussis vaccines, one containing only LPF toxoid (25 micrograms) and the other containing LPF toxoid (25 micrograms) and FHA (25 micrograms) and each combined with diphtheria and tetanus toxoids, were evaluated in two groups of 25 infants. A third group of 25 infants served as controls and received a DTP whole-cell pertussis vaccine. Infants given either acellular pertussis vaccine had significantly fewer local and systemic reactions than infants given whole-cell vaccine. Among the three vaccine groups, infants given the LPF vaccine (single component) had the highest concentration of antibody to LPF after three immunizations. Infants receiving the LPF/FHA vaccine (two-component) had the highest concentration of antibody to FHA after three immunizations. Infants vaccinated with the two-component vaccine had a significantly lower serological response to LPF than infants given the single component vaccine, as measured by either enzyme-linked immunosorbent assay or CHO cell assay. Further studies are necessary to determine why differences in immunogenicity of the two investigational vaccines occurred.	E. L. Anderson, C. M. Mink, B. S. Berlin, C. N. Shih, F. F. Tung and R. B. Belshe	Vaccine
220	Immunogenicity, reactogenicity and safety of the human rotavirus vaccine RIX4414 (Rotarix?) oral suspension (liquid formulation) when co-administered with expanded program on immunization (EPI) vaccines in Vietnam and the Philippines in 2006-2007	Evaluation of immunogenicity and safety of a 2-dose liquid formulation of human rotavirus vaccine, RIX4414 following WHO's Expanded Program on Immunization (EPI) schedule (0, 1, and 2 months; Month 0 indicates day of enrollment) in Vietnam and the Philippines. Infants aged 6-10 (mean=8.7 ± 1.07 weeks Vietnam) and 5-10 weeks (mean=6.6 ± 1.03 weeks Philippines) received two doses of RIX4414 vaccine (V) and one dose of placebo (PL) or three placebo doses concomitantly with commercially available diphtheria-tetanus-whole-cell pertussis, hepatitis B and oral poliovirus vaccines. The vaccination schedules were: V-V-PL, V-PL-V and PL-PL-PL (Vietnam); PL-V-V, V-PL-V and PL-PL-PL (Philippines). Anti-rotavirus seroconversion rate was assessed pre-vaccination and post-vaccination (ELISA cut-off=20 U/ml). 375 infants were enrolled in each country. Seroconversion rates at one month post-Dose 2 of RIX4414 were Vietnam 63.3% (95% CI: 54.3-71.6) in V-V-PL group and 81.5% (95% CI: 73.4-88) in V-PL-V group; Philippines 70% (95% CI: 61-78) in PL-V-V group and 59.2% (95% CI: 49.8-68) in V-PL-V group. Frequencies of solicited (8-day post-each dose) and unsolicited symptoms (31-day post-each dose) were similar. Two-doses of rotavirus vaccine administered within the WHO EPI offer flexibility in existing schedule, though both schedules provides good immune responses.	D. D. Anh, C. C. Carlos, D. V. Thiem, Y. Hutagalung, S. Gatchalian, H. L. Bock, I. Smolenov, P. V. Suryakiran and H. H. Han	Vaccine
86	Comparison of a three-component acellular pertussis vaccine with a whole-cell pertussis vaccine in 4- through 6-year-old children. Elmwood Pediatric Associates, Pennridge Pediatric Associates	OBJECTIVE: To compare the safety and immunogenicity of a three-component acellular pertussis (DTaP) vaccine containing pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin with whole-cell pertussis (DTwP) vaccine in 4- through 6-year-old children. PARTICIPANTS: One hundred seventy-two healthy 4- through 6-year-old children previously immunized with the DTwP vaccine at or near 2, 4, 6, and 18 months of age. INTERVENTIONS: Prevaccination serum samples were obtained on all study participants. One hundred twelve children received 0.5 mL of the DTaP vaccine intramuscularly. Fifty-three children received 0.5 mL of a commercially available DTwP vaccine intramuscularly. Approximately 30 days following vaccination, additional serum samples were obtained. MEASUREMENTS: Parents monitored adverse reactions for 7 days following immunization. Significantly fewer children in the DTaP group reported temperatures of greater than 38.1 degrees C and an area of redness of more than 10 mm and moderate-to-severe pain at the injection site. RESULTS: Antibody responses to PT, FHA, pertactin, and diphtheria and tetanus toxoids were measured by enzyme-linked immunosorbent assay. Among subjects who were seronegative prior to vaccination, response was defined as the detection of antibody levels following vaccination; among children with detectable antibody levels prior to vaccination, in terms of the rise in antibody titers. Data using a twofold and a fourfold rise in antibody titers as criteria to define response were evaluated. Children in the DTaP group had significantly greater increases in geometric mean titers of antibodies against PT, FHA, and pertactin. Over 90% of the DTaP group responded to PT, FHA, and pertactin according to the criteria of both the twofold and the fourfold rise in antibody titers. Significantly fewer of the DTwP group responded to PT, FHA, and pertactin with at least a fourfold rise in antibody titers. When analyzing subjects with at least a twofold increase in antibody titers, a statistically significant difference remained in regard to anti-FHA antibodies. All study subjects had protective antibody titers against diphtheria and tetanus toxoids following vaccination. The geometric mean titer of antibodies against tetanus was significantly greater in the DTwP group than in the DTaP group. CONCLUSION: The three-component DTaP vaccine administered as a booster immunization in 4-through 6-year-old children produced less fever and less redness and pain at the injection site than the DTwP vaccine and was as immunogenic as the DTaP vaccine.	P. W. Annunziato, E. P. Rothstein, H. H. Bernstein, M. M. Blatter, K. S. Reisinger and M. E. Pichichero	Archives of pediatrics & adolescent medicine
334	Vaccination against whooping-cough: relation between protection in children and results of laboratory tests: a report to the Whooping-Cough Immunization Committee of the Medical Research Council and to the Medical Officers of Health for Cardiff, Leeds, Leyton, Manchester, Middlesex, Oxford, Poole, Tottenham, Walthamstow, and Wembley		Anon	Br Med J
389	Vaccination against whooping cough relation between protection in children and results of laboratory tests: a report to the Whooping Cough Immunization Committee of the Medical Research Council and to Medical Officers of Health		Anon	Br Med J
403	Randomised trial to assess benefits and safety of vitamin A supplementation linked to immunisation in early infancy. WHO/CHD Immunisation-Linked Vitamin A Supplementation Study Group Lancet 1999 Jan 9;353(9147):154	BACKGROUND: The benefits and safety of vitamin A supplementation linked to immunisation in infancy need to be assessed before it can be widely recommended. We assessed the safety and benefits of maternal postpartum and infant vitamin A supplementation administered with each of the three diphtheria-tetanus-pertussis (DPT) and poliomyelitis immunisations and with a fourth dose with measles immunisation. METHODS: From January, 1995, we enrolled 9424 mother-infant pairs from Ghana, India, and Peru in this randomised, double-blind, placebo-controlled trial. 4716 mothers of infants in the vitamin A group received 200000 IU vitamin A, and their infants were given 25000 IU vitamin A with each of the first three doses of DPT/poliomyelitis immunisation at 6, 10, and 14 weeks. In the control group, 4708 mothers and their infants received placebo at the same times. At 9 months, with measles immunisation, infants in the vitamin A group were given a further dose of 25000 IU and those in the control group received 100000 IU vitamin A. Infants were followed up to age 12 months. The primary outcome measures were vitamin A status, signs of acute toxic effects, anthropometric indicators, and severe morbidity. Analysis was by intention to treat. FINDINGS: 3933 (93%) of the eligible 4212 infants on vitamin A and 3938 (93%) of the eligible 4227 controls received all four study doses. At the 6-month follow-up, there was a small decrease in vitamin A deficiency in the vitamin A group compared with controls (serum retinol < or =0.70 micromol/L 101 [29.9%] vs 122 [37.1%; 95% CI of the difference -14.3% to -0.2%]). This effect was no longer apparent at 9 and 12 months. There were no significant between-group differences in mortality throughout the study. The rate ratio to compare all deaths up to age 9 months in the two groups was 0.96 (95% CI 0.73 to 1.27). Fewer than 1% of the infants had bulging fontanelle. The intervention had no effect on anthropometric status, or on overall or severe morbidity. INTERPRETATION: The trial confirmed the safety of the intervention, but shows no sustained benefits in terms of vitamin A status beyond age 6 months or infant morbidity.	Anon	Lancet
38	Efficacy of short-term treatment of pertussis with clarithromycin and azithromycin	The recommended treatment for pertussis is erythromycin, 40 to 50 mg/kg per day for 2 weeks. The newly developed macrolides, clarithromycin and azithromycin, have been demonstrated to be superior to erythromycin because of improved absorption and a longer half-life. As a result, we conducted two separate comparison studies to evaluate the efficacies of clarithromycin, 10 mg/kg per day, twice a day for 7 days, and azithromycin, 10 mg/kg per day, once a day for 5 days, compared with the standard erythromycin regimen. A total of 17 patients, including 10 infants 1 year of age or less, for whom pertussis had been confirmed by culture, were allocated to receive either clarithromycin or azithromycin treatment, and each patient was matched (age, sex, and immunization status) with historical control subjects who had been treated with erythromycin. Eradication rates examined at 1 week after treatment were as follows: 9 of 9 with clarithromycin versus 16 of 18 with erythromycin (psi M-H = 1.13), and 8 of 8 with azithromycin versus 13 of 16 with erythromycin (psi M-H = 1.23). No bacterial relapse after treatment was detected in either group. All isolated strains of Bordetella pertussis were susceptible to clarithromycin, azithromycin, and erythromycin, and no change in drug susceptibility has been confirmed for the past 20 years in Japan. Because of the very low incidence of pertussis resulting from widespread use of acellular pertussis vaccination, this study did not enroll a large number of patients; however we conclude that short-term treatment with clarithromycin or azithromycin is expected to be equal or superior to the standard long-term erythromycin regimen for pertussis.	T. Aoyama, K. Sunakawa, S. Iwata, Y. Takeuchi and R. Fujii	The Journal of pediatrics
135	A fully liquid DTaP-IPV-Hep B-PRP-T hexavalent vaccine for primary and booster vaccination of healthy Mexican children	OBJECTIVES: To evaluate an investigational, fully liquid hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae type b (DTaP-IPV-Hep B-PRP-T: Hexaxim?) vaccine for primary and booster vaccination of healthy children in Mexico. METHODS: Infants (N=1189) were randomized to receive one of three lots of the DTaP-IPV-Hep B-PRP-T vaccine or a licensed hexavalent control vaccine (Infanrix? hexa) for primary vaccination at 2, 4 and 6 months. All participants who completed the primary series and agreed to participate in the booster part of the study received a dose of the investigational vaccine at 15-18 months of age. Validated serological assays and parental reports were used to assess immunogenicity and safety, respectively. RESULTS: Post-primary vaccination, ?95.8% of participants in both the DTaP-IPV-Hep B-PRP-T and control groups were seroprotected (SP) against diphtheria, tetanus, poliovirus, hepatitis B and PRP, or had seroconverted (SC) to the pertussis toxin (PT) and filamentous hemagglutinin (FHA) pertussis antigens. The SP/SC rates induced by the three DTaP-IPV-Hep B-PRP-T lots were equivalent. No differences in SP/SC rates were observed between the pooled lots of investigational vaccine and the control vaccine. Antibody persistence at 15-18 months was comparable between groups, with strong increases in all antibody concentrations post-DTaP-IPV-Hep B-PRP-T booster. Both vaccines were well tolerated for primary vaccination, as was the booster dose of DTaP-IPV-Hep B-PRP-T. CONCLUSION: These study findings confirm the suitability of the combined, fully liquid DTaP-IPV-Hep B-PRP-T vaccine for inclusion in routine childhood vaccination schedules.	A. G. Aquino, M. G. Brito, C. E. Doniz, J. F. Herrera, M. Macias, B. Zambrano, E. Plennevaux and E. Santos-Lima	Vaccine
419	Safety, immunogenicity, and protective efficacy of two doses of RIX4414 live attenuated human rotavirus vaccine in healthy infants	OBJECTIVE: To determine the safety, immunogenicity and efficacy of two doses of rotavirus vaccine in healthy Brazilian infants. METHODS: A randomized, multicenter, double-blind, placebo-controlled trial was conducted in Brazil, Mexico and Venezuela. Infants received two oral doses of vaccine or placebo at 2 and 4 months of age, concurrently with routine immunizations, except for oral poliomyelitis vaccine (OPV). This paper reports results from Belém, Brazil, where the number of subjects per group and the viral vaccine titers were: 194 (10(4.7) focus forming units - FFU), 196 (10(5.2) FFU), 194 (10(5.8) FFU) and 194 (placebo). Anti-rotavirus (anti-RV) antibody response was assessed in 307 subjects. Clinical severity of gastroenteritis episodes was measured using a 20-point scoring system with a score of >or= 11 defined as severe GE. RESULTS: The rates of solicited general symptoms were similar in vaccine and placebo recipients. At 2 months after the second dose, a serum IgA response to RV occurred in 54.7 to 74.4% of vaccinees. No interference was seen in the immunogenicity of routine vaccines. Vaccine efficacy against any rotavirus gastroenteritis (RVGE) was 63.5% (95%CI 20.8-84.4) for the highest concentration (10(5.8) FFU). Efficacy was 81.5% (95%CI 44.5-95.4) against severe RVGE. At its highest concentration (10(5.8) FFU), RIX4414 provided 79.8% (95%CI 26.4-96.3) protection against severe RVGE by G9 strain. CONCLUSIONS: RIX4414 was highly immunogenic with a low reactogenicity profile and did not interfere with seroresponse to diphtheria, tetanus, pertussis, hepatitis B and Hib antigens. Two doses of RIX4414 provided significant protection against severe GE caused by RV.	E. C. Araujo, S. A. Clemens, C. S. Oliveira, M. C. Justino, P. Rubio, Y. B. Gabbay, V. B. Silva, J. D. Mascarenhas, V. L. Noronha, R. Clemens, R. H. Gusmão, N. Sanchez, T. A. Monteiro and A. C. Linhares	Jornal de pediatria
404	[Safety, immunogenicity, and protective efficacy of two doses of RIX4414 live attenuated human rotavirus vaccine in healthy Brazilian infants]	Objective: To determine the safety, immunogenicity and efficacy of two doses of rotavirus vaccine in healthy Brazilian infants. Methods: A randomized, multicenter, double-blind, placebocontrolled trial was conducted in Brazil, Mexico and Venezuela. Infants received two oral doses of vaccine or placebo at 2 and 4 months of age, concurrently with routine immunizations, except for oral poliomyelitis vaccine (OPV). This paper reports results from Belem, Brazil, where the number of subjects per group and the viral vaccine titers were: 194 (104.7 focus forming units - FFU), 196 (105.2 FFU), 194 (105.8 FFU) and 194 (placebo). Anti-rotavirus (anti-RV) antibody response was assessed in 307 subjects. Clinical severity of gastroenteritis episodes was measured using a 20-point scoring system with a score of [greater-than or equal to] 11 defined as severe GE. Results: The rates of solicited general symptoms were similar in vaccine and placebo recipients. At 2 months after the second dose, a serum IgA response to RV occurred in 54.7 to 74.4% of vaccinees. No interference was seen in the immunogenicity of routine vaccines. Vaccine efficacy against any rotavirus gastroenteritis (RVGE) was 63.5% (95%CI 20.8-84.4) for the highest concentration (105.8 FFU). Efficacy was 81.5% (95%CI 44.5-95.4) against severe RVGE. At its highest concentration (105.8 FFU), RIX4414 provided 79.8% (95%CI 26.4-96.3) protection against severe RVGE by G9 strain. Conclusions: RIX4414 was highly immunogenic with a low reactogenicity profile and did not interfere with seroresponse to diptheria, tetanus, pertussis, hepatitis B and Hib antigens. Two doses of RIX4414 provided significant protection against severe GE caused by RV. Copyright copyright 2007 by Sociedade Brasileira de Pediatria. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	E. C. Araujo, S. A. C. Clemens, C. S. Oliveira, M. C. A. Justino, P. Rubio, Y. B. Gabbay, V. B. Silva, J. D. P. Mascarenhas, V. L. Noronha, R. Clemens, R. H. P. Gusmao, N. Sanchez, T. A. F. Monteiro and A. C. Linhares	Jornal de Pediatria
339	Comparative Immunogenicity of Different 5-Component Acellular Pertussis Vaccine Formulations in Infants		C. Archana and et al.	Pediatric Academic Society
124	Comparison of the reactogenicity and immunogenicity of a combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polio (DTPa-HBV-IPV) vaccine, mixed with the Haemophilus influenzae type b (Hib) conjugate vaccine and administered as a single injection, with the DTPa-IPV/Hib and hepatitis B vaccines administered in two simultaneous injections to infants at 2, 4 and 6 months of age	An open, randomised, multicentre trial was performed to compare the reactogenicity and safety profile of the administration of a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio (DTPa-HBV-IPV) vaccine administered in one injection mixed with Haemophilus influenzae type b (Hib) conjugate vaccine (Group 1) with that of a pentavalent DTPa-IPV vaccine mixed with a Hib vaccine (DTPa-IPV/Hib), simultaneously administered with HBV (Group 2) in two injections in opposite thighs, as a primary vaccination course, to healthy infants at 2, 4 and 6 months of age. A total of 235 completed the study, 120 from Group 1 and 115 from Group 2. Blood samples (pre-vaccination and 1 month after the third dose) were obtained from a subset of infants (Group 1: 40; Group 2: 31) to assess the immune response to vaccination. Local and general solicited symptoms were recorded by parents on diary cards. Seven hundred and five diary cards (Group 1: 360; Group 2: 345) were collected. The clinically relevant and most commonly reported local reaction was pain (infant cried when the limb was moved) in 2.5% (Group 1) and 1.2% (Group 2) of diary cards. Fever was more frequently reported in Group 1 (21% of diary cards) than in Group 2 (12% of diary cards). However only 3 and 2% of doses in Groups 1 and 2, respectively, were responsible for a rectal temperature between 38.6 and 39.5 degrees C and only one case (Group 2) had > or =39.5 degrees C. Other clinically relevant general symptoms were rarely recorded: irritability (2-2.8%), loss of appetite (0.3-0.6%) and drowsiness (0.3-0.3%). All subjects included in the immunogenicity analysis had seroprotective titres to diphtheria, tetanus, polio virus types 1 and 3, Hib. Almost all subjects were seroprotected for anti-polio type 2 and hepatitis B (with the exception of 1 subject in Group 1 for each antigen). The vaccines response rates to pertussis antigens were over 97 and 90% in Groups 1 and 2, respectively. This study shows that, from a clinical perspective, the DTPa-HBV-IPV/Hib vaccine given in a single injection has a similar reactogenicity and safety profile to that of two licensed vaccines (DTPa-IPV/Hib, HBV) given in two simultaneous injections to infants at 2, 4 and 6 months of age. This is a valuable advantage, since in some countries, such as Spain and the UK, an additional injection (for the administration of meningococcal C conjugate vaccine) has been recently included in the infants' vaccination calendars.	J. Arístegui, R. Dal-Ré, J. Díez-Delgado, J. Marés, J. M. Casanovas, P. García-Corbeira, E. Frutos, D. Esso, J. Verdaguer, J. Flor, F. Moraga, R. Boceta and J. A. García-Martínez	Vaccine
330	Reactogenicity and safety of DTPa vaccine and Haemophilus influenzae type b conjugate vaccine (Hib) in a single injection vs DTPw and Hib as separate injections as a booster vaccination in 18-month-old children	Objective: To compare the reactogenicity and safety of the administration of diphtheria-tetanus-acellular pertussis (DTPa) and Haemophilus influenzae type b conjugate (Hib) vaccines in one injection with those of the simultaneous administration of diphtheria-tetanus-whole cell pertussis (DTPw) and Hib vaccines in opposite limbs as booster doses to 18-month-old children previously primed with three doses of DTPw and Hib vaccines as a primary vaccination course. Design and Setting: Nonblind, prospective, randomised, multicentre comparative study set in Spain. Patients and Participants: 216 children (17.2 +/- 0.99 months old). Methods: Children were randomised to receive DTPa/Hib (group 1; n = 111) or DTPw + Hib (group 2; n = 105) and were followed for up to 30 days post-vaccination. All children received oral polio vaccine concomitantly. Local and general symptoms were recorded by parents on diary cards. Results: The incidences of any solicited local reaction and any solicited general symptom 'probably related' or 'suspected to be related' to vaccination were statistically significantly higher (p < 0.0001) in group 2 than in group 1. Pain at the injection site was the most commonly reported local reaction, both in terms of any pain (40% in group 1; 89% at the DTPw site in group 2; p < 0.0001) and in pain that caused the child to cry when the limb was moved (1% and 42%; p < 0.0001). Any redness or swelling were significantly more common (p < 0.0001) at the DTPw injection site (71% and 60%, respectively) than at the DTPa/Hib site (34% and 27%). Fever (rectal temperature >=38 [degree] C) was recorded for 10% and 56% of participants in groups 1 and 2, respectively (p < 0.0001). Only one case in group 1 and three cases in group 2 had fever >39.5 [degree] C. Fussiness (group 1: 28%; group 2: 71%), loss of appetite (15% and 37%, respectively), and restlessness (16% and 34%, respectively) were also statistically significantly more frequent (at least p < 0.003) in DTPw + Hib recipients. Analgesics/antipyretics were prescribed as prophylactic treatment in only <8% of cases; however, antipyretics were significantly more often prescribed (p < 0.0001) after vaccination in group 2 children (46%) than in group 1 children (6%). Unsolicited symptoms were recorded for 33 participants, including 22 cases [group 1: one case; group 2 (DTPw limb): 21 cases] of lameness that resolved within 1 to 5 days (median 1 day). Conclusions: Administration of DTPa/Hib in one injection leads to better reactogenicity and safety profiles than the administration of DTPw + Hib as two injections as booster doses to 18-month-old children primed with DTPw and Hib vaccines. Number of References 21. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	J. Aristegui, P. Garcia-Corbeira, J. Flor, R. Dal-Re, J. Mares, F. Moraga and M. Campins	Clinical Drug Investigation
188	Newborn universal immunisation against hepatitis B: immunogenicity and reactogenicity of simultaneous administration of diphtheria/tetanus/pertussis (DTP) and oral polio vaccines with hepatitis B vaccine at 0, 2 and 6 months of age	The reactogenicity and immunogenicity of the administration of recombinant vaccine against hepatitis B simultaneously (but at separate sites) with diphtheria/tetanus/pertussis (DTP) and oral polio vaccines were examined. Six hundred and twenty-six children (group I) were given hepatitis B vaccine at 0, 2 and 6 months of age; the other vaccines were administered at 2, 4 and 6 months of age. A control group of 731 children (group II) received only DTP and oral polio vaccines. The results showed that 93% of the infants in group I had anti-HBs titres above the protective level ( > or = 10 mIU ml-1) after vaccination. There were no differences in the immune responses for DTP and polio between the two study groups. The vaccine efficacy against poliomyelitis was 96% for serotype I, 100% for serotype II and 97-98% for serotype III. Of the infants in both groups, 97% had antibodies against B. pertussis; all children were positive for tetanus and diphtheria. There were no differences in the incidences of general reactions between groups. Local swelling and redness were reported following 4.2 and 4.4%, respectively, of all injections of hepatitis B vaccine. These reactions were reported following 31 and 33%, respectively, of all doses of DTP vaccine. It can be concluded that the simultaneous administration of hepatitis B vaccine with the DTP and polio vaccines is well-tolerated; hepatitis B vaccine remained highly immunogenic and did not interfere with the immune response to the other antigens.	J. Aristegui, J. Muñiz, A. Pérez Legorburu, M. Imaz, J. P. Arrate, M. D. Suárez and M. D. Goiri	Vaccine
407	The effect of concurrent use of hepatitis B and Bacille Calmette-Guerin vaccination on anti-hepatitis B response	OBJECTIVE: Bacille Calmette-Guerin (BCG) is given at 2-months of age; diphtheria toxoid, tetanus toxoid, whole cell pertussis, oral polio are given at 2, 3, 4 months, and hepatitis B virus (HBV) vaccine is given at 3, 4, 9 months of age. The aim was to evaluate the sero-protection rate of HBV vaccine which has been given at 2, 3, and 9 months of age and coincided with BCG vaccine at the first dose. METHODS: Hepatitis B virus vaccine was administered to 3 groups of infants at 2, 3, 9 months (n=20), 3, 4, 9 months (n=20) concurrently with BCG or other vaccines, and at 0, 1, 6 months with no other coinciding another vaccine (n=20). These 60 infants who were born between June 2001 and September 2001 have been vaccinated at the Akdeniz University School of Medicine, Antalya, Turkey. Antibodies to hepatitis B surface antigen analyzed by enzyme-linked immunosorbent assay. RESULTS: The simultaneous administration of BCG and HBV vaccines did not influence the immune response to HBV vaccine. We showed that all 3 schedules can induce the sero-protective levels of antibody concentrations to HBV both one month and one year after the vaccination. CONCLUSION: Bacille Calmette-Guerin and HBV vaccinations can be performed at the same time in endemic countries.	R. Artan, M. Erol, S. Velipasaoglu and O. Yegin	Saudi Med J
450	The effect of concurrent use of hepatitis B and Bacille Calmette-Guérin vaccination on anti-hepatitis B response	OBJECTIVE: Bacille Calmette-Guerin (BCG) is given at 2-months of age; diphtheria toxoid, tetanus toxoid, whole cell pertussis, oral polio are given at 2, 3, 4 months, and hepatitis B virus (HBV) vaccine is given at 3, 4, 9 months of age. The aim was to evaluate the sero-protection rate of HBV vaccine which has been given at 2, 3, and 9 months of age and coincided with BCG vaccine at the first dose. METHODS: Hepatitis B virus vaccine was administered to 3 groups of infants at 2, 3, 9 months (n=20), 3, 4, 9 months (n=20) concurrently with BCG or other vaccines, and at 0, 1, 6 months with no other coinciding another vaccine (n=20). These 60 infants who were born between June 2001 and September 2001 have been vaccinated at the Akdeniz University School of Medicine, Antalya, Turkey. Antibodies to hepatitis B surface antigen analyzed by enzyme-linked immunosorbent assay. RESULTS: The simultaneous administration of BCG and HBV vaccines did not influence the immune response to HBV vaccine. We showed that all 3 schedules can induce the sero-protective levels of antibody concentrations to HBV both one month and one year after the vaccination. CONCLUSION: Bacille Calmette-Guerin and HBV vaccinations can be performed at the same time in endemic countries.	R. Artan, M. Erol, S. Velipasaoglu and O. Yegin	Saudi medical journal
211	Safety and efficacy of the RTS,S/AS01E candidate malaria vaccine given with expanded-programme-on-immunisation vaccines: 19 month follow-up of a randomised, open-label, phase 2 trial	BACKGROUND: The RTS,S/AS01(E) candidate malaria vaccine is being developed for immunisation of infants in Africa through the expanded programme on immunisation (EPI). 8 month follow-up data have been reported for safety and immunogenicity of RTS,S/AS01(E) when integrated into the EPI. We report extended follow-up to 19 months, including efficacy results. METHODS: We did a randomised, open-label, phase 2 trial of safety and efficacy of the RTS,S/AS01(E) candidate malaria vaccine given with EPI vaccines between April 30, 2007, and Oct 7, 2009, in Ghana, Tanzania, and Gabon. Eligible children were 6-10 weeks of age at first vaccination, without serious acute or chronic illness. All children received the EPI diphtheria, tetanus, pertussis (inactivated whole-cell), and hepatitis-B vaccines, Haemophilus influenzae type b vaccine, and oral polio vaccine at study months 0, 1, and 2, and measles vaccine and yellow fever vaccines at study month 7. Participants were randomly assigned (1:1:1) to receive three doses of RTS,S/AS01(E) at 6, 10, and 14 weeks (0, 1, 2 month schedule) or at 6 weeks, 10 weeks, and 9 months (0, 2, 7 month schedule) or placebo. Randomisation was according to a predefined block list with a computer-generated randomisation code. Detection of serious adverse events and malaria was by passive case detection. Antibodies against Plasmodium falciparum circumsporozoite protein and HBsAg were monitored for 19 months. This study is registered with ClinicalTrials.gov, number NCT00436007. FINDINGS: 511 children were enrolled. Serious adverse events occurred in 57 participants in the RTS,S/AS01(E) 0, 1, 2 month group (34%, 95% CI 27-41), 47 in the 0, 1, 7 month group (28%, 21-35), and 49 (29%, 22-36) in the control group; none were judged to be related to study vaccination. At month 19, anticircumsporozoite immune responses were significantly higher in the RTS,S/AS01(E) groups than in the control group. Vaccine efficacy for the 0, 1, 2 month schedule (2 weeks after dose three to month 19, site-adjusted according-to-protocol analysis) was 53% (95% CI 26-70; p=0·0012) against first malaria episodes and 59% (36-74; p=0·0001) against all malaria episodes. For the entire study period, (total vaccinated cohort) vaccine efficacy against all malaria episodes was higher with the 0, 1, 2 month schedule (57%, 95% CI 33-73; p=0·0002) than with the 0, 1, 7 month schedule (32% CI 16-45; p=0·0003). 1 year after dose three, vaccine efficacy against first malaria episodes was similar for both schedules (0, 1, 2 month group, 61·6% [95% CI 35·6-77·1], p<0·001; 0, 1, 7 month group, 63·8% [40·4-78·0], p<0·001, according-to-protocol cohort). INTERPRETATION: Vaccine efficacy was consistent with the target put forward by the WHO-sponsored malaria vaccine technology roadmap for a first-generation malaria vaccine. The 0, 1, 2 month vaccine schedule has been selected for phase 3 candidate vaccine assessment. FUNDING: Program for Appropriate Technology in Health Malaria Vaccine Initiative; GlaxoSmithKline Biologicals.	K. P. Asante, S. Abdulla, S. Agnandji, J. Lyimo, J. Vekemans, S. Soulanoudjingar, R. Owusu, M. Shomari, A. Leach, E. Jongert, N. Salim, J. F. Fernandes, D. Dosoo, M. Chikawe, S. Issifou, K. Osei-Kwakye, M. Lievens, M. Paricek, T. Möller, S. Apanga, G. Mwangoka, M. C. Dubois, T. Madi, E. Kwara, R. Minja, A. B. Hounkpatin, O. Boahen, K. Kayan, G. Adjei, D. Chandramohan, T. Carter, P. Vansadia, M. Sillman, B. Savarese, C. Loucq, D. Lapierre, B. Greenwood, J. Cohen, P. Kremsner, S. Owusu-Agyei, M. Tanner and B. Lell	The Lancet infectious diseases
227	Lot-to-lot consistency study of the fully liquid pentavalent DTwP-HepB-Hib vaccine Quinvaxem (®) demonstrating clinical equivalence, suitability of the vaccine as a booster and concomitant administration with measles vaccine	This double-blind, randomized study evaluated the immunogenicity and safety of three production lots of the fully liquid combination DTwP-Hep-Hib vaccine, Quinvaxem (®) (Crucell, The Netherlands) in 360 healthy infants aged 42-64 d old given at 6, 10 and 14 weeks of age (Core Study). The Core Study was followed by an open-label Booster Phase evaluating immunogenicity and safety of a booster dose of Quinvaxem (®) given with either concomitant or deferred measles vaccine in 227 infants who completed the Core Study. One month after the third dose of Quinvaxem (®) immune responses reflecting seroprotection or seroconversion were observed in more than 90% of infants for all three vaccine lots. Quinvaxem (®) elicited a strong booster response as demonstrated by a large increase in antibodies against all antigens, which appeared to be unaffected by concomitant administration of the measles vaccine. Safety results were in line with previous reports for Quinvaxem (®) with no unexpected adverse events (AEs) being reported. In the Core Study and Booster Phase, Quinvaxem (®) was well tolerated. No study vaccine-related serious AEs were reported. Thus, Quinvaxem (®) was immunogenic and well-tolerated when administered to infants according to a 6-10-14 week vaccination schedule. The three production lots had consistent reactogenicity and immunogenicity profiles. The booster dose of Quinvaxem (®) was also immunogenic and safe, regardless of whether a monovalent measles vaccine was administered concomitantly or one month later.	S. Aspinall, D. Traynor, P. Bedford and K. Hartmann	Human vaccines & immunotherapeutics
61	Dose-response to a two-component acellular pertussis vaccine in infants and comparison with whole-cell vaccine	In an effort to determine the optimal dose of pertussis toxoid (PT) and filamentous haemagglutinin (FHA) for use in acellular pertussis vaccines we compared the immunogenicity and safety of acellular pertussis vaccine combined with diphtheria and tetanus toxoids containing 12.5 microg (DTaP-12.5) or 25 microg (DTaP-25) each of PT and FHA with a whole cell pertussis vaccine in infants immunized at 2, 4 and 6 months of age. Recipients of acellular vaccines developed higher anti-FHA concentrations and more rapid anti-PT serological responses that infants who received whole cell pertussis vaccine combined with diphtheria and tetanus toxoids (DPT). A dose response was noted; infants immunized with DTaP-25 developed significantly (P<0.03) higher anti-FHA and anti-PT levels than infants who received DTaP-12.5. No rise in the agglutinin titres was noted for recipients of the acellular vaccines although this vaccine stimulated increases in agglutinins when given as the fourth or fifth dose to children who had received three doses of DTP. The rates of erythema, induration, pain, irritability, crying, increased sleepiness, and decreased appetite were significantly (P</=0.05) lower in infants who received acellualr vaccines than in infants who received DTP. When the data from the injections at 2, 4 and 6 months of age were combined, no significant differences in the rates of any adverse event were noted for recipients of DTaP-12.5 or DTaP-25. The rates of most adverse reactions following DTP decreased from the first to the third immunization except fever, which increased. For acellular vaccine recipients, the rates of fever and erythema increased somewhat from the first to the third injection but remained far below the rates following DTP. The acellular vaccine was safe and immunogenic, and a dose-response effect was demonstrated.	B. S. Auerbach, A. M. Lake, M. E. Wilson, F. F. Willingham, J. Shematek, L. Moulton, A. Deforest and N. A. Halsey	Biologicals : journal of the International Association of Biological Standardization
83	Vaccine- and antigen-dependent type 1 and type 2 cytokine induction after primary vaccination of infants with whole-cell or acellular pertussis vaccines	Cytokine profiles were examined 1 month after primary vaccination of infants with a whole-cell pertussis vaccine (wP) (Connaught) or either of two acellular pertussis vaccines, aP-Chiron Biocine (aP-CB) or aP-SmithKline Beecham (aP-SB), each combined with diphtheria-tetanus toxoids (DT), in Bordetella pertussis antigen-stimulated or unstimulated peripheral blood mononuclear cells (PBMC). Pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (PRN) were used as antigens, and the children were defined as responsive when their PBMC proliferated in response to these antigens. The controls were either children who received only DT or children who received pertussis vaccine but whose PBMC did not proliferate upon stimulation with B. pertussis antigens (unresponsive children). Antigen-stimulated PBMC of responsive wP recipients were characterized by an elevated production of T-helper-cell type 1 cytokines gamma interferon (IFN-gamma) and interleukin 2 (IL-2), low to minimal production of IL-5, and no production of IL-4. The PBMC of aP vaccine-responsive recipients showed, in addition to the elevated IFN-gamma production, a consistent, antigen-dependent production of type 2 cytokines (IL-4 and IL-5), with PRN being the most and PT being the least effective antigen. Type 2 cytokine induction was more pronounced in aP-SB than in aP-CB recipients, as shown by the presence of IL-4 mRNA transcripts and higher IL-5 production in the former (161.6 +/- 36 and 47.9 +/- 44 pg/ml [mean +/- standard error for five subjects each], respectively, after PRN stimulation). Appreciable, antigen-unstimulated (constitutive) IFN-gamma production was also detected in PBMC cultures of all vaccinees. However, this spontaneous IFN-gamma production was, in most vaccinees, significantly lower than the antigen-driven cytokine production. In contrast, no constitutive type 2 cytokine production was ever observed in any vaccine group. PBMC from the two control groups (either DT or pertussis vaccine recipients) did not show any type 2 cytokine production, while IFN-gamma production was comparable in both antigen-stimulated and unstimulated conditions. Absence of type 2 cytokines and low levels of constitutive IFN-gamma production were also seen in prevaccination children. Thus, pertussis vaccines induce in infants a basically type 1 cytokine profile, which is, however, accompanied by some production of type 2 cytokines. The latter are more expressed by aP-SB than by aP-CB recipients, and with PRN than with other antigens, and they are minimally expressed in wP recipients and with PT as antigen. Our data also highlight a constitutive IFN-gamma production in infancy, which might reflect natural immunization and/or the burden of concomitant vaccinations and which may have an impact on T-helper-cell cytokine pattern polarization consequent to pertussis vaccination.	C. M. Ausiello, F. Urbani, A. Sala, R. Lande and A. Cassone	Infection and immunity
106	Immunogenicity and reactogenicity of a novel hexavalent DTPa-HBV-IPV/Hib vaccine compared to separate concomitant injections of DTPa-IPV/Hib and HBV vaccines, when administered according to a 3, 5 and 11 month vaccination schedule	UNLABELLED: In an open randomised trial, 312 eligible infants were enrolled to receive either a single injection of the hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B virus-inactivated polio/ Haemophilus influenzae b (DTPa-HBV-IPV/Hib) vaccine, or concomitant injections of commercial DTPa-IPV/Hib and HBV vaccines (comparator). Vaccines were administered at 3, 5 and 11 months of age. The statistical approach for non-inferiority showed that the DTPa-HBV-IPV/Hib vaccine was at least as immunogenic as the comparator vaccines in terms of immunogenicity of all antigens 1 month after the 2nd dose. Non-inferiority criteria were also met immediately before and 1 month after the 3rd dose for all antigens except poliovirus type 3 prior to the 3rd dose. The majority of subjects were seroprotected against diphtheria, tetanus, polyribosyl-ribitol-phosphate, hepatitis B and poliovirus after the 2nd dose and maintained seroprotective antibody levels until the 3rd dose. A marked difference was observed in anti-HBs antibody geometric mean antibody concentrations (GMCs) at 1 month after the 2nd dose (higher GMCs in DTPa-HBV-IPV/Hib group). Reactogenicity (incidence of solicited local and general symptoms) was similar between the two study groups and no vaccine-related serious adverse events occurred. CONCLUSION: the new diphtheria-tetanus-acellular pertussis-hepatitis B virus-inactivated polio/ Haemophilus influenzae b vaccine administered at 3, 5 and 11 months of age was safe and at least as immunogenic as the comparator vaccines thus providing an effective and more comfortable option for this infant vaccination schedule.	M. Avdicová, V. Prikazský, H. Hudecková, L. Schuerman and P. Willems	European journal of pediatrics
90	A beta-adrenergic stimulant, salbutamol, in the treatment of pertussis		M. K. Badr-El-Din, G. H. Aref, A. S. Kassem, M. A. Abdel-Moneim and A. A. Abbassy	The Journal of tropical medicine and hygiene
252	Vitamin A supplementation of women postpartum and of their infants at immunization alters breast milk retinol and infant vitamin A status	Vitamin A supplementation of lactating mothers and of infants at the time of diphtheria-pertussis-tetanus (DPT) and oral polio vaccine (OPV) immunizations have both been suggested as measures to prevent deficiency among infants. This multicenter randomized, double-blind, placebo-controlled trial was conducted in Ghana, India and Peru to determine the effect of maternal vitamin A supplementation on breast milk retinol and of maternal and infant supplementation on infant vitamin A status. Mothers in the intervention group received 60 mg vitamin A (as retinol palmitate) at 18-42 d postpartum; their infants were given 7.5 mg three times, i.e., at 6, 10 and 14 wk of age with DPT and OPV immunizations. Mothers and infants in the comparison group received a placebo. Maternal supplementation resulted in higher breast milk retinol at 2 mo postpartum [difference in means 7.1, 95% confidence interval (CI), 3.4, 10.8 nmol/g fat] and lower proportion of mothers with breast milk retinol < or = 28 nmol/g fat (15.2 vs. 26.6%, 95% CI of difference -16.6, -4.1%). At 6 and 9 mo, maternal supplementation did not affect breast milk retinol or the proportion of mothers with low breast milk retinol. Vitamin A supplementation of the mothers and their infants reduced the proportion of infants with serum retinol < or = 0.7 micro mol/L (30.4 vs. 37%, 95% CI of difference -13.7, 0.6%) and that with low vitamin A stores as indicated by the modified relative dose response (MRDR) > 0.06 (44.2 vs. 52.9%, 95% CI of difference -16.6, -0.9%) at 6 mo. Supplementation had no effect at 9 mo. The beneficial effect of supplementation on breast milk retinol and infants' vitamin A status varied by site. It was greatest in India followed by Ghana and Peru. At the doses used, maternal supplementation improved breast milk retinol status at 2 mo (P < 0.001) and maternal and infant supplementation modestly increased (P = 0.03) infant vitamin A status at 6 mo of age. Additional strategies to improve vitamin A status of 6- to 9-mo-old infants must be considered.	R. Bahl, N. Bhandari, M. A. Wahed, G. T. Kumar and M. K. Bhan	The Journal of nutrition
306	Immunization of babies with diphtheria tetanus pertussis prophylactic		M. Barr, A. T. Glenny and N. R. Butler	Br Med J
295	Need for equivalence testing of efficacy of alternative antibiotics for treatment of pertussis		A. L. Baughman and K. M. Bisgard	Pediatr Infect.Dis.J
455	Effects of pholcodine and salbutamol on citric acid induced cough in normal subjects	Cough may be the presenting feature of asthma in adults and children. Treatments for asthma, such as beta stimulant drugs, are known to be effective in controlling the symptom. Ellul-Micaleff demonstrated the efficacy of oral terbutaline sulphate in a double blind, placebo controlled crossover study of 30 patients with chronic 'allergic' cough. In whopping cough inhaled salbutamol has been found to reduce the frequency and intensity of the whoop but not the cough. In contrast, Pavesio and Ponzone found a reduction in cough as well as whoop with oral salbutamol. The effectiveness of antitussive agents has been assessed most often by the action on cough induced by agents such as critic acid rather than spontaneous cough. Many techniques have been used to assess these effects. We have used the technique of establishing the threshold for citric acid induced coughs to compare the actions of placebo, oral salbutamol, oral pholcodine, and their combination in nine non-asthmatic subjects. Pholcodine has been shown to raise the threshold of coughing in response to citric acid inhalation and was induced in this study as a positive control. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	N. Belcher and P. J. Rees	Thorax
20	Immunogenicity of a three-component acellular pertussis vaccine administered at birth	OBJECTIVE: To evaluate within the first 6 months of birth the immunogenicity of a 3-component acellular pertussis (aP) vaccine containing filamentous hemagglutinin (FHA), pertactine (PRN), and genetically detoxified pertussis toxin (PT) in infants who received a dose of vaccine at birth, in addition to the recommended schedule administered at 3, 5, and 11 months. Furthermore, we investigated the influence of maternal antibodies on aP vaccine response. METHODS: We used enzyme-linked immunosorbent assay to evaluate immunoglobulin G antibody levels in 45 infants immunized at birth and at 3, 5, and 11 months (group 1) and in 46 infants immunized at the ages of 3, 5, and 11 months (group 2). All mothers were also tested at delivery. RESULTS: At the age of 5 months the geometric mean titer of anti-PT, anti-FHA, and anti-PRN was significantly greater in group 1 (who had received 2 doses) than in group 2 (1 dose). At 6 months geometric mean titers were significantly higher in group 1 than in group 2 for anti-PRN and anti-FHA, whereas no significant differences were observed for anti-PT. CONCLUSIONS: Immunization at birth may be important for an earlier prevention of the pertussis disease in infants under 6 months, especially in Italy, where the recommended ages for aP vaccine administration are 3, 5, and 11 months.	C. Belloni, A. Silvestri, C. Tinelli, M. A. Avanzini, M. Marconi, F. Strano, G. Rondini and G. Chirico	Pediatrics
225	Diphtheria-tetanus-pertussis vaccination administered after measles vaccine: increased female mortality?	In low-income countries, children should receive 3 doses of diphtheria-tetanus-pertussis vaccine (DTP) at 6, 10 and 14 weeks of age, and measles vaccine at 9 months of age. However, there is often a delay in administering the vaccines, and DTP is often given after measles vaccine. Previous observations suggest that this practice is associated with increased mortality for female, but not for male children. Within a vitamin A trial in Guinea-Bissau, vaccination status was registered at the time of measles vaccination at 9 months; 141 (31%) of 455 children were missing 1 or more DTP vaccines and were likely to receive them afterward. We examined whether missing DTP vaccine at this time point was associated with sex-differential effects on mortality. In female children, missing DTP was associated with 3.55 (95% confidence interval: 1.23-10.26) times higher risk of dying before 36 months of age, whereas it made no difference in male children (0.97 [0.34-2.80]). The result supports that receiving DTP after measles vaccine affects female children negatively.	C. S. Benn and P. Aaby	The Pediatric infectious disease journal
219	Does vitamin A supplementation interact with routine vaccinations? An analysis of the Ghana Vitamin A Supplementation Trial	BACKGROUND: The World Health Organization recommends vitamin A supplementation (VAS) at vaccination contacts after 6 mo of age to reduce mortality. However, it is unknown whether the effect of VAS is independent of vaccinations. One of the original VAS trials from Ghana had collected vaccination information. OBJECTIVE: We reanalyzed the data to explore the hypothesis that VAS reduces mortality in children who had bacille Calmette-Guérin or measles vaccine as their most recent vaccine but increased mortality when diphtheria-tetanus-pertussis vaccine (DTP) was the most recent vaccine. On the basis of previous studies, we expected the effects to be strongest in girls. DESIGN: At enrollment, children aged 6-90 mo were randomly assigned to receive VAS or placebo every 4 mo for 2 y. Vaccination status was assessed at enrollment and after 1 and 2 y by reviewing the children's health cards. Lack of a health card was presumed to mean that the child had not been vaccinated. RESULTS: VAS had a beneficial effect only in children with no record of vaccination at enrollment (n = 5066); the mortality rate ratio (MRR) was 0.64 (95% CI: 0.47, 0.88) compared with 0.95 (95% CI: 0.72, 1.26) in children with one or more vaccinations (n = 6656). Among vaccinated children, the effect of VAS differed between boys (MRR: 0.74; 95% CI: 0.51, 1.08) and girls (MRR: 1.18; 95% CI: 0.84, 1.67) (P = 0.046 for interaction). VAS had a negative effect in measles-vaccinated girls who were missing one or more doses of DTP at enrollment, a group who often received DTP during follow-up (MRR: 2.60; 95% CI: 1.41, 4.80). CONCLUSIONS: The effect of VAS differed by vaccination status. This is potentially problematic because VAS is provided at vaccination contacts.	C. S. Benn, P. Aaby, J. Nielsen, F. N. Binka and D. A. Ross	The American journal of clinical nutrition
224	The effect of high-dose vitamin A supplementation administered with BCG vaccine at birth may be modified by subsequent DTP vaccination	Unexpectedly, we found no overall beneficial effect on mortality in a randomised trial of vitamin A supplementation (VAS) or placebo administered with BCG vaccine at birth in Guinea-Bissau. We conducted an explorative analysis to examine whether subsequent diphtheria-tetanus-pertussis (DTP) vaccinations had modified the effect of VAS at birth. VAS was associated with a weak tendency for decreased mortality as long as BCG was the most recent vaccination, the mortality rate ratio being 0.86 (0.48-1.54); 0.82 (0.32-2.08) in girls and 0.89 (0.43-1.88) in boys. However, after DTP vaccination VAS at birth was associated with increased mortality in girls (2.19 (1.09-4.38)), whereas no difference was seen for boys (0.90 (0.44-1.82)) (p=0.08 for equal effect of VAS in the two sexes if DTP is the last vaccine). The explanation for the lack of beneficial effect in our setting may have been that VAS at birth interacted negatively with subsequent DTP vaccinations in girls.	C. S. Benn, A. Rodrigues, M. Yazdanbakhsh, A. B. Fisker, H. Ravn, H. Whittle and P. Aaby	Vaccine
184	Reducing immunization discomfort in 4- to 6-year-old children: a randomized clinical trial	OBJECTIVE: The goal was to test a multifaceted distraction method designed to reduce injection-associated pain in school-aged children. METHODS: A clinical trial evaluated 41 children, 4 to 6 years of age, who were given 3 standard prekindergarten immunizations; 21 were assigned randomly to an office routine control group, whereas 20 received a multifaceted, discomfort-reducing intervention. The intervention added verbal suggestions of diminished sensation and a visual focusing activity to the use of ethyl chloride, an established pain-reducing measure. The distraction materials used for the intervention consisted of topical ethyl chloride spray, an improvised, plastic, multipronged arm gripper, and a vibrating instrument descending on the contralateral arm, which provided the focusing task and visual distraction. RESULTS: According to patient and parent Faces Pain Scale-Revised scores and nonblinded, video-taped observations scored according to the face-legs-activity-crying-consolability method, the intervention group showed highly significant reductions in pain and discomfort, compared with the control group (patient self-report, P < .0013; parent report, P < .0002; observation score, P < .0001). CONCLUSION: This multifaceted distraction intervention reduced significantly the pain and discomfort of childhood immunizations in children 4 to 6 years of age.	F. R. Berberich and Z. Landman	Pediatrics
170	Immunogenicity, safety, and reactogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine and DTPa-IPV-Hib when coadministered as a 3-dose primary vaccination schedule in The Netherlands: a randomized controlled trial	BACKGROUND: Recent reviews have highlighted the unpredictability of immunologic interference when multivalent conjugated vaccines are coadministered with other pediatric vaccines. OBJECTIVE: To evaluate immunogenicity, safety, and reactogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV; Synflorix, GlaxoSmithKline Biologicals) and DTPa-IPV-Hib (Pediacel, Sanofi Pasteur MSD) when coadministered as a 3-dose primary vaccination course. MATERIAL AND METHODS: In a single-blind, single-center, randomized controlled trial in the Netherlands, healthy infants (n = 780) were randomly assigned (1:1:1) to receive either (1) PHiD-CV + DTPa-HBV-IPV/Hib (Infanrix Hexa, GlaxoSmithKline Biologicals), (2) PHiD-CV + DTPa-IPV-Hib, or (3) 7-valent pneumococcal conjugate vaccine (Prevenar/Prevnar, Pfizer Inc.) + DTPa-IPV-Hib at 2, 3, and 4 months of age. Blood samples were collected 1 month after dose 3. Diary cards were used to record safety and reactogenicity. RESULTS: Antibody concentrations elicited by PHiD-CV coadministered with DTPa-IPV-Hib were noninferior to those following DTPa-HBV-IPV/Hib coadministration for 9 of 10 vaccines pneumococcal serotypes and protein D. For serotype 18C (conjugated to tetanus toxoid), the antibody concentration was higher with DTPa-HBV-IPV/Hib coadministration (1.73 vs. 1.07 ?g/mL). The percentages of infants with antibody concentrations ?0.2 ?g/mL (68.9%-100% in the PHiD-CV + DTPa-HBV-IPV/Hib group vs. 64.9%-100% in the PHiD-CV + DTPa-IPV-Hib group) and with measurable opsonophagocytic activity (56.1%-100% in the PHiD-CV + DTPa-HBV-IPV/Hib group vs. 61.1%-100% in the PHiD-CV + DTPa-IPV-Hib group) were comparable for all serotypes in both PHiD-CV groups. Group differences in antibody responses to the DTPa-IPV-Hib antigens remained within the predefined limit for noninferiority. Safety and reactogenicity profiles were comparable across groups. CONCLUSIONS: : PHiD-CV and DTPa-IPV-Hib were immunogenic and well tolerated when coadministered as a 3-dose primary vaccination course.	M. R. Bergh, J. Spijkerman, N. François, K. Swinnen, D. Borys, L. Schuerman, R. H. Veenhoven and E. A. Sanders	The Pediatric infectious disease journal
107	Safety and immunogenicity of fully liquid DTaP?-IPV-Hib pediatric combination vaccine (Pediacel®) compared to DTaP?-HBV-IPV/Hib (Infanrix® Hexa) when coadministered with heptavalent pneumococcal conjugate vaccine (PCV7) as a booster at 11-18 months of age: a phase III, modified double-blind, randomized, controlled, multicenter study	This study compared the safety and immunogenicity of DTaP?-IPV-Hib vaccine (followed by monovalent hepatitis B vaccine [HBV]) and DTaP?-HBV-IPV/Hib vaccines, both coadministered with PCV7, as a fourth-dose booster in toddlers 11-18 months who had a hexavalent vaccine primary series. The fever rate within 4 days of DTaP?-IPV-Hib was noninferior to DTaP?-HBV-IPV/Hib. DTaP?-IPV-Hib induced a marked immune response and had a similar safety and immunogenicity profile compared with DTaP?-HBV-IPV/Hib. Fully liquid DTaP?-IPV-Hib can be used as a booster after a hexavalent vaccine primary series; where required, a fourth dose of monovalent HBV can be administered after DTaP?-IPV-Hib (NCT ID: NCT00355654).	R. Berner, F. Boisnard, S. Thomas, G. Mwawasi and D. Reynolds	Vaccine
53	Comparison of acellular pertussis vaccine with whole cell vaccine as a booster in children 15 to 18 months and 4 to 6 years of age	The safety and immunogenicity of a booster dose of a new acellular pertussis component diphtheria-tetanus toxoids-pertussis vaccine (DTaP) were compared with whole cell pertussis component diphtheria-tetanus toxoids-pertussis vaccine (DTwP). Fifty children ages 15 to 18 months and 50 children ages 4 to 6 years were studied. The incidence of adverse reactions observed during the first 72 hours after vaccination in the DTaP/DTwP vaccinees were: pain, 32%/92% (P < 0.001); redness, 14%/24% (P = 0.2); swelling, 2%/14% (P < 0.03); fever, 52%/90% (P < 0.001); drowsiness, 14%/34% (P < 0.05); fussiness, 32%/88% (P < 0.001); and unusually poor appetite, 6%/42% (P < 0.001). The geometric mean titers of anti-pertussis toxin and anti-filamentous hemagglutinin antibody were also significantly (P < 0.001) higher in the DTaP compared to the DTwP recipients. When administered as a booster dose this DTaP vaccine, which has been chosen by the NIH for the second pertussis vaccine clinical efficacy trial, was more immunogenic for pertussis toxin and filamentous hemagglutinin and caused fewer and less severe adverse reactions compared with the Connaught DTwP vaccine used in this study.	D. I. Bernstein, V. E. Smith, G. M. Schiff, H. M. Rathfon and J. A. Boscia	The Pediatric infectious disease journal
112	Immunogenicity and safety of a combined diphtheria, tetanus, 5-component acellular pertussis, inactivated poliomyelitis, Haemophilus type b conjugate vaccine when administered concurrently with a pneumococcal conjugate vaccine: a randomized, open-label, phase 3 study	A phase 3 randomized, multicenter study evaluated the safety and immunogenicity of a combined diphtheria, tetanus, 5-component acellular pertussis, inactivated poliomyelitis, Haemophilus influenzae type b conjugate vaccine (DTaP(5)-IPV/Hib) administered at the same visit with 7-valent pneumococcal conjugate vaccine (PCV7, concurrent group) or at separate visits (separated by ? 15 days; staggered group). DTaP(5)-IPV/Hib was administered at 2, 4, 6, and 15 months of age, and PCV7 was administered concurrently or at 3, 5, 7, and 16 months of age. The study results found that DTaP(5)-IPV/Hib is safe and immunogenic when given concurrently with 7-valent pneumococcal conjugate vaccine.	H. H. Bernstein and F. Noriega	Vaccine
67	Reactogenicity and immunogenicity of a three-component acellular pertussis vaccine administered as the primary series to 2, 4 and 6 month old infants in the United States	Five hundred and fifty-seven infants received either an acellular pertussis (DTaP) vaccine containing pertussis toxoid (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) or one of two commercially available whole-cell pertussis (DTP) vaccines at 2, 4 and 6 months. One month after the third immunization, IgG antibody values to pertussis toxoid, filamentous hemagglutinin and PRN were significantly greater following DTaP than either DTP (P < 0.05). When reactions within 48 h after all three doses of vaccine were combined, fever 101 degrees, > or = moderate fussiness, > or = moderate pain, swelling 10 mm, and erythema 10 mm occurred less often after DTaP compared with DTP-Connaught (P < 0.001). The same adverse events were also less after DTaP compared with DTP-Lederle (P < 0.05), except for erythema 10 mm. This three-component DTaP vaccine produced fewer adverse events and greater antibody values to PT, FHA and PRN in comparison with either licensed DTP vaccine when given as the primary series.	H. H. Bernstein, E. P. Rothstein, M. E. Pichichero, J. L. Green, K. S. Reisinger, M. M. Blatter, J. Halpern, A. M. Arbeter, D. I. Bernstein and V. Smith	Vaccine
377	Influence of high titers of maternal antibody on the serologic response of infants to diphtheria vaccination at three, five and twelve months of age	Diphtheria antitoxin was determined in serum from 44 pregnant women, of whom 26 had received one injection of diphtheria toxoid during pregnancy. Their infants were vaccinated with a combined diphtheria-tetanus vaccine at 3, 5 and 12 months of age. This vaccination schedule has been used in Sweden since 1986, replacing the old schedule of vaccination at 3, 4.5 and 6 months of age originally designed for diphtheria-tetanus-pertussis vaccine, which had not been used after cessation of general vaccination against pertussis in 1979. Serum samples from the infants were obtained at 3, 7 and 18 months of age. After 2 injections infants of mothers with high antitoxin titers, > or = 0.1 IU/ml, tended to have lower antitoxin titers than infants of mothers with low antitoxin concentrations (P = 0.067). All children had, however, antitoxin above the minimum protective level of 0.01 IU/ml. Median antitoxin titers were 1.6 IU/ml in both groups after the third booster injection. Four infants of mothers who had been vaccinated during pregnancy and who had titers of > or = 0.4 IU/ml did not reach the 0.1 IU/ml level after 2 injections: all 4 responded with high antitoxin titers after the third dose. Thus all infants were primed by 2 doses of vaccine, irrespective of maternal antibody concentration. The repressive effect of maternal antibody on titers noted after 2 doses was no longer observed after the third, booster dose.	B. Björkholm, M. Granström, J. Taranger, M. Wahl and L. Hagberg	The Pediatric infectious disease journal
47	Diphtheria-tetanus-acellular pertussis and inactivated poliovirus vaccines given separately or combined for booster dosing at 4-6 years of age	BACKGROUND: In the United States, diphtheria-tetanus-acellular pertussis (DTaP) and inactivated poliovirus (IPV) booster vaccinations are recommended for children 4-6 years of age. A combined DTaP-IPV vaccine is being developed, which would reduce by one the number of injections in this age group. METHODS: Children 4-6 years of age were randomized (1:1:1:1) to receive booster vaccination with 1 of 3 combined DTaP-IPV lots plus the measles, mumps, and rubella vaccine (N = 3156 for pooled lots) or separate doses of DTaP + IPV + measles, mumps, and rubella vaccine (N = 1053). Immunogenicity was assessed in a subset of children (N = 1331). Safety (solicited and unsolicited symptoms) including detailed assessment of local swelling reactions, was assessed in all children. RESULTS: Increases in antibody geometric mean concentrations/titers 1 month after vaccination were observed for the diphtheria, tetanus, acellular pertussis, and polio antigens. At least 92.2% of combined DTaP-IPV subjects and 92.6% of separate DTaP + IPV subjects had a postvaccination booster response for one or more DTaP antigens. Booster responses to one or more poliovirus antigens were observed in at least 96.6% of combined DTaP-IPV subjects and 92.8% of separate DTaP + IPV subjects. The combined DTaP-IPV vaccine was noninferior to separately administered DTaP and IPV vaccines with respect to DTaP antigen booster response rates and poliovirus antibody geometric mean titers ratios. Reporting of solicited local and systemic events was comparable between both groups. CONCLUSIONS: The combination DTaP-IPV vaccine provided immunogenicity and reactogenicity that is comparable to separately administered DTaP and IPV vaccines, with the advantage of requiring one less injection.	S. Black, L. R. Friedland, K. Ensor, W. M. Weston, B. Howe and N. P. Klein	The Pediatric infectious disease journal
180	Immunogenicity and safety of a combined DTaP-IPV vaccine compared with separate DTaP and IPV vaccines when administered as pre-school booster doses with a second dose of MMR vaccine to healthy children aged 4-6 years	Combination vaccines represent one solution to the problem of increased numbers of injections during single clinic visits. A combined DTaP-IPV (Infanrix-IPV) vaccine has been developed for use as a pre-school booster. Four hundred healthy children aged 4-6 years previously primed with 4 doses of DTaP vaccine (Infanrix), 3 doses of poliovirus vaccine and 1 dose of MMR vaccine were randomized to receive single doses of either the combined DTaP-IPV vaccine or separate DTaP and IPV vaccines in a Phase II trial (DTaP-IPV-047). All children also received a second dose of MMR vaccine. Immunogenicity was assessed in serum samples taken before and 1 month after booster administration. Safety was actively assessed for 42 days post-vaccination. Non-inferiority of the DTaP-IPV vaccine to separate DTaP and IPV vaccines was demonstrated for all DTaP antigen booster response rates and poliovirus geometric mean titers of antibody ratios. Post-vaccination, > or =99.4% of children in both groups had seroprotective levels of anti-diphtheria and anti-tetanus antibodies (> or =0.1IU/mL) and seroprotective anti-poliovirus antibody titers (> or =1:8). All children in both groups were seropositive for measles, mumps and rubella antibodies, with similar post-vaccination geometric mean concentrations/titers. No significant differences were observed in the incidence of solicited local or general symptoms, unsolicited symptoms and serious adverse events between the two groups. This combined DTaP-IPV appeared safe and immunogenic when given as a booster dose at 4-6 years of age. The DTaP-IPV vaccine had no negative effect on the response to co-administered MMR vaccine, making it well-suited for use as a pre-school booster.	S. Black, L. R. Friedland, A. Schuind and B. Howe	Vaccine
316	Safety and immunogenicity of Chiron/Biocine (R) recombinant acellular pertussis-diphtheria-tetanus vaccine in infants and toddlers	Objective. To evaluate the safety and immunogenicity of the recombinant acellular pertussis-diphtheria-tetanus (aPDT) vaccine (C-aPDT, Chiron/Biocine (R)). Study design. This is a randomized blinded trial evaluating the safety and immunogenicity of the recombinant aPDT vaccine (C- aPDT, Chiron/Biocine (R)) in 2000 infant recipients compared with 498 controls who received whole cell diphtheria-pertussis-tetanus (wDPT; Connaught) vaccine at 2, 4 and 6 months of age. In addition the safety and immunogenicity of the same C-aPDT vaccine were evaluated as a booster dose in a subset of the same population when given at 15 to 18 months of age and compared with licensed Lederle aPDT vaccine. Results. The C-aPDT vaccine was associated with very few local or systemic reactions when compared with wDPT. In toddlers the local and systemic side effects observed were similar after either acellular vaccine. When the immunogenicity of the C-aPDT vaccine was compared with the wDPT (Connaught) in infancy, the vaccines were equivalent for anti-diphtheria response, the wDPT developed higher anti-tetanus response and the C-aPDT vaccine was significantly more immunogenic for all other antigens tested. In toddlers the C-aPDT acellular vaccine exhibited equal or improved immunogenicity for antigens tested as compared with Lederle aPDT except fora higher anti-filamentous hemagglutinin response with the Lederle aPDT vaccine. Conclusion. The Chiron/Biocine (R) aPDT vaccine offers an improved safety profile as well as improved immunogenicity when compared with a licensed wDPT product. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	S. B. Black, H. R. Shinefield, R. Bergen, C. Hart, R. Kremers, A. Lavetter, J. Lemesurier, P. A. Morozumi, P. Ray, E. M. Lewis, B. Fireman, J. Schwalbe, P. Hallam, M. Shandling, C. Dekker, D. M. Granoff, A. Izu and A. Podda	Pediatric Infectious Disease Journal
283	Sample size and power for prospective analysis of relative risk	In a placebo-controlled vaccine efficacy trial or a trial of equivalence of vaccines, one may wish to show that relative risk of disease is less than a specified value R0, not equal to one. This paper compares three methods for estimating relative risk in the binomial setting, based on a logarithmic transformation, likelihood scores, and a Poisson approximation. Exact power and size of test are calculated by enumeration of possible binomial outcomes, and power is approximated from asymptotic formulations. Although the score method is generally preferable, for most studies of practical interest the log and score methods are comparable, and the Poisson method is also appropriate for small risks, up to about 0.05. When true and null relative risks are less than one, unequal allocation of study individuals can increase power, and the asymptotic formula for the log method may substantially underestimate power; in such a study the power approximation for the score method is more reliable, even if the log method is used in analysis. Exact power calculations are helpful in planning studies. The log and Poisson methods, but not the score method, apply readily in the case of unequal follow-up.	W. C. Blackwelder	Statistics in medicine
78	Long term serologic follow-up after pertussis immunization	Neutralizing antibodies to pertussis toxin (antitoxin) were determined in 201 blood samples from 4-year-old children. They had received primary immunization at 6 to 8 months of age with an acellular (n = 149) or a whole cell (n = 52) pertussis vaccine and 195 of them had received a booster dose of the acellular vaccine 9 to 16 months later. Data on exposure to pertussis and occurrence of pertussis were also collected. There was a rapid decrease of antitoxin between immediate postbooster titers and those measured 24 months later. This decrease per month was significantly greater than that after the primary immunization series (P less than 0.001). Neither the number nor the spacing of acellular vaccine doses given for primary series influenced the titers found 24 months after the booster. An antitoxin response was still measurable in 86% of the 196 four-year-old children. None of 19 exposed children developed whooping cough, which suggested that the antibody concentrations during the follow-up period were sufficient for protection. The results indicate a need for long term follow-up studies in the evaluation of new vaccines and immunization schedules.	M. Blennow and M. Granström	The Pediatric infectious disease journal
77	Protective efficacy of a whole cell pertussis vaccine	A trial of the efficacy of a plain whole cell pertussis vaccine was conducted in Sweden. In this non-blinded trial 525 infants aged 2 months who were born on days with an even number received three doses of vaccine one month apart and 615 infants of the same age who were born on days with an odd number were enrolled as controls. During the 18 months of follow up there were 55 cases of pertussis. The attack rate was 1.5% (8/525) among the vaccinated children and 7.6% (47/615) among the unvaccinated children (p less than 0.001). The estimated efficacy of the vaccine was 80% (95% confidence interval 58 to 90). The estimated efficacy of pertussis vaccine was similar to that observed in British trials over 30 years ago.	M. Blennow, P. Olin, M. Granström and R. H. Bernier	British medical journal (Clinical research ed.)
58	Overview of the clinical development of a diphtheria-tetanus--acellular pertussis vaccine	A tricomponent acellular pertussis vaccine containing pertussis toxoid, filamentous hemagglutinin, and pertactin combined with diphtheria and tetanus toxoids (DTPa) was developed as a less reactogenic alternative to the traditional whole cell pertussis (DTPw) vaccine. In studies of DTPa as a primary vaccination and as a booster dose in DTPa- or DTPw-primed children, the vaccine was safe, well-tolerated, and highly immunogenic; it was less reactogenic than DTPw but at least as immunogenic. A three-dose primary vaccination sequence with DTPa vaccine in the first 6 months of life protects against pertussis under conditions of high infectious pressure. These results support the licensing of the vaccine for primary and booster vaccination in a growing number of countries. Combined DTPa-based pediatric vaccines are in clinical development.	H. Bogaerts, C. Capiau, P. Hauser, J. C. Mareschal, V. Mélot and D. Simons	The Journal of infectious diseases
417	Efficacy of Haemophilus influenzae type b conjugate vaccine PRP-T	Efficacy of the Haemophilus influenzae type b (Hib) conjugate vaccine PRP-T (Pasteur-Merieux) was evaluated in a controlled community intervention study in the Oxford region, UK. PRP-T was offered to infants from May 1, 1991 in three of the region's eight districts and from July 1, 1991, in a fourth district. It was given by separate injection in addition to the standard diphtheria, tetanus, and pertussis vaccine according to an accelerated 2, 3, and 4 month schedule without a booster dose in the second year of life. By October 1, 1992, more than 90% of infants in vaccine districts had received at least one dose of PRP-T. None of the infants given three doses had developed Hib infection, whereas 11 infections occurred in the control population (vaccine efficacy 100%, 95% CI 80-100%). Intention-to-treat analysis also showed a high estimate of efficacy for the vaccine (90%, 50-99%). Follow-up of study children until November 1, 1993, has shown only 1 vaccine failure in an infant, and no invasive infections in those older than 1 year (average age 22 months). PRP-T vaccine had high protective efficacy with an accelerated immunisation schedule. Furthermore, the vaccine appears to remain protective through the second year of life without a booster dose. These findings provide encouragement for use of PRP-T in the Expanded Programme of Immunisation.	R. Booy, S. Hodgson, L. Carpenter, R. T. Mayon-White, M. P. Slack, J. A. Macfarlane, E. A. Haworth, M. Kiddle, S. Shribman and J. S. Roberts	Lancet
181	Immunogenicity and safety in infants of a DTwPHib full liquid vaccine	AIM: Combining paediatric vaccines is a rational solution to reduce the number of injections during a single clinical visit, to maintain parents' compliance and to extend vaccine coverage. Different diphtheria, tetanus and whole cell pertussis (DTwP)-containing combination vaccines are licensed and used world-wide. This study assessed the immunogenicity and safety in infants of a combined diphtheria-tetanus-whole cell pertussis-Haemophilus influenzae type b-CRM197 conjugate full liquid vaccine. METHODS: The safety and efficacy of a combined ready-to-use liquid vaccine containing diphtheria and tetanus toxoids, cell suspension of Bordetella pertussis and H. influenzae type b-CRM197 conjugate vaccine (DTwPHib) were assessed in infants eligible for the local Expanded Programme on Immunization (EPI) in Valencia, Spain. The comparative group received separate injections of reference vaccines DTwP + Hib. RESULTS: Local and systemic reactions and adverse events were generally mild and similar in the two groups. DTwPHib elicited anti-PRP antibody titres > or = 0.15 microg ml(-1) in 97% and DTwP + Hib in 94% of infants. Furthermore, 89% of DTwPHib and 78% of DTwP + Hib recipients attained anti-PRP antibody titres > or = 1.0 microg ml(-1), signifying long-term protection. The anti-PRP geometric mean titre was significantly higher in the combined DTwPHib vaccine group (6.65 vs 3.57 microg ml(-1)). In both groups, 99% of infants achieved protective (> or = 0.01 IU ml(-1)) anti-diphtheria antibody levels and all children achieved protective (> or = 0.1 IU ml(-1)) anti-tetanus antibody levels. DTwPHib caused a > or = 2-fold increase in anti-pertactin antibody titres in 91% and a > or = 4-fold increase in 82% of recipients. The corresponding proportions in the DTwP + Hib group were 95% and 90%. DTwPHib induced a > or = 2-fold increase in anti-Aggl2 and 3 antibody levels in 79% and a > or = 4-fold increase in 73% of recipients. The corresponding proportions among DTwP + Hib infants were 85 and 82%. CONCLUSION: Overall, the combined liquid vaccine DTwPHib is a safe and effective immunogenic vaccine for EPI use in infants.	F. I. Botet Asensi, A. Veronese, M. Carmen Otero, M. Desamparados Tamarit Pérez, J. L. Hontangas Lopez and S. Viviani	Acta paediatrica (Oslo, Norway : 1992)
345	Combined prophylactics. Variations in response in children to diphtheria toxoid produced by addition of tetanus toxoid and H. Pertussis vaccine		G. Bousfield and L. B. Holt	British Medical Journal
348	Combined prophylactics: variations in response, in children, to diphtheria toxoid and H. pertussis vaccine		G. Bousfield and L. B. Holt	Br Med J
414	Safety and immunogenicity of three lots of meningococcal serogroup C conjugate vaccine administered at 2, 3 and 4 months of age	The reactogenicity and immunogenicity of meningococcal serogroup C conjugate (MenC) vaccine was assessed in 322 infants vaccinated at 2, 3, and 4 months of age, with concomitant administration of mixed diphtheria-tetanus-whole-cell pertussis vaccine and Haemophilus influenzae type b conjugate vaccine (DTwP-Hib) and oral polio vaccine. All infants in whom post-vaccination meningococcal C anticapsular IgG levels were assayed (n = 265) attained > or = 2 microg ml(-1). Serum bactericidal titres were assayed for a proportion of subjects (n = 171), 98% of whom obtained a reciprocal titres > or = 8. Local reactions were less frequent at the MenC injection site than at the DTP-Hib site. Systemic events were frequent, but consistent with established DTwP-Hib experience. The study demonstrates that MenC vaccine is immunogenic and well tolerated in infants at manufacturing scale production levels.	J. C. Bramley, T. Hall, A. Finn, R. B. Buttery, D. Elliman, S. Lockhart, R. Borrow and I. G. Jones	Vaccine
272	"I hardly cried when I got my shot!" Influencing children's reports about a visit to their pediatrician	We examined, in 2 phases, the influence of postevent suggestions on children's reports of their visits to a pediatrician. Phase 1 examined the effect of giving one of 3 types of feedback to 5-year-old children immediately following their Diphtheria Pertussis Tetanus (DPT) inoculation. Children were given pain-affirming feedback (the shot hurt), pain-denying feedback (the shot did not hurt), or neutral feedback (the shot is over). 1 week later, they did not differ in their reports concerning how much the shot hurt or how much they cried. In Phase 2, the same children were visited approximately 1 year after their inoculation. During 3 separate visits, they were either given additional pain-denying or neutral feedback. They were also given misleading or nonmisleading information about the actions of the pediatrician and the assistant. Children given pain-denying feedback reported that they cried less and that the shot hurt less than did children given neutral feedback. Those who were given misleading information about the actions of the assistant and the pediatrician made more false allegations about their actions than did children who were not given this information. These results challenge the view that suggestibility effects are confined to peripheral, nonaction events; in this study children's reports about salient actions involving their own bodies in stressful conditions were influenced.	M. Bruck, S. J. Ceci, E. Francoeur and R. Barr	Child development
163	Effectiveness of chart prompt about immunizations in an urban health center	OBJECTIVE: To determine whether a nurse-initiated chart review and prompt to physicians is an effective method to increase immunization rates. STUDY DESIGN: This study was a controlled trial with systematic assignment of children to intervention or control groups based on chart number. Each day, a nurse reviewed the charts of children to be seen that day who were in the intervention group. The nurse prepared a 1-page form about the child's immunization status that requested permission from the physician to administer needed vaccines and attached the form to the chart. The duration of the study period was 1 year. POPULATION: Nine hundred ninety-seven pediatric patients attending 2 inner-city primary care health centers. OUTCOME MEASURED: On-time immunization rates in both groups. RESULTS: Among children eligible to receive vaccines during the study period, a higher percentage in the intervention group received on-time vaccines for diphtheria/tetanus/pertussis-4 (DTP4; 51% vs 36%; P=.03), oral polio vaccine-3 (OPV3; 70% vs 56%, P=.04), and measles/mumps/rubella-1 (42% vs 26%; P=.01) than did children in the control group. No statistically significant differences were noted for DTP3, DTP5, hepatitis B3, or OPV4. No statistically significant difference was noted for the combined series (ie, all age-appropriate immunizations as recommended by the 1995 Childhood Immunization Schedule of the Centers for Disease Control and Prevention). CONCLUSIONS: The chart prompt increased on-time immunizations for some antigens.	I. T. Burns, R. K. Zimmerman and T. A. Santibanez	The Journal of family practice
364	Treatment of pertussis with streptomycin-inhalations		F. Buser and R. Martin du Pan	Schweizerische Rundsdchau fur Medizinische Praxis
354	Response of infants to pertussis vaccine at one week and to poliomyelitis, diphtheria, and tetanus vaccine at six months		N. R. Butler, B. D. R. Wilson, P. F. Benson, J. A. Dudgeon, J. Ungar and A. J. Beale	Lancet
110	Comparative trial to assess the reactogenicity of the diphtheria-tetanus-acellular pertussis (DTPa) vaccine plus Haemophilus influenzae type B (Hib) conjugate vaccine and that of the diphtheria-tetanus-whole cell pertussis (DTPw) vaccine plus Hib conjugate vaccine, administered in single injection a	BACKGROUND: The diphtheria-tetanus-whole-cell pertussis (DTPw) vaccine is being replaced in Western countries,and in several Spanish Autonomous Communities, by the diphtheria-tetanus-acellular pertussis (DTPa) vaccine. Although the administration of booster doses of DTPw or DTPa and Haemophilus influenzae type b conjugate (Hib) vaccines to toddlers is a current practice ina number of countries, there are few data comparing the reactogenicity profiles of their administration as a single injection. SUBJECTS AND METHOD: An open,prospective, randomised, multicentre trial was conducted to compare the reactogenicity profile of a single injection of DTPa and Hib vaccines (DTPa/Hib) with that of a single injection of DTPw and Hib vaccines (DTPw/Hib) as booster doses to toddlers--previously primed with DTPw and Hib vaccines. 200 children (15.1 +/-1.0 months-old) were randomised to receive DTPa/Hib (group 1;n = 101) or DTPw/Hib (group 2; n = 99) and followed up to 30 days post-vaccination. All subjects received the oral polio vaccine concomitantly. Local and general symptoms were recorded by parents on diary cards. RESULTS: Incidences of any local reaction and any general symptom <probably related>/<suspected>to vaccination were reported more frequently in group 2 than in group 1 (p < 0.0001). Pain at the injection site was reported by 29% and 66% of subjects in groups 1 and 2, respectively (p< 0.0001). Pain such that the child cried when limb was moved was also more frequently recorded in group 2 (15%) than in group 1 (1%) (p < 0.0001). Differences in prevalence of any swelling(16% in group 1, 30% in group 2) and swelling > 20 mm reached statistical significance (p (3/4) 0.012). Fever (rectal temperature>= 38 degrees C) was reported by 17% and 41 % in groups 1 and 2 subjects, respectively (p < 0.0001). Fussiness, loss of appetite and restlessness were also more frequently reported in DTPw/Hib subjects and reached statistical significance (at least p = 0.015).Analgesics/antipyretics were prescribed as a prophylactic treatment in only 14% of cases (9 and 19 subjects in groups 1 and 2, respectively;p = 0.0424). Antipyretic treatment after vaccination was significantly more prescribed in group 2 (27 cases) than in group 1 (8) (p <0.015). CONCLUSION: The administration of DTPa/Hib as a single injection leads to a better reactogenicity profile than the administration of DTPw/Hib, also as a single injection, as booster doses to toddlers primed with DTPw and Hib vaccines.	F. Calbo, R. Dal-Ré, J. Díez-Delgado, S. Oña, F. Sánchez-Prados and P. García-Corbeira	Medicina clínica
422	Antibody responses of three Haemophilus influenzae type b conjugate vaccines after one, two and three doses in Filipino children	Differences in the magnitude of antibody response after one, two or three doses of Haemophilus influenzae type b conjugate vaccines have been reported which may influence decision-making regarding which vaccine should be used. This is of particular importance in developing countries where children may not receive a full immunization series and the vaccination schedule may be delayed. Serum antibody responses to three Hib capsular polysaccharide protein conjugate vaccines (PRP-OMP, HbOC and PRP-T) were evaluated in 102 Filipino infants. Vaccination was carried out at 6, 10 and 14 weeks of age based on the national Expanded Programme on Immunization (EPI) schedule together with diphtheria-tetanus-pertussis, hepatitis B and oral poliomyelitis vaccines. Sera were collected at 6 weeks and 1 month after each vaccination. Anti-Hib polysaccharide antibody concentrations were determined by Farrtype radioimmunoassay (RIA) and enzymeimmunoassay (EIA), Following the first dose, the geometric mean concentrations (GMC, micrograms ml-1) for PRP-OMP, HbOC and PRP-T were 0.69, 0.27 and 0.38, respectively. After two doses, there was a significant response (P < 0.05) to PRP-OMP and PRP-T (0.89 and 1.47) but not for HbOC (0.37). Differences in the GMC after the primary series were significant (pairwise P < 0.05): GMC was highest for PRP-T (4.0), followed by HbOC (1.6) and PRP-OMP (1.1). All three Hib vaccines were immunogenic when given in the local EPI schedule in Filipino infants although significant differences in the kinetics and magnitude of antibody responses were noted. The anti-Hib antibody concentrations determined by RIA and EIA were also compared in order to validate the latter for use in laboratories where it is feasible. There was a good correlation (r2 = 76%; P = 0.0001) in the Hib antibody titres obtained by both assays.	M. R. Capeding, H. Nohynek, H. Käyhty, L. G. Pascual, E. S. Sunico, A. A. Tamundong and P. Ruutu	Vaccine
194	Absence of an increase in cardiorespiratory events after diphtheria-tetanus-acellular pertussis immunization in preterm infants: a randomized, multicenter study	OBJECTIVE: The American Academy of Pediatrics recommends immunization of preterm infants at 2 months' chronological age with diphtheria-tetanus-acellular pertussis vaccine, regardless of birth weight and gestational age. Several investigators have reported an increased incidence of cardiorespiratory events in preterm infants after immunization. Consequently, many primary care providers do not adhere to American Academy of Pediatrics guidelines. The purpose of this study was to reexamine the relationship between diphtheria-tetanus-acellular pertussis and cardiorespiratory events in preterm infants by using a random control study design and an objective assessment of cardiorespiratory events. METHODS: Ten hospitals enrolled 191 infants who were born at <37 weeks' gestational age at 56 to 60 days' chronological age. Infants were randomly assigned to a group that received diphtheria-tetanus-acellular pertussis immunization (n = 93) or a control group that did not (n = 98). Recording monitors were used continuously during the next 48 hours to document prolonged apnea and prolonged bradycardia. The presence and number of episodes during the 48-hour period were compared between groups by using chi(2) and t tests. RESULTS: In the diphtheria-tetanus-acellular pertussis group, 16.1% experienced at least 1 episode of prolonged apnea compared with 20.4% of control infants. One or more prolonged bradycardia events occurred in 58.1% of immunized infants and 56.1% of the control infants. The frequency of episodes was not significantly different between groups. The immunization group and the control group each had an average of 0.5 episodes of prolonged apnea. The mean number of prolonged bradycardia episodes was 2.6 in the immunization group and 2.7 in the control group. CONCLUSIONS: Preterm infants who received diphtheria-tetanus-acellular pertussis at 2 months after birth were no more likely to experience prolonged apnea and bradycardia than were control infants. This study supports the American Academy of Pediatrics recommendation regarding diphtheria-tetanus-acellular pertussis immunization at 2 months of age for preterm infants.	T. Carbone, B. McEntire, D. Kissin, D. Kelly, A. Steinschneider, K. Violaris and N. Karamchandani	Pediatrics
256	A randomized double-blind, placebo-controlled trial of the EMLA patch for the reduction of pain associated with intramuscular injection in four to six-year-old children	UNLABELLED: The effectiveness of a eutectic mixture lidocaine-prilocaine topical anaesthetic cream (EMLA) patch compared with a placebo patch in the reduction of pain associated with intramuscular immunization was evaluated. As part of the study, 161 children (aged 4-6-y) undergoing routine diphtheria, pertussis, tetanus and polio (DPTP) immunization in five urban and five rural private office settings were randomly assigned to an EMLA patch (n = 83) or a placebo patch control group (n = 78). Pain measurements included: child's self-report on a Faces Pain Scale; facial action on the Child Facial Coding System; the Children's Hospital of Eastern Ontario Pain Scale and parent and technician ratings on a Visual Analogue Scale. Parents also rated their own and their child's immunization-related anxiety on a Visual Analogue Scale. The EMLA patch group had significantly less pain on all four pain measures compared with the placebo group. Of the children in the placebo group, 43% had clinically significant pain, compared with 17% of children in the EMLA patch group. No severe adverse symptoms occurred as a result of either EMLA or placebo patch application. CONCLUSION: The EMLA patch reduced immunization pain in 4 to 6-y-old children during needle injection.	K. L. Cassidy, G. J. Reid, P. J. McGrath, D. J. Smith, T. L. Brown and G. A. Finley	Acta paediatrica (Oslo, Norway : 1992)
277	The pain response of infants in Turkey to vaccination in different injection sites	This study was carried out with the aim of comparing pain responses of children who receive intramuscular (IM) vaccination in deltoid muscle versus the pain responses of those who receive IM vaccination in the vastus lateralis. A total of 185 infants were randomly assigned to one of the two study groups. The deltoid group and the vastus lateralis group were vaccinated respectively in the deltoid muscle and the vastus lateralis. Our results indicated that pain response of infants was similar in each group. However, crying duration of the children who received the vastus lateralis vaccination was shorter than that of the deltoid group after the procedure.	A. Celebioglu, R. B. Akpinar and A. Tezel	Applied nursing research : ANR
270	Effect of oral sucrose on pain during DPT immunization in older infants		D. Chattopadhyay, P. Kundu, S. Gunri and S. Bisoi	Indian journal of public health
120	Immunogenicity and reactogenicity of two regimens of diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio and Haemophilus influenzae type b vaccines administered to infants primed at birth with hepatitis B vaccine	An open, randomized study evaluated the immune response and safety of two different regimens of diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b (DTPa-HBV-IPV-Hib) immunization in infants primed at birth with hepatitis B vaccine. One-half of the 150 healthy, full-term infants received a DTPa HBV-IPV-Hib vaccine at 1 1/2, 3 and 5 months of age; the other received a DTPa-IPV-Hib vaccine at 1 1/2, 3 and 5 months of age with separate HBV vaccine at 1 and 5 months of age. Immune response was similar following the two regimens with 100% of the vaccinees seroprotected for HBV, diphtheria, tetanus, Hib and poliovirus types 2 and 3 diseases after the full vaccination course. One vaccinee in the DTPa HBV-HPV- Hib group failed to respond to the poliovirus type 1 antigen. Response to the three pertussis antigens ranged from 92-97% in the DTPa-IPV-Hib plus separate HBV group and 100% in the DTPa HBV-IPV-Hib group. The most frequently reported post-vaccination symptoms were irritability in the DTPa-IPV-Hib plus separate HBV group (49% of vaccinees) and fever, defined as axillary temperature > or =37.5 degrees C, in the DTPa HBV- IPV-Hib group (50% of vaccinees).	H. K. Cheng, V. S. Rajadurai, Z. Amin, B. Sriram, M. F. Yee, H. H. Han, H. L. Bock and A. Safary	The Southeast Asian journal of tropical medicine and public health
22	[Evaluation of the usefulness of Bordetella pertussis toxins for serodiagnosis of whooping cough]	The results of serological tests for the detection of antibodies against pertussis toxin by means of the ELISA test, and endotoxin of B. pertussis in the passive haemagglutination test were analysed. The levels of IgG, IgM and IgA antibodies were determined for 95% of serum samples of 108 children in control group (without evidence of respiratory infections) for establishing of the correlation of these with the age of these children. In the light of these data the results were evaluated of testing of 136 serum samples taken from 127 children with suspected whooping-cough. The highest diagnostic importance had the demonstration of high IgA or/and IgG immunoglobulins level against pertussis toxin in ELISA test, or tracing of the rate of rise of antipertussis antibodies in the passive haemagglutination test with B. pertussis endotoxin in children with clinical symptoms of whooping-cough.	M. Chodorowska and D. Kukli?ska	Medycyna do?wiadczalna i mikrobiologia
409	Primary and booster salivary antibody responses to a 7-valent pneumococcal conjugate vaccine in infants	Salivary anticapsular antibody responses to a 7-valent pneumococcal conjugate vaccine (7VPnC) were measured in healthy infants. Infants received diphtheria-tetanus-pertussis/Haemophilus influenzae type b (DTP/Hib; group 1), DTP/Hib and 7VPnC (group 2), or DTP and 7VPnC/Hib (group 3) at ages 2, 3 and 4 months. All children received 23-valent pneumococcal polysaccharide vaccine at age 13 months. Salivary IgA and IgG responses to primary immunizations were generally poor. IgA mean concentrations at age 5 months were higher in the treatment groups than in control subjects for serotype 14 only (P<.001). At age 13-14 months, there were marked increases in IgA (mean fold difference, 3.7-4.9) and IgG (mean fold difference, 4. 1-11.7) levels for serotypes 4, 9V, 14, and 19F and serotypes 4, 18C, 19F, and 23F, respectively, in the treatment groups. This contrasts with low IgA (1.2 and 1.4) and IgG (1.3 and 2.2) mean fold differences for non-7VPnC serotypes 1 and 5. The results suggest that 7VPnC primes for mucosal memory responses in infants.	S. Choo, Q. Zhang, L. Seymour, S. Akhtar and A. Finn	The Journal of infectious diseases
13	A trial of acellular pertussis vaccine in hospital workers during the Cincinnati pertussis epidemic of 1993	The safety and immunogenicity of acellular pertussis (AP) vaccine in outbreak control was determined in a randomized, double-blind, controlled trial. Participants received AP vaccine (n=102), which contained 25 microg of pertussis toxoid (PT) and 3 microg of filamentous hemagglutinin (FHA), or licensed meningococcal vaccine (MN; n=97). Local reactions (pain or tenderness, redness, swelling, and induration) and systemic reactions (fever, sleepiness or lethargy, and irritability) were similar among AP and MN vaccinees. One month after AP vaccination, the geometric mean level of IgG anti-PT was 33.1 microg/mL, with 2-fold increases in 85% of patients and 4-fold increases in 73% of patients; for IgG anti-FHA, the respective values were 34.7 microg/mL, 92%, and 63%. After 6 months of follow-up, no serological evidence of pertussis was seen among symptomatic or asymptomatic subjects. However, recent evidence of Bordetella pertussis infection before immunization was shown. Thus, AP vaccine was safe and immunogenic in adults.	C. D. Christie, K. M. Garrison, L. Kiely, R. K. Gupta, J. Heubi and C. D. Marchant	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
121	Concomitant use of the 3-dose oral pentavalent rotavirus vaccine with a 3-dose primary vaccination course of a diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio-Haemophilus influenzae type b vaccine: immunogenicity and reactogenicity	BACKGROUND: The pentavalent rotavirus vaccine (PRV), RotaTeq, can be concomitantly administered with most routine childhood vaccines. This study evaluated the immunogenicity and reactogenicity of PRV when used concomitantly with a hexavalent vaccine containing diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b. METHODS: Healthy infants (N = 403) received hexavalent vaccine concomitantly with either PRV or placebo at 2, 3, and 4 months of age. Antibody responses were measured immediately before and 42 +/- 3 days after vaccination. Parents/legal guardians recorded all adverse events for 14 days after vaccination. RESULTS: Seroprotective titers for hepatitis B (hepatitis B surface antigen > or =10 mIU/mL) were achieved by 97.8% of subjects in both vaccine treatment groups. Seroprotective titers to H. influenzae type b (polyribosylribitol phosphate > or =0.15 microg/mL) were achieved by 91.4% of subjects receiving both vaccines and 95.1% of subjects receiving only hexavalent vaccine. Seroprotective titers to diphtheria, tetanus, and poliovirus were also comparable between the vaccine treatment groups, as were geometric mean antibody titers to the pertussis antigens. Among PRV recipients, 92% had a > or =3-fold rise in serum antirotavirus immunoglobulin A levels. Concomitant administration was well tolerated. The incidence of adverse events was similar for both groups, with no statistically significant increases in fever, vomiting, diarrhea, or irritability. CONCLUSIONS: In this study, concomitant administration of PRV with hexavalent vaccine was well tolerated and the immune responses to the antigens of the hexavalent vaccine were noninferior when compared with those of the control group. In addition, PRV was immunogenic when administered concomitantly with hexavalent vaccine.	M. Ciarlet, S. He, S. Lai, M. Petrecz, G. Yuan, G. F. Liu, E. Mikviman, P. M. Heaton, F. Panzer, T. Rose, D. Y. Koller, P. Damme and F. Schödel	The Pediatric infectious disease journal
380	Feasibility study of the immunogenicity and safety of a novel DTPw/Hib (PRP-T) Brazilian combination compared to a licensed vaccine in healthy children at 2, 4, and 6 months of age	Vaccination of infants with conjugated Haemophilus influenzae type b (Hib) vaccines has been proven to reduce Hib meningitis by 95% and pneumoniae by 20%. The routine use of Hib vaccine is facilitated by the introduction of combination vaccines into the EPI (Expanded Plan of Immunization). The objective of this study was to compare the immunogenicity and reactogenicity of an extemporaneously mixed DTPw/Hib (diphtheria-tetanus-whole cell pertussis) combination, using the technology of two Brazilian manufacturers, against a licensed DTPw/Hib European combination in 108 infants vaccinated at 2, 4 and 6 months according to the local national schedule. The Brazilian combination was highly immunogenic with Hib seroprotection rates (anti-PRP > 0.15 mg /ml of 98% after 2 doses and 100% after 3). Also for tetanus and pertussis the new Brazilian combination was as immunogenic as the European counterpart, except the diphtheria seroprotection rates and titers were lower. There was also no clinically relevant difference in reactogenicity. If these feasibility results are confirmed, the Brazilian DTPw/Hib combination should help to boost the uptake of Hib vaccination in Brazil.	S. C. Clemens, T. Azevedo and A. Homma	Revista da Sociedade Brasileira de Medicina Tropical
63	Safety and immunogenicity of live attenuated quadrivalent human-bovine (UK) reassortant rotavirus vaccine administered with childhood vaccines to infants	The safety and immunogenicity of an orally administered, live rotavirus vaccine comprised of four strains, each with a titer of 10(5.3) or 10(5.8) pfu, and each having 10 genes from the UK bovine strain and the VP7 gene from human rotavirus serotype 1, 2, 3, or 4, were evaluated in adults, young children and infants in randomized, double-blind phase 1 trials. Three doses of rotavirus vaccine or placebo given with childhood immunizations to infants at 2, 4, and 6 months of age were well tolerated and did not inhibit antibody responses to childhood vaccines which included DTP, Hib, hepatitis B and OPV. Serum rotavirus antibody responses were detected in 12 of 20 infants after 1 dose, and in 19/19 of the vaccinees after three doses. Neutralizing antibody responses were detected more often against the bovine rotavirus UK strain (95%) than to human rotavirus VP7 serotypes 1 (37%), 2 (32%), 3 (32%) or 4 (32%). The efficacy of this quadrivalent rotavirus vaccine needs to be evaluated further.	M. L. Clements-Mann, R. Dudas, Y. Hoshino, P. Nehring, E. Sperber, M. Wagner, I. Stephens, R. Karron, A. Deforest and A. Z. Kapikian	Vaccine
266	Vapocoolant spray is equally effective as EMLA cream in reducing immunization pain in school-aged children	BACKGROUND: Untreated immunization pain causes undue distress and contributes to underimmunization through physician, and possibly parental, resistance to multiple simultaneous injections. OBJECTIVE: To compare the efficacies of two pain management methods in reducing immediate immunization injection pain and distress in school-aged children. DESIGN: A randomized, controlled clinical trial of eutectic mixture of local anesthetics (EMLA) cream and vapocoolant spray. PATIENTS: Children aged 4 to 6 years and scheduled to receive diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) during health supervision visits. INTERVENTIONS: Enrolled children were randomized to one of three treatment groups: 1) EMLA cream + distraction; 2) vapocoolant spray + distraction; or 3) distraction alone (control). The specific pharmacologic pain control interventions consisted of EMLA cream (2.5% lidocaine, 2.5% prilocaine [Astra Pharmaceutical Products, Inc, Westborough, MA] $15. 00/patient; applied 60 minutes before injection) and vapocoolant spray (Fluori-Methane [Gebauer Company, Cleveland, OH] $0. 50/patient; applied via spray-saturated cotton ball for 15 seconds immediately before injection). MAIN OUTCOME MEASURES: The blinded investigator (BI) measured (by edited videotape) cry duration and the number of pain behaviors using the Observational Scale of Behavioral Distress. Pain visual analog scales (linear and faces scales) were completed by the child, parent, nurse, and the BI. RESULTS: Sixty-two children, aged 4.5 +/- 0.4 years (mean +/- SD) were randomized. The three treatment groups had similar subject characteristics. All pain measures and cry duration were similar for EMLA and vapocoolant spray. Both EMLA and spray were significantly better than control. Results for spray vs control: cry duration (seconds): 8.5 +/- 21.0 vs 38.6 +/- 50.5; number of pain behaviors: 1.2 +/- 1.9 vs. 3.1 +/- 2.1; child-scored faces scale: 2.0 +/- 2.4 vs. 4.1 +/- 2.3; parent-scored faces scale: 1.6 +/- 1.6 vs. 3.0 +/- 1.7; nurse-scored faces scale: 1.6 +/- 1.2 vs. 3.1 +/- 1.4; and BI-scored faces scale: 1.0 +/- 1.5 vs. 2.4 +/- 1.4. CONCLUSIONS: When combined with distraction, vapocoolant spray significantly reduces immediate injection pain compared with distraction alone, and is equally effective as, less expensive, and faster-acting than EMLA cream. As an effective, inexpensive, and convenient pain control method, vapocoolant spray may help overcome physician and parent resistance to multiple injections that leads to missed opportunities to immunize.	E. Cohen Reis and R. Holubkov	Pediatrics
91	Enhanced ex vivo stimulation of Mycobacterium tuberculosis-specific T cells in human immunodeficiency virus-infected persons via antigen delivery by the Bordetella pertussis adenylate cyclase vector	The genetically detoxified Bordetella pertussis adenylate cyclase is a promising delivery system for immunodominant tuberculosis antigens in gamma interferon release assays. This system has not been evaluated in human immunodeficiency virus (HIV)-infected persons in high tuberculosis prevalence areas. A whole-blood gamma interferon release assay with Mycobacterium tuberculosis antigens (early-secreted antigenic target 6, culture filtrate protein 10, alpha-crystallin 2, and TB10.3) delivered by adenylate cyclase in addition to native tuberculosis antigens (without adenylate cyclase delivery) was evaluated in 119 adults in Khayelitsha Township, Cape Town, South Africa. Results were compared to tuberculin skin test results of 41 HIV-positive and 42 HIV-negative asymptomatic persons, in addition to 36 HIV-positive persons with recently diagnosed smear- or culture-positive pulmonary tuberculosis. Delivery of tuberculosis antigens by adenylate cyclase decreased by 10-fold the amount of antigen required to restimulate T cells. Furthermore, the responses of HIV-positive persons with a low response to native tuberculosis antigens were enhanced when these antigens were delivered by adenylate cyclase. When gamma interferon responses to the tuberculosis antigens (with or without delivery by adenylate cyclase) were combined, a significantly higher number of patients were scored positive than by tuberculin skin testing. Ex vivo responses to tuberculosis antigens delivered by adenylate cyclase are maintained in the context of HIV infection. Our findings suggest that the majority of those in this population are infected with tuberculosis, which is of significant public health importance.	T. G. Connell, M. S. Shey, R. Seldon, M. X. Rangaka, G. Cutsem, M. Simsova, Z. Marcekova, P. Sebo, N. Curtis, L. Diwakar, G. A. Meintjes, C. Leclerc, R. J. Wilkinson and K. A. Wilkinson	Clinical and vaccine immunology : CVI
100	Optimal technique for intramuscular injection of infants and toddlers: a randomised trial	OBJECTIVE: To compare the rates of adverse reactions and parental approval ratings for three different techniques for anterolateral thigh vaccination in children aged 2, 4, 6 and 18 months. DESIGN: Randomised, observer-blind trial. PARTICIPANTS: 375 children who received pertussis-containing vaccines in a regional New South Wales town between 29 May 2001 and 30 June 2002. INTERVENTIONS: Children were randomised to receive intramuscular injection with acellular pertussis-containing and Haemophilus influenzae type b vaccines with one of three recognised injection techniques (Australian, World Health Organization or United States). MAIN OUTCOME MEASURES: Local adverse reactions (bruising and redness/swelling), systemic adverse reactions (irritability, perceived fever, persistent crying/screaming, drowsiness, vomiting/poor feeding) and parental acceptance were assessed 24 hours after injection. RESULTS: 361 children (96%) were evaluated 24 hours after vaccination. The WHO technique resulted in significantly fewer children, than with the other two techniques, with the systemic adverse reaction variable "irritability" (P = 0.0039). There was a significant difference between the technique groups overall for the local adverse reaction "bruising" with acellular pertussis-containing vaccines (P = 0.0418), due to a lower reaction rate in the WHO group compared with the US group (P = 0.0356). CONCLUSION: The WHO technique appears to be the optimal technique for anterolateral thigh injection in children--it ensures that the injection is intramuscular, results in fewer adverse reactions, and is the easiest technique to perform as it does not require angling of the needle to the long axis of the femur.	I. F. Cook and J. Murtagh	The Medical journal of Australia
302	Simultaneous administration of diphtheria-tetanus-pertussis-polio and hepatitis B vaccines in a simplified immunization program: Immune response to diphtheria toxoid, tetanus toxoid, pertussis, and hepatitis B surface antigen	We studied the interactions of hepatitis B vaccine with other vaccines used in the World Health Organization expanded programs of immunization. Three groups of Senegalese children were vaccinated with hepatitis B vaccine (HB) alone, diphtheria-tetanus-pertussis (DTP)-polio vaccine alone, or a combination of hepatitis B vaccine and DTP-polio vaccines simultaneously. The immune responses to HBsAg, tetanus toxoid, diphtheria toxoid, and pertussis were measured after one and two vaccinations at 6-month intervals. The immune responses to the combination of HB vaccine and DTP-polio vaccines were similar to the immune responses observed after administration of each vaccine alone. In addition, no adverse reactions were noted. These experimental trials also demonstrated that with a DTP-polio vaccine containing 30Lf of tetanus and diphtheria toxoids, two doses given at 6-month intervals are sufficient to provide a satisfactory immune response. In the case of pertussis and HB vaccines; however, a third dose is necessary. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	P. Coursaget, B. Yvonnet and E. H. Relyveld	Infection & Immunity
406	Reduced response to multiple vaccines sharing common protein epitopes that are administered simultaneously to infants	The plethora of newly discovered vaccines implies that, in the future, many vaccines will have to be administered simultaneously to infants. We examined the potential interference with the immune response of several coadministered vaccines containing the same protein component, namely, tetanus toxoid (TT). Infants simultaneously receiving a tetravalent pneumococcal vaccine conjugated to TT (PncT) and a diphtheria. tetanus- pertussis-poliovirus-Haemophilus influenzae type b-tetanus conjugate vaccine showed significantly lower anti-H. influenzae type b polysaccharide (polyribosylribitol phosphate [PRP]) antibody concentrations than those receiving either a tetravalent pneumococcal vaccine conjugated to diphtheria toxoid or placebo. A dose range study showed that anti-PRP antibody concentrations were inversely related to the TT content of the PncT vaccines administered in infancy. Postimmunization antitetanus antibody concentrations were also affected adversely as the Tr content of the coadministered vaccines was increased. This phenomenon, which we believe derives from interference by a common protein carrier, should be taken into account when the introduction of an immunization program including multiple conjugate vaccines is considered. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	R. Dagan, J. Eskola, C. Leclerc and O. Leroy	Infection and Immunity
294	Immunogenicity of a combined diphtheria-tetanus-acellular pertussis vaccine in adults	Two clinical studies were undertaken to evaluate the immunogenicity of an adult-type dTpa booster vaccine (Boostrix by GlaxoSmithKline Biologicals). Blood samples taken prior to vaccination showed that 24.4 and 13.0% of subjects were seronegative for diphtheria and tetanus antibodies, respectively. Moreover, about one-third of the vaccinees had no detectable levels of antibodies to pertussis toxoid (PT) or pertactin (PRN). One month post-vaccination, more than 93% of all individuals, regardless of age or type of vaccine received, had seroprotective antibody levels for diphtheria and tetanus (> or = 0.1IU/ml). In those individuals vaccinated with the adult-type dTpa vaccine (Boostrix), more than 98% were found to be seropositive for antibodies to all three pertussis antigens (PT, filamentous haemogluttin (FHA), and PRN). These data suggest that immunity to diphtheria, tetanus and pertussis (DTP) in adults wanes and that booster vaccination with an adult-type combined dTpa vaccine would boost the serological response to diphtheria antitoxin, tetanus antitoxin and antibodies to Bordetella pertussis PT, FHA and PRN.	P. Damme and M. Burgess	Vaccine
34	Immunogenicity of the reduced-antigen-content dTpa vaccine (Boostrix(®)) in adults 55 years of age and over: a sub-analysis of four trials	BACKGROUND: Older adults, especially those over 65 years, are at risk of more severe morbidity from diphtheria, tetanus and pertussis and may transmit pertussis to unvaccinated or not yet fully vaccinated infants, but data on their response to reduced-antigen-content tetanus, diphtheria and acellular pertussis (dTpa) vaccines are lacking. METHODS: A sub-analysis pooled immunogenicity results in 293 adults aged 55+ years (mean age 64.4 years) from four randomised, controlled clinical trials of dTpa vaccine (Boostrix(®), GlaxoSmithKline Biologicals) with or without IPV co-administration, or dTpa-IPV (Boostrix(®) IPV). RESULTS: Seroprotective antibody levels were achieved by 82.8% for diphtheria and 94.5% for tetanus. For pertussis antigens, the booster response rate, defined as initially seronegative subjects [<5EU/mL] reaching ?5EU/mL; or a ?2-fold increase in antibody concentration if initially seropositive was 89.2% for pertussis toxoid, 95.8% for filamentous haemagglutinin and 94.5% for pertactin. Post-booster geometric mean concentrations (GMC) increased for all antigens. Post-booster anti-tetanus and anti-PRN GMCs tended to be higher in 55- to 64-year olds than in those aged 65+. CONCLUSION: Larger numbers of subjects over 75 years are needed to better define responses in advanced age, but these data suggest that a single booster dose of dTpa or dTpa-IPV induces good immunological responses in most, and that these vaccines could be readily integrated into existing programmes.	P. Damme, P. McIntyre, E. Grimprel, S. Kuriyakose, J. M. Jacquet, K. Hardt, M. Messier and O. Meeren	Vaccine
28	Magnitude of interference after diphtheria-tetanus toxoids-acellular pertussis/Haemophilus influenzae type b capsular polysaccharide-tetanus vaccination is related to the number of doses administered	We compared the antibody response to Haemophilus influenzae type b capsular polysaccharide (PRP) after 1, 2, or 3 doses of a diphtheria-tetanus toxoids-acellular pertussis (DTaP) vaccine combined with a PRP-tetanus conjugate (PRP-T) vaccine, followed by separate injections of DTaP and PRP-T vaccines for the last 1 or 2 doses. Healthy infants were recruited from pediatric practices and were immunized according to recommended schedules. A significant decrease in the mean anti-PRP (from 5.25 to 2.68 microg/mL) and anti-tetanus toxoid antibody responses (from 0.13 to 0.09 Eq/mL) was observed as the number of doses of the DTaP/PRP-T combination vaccine increased (P<.02 and P=.01, respectively). In contrast, the mean anti-diphtheria toxoid antibody response increased with increasing numbers of DTaP/PRP-T doses (P=.0001). The effects of interference were not eliminated by the completion of the primary series with 1 or 2 doses of the DTaP and PRP-T vaccines given separately.	R. S. Daum, C. E. Zenko, G. Z. Given, G. A. Ballanco, H. Parikh and K. Germino	The Journal of infectious diseases
37	Absence of a significant interaction between a Haemophilus influenzae conjugate vaccine combined with a diphtheria toxoid, tetanus toxoid and acellular pertussis vaccine in the same syringe and inactivated polio vaccine	BACKGROUND: We compared the antibody response to Haemophilus influenzae type b capsular polysaccharide (PRP) after three doses of a diphtheria toxoid, tetanus toxoid and acellular pertussis vaccine (DTaP) combined with a PRP-tetanus conjugate (PRP-T) in infants randomized to receive oral polio vaccine (OPV) or inactivated polio vaccine (IPV). The polio vaccine was given separately at the same visit. METHODS: Three hundred fifty-six infants from pediatric practices in suburban Chicago and New Orleans were randomized into two groups. Group A received OPV at 2 and 4 months of age; Group B received IPV at 2 and 4 months of age. Both groups received DTaP/PRP-T at 2, 4 and 6 months of age and hepatitis B vaccine at 2 and 4 months of age. A serum sample was obtained before immunization (age 2 months) and 1 month after 3 doses of DTaP/PRP-T (age 7 months). Sera were assayed for antibody responses to all relevant vaccine antigens. RESULTS: No significant vaccine antigen interference was found when polio immunization was provided by IPV or OPV for anti-PRP, diphtheria, tetanus or pertussis antibodies. OPV recipients had a significantly higher mean antibody response to serotype 1 (P = 0.03) and 2 (P = 0.0001) poliovirus. CONCLUSION: Whether polio immunization was accomplished with IPV or OPV did not significantly influence the antibody responses in sera obtained at 7 months of age for anti-PRP, anti-diphtheria and anti-tetanus toxoid antibodies and antibodies to pertussis antigens, when DTaP/PRP-T was given in the primary series.	R. S. Daum, C. E. Zenko, G. Z. Given, G. A. Ballanco, H. Parikh, E. Vidor and X. Liu	The Pediatric infectious disease journal
286	Comparison between chloramphenicol and sulfadiazine/trimethoprim in whooping-cough	61 children aged 1-12 mth with whooping cough participated in a randomized double blind investigation. 43 children completed the trial. One group was treated with chloramphenicol 50 mg per kg body weight in four divided doses, another group with 30 mg/6 mg sulfadiazine/trimethoprim per kg body weight in four divided doses. The treatment period was six days, followed by an observation period of six further days. The clinical course of the disease estimated by the number of bouts of coughing per day was identical in the two groups. If a choice is be made between the above two preparations, we suggest sulfadiazine/trimethoprim because of presumably fewer side- effects. However, it is doubtful at present whether the clinical course of whooping cough is influenced at all by antimicrobial agents. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	H. Degn, A. T. Jacobsen and A. Gjerris	Ugeskr-Laeg
460	Immunogenicity of 20 microg of recombinant DNA hepatitis B vaccine in healthy neonates: A comparison of three different vaccination schemes	The immunogenicity of a full dose (20 microg) of recombinant DNA yeast-derived hepatitis B vaccine (Engerix-B) was assessed in healthy neonates in order to compare three candidate vaccination schemes. After randomization 162 newborns of hepatitis B surface antigen (HBsAg) negative mothers entered the study. Neonates received hepatitis B vaccine according to a four dose vaccination scheme starting either at month 3 (scheme I: months 3, 4, 5, and 11) or at birth (scheme III: months 0, 1, 2, and 11). Another group of neonates received hepatitis B vaccine according to a three-dose scheme starting at birth (scheme II: months 0, 1, and 6). Serious adverse reactions were not observed; 2.5% of the vaccinated newborns suffered mild transient local symptoms. The vaccine was highly immunogenic irrespective of vaccination scheme; all infants developed anti-HBs levels greater than or equal to10 IU/L, 97% greater than or equal to100 IU/L. The immunogenicity of hepatitis B vaccine after primary and booster vaccinations, administered in the four-dose scheme started at birth, was significantly higher (P < 0.05) than in the three-dose scheme started at birth. Hepatitis B vaccination according to the four-dose scheme started at month 3 produced significantly higher (P < 0.05) antibody levels in comparison to the four-dose scheme started directly after birth. This study showed that a four dose hepatitis B vaccination scheme starting at month 3 resulted in the highest antibody levels of the three schemes investigated and can be recommended for incorporation in the Expanded Programme on Immunization in The Netherlands. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	C. R. Del, P. M. Grosheide, M. Voogd, W. M. Huisman, R. A. Heijtink and S. W. Schalm	J. Med. Virol.
185	Association of reactions after consecutive acellular or whole-cell pertussis vaccine immunizations	OBJECTIVE: To evaluate the relative frequency of adverse reactions after initial and subsequent immunizations among infants receiving primary immunization with acellular (DTaP) or whole-cell (DTP) pertussis vaccine with diphtheria and tetanus combined. METHODS: We examined the occurrence of common reactions in 2127 infants within 48 hours after immunization at 2, 4, and 6 months with one of 13 DTaP or with Lederle DTP (WCL). Data on at least two consecutive immunizations were available for 357 WCL recipients and 1770 DTaP recipients. For these analyses, reactions evaluated included fever of 100.4 degrees F (38 degrees C) or greater, redness of 21 mm or larger, swelling of 21 mm or larger, moderate or severe pain, moderate or severe fussiness, loss of appetite, drowsiness, and vomiting. RESULTS: With one exception, reactions were approximately 1.5 to 8 times more likely to occur in WCL recipients if the same reaction had been observed at the previous immunization (the single exception was redness after the second immunization). Both initial and repeated reactions were less likely in DTaP than in WCL recipients. As with WCL recipients, risks of repeated reactions in DTaP recipients were higher than the risks of initial reactions (from 2.5 to 24 times as high). CONCLUSION: Reactions after a second or third immunization with either WCL or DTaP vaccine are more likely to occur in infants who had the same reaction after the preceding immunization. Absolute risks of repeated reactions tended to be lower after DTaP vaccine than after the WCL vaccine.	M. A. Deloria, W. C. Blackwelder, M. D. Decker, J. A. Englund, M. C. Steinhoff, M. E. Pichichero, M. B. Rennels, E. L. Anderson and K. M. Edwards	Pediatrics
147	Quality of the Haemophilus influenzae type b (Hib) antibody response induced by diphtheria-tetanus-acellular pertussis/Hib combination vaccines	It has been repeatedly observed that mixing Haemophilus influenzae type b (Hib) conjugate vaccines with acellular pertussis-containing vaccines (diphtheria-tetanus-acellular pertussis [DTPa]) resulted in a reduced magnitude of the anti-polyriboseribitolphosphate antibody response compared to that obtained when Hib vaccines were administered separately and not mixed. Nevertheless, the quality and functionality of the immune responses have been shown to be the same. With the purpose of investigating the quality of the anti-Hib immune responses that are elicited under different vaccination regimens, we report here four primary and booster-based pediatric clinical trials in which Hib vaccine was either mixed with DTPa or diphtheria-tetanus-whole-cell pertussis (DTPw)-based vaccines or was coadministered. Our results show that avidity maturation of the antibodies was lower when primary vaccination involved DTPa mixed with Hib compared to when DTPa and Hib were coadministered. No such difference was observed between mixed and separately administered Hib when associated with DTPa-hepatitis B virus-inactivated poliovirus or DTPw-based vaccines. All different combinations and regimens elicited the same opsonophagocytic and bactericidal activity as well as the same ability to protect in a passive infant rat protection assay. The functional activity of mixed DTPa-based and Hib vaccines was similar to that of mixed DTPw-based/Hib combinations. In conclusion, in vitro and in vivo data as well as postmarketing vaccine effectiveness data attest to the ability of DTPa-based/Hib combination vaccines to effectively prevent Hib-induced disease in children.	P. A. Denoël, D. Goldblatt, I. Vleeschauwer, J. M. Jacquet, M. E. Pichichero and J. T. Poolman	Clinical and vaccine immunology : CVI
223	Evaluation of the immunogenicity and safety of an indigenously developed DTwP-Hib tetravalent combination vaccine (Shan 4) with EasyFourTM in Indian infants administered per EPI schedule: a phase III trial	The study was planned to assess and compare immunogenicity and safety of an indigenous DTPw-Hib combination vaccine (Shan 4) with EasyFour, the available DTwP-Hib vaccine in India. Overall 210 healthy infants, six to eight weeks of age, were randomized to receive three doses of either Shan 4 or EasyFour at 6, 10 and 14 weeks of age. Antibodies were analyzed prior to and four to six weeks post third vaccine dose. Solicited and unsolicited local and systemic events in the follow up period after each dose were recorded. Post vaccination 100% of the infants in Shan 4 and EasyFour groups had seroprotective concentrations of Anti PRP-T IgG antibodies, IgG anti-diphtheria toxoid antibodies and IgG anti-tetanus toxoid antibodies. Following third dose of vaccination 86.99% subjects in the Shan 4 group and 73.85% subjects in the EasyFour group seroconverted for anti-pertussis antibody titres. Two Serious Adverse Events (SAE s) were reported during the course of the study, all unrelated to the respective vaccine administered. Most commonly reported adverse events in both the groups were pain at injection site, mild fever (<103°F) and minor swelling at injection site. The study proved that Shan 4 was safe and immunogenic compared to the available licensed vaccine.	M. S. Dhingra, R. Rao, S. Bhat, R. Joshi, V. Kalra, H. R. Parikh, S. N. Rao, G. R. Sethi, N. Shah and M. Muzaffaruddin	Human vaccines
353	Evaluation of the immunogenicity and safety of an indigenously developed DTwP-Hib tetravalent combination vaccine (Shan 4) with Easyfour in Indian infants administered per EPI schedule: a phase III trial	The study was planned to assess and compare immunogenicity and safety of an indigenous DTPw-Hib combination vaccine (Shan 4) with EasyFour, the available DTwP-Hib vaccine in India. Overall 210 healthy infants, six to eight weeks of age, were randomized to receive three doses of either shan 4 or EasyFour at 6, 10 and 14 weeks of age. Antibodies were analyzed prior to and four to six weeks post third vaccine dose. Solicited and unsolicited local and systemic events in the follow up period after each dose were recorded. Post vaccination 100% of the infants in Shan 4 and EasyFour groups had seroprotective concentrations of Anti PRP-T IgG antibodies, IgG anti-diphtheria toxoid antibodies and IgG anti-tetanus toxoid antibodies. Following third dose of vaccination 86.99% subjects in the Shan 4 group and 73.85% subjects in the EasyFour group seroconverted for anti-pertussis antibody titres. Two Serious Adverse Events (SAEs) were reported during the course of the study, all unrelated to the respective vaccine administered. Most commonly reported adverse events in both the groups were pain at injection site, mild fever (<103degreeF) and minor swelling at injection site. The study proved that Shan 4 was safe and immunogenic compared to the available licensed vaccine. 2010 Landes Bioscience.	M. S. Dhingra, R. Rao, S. Bhat, R. Joshi, V. Kalra, H. R. Parikh, S. N. Rao, G. R. Sethi, N. Shah and M. Muzaffaruddin	Human Vaccines
190	A randomized, multicenter, open-label clinical trial to assess the immunogenicity of a meningococcal C vaccine booster dose administered to children aged 14 to 18 months	BACKGROUND: A booster meningococcal C (MenC) vaccine dose is recommended after the first year of life. The objective of this study was to assess its immunogenicity and factors that modify the immunoresponse. METHODS: An open label study in which 389 children 14 to 18 months of age, previously primed with 3 doses of a MenC vaccine conjugated with CRM197 (MenC-CRM) or with 2 doses of a MenC vaccine conjugated with tetanus toxoid (MenC-TT), were randomized to be boosted with either of these vaccines and a DTaP-IPV-Hib vaccine at the same time. Immunogenicity against MenC and Haemophilus influenzae type b was assessed before and 1 month after the booster dose. RESULTS: Before the second year booster, 44.9% of the studied children had MenC bactericidal (SBA) seroprotection rate of > or =1:8, with no differences related to the vaccine used for priming, whereas the anti Hib antibody concentration was higher in children primed with the MenC-TT (0.59; 95% CI: 0.49-0.71 vs. 0.39; 95% CI: 0.32-0.48).One month after the MenC vaccine booster 99.5% of the children had SBA > or =1:128. Children primed with MenC-TT reached higher SBA titers: 6520 (95% CI: 5359-7932) than those primed with MenC-CRM: 1903 (95% CI: 1600-2262). Children primed with MenC-CRM had SBA titers of 2061 (95% CI: 1599-2627) when boosted with MenC-TT and 1746 (95% CI: 1378-2213) when boosted with MenC-CRM. Children primed with MenC-TT had SBA titers of 6786 (95% CI: 5023-9167) and 6278 (95% CI: 4841-8144) when boosted with MenC-TT or MenC-CRM. There was no difference in the PRP antibody concentration after boosting. CONCLUSIONS: A booster MenC dose induces high SBA and anti Hib response with over 99% of children seroprotected. Children primed with a MenC-TT vaccine reached SBA titers 3.5 times higher no matter which vaccine was used for boosting.	J. Díez-Domingo, M. V. Cantarino, J. M. Torrentí, M. I. Sansano, A. J. Rosich, A. H. Merino, A. G. Miguel, J. B. González and M. D. Marcos	The Pediatric infectious disease journal
102	Immunogenicity and reactogenicity of a combined adsorbed tetanus toxoid, low dose diphtheria toxoid, five component acellular pertussis and inactivated polio vaccine in six-year-old children	BACKGROUND: The objective of this study was to assess the immunogenicity and reactogenicity of the combined adsorbed tetanus toxoid, low dose diphtheria toxoid, 5-component acellular pertussis and inactivated polio vaccine (TdcP-IPV) as compared with a pediatric dose diphtheria formulation, combined with adsorbed tetanus toxoid and 3-component acellular pertussis (DTacP), in 6-year-old children who were immunized with 4 doses of diphtheria-tetanus-whole cell cellular pertussis (DTwcP) plus oral polio vaccine (OPV) before 2 years of age, according to the local Spanish vaccination calendar. METHODS: One hundred ninety-four healthy 6-year-old children were randomized to receive 1 dose of TdcP-IPV or 1 dose of DTacP and OPV. RESULTS: One month postvaccination, antidiphtheria and antitetanus titers were > or =0.1 IU/mL in 100% of patients in both study groups. TdcP-IPV reached 100% seroprotection rates against polio types 1, 2 and 3. In OPV recipients, these rates were 100, 100 and 96.8%, respectively. Seropositivity rates for pertussis toxin, filamentous hemagglutinin, pertactin and fimbrial components of the TdcP-IPV vaccine were 97.9, 89.6, 90.6 and 100%. The incidence of local and systemic reactions was 50.5 and 39.2% in the TdcP-IPV group and 59.4 and 38.5% in the DTacP plus OPV group, and no serious adverse events were reported. CONCLUSIONS: TdcP-IPV vaccine was shown to be immunogenic and safe when given as a booster in children 6 years of age who were primed with 4 doses of DTwcP and OPV.	J. Diez-Domingo, J. D. Delgado, A. Ballester, J. M. Baldó, M. V. Planelles, M. Garcés, M. Graullera, M. I. Ubeda, F. Sánchez, M. M. Sánchez, E. Azor, A. Cabrera, F. López, M. Alvarez, M. San-Martín, A. González, F. Boisnard and S. Thomas	The Pediatric infectious disease journal
231	Effect of needle length on incidence of local reactions to routine immunisation in infants aged 4 months: randomised controlled trial	OBJECTIVE: To compare rates of local reactions associated with two needle sizes used to administer routine immunisations to infants. DESIGN: Randomised controlled trial. SETTING: Routine immunisation clinics in eight general practices in Buckinghamshire. PARTICIPANTS: Healthy infants attending for third primary immunisation due at 16 weeks of age: 119 infants were recruited, and 110 diary cards were analysed. Interventions: Immunisation with 25 gauge, 16 mm, orange hub needle or 23 gauge, 25 mm, blue hub needle. MAIN OUTCOME MEASURES: Parental recordings of redness, swelling, and tenderness for three days after immunisation. RESULTS: Rate of redness with the longer needle was initially two thirds the rate with the smaller needle (relative risk 0.66 (95% confidence interval 0.45 to 0.99), P=0.04), and by the third day this had decreased to a seventh (relative risk 0.13 (0.03 to 0.56), P=0.0006). Rate of swelling with the longer needle was initially about a third that with the smaller needle (relative risk 0.39 (0.23 to 0.67), P=0.0002), and this difference remained for all three days. Rates of tenderness were also lower with the longer needle throughout follow up, but not significantly (relative risk 0.60 (0.29 to 1.25), P=0.17). CONCLUSIONS: Use of 25 mm needles significantly reduced rates of local reaction to routine infant immunisation. On average, for every five infants vaccinated, use of the longer needle instead of the shorter needle would prevent one infant from experiencing any local reaction. Vaccine manufacturers should review their policy of supplying the shorter needle in vaccine packs.	L. Diggle and J. Deeks	BMJ (Clinical research ed.)
176	Effect of needle size on immunogenicity and reactogenicity of vaccines in infants: randomised controlled trial	OBJECTIVES: To assess the immunogenicity of vaccines for infants and to investigate whether the incidence of reactogenicity is reduced after each immunisation dose using needles of varying lengths and gauges. DESIGN: Randomised controlled trial. SETTING: 18 general practices within two UK primary care trusts. PARTICIPANTS: 696 healthy infants vaccinated at 2, 3, and 4 months of age, with follow-up to 5 months of age. INTERVENTIONS: Combined diphtheria, tetanus, whole cell pertussis, and Haemophilus influenzae type b vaccine and a serogroup C meningococcal glycoconjugate vaccine administered using either a wide, long needle (23 gauge/0.6 mm diameter, 25 mm), a narrow, short needle (25 gauge/0.5 mm diameter, 16 mm), or a narrow, long needle (25 gauge, 25 mm). MAIN OUTCOME MEASURES: Local and general reactions recorded by parents for three days after each dose; and diphtheria, tetanus, and H influenzae type b antibody concentrations and functional antibody against serogroup C Neisseria meningitidis 28-42 days after the third dose. RESULTS: Local reactions to diphtheria, tetanus, whole cell pertussis, H influenzae type b vaccinations decreased significantly with wide, long needles compared with narrow, short needles. At all three doses one less infant experienced local reactions at days 1, 2, or 3 for every six to eight vaccinated. Significantly fewer infants vaccinated with the long needle experienced severe local reactions. Non-inferiority of the immune response was shown using a wide, long needle rather than a narrow, short needle for serogroup C meningococcal glycoconjugate vaccine and for diphtheria but not for H influenzae type b or tetanus, although no evidence was found of a decrease. Little difference was found between needles of the same length but different gauges in local reaction or immune response. CONCLUSIONS: Long (25 mm) needles for infant immunisations can significantly reduce vaccine reactogenicity at each dose while achieving comparable immunogenicity to that of short (16 mm) needles. Trial registration Current Controlled Trials ISRCTN62032215 [controlled-trials.com].	L. Diggle, J. J. Deeks and A. J. Pollard	BMJ (Clinical research ed.)
308	Diagnosis of pertussis by fluorescent antibody staining of nasopharyngeal smears		P. Donaldson and J. A. Whitaker	Am. J. of Diseases of Children
244	The use of breast-feeding for pain relief during neonatal immunization injections	The objective of this study was to examine the pain-relieving effect of breast-feeding during immunization injections in healthy neonates. Sixty-six healthy infants returning to a clinic for their second-, third-, or fourth-month immunization with intramuscular diphtheria, tetanus, and pertussis were randomized to be breast-fed before, during, and after the injection or to be given the injection according to routine clinic procedure (no breast-feeding). To assess the pain responses of the neonates during and after immunization, we noted their heart rates, oxygen saturation levels, and length of crying. The crying time was shorter in the experimental (breast-feeding) group (M +/- SD duration, 35.85 +/- 40.11 seconds) than in the control group (M +/- SD duration, 76.24 +/- 49.61 seconds; p = .001). The heart rate and oxygen saturation levels were almost the same in both groups. We concluded that breast-feeding, maternal holding, and skin-to-skin contact significantly reduced crying in infants receiving an immunization injection for diphtheria, tetanus, and pertussis.	E. Efe and Z. C. Ozer	Applied nursing research : ANR
315	Experiences in the Treatment of Pertussis with Chloramphenicol and Pertussis-Hyperimmun-Globulin		W. Eichlseder	Medizinische Klinik
301	Investigation into the effectivtiy of pertussis-hyperimmune globulin and Chloramphenicol on whooping cough in a double-blind study		W. Eichlseder	Archiv fur Kinderheilkunde
416	The impact of helminths on the response to immunization and on the incidence of infection and disease in childhood in Uganda: design of a randomized, double-blind, placebo-controlled, factorial trial of deworming interventions delivered in pregnancy and early childhood [ISRCTN32849447]	BACKGROUND: Helminths have profound effects on the immune response, allowing long-term survival of parasites with minimal damage to the host. Some of these effects "spill-over", altering responses to non-helminth antigens or allergens. It is suggested that this may lead to impaired responses to immunizations and infections, while conferring benefits against inflammatory responses in allergic and autoimmune disease. These effects might develop in utero, through exposure to maternal helminth infections, or through direct exposure in later life. PURPOSE: To determine the effects of helminths and their treatment in pregnancy and in young children on immunological and disease outcomes in childhood. METHODS: The trial has three randomized, double-blind, placebo-controlled interventions at two times, in two people: a pregnant woman and her child. Pregnant women are randomized to albendazole or placebo and praziquantel or placebo. At age 15 months their children are randomized to three-monthly albendazole or placebo, to continue to age five years. The proposed designation for this sequence of interventions is a 2 x 2(x2) factorial design. Children are immunized with BCG and against polio, Diphtheria, tetanus, Pertussis, Haemophilus, hepatitis B and measles. Primary immunological outcomes are responses to BCG antigens and tetanus toxoid in whole blood cytokine assays and antibody assays at one, three and five years of age. Primary disease outcomes are incidence of malaria, pneumonia, diarrhoea, tuberculosis, measles, vertical HIV transmission, and atopic disease episodes, measured at clinic visits and twice-monthly home visits. Effects on anaemia, growth and intellectual development are also assessed. CONCLUSION: This trial, with a novel design comprising related interventions in pregnant women and their offspring, is the first to examine effects of helminths and their treatment in pregnancy and early childhood on immunological, infectious disease and allergic disease outcomes. The results will enhance understanding of both detrimental and beneficial effects of helminth infection and inform policy.	A. M. Elliott, M. Kizza, M. A. Quigley, J. Ndibazza, M. Nampijja, L. Muhangi, L. Morison, P. B. Namujju, M. Muwanga, N. Kabatereine and J. A. Whitworth	Clinical trials (London, England)
249	[1st results with a quintuple vaccine against measles, diphtheria, whooping cough, tetanus and poliomyelitis]		G. Enders-Ruckle, H. Spiess and H. Wolf	Deutsche medizinische Wochenschrift (1946)
296	Pertussin 30: preventive for whooping cough		J. M. English	Comm Br Homoeopath Res Grp
182	Antibody titers and immune response to diphtheria-tetanus-pertussis and measles-mumps-rubella vaccination in children treated for acute lymphoblastic leukemia	The objective of this study was to investigate the diphtheria-tetanus-pertussis and/or measles-mumps antibody titers before and after vaccination at various time points of acute lymphoblastic leukemia (ALL) therapy and to suggest an appropriate vaccination approach for ALL patients. The authors studied 37 ALL patients and 14 healthy control subjects, divided into three groups. In group 1 (newly diagnosed patients), baseline anti-diphtheria, anti-tetanus, and anti-pertussis titers were determined. Patients in group 2 (on maintenance chemotherapy) and group 3 (patients not receiving therapy for 3-6 months) were vaccinated with diphtheria-tetanus with or without acellular pertussis; group 3 and control subjects were also given measles-mumps-rubella vaccine. Preimmunization and 1-month postimmunization titers were drawn. Preimmunization anti-diphtheria and anti-tetanus antibody titers between the groups and the controls were statistically similar. The seropositivity rate for anti-measles antibody in group 3 was significantly lower than controls. After vaccination, all of the patients developed protective anti-diphtheria and anti-tetanus antibody titers. The seroconversion rates of group 3 and controls for anti-measles and anti-mumps antibodies were statistically similar. The results showed that patients on maintenance therapy and after cessation of therapy made good antibody responses to diphtheria and tetanus toxoids, but response to measles and mumps vaccines was not as sufficient as toxoid vaccines. Children with ALL can receive the appropriate vaccines during and after maintenance treatment.	T. E. Ercan, L. Y. Soycan, H. Apak, T. Celkan, A. Ozkan, E. Akdenizli, O. Kasapçopur and I. Yildiz	Journal of pediatric hematology/oncology
322	Simultaneous administration of Haemophilus influenzae type b capsular polysaccharide-diphtheria toxoid conjugate vaccine with routine diphtheria-tetanus-pertussis and inactivated poliovirus vaccinations of childhood	A Haemophilus influenzae type b capsular polysaccharide-diphtheria toxoid conjugate vaccine (PRP-D) is capable of protecting infants against invasive H. influenzae diseases. Therefore it is very likely that it will be incorporated in routine vaccination schedules during the next few years. In order to test the suitability of simultaneous administration of PRP-D and other vaccines we administered it to 25 infants mixed with diphtheria-tetanus-pertussis vaccine at 3, 4 and 6 months and simultaneously, but in a separate syringe, with inactivated polio vaccine at 12 months. A comparison group of equal size received only diphtheria-tetanus-pertussis and inactivated poliovirus vaccines. The concentration of postvaccination antibodies to diphtheria toxoid was 0.411 IU/ml in the group that received PRP-D vs. 0.352 IU/ml in the comparison group, to tetanus toxoid 3.666 vs. 3.668 IU/ml and the neutralization titer to poliovirus type 1 was 370 vs. 320 units in the comparison group, to type 2 titer values were 230 vs. 270 units and to type 3, respectively, 210 vs. 290 units. Thus the seroresponse to antigens in routine vaccines was not affected by the presence of PRP-D in the vaccination schedule, and PRP-D can safely and effectively be included in the vaccination schedule of infancy	J. Eskola, H. Kayhty, L. K. Gordon, T. Hovi, M. Stenvik, P. R. Ronnberg, E. Kela and H. Peltola	Pediatric Infectious Disease Journal
420	Efficacy of a pneumococcal conjugate vaccine against acute otitis media	BACKGROUND: Ear infections are a common cause of illness during the first two years of life. New conjugate vaccines may be able to prevent a substantial portion of cases of acute otitis media caused by Streptococcus pneumoniae. METHODS: We enrolled 1662 infants in a randomized, double-blind efficacy trial of a heptavalent pneumococcal polysaccharide conjugate vaccine in which the carrier protein is the nontoxic diphtheria-toxin analogue CRM197. The children received either the study vaccine or a hepatitis B vaccine as a control at 2, 4, 6, and 12 months of age. The clinical diagnosis of acute otitis media was based on predefined criteria, and the bacteriologic diagnosis was based on a culture of middle-ear fluid obtained by myringotomy. RESULTS: Of the children who were enrolled, 95.1 percent completed the trial. With the pneumococcal vaccine, there were more local reactions than with the hepatitis B vaccine but fewer than with the combined whole-cell diphtheria-tetanus-pertussis and Haemophilus influenzae type b vaccine that was administered simultaneously. There were 2596 episodes of acute otitis media during the follow-up period between 6.5 and 24 months of age. The vaccine reduced the number of episodes of acute otitis media from any cause by 6 percent (95 percent confidence interval, -4 to 16 percent [the negative number indicates a possible increase in the number of episodes]), culture-confirmed pneumococcal episodes by 34 percent (95 percent confidence interval, 21 to 45 percent), and the number of episodes due to the serotypes contained in the vaccine by 57 percent (95 percent confidence interval, 44 to 67 percent). The number of episodes attributed to serotypes that are cross-reactive with those in the vaccine was reduced by 51 percent, whereas the number of episodes due to all other serotypes increased by 33 percent. CONCLUSIONS: The heptavalent pneumococcal polysaccharide-CRM197 conjugate vaccine is safe and efficacious in the prevention of acute otitis media caused by the serotypes included in the vaccine.	J. Eskola, T. Kilpi, A. Palmu, J. Jokinen, J. Haapakoski, E. Herva, A. Takala, H. Käyhty, P. Karma, R. Kohberger, G. Siber and P. H. Mäkelä	The New England journal of medicine
198	Effect of an audiovisual message for tetanus booster vaccination broadcast in the waiting room	BACKGROUND: General practitioners (GPs) often lack time and resources to invest in health education; audiovisual messages broadcast in the waiting room may be a useful educational tool. This work was designed to assess the effect of a message inviting patients to ask for a tetanus booster vaccination. METHODS: A quasi experimental study was conducted in a Belgian medical practice consisting of 6 GPs and 4 waiting rooms (total: 20,000 contacts/year). A tetanus booster vaccination audiovisual message was continuously broadcast for 6 months in 2 randomly selected waiting rooms (intervention group--3 GPs) while the other 2 waiting rooms remained unequipped (control group--3 GPs). At the end of the 6-month period, the number of vaccine adult-doses delivered by local pharmacies in response to GPs' prescriptions was recorded. As a reference, the same data were also collected retrospectively for the general practice during the same 6-month period of the previous year. RESULTS: During the 6-month reference period where no audiovisual message was broadcast in the 4 waiting rooms, the number of prescriptions presented for tetanus vaccines was respectively 52 (0.44%) in the intervention group and 33 (0.38%) in the control group (p = 0.50). By contrast, during the 6-month study period, the number of prescriptions differed between the two groups (p < 0.0001), rising significantly to 91 (0.79%) in the intervention group (p = 0.0005) while remaining constant in the control group (0.38% vs 0.39%; p = 0.90). CONCLUSIONS: Broadcasting an audiovisual health education message in the GPs' waiting room was associated with a significant increase in the number of adult tetanus booster vaccination prescriptions delivered by local pharmacies.	C. Eubelen, F. Brendel, J. L. Belche, A. Freyens, S. Vanbelle and D. Giet	BMC family practice
402	Dextromethorphan and caffeine as probes for simultaneous determination of debrisoquin-oxidation and N-acetylation phenotypes in children	The feasibility and reliability of simultaneously determining debrisoquin oxidation and N-acetylation phenotypes was assessed in children with use ot two innocuous substrate probes given by mouth, 30 mg dextromethorphan (Pertussin ES) and 25 to 46 mg caffeine (Cocal-Cola beverage). Twenty-six children and adolescents (aged 3 to 21 years) were studied three times, once with each substrate given alone and once with the two substrates given together. Urine was collected for 4 hours, and the molar urinary metabolic ratios for dextromethorphan:dextrorphan and for two caffeine metabolites (AFMU:1X) were determined by HPLC ultraviolet assays. The urinary metabolic ratios for both substrates were not significantly different when the substrates were given alone compared with when they were given together. There was also no difference in either the oxidation or acetylation phenotype assignments when the two substrates were given alone and when they were given together. No adverse effects were observed. We conclude that dextromethorphan and caffeine can be given together to simultaneously determine oxidation and acetylation phenotypes and can thereby provide an innocuous, noninvasive method for the assessment of polymorphic drug metabolism in various pediatric populations. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	W. E. Evans, M. V. Relling, W. P. Petros, W. H. Meyer, J. Mirro Jr and W. R. Crom	Clinical Pharmacology & Therapeutics
183	Primary and booster vaccination with DTPw-HB/Hib pentavalent vaccine in Costa Rican children who had received a birth dose of hepatitis B vaccine	OBJECTIVE: The DTPw-HB/Hib pentavalent combination vaccine has been developed following recommendations of the World Health Organization for the introduction of hepatitis B (HB) and Haemophilus influenzae type b (Hib) vaccines into routine childhood vaccination programs. The objectives of this study were to: 1) analyze the immunogenicity and the reactogenicity of the DTPw-HB/Hib pentavalent combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination in a group of children who had received a dose of HB vaccine at birth and 2) in the second year of life to assess the antibody persistence as well as the response to a DTPw-HB/Hib or DTPw/Hib booster. METHODS: In the first part of the study (primary-vaccination stage), conducted in 1998-1999, we analyzed the immunogenicity and reactogenicity of the DTPw-HB/Hib combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination at 2, 4, and 6 months of age in 207 Costa Rican children who had received a dose of HB vaccine at birth. Later, in the booster-vaccination stage of the study, in 1999-2000, in a subset of the children (69 toddlers, now 15-18 months old), antibody persistence was measured, and response to a DTPw-HB/Hib or DTPw/Hib booster was also assessed. RESULTS: In both primary-vaccination groups, at least 97.5% of the infants reached protective levels of antibodies (seropositivity) against the antigens employed in the vaccines. The DTPw-HB/Hib pentavalent combination vaccine did not result in more local reactions than did the DTPw-HB vaccine alone, and, in terms of general reactions, there was no clinically significant difference between the combination or separate injections, and with the pentavalent vaccine having the benefit of needing one less injection. Nine months after the third dose of the primary-vaccination course, antibody persistence was similar in both groups, with over 93% of children still having protective/seropositive titers for Hib, HB, and tetanus and about 50% for diphtheria and Bordetella pertussis. At 15 months of age, virtually all the toddlers responded with a strong boost response to all the vaccine antigens, whether they received the DTPw-HB/Hib pentavalent vaccine or the DTPw/Hib vaccine as a booster. Both booster regimens were equally well tolerated, indicating that up to five doses of the HB vaccine can be given without impact on safety. CONCLUSIONS: Our study confirms that the DTPw-HB/Hib pentavalent vaccine is highly immunogenic as a primary vaccination in children who received an HB vaccine at birth, with the pentavalent combination inducing both persisting immunity and boostable memory. The pentavalent vaccine was safe both for primary and booster vaccinations. Thus, this study in Costa Rican infants supports the routine use of the pentavalent DTPw-HB/Hib vaccine as part of childhood vaccination programs in Latin America and the Caribbean.	I. Faingezicht, M. L. Avila-Aguerro, Y. Cervantes, M. Fourneau and S. A. Clemens	Revista panamericana de salud pública = Pan American journal of public health
445	The impact of physician bonuses, enhanced fees, and feedback on childhood immunization coverage rates	OBJECTIVES: The purpose of this study was to examine the effects on immunization coverage of 3 incentives for physicians--a cash bonus for practice--wide increases, enhanced fee for service, and feedback. METHODS: Incentives were applied at 4-month intervals over 1 year among 60 inner-city office-based pediatricians. At each interval, charts of 50 randomly selected children between 3 and 35 months of age were reviewed per physician. RESULTS: The percentage of children who were up to date for diphtheria, tetanus, and pertussis and Haemophilus influenzae type b; polio; and measles-mumps-rubella immunization in the study's bonus group improved by 25.3 percentage points (P < .01). No significant changes occurred in the other groups. However, percentage of immunizations received outside the participating practice also increased significantly in the bonus group (P < .01). Levels of missed opportunities to immunize were high in all groups and did not change over time. Physicians' knowledge of contraindications was low. CONCLUSIONS: Bonuses sharply and rapidly increased immunization cover-age in medical records. However, much of the increase was the result of better documentation. A bonus is a powerful incentive, but more structure or education may be necessary to achieve the desired results.	G. Fairbrother, K. L. Hanson, S. Friedman and G. C. Butts	American journal of public health
5	[Evaluation of the reactogenicity and immunogenic potency of combined vaccine "Bubo-Kok" in the immunization of children against diphtheria, tetanus, pertussis and viral hepatitis B]	Combined vaccine "Bubo-Kok" is characterized by safety and high immunological activity. The number of postvaccinal reactions in children aged 1 and 2 years, immunized with vaccine "Bubo-Kok", was not statistically different from those in groups of children immunized with adsorbed DPT vaccine, as well with such vaccine in combination with vaccine against hepatitis B. After the completion of the primary course of immunization 100% of children had protective antibody titers against diphtheria, tetanus and hepatitis B. Antibody titers against pertussis, equal to or exceeding protective titers, were found in more than 70% of immunized children. The immunogenic potency of vaccine "Bubo-Kok" with respect to all its components was not inferior to that of adsorbed DPT vaccine and vaccine against hepatitis B, when introduced simultaneously in different areas of the body. Vaccine "Bubo-Kok" successfully passed state trials and was recommended for registration.	I. V. Fel'dblium, A. M. Nikolaeva, A. V. Kuz'ianin, V. N. Borisova, V. A. Mel'nikov, R. P. Chuprinina, O. V. Perelygina, N. V. Shalunova, V. D. Semenova, D. V. Griaznova, E. V. Pushkareva, A. Uvitski, I. A. Alekseeva, O. A. Konopleva, M. V. Budanov and I. M. Iakovleva	Zhurnal mikrobiologii, epidemiologii, i immunobiologii
73	Comparison of acellular (B type) and whole-cell pertussis-component diphtheria-tetanus-pertussis vaccines as the first booster immunization in 15- to 24-month-old children	We compared an acellular (B type) pertussis-component diphtheria-tetanus-pertussis (DTP-Ac) vaccine containing equal amounts of filamentous hemagglutinin and lymphocytosis-promoting factor with a conventional whole-cell vaccine as the first booster immunization in 162 healthy children 15 to 24 months of age. Fewer local reactions (e.g., erythema, swelling, and tenderness at the injection site) were seen in DTP-Ac vaccine recipients during the first 48 hours of observation. This group also had fewer episodes of fever (> or = 38 degrees C) and other systemic reactions (e.g., irritability, drowsiness, and anorexia). Overall, 57% of the DTP-Ac vaccine recipients had no obvious adverse reactions, in contrast to 5% in the comparison group. At 4 to 8 weeks after vaccination, serum antibody responses to filamentous hemagglutinin and lymphocytosis-promoting factor were greater in recipients of the acellular vaccine as determined by an enzyme-linked immunosorbent assay. We conclude that this B-type acellular vaccine is both immunogenic and much less likely to cause an adverse reaction than a currently licensed whole-cell vaccine, and is suitable for routine booster immunizing doses to protect against pertussis.	S. Feldman, S. Perry, M. Andrew, L. Jones and J. E. Moffitt	The Journal of pediatrics
356	Comparison of acellular (AcP) vs whole cell (WcP) pertussis vaccine combined with diphtheria (D)/tetanus (T) toxoid (DTAcP vs DTWcP) for the 18 month booster immunization (N=163) [abstract]		S. Feldman, S. Perry, M. Andrews, L. Jones and J. Moffitt	Pediatric Research
425	Randomized trial of the immunogenicity of fractional dose regimens of PRP-T Haemophilus influenzae type b conjugate vaccine	To assess the immunogenicity of more economical regimens of Haemophilus influenzae type b (Hib) conjugate vaccine, a randomized trial of fractional doses of polyribosylribitol phosphate-tetanus toxoid (PRP-T) Hib vaccine was undertaken in the Dominican Republic. Six hundred children were assigned to one of six regimens with PRP-T vaccine: full-dose, half-dose, and one-third-dose of Hib vaccine given separately or combined with diphtheria, tetanus, and pertussis (DTP) vaccine at ages 2, 4, and 6 months. Regimens that elicited antibody levels > 1.0 microg/mL in >70% of children and < or = 0.15 microg/mL in > 90% of children were considered acceptable. At 1 month post Dose 3, all regimens met the criteria for acceptable response. Among those who received Hib as a separate injection, geometric mean concentrations of anti-PRP bodies (GMCs) at age 1 month post Dose 3 were 11.2, 11.9, and 16.3 in the full, half, and one-third dose groups, respectively. Among those who received Hib and DTP combined, the GMCs were 6.4, 5.2, and 5.7 in the full-, half-, and one-third-dose groups respectively.	J. Fernández, S. Balter, J. Feris, E. Gómez, Z. Garib, P. L. Castellanos, J. Sánchez, S. Romero-Steiner and O. S. Levine	The American journal of tropical medicine and hygiene
109	Booster vaccination of pre-school children with reduced-antigen-content diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine co-administered with measles-mumps-rubella-varicella vaccine: a randomized, controlled trial in children primed according to a 2 + 1 schedule in infancy	BACKGROUND: Pertussis occurs in older children, adolescents and adults due to waning immunity after primary vaccination. Booster vaccination for pre-school children has been recommended in Italy since 1999. In this study (NCT00871000), the immunogenicity, safety and reactogenicity of a booster dose of reduced-antigen content diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine (dTpa-IPV; GSK Biologicals Boostrix?-Polio; 3-component pertussis) vs. full-strength DTPa-IPV vaccine (sanofi-pasteur--MSD Tetravac?; 2-component pertussis) was evaluated in pre-school Italian children. METHODS: Healthy children aged 5-6 y primed in a routine vaccination setting with three doses of DTPa-based vaccines were enrolled and randomized (1:1) in this phase IIIb, booster study to receive a single dose of dTpa-IPV or DTPa-IPV; the MMRV vaccine was co-administered. Antibody concentrations/titers against diphtheria, tetanus, pertussis and poliovirus 1-3 were measured before and one month post-booster. Reactogenicity and safety was assessed. RESULTS: 305 subjects were enrolled of whom 303 (dTpa-IPV = 151; DTPa-IPV = 152) received booster vaccination. One month post-booster, all subjects were seroprotected/seropositive for anti-diphtheria, anti-tetanus, anti-PT, anti-FHA and anti-poliovirus 1-3; 99.3% of dTpa-IPV and 60.4% of DTPa-IPV subjects were seropositive for anti-PRN; 98-100% of subjects were seropositive against MMRV antigens post-booster. Pain at the injection site (dTpa-IPV: 63.6%; DTPa-IPV: 63.2%) and fatigue (dTpa-IPV: 26.5%; DTPa-IPV: 23.7%) were the most commonly reported solicited local and general symptoms, during the 4-d follow-up period. No SAEs or fatalities were reported. CONCLUSIONS: The reduced-antigen-content dTpa-IPV vaccine was non-inferior to full-strength DTPa-IPV vaccine with respect to immunogenicity. The vaccine was well-tolerated and can be confidently used as a booster dose in pre-school children.	G. Ferrera, M. Cuccia, G. Mereu, G. Icardi, G. Bona, S. Esposito, F. Marchetti, M. Messier, S. Kuriyakose and K. Hardt	Human vaccines & immunotherapeutics
461	Tetravalent immunization with DPT and an inactivated polio vaccine. <ORIGINAL> VACCINATION TETRAVALENTE DIPHTERIQUE, TETANIQUE, COQUELUCHEUSE ET POLIOMYELITIQUE INACTIVEE	Two hundred forty-nine infants were immunized after being randomly allocated to the classical Tetracoq vaccine or to inactivated poliomyelitis vaccines prepared on monkey kidney cells or on Vero-type continuous cell lines either mixed with DPT or placed in a 2-compartment seringe separating (by-pass) the polio vaccine from the DPT. The 3 preparations were well tolerated and led to a good immune response: the first after 3 injections, the second and third after the second injection. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	C. Fillastre, P. Bregere and N. Guerin	Arch Fr Pediatr
242	[Tetravalent diphtheria, tetanus, pertussis and inactivated poliomyelitis vaccine]	Two hundred forty-nine infants were immunized after being randomly allocated to the classical Tetracoq vaccine or to inactivated poliomyelitis vaccines prepared on monkey kidney cells or on Vero-type continuous cell lines either mixed with DPT or placed in a 2-compartment syringe separating (by-pass) the polio vaccine from the DPT. The 3 preparations were well tolerated and led to a good immune response: the first after 3 injections, the second and third after the second injection.	C. Fillastre, P. Brégère and N. Guérin	Archives françaises de pédiatrie
267	Clinical trial of concentrated inactivated polio vaccine in a simplified immunization program	The aims of the trial were: 1) to verify the effectiveness of injectable polio vaccine (inactivated) combined with concentrated diphtheria and tetanus toxoid, in one or two injections given at an interval of 6 months; 2) to compare the killed polio vaccine with the oral vaccine which is recommended in the Ivory Coast program: 4 doses in 15 months. The effectiveness of the immunizations is judged by the serum antibody levels 8 to 12 weeks following immunization. The comparative study of 2 inactivated polio vaccines A and C with live oral vaccine showed the superiority of inactivated vaccine, which resulted in good seroconversion after a single dose. The increase in the serologic response is proportional to the antigenic mass since it appears that the concentration of vaccine C is double that of A.	C. Fillastre, C. Emmou, M. Meyran, M. Schlumberger and N. Guérin	Developments in biological standardization
233	Effect of vitamin A supplementation with BCG vaccine at birth on vitamin A status at 6 wk and 4 mo of age	BACKGROUND: The effect of vitamin A supplementation (VAS) at birth on subsequent vitamin A status has not been studied. OBJECTIVE: The objective was to study the effect of 50,000 IU vitamin A administered with BCG vaccine at birth on vitamin A status in both sexes. DESIGN: Within a randomized placebo-controlled trial of VAS, we obtained blood from 614 children at 6 wk of age and from 369 mother-infant pairs at 4 mo of age. We assessed vitamin A status on the basis of serum retinol-binding protein (RBP) and measured serum C-reactive protein to monitor for concurrent infections. RESULTS: RBP concentrations indicated vitamin A deficiency in 32% of the children at age 6 wk and in 16% at age 4 mo. VAS was not associated with higher RBP concentrations overall or in either sex. However, the effect of VAS varied with maternal education (P for interaction = 0.004): At age 6 wk, VAS was associated with higher (9%; 95% CI: 2, 17%) RBP concentrations in children of noneducated mothers but not in children of educated mothers. Overall, RBP concentrations increased between 6 wk and 4 mo of age. The increase correlated inversely with the number of diphtheria-tetanus-pertussis (DTP) vaccines received in the interval (P = 0.009), particularly in girls (P for interaction = 0.01) and in vitamin A recipients (P = 0.01). CONCLUSIONS: Overall, VAS at birth had no effect on vitamin A status. However VAS may temporarily improve vitamin A status in the subgroup of children of noneducated mothers. In vitamin A recipients, subsequent DTP vaccines affected vitamin A status negatively. The main trial was registered at clinicaltrials.gov as NCT00168597.	A. B. Fisker, I. M. Lisse, P. Aaby, J. G. Erhardt, A. Rodrigues, B. M. Bibby and C. S. Benn	The American journal of clinical nutrition
51	A comparison of local reactions to two formulations of DPT vaccine		T. Freeman, W. Cuff, P. Duclos, M. A. Stewart, B. Morris and D. Cloutier-Fisher	Canada communicable disease report = Relevé des maladies transmissibles au Canada
276	Health diaries for monitoring events following immunization		T. R. Freeman, M. Stewart, R. Birtwhistle and D. C. Fisher	Canadian journal of public health = Revue canadienne de santé publique
273	Blowing away shot pain: a technique for pain management during immunization	OBJECTIVE: To study the effect of an active distraction technique on pain in preschool children receiving diphtheria, pertussis, and tetanus immunization. DESIGN: Randomized, unblinded controlled study. SETTING: Columbus Public Health Department Immunization Clinics. PARTICIPANTS: One hundred forty-nine 4- to 7-year-old children. INTERVENTION: Children were taught to blow out air repeatedly during the injection, as if they were blowing bubbles. RESULTS: Children who were taught to blow out air during their shots had significantly fewer pain behaviors (P < .04) and demonstrated a trend toward lower subjectively reported pain (P = .06). There was no significant difference in the nurse or parent visual analog scale scores. CONCLUSIONS: A simple distraction technique can be effective in helping children cope with the pain of immunization. The use of such a technique to relieve the pain and distress associated with even a brief painful procedure should be encouraged.	G. M. French, E. C. Painter and D. L. Coury	Pediatrics
311	Immunogenicity and reactogenicity following primary immunisation with a combined DTaP-HBV vaccine and a Haemophilus influenzae type B vaccine administered by separate or mixed injection	Objectives: The aim of this open, randomised, multicentre trial was to evaluate the immunogenicity and reactogenicity of the tetravalent diphtheria-tetanus-acellular pertussis-hepatitis B (DTaP-HBV) vaccine when given either as a mixed or as a separate concomitant injection with the Haemophilus influenzae type b (Hib) vaccine at 3, 5 and 11 months of age. Methods: Antibody against diphtheria, tetanus, pertussis (ELISA), hepatitis B (radioimmunoassay) and Hib polyribosylribitol phosphate (PRP) [radiolabeled antigen binding assay] was determined. Solicited local and systemic adverse events were evaluated on the day of each vaccination and for three subsequent days. Follow-up of unsolicited and serious adverse events was conducted for 30 days following each vaccination. Results: A total of 360 subjects were enrolled in the study. After completion of the three-dose vaccination course, seroprotective antibody concentrations against diphtheria, tetanus and hepatitis B, together with a pertussis vaccine response, were seen in almost all subjects with immunogenicity results (n = 336). All subjects had post-vaccination Hib anti-PRP antibody concentrations of at least 0.15 mug/mL, and 97.0% and 99.4%, respectively, of the subjects receiving a single or separate injections had Hib anti-PRP antibody concentrations >=1.0 mug/mL. Addition of the Hib vaccine to the tetravalent DTaP-HBV vaccine did not increase the incidence of local or systemic reactions. Conclusions: Combination of DTaP-HBV and Hib vaccines in a single injection is safe, immunogenic and well tolerated, and thus has the potential to simplify the childhood immunisation schedule in Italy. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	G. Gabutti, G. Bona, P. Dentico, F. Bamfi, K. Hardt and S. Majori	Clinical Drug Investigation
70	Comparative biological activities of whole cell pertussis vaccine and a new acellular preparation	The biological activities of whole-cell pertussis vaccine and a new acellular preparation were compared. It was observed that both preparations were similarly effective in inducing protection in mice against intracerebral challenge with B. pertussis, however, the acellular preparation was approximately 200-fold more potent. A close relationship between the degree of pertussis toxin purification and the increase in potency was observed. Neither preparation affected the weight gain of the animals within the doses employed. As expected, both preparations had histamine-sensitizing activity and leukocyte-promoting activity. It is suggested that this preparation, obtained using very simple methodology, can be considered as a potentially useful acellular pertussis vaccine.	J. A. García-Sánz, J. Ruiz-Puente, J. Jiménez-Paredes, M. González-Pacheco and H. Villalva-Posada	Vaccine
186	Immunogenicity and safety of human papillomavirus-16/18 AS04-adjuvanted cervical cancer vaccine coadministered with combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine to girls and young women	PURPOSE: Many countries recommend human papillomavirus (HPV) vaccination in female adolescents at an age when other vaccines are routinely administered. This open, randomized, multicenter study (108464/NCT00426361) evaluated coadministration of HPV-16/18 AS04-adjuvanted vaccine with diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine (dTpa-IPV). METHODS: Healthy females aged 10-18 years were randomized to receive HPV vaccine at months 0, 1, and 6 (n = 248), HPV vaccine coadministered with dTpa-IPV at month 0 and HPV vaccine at months 1 and 6 (n = 255), or dTpa-IPV at month 0 followed by HPV vaccine at months 1, 2, and 7 (n = 248). Immunogenicity was evaluated at months 0, 1, and 7 or 8 (depending on group). Vaccine reactogenicity and safety were also assessed. RESULTS: Coadministered dTpa-IPV and HPV vaccine was noninferior to dTpa-IPV alone in terms of seroprotection against diphtheria (99.2% and 100%), tetanus (100% and 100%) and poliovirus types 1, 2, and 3 (> or = 99.6%), and geometric mean antibody concentrations (ELISA Units/mL) for pertussis toxoid (84 vs. 75), filamentous hemagglutinin (612 and 615) and pertactin (426 and 360) at month 1. Coadministered dTpa-IPV and HPV vaccine was noninferior to HPV vaccine alone in terms of seroconversion rates for HPV-16 (99.5% and 100%) and HPV-18 (99.5% and 100%) and geometric mean antibody titers (ELISA Units/mL) for HPV-16 (15,608 and 18,965) and HPV-18 (6,597 and 6,902) at month 7. Coadministration was generally well tolerated. The reactogenicity of dTpa-IPV and the first dose of HPV vaccine was similar. CONCLUSIONS: Results from this study support coadministration of the HPV-16/18 AS04-adjuvanted vaccine with dTpa-IPV vaccine in females aged 10-18 years.	J. Garcia-Sicilia, T. F. Schwarz, A. Carmona, K. Peters, J. E. Malkin, P. M. Tran, U. Behre, E. B. Iturbe, G. Catteau, F. Thomas, K. Dobbelaere, D. Descamps and G. Dubin	The Journal of adolescent health : official publication of the Society for Adolescent Medicine
228	BCG vaccination among West African infants is associated with less anergy to tuberculin and diphtheria-tetanus antigens	To examine risk factors for anergy, delayed-type hypersensitivity was assessed among 884 infants participating in a vaccine trial in Guinea-Bissau. The infants were skin-tested at 7.5 months of age with a panel of seven intradermal antigens. Risk factors for anergy to tuberculin or anergy to both the diphtheria and tetanus antigens were determined in relation to Bacillus Calmette-Guérin (BCG) vaccination, diphtheria-tetanus-pertussis (DTP) vaccination, and measles vaccination. We found sick children to be more anergic to tuberculin and diphtheria-tetanus antigens than healthy children (OR=2.49 (95% confidence interval 1.40-4.55)). There was a higher prevalence of anergy to tuberculin in the rainy season than in the dry season (OR=1.67 (1.25-2.23)). Children who had taken antimalarials within the last week had a higher prevalence of anergy to tuberculin (OR=1.41 (1.02-1.92)). BCG vaccination was significantly associated with less anergy to tuberculin and diphtheria-tetanus antigens (OR=0.42 (0.28-0.63), OR=0.77 (0.60-0.99), respectively). Children vaccinated with BCG before 1 month of age were more anergic to tuberculin than children vaccinated after 1 month (OR=1.61 (1.19-2.19)). DTP vaccination was associated with less anergy to diphtheria-tetanus antigens (OR=0.40 (0.32-0.49)), but not to tuberculin. Children with a positive reaction to tuberculin were less likely to be anergic to diphtheria-tetanus antigens (OR=0.36 (0.26-0.49)) than children with a negative tuberculin reaction. Children who were vaccinated with BCG before they received their last DTP vaccine were less anergic to diphtheria-tetanus antigens (OR=0.40 (0.16-0.88)) than other DTP-vaccinated children. In conclusion, current disease, rainy season, age below 1 month of age at the time of BCG vaccination, and administration of chloroquine or quinimax within the last 7 days were risk factors for anergy to tuberculin among 7.5-month-old infants. BCG vaccination and a positive tuberculin reaction were associated with a lower prevalence of anergy to both tuberculin and diphtheria-tetanus. Thus, BCG vaccination may contribute to better cell-mediated immune responses among infants.	M. L. Garly, C. Balé, C. L. Martins, M. A. Baldé, K. L. Hedegaard, H. C. Whittle and P. Aaby	Vaccine
423	BCG scar and positive tuberculin reaction associated with reduced child mortality in West Africa. A non-specific beneficial effect of BCG?	Previous studies have suggested that the bacille Calmette-Guérin (BCG) vaccine may have a non-specific beneficial effect on childhood survival in areas with high mortality. We examined whether BCG-vaccinated children with a BCG scar or a positive tuberculin reaction had better survival than children without such reactions. As part of an ongoing two-dose measles vaccine trial for which children were recruited at 6 months of age, we examined 1813 children for BCG scar at 6 months of age and 813 BCG-vaccinated children were skin-tested for delayed hypersensitivity to tuberculin, tetanus and diphtheria. We found that BCG-vaccinated children with a BCG scar had significantly lower mortality compared with BCG scar-negative children, the mortality ratio in the first 12 months of follow-up being 0.41 (0.25-0.67). BCG-vaccinated children with a positive tuberculin test had a mortality ratio of 0.45 (0.24-0.85) compared with tuberculin negative children. These results were unchanged by control for potential confounders or using different cut-off points for a tuberculin-positive response. Exclusion of dead children who had HIV antibodies did not modify the estimate (mortality rate (MR)=0.46 (0.23-0.94)). After censoring for tuberculosis (TB) exposure at home, the mortality ratios for having a scar and being tuberculin-positive were 0.46 (0.27-0.79) or 0.42 (0.21-0.84), respectively. Children positive to tetanus or diphtheria in the skin test had the same mortality as children not responding to these vaccine-related antigens. Thus, BCG scar and a positive tuberculin reaction were associated with better survival in early childhood in an area with high mortality. Since nothing similar was found for responders to diphtheria-tetanus-pertussis (DTP) vaccine, and the effect could not be explained by protection against tuberculosis, the effect of BCG vaccination could be due to non-specific immune-stimulation protecting against other infections.	M. L. Garly, C. L. Martins, C. Balé, M. A. Baldé, K. L. Hedegaard, P. Gustafson, I. M. Lisse, H. C. Whittle and P. Aaby	Vaccine
137	Randomized trial on the safety, tolerability, and immunogenicity of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis vaccine in adolescents and young adults	This study evaluated the safety, tolerability, and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine, MenACWY-CRM, when administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis (Tdap) vaccine, in subjects aged 11 to 25 years. Subjects received either MenACWY-CRM and Tdap, MenACWY-CRM and saline placebo, or Tdap and saline placebo. No significant increase in reactogenicity and no clinically significant vaccine-related adverse events (AEs) occurred when MenACWY-CRM and Tdap were administered concomitantly. Similar immunogenic responses to diphtheria, tetanus, and meningococcal (serogroups A, C, W-135, and Y) antigens were observed, regardless of concomitant vaccine administration. Antipertussis antibody responses were comparable between vaccine groups for filamentous hemagglutinin and were slightly lower, although not clinically significantly, for pertussis toxoid and pertactin when the two vaccines were administered concomitantly. These results indicate that the investigational MenACWY-CRM vaccine is well tolerated and immunogenic and that it can be coadministered with Tdap to adolescents and young adults.	R. Gasparini, M. Conversano, G. Bona, G. Gabutti, A. Anemona, P. M. Dull and F. Ceddia	Clinical and vaccine immunology : CVI
30	Immunogenicity, reactogenicity and safety of three-dose primary and booster vaccination with combined diphtheria-tetanus-whole-cell pertussis-hepatitis B-reduced antigen content Haemophilus influenzae type b vaccine in Filipino children	OBJECTIVES: To evaluate the immunogenicity, reactogenicity and safety of primary and booster vaccination with DTPw-HBVLT/Hib2.5 vaccine containing low thiomersal and reduced quantities of Hib polysaccharide (PRP). BACKGROUND: Combined DTP vaccines have high global coverage. Thus, the addition of new antigens to existing DTP vaccines is the most effective way to ensure high coverage. METHODS: 192 healthy infants were randomized to receive the investigational DTPw-HBVLT/Hib2.5 vaccine or licensed DTPw-HBV/Hib10 at 6, 10, 14 weeks. Immune memory to the Hib antigen was assessed through administration of plain PRP challenge at 10 months in 50% of subjects. Challenged and unchallenged subjects respectively received a DTP-HBV or DTPa-HBV/Hib booster at 15-18 months of age. Antibody responses were measured using enzyme-linked immunosorbent assay (ELISA) and reactogenicity was assessed using diary cards. RESULTS: One month post-primary vaccination, 100% and ? 93.7% of subjects in both groups had anti-PRP antibody concentrations ? 0.15 ?g/mL and ? 1.0 ?g/mL, respectively. Robust responses to PRP were observed after the 10 month plain PRP challenge and booster responses were observed in unchallenged subjects after the booster dose at 15-18 months of age. Post-primary and post-booster responses to the other vaccine antigens were at least as high in the DTPw-HBVLT/Hib2.5 group versus the DTPw-HBV/Hib10 group. The reactogenicity profile of the DTPw-HBVLT/Hib2.5 vaccine was acceptable. CONCLUSION: The DTPw-HBVLT/Hib2.5 combination vaccine with reduced thiomersal and Hib content had equivalent immunogenicity and tolerability versus the full standard DTPw-HBV/Hib10 vaccine. DTPw-HBVLT/Hib2.5 or DTPw-HBV/Hib10 vaccines can contribute to reducing childhood diseases through ensuring high vaccine coverage in mass vaccination programs. ClinicalTrials.gov identifiers: NCT 01061541, NCT00158808.	S. R. Gatchalian, G. Ramakrishnan, H. L. Bock, I. Lefevre and J. M. Jacquet	Human vaccines
174	Safety and immunogenicity of a combined diphtheria-tetanus-acellular pertussis-hepatitis B vaccine administered according to two different primary vaccination schedules. Multicenter Working Group	The reactogenicity and immunogenicity of a tetravalent diphtheria-tetanus-acellular pertussis-hepatitis B (DTPa-HB) vaccine (SmithKline Beecham) were studied in 565 infants immunized according to one of two different schedules, at 2, 4 and 6 months of age (group A n = 208) or at 3, 5 and 11 months of age (group B n = 357). The incidences of local and general reactions within the first 8 days after vaccination were similar in the two groups of infants, the vast majority being mild in intensity and occurring within 2-3 days of vaccine administration. Severe local symptoms were rare: pain after 0.6% of all doses, redness after 0.5% and 1.3%, and swelling after 0.3% and 1.5%, in group A and B, respectively. Only one infant in group A and one in group B had a temperature > 39.0 degrees C. Both schedules proved satisfactory in obtaining high levels of antibodies against all antigens. The rates of serologic response against the different antigens reached 100% in both groups. Antibody titres against all vaccine components were elevated following both schedules, but after the third dose of vaccine geometric mean antibody titres (GMTs) against D toxoid, filamentous haemagglutinin (FHA), pertactin (PRN) and hepatitis B (HB) were significantly higher in the 3, 5, 11 group than after the 2, 4, 6 schedule. Antibody titres measured at 7 months of age in the group immunized at 2, 4 and 6 months were higher than those reached at 6 months of age in infants immunized at 3, 5 and 11 months, but FHA and PRN were within the range of DTPa vaccine with proven efficacy. We conclude that DTPa-HB vaccine was safe, well tolerated and highly immunogenic. Both vaccination schedules (2, 4, 6 and 3, 5, 11) can be considered suitable for mass immunization programmes.	G. Giammanco, A. Moiraghi, C. Zotti, S. Pignato, S. Li Volti, A. Giammanco and R. Soncini	Vaccine
320	Safety and immunogenicity of a combined diphtheria-tetanus-acellular pertussis-hepatitis B vaccine administered according to two different primary vaccination schedules	The reactogenicity and immunogenicity of a tetravalent diphtheria- tetanus-acellular pertussis-hepatitis B (DTPa-HB) vaccine (SmithKline Beecham) were studied in 565 infants immunized according to one of two different schedules, at 2, 4 and 6 months of age (group A n = 208) or at 3, 5 and 11 months of age (group B n = 357). The incidences of local and general reactions within the first 8 days after vaccination were similar in the two groups of infants, the vast majority being mild in intensity and occurring within 2-3 days of vaccine administration. Severe local symptoms were rare: pain after 0.6% of all doses, redness after 0.5% and 1.3%, and swelling after 0.3% and 1.5%, in group A and B, respectively. Only one infant in group A and one in group B had a temperature > 39.0 [degree] C. Both schedules proved satisfactory in obtaining high levels of antibodies against all antigens. The rates of serologic response against the different antigens reached 100% in both groups. Antibody titres against all vaccine components were elevated following both schedules, but after the third dose of vaccine geometric mean antibody titres (GMTs) against D toxoid, filamentous haemagglutinin (FHA), pertactin (PRN) and hepatitis B (HB) were significantly higher in the 3, 5, 11 group than after the 2, 4, 6 schedule. Antibody titres measured at 7 months of age in the group immunized at 2, 4 and 6 months were higher than those reached at 6 months of age in infants immunized at 3, 5 and 11 months, but FHA and PRN were within the range of a DTPa vaccine with proven efficacy. We conclude that DTPa-HB vaccine was safe, well tolerated and highly immunogenic. Both vaccination schedules (2, 4, 6 and 3, 5, 11) can be considered suitable for mass immunization programmes. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	G. Giammanco, A. Moiraghi, C. Zotti, S. Pignato, S. Li Volti, A. Giammanco and R. Soncini	Vaccine
93	Immunogenicity of a combination vaccine containing diphtheria toxoid, tetanus toxoid, three-component acellular pertussis, hepatitis B, inactivated polio virus, and Haemophilus influenzae type b when given concomitantly with 13-valent pneumococcal conjugate vaccine	Two randomized trials of 13-valent pneumococcal conjugate vaccine (PCV13) relative to PCV7 evaluated the immune responses of coadministered antigens comprising Infanrix(®) hexa/Infanrix(®)-IPV+Hib (diphtheria, tetanus, 3-component acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b). After the 3-dose infant series, immunogenic noninferiority was demonstrated for all concomitantly administered antigens between the PCV13 and PCV7 groups. All antigens elicited good booster responses after the toddler dose except pertussis toxoid; however, 99.6% subjects achieved pertussis toxoid protective antibody level ?5EU/mL in both groups. These results support the concomitant administration of PCV13 and Infanrix hexa/Infanrix-IPV+Hib as part of routine immunization schedules.	F. Gimenez-Sanchez, D. M. Kieninger, K. Kueper, F. Martinon-Torres, E. Bernaola, J. Diez-Domingo, K. Steul, C. Juergens, A. Gurtman, P. Giardina, J. Z. Liang, W. C. Gruber, E. A. Emini and D. A. Scott	Vaccine
56	A comparison of 2 strategies to prevent infection following pertussis exposure in vaccinated healthcare personnel	BACKGROUND: Antibiotic postexposure prophylaxis (PEP) following pertussis exposure is recommended but has never been evaluated in healthcare personnel (HCP) vaccinated with acellular pertussis vaccine (Tdap). METHODS: Tdap-vaccinated HCP were randomized to receive azithromycin PEP or no PEP following pertussis exposure. Acute and convalescent nasopharyngeal swabs and sera were obtained for pertussis testing by polymerase chain reaction (PCR) and anti-pertussis toxin (PT) immunoglobulin G, respectively. A nasopharyngeal aspirate was also collected for PCR and culture from subjects who reported respiratory symptoms within 21 days following identification of the exposure. Pertussis infection was defined as a positive culture or PCR, a 2-fold rise in anti-PT titer, or a single anti-PT titer of ?94 enzyme-linked immunosorbent assay units/mL. Daily symptom monitoring without PEP was considered noninferior to PEP after pertussis exposure if the lower limit of the 1-sided 95% confidence interval (CI) for the reduction in pertussis was greater than -7%. RESULTS: During 30 months of study, 86 subjects were randomized following a pertussis exposure. Using the predefined definition of infection, pertussis infection did not develop in 41 (97.6%) of 42 subjects who received azithromycin PEP and 38 (86.4%) of 44 subjects who did not receive PEP (absolute risk difference, -11.3%; lower bound of the 1-sided 95% CI, -20.6%; P = .81). However, no subject developed symptomatic pertussis confirmed with culture or a specific PCR assay, and possibly no subject developed subclinical pertussis infection based upon additional serologic testing. CONCLUSIONS: Using the predefined definition of pertussis infection, noninferiority for preventing pertussis following exposure was not demonstrated for daily symptom monitoring of Tdap-vaccinated HCP without PEP when compared with antibiotic PEP. However, the small number of exposed HCP warrants further study of this approach. CLINICAL TRIAL REGISTRATION: NCT00469274.	W. P. Goins, K. M. Edwards, C. L. Vnencak-Jones, M. T. Rock, M. Swift, V. Thayer, W. Schaffner and T. R. Talbot	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
312	Safety and immunogenicity of a fully liquid vaccine containing five-component pertussis-diphtheria-tetanus-inactivated poliomyelitis- Haemophilus influenzae type b conjugate vaccines administered at two, four, six and 18 months of age	OBJECTIVE: The safety, immunogenicity and lot consistency of a fully liquid, five-component acellular pertussis combination vaccine, comprised of diphteria, tetanus and acellular pertussis, inactivated polio vaccine, Haemophilus influenzae type b (DTaP-IPV-Hib [Pediacel, sanofi pasteur, Canada]) were assessed and compared with that of Hib vaccine reconstituted with the five-component acellular pertussis combination vaccine (DTaP-IPV//Hib, Pentacel [sanofi pasteur, Canada]). METHODS: Infants were recruited at vaccine study centres in Montreal, Quebec; Simon Fraser Healuh Region, British Columbia, and southern Alberta after the protocol had been approved by the relevant institutional ethics committees. Written informed consent was obtained from the parents or guardians of all subjects. At two months of age, the infants were randomly assigned to receive one of three consecutive production lots of DTaP-IPV-Hib by intramuscular injection. Reactions to vaccinations were assessed by parental observation and through telephone interviews conducted by study nurses. Blood samples were obtained at two, six, seven, 18 and 19 months of age for measurement of antibodies to vaccine antigens. RESULTS: Most injection site and systemic reactions were mild or moderate, and of brief duration. All infants were protected against tetanus, diphtheria and all three polio serotypes after both primary and booster vaccinations. Antibody responses to pertussis antigens were similar to those observed in Swedish infants, in whom the five-component vaccine was shown to be 85% effective. Proportions of infants with antipolyribosylribitol phosphate antibody of 0.15 mug/mL or greater and 1.0 mug/mL or greater, were 97.9% and 88.9%, respectively, following primary immunization, and 100% and 99% following booster vaccination. Safety and immunogenicity results with both reconstituted and fully liquid combination vaccines were comparable. CONCLUSIONS: The fully liquid combination vaccine was comparable in terms of safety and immunogenicity with the reconstituted combination vaccine. copyright2007 Pulsus Group Inc. All rights reserved. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	R. Gold, L. Barreto, S. Ferro, J. Thippawong, R. Guasparini, W. Meekison, M. Russell, E. Mills, D. Harrison and P. Lavigne	Canadian Journal of Infectious Diseases and Medical Microbiology
305	What do parents learn by reading a DPT vaccine information form?	Objective: Information forms are commonly used to inform parents about childhood vaccination. This study assessed the knowledge of mothers about pertussis and pertussis vaccine before and after reading a form about diphtheria-pertussis-tetanus (DPT) vaccine. Design: A test was administered to mothers before and after the first vaccination of their infant. By random allocation, one-half of the mothers received the form (study group) in addition to the routine counselling by a public health nurse given to the others (control group). Setting: Public health immunization clinics in suburban Vancouver, British Columbia. Subjects: One hundred and fifty-one mothers who were scheduled to bring their infant for the first DPT immunization were recruited, of whom 145 (96%) completed the study. Interventions: A test consisting of 20 true/false questions was administered by telephone two weeks before and two weeks after the first DPT vaccination. Additional data about sources of vaccine information, maternal education, number of children and maternal age were obtained. Outcome measures: Mean scores and mean change in scores on test. Results: The mean changes in scores between tests 1 and 2 in study and control groups were +22.2% and +6.9%, respectively, on the disease-related questions (P < 0.001) and +14.6% and +10.7%, respectively, on the vaccine-related questions (P = 0.16). The forms were considered to be very useful by the mothers and clearly enabled them to score higher on a test of their knowledge of pertussis and pertussis vaccine. Conclusions: Reading a DPT vaccine form enabled mothers to improve their knowledge of pertussis and pertussis vaccine. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	R. Gold and G. L. Bjornson	Can. J. Infect. Dis.
114	Safety and immunogenicity of Haemophilus influenzae vaccine (tetanus toxoid conjugate) administered concurrently or combined with diphtheria and tetanus toxoids, pertussis vaccine and inactivated poliomyelitis vaccine to healthy infants at two, four and six months of age	The safety and immunogenicity of Haemophilus influenzae vaccine (tetanus toxoid conjugate (PRP-T) administered concurrently in separate sites or mixed in the same syringe with diphtheria and tetanus toxoids, pertussis vaccine and inactivated poliomyelitis vaccine were assessed in 439 infants at 2, 4 and 6 months of age. The proportions with local redness, tenderness and swelling in the separate and combined groups were 18% vs. 11% (P < 0.001), 27% vs. 24% and 15% vs. 13%, respectively. Systemic reactions occurred at similar rates in both groups. The combined vaccine induced tetanus and diphtheria antitoxin titers > or = 0.01 IU/ml in 99.5 and 99.1% of infants, pertussis agglutinin titers > or = 64 in 92.4%, anti-polyribosylribitol phosphate titers > or = 0.15 microgram/ml in 93.8% and > or = 1.0 microgram/ml in 75% and polio-neutralizing titers > or = 8 in > 98% of infants. However, antibody concentrations to PRP-T, some pertussis antigens and tetanus toxoid were significantly lower after combined than after separate injections of DPT/diphtheria and tetanus toxoids, pertussis vaccine and inactivated poliomyelitis vaccine and PRP-T. The clinical significance of these differences is not known, but the interactions observed among the components of the pentavalent vaccine may be of concern because they might influence antibody persistence until the fourth dose is administered.	R. Gold, D. Scheifele, L. Barreto, S. Wiltsey, G. Bjornson, W. Meekison, R. Guasparini and L. Medd	The Pediatric infectious disease journal
264	Potential toxicity of vitamin A supplementation in infancy		S. Gomber	Indian pediatrics
443	Immunogenicity of low dose intradermal hepatitis B vaccine and its comparison with standard dose intramuscular vaccination	OBJECTIVE: A prospective study was carried out in the well baby and immunization clinics of tertiary care hospital to compare the immunogenicity of low dose hepatitis B vaccine (HBV) given intradermally versus standard dose given intramuscularly. METHODS: One hundred ninety six term, healthy, Australia antigen negative and exclusively breast fed babies were allocated into two groups in a simple randomized manner. In group I, hepatitis B vaccine was given in low dose (2 mcg) by intradermal route whereas in group II it was administered in standard dose (10 mcg) by intramuscular route. Diphtheria, pertussis, tetanus (DPT) and oral polio vaccine (OPV) were co-administered with HBV in both the groups at 6, 10 and 14 weeks of age at different sites. One hundred seventy seven infants could be regularly followed up and tested for anti-HBs titres by third generation ELISA test using mono-ELISA anti-HBs 3.0 kits. Geometric mean titres of anti-HBs were estimated in each group and compared. Student's t-test was used for statistical analysis. RESULTS: Seroprotective anti-HBs titres (titre greater than 10 mIU/mL) were achieved in 87 of 88 (98.8 percent) children having received intramuscular doses as compared to 82 of 89 (92.1 percent) children in the intradermal group. The geometric mean titres of the intradermal group were 92.71 mIU/mL (95 percent C.I. 68.85-124.85), significantly lower than 331.66 mIU/mL (95 percent C.I. 245.12-448.78), noticed in the intramuscular group. There were no significant adverse reactions in both the groups. Hepatitis B vaccine is immunogenic when co-administered with DPT and OPV vaccine. The intradermal hepatitis B administration is less effective with lower immunogenicity than the intramuscular vaccination.	S. Gomber, R. Sharma and V. G. Ramachandran	Indian pediatrics
128	The effects of renal impairment, peritoneal dialysis, and hemodialysis on serum sodium colistimethate levels		N. J. Goodwin and E. A. Friedman	Annals of internal medicine
424	Protective efficacy and safety of three antimalarial regimens for intermittent preventive treatment for malaria in infants: a randomised, double-blind, placebo-controlled trial	BACKGROUND: Administration of sulfadoxine-pyrimethamine at times of vaccination-intermittent preventive treatment in infants (IPTi)-is a promising strategy to prevent malaria. However, rising resistance to this combination is a concern. We investigated a shortacting and longacting antimalarial drug as alternative regimens for IPTi.METHODS: We undertook a double-blind, placebo-controlled trial of IPTi in an area of high resistance to sulfadoxine-pyrimethamine at sites of moderate (n=1280 infants enrolled) and low (n=1139) intensity of malaria transmission in Tanzania. Infants aged 8-16 weeks were randomly assigned in blocks of 16 to sulfadoxine (250 mg) plus pyrimethamine (12.5 mg; n=319 in moderate-transmission and 283 in low-transmission sites), chlorproguanil (15 mg) plus dapsone (18.75 mg; n=317 and 285), mefloquine (125 mg; n=320 and 284), or placebo (n=320 and 284), given at the second and third immunisations for diphtheria, pertussis, and tetanus, and for measles. Research team and child were masked to treatment. Recruitment was stopped early at the low-transmission site because of low malaria incidence. The primary endpoint was protective efficacy against all episodes of clinical malaria at 2-11 months of age. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00158574.FINDINGS: All randomly assigned infants were analysed. At the moderate-transmission site, mefloquine had a protective efficacy of 38.1% (95% CI 11.8-56.5, p=0.008) against clinical malaria in infants aged 2-11 months, but neither sulfadoxine-pyrimethamine (-6.7%, -45.9 to 22.0) nor chlorproguanil-dapsone (10.8%, -24.6 to 36.1) had a protective effect. No regimen had any protective efficacy against anaemia or hospital admission. Mefloquine caused vomiting in 141 of 1731 (8%) doses given on day 1 (odds ratio vs placebo 5.50, 95% CI 3.56-8.46). More infants died in the chlorproguanil-dapsone and mefloquine groups (18 and 15, respectively) than in the sulfadoxine-pyrimethamine or placebo groups (eight deaths per group; p=0.05 for difference between chlorproguanil-dapsone and placebo).INTERPRETATION: IPTi with a longacting, efficacious drug such as mefloquine can reduce episodes of malaria in infants in a moderate-transmission setting. IPTi with sulfadoxine-pyrimethamine has no benefit in areas of very high resistance to this combination. The appropriateness of IPTi should be measured by the expected incidence of malaria and the efficacy, tolerability, and safety of the drug.FUNDING: IPTi Consortium and the Gates Malaria Partnership.	R. D. Gosling, S. Gesase, J. F. Mosha, I. Carneiro, R. Hashim, M. Lemnge, F. W. Mosha, B. Greenwood and D. Chandramohan	Lancet
436	Immunogenicity and tolerability of recombinant serogroup B meningococcal vaccine administered with or without routine infant vaccinations according to different immunization schedules: a randomized controlled trial	CONTEXT: In the absence of an effective vaccine, serogroup B Neisseria meningitidis (MenB) remains a major cause of invasive disease in early childhood in developed countries. OBJECTIVE: To determine the immunogenicity and reactogenicity of a multicomponent MenB vaccine (4CMenB) and routine infant vaccines when given either concomitantly or separately. DESIGN, SETTING, AND PARTICIPANTS: Phase 2b, multicenter, open-label, parallel-group, randomized controlled study of 1885 infants enrolled at age 2 months from August 2008 to July 2010 in Europe. INTERVENTION: Participants were randomized 2:2:1:1 to receive (1) 4CMenB at 2, 4, and 6 months with routine vaccines (7-valent pneumococcal and combined diphtheria, tetanus, acellular pertussis, inactivated polio, hepatitis B, Haemophilus influenzae type b vaccines); (2) 4CMenB at 2, 4, and 6 months and routine vaccines at 3, 5, and 7 months; (3) 4CMenB with routine vaccines at 2, 3, and 4 months; or (4) routine vaccines alone at 2, 3, and 4 months. MAIN OUTCOME MEASURES: Percentage of participants with human complement serum bactericidal activity (hSBA) titer of 1:5 or greater against 3 MenB strains specific for vaccine antigens (NZ98/254, 44/76-SL, and 5/99). RESULTS: After three 4CMenB vaccinations, 99% or more of infants developed hSBA titers of 1:5 or greater against strains 44/76-SL and 5/99. For NZ98/254, this proportion was 79% (95% CI, 75.2%-82.4%) for vaccination at 2, 4, and 6 months with routine vaccines, 86.1% (95% CI, 82.9%-89.0%) for vaccination at 2, 4, and 6 months without routine vaccines, and 81.7% (95% CI, 76.6%-86.2%) for vaccination at 2, 3, and 4 months with routine vaccines. Responses to routine vaccines given with 4CMenB were noninferior to routine vaccines alone for all antigens, except for the responses to pertactin and serotype 6B pneumococcal polysaccharide. Fever was seen following 26% (158/602) to 41% (247/607) of 4CMenB doses when administered alone, compared with 23% (69/304) to 36% (109/306) after routine vaccines given alone and 51% (306/605) to 61% (380/624) after 4CMenB and routine vaccines administered together. CONCLUSION: A 4CMenB vaccine is immunogenic against reference strains when administered with routine vaccines at 2, 4, and 6 or at 2, 3, and 4 months of age, producing minimal interference with the response to routine infant vaccinations. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00721396.	N. Gossger, M. D. Snape, L. M. Yu, A. Finn, G. Bona, S. Esposito, N. Principi, J. Diez-Domingo, E. Sokal, B. Becker, D. Kieninger, R. Prymula, P. Dull, E. Ypma, D. Toneatto, A. Kimura and A. J. Pollard	JAMA : the journal of the American Medical Association
150	Safety and immunogenicity of a recombinant hepatitis B vaccine administered to infants at 2, 4 and 6 months of age. The Kaiser-UCLA Vaccine Study Group	A recombinant hepatitis B vaccine was administered to over 5000 infants in a prospective, randomized and blinded study. Infants were given either recombinant hepatitis B vaccine (Engerix-B, SmithKline Beecham Pharmaceuticals, 10 micrograms dose-1) or a Haemophilus influenzae type b (Hib) conjugate vaccine at 2, 4 and 6 months of age simultaneously with diphtheria-tetanus-pertussis and oral polio vaccines. Adverse reactions were ascertained by parental reports and interviews, and review of medical records. Blood specimens collected from 269 infants given hepatitis B vaccine were assayed for antibody to hepatitis B surface antigen (anti-HBs) by enzyme immunoassay. Infants given hepatitis B vaccine experienced low rates of adverse reactions that were similar or lower than the rates in infants given Hib conjugate vaccine. The geometric mean anti-HBs concentrations were 9.6 mIU ml-1 after one dose, 333 mIU ml-1 after two doses and 1812 mIU ml-1 after three doses (99% had levels > or = 10 mIU ml-1). Antibody responses to diphtheria and tetanus toxoids were unaffected by simultaneous administration of hepatitis B or Hib conjugate vaccine. Engerix-B vaccine was safe and immunogenic when given with other routine childhood immunizations at 2, 4 and 6 months of age, and should provide long-term protection against hepatitis B virus infection.	D. P. Greenberg, C. M. Vadheim, S. M. Marcy, S. Partridge, J. Jing, C. Y. Chiu, T. Greene, H. S. Margolis and J. I. Ward	Vaccine
216	Safety and immunogenicity of a combination diphtheria-tetanus toxoids-acellular pertussis-hepatitis B vaccine administered at two, four and six months of age compared with monovalent hepatitis B vaccine administered at birth, one month and six months of age	OBJECTIVE: To evaluate the safety and immunogenicity of diphtheria-tetanus toxoids-acellular pertussis (DTPa)-hepatitis B (HepB) combination vaccine given at 2, 4 and 6 months of age compared with monovalent HepB vaccine given at birth, 1 month and 6 months of age and DTPa vaccine given at 2, 4 and 6 months of age. METHODS: Healthy infants were randomized to receive a combination DTPa-HepB vaccine (diphtheria and tetanus toxoids, acellular pertussis antigens and hepatitis B surface antigen), concomitantly with type b and oral poliovirus vaccines at 2, 4 and 6 months of age (Group 1) or HepB vaccine given at birth, 1 month and 6 months of age and DTPa, type b and oral poliovirus vaccines given at 2, 4 and 6 months of age (Group 2). Antibody responses were evaluated at birth, 2 months and 7 months of age. Safety was evaluated after each immunization using diary cards and parental interviews. RESULTS: One month after the third dose (7 months of age), the geometric mean concentration of antibody to hepatitis B surface antigen was approximately 3.5-fold higher in Group 2 than in Group 1 infants (3643 and 1052 mIU/ml, respectively; < 0.001). Nevertheless the rates of seroprotection to HepB (antibody to hepatitis B surface antigen > or =10 mIU/ml) in Groups 1 and 2 were similar, 99 and 100%, respectively. Also the postvaccination geometric mean concentrations and rates of seroprotection or vaccine response to all of the other vaccine antigens evaluated were similar or greater in Group 1 than in Group 2. The rates of adverse events were similar between the two groups, with fussiness and soreness at any injection site reported most frequently. CONCLUSIONS: The DTPa-HepB combination vaccine was safe and immunogenic when given to infants at 2, 4 and 6 months of age. Equivalent rates of seroprotection to hepatitis B were achieved despite a reduction of the interval between the second and third doses from 5 months in Group 2 to 2 months in Group 1. Hepatitis B-containing combination vaccines should reduce the number of vaccine injections required in childhood and maintain excellent seroprotection against multiple pathogens.	D. P. Greenberg, V. K. Wong, S. Partridge, B. J. Howe and J. I. Ward	The Pediatric infectious disease journal
385	Passive-active immunization in infants of hepatitis Be antigen-positive mothers. Comparison of the efficacy of early and delayed active immunization	OBJECTIVE: To assess the efficacy of late active immunization against hepatitis B concomitant with diphtheria, pertussis, tetanus, and polio vaccine in high-risk infants receiving hepatitis B immune globulin at birth. DESIGN: Randomized study of infants born to mothers positive for hepatitis B surface antigen (HBsAg) and hepatitis Be antigen (HBeAg). SETTING: Three large city hospitals and one rural area providing prenatal care and obstetric services. SUBJECTS: Eighty neonates of HBsAg- and HBeAg-positive carrier mothers received 0.5 mL/kg of body weight hepatitis B immune globulin within 2 hours of birth and hepatitis B vaccine (10 micrograms) at 0, 1, 2, and 11 months of age (group A) or at 3, 4, 5, and 11 months of age concomitant with diphtheria, pertussis, tetanus, and polio immunization (group B). A second dose of hepatitis B immune globulin was given to infants on schedule B at 3 months. MAIN OUTCOME MEASURES: Blood samples were collected at 0, 3, 6, 11, and 12 months of age and tested for antibodies against hepatitis B core antigen and HBsAg. Follow-up visits were scheduled annually up to 5 years of age. RESULTS: Eight infants were excluded from analysis. During the study period, six children became HBsAg carriers, three in each group, which corresponds to a 5-year incidence of infection of 9% and 8% for groups A (three of 35) and B (three of 37), respectively. Subclinical infections (persistent anti-HBc positivity beyond month 12 or appearance of anti-HBc) were encountered in another eight infants (four in each group). CONCLUSION: Late active immunization starting at 3 months of age appears to provide similar protective efficacy as active immunization starting at birth when combined with hepatitis B immune globulin at 0 and 3 months of age.	P. M. Grosheide, R. Canho, R. A. Heijtink, A. S. Nuijten, J. Zwijnenberg, J. R. Bänffer, Y. W. Wladimiroff, M. J. Botman, J. A. Mazel and G. C. Gast	American journal of diseases of children (1960)
269	Anti-HBs levels in infants of hepatitis B carrier mothers after delayed active immunization with recombinant vaccine concomitant with DTP-polio vaccine: is there need for a second dose of HBIg? Dutch Study Group on Prevention of Neonatal Hepatitis B	The need for an additional dose of hepatitis B immune globulin (HBIg) was studied by comparing infants receiving 1 ml HBIg at birth followed by hepatitis B immunization, concomitant with DTP-polio vaccine, at 3, 4, 5 and 11 months (schedule E), with infants receiving the same schedule with additional HBIg at 3 months (schedule F). The immune response to recombinant hepatitis B vaccine (20 micrograms) was evaluated in 195 infants born to HBsAg-positive mothers allocated to groups E and F and compared with historic controls who received plasma vaccine (10 micrograms) according to schedule F. Blood samples were drawn at 0, 3, 4, 6, 11, 12 and 24 months of age. No difference in efficacy between the two schedules was observed; 8 and 6% of infants born to HBeAg-positive HBsAg carrier mothers in groups E and F, respectively, became HBsAg carriers. Passively acquired antibodies at birth remained present for about 5 months in most infants. The seroprotection rates (anti-HBs > or = 10 IU l-1) were over 90% at all time points and similar for groups E and F. The titres of anti-HBs attained during the first 6 months were statistically lower (p < or = 0.02) for group E than for group F but similar thereafter. Anti-HBs titres in infants receiving the recombinant vaccine were significantly lower than in infants receiving the plasma vaccine (p < 0.001). Supplemental doses of HBIg in infants receiving a high dose of HBIg ( > 200 IU) at birth and the first dose of vaccine at the age of 3 months are not advised.	P. M. Grosheide, R. Canho, M. Voogd, R. A. Heijtink and S. W. Schalm	Vaccine
463	Anti-HBs levels in infants of hepatitis B carrier mothers after delayed active immunization with recombinant vaccine concomitant with DTP-polio vaccine: Is there need for a second dose of HBIg?	The need for an additional doss of hepatitis B immune globulin (HBIg) was studied by comparing infants receiving 1 ml HBIg at birth followed by hepatitis B immunization, concomitant with. DTP-polio vaccine, at 3, 4, 5 and 11 months (schedule E), with infants receiving the same schedule with additional HBIg at 3 months (schedule F). The immune response to recombinant hepatitis B vaccine (20 mug) was evaluated in 195 infants born to HBsAg-positive mothers allocated to groups E and F and compared with historic controls who received plasma vaccine (10 mug) according to schedule F. Blood samples were drawn at 0, 3, 4, 6, 11, 12 and 24 months of age. No difference in efficacy between the two schedules was observed; 8 and 6% of infants bent to HBeAg-positive HBsAg carrier mothers in groups E and F, respectively, became HBsAg carriers. Passively acquired antibodies at birth remained present for about 5 months in most infants. The seroprotection rates (anti-HBs >= 10 IU l-1) were over 90% at all time points and similar for groups E and F. The titres of anti-HBs attained during the first 6 months were statistically lower (p <= 0.02) for group E than for group F but similar thereafter. Anti-HBs titres in infants receiving the recombinant vaccine were significantly lower than in infants receiving the plasma vaccine (p << 0.001). Supplemental doses of HBIg in infants receiving a high dose of HBIg (> 200 IU) at birth and the first dose of vaccine at the age of 3 months are not advised. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	P. M. Grosheide, R. Canho, M. Voogd, R. A. Heijtink and S. W. Schalm	Vaccine
383	Early atopic disease and early childhood immunization--is there a link?	BACKGROUND: There are frequent concerns about early immunizations among the parents of children at heightened risk for atopy. The study assessed the effect of vaccine immunization before the first birthday on eczema severity and allergic sensitization in the second year of life. METHODS: A total of 2184 infants, aged 1-2 years, with established atopic dermatitis and a family history of allergy, from 97 study centres in 10 European countries, South Africa and Australia were included. Exposure to vaccines (diphtheria, tetanus, pertussis, polio, Haemophilus influenzae Type B, hepatitis B, mumps, measles, rubella, varicella, BCG, meningococci and pneumococci) and immunization dates were recorded from immunization cards. Immunoglobulin E (IgE) was determined by RAST and eczema severity was assessed by scoring atopic dermatitis (SCORAD). RESULTS: Immunization against any target was not associated with an increased risk of allergic sensitization to food or inhalant allergens. Varicella immunization (only 0.7% immunized) was inversely associated with total IgE > 30 kU/l (OR 0.27; 95% CI 0.08-0.87) and eczema severity (OR 0.34; 95% CI 0.12-0.93). Pertussis immunization (only 1.7% nonimmunized) was inversely associated with eczema severity (OR 0.30; 95% CI 0.10-0.89). Cumulative received vaccine doses were inversely associated with eczema severity (P = 0.0107). The immunization coverage of infants before and after the onset of atopic dermatitis was similar. CONCLUSION: In children at heightened risk for atopy, common childhood immunization in the first year is not associated with an increased risk of more severe eczema or allergic sensitization. Parents of atopic children should be encouraged to fully immunize their children.	C. Grüber, J. Warner, D. Hill and V. Bauchau	Allergy
122	Safety, tolerability and immunogenicity of VAQTA given concomitantly versus nonconcomitantly with other pediatric vaccines in healthy 12-month-old children	BACKGROUND: The objective of this study is to assess whether hepatitis A vaccine is immunogenic and well tolerated when administered to 12-month-old children alone or concomitantly with other routinely administered pediatric vaccines. METHODS: Six hundred seventeen healthy 12-month-old children were randomized to receive dose 1 of hepatitis A vaccine given alone or concomitantly with measles-mumps-rubella vaccine and varicella vaccine and dose 2 of hepatitis A vaccine given alone or concomitantly with diphtheria-tetanus-acellular pertussis vaccine and optionally with oral or inactivated poliovirus vaccine. Participants were followed for clinical adverse experiences and serologic responses to all vaccine antigens. Antibody responses were compared with historical controls for some indices. RESULTS: The safety profile was generally comparable whether hepatitis A vaccine was administered alone or concomitantly with other vaccines. When administered alone, the hepatitis A seropositivity rate was 98.3% and 100% for dose 1 and dose 2, respectively, and after dose 2 was similar to historical rates and the geometric mean titers were similar between initially seropositive and initially seronegative subjects (6207 and 6810 mIU/mL, respectively). After concomitant administration with hepatitis A vaccine, antibody responses to measles, mumps, rubella, diphtheria, tetanus and filamentous hemagglutinin (98.8%, 99.6%, 100%, 98.6%, 100% and 83.3%, respectively) were similar to historical controls and response to poliovirus was demonstrated, but immune responses to varicella zoster virus (79%) and pertussis toxoid (76%) were inferior to historical controls. CONCLUSIONS: Hepatitis A vaccine is highly immunogenic and generally well tolerated when administered to healthy children as young as 12 months of age regardless of initial hepatitis A serostatus and can be administered concomitantly with measles-mumps-rubella vaccine and oral or inactivated poliovirus vaccine.	F. A. Guerra, J. Gress, A. Werzberger, K. Reisinger, E. Walter, H. Lakkis, A. D. Grosso, C. Welebob and B. J. Kuter	The Pediatric infectious disease journal
280	Active immunotherapy in treatment of acute leukaemia	Active non-specific immunotherapy has been used to prolong remissions in acute lymphoblastic leukaemia. The series reported here used Bordetella pertussis vaccine in a controlle trial after intensive chemotherapy. Possibly immunotherapy delayed the onset of relapse in the treated patients, but no long-term remissions were obtained. Further work is needed to establish the role of immunotherapy in general, and the use of B. pertussis vaccine in particular, in the treatment of acute leukaemia.	R. J. Guyer and D. Crowther	British medical journal
314	Immunogenicity and safety of a tetravalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine	The objective of this study was to investigate whether a tetravalent vaccine containing diphtheria, tetanus, monocomponent acellular pertussis and inactivated poliovirus (DTaP-IPV) was immunogenic and safe compared with the vaccination regime used in Denmark at the time of the study. The study was performed as an open controlled study in which 270 Danish children were enrolled at their 5 weeks' routine examination. The children were allocated to receive either (i) DTaP-IPV (12.5 Lf, 7 Lf, 40 mug, 40, 8, 32 DU) at 3, 5 and 12 months of age (n = 186) or (ii) DT-IPV (50 Lf, 12.5 Lf, 40, 8, 32 DU) at 5, 6 and 15 months of age plus whole-cell pertussis vaccine (>= 4 IU) at 5 and 9 weeks and at 10 months of age (n = 84). No hypotonic hyporesponsive episodes or other vaccine-related serious adverse events were seen. Local reactions, febrile and crying episodes with the investigational vaccine (DTaP-IPV) were similar to the reactions seen with the existing DT-IPV vaccine. One month after completing the vaccination schedule, all children had antibodies above the defined protective antibody concentrations to polio, tetanus and diphtheria. For pertussis toxin, there was a significantly better response in the investigational vaccine group. We therefore conclude that, when used according to the schedule tested, the tetravalent DTaP-IPV vaccine is safe and immunogenic. In addition, the number of visits and the number of injections necessary are reduced with this vaccine and vaccination schedule. Number of References 14. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	A. Gyhrs, E. Lyngholm, S. O. Larsen, H. Aggerbeck and I. Heron	Scandinavian Journal of Infectious Diseases
172	A new DTPa-HBV-IPV vaccine co-administered with Hib, compared to a commercially available DTPw-IPV/Hib vaccine co-administered with HBV, given at 6, 10 and 14 weeks following HBV at birth	Three hundred and twenty eligible infants were enrolled in an open randomized clinical trial and allocated to one of two groups to receive either separate concomitant injections of a candidate combined DTPa-HBV-IPV and commercial Hib vaccine (candidate administration: DTPa-HBV-IPV+Hib) or separate concomitant injections of licensed DTPw-IPV mixed in the same syringe with Hib and HBV vaccines (comparator administration: DTPw-IPV/Hib+HBV). Vaccines were administered at 6, 10 and 14 weeks of age preceded by a monovalent dose of HBV at birth. The candidate vaccine administration was shown to be at least as immunogenic (primary objective) as the candidate administration with respect to the diphtheria, tetanus, polio, HBs and PRP seroprotection rates (primary endpoints). Post vaccination, both vaccine administrations showed an equivalent level of seroprotection with nearly all subjects (>96%) acquiring seroprotective titers against diphtheria, tetanus, polioviruses, HBsAg and PRP antigens. A markedly higher anti-HBs response post dose 2 at week 14 in the group receiving the candidate vaccine, 98.6% of subjects had seroprotective titers (GMT of 505.7 mIU/ml) compared with only 88.7% (GMT of 107.5 mIU/ml) in the comparator group. There was a lower incidence of adverse events following the DTPa-based candidate administration compared with the DTPw-based comparator. Despite the early age and short interval between doses, both administrations were immunogenic, with the concomitant administration of DTPa-HBV-IPV and Hib vaccines showing an improved tolerability over the commercial vaccines DTPw-IPV/Hib and HBV.	R. Gylca, V. Gylca, O. Benes, A. Melnic, V. Chicu, C. Weisbecker, P. Willems and A. Kaufhold	Vaccine
145	Combined Haemophilus influenzae type b and Neisseria meningitidis serogroup C (HibMenC) or serogroup C and Y-tetanus toxoid conjugate (and HibMenCY) vaccines are well-tolerated and immunogenic when administered according to the 2,3,4 months schedule with a fourth dose at 12-18 months of age	Combined HibMenCY and HibMenC conjugate vaccines may facilitate inclusion of vaccination against MenC and MenY into routine vaccination schedules, without additional injections. Immunogenicity and reactogenicity of vaccination with three different formulations of a novel HibMenCY-conjugate vaccine, or a HibMenC-conjugate vaccine was assessed. Infants were randomized to receive either Hib(2.5 µg)-MenC(5 µg)-MenY(5 µg)-TT, Hib(5 µg)-MenC(10 µg)-MenY(10 µg)-TT, Hib(5 µg)-MenC(5 µg)-MenY(5 µg)-TT or Hib(5 µg)-MenC(5 µg)-TT vaccines co-administered with DTPa-HBV-IPV at 2-3-4 months of age. Controls received licensed conjugate MenC-CRM197 vaccine co-administered with DTPa-HBV-IPV/Hib. A fourth dose was administered to a subset of children at age 12-18 months. Anti-PRP concentrations and meningococcal bactericidal (rSBA-MenC/Y) titres were measured prior to and one month post third and fourth vaccination dose. Solicited local, general symptoms and unsolicited adverse events were recorded for 7 and 30 days after each vaccination, respectively. Post dose 3, all subjects had anti-PRP antibody levels ? 0.15 µg/ml and rSBA-MenC ? 1:8. 97.0%-98.6% of HibMenCY recipients had rSBA-MenY ? 1:8. Pre-dose-4, 95.6%-100% of HibMenCY and HibMenC recipients had anti-PRP ? 0.15 µg/ml and 90.7%-97.6% recipients had rSBA-MenC titres ? 1:8. In HibMenCY groups, 78.6%-86.7% had persisting rSBA-MenY ? 1:8. The post-dose-4 response was robust after all vaccines with all subjects having anti-PRP ? 1 µg/ml and 92.3%-100% rSBA-MenC ? 1:128. All HibMenCY recipients had rSBA-MenY ? 1:128. Vaccination with the novel Hib-meningococcal vaccines had a safety profile similar to control. HibMenCY and HibMenC conjugate vaccine formulations given at 2-3-4 months of age with a fourth dose in the second year of life were immunogenic and had a comparable safety profile to licensed vaccines. (study 792014 and 100381;www.clinicaltrial.govID:NCT00129116)	P. Habermehl, G. Leroux-Roels, R. Sänger, G. Mächler and D. Boutriau	Human vaccines
370	First Time Administration of Neonatal Immunization with Acellular Pertussis Vaccines		N. B. Halasa, A. O'Shea, A. Rothman, B. Lafleur and K. M. Edwards	Pediatric Academic Societies Annual Meeting; 2005 May 14-17; Washington DC, United States
1	Bordetella pertussis, Bordetella parapertussis, Mycoplasma pneumoniae, Chlamydia pneumoniae and persistent cough in children	Material collected during a prospective pertussis vaccine trial in 1992-95 was examined for Bordetella pertussis (culture and serology), Bordetella parapertussis (culture), Mycoplasma pneumoniae and Chlamydia pneumoniae (PCR). From 64% (99/155) of episodes with cough for less than 100 d, 115 aetiological agents were identified in one southern and one northern subset of DT-recipients. The most common single agent was B. pertussis, representing 56%(64/115), with a median cough period of 51 d, followed by M. pneumoniae 26%(30/115), 23 d, C. pneumoniae 17% (19/115), 26 d, and B. parapertussis 2% (2/115). For co-infections, the median duration of cough was about 60 d. Spasmodic cough for 21 d or more (clinical WHO criteria for pertussis) was present in 82% (41/50) of infections with B. pertussis as single agent, 38% (17/45) with B. parapertussis, 38% (5/13) with C. pneumoniae, 26% (5/19) with M. pneumoniae and 30%(17/56) in cases where no aetiology was found. In children with cough for more than 100 d (n = 78) using all vaccine arms, B. pertussis was responsible in 83% (65/78), in 21%(16/78) together with other agents. Acellular vaccines were more efficient against serious disease than whole cell vaccine. Antibiotic treatment was more common at the southern (34%) study site than at the northern one (12%). The findings indicate that diagnosis should rely on laboratory confirmation, both for rational treatment of an individual case and for monitoring outbreaks.	H. O. Hallander, J. Gnarpe, H. Gnarpe and P. Olin	Scandinavian journal of infectious diseases
52	Pertussis antitoxin decay after vaccination with DTPa. Response to a first booster dose 3 1/2-6 1/2 years after the third vaccine dose	Longitudinal serum samples were collected from 542 children that had participated in a Swedish pertussis vaccine trial 1992-1995 [Gustafsson L, Hallander HO, Olin P, Reizenstein E, Storsaeter J. A controlled trial of a two-component acellular, a five-component acellular, and a whole-cell pertussis vaccine. N Engl J Med 1996;334(6):349-355] and who did not contract pertussis. The sera were analyzed for post vaccination antibody decay and for booster response of anti-PT (IgG antibodies against pertussis toxin), as measured by ELISA. Generally, an initial rapid decay of antitoxin antibody concentration was followed by a slower decay; the change occurring when the geometric mean level of antitoxin concentration reached 8-9 ELISA Units/mL (EU/mL). The time needed to reach this level was 8-9 months after the third dose in a 2, 4, and 6 months schedule. A "best-fit" combined regression model was used to predict when 50% of the children have less than the minimum level of detection of anti-PT (1EU/mL). This occurred about 65 months after dose 3 at an age of 6 years. The anti-PT response to a booster dose was evident but the post-booster geometric mean values decreased with number of years after the third dose and the response appeared later. The results indicate that a pre-school booster might be considered at 6 years of age or earlier.	H. O. Hallander, L. Gustafsson, M. Ljungman and J. Storsaeter	Vaccine
15	Should fimbriae be included in pertussis vaccines? Studies on ELISA IgG anti-Fim2/3 antibodies after vaccination and infection	The anti-Fim response and long-term persistence after vaccination and infection may be of importance in understanding population immunity. Longitudinal serum samples (n = 1330) from 542 non-infected children related to a Swedish vaccine trial showed that the post vaccination (DTPa5) antibody decay curve for pertussis ELISA IgG anti-fimbriae2/3 (anti-Fim2/3) was bi-phasic. A slower one followed an initial rapid decay approximately 5-6 months after the third dose at 12 months of age. After 71 months, however, 60% still had concentrations above > or =5 EU/ml, a level that had been shown to correlate with decreased risk of disease. Booster responses after re-vaccination with DTPa5 at 4, 5 and 6 years of age were strong and appeared within 1 week after vaccination, indicating immune memory. Ninety-six young children with verified pertussis infection, for whom we had serum samples both before, during and after the infection, showed a high response if they had been primed with fimbriae (either DTPa5 or DTPwc). In contrast, 76% of infected children not primed with fimbriae (a DTPa2 or DT group) only had concentrations below the minimum level of detection in all samples taken during and after the infection. In two Swedish seroepidemiological surveys, one from 1997 just after reintroduction of universal childhood vaccination against pertussis and one from 2007, the proportion of children 2-3 years with anti-Fim2/3 concentrations <5 EU/ml was similar and above 90%. This reflects that the two- or three-component pertussis vaccines (DTPa2 and DTPa3) that were introduced in Sweden in 1996 do not induce anti-Fim2/3 antibodies. In previous studies it was shown in multivariate analyses that levels of IgG anti-Fim2/3 > or =5 EU/ml reduced short-term risk of pertussis in small children. As the antibody response to Fim2/3 after infection is poor in children who have not been primed earlier in life, inclusion of immunogenic Fim2/3 in future pertussis vaccines should be considered.	H. O. Hallander, M. Ljungman, M. Jahnmatz, J. Storsaeter, L. Nilsson and L. Gustafsson	APMIS : acta pathologica, microbiologica, et immunologica Scandinavica
199	Kinetics of the antibody response to tetanus-diphtheria-acellular pertussis vaccine in women of childbearing age and postpartum women	BACKGROUND: Because adolescents and adults act as a primary source of pertussis infection for infants, vaccination of mothers immediately postpartum is a potential strategy to reduce transmission (cocoon strategy). For this to be effective, high levels of antibodies must be achieved rapidly after vaccination. We sought to determine whether the antibody response to tetanus-diphtheria-acellular pertussis vaccine (Tdap) is sufficiently rapid to support the cocoon strategy. METHODS: Two sequential studies were performed. The first was a nonrandomized, open study of a 5-pertussis-component Tdap vaccine (tetanus toxoid, diphtheria toxoid, pertussis toxoid [PT], filamentous hemagglutinin [FHA], fimbriae types 2 and 3 [FIM], and pertactin [PRN]) given to women of childbearing age; the second was a randomized, open study of Tdap or no vaccine in postpartum women. Serum levels of immunoglobin (Ig) G and IgA against pertussis antigens, serum levels of IgG against diphtheria and tetanus, and breast milk levels of IgA against pertussis antigens were measured at various times after vaccination. RESULTS: In both studies, the antibody response was relatively rapid, with serum IgG and IgA levels beginning to increase noticeably by days 5-7 and approaching peak levels by day 14. Greater than 68% and 84.4% of IgG and IgA responders, respectively, achieved ? 90% of their maximum titer by day 14. The diphtheria and tetanus antibody kinetics followed a similar time course. Breast milk levels of IgA against PT, FHA, and FIM were first detectable at day 7, peaked by day 10, and then slowly decreased through day 28. Antibodies against PRN showed a similar response, although the peak occurred at day 14. There were no significant antibody responses in the control group. CONCLUSIONS: Although the antibody response to a dose of Tdap in healthy nonpregnant women of child-bearing age and postpartum women occurs by day 14 and is suggestive of an anamnestic immune response, it may not be sufficiently rapid to protect infants in the first weeks of life.	B. A. Halperin, A. Morris, D. Mackinnon-Cameron, J. Mutch, J. M. Langley, S. A. McNeil, D. Macdougall and S. A. Halperin	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
81	Safety and immunogenicity of a five-component acellular pertussis vaccine with varying antigen quantities		S. A. Halperin, L. Barreto, B. J. Eastwood, B. Law and E. A. Roberts	Archives of pediatrics & adolescent medicine
10	Acellular pertussis vaccine as a booster dose for seventeen- to nineteen-month-old children immunized with either whole cell or acellular pertussis vaccine at two, four and six months of age	The safety and immunogenicity of two formulations of an acellular pertussis vaccine as a booster at 17 to 19 months of age were assessed in children immunized at 2, 4 and 6 months of age with acellular or whole cell pertussis vaccine. In Study I 86 children primed with a five-component acellular vaccine combined with diphtheria and tetanus toxoids or with a whole cell pertussis-diphtheria-tetanus vaccine were boosted with the same vaccine. Local reactions (64% vs. 93%; relative risk, 0.7; 95% confidence interval, 0.5 to 0.9) and systemic reactions (68% vs. 97%; relative risk, 0.7; 95% confidence interval, 0.5 to 0.9) were less common after the fourth dose of acellular vaccine than after the fourth dose of whole cell vaccine. In Study II 96 children primed with either an acellular or whole cell pertussis vaccine were boosted with an acellular vaccine. Local adverse reactions after booster immunization with acellular vaccine were more common in children primed with acellular vaccine than those primed with whole cell vaccine (68% vs. 33%; relative risk, 2.1; 95% confidence interval, 1.3 to 3.3). Antibody response to pertussis toxin, filamentous hemagglutinin and fimbriae were higher before and 1 month after the booster dose in children primed with the acellular vaccine. We conclude that the acellular pertussis vaccine is safe and immunogenic when used for the booster dose in children primed with either whole cell or acellular vaccine but is associated with local reactions.	S. A. Halperin, E. Mills, L. Barreto, C. Pim and B. J. Eastwood	The Pediatric infectious disease journal
448	Inactivated poliovirus vaccine alone or sequential inactivated and oral poliovirus vaccine in two-, four- and six-month-old infants with combination Haemophilus influenzae type b/hepatitis B vaccine	BACKGROUND: Advisory committees have recommended the increased use of inactivated poliovirus vaccine (IPV) for children. OBJECTIVES: The purpose of this study was to assess the safety and immunogenicity of three schedules using IPV administered with diphtheria and tetanus toxoids and whole cell pertussis vaccines in a dual-chambered syringe. Children also received a combination of Haemophilus influenzae type b (Hib) and hepatitis B vaccines (COMVAX). METHODS: All infants (n = 295) received IPV and COMVAX at 2 and 4 months of age and IPV, oral poliovirus vaccine (OPV) or both vaccines at 6 months and OPV at 15 months of age. RESULTS: After two doses of IPV 96 to 100% of infants had antibodies to poliomyelitis viruses types 1, 2 and 3, and after a third dose of vaccine (IPV or OPV) all but one child had antibodies to all three poliovirus types. After two doses of COMVAX 89 and 96% of children had protective levels of antibody to Hib and hepatitis B, respectively. CONCLUSIONS: IPV is highly immunogenic in a two-dose schedule. Administration of a third dose of IPV or a dose of OPV at 6 months of age is highly effective. Simultaneous administration of a combination H. influenzae type b/hepatitis B vaccine did not interfere with the response to IPV.	N. A. Halsey, M. Blatter, G. Bader, M. L. Thoms, F. F. Willingham, J. C. O'Donovan, L. Pakula, F. Berut, K. S. Reisinger and C. Meschievitz	The Pediatric infectious disease journal
245	A polymerase chain reaction for the diagnosis of Haemophilus influenzae type b disease in children and its evaluation during a vaccine trial	BACKGROUND: Determination of the etiology of pneumonia in young children is difficult because blood culture, the usual method of diagnosis, is positive in only a small proportion of cases. For this reason vaccine trials that include bacterial pneumonia as an endpoint must be large. OBJECTIVES: To determine whether a diagnostic test based on a polymerase chain reaction could be used as an alternative to conventional blood culture for diagnosis of invasive Haemophilus influenzae type b (Hib) infections in young children investigated during the course of a large vaccine trial. METHODS: DNA was extracted from blood culture supernatants and probed for the presence of Hib DNA with a PCR assay with primers derived from the cap gene locus of Hib. Results of the PCR assay were compared with those obtained by conventional culture techniques. RESULTS: Blood cultures were obtained from 1544 children with suspected pneumonia, meningitis or septicemia and from 31 healthy control children who were contacts of cases. Blood culture supernatants were tested for Hib DNA in the PCR test. The sensitivity and specificity of a positive PCR test in blood culture supernatant as against culture of Hib from any normally sterile site were 100 and 99%, respectively. Eleven children had positive Hib PCR tests on blood culture supernatants but were negative by culture. In one of these cases Hib was isolated from a lung aspirate and in two other patients H. influenzae strains other than Hib were obtained from the cerebrospinal fluid. Eight of these 11 children were in the control group. When the results of the PCR assay were used to determine vaccine efficacy, a value of 86% was obtained compared with a figure of 95% obtained when conventional culture techniques were used. CONCLUSIONS: An Hib PCR assay on blood culture supernatants proved to be sensitive and specific for the diagnosis of Hib disease in children. The distribution of PCR-positive, culture-negative cases between Hib-vaccinated and control groups paralleled that of culture-positive cases, suggesting that most of these children had been infected with Hib. A trial of a highly efficacious vaccine provides a novel way for evaluating new diagnostic tests for which there is no standard diagnostic test of 100% reliability.	M. Hassan-King, R. Adegbola, I. Baldeh, K. Mulholland, C. Omosigho, A. Oparaugo, S. Usen, A. Palmer, G. Schneider, O. Secka, M. Weber and B. Greenwood	The Pediatric infectious disease journal
438	Analgesic properties of oral sucrose during routine immunizations at 2 and 4 months of age	OBJECTIVE: The purpose of this work was to evaluate the analgesic properties of oral sucrose during routine immunizations in infants at 2 and 4 months of age. PATIENTS AND METHODS: A prospective, randomized, placebo-controlled clinical trial was conducted at a pediatric ambulatory care clinic. One-hundred healthy term infants scheduled to receive routine immunizations were recruited, randomly stratified into 2- or 4-month study groups, and further randomly assigned to receive 24% oral sucrose and pacifier or the sterile water control solution. The study preparations were administered 2 minutes before the combined diphtheria-tetanus-acellular pertussis, inactivated polio vaccine, and hepatitis B vaccine. Haemophilus influenzae type b vaccine was administered 3 minutes after the combined injection, followed by the pneumococcal conjugate vaccine, 2 minutes after the H. influenzae type b injection. The University of Wisconsin Children's Hospital Pain Scale measured serial acute pain responses for the treatment and control groups at baseline and 2, 5, 7, and 9 minutes after solution administration. Repeated-measures analysis of variance examined between-group differences and within-subject variability of treatment effect on overall pain scores. RESULTS: Two- and 4-month-old infants receiving oral sucrose (n = 38) displayed reductions in pain scores 2 minutes after solution administration compared with 2- and 4-month-old infants in the placebo group (n = 45). Between-group comparisons for the oral sucrose and placebo groups showed lower pain responses at 5, 7, and 9 minutes after solution administration. The oral sucrose and placebo groups demonstrated their highest mean pain score at 7 minutes, with a mean pain score of 3.8 and 4.8, respectively. At 9 minutes, the placebo group had a mean pain score of 2.91 whereas the mean pain score for the oral sucrose group returned to near baseline, reflecting a 78.5% difference in mean pain score (oral sucrose - placebo) relative to the placebo mean. CONCLUSIONS: Oral sucrose is an effective, easy-to-administer, short-acting analgesic for use during routine immunizations.	L. A. Hatfield, M. E. Gusic, A. M. Dyer and R. C. Polomano	Pediatrics
92	Cytokine mRNA expression and proliferative responses induced by pertussis toxin, filamentous hemagglutinin, and pertactin of Bordetella pertussis in the peripheral blood mononuclear cells of infected and immunized schoolchildren and adults	Pertussis infection is increasingly recognized in older children and adults, indicating the need of booster immunizations in these age groups. We investigated the induction of pertussis-specific immunity in schoolchildren and adults after booster immunization and natural infection. The expression of mRNA of gamma interferon (IFN-gamma), interleukin-2 (IL-2), IL-4, and IL-5 in the peripheral blood mononuclear cells (PBMCs) was assayed by reverse transcription-PCR. The PBMCs of 17 children immunized with one dose of an acellular vaccine containing pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (PRN) significantly proliferated in vitro after stimulation with the vaccine antigens. The PBMCs of seven infected individuals markedly proliferated in the presence of PT and FHA, but the cells of only two of these subjects responded to PRN. At least one of the antigens induced mRNA for IL-4 and/or IL-5 in the cells of 93% of tested vaccinees and patients, and FHA induced IFN-gamma mRNA in the cells of two-thirds of them. Expression of mRNA for IFN-gamma correlated with the production of the cytokine protein. Anti-FHA immunoglobulin G antibodies significantly correlated with FHA-induced proliferative responses both before and after immunization. These results show that booster immunization with acellular pertussis vaccine induces both antibody- and cell-mediated immune responses in schoolchildren. Further, booster immunization and natural infection seem to induce the expression of mRNA of T-helper 1 (Th1) and Th2 type cytokines in similar manners. This observation supports the use of acellular pertussis vaccines for booster immunizations of older children, adolescents, and adults.	Q. He, N. N. Tran Minh, K. Edelman, M. K. Viljanen, H. Arvilommi and J. Mertsola	Infection and immunity
14	Outcomes of Bordetella pertussis infection in different age groups of an immunized population	Outcomes of Bordetella pertussis infection were studied in 3 age groups (1-3, 4-6, and 7-15 years) during outbreaks in one day care center (n = 29) and in two elementary schools (n = 210). A total of 76 children were confirmed as having B. pertussis infection; 74 were confirmed by polymerase chain reaction (PCR) and 18 by culture. A positive PCR result was less common in children 1-3 years old than in those 4-6 (P = .006). Asymptomatic B. pertussis infection was more common in preschool children than in schoolchildren (P < .001), whereas schoolchildren presented with symptoms compatible with clinical pertussis more often than preschool children (60/210 vs. 3/29, P = .029). In the community of 12,691, the attack rate (laboratory-confirmed patients/100,000) was 317 in children < 4 years, 1838 in children 4-6 years, 2535 in children 7-15 years, and 248 in persons > 15 years. The protection provided by conventional pertussis vaccine is evidently rather short-lived, and booster vaccinations are needed to eradicate pertussis among schoolchildren and adults.	Q. He, M. K. Viljanen, S. Nikkari, R. Lyytikäinen and J. Mertsola	The Journal of infectious diseases
26	Safety evaluation of one whole-cell and three acellular pertussis vaccines in Stockholm trial II		H. Heijbel, F. Rasmussen and P. Olin	Developments in biological standardization
42	Comparative Efficacy of the Lederle/Takeda acellular pertussis component DTP (DTaP) vaccine and Lederle whole-cell component DTP vaccine in German children after household exposure. Pertussis Vaccine Study Group	BACKGROUND: A household contact substudy was performed as part of a prospective, cohort pertussis vaccine efficacy trial in Germany. DESIGN: Infants received four doses of either the Lederle/Takeda acellular pertussis component diphtheria-tetanus toxoids (DTP) vaccine (DTaP) or Lederle whole-cell component DTP vaccine at 3, 4.5, 6, and 15 to 18 months of age (Wyeth-Lederle Vaccines and Pediatrics, Pearl River, NY). An open control group received three doses of diphtheria and tetanus toxoids vaccine (DT) at 3, 4.5, and 15 to 18 months of age. Vaccine efficacy rates were calculated using a number of principal and ancillary case definitions for primary, secondary, and noncases by analyzing secondary attack rates in study infants after exposure to pertussis in the household using 7- to 28- and 7- to 42-day postexposure observation periods and the inclusion and the exclusion of noncases who received macrolide antibiotics or trimethoprim-sulfamethoxazole during the exposure period. RESULTS: During a 3.5-year study period, 10271 infants (DTP or DTaP, n = 8532; DT, n = 1739) were enrolled and actively followed along with all household members for cough illnesses. Depending on the case definition, 160 to 519 household exposures to pertussis were identified. In general, secondary attack rates in DT recipients were low and this was primarily because of the frequent use of antimicrobial prophylaxis. Using the principal case definitions and the exclusion of noncases who received macrolide antibiotics or trimethoprim-sulfamethoxazole during the exposure period and the 7- to 42-day observation period, the efficacy of DTP against cough illness of greater than or equal to 7 days duration caused by Bordetella pertussis was 84% (95% confidence interval [CI] = 65-93) and that of DTaP was 58% (95% CI = 30-75). Using similar criteria, the efficacy against typical pertussis (greater than or equal to 21 days of cough with either paroxysms, whoop, or posttussive vomiting) was 94% (95% CI = 77-99) and 86% (95% CI = 62-95) for DTP and DTaP, respectively. The efficacy against any cough illness (with or without) laboratory confirmation was 54% (95% CI = 32-69) and 38% (95% CI = 13-56) for DTP and DTaP, respectively. CONCLUSION: This household contact substudy within our cohort study, with active investigator-generated surveillance, was a severe test of vaccine efficacy. Both vaccines (DTP and DTaP) are better at preventing typical pertussis than mild illness. When case definitions similar to those in other recent trials are used, the Lederle/Takeda vaccine has an efficacy similar to other multicomponent DTaP vaccines.	U. Heininger, J. D. Cherry, K. Stehr, S. Schmitt-Grohé, M. Uberall, S. Laussucq, T. Eckhardt, M. Meyer and J. Gornbein	Pediatrics
25	Clinical validation of a polymerase chain reaction assay for the diagnosis of pertussis by comparison with serology, culture, and symptoms during a large pertussis vaccine efficacy trial	OBJECTIVE: To assess the diagnostic sensitivity and specificity of a Bordetella pertussis polymerase chain reaction (PCR) assay using nasopharyngeal (NP) specimens from subjects with cough illnesses participating in a large pertussis vaccine efficacy trial. DESIGN: From 1991 to 1994, we conducted a large pertussis vaccine efficacy trial in Germany to determine the efficacy of the Lederle/Takeda acellular pertussis component diphtheria-tetanus toxoids in comparison with the Lederle whole-cell component diphtheria-tetanus toxoids vaccine. In the final year of the follow-up period of this trial, a second NP specimen for PCR, in addition to a culture specimen and blood for specific serology (enzyme-linked immunosorbent assay), was collected by use of a Dacron swab in subjects or family members with cough illnesses >/=7 days duration or in subjects with exposure to a cough illness in a household member to establish a diagnosis of B pertussis infection. Oligonucleotide primers (pTp1 and pTp2) that amplify a 191-bp-sized DNA fragment from the pertussis toxin operon, which is specific for B pertussis, were used. The PCR-amplified products were visualized by dot blot analysis followed by hybridization with a digoxigenin labeled probe and rated as 1+, 2+, or 3+ in comparison with positive controls representing approximately 1 to 10, 11 to 50, and >50 B pertussis organisms, respectively. In the present analysis, we compare PCR findings with those of serology, culture, positive household contact, and clinical characteristics of cough illnesses. RESULTS: Of 392 subjects with NP specimens obtained for PCR, 376 also had NP specimens collected for culture and 282 had serum specimens. PCR and culture were positive in 86 (22%) and 23 (6%) subjects, respectively. Of the positive PCR specimens, 40 were rated 3+, 32 were rated 2+, and 14 were rated 1+; 3+ positive specimens were more prevalent among DT recipients compared with pertussis vaccine recipients. Illnesses in subjects with 3+ positive PCR results were more typical of pertussis than were those in subjects with 2+ and 1+ positive results with a mean duration of cough of 48 days versus 43 and 42 days, respectively; presence of paroxysms, whoop or vomiting in 38% versus 17% and 10%, respectively; and a clinical diagnosis of definite or probable pertussis by the investigators of 26% versus 7% and 4%, respectively. Using serologic evidence of infection as the standard, sensitivity of PCR was 61%, and specificity was 88%. For 3+ positive PCR results, the respective values were 42% and 97%. CONCLUSION: Our findings demonstrate that PCR is more sensitive than conventional culture for the diagnosis of pertussis. They also demonstrate a high specificity of PCR when serology with or without other confirmative criteria (culture and household contact) is used as the reference. Analysis of semiquantitative PCR results revealed that subjects with a 3+ PCR more frequently experienced typical illness compared with patients with 1+ or 2+ PCR. Although specific serologic study remains a necessity in pertussis research its modification for diagnosis in the clinical setting results in low sensitivity and specificity. Therefore, because PCR is more sensitive than culture and is easy to perform, it is a useful addition in the clinical setting.	U. Heininger, G. Schmidt-Schläpfer, J. D. Cherry and K. Stehr	Pediatrics
4	The efficacy of a whole cell pertussis vaccine and fimbriae against Bordetella pertussis and Bordetella parapertussis infections in respiratory mouse model		U. Heininger, K. Stehr and J. D. Cherry	Vaccine
18	[The microagglutination test--a simple and sensitive procedure for serodiagnosis of pertussis infections]	The microagglutination assay is a useful method for the diagnosis of B. pertussis infections. In a group of 30 patients with culture proven pertussis 27 (90%) had > or = fourfold increases in titers between acute and convalescent phase serum specimens. The microagglutination test offers several advantages over other more sophisticated B. pertussis antibody tests: only 50 microliters of serum is required, it is a standardized test, which doesn't require specialized technical expertise or equipment, it is easy to perform and good results are noted in a broad age range of patients. Disadvantages of the microagglutination test are: two separate serum specimens are necessary (acute and convalescent phase), the test does not differentiate IgA and IgG antibodies and the temporal association with recent immunization can lead to false positive results. In our opinion the microagglutination test is a useful method for the diagnosis of B. pertussis infections. This is especially true in cases where more sophisticated serologic tests such as ELISA can not be performed immediately but physicians and patients expect to get a result quickly.	U. Heininger, K. Stehr, S. Schmitt-Grohe, M. Uberall, C. Lorenz, R. Rost and J. D. Cherry	Klinische Pädiatrie
116	Immunogenicity of Haemophilus influenzae type b capsular polysaccharide vaccines in 18-month-old infants	Haemophilus influenzae vaccine containing polyribosyl ribitol phosphate (PRP) or PRP covalently linked to diphtheria toxoid (PRP-D) was given to 94 healthy infants 17 to 22 months of age at the same time, but not at the same site, as a diphtheria-tetanus-pertussis booster. Systemic reactions were similar in the two vaccine groups and resembled those expected with the diphtheria-tetanus-pertussis injection alone. Six (13%) and seven (14%) of the PRP and PRP-D recipients, respectively, had minor local reactions to the Haemophilus vaccine. Among the 77 children who were not already naturally immune (ie, anti-PRP antibody concentration of less than or equal to 0.15 micrograms of protein per milliliter) before vaccination, PRP-D was significantly more effective than PRP in inducing protective levels of antibody. Only 15 (43%) of the 35 nonimmune PRP recipients achieved a concentration of greater than or equal to 0.15 microgram/mL and only seven (20%) reached a concentration greater than or equal to 1.0 micrograms/mL following vaccination. In contrast, 34 (81%) of the 42 nonimmune recipients of PRP-D had a concentration of greater than or equal to 0.15 microgram/mL following vaccine and 32 (62%) had a concentration of greater than or equal to 1.0 micrograms/mL (P less than or equal to .001). These results suggest that more than one-half of nonimmune 18-month-old infants will not respond to PRP with protective levels of antibody. In light of the current data, recommendation for revaccination at 24 months of age for those immunized at any younger age is appropriate.	J. O. Hendley, J. G. Wenzel, K. M. Ashe and J. S. Samuelson	Pediatrics
457	On the therapy of whooping cough		J. Heusser	Der Kinderarzt.
192	The reactogenicity and immunogenicity of commercial Haemophilus influenzae type b conjugate vaccines		J. F. Heyse and K. M. Kaplan	European journal of pediatrics
378	Simultaneous administration of rhesus rotavirus vaccine and oral poliovirus vaccine: immunogenicity and reactogenicity	Rotavirus vaccine could be administered most efficiently if it were incorporated into routine childhood immunizations and did not interfere with the immune response to the other vaccines, principally oral poliovirus vaccine (OPV). We conducted a placebo-controlled randomized trial giving oral rhesus rotavirus vaccine (RRV) (strain MMU 18006) alone and together with a child's first dose of OPV and diphtheria-tetanus toxoids-pertussis to examine the possible interaction of these vaccines. A total of 102 infants 2 to 3 months of age were randomized into 3 groups to receive (1) RRV with OPV, (2) placebo with OPV and (3) RRV 2 weeks after OPV. All infants were given diphtheria-tetanus toxoids-pertussis. Serum samples were collected at the time of OPV immunization and 3 to 5 weeks later. Three to 5 weeks after OPV immunization 60% of infants had a 4-fold rise in neutralization titer to at least one of the three poliovirus serotypes. The rate of antibody response to poliovirus did not differ by RRV groups but a lower rate was correlated with a shorter interval (3 vs. 5 weeks) between OPV vaccination and antibody measurement. Fifty-six percent of infants had a 4-fold rise of IgA and 62% had a 4-fold rise of neutralizing antibody to RRV; this rise did not differ according to time of OPV immunization. RRV was not associated with side effects and may be safely given with OPV to infants 2 to 3 months of age.	M. S. Ho, R. L. Floyd, R. I. Glass, M. A. Pallansch, B. Jones, B. Hamby, P. Woods, M. E. Penaranda, A. Z. Kapikian and G. Bohan	The Pediatric infectious disease journal
226	Combined diphtheria-tetanus-pertussis vaccine for tetanus-prone wound management in adults	INTRODUCTION: Booster vaccination against tetanus, diphtheria and pertussis is recommended throughout life. Adults are difficult to reach and vaccination coverage in this group is often inadequate. The use of a reduced-antigen content combined diphtheria-tetanus-acellular pertussis ('adult' dTpa) vaccine for tetanus prophylaxis in emergency room wound management provides an opportunity to boost immunity against three infections simultaneously, thereby optimizing the efficiency of medical interventions with adults assessed. METHODS: A single-blind, randomized, controlled study of 320 healthy adults, the anti-tetanus antibody response within 10 days following vaccination with Boostrix (reduced-antigen diphtheria-tetanus-acellular pertussis). RESULTS: The anti-tetanus antibody response to the reduced-antigen diptheria-tetanus-acellular pertussis vaccine was equivalent to Tetavax, a licensed monovalent tetanus-toxoid vaccine. CONCLUSION: The use of diphtheria-tetanus-acellular pertussis is a safe and effective way to provide vaccination to adults against three diseases during emergency room visits for wound management.	T. Hoel, J. M. Wolter and L. M. Schuerman	European journal of emergency medicine : official journal of the European Society for Emergency Medicine
408	Validation of the combined toxin-binding inhibition test for determination of neutralizing antibodies against tetanus and diphtheria toxins in a vaccine field study in Viet Nam	Determination of seroconversion and measurement of protective antibody levels in children against vaccine components are essential for gauging and monitoring the efficacy of paediatric vaccination programmes. For this purpose, we assessed the combined toxin-binding inhibition (ToBI) test for determining neutralizing antibodies to tetanus and diphtheria in a diphtheria-pertussis-tetanus (DPT) vaccine field trial in Viet Nam. A simple procedure involving collection of blood samples on filter-paper was found to be a suitable alternative to collection by venepuncture, despite a reduction in the sensitivity of the ToBI test as a result of the step necessary to elute the antibodies from the filter-paper. The results obtained demonstrate that the ToBI test can feasibly be carried out under field conditions. Preliminary results obtained with the ToBI test in DPT field trials indicate that a fourth dose of DPT vaccine one year after the third dose should be considered by developing countries.	H. A. Hong, N. T. Ke, T. N. Nhon, N. D. Thinh, J. W. Gun, J. T. Hendriks and J. G. Kreeftenberg	Bull World Health Organ
331	Pertussis-treatment. Comparison on Erythromycin-estolate and - ethylsuccinate		J. E. Hoppe	Der Kinderarzt
358	Comparison of Erythromycin-estolate and Erythromycin-athylsuccinate for Pertussis treatment		J. E. Hoppe	Monatsschrift fur Kinderheilkunde
29	Comparison of erythromycin ethylsuccinate and co-trimoxazole for treatment of pertussis	Fifty-five ambulatory children with early culture-proven pertussis were treated for two weeks either with erythromycin ethylsuccinate (n = 28) (50-80 mg/kg/day in three doses during meals) or with co-trimoxazole (n = 27) (6-10 mg trimethoprim/kg/day in two doses after meals). After completion of treatment, all patients in the erythromycin group were culture-negative, while in the co-trimoxazole group one child was still culture-positive. In this case vomiting may have played a role. Both agents appear to be able to eradicate Bordetella pertussis from the nasopharynx of patients with early whooping cough.	J. E. Hoppe, U. Halm, H. J. Hagedorn and A. Kraminer-Hagedorn	Infection
162	The effect of reconstitution of an Haemophilus influenzae type b-tentanus toxoid conjugate (PRP-T) vaccine on the immune responses to a diphtheria-tetanus-whole cell pertussis (DTwP) vaccine: a five-year follow-up	Controversial results have been obtained from previous studies on the combined administration of Haemophilus influenzae type b-tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-whole-cell pertussis (DTwP) combination vaccines, with regard to possible reciprocal interference between the constituent antigens. To document the priming effect and possible long-term immunogenic interference of PRP-T and DTwP combination vaccines, a randomized, double-blind, controlled study was conducted in Belgium. A total of 168 healthy infants received, at 3, 4 and 5 months of age, DTwP vaccine mixed just prior to injection either with PRP-T vaccine (group A, DTwP//PRP-T, N = 85) or with placebo (group B, DTwP//Placebo, N = 83). At the age of 14 months, children of both groups were randomized to receive either a dose of DTwP//PRP-T vaccine (subgroups A1 and B1) or a dose of Hib polysaccharide (PRP) vaccine (subgroups A2 and B2). Those children in subgroups A1 and B1 had an additional serum sample taken at the age of 5 years (at the time of a DT booster). The immune response to Hib polysaccharide at the age of 4, 5 and 6 months confirmed the excellent immunogenicity profile of PRP-T in infants. In addition, the vigorous anamnestic response (i.e. a 20-fold increase of GMT) to a booster dose of the plain capsular polysaccharide (PRP) reflected the efficient Hib-priming induced by the combined DTwP//PRP-T vaccine. Reconstitution of PRP-T with DTwP did not affect the immune response to diphtheria toxoid or pertussis agglutinins. Nevertheless, at almost any time point during the five-year follow-up, the tetanus antitoxin GMT values were significantly lower in the DTwP//PRP-T group (A and A1) than in the DTwP//Placebo group (B and B1). Despite the suppressive effect on GMT values, intergroup differences in rates of seroprotection were never significant, except after doses 2 and 3 for which there were lower percentages of children in group A with antitoxin titers > 0.05 IU/mL and > 1.0 IU/mL. In the group primed with the combined DTwP//PRP-T vaccine, (1) a DT booster dose at the age of 5 years provoked a 150-fold increase in tetanus antitoxin GMT, (2) a high tetanus antitoxin GMT value was attained (GMT = 19.3 IU/mL) and (3) all children in this group had tetanus antitoxin titers > 1.0 IU/mL, so it may be concluded that all these children will still be protected against tetanus until at least the age of the next recommended booster dose (i.e. the age of 15 years). No differences in the occurrence of adverse events were observed between the groups who received the DTwP//PRP-T vaccine or the DTwP//Placebo vaccine, both vaccines being associated with events customarily attributable to DTwP (data not shown). Our results indicate (1) that the combination vaccine, DTwP//PRP-T, represents a safe and effective alternative for the existing uncombined vaccines and (2) that the long-term effect of interference between the components of future combination vaccines should be studied with subsequent booster doses, followed by the evaluation of persistence of antibodies over several years.	K. Hoppenbrouwers, M. Roelants, C. Ethevenaux, C. Vandermeulen, J. Knops and J. Desmyter	Vaccine
69	Pertussis immunization with acellular vaccines in Ghanaian children	In the present study, the persistence of antibodies to pertussis antigens was assessed in 51 Ghanaian children immunized with one of two acellular vaccines and one whole cell vaccine in early infancy. The effect of a booster dose 1 year after primary immunization was also examined. Antibody titres to pertussis toxin (PT) and filamentous haemagglutinin (FHA) were measured 1 month and 1 year after primary immunization and 1 month after the booster dose. Although geometric titres (GMTs) to FHA were significantly higher in the two types of acellular vaccinees in the whole cell vaccinees 1 month after primary immunization, GMTs to FHA and PT after 1 year were not significantly different in the three groups. Geometric mean titres to PT and FHA following the booster dose were significantly higher in the acellular vaccinees than in the whole cell vaccinees. Seropositivity rates to PT and FHA in the acellular vaccinees, which were more than 93.3% 1 month after primary immunization, ranged from 50.0 to 77.8% after 1 year. In conclusion, the acellular vaccines did not produce higher antibody levels than the whole cell vaccine 1 year after primary immunization. The booster dose was essential to maintaining sufficient seropositivity to pertussis antigens.	H. Hori, A. Afari, B. D. Akanmori, Y. Kamiya, H. Sakatoku, F. K. Nkrumah, H. Kamiya, M. Chazono and K. Fukai	Annals of tropical paediatrics
250	Effect of local massage on vaccination: DTP and DTPa	We previously demonstrated that local massage for one minute can enhance immunogenicity of diphtheria, tetanus, and whole-cell pertussis (DTPw) vaccination. This study further analyzes the effects of more intense local manipulation on infants after DTPw and DTPa (diphtheria, tetanus, and acellular pertussis) vaccination. A total of 808 infants aged two months were recruited to be vaccinated with either DTPw or DTPa. Vaccinees in both groups were further divided into two groups; those receiving local manipulation (massage and hot packing after vaccinations) and those receiving only vaccinations. Results showed that safety profiles were largely similar between those who had local manipulation following vaccination and those without. The only significant difference was more frequent local reactions including pain and swelling following the first two doses in both the DTPa and DTPw groups receiving manipulation compared with the groups not receiving manipulation. Serologic tests revealed that local manipulation had no significant effect on antibody response to pertussis toxin and filamentous hemagglutinin, and diphtheria and tetanus toxins. The effect of local massage on DTPw was related to the intensity of local massage. Too vigorous a local manipulation caused adverse local reactions and no beneficial effect on antibody response. As for the infants receiving DTPa and local massages for two minutes with hot packing, no significant effect on either the reactogenicity or immunogenicity was found.	F. Y. Huang and L. M. Huang	Acta paediatrica Taiwanica = Taiwan er ke yi xue hui za zhi
394	[Immunization of hepatitis B vaccine integrated with expanded program on immunization schedule in children]	We studied the immunization of hepatitis B vaccine integrated with of EPI. 180 children (0-9 months of age) from three towns of Shunde County were randomly divided in to three groups (two trial groups and one control group). Which were vaccinated by three different immunization schedule. The serum antibodies to different vaccines were measured before and after immunization. The results show that the seroconversion rate and GMT of each EPI vaccine are conformed with the expected EPI indexes. The seroconversion rate of anti-HBs antibody is found no significantly different among the three groups. The titres of pertussis agglutinating and three types polio neutralizing antibody is higher in trial groups than that in the control group. We conclude that the immunization of hepatitis B vaccine can be integrated into the EPI schedule. And third dose of hepatitis B vaccine can be simultaneously given with measles vaccine.	J. Huang	Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi
433	Immunogenicity after one, two or three doses and impact on the antibody response to coadministered antigens of a nonavalent pneumococcal conjugate vaccine in infants of Soweto, South Africa	BACKGROUND: Children <6 months of age are at increased risk of pneumococcal disease. The early immunogenicity of conjugate vaccines therefore may be important to prevent disease in young children. OBJECTIVES: To determine the immunogenicity of a nonavalent pneumococcal conjugate vaccine after one dose, two doses and three doses and its impact on the antibody response to coadministered antigens. METHODS: A total of 500 infants from Soweto were immunized at 6, 10 and 14 weeks of age with either placebo (n = 250) or 9-valent pneumococcal conjugate vaccine (n = 250) containing serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F and 23F conjugated to CRM(197) mutant diphtheria protein. Blood was taken for determination of serotype-specific IgG before the first dose and 1 month after each dose. RESULTS: Before the first dose at 6 weeks of age >80% of infants had >0.15 microg/ml antibody to six of the nine antigens, >70% to serotypes 18C and 23F and >50% to serotype 4. Geometric mean concentrations (GMCs) after one dose ranged from 0.27 microg/ml for serotype 23F to 2.98 microg/ml for serotype 1; >90% of infants had serotype-specific antibody >0.15 microg/ml except for serotypes 23F (70%) and 6B (80%). After two doses GMCs ranged from 1.14 microg/ml for serotype 23F to 5.68 microg/ml for serotype 1; >95% of infants had serotype-specific antibody >0.15 microg/ml and >75% had >0.5 microg/ml for all nine serotypes. GMCs after three doses ranged from 2.73 microg/ml for serotype 23F to 6.18 microg/ml for serotype 5; >98% of infants had serotype-specific antibody >0.15 microg/ml and >92% had >0.5 microg/ml for all nine serotypes. Antibody concentrations after three doses were significantly higher to Haemophilus influenzae type b-polyribosylribitol phosphate vaccine in children who received pneumococcal conjugate vaccine, but they had lower antibodies to pertussis toxin than controls. CONCLUSIONS: A single dose of this pneumococcal conjugate vaccine produces a potentially protective antibody response to most serotypes in the majority of children in this population.	R. E. Huebner, N. Mbelle, B. Forrest, D. V. Madore and K. P. Klugman	The Pediatric infectious disease journal
241	Dose response of CRM197 and tetanus toxoid-conjugated Haemophilus influenzae type b vaccines	High vaccine cost has limited use of conjugate vaccines in the developing world where the disease burden is greatest. Fixed fractional doses of Haemophilus influenzae type b (Hib) vaccines have been shown to be immunogenic, but dose responses of these vaccines in humans are needed to determine the lowest immunogenic dose as an option for lowering vaccine cost. We randomized children to receive one of five doses (0.625, 1.25, 2.5, 5.0 and 10 microg) of either a diphtheria CRM197 or tetanus toxoid-conjugated Hib vaccine. The children received a primary three-dose series at 6, 10, and 14 weeks of age and a booster dose at 9 months. Anti-PRP IgG antibodies were measured at each vaccination, at 18 weeks, and at one week following the booster dose. Concentrations of > or =1.25 microg of HibCRM197 vaccine produced mean anti-PRP responses at 18 weeks of > or =5.72 microg/ml and > or =0.15 microg/ml was achieved in >98% of the children with at least 79% reaching anti-PRP concentrations of > or =1.0 microg/ml. Concentrations of > or =1.25 microg of Hib-tetanus vaccine produced mean anti-PRP responses at 18 weeks of > or =8.63 microg/ml and > or =0.15 microg/ml was achieved in 100% of the children with at least 88.9% reaching anti-PRP concentrations of > or =1.0 microg/ml. While mean antibody concentrations after either vaccine decreased over time, the proportion of children with antibody levels of > or =0.15 microg/ml had not changed significantly at the 9 month measurement. Immunologic memory was demonstrated by significant increases in mean antibody concentrations one week after the booster dose for doses > or =1.25 microg of HibCRM197 and Hib-tetanus to mean concentrations > or =37.71 and 16.07 microg/ml, respectively. There were no differences in antibody responses for vaccine doses > or =1.25 microg of the same vaccine or between the same concentrations of the two different vaccines. Our data suggest that doses of these vaccines of > or =1.25 microg may be sufficient to stimulate an immune response that offers both short and longer term protection from invasive Hib disease.	R. E. Huebner, M. Nicol, R. Mothupi, H. Käyhty, N. Mbelle, E. Khomo and K. P. Klugman	Vaccine
246	Vaccine-related pain: randomised controlled trial of two injection techniques	OBJECTIVE: To compare acute pain response during immunisation in infants using a slow standard of care injection technique versus a rapid pragmatic technique.DESIGN: Randomised controlled trial.SETTING: Single-centre, urban paediatric primary care practice.SUBJECTS: Healthy infants 4-6 months of age receiving their routine DPTaP-Hib immunisation.INTERVENTIONS: Standard of care group: slow aspiration prior to injection, slow injection and slow withdrawal. Pragmatic group: no aspiration, rapid injection and rapid withdrawal.MAIN OUTCOME MEASURES: Immediate infant pain measured by the Modified Behavior Pain Scale (MBPS), crying and parent/paediatrician visual analogue scale (VAS).RESULTS: 113 infants participated; there were no observed differences in age, birth order or prior analgesic use. Mean MBPS scores (95% confidence interval (CI)) were higher (p<0.001) for the standard group compared to the pragmatic group, 5.6 (5 to 6.3) vs 3.3 (2.6 to 3.9). The standard group was more likely to cry, 47/57 (82%) vs 24/56 (43%), to cry longer, median (interquartile range (IQR)) 14.7 s (8.7-35.6) vs 0 s (0-11.30), and to take longer to have the vaccine injected, median (IQR) 8.8 s (7.9-10.3) vs 0.9 s (0.8-1.1), p<0.001 for all comparisons. The median (IQR) VAS scores by parents and paediatricians were higher for the standard group: VAS parent, 3.5 (1.6-5.5) vs 1.9 (0.1-3.1) and VAS paediatrician, 2.8 (2.0-5.1) vs 1.4 (0.2-2.4). There were no adverse events.CONCLUSION: Immunisation using a pragmatic rapid injection technique is less painful than a slow standard of care technique and should be recommended for routine intramuscular immunisations.	M. Ipp, A. Taddio, J. Sam, M. Gladbach and P. C. Parkin	Archives of disease in childhood
446	Challenges and successes of immunization registry reminders at inner-city practices	OBJECTIVES: To assess the effectiveness of two serial registry reminder protocols and the interactive effects of reminders with child characteristics on immunization rates. METHODS: At an inner city practice network in New York City we randomized 1662 children aged 6 weeks-15 months due or late for a diphtheria-tetanus-pertussis (DTaP) to 3 groups: continuous reminders (as needed), limited reminders (up to 3) and controls, for 6 months. Reminders were triggered by the hospital registry and immunizations were tracked with both the hospital and city registries. Analyses were based on intention to treat. RESULTS: At randomization, the study groups were comparable (9.2 months of age, 77% Latino, 86% Medicaid, 49.3% up-to date). A quarter of the children were sent false reminders, 15% had incorrect contact information, and 15% had missed opportunities for vaccination. In the univariate analysis, reminders improved coverage rates, but only for the children sent continuous reminders (51.2% vs. 44.9% controls, p < .01). Multivariate analysis showed reminders had no independent effect on immunization outcomes. Age, up-to-date and Medicaid status at randomization were strong predictors of a child receiving any subsequent immunization. However, reminders interacted synergistically with Medicaid to increase the likelihood of receiving an immunization. CONCLUSION: At an inner city practice network, registry reminders were not effective at improving immunization outcomes due to major system barriers. Immunization registries are powerful vehicles for identifying children in need of immunizations and generating reminders but system challenges must be addressed if this promise is to be achieved in inner city practices.	M. M. Irigoyen, S. Findley, D. Wang, S. Chen, F. Chimkin, O. Pena and E. Mendonca	Ambulatory pediatrics : the official journal of the Ambulatory Pediatric Association
390	Studies on rokitamycin in pediatrics	Pharmacokinetic, bacteriological and clinical studies on a new macrolide antibiotic, rokitamycin (RKM) dry syrup for pediatric use, were done, and results as summarized below were observed: 1. Five children with ages between 6 and 10 years were administered orally with RKM at a dose level of 10 mg/kg either at 30 minutes before or 30 minutes after meal on a crossover design, and plasma concentrations and urinary excretion rates of the drug were measured. Plasma concentrations of RKM following the administration before meal were 0.50 microg/ml at 1/2 hour, 0.43 microg/ml at 1 hour, 0.15 microg/ml at 2 hours, 0.03 microg/ml at 4 hours, and not detectable at 6 hours. Plasma concentrations following the administration after meal were 0.11 microg/ml at 1/2 hour, 0.15 microg/ml at 1 hour, 0.09 microg/ml at 2 hours, 0.03 microg/ml at 4 hours, and not detectable at 6 hours. The 0 similar 6 hour urinary recovery rates were 1.41% following the administration before meal, and 0.93% following the administration after meal. These results suggested that the drug might be absorbed more rapidly, giving a higher plasma concentration, when administered before meal than when administered after meal. Changes in plasma concentrations of RKM following the administration of 10 mg/kg before meal were similar to those of two 100 mg RKM tablets (TMS-19-Q.GC tablets) to adult patients. Therefore, it seemed optimal to administer 10 mg/kg 3 times daily at fasting to children as a rule. 2. A total of 39 patients with ages between 1 month and 11 years with pediatric infections were medicated with RKM dry syrup, and investigated for clinical response, bacteriological response and side effects to the drug. Clinical responses to the drug were evaluated in 2 patients with acute pharyngitis, 12 with acute purulent tonsillitis, 1 with acute bronchitis, 9 with acute pneumonia (including 3 with mycoplasmal pneumonia), 1 with acute purulent lymphadenitis, 2 with acute purulent otitis media, 1 with pertussis and 2 with acute enteritis: responses were excellent in 17, good in 11 and fair in 2 of them, hence the efficacy rate was 93.3%. Four strains of Streptococcus pyogenes and 3 of Haemophilus influenzae were isolated as pathogens from 7 cases, and bacteriological responses were that 1 of S. pyogenes was eradicated, but the other 6 remained, thus the eradication rate was 14.3%. Neither side effects nor abnormal laboratory test values were found in any patients. Also, none of the patients refused or complained of difficulty in the oral administration of the drug. The results suggested that RKM dry syrup would be clinically very effective in treating various pediatric infections, including the infections for which other macrolides had been taken as primary treatment, and be associated with no safety problems, although some difficulties were encountered for the eradication of some strains. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	N. Iwai, M. Miyazu, H. Nakamura, M. Katayama and K. Kasai	Jpn J Antibiot
234	Prophylaxis with acetaminophen or ibuprofen for prevention of local reactions to the fifth diphtheria-tetanus toxoids-acellular pertussis vaccination: a randomized, controlled trial	BACKGROUND: The frequency of local vaccination reactions increases with successive doses of diphtheria-tetanus toxoids-acellular pertussis (DTaP) vaccine, and local reactions occur for the majority of children receiving the fifth DTaP vaccination. It is not known whether these reactions can be prevented with prophylactic use of acetaminophen or ibuprofen. METHODS: In this 3-group, randomized, blinded, controlled trial, 372 children were assigned randomly, in a 2:2:1 ratio, to receive 3 doses of acetaminophen, ibuprofen, or placebo. The first dose of study medication was administered within 2 hours before the fifth DTaP vaccination, and the remaining 2 doses were given at 6-hour intervals. The primary outcome measures included a local reaction with an area of redness or discoloration > or =5 cm in diameter on the evening of or during the 2 days after vaccination, an increase in mid-limb circumference of > or =2 cm on the evening of or during the 2 days after vaccination, and a persistent local reaction, defined as an area of redness or discoloration present on the third day after vaccination. RESULTS: Local reactions with a > or =5-cm area of redness or discoloration were reported for 35% of children in the placebo group, compared with 33% of children in the acetaminophen group and 37% of children in the ibuprofen group. There was also no significant difference between the placebo and treatment groups in the proportions of children with a > or =2-cm increase in mid-limb circumference or with a persistent local reaction. CONCLUSIONS: We did not find evidence that prophylaxis with acetaminophen or ibuprofen offers a clinically significant benefit in prevention of local reactions to the fifth DTaP vaccination.	L. A. Jackson, M. Dunstan, P. Starkovich, J. Dunn, O. Yu, J. C. Nelson, T. Rees and A. Zavitkovsky	Pediatrics
284	A randomized placebo-controlled trial of acetaminophen for prevention of post-vaccination fever in infants	BACKGROUND: Fever is common following infant vaccinations. Two randomized controlled trials demonstrated the efficacy of acetaminophen prophylaxis in preventing fever after whole cell pertussis vaccination, but acetaminophen prophylaxis has not been evaluated for prevention of fever following contemporary vaccines recommended for infants in the United States. METHODS: Children six weeks through nine months of age were randomized 1:1 to receive up to five doses of acetaminophen (10-15 mg per kg) or placebo following routine vaccinations. The primary outcome was a rectal temperature ?38°C within 32 hours following the vaccinations. Secondary outcomes included medical utilization, infant fussiness, and parents' time lost from work. Parents could request unblinding of the treatment assignment if the child developed fever or symptoms that would warrant supplementary acetaminophen treatment for children who had been receiving placebo. RESULTS: A temperature ?38°C was recorded for 14% (25/176) of children randomized to acetaminophen compared with 22% (37/176) of those randomized to placebo but that difference was not statistically significant (relative risk [RR], 0.63; 95% CI, 0.40-1.01). Children randomized to acetaminophen were less likely to be reported as being much more fussy than usual (10% vs 24%) (RR, 0.42; 95% CI, 0.25-0.70) or to have the treatment assignment unblinded (3% vs 9%) (RR, 0.31; 95% CI, 0.11-0.83) than those randomized to placebo. In age-stratified analyses, among children ?24 weeks of age, there was a significantly lower risk of temperature ?38°C in the acetaminophen group (13% vs. 25%; p?=?0.03). CONCLUSION: The results of this relatively small trial suggest that acetaminophen may reduce the risk of post-vaccination fever and fussiness. TRIAL REGISTRATION: Clinicaltrials.gov NCT00325819.	L. A. Jackson, D. Peterson, J. Dunn, S. J. Hambidge, M. Dunstan, P. Starkovich, O. Yu, J. Benoit, C. P. Dominguez-Islas, B. Carste, P. Benson and J. C. Nelson	PloS one
467	Effect of captopril on myocardial beta-adrenoceptor density and Gi alpha-proteins in patients with mild to moderate heart failure due to dilated cardiomyopathy	In end-stage heart failure due to idiopathic dilated cardiomyopathy beta 1-adrenoceptors are downregulated and Gi alpha-proteins are upregulated. The aim of the present study was to investigate the influence of the angiotensin-converting enzyme inhibitor captopril on beta-adrenoceptor density and Gi alpha-proteins in sequential endomyocardial biopsies. Nineteen patients with mild to moderate congestive heart failure due to idiopathic dilated cardiomyopathy (NYHA Class II-III) were studied before and after 8-11 weeks of therapy. Patients were randomised into a captopril and a control group; 9 patients received captopril 12.5-50 mg per day, (divided in 2-3 doses) p.o. in addition to "conventional" therapy with digoxin and diuretics, and 10 controls received "conventional" therapy only. Echocardiography, spiroergometry, right heart catheterisation and endomyocardial biopsies were performed before (baseline) and after treatment. Compared to baseline, captopril increased total beta-adrenoceptor density by selectively increasing beta 1-adrenoceptors (31.6 vs 41.2 fmol.mg-1; p < 0.05) but had no significant effect on Gi alpha-proteins. The results indicate that treatment with angiotensin-converting enzyme inhibitors partly restores myocardial beta 1-adrenoceptor density, and this action effect may contribute to the clinical improvement of patients with idiopathic dilated cardiomyopathy treated in this way.	H. Jakob, M. Sigmund, T. Eschenhagen, U. Mende, M. Patten, W. Schmitz, H. Scholz, J. Schulte am Esch, M. Steinfath and P. Hanrath	European journal of clinical pharmacology
395	Adverse events after immunisation with aluminium-containing DTP vaccines: systematic review of the evidence	We have reviewed evidence of adverse events after exposure to aluminium-containing vaccines against diphtheria, tetanus, and pertussis (DTP), alone or in combination, compared with identical vaccines, either without aluminium or containing aluminium in different concentrations. The study is a systematic review with meta-analysis. We searched the Cochrane Vaccines Field Register, the Cochrane Library, Medline, Embase, Biological Abstracts, Science Citation Index, and the Vaccine Adverse Event Reporting System website for relevant studies. Reference lists of retrieved articles were scanned for further studies. We included randomised and semi-randomised trials and comparative cohort studies if the report gave sufficient information for us to extract aluminium concentration, vaccine composition, and safety outcomes. Two reviewers extracted data in a standard way from all included studies and assessed the methodological quality of the studies. We identified 35 reports of studies and included three randomised trials, four semi-randomised trials, and one cohort study. We did a meta-analysis of data from five studies around two main comparisons (vaccines containing aluminium hydroxide vs no adjuvant in children aged up to 18 months and vaccines containing different types of aluminium vs no adjuvants in children aged 10-16 years). In young children, vaccines with aluminium hydroxide caused significantly more erythema and induration than plain vaccines (odds ratio 1.87 [95% CI 1.57-2.24]) and significantly fewer reactions of all types (0.21 [0.15-0.28]). The frequencies of local reactions of all types, collapse or convulsions, and persistent crying or screaming did not differ between the two cohorts of the trials. In older children, there was no association between exposure to aluminium-containing vaccines and onset of (local) induration, swelling, or a raised temperature, but there was an association with local pain lasting up to 14 days (2.05 [1.25-3.38]). We found no evidence that aluminium salts in vaccines cause any serious or long-lasting adverse events. Despite a lack of good-quality evidence we do not recommend that any further research on this topic is undertaken.	T. Jefferson, M. Rudin and C. Pietrantonj	Lancet Infect Dis
372	Safety and immunogenicity of a booster dose of a candidate acellular pertussis vaccine in healthy children [abstract]		M. Just, H. Bogaerts, J. Boscia, G. Moonsammy and F. Andre	Pediatric Research
274	Two trials of an acellular DTP vaccine in comparison with a whole-cell DTP vaccine in infants: evaluation of two PT doses and two vaccination schedules	The present trials being carried out in Switzerland and Turkey, the reactogenicity and immunogenicity of acellular DTP vaccines containing either 25 micrograms or 8 micrograms of PT and 25 micrograms of FHA were compared with those of a conventional whole-cell DTP vaccine during a primary vaccination course following either a 0-1-2 schedule starting at three months of age (Switzerland) or a 0-2-4 schedule starting at two months of age (Turkey). The whole-cell vaccine was associated with significantly more local reactions than the acellular vaccines; general reactions were also more frequent among whole-cell recipients. The 25 micrograms PT dose vaccine was no more reactogenic than the 8 micrograms PT dose vaccine. There was no evidence of increases in frequencies of local or general reactions from one acellular vaccine dose to the next. The 25 micrograms PT dose acellular DTP vaccine resulted in immune responses to all four antigens (PT, FHA, diphtheria and tetanus toxoids) at least equivalent to those observed with whole-cell vaccination. Significantly lower anti-PT antibody levels were seen with the 8 micrograms PT dose vaccine.	M. Just, G. Kanra, H. Bogaerts, R. Berger, M. Ceyhan and J. Pêtre	Developments in biological standardization
32	Primary vaccination of infants with a combined diphtheria-tetanus-acellular pertussis-hepatitis B vaccine		G. Kanra, M. Ceyhan, Z. Ecevit, H. Bogaerts, D. Grave, P. Hauser and P. Desmons	The Pediatric infectious disease journal
144	Acellular pertussis diphtheria-tetanus toxoids-pertussis booster vaccine at five years of age		G. Kanra, M. Ceyhan, B. Topal, H. Bogaerts and D. Vandevoorde	The Pediatric infectious disease journal
161	Safety and immunogenicity of a new fully liquid DTPw-HepB-Hib combination vaccine in infants	We assessed the safety and immunogenicity of a fully liquid, DTPw-HepB-Hib combination vaccine (Quinvaxem) in comparison with separately administered DTPw-Hib and hepatitis B vaccines. Infants participating in this open-label, randomized, phase II study received a primary vaccination course using a 2-3-4 month schedule. Blood samples were taken immediately prior to the first and one month after the third vaccination. Adverse events were assessed over a 7-day post-vaccination period using subject diaries. After completion of the primary vaccination course, 94.7% [95% CI: 89.8-97.7%] of infants receiving the combination vaccine achieved protective anti-HBs antibody titers (> or = 10 mIU/mL) with a mean 39-fold increase in GMTs in comparison with 99.3% [95% CI: 96.3-100%] seroprotection and a mean 29-fold GMT increase in the comparator group. Diphtheria, tetanus and Haemophilus influenzae type b (Hib) seroprotection rates and pertussis seroconversion rates were also similar between the two groups. There was no statistically significant difference in GMTs for diphtheria between the two groups, but significant differences were shown for tetanus, Hib, and pertussis with higher GMTs for each antigen observed in the comparator group. The combination vaccine was well tolerated, with fever (body temperature > or = 38 degrees C) being the most frequently reported adverse event in both the DTPw-HepB-Hib (12.5% [95% CI: 7.7-18.8%]) and comparator (12.6% [95% CI: 7.7-19.0%]) groups. This study demonstrated that the fully liquid DTPw-HepB-Hib combination vaccine has safety and immunogenicity profiles similar to the DTPw-Hib and hepatitis B vaccines when administered separately.	G. Kanra, A. Kara, O. Demiralp, M. Contorni, A. K. Hilbert, C. Spyr and S. Viviani	Human vaccines
44	Immunogenicity and safety of Haemophilus influenzae type b-tetanus protein conjugate vaccine alone or mixed with diphtheria-tetanus-pertussis vaccine in infants	Haemophilus capsular polysaccharide-tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-pertussis (DTP) vaccines were administered in a single syringe (group 1) or separate syringes (group 2) to 284 infants at 2, 4, and 6 months of age. Group 1 infants had a slightly greater incidence of local reactions. Systemic reactions were similar. The geometric mean titers of polyribosylribitol phosphate (PRP) serum antibody concentrations after the third dose of PRP-T vaccine were 4.8 and 4.3 micrograms/ml for groups 1 and 2, respectively. Antibody responses to DTP antigens were also similar. The immunogenicity and safety of the PRP-T and DTP vaccines are equivalent when the vaccines are administered in separate syringes or the same syringe to infants.	S. L. Kaplan, B. A. Lauer, M. A. Ward, B. L. Wiedermann, K. M. Boyer, C. M. Dukes, D. M. Schaffer, J. Paisley, R. Mendelson and F. Pedreira	The Journal of pediatrics
384	Effect of a monetary sanction on immunization rates of recipients of aid to families with dependent children	CONTEXT: Immunization rates among low-income families have lagged behind those for the general community, with several possible barriers cited in the literature. OBJECTIVE: To evaluate the effect of an initiative aimed at improving immunization rates among low-income preschool children by imposing a sanction on families who failed to provide proof of up-to-date immunization status. DESIGN AND SETTING: Randomized, controlled before-after trial conducted from January 1, 1993, through December 31, 1996, in Muscogee County, Georgia. PARTICIPANTS: A total of 2500 families with children aged 6 years or younger who received Aid to Families with Dependent Children assistance. INTERVENTION: Families in the intervention group (n=1500) were informed that receipt of the welfare benefit for any preschool-aged children was contingent on provision of proof of up-to-date immunization status at the beginning of welfare eligibility and, subsequently, semiannually or annually. Case families in the control group (n=1000) were encouraged to immunize their preschool children but were not informed of any aid sanctions nor did such sanctions apply to them. MAIN OUTCOME MEASURE: Age-appropriate rates of 5 immunizations (measles-mumps-rubella; poliovirus; diphtheria and tetanus toxoids and pertussis; Haemophilus influenzae type b; and hepatitis B), based on examination (with family's written consent) of medical provider records, compared among intervention-group vs control-group families. RESULTS: There were no significant differences at baseline between intervention and control families in immunization rates of preschool children. Families in the intervention group were significantly more likely than families in the control group to have up-to-date immunization status in all 4 years of the study for all 5 immunizations (with 3 exceptions). At age 2 years, 72.4% of children in the intervention group vs 60.6% of those in the control group achieved vaccine series completion, which included 4 diphtheria and tetanus toxoids and pertussis, 3 poliovirus, and 1 measles-mumps-rubella (P<.001). Sanctions were implemented only 11 times. There was relatively little increased burden on the part of families to comply with requirements. CONCLUSION: In our study, a monetary sanction in a population receiving welfare benefits stimulated a significant increase in childhood immunization rates, suggesting that when welfare recipients are given an incentive to keep their children's immunizations up-to-date, most are able to do so. JAMA. 2000;284:53-59	L. C. Kerpelman, D. B. Connell and W. J. Gunn	JAMA : the journal of the American Medical Association
327	Immunogenicity of FDA DTP versus WHO DTP	Background: The aim of this report was to study the immunogenicity of three doses of DTP in six-week-old Saudi infants when given either as World Health Organization (WHO) DTP or Federal Drug Administration (FDA) DTP formula. Methods: As part of the Haemophilus influenzae type b immunization research protocol, six-week-old infants were randomized into three groups to receive three doses of HbOC and WHO DTP formula, HbOC and FDA DTP formula, or in a control group to receive the usual vaccines without HbOC, at six weeks, three months and five months. Antibody level for PRP, tetanus, diphtheria and pertussis were measured after the third dose. The results of diphtheria, pertussis and tetanus are presented in this paper. Results: After three doses, no difference was found between anti-PRP when given with either FDA DTP or WHO DTP formula. Also anti-tetanus and anti-diphtheria antibodies were significantly higher in the group vaccinated with HbOC and FDA DTP formula, compared to children vaccinated with WHO DTP formula. No negative interactions with other vaccines were observed after the third dose. Conclusion. Although diphtheria and tetanus antigens in the FDA formula are half the concentration in the WHO formula, they are more antigenic. There is a need for methods of potency assay to be re-evaluated. Number of References 12. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	M. Khalil, Y. Al-Mazrou, M. Al-Howasi and M. Al-Jeffri	Annals of Saudi Medicine
62	Vaccines: World Health Organization versus Federal Drug Administration recommended formula	Vaccines produced in accordance with WHO formulas, differ in concentration from those used in United States according to FDA formulas. We aimed to compare the immunogenicity of both formulas. Infants who were 6 weeks old were randomly put into 3 groups to receive 3 doses of vaccines at 6 weeks, 3 months and 5 months of age. The vaccines consisted of Haemophilus influenzae type b vaccine, diphtheria-tetanus-pertussis and oral polio vaccine. Antibody levels for polyribosylribitol phosphate (PRP), tetanus, diphtheria and poliovirus were measured 1 month after the third dose of vaccines. Although diphtheria and tetanus antigens in the FDA formula are half the concentration of the WHO formula, anti-tetanus and anti-diphtheria antibodies were significantly higher. No difference was found between groups regarding oral poliovirus vaccine.	M. K. Khalil, Y. Y. al-Mazrou and Y. S. al-Ghamdi	Eastern Mediterranean health journal = La revue de santé de la Méditerranée orientale = al-Majallah al-?i???yah li-sharq al-mutawassi?
281	A phase II multicenter evaluation of several candidate pertussis vaccines in infants		D. L. Klein	Developments in biological standardization
166	Induction of immunologic memory following primary vaccination with the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine in infants	BACKGROUND: Induction of immunologic memory was assessed following primary vaccination with 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). METHODS: Infants were randomized (1:1) to receive 3 doses of PHiD-CV or 7vCRM (7-valent CRM197-conjugated pneumococcal conjugate vaccine [PCV]) at 2, 3, and 4 months of age followed by 23-valent pneumococcal polysaccharide vaccine (23vPS) booster dose at 11 to 14 months of age. Pneumococcal geometric mean antibody concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers were measured. RESULTS: Postprimary immune responses were consistent with those in previous PHiD-CV and 7vCRM studies. Following 23vPS boosting, vaccine serotype-specific antibody GMCs increased 6.5- to 33.3-fold and 4.8- to 32.2-fold versus prebooster in the PHiD-CV and 7vCRM groups, respectively. Postbooster OPA titers increased 2.8- to 38.8-fold and 2.6- to 58.9-fold, respectively. Postbooster antibody GMCs exceeded postprimary levels but, for some serotypes, postbooster OPA geometric mean titers were lower than postprimary in both groups. An additional dose of the same PCV received for priming was administered to 52 children aged 46 to 50 months, resulting in higher responses versus postprimary vaccination for all serotypes, but not always higher than post-23vPS booster. CONCLUSIONS: Induction of immunologic memory following PHiD-CV priming was confirmed. Additional PCV boosting in 4-year-olds did not provide strong evidence of hyporesponsiveness induced by previous 23vPS boosting. However, our results did not rule out depletion of the memory B cell pool following 23vPS vaccination, resulting in subsequent attenuated immune responses, and therefore support the use of PCV rather than 23vPS for booster vaccination in the second year of life.	M. Knuf, H. Pankow-Culot, D. Grunert, M. Rapp, F. Panzer, R. Köllges, A. Fanic, A. Habib, D. Borys, I. Dieussaert and L. Schuerman	The Pediatric infectious disease journal
139	An investigational tetravalent meningococcal serogroups A, C, W-135 and Y-tetanus toxoid conjugate vaccine co-administered with Infanrix? hexa is immunogenic, with an acceptable safety profile in 12-23-month-old children	Tetravalent meningococcal serogroups ACWY conjugate vaccines will provide an advantage to those at most risk of invasive meningococcal disease; namely young children. Co-administration of ACWY-TT with DTaP-HBV-IPV/Hib was assessed in a randomized trial in 793 children aged 12-23 months. Pre-specified criteria for non-inferiority of immunogenicity following co-administration versus separate ACWY-TT and DTaP-HBV-IPV/Hib administration were reached. One month post-vaccination, ? 97.3% of ACWY-TT vaccinees had rSBA titres ? 1:8 (all serogroups). Seroprotection/seropositivity rates against DTaP-HBV-IPV/Hib antigens were ? 98.2%. The safety profile of co-administration was similar to that of DTaP-HBV-IPV/Hib alone. ACWY-TT and DTaP-HBV-IPV/Hib co-administration during the second year would facilitate introduction of ACWY-TT into routine toddler vaccination schedules.	M. Knuf, A. Pantazi-Chatzikonstantinou, U. Pfletschinger, I. Tichmann-Schumann, H. Maurer, L. Maurer, T. Fischbach, H. Zinke, H. Pankow-Culot, V. Papaevangelou, V. Bianco, M. Wielen and J. M. Miller	Vaccine
71	Booster vaccination after neonatal priming with acellular pertussis vaccine	After a birth dose of acellular pertussis (aP) and diphtheria (DT)aP-hepatitis B virus (HBV)-inactivated polio vaccine (IPV)/Haemophilus influenza type b (Hib) at 2, 4, and 6 months, a booster dose of DTaP-HBV-IPV/Hib at 12 to 23 months induced strong anti-pertussis booster responses. Thus, neonatal aP priming did not lead to immune tolerance to pertussis antigens. However, it elicited bystander interference on HBV, Hib, and diphtheria responses.	M. Knuf, H. J. Schmitt, J. M. Jacquet, A. Collard, D. Kieninger, C. U. Meyer, C. A. Siegrist and F. Zepp	The Journal of pediatrics
117	Immunogenicity and reactogenicity of diphtheria, tetanus and pertussis toxoids combined with inactivated polio vaccine, when administered concomitantly with or as a diluent for a Hib conjugate vaccine	In an open trial, 400 infants were randomized to vaccination with a combined diphtheria-tetanus-pertussis-inactivated polio vaccine (DTaP-IPV) either mixed with a Haemophilus influenzae type b (Hib) tetanus toxoid conjugate immediately before injection (DTaP-IPV/Hib (mix)) or given concurrently with the Hib conjugate at separate injection sites (DTaP-IPV+Hib (sep)). The pertussis component consisted of pertussis toxoid alone. The vaccines were given intramuscularly at 3, 5 and 12 months of age. No vaccine-related serious adverse events occurred. Local reactions were evaluated from diary cards completed by the parents. Infants who received DTaP-IPV/Hib (mix) experienced fewer local reactions. Sera were obtained 28-45 days after the second and third vaccinations. Total Hib capsular antibodies were similar in the two groups after the second injection but lower in the group receiving DTaP-IPV/Hib (mix) than in the group receiving DTaP-IPV+Hib (sep) after the third injection (geometric mean 6.1 vs 10.4 microg/ml). Mixing of the vaccines also led to somewhat lower diphtheria toxin antibodies (5.9 vs. 7.7 IU/ml after the third injection) while tetanus antibodies were higher (3.9 vs. 2.5 IU/ml after the third injection). Antibodies against pertussis toxin and the three polio virus types were similar in the two groups. The moderate impairment of the Hib antibody response caused by mixing of the Hib conjugate with aluminium adsorbed DTaP may be due to physicochemical interference but is probably of little clinical importance because of the ability of the Hib conjugates to induce an immunologic memory.	N. Knutsson, B. Trollfors, J. Taranger, E. Bergfors, V. Sundh, T. Lagergård, E. Ostergaard, H. Cicirello and H. Käyhty	Vaccine
328	Response of preterm infants to diphtheria-tetanus-pertussis vaccine	The American Academy of Pediatrics recommendation that immunization of preterm infants with diphtheria-tetanus-pertussis (DTP) vaccine should begin at 2 months after birth, regardless of gestational age, is based on limited data. A prospective study was conducted to determine the immunogenicity and safety of DTP vaccine in preterm infants. One hundred ten preterm and 146 full term infants received doses of DTP at 2, 4 and 6 months after birth. Adjusted analysis of the antibody responses indicated that after three doses mean titers among preterm infants to each vaccine component were comparable to those of full term infants. Adjusted analysis of the incidence of adverse events indicated that the risk of adverse events in preterm infants was not significantly higher than that in full term infants. DTP vaccine is immunogenic and safe in preterm infants when the series is initiated at 2 months after birth, and this study supports the current recommendation of the American Academy of Pediatrics	B. A. Koblin, T. R. Townsend, A. Munoz, I. Onorato, M. Wilson and B. F. Polk	Pediatric Infectious Disease Journal
319	Immunogenicity, reactogenicity and safety of a diphtheria-tetanus-acellular pertussis-inactivated polio and Haemophilus Influenzae type b combination vaccine in a placebo-controlled rotavirus vaccine study	Introduction: In recent years, acellular pertussis combination vaccines have facilitated compliance with and coverage of the national immunisation programme in Singapore. This phase-II study (Rota-007) evaluated the immunogenicity, reactogenicity and safety of a DTPa-IPV/Hib combined vaccine when co-administered with a rotavirus vaccine. Materials and Methods: A total of 2464 children aged 3 months were vaccinated with DTPa-IPV/Hib together with a randomised 1:3 ratio of either placebo (n = 653) or 1 of 3 different formulations of a rotavirus vaccine. Blood samples were collected for immunogenicity analysis 1 month after the third DTPa-IPV/Hib vaccine dose in a subset of subjects (n = 640). Local and general reactogenicity and unsolicited adverse events were recorded during the follow-up after each vaccination. Results: Serological analysis showed >95% response for all antigens in the co-administered DTPa-IPV/Hib vaccine, with no difference between the rotavirus vaccine and placebo groups. No differences in adverse events and reactogenicity were reported in the rotavirus vaccine and placebo groups. Only 0.2% of the subjects reported Grade 3 adverse events. Three subjects (from the vaccine groups) died during the study, which were assessed by the investigators as unrelated to vaccination. No deaths were reported in the placebo group. Conclusion: The combined DTPa-IPV/Hib vaccine is safe, well tolerated and highly immunogenic when given alone or coadministered with the rotavirus vaccine for infants in Singapore. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	B. P. Kong, H. Q. Seng, S. L. Fong, P. Goh, L. T. Yee, S. K. Datta, H. H. Han and H. L. Bock	Annals of the Academy of Medicine Singapore
19	Immunogenicity of acellular pertussis vaccines using two vaccines for primary immunization		C. H. König, P. Herden, D. Palitzsch, B. Schneeweiss and N. Bier	The Pediatric infectious disease journal
255	[The PRP-D vaccination of Danish children. A study of immunogenicity of a Haemophilus influenzae type b vaccine coadministered with Di-Te-Pol to Danish children]	The aim of this study was to examine the immunogenicity of a Haemophilus influenzae type b (Hib) vaccine (PRP-D) in Danish children younger than 18 months of age, given at the same time as a diphtheria-, tetanus- and polio-vaccine at the age of five, six and 15 months. The study was carried out as a multicentre study, where 21 children were vaccinated by their general practitioners. Blood samples were drawn just before and four weeks after each of the three vaccinations and the concentration of Hib-antibodies were determined using an ELISA-technique. Before the first vaccination none of the 21 children had antibody levels above 1 microgram/ml, which is believed to be the level which provides long-lasting protection, whereas after the first, second and third vaccination respectively 24, 48 and 100% of the children had antibody levels above 1 microgram/ml. There were only mild and short-lived side effects. The PRP-D vaccine given at the same time as Di-Te-Pol is safe, without serious side-effects and immunogenic in Danish children.	H. B. Konradsen, T. Ejlertsen and J. Henrichsen	Ugeskrift for laeger
115	Immunogenicity and safety study of a new DTaP-IPV-Hep B-PRP-T combined vaccine compared to a licensed DTaP-IPV-Hep B//PRP-T comparator, both concomitantly administered with a 7-valent pneumococcal conjugate vaccine at 2, 4, and 6 months of age in Thai infants	OBJECTIVE: To assess a new, fully-liquid, hexavalent DTaP-IPV-Hep B-PRP-T vaccine (diphtheria toxoid (D), tetanus toxoid (T), acellular pertussis (aP), inactivated poliovirus (IPV), hepatitis B (Hep B), and Haemophilus influenzae type b polysaccharide conjugated to tetanus protein (PRP-T) antigens) compared to a licensed DTaP-IPV-Hep B//PRP-T vaccine following primary series co-administration with a 7-valent pneumococcal conjugate vaccine (PCV7).METHODS: This was a randomized, phase III, observer-blind study in Thai infants (N=412), who received DTaP-IPV-Hep B-PRP-T or DTaP-IPV-Hep B//PRP-T at 2, 4, and 6 months of age, co-administered with PCV7. All received Hep B at birth. Non-inferiority for Hep B ? 10 mIU/ml and PRP ?0.15?g/ml was analyzed (DTaP-IPV-Hep B-PRP-T relative to DTaP-IPV-Hep B//PRP-T) at 1 month post-primary. Seroprotection/seroconversion and geometric mean titers (GMTs) were analyzed descriptively for all hexavalent components. Safety was evaluated from parental reports.RESULTS: Anti-Hep B and anti-PRP antibody seroprotection rates were high for DTaP-IPV-Hep B-PRP-T (n=189) and DTaP-IPV-Hep B//PRP-T (n=190), and non-inferiority was demonstrated. Anti-D and anti-T ? 0.01 IU/ml, anti-polio types 1, 2, and 3 ? 8 (1/dil), and anti-PT and anti-FHA seroconversion were high and similar in each group. For DTaP-IPV-Hep B-PRP-T and DTaP-IPV-Hep B//PRP-T, anti-Hep B ? 100 mIU/ml was 98.4% and 99.5% (GMTs 2477 and 2442 mIU/ml), respectively; anti-PRP ? 1.0 ?g/ml was 85.2% and 71.1% (GMTs 5.07 and 2.41 ?g/ml), respectively. Safety profiles were comparable. There were no vaccine-related serious adverse events.CONCLUSIONS: Following co-administration with PCV7 the investigational DTaP-IPV-Hep B-PRP-T vaccine was safe and immunogenic. Non-inferiority to DTaP-IPV-Hep B//PRP-T was shown for Hep B and PRP.	P. Kosalaraksa, U. Thisyakorn, S. Benjaponpitak, K. Chokephaibulkit and E. Santos-Lima	International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
173	[Vaccination of children born from HIV-infected mothers against Haemophilus influenzae type b infection]	Course of postvaccinal period after injection of vaccine against Haemophilus influenzae type b administered simultaneously with vaccines of Russian national immunization schedule was studied in children born from HIV-infected mothers. Good tolerability of the vaccine administered concomitantly with diphtheria-tetanus-whole cell pertussis and inactivated polio vaccines (Imovax Polio), which is comparable with tolerability in healthy children, was demonstrated. Prevaccination titers of antibodies and their dynamics during immunization process were described. Increase of levels of antibodies was detected both in the group of children with perinatal contact with HIV infection and in the group of HIV-infected children.	M. P. Kostinov, D. V. Pakhomov, N. F. Snegova, T. N. Nikitina and T. N. Zinkina	Zhurnal mikrobiologii, epidemiologii, i immunobiologii
323	Changes in anti-pertussis titers in adults following pertussis vaccine [Abstract]	American Academy of Allergy, Asthma and Immunology (AAAAI) 62nd Annual Meeting, March 3-7, 2006, Miami Beach, Florida, USA	S. I. Krassilnikova, C. Mende and T. J. Craig	Journal of Allergy and Clinical Immunology
453	Comparison of five different vaccination schedules with Haemophilus influenzae type b-tetanus toxoid conjugate vaccine	OBJECTIVE: To compare seroresponses to five different vaccination schedules for Haemophilus influenzae type b (Hib)-tetanus toxoid conjugate (PRP-T) vaccine in infants. DESIGN: Four different two-dose schedules were compared, with doses given at 1 and 3 months, 2 and 4 months, 2 and 6 months, or 4 and 6 months of age. One group received three doses at 2, 4, and 6 months of age. The PRP-T vaccine was given in the same syringe with diphtheria-tetanus-pertussis (DTP) vaccine; inactivated polio vaccine (IPV) was given in a separate syringe. Anti-Hib polysaccharide antibodies were measured by radioimmunoassay in sera taken before each immunization, 1 month after the second dose, at 7 and at 12 to 24 months of age. SUBJECTS: A total of 196 healthy infants were enrolled between November 1990 and November 1992. RESULTS: After one dose of PRP-T there were no significant differences in geometric mean antibody concentrations (0.09 to 0.13 microgram/ml) or in fold responses among the schedules. The response to the second dose was significantly higher than the response to the first dose given at the same age. The geometric mean antibody concentration was lower in the group vaccinated at 1 and 3 months than in the groups vaccinated at 2 and 4 months, 2 and 6 months, or 4 and 6 months. The three-dose schedule resulted in a significantly higher final antibody concentration than the best two-dose schedule (p <0.001). In most children (64% to 93%), the antibody concentration remained at least 0.15 microgram/ml up to the age of 12 to 24 months. CONCLUSIONS: The Hib conjugate vaccine, PRP-T, administered concomitantly with DTP vaccine and IPV, was immunogenic with schedules starting at 1 to 4 months of age. Two injections of PRP-T vaccine were immunogenic enough to maintain protection up to 12 to 18 months of age.	S. Kurikka, H. Käyhty, L. Saarinen, P. Rönnberg, J. Eskola and P. H. Mäkelä	The Journal of pediatrics
317	[Bacteriological and clinical studies of biapenem (L-627) in pediatrics]	Bacteriological and clinical studies in the pediatric field have been performed on biapenem (L-627), a newly-developed carbapenem antibiotic, and the following results were obtained. 1. In the pharmacokinetic study, the plasma concentration of L-627 showed dose-dependant change: Cmax was 14.6 micrograms/ml and AUC was 15.4 micrograms.hr/ml with the administration of 6 mg/kg, while Cmax was 49.2 micrograms/ml and AUC was 60.1 micrograms.hr/ml with the administration of 12 mg/kg. After the administration of 6 mg/kg, the urinary concentration reached maximum within 2 hours and the cumulative urinary excretion rate in the first 6 hours was 49.4%. 2. Antibacterial activities of L-627 against 27 strains of clinical isolates were determined. MICs of L-627 against such Gram-positive cocci as Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes were sufficiently low, and those against such Gram-negative rods as Haemophilus influenzae, Escherichia coli and Bordetella pertussis were satisfactory and as low as those of imipenem or ceftazidime. 3. Clinical efficacies of L-627 were evaluated in 36 cases of bacterial infections. The overall efficacy rate was 100%, and excellent responses in 26 cases and good in 10 cases were obtained. As for bacteriological efficacies, all strains except 1 of B. pertussis were eradicated and a high eradication rate of 96.6% was obtained. 4. No side effects were observed in 37 evaluated cases. As abnormal laboratory test results, eosinophilia was noted in 2 cases (5.4%), but they returned to normal values rapidly after the drug was discontinued. From these results, it has been concluded that L-627 is a safe and effective drug to be used in treatment of pediatric infectious diseases.	Y. Kusumoto, H. Akita, Y. Sato, S. Iwata, Y. Takeuchi, T. Abe, K. Sunakawa and T. Yokota	The Japanese journal of antibiotics
287	Risk factors for acellular and whole-cell pertussis vaccine failure in Senegalese children	Although use of acellular pertussis vaccine was associated with a higher rate of vaccine failure than that of whole-cell vaccine in the Senegal Pertussis Trial conducted in 1990-1994 on 4189 children, risk factors for vaccine failure regarding exposure and susceptibility to pertussis have not been studied so far. Pertussis occurred in 346 vaccinated children. Three factors were found to be associated with vaccine failure, independently of the vaccine type, namely the degree of exposure, birth rank, and time since weaning. In the whole-cell vaccine group, the risk of failure increased with birth rank [RR = 2.95 (1.51-5.75)] and was higher in non stunted children [RR = 1.43 (1.05-1.94)]. In the acellular vaccine group, the risk of failure increased with age at exposure to B. pertussis [RR = 2.24 (1.21-4.12) after 18 months of age] and the degree of exposure [RR = 2.14 (1.17-3.93) when the child shared the hut of an index case]. These results highlight the influence of environmental factors on the success of pertussis vaccination. However, they do not explain the shorter duration of protection provided by the acellular vaccine compared to the whole-cell vaccine which persist after controlling and thus might be related to the nature of the vaccine.	K. Lacombe, A. Yam, K. Simondon, S. Pinchinat and F. Simondon	Vaccine
54	Acellular vaccines for pertussis		E. Lagace	The Journal of family practice
148	Lot-to-lot consistency of a combined hexavalent diptheria-tetanus-acellular-pertussis, hepatitis B, Inactivated polio and haemophilus B conjugate vaccine, administered to healthy chilean infants at two, four and six months of age	OBJECTIVES: To assess the safety, immunogenicity and lot consistency of a liquid hexavalent combined vaccine (DTaP-IPV-PRP approximately T-HBs, HEXAVAC) (Sanofi-Pasteur MSD, France) administered to infants at two, four and six months of age. METHODS: A total of 1028 infants were vaccinated with one of three vaccine lots, in a randomized, double-blind fashion. Equivalence testing was used to compare post-vaccination seroprotection/seroconversion rates and geometric mean titers (GMTs) for each antigen between the three lots. Blood samples were drawn before vaccination and one month after the third dose. Local and systemic adverse events were monitored for three days following each injection. RESULTS: Equivalence between lots was demonstrated for all antigens, on post-dose 3 seroprotection/seroconversion rates and GMTs. Reported rates of local and systemic adverse events tended to increase with subsequent doses. Altogether, 11.8% of the infants reported at least one adverse local event (mainly redness and induration/swelling) after the first dose and 36.1% after the third dose. Systemic adverse events (mainly irritability and fever) were reported by 39.2% of the infants after the first dose and by 57.5% after the third one. CONCLUSION: Three separate lots of the liquid hexavalent combined vaccine induced consistently protective antibody responses against all antigens. These results and the well established clinical tolerability of this combined vaccine make it suitable for primary immunization of infants at two, four and six months of age.	R. Lagos, A. Hoffenbach, M. Scemama, M. Dupuy, F. Schodel, L. Hessel and M. Levine	Human vaccines
160	Immunogenicity, safety, and reactogenicity of the 10-valent pneumococcal non-typeable Hemophilus influenzae protein D conjugate vaccine (PHiD-CV) when co-administered with the DTPw-HBV/Hib vaccine in Indian infants: a single-blind, randomized, controlled study	In India, pneumococcal diseases are major causes of child mortality, and effective vaccines against Streptococcus pneumoniae are needed. This single-blind, randomized study assessed the immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Hemophilus influenzae (NTHi) protein D conjugate vaccine (PHiD-CV) co-administered with DTPw-HBV/Hib in Indian infants as 3-dose primary vaccination course. A total of 360 infants were randomized (2:1) to receive either PHiD-CV co-administered with DTPw-HBV/Hib (PHiD-CV group) or a Hib vaccine co-administered with DTPw-HBV (control group) at 6, 10, and 14 weeks of age. For each vaccine pneumococcal serotype, the percentage of infants in the PHiD-CV group with antibody concentrations ? 0.2 µg/mL one month after the third vaccine dose was at least 98.3%, except for serotypes 6B (77.7%) and 23F (89.5%), and opsonophagocytic activity titers ? 8 were measured in at least 95.7% of infants, except for serotypes 1 (90.5%) and 6B (84.5%). In addition, all the infants in the PHiD-CV group were seroprotected against diphtheria, tetanus, Hib, and hepatitis B or seropositive for antibodies against pertussis and NTHi protein D (except one infant). Incidences of solicited local and general symptoms were comparable between groups, except for fever (axillary temperature ? 37.5°C), which seemed to occur more frequently in the PHiD-CV group. In conclusion, PHiD-CV was shown to be immunogenic and well-tolerated when co-administered with DTPw-HBV/Hib in Indian infants.	S. Lalwani, S. Chatterjee, J. Chhatwal, V. P. Verghese, S. Mehta, F. Shafi, D. Borys, M. Moreira and L. Schuerman	Human vaccines & immunotherapeutics
49	Pre-exposure purified vero cell rabies vaccine and concomitant routine childhood vaccinations: 5-year post-vaccination follow-up study of an infant cohort in Vietnam	Children have a high risk of exposure to rabies in countries where the disease is endemic. This prospective, 5-year study followed two groups of children who had received diphtheria, tetanus, whole-cell pertussis and inactivated poliomyelitis vaccine (DTP-IPV) at 2, 3, 4 months and 1 year (Group B) or concomitant with three doses of purified Vero cell rabies vaccine (PVRV), given at 2, 4 months and 1 year (Group A). Antibody determinations were made annually for 5 years. Data were available from a total of 72 subjects; 30 in Group A and 32 in Group B. In Group A, the percentage of patients immunized against rabies (anti-rabies > or = 0.5 IU/ml) decreased from 100% after the third vaccination to 63%, 5 years later. After 5 years, 93.8% in Group A and 96.7% in Group B had seroprotective diphtheria antibody titers > or = 0.01 IU/ml, and all subjects had anti-polio (type 1, 2 and 3) seroprotective titers > or = 5 1:dil. We conclude that co-administration of PVRV with DTP-IPV elicited protective antibody concentrations to all antigens that persist for at least 5 years, with continued protection against rabies in over 60% of subjects. These results are consistent with integration of pre-exposure rabies vaccination into the Expanded Program on Immunization (EPI) in countries where rabies is endemic.	J. Lang, E. Feroldi and N. C. Vien	Journal of tropical pediatrics
213	Booster vaccination at 1 year with a rabies vaccine associated with DTP-IPV in infants living in a rabies endemic country		J. Lang, N. Rongrre, S. Plotkin, D. Q. Hoa, N. V. Gioi and T. T. Le	Journal of tropical pediatrics
258	A pilot study to quantify parental anxiety associated with enrollment of an infant or toddler in a phase III vaccine trial	We sought to measure the anxiety felt by parents at the time of entry into a randomized controlled vaccine trial, and to determine if anxiety level was associated with parental demographic variables or past experience. The children were 2-month-old infants entering a randomized controlled clinical trial (RCT) of a diphtheria-tetanus toxoid-acellular pertussis vaccine adsorbed with Haemophilus influenzae B conjugate, or toddlers enrolling in a RCT of a Meningococcal C conjugate vaccine. Nurses interviewed parents to collect demographic data and parents self-administered the Spielberger Self-evaluation Questionnaire (State Anxiety STAI-Y-I) [Manual for the State-Trait Anxiety Inventory (Form Y) (Self-evaluation Questionnaire), Consulting Psychologists Press Inc., Palo Alto, 1983], a validated instrument measuring the temporary condition of "state anxiety." A regression tree (CART) (S-Plus) was used to identify factors associated with higher anxiety scores. Parents of 97 children enrolled. Anxiety scores ranged from 22.75 (lower anxiety) to 36.43 (higher anxiety). The regression tree identified a structured tree with six branches. The highest anxiety scores occurred in fathers with education less then grade 8, mothers with education less than high school, birth order of the child less then the third, previous serious illness in the family, or lack of experience with research. In a group of parents agreeing to enroll their infant or toddler in a vaccine study, certain attributes and experiences were associated with higher anxiety at the time of immunization in the context of a RCT. These factors should be considered by vaccine researchers in the recruitment process of clinical trials.	J. M. Langley, S. A. Halperin and B. Smith	Vaccine
363	Systematic vaccination by a combined vaccine (diphtheria, tetanus, pertussis) during infancy. Serological and clinical studies		G. Laurell, T. Mellbin, E. Rabo, B. Vahlquist and P. Zetterquist	Klinische Wochenschrift
21	Immune responses and antibody decay after immunization of adolescents and adults with an acellular pertussis vaccine: the APERT Study	As part of a prospective acellular pertussis (ACP) vaccine efficacy trial, 5 serum samples were obtained, over an 18-month period, from 101 ACP-vaccine recipients and 99 control subjects, to assess ACP antibody response and decay. Immunoglobulin (Ig) G and IgA antibodies to pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae 2/3 (FIM) were measured by enzyme-linked immunosorbant assay, and titers of agglutinin were determined. Of the subjects, 16%-19% had preimmunization values of antibodies to PT that were above the assay's limit of quantitation (LOQ); in contrast, 36%-63% of the subjects had preimmunization values of antibodies to FHA, PRN, or FIM that were above the LOQ. Substantial increases in titers of IgG and IgA antibodies to the 3 ACP antigens (PT, FHA, and PRN) were observed. Over the 18-months, the percent decay in IgG and IgA antibodies ranged from 56% to 73% and from 57% to 70%, respectively; the IgG antibody response and decay suggests that geometric mean titers likely remain above the LOQ for 2-9 years and above the threshold of detection for 4-13 years. These findings support the use of ACP booster immunizations for adolescents and adults, to provide sustained levels of antibody.	T. Le, J. D. Cherry, S. J. Chang, M. D. Knoll, M. L. Lee, S. Barenkamp, D. Bernstein, R. Edelman, K. M. Edwards, D. Greenberg, W. Keitel, J. Treanor and J. I. Ward	The Journal of infectious diseases
46	Health-state valuations for pertussis: methods for valuing short-term health states	BACKGROUND: The incidence of reported adolescent and adult pertussis continues to rise in the United States. Acellular pertussis vaccines for adolescents and adults have been developed and may be available soon for use in the U.S. Our objectives were: (1) to describe patient valuations of pertussis disease and vaccination; and (2) to compare valuations for short-term and long-term health states associated with pertussis. METHODS: We conducted telephone surveys with 515 adult patients and parents of adolescent patients with pertussis in Massachusetts to determine valuations of pertussis-related health states for disease and vaccination using time trade-off (TTO) and contingent valuation (CV) techniques. Respondents were randomized to complete either a short-term or long-term TTO exercise. Discrimination between health states for each valuation technique was assessed using Tukey's method, and valuations for short-term vs. long-term health states were compared using the Wilcoxon rank-sum test. RESULTS: Three hundred three (59%) and 309 (60%) respondents completed and understood the TTO and CV exercises, respectively. Overall, respondents gave lower valuations (lower TTO and higher CV values) to avoid a given state for adolescent/adult disease compared to vaccine adverse events. Infant complications due to pertussis were considered worse than adolescent/adult disease, regardless of the method of valuation. The short-term TTO resulted in lower mean valuations and larger mean differences between health states than the long-term TTO exercise. CONCLUSION: Pertussis was considered worse than adverse events due to vaccination. Short-term health-state valuation is better able to discriminate among health states, which is useful for cost-utility analysis.	G. M. Lee, J. A. Salomon, C. W. LeBaron and T. A. Lieu	Health and quality of life outcomes
9	No adverse impact on protection against pertussis from combined administration of Haemophilus influenza type b conjugate and diphtheria-tetanus toxoid-pertussis vaccines in the same syringe	To assess whether combining a Haemophilus influenzae type b conjugate vaccine (PRP-T) and diphtheria-tetanus toxoid-pertussis (DTP) vaccine in a single syringe would impact adversely the antibody response and clinical protection conferred by pertussis vaccine, surveillance and a nested serosurvey were conducted among infants in a large-scale evaluation of PRP-T in Santiago. Infants received either combined PRP-T/DTP or DTP only at 2, 4, and 6 months of age. At 8 months, pertussis agglutinin, anti-pertussis toxin, and anti-filamentous hemagglutinin antibody levels in the PRP-T/DTP (137.7, 23.1, and 12.2, respectively) and DTP (142.9, 20.6, and 13.0, respectively) groups were comparable. The incidence of pertussis was similar among infants assigned to health centers administering combined PRP-T/DTP and those administering DTP alone (13.1 vs. 12.2 cases/10(5) child-years). Combined PRP-T/DTP vaccine did not diminish protection against pertussis.	O. S. Levine, R. Lagos, G. A. Losonsky, O. San Martin, P. Abrego, C. Bustamante, S. S. Wasserman and M. M. Levine	The Journal of infectious diseases
297	No adverse impact on protection against pertussis from combined administration of Haemophilus influenzae type b conjugate and diphtheria- tetanus toxoid-pertussis vaccines in the same syringe	To assess whether combining a Haemophilus influenzae type b conjugate vaccine (PRP-T) and diphtheria-tetanus toxoid-pertussis (DTP) vaccine in a single syringe would impact adversely the antibody response and clinical protection conferred by pertussis vaccine, surveillance and a nested serosurvey were conducted among infants in a large-scale evaluation of PRP-T in Santiago. Infants received either combined PRP-T/DTP or DTP only at 2, 4, and 6 months of age. At 8 months, pertussis agglutinin, anti-pertussis toxin, and anti-filamentous hemagglutinin antibody levels in the PRP-T/DTP (137.7, 23.1, and 12.2, respectively) and DTP (142.9, 20.6, and 13.0, respectively) groups were comparable. The incidence of pertussis was similar among infants assigned to health centers administering combined PRP-T/DTP and those administering DTP alone (13.1 vs. 12.2 cases/105 child-years). Combined PRP- T/DTP vaccine did not diminish protection against pertussis. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	O. S. Levine, R. Lagos, G. A. Losonsky, O. San Martin, P. Abrego, C. Bustamante, S. S. Wasserman and M. M. Levine	Journal of Infectious Diseases
72	A double-blind study comparing an acellular pertussis-component DTP vaccine with a whole-cell pertussis-component DTP vaccine in 18-month-old children	An acellular pertussis-component diphtheria-tetanus-pertussis (AC-DTP) vaccine was compared with a currently licensed, whole-cell pertussis-component DTP (WC-DTP) vaccine for reactogenicity and immunogenicity when given as the fourth DTP immunization in sixty 18- to 24-month-old children. Reactions over the first 48 hours were significantly less common in the AC-DTP vaccine recipients, as follows (WC-DTP/AC-DTP): fever, 85%/5%; redness, 70%/12.5%; tenderness, 100%/22.5%; swelling, 35%/10%; fretfulness, 70%/12.5%; anorexia, 35%/2.5%; and vomiting, 10%/0%. Antibody responses to pertussis antigens (agglutinogens, lymphocytosis-promoting factor, and filamentous hemagglutinin), diphtheria toxoid, and tetanus toxoid in AC-DTP vaccine recipients were comparable with those in WC-DTP vaccine recipients. The AC-DTP vaccine evaluated in this trial seems to be as immunogenic as WC-DTP vaccine while being markedly less reactogenic.	K. Lewis, J. D. Cherry, H. J. Holroyd, L. R. Baker, F. E. Dudenhoeffer and R. G. Robinson	American journal of diseases of children (1960)
392	[Adverse reactions induced by simultaneous immunization with Hib-TT conjugate vaccine and DTPw in infants]	Objective: To observe the adverse reactions induced by simultaneous immunization with Haemophilus influenzae type b(Hib)-tetanus(TT) conjugate vaccine and DTPw in infants in China. Methods: A total of 472 healthy infants aged 11-17 weeks were subjected to an open and randomized study. Divide the infants into DTPw and DTPw + Hib-TT groups randomly. The 238 infants in DTPw + Hib-TT group were immunized simultaneously with 0.5 ml of DTPw and 0. 5 ml of Hib-TT in separated site at ages of 3, 4 and 5 months, and the other 234 infants in DTPw group with 0.5 ml of DTPw alone. Observe the solicited and unsolicited adverse reactions within 4 d and record the unsolicited adverse reactions reported within 30 d after each immunization for statistical analysis. Results: The incidences of adverse reactions with in 4 d after immunization in DTPw + Hib-TT and DTPw groups were 49.1% and 46% respectively, which showed no significant difference. However, the incidences of unsolicited adverse reactions, prominent with upper respiratory infection and pharyngitis, within 30 d in the two groups were 9.9% and 9.8% respectively. No severe adverse reaction was reported. Conclusion: The simultaneous immunization with Hib-TT and DTPw was safe and well-tolerant. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	F. X. Li, R. C. Li and Y. P. Li	Chinese Journal of Biologicals
206	Safety and immunogenicity of a diphtheria, tetanus, acellular pertussis and Haemophilus influenzae Type b combination vaccine compared with separate administration of licensed equivalent vaccines in Chinese infants and toddlers for primary and booster immunization	To evaluate the safety and immunogenicity of a diphtheria, tetanus, acellular pertussis and Haemophilus infuenzae Type b (DTaP/Hib) combination vaccine first developed by a Chinese manufacturer, a randomized, two-stage, parallel controlled, single center clinical trial was conducted in Dafeng, Jiangsu Province of China. A total of 720 infants were enrolled and randomly assigned to two groups with a 2:1 allocation. In Stage I, 480 subjects in Group T were administered with 3 doses of the DTaP/Hib vaccine at 3, 4 and 5 months of age, respectively, while 240 subjects in Group C received separate licensed DTaP vaccine and Hib conjugate vaccine on the same schedule. In Stage II, 633 primed toddlers (431 of Group T and 202 of Group C) were given a booster dose at 18 months of age. Sera samples were collected at pre-dose 1, 4 weeks post-dose 3, pre-dose 4 and 4 weeks post-dose 4, respectively. Levels of protective antibodies were measured by Enzyme Linked Immunoadsorbent Assay (ELISA). Immunogenicity was evaluated with regard to geometric mean concentrations (GMCs), seroconversion rates and seroprotection rates of the antibodies. Solicited adverse reactions were recorded for 3 days after each dose; unsolicited adverse events and serious adverse events were monitored for 28 days after vaccination. Results showed that seroconversion rates of anti-pertussis toxoid (PT), anti-filamentous hemagglutinin (FHA), anti-diphtheria toxoid (DT), anti-tetanus toxid (TT) and anti-polyribosyl-ribitol-phosphate (PRP) in Group T (Stage I: 98.06%, 97.33%, 100%, 100%, 98.79%; Stage II: 99.18%, 83.42%, 99.18%, 63.32%, 85.05%) were comparable to that of Group C (Stage I: 95.26%, 93.16%, 100%, 100%, 98.42%; Stage II: 98.89%, 83.89%, 98.33%, 53.89%, 76.67%). Nearly 100% of the subjects in both groups achieved seroprotective levels of anti-DT (> or = 0.1IU/ml), anti-TT (> or = 0.1IU/ml) and anti-PRP (> or = 0.15 microg/ml) after primary and booster vaccination. The frequencies of local induration, swelling and redness as well as general reactions such as fever, diarrhea and anaphylaxis were low and acceptable in both groups. In conclusion, the DTaP/Hib vaccine was demonstrated to be non-inferior to the control vaccines on safety and immunogenicity. There could be a bright future for the DTaP/Hib vaccine to be widely used in the universal vaccination of Chinese children.	G. Li, H. Zhang, W. Zhou, Q. Ye, F. Li, H. Wang, Q. Hou, Y. Xu, X. Ma, Y. Tan, L. Wang, Y. Li, H. Li, F. Meng, Q. Liang, A. Liu, C. Qin, W. Wei, J. Liu, C. Ruan, W. Tao, S. Zhang, H. Zheng and F. Zhu	Vaccine
366	Clinical observation of Mist. Mei Hua for pertussis		H. P. Li, H. L. Liang, H. X. Shi, H. Yang, J. H. Wei, S. P. Xie and F. Guo	China Journal of Traditional Chinese Medicine and Pharmacy [Zhong Guo Yi Yao Xue Bao]
470	[A study on the safety of four vaccines of children epi at the same time and the results of the immunological responses after vaccination]. [Chinese]	The safety of the synthetic immunization of BCG, DPT, TOPV and MV and the results of studying on the immunological responses were reported. 337 preliminary immunized children of 3-24 month-age were voluntarily classified. The clinical reactions and the serological results of vaccination were systematically analyzed. It was identified that the effect of the synthetic immunization of four vaccines or three vaccines was similar to that of the individual immunization, i.e., the clinical reactions were slight and the effect was good after immunization. It was confirmed that the synthetic immunization could simplify the procedure of immunization and save manpower and cost. And it could solve the contradiction of the time space of vaccination, increase the vaccination coverage. It had comparative high social and economic benefit and fit for spreading in remote mountain area and minority nationality areas.	L. Li	Chung-Hua Liu Hsing Ping Hsueh Tsa Chih// Chinese Journal of Epidemiology
415	[Safety and immunogenicity of a 7-valent pneumococcal conjugate vaccine (Prevenar) booster dose in healthy Chinese toddlers]	OBJECTIVE: To evaluate the safety and immunogenicity of the booster dose of 7 valent pneumococcal conjugate vaccine (PCV7) to the healthy Chinese toddlers who had received 3 primary doses.METHODS: Four hundred and eighty-eight Chinese toddlers received a booster dose of PCV7 at age of 12-15 months following a primary series of the vaccine given at ages 3, 4, 5 months separately with Diphtheria Tetanus Acellular Pertussis Combined Vaccine (DTaP) in Group 1 or concurrently with DTaP in Group 2. Following the booster dose immunization, each subject was followed up for 30 days to observe the safety of the vaccine. Blood samples were taken from a subset of subjects prior and post 30 days the booster dose immunization to evaluate immunogenicity.RESULTS: A high proportion of subjects in Group 1 (89%) and Group 2 (91%) remained afebrile after the booster dose. Local reactions to the PCV7 booster dose were generally mild. For each serotype, the rise in GMC (post-/pre-vaccination) showed a statistically significant difference (P<0.0001) between both groups.CONCLUSION: PCV7 administered as a booster dose is generally safe, well tolerate, and immunogenic in healthy Chinese toddlers.	R. C. Li, F. X. Li and Y. P. Li	Zhongguo yi miao he mian yi
208	Safety and immunogenicity of a 7-valent pneumococcal conjugate vaccine (Prevenar): primary dosing series in healthy Chinese infants	This was a randomized safety/immunogenicity evaluation of PCV7 primary series at 3, 4, 5 months in healthy Chinese infants. Eight hundred subjects were randomized to Group 1 (PCV7 > or =7 days before DTaP), or Group 2 (PCV7 with DTaP), or Group 3 (DTaP only). Erythema and induration/swelling were recorded at the PCV7 injection site at any individual dose in no more than 12% and 8% of subjects, respectively, and neither exceeded 2.5 cm in >1% of subjects. Fever >38.0 degrees C was observed in <13% of subjects at any individual dose. For each vaccine serotype, at least 90% of subjects (Groups 1 and 2) had IgG concentrations > or = 0.35 microg/mL after dose 3, except type 6B (Group 2) with 83.3%. PCV7 had an acceptable safety profile and was immunogenic in Chinese infants.	R. C. Li, F. X. Li, Y. P. Li, S. Y. Guo, Y. Nong, Q. Ye, K. X. Fang, S. C. Wei, Z. Wang and S. Lockhart	Vaccine
217	[Safety and immunogenicity of the diphtheria, tetanus, accellular pertussis plus hemophilus influenza type b combined vaccine (DTaP-Hib) to Chinese infants]	OBJECTIVE: To evaluate the safety and immunogenicity of combined diphtheria, tetanus, accellular pertussis Plus hemophilus influenza type b vaccine (DTaP-Hib)to Chinese infants.METHODS: Safety study (study A), and immunogenicity and safety study (study B) were conducted in infants aged 3, 4 and 5 months. The immune response and safety of the DTaP-Hib vaccine were compared after administered DTaP and Hib separately based on specified criteria.RESULTS: A total of 690 healthy infants received primary vaccination with combined DTaP-Hib or administered DTaP and Hib(DTaP+Hib) separately. Immunogenicity was assessed before and one month after vaccination in a subjet. The tolerance of DTaP-Hib vaccine was at least as same as administered DTaP+Hib separately. The differences of local and general adverse events following immunigation (AEFI) between groups had no difference statisticaly significantly. At least 97.5% of DTaP-Hib recipients had seroprotection against diphtheria, tetanus and Hib, and response to acellular pertussis antigens one month after primary vaccination. The immune response of the DTaP-Hib vaccine was comparable to administered DTaP+Hib based on specified criteria separately.CONCLUSION: The combined DTaP-Hib vaccine gets expected safety and immunogenicity.	Y. P. Li, S. M. Zhang and Q. Ye	Zhongguo yi miao he mian yi
421	Effects of vaccine information pamphlets on parents' attitudes	OBJECTIVES: To describe how parents actually use federally mandated vaccine information pamphlets and to evaluate the pamphlets' effects on parents' opinions about vaccination. DESIGN: A controlled trial of vaccine information pamphlets based on a survey mailed to parents who either received (n = 140) or did not receive (n = 167) the pamphlets. STUDY POPULATION: Parents of infants aged 2 to 8 months in a suburban, mainly upper-middle class private group practice in northern California. RESULTS: More than 90% of parents believed that they had enough information to decide whether their child should be vaccinated, even among those who did not receive the pamphlets. Among parents who received the pamphlets, fewer than half (38%) read them thoroughly, and most (63%) said that they should be distributed only on the first visit for vaccinations. Parents who received the pamphlets did not differ from those who did not in terms of the proportions who would have liked more time to be spent discussing vaccines (34% vs 34%) or who were anxious about how the diphtheria and tetanus toxoids and pertussis vaccine would affect their child (60% vs 52%). CONCLUSIONS: Vaccine information pamphlets, when used as an adjunct to discussions with physicians and nurses, have little effect on the opinions of well-educated parents. Future research and policy changes might focus on how to make the contents of the pamphlets less frightening and on allowing greater flexibility in how they are distributed.	T. A. Lieu, J. H. Glauber, E. Fuentes-Afflick and B. Lo	Archives of pediatrics & adolescent medicine
98	Safety and reactogenicity of DTPa-HBV-IPV/Hib and DTPa-IPV/I-Hib vaccines in a post-marketing surveillance setting	Combination vaccines have been shown to improve the timeliness of vaccination and vaccine coverage. Safety and reactogenicity of combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus and Haemophilus influenzae type b vaccine (DTPa-IPV/Hib, Infanrix IPV+Hib, GlaxoSmithKline Biologicals) was assessed in two clinical studies. In Study A, 2,590 subjects received DTPa-IPV/Hib at 3, 4 and 5 months of age with a booster at 18 months. In Study B, 702 subjects received the same schedule but with DTPa-hepatitis B-IPV/Hib (DTPa-HBV-IPV/Hib, Infanrix hexa, GlaxoSmithKline Biologicals) vaccine administered at 5 months of age. Reactogenicity was assessed for four days after each dose using diary cards. Serious adverse events (SAEs) were assessed until 24 months of age. The vaccines were well tolerated. After primary vaccination, irritability was the most frequently reported grade 3 general symptom (0.8% of doses in both studies). Fever (axillary) > 39 degrees C was infrequent (0.3% of doses in Study A; 0.5% of doses in Study B). After the booster dose, the most frequently reported grade 3 symptom was redness (5%) in Study A and pain (0.5%) in Study B. An axillary temperature > 39 degrees C was reported in 1.1% of subjects. Throughout the study period, 646 SAEs were reported, of which 6 SAEs were considered to be vaccination-related. The reactogenicity and safety profile of the combined DTPa-IPV/Hib vaccine was good when used for primary and booster vaccinations in over 3,000 Singaporean infants. Substitution of DTPa-IPV/Hib with DTPa-HBV-IPV/Hib at Month 5 reduced the number of injections required at this age by one.	F. S. Lim, K. B. Phua, B. W. Lee, S. H. Quak, Y. L. Teoh, G. Ramakrishnan, H. H. Han, O. Meeren, J. M. Jacquets and H. L. Bock	The Southeast Asian journal of tropical medicine and public health
60	Specific immune response in adult medical personnel immunized with acellular pertussis vaccine with special emphasis on T helper cell response	Recent epidemiologic data have indicated that adults are the most important reservoir that transmit pertussis to children. However, conventional whole cell pertussis vaccine is contraindicated in adults and children over 7 years of age because of the unacceptably high rate of adverse reactions. The aim of this study is to evaluate the specific cellular immune responses and adverse reactions to a less reactogenic acellular pertussis vaccine in adult volunteers. Eighty healthy medical personnel in Chang Gung Children's Hospital were enrolled. Volunteers in each group received: (1) Td + full strength acellular pertussis vaccine (PT, 1 microgram/0.5 ml; FHA, 4 micrograms/0.5 ml); (2) Td + half strength acellular pertussis vaccine; (3) Td alone. Lymphocyte phenotypic analysis, antigen-specific antibody titers, antigen-specific proliferative response and cytokine levels were evaluated before and 1 month after vaccination. Our data revealed: (1) the adverse reactions were minimal; (2) phenotypic analysis showed no non-specific activation of helper T or memory T cell after vaccination; (3) both PT and FHA-specific antibody titers increased significantly after vaccination, (4) PT antigens had a mitogenic effect on cord blood mononuclear cells and peripheral blood mononuclear cells of the adult volunteers; (5) FHA-specific T cell proliferative responses significantly increased after vaccination; (6) the cytokine production pattern showed predominant activation of Th 1 cells as reflected in increased production of gamma-IFN after vaccination. Acellular pertussis vaccine can effectively induce both humoral and cellular immune response in adults.	T. Y. Lin and B. L. Chiang	Vaccine
146	One-year post-primary antibody persistence and booster immune response to a fully liquid five-component acellular pertussis, diphtheria, tetanus, inactivated poliomyelitis, Haemophilus influenzae type b conjugate vaccine	OBJECTIVE: To evaluate antibody persistence one year after three-dose primary vaccination and booster immune response during the second year of life for a fully liquid diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis-Haemophilus influenzae type b (DTaP-IPV-PRP approximately T) vaccine. METHODS: Infants at 18-19 months of age were given a booster dose of either DTaP-IPV-PRP approximately T (group A) or DTaP-IPV plus PRP approximately T at separate injection sites (group B), after primary vaccination at two, four and six months of age, with the same vaccines. Antibody concentrations were measured pre- and post-booster. Reactogenicity and safety were evaluated from parent reports. RESULTS: Before the booster dose, 93.1% of group A and 95.1% of group B children still had anti-PRP antibody titers > or =0.15 microg/ml. All children had antibody levels believed to protect against tetanus, polio 1 (except one subject in group B), polio 2, polio 3, and diphtheria (except one subject in group A). At least 94% of children still had antibody concentrations > or =5 ELISA units (EU) to pertussis antigens (pertussis toxoid (PT), filamentous hemagglutinin (FHA), pertactin (PRN), fimbriae 2 and 3 (FIM2+3)). One month after the booster dose, all subjects achieved antibody concentrations or titers believed to be protective for PRP (polyribose ribitol phosphate)(> or =1 microg/ml), diphtheria and tetanus (> or =0.1 IU/ml) and poliovirus types 1, 2, and 3 (> or =81/dil.), and at least 90.5% of subjects had four-fold increases in antibody concentrations to pertussis antigens following the booster. Anti-PRP geometric mean titers (GMTs) increased from 1.07 to 59.6 microg/ml and from 1.8 to 62.2 microg/ml in groups A and B, respectively. Both vaccine groups showed low reactogenicity rates. CONCLUSIONS: The fully liquid pentavalent DTaP-IPV-PRP approximately T vaccine is highly immunogenic, with good antibody persistence for each antigen approximately one year after primary vaccination and strong booster responses at 18-19 months of age. Because this combined vaccine is fully liquid, requiring no reconstitution of lyophilized PRP approximately T, the ease of use and proper administration are improved.	T. Y. Lin, Y. H. Wang, Y. C. Huang, C. H. Chiu, P. Y. Lin, C. J. Chen, P. Chavand and E. Ortiz	International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
442	Controlled trial of immune response of preterm infants to recombinant hepatitis B and inactivated poliovirus vaccines administered simultaneously shortly after birth	AIM: The study was conducted to evaluate the immunogenicity of an early, extra dose of enhanced inactivated poliovirus vaccine (IPV) administered simultaneously with recombinant hepatitis B vaccine (HBV) to preterm infants shortly after birth. METHODS: Three groups were studied. Fifty preterm infants received IPV intramuscularly within 24 hours of birth, in addition to routine recommended childhood immunisations. Fifty two preterm infants and 35 full term infants received routine immunisations only (routine vaccination timing: HBV at birth, 1 and 6 months of age; IPV at 2 and 4 months; oral polio vaccine (OPV) at 4 and 6 months; diphtheria-tetanus-pertussis (DTP) at 2, 4, and 6 months; and Haemophilus influenzae B vaccine at 2 and 4 months). Blood samples were taken at birth, 3 and 7 months of age from all infants, and at 1 month of age from preterm infants only. RESULTS: At birth, a lower percentage of both study and control preterm infants had antipoliovirus type 3 titres >/= 1:8 than full term infants. At 1 and 3 months of age significantly more early IPV infants had antipoliovirus type 3 titres >/= 1:8 than routinely vaccinated preterm infants (p < 0.05). At 7 months of age there were no significant differences in percentage of antipoliovirus titres >/= 1:8 or geometric mean times (GMTs) between the early IPV group and the routinely vaccinated preterm group. At 3 and 7 months of age, the percentage of positive antihepatitis B titres (>/= 1:10) and the GMT of the early IPV preterm group did not differ significantly from those of preterm controls. There was no significant difference in percentage of positive antihepatitis B titres between the early IPV group and full term controls at any time. GMTs for hepatitis B antibodies were significantly lower in the early IPV preterm group than in full term controls at 3 and 7 months of age. CONCLUSIONS: Administration of an additional dose of IPV simultaneously with routine HBV to preterm infants shortly after birth provides early protection from poliovirus and hepatitis B infection, and does not interfere with poliovirus antibody production at the age of 7 months.	N. Linder, R. Handsher, B. German, L. Sirota, M. Bachman, S. Zinger, E. Mendelson and A. Barzilai	Archives of disease in childhood. Fetal and neonatal edition
428	A randomized trial of the effectiveness of computer-generated telephone messages in increasing immunization visits among preschool children	OBJECTIVE: To assess the effectiveness of computer-generated telephone reminder and recall messages in increasing preschool immunization visits. DESIGN: Randomized, controlled trial. SETTING: Fourteen counties in urban and rural Georgia. STUDY PARTICIPANTS: Children (N = 8002) who were younger than 2 years; had telephone numbers listed in preexisting computerized immunization databases; and were due or late for immunization(s) during the 4-month enrollment period. INTERVENTION: Households of children were randomized to receive or not receive a general or vaccine-specific computer-generated telephone reminder or recall message the day before the child was due, or immediately after randomization if the child was late. MAIN OUTCOME MEASURE: The rates of immunization visits during the 30-day follow-up period. RESULTS: Of the 4636 children whose households were randomized to receive a message, 1684 (36.3%) visited the health department within 30 days compared with 955 (28.4%) of the 3366 children whose households were not contacted (risk ratio [RR] = 1.28; 95% confidence interval [CI] = 1.20 to 1.37; P < .01). Immunization visits were more frequent (41.1%) among the 3257 children whose households actually received the message (RR = 1.45; 95% CI = 1.36 to 1.56; P < .01). Improvement in immunization visits was similar for general and specific messages, greater for recall than reminder messages, and greatest for children who were late for the third dose of the diphtheria-tetanus-pertussis vaccine and the measles-mumps-rubella vaccine. CONCLUSION: These data suggest a simple and effective way to increase preschool immunization visits, particularly for vaccines associated with the lowest immunization rates.	R. W. Linkins, E. F. Dini, G. Watson and P. A. Patriarca	Archives of pediatrics & adolescent medicine
326	On the antibiotic therapy of pertussis and its limits		F. Loeber	Munchener Medizinische Wochenschrift
167	Safety and immunogenicity of combined or associated administration of PRP-T vaccine with diphtheria, tetanus and pertussis vaccine in Thai children	To assess whether the combination of a diphtheria, tetanus and pertussis vaccine with a Haemophilus influenzae type b conjugate vaccine (PRP-T) had any effect on immunogenicity or safety compared with separate administration of the vaccines, 158 infants were randomized to receive the vaccines either in association or as a combination at 2, 4, and 6 months of age. A total of 126 infants (59 associated, 67 combination) completed the three-dose regimen and were analysed for immunogenicity and safety. With respect to safety, there were no significant differences between the two groups. The combination vaccine was well tolerated with adverse reactions consisting mainly of transient pain, redness, induration and some low-grade fever. With respect to immunogenicity, response to PRP-T vaccine was good. Following just two doses, all infants achieved anti-PRP titers >0.15 microg/ml, regardless of whether the vaccine was given in combination or association. Following three doses, 98.5 per cent of infants in the combination group and 98.3 per cent in the association group had titers higher than 1.0 microg/ml.	S. Lolekha, A. Hiranchote and S. Simasathien	Journal of tropical pediatrics
285	Serologic evidence of subclinical pertussis in immunized children	Incidental to a vaccine study involving 783 immunized children conducted at two study sites, inner city children had significantly higher geometric mean pertussis agglutinin titers compared with suburban children just before the fourth dose of diphtheria-tetanus-whole cell pertussis vaccine (47 vs. 25; P less than 0.001). Higher titers in the inner city were correlated with residence in census tracts where cases of pertussis were reported. Three hundred thirty-two children in a placebo arm of the study who were clinically observed and had paired serum samples taken during a 2- to 4-month period were analyzed for evidence of natural Bordetella infection. Twelve (11%) inner city children and three (1.3%) suburban children had spontaneous 4-fold or greater rises in at least two different pertussis antibodies measured (agglutinin, antitoxin or enzyme-linked immunosorbent assay for IgG to pertussis toxin, IgG and IgA to filamentous hemagglutinin). Eighty percent of these children had IgA to filamentous hemagglutinin. Nine of 12 inner city children with serologic evidence of pertussis lived within 6 blocks of a case of pertussis reported within 1 month of the observed antibody rise in study subjects; none had a household member with pertussis and none had symptomatic disease	S. S. Long, H. W. Lischner, A. Deforest and J. L. Clark	Pediatric Infectious Disease Journal
168	[Immunogenicity and safety of Di-Te-Ki-Pol vaccine "SSI" in Danish infants]	This study compared a tetravalent DTaP-IPV vaccine (Di-Te-Ki-Pol vaccine "SSI") with the vaccination regimen used in Denmark at that time, DT-IPV plus wholecell pertussis vaccine. Two hundred and seventy children were included at their five-week routine examination. The children were allocated to one of the two vaccination regimens. No hypotonic-hyporesponsive episodes or other vaccine-related serious adverse events were seen. Local reactions, febrile and crying episodes following the investigational vaccine were similar to the reactions seen after Di-Te-Pol vaccine. All children achieved protective antibody levels to polio, diphtheria and tetanus after completing the vaccination schedule. A significantly better response to pertussis toxin was seen after the investigational vaccine. We conclude that the Di-Te-Ki-Pol vaccine is safe and immunogenic when used according to the schedule tested.	E. Lyngholm, A. F. Gyhrs, S. M. Bang and I. Heron	Ugeskrift for laeger
35	Immunogenicity and safety of an acellular pertussis, diphtheria, tetanus, inactivated poliovirus, Hib-conjugate combined vaccine (Pentaxim) and monovalent hepatitis B vaccine at 6, 10 and 14 weeks of age in infants in South Africa	OBJECTIVE: To assess the immunogenicity and safety data for a pentavalent combination vaccine containing acellular pertussis, inactivated poliovirus, and Haemophilus influenzae (Hib) polysaccharide-conjugate antigens.METHODS: A DTaP-IPV//PRP T vaccine (Pentaxim) was given at 6, 10 and 14 weeks of age to 212 infants in South Africa. Monovalent hepatitis B vaccine was given concomitantly. Immunogenicity was assessed using seroprotection and seroconversion rates; safety was assessed by monitoring for solicited injection site and systemic adverse events, and follow-up monitoring for unsolicited adverse events and serious adverse events.RESULTS: Immunogenicity was high for each vaccine antigen, and similar to a reference study done in France using a similar (2, 3 and 4 months of age) administration schedule. After the third dose, 94.6% of participants had anti-PRP > or = 0.15 microg/ml. The anti-PRP geometric mean antibody titre (GMT) was 2.0 microg/ml. The seroprotection rates for diphtheria and tetanus (> or = 0.01 IU/ml), poliovirus types 1, 2 and 3 (> or = 8 1/dil U) and hepatitis B were all 100%. Anti-polio GMTs were very high, 1 453, 1 699 and 2 398 (1/dil U) for types 1, 2 and 3, respectively. The seroconversion/vaccine response rates to pertussis antigens (4-fold increase in antibody concentration) were 97.5% for PT and 83.9% for FHA.CONCLUSIONS: The DTaP-IPV//PRP T vaccine was highly immunogenic at 6, 10 and 14 weeks of age in infants in South Africa, was compatible with the monovalent hepatitis B vaccine, and was well tolerated.	S. A. Madhi, C. Cutland, S. Jones, M. Groome and E. Ortiz	South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde
140	Immunogenicity and safety of an investigational fully liquid hexavalent combination vaccine versus licensed combination vaccines at 6, 10, and 14 weeks of age in healthy South African infants	BACKGROUND: Assessment of primary vaccination of a new fully liquid, hexavalent investigational DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim) in South African infants.METHODS: Infants were randomized to the following at 6, 10, and 14 weeks of age (Expanded Program on Immunization schedule): DTaP-IPV-Hep B-PRP-T (Group 1; N = 286); DTwP-Hib, hepatitis B, and OPV vaccines (Group 2; N = 286); or DTaP-IPV-Hep B-PRP-T vaccine with hepatitis B vaccine at birth (Group 3; N = 143). Antibody titers were measured before vaccination (pertussis toxoid, filamentous hemagglutinin) and postprimary vaccination (all valences). Noninferiority analyses were performed for Group 1 versus Group 2 for seroprotection rates. Safety was evaluated from parental reports.RESULTS: Noninferiority (Group 1 minus Group 2) was demonstrated for anti-HBs, -PRP, -diphtheria, -tetanus, and -polio 1, 2, 3 (lower 95% confidence interval for the difference was -8.20 to 3.46). Anti-HBs antibody titers ?10 mIU/mL and anti-PRP ?0.15 ?g/mL were ?95.4% in each group. Seroprotection rates were also high for the other antigens. Seroconversion rates (4-fold increase from pre- to postvaccination) were 93.6%, 83.2%, and 95.1% in Groups 1, 2, and 3, respectively, for anti-pertussis toxoid and 93.1%, 57.7%, and 90.0% for anti-filamentous hemagglutinin. Anti-HBs GMTs were 330, 148, and 1913 mIU/mL for Groups 1, 2, and 3, respectively. Reactogenicity was similar in each group. Fever ?39.0°C occurred in 1.7%, 0.4%, and 0.0% of infants in Groups 1, 2, and 3, respectively; no extensive limb swelling, hypotonic-hyporesponsive episodes, or vaccine-related serious adverse events were reported.CONCLUSIONS: The new, fully liquid, investigational hexavalent vaccine in the Expanded Program on Immunization schedule, with/without hepatitis B at birth, is highly immunogenic and safe compared with control vaccines, warranting further development.	S. A. Madhi, I. Mitha, C. Cutland, M. Groome and E. Santos-Lima	The Pediatric infectious disease journal
466	Zinc supplementation as adjunct therapy in children with measles accompanied by pneumonia: a double-blind, randomized controlled trial	BACKGROUND: Zinc deficiency, common in developing countries, is associated with decreased immunocompetence. Zinc supplementation benefits children with acute and persistent diarrhea and prevents pneumonia. Most deaths from vaccine-preventable diseases are from measles and whooping cough; pneumonia is the most common complication of measles and often the proximate cause of related deaths. OBJECTIVE: We evaluated the effect of zinc supplementation on episodes of illness in children with measles accompanied by pneumonia. DESIGN: In a double-blind, randomized controlled trial, children aged 9 mo-15 y who were admitted to the Infectious Diseases Hospital in Calcutta with clinically severe measles accompanied by pneumonia and who had been ill for </= 7 d were randomly assigned to receive zinc (20 mg, in elemental form as acetate, twice daily for 6 d) or a placebo. All patients received standard treatment with antibiotics and an initial 100 000-IU dose of vitamin A (as palmitate) by mouth. RESULTS: Time-to-event analysis using the Cox proportional hazards model (42 in the zinc group and 43 in the placebo group) showed that the time needed for the resolution of fever and tachypnea, the return of appetite, and the achievement of a "much improved" or "cured" status was not different between the 2 groups. A high proportion of children had low serum retinol and zinc concentrations. Improvement in serum zinc and retinol concentrations after 6 d of treatment was not different between the 2 groups. CONCLUSION: Children with severe measles accompanied by pneumonia treated with antibiotics and vitamin A did not show any additional benefit from also receiving a zinc supplement.	D. Mahalanabis, A. Chowdhury, S. Jana, M. K. Bhattacharya, M. K. Chakrabarti, M. A. Wahed and M. A. Khaled	The American journal of clinical nutrition
469	Vitamin A megadoses during early infancy on serum retinol concentration and acute side effects and residual effects on 6 month follow-up	We evaluated the safety and efficacy of 3 oral doses of 50,000 IU vitamin A at monthly intervals in predominantly breastfed infants from poor urban Bangladesh aged 6 to 17 weeks along with DPT and oral polio vaccines in a randomised double-masked controlled trial. Ninety-seven infants received vitamin A and 103 received placebo. Initial fasting serum retinol concentrations were very low in most infants (52% < 10 microg/dl and 74% < 15 microg/dl) which improved in both groups but was still less than 15 microg/dl in 30% of those who received vitamin A. Nine infants in the vitamin A group and 2 in the placebo group had bulged fontanelle after the second and/or third dose (RR=4.78, 95% CI 1.06-21.54, P<0.025) which resolved in 48 hours. In conclusion young infants from a deprived urban community in Bangladesh were deficient in vitamin A; a large proportion remained deficient even after three large doses of vitamin A. In spite of deficiency, bulged fontanelle, an apparent toxic manifestation, occurred in 9.3% with this dosage schedule of vitamin A. Alternative and/or complementary approaches e.g. maternal supplementation are needed to prevent vitamin A deficiency in under 6 mouth infants in developing countries. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	D. Mahalanabis, M. M. Rahman, M. A. Wahed, M. A. Islam and D. Habte	Nutrition Research
101	Immunogenicity and safety of a new liquid hexavalent combined vaccine compared with separate administration of reference licensed vaccines in infants	OBJECTIVE: The immunogenicity and safety of a new liquid hexavalent vaccine (diphtheria-tetanus-acellular pertussis-inactivated polio vaccine-hepatitis B-polyribosyl ribitol phosphate conjugated to tetanus protein; Hexavac; Aventis Pasteur MSD, Lyon, France) are compared with those of reference vaccines [diphtheria-tetanus-acellular pertussis-inactivated polio vaccine reconstituting lyophilized purified Haemophilus influenzae polysaccharide conjugated to tetanus protein vaccine (Pentavac; Aventis Pasteur MSD) and hepatitis B vaccine (H-B-Vax II; Aventis Pasteur MSD)] injected separately at the same visit in a prospective multicenter, comparative, open label trial. METHODS: Infants were randomized to receive Hexavac (n = 423) or Pentavac and H-B-Vax II (n = 425) as a primary immunization series at 2, 4 and 6 months of age. Seroprotection and seroconversion rates against all antigens at 1 month after the primary series were compared between the two vaccine groups with 95% confidence intervals (CI0.95) and were considered clinically equivalent (not inferior) when the upper limit of the 95% confidence interval on the difference (reference, hexavalent) was below predefined differences. RESULTS: Hexavac met and surpassed the pre-defined criteria for clinical equivalence to Pentavac and H-B-Vax II given concomitantly. It elicited similar seroprotection and seroconversion rates against all antigens. Seroprotection and seroconversion rates obtained 1 month after the third dose of Hexavac were >90% for all antigens. The postimmunization antibody geometric mean titers (GMT) for hepatitis B and purified Haemophilus influenzae polysaccharide were about 2-fold higher in infants who received the reference vaccines than in infants who had received Hexavac. GMTs for poliovirus antibodies tended to be enhanced in infants vaccinated with Hexavac. GMTs for all other antigens were very similar among both groups. Hexavac was generally well-tolerated. At least one local reaction was reported in 20.3% of Hexavac injections compared with 15.8% at the Pentavac injections site and 3.8% at the H-B-Vax II injections site. These reactions were generally mild and transient. At least one systemic adverse event was reported in 45.7% of Hexavac injections compared with 42.2% of Pentavac and H-B-Vax II injections (mild fever, irritability and drowsiness were most frequently reported). The frequency of adverse events was not significantly different between groups. No vaccine-related serious adverse event occurred during the study. CONCLUSION: This liquid hexavalent vaccine was generally well-tolerated and provided immune responses adequate to be protective against six infectious diseases with a single injection, given at 2, 4 and 6 months of age.	E. Mallet, P. Fabre, E. Pines, H. Salomon, T. Staub, F. Schödel, P. Mendelman, L. Hessel, G. Chryssomalis, E. Vidor and A. Hoffenbach	The Pediatric infectious disease journal
113	Randomized trial to assess immunogenicity and safety of Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine in infants	BACKGROUND: Study assessed the immunogenicity and safety of an investigational Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY-TT) in infants. METHODS: In a single-blinded, controlled study, 609 infants were randomized 1:1 to receive primary vaccination (2, 4, and 6 months) with either HibMenCY-TT or monovalent Haemophilus influenzae type b tetanus toxoid conjugate vaccine (Hib-TT), co-administered with combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus vaccine and 7-valent pneumococcal conjugate vaccine. A second control group of 3- to 5-year-old children received a single dose of licensed meningococcal ACWY polysaccharide vaccine (MPSV4). Immunogenicity was measured before and 1 month after dose 3/MPSV4 using human (hSBA) and rabbit complement bactericidal assays (rSBA) and enzyme-linked immunosorbent assay assays for IgG antibodies to MenC and MenY polysaccharides. Anti-polyribosylribitol phosphate antibody concentrations were measured 1 month after the third dose. Safety was also assessed. RESULTS: One month after primary vaccination statistically significantly more HibMenCY-TT than Hib-TT vaccines had anti-PRP antibody concentrations > or =1.0 microg/mL (93.5% vs. 85.8%). The percentage of HibMenCY-TT recipients with hSBA titers > or =1:8 (MenC: 95.9%, MenY: 89.4%) was statistically significantly higher than for MPSV4 recipients (MenC: 30.2%, MenY: 47.5%). The percentage of subjects reporting any severe (grade 3) symptom within 4 days of each vaccination was: 11.5% (HibMenCY-TT) and 24.8% (Hib-TT) (group difference, 13.27%, 95% CI: [7.22;19.29], P < 0.001). CONCLUSION: The investigational HibMenCY-TT vaccine was well tolerated and immunogenic in infants, induced Hib immune responses that were comparable to licensed Hib-TT vaccine, and induced high levels of bactericidal antibodies against N. meningitidis serogroups C and Y.	C. D. Marchant, J. M. Miller, G. S. Marshall, M. Blatter, E. Aris, L. R. Friedland and D. Boutriau	The Pediatric infectious disease journal
111	Immunity and immunization of children against diphtheria in Sweden	The level of immunity to diphtheria and the effect of vaccination with different doses of diphtheria toxoid was investigated. The 457 study children, 6, 10 and 16 years of age, had as infants received routine primary vaccination with three doses of diphtheria-tetanus-toxoid or diphtheria-tetanus-pertussis vaccine, and the 16 year-olds also had received a booster dose of tetanus with a small dose of diphtheria at the age of ten. Prior to the study booster, 15% of the 6-year-olds had antitoxin levels against diphtheria less than 0.01 IU/ml, the given minimum level for protection. Of the 10-year-olds, 48% had titres less than 0.01 IU/ml, while the corresponding figure for the 16-year-olds was 24%. After a booster injection of 0.1, 0.25 or 0.5 ml of diphtheria-tetanus vaccine, more than 97% of the children showed titre levels greater than or equal to 0.1 IU/ml, while levels of greater than or equal to 1 IU/ml, indicating titres sufficient for long-term protection, were attained by 23-96%. Systemic reactions were few and moderate. Local reactions were of little clinical significance. In a group of 5-years-olds given diphtheria-tetanus primary vaccinations over wider intervals, only 1.4% had antitoxin titres less than 0.01 IU/ml. The results show a need for serologic monitoring of vaccination programmes.	A. Mark, B. Christenson, M. Granström, A. Strandell, B. Wickbom and M. Böttiger	European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology
99	Co-administration of a novel Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine does not interfere with the immune response to antigens contained in infant vaccines routinely used in the United States	An investigational combined Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine (HibMenCY-TT) has been developed to protect infants from invasive disease caused by Hib and these meningococcal serogroups without adding injections to the immunization schedule. Incorporation of this novel vaccine into the US vaccination schedule will require demonstration of a lack of immunologic interference with other routine pediatric vaccines. This study assessed the immune response to 7-valent pneumococcal conjugate vaccine (PCV7) and combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus vaccine (DTaP-HepB-IPV) when separately co-administered with HibMenCY-TT as compared to a US-licensed H. influenzae type b tetanus toxoid conjugate vaccine (Hib-TT) at 2, 4, 6 (N=606) and 12-15 months of age (N=366). HibMenCY-TT was non-inferior to Hib-TT in terms of antibody responses to all Streptococcus pneumoniae serotypes contained in PCV7 and the diphtheria, tetanus, pertussis, hepatitis B and poliovirus antigens contained in DTaP-HepB-IPV one month after the third vaccine dose, and the anti-tetanus geometric mean antibody concentration (GMC) was significantly higher in the HibMenCY-TT group than in the Hib-TT group. In an exploratory analysis, no significant differences in the proportion of subjects with anti-pneumococcal antibody concentrations ?0.2 µg/ml or anti-pneumococcal GMC were seen between the two groups after the fourth vaccine dose. A schedule of HibMenCY-TT given concomitantly with PCV7 and DTaP-HepB-IPV would be expected to protect infants against all of the targeted diseases.	G. S. Marshall, C. D. Marchant, M. Blatter, L. R. Friedland, E. Aris and J. M. Miller	Human vaccines
27	Primary and booster immunization with a diphtheria, tetanus, acellular pertussis, hepatitis B (DTPa-HBV) and Haemophilus influenzae type b (Hib) vaccine administered separately or together is safe and immunogenic	OBJECTIVES: The aim of this study was to evaluate the safety and immunogenicity of DTPa-HBV and Hib vaccines given mixed or separately to 360 healthy infants at 2, 4, and 6 months of age. METHODS: Immune memory was assessed in lower responders (post-primary anti-PRP <0.545 microg/ml), through administration of plain polyribosylribitol phosphate (PRP) at 12-15 months. All subjects received a DTPa-HBV/Hib booster at 18-19 months. RESULTS: One month after primary vaccination, 98% had seroprotective antibody levels against HBV and 94-97% against Hib (anti-PRP> or =0.15microg/ml). A statistically significant difference between groups was observed in the proportion of subjects who achieved anti-PRP antibodies > or =1.0microg/ml post-primary vaccination; 68.1% for DTPa-HBV/Hib and 84.5% for DTPa-HBV and Hib. PRP administered to lower responders produced a 7-fold increase in anti-PRP antibodies, indicative of immunological memory. After DTPa-HBV/Hib booster vaccination, 96-100% of subjects had seroprotective antibody concentrations against Hib, hepatitis B, tetanus, and diphtheria and high vaccine response rates against pertussis toxoid, filamentous hemagglutinin, and pertactin. CONCLUSION: A robust and protective Hib response was demonstrated following plain PRP and/or a booster conjugate Hib vaccine in both lower and higher Hib responders.	H. Marshall, P. McIntyre, D. Roberton, L. Dinan and K. Hardt	International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
141	A comparison of booster immunisation with a combination DTPa-IPV vaccine or DTPa plus IPV in separate injections when co-administered with MMR, at age 4-6 years	This study evaluated GSK's combined DTPa-IPV vaccine (Infanrix-IPV) given as a fifth consecutive acellular pertussis booster dose in conjunction with the second dose of MMR vaccine (Priorix) in children aged 4-6 years. The immunogenicity and reactogenicity of this vaccine regimen was compared with separate injections of DTPa and IPV when given concomitantly with MMR. A cohort of 362 children previously primed with four doses of DTPa and OPV, and a single dose of MMR were randomized to receive either DTPa-IPV+MMR (N=181) or DTPa+IPV+MMR (N=181). Antibody concentrations were measured prior to and 1 month after the booster dose. After immunisation all subjects from both groups had seroprotective antibody levels against diphtheria, tetanus and the three poliovirus serotypes, > or = 96% showed vaccine response to PT, FHA and PRN, all were seropositive to mumps and rubella, and all but one subject were seropositive to measles. Immunogenicity results for each component antigen were similar for DTPa-IPV and separately co-administered DTPa and IPV. Local reactions were common with 24.0% and 31.1% of children experiencing swelling >50mm at the DTPa-IPV and DTPa injection sites, respectively. The DTPa-IPV combination did not increase the incidence or intensity of adverse events compared with separately administered DTPa+IPV. The response to the concomitantly administered MMR vaccine was similar in the two groups and similar to previously reported responses for a second dose of MMR. This combined DTPa-IPV vaccine has a similar reactogenicity profile to DTPa, is immunogenic when given as a booster dose at 4-6 years of age, and has no impact on the immunogenicity of a co-administered second dose of MMR vaccine.	H. Marshall, T. Nolan, D. Roberton, P. Richmond, S. Lambert, J. M. Jacquet and L. Schuerman	Vaccine
275	Effectiveness of measles vaccine given simultaneously with DTP		R. Marshall, J. P. Habicht, P. J. Landrigan, W. H. Foege and H. Delgado	The Journal of tropical pediatrics and environmental child health
6	Antigenic variants in Bordetella pertussis strains isolated from vaccinated and unvaccinated children	Bordetella pertussis shows polymorphism in two proteins, pertactin (Prn) and the pertussis toxin (PT) S1 subunit, which are important for immunity. A previous study has shown antigenic shifts in these proteins in the Dutch B. pertussis population, and it was suggested that these shifts were driven by vaccination. The recent Italian clinical trial provided the opportunity to compare the frequencies of Prn and PT S1 subunit variants in strains isolated from unvaccinated children, and from children vaccinated with two acellular and one whole-cell pertussis vaccine. Four Prn variants (Prn1, Prn2, Prn3 and Prn5) were found in the 129 strains analysed. Prn1, Prn2 and Prn3 have been described previously, whereas Prn5 is a novel variant. Prn1, Prn2, Prn3 and Prn5 were found in, respectively, 6, 41, 51 and 2% of the strains. The B. pertussis strains used to produce the vaccines administered in the clinical trial were found to produce Prn1, or a type which differed from Prn1 in one amino acid. The frequency of the Prn1 variant was found to be lowest in the strains isolated from vaccinated groups, suggesting that Prn1 strains are more affected by vaccine-induced immunity than Prn2 and Prn3 strains. Only one PT S1 type (S1A) was observed in the examined strains, which was distinct from the types produced by the vaccine strains (S1B and S1D). The S1A type also predominates in the Dutch B. pertussis population. The genetic relationship among B. pertussis strains analysed by IS1002-based DNA fingerprinting revealed that three fingerprint types predominate, representing more than 70% of the strains. Prn2 strains showed a greater variety of fingerprint types compared to Prn3, suggesting that Prn3 has emerged more recently. The results are discussed in the light of vaccine-driven evolution.	P. Mastrantonio, P. Spigaglia, H. Oirschot, H. G. Heide, K. Heuvelman, P. Stefanelli and F. R. Mooi	Microbiology (Reading, England)
212	Pattern of functional antibody activity against Haemophilus influenzae type B (Hib) in infants immunized with diphtheria-tetanus-pertussis/Hib Brazilian combination vaccine	We evaluated the functional activity of Haemophilus influenzae B (Hib) antibodies elicited in a group of infants immunized with the diphtheria-tetanus-pertussis vaccine combined with an Hib vaccine produced totally in Brazil after technological transfer of Hib vaccine production from Glaxo SmithKline, Belgium. Blood samples from immunized infants (N = 985) were collected for the determination of Hib antibodies. Total Ig and IgM and IgG subclasses of antibodies against polyribosyl ribitol phosphate (PRP) were analyzed by ELISA. Almost all vaccinees (97.56%, 961/985) developed a strong anti-PRP IgG antibody response (>or=1.0 microg/mL), while an anti-PRP IgM response was observed in 64.24% (634/985) of them (>or=0.15 microg/mL). Only 18.88% (186/985) of the infants in the group with high PRP antibody IgG concentrations (>or=1.0 microg/mL) developed a high IgM antibody response. Anti-PRP IgG antibody levels were significantly higher than anti-PRP IgM. These results demonstrate the predominance of IgG antibodies over IgM antibodies in response to PRP, with a ratio of 17:1. IgG antibodies were predominantly of the IgG1 subclass. An increase in IgG avidity was also observed during the course of immunization.	D. C. Matos, A. M. Silva, P. C. Neves, R. M. Martins, A. Homma and R. Marcovistz	Brazilian journal of medical and biological research = Revista brasileira de pesquisas médicas e biológicas / Sociedade Brasileira de Biofísica ... [et al.]
43	High levels of antibody in adults three years after vaccination with a reduced antigen content diphtheria-tetanus-acellular pertussis vaccine	There is increasing interest in prevention of pertussis in adults by vaccination, but little is known about the duration of the antibody response to pertussis, diphtheria or tetanus in reduced antigen content vaccines formulated for adult use. Follow-up of a clinical trial including 550 adults comparing responses to reduced antigen content diphtheria-tetanus-acellular pertussis (dTpa) vaccine, or a licensed Td vaccine, provided the opportunity to evaluate this. Blood samples were collected at 0, 1, 12, 24 and 36 months following vaccination; of the original cohort of 550, 387 subjects (dTpa group N=310, Td+pa group N=77) were tested at month 36. Following a decrease in antibody levels against all vaccine antigens between one and 24 months following vaccination, levels stabilized during the third year, remaining higher at 36 months than pre-vaccination for all vaccine antigens. In particular, more than 90% of subjects remained seropositive for pertussis toxin and pertactin antibodies at 36 months after vaccination, suggesting ongoing protection against pertussis. Adult-formulated dTpa vaccines could replace Td for routine booster vaccination of older individuals.	P. B. McIntyre, F. M. Turnbull, A. M. Egan, M. A. Burgess, J. M. Wolter and L. M. Schuerman	Vaccine
132	Comparison of the safety and immunogenicity of concomitant and sequential administration of an adult formulation tetanus and diphtheria toxoids adsorbed combined with acellular pertussis (Tdap) vaccine and trivalent inactivated influenza vaccine in adults	The annual contact for influenza vaccination provides an opportunity to ensure that adults have received other recommended vaccines such as Tdap. Healthy 19-64 year-olds were randomized to receive concomitant administration of Tdap and influenza vaccines or influenza vaccine followed (in 4-6 weeks by) Tdap. 720 participants were enrolled. No clinically relevant between-group differences were observed in the rates or severities of erythema, swelling, or pain at the Tdap injection site. Injection-site pain was the most commonly reported adverse event (66.6% concomitant administration group versus 60.8% sequential administration group); most pain was graded as mild and resolved by day 3. Seroprotection and seroresponse rates for all influenza strains were comparable between the two groups. For diphtheria and tetanus, seroprotection rates and post-vaccination GMTs were non-inferior in the concomitant administration group compared to the sequential administration group. A trend for lower antibody responses to pertussis antigens PT, FHA, and FIM was observed after concomitant administration and, for PRN, this difference failed the non-inferiority criteria. While there is a small diminution in antibody response to tetanus and pertussis antigens, concomitant administration of Tdap and influenza vaccine was well tolerated and immunogenic and may offer practical advantages including convenience, compliance, and cost-savings.	S. A. McNeil, F. Noya, M. Dionne, G. Predy, W. Meekison, C. Ojah, S. Ferro, E. L. Mills, J. M. Langley and S. A. Halperin	Vaccine
410	Successful promotion of hepatitis B vaccinations among Vietnamese-American children ages 3 to 18: results of a controlled trial	OBJECTIVE: Chronic infection with the hepatitis B virus is endemic in Southeast Asian populations, including Vietnamese. Previous research has documented low rates of hepatitis B vaccine coverage among Vietnamese-American children and adolescents ages 3 to 18. To address this problem, we designed and tested in a controlled trial 2 public health outreach "catch-up" campaigns for this population. DESIGN: In the Houston, Texas metropolitan area, we mounted a media-led information and education campaign, and in the Dallas metropolitan area, we organized a community mobilization strategy. We evaluated the success of these interventions in a controlled trial, using the Washington, DC metropolitan area as a control site. To do so, we conducted computer-assisted telephone interviews with random samples of approximately 500 Vietnamese-American households in each of the 3 study sites both before and after the interventions. We assessed respondents' awareness and knowledge of hepatitis B and asked for hepatitis B vaccination dates for a randomly selected child in each household. When possible, we validated vaccination dates through direct contact with each child's providers. RESULTS: Awareness of hepatitis B increased significantly between the pre- and postintervention surveys in all 3 areas, and the increase in the media education area (+21.5 percentage points) was significantly larger than in the control area (+9.0 percentage points). At postintervention, significantly more parents knew that free vaccines were available for children in the media education (+31.9 percentage points) and community mobilization (+16.7 percentage points) areas than in the control area (+4.7 percentage points). An increase in knowledge of sexual transmission of hepatitis B virus was significant in the media education area (+14.0 percentage points) and community mobilization (+13.6 percentage points) areas compared with the control area (+5.2 percentage points). Parent- or provider-reported data (n = 783 for pre- and n = 784 for postintervention surveys) suggest that receipt of 3 hepatitis B vaccinations increased significantly in the community mobilization area (from 26.6% at pre- to 38.8% at postintervention) and in the media intervention area (28.5% at pre- and 39.4% at postintervention), but declined slightly in the control community (37.8% at pre- and 33.5% at postintervention). Multiple logistic regression analyses estimated that the odds of receiving 3 hepatitis B vaccine doses were significantly greater for both community mobilization (odds ratio 2.15, 95% confidence interval 1.16-3.97) and media campaign (odds ratio 3.02, 95% confidence interval 1.62-5.64) interventions compared with the control area. The odds of being vaccinated were significantly greater for children who had had at least 1 diphtheria-tetanus-pertussis shot, and whose parents were married, knew someone with liver disease, had heard of hepatitis B, and had greater knowledge about hepatitis B. The odds of being vaccinated were significantly lower for older children. CONCLUSIONS: Both community mobilization and media campaigns significantly increased the knowledge of Vietnamese-American parents about hepatitis B vaccination, and the receipt of "catch-up" vaccinations among their children.	S. J. McPhee, T. Nguyen, G. L. Euler, J. Mock, C. Wong, T. Lam, W. Nguyen, S. Nguyen, M. Q. Huynh Ha, S. T. Do and C. Buu	Pediatrics
17	Relationships between functional assays and enzyme immunoassays as measurements of responses to acellular and whole-cell pertussis vaccines	OBJECTIVE: To examine the relationships between functional assays and antigen-specific enzyme immunoassays in sera from a multicenter trial of 13 different experimental acellular pertussis vaccines and 2 licensed whole-cell vaccines, and to determine whether correlations previously observed among assays of specimens from pertussis patients and whole-cell vaccinees would apply to specimens from infants immunized with purified components in acellular vaccines. METHODS: Postimmunization sera were assayed for immunoglobulin G antibodies to pertussis toxin (PT), filamentous hemagglutinin, pertactin (PRN), and a mixture of types 2 and 3 fimbriae (FIM) by enzyme-linked immunosorbent assay, for whole-cell agglutinins (AGGs) and for PT-neutralizing antibodies by the Chinese hamster ovary (CHO) cell assay. Assay results were compared for individual sera, as well as for geometric mean antibody concentrations or titers (GMTs) calculated by vaccine or overall. RESULTS: For the 15 vaccines, the PT GMTs were highly correlated with the CHO assay GMTs (r = .92), and the FIM GMTs were highly correlated with the AGG GMTs (r = .96). For individual postvaccination sera, there was a significant correlation between the CHO titers and levels of antibody to PT whether the 15 vaccines were considered separately (.59 < or = r < or = .85) or combined (r = .81). For individual sera from infants immunized with the two whole-cell vaccines or any of the four acellular vaccines containing FIM, a strong correlation between AGG titer and FIM antibody was observed whether the vaccines were considered separately (.83 < or = r < or = .91) or together (r = .86). One vaccine without detectable FIM produced a measurable AGG response; for this vaccine, a moderate but significant correlation (R = .58) between PRN antibody and AGG titer was observed. CONCLUSION: These data indicate that appropriate antigen-specific enzyme-linked immunosorbent assays will furnish results similar to those provided by the CHO and AGG assays in the evaluation of the immunogenicity of component vaccines. Antibodies to FIM seem to include the most important AGGs; however, there is evidence that agglutination by PRN antibody may be detected in the absence of antibody to FIM.	B. D. Meade, F. Lynn, G. F. Reed, C. M. Mink, T. A. Romani, A. Deforest and M. A. Deloria	Pediatrics
151	Immunogenicity of Infanrix? hexa administered at 3, 5 and 11 months of age	A pooled analysis of data from four vaccination studies conducted in Europe was undertaken to assess the immunogenicity of Infanrix? hexa (DTPa-HBV-IPV/Hib, GlaxoSmithKline Biologicals) when administered in a total of 702 healthy infants at 3, 5 and 11-12 months of age. One month after dose 2, between 96.3% and 100% of subjects had seroprotective antibodies against diphtheria, tetanus, hepatitis B and poliovirus types 1, 2 and 3; 91.7% against Hib and ?99.0% were seropositive for each pertussis antigen. One month after the third dose, 98.9-100% of subjects were seroprotected/seropositive for all vaccine antigens. Geometric mean antibody concentrations/titres for each vaccine antigen increased by 6.7-52.9 fold after the third vaccine dose. No serious adverse events in DTPa-HBV-IPV/Hib recipients were vaccine related. Infanrix? hexa induces an adequate immune response after 2-dose primary plus booster doses when administered according to a 3, 5 and 11 months schedule.	O. Meeren, S. Kuriyakose, D. Kolhe and K. Hardt	Vaccine
342	Pertussis-specific celluar immunological answer after combined immunisation with DTaP-HBV-Hib mi/ without IPV		C. U. Meyer, P. Habermehl, P. Schmidtke, A. Schuind, A. Kaufhold, M. Slaoui and F. Zepp	Monatsschrift fur Kinderheilkunde
23	Serological evidence of pertussis in patients presenting with cough in general practice in Birmingham	Three hundred and fifty-six patients in a large suburban practice (registered population 10,400), were diagnosed clinically with acute laryngitis/tracheitis or whooping cough (acute spasmodic cough of three weeks duration) between March 1996 and November 1997. Forty out of 145 who provided specimens for serological testing had evidence of recent infection with Bordetella pertussis. During the study a further 18 patients (mostly younger patients who presented early) had a diagnosis of pertussis confirmed by culture. Fifty-eight cases of pertussis in this population and time period was equivalent to an annual incidence of 330 per 100,000, whereas statutory notifications of pertussis in England and Wales suggested an incidence of less than 4 per 100,000 in the same period. Whooping cough remains an important cause of respiratory illness in all age groups. These results are a reminder for general practitioners to be alert to the diagnosis and a prompt to reconsider national vaccination policy.	E. Miller, D. M. Fleming, L. A. Ashworth, D. A. Mabbett, J. E. Vurdien and T. S. Elliott	Communicable disease and public health / PHLS
136	Metabolic and hematologic effects and immune complex formation related to pertussis immunization	Selected metabolic, hematologic, and immunologic functions were evaluated in 3- to 6-mo-old Finnish infants who received whole-cell pertussis-component diphtheria and tetanus toxoids and pertussis vaccine, adsorbed (DTP) vaccine, and in 4- to 6-y-old Los Angeles children who received either a licensed DTP vaccine or an acellular pertussis component DTP vaccine. One d after immunization, there was an increase in total leukocytes and neutrophils and a decrease in lymphocytes in all vaccinees. In 4- to 6-y-old children the leukocytosis and neutrophilia were greater in recipients who received the standard DTP vaccine than in vaccinees who received an acellular pertussis component DTP vaccine. In infants there was an increase in the mean plasma insulin concentration but no change in the glucose concentration 24 h after immunization; no increase in the mean plasma insulin was noted in the 4- to 6-y-old children. Three 4- to 6-y-old vaccinees had higher circulating immune complex concentrations after immunization and two of these children had high clinical reaction scores. The etiology of adverse reactions after DTP immunization is multifactorial. In contrast with findings in animals, our findings do not demonstrate a clinically significant effect due to lymphocytosis-promoting factor on glucose metabolism in vaccinated children. Neutrophilia in vaccinees is probably due to endotoxin, and some reactions may be due to circulating immune complexes.	C. M. Mink, M. Uhari, D. A. Blumberg, M. Knip, K. Lewis, P. D. Christenson, M. Toyoda, S. C. Jordan, S. R. Levin and J. D. Cherry	Pediatric research
391	Double-blind study on the effectiveness of chlophedianol-sobrerol in the treatment of infantile whooping-cough	Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	M. Miraglia del Giudice, A. F. Capristo and G. Mirra	Minerva Pediatrica
300	Induction of Bordetella pertussis-specific immune memory by DTPa vaccines		S. Morel, P. Denoel, F. Godfroid, C. Cortvrindt, N. Vanderheyde and J. Poolman	Vaccine
65	Comparison of acellular and whole-cell pertussis-component DTP vaccines. A multicenter double-blind study in 4- to 6-year-old children	An acellular pertussis-component combined diphtheria and tetanus toxoids, and pertussis (APDT) vaccine adsorbed was compared with a licensed whole-cell pertussis-component combined diphtheria and tetanus toxoids, and pertussis (DTP) vaccine adsorbed for reactogenicity and immunogenicity when given as the fifth DTP immunization to eighty-two 4- to 6-year-old children. The reaction rates with both vaccines were low; APDT vaccine recipients had significantly less pain and warmth at the injection site than did DTP vaccine recipients. Antibody responses to pertussis antigens (lymphocytosis-promoting factor, filamentous hemagglutinin, and agglutinogens) and to diphtheria and tetanus toxoids were all brisk. The APDT vaccine recipients had a more marked response in antibodies to filamentous hemagglutinin and a less marked response in agglutinins than whole-cell vaccine recipients. On the day after immunization, both APDT and DTP vaccine recipients had an increase in mean leukocyte and neutrophil counts. This APDT vaccine is immunogenic and less reactogenic than a DTP vaccine with a whole-cell pertussis component when administered as a booster to 4- to 6-year-old children.	C. M. Morgan, D. A. Blumberg, J. D. Cherry, K. S. Reisinger, M. M. Blatter, J. L. Blumer, C. L. Dekker, M. G. Stout and P. D. Christenson	American journal of diseases of children (1960)
237	Initiatives to improve childhood immunisation uptake: a randomised controlled trial		M. Z. Morgan and M. R. Evans	BMJ (Clinical research ed.)
375	[Basic and clinical study of meropenem in pediatric field]	Meropenem (MEPM), a novel parenteral carbapenem antibiotic, was examined in a cooperative study involving 12 pediatric and 1 neonatologic facilities. The results are summarized as follows. 1. Antibacterial activity Antibacterial activity of MEPM against stock organisms including 31 strains of Streptococcus agalactiae, 14 of Listeria monocytogenes, 4 of Bordetella pertussis and 3 of Neisseria meningitidis ranged from 0.025 to 0.10 micrograms/ml in MIC90's, which were equal or lower than those of control drugs such as imipenem cefazolin, cefotiam, cefotaxime, ceftazidime and latamoxef. MICs against clinical isolates were as follows: In Gram-positive bacteria, MICs were 0.20 micrograms/ml to 6.25 micrograms/ml against 3 strains of Staphylococcus aureus, and 0.025 micrograms/ml or less against 4 of Streptococcus pneumoniae. In Gram-negative bacilli, MICs were 0.10 micrograms/ml to 0.20 micrograms/ml against 3 strains of Haemophilus influenzae and 0.78, 0.10 and 0.78 micrograms/ml, respectively, against one strain each of Enterobacter cloacae, Morganella morganii and Pseudomonas aeruginosa. MIC against 1 strain of Peptococcus saccharolyticus was < or = 0.025 micrograms/ml. 2. Pharmacokinetics Maximum plasma concentrations after intravenous infusion of MEPM over 30 minutes at doses of 10, 20 and 40 mg/kg, respectively, to 3 different groups of 3 children (total 9 cases) were observed at the completion of the treatment. Mean maximum concentrations in the 3 groups were 36.3, 69.5 and 129.8 micrograms/ml, respectively, exhibiting clear dose response. Mean plasma half lives in beta phase were 0.94, 0.86 and 0.94 hours, respectively, exhibiting no difference by doses, and this trend was observed also by HPLC. Urinary excretion rates in the first 6 hours after dose in the 10, 20 and 40 mg/kg groups were 67.3, 65.6 and 68.4%, respectively. Concentrations of MEPM in cerebrospinal fluid were determined in 2 cases of pyogenic meningitis. In 1 case, 500 mg (5.9 mg/kg) of MEPM was infused intravenously over 30 minutes and concentrations on Days 6, 8 and 15 observed at 190, 60 and 100 minutes after respective doses were 0.13, 0.10 micrograms/ml and less than the detection limit. Cerebrospinal fluid-plasma concentration ratio was determinable only on Day 8 and was 2.8%. In another case to which 250 mg (38.5 mg/kg) of MEPM was infused intravenously over 30 minutes, the concentration at Days 6, 7 and 10, 1 hour after the dose were less than the detection limit on day 6, and 2.04 and 2.62 micrograms/ml, respectively on days 7 and 10. 3. Clinical efficacy Clinical efficacies were evaluated in 49 cases and the efficacy rate was 93.9%.(ABSTRACT TRUNCATED AT 400 WORDS)	T. Motohiro, S. Oki, N. Tsumura, H. Sasaki, K. Oda, T. Koga, Y. Sakata, F. Yamashita, N. Takajo and K. Aida	The Japanese journal of antibiotics
45	Safety and immunogenicity of Haemophilus influenzae type B-Neisseria meningitidis group B outer membrane protein complex conjugate vaccine mixed in the syringe with diphtheria-tetanus-pertussis vaccine in young Gambian infants	To ensure compliance and to reduce costs it is important, especially in less developed countries, that programs of child immunization should require as few clinic attendances and as few injections as possible. Therefore we have investigated whether a Haemophilus influenzae type b conjugate vaccine could be given safely and effectively with diphtheria-tetanus-pertussis vaccine (DTP). One hundred twenty-six Gambian infants were given both polyribosylribitol phosphate (PRP)-outer membrane protein complex (PedvaxHIB) and DTP on the same day at 8, 12 and 16 weeks of age; 60 were given the vaccines mixed in the syringe and 66 were given the vaccines separately. To minimize the injection volume the dose of PRP-OMPC used in both groups was 7.5 micrograms, which is half the usual dose. There were no significant differences in anti-PRP antibody titers between the groups after 1, 2 or 3 doses. The geometric mean titers of antibody for the two groups combined were 0.29 micrograms/ml 1 month after the first dose, 1.03 micrograms/ml after the second dose and 1.11 micrograms/ml after the third dose. Concentrations of antibodies to diphtheria, tetanus and pertussis 1 month after the third dose were not significantly different between the two groups. Systemic side effects were reported with equal frequency in the two groups and were similar to those reported elsewhere for DTP. Tenderness at the injection site was more common where the combined injection (0.75 ml) had been given than where DTP alone (0.5 ml) had been given. The main drawback to the use of these 2 vaccines together is the complexity of the mixing procedure used in this clinical trial.	E. K. Mulholland, V. I. Ahonkhai, A. M. Greenwood, L. C. Jonas, L. J. Lukacs, C. M. Mink, J. M. Staub, J. Todd, P. P. Vella and B. M. Greenwood	The Pediatric infectious disease journal
399	Randomised trial of Haemophilus influenzae type-b tetanus protein conjugate for prevention of pneumonia and meningitis in Gambian infants	Background. In developing countries, pneumonia and meningitis due to Haemophilus influenzae type b (Hib) are common in children under age 12 months and the mortality from meningitis is high. Protein-polysaccharide conjugate vaccines have brought Hib disease under control in industrialised countries. We did a double-blind randomised trial in The Gambia to assess the efficacy of a Hib conjugate vaccine for the prevention of meningitis, pneumonia, and other invasive diseases due to Hib. Methods. Between March, 1993, and October, 1995, 42,848 infants were randomly allocated the conjugate vaccine Hib polysaccharide tetanus protein (PRP-T) mixed with diphtheria-tetanus-pertussis vaccine (DTP), or DTP alone at age 2 months, 3 months, and 4 months. Children who presented with signs of invasive Hib were investigated by blood culture and, where appropriate, by lumbar puncture, chest radiograph, or percutaneous lung aspirate. Children were followed up for between 5 and 36 months. Findings. The median ages at which children received the study vaccine were 11 weeks, 18 weeks, and 24 weeks. 83% of children enrolled received all three doses of vaccine. 17 cases of culture-positive Hib pneumonia, 28 of Hib meningitis, and five of other forms of invasive Hib disease were detected amongst the study children. The efficacy of the vaccine for the prevention of all invasive disease after three doses was 95% (PRP-T vaccinees 1, controls 19 (95% CI 67-100)), for the prevention of Hib pneumonia after two or three doses, 100% (vaccinees 0, controls 10 (55-100)), and for the prevention of radiologically defined pneumonia at any time after enrolment, 21.1% (PRP-T vaccinees 198, controls 251 (4.6-34.9)). Interpretation. PRP-T conjugate Hib vaccine prevented most cases of meningitis and pneumonia due to Hib in Gambian infants. The reduction in the overall incidence of radiologically defined pneumonia in PRP-T vaccinees suggests that about 20% of episodes of pneumonia in young Gambian children are due to Hib. The introduction of Hib vaccines into developing countries should substantially reduce childhood mortality due to pneumonia and meningitis. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	K. Mulholland, S. Hilton, R. Adegbola, S. Usen, A. Oparaugo, C. Omosigho, M. Weber, A. Palmer, G. Schneider, K. Jobe, G. Lahai, S. Jaffar, O. Secka, K. Lin, C. Ethevenaux and B. Greenwood	Lancet
74	Pertussis in a rural area of Kenya: epidemiology and results of a vaccine trial	Pertussis surveillance was carried out from 1974 to 1981 among a population of 24 000 in the Machakos district of Kenya by fortnightly or monthly home visits. The diagnosis was verified by a physician according to standard criteria including bacteriological and haematological findings. Since not all cases could be diagnosed with certainty, each case was scored from 0 to 3 according to the probability of pertussis. During the surveillance a vaccine trial was carried out: 436 children receiving two diphtheria-pertussis-tetanus (DPT) immunizations 6 months apart were compared with 466 children receiving the conventional three doses 3 months apart.The agglutinating antibody response was determined in approximately 100 children in the trial at 1 month, 2 years, 3(1/4) years and 4(1/4) years after completing the immunizations. The results showed no difference in titres between the 2-dose and 3-dose groups at one month after the last immunization. Waning of antibodies proceeded more rapidly in the 2-dose group, the differences between both groups becoming statistically significant after 2 years.Two epidemic waves of pertussis occurred during the seven years of surveillance. A third epidemic did not materialize, possibly because of increased herd immunity due to the immunizations. The case fatality rate was 1% and was highest (2.6%) among infants. During the 4 years following completion of the immunizations, 36 children in the vaccine trial, based on the cumulative probability of pertussis, yielded 16.7 cases. The number of "cases" so defined did not differ significantly between the two immunized groups, although there was a suggestion of greater protection with the 3-dose schedule. Compared with the observed number of "cases" among 1281 children of the same birth cohorts not included in the trial, the reduction among the trial children (both immunized groups) was 54%.	A. S. Muller, J. Leeuwenburg and A. M. Voorhoeve	Bulletin of the World Health Organization
79	Evaluation of the pertussis components of diphtheria-tetanus-pertussis vaccine	The adjuvant and antigen components of the pertussis fraction of diphtheria-tetanus-pertussis (DTP) vaccine were evaluated. Four preparations of DTP vaccine composed of either whole cell (Wc) or extracted (E) pertussis antigen combined with either an aluminum phosphate (Ph) or alum (Al) adjuvant were compared. Local reactions were similar in all four vaccines after the first two immunizations but were significantly increased in incidence and severity following the third immunization with vaccine WcPh. This appeared to be due to the Ph adjuvant rather than the antigen component. Febrile reactions were experienced more often (P = .0009) and with higher temperatures (P = .0001) with the WcPh vaccine following the first immunization. This appeared to be due to the Wc component. Comparing the pooled Wc groups with the pooled E groups revealed a greater febrile response in the Wc group after both the first (P = .0008) and the second (P = .03) immunization. Local reactions appear temporally and etiologically to be distinct from febrile reactions. The pooled Wc antigen group produced a higher geometric mean titer than the pooled E antigen group (P = .05). Serologic responses, with respect to geometric mean titer, were not significantly different among the individual vaccines. This study suggests that the combination of whole cell and aluminum phosphate, which is currently in use in the United States, is probably not the optimal formulation for pertussis vaccine.	M. D. Murphy, J. Rasnack, H. D. Dickson, M. Dietch and P. A. Brunell	Pediatrics
412	Low-income minority mothers' reports of infant health care utilisation compared with medical records	This study aimed to investigate mothers' reporting of the nature, location, frequency and content of health care visits for their infants, as compared with data abstracted from the infants' medical records. It was part of a community-based parenting intervention designed to improve preventive health care utilisation among minority mothers in Washington, DC. Mothers >or=18 years old with newborn infants and with poor or no prenatal care were enrolled in the study. A total of 160 mother-infant dyads completed the 12-month study. Mothers were interviewed when the infants were 4, 8 and 12 months old, and were asked to recall infant visits to all health care providers. Medical records from identified providers were used for verification. The number and type of immunisations given, types of providers visited, and reason for the visits were compared. Only about a quarter of mothers agreed with their infants' medical records on the number of specific immunisations received. The mothers reported fewer polio (1.8 vs. 2.1, P = 0.006), diphtheria and tetanus toxoids and pertussis (DTP) (1.8 vs. 2.2, P = 0.002), and Haemophilus influenzae type b (HiB) (1.3 vs. 2.1, P < 0.0001) immunisations than were recorded. Similarly, about a quarter of the mothers were unaware of any polio, DTP or hepatitis B immunisations given, as documented in the medical records, and 38% did not know that their infant was immunised for HiB. Nearly half of the mothers recalled more infant doctors' visits than were recorded in the medical records (4.1 vs. 3.6 visits, P = 0.017). The mothers generally disagreed with the providers about the reason for a particular visit and reported fewer sick-baby visits (1.5 vs. 3.3, P < 0.0001) than the providers recorded. Mothers' reports and medical records matched in only 19% of the cases. In 47%, mothers under-reported and in 34% over-reported the total number of visits. The strongest agreement between mothers' reports and medical records was in the case of emergency room visits (63%). In conclusion, in this population, mothers' reporting did not match that of providers with respect to specific information: the number of immunisations, the location where services were provided, and the classification of sick- vs. well-baby visits. Future studies that evaluate health care utilisation data should take these discrepancies into consideration in their selection of information source, and in their interpretation of the data.	K. D. Murray, A. A. El-Mohandes, M. N. El-Khorazaty and M. Kiely	Paediatric and perinatal epidemiology
282	Simultaneous infection with Bordetella pertussis and respiratory syncytial virus in hospitalized children	We compared three groups of hospitalized children with Bordetella pertussis infection, respiratory syncytial virus (RSV) infection and dual B. pertussis/RSV infections in an effort to establish clinical and laboratory criteria by which to distinguish children with dual infections from children infected with either organism alone. The groups were compared for admission laboratory data, history of present illness, perinatal history and immunization history. Children with pertussis were more likely to have been premature (less than 37 weeks gestation) than children with RSV infections only (11 of 29 vs. 1 of 22, chi square test, 5.94, P less than 0.02). Other than B. pertussis and RSV fluorescent antibody testing and culture, there were no laboratory or clinical criteria by which to differentiate these children consistently at the time of hospital admission. For purposes of medical management and infection control, pertussis or simultaneous infection with pertussis should be considered in young children hospitalized for presumed viral respiratory illness	W. L. Nelson, R. S. Hopkins, M. H. Roe and M. P. Glode	Pediatric Infectious Disease
16	Genetic approaches to a vaccine for pertussis		L. Nencioni, M. Pizza, G. Volpini, A. Podda and R. Rappuoli	Advances in experimental medicine and biology
230	Vitamin A supplements are well tolerated with the pentavalent vaccine	The Expanded Programme on Immunisation provides an opportunity to deliver vitamin A supplements to young infants in order to improve their vitamin A status. However, concerns have been raised about the safety of administering high dose vitamin A supplements to infants less than 6 months of age in developing countries. A randomized controlled trial was carried out by the Kintampo Health Research Centre to assess the safety and immunogenicity of administering 15 mg retinol equivalent (RE)1 vitamin A alongside the pentavalent "diphtheria-polio-tetanus-Haemophilus influenzae b-hepatitis B vaccine" at 6, 10 and 14 weeks of age. All mothers received a post-partum supplement of 120 mg RE vitamin A as per national policy. Mothers of infants who had been vaccinated were visited 24 h after vaccination to assess the side effects of the vaccine. They were also interviewed about adverse events which may have occurred in the past 4 weeks since the child was vaccinated. There were significantly fewer reports of illnesses and fever in infants who had been given vitamin A compared to infants in the control group. The pentavalent vaccine was found to be tolerable when administered with vitamin A according to the WHO/EPI schedule for infant immunisation at 6, 10 and 14 weeks. There were few complaints made by the mothers of the children which were not thought to be related to giving vitamin A with the vaccines. There were six deaths in the trial, five in the intervention group and one in the control RR 4.65 (0.55-39.5), p = 0.12. Due to the high point estimate of 4.65, we wish to urge caution in administering high doses of vitamin A to young infants with the pentavalent vaccine at 6, 10 and 14 weeks of age.	S. Newton, S. Owusu-Agyei, S. Filteau, T. Gyan and B. R. Kirkwood	Vaccine
235	Haemophilus influenzae type b conjugate vaccine diluted tenfold in diphtheria-tetanus-whole cell pertussis vaccine: a randomized trial	BACKGROUND: Despite their proven efficacy Haemophilus influenzae type b (Hib) conjugate vaccines are not given to most children in the developing world in the face of an estimated global Hib disease burden of nearly 2 million cases per annum. A major barrier to the introduction of the vaccine would be overcome by diluting the vaccine 10-fold in diphtheria-tetanus-whole cell pertussis (DTP). We report a randomized trial comparing the use of Hib conjugate vaccine diluted in a multidose vial of DTP with that of the full Hib dose. METHODS: We randomized 168 infants to receive either the full dose Hib polysaccharide-tetanus toxoid conjugate (PRP-T) vaccine or a 1/10 dilution prepared by reconstituting the full dose in a 10-dose DTP vial. Infants were vaccinated at 6, 10 and 14 weeks of age and received a full dose as a test of immunologic memory at 9 months of age. Sera were collected at each visit and at 1 week after the booster dose. Serum anti-capsular PRP antibody concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: After the primary vaccination series, 95% of infants in the full dose arm and 94% of infants in the 1/10 dose arm achieved anti-PRP IgG antibody concentrations of > or = 1.0 microg/ml. Infants receiving the diluted vaccine had significantly higher titers of anti-PRP antibody in response to the booster dose (151.36 microg/ml vs. 68.55 microg/ml, P = 0.009). CONCLUSIONS: The 1/10 dose of PRP-T was as immunogenic and safe as the full dose. The technique of diluting a single dose of PRP-T in a 10-dose DTP vial could potentially allow the widespread introduction of Hib vaccine in resource-poor countries currently unable to afford full dose Hib conjugate vaccine.	M. Nicol, R. Huebner, R. Mothupi, H. Käyhty, N. Mbelle, E. Khomo and K. P. Klugman	The Pediatric infectious disease journal
187	A fourth dose of DTPa-IPV vaccine given to 4-6 year old children in Italy and Sweden following primary vaccination at 3, 5 and 11-12 months of age	Healthy 4-6 y old children from Italy and Sweden immunized with DTPa and inactivated or oral polio vaccines at 3, 5 and 11-12 months of age, received 1 dose of combined DTPa-IPV (n = 211) or DTPa + IPV as separate doses (n = 205) in a randomized trial. The pre-booster seroprotection rates were similar in each group and were above 60% against all antigens except diphtheria (31.3% and 37.0%) and PT (21.5% and 25.9%) in the DTPa-IPV and DTPa + IPV groups, respectively. At least 99.5% of subjects had seroprotective antibody levels against diphtheria, tetanus and polioviruses and > or = 96% showed a vaccine response to each pertussis antigen after vaccination. Post-booster antibody levels increased at least 51-fold for anti-diphtheria and anti-tetanus, at least 18-fold for anti-pertussis antibodies and at least 32-fold for antibodies against all 3 poliovirus types, compared to prior levels. DTPa-IPV was comparable to DTPa + IPV in terms of seroprotection rates and mean antibody levels against each vaccine antigen. Similar reactogenicity profiles were observed between groups including swelling > 50 mm [13% (9.1, 18.7) vs 17% (12.4, 23.4)] or involving an adjacent joint [0% (-,-) vs 1.5% (0.3, 4.3)] and were consistent with previous reports. The combined DTPa-IPV vaccine could be used to add DTP valences to the IPV vaccine currently given to children in Scandinavia and Italy at 4-6 y of age and reinforce protection against 4 diseases.	L. Nilsson, G. Faldella, J. M. Jacquet, J. Storsaeter, S. A. Silfverdal and L. Ekholm	Scandinavian journal of infectious diseases
64	Pertussis IgE and atopic disease	BACKGROUND: Pertussis toxin (PT) stimulates IgE production in animals, and pertussis vaccination and whooping cough may have similar effects in man. METHODS: We analyzed IgE responses to PT (PT-IgE) in sera from children primarily immunized with three doses of either an acellular 2- or 5-component vaccine, or a whole-cell (Wc) pertussis vaccine, and in children after whooping cough. The study comprised 50 children with both atopic disease and positive skin prick test, 99 nonatopic controls, and 40 children with verified pertussis. RESULTS: Immunoglobulin E antibodies against PT were demonstrated in 19% and 24% of sera from vaccinated children at 7 and 12 months, respectively, and in 9% at 2.5 years. At 7 months, PT-IgE was more common after vaccination with acellular (24%) than with the Wc vaccine (3%, P = 0.02). PT-IgE was also more common (P = 0.001) after vaccination in children classified as atopic (36%) than in the control group (10%). Thirty percent of the children with pertussis had PT-IgE, more often so in atopic than nonatopic children (P = 0.02). CONCLUSIONS: Transient production of PT-IgE seems to be common after primary pertussis immunization with acellular vaccines, and after whooping cough, particularly in atopic subjects.	L. Nilsson, C. Grüber, M. Granström, B. Björkstén and N. I. Kjellman	Allergy
355	Atopic disease at 7 years pertussis vaccination in infancy. Results from a randomised controlled trial of three vaccines		L. Nilsson, N. I. M. Kjellman and B. BjÃ¶rkstÃ©n	European Respiratory Journal
85	Comparative trial of cephacetrile versus cephaloridine in the treatment of secondary respiratory infections in childhood pertussis		F. Nola and M. L. Soranzo	Arzneimittel-Forschung
189	A combined liquid Hib (PRP-OMPC), hepatitis B, diphtheria, tetanus and whole-cell pertussis vaccine: controlled studies of immunogenicity and reactogenicity	We evaluated the immunogenicity and reactogenicity of a new liquid pentavalent combination vaccine, which incorporates a diphtheria, tetanus and whole-cell pertussis vaccine (DTP) with Hib (PRP-OMPC) and hepatitis B vaccine (HB), in a series of three studies involving 2156 infants. The vaccination schedule was 2, 4, 6 and 18 months for all studies. In addition, subjects in the third study also received a dose of monovalent hepatitis B vaccine at birth. The principal study was a randomised double blind trial of two separate, but concurrently administered vaccines in each of three groups: pentavalent vaccine [DTP-Hib-HB] plus placebo (Group A, n=619); quadrivalent vaccine [DTP-HB] plus Hib vaccine (Group B, n=620); and bivalent vaccine [Hib-HB] plus DTP (Group C, n=226). The second study (Group D, n=231) was an open trial of three separate, but concurrently administered licensed control vaccines (DTP, Hib and HB). The third study (Group E, n=460) administered a dose of monovalent hepatitis B vaccine at birth followed by pentavalent vaccine as for Group A. Subjects were bled prior to the 2- and 18-month vaccinations, and a month after the 6- and 18-month vaccinations. A diary card was used to record subject temperatures and other systemic and local clinical signs for 7 days after each vaccination. The pentavalent vaccine, whether or not preceded by a birth dose of hepatitis B vaccine, was generally well tolerated at all administration times, and had a reactogenicity profile similar to that observed for licensed vaccine controls. Diphtheria and tetanus antibody levels were substantially above protective levels in all study groups. The anti-HBs responses (% > or = 10 mIU/ml) following the 6-month dose of vaccines were, respectively, for Groups A-E: 83.2, 91.7, 96.5, 98.8 and 93.9%, and following the 18-month doses: 87.9, 97.5, 98.8, 98.8 and 92.8%. Anti-PRP responses (% > or = 1.0 microg/ml) following the 6-month dose for Groups A-D were 86.0, 90.5, 91.2, and 74.4%, and after the 18-month dose for Groups A-E were 97.3, 98.3, 98.1, 97.0, and 99.5%. Consistently higher geometric mean titres (GMTs) for pertussis antibodies to agglutinogens (Agg2, Agg3) and pertactin were recorded for the pentavalent vaccine compared to the licensed control vaccine, though they were somewhat lower for pertussigen (PT). Except for the hepatitis B response, antibody responses induced by the pentavalent vaccine to all antigens with a schedule commencing at 2 months of age and completed at 18 months were equivalent to responses to the same antigens induced by the separate, but concurrently administered licensed control vaccines. A regimen of a birth dose of hepatitis B vaccine followed by pentavalent vaccine at 2, 4, 6 and 18 months was not countered by any clinically significant decrease in seroresponses.	T. Nolan, G. Hogg, M. A. Darcy, M. Skeljo, J. Carlin and J. Boslego	Vaccine
154	DTPa-HBV-IPV vaccine for primary vaccination of infants	AIM: Combined vaccines have an increasingly important role to play in delivering these antigens acceptably. We describe the immunogenicity and reactogenicity of a combined DTPa-HBV-IPV vaccine (diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus (DTPa-HBV-IPV: Infanrix penta) ) when administered for the primary vaccination of infants resulting from a study where the primary objective was to demonstrate non-inferiority of the immune response induced by DTPa-HBV-IPV using an industrial-scale IPV production process. METHODS: Three hundred and fourteen infants received primary immunisation with DTPa-HBV-IPV at 2, 4 and 6 months of age. Routine Haemophilus influenzae immunisation was performed at 2 and 4 months of age at a separate injection site. Blood samples were taken at 2 and 7 months of age. Reactogenicity was assessed using diary cards for 7 days after each dose. RESULTS: One month after the primary course, at least 98.9% of subjects achieved seroprotective antibody concentrations/titres against diphtheria, tetanus, hepatitis-B and polio types 1, 2 and 3. More than 97% had a vaccine response to pertussis antigens. The incidence of local injection site reactions after DTPa-HBV-IPV was similar to that for the Haemophilus influenzae vaccine site. General reactions of Grade 3 intensity were uncommon. CONCLUSIONS: The DTPa-HBV-IPV vaccine is a new combination of vaccines previously available separately, with established effectiveness and safety profiles. Combined vaccines reduce storage requirements and minimise the number of injections required, thereby reducing distress for infants and parents. DTPa-HBV-IPV was immunogenic with an acceptable safety profile and could replace separate administration of DTPa, HBV and IPV vaccines in infants.	T. Nolan, S. Lambert, D. Roberton, H. Marshall, P. Richmond and C. Streeton	Journal of paediatrics and child health
158	A novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus-toxoid conjugate vaccine is immunogenic and induces immune memory when co-administered with DTPa-HBV-IPV and conjugate pneumococcal vaccines in infants	Immunogenicity and safety of a novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus-toxoid conjugate vaccine (Hib-MenCY-TT) candidate was evaluated when co-administered with DTPa-HBV-IPV(Pediarix)+PCV7(Prevnar) at 2-4-6 months of age. Anti-PRP concentrations >or= 1.0 microg/mL were observed in 92.9-98.7%, rSBA-MenC/Y titres >or= 1:8 in >98%, rSBA-MenC/Y titres >or= 1:128 in >95.8 and >89.9% subjects. PRP and MenC responses were similar to respective controls (ActHIB and Menjugate) including for antibody persistence. Response to co-administered vaccines was not impaired. Polysaccharide challenge (PRP, PSC, PSY at 11-14 months of age) evidenced immune memory was induced for Hib, MenC/Y conjugate components. The safety profile of Hib-MenCY-TT was similar to controls. Hib-MenCY-TT administered according to the current US Hib vaccine schedule has the potential to induce protective antibodies against Hib and meningococcal-CY disease in infants and toddlers.	T. Nolan, S. Lambert, D. Roberton, H. Marshall, P. Richmond, C. Streeton, J. Poolman and D. Boutriau	Vaccine
202	Impact of osmolality on burning sensations during and immediately after intramuscular injection of 0.5 ml of vaccine suspensions in healthy adults	A randomised placebo controlled double-blind cross-over trial was performed on twenty healthy adults to assess the effect of osmolality (300,600,850 and 1100 mOsm) on local tolerance of an intramuscular injection (0.5 ml) of five suspensions containing the same components as the excipients of a combined Diphtheria-Tetanus-acellular Pertussis-inactivated Poliomyelitis-Haemophilus influenzae type b paediatric vaccine (DtacP-IPV-Hib, PENTAVAC). The results did not show any dose-effect relationship between burning or pain sensations and the different osmolalities tested. Although mild and not clinically relevant, these sensations seemed to occur more frequently following injection of an isotonic saline solution (P<0.05). Thus, the osmolality of vaccine like suspensions does not appear to be a potential cause of local pain or burning sensation after their administration.	P. Nony, P. Girard, S. Chabaud, L. Hessel, C. Thébault and J. P. Boissel	Vaccine
368	The antibiotic treatment of pertussis		W. Oberbauer	Munchener Medizinische Wochenschrift
456	On the treatment of whooping cough with Streptomycin and Aureomycin		W. Oberbauer	Archiv fur Kinderheilkunde
465	The immunological response of Nigerian infants to attenuated and inactivated poliovaccines	A comparison was made of the immunity conferred by injected formalin-killed poliomyelitis vaccine and orally administered attenuated poliomyelitis vaccine in Nigerian infants under tropical conditions where interfering enteroviruses have caused poor conversion rates with attenuated poliomyelitis vaccine. Two hundred and thirty infants completed the immunization schedules. The levels of antibodies to polioviruses were assessed before immunization and at periodic intervals during the trial. Seventy-four per cent, 72% and 85% of the children lacked antibodies to poliovirus types 1, 2 and 3 respectively at 6 months if they received no vaccine, the comparative proportions respectively were 52%, 8% and 48% if they had oral attenuated poliovaccine and 2%, 4% and 0% if they had three doses of inactivated poliovaccine. It is suggested that killed poliovaccine incorporated in a quadruple vaccine may have a place in developing countries like Nigeria in the control of diphtheria, tetanus, whooping cough and poliomyelitis.	S. O. Oduntan, A. O. Lucas and E. M. Wennen	Annals of tropical medicine and parasitology
248	The effect of patient education on pediatric immunization rates	BACKGROUND: Over the last decade, the immunization rate among preschool children has decreased, especially in the lower socioeconomic population. During this period, reports of outbreaks of immunizable diseases, especially pertussis and measles, have correspondingly increased. This study was designed to evaluate the effect of a brief patient education encounter with new mothers on pediatric immunization rates. METHODS: Two hundred thirty-eight mothers and infants were assigned to an intervention or control group. On the first day postpartum, the mothers in the intervention group participated in a 10- to 15-minute discussion on the importance of immunizations and were given a patient education handout. A reminder letter was mailed to the intervention group at 2 months postpartum. The control group received no special intervention. Infants were followed for their 2- and 4-month immunizations for diphtheria, pertussis, and tetanus and oral polio vaccine (DPT/OPV). At 1 year of age, the infants' immunization records were assessed for the completion of their first three DPT/OPV immunizations. RESULTS: There was no statistically significant difference, by chi-square analysis, in the immunization rates of the control and intervention groups at 2, 4, or 12 months of age. At 1 year of age, 29 of 122 (24%) of the control group had received all three DPT/OPV immunizations, compared with 33 (28%) of 116 infants in the intervention group. CONCLUSIONS: Concordant with similar studies, the immunization rate among infants of parents of lower socioeconomic status (26%) is low. An educational intervention presented to mothers in the postpartum period did not improve the rate of immunization by the age of 12 months. There are undoubtedly several reasons for this failure. Other means to improve immunization rates of infants should be developed and tested.	K. C. Oeffinger, S. P. Roaten, M. A. Hitchcock and P. K. Oeffinger	The Journal of family practice
75	The Swedish efficacy trial of acellular pertussis vaccines--update and time for reflection	The trial cohort from the Swedish efficacy trial conducted during 1986-1987 is still under non-blinded surveillance. During post-trial follow-up until March 11, 1990, efficacy of the mono-component vaccine, JNIH-7, was estimated to be 65% (95% confidence interval, CI, 49-76%) and the efficacy of the two-component vaccine, JNIH-6, to 77% (95% CI 64-85%). For culture-confirmed cases with more than 30 days of cough efficacy for JNIH-7, was 79% (95% CI 66-87%) and for JNIH-6, 92% (95% CI 83-96%). The data indicate that two doses of acellular pertussis vaccine provide protection for 3 1/2 years or more. Continued analysis of data from the trial suggests that acellular pertussis vaccines protect against typical illness to the same extent as whole cell vaccines and that protection against infection may be augmented by adding one or more components to a pertussis toxoid-based vaccine. In spite of promising efficacy data, acellular pertussis vaccines are still not licensed outside Japan. The need for direct comparisons with efficacy and safety of whole cell vaccines will be discussed and salient problems of case definitions and case ascertainment in clinical trials will be emphasised.	P. Olin	Developments in biological standardization
292	Acellular pertussis vaccines - A question of efficacy	Whole cell pertussis vaccine is considered to offer at least 80% protection against typical whooping cough. The quest for an equally effective but less reactogenic vaccine is now drawing to a close. During the forthcoming year a number of efficacy trials of acellular pertussis vaccines will be terminated. A variety of vaccines containing one, two, three or five purified pertussis antigens are being tested in Germany, Italy, Senegal and Sweden. About 30 000 infants have been enrolled in placebo-controlled studies and more than 100 000 in whole cell vaccine-controlled trials. The final plans for analysis of a Swedish placebo-controlled trial of whole cell and acellular vaccines is presented. Due to the unexpected high incidence of pertussis in Sweden during 1993-1994, relative risk comparisons between vaccines will be attempted in that trial, in addition to estimating absolute efficacy. A crucial issue is to what extent data may be compared between trials, given differences in design, vaccination schedules, and chosen endpoints. A primary case definition of laboratory-confirmed pertussis with at least 21 days of paroxysmal cough have been adopted in most trials. Pre-planned meta- analysis using this single endpoint will facilitate comparisons between vaccines. Serological correlates to protection in individuals will be sought in the ongoing placebo-controlled trials. The concept of a serological correlate valid for a vaccinated population but not necessarily for the vaccinated individual, as is the case with Hib vaccines, may turn out to be the only alternative to performing large efficacy trials in the future. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	P. Olin	Journal of Hospital Infection.
203	Immunogenicity, reactogenicity, and safety of a seven-valent pneumococcal conjugate vaccine (PCV7) concurrently administered with a fully liquid DTPa-IPV-HBV-Hib combination vaccine in healthy infants	AIM OF THE STUDY: To evaluate the immunogenicity, safety and reactogenicity of a seven-valent pneumococcal conjugate vaccine (PCV7) when given concomitantly with a fully liquid DTaP-IPV-HBV-Hib combination vaccine. METHODS: Two hundred and sixty-six healthy infants in France (n=136) and Germany (n=130) were randomized to receive DTaP-IPV-HBV-Hib and PCV7 (test group) at the age of 2, 3 and 4 months (primary series) and 12-15 months (booster dose), or to receive DTaP-IPV-HBV-Hib at the same time points but PCV7 at the ages of 5, 6, 7 and 13-16 months (control group). Antibody levels to all vaccine antigens were measured before dose 1, 1 month after dose 3, at the time of booster, and 1 month later. Safety data were collected after each vaccine dose. RESULTS: Two hundred and fifty-seven infants (test group, 131; control group, 126) completed the primary immunization series and two hundred and forty-five received the booster dose (test group, 125; control group, 120). Depending on the serotype, 92.8-100% of subjects in the test group achieved antibody levels >or=0.15 microg/mL for PCV7 antigens at 5 months of age, and 89.7-99.1% of them antibody levels >or=0.50 microg/mL 1 month after booster. For DTaP-IPV-HBV-Hib, there was no statistically significant difference between the two groups in the proportion of infants that achieved pre-defined seroprotective levels for each antigen at 5 months and 1 month after booster. Frequency of local and systemic reactions was similar in both groups except for fever above 38.0 degrees C, which was more frequent in the test group after dose 1, 2 or 4. Fever >39.0 degrees C was only reported from three children in each group. CONCLUSION: The PCV7 vaccine was highly immunogenic, well tolerated, and safe when coadministered with the DTPa-IPV-HBV-Hib vaccine at 2, 3, and 4 months of age and a booster dose at 12-15 months. In this study, PCV7 did not show any relevant influence on the immunogenicity and safety of the concurrently administered DTPa-IPV-HBV-Hib vaccine.	C. Olivier, B. H. Belohradsky, S. Stojanov, E. Bonnet, G. Petersen and J. G. Liese	Vaccine
138	Combined Haemophilus Influenzae type B-Neisseria meningitidis serogroup C vaccine is immunogenic and well tolerated in preterm infants when coadministered with other routinely recommended vaccines	BACKGROUND: Preterm infants are at greater risk of morbidity from vaccine-preventable diseases. Therefore, their responses to vaccination are of particular interest. METHODS: In this open, controlled, Spanish multicenter study, we assessed immunogenicity and safety following primary vaccination of 163 preterm infants (n = 56, <31 weeks' gestation; n = 107, 31-36 weeks' gestation) and 150 full-term infants (>36 weeks' gestation), with Haemophilus Influenzae type B (Hib)-MenC-TT, DTaP(diphtheria-tetanus-acellular pertussis vaccine)-HepB-IPV, and PCV7 at 2 to 4-6 months of age followed by booster vaccination at 16 to 18 months of age. Serum bactericidal activity (rabbit complement) against MenC, and antibodies to Hib and hepatitis b (anti-HBs) were determined. Local/general symptoms were assessed after each vaccination via diary cards. Serious adverse events were recorded throughout the study. RESULTS: There were no statistically significant differences between preterm and full-term infants in either Hib or MenC seroprotection rates or geometric mean concentrations at 1 month postdose 3, before or 1 month postbooster. Postdose 3, >99% of participants had seroprotective anti-HBs antibody concentrations. Anti-HBs geometric mean concentrations was significantly lower in the <31-week group compared with other groups and this difference persisted until 16 to 18 months of age. Hib-MenC-TT vaccine was well tolerated at all ages. There was one death caused by meningococcal serogroup-B sepsis (full term). No serious adverse events were assessed by the investigator as being vaccine related. CONCLUSIONS: Hib-MenC-TT vaccine had a similar immunogenicity and safety profile in preterm and full-term infants. These results demonstrate that preterm infants can be safely vaccinated with Hib-MenC-TT at the recommended chronologic age without impacting the responses to the Hib and MenC antigens.	F. Omeñaca, J. Arístegui, J. C. Tejedor, D. Moreno-Perez, J. Ruiz-Contreras, J. M. Merino, M. Muro Brussi, T. Sánchez-Tamayo, J. Castro Fernandez, L. Cabanillas, K. Peddiraju, N. Mesaros and J. M. Miller	The Pediatric infectious disease journal
175	Reactogenicity of DTPa-HBV/Hib vaccine administered as a single injection vs DTPa-HBV and Hib vaccines administered simultaneously at separate sites, to infants at 2, 4 and 6 months of age	An open, randomised, multicentre trial was performed to assess the reactogenicity and safety profile of the administration of a candidate Haemophilus influenzae type b (Hib) conjugate vaccine with a quadrivalent diphtheria-tetanus-acellular pertussis-hepatitis B (DTPa-HBV) vaccine as a single injection (Group 1) versus the simultaneous administration of the latter vaccine (DTPa-HBV) and an available Hib conjugate vaccine (Group 2) in opposite thighs, as a primary vaccination course to healthy infants at 2, 4 and 6 months of age. Eight hundred and eighty five infants (9.3+/-1.4 weeks old) were randomly allocated to Group 1 (n=665) and Group 2 (n=221). Oral polio vaccine was given concomitantly to all subjects. Blood samples (pre-vaccination and 1 month after the third dose) were obtained from a subset of infants (Group 1, 73; Group 2, 22) for serological determinations. Local and general symptoms were recorded by parents on diary cards. 2614 diary cards (Group 1, 1966; Group 2, 648) were collected. There were no statistically significant differences in the incidence of local and general symptoms between groups. Pain such that the infant cried when limb was moved was reported in 0.6 and 0.2% in groups 1 and 2, respectively. Redness and swelling (>20 mm in diameter) were recorded between 2.1 and 3% in both groups. Fussiness preventing normal activities was the most frequently reported general symptom in both groups (1.6 and 1.9% in groups 1 and 2, respectively). Fever (rectal temperature >39.5 degrees C) was reported in 0.4% (Group 1) and 0.3% (Group 2). All subjects included in the immunogenicity analysis had seroprotective or seropositive titres to the diphtheria, tetanus, hepatitis B and pertussis components of the vaccines. About 99 and 100% of infants had anti-PRP titres > or =0.15 mcg/ml in groups 1 and 2, respectively. This study indicates that DTPa-HBV vaccine given in a single injection with a candidate Hib conjugate vaccine has a similar reactogenicity profile to that of two commercially available vaccines (DTPa-HBV, Hib) given in two simultaneous injections to infants 2, 4 and 6 months of age.	F. Omeñaca, R. Dal-Ré, V. D'Apuzzo, C. Kattamis, H. P. Gnehm, J. García-Sicilia and P. García-Corbeira	Vaccine
398	The effect of zinc supplementation during pregnancy on immune response to hib and BCG vaccines in Bangladesh	An essential role for zinc in development of the fetal immune system has been documented. However, the effect of antenatal zinc supplementation on infants' postnatal immune response to vaccinations is unknown. The objective of this study was to evaluate the effect of zinc supplementation during pregnancy on immune response to the Bacillus Calmette-Guerin (BCG) vaccine and the Haemophilus influenzae type b (Hib) component of the combined diphtheria, tetanus toxoid and pertussis (DTP)- Haemophilus influenzae type-b (Hib)- conjugate vaccine in poor Bangladeshi infants. We immunized 405 infants whose mothers were supplemented daily with 30 mg elemental zinc or placebo beginning at 12-16 weeks gestation with the standard BCG vaccine at birth. A subcohort of 203 infants were in addition immunized at 1-month intervals with three doses of DTP-Hib vaccine starting at 9 weeks of age. The delayed hypersensitivity (PPD) skin test was performed in 345 infants at 24 weeks of age. Hib polysaccharide (PRP) antibodies were assessed for 91 infants at 4 and 24 weeks of age. In infants born with low birth weight (LBW) a lower proportion of negative responses to PPD skin test were observed in the zinc (66.2%) compared to placebo (78.5%) group (p = 0.07). No differences were observed in normal birth weight infants. There were no differences in proportion of infants above the protective thresholds for anti-PRP antibodies between zinc (81%) and placebo (89%) group. Geometric mean PRP antibody titres at 4 and 24 weeks of age were not different between groups. Zinc supplementation during pregnancy did not enhance immune response to Hib-conjugate vaccine but there was a suggestion of improved delayed hypersensitivity immune responses to BCG-vaccine in Bangladeshi LBW infants. copyright 2006 Oxford University Press. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	S. J. M. Osendarp, G. J. Fuchs, J. M. A. Raaij, H. Mahmud, F. Tofail and R. E. Black	Journal of Tropical Pediatrics
473	Immunization with the heptavalent pneumococcal conjugate vaccine in Bangladeshi infants and effects of zinc supplementation	Background: Zinc deficiency is known to impair immunologic functions. However, the effect of zinc supplementation on immune response to polysaccharide vaccines is not known. Objective: To determine the immunogenicity of the heptavalent Pneumococcal protein conjugate (PNC) vaccine in poor Bangladeshi infants and to assess the effect of zinc supplementation on immune response to the PNC vaccine. Design: We immunized a sub-cohort of 241 infants who had previously received three doses of a Hib conjugate vaccine with three doses of the heptavalent PNC vaccine at 4 weeks intervals beginning at 18 +/- 1 weeks of age. The infants were supplemented with daily 5 mg zinc or placebo from 4 to 33 weeks of age. Response to each of the seven PNC serotypes were assessed at 4, 24 and 33 weeks of age. Results: After three doses of PNC, at 29 weeks of age, geometric mean titres for the pneumococcal serotypes ranged from 3.68 to 13.34 mug/ml. Titres were significantly higher for infants who had received PNC compared to infants who had only received DTP-Hib. Zinc supplementation resulted in higher titres for serotype 9V (4.09 mug/ml; [95% CI: 3.27; 5.10] and 3.33 mug/ml; [95% CI: 2.79; 3.96] for zinc and placebo group, respectively; p < 0.05) after three doses but had no effect on other serotypes. Conclusions: A heptavalent PNC vaccine proved to be safe and immunogenic in Bangladeshi infants. Zinc supplementation enhanced the immune response to only one of the serotypes (9V). However, there was no effect on other serotypes. copyright 2007 Elsevier Ltd. All rights reserved. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	S. J. M. Osendarp, H. Prabhakar, G. J. Fuchs, J. M. A. Raaij, H. Mahmud, F. Tofail, M. Santosham and R. E. Black	Vaccine
396	Safety and efficacy of yellow fever vaccine in children less thanone-year-old	In a clinical trial of stabilized yellow fever vaccine from Institute Pasteur in 77 children aged seven to eight months, fever was the most significant immediate and delayed side effect. Fever occurred in 12 (15.6%) children with in 48 hours of vaccination while it occurred in 10 (12.9%) children within ten days of vaccination. Other recorded side effects were pain at innoculation site in four (5.2%) children and vomiting in one (1.3%) child. Temperature recorded in 20 of the 22 febrile episodes ranged from 37.8 degrees C to 38.6 degrees C. One of the two patients who had temperatures of 39 degrees C and above had malaria parasites in her blood film. All episodes of fever except one responded to antipyretic. There was no episode of febrile convulsion and no feature suggestive of encephalitis. Of the 20 children who had neutralization test carried out against yellow fever virus six weeks after vaccination, the test was positive in post vaccination sera of 12 (60%) children whose pre-vaccination sera were negative. Two others showed evidence of partial protection. Although the seroconversion rate of 60% is less than reported in adults and older children, the result of this study shows that yellow fever vaccine is safe and fairly effective in infants. It is our suggestion that if a larger trial confirms our findings, the vaccine may be incorporated into the expanded programme on immunization (EPI) to be given at the age of seven months after completion of diptheria, tetanus, pertussis and poliomyelitis vaccinations and before measles vaccination is due.	K. Osinusi, F. M. Akinkugbe, O. A. Akinwolere and A. Fabiyi	West African journal of medicine
205	Influence of Mycobacterium bovis bacillus Calmette-Guérin on antibody and cytokine responses to human neonatal vaccination	The immaturity of the immune system increases the susceptibility of young infants to infectious diseases and prevents the induction of protective immune responses by vaccines. We previously reported that Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination induces a potent Th1 response to mycobacterial Ags in newborns. In this study, we evaluated the influence of BCG on the response to unrelated vaccines given in early life. Newborns were randomly allocated to one of three study groups receiving BCG at birth, when infants received their first dose of hepatitis B and oral polio vaccines; at 2 mo of age, when infants received their first dose of diphtheria and tetanus vaccines; or at 4.5 mo of age, when immune responses to vaccines were measured. Administration of BCG at the time of priming markedly increased the cellular and Ab responses to the hepatitis B vaccine, but had only a limited influence on the cytokine response to tetanus toxoid and no effect on the Ab responses to tetanus and diphtheria toxoids. Although BCG induced a potent Th1-type response to mycobacterial Ags, it promoted the production of both Th1- and Th2-type cytokines in response to unrelated vaccines. The effect of BCG was apparent at the systemic level, as it increased the Ab response to oral polio vaccine. These results demonstrate that BCG influences the immune response to unrelated Ags in early life, likely through its influence on the maturation of dendritic cells.	M. O. Ota, J. Vekemans, S. E. Schlegel-Haueter, K. Fielding, M. Sanneh, M. Kidd, M. J. Newport, P. Aaby, H. Whittle, P. H. Lambert, K. P. McAdam, C. A. Siegrist and A. Marchant	Journal of immunology (Baltimore, Md. : 1950)
475	Influence of Mycobacterium bovis bacillus Calmette-Guerin on antibody and cytokine responses to human neonatal vaccination	The immaturity of the immune system increases the susceptibility of young infants to infectious diseases and prevents the induction of protective immune responses by vaccines. We previously reported that Mycobacterium bovis bacillus Calmette-Guerin (BCG) vaccination induces a potent Th1 response to mycobacterial Ags in newborns. In this study, we evaluated the influence of BCG on the response to unrelated vaccines given in early life. Newborns were randomly allocated to one of three study groups receiving BCG at birth, when infants received their first dose of hepatitis B and oral polio vaccines; at 2 mo of age, when infants received their first dose of diphtheria and tetanus vaccines; or at 4.5 mo of age, when immune responses to vaccines were measured. Administration of BCG at the time of priming markedly increased the cellular and Ab responses to the hepatitis B vaccine, but had only a limited influence on the cytokine response to tetanus toxoid and no effect on the Ab responses to tetanus and diphtheria toxoids. Although BCG induced a potent Th1-type response to mycobacterial Ags, it promoted the production of both Th1- and Th2-type cytokines in response to unrelated vaccines. The effect of BCG was apparent at the systemic level, as it increased the Ab response to oral polio vaccine. These results demonstrate that BCG influences the immune response to unrelated Ags in early life, likely through its influence on the maturation of dendritic cells.	M. O. Ota, J. Vekemans, S. E. Schlegel-Haueter, K. Fielding, M. Sanneh, M. Kidd, M. J. Newport, P. Aaby, H. Whittle, P. H. Lambert, K. P. McAdam, C. A. Siegrist and A. Marchant	Journal of immunology (Baltimore, Md. : 1950)
426	General non-specific morbidity is reduced after vaccination within the third month of life--the Greifswald study	OBJECTIVES: The incidence of many serious infectious diseases fundamentally decline as a success of consequent vaccination regimens. However, it is a matter of discussion if vaccination might cause unspecific negative side effects on the immune system. To answer this, we performed a clinical study on children with the question as to whether there is an enhanced frequency of infection diseases after vaccination or not. METHODS: The study population (n=496) was randomized to a group of vaccinated children (first vaccination on the 60th day of life, n=201) and a group of unvaccinated children (first vaccination on the 90th day of life, n=295). Frequencies of unspecific, morbidity-related signs were recorded by the mothers with a diary card. These data were taken for further statistical analysis to determine if the factor "vaccination" does have a significant effect on the variable "morbidity". RESULTS: Various infectious disease-associated symptoms (vomiting, coughing, signs of rhinitis, restlessness, rash and pain) were significantly less often seen in vaccinated than in non-vaccinated children. CONCLUSIONS: Our study revealed that children who received vaccination against diphtheria, pertussis, tetanus, HiB and poliomyelitis simultaneously within the third month of life do not exhibit enhanced frequencies of infectious disease-associated symptoms. In contrary, the frequencies of infection-associated symptoms were found to be significantly reduced. This might be caused by a vaccination-associated unspecific enhancement of immunological activity (e.g. mediated by interleukin 2) or by other presently still unknown factors.	S. Otto, B. Mahner, I. Kadow, J. F. Beck, S. K. Wiersbitzky and R. Bruns	The Journal of infection
268	Does improving maternal knowledge of vaccines impact infant immunization rates? A community-based randomized-controlled trial in Karachi, Pakistan	BACKGROUND: In Pakistan, only 59-73% of children 12-23 months of age are fully immunized. This randomized, controlled trial was conducted to assess the impact of a low-literacy immunization promotion educational intervention for mothers living in low-income communities of Karachi on infant immunization completion rates. METHODS: Three hundred and sixty-six mother-infant pairs, with infants aged ? 6 weeks, were enrolled and randomized into either the intervention or control arm between August - November 2008. The intervention, administered by trained community health workers, consisted of three targeted pictorial messages regarding vaccines. The control group received general health promotion messages based on Pakistan's Lady Health Worker program curriculum. Assessment of DPT/Hepatitis B vaccine completion (3 doses) was conducted 4-months after enrollment. A Poisson regression model was used to estimate effect of the intervention. The multivariable Poisson regression model included maternal education, paternal occupation, ownership of home, cooking fuel used at home, place of residence, the child's immunization status at enrollment, and mother's perception about the impact of immunization on child's health. RESULTS: Baseline characteristics among the two groups were similar. At 4 month assessment, among 179 mother-infant pairs in the intervention group, 129 (72.1%) had received all 3 doses of DPT/Hepatitis B vaccine, whereas in the control group 92/178 (51.7%) had received all 3 doses. Multivariable analysis revealed a significant improvement of 39% (adjusted RR = 1.39; 95% CI: 1.06-1.81) in DPT-3/Hepatitis B completion rates in the intervention group. CONCLUSION: A simple educational intervention designed for low-literate populations, improved DPT-3/Hepatitis B vaccine completion rates by 39%. These findings have important implications for improving routine immunization rates in Pakistan.	A. Owais, B. Hanif, A. R. Siddiqui, A. Agha and A. K. Zaidi	BMC public health
149	Evaluation of a combined tetravalent diphtheria, tetanus, whole-cell pertussis and hepatitis B candidate vaccine administered to healthy infants according to a three-dose vaccination schedule	A vaccine combining hepatitis B with diphtheria, tetanus and whole-cell Bordetella pertussis (DTPwHBV) would facilitate the attainment of universal vaccination of infants against hepatitis B. A candidate vaccine was administered to 42 infants beginning at 7-15 weeks of age. Antibodies were measured from pre- and postvaccination blood samples. After three doses, at least 94.9% of the infants were protected against hepatitis B, diphtheria and tetanus. Responses to B. pertussis were considered adequate. No serious adverse events were reported. These results indicate that this candidate vaccine is safe and immunogenic when administered to infants according to a three-dose schedule, with doses 2 months apart.	G. Papaevangelou, E. Karvelis, D. Alexiou, K. Kiossoglou, A. Roumeliotou, A. Safary, F. Collard and P. Vandepapeliere	Vaccine
118	Clinical immunogenicity and tolerance studies of liquid vaccines delivered by jet-injector and a new single-use cartridge (Imule): comparison with standard syringe injection. Imule Investigators Group	A new needleless jet-injector, Mini-Imojet, was developed that administers liquid vaccines from a single-use, pre-filled cartridge named Imule, which avoids the risk of cross-contamination. We conducted clinical trials in several settings in France and West Africa to compare the immunogenicity and tolerance of five vaccines (influenza vaccine, Vi capsular polysaccharide typhoid vaccine, tetanus toxoid vaccine, diphtheria-tetanus-whole cell pertussis vaccine, and inactivated hepatitis A vaccine) administered with the Imule system vs standard syringe technique. In each vaccine study, all subjects of either group were tested for serum antibody titres to calculate the geometrical mean titres and seroconversion rates after complete vaccination. Immediate local-reactions were noted after each injection, and local and general reactions were evaluated during a predetermined period of follow-up. When delivered by the Imule technique, all the administered vaccines were of equivalent or superior immunogenicity, compared to the syringe technique. The tolerance to vaccines injected by the Imule system was acceptable in all studies. The most frequently observed reactions were mild (e.g. minor bleeding, superficial papules, erythema and induration) and could be considered to be inherent to the injection technique. The technical and safety advantages of the Mini-Imojet/Imule system, compared to sterilizable, standard disposable or autodestruct syringes and to classical multi-dose vial jet-injectors, reinforces the interest of this new injection technique for collective immunizations.	I. Parent du Châtelet, J. Lang, M. Schlumberger, E. Vidor, G. Soula, A. Genet, S. M. Standaert and P. Saliou	Vaccine
432	Serological response and poliovirus excretion following different combined oral and inactivated poliovirus vaccines immunization schedules	A controlled study was conducted in Karachi, Pakistan to compare humoral and mucosal immune responses against polioviruses in infants who received oral poliovirus vaccine (OPV) at birth and at 6, 10, and 14 weeks according to the Expanded Program on Immunization (EPI) with infants who received either three doses of inactivated poliovirus vaccine (IPV) at 6, 10, and 14 weeks together with OPV or one additional dose of IPV at 14 weeks together, with the last dose of OPV. A total of 1429 infants were enrolled; 24-week serum specimens were available for 898 infants (63%). They all received a challenge dose of OPV type 3 at 24 weeks of age. The addition of three doses of IPV to three doses of OPV induced a significantly higher percentage of seropositive children at 24 weeks of age for polio 1 (97% versus 89%, P<0.001) and polio 3 (98% versus 92%) compared to the EPI schedule. However, the one supplemental dose of IPV at 14 weeks did not increase the serological response at 24 weeks. Intestinal immunity against the challenge dose was similar in the three groups. Combined schedules of OPV and IPV in the form of diphtheria-pertussis-tetanus-IPV vaccine (DPT-IPV) may be useful to accelerate eradication of polio in developing countries.	I. Parent du Châtelet, A. T. Merchant, S. Fisher-Hoch, S. P. Luby, S. A. Plotkin, T. Moatter, M. Agboatwalla and J. B. McCormick	Vaccine
359	Immunogenicity, reactogenicity and safety of a diphtheria-tetanus-acellular pertussis-inactivated polio and Haemophilus influenzae type b vaccine in a placebo-controlled rotavirus vaccine study	INTRODUCTION: In recent years, acellular pertussis combination vaccines have facilitated compliance with and coverage of the national immunisation programme in Singapore. This phase-II study (Rota-007) evaluated the immunogenicity, reactogenicity and safety of a DTPa-IPV/Hib combined vaccine when co-administered with a rotavirus vaccine. MATERIALS AND METHODS: A total of 2464 children aged 3 months were vaccinated with DTPa-IPV/Hib together with a randomised 1:3 ratio of either placebo (n=653) or 1 of 3 different formulations of a rotavirus vaccine. Blood samples were collected for immunogenicity analysis 1 month after the third DTPa-IPV/Hib vaccine dose in a subset of subjects (n = 640). Local and general reactogenicity and unsolicited adverse events were recorded during the follow-up after each vaccination. RESULTS: Serological analysis showed >95% response for all antigens in the co-administered DTPa-IPV/Hib vaccine, with no difference between the rotavirus vaccine and placebo groups. No differences in adverse events and reactogenicity were reported in the rotavirus vaccine and placebo groups. Only 0.2% of the subjects reported Grade 3 adverse events. Three subjects (from the vaccine groups) died during the study, which were assessed by the investigators as unrelated to vaccination. No deaths were reported in the placebo group. CONCLUSION: The combined DTPa- IPV/Hib vaccine is safe, well tolerated and highly immunogenic when given alone or coadministered with the rotavirus vaccine for infants in Singapore.	K. B. Phua, S. H. Quak, F. S. Lim, P. Goh, Y. L. Teoh, S. K. Datta, H. H. Han and H. L. Bock	Annals of the Academy of Medicine, Singapore
291	Fifth vaccination with dipthteria, tetanus and acellular pertussis is beneficial in four- to six-year-olds	OBJECTIVE: Diphtheria, tetanus and pertussis serum antibody titers were assessed before a fifth dose of diphtheria-tetanus-acellular pertussis (DTaP) or diphtheria-tetanus-whole cell pertussis (DTwP) vaccination at age 4 to 6 years. METHODS: Healthy children who had participated in a series of National Institutes of Health-sponsored trials assessing DTwP and DTaP vaccines provided prevaccination sera before a fifth dose of DTwP or DTaP. The trial design was prospective, randomized and double blind. Diphtheria, tetanus and pertussis antibody titers were measured by enzyme-linked immunosorbent assay. Pertussis results are expressed in enzyme-linked immunosorbent assay units/ml based on US Food and Drug Administration reference sera. Tetanus and diphtheria toxin concentrations are expressed in IU/ml with a WHO international reference sera as a standard. RESULTS: For diphtheria 100% of the children had antibody titers above the minimum protective level of 0.01 IU/ml and 86 to 100% (depending on prior vaccine product) had titers >0.1 IU/ml. However, only 0 to 40% of the children had antibody titers > or =1.0 IU/ml, a titer associated with more certain durable protection. For tetanus none of the children had an antibody titer below 0.01 IU/ml, and 93 to 100% had titers > or =0.1 IU/ml, a titer associated with more certain, durable protection. For pertussis the geometric mean concentrations of antibody before booster were uniformly very low, and the percentage of children exceeding the minimum detectable titer of antibody by 4-fold was also low. CONCLUSION: Before a 4- to 6-year-old booster, a large proportion of children have titers of antibody to diphtheria below the certain, durable protective level. Because serologic correlates and minimum protective titers of antibody to pertussis antigens have not been established, the relevance of the low titers determined in the current study is unknown but a potential concern	M. E. Pichichero, E. L. Anderson, M. B. Rennels, K. M. Edwards and J. A. England	Pediatr Infect.Dis.J
105	Acellular pertussis vaccine: immunogenicity and safety of an acellular pertussis vs. a whole cell pertussis vaccine combined with diphtheria and tetanus toxoids as a booster in 18- to 24-month old children	An acellular pertussis vaccine principally containing two purified pertussis antigens, filamentous hemagglutinin and lymphocytosis-promoting factor, combined with diphtheria and tetanus toxoids was compared to conventional diphtheria-tetanus toxoids-whole cell pertussis for adverse effects and serologic responses in a group of 120 children who were from 18 to 24 months of age. Three vaccinations at 2, 4 and 6 months of age with diphtheria-tetanus toxoids-whole cell pertussis had been administered previously. Adverse effects occurred more frequently with the diphtheria-tetanus toxoids-whole cell pertussis than with diphtheria-tetanus toxoids-acellular pertussis vaccine. Fever occurred significantly more often and to a higher degree in the whole cell pertussis vaccine recipients with a peak difference occurring 6 hours after immunization (P = 0.00008). Local swelling, redness, warmth and tenderness at the injection site also occurred significantly more frequently following whole cell pertussis vaccination. No major sequelae were noted in either group. The antibody responses to lymphocytosis-promoting factor were similar for the two vaccines. The diphtheria-tetanus toxoids-acellular pertussis vaccine produced significantly lower pertussis agglutinin titers (P = 0.00001) but significantly higher antibody to filamentous hemagglutinin (P = 0.05) and to diphtheria (P = 0.03). The protective role of antibody to pertussis agglutinins vs. filamentous hemagglutinin and lymphocytosis-promoting factor continues as a central issue in the quest for a new pertussis vaccine. A clinical efficacy trial is needed.	M. E. Pichichero, J. T. Badgett, G. C. Rodgers, S. McLinn, B. Trevino-Scatterday and J. D. Nelson	The Pediatric infectious disease journal
329	Pediatric diphtheria and tetanus toxoids-adsorbed vaccine: immune response to the first booster following the diphtheria and tetanus toxoids vaccine primary series	Diphtheria and tetanus toxoids (DT) vaccine should be given to children at 2, 4 and 6 months of age when there are contraindications to the administration of pertussis vaccine. We have previously reported that such children develop protective antitoxin antibody levels to diphtheria and tetanus antigens. This follow-up study evaluates the decay in antitoxin antibody levels and the booster response elicited to DT antigen when a fourth dose is given at approximately 18 months of age. Twenty-three children receiving DT vaccine were compared to 38 receiving diphtheria and tetanus toxoids-pertussis (DTP) vaccine. The prebooster antibody titer to diphtheria and tetanus at approximately 18 months of age had declined below the recommended protective level in one child who had received DT vaccine and in three children who had received DTP. Following the 18-month booster dose of DT and DTP vaccine, all of the children had protective titers to diphtheria and tetanus toxin. These results suggest that the adjuvant effects of pertussis vaccine are not required to achieve adequate immunization to diphtheria and tetanus when currently available DT vaccine is used in early childhood	M. E. Pichichero, R. M. Barkin and J. S. Samuelson	Pediatric Infectious Disease
57	Acellular pertussis vaccine booster combined with diphtheria and tetanus toxoids for adolescents	BACKGROUND: The incidence of pertussis is increasing, especially in adolescents, attributed in part to waning of immunity after childhood immunization. Recently licensed in the United States for use in adolescents, acellular pertussis vaccines will provide an immunogenic and safe option for booster immunization against pertussis. METHODS: This prospective, randomized, observer-blinded, multicenter, comparative study evaluated the safety and immunogenicity of a vaccine formulated with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis antigens (Tdap) compared with tetanus and diphtheria toxoids vaccine (Td) for booster immunization in adolescents. There were 4114 healthy adolescents aged 10 to 18 years who completed childhood vaccination against diphtheria, tetanus, and pertussis who were enrolled, randomized, and received study vaccine. RESULTS: Local and general symptoms were comparable between the Tdap and Td groups. The immune response of Tdap was comparable with Td vaccine for tetanus and diphtheria seroprotection and booster responses. In addition, geometric mean concentrations of antibody to pertussis antigens, pertussis toxoid, filamentous hemagglutinin, and pertactin exceeded the antibody response elicited after infant immunization with diphtheria and tetanus toxoids and acellular pertussis antigens (DTaP) that had proven efficacy against pertussis. CONCLUSIONS: In adolescents, the studied Tdap was safe and immunogenic and induced pertussis antibodies that were higher than those associated with efficacy in infants.	M. E. Pichichero, M. M. Blatter, W. A. Kennedy, J. Hedrick, D. Descamps and L. R. Friedland	Pediatrics
197	Defining the key parameters for comparing reactions among acellular and whole-cell pertussis vaccines	OBJECTIVE: To facilitate future vaccine reaction data collection and analysis, we sought to determine the minimum data set required to describe accurately and to compare common reactions after the administration of acellular (DTaP) or whole-cell (DTP) pertussis vaccine with diphtheria and tetanus toxoids combined. METHODS: Thirteen DTaP and 2 DTP vaccines were studied in a multicenter trial involving 2342 infants who received a primary series of vaccinations at 2, 4, and 6 months of age. Temperature, fussiness, redness, swelling and pain at the injection site, antipyretic use, drowsiness, loss of appetite, and vomiting were evaluated. Reactions were assessed at 3 hours and (if not immunized in the evening) 6 hours after immunization, at bedtime each evening for 7 evenings, and on the 14th evening after immunization. RESULTS: Two reaction assessment approaches were compared: (1) analysis of all reactions, regardless of the degree of severity; and (2) a condensation of the data to five key reactions (fever > 100 degrees F, moderate or more fussiness, any local redness, any local swelling, and moderate or more local pain). We found that the onset of reactions was infrequent beyond the second evening, and that collection and analysis of reaction data beyond that time did not further discriminate among the vaccines. Information regarding antipyretic use, loss of appetite, drowsiness, or vomiting did not assist in differentiating among these vaccines. CONCLUSION: Monitoring the occurrence of fever greater than 100 degrees F, moderate or severe fussiness, injection site redness or swelling, and moderate or severe injection site pain occurring through the second evening after immunization will provide the minimum data set needed to discriminate among DTaP and DTP vaccines with respect to the common adverse reactions.	M. E. Pichichero, C. Christy, M. D. Decker, M. C. Steinhoff, K. M. Edwards, M. B. Rennels, E. L. Anderson and J. A. Englund	Pediatrics
40	Acellular pertussis vaccination of 2-month-old infants in the United States	This is the first study in children from the United States that evaluates the immunogenicity of and adverse reactions to the Connaught/Biken two-component acellular pertussis vaccine compared with whole-cell pertussis vaccine when given as a primary immunization series at 2, 4, and 6 months of age. Three hundred eighty infants were studied; 285 received acellular diphtheria-tetanus toxoids-pertussis (DTP (ADTP)) and 95 received whole-cell DTP (WDTP). Following the third dose, ADTP vaccination produced higher antibody responses than WDTP to lymphocytosis-promoting factor (enzyme-linked immunosorbent assay IgG geometric mean titer (GMT) = 131 vs 9 and Chinese hamster ovary cell assay GMT = 273 vs 16) and to filamentous hemagglutinin (IgG GMT = 73 vs 10) (all P less than .0001). Agglutinin responses were higher in WDTP compared with ADTP recipients (GMT = 50 vs 37; P = .02). Local reactions were fewer for all three doses following ADTP vaccination. Fever, irritability, drowsiness, anorexia, vomiting, and unusual crying all occurred less frequently in ADTP compared with WDTP recipients for one or more of the three doses. We conclude that this two-component ADTP vaccine when given as a primary series produces greater immunogenicity and fewer adverse effects than the currently licensed WDTP vaccine.	M. E. Pichichero, A. B. Francis, M. M. Blatter, K. S. Reisinger, J. L. Green, S. M. Marsocci and F. A. Disney	Pediatrics
82	Comparison of a three-component acellular pertussis vaccine with whole cell pertussis vaccine in two-month-old children	An acellular pertussis vaccine (DTaP) containing pertussis toxoid, filamentous hemagglutinin and the 69-kDa outer membrane protein (pertactin) was compared with United States-licensed whole cell pertussis vaccine (DTwP) as a three dose sequence at 2, 4 and 6 months of age. Eighty infants were enrolled; 62 received DTaP and 18 received DTwP. Sixty-two infants had preimmunization and 1 month postimmunization sera available for pertussis antibodies. No infant experienced a serious adverse reaction. Significantly fewer infants in the DTaP group experienced irritability (P < 0.001) and moderate to severe injection site pain and redness (P < 0.001, and P = 0.03, respectively). The DTaP group also had significantly greater increases in geometric mean titers of antibodies against filamentous hemagglutinin (P < 0.001) and pertactin (P = 0.006). This three-component DTaP vaccine induced an antibody response to pertussis toxin, filamentous hemagglutinin and pertactin but caused fewer adverse reactions than DTwP when administered as a primary series of immunization to 2-month-old infants.	M. E. Pichichero, J. L. Green, A. B. Francis, S. M. Marsocci, A. M. Lynd and T. Litteer	The Pediatric infectious disease journal
156	Combined tetanus, diphtheria, and 5-component pertussis vaccine for use in adolescents and adults	CONTEXT: Increasing reports of pertussis among US adolescents, adults, and their infant contacts have stimulated vaccine development for older age groups. OBJECTIVE: To assess the immunogenicity and reactogenicity of a tetanus-diphtheria 5-component (pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3) acellular pertussis vaccine (Tdap) in adolescents and adults. DESIGN, SETTING, AND PARTICIPANTS: A prospective, randomized, modified double-blind, comparative trial was conducted in healthy adolescents and adults aged 11 through 64 years from August 2001 to August 2002 at 39 US clinical centers. INTERVENTIONS: A single 0.5-mL intramuscular dose of either Tdap or tetanus-diphtheria vaccine (Td). MAIN OUTCOME MEASURES: Antibody titers to diphtheria and tetanus toxoids for Tdap and Td were measured in sera collected from subsets of adolescents and adults, before and 28 days after vaccination. For pertussis antigens, titers in sera from Tdap vaccinees were assessed vs those from infants who received analogous pediatric diphtheria-tetanus-acellular pertussis vaccine (DTaP) in a previous efficacy trial. Safety was assessed via solicited local and systemic reactions for 14 days and adverse events for 6 months following vaccination. RESULTS: A total of 4480 participants were enrolled. For both Tdap and Td, more than 94% and nearly 100% of vaccinees had protective antibody concentrations of at least 0.1 IU/mL for diphtheria and tetanus, respectively. Geometric mean antibody titers to pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3 exceeded (by 2.1 to 5.4 times) levels in infants following immunization at 2, 4, and 6 months with DTaP. The incidence of solicited local and systemic reactions and adverse events was generally similar between the Tdap and Td groups. CONCLUSIONS: This Tdap vaccine elicited robust immune responses in adolescents and adults to pertussis, tetanus, and diphtheria antigens, while exhibiting an overall safety profile similar to that of a licensed Td vaccine. These data support the potential routine use of this Tdap vaccine in adolescents and adults.	M. E. Pichichero, M. B. Rennels, K. M. Edwards, M. M. Blatter, G. S. Marshall, M. Bologa, E. Wang and E. Mills	JAMA : the journal of the American Medical Association
96	Kinetics of booster responses to Haemophilus influenzae type B conjugate after combined diphtheria-tetanus-acelluar pertussis-Haemophilus influenzae type b vaccination in infants		M. E. Pichichero, T. Voloshen and S. Passador	The Pediatric infectious disease journal
11	Effect of priming with diphtheria and tetanus toxoids combined with whole-cell pertussis vaccine or with acellular pertussis vaccine on the safety and immunogenicity of a booster dose of an acellular pertussis vaccine containing a genetically inactivated pertussis toxin in fifteen- to twenty-one-month-old children. Italian Multicenter Group for the Study of Recombinant Acellular Pertussis Vaccine	OBJECTIVE: To evaluate the safety and the immunogenicity of a booster dose of recombinant acellular pertussis vaccine combined with diphtheria and tetanus toxoids (DTaP, Biocine SpA) in 15- to 21-month-old children primed in infancy with either whole-cell diphtheria-tetanus-pertussis (DTwP) vaccine or DTaP vaccine. DESIGN: Open-label second phase of a double-masked, controlled trail, with masked analysis of serum samples. Participants and setting: Three hundred fifty children, 15 to 21 months of age, who had been primed at 2, 4, and 6 months of age with either three doses of DTaP vaccine (n = 173) or DTwP vaccine (n = 177). The children were enrolled in eight vaccination centers in Italy. INTERVENTIONS: All children received a booster dose of the DTaP vaccine and were examined for safety at 48 hours and at 7 days after vaccination. Serum samples for evaluation of immunogenicity were obtained from 196 (55%) of the 350 children. MAIN OUTCOME MEASURES: IgG antibodies to pertussis toxin (Ptox), filamentous hemagglutinin, 69-kilodalton protein, and tetanus toxoid were measured by enzyme-linked immunosorbent assay. Pertussis toxin-neutralizing antibodies were measured by the Chinese hamster ovary cell toxin neutralization assay. MAIN RESULTS: Adverse reactions to DTaP were infrequent, and there was no difference in the incidence of local or systemic reactions in children given DTaP as a fourth dose in comparison with a first dose. One month after the DTaP booster vaccination, both groups had 6- to 40-fold increases in serum antibody concentrations to all antigens tested; the concentrations against the three pertussis antigens were higher in the DTaP-primed children (p < 0.05). The antibody titers to diphtheria and tetanus toxoids were higher in the DTwP-primed group (p < 0.05), but both groups had protective titers. The geometric mean ratio of anti-Ptox neutralizing antibody per unit of IgG anti-Ptox antibody was higher in the DTaP-primed group (p < 0.001). CONCLUSIONS: There are quantitative and qualitative differences in booster responses to DTaP vaccine in young children, depending on whether they were given DTaP or DTwP as primary immunization. This DTaP vaccine is safe and highly immunogenic as a booster.	A. Podda, G. Bona, G. Canciani, A. M. Pistilli, B. Contu, R. Furlan, T. Meloni, D. Stramare, L. Titone and R. Rappuoli	The Journal of pediatrics
24	Sero epidemiology of Bordetella pertussis immune responses in a healthy population in northern Greece	A seroepidemiological study was conducted on a representative sample of the northern Greek population (healthy individuals, age range=1 day to 80 years) to assess the prevalence of antibodies to pertussis toxin (PT) and filamentous hemagglutinin (FHA). Antibody concentrations were significantly elevated with age (analysis of variance (ANOVA), P<0.001). In addition, a significant increase in antibody levels was detected in subjects >50 years old compared to children aged 5-10 years (post-hoc Scheffe analysis, P=0.007). These data suggest that pertussis occurs frequently in Greek adults, and that sometimes a fifth booster vaccine dose is not given after the second year of life. Routine revaccination with the acellular vaccine for children >4 years of age, adolescents, and adults should be considered in order to ensure effective protection of the whole population.	A. Polyzou, S. Pournaras, U. Dafni, D. Sofianou, E. Christeli, S. Patrinos and A. Tsakris	Journal of clinical laboratory analysis
191	Clinical relevance of lower Hib response in DTPa-based combination vaccines	Combination vaccines are essential to enable administration of all the required antigens in routine infant immunisation schedules at any single visit. Some combinations of diphtheria-tetanus-acellular pertussis (DTPa) with Haemophilus influenzae type b (Hib) conjugate vaccines have been shown to result in lower Hib titres than when Hib is administered separately. While confirming that a primary series with a DTPa-HBV-IPV/Hib combination gives lower antibody levels than separate Hib conjugates, we show that the nature (isotype and IgG subclasses) and function (avidity and opsonic activity) of the antibodies are the same, and immunologic memory is induced. It is likely therefore that the DTPa-HBV-IPV/Hib combination will be efficacious against Hib disease.	J. Poolman, A. Kaufhold, D. Grave and D. Goldblatt	Vaccine
41	Experience of combined tetravalent diphtheria, tetanus, whole-cell pertussis and hepatitis B vaccine in Thailand	In 1992, hepatitis B (HB) vaccination of all newborns was officially included in the national expanded program on immunization (EPI), since satisfactory levels of immunity had been attained among the target populations of Chiang Mai and Chon Buri Province during the trial period, 1989 and 1992. In order to facilitate this process and to reduce the administrative costs created by integration of the additional vaccine, the option of combining HB vaccine with the DTP vaccine was investigated. Thus, in 1991 our group performed a clinical study of Smith Kline Beecham Biological's DTP-HB vaccine, administering it to 160 infants of HBsAg negative mothers at the age of 2, 4 and 6 months, respectively. We found the evoked immune responses to be at least equal to, if not higher, than those achieved with the monovalent vaccine. Likewise, any adverse reactions were comparable to those observed after administering either DTP or HB vaccine separately. According to our additional data, we consider HB vaccination at birth, followed by the combined DTP-HB vaccine at the ages of 2, 4, 6 and 18 months, respectively, most advantageous and we would recommend integrating this regimen into the basic immunization service. Thus, the possibility of eradicating hepatitis B infection altogether might eventually be provided.	Y. Poovorawan	The Southeast Asian journal of tropical medicine and public health
251	Comparison study of combined DTPw-HB vaccines and separate administration of DTPw and HB vaccines in Thai children	The safety, immunogenicity and tolerability of two different DTPw-HBV combination vaccines, containing 5 and 10 microg of HBsAg; were investigated in comparison with separate administration of DTPw and HBV (10 microg of HBsAg). A three dose primary vaccination course at 2, 4 and 6 months of age was followed by a booster dose at 18 months. All vaccines were safe and well tolerated. The DTPw-HBV combination vaccine containing 10 microg of HBsAg elicited significantly higher anti-HBs titres than the other two vaccines after the primary and booster vaccination course. All vaccines elicited a high response against the other components. Based on these results, DTPw-HBV (10 microg HBsAg) was the most effective vaccine at this schedule.	Y. Poovorawan, A. Theamboonlers, S. Sanpavat, V. Chongsrisawat, P. Willems and A. Safary	Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand
59	Long-term antibody persistence after booster vaccination with combined tetravalent diphtheria tetanus, whole-cell Bordetella pertussis and hepatitis B vaccine in healthy infants	Combining HB vaccine with routine paediatric vaccines has been recognized as the best means of universal vaccination against hepatitis B. Our objective was to evaluate the long-term antibody persistence of such a combined vaccine in an area of high hepatitis B endemicity. We have shown that a DTPw-HB vaccine was safe and immunogenic when given as a booster dose at 18 months of age. One month after the booster dose of DTPw-HB vaccine, at least 97.8% of subjects had seroprotective anti-HBsAg levels, and 1 year later at least 93.9% of these subjects remained seroprotected against HBsAg. Immune responses to the DTPw components were similar or greater than those of the commercial DTPw vaccine given to the control group. This DTPw-HB vaccine, which showed good long-term anti-HBsAg antibody persistence, could advantageously replace separate DTPw and HB vaccines in areas of high hepatitis B endemicity in terms of clinical, economic and strategic benefits.	Y. Poovorawan, A. Theamboonlers, S. Sanpavat, S. Chumdermpadetsuk, A. Safary and P. Vandepapeliere	Annals of tropical paediatrics
379	The immunogenicity and reactogenicity of combined tetravalent diphtheria, tetanus,pertussis and hepatitis B vaccine in infants		Y. Poovorawan, A. Theamboonlers, S. Sanpavat, W. Pongpunlert, S. Chumdermpadetsuk and A. Safary	Proceedings of the International Symposium on Viral Hepatitis and Liver Disease Viral Hepatitis and Liver Disease
290	Evaluation of serum and salivery IgA against pertussis toxin in volunteers immunized with the genetically inactivated mutant PT-9K/129G pertussis toxin	Study Objective: To ascertain whether subjects immunized with an acellular pertussis vaccine develop specific IgA antibodies. Design: Prospective study of 29 persons receiving vaccine and placebo (18 and 11 subjects respectively) before and after the administrations. Subjects: Adult volunteers aged 25-58 years. Interventions: Subjects were immunized or received placebo. The vaccine was an acellular pertussis vaccine containing an inactivated pertussis toxin (PT-9K/129G), obtained from a mutant bacterial strain of Bordetella pertussis. Sixteen subjects out of the group of vaccinees and 9 of the placebo group received a further dose one month after the first one. Saliva and blood samples were collected just before and one month after the first administration and 42 days after the second dose. Measurements and Main Results: An ELISA method for the detection of specific IgA antibodies in saliva and sera was used. A statistically significant increase in the titres of specific serum IgA (IgA anti-PT) occurred in vaccinated subjects. The titres were not boosted by the second vaccine dose. No significant rise of secretory IgA anti-PT was observed in saliva after both vaccine and placebo administrations. Conclusions: Although our results need further confirmation and the bactericidal effect of serum IgA is controversial, the demonstration that the mutant PT-9K/129G toxin induces also an increase in specific IgA serum antibodies confirms that the inactivated pertussis toxin has a good immunogenic power. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	T. Pozzi, R. Mancini, L. Nencioni, N. Nante, P. Bonanni and R. Gasparini	Journal of Preventive Medicine and Hygiene
374	A phase I randomized, double-blind, controlled trial of 2009 influenza A (H1N1) inactivated monovalent vaccines with different adjuvant systems	METHODS: We conducted a phase I, multicenter, randomized, double-blind, placebo-controlled, multi-arm (10) parallel study involving healthy adults to evaluate the safety and immunogenicity of influenza A (H1N1) 2009 non-adjuvanted and adjuvanted candidate vaccines. Subjects received two intramuscular injections of one of the candidate vaccines administered 21 days apart. Antibody responses were measured by means of hemagglutination-inhibition assay before and 21 days after each vaccination. The three co-primary immunogenicity end points were the proportion of seroprotection >70%, seroconversion >40%, and the factor increase in the geometric mean titer >2.5. RESULTS: A total of 266 participants were enrolled into the study. No deaths or serious adverse events were reported. The most commonly solicited local and systemic adverse events were injection-site pain and headache, respectively. Only three subjects (1.1%) reported severe injection-site pain. Four 2009 influenza A (H1N1) inactivated monovalent candidate vaccines that met the three requirements to evaluate influenza protection, after a single dose, were identified: 15 ?g of hemagglutinin antigen without adjuvant; 7.5 ?g of hemagglutinin antigen with aluminum hydroxide, MPL and squalene; 3.75 ?g of hemagglutinin antigen with aluminum hydroxide and MPL; and 3.75 ?g of hemagglutinin antigen with aluminum hydroxide and squalene. CONCLUSIONS: Adjuvant systems can be safely used in influenza vaccines, including the adjuvant monophosphoryl lipid A (MPL) derived from Bordetella pertussis with squalene and aluminum hydroxide, MPL with aluminum hydroxide, and squalene and aluminum hydroxide.	A. R. Precioso, J. L. Miraglia, L. M. Campos, A. C. Goulart, C. Timenetsky Mdo, M. R. Cardoso, E. Luna, G. Mondini, S. Guedes Jda and I. Raw	Vaccine
351	Pertussis agglutinins in vaccinated children: better response with adjuvant		N. W. Preston, R. I. Mackay, F. N. Bamford, J. E. Crofts and W. L. Burland	J Hyg Lond
50	The Senegal pertussis trial: safety and surveillance of adverse reactions	In the Senegal pertussis trial, common adverse reactions were actively monitored during the pilot phase II study, while the frequency of severe adverse reactions was monitored as a secondary objective within the phase III efficacy trial. Since the trial was conducted in Niakhar, an area in rural West Africa under intensive surveillance, the safety monitoring during the study was incorporated within the general surveillance system. This was a two-step procedure: detection of a potential reaction by a field worker, followed by confirmation report by a physician. The frequency of severe reactions was low among both pertussis vaccine groups, receiving either the two-component acellular vaccine or the whole-cell vaccine currently used in the Senegal Expanded Programme on immunisation. Among severe reactions, only persistent crying was found to be at a significantly higher rate in the whole-cell group. Common adverse reactions were more frequent in the whole-cell group.	M. P. Preziosi, M. Ndiaye, A. Coll-Seck and F. Simondon	Developments in biological standardization
171	Higher anti-hepatitis B response with combined DTPw-HBV vaccine compared with separate administration in healthy infants at 3, 4 and 5 months of age in Slovakia	To help achieve universal infant immunisation against hepatitis B, the World Health Organisation has recommended the development of a combined diphtheria, tetanus and pertussis (DTP) and hepatitis B vaccine (HBV). The advantages come from the fact that DTP coverage is estimated to be over 80% worldwide and a combined DTP-HB vaccine would increase the coverage of HBV. This study was conducted to compare the immunogenicity and reactogenicity of a combined DTP-HB vaccine with separate, concomitant administration of DTP and HBV vaccines. One hundred and twenty infants were randomised in a 1:1 ratio to one of the two vaccination regimens, given as three injections at approximately 3, 4 and 5 months of age. The only difference in immunogenicity between the two regimens was a higher antibody response to hepatitis B in the group given the combined vaccine, possibly as a result of the adjuvant effect of the whole cell pertussis component of the DTP vaccine. Both vaccine regimens were well tolerated.	V. Prikazsky and H. L. Bock	International journal of clinical practice
157	Immunogenicity and safety of four different doses of Haemophilus influenzae type b-tetanus toxoid conjugated vaccine, combined with diphtheria-tetanus-pertussis vaccine (DTP-Hib), in Indonesian infants	Widespread use of Haemophilus influenzae type b (Hib) conjugated vaccine in industrialized countries has resulted in a dramatic decline in the incidence of invasive Hib diseases, but the vaccine's cost has prevented its inclusion in basic immunization programs in developing countries. To overcome this problem, combination with diphtheria-tetanus-pertussis (DTP) vaccine or reduction in the dose of Hib vaccine has been proposed. To evaluate the immunogenicity and adverse reactions from lower doses of Hib-polyribosylphosphate (PRP) conjugated with tetanus toxoid (PRP-T), a double-blind study was conducted in Jakarta, Indonesia, and its suburbs. A total of 1048 infants 6 weeks to 6 months of age received three doses of DTP vaccine combined with the usual 10 microg dose or with a reduced dose of 5, 2.5 or 1.25 microg of PRP-T at two-monthly intervals. Antibodies were measured prior to the first dose and 4-6 weeks following the third dose. Adverse reactions were similar among all four groups. The only significant difference was a higher rate of irritability (p<0.02) and of temperature elevation >38 degrees C (p<0.009) after doses 1 and 2 in the lowest dose group (1.25 microg PRP-T) compared to the other groups. All participants tested had a 4-fold increase in antibodies against all DTP antigens. In addition, after a fourth booster dose of Hib, 99.6% of infants produced >or=0.15 microg/ml of antibody to Hib-PRP, and 96.4% showed levels >or=1.0 microg/ml after primary immunization, level that correlate with short- and long-term immunity, respectively. Antibody titers to the PRP antigen showed no significant differences among dosage groups with the exception of the 5.0 microg group, which had a significantly higher GMC than the 1.25 microg group (p<0.012). This study demonstrates that primary vaccination with half, one-fourth, or one-eighth of the usual dose of PRP-T, combined with DTP vaccine, produces protective immune responses, and has side effects that are comparable to DTP vaccination alone. In these lower dosages, PRP-T conjugate vaccine can lower vaccine costs to a level that is affordable for infant immunization programs in developing countries.	N. H. Punjabi, E. L. Richie, C. H. Simanjuntak, S. J. Harjanto, F. Wangsasaputra, S. Arjoso, A. Rofiq, M. Prijanto, n. Julitasari, U. Yela, C. Herzog and S. J. Cryz	Vaccine
367	Treating 30 pertussis cases in convulsion cough stage with Bai Zi Ping Ke Tang		J. W. Qu	Liaoning Journal of Traditional Chinese Medicine [Liao Ning Zhong Yi Za Zhi]
133	A randomized, dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b (DTPw-HBV-IPV/Hib) vaccine vs. co-administration of DTPw-HBV/Hib and IPV vaccines in 12 to 24 months old Filipino toddlers	As progress toward global poliovirus eradication continues, more and more countries are moving away from use of oral poliovirus vaccines (OPV) to inactivated poliovirus vaccines (IPV) in national vaccination schedules. Reduction of antigen dose in IPV could increase manufacturing capacity and facilitate the change from OPV to IPV. Combination vaccines reduce the number of injections required to complete vaccination, thus playing an important role in maintaining high vaccine coverage with good public acceptability. Three formulations of a combined, candidate hexavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b conjugate vaccine (DTPw-HBV-IPV/Hib, GlaxoSmithKline Biologicals) differing only in IPV antigen content (full-dose, half-dose and one-third dose as compared with available stand-alone IPV vaccines), were evaluated when administered to healthy toddlers. Controls received separately administered licensed DTPw-HBV/Hib and IPV vaccines. Immunogenicity was assessed before and one month after vaccination. Safety and reactogenicity data were assessed for 30 d after vaccination. A total of 312 Filipino children were vaccinated in their second year of life. Each DTPw-HBV-IPV/Hib formulation was non-inferior to control in terms of pre-defined criteria for IPV immunogenicity. Post-vaccination GMTs against each poliovirus type were increased between 4.2- and 37.9-fold over pre-vaccination titers. Non-inferiority to other vaccine antigens was also demonstrated. The safety profile of the 3 DTPw-HBV-IPV/Hib formulations resembled licensed DTPw-HBV/Hib Kft and IPV in terms of the frequency and intensity of adverse reactions after vaccination. Further investigation of DTPw-HBV-IPV/Hib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted. This study is registered at www.clinicaltrials.gov NCT number: NCT01106092.	B. Quiambao, O. Meeren, D. Kolhe and S. Gatchalian	Human vaccines & immunotherapeutics
207	Recurrence of extensive injection site reactions following DTPa or dTpa vaccine in children 4-6 years old	OBJECTIVES: The aim of this study was to compare the immunogenicity and reactogenicity of a lower dose diphtheria, tetanus and pertussis vaccine (dTpa) with the recommended vaccine (DTPa) given as a fifth dose to 4-6-year old children who previously experienced an extensive injection site reaction (ISR). MATERIAL AND METHODS: Children aged 4-6 years who had experienced an extensive ISR following a 4th dose of DTPa were recruited and randomly assigned to receive either the recommended DTPa or the lower dose dTpa vaccine. Parents recorded local reactions and systemic events for 15 days following vaccination. Immunogenicity was assessed pre and post vaccination by ELISA for diphtheria (D), tetanus (T), pertussis toxin (PT), filamentous haemagglutinin (FHA), and pertactin (PRN). RESULTS: A total of 53 participants were vaccinated. There was a 72% recurrence rate of ISR, with a trend (p=0.055) towards fewer ISR in the dTpa (61.5%) compared with the DTPa group (85.2%). There was no difference in reports of pain or irritability between groups. All participants had seroprotective levels of antibody to D and T and seroresponse to each of the 3 pertussis antigens following vaccination with higher GMCs in DTPa vs dTpa group. There was no increase in antibody avidity observed post vaccination, regardless of vaccine given. CONCLUSION: Recurrence of ISR with the 5th dose of diphtheria, tetanus and pertussis vaccination in children who have previously experienced an extensive ISR is high. Vaccination with a dTpa vaccine may reduce the risk of fifth dose ISR.	P. Quinn, M. Gold, J. Royle, J. Buttery, P. Richmond, P. McIntyre, N. Wood, S. S. Lee and H. Marshall	Vaccine
238	Intra-oral administration of sweet-tasting substances and infants' crying response to immunization: a randomized, placebo-controlled trial	The analgesic effects of four solutions administered intra-orally (25 and 50% sucrose solutions, hydrogenated glucose, and a sterile water placebo) were tested in groups of babies receiving routine DTP (diphtheria, tetanus, and pertussis) and HIB (Haemophilus influenzae type B) injections at the first, second, or third immunization. The duration of the baby's cry during 3 min following DTP and HIB injections was measured as main outcome. For all three immunization groups, the babies receiving the placebo generally spent most time crying. For both the DTP and HIB injections, the difference between 50% sucrose and placebo was most evident in the group receiving the 3rd immunization. Intra-oral administration of the 50% sucrose solution, compared to placebo, appeared to reduce the cry response to painful experiences in babies beyond the neonatal period.	L. A. Ramenghi, A. V. Webb, P. M. Shevlin, M. Green, D. J. Evans and M. I. Levene	Biology of the neonate
178	A new combined DTP-HBV-Hib vaccine--strategy for incorporation of Hib vaccination into childhood immunisation programmes	OBJECTIVES: To evaluate the immunogenicity and reactogenicity of a pentavalent vaccine prepared by extemporaneously mixing diphtheria-tetanus pertussis-hepatitis B vaccine (DTP-HBV) and lyophilised Haemophilus influenzae type B (Hib)-tetanus conjugate vaccines in the same syringe, compared with the same vaccines given as separate, concomitant administrations. DESIGN: Open, randomised comparative study. SETTING: Durban, South Africa. SUBJECTS: A total of 120 healthy male and female infants were enrolled in the trial and randomised into two groups; group 1 received the combined administration (DTP-HBV-Hib), and group 2 received separate administrations of DTP-HBV and Hib vaccines. Vaccines were given as a three-dose primary vaccination course at 2, 4 and 6 months [corrected] of age. OUTCOME MEASURES: Antibody levels were measured using standard techniques and local and general solicited symptoms were recorded using diary cards. RESULTS: All subjects had seroprotective titres against diphtheria and tetanus; and antipolyribose-ribitol phosphate (PRP) titres > or = 0.15 microgram/ml 1 month after the final dose. A vaccine response (defined as post-vaccination titres > or = 15 ELISA (EL).U/ml in initially seronegative subjects; and as post-vaccination titres > or = pre-vaccination titres in initially seropositive subjects) against the pertussis component was seen in 83% and 85% of subjects in the groups receiving combined and separate administration. No differences were seen in any of the geometric mean titres (GMTs) between the two administrations either 2 months after the second dose or 1 month after the final dose. There was no observed increase in reactogenicity in the group receiving the mixed administration. CONCLUSIONS: The results demonstrate that combined DTP-HBV-Hib vaccine is well tolerated and immunogenic.	A. Ramkissoon, H. M. Coovadia, P. Jugnundan, P. Willems and B. R. Clemens	South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde
405	Effective pain reduction for multiple immunization injections in young infants	Background: Infants experience undue pain with multiple immunization injections. Objective: To assess the effectiveness, feasibility, and parental acceptance of a simple combination pain reduction intervention for infants receiving multiple immunization injections. Design: Randomized, controlled, clinical trial. Setting: Academic hospital-based primary care centre (Children's Hospital of Pittsburgh Primary Care Center) in Pittsburgh, Pennsylvania, USA. Participants: Infants receiving their two-month immunizations, consisting of four injections (diphtheria and tetanus toxoids and acellular pertussis vaccine, inactivated poliovirus vaccine, Haemophilus influenzae b conjugate and hepatitis B vaccine [Comvax], and heptavalent pneumococcal conjugate vaccine [Prevnar]). Interventions: Subjects were randomly assigned to the intervention or control group for administration of four injections. The intervention group received sucrose and oral tactile stimulation (with a pacifier or a bottle) and were held by their parents during immunization. The control group did not receive these interventions (standard practice). Main Outcome Measures: Blinded assessment of audiotaped crying, heart rate, parent preference for future use of the injection technique, and nurse-rated ease of vaccine administration. Results: One hundred sixteen infants (mean±SD age, 9.5±2.0 weeks) participated. The median (25th-75th percentile range) first cry duration was 19.0 (5.8-62.8) seconds for the intervention group compared with 57.5 (31.0-81.5) seconds for the control group (P=0.002). Parents of the intervention group reported a stronger preference for future use of the injection procedure. For intervention vs. control, the median (25th-75th percentile) parent preference visual analogue scale score was 97.0 (82.0-100.0) vs. 44.0 (5.0-77.2) (P<0.001) (100 indicates definitely prefer). Nurse-rated ease of vaccine administration was equivalent for both treatment groups. Conclusions: Combining sucrose, oral tactile stimulation, and parental holding is associated with significantly reduced crying in infants receiving multiple immunization injections. Parents state a strong preference for future use of this method, and nurses find the intervention injection technique easy to apply.	E. C. Reis, E. K. Roth, J. L. Syphan, S. E. Tarbell and R. Holubkov	Pediatric research
214	Safety, tolerability, and immunogenicity of gardasil given concomitantly with Menactra and Adacel	OBJECTIVES: Multinational phase III trials of a human papillomavirus vaccine, Gardasil, have shown the vaccine to be generally well-tolerated, efficacious, and immunogenic. We evaluated the immunogenicity and safety of Gardasil administered concomitantly with Menactra and Adacel. METHODS: In this open-label study, boys (n = 394) and girls (n = 648) aged 10 to 17 were randomly assigned in a 1:1 ratio as follows: group A (concomitant administration) received a 0.5-mL dose of Gardasil at day 1, month 2, and month 6 and a 0.5-mL dose of Menactra and Adacel on day 1; group B (nonconcomitant administration) received Gardasil at day 1, month 2, and month 6 and Menactra and Adacel at month 1. Antibody levels for all vaccine components were measured. Systemic, injection-site, and serious adverse experiences (AEs) were monitored. RESULTS: Immune responses after concomitant administration of the 3 vaccines were noninferior to nonconcomitant administration. Seroconversion for Gardasil was > or = 99% in both groups A and B. For Menactra and Adacel, concomitant administration of the vaccines was demonstrated to be noninferior to nonconcomitant administration. Concomitant administration was generally well-tolerated. No participants withdrew because of an AE. One serious AE of transient muscular weakness of <24 hours' duration after the third Gardasil injection was reported in group B and was deemed possibly vaccine-related by the investigator. CONCLUSIONS: Overall, concomitant administration was generally well-tolerated and did not interfere with the immune response to the respective vaccines. Concomitant administration should minimize the number of visits required to deliver each vaccine individually, leading to increased compliance and more effective disease prevention.	K. S. Reisinger, S. L. Block, M. Collins-Ogle, C. Marchant, M. Catlett, D. Radley, H. L. Sings, R. M. Haupt and E. I. Garner	Pediatrics
2	Validation of nested Bordetella PCR in pertussis vaccine trial	A nested PCR, using a 239-bp sequence in the pertussis toxin promoter region, was developed and evaluated. The assay differentiates Bordetella pertussis, Bordetella parapertussis, and Bordetella bronchiseptica by restriction enzyme analysis of the amplified fragments. The diagnostic performance of the PCR was evaluated in a Swedish pertussis vaccine efficacy trial which took place from 1992 to 1995, including study children and household members and using culture and serology for laboratory confirmation of suspected cases. In total 2,421 nasopharyngeal aspirates were analyzed. The total diagnostic sensitivity for B. pertussis was 90.2% (194 of 215). During the study period samples were processed with and without the cation-exchange resin Chelex. The PCR diagnostic sensitivity for B. pertussis among the Chelex-treated aspirates was 94.9% (75 of 79), and that for B. pertussis among 124 aspirates in a consecutive non-Chelex-treated material was 89.5% (111 of 124). After Chelex treatment of the 13 PCR-negative samples, an additional six became PCR positive, giving a final sensitivity of 94.3%. In addition, PCR was positive for B. pertussis with 57 of 1,744 samples negative by culture but with available serological data. The specificity of PCR with these samples was supported by a significant increase in antibody levels between acute and convalescent sera in 45 cases and by epidemiological or clinical data in all but two of the remaining cases. PCR was also positive for B. pertussis with 26 of 415 aspirates from episodes lacking serology. The diagnostic sensitivity of PCR for B. parapertussis was 74.0% (37 of 50). There were an additional seven culture-negative B. parapertussis PCR findings, six from cases with significant antibody increases against filamentous hemagglutinin only and one from a case lacking serology. There were no samples positive for B. bronchiseptica. In conclusion, PCR detection of B. pertussis and/or B. parapertussis enabled us to identify 90 positive nasopharyngeal aspirates, in addition to the 262 culture-positive samples (an increase of 34%). Relating these cases to serology and clinical data indicated a PCR specificity approaching 100%.	E. Reizenstein, L. Lindberg, R. Möllby and H. O. Hallander	Journal of clinical microbiology
324	Safety of a fifth dose of diphtheria and tetanus toxoid and acellular pertussis vaccine in children experiencing extensive, local reactions to the fourth dose	Extensive local reactions have been reported after booster doses of diphtheria and tetanus toxoid and acellular pertussis vaccine, but few data are available on revaccination after these reactions. Of 20 children with extensive local reactions after dose 4, only 4 experienced entire upper arm swelling and 7 had swelling >5 cm after dose 5. These reactions were well tolerated and support revaccination	M. B. Rennels, S. Black, E. J. Woo, S. Campbell and K. M. Edwards	Pediatr Infect Dis J
104	Comparison of acellular pertussis-diphtheria-tetanus toxoids and Haemophilus influenzae type b vaccines administered separately vs. combined in younger vs. older toddlers		M. B. Rennels, M. J. Hohenboken, K. S. Reisinger, D. A. Clements, E. B. Walter, M. M. Blatter, J. Nonenmacher and J. G. Hackell	The Pediatric infectious disease journal
55	Simultaneous administration of Haemophilus influenzae type b vaccine with acellular or whole-cell pertussis vaccine: effects on reactogenicity and immune responses to pertussis vaccines	OBJECTIVE: To evaluate the effect of simultaneous Haemophilus influenzae type b conjugate (Hib) vaccination on the safety and immunogenicity of selected acellular (DTaP) and whole-cell (DTP) pertussis vaccines with diphtheria and tetanus toxoids combined. METHODS: Enrollment of infants into a large multicenter study of the safety and immunogenicity of 13 DTaP and 2 DTP vaccines was partially completed when the first Hib vaccine, HbOC (Haemophilus b oligosaccharide conjugate vaccine), was licensed for use in infants. Thereafter, at each immunization most infants received HbOC simultaneously with DTaP (or DTP), administered in opposite thighs. Postvaccination geometric mean titers or concentrations (GMTs) of pertussis antibodies as measured by six different assays were compared pairwise among groups of infants receiving 0, 1, 2, or 3 simultaneous HbOC immunizations. The incidence of reactions was compared between infants who received only DTaP or DTP and those who received HbOC simultaneously. RESULTS: Comparison of postvaccination GMTs was possible among groups of infants receiving different numbers of simultaneous immunizations for 10 of the 13 DTaP and both DTP vaccines. Increased HbOC exposure had no consistent dose-response effect on antibody titers for DTaP or DTP vaccines in any assay. Significant differences between groups in postvaccination GMTs were observed with 4 DTaP vaccines in 1 to 2 assays each; the GMTs were higher with increasing HbOC exposure for 2 DTaP vaccines and lower for 2 others. There was no significant increase in reactions with simultaneous HbOC and DTaP immunization. CONCLUSIONS: Based on these retrospective analyses, there did not seem to be an interference in pertussis immunogenicity or alteration in reactogenicity associated with the simultaneous administration of HbOC and DTaP. These findings are encouraging with respect to the development of DTaP-Hib combination vaccines.	M. B. Rennels, G. F. Reed, M. D. Decker, K. M. Edwards, M. E. Pichichero, M. A. Deloria, J. A. Englund, E. L. Anderson, M. C. Steinhoff and A. Deforest	Pediatrics
347	Sabin vaccine and combined diphtheria-tetanus-pertussis-immunisation		L. Rethy, J. Maroczi and I. Joo	Lancet
3	Laboratory investigation of immune responses to acellular pertussis vaccines when used for boosting adolescents after primary immunisation with whole cell pertussis vaccines: a comparison with data from clinical study	The lack of unequivocal immunological correlates of human protection and an absence of a validated animal model for acellular pertussis vaccines, compounded by limited opportunity to undertake efficacy studies in humans and laboratory evaluation side by side, has made it difficult to compare vaccines and formulations. In the present study, the effect on the booster response to pertussis in adolescents primed in infancy with whole cell pertussis vaccine, of three low dose acellular pertussis/diphtheria/tetanus toxoid (TdPa) formulations with or without inactivated poliomyelitis vaccine (IPV) components, was investigated. To assess the relationship between laboratory vaccine evaluation and clinical trial performance, parallel evaluation of the same TdPa vaccines were carried out in a mouse booster model with whole cell pertussis vaccine priming. Prior to boosting, the clinical subjects had low cell mediated immune responses (CMI) responses to pertussis vaccine components. After boosting, all TdPa formulations stimulated CMI responses to the pertussis vaccine components assessed. The booster responses to the pertussis antigens remained skewed towards Th1 type even though acellular pertussis vaccines were used. In general the antibody and CMI responses to pertussis antigens in the mouse model followed the trend seen in the human subjects. Protection against aerosol challenge with virulent Bordetella pertussis was related to the magnitude of the antibody and CMI responses in the mouse model. As in the human subjects, the responses remained skewed towards Th1 type.	E. Reynolds, B. Walker, D. Xing, J. Southern, C. Asokanathan, B. Dagg, M. Corbel and E. Miller	Vaccine
349	Differences of humoral and cellular immune response to an acellular pertussis booster in adolescents with a whole cell or acellular primary vaccination		N. Rieber, A. Graf, B. H. Belohradsky, D. Hartl, S. Urschel, M. Riffelmann, C. H. Wirsing von Konig and J. Liese	Vaccine
393	Low-cost on-the-job peer training of nurses improved immunization coverage in Indonesia	In Indonesia responsibility for immunizations is placed on local government health centres and on the nurses who provide the immunizations at each centre. An on-the-job peer training programme for these nurses, which was designed to improve the immunization performance of poorly performing health centres in terms of coverage and practice in Maluku province, was evaluated. Experienced immunization nurses were sent to health centres where nurses were inexperienced or performing poorly; the experienced nurses spent 1-2 weeks providing on-the-job training for the less experienced ones. An evaluation of the 13 centres that participated in the programme and the 95 that did not found that the programme increased both immunization coverage and the quality of practice. Coverage of diphtheria/pertussis/tetanus (DPT), polio, and measles vaccinations rose by about 39% in all 13 participating centres when compared with non-participating centres, and by about 54% in the 11 centres that had a functioning transportation system during the year after training. These results reflect increases in the actual number of doses given and improvements in the accuracy of reports. Potential threats to the study's validity were examined and found not to be significant. The out-of-pocket cost of the training programme was about US$ 53 per trainee or about US$ 0.05 per additional vaccine reported to have been given. The marginal cost per additional fully immunized child was estimated to be US$ 0.50	J. S. Robinson	Bulletin of the World Health Organization
254	Tetanus immunity after diphtheria, tetanus toxoids, and acellular pertussis vaccination in children with clinically stable HIV infection	BACKGROUND: HIV infection often impairs the immune response to childhood vaccines. OBJECTIVE: We sought to study the ability of HIV-infected children receiving highly active antiretroviral therapy (HAART) to generate a booster response to immunization with a recall antigen to which they had lost humoral immunity. METHODS: Diphtheria, tetanus toxoids, and acellular pertussis (DTaP) vaccination was given at either 16 or 36 weeks after initiation of HAART to 37 HIV-infected children 2 to 9 years of age with a history of DTaP or diphtheria-tetanus-pertussis receipt who had negative tetanus antibody titers (<or=1:243) at baseline. RESULTS: There was a clear increase in tetanus titers after vaccination, with an increase of 27-fold over the baseline values at weeks 4 and 8. The effect on tetanus titers faded to a 9-fold and 3-fold increase over baseline values at weeks 18 and 32, respectively. DTaP vaccination did not affect HIV-1 RNA viral load or CD4 percentage or cell count. There was no increase in either acute or long-term adverse events associated with the DTaP vaccination. CONCLUSION: Although children with stable HIV infection receiving HAART can mount antigen-specific responses to tetanus immunization, the durability of these responses might be limited. Long-term monitoring of specific immune function in such children is indicated.	H. M. Rosenblatt, L. Y. Song, S. A. Nachman, K. E. Stanley, P. A. Krogstad, G. M. Johnson and A. A. Wiznia	The Journal of allergy and clinical immunology
430	Effect of revaccination with BCG in early childhood on mortality: randomised trial in Guinea-Bissau	OBJECTIVE: To determine whether BCG revaccination at 19 months of age reduces overall child mortality.DESIGN: Randomised trial, with follow-up to age 5.SETTING: A health project in Bissau, Guinea-Bissau, which maintains a health and demographic surveillance system in an urban area with 90 000 inhabitants.PARTICIPANTS: 2871 children aged 19 months to 5 years with low or no reactivity to tuberculin and who were not severely sick on the day of enrollment.INTERVENTION: BCG vaccination or no vaccination (control).MAIN OUTCOME MEASURE: Hazard ratios for mortality.RESULTS: 77 children died during follow-up. Compared with controls, the BCG revaccinated children had a hazard ratio of 1.20 (95% confidence interval 0.77 to 1.89). Two hundred and fifty children were admitted to hospital for the first time between enrollment and the end of the study, with an incidence rate ratio for BCG revaccinated children versus controls of 1.04 (0.81 to 1.33). The trial was stopped prematurely because of a cluster of deaths in the BCG arm of the study. This increase in mortality occurred at a time when many children had received missing vaccinations or vitamin A or iron supplementation; the hazard ratio for BCG revaccinated children compared with controls was 2.69 (1.05 to 6.88) in the period after these campaigns. Throughout the trial, the effect of BCG revaccination on mortality was significantly different (P=0.006) in children who had received diphtheria-tetanus-pertussis (DTP) booster vaccination before enrollment (hazard ratio 0.36, 0.13 to 0.99) and children who had not received the booster before enrollment (1.78, 1.04 to 3.04).CONCLUSIONS: There was no overall beneficial effect of being revaccinated with BCG. The effect of BCG revaccination on mortality might depend on other health interventions. Trial registration Clinical Trials ICA4-CT-2002-10053-REVAC.	A. E. Roth, C. S. Benn, H. Ravn, A. Rodrigues, I. M. Lisse, M. Yazdanbakhsh, H. Whittle and P. Aaby	BMJ (Clinical research ed.)
288	An acellular pertussis vaccine in healthy adults: Safety and immunogenicity	Recent data indicate that Bordetella pertussis can be an important cause of illness in adolescents and adults. In a randomized observer- and subject- blinded study, adults (>=18 years of age) received an acellular pertussis (aP) vaccine containing genetically inactivated pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN), or a saline placebo, and were monitored for safety and immunogenicity. IgG antibodies to PT, FHA, and PRN were measured by enzyme-linked immunosorbent assay (ELISA) and PT neutralization by a Chinese hamster ovary (CHO) cell assay. Local reactions, more common in the aP group, were mild and transient. One month after immunization, geometric mean ELISA antibody concentrations for the aP and placebo groups, respectively, were: anti-PT, 463 and 7.6; anti-FHA, 417 and 18; and anti-PRN, 855 and 14. The anti-PT neutralization titers for the aP and placebo groups were 1:3439 and 1:58 respectively. This aP vaccine is a safe and immunogenic candidate booster vaccine against pertussis for adults. Number of References 46. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	E. P. Rothstein, E. L. Anderson, M. D. Decker, G. A. Poland, K. S. Reisinger, M. M. Blatter, R. M. Jacobson, C. M. Mink, D. Gennevois, A. E. Izu, F. Sinangil, A. G. M. Langenberg, R. P. Schiller, T. J. Hipp, R. L. Souder, T. I. Kennedy, D. R. Faccenda and D. Casher	Vaccine
371	Safety and immunogenicity of a two component acellular pertussis-diphtheria-tetanus toxoid vaccine in 4-6 year old American children [abstract]		E. P. Rothstein, M. E. Pichichero, A. J. Kovel and C. K. Meschievitz	Pediatric Research
427	Dose response and efficacy of a live, attenuated human rotavirus vaccine in Mexican infants	OBJECTIVE: Immunization against rotavirus has been proposed as the most cost-effective intervention to reduce the disease burden associated with this infection worldwide. The objective of this study was to determine the dose response, immunogenicity, and efficacy of 2 doses of an oral, attenuated monovalent G1[P8] human rotavirus vaccine in children from the same setting in Mexico, where the natural protection against rotavirus infection was studied. METHODS: From June 2001 through May 2003, 405 healthy infants were randomly assigned to 1 of 3 vaccine groups (virus concentrations 10(4.7), 10(5.2), and 10(5.8) infectious units) and to a placebo group and were monitored to the age of 2 years. The vaccine/placebo was administered concurrently with diphtheria-tetanus toxoid-pertussis/hepatitis B/Haemophilus influenzae type b vaccine at 2 and 4 months of age. After the administration of the first vaccine/placebo dose, weekly home visits to collect information regarding infant health were conducted. Stool samples were collected during each gastroenteritis episode and tested for rotavirus antigen and serotype. RESULTS: The vaccine was well tolerated and induced a greater rate of seroconversion than observed in infants who received placebo. For the pooled vaccine groups, efficacy after 2 oral doses was 80% and 95% against any and severe rotavirus gastroenteritis, respectively. Efficacy was 100% against severe rotavirus gastroenteritis and 70% against severe gastroenteritis of any cause with the vaccine at the highest virus concentration (10(5.8) infectious units). The predominant infecting rotavirus serotype in this cohort was wild-type G1 (85%). Adverse events, including fever, irritability, loss of appetite, cough, diarrhea, and vomiting, were similar among vaccinees and placebo recipients. CONCLUSION: This new oral, live, attenuated human rotavirus vaccine was safe, immunogenic, and highly efficacious in preventing any and, more importantly, severe rotavirus gastroenteritis in healthy infants. This vaccine produced comparable protection to natural infection.	G. M. Ruiz-Palacios, M. L. Guerrero, A. Bautista-Márquez, H. Ortega-Gallegos, F. Tuz-Dzib, L. Reyes-González, G. Rosales-Pedraza, J. Martínez-López, E. Castañón-Acosta, Y. Cervantes, S. Costa-Clemens and B. DeVos	Pediatrics
289	Trial of a new accellular pertussis vaccine in healthy adult volunteers	Immunogenicity and reactogenicity of a new acellular pertussis vaccine were tested in healthy adults. The vaccine contained three constituents of Bordetella pertussis; filamentous haemagglutinin, pertussis toxin (PT) and fimbriae bearing agglutinogens 2 and 3. The constituents were separately purified, treated with formaldehyde and combined with one of two aluminium adjuvants. Subjects received one dose of vaccine or an appropriate adjuvant-only preparation and were monitored for clinical responses for 7 days. Results with the two forms of vaccine were similar. Of 35 vaccinees, none had a temperature higher than 37 [degree] C or a severe reaction, one had a moderate reaction (possibly due in part to intercurrent infection) and nine had mild reactions confined to localized discomfort and/or erythema or induration at the injection site. All vaccinnees had good serum antibody responses to vaccine antigens measured by ELISA and PT, by neutralization of its effects on Chinese hamster ovary cells. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	D. A. Rutter, L. A. E. Ashworth, A. Day, S. Funnell, F. Lovell and A. Robinson	Vaccine
472	Booster vaccination with hexavalent DTPa-HBV-IPV/Hib vaccine in the second year of life is as safe as concomitant DTPa-IPV/Hib + HBV administered separately	The safety and reactogenicity of a booster dose of GSK Biologicals' hexavalent DTPa-HBV-IPV/Hib vaccine (N=4725) was compared with the separate administration of GSK Biologicals' DTPa-IPV/Hib and HBV vaccines (N=4474) in two open, randomized multicenter studies (A and B). Solicited symptoms occurring within 4 days of vaccination were recorded on diary cards and serious adverse events (SAEs) were collected throughout the study period. In Study A (N=1149), incidences of solicited symptoms were similar in both groups; there were no SAEs either reported within 4 days of vaccination or considered to be causally related to vaccination. In study B (N=8050), where fever was the only solicited symptom, rectal temperature > or =39.5 degrees C was observed in 2.5% and 2.8% of the subjects, respectively. Fever > or =40.0 degrees C was rare (0.6%), and only two cases of febrile convulsions were recorded during the 4 days following vaccination both in the control group. Large swelling reactions (defined as local injection site swelling with diameter >50 mm, noticeable diffuse injection site swelling or noticeable increased circumference of the injected limb) were reported following 2.3% of the booster vaccine doses, regardless of the vaccine used. Extensive swelling reactions involving an adjacent joint were reported in 0.1% of the subjects. Two SAEs, both reported after booster doses of DTPa-IPV/Hib and HBV vaccines administered separately, were considered by the investigators to be related to vaccination. Both resolved completely without sequelae. The hexavalent DTPa-HBV-IPV/Hib vaccine and the DTPa-IPV/Hib and HBV vaccines administered separately have similar good reactogenicity and safety profiles when given as booster doses in the second year of life.	R. Saenger, G. Maechler, M. Potreck, F. Zepp, M. Knuf, P. Habermehl and L. Schuerman	Vaccine
8	Sustained efficacy during the first 6 years of life of 3-component acellular pertussis vaccines administered in infancy: the Italian experience	BACKGROUND: In 1992-1993, a randomized, double-blind, placebo-controlled clinical trial of two 3-component acellular pertussis vaccines was started in 4 of Italy's 20 regions. During the trial, the children had been randomized to receive 3 doses of 1 of 2 acellular pertussis vaccines combined with diphtheria and tetanus toxoids (DT) or of a DT vaccine only, at 2, 4, and 6 months of age. Both diphtheria-tetanus-acellular pertussis (DTaP) vaccines, 1 manufactured by SmithKline Beecham (DTaP SB; Infanrix) and 1 manufactured by Chiron Biocine (DTaP CB; Triacelluvax), contain pertussis toxin (PT), filamentous hemagglutinin, and pertactin. The results of the first period of follow-up, which ended in 1994 (stage 1), showed that both vaccines had a protective efficacy of 84% in the first 2 years of life; when the trial's follow-up was extended under partial blinding until the participating children had reached 33 months of age (stage 2 of the follow-up), these high levels of efficacy had persisted. Therefore, the objective of this study was to estimate the persistence of protection from 3 to 6 years of age of the 2 3-component DTaP vaccines administered as primary immunization in infancy. METHODS: An unblinded prospective longitudinal study of vaccinated and unvaccinated children in 4 Italian regions, with active surveillance of cough, was conducted by study nurses, and Bordetella pertussis infections were confirmed laboratory. The present study (stage 3) included those children who completed stage 2 of the follow-up and were still under active surveillance as of October 1, 1995, accounting for 4217 children who had received DTaP SB (representing 94% of the vaccine's recipients in the initial phase of the trial), 4215 who had received DTaP CB (95% of the original recipients), and 266 who had received DT only (18% of the original recipients). Because the parents of most of the original DT placebo group accepted pertussis vaccination during stage 2 in 1995, an additional 856 children were recruited in the DT group at the initiation of stage 3. These additional children were identified from the census list of children born in the same period and living in the same areas as the trial participants but who had been vaccinated in infancy with DT only. Eligible children were included in stage 3 if they had no history of either pertussis or pertussis vaccination and if a serum sample obtained at the time of enrollment had undetectable immunoglobulin G (IgG) against PT. Parental consent to participate in the study was obtained. Active surveillance for pertussis was conducted in the field by 72 study nurses through monthly contact with each family in the study. A cough episode that lasted >/=7 days was considered to be a laboratory-confirmed infection by Bordetella pertussis if at least 1 of the following 5 criteria (listed in hierarchic order) was met: 1) B pertussis was obtained from nasopharyngeal culture (culture-confirmed infection); 2) the enzyme-linked immunosorbent assay (ELISA) IgG or IgA titer against PT in the convalescent-phase serum sample increased by at least 100% compared with the acute-phase sample; 3) the PT-neutralizing titers in Chinese hamster ovary assay in the convalescent-phase sample increased by at least 4-fold compared with the acute-phase sample; 4) the ELISA IgG or IgA titer against filamentous hemagglutinin in the convalescent-phase sample increased by at least 100% and the culture or the polymerase chain reaction assay on the nasopharyngeal aspirate was negative for B parapertussis; and 5) the ELISA IgG PT titer in 1 of the 2 serum samples exceeded the geometric mean titer computed on convalescent sera of the children with a culture-confirmed B pertussis infection in each study group. Incidence of laboratory-confirmed B pertussis infection, using case definitions that varied in terms of duration and type of cough, was computed and the proportion of cases prevented among DTaP recipients in comparison with DT recipients was calculated. RESULTS: A total of 391 laboratory-confirmed infections were identified n the 3-year follow-up period (138 DTaP SB, 126 DTaP CB, 127 DT recipients, respectively). The mean duration of cough in children with laboratory-confirmed infection was 48, 47, and 70 days for the DTaP SB, DTaP CB, and DT recipients, respectively; the mean duration of spasmodic cough was 15, 13, and 23 days, respectively. When using the primary case definition (ie, laboratory-confirmed B pertussis infection and >/=14 days of spasmodic cough or >/=21 days of any cough), the efficacy was 78% for the DTaP SB vaccine (95% confidence interval [CI]: 71%-83%) and 81% for the DTaP CB vaccine (95% CI: 74%-85%). When using the case definition based on a more severe clinical presentation (>/=21 days of spasmodic cough), the vaccine efficacy was 86% (95% CI: 79%-91%) for both vaccines. When using the case definition based on milder clinical presentation (any cough for >/=7 days), the efficacy was 76% (95% CI: 69%-81%) for the DTaP SB vaccine and 78% (95% CI: 72%-83%) for the DTaP CB vaccine. CONCLUSIONS: The persistence of protection through 6 years of age suggests that the fourth DTaP dose could be postponed until preschool age in children who received 3-component acellular pertussis vaccines in infancy, provided that immunity to diphtheria and tetanus is maintained. Additional booster doses could be administered at older ages to reduce reactogenicity induced by multiple administrations and to optimize the control of pertussis in adolescents and young adults.	S. Salmaso, P. Mastrantonio, A. E. Tozzi, P. Stefanelli, A. Anemona, M. L. Ciofi degli Atti and A. Giammanco	Pediatrics
310	Persistence of protection through 33 months of age provided by immunization in infancy with two three-component acellular pertussis vaccines	A large, randomized, placebo-controlled clinical trial in Italy on two three-component pertussis vaccines, given as DTaP in infancy, one manufactured by SmithKline and Beecham (SB) and one by Chiron Biocine (CB), found each vaccine to be 84% efficacious through the average age of 24 months. The cohort of children enrolled in the trial was followed with unmodified case ascertainment procedures for nine additional calendar months, during which partial unblinding occurred, for the unvaccihated randomized group. For the DTaP groups, the specific vaccine assignment remained double- blinded throughout the entire additional observation period. Pertussis was defined as paroxysmal cough lasting at least 21 days and confirmed by culture or serology. In the additional 9 months the observed absolute efficacy was 78% (95% CI, 62-87%) for SB DTaP vaccine and 89% (95% CI, 79-94%) for CB DTaP. The relative risk of developing pertussis in SB DTaP recipients compared to CB DTaP vaccinees was 1.99 (95% CI, 1.13-3.51). By combining observations from the initial and additional follow-up periods, the overall observed vaccine efficacy through an average age of 33 months of SB DTaP was 80% and of CB DTaP, 85%. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	S. Salmaso, P. Mastrantonio, S. G. F. Wassilak, M. Giuliano, A. Anemona, A. Giammanco, A. E. Tozzi, A. Degli, D. Greco, P. Panei, G. Scuderi, S. Luzi, G. Canganella, F. R. Meduri, P. Stefanelli, M. Bottone, T. Sofia, A. Chiarini, M. Maggio, S. Taormina, M. Genovese, A. Moiraghi, A. Barale, T. S. Di, S. Malaspina, E. Vasile, P. Ferraro, L. P. L. Dal, M. L. De, L. Robino, E. Giraldo, N. Coppola, P. Materassi, G. T. Castellani, F. Basso, S. Barbuti, M. Quarto, P. Lpalco, P. D'Orazio and C. Germinario	Vaccine
39	Case definitions	The definition of a case of pertussis is an essential point in evaluating and comparing the results from the seven studies on pertussis vaccines presented at the Symposium. An assessment of the impact of case definition on the evaluation of vaccine efficacy has been performed on the Italian data-set, by comparing the clinical presentation of cough illnesses which were laboratory-confirmed as B. pertussis infection with those not-confirmed, by study vaccine. The results show that the estimate of vaccine efficacy is greatly variable by the choice of case definition and dependent on the study design. The assessment of the effect of each vaccine should be performed by using various clinical endpoints and the method used in detection of suspected cases in each study should be carefully evaluated to verify comparability of results.	S. Salmaso, A. Moiraghi, A. Barale, P. Ferraro, P. Dal Lago, N. Coppola, P. Materassi, S. Barbuti, P. Lo Palco and A. Anemona	Developments in biological standardization
209	Immunogenicity of hepatitis B vaccines among infant recipients of acellular and whole cell pertussis DTP vaccines	The study was conducted to assess the immunogenicity of three doses of two recombinant hepatitis B virus (HBV) vaccines, administered simultaneously with a DT vaccine or one of three different pertussis vaccines combined with diphtheria and tetanus toxoids. The study population consisted of 1237 children selected from the cohort of 15,601 children enrolled in the Italian trial on pertussis vaccines. HBV vaccination was performed at 2, 4 and 12 months of age, with the first two doses concurrent with OPV and DTP vaccination. The DTP vaccines administered in the pertussis trial included one whole cell DTP, licensed in the USA, and two three-component acellular DTaPs, manufactured in Europe. Immunogenicity to HBV was evaluated on serum samples collected 9 months after the third dose of HBV vaccine. Antibodies against HBsAg were detected by ELISA and expressed in mlU/ml. In 13 children, the antibody response was below the protective level of 10 mlU/ml-1. No statistical difference was found among the various study groups with respect to the proportion of children showing protective response. Higher humoral response was observed in children receiving mixed HBV vaccines in each pertussis study groups.	S. Salmaso, A. Piscitelli, M. Rapicetta, P. Chionne, E. Madonna and C. Argentini	Vaccine
159	Evaluation of the two-needle strategy for reducing reactions to DPT vaccination	Using a blinded crossover design, we tested the hypothesis that changing the needle on the syringe after drawing up diphtheria-pertussis-tetanus vaccine and before injecting it reduces local complications by eliminating deposition of aluminum phosphate adjuvant in the subcutaneous track of the needle. Two hundred twenty-three children (52.7%) received a two-needle vaccination while 200 (47.3%) received a one-needle vaccination. Three hundred forty-six parents (81.8%) returned a questionnaire reporting their child's reaction within 48 hours of injection. There was no significant difference in the occurrence of redness, swelling, tenderness, or limp or in parental measurements of redness and swelling between the one- and two-needle groups. Moreover, we found no differences in the frequency of systemic side effects, including fever, vomiting, anorexia, and crying. These results do not support the practice of changing needles to reduce diphtheria-pertussis-tetanus vaccine reactions.	M. E. Salomon, R. Halperin and J. Yee	American journal of diseases of children (1960)
376	Tian Tu Acupoint(TV 22) blocking in treating cough syndrome like whooping cough in 995 cases		X. C. Sang and Z. Y. Yin	Shandong Journal of Traditional Chinese Medicine [Shan Dong Zhong Yi Za Zhi]
195	DTPw-HB and Hib primary and booster vaccination: combined versus separate administration to Latin American children	This multicentre study was designed to establish the reactogenicity and immunogenicity profiles of primary and booster vaccination with diphtheria, tetanus, and pertussis whole-cell-hepatitis B/Haemophilus influenzae type-b (DTPw-HB/Hib) administered as either a syringe mix or as separate injections in 400 Latin American children. Both vaccine regimens were equally well tolerated and elicited post-primary excellent seropositivity rates at or close to 100% for all five component antigens. With regard to HB, 100% of subjects in the combined vaccination group, and 98.8% subjects in the separate injection vaccination group reached seroprotective antibody concentrations (>or=10 mIU/ml) 1 month after the primary vaccination course. Equally high anti-PRP antibody concentrations were reached 1 month after vaccination, with 100% of seroprotected subjects in the combined vaccination group (antibody concentrations >or=0.15 microg/ml), against 99.4% in the separate injection vaccination group. Seroprotective anti-HBs and anti-PRP antibody concentration levels persisted approximately 1 year after the primary vaccination course, just prior to booster vaccination. Finally, a significant increase of all antibody concentrations could be observed after the booster vaccination, since all but one subject in the separate injection vaccination group had protective levels of anti-HBs and anti-PRP antibodies 1 month after the booster dose. These results suggest that the combination of DTPw-HB and Hib vaccines provides an effective means for increasing vaccine coverage in childhood vaccination programmes.	J. I. Santos, A. Martin, T. Leon, L. Rivera, M. E. Gaitán, C. Rio, G. Oselka, Y. Cervantes, P. Rubio, S. A. Clemens and J. S. Mendonça	Vaccine
119	Serological evaluation of poliomyelitis oral and inactivated vaccines in an urban low-income population at Rio de Janeiro, Brazil	Oral and inactivated poliomyelitis vaccines (OPV and IPV), were given to 160 children two months old, in a low income population at Rio de Janeiro. The vaccination was repeated 2 and 4 months later, always in association with diphtheria, tetanus and pertussis (DPT) vaccine. Blood specimens were collected before vaccination at the time of the third dose of vaccine and later at the time of measles vaccination, when the children were nine months old. The serological response to two doses of IPV showed high titres of antibody in all but one child and 100% conversion after three doses. Although poliomyelitis has been controlled in Brazil by the use of OPV in large mass campaigns, the results obtained with IPV support the possibility of its use in the basic immunization schedule, providing lower costs could be achieved for the inactivated vaccine.	H. G. Schatzmayr, Y. Maurice, M. Fujita and A. M. Fillipis	Vaccine
48	A modified vaccine reduces the rate of large injection site reactions to the preschool booster dose of diphtheria-tetanus-acellular pertussis vaccine: results of a randomized, controlled trial	BACKGROUND: Large injection site reactions commonly follow booster doses of diphtheria-tetanus-acellular pertussis (DTaP) vaccines at 4-6 years of age. A vaccine with lower diphtheria and pertussis dosage (Tdap) might be better tolerated for this dose. METHODS: We conducted a randomized, controlled, evaluator-blinded comparison of local reactions to DTaP.inactivated poliomyelitis vaccine (IPV) or Tdap booster vaccinations, in 4- to 5.5-year-old children. Reactions were assessed daily by parents and after 48 hours by study nurses. Serologic responses were measured before and 4 weeks after vaccination and examined in relation to large local reactions (>or=50 mm redness and/or swelling). RESULTS: 288 children were vaccinated, 145 with DTaP.IPV and 143 with Tdap, and after 48 hours examiners noted local redness >or= 50mm in 17.2 and 6.3%, respectively (P = 0.004). DTaP.IPV vaccinees initially experienced local pain (in 54%) which limited arm motion (in 37%), but symptoms largely resolved by 48 hours. Tdap vaccinees had fewer symptoms (pain in 20%, limited arm motion in 14%). Children with large reactions to DTaP.IPV more often than nonreactors had elevated preimmunization antibody concentrations to 1 or more of diphtheria, pertussis toxin or pertactin and elevated postimmunization antibody concentrations to all antigens except fimbriae. Booster responses to Tdap were reduced with the smaller antigen doses but were generally satisfactory. CONCLUSIONS: This preschool DTaP.IPV booster vaccination caused large local reactions in 1 in 5 children, with transient discomfort. With Tdap vaccine, such reactions were significantly fewer but not eliminated. A Tdap.IPV vaccine warrants study for routine use at 4-6 years of age.	D. W. Scheifele, S. A. Halperin, J. J. Ochnio, A. C. Ferguson and D. M. Skowronski	The Pediatric infectious disease journal
253	Reactogenicity and immunogenicity of a booster dose of a combined diphtheria, tetanus, and tricomponent acellular pertussis vaccine at fourteen to twenty-eight months of age	OBJECTIVES: The primary objective was to assess the nature and incidence of adverse events after a fourth dose of a tricomponent acellular pertussis-diphtheriatetanus vaccine given in the second year of life after primary vaccination with the same vaccine at 3, 4, and 5 months of age. A secondary objective was to analyze the immunogeniecity of the booster vaccination. DESIGN: Of the 5361 children enrolled (aged 14 to 28 months), adverse reactions were specifically solicited from the first 1863 enrollees for the first 4 days after vaccination and then were unsolicited for the remainder of the 4 weeks of follow-up (group 1). In the next 3498 subjects, safety and reactogenicify were entirely unsolicited for this 4-week period (group 2). Immunogenicity was analyzed by means of prebooster and postbooster serum antibody titers for all vaccine components in a random subgroup of 197 children from group 1. RESULTS: Soliciting symptoms elicited reports of at least one symptom in 1314 of 1809 children in group 1 (72.6%), including 993 (54.9%) with local and 885 (48.9%) with general symptoms during the first 4 days after vaccination. When symptoms were gathered in an unsolicited fashion, only 580 of 3498 children in group 2 (16.6%) had a reported symptom during this time, consisting of 344 (9.8%) local and 319 (9.1%) general symptoms, respectively. An unsolicited symptom, areactive edematous swelling of the whole thigh, occurred in 62 children (1.1%), with 45 and 17 reports in groups 1 and 2, respectively. The vast majority of all reported symptoms were mild to moderate, and all children recovered without sequelae. Fourteen serious adverse events were reported, but none was considered to be related to the vaccination. Immunogenicity analysis showed a vaccine response to pertussis toxin in 99.5% of subjects, to filamentous hemagglutinin in 98.5%, and to pertactin (69 kd outer membrane protein) in 99%. All subjects had postvaccination antibody titers of 0.1 IU/ml or greater against diphtheria and tetanus toxoids.	H. J. Schmitt, K. Beutel, A. Schuind, M. Knuf, S. Wagner, S. Müschenborn, H. Bogaerts, H. L. Bock and R. Clemens	The Journal of pediatrics
193	Two versus three doses of a meningococcal C conjugate vaccine concomitantly administered with a hexavalent DTaP-IPV-HBV/Hib vaccine in healthy infants	The immunogenicity and reactogenicity of a meningococcal serogroup C (MenC) conjugate vaccine given concomitantly with DTaP-IPV-HBV/Hib vaccine according to a two- or three-dose schedule in healthy infants was evaluated. At 1 month post-vaccination, 98% (two doses) and 100% (three doses) of subjects had serum bactericidal antibody using human complement assay (hSBA) titres > or =1:8; at 12 months of age > or =89% of subjects in each group remained seroprotected. Induction of immunological memory, as evaluated by administration of a meningococcal serogroup A/C polysaccharide vaccine challenge dose, was similar for both regimens and no interference was observed in the immune response to MenC or hepatitis B virus antigens. Reactogenicity was similar in each group. MenC conjugate vaccine given concomitantly with DTaP-IPV-HBV/Hib to healthy infants in the first year of life using a two-dose schedule is as safe and immunogenic as a three-dose regimen.	H. J. Schmitt, K. S. Steul, A. Borkowski, F. Ceddia, E. Ypma and M. Knuf	Vaccine
31	Minor adverse events in a comparative efficacy trial in Germany in infants receiving either the Lederle/Takeda acellular pertussis component DTP (DTaP) vaccine, the Lederle whole-cell component DTP (DTP) or DT vaccine. The Pertussis Vaccine Study Group	Minor adverse events were evaluated in a comparative efficacy trial in Germany in infants who received either the Lederle/Takeda acellular pertussis component DTP (DTaP) vaccine, the Lederle whole-cell component DTP (DTP) or DT vaccine. Vaccinees received four doses (at three, four-and-a half, six and 15-18 months of age) of either DTP or DTaP vaccine or three doses (at three, four-and-a half and 15-18 months of age) of DT vaccine. The reactogenicity analysis included 4,273 DTaP, 4,259 DTP and 1739 DT vaccinees. Local reactions (erythema and induration) and systemic events (fever, fretfulness, drowsiness and anorexia) were more common after each dose of DTP vaccine than after the DTaP and DT vaccine doses. Erythema, induration and fever increased in frequency in DTaP and DT recipients with increasing series number. Erythema, induration and fever after the first two doses of vaccine were more frequent in DT recipients than DTaP vaccinees. Antipyretics were more commonly used in DTP recipients than in DTaP vaccinees.	S. Schmitt-Grohé, K. Stehr, J. D. Cherry, U. Heininger, M. A. Uberall, S. Laussucq and T. Eckhardt	Developments in biological standardization
361	Clinical study with acellular pertussis vaccine as a booster vaccination		B. Schneeweiss, H. L. Bock, H. G. G. Bogaerts, H. Koditz, H. Schulte-Wissermann, S. Wiersbitzky, R. Sanger and R. Clemens	Der Kinderarzt
352	Reaktogenititivity and immunogenitivity of a combined dipheria-tetanus-trivalent acellular perussis vaccine (DTPa) from SmithKline Beecham in comparison to usual diptheria-tetanus-whole germ pertussis vaccine (DTPw) in a booster vaccination		B. Schneeweiss, H. Koditz, F. Schulte-Wissermann, R. Sanger, H. L. Bock, H. Bogaerts and R. Clemens	Monatsschrift fur Kinderheilkunde
343	Booster vaccination with the new acelluar diptheria-tetanus-pertussis (DTPa)-vaccine?Immunogenitivity and reactogenitivity in comparison to DTPw in DTPw basic immunised children		B. Schneeweiss, H. Koditz, F. Schulte-Wissermann, R. Sanger, H. L. Bock and R. Clemens	Monatsschrift fur Kinderheilkunde
411	Integration of hepatitis B vaccination into rural African primary health care programmes	OBJECTIVE: To determine the efficacy of hepatitis B vaccine when added to the routine expanded programme on immunisation under field conditions in rural Africa. DESIGN: Infants were immunised according to two schedules--an early schedule at birth, 3 months, and 6 months and a later schedule to correspond with routine vaccination in the expanded programme on immunisation at 3 months, 4 1/2 months, and 6 months. SETTING: Venda, northern Transvaal, South Africa, a self governing region of 7460 square kilometers varying from rural villages to small towns. SUBJECTS: The 1989 birth cohort of Venda. MAIN OUTCOME MEASURES: Coverage for hepatitis B vaccine at first, second, and third doses; serological assessment of vaccine efficacy by prevalence of antibodies to hepatitis B surface antigen in infants who had completed the three dose course of immunisation; antibodies to hepatitis B core antigen to determine if natural infection occurred. RESULTS: Vaccine coverage for hepatitis B dropped sharply from 99% to 53% to 39% for the first, second, and third dose respectively. In contrast, vaccine coverage was maintained at 97-99% for the three doses of poliomyelitis vaccine. Serological evaluation of vaccine efficacy showed that only 3.5% of recipients of all three doses failed to develop antibodies to hepatitis B surface antigen. Only 6.6% of vaccine recipients were vaccinated according to either the early or later schedules whereas 93.4% received their doses of vaccine at intervals beyond the limits of either of the planned schedules. There was, however, no significant difference in seroconversion to the surface antigen between the "unscheduled" or scheduled groups of those who were vaccinated according to the early or late schedules. The pattern of prevalence of antibodies to hepatitis B core antigen, which showed a sharp fall in children aged over 7 months, suggested that the antibodies were acquired passively rather than by active infection. CONCLUSIONS: Supplementation of the present expanded programme on immunisation with hepatitis B vaccine in rural Africa is fraught with difficulties. However, the vaccine was effective within a fairly wide spacing of dosage. Adding hepatitis B vaccine to diphtheria, tetanus, and pertussis as a tetravalent vaccine is proposed as a means of effectively integrating it into the expanded programme on immunisation in Third World settings.	B. D. Schoub, S. Johnson, J. M. McAnerney, N. Blackburn, M. C. Kew, J. P. McCutcheon and N. D. Carlier	BMJ (Clinical research ed.)
439	Sensitization of human alpha 1- and alpha 2-adrenergic venous responses by guanadrel sulfate	The alpha 1- and alpha 2-adrenergic venoconstriction in dorsal hand veins of normal subjects was determined by infusion of phenylephrine or clonidine. Oral administration of prazosin reduced the constriction response to phenylephrine but not to clonidine. Subjects were treated for 3 weeks in a randomized crossover design with placebo or guanadrel sulfate. Guanadrel reduced sympathetic tone (i.e., plasma norepinephrine and norepinephrine release rate), whereas venous responses to phenylephrine and clonidine were both augmented during guanadrel treatment. The effect on phenylephrine responses was primarily attributable to a decrease in the median effective concentration with a small increase in maximum response. Clonidine showed a markedly increased maximum response with a small increase in the median effective concentration. Platelet alpha 2-adrenergic receptors increased slightly but there was no change in the amount of platelet pertussis toxin substrate during guanadrel treatment. Thus reduction in sympathetic tone in normal young men results in increased venous responses to both alpha 1- and alpha 2-agonists.	M. A. Sekkarie, B. M. Egan, R. R. Neubig and M. A. Supiano	Clinical pharmacology and therapeutics
434	Depressed immune response to tetanus in children with vitamin A deficiency	A randomized, double-masked, placebo-controlled clinical trial was conducted with 236 preschool children, age 3-6 y, in Indonesia to assess immune status in mild vitamin A deficiency. The immune response to tetanus immunization was used as a measure of immune competence. Clinically normal children (n = 118) and children with mild xerophthalmia (n = 118) were randomly assigned to receive oral vitamin A (60,000 micrograms retinol equivalent) or placebo treatment for a total of four study groups. Two weeks after treatment, children were immunized with diphtheria-pertussis-tetanus vaccine. The immunoglobulin G (IgG) responses to tetanus at baseline and 3 wk following immunization were measured by ELISA. After adjusting for previous tetanus immunization, clinically normal and xerophthalmic children receiving vitamin A had a significantly greater IgG response to tetanus than clinically normal and xerophthalmic children receiving placebo (P less than 0.05). These results suggest that children with mild vitamin A deficiency have a relative immune depression compared with children who have been supplemented to normal vitamin A levels.	R. D. Semba, n. Muhilal, A. L. Scott, G. Natadisastra, S. Wirasasmita, L. Mele, E. Ridwan, K. P. West and A. Sommer	The Journal of nutrition
444	Angiotensin II-induced oxidative burst is fluvastatin sensitive in neutrophils of patients with hypercholesterolemia	The aim of this study was to investigate the effect of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor fluvastatin (Flu) on angiotensin II (AII)-stimulated neutrophils of patients with hypercholesterolemia. Results suggest that a 6-week-long Flu administration completely counteracted the AII-induced increase in superoxide anion and leukotriene C4 production of the neutrophils of patients with hypercholesterolemia. However, the failure of signal processing through pertussis toxin-sensitive G protein, the increase in [Ca2+]i in membrane-bound protein kinase C activity, and the increase in neutrophil-bound cholesterol content were only partially restored by Flu. In addition, Flu had no effect on the increased membrane rigidity of the neutrophils of patients with hypercholesterolemia. To sum it up, Flu administration had a beneficial effect on AII-triggered reactive oxygen species generation; it resulted in partial restoration of signaling processes and of membrane composition, but membrane fluidity remained unchanged.	I. Seres, G. Fóris, D. Páll, B. Kosztáczky, G. Paragh, Z. Varga and G. Paragh	Metabolism: clinical and experimental
215	Immunogenicity and safety of an indigenously developed DTPw hepatitis B combination vaccine in Indian infants	OBJECTIVE: To evaluate the safety and immunogenicity of an indigenous hepatitis B, diphtheria, tetanus and B. pertussis tetravalent vaccine (Shantetra) in comparison with Tritanrix HBTM in healthy Indian infants. DESIGN: Multicentric, randomized, single blind intention-to-treat study with 12-18 weeks of follow up period. SETTING: 5 out patient departments at tertiary care referral centers across India. PARTICIPANTS: 151 infants were randomized in a 2:1 ratio to recruit 101 in the Shantetra and 50 in the Tritanrix HBTM groups respectively. A total of 136 subjects completed the study. No patients were withdrawn from the study due to any adverse effects. INTERVENTIONS: Recruited subjects were randomized to receive three doses of either of the two DTPw-Hepatitis B combination vaccines as per the EPI schedule. MAIN OUTCOME MEASURES: Monitoring the humoral immune response (seroconversion rates) induced by each antigenic component three to six weeks after the last dose of vaccine in both the groups. RESULTS: Seroprotective immune response was observed in 98.9% subjects for diphtheria, tetanus and hepatitis B components in the Shantetra group as compared to 95.5% subjects in the Tritanrix HB group. Anti pertussis antibody response was seen in 89% and 91.1% in the Shantetra and Tritanrix HB groups, respectively. The commonly observed adverse events in both the groups were, pain at injection site, mild fever and transient crying. CONCLUSION: The safety and immunogenicity of indigenously developed DTPwHepatitis B combination vaccine was demonstrated in the present study.	R. Shah, M. B. Raghu, A. Shivananda, S. Mangayarkarasi, I. Rao, R. Rao, P. Bhusari, C. A. Joseph and R. Reddy	Indian pediatrics
130	Immunogenicity and reactogenicity of DTPa-IPV/Hib vaccine co-administered with hepatitis B vaccine for primary and booster vaccination of Taiwanese infants	Immunogenicity and reactogenicity of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (Hib) conjugate vaccine (DTPa-IPV/Hib, Infanrix?-IPV + Hib) was assessed when co-administered with hepatitis B (HBV) vaccine. Seventy healthy infants received DTPa-IPV/Hib at 1.5, 3.5, 6 and 15-18 months, and HBV at birth, 1.5, 6 and 15-18 months of age. Serological responses were assessed. Diphtheria, tetanus, Hib and pertussis seroprotection/seropositivity rates were 100% after primary vaccination. Post-primary immune responses to poliovirus could not be evaluated for technical reasons. However, after the booster dose, seroprotection/seropositivity rates, including poliovirus, were 100%. Over 95% were seroprotected against HBV. Post-booster geometric mean antibody concentrations/titers (GMC/GMTs) rose from 14-fold to 45-fold, indicating effective priming against all antigens, including polioviruses. DTPa-IPV/Hib was well tolerated alone or co-administered with HBV. No serious adverse events were considered related to vaccination. Primary and booster vaccination with combined DTPa-IPV/Hib and HBV was immunogenic and well tolerated. Combination vaccines enable vaccine providers to conveniently provide routine pediatric immunizations, with minimal discomfort.	P. L. Shao, C. Y. Lu, Y. C. Hsieh, H. L. Bock and L. M. Huang	Journal of the Formosan Medical Association = Taiwan yi zhi
179	A phase III randomized, controlled study to assess the immunogenicity and tolerability of DTPw-HBV-Hib, a liquid pentavalent vaccine in Indian infants	Immunogenicity and tolerability of two liquid pentavalent vaccines, Pentavac(®) (new vaccine), and Easyfive(®) (available in the market) was assessed in a multicentre study in India. In all, 484 infants aged 6-8 weeks were enrolled, and their blood samples were assessed prior to the first dose and one month after the third dose. A 100% seroprotection rate was achieved with both vaccines' antigens, except pertussis for which the response was 95% and 96%, respectively, for the two vaccines. A diary-based recording of adverse events showed that the two most common events were pain at the injection site and restricted limb movements and were less frequent (p<0.001) among the recipients of the new vaccine. The new vaccine meets all criteria of childhood vaccination. Its low reactogenicity and low cost are valid reasons to recommend this vaccine for general use.	H. Sharma, S. Yadav, S. Lalwani, V. Gupta, S. Kapre, S. Jadhav, A. Chakravarty, S. Parekh and S. Palkar	Vaccine
259	A phase III randomized, controlled study to assess and compare the immunogenicity and tolerability of single and multi-dose vials of DTwP-Hib, a fully liquid quadravalent vaccine and their comparison with TETRAct-Hib vaccine in Indian infants aged 6-14 weeks	Both WHO and IAP encourage using combination vaccines, wherever feasible. The phase III trial reported here was conducted to assess and compare the immunogenicity, tolerability and safety of two quadravalent vaccines, Quadrovax(®) (new vaccine), and TETRAct-Hib(®) (available in the market) in a multicentre study, in India. In all, 361 infants aged 6-8 weeks were enrolled, out of which 339 completed the study. The vaccination was done at 6-10-14 weeks following EPI/WHO recommended immunization schedule. Blood samples were collected prior to the administration of first dose and one month after the third dose. Postvaccination, geometric mean titres for each component did not differ significantly between the single dose vial and multi dose vial subgroups and among the two study groups. Adverse events observed were within the range quoted in literature. Quadrovax(®) vaccine manufactured by SIIL was found to be safe, immunogenic and non-inferior to the comparator vaccine. The quadravalent vaccine is best recommended in the second year of life when children receive their booster dose at 15-18 months. It can be given to infants during primary immunization series at 6, 10 and 14 weeks of age when Hepatitis B vaccine is given in a separate arm or to infants at 10 weeks who receive the Hepatitis B vaccine separately following the 0, 6 and 14 weeks or 0, 1 and 6 months schedule.	H. Sharma, S. Yadav, V. Patil, B. Chacko, S. Kapre, S. Jadhav, S. Ravetkar, S. Bahl, S. Parekh, A. Chakravarty, G. Ashtagi and A. Prasath	Vaccine
321	Safety and immunogenicity of diphtheria-tetanus-pertussis vaccine and hepatitis B vaccine as a new tetravalent combination (DTwP/HB) administered alone and at separate sites (DTwP and HB) including comparison with standard commercially available combination vaccine in Indian infants 6-14 weeks of age	An open, comparative study was conducted at two tertiary care hospitals in India to assess immunogenicity and reactogenicity following administration of the DTwP/HB combination vaccine (Q-Vac) alone and DTwP and HB (Genevac B) vaccines at separate sites. These vaccines manufactured by Serum Institute of India, Ltd. (SIIL), Pune were compared with DTwP/HB vaccine (Tritanrix HB) manufactured by GlaxoSmithKline (GSK) in infants aged 6 - 14 weeks. The sample size comprised 447 infants who received DTwP/HB vaccine (Group A-150, SIIL) or DTwP and HB (Group B-147, SIIL) vaccines at separate sites or DTPw/HB vaccine (Group C-150, GSK), in a dose of 0.5 ml intra-muscularly. Pre and postvaccination IgG antibodies were determined by ELISA. Postvaccination, in Group A seroprotection was 99.3%, 100%, 96% and 100% to Diphtheria, Tetanus, Pertussis and HBs components respectively. In Group B (n = 147) it was 98.6%, 100%, 95.9% and 99.3% and in Group C (n = 150), it was 96%, 99.3%, 93.3% and 98.6% to D, T, P and HBs component of the vaccine. Postvaccination, geometric mean titres for each component were comparable across three groups by analysis of variance (ANOVA). Adverse events observed were within the range quoted in literature and no Serious Adverse Event (SAE) was observed. Reactogenicity profile in all three groups was comparable. Q-Vac vaccine manufactured by SIIL was found to be safe and immunogenic. Hepatitis B (HB) component did not interfere with the immune response to DTwP components of the vaccine. copyright2009 Landes Bioscience. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	H. J. Sharma, A. K. Dutta, S. M. Joshi, S. Malik, S. Bhardwaj, G. S. Namjoshi and S. S. Parekh	Human Vaccines
218	Immunogenicity and safety of an indigenously manufactured reconstituted pentavalent (DTwP-HBV+Hib) vaccine in comparison with a foreign competitor following primary and booster immunization in Indian children	OBJECTIVE: An open label, controlled clinical study was conducted in Indian infants aged 6-14 weeks to compare the immunogenicity and safety of a reconstituted pentavalent vaccine (DTwP-HBV+Hib) of Serum Institute of India Ltd (SIIL) with TritanrixHB+Hiberix vaccine of Glaxo Smithkline (GSK). METHODS: Eligible infants were randomized to receive three doses of the study / comparator vaccine. The vaccines were reconstituted prior to administration, by mixing DTwP-HBV (liquid) with the Hib (lyophilized) vaccine. IgG antibody titres were assessed by ELISA at baseline and after one month following the 3-dose primary immunization schedule. Safety was evaluated after each dose. Further, safety and immunogenicity was also evaluated following a booster dose in the same cohort of children (aged between 15-24 months). SETTING: Tertiary-care hospitals in India Important outcome measures: Immunogenicity and safety following a 3-dose primary vaccination series and a booster vaccination. RESULTS: Post-primary immunization, 100% seroprotection was noted for Diphtheria, Tetanus, Hepatitis B and PRP-Hib components in both the vaccine groups. For pertussis, response was 96.1% in SIIL and 95.4% in GSK group. The overall safety profile as well as persistence of antibodies against all vaccine components up to the time of booster immunization was comparable between the SIIL and GSK groups. A marked rise of all antibody concentrations indicated effective priming. The booster dose was safe, well tolerated with a significant increase in antibody concentrations of all the vaccine antigens in both the groups. CONCLUSION: DTwP-HBV+Hib vaccine of SIIL was found to be safe and immunogenic. This Indian vaccine compared well with the licensed vaccine and is a cost-effective alternative for incorporating into the immunization schedule of various countries so as to control worldwide Hepatitis B and Hib infections.	H. J. Sharma, S. Yadav, S. K. Lalwani, S. V. Kapre, S. S. Jadhav, A. Chakravarty, S. S. Parekh, S. Palkar, S. H. Bhardwaj, G. S. Namjoshi and V. Verma	Human vaccines
278	Safety and immunogenicity of hydrogen peroxide-inactivated pertussis toxoid in 18-month-old children	The immunogenicity and adverse effects of an acellular pertussis vaccine consisting of a purified pertussis toxin inactivated with hydrogen peroxide (PTxd) was evaluated. Children aged 15 to 30 months were injected with 10 (n = 33) or 50 micrograms (n = 34) of PTxd or with diphtheria and tetanus toxoids and whole cell pertussis vaccine (DTP) (n = 34). All children had previously received three doses of DTP during infancy. Both dosages of PTxd induced higher IgG antibody (p less than 0.05 for 10 micrograms dose and p less than 0.01 for 50 micrograms dose) and pertussis antitoxin responses (p less than 0.01 for 50 micrograms dose) than DTP. The 50 micrograms dose gave slightly higher (though not significantly) antibody responses than the 10 micrograms dose of PTxd. None of the vaccines induced detectable IgM or IgA antibody responses to pertussis toxin. At 24 h, local reactions occurred in none of the children injected with 10 micrograms PTxd, 12% with 50 micrograms PTxd and 78% with DTP. Fever at 24 h occurred in 13% after 10 micrograms PTxd, in none after 50 micrograms PTxd and in 53% after DTP. Recipients of DTP, but not of PTxd, had significant increases in neutrophils and decreases in lymphocytes and haematocrit at 24 h (all p less than 0.05). None of the groups showed changes in blood glucose at 24 h. PTxd induced pertussis toxin antibody levels similar to those observed in patients convalescing from natural pertussis. This acellular pertussis vaccine deserves further evaluation for safety and immunogenicity in infants and for efficacy in preventing pertussis.	G. R. Siber, N. Thakrar, B. A. Yancey, L. Herzog, C. Todd, N. Cohen, R. D. Sekura and C. U. Lowe	Vaccine
418	Effects of metoprolol on myocardial beta-adrenoceptors and G(ialpha)-proteins in patients with congestive heart failure	Objective: In human heart failure downregulation of beta-adrenoceptors and upregulation of G(i)-protein alpha-subunits (G(ialpha)) results desensitization of the myocardial beta-adrenergic signal transduction pathway and reduced positive inotropic effects of catecholamines. Metoprolol treatment has been shown to restore the reduced beta-adrenoceptor density in dilated cardiomyopathy. The main objective of the present study was to investigate whether metoprolol also decreases the elevated inhibitory G(ialpha) levels in patients suffering from congestive heart failure. Methods: Total G(ialpha) was determined by pertussis toxin-catalysed ADP ribosylation and beta1- and beta2-adrenoceptor densities by radioligand binding in right ventricular myocardial biopsies of 18 patients with dilated or ischaemic cardiomyopathy (NYHA II-IV) before and after 3 months of therapy. Nine controls were treated with conventional therapy only [diuretics, digitalis, nitrates, angiotensin-converting enzyme (ACE) inhibitors], and nine received the beta1-selective blocker metoprolol in addition (mean 98 +/- 12 mg daily). Results: In biopsies from patients treated with metoprolol, G(ialpha) significantly decreased to 74% of predrug value and total beta-adrenoceptor increased by a selective increase in beta1-adrenoceptors (44.7 vs 34.0 fmol. mg-1 protein). These effects were accompanied by significantly increased oxygen uptake at the anaerobic threshold (8.65 vs 6.95 ml. kg-1. min-1). In the control group no significant changes in biochemical and clinical parameters occurred. Conclusion: Metoprolol partly reverses G(ialpha)-upregulation and beta-adrenoceptor downregulation in heart failure, which might contribute to the clinical improvement of patients treated with beta-blockers. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	M. Sigmund, H. Jakob, H. Becker, P. Hanrath, C. Schumacher, T. Eschenhagen, W. Schmitz, H. Scholtz and M. Steinfath	European Journal of Clinical Pharmacology
222	Comparison of enhanced potency inactivated poliovirus vaccine (EIPV) versus standard oral poliovirus vaccine (OPV) in Thai infants	Enhanced potency inactivated poliovirus vaccine (EIPV), combined with diphtheria-tetanus-pertussis (DTP) vaccine, was compared with oral poliovirus vaccine (OPV) regarding immunogenicity in Thai infants, vaccinated at 2, 4 and 6 months of age. EIPV induced significantly higher seroconversion rates than OPV to all 3 poliovirus types after the second and third immunization. After 3 doses of each vaccine, at 7 months of age, all infants receiving EIPV proved seropositive for poliovirus type 1, type 2 and type 3 neutralizing antibodies, whereas of those receiving OPV, 9% remained seronegative (titre < 1:4) for type 1 (p = 0.0042) and 11% for type 3 (p = 0.0013). All participating children were given an additional dose of OPV at the age of 9 months and tested again at 12 months of age. At that point, virtually all infants had poliovirus neutralizing antibodies, but the geometric mean titres to each poliovirus type were significantly higher in the vaccinees who had received EIPV. It is concluded that the greater immunogenicity of EIPV vis-à-vis 3 doses of OPV may be biologically significant for protection against poliovirus types 1 and 3 in countries where cases of poliomyelitis occur in young children. These findings warrant considering EIPV, alone or in combination with OPV, for an immunization programme in Thailand and similar countries in the future.	S. Simasathien, S. Migasena, C. Beuvery, G. Steenis, R. Samakoses, P. Pitisuttitham and T. Vesikari	Scandinavian journal of infectious diseases
243	A randomized double-blind trial comparing a two-component acellular to a whole-cell pertussis vaccine in Senegal	A randomized, double-blind trial comparing a diphtheria-tetanus-acellular pertussis vaccine (DTaP) (pertussis toxoid and filamentous hemagglutinin) with a whole-cell vaccine (DTwP) was conducted. A case-contact study was nested in the trial to estimate absolute efficacy. From 1990 through 1994, 4181 children were randomized to receive one of the vaccines at 2, 4, and 6 months. Severe adverse events were monitored weekly during two visits after vaccination. Fewer serious adverse events were observed after DTaP. Surveillance for cough illnesses persisting more than 7 days, in children under 15 years of age, was made by weekly home visits. Examining physicians, blind to vaccination status, took samples for culture and serologic testing. Pertussis was defined as 21 or more days of cough confirmed by culture, serology, or contact with a culture-confirmed person. Beginning 28 days after the third vaccine dose, the overall ratio of pertussis incidence in the DTaP group relative to the DTwP group (RRac/wc) was 1.54 (95% CI, 1.23-1.93). In children younger than 18 months of age, RRac/wc was 1.16 (95% CI, 0.77-1.73) and 1.76 (95% CI, 1.33-2.33) in children older than 18 months, which suggests a shorter duration of protection with the acellular vaccine (P = 0.090). Absolute efficacy estimates derived from the case-contact study confirmed the lower protection afforded by the acellular vaccine compared with the whole-cell vaccine: 31% (95% CI, 7-49) versus 55% against the protocol case definition, and 85% (95% CI, 66-93) versus 96% for the more severe WHO case definition. Although vaccination with DTaP provided a lower degree of protection than the highly effective DTwP, this difference was less prominent before 18 months of age, the customary age for a fourth dose. The safer DTaP vaccine may prove a valuable substitute for whole-cell vaccines when used in a schedule that includes a booster-dose.	F. Simondon, M. P. Preziosi, A. Yam, C. T. Kane, L. Chabirand, I. Iteman, G. Sanden, S. Mboup, A. Hoffenbach, K. Knudsen, N. Guiso, S. Wassilak and M. Cadoz	Vaccine
304	A randomized dowble-blind trial comparing a two-component acellular to a whole-cell pertussis vaaccine in Senegal	A randomized double-blind trial comparing a diphtheria-tetanus-acellular pertussis vaccine (DTaP) (pertussis toxoid and filamentous hemagglutinin) with a whole-cell vaccine (DTwP) was conducted A case-contact study was nested in the trial to estimate absolute efficacy. From 1990 through 1994, 4181 children were randomized to receive one of the vaccines at 2, 4, and 6 months. Severe adverse events were monitored weekly during two visits after vaccination. Fewer serious adverse events were observed after DTaP. Surveillance for cough illnesses persisting more than 7 days, in children under 15 years of age, was made by; weekly home visits. Examining physicians, blind to vaccination status, took samples for culture and serologic testing. Pertussis was defined as 21 or more days of cough confirmed by culture, serology, or contact with a culture-confirmed person. Beginning 28 days after the third vaccine dose, the overall ratio of pertussis incidence in the DTaP group relative to the DTwP group (RR(ac/wc)) was 1.54 (95% CI, 1.23-1.93). In children younger than 18 months of age, RR(ac/wc) was 1.16 (95% CI, 9.77-1.73) and 1.76 (95% CI, 1.33-2.33) in children older than 18 months, which suggests a shorter duration of protection with the acellular vaccine (P = 0.090). Absolute efficacy estimates derived from the case-contact study confirmed the lower protection afforded by the acellular vaccine compared with the whole-cell vaccine: 31% (95% CI, 7-49) versus 55% against the protocol case definition, and 85% (95% CI, 66-93) versus 96% for the more severe WHO case definition. Although vaccination with DTaPprovided a lower degree of protection than the highly effective DTwP this difference was less prominent before 18 months of age, the customary age for a fourth dose. The safer DTaP vaccine may prove a valuable substitute for whole-cell vaccines when used in a schedule that includes a booster dose. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	F. Simondon, M. P. Preziosi, A. Yam, C. Toure-Kane, L. Chabirand, I. Iteman, G. Sanden, S. Mboup, A. Hoffenbach, K. Knudsen, N. Guiso, S. Wassilak and M. Cadoz	Vaccine
127	DT5aP-Hib-IPV and MCC vaccines: preterm infants' response to accelerated immunisation	AIMS: To describe the immune response of preterm infants to combined diphtheria/tetanus/5 component acellular pertussis-Haemophilus influenzae type b inactivated polio vaccine (DT5aP-Hib-IPV) and meningococcal serogroup C conjugate vaccine (MCC) under accelerated schedule. To compare results with term infants immunised with DT5aP-Hib-IPV and with historical data from preterm infants immunised with a DT3 component aP-Hib vaccine. METHODS: Prospective observational study in preterm infants born at <32 weeks gestation with comparison to contemporary cohort of term infants. DT5aP-Hib-IPV and MCC vaccines were given at 2, 3, and 4 months. RESULTS: Fifty preterm infants (mean gestational age 28.5 weeks) completed the study. After three doses of vaccines Hib polysaccharide IgG geometric mean concentration (GMC) was 1.21 microg/ml with 80% > or =0.15 microg/ml; MCC serum bactericidal assay geometric mean titre (GMT) was 1245 with 100% > or =8. All infants achieved protective titres to diphtheria, tetanus, and the three poliovirus types with > or =80% achieving protective rises in IgG against the five pertussis antigens. CONCLUSION: Preterm infants immunised with DT5aP-Hib-IPV and MCC vaccines show IgG responses to Hib and MCC greater than seen historically in both term and preterm infants with a DT3aP-Hib vaccine, and for pertussis antigens and poliovirus type 1 responses similar to that seen in term infants immunised with DT5aP-Hib-IPV. Responses to poliovirus types 2 and 3 are reduced, but all infants achieved protective titres.	M. H. Slack, S. Cade, D. Schapira, R. J. Thwaites, A. Crowley-Luke, J. Southern, R. Borrow and E. Miller	Archives of disease in childhood
239	Effect of probiotic supplementation in the first 6 months of life on specific antibody responses to infant Hepatitis B vaccination	Probiotics have been shown to enhance specific immune responses to vaccines. We aim to assess the effect of probiotic supplementation on specific IgG antibody responses to Hepatitis B (HepB) vaccination in infants. Compared to controls, probiotic supplementation improved HepB surface antibody responses in subjects receiving monovalent doses of HepB vaccine at 0, 1 month and a DTPa-HepB combination vaccine at 6 months [placebo (n=28): 187.97 (180.70-195.24), probiotic (n=29): 345.70 (339.41-351.99)mIU/ml] (p=0.069), but not those who received 3 monovalent doses [placebo (n=68): 302.34 (296.31-308.37), probiotic (n=77): 302.06 (296.31-307.81)mIU/ml] (p=0.996). Probiotics may enhance specific antibody responses in infants receiving certain Hepatitis B vaccine schedules.	S. E. Soh, D. Q. Ong, I. Gerez, X. Zhang, P. Chollate, L. P. Shek, B. W. Lee and M. Aw	Vaccine
400	Controlled clinical study of sucrose administration to reduce the duration of crying in infants undergoing vaccination	Objective: To evaluate the effect of an oral sucrose solution on infant crying times in immunization clinics. Methodology: Randomised, double blind, placebo-controlled trial involving a 75% sucrose solution or drinking water as a control. Patients: A total of 323 infants receiving 1, 2, 4 or 6-month intramuscular immunization against hepatitis B virus or against diphtheria, tetanus, pertussis and haemophilus influenzae type B (DTPHib). Methods: The duration of infant crying was recorded during and immediately after intramuscular vaccine injection until it ceased in the mothers' arms. Results: The administration of 2 ml 75% sucrose reduced the infant crying time after immunization against hepatitis B virus or DTPHib, with a mean difference of 5.05 seconds (95% CI between -9.2835 and -0.8110 seconds) (p < 0.02). The number of children to whom it was necessary to administer 2 ml of sucrose prior to immunization to obtain a crying time of less than or equal to 25 seconds (mean duration of crying in the sucrose group) was 11 (95% CI = 5 to infinite). Conclusions: During intramuscular immunization, the administration of sucrose solutions at high concentrations has only clinically modest effects in terms of reducing the duration of crying. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	J. Soriano Faura and A. Gomez Gil	Acta Pediatrica Espanola
87	The influence of types of decision support on physicians' decision making	OBJECTIVE: To determine whether physicians' post-test probability estimates are influenced by receiving test characteristics and impact their subsequent clinical decisions. DESIGN: Questionnaire based randomised controlled trial. SETTING: Mailed survey with a vignette describing an infant whose pretest likelihood of pertussis was 30% and direct fluorescent-antibody (DFA) test was negative for pertussis. SUBJECTS: Nationally representative sample of US paediatricians (n = 1502). INTERVENTIONS: Random receipt of no additional information (controls), the DFA's sensitivity and specificity (TC group) or the test's sensitivity and specificity with their definitions (TCD group). MAIN OUTCOME MEASURES: Estimated post-test probability (PTP) of pertussis, PTP of 0.50, "nearly correct" PTP (+/-5%), intended erythromycin management and intended hospital disposition. ANALYSES: Chi2 and t tests. RESULTS: Despite the negative DFA result, 67% of the 635 (49.7%) participants who responded estimated a PTP higher than the pretest probability of 30%; the overall mean estimated PTP was 0.41 (SD 0.26) (correct answer: 0.18). The TCD group's mean PTP was significantly higher than controls' mean PTP (0.45 vs 0.38, p<0.001), while the TC and control groups' mean PTP did not differ significantly (0.41 vs 0.38, p = 0.16). With decision support significantly more TC and TCD participants compared to controls estimated the PTP as 0.50 (38% vs 17%, p<0.001; 41% vs 17%, p<0.001, respectively) and also estimated a nearly correct PTP more often (20% vs 13%, p = 0.06; 19% vs 13%, p = 0.08, respectively). The mean PTP of participants intending to discontinue erythromycin therapy or discharge the patient home was significantly lower than that of participants who intended continuing erythromycin or hospitalisation (0.20 vs 0.43, p<0.001; 0.40 vs 0.49, p = 0.005, respectively). CONCLUSIONS: Paediatricians differed in their response to information about test characteristics. For many, it increased errors in estimating post-test probability; for others, it reduced errors. Estimated post-test probability was logically associated with intended clinical management.	C. M. Sox, J. N. Doctor, T. D. Koepsell and D. A. Christakis	Archives of disease in childhood
88	Pediatricians' clinical decision making: results of 2 randomized controlled trials of test performance characteristics	OBJECTIVE: To determine whether presenting test performance characteristics influences clinical management. DESIGN: Two questionnaire-based, randomized controlled trials. SETTING: Mailed surveys with 2 clinical vignettes. PARTICIPANTS: Randomly selected US pediatricians (N=1502). INTERVENTION: Vignette-specific, randomly assigned test information: no additional information (control), test characteristics (TC), or TC defined. In the pertussis vignette, the TC group received the direct fluorescent antibody test's sensitivity and specificity, and the TC defined group received the same information with definitions. In the urinalysis vignette, the TC group received the false-positive rate of persistent microhematuria in predicting renal disease, and the TC defined group received a definition of this information. MAIN OUTCOME MEASURES: In the pertussis vignette, diagnostic test choice and management of erythromycin therapy and hospital discharge plans. In the urinalysis vignette, serum laboratory testing and nephrology referral plans. RESULTS: Six hundred fifty-three participants (49.5% of those eligible) returned completed surveys. In the pertussis vignette, significantly more of the TC (73%) and TC defined (71%) groups ordered the best-performing test than did controls (21%) (P<.001 for both comparisons). Receiving test characteristics did not significantly affect erythromycin therapy or hospital discharge plans (P>or=.40). In the urinalysis vignette, the TC defined group referred to nephrology (30%) and checked laboratory tests (88%) significantly more often than did controls (19%, P=.01; 78%, P=.01, respectively), but the TC and control groups' testing and referral plans did not differ significantly (22% vs 19%, P=.36; 75% vs 78%, P=.48, respectively). CONCLUSION: Providing test performance characteristics influenced certain clinical decisions, sometimes in unexpected ways.	C. M. Sox, T. D. Koepsell, J. N. Doctor and D. A. Christakis	Archives of pediatrics & adolescent medicine
279	Taking the "ouch" out of injections for children. Using distraction to decrease pain	PURPOSE: This research compared the effect of two forms of distraction on injection pain in a convenience sample of preschool children. DESIGN: A quasi-experimental study of 105 children (53 girls and 52 boys) ages 4 to 6 years needing DPT immunizations. Data were collected at three sites: two school-based immunization clinics and one public health center with a walk-in immunization program. METHODS: Study children were randomly assigned to receive one of three treatments with their DTP injection: touch, bubble-blowing, or standard care. Prior to injection, a measure of medical fear was obtained (Child Medical Fear Scale) and pain was measured through use of the Oucher Scale. DATA ANALYSIS: Planned comparisons within analysis of variance (ANOVA) tested the differences in pain scores by treatment. Factorial ANOVA was used to determine the influence of age or gender on treatment, and the effect of medical fear on pain was analyzed using correlational statistics and factorial ANOVA. RESULTS: Both forms of distraction, touch and bubble-blowing, significantly reduced pain perception. There were no interaction effects of either age or gender. Fear was a significant covariate, but distraction was effective even when fear was not held constant. CLINICAL IMPLICATIONS: Distraction appears to be an effective method for decreasing injection pain in young children. It is an easy, practical nursing intervention to help children cope with this common, painful experience.	L. Sparks	MCN. The American journal of maternal child nursing
387	Whooping-cough immunization: clinical follow-up of first Barking field trial, 1955		V. Spiller and F. L. Groarke	Br Med J
94	Improved disease reporting: a randomized trial of physicians	OBJECTIVES: To determine if a heightened, passive surveillance system increases the number of physicians reporting two notifiable diseases during a six-month period. METHODS: We conducted a randomized trail among 145 community-based primary care physicians in two counties in Eastern Ontario. Intervention group physicians received a three-part intervention aimed at improving their communication with the health unit to whom all physicians are mandated to report notifiable diseases. The control group physicians remained part of the usual disease reporting system. The outcome was assessed by a relative risk comparing the number of physicians reporting among the intervention group to that in the control group. RESULTS: Seventy physicians received the intervention and 75 physicians were in the control group. The relative risk for the number of physicians reporting at least one case was 5.9 (95% CI 2.6-13.2). CONCLUSIONS: The intervention had an impact on reporting of notifiable diseases by physicians.	S. G. Squires, K. J. Aronson, R. S. Remis and J. R. Hoey	Canadian journal of public health = Revue canadienne de santé publique
381	Administration of hepatitis A vaccine at 6 and 12 months of age concomitantly with hexavalent (DTaP-IPV-PRP[similar to]T-HBs) combination vaccine	Background: Administration of two doses of hepatitis A (HA) vaccine to children [greater-than or equal to]2 years of age has been shown to be protective. The present study assessed whether HA vaccine can be administered as early as 6 months of age and whether it can be administered concomitantly with a hexavalent (HV) vaccine at this age. Methods: In an open label, randomized, parallel group study, the liquid HV vaccine (HEXAVAC) (diphtheria, tetanus, 2-component acellular pertussis, inactivated poliomyelitis vaccine, Haemophilus influenzae type b conjugated to tetanus protein and hepatitis B) was administered at 2, 4, 6, and 12 months of age to all children. HA vaccine (VAQTA) was given at 7 and 13 months in the separate administration group (Group 1) and at 6 and 12 months in the concomitant administration group (Group 2). Serum samples were obtained at 2, 7, 12, and 14 months in Group 1 and at 2, 7, 12, and 13 months in Group 2. The primary immunogenicity outcomes were the seroconversion rates for HA 1 month after the second dose of HA vaccine in initially seronegative subjects, and the seroconversion rates for each HV antigen 1 month after the third dose of the HV vaccine (both at 7 months of age). Results: HA seropositivity rates 1 month after the second dose were 100% in both groups, regardless of initial serostatus. The responses to each HV antigen 1 month after the third dose were similar in both groups. The vaccines were generally well tolerated in both groups regardless of vaccine(s) administered. Conclusions: A schedule of two doses of HA vaccine, 6 months apart beginning at 6 months of age is highly immunogenic and well tolerated when administered alone or concomitantly with HV vaccine at 6 and 12 months of age. copyright 2007 Elsevier Ltd. All rights reserved. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	S. Stojanov, J. G. Liese, B. H. Belohradsky, C. Vandermeulen, K. Hoppenbrouwers, M. Wielen, P. Damme, B. Georges, M. Dupuy, M. Scemama, M. Watson, A. Fiquet, J. E. Stek, G. T. Golm, F. P. Schodel and B. J. Kuter	Vaccine
449	Administration of hepatitis A vaccine at 6 and 12 months of age concomitantly with hexavalent (DTaP-IPV-PRP approximately T-HBs) combination vaccine	BACKGROUND: Administration of two doses of hepatitis A (HA) vaccine to children > or = 2 years of age has been shown to be protective. The present study assessed whether HA vaccine can be administered as early as 6 months of age and whether it can be administered concomitantly with a hexavalent (HV) vaccine at this age. METHODS: In an open label, randomized, parallel group study, the liquid HV vaccine (HEXAVAC) (diphtheria, tetanus, 2-component acellular pertussis, inactivated poliomyelitis vaccine, Haemophilus influenzae type b conjugated to tetanus protein and hepatitis B) was administered at 2, 4, 6, and 12 months of age to all children. HA vaccine (VAQTA) was given at 7 and 13 months in the separate administration group (Group 1) and at 6 and 12 months in the concomitant administration group (Group 2). Serum samples were obtained at 2, 7, 12, and 14 months in Group 1 and at 2, 7, 12, and 13 months in Group 2. The primary immunogenicity outcomes were the seroconversion rates for HA 1 month after the second dose of HA vaccine in initially seronegative subjects, and the seroconversion rates for each HV antigen 1 month after the third dose of the HV vaccine (both at 7 months of age). RESULTS: HA seropositivity rates 1 month after the second dose were 100% in both groups, regardless of initial serostatus. The responses to each HV antigen 1 month after the third dose were similar in both groups. The vaccines were generally well tolerated in both groups regardless of vaccine(s) administered. CONCLUSIONS: A schedule of two doses of HA vaccine, 6 months apart beginning at 6 months of age is highly immunogenic and well tolerated when administered alone or concomitantly with HV vaccine at 6 and 12 months of age.	S. Stojanov, J. G. Liese, B. H. Belohradsky, C. Vandermeulen, K. Hoppenbrouwers, M. Wielen, P. Damme, B. Georges, M. Dupuy, M. Scemama, M. Watson, A. Fiquet, J. E. Stek, G. T. Golm, F. P. Schödel and B. J. Kuter	Vaccine
431	Immunogenicity and safety of a trivalent tetanus, low dose diphtheria, inactivated poliomyelitis booster compared with a standard tetanus, low dose diphtheria booster at six to nine years of age	Objective. To compare the immunogenicity and safety of a trivalent tetanus-diphtheria (low toxoid content)-inactivated poliomyelitis vaccine, Td-IPV (Revaxis; Pasteur Merieux), with a tetanus-diphtheria (low toxoid content) vaccine, Td (Td-Impfstoff Merieux; Pasteur Merieux), when administered as a booster to children age 6 to 9 years. Methods. A group of 301 children were randomized and vaccinated with Td-IPV (n = 150) or Td (n = 151) in this open, controlled, multicenter trial. Serum specimens were obtained before and 28 days after vaccination. Safety was assessed for up to 28 days postvaccination by parental diary cards. Solicited local and systemic reactions were recorded for 7 days after vaccination. Results. Seroprotection (enzyme-linked immunosorbent assay titer, >=0.10 IU/ml) against tetanus and diphtheria was induced by either Td-IPV or Td in all subjects. Tetanus and diphtheria geometric mean titer were higher after Td (34.0 and 5.74 IU/ml) than after Td-IPV (15.9 and 4.38 IU/ml). All subjects boosted with Td-IPV were seroprotected against each type of poliovirus (neutralizing antibody titer, >=5/dilution). The most frequently reported solicited local and systemic symptoms were pain triggered by movement of the arm (54% vs. 39.1%) and headache (17.3% vs. 7.3%), after Td-IPV and Td, respectively. All other events were similar between the two groups. Reactions were generally mild and all were temporary. Conclusions. A booster dose of Td-IPV induced in all children seroprotection against tetanus, diphtheria and poliomyelitis. The overall safety profile of the two vaccines was acceptable. Number of References 22. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	S. Stojanov, J. G. Liese, H. Bendjenana, E. Harzer, M. Barrand, S. Jow, M. Dupuy, B. H. Belohradsky, A. Cordero Cd, K. Helm, M. R. Holtorf, S. Kiran, G. Knapp, K. Landvogt, G. V. Pilgrim, H. Preidel, H. Sandbrink, H. Schopfer and G. Voigt	Pediatric Infectious Disease Journal
68	Relative efficacy of two acellular pertussis vaccines during three years of passive surveillance	Prolonged unblinded passive surveillance of the trial cohort from the Swedish 1986-87 pertussis vaccine efficacy trial indicates that a two-component vaccine, containing pertussis toxoid and filamentous haemagglutinin, provided better long-term protection against pertussis than a monocomponent pertussis toxoid vaccine. The relative risk (RR) for culture-confirmed pertussis was 1.5 (95% confidence interval (CI) 1.0-2.4), and RR for pertussis according to parents' diagnoses was also 1.5 (95% CI 1.1-2.1), for the monocomponent vaccine compared with the two-component vaccine.	J. Storsaeter and P. Olin	Vaccine
196	A fully liquid DTPw-HepB-Hib combination vaccine for booster vaccination of toddlers in El Salvador	OBJECTIVES: To compare the safety and immunogenicity of a booster dose of a fully liquid diphtheria-tetanus-whole cell pertussis-hepatitis B-Haemophilus influenzae type b (DTPw-HepB-Hib) vaccine to the separate administration of commercially available DTPw and Hib vaccines in healthy toddlers. METHODS: An open-label, randomized, parallel-group, Phase III study conducted at six centers in San Salvador, El Salvador, during February-June 2006. Toddlers (15-24 months of age) were eligible to participate if they had received primary immunization at 2, 4, and 6 months of age with a commercial DTPw-HepB/Hib vaccine requiring reconstitution. Participants received either one booster dose of DTPw-HepB-Hib fully liquid vaccine or DTPw and Hib vaccines administered separately. Blood samples were taken immediately prior to and at 1 month post-vaccination. For a 5-day period following vaccination, solicited adverse events were collected in subject diaries and assessed. RESULTS: The combined DTPw-HepB-Hib fully liquid vaccine was non-inferior to the separately administered DTPw and Hib vaccines, in terms of seroprotection/seroconversion rates for all antigens evaluated. The combination vaccine elicited a strong booster response as demonstrated by a large increase in antibodies against all vaccine antigens. The geometric mean concentrations (GMCs) of all antibodies in the DTPw-HepB-Hib group exceeded the seroprotection/seroconversion thresholds by very large margins, although for some antigens they were somewhat lower than the corresponding titers in the comparator group. With the combination vaccine, considerably fewer solicited local and systemic adverse events, such as fever and irritability, were reported than with the comparator vaccines. CONCLUSIONS: This study demonstrates that the fully liquid combined DTPw-HepB-Hib vaccine is highly immunogenic and has a favorable safety profile when given as a booster vaccination to toddlers who have received a primary vaccination course with a different pentavalent vaccine that requires reconstitution.	E. Suárez, E. J. Asturias, A. K. Hilbert, C. Herzog, U. Aeberhard and C. Spyr	Revista panamericana de salud pública = Pan American journal of public health
89	Pertussis in infancy does not increase the risk of asthma		M. Sundqwist, B. Trollfors and J. Taranger	Pediatrics
247	Current poliomyelitis immunization policy in the United States		R. W. Sutter, I. M. Onorato and P. A. Patriarca	Pediatric annals
435	Defining surrogate serologic tests with respect to predicting protective vaccine efficacy: poliovirus vaccination	Inactivated and trivalent oral poliovirus vaccines contain either formalin-inactivated or live, attenuated poliovirus, respectively, of the three serotypes. Interference among the three attenuated poliovirus serotypes was minimized with a "balanced-formulation" vaccine, and serologic responses after IPV were optimized by adjusting the antigenic content of each inactivated poliovirus serotype. Seroconversion is dependent on both the relative content as well as the absolute quantity of virus in the vaccine. The "gold standard" method to assess humoral antibody responses following vaccination is the neutralization assay. Any detectable titer of neutralizing antibody against poliovirus is considered protective against clinical paralytic diseases. Recently, standard procedures were adopted for conducting neutralization assays. Efforts are being undertaken now to develop a combined diphtheria and tetanus toxoids and pertussis vaccine and IPV vaccine in the United States using a dual-chambered syringe that mixes the content of both vaccines at the time of injection; this approach is necessary to overcome the potential detrimental effect of thimerosal on IPV (the preservative in DTP). Other vaccines that combine DTP and/or Haemophilus influenzae type b and/or hepatitis B with IPV appear feasible but require further investigation. New combination vaccines should induce similar or superior levels of neutralizing antibody in serum for individual protection against paralytic disease and mucosal immunity that effectively decreases viral replication in the intestine and pharynx for population protection against transmission of poliovirus.	R. W. Sutter, M. A. Pallansch, L. A. Sawyer, S. L. Cochi and S. C. Hadler	Annals of the New York Academy of Sciences
340	Treatment of pertussis with aerosporin		P. N. Swift	Lancet
388	Effect of neonatal circumcision on pain responses during vaccination in boys	Using data from one of our randomised trials, we investigated post- hoc whether male neonatal circumcision is associated with a greater pain response to routine vaccination at 4 or 6 months. Pain response during routine vaccination with diphtheria-pertussis-tetanus (DPT) alone or DPT followed by Haemophilus influenzae type b conjugate (HIB) was scored blind. 42 boys received DPT and 18 also received HIB. After DPT, median visual analogue scores by an observer were higher in the circumcised group (40 vs 26 mm, p = 0.03). After HIB, circumcised infants had higher behavioural pain scores (8 vs 6, p = 0.01) and cried longer (53 vs 19 s, p = 0.02). Thus neonatal circumcision may affect pain response several months after the event. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	A. Taddio, M. Goldbach, M. Ipp, B. Stevens and G. Koren	Lancet.
236	Double-blind study comparing the immunogenicity of a licensed DTwPHib-CRM197 conjugate vaccine (Quattvaxem) with three investigational, liquid formulations using lower doses of Hib-CRM197 conjugate	We performed a double-blind clinical study to evaluate the safety and immunogenicity of four formulations of a DTwPHib full liquid vaccine, three of which contained fractional doses of the 10 microg-dose of CRM197-Hib conjugate vaccine. A total of 261 infants were enrolled and randomised to receive at 3, 4 and 5 months of age, in a double-blind fashion, one of the four DTwPHib vaccine formulations containing 10, 5, 2.5 or 1.25 microg of CRM197-Hib conjugate. Post-immunization reactions were similar in the four vaccine groups, they were mild, transient and resolved without sequelae. The seroconversion rates to anti-PRP titres > or = 0.15 microg/mL were 100%, 98%, 97% and 98% in the groups 10, 5, 2.5 and 1.25 microg, respectively. The seroconversion rates to anti-PRP titres > or =1 microg/mL were 95%, 97%, 88% and 90%, again respectively. Anti-PRP GMTs were 18, 17, 7.82 and 6.94 microg/mL, respectively. All subjects were protected against tetanus and diphtheria, and >80% seroconverted to pertussis. High, and similar, levels of anti-PRP GMTs were elicited by the formulations with 10 and 5 microg of CRM197-Hib conjugate. Although the formulations with 2.5 and 1.25 microg of CRM197-Hib elicited lower levels of anti-PRP GMTs, they were immunogenic and are possible candidates for further development.	E. Tamm, A. Veronese, M. Contorni, S. Meriste, P. Nacci and S. Viviani	Vaccine
293	Effect of injection site on reactogenicity and immunogenicity of acellular and whole-cell pertussis component diphtheria-tetanus-pertussis vaccines in infants	The effect of injection site on reactogenicity and specific immunogenicity was assessed in participants in a pertussis vaccine efficacy trial. The percent of DTwP and DTaP recipients with any reaction was slightly lower in subjects injected in the buttock compared with those injected in the thigh. This finding was most common in DTwP recipients. Geometric mean antibody values to pertactin, filamentous hemagglutinin and fimbriae (Bordetella pertussis antigens) were lower in DTaP vaccinees when buttock was utilized as the injection site. Our findings present evidence against the use of the buttock as the site of immunization for DTaP vaccines since the benefit with regards to reactogenicity is minimal and the immunologic response to an important antigen of B. pertussis, pertactin, is decreased.	T. Tapiainen, J. D. Cherry and U. Heininger	Vaccine
155	Vaccination of infants with a four-dose and a three-dose vaccination schedule	Swedish infants were vaccinated with diphtheria, tetanus and pertussis toxoids, inactivated poliovirus vaccine and a Haemophilus influenzae type b - tetanus toxoid conjugate vaccine at 2, 4, 6 and 15 months (US vaccination program, 'US arm', n=118) or at 3, 5 and 12 months of age (Swedish vaccination program, 'Swedish arm', n=103). The antigen amounts in the diphtheria and tetanus vaccines were higher in the Swedish than in the US arm while the amounts in the other vaccines were the same in both arms. There were no serious side effects. Local reactions increased with the numbers of doses but did not differ significantly between the groups. Serum was obtained at 2, 7, 15 and 16 months in the US arm and at 3, 6, 12 and 13 months of age in the Swedish arm. A fifth serum was obtained in both groups at 4 yr of age. For vaccines with the same antigen amount the following was observed: a. three doses at 2, 4 and 6 months were more immunogenic than two doses at 3 and 5 months; b. the third dose in the Swedish arm was more immunogenic than the third dose in the US arm; c. the fourth dose in the US arm induced higher antibodies than the third dose in the Swedish arm (except for pertussis toxin antibodies that were similar in both groups) and the differences tended to remain at the age of 4 yr. Children in the Swedish arm received a higher diphtheria toxoid dose (25 Lf) than in the US arm (15 Lf) which led to higher diphtheria toxin antibodies in the Swedish arm at comparable ages. Children in the Swedish arm received a higher tetanus toxoid dose (7 Lf) than in the US arm (6 Lf). Tetanus antibodies were similar at comparable ages. In conclusion, the immunogenicity of vaccines in infancy can be improved by increasing the number of doses, by prolonging the intervals between doses and by increasing the antigen amount in the vaccine.	J. Taranger, B. Trollfors, N. Knutsson, V. Sundh, T. Lagergård and E. Ostergaard	Vaccine
382	Immunogenicity and reactogenicity of primary immunization with a novel combined Haemophilus influenzae Type b and Neisseria meningitidis Serogroup C-tetanus toxoid conjugate vaccine coadministered with a Diphtheria-tetanus-acellular Pertussis-hepatitis B-inactivated poliovirus vaccine at 2, 4 and 6 months Clinical evaluation of a new starter formula for infants containing live Bifidobacterium longum BL999 and prebiotics	BACKGROUND: This phase II study evaluated the immunogenicity and reactogenicity of primary vaccination with a novel Hib-MenC conjugate vaccine (GlaxoSmithKline [GSK] Biologicals) coadministered with DTPa-HBV-IPV (GSK Biologicals) at 2, 4 and 6 months. METHODS: Healthy infants were randomized to receive Hib-MenC coadministered with DTPa-HBV-IPV (N = 117) or MenC-CRM (Wyeth) coadministered with DTPa-HBV-IPV/Hib (GSK Biologicals; N = 120) at 2, 4 and 6 months. Antibody concentrations were measured before vaccination and after doses 2 and 3. Solicited local and general symptoms, unsolicited symptoms and serious adverse events (SAEs) were recorded. RESULTS: All subjects in the Hib-MenC group had seroprotective titers of anti-PRP antibodies (>or=0.15 microg/mL) and SBA-MenC titers (>or=1:8) 1 month after the third dose. These responses were noninferior to those seen in the control group, in which a 99.1% seroprotection rate was observed for both Hib and MenC. At that time, anti-PRP and SBA-MenC GMTs were significantly higher in the Hib-MenC group (12.8 microg/mL and 2467.1 microg/mL, respectively) than in the control group (3.8 microg/mL and 1833.7 microg/mL). High seroprotection rates were already observed after the second dose of Hib-MenC; 96.4% and 100% of subjects were seroprotected to Hib and MenC, respectively. Immune responses to coadministered antigens were unimpaired; seroprotection/vaccine response rates >or=96.5% were recorded postdose 3 in the Hib-MenC group. No differences in reactogenicity were seen between the 2 study groups. CONCLUSIONS: Coadministration of a Hib-MenC conjugate vaccine with DTPa-HBV-IPV is well tolerated and immunogenic, and does not impair the immune response to any of the coadministered antigens OBJECTIVES: The larger number of bifidobacteria in the intestine of breast-fed infants has been associated with their better health compared with formula-fed infants. We assessed the safety and tolerability of an experimental formula containing 2 x 10(7) colony-forming units of Bifidobacterium longum BL999 and 4 g/L of a prebiotic mixture containing 90% galacto-oligosaccharides and 10% fructo-oligosaccharides. METHODS: A 7-mo prospective, randomized, reference-controlled, double-blinded trial was performed in infants who were not breast fed after the 14th day of birth. One hundred thirty-eight infants were enrolled and assigned to receive the control or experimental formula until they were 112 d old. Mean weight gain (primary outcome) and recumbent length, head circumference, tolerability (gastrointestinal symptoms), and overall morbidity (secondary outcomes) were measured at 14, 28, 56, 84, and 112 d of age. RESULTS: Equivalence in mean weight gain between the two groups was shown. The treatment difference in the intention-to-treat and per-protocol populations were within the predefined equivalence boundaries of +/-3.9 g/d. No statistically significant difference in recumbent length, head circumference, or incidence of adverse events was found between the two groups. Infants in the experimental group had fewer incidences of constipation and had stool characteristics that suggest that the experimental formula was tolerated well. Furthermore, these infants showed a trend toward fewer respiratory tract infections. CONCLUSIONS: The starter formula containing BL999 and galacto-oligosaccharides/fructo-oligosaccharides is safe and well-tolerated	J. C. Tejedor, M. Moro, J. Ruiz-Contreras, J. Castro, J. A. Gomez-Campdera, M. L. Navarro, J. M. Merino, A. Martin-Ancel, J. Roca, M. Garcia-Del-Ri, A. Jurado, F. J. ez-Delgado, F. Omenaca, J. Garcia-Sicilia, R. Boceta, P. Garcia-Corbeira, A. Collard, D. Boutriau, L. Schuerman, J. M. Jacquet, G. Puccio, C. Cajozzo, F. Meli, F. Rochat, D. Grathwohl and P. Steenhout	Pediatr Infect Dis J
131	Immunogenicity and reactogenicity of primary immunization with a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio-Haemophilus influenzae type B vaccine coadministered with two doses of a meningococcal C-tetanus toxoid conjugate vaccine	BACKGROUND: This study evaluated the concurrent use of meningococcal C tetanus conjugate (MenC-TT) vaccine (NeisVac-C) with DTaP-based combinations, according to 2 vaccination schedules, one of which included hepatitis B vaccination at birth (Trial DTaP-HBV-IPV/Hib-097). METHODS: Healthy infants were randomized to receive either DTaP-HBV-IPV/Hib (Infanrix hexa) at 2, 4, and 6 months (N = 115) or HBV at birth followed by DTaP-HBV-IPV/Hib at 2 and 6 months and DTaP-IPV/Hib (Infanrix-IPV Hib) at 4 months (N = 115). In both groups 2 doses of MenC-TT conjugate were coadministered at 2 and 4 months, and compared with 3 doses of MenC-CRM197 conjugate (Meningitec) coadministered at 2, 4, and 6 months with DTaP-HBV-IPV/Hib (N = 120). Antibody concentrations were measured at 2, 6 and 7 months. Solicited local and general symptoms, unsolicited symptoms, and serious adverse events (SAEs) were recorded. RESULTS: All MenC-TT recipients had seroprotective concentrations of anti-PRP antibodies (> or = 0.15 microg/mL) 1 month after the third vaccine dose and all had SBA-MenC titers > or = 1:8 after the second dose of MenC-TT. These responses were noninferior to those seen after 3 doses of DTaP-HBV-IPV/Hib and MenC-CRM. Anti-PRP antibody GMCs were significantly higher in MenC-TT than MenC-CRM vaccinees (7.9, 7.3, 3.8 microg/mL, respectively). Immune responses to all other coadministered antigens were unimpaired, with seroprotection/seropositivity rates > or = 98.1% in MenC-TT vaccinees. All schedules studied were well tolerated, with no differences in reactogenicity between the study groups. CONCLUSIONS: Coadministration of DTaP-HBV-IPV/Hib or DTaP-IPV/Hib with 2 doses of MenC-TT conjugate vaccine is safe, well tolerated, and immunogenic, with no impairment of the response to the coadministered antigens.	J. C. Tejedor, M. Moro, J. Ruiz-Contreras, J. Castro, J. A. Gómez-Campderá, M. L. Navarro, J. M. Merino, A. Martín-Ancel, J. Roca, M. García-del-Río, A. Jurado, F. J. Díez-Delgado, F. Omeñaca, J. García-Sicilia, R. Boceta, P. García-Corbeira, J. M. Jacquet, A. Collard and L. Schuerman	The Pediatric infectious disease journal
262	Effects of lowering the aluminium content of a dTpa vaccine on its immunogenicity and reactogenicity when given as a booster to adolescents	As aluminium in vaccines has been associated with the incidence of local side effects occurring after vaccination, this observer-blind randomised clinical trial was designed to evaluate the effect of lowering the aluminium content of a combined reduced-antigen-content dTpa vaccine on immunogenicity and safety when administered to healthy adolescents aged 10-18 years. A total of 647 subjects were enrolled, 224 (35%) received a dTpa formulation with 0.5 mg aluminium, 209 (32%) a formulation with 0.3 mg aluminium and 214 (33%) a formulation with 0.133 mg aluminium. One month after boostering, all subjects were seroprotected against diphtheria and tetanus toxoids. All subjects were seropositive for anti-FHA and anti-PRN but 4% of the initially seronegatives in both reduced aluminium groups did not seroconvert for anti-PT. Booster responses did not differ significantly between groups for any antibody, but post booster vaccination anti-PT GMC's differed significantly between groups and decreased when vaccine aluminium content decreased. No clear difference between study groups in local or general side effects was demonstrated. The most frequently reported symptoms after vaccination were injection site pain (89.5-90.7%), fatigue (42.1-47.4%) and headache (41.1-45.1%). This study showed that the aluminium content has a specific influence on the immunogenicity of this dTpa vaccine.	H. Theeten, P. Damme, K. Hoppenbrouwers, C. Vandermeulen, E. Leback, E. M. Sokal, J. Wolter and L. Schuerman	Vaccine
386	The Vi conjugate typhoid vaccine is safe, elicits protective levels of IgG anti-Vi, and is compatible with routine infant vaccines	Typhoid fever remains a serious problem in developing countries. Current vaccines are licensed for individuals who are 5 years old or older. A conjugate of the capsular polysaccharide (CP) of Salmonella enterica serovar Typhi (Vi) bound to recombinant exoprotein A of Pseudomonas aeruginosa (Vi-rEPA) enhanced Vi immunogenicity and protected 2- to 5-year-olds in Vietnam. In this study, Vi-rEPA was evaluated for use in infants. A total of 301 full-term Vietnamese infants received Expanded Program on Immunization (EPI) vaccines alone or with Vi-rEPA or Haemophilus influenzae type b-tetanus toxoid conjugate (Hib-TT) at 2, 4, and 6 months and Vi-rEPA or Hib-TT alone at 12 months. Infants were visited 6, 24, and 48 h after each injection to monitor adverse reactions. Maternal, cord, and infant sera were assayed for IgG anti-Vi and for IgG antibodies to Hib CP and the diphtheria, tetanus, and pertussis toxins at 7, 12, and 13 months. No vaccine-related serious adverse reactions occurred. In the Vi-rEPA group, the IgG anti-Vi geometric mean (GM) increased from the cord level of 0.66 to 17.4 enzyme-linked immunosorbent assay units (EU) at 7 months, declined to 4.76 EU at 12 months, and increased to 50.1 EU 1 month after the 4th dose (95% of infants had levels of >=3.5 EU, the estimated protective level). Controls had no increase of the IgG anti-Vi GM. Infants with cord anti-Vi levels of <3.5 EU responded with significantly higher IgG anti-Vi levels than those with levels of >=3.5 EU. Anti-diphtheria, -tetanus, and -pertussis toxin levels were similar in all groups. Vi-rEPA was safe, induced protective anti-Vi levels, and was compatible with EPI vaccines, and it can be used in infants. High cord IgG anti-Vi levels partially suppressed infant responses to Vi-rEPA. Copyright 2011, American Society for Microbiology. All Rights Reserved.	V. D. Thiem, F. Y. C. Lin, D. G. Canh, N. H. Son, D. D. Anh, N. D. Mao, C. Chu, S. W. Hunt, J. B. Robbins, R. Schneerson and S. C. Szu	Clinical and Vaccine Immunology
232	Oral glucose as an analgesic to reduce infant distress following immunization at the age of 3, 5 and 12 months	AIM: To evaluate oral glucose as an analgesic to reduce infant distress after immunization during the first year of life and to investigate if these effects change during this period. METHODS: A prospective controlled trial of the effectiveness of glucose on crying response to immunizations at 3, 5 and 12 months of age. A total of 110 infants were randomized to receive 2 mL of 30% glucose or water. The same solution was given at 3, 5 and 12 months. Crying was registered from onset of the injection up to 120 seconds. Infanrix Polio Hib was administered intra-muscular in the thigh. Observation nurse and parents were blind to the nature of the solution. RESULTS: Administration of glucose reduced the mean crying time by 22% at 3 months, 62% at 5 months and 52% at 12 months. The difference was significant at 5 and at 12 months. In the water group, there was a significant correlation between the children who cried at 3 months and who subsequently cried at 5 and 12 months. No correlations were found in the glucose group. CONCLUSION: Sweet solution can be used as a simple and safe method to reduce the distress following immunization in infants up to 12 months.	M. Thyr, A. Sundholm, L. Teeland and V. A. Rahm	Acta paediatrica (Oslo, Norway : 1992)
447	Comparison of the immunogenicity and reactogenicity of two commercially available hexavalent vaccines administered as a primary vaccination course at 2, 4 and 6 months of age	Infants (N = 459) were randomly assigned to receive either Infanrix hexa or Hexavac vaccines at 2, 4 and 6 months of age as a primary vaccination schedule. The immunogenicity of the hepatitis B component was statistically significantly higher for Infanrix hexa compared to Hexavac in terms of both seroprotection (98.6% versus 94.7%, p = 0.0302) and GMCs (905.6 versus 226.4, p < 0.0001). Significantly (p < or =0.0001) higher antibody levels against diphtheria and the 3 polio components were also induced by Infanrix hexa. The responses to tetanus, Hib and pertussis components were similar. The incidences of clinically relevant solicited symptoms, unsolicited symptoms or serious adverse events were low in both groups.	I. Tichmann, H. Preidel, D. Grunert, S. Habash, R. Schult, R. Maier, P. K. Gildberg, H. C. Sengespeik, F. Meurice and R. Sänger	Vaccine
344	Local and systemic reactions to diptheria tetanus and pertussis vaccine (DTPw) - a comparison of different administration sites	P60	A. J. Tidemann and M. Gold	Journal of Paediatrics & Child Health
265	Acellular pertussis vaccines containing genetically detoxified pertussis toxin induce long-lasting humoral and cellular responses in adults	New generation pertussis vaccines, containing only purified Bordetella pertussis antigens, have been proven safe, immunogenic and efficacious. They have, however, raised new questions regarding the mechanism of protection from whooping cough and the duration of the immune response following vaccination. In addition to the antibody (Ab) titer, the level of pertussis toxin (PT) neutralizing antibodies may be very important in protection and the role of cell-ediated immunity needs to be defined. We have previously reported the safety and immunogenicity results of two phase I trials in adult volunteers with two acellular pertussis vaccines containing genetically detoxified PT alone or in combination with filamentous hemagglutinin (FHA) and 69K protein. In this work, we present the results of a long term follow-up study of the immune response in the same vaccinees. We evaluated the Ab response, the PT neutralizing titer and the peripheral blood T cell response up to 4 years following vaccination. Our results show that in adults the level of antibodies to PT, FHA and 69K and the PT neutralizing titers slightly decline between 2.5 and 12 months after the last vaccine dose, but they remain high in the following 2-4 years, showing levels 10-100 times higher than pre-vaccination values. The T cell responses were more heterogeneous among vaccinees but they did not show any significant decline throughout the period monitored.	A. Tommaso, M. Bartalini, S. Peppoloni, A. Podda, R. Rappuoli and M. T. Magistris	Vaccine
66	Two primary doses of diphtheria-tetanus-acellular pertussis vaccine induce immunological responses to Bordetella pertussis as strong as those induced by three primary doses	Pertussis vaccinations are administered worldwide under various conditions and schedules with diphtheria-tetanus-pertussis (DTP). In Japan, a general vaccination with three primary doses of diphtheria-tetanus-acellular pertussis (DTaP) at 4-week intervals and one booster dose 12 months after the primary series have been used since 1981. Decreasing the number of doses of the vaccination would lessen the physical and economic costs. To compare the immunological response to two versus three primary doses, we assessed antibody and cellular immune responses in health children. The anti-filamentous hemagglutinin (anti-FHA) and anti-pertussis toxin (anti-PT) antibody responses to two primary doses of DTaP before a booster were significantly lower than the responses to three primary doses. Although these antibody levels were low in children who received two primary doses, the FHA-induced DNA synthesis was equal to that of the children who received three doses. The anti-FHA and anti-PT antibody levels 4 weeks after the booster following two doses were similar to the levels following three doses, and high antibody titers were maintained over a long period. In areas where contact with bacteria is expected, two primary doses of DTaP may be adequate to induce the necessary level of immunological responses.	T. Tomoda, H. Ogura and T. Kurashige	Vaccine
309	Erythromycin estolate for treatment of pertussis		D. Torre, F. Maggiolo, C. Quadrelli and C. Sampietro	Pediatric Infectious Disease
307	Treatment with steroids in children with pertussis [letter; comment]		D. Torre, R. Tambini, G. Ferrario and G. Bonetta	Pediatric Infectious Disease Journal
429	[Bacteriological, pharmacokinetic and clinical studies of SY5555 dry syrup in the pediatric field]	Bacteriological, pharmacokinetic and clinical studies on SY5555 dry syrup (powder which is dissolved before use), a new penem antibiotic for oral use, were performed. The following results were obtained. 1. Antibacterial activities. MICs of SY5555, clavulanic acid/amoxicillin (CVA/AMPC), cefotiam (CTM), cefpodoxime (CPDX), cefaclor (CCL) and cefdinir (CFDN) were determined against clinically isolated Staphylococcus aureus, coagulase negative staphylococci, Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli and Enterobacter cloacae at a dose of 10(6) CFU/ml. MICs of SY5555 against S. aureus, CNS, S. pneumoniae, S. pyogenes, H. influenzae, M. catarrhalis, E. coli and E. cloacae were 0.2, 0.2, 0.2, < or = 0.025, 0.78, 0.2, 0.78 and 3.13 micrograms/ml, respectively, showing excellent antibacterial effects on these pathogens. Although the effects of SY 5555 against H. influenzae and E. coli were slightly inferior to those of CPDX and CFDN, the drug showed the most excellent antibacterial effect on other strains as compared with the control drugs. 2. Absorption and excretion In this study, plasma concentrations and urinary recovery rates were examined after administration of SY5555 at doses of 5 and 10 mg/kg (potency) after meals. With both 5 and 10 mg/kg doses, peak plasma concentrations were reached 1 hour after administration, at 0.25-2.61 micrograms/ml (mean 1.47 micrograms/ml) and 1.08-2.17 micrograms/ml (mean 1.74 micrograms/ml), respectively. The plasma levels rapidly decreased to 0.06-0.19 micrograms/ml (0.12 micrograms/ml) and 0.0503-0.0637 micrograms/ml) after 6 hours. The half-lives 1.12 hours in the 5 mg/kg group and 1.0 hour in the 10 mg/kg group. The urinary recovery rates were determined in the first 8 hours after administration in the 5 mg/kg and 6 hours in the 10 mg/kg group, and the values were as low as 1.05-12.3% and 1.6-4.33%, respectively. 3. Clinical results The clinical responses were examined in a total of 73 cases including 4 acute pneumonia, 13 acute bronchitis, 11 tonsillitis, 3 pharyngitis, 12 scarlet fever, 2 pertussis, 6 urinary tract infection, 6 otitis media, 7 lymphadenitis, 2 staphylococcal scalded skin syndrome, 2 phlegmon, 4 impetigo and 1 purulent parotitis. The treatment was effective or better in 66 of 70 cases with an efficacy rate of 94.3% (3 undeterminable cases were excluded). Bacteriological effects were examined during the clinical course for detected or suspected pathogens found before administration of SY5555. The effects were determined in 50 cases including 7 cases of polymicrobacterial infections, 57 strains in total. Eight strains, however, persisted, hence the overall eradication rate was 86.0%.(ABSTRACT TRUNCATED AT 400 WORDS)	Y. Toyonaga, T. Ishihara, T. Tezuka and H. Nakamura	The Japanese journal of antibiotics
333	Effects of islet-activating protein (IAP) on blood glucose and plasma insulin in healthy volunteers (phase 1 studies)	Islet-activating protein (IAP) is a new active substance purified from the culture medium of Bordetella pertussis. The active protein possesses a molecular weight of 77,000 and an isoelectric point of pH 7.8. The nature of IAP-action is characterized by enhancement of insulin secretory response to glucose and other stimulants. A single injection of IAP into spontaneous diabetes rat resulted in normalization of their glucose intolerance over a period of a month. Acute and chronic animal toxicity tests showed that LD50 of IAP was 127 mug/kg in mice and 114 mug/kg in rats. After these animals experiments, phase 1 studies were designed and undertaken to establish dosage, duration of action and other factors. IAP of 0.5 mug/kg or 1.0 mug/kg did not bring about any serious toxic or adverse effects in five volunteers. On the 4th day of a single injection of IAP, insulin secretory response was proved to be enhanced. Follow-up studies showed that the IAP-action continued over a month or at most two months. Two features of IAP, i.e., the enhancement of insulin secretory response and the long duration of the action, were confirmed in healthy persons as well as in animals. As expected, IAP has a strong antigenic reaction resulting in formation of IgG antibody and possibly IgE antibody. The antigenicity of IAP causes some hindrance to clinical usefulness. For avoidance of anaphylactic reaction, IAP should be given repeatedly with care. The problem concerning antigen-antibody reaction should be overcome as soon as possible before the clinical use of IAP as a medicament. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	T. Toyota, Y. Kai and M. Kakizaki	Tohoku Journal of Experimental Medicine
134	Reactogenicity and immunogenicity at preschool age of a booster dose of two three-component diphtheria-tetanus-acellular pertussis vaccines in children primed in infancy with acellular vaccines	OBJECTIVES: To determine the reactogenicity and immunogenicity of a fourth dose of 2 three-component acellular pertussis vaccines combined with diphtheria-tetanus-acellular pertussis (DTaP) when administered at preschool age to children primed in infancy with 3 doses of the same DTaP and who had received a diphtheria-tetanus (DT) dose at the age of 12 months. SETTING: Local health units of 4 Italian regions. STUDY DESIGN: Three thousand five hundred twenty-two children, who had been randomized in the first year of life to be immunized with a DTaP vaccine by either SmithKline Beecham or Chiron Biocine, were offered a booster of the same vaccine or, if refusing, a DT vaccine at the age of 5 to 6 years. Families of children were aware of the vaccine administered. The occurrence of adverse events was compared between the children who received a DTaP booster and those boosted with a DT only. Antibody titers to pertussis vaccine components (pertussis toxin, filamentous hemoagglutinin, and pertactin) were determined on 558 paired sera taken before and 30 days after the DTaP booster administration. RESULTS: Four episodes of temperature >/=39.5 degrees C, 2 in each DTaP group, were recorded. Fever >/=38 degrees C occurred infrequently in both DTaP and DT recipients (DTaP range: 2.5%-2.8%; DT range: 0%-4.8%), as did irritability (DTaP range: 10.1%-11.7%; DT range: 7.4%-12.6%). The frequency of local reactions was significantly higher for DTaP recipients (range: 44.0%-52.8%), with respect to DT recipients (range: 29.5%-44.4%). Extensive local reactions were observed in 1.2% of DTaP recipients and in.5% of DT recipients. Both DTaP vaccines induced high antibody titers against pertussis toxin, filamentous hemoagglutinin, and pertactin, with an increase of >10 times the prebooster geometric mean titers. CONCLUSIONS: A booster dose of DTaP at preschool age in children primed with the same acellular pertussis vaccine is safe and immunogenic. However, the frequency of local reactions is higher compared with that following primary immunization and with that following booster with DT only, and parents should be informed of the potential for these reactions to occur.	A. E. Tozzi, A. Anemona, P. Stefanelli, S. Salmaso, M. L. Ciofi degli Atti, P. Mastrantonio and A. Giammanco	Pediatrics
454	Neuropsychological performance 10 years after immunization in infancy with thimerosal-containing vaccines	OBJECTIVE: Thimerosal, a mercury compound used as a preservative in vaccines administered during infancy, has been suspected to affect neuropsychological development. We compared the neuropsychological performance, 10 years after vaccination, of 2 groups of children exposed randomly to different amounts of thimerosal through immunization. METHODS: Children who were enrolled in an efficacy trial of pertussis vaccines in 1992-1993 were contacted in 2003. Two groups of children were identified, according to thimerosal content in vaccines assigned randomly in the first year of life (cumulative ethylmercury intake of 62.5 or 137.5 microg), and were compared with respect to neuropsychological outcomes. Eleven standardized neuropsychological tests, for a total of 24 outcomes, were administered to children during school hours. Mean scores of neuropsychological tests in the domains of memory and learning, attention, executive functions, visuospatial functions, language, and motor skills were compared according to thimerosal exposure and gender. Standard regression coefficients obtained through multivariate linear regression analyses were used as a measure of effect. RESULTS: Nearly 70% of the invited subjects participated in the neuropsychological assessment (N = 1403). Among the 24 neuropsychological outcomes that were evaluated, only 2 were significantly associated with thimerosal exposure. Girls with higher thimerosal intake had lower mean scores in the finger-tapping test with the dominant hand and in the Boston Naming Test. CONCLUSIONS: Given the large number of statistical comparisons performed, the few associations found between thimerosal exposure and neuropsychological development might be attributable to chance. The associations found, although statistically significant, were based on small differences in mean test scores, and their clinical relevance remains to be determined.	A. E. Tozzi, P. Bisiacchi, V. Tarantino, B. Mei, L. D'Elia, F. Chiarotti and S. Salmaso	Pediatrics
261	Repeat whole cell vaccinations should be avoided after hypotonic-hyporesponsive episodes		A. E. Tozzi, M. L. Ciofi degli Atti, S. Salmaso and A. Anemona	BMJ (Clinical research ed.)
36	Common side effects in the Italian and Stockholm I trials	We have compared the frequency of common side effects observed following vaccination in the Italian and Stockholm I Trials. A higher proportion of DTPwc vaccinees in the two trials experienced side effects compared with DTaP and DT vaccinees. Fever, local redness and tenderness were more frequently observed in all study groups in the Stockholm I Trial when compared to the Italian Trial. Despite the similarities in study design, parental recall bias, site of injection, simultaneous administration of other vaccines, and antipyretic use could have played a role in the differences observed.	A. E. Tozzi and P. Olin	Developments in biological standardization
80	Immune responses to pertussis antigens eight years after booster immunization with acellular vaccines in adults	Pertussis-specific antibody and cell-mediated immune (CMI) responses were studied in adults 8 years after booster immunization with either a bicomponent (pertussis toxin and filamentous hemagglutinin) or a monocomponent (pertactin) acellular vaccine and in age-matched healthy controls. The levels of vaccine-induced antibodies were also compared between the serum samples collected before, 1 month, 4 years, and 8 years after immunization. Over the follow-up period, geometric mean values (GMV) of antibodies to the vaccine antigens decreased in both groups of vaccinees. However, the 8-year postimmunization GMV were 3-20 times higher than preimmunization GMV (all P values <0.01). Moreover, both antibody and CMI responses to the vaccine antigens were significantly higher in the vaccinees than in the controls (all P<0.01 for antibody; all P<0.001 for CMI responses). The results show that antibody and CMI responses induced by acellular pertussis vaccines can persist for up to 8 years after booster immunization of adults primed with whole-cell vaccine.	N. N. Tran Minh, Q. He, K. Edelman, A. Putto-Laurila, H. Arvilommi, M. K. Viljanen and J. Mertsola	Vaccine
200	A new DTPw-HB/Hib combination vaccine for primary and booster vaccination of infants in Latin America	OBJECTIVES: In 1998 the World Health Organization (WHO) recommended the inclusion of Haemophilus influenza type B (Hib) conjugate vaccines in infant immunization programs, whenever in accordance with national priorities. GlaxoSmithKline Biologicals has developed a new pentavalent combined diphtheria-tetanus-whole cell pertussis-hepatitis B/Hib (DTPw-HB/Hib) vaccine containing 5 microg of polyribosylribitol phosphate (PRP), and we assessed the immunogenicity and reactogenicity of primary and booster vaccination of healthy children with this new vaccine compared with a reference regimen consisting of the licensed DTPw-HB (Tritanrix) and Hib (Hiberix) vaccines given as simultaneous concomitant injections. METHODS: We performed a randomized, double-blind study from September 1998 to August 1999 to establish the immunogenicity and reactogenicity of primary and booster vaccination of healthy children with the new pentavalent combined DTPw-HB/Hib vaccine given as a single injection, compared with the reference regimen. RESULTS: Both vaccination regimens elicited excellent immune responses, with all subjects in both groups achieving seroprotective anti-PRP antibody concentrations of > or = 0.15 microg/mL one month after primary vaccination. The combined DTPw-HB/Hib vaccine was non-inferior to the licensed vaccines in terms of seroprotection/seropositivity/vaccine response rates for all antigen components. Persistence of antibodies against all study vaccine antigens up to the time of booster vaccination was comparable between groups, and a marked increase of all antibody concentrations was observed after the booster dose. Both vaccine regimens were similar in terms of their overall reactogenicity profiles. CONCLUSIONS: Our results indicate that the new DTPw-HB/Hib pentavalent combination vaccine provides an efficient and reliable way of implementing WHO recommendations for controlling hepatitis B and Hib infections on a worldwide basis.	M. Tregnaghi, P. López, C. Rocha, L. Rivera, M. P. David, R. Rüttimann and L. Schuerman	Revista panamericana de salud pública = Pan American journal of public health
129	Immunogenicity and safety of an investigational hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae B conjugate combined vaccine in healthy 2-, 4-, and 6-month-old Argentinean infants	BACKGROUND AND AIMS: Assessment of a new, fully liquid, investigational hexavalent DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim, Sanofi Pasteur), containing the same active ingredients as Pentaxim (DTaP-IPV//PRT-T) and 10 ?g Hansenula polymorpha-derived recombinant hepatitis B (Hep B) surface antigen, Sanofi Pasteur, in Argentinean infants. METHODS: Infants born to Hep B surface antigen seronegative mothers were randomized to receive the DTaP-IPV-Hep B-PRP-T vaccine or Pentaxim and Engerix B Pediatrico (Hep B monovalent) vaccines at 2, 4, 6 months of age. Antibody titers were measured before and 1 month after 3-month primary vaccination. Noninferiority analyses were performed on seroprotection/seroconversion rates. Safety was evaluated descriptively up to 1 month after primary vaccination. RESULTS: A total of 624 participants were enrolled, 312 participants were randomized to each group, and 604 participants completed the trial. The DTaP-IPV-Hep B-PRP-T vaccine was demonstrated as noninferior to the Pentaxim and Hep B monovalent vaccines with seroprotection/seroconversion rates 1 month postdose 3 for each valence. The anti-Hep B geometric mean titer 1-month postdose 3 for the investigational DTaP-IPV-Hep B-PRP-T primary series was similar to the monovalent Hep B control. The overall incidence of adverse events was similar among the 2 groups. CONCLUSIONS: The new, fully liquid, investigational DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim) is highly immunogenic and safe when compared with licensed comparators, warranting further development.	M. W. Tregnaghi, B. Zambrano and E. Santos-Lima	The Pediatric infectious disease journal
153	Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with Diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines in children 15 months of age	BACKGROUND: This study (NCT00197236) evaluated the safety and immunogenicity of a hepatitis A virus (HAV) vaccine when coadministered with diphtheria-tetanus-acellular pertussis (DTaP) and Haemophilus influenzae type b (Hib) vaccines in children 15 months of age. METHODS: This was an open-labeled, multicenter study with healthy subjects enrolled and randomized (1:1:1) into 3 treatment groups. A total of 394 subjects received the first study vaccinations at 15 months of age. Group HAV (N = 135) received 2 doses of HAV vaccine 6 to 9 months apart. Group HAV+DTaP+Hib (N = 127) received HAV vaccine coadministered with DTaP and Hib vaccines and the second dose of HAV vaccine, 6 to 9 months later. Group DTaP+Hib?HAV (N = 132) received the DTaP and Hib vaccines at 15 months of age, followed by HAV vaccine 30 days later and the second dose of HAV vaccine 7 to 10 months after the DTaP+Hib vaccines. Immune responses were evaluated before the first study vaccination and 30 days after each vaccine dose. Solicited, unsolicited, and serious adverse events were collected. RESULTS: After 2 doses of the HAV vaccine, all subjects in the 3 groups were seropositive. The geometric mean concentration of anti-HAV antibodies ranged between 1625.1 and 1904.4 mIU/mL. Coadministration of the 3 vaccines did not impact immunogenicity of the HAV, DTaP, or Hib vaccines. Vaccines were well tolerated in all groups. CONCLUSIONS: A 2-dose schedule of HAV vaccine was well tolerated and immunogenic when administered to children starting at 15 months of age. Immune responses to the DTaP or Hib vaccines were similar whether they were administered alone or were coadministered with the HAV vaccine.	A. F. Trofa, N. P. Klein, I. M. Paul, M. G. Michaels, M. Goessler, V. Chandrasekaran and M. Blatter	The Pediatric infectious disease journal
7	Effect of erythromycin and amoxycillin on Bordetella pertussis in the nasopharynx	The effectiveness of oral erythromycin and amoxycillin in eradicating Bordetella pertussis from the nasopharynx was compared. Erythromycin in a dosage of 40--50 mg/kg/day was significantly more effective than amoxycillin in a dosage of 25--30 mg/kg/day. The organism did not disappear in three cases receiving a lower dosage of erythromycin. As antibiotic treatment does not affect the clinical course of fully-developed whooping cough, erythromycin is indicated primarily when particularly susceptible individuals are threatened by exposure. In such cases erythromycin should be given as soon as whooping cough is suspected.	B. Trollfors	Infection
365	Pertussis after end of a mass vaccination project--end of the "vaccination honey-moon"		B. Trollfors, L. Dotevall, V. Sundh and C. Welinder-Olsson	Vaccine
298	Diphtheria, tetanus and pertussis antibodies in 10-year-old children before and after a booster dose of three toxoids: Implications for the timing of a booster dose	In an open study, 502 10-year-old children, who had received primary vaccination against diphtheria and tetanus in infancy and had varying histories of pertussis disease and vaccination, were vaccinated with diphtheria-tetanus vaccine (DT) alone or with the addition of 20 mug or 40 mug of pertussis toxoid. Diphtheria toxin neutralising antibodies, pertussis toxin IgG and tetanus toxoid IgG antibodies were measured before and 1 month after the booster. All toxoids were highly immunogenic. In pertussis toxoid recipients, median levels of pertussis toxin IgG increased to 16.5 U/ml (DTaP20) and to 36 U/ml (DTaP40) in children with non-detectable (< 1 U/ml) antibodies before vaccination and to > 400 U/ml in children (both DTaP20 and DTaP40) with detectable antibodies before vaccination. A total of 60 children (12%) with non-detectable (< 0.01 IU/ml) diphtheria antibodies and 36 children (7%) with non-detectable (< 0.01 IU/ml) tetanus antibodies before the booster had lower median antibody concentrations post-vaccination than children with detectable antibodies before the booster (diphtheria: 5.12 vs. 20.48 IU/ml; tetanus: 4.0 vs. 10.0 IU/ml). There were no differences in diphtheria and tetanus antibodies after vaccination between children who did and did not receive pertussis toxoid. Conclusion: 10-year-old children with non-detectable diphtheria and tetanus antibodies before the booster had lower post-vaccination antibodies than those with detectable antibodies before the booster indicating a poor immunological memory. Addition of pertussis toxoid to diphtheria-tetanus vaccine did not affect the antibody responses to diphtheria and tetanus toxoids when the three toxoids were combined as a booster. Even though immunity to diphtheria and tetanus was only estimated by surrogate markers (serum antitoxin antibodies) the results indicate that a lower age for the booster dose of diphtheria-tetanus vaccine or diphtheria-tetanus acellular pertussis vaccine should be considered. copyright Springer-Verlag 2005. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	B. Trollfors, N. Knutsson, J. Taranger, A. Mark, E. Bergfors, V. Sundh and T. Lagergard	European Journal of Pediatrics
474	Immunogenicity of hepatitis B vaccine simultaneously administered with the expanded programme on immunisation (EPI)	To assess the immunogenicity of hepatitis B vaccine simultaneously administered with the Expanded Programme on Immunisation (EPI) vaccines, a total of 300 consecutive infants, ranging in age between 6 weeks and 6 months, were alternatively assigned to the revised EPI and to EPI plus plasma-derived hepatitis B vaccine (Hevac B Pasteur). Four dosages (2 mcg or 0.5 ml each) of hepatitis B vaccine were given intramuscularly. HBsAg, anti-HBc, and anti-HBs were determined at day 0 and at day 210 in both groups by radioimmunoassay methods. The anti-HBs titre levels and geometric mean titres (GMTs) were determined at day 180 and day 210. There were three new hepatitis B virus infections in the control group and none in the study group by day 210. The seroconversion rates in the study group were 66% at day 180 and 84% at day 210, the respective GMTs being 116 and 940. Although the duration of observation is short (7 months) and the difference in the rate of infection between the two groups is not statistically significant (P > 0.05), the immunogenicity of the vaccine appears to be good. The simultaneous administration of hepatitis B vaccine and the EPI vaccines is logistically ideal. However, we suggest a further study using a larger dose of the Hevac B Pasteur vaccine to find out if a higher seroconversion rate than the 84% observed in this study could be achieved. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	E. Tsega, B. Tafesse, E. Nordenfelt, G. Wolde-Hawariat, B. G. Hansson and J. Lindberg	Journal of Medical Virology
103	Haemophilus influenzae type b conjugate vaccine trial in Oxford: implications for the United Kingdom	The safety and immunogenicity of a Haemophilus influenzae type b conjugate vaccine was investigated in 103 infants immunised at 3, 5, and 9 months of age; the infants also received diphtheria, pertussis, and tetanus and polio vaccines. Side effects were compared with 99 matched infants receiving diphtheria, pertussis, and tetanus and polio vaccines only. No serious side effects were observed and the incidence of minor side effects was no greater in the recipients of H influenzae type b conjugate vaccine. Two doses of the vaccine (standard and low) were compared: geometric mean titres of serum anticapsular antibody rose from 0.11 microgram/ml before immunisation to 26.4 micrograms/ml after three immunisations with the standard dose and 14.6 micrograms/ml with the low dose. The geometric mean titre among 21 unimmunized infants at this age was 0.06 micrograms/ml. Both doses therefore generated antibody concentrations likely to be protective after three immunisations. There were no non-responders. Incorporation of an H influenzae type b conjugate vaccine into the primary immunisation schedule has the potential for preventing over 1000 cases of systemic H influenzae type b disease and 50 deaths each year in the United Kingdom.	G. Tudor-Williams, J. Frankland, D. Isaacs, R. T. Mayon-White, J. A. MacFarlane, D. G. Rees and E. R. Moxon	Archives of disease in childhood
335	A single blinded randomised trial comparing two adult acellular pertussis vaccines with a licensed adult diphtheria-tetanus vaccine (ADT) [abstract]	Paper presented at Immunisation beyond 2000: 6th National Public Health Association Immunisation Conference, Melbourne, Australia, 4-5 November, 1998. [By permission, Australasian Medical Index, National Library of Australia]	F. Turnbull, T. Heath, B. Jalaludin, M. Burgess and A. Ramalho	6th National Public Health Association Immunisation Conference
360	A single blinded randomised trial comparing two adult acellular pertussis vaccines with a licensed adult diphtheria-tetanus vaccine (ADT)		F. Turnbull, T. Heath, B. Jalaludin, M. Burgess and A. Ramalho	Journal of Paediatrics & Child Health
33	Severe adverse events in a comparative efficacy trial in Germany in infants receiving either the Lederle/Takeda acellular pertussis component DTP (DTaP) vaccine, the Lederle whole-cell component DTP (DTP) or DT vaccine. The Pertussis Vaccine Study Group	Severe adverse events were evaluated in a comparative efficacy trial in Germany in infants who received either the Lederle/Takeda acellular pertussis component DTP (DTaP) vaccine, the Lederle whole-cell component DTP (DTP) or DT vaccine. Vaccinees received four doses (at three, four-and-a half, six and 15-18 months of age) of either DTP or DTaP vaccine or three doses at three, four-and-a half and 15-18 months of age) of DT vaccine. The analysis included 4,273 DTaP recipients, 4,259 DTP recipients and 1,739 DT vaccinees. Convulsions within three days of vaccination occurred in 1/15,912 doses in DTaP recipients and 1/3,926 doses in DTP vaccinees (p = 0.22). Persistent inconsolable crying was more common in DTP vaccinees (1/113 doses) compared with DTaP (1/497 doses, p < 0.001) and DT (1/359 doses, p < 0.001) recipients. High fever (< or = 40.5 degrees C) was less frequent in DTaP vaccinees (1/16,239 doses) compared with DTP (1/5,359) and DT recipients (1/4,665). One hypotonic-hyporesponsive episode was observed.	M. A. Uberall, K. Stehr, J. D. Cherry, U. Heininger, S. Schmitt-Grohé, S. Laussucq and T. Eckhardt	Developments in biological standardization
271	Redesigned immunization card and center-based education to reduce childhood immunization dropouts in urban Pakistan: a randomized controlled trial	In Pakistan during 2000-2004, about 11-13% of children who received the first dose of diphtheria-pertussis-tetanus (DPT1) failed to complete its third dose (DPT3). We assessed the effect of a redesigned immunization card and center-based education to mothers on DPT3 completion. We enrolled 1500 mother-child units at DPT1, randomized them to three intervention and one standard care groups, and recorded their DPT3 visits during a 90-day follow-up. In multivariable analysis, a significant increase of 31% (adjusted RR=1.31, 95% CI=1.18-1.46) in DPT3 completion was estimated in the group that received both redesigned card and center-based education compared with the standard care group.	H. R. Usman, S. Akhtar, F. Habib and I. Jehan	Vaccine
257	Determinants of third dose of diphtheria-tetanus-pertussis (DTP) completion among children who received DTP1 at rural immunization centres in Pakistan: a cohort study	OBJECTIVE: In Pakistan, a high proportion of children fail to complete third dose of diphtheria-tetanus-pertussis (DTP3) after having received the first dose (DTP1). A cohort study was conducted to identify the factors predicting three doses of diphtheria-tetanus-pertussis (DTP3) completion among children who have received DTP1 at six centres of Expanded Programme on Immunization (EPI) in rural Pakistan.METHOD: We analyzed a cohort of mother-child pairs enrolled at DTP1 between November 2005 and May 2006 in the standard care group of a larger randomized controlled trial. Data were collected from mothers on a structured questionnaire at enrollment, and each child was followed up at clinic visits for 90 days to record dates of DTP2 and DTP3. Multivariable log-binomial regression analysis was performed to identify the independent predictors of DTP3 completion.RESULTS: Only 39% (149/378) of enrolled children completed DTP3 during the follow-up period. After adjusting for the centre of enrollment in multivariable analysis, DTP3 completion was higher among children who were < or =60 days old at enrolment [adjusted risk ratio (Adj. RR) 1.39, 95% confidence interval (CI): 1.06-1.82], who were living in a household with monthly household income >Rs. 3000 (US$ 50) (Adj. RR 1.76, 95% CI: 1.16-2.65), and who were living < or =10 min away from EPI centre (Adj. RR 1.31, 95% CI: 1.04-1.66).CONCLUSIONS: Interventions targeting childhood immunization dropouts should focus on bringing more children to EPI centres on-time for initial immunization. Relocation of existing EPI centres and creation of new EPI centres at appropriate locations may decrease the travel time to the EPI centres and result in fewer immunization dropouts.	H. R. Usman, S. Kristensen, M. H. Rahbar, S. H. Vermund, F. Habib and E. Chamot	Tropical medicine & international health : TM & IH
95	Does concomitant injection of a combined diphtheria-tetanus-acellular pertussis - hepatitis B virus - inactivated polio virus vaccine influence the reactogenicity and immunogenicity of commercial Haemophilus influenzae type b conjugate vaccines?	UNLABELLED: Does concomitant injection of a combined diphtheria-tetanus-acellular pertussis - hepatitis B virus - inactivated polio virus vaccine influence the reactogenicity and immunogenicity of commercial Haemophilus influenzae type b conjugate vaccines? The immunogenic responses and local reactions to four Haemophilus influenzae type b (Hib) conjugate vaccines licensed for primary immunisation (Hiberix, ActHib, Pedvax, HibTITER) when administered concomitantly but in the opposite thigh with a candidate diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus vaccine were studied in 549 healthy infants at 3, 4.5 and 6 months of age. Local reactions were mild, but different between the four groups, a tetanus conjugate Hib vaccine showing the fewest reactions. All local reactions resolved without sequelae. There was no apparent general reaction. The immunogenic response was similar with all four vaccines, geometric mean concentrations ranging from 4.95 to 7.2 microg/ml. All but one subject had antipolyribosylribitol phosphate polysaccharide antibody titres > or =0.15 microg/ml, and 88.0% to 96% achieved high titres (>1.0 microg/ml) generally associated with long-term protection against Hib disease. CONCLUSION: There does not appear to be any interference with the immune response when current commercial Haemophilus influenzae type b conjugate vaccines are concomitantly administered with a candidate diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus vaccine as separate injections.	V. Usonis and V. Bakasenas	European journal of pediatrics
169	A clinical trial examining the effect of increased total CRM(197) carrier protein dose on the antibody response to Haemophilus influenzae type b CRM(197) conjugate vaccine	CRM(197) is a carrier protein in certain conjugate vaccines. When multiple conjugate vaccines with the same carrier protein are administered simultaneously, reduced response to vaccines and/or antigens related to the carrier protein may occur. This study examined responses of infants who, in addition to diphtheria toxoid/tetanus toxoid/acellular pertussis vaccine (DTaP) received either diphtheria CRM(197)-based Haemophilus influenzae type b conjugate vaccine (HbOC) or HbOC and a diphtheria CRM(197)-based combination 9-valent pneumococcal conjugate vaccine/meningococcal group C conjugate vaccine. Administration of conjugate vaccines with CRM(197) carrier protein load >50 microg did not reduce response to CRM(197) conjugate vaccines or immunogenicity to immunologically cross-reactive diphtheria toxoid.	V. Usonis, V. Bakasenas, S. Lockhart, S. Baker, W. Gruber and F. Laudat	Vaccine
165	Feasibility study of a combined diphtheria-tetanus-acellular pertussis-hepatitis B (DTPa-HBV) vaccine, and comparison of clinical reactions and immune responses with diphtheria-tetanus-acellular pertussis (DTPa) and hepatitis B vaccines applied as mixed or injected into separate limbs	The feasibility of a combined diphtheria-tetanus-acellular pertussis-hepatitis B (DTPa-HBV) vaccine was assessed and a comparison made of immunogenicity and reactogenicity to DTPa and HBV vaccines mixed in one syringe and to concomitant but separate injections as a primary vaccination course in three groups of infants at 3, 4.5 and 6 months of age. All subjects attained protective levels of anti-HBs antibodies 1 month after the primary course with higher geometric mean titres (GMTs) in the combined or mixed vaccinations. GMTs for pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (PRN) were as good or better in the groups administered the combined formulation and the extemporaneously mixed vaccines than the separate administration. No serious adverse event related to the vaccination was reported in this study. Neither the combined formulation of DTPa and HBV vaccines nor the extemporaneous mixture increased the incidence or severity of adverse reactions compared with the separate administration of DTPa. This study shows the feasibility of a combined DTPa-HBV vaccine and the data support, in the interim, the mixing of DTPa and HBV vaccines which are tested in clinical trials for infant immunization.	V. Usonis, V. Bakasenas, P. Willems and R. Clemens	Vaccine
471	Practice-based continuing education combined with process improvement methods improves delivery of preventive services to children		J. L. Vacek	Evidence-Based Healthcare
299	Study of pertussis vaccines in infants: Comparison of response to acellular pertussis DTP vaccines containing 25 mug of FHA and either 25 or 8 mug of PT with response to whole-cell pertussis DTP vaccine	Clinical and serological responses of infants to primary vaccination with diphtheria-tetanus-acellular pertussis (DTPa) vaccines containing 25 mug of filamentous haemagglutinin (FHA) and either 25 or 8 mug of pertussis toxoid (PT) were compared in a double-blind randomized study with responses of infants receiving whole-cell pertussis DTP vaccine (DTPw). In total, 308 healthy infants were enrolled to receive three vaccine doses at 3, 4 and 5 months of age. DTPa recipients had significantly lower incidences of local reactions and fever than the DTPw recipients. No differences in reactogenicity were observed between DTPa groups receiving 8 and 25 mug doses of PT. After vaccination, an immune response to PT was seen in 96% of 25 mug PT DTPa recipients, 94% of DTPw recipients and 86% of 8 mug PT DTPa recipients. The geometric mean anti-PT neutralizing antibody titre was significantly higher for 25 mug PT dose recipients (34.9 Chinese hamster ovary (CHO)) as compared with 8 mug PT dose recipients (21.0 CHO). The results support the use of the higher dose of PT in acellular pertussis vaccine preparations. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	H. Vanura, M. Just, F. Ambrosch, R. M. Berger, H. Bogaerts, J. Wynen, D. Vandevoorde and G. Wiedermann	Vaccine
12	An open-label, randomized, multicenter study of the safety, tolerability, and immunogenicity of quadrivalent human papillomavirus (types 6/11/16/18) vaccine given concomitantly with diphtheria, tetanus, pertussis, and poliomyelitis vaccine in healthy adolescents 11 to 17 years of age	BACKGROUND: GARDASIL/SILGARD is a quadrivalent human papillomavirus (HPV) vaccine with activity against HPV 6/11/16/18. In many countries, GARDASIL is recommended for routine use among adolescents at the same age as other vaccines. In this study, we evaluated the immunogenicity and safety of GARDASIL administered concomitantly with REPEVAX (diphtheria, tetanus, acellular pertussis, and poliomyelitis vaccine). METHODS: This was an open-label, randomized, multicenter study. We enrolled males (n = 260) and females (n = 583) aged 11 to 17 years. All subjects received a 0.5 mL dose of GARDASIL at day 1, month 2, and month 6, and a 0.5 mL dose of REPEVAX either on day 1 (opposite limb from GARDASIL) or at month 1. Antibody levels for all vaccine components were measured. We monitored systemic and injection-site adverse experiences (AEs) and serious adverse experiences. RESULTS: Immune response for all GARDASIL antigens following concomitant administration of the vaccines was demonstrated noninferior to nonconcomitant administration. Seroconversion for HPV 6, 11, 16, and 18 was >99.7% in both concomitant and nonconcomitant vaccination groups. For REPEVAX, noninferiority of immune response was established for diphtheria, tetanus, and all polio and pertussis antigens. Concomitant administration of the 2 vaccines was generally well-tolerated, although there was a small increase in headache and injection-site swelling in the concomitant group. CONCLUSION: Overall, concomitant administration of GARDASIL and REPEVAX was generally well-tolerated and did not interfere with the immune response to either vaccine. Concomitant administration of vaccines would minimize the number of visits required to deliver each vaccine individually.	T. Vesikari, P. Damme, N. Lindblad, U. Pfletschinger, D. Radley, D. Ryan, S. Vuocolo, R. M. Haupt and D. Guris	The Pediatric infectious disease journal
313	Concurrent administration of rhesus rotavirus tetravalent (RRV-TV) vaccine with pentavalent diphtheria-pertussis-tetanus-Haemophilus influenzae b-inactivated polio and hepatitis B vaccines	To investigate the incorporation of oral rhesus-human reassortant rotavirus tetravalent (RRV-TV) vaccine into a routine immunization programme, RRV-TV or oral placebo was coadministered with a pentavalent diphtheria- tetanus-whole-cell pertussis-Haemophilus influenzae b (Hib)-inactivated polio vaccine and hepatitis B vaccine following a 3-4-5-mo schedule in a double- blind trial involving 249 infants. Seroconversion rates after 3 doses of rotavirus vaccine were 80% for rotavirus immunoglobulin A (IgA) and 93% for RRV neutralizing antibodies. Rotavirus vaccine did not interfere with the immune responses to diphtheria, tetanus, pertussis, Hib, poliovirus 1, 2 and 3, or hepatitis B. Following the first, second and third doses of vaccine, fever > 38 [degree] C on the day of vaccination was seen in 31%, 24% and 24%, respectively, with no difference between RRV-TV- and placebo-vaccinated children. This fever was presumably due to the whole-cell pertussis vaccine. Those vaccinees who received concomitant RRV-TV vaccine had another peak of fever around d 4 after the first dose, when 25% of them had fever > 38 [degree] C and 3% > 39 [degree] C. It is concluded that RRV-TV rotavirus vaccine can be given concurrently with other childhood immunizations following a 3-4-5-mo vaccination schedule. However, febrile reactions to RRVTV rotavirus vaccine are common when the first dose is given at the age of 3 mo. Number of References 19. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	T. Vesikari, J. Joensuu, M. Baer, H. Kayhty, R. M. Olander, H. Sormunen, A. Miettinen, R. L. Ward and T. Guillot	Acta Paediatrica
437	Results from a randomized clinical trial of coadministration of RotaTeq, a pentavalent rotavirus vaccine, and NeisVac-C, a meningococcal serogroup C conjugate vaccine	RotaTeq (Merck & Co. Inc./Sanofi Pasteur MSD) is a three-dose, oral pentavalent rotavirus vaccine for the immunization of infants from 6 weeks of age for the prevention of rotavirus gastroenteritis. The primary objective of the present trial was to demonstrate that RotaTeq can be coadministered with meningococcal serogroup C conjugate vaccine (MenCC; NeisVac-C; Baxter Healthcare) to healthy infants without impairing the protective immune responses to MenCC. This was an open-label, randomized, comparative study conducted in Finland. The study was designed to assess concomitant versus sequential administration of RotaTeq and MenCC on the immune response to both vaccines. Healthy infants (n = 247), aged 6 to 7 weeks, were recruited. Coadministration of MenCC with RotaTeq was noninferior to sequential administration for the seroprotection rate against meningococcal serogroup C (the proportion of infants with a serum bactericidal antibody titer using baby rabbit complement of ? 8 was 100% in both groups). The other responses to MenCC (titer of ? 1:128, ? 4-fold increase in titer, and geometric mean titers [GMTs]) and the responses to RotaTeq (IgA and SNA response to G1 to G4 and P1A[8], GMTs, and ? 3-fold increase in titer) were comparable between groups, including a ? 3-fold IgA increase in >96% of the infants in both groups. Concomitant administration of the first doses of MenCC, diphtheria and tetanus toxoids and acellular pertussis vaccine, inactivated poliovirus vaccine, and Haemophilus influenzae type b conjugate vaccine (DTaP-IPV-Hib), and RotaTeq was associated with a higher rate of vomiting and diarrhea than concomitant administration of MenCC and DTaP-IPV-Hib, but that was not observed after the second concomitant administration. The convenience of concomitant administration of RotaTeq and MenCC may, however, outweigh the additive effect of mostly mild adverse events reported after the individual administration of each vaccine. These results support the coadministration of RotaTeq and MenCC.	T. Vesikari, A. Karvonen, R. Borrow, N. Kitchin, M. Baudin, S. Thomas and A. Fiquet	Clinical and vaccine immunology : CVI
125	Immunogenicity and safety of the human rotavirus vaccine Rotarix co-administered with routine infant vaccines following the vaccination schedules in Europe	This study assessed the immunogenicity and safety of a human rotavirus vaccine RIX4414; the effect of co-administration of childhood vaccines on the immune responses was also assessed. Healthy infants aged 6-14 weeks received two doses of RIX4414/placebo concomitantly with the primary childhood vaccination (Infanrix hexa, Infanrix quinta,Meningitec and/or Prevnar), respecting the vaccination schedule of each country. Anti-rotavirus IgA seroconversion rate (ELISA cut-off 20 U/ml) was measured pre-vaccination and 1-2 months post-Dose 2. Immune response against diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, inactivated polio virus, pneumococcal polysaccharide conjugate (France and Germany) and meningococcal group C conjugate vaccines (Spain) were measured approximately 1-month post-Dose 3. An overall anti-rotavirus IgA seroconversion rate of 86.5%(95% CI: 83.9-88.8) was observed in the RIX4414 group 1-month post-Dose 2. The seroconversion rate in Finland and Italy (3 and 5-month schedule) was 94.6%(95% CI: 90.0-97.5) and 92.3%(95% CI: 64.0-99.8), respectively. Immune response to the childhood vaccines was unaffected following co-administration with RIX4414. Reactogenicity profile was similar for RIX4414 and placebo groups. RIX4414 was immunogenic and well tolerated in European infants and the co-administration of routine childhood vaccines with RIX4414 did not negatively impact the immune responses to these vaccines.	T. Vesikari, A. Karvonen, R. Prymula, V. Schuster, J. C. Tejedor, F. Thollot, P. Garcia-Corbeira, S. Damaso, H. H. Han and A. Bouckenooghe	Vaccine
397	Purulent nasal discharge	Purulent nasal discharge is a common presenting symptom associated with infections of the upper respiratory tract. The most likely diagnoses are uncomplicated viral upper respiratory infections and bacterial sinusitis. Allergy may be an underlying problem in children with sinusitis. Less common considerations are adenoiditis, infections caused by B. pertussis, C. diphtheriae or Treponema pallidum or intranasal structural problems.	E. R. Wald	The Pediatric infectious disease journal
369	Clinical observation Tan Ke Jing for pertussis in 86 cases		W. J. Wang	Jiangsu Journal of Traditional Chinese Medicine [Jiang Su Zhong Yi]
303	Pertussis epidemiology and acellular pertussis vaccine efficacy in older children: NIH APERT multicenter pertussis trial		J. Ward	Pediatric Research
126	Safety and immunogenicity of Haemophilus type b-tetanus protein conjugate vaccine, mixed in the same syringe with diphtheria-tetanus-pertussis vaccine in young infants	As new vaccines are developed there is increasing interest in reducing the number of injections given to children by combining vaccines in one syringe. We studied the safety and immunogenicity of Haemophilus influenzae type b-tetanus protein conjugate vaccine (PRP-T) administered at ages 2, 4 and 6 months mixed in the same syringe with DTP vaccine and its effects on the seroresponse to DTP vaccine. A group of 112 healthy 2-month-old infants received DTP-PRP-T or DTP-placebo mixed immediately before immunization in the same syringe. The addition of PRP-T to DTP did not increase the rate of local or systemic reactions. After the first, second and third dose, the PRP-T recipients showed a geometric anti-PRP antibody mean of 0.13, 2.31 and 6.40 micrograms/ml vs. 0.07, 0.05 and 0.05 micrograms/ml among the DTP-placebo recipients, respectively. Of the PRP-T recipients, 94 and 98% attained antibody concentration of greater than or equal to 0.15 micrograms/ml protein after the second and third dose, respectively, and 65 and 94% attained a concentration of greater than or equal to 1.0 micrograms/ml after the second and third dose, respectively. At the age of 1 year 94 and 52% of the DTP-PRP-T recipients vs. 12% and 0% of the placebo recipients still maintained titers of greater than or equal to 0.15 and greater than or equal to 1.0 micrograms/ml, respectively. The administration of DTP in the same syringe with PRP-T did not affect significantly the antibody response to diphtheria and tetanus toxoid and to pertussis agglutinins. It is concluded that PRP-T vaccine could be administered in the same syringe as DTP.	N. Watemberg, R. Dagan, Y. Arbelli, I. Belmaker, A. Morag, L. Hessel, B. Fritzell, A. Bajard and L. Peyron	The Pediatric infectious disease journal
373	Extracted pertussis antigen		C. Weihl, H. D. Riley and J. H. Lapin	Am J of Diseases of Children
346	Immunogenity and side effects of a combined diptheria-pertussis-tetanus adsorbate and haemophilus influenzae conjugate vaccine (HibDPT-Vaccinol®)		J. Wendisch, M. Just, D. Gremmelmeier, G. Weissbach and P. Herden	Monatsschrift fur Kinderheilkunde
336	Immunogenity and side effects of a combined diptheria-pertussis-tetanus adsorbate and haemophilus influenzae conjugate vaccine		J. Wendisch, M. Just, G. Weissbach, P. Herden and W. Schaart	Der Kinderarzt
325	Immunogenicity and safety of human papillomavirus-16/18 AS04-adjuvanted vaccine coadministered with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine and/or meningococcal conjugate vaccine to healthy girls 11 to 18 years of age: Results from a randomized open trial		C. M. Wheeler, B. M. Harvey, M. E. Pichichero, M. W. Simon, S. P. Combs and M. M. Blatter	Pediatric infectious disease journal
341	Th2-polarisation of cellular immune memory to neonatal pertussis vaccination		O. J. White, J. Rowe, P. Richmond, H. Marshall, P. McIntyre, N. Wood and P. G. Holt	Vaccine
459	Oral immunisation of newborn against whooping cough		B. Wiegl, C. Meitinger, D. Thiel and R. Janetschek	Monatsschrift fur Kinderheilkunde
332	Tolerability and immunogenicity of acellular pertussis 3 component vaccine (DTPa) in comparison to classic DTPg vaccine	Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	S. Wiersbitzky	Monatsschrift fur Kinderheilkunde
357	Reactogenicity an immunogenicity of a three-component acellular pertussis DTPa vaccine compared to the conventional whole-cell DtPg vaccine		S. Wiersbitzky, H. L. Bock, R. Bruns, R. Clemens, G. Graul, H. Koditz, H. Padelt, B. Schneeweiss and W. Mesister	Monatsschrift fur Kinderheilkunde
263	[Toxic infant gastroenteritis acuta after DPT preventive vaccination?]		S. Wiersbitzky and R. Bruns	Kinderärztliche Praxis
318	Reactogenity and immunogenity of a combined acellular tri-component-pertussis-diptheria-tetanus vaccine (aPDT) from SmithKline Beecham in comparison to usual whole germ Pertussis-diptheria-tetanus vaccines		S. Wiersbitzky, R. Bruns, B. Schneeweiss, H. Koditz, G. Graul, H. Padelt, H. L. Bock and H. Bogaerts	Monatsschrift fur Kinderheilkunde
350	Basic immunisation with the new acellular diptheria-tetanus-pertussis (DTPa) vaccine - immunogenity and toleration in comparison to usual DTP vaccines		S. Wiersbitzky, R. Bruns, B. Schneeweiss, H. Koditz, G. Graul, H. Padelt, H. L. Bock and H. Bogaerts	Monatsschrift fur Kinderheilkunde
76	Agglutinin response to pertussis vaccine. I. Effect of dosage and interval		J. Wilkins, F. F. Williams, P. F. Wehrle and B. Portnoy	The Journal of pediatrics
152	Four is better than nine. a combined diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine for routine immunization in Malaysia	Malaysian infants would have to receive nine injections during the first few months of life in order to be protected against disease caused by hepatitis B (HBV), diphtheria, tetanus, pertussis and Haemophilus influenzae type b (Hib) if single HBV and Hib vaccines were used. We evaluated a combined DTPw-HBV/Hib vaccine administered at 1.5, 3 and 5 months after a birth dose of hepatitis B vaccine (HBV). One month after completion of the primary vaccination, 99% of subjects had seroprotective anti-HBV antibody levels, and at least 98% had seroprotective antibodies against diphtheria, tetanus, and Hib, and were seropositive for pertussis antibodies. The immune response to the combined vaccine was comparable to that induced by separate injections with DTPw, HBV and Hib vaccines. Overall, the DTPw-HBV/Hib vaccine was as well tolerated as separate administration of DTPw, HBV and Hib vaccines. The combined DTPw-HBV/Hib vaccine induces protection against five diseases as recommended in the Malaysian routine vaccination schedule. Use of the combined DTPw-HBV/Hib vaccine can reduce the required number of injections from nine to four in the first few months of life.	S. L. Wong, P. Soosai, Y. L. Teoh, H. H. Han, I. Lefevre and H. L. Bock	The Southeast Asian journal of tropical medicine and public health
97	Acellular pertussis vaccine at birth and one month induces antibody responses by two months of age	BACKGROUND: Infants less than 3 months of age are at highest risk of hospitalization and death from pertussis. Several studies have examined antibody responses to pertussis vaccines at birth but no previous study has evaluated 2 doses of monovalent acellular pertussis vaccine (aPV) before 2 months of age. METHODS: Seventy-six newborns were randomized at birth to 3 groups-aPV at birth and 1 month, aPV at birth, and control. All infants received hepatitis B vaccine (HBV) at birth followed at 2, 4, and 6 months by a combination vaccine including aPV, diphtheria, tetanus, Haemophilus influenzae type b (Hib), hepatitis B, polio antigens and 7 valent conjugate pneumococcal vaccine. IgG antibody responses to pertussis toxoid (PT), filamentous hemagglutinin (FHA), and pertactin (PRN) were measured in maternal serum and in infants at 2, 4, 6, and 8 months of age. Antibody responses to hepatitis B, diphtheria, tetanus, and Hib were measured at 8 months only. A parental diary and active telephone follow-up occurred for 7 days after each vaccination. RESULTS: The aPV birth dose was well tolerated. By 2 months of age, 22 of 25 (88%) of 2 dose recipients had detectable IgG antibody to PT (IgG PT) compared with 9 of 21 (43%) who received a birth dose only and 3 of 20 (15%) of controls. Infants in the 2 dose group had a geometric mean concentration (GMC) of IgG PT of 16 ELISA units per mL (EU/mL), 95% CI: 11 to 25, significantly higher than birth dose only (5 EU/mL, 95% CI: 3-8) and controls (3 EU/mL, 95% CI: 2-5). At 8 months of age, following 5, 4, and 3 doses of aP-containing vaccine, respectively, IgG PT had plateaued but IgG to FHA and PRN increased with successive doses. There was a trend to lower antibody responses for hepatitis B and Hib with higher numbers of Pa doses. CONCLUSION: These data suggest that aPV at birth and 1 month induces significantly higher IgG antibody against pertussis antigens by 2 months of age without reducing subsequent pertussis antibody responses. Larger and more detailed studies of aPV from birth are needed to evaluate other antibody responses and the potential of this approach to reduce death and morbidity from Bordetella pertussis infection in the first 3 months of life.	N. Wood, P. McIntyre, H. Marshall and D. Roberton	The Pediatric infectious disease journal
413	The impact of different doses of vitamin A supplementation on male and female mortality. A randomised trial from Guinea-Bissau	BACKGROUND: Vitamin A supplementation (VAS) given to children between 6 months and 5 years of age is known to reduce mortality in low-income countries. We have previously observed that girls benefit more from a lower dose of VAS than the one recommended by WHO, the effect being strongest if diphtheria-tetanus-pertussis vaccine (DTP) was the most recent vaccination. We aimed to test these observations. METHODS: During national immunisations days in Guinea-Bissau, West Africa, combining oral polio vaccination and VAS, we randomised 8626 children between 6 months and 5 years of age to receive the dose of VAS recommended by WHO or half this dose. Mortality rate ratios (MRRs) were assessed after 6 and 12 month. RESULTS: The overall mortality rate among participants was lower than expected. There was no significant difference in mortality at 6 months and 12 months of follow up between the low dose VAS group and the recommended dose VAS group. The MRRs were 1.23 (0.60-2.54) after 6 months and 1.17 (0.73-1.87) after 12 months. This tendency was similar in boys and girls. The low dose was not associated with lower mortality in girls if the most recent vaccine was DTP (MRR = 0.60 (0.14-2.50) after 6 months). CONCLUSION: Our sample size does not permit firm conclusions since mortality was lower than expected. We could not confirm a beneficial effect of a lower dose of VAS on mortality in girls. TRIAL REGISTRATION: The study was registered under clinicaltrials.gov, number NCT00168636.	D. Yakymenko, C. S. Benn, C. Martins, B. R. Diness, A. B. Fisker, A. Rodrigues and P. Aaby	BMC pediatrics
143	Safety and immunogenicity of a pentavalent diphtheria, tetanus, pertussis, hepatitis B and polio combination vaccine in infants	INTRODUCTION: The objectives of this study were to evaluate the safety and immunogenicity of a new combination vaccine (DTaP-HB-IPV) containing diphtheria, tetanus, acellular pertussis and hepatitis B (HB) and a new inactivated poliovirus vaccine (IPV) manufactured by GlaxoSmithKline (GSK). This vaccine was given in an all IPV or sequential IPV and oral polio vaccine (OPV) schedule. Another combination vaccine, DTaP-HB (GSK), was similarly evaluated given with OPV or IPV. METHODS: Four hundred infants were randomized into one of four study groups and immunized at 2, 4 and 6 months of age. Group A received three doses of DTaP-HB-IPV; Group B received DTaP-HB-IPV at 2 and 4 months and DTaP-HB with OPV (Orimune) at 6 months; Group C received three doses of DTaP-HB with licensed IPV (IPOL) administered separately; Group D received separate doses of OPV, DTaP (Infanrix; GSK) and HB (Engerix; GSK). All subjects received conjugate Haemophilus influenzae type b vaccine (Hib) (OmniHIB) at 2, 4 and 6 months of age given at a separate injection site. Subjects who returned at 12 to 18 months of age (229) received booster immunization with DTaP and Hib. Safety was evaluated after each vaccine dose. Blood was drawn before the first dose and one month after the third dose as well as before and after the booster dose. RESULTS: There were no vaccine-related serious adverse events in any group after any vaccine dose. Minor systemic and local adverse events were also not significantly different among the four groups after any dose. There were no differences in the immune response rates for Hib, HB, polio (types 1, 2 and 3), diphtheria, tetanus or pertussis antigens (pertussis toxin, filamentous hemagglutinin, pertactin) among groups, although there were some quantitative differences in specific antibody titers among groups. DTaP-HB-IPV and DTaP-HB combination vaccines had safety and immunogenicity equivalent to those of standard individually administered vaccines. The new IPV was not inferior to IPOL. CONCLUSION: Use of the pentavalent combination vaccine would greatly reduce the number of required injections during the first 2 years of life, thereby simplifying the immunization schedule, enhancing compliance and facilitating acceptance of additional injections engendered by introduction of newer vaccines.	S. H. Yeh, J. I. Ward, S. Partridge, S. M. Marcy, H. Lee, J. Jing, E. S. Curry and B. J. Howe	The Pediatric infectious disease journal
468	[Immune response and reactions to simultaneous administration of hepatitis b vaccine with routine vaccine in children. I. Immune response and reactions to simultaneous administration of dpt, topv and hepatitis b vaccine]. [Chinese]	This paper reports the result of the immune response and reactions to simultaneous administration of DPT, TOPV and hepatitis B vaccine. 180 children (0-5 months of age) were divided into three groups. Group one was vaccinated with hepatitis B vaccine alone, group two was vaccinated with DPT, TOPV vaccine, and group three was vaccinated with hepatitis B vaccine, DPT and TOPV vaccine simultaneously. The result of the immune response to the combination of hepatitis B with DPT, TOPV vaccines were similar to that observed after immunization with each vaccine alone. The general reactions of all vaccines were mild, no significant difference between each group was noted. The study demonstrated that children can be immunized with hepatitis B vaccine and DPT, TOPV vaccines simultaneously.	C. D. Yuan	Chung-Hua Liu Hsing Ping Hsueh Tsa Chih// Chinese Journal of Epidemiology
123	Challenge with a hepatitis B vaccine in two cohorts of 4-7-year-old children primed with hexavalent vaccines: an open-label, randomised trial in Italy	BACKGROUND AND AIMS: The anamnestic response to a challenge dose of vaccine can assess immune memory and protection against hepatitis B infection. This study investigated responses to a challenge dose of monovalent hepatitis B vaccine in children immunised with three doses of either Hexavac or Infanrix-Hexa during infancy. METHODS: This open-label, randomised, controlled, four-arm study enrolled 410 healthy children aged 4-7 years who had received either Hexavac (n=201) or Infanrix-Hexa (n=209) at 3, 5 and 11 months of life. Children received a single intramuscular challenge dose of either hepatitis B vaccine, HBVaxPro (Hexavac, n=34; Infanrix-Hexa, n=28) or Engerix-B (Hexavac, n=167; Infanrix-Hexa, n=181). Hepatitis B surface antibody (anti-HBs) concentrations were measured before and 1 month after the challenge vaccine dose. The analysis was descriptive and no formal hypothesis was tested. RESULTS: One month post-challenge, 91.2% of children in the Hexavac group (95% confidence interval [CI] 86.3, 94.8) and 98.0% (95% CI 94.9, 99.4) in the Infanrix-Hexa group had anti-HBs concentrations ?10 mIU/ml (primary endpoint). In a post hoc analysis, most children with pre-challenge anti-HBs concentration <10 mIU/ml achieved anti-HBs concentrations ?10 mIU/ml (Hexavac group, 85.3% [95% CI 77.6, 91.2]; Infanrix-Hexa group, 91.9% [95% CI 78.1, 98.3]). Both challenge vaccines were well tolerated. CONCLUSIONS: These data suggest that immune memory persists for long-term (5 years) after a primary vaccination in infancy with a hexavalent vaccine (Hexavac or Infanrix-Hexa).	A. Zanetti, A. Parlato, L. Romanò, M. G. Desole, G. Ferrera, F. Giurdanella, M. Zuliani, P. Richard, S. Thomas and A. Fiquet	Vaccine
108	Safety and reactogenicity of a novel DTPa-HBV-IPV combined vaccine given along with commercial Hib vaccines in comparison with separate concomitant administration of DTPa, Hib, and OPV vaccines in infants	OBJECTIVE: Combination vaccines simplify vaccine administration and have the potential to promote compliance and cost-effectiveness by decreasing the number of injections needed to immunize a child. The objective of this study was to assess the safety and reactogenicity of the diphtheria-tetanus toxoid-acellular pertussis-hepatitis B virus-inactivated polio virus (DTPa-HBV-IPV) vaccine when coadministered with different Haemophilus influenzae type B (Hib) vaccines in comparison with separate, commercially available, control vaccines in a 3-dose primary vaccination series. METHODS: An open-label, randomized, parallel-group study in 5318 infants who were 8 to 16 weeks of age at enrollment was conducted in 90 centers in Germany. The incidence of adverse events that occurred in infants who received the DTPa-HBV-IPV candidate vaccine coadministered with 1 of 4 different Hib vaccines (given in separate sites; groups 1-4) was compared with the incidence that occurred in infants who received commercially available control vaccines (DTPa, Hib, and oral polio virus [OPV] vaccine; group 5) administered separately. The vaccines were given as a 3-dose primary series at 3, 4, and 5 months of age. Infants were assessed for solicited local and general adverse events for 4 days and for unsolicited adverse events for 30 days after each vaccine dose. The primary endpoint was to rule out a 7.5% increase in infants who experienced grade 3 (defined as preventing normal everyday activities unless otherwise specified) solicited local and general adverse events over the 3-dose primary course after the combined DTPa-HBV-IPV vaccine coadministered with Hib as compared with commercially available vaccines. RESULTS: During the 3-dose primary course, 490 of 3029 infants (16.2%) in the pooled DTPa-HBV-IPV vaccine groups and 151 of 744 (20.3%) in the control vaccine group experienced a grade 3 adverse event (rate difference [control minus combination] 4.1%; 90% confidence interval, 1.41-7.13). The lower limit of the 90% confidence interval of the observed difference remained above the prespecified -7.5% limit for noninferiority, thereby meeting the primary endpoint. The incidences of local injection-site reactions were similar for the DTPa-HBV-IPV and DTPa injection sites. Significant differences in the incidence of both local and general adverse events were observed depending on which of the Hib vaccines was coadministered. Infants who received Hib N meningitidis outer-membrane complex protein conjugate vaccine had greater incidences of fever and, to a lesser extent, greater reactions at the Hib injection site than did infants who received other Hib vaccines. CONCLUSIONS: The combination DTPa-HBV-IPV vaccine administered concomitantly with Hib vaccine at separate sites was at least as safe as coadministration of individual DTPa, Hib, and OPV vaccines in terms of the defined endpoints for safety.	F. Zepp, A. Schuind, C. Meyer, R. Sänger, A. Kaufhold and P. Willems	Pediatrics
458	[Acupuncture and cupping for treatment of 120 cases of whooping cough syndrome]		L. M. Zhang	Shanghai Journal of Acupuncture and Moxibustion
464	Mucosal immune responses to meningococcal conjugate polysaccharide vaccines in infants	Background. Serogroup C meningococcal conjugate polysaccharide vaccines have been reported to induce significant serum IgG antibodies and immunologic memory in infants. Because meningococcus is a mucosal pathogen colonizing the nasopharynx, local mucosal immune responses may play an important role in host defense against infection and carriage. We have investigated the mucosal IgA and IgG antibody responses to two meningococcal C conjugate vaccines in the saliva of healthy infants. Methods. Specific salivary IgA and IgG antibodies to two meningococcal C polysaccharide conjugate vaccines (Menjugate from Chiron Corp., n = 46; and Meningitec from Wyeth Lederle, n = 54) were investigated by immunoassay in infants after parenteral vaccinations at the ages of 2, 3 and 4 months. Unstimulated saliva samples were collected immediately before the first immunization and 1 month after the third immunizations. Forty healthy infants receiving the same routine vaccines but no meningococcal C vaccine were recruited as controls. Results. There were significant increases in meningococcal C polysaccharide-specific IgG antibody concentrations postvaccination compared with prevaccination concentrations in both vaccinated groups (both P < 0.001), but no change in the control group. There were no significant increases in specific IgA postvaccination geometric mean concentrations in either the vaccine or the control groups. The number of IgA positives postvaccination increased slightly in the Wyeth vaccine group vs. controls (P < 0.05). Conclusions. Significant salivary IgG antibodies to meningococcal C polysaccharide were observed after parenteral immunization with two meningococcal C conjugate vaccines, whereas there was no significant increase in specific IgA antibody levels for these two vaccines. Number of References 30. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	Q. Zhang, E. Pettitt, R. Burkinshaw, G. Race, L. Shaw and A. Finn	Pediatric Infectious Disease Journal
337	Aureomycin and Terramycin in the treatment of pertussis		H. Zischinsky	Munchener Medizinische Wochenschrift
401	Diet and antibody response to vaccinations in healthy infants	Antibody responses to poliovirus, diphtheria, pertussis, or tetanus vaccine were compared in five groups of infants. The 62 infants had been brought up on breast milk or on one of four types of artificial feed in the first five months of life. The types of artificial feed varied in quality and quantity of protein; they were high or low protein cow's milk, an adapted formula (with a casein/albumin ratio of 40/60), and a formula based on soy flour. After the age of 5 months, all infants were put on the same diet. The general pattern of antibody responses as determined by antibody levels when the infants were 5 and 8 months old was that those fed on breast milk or high-protein cow's milk had adequate and sustained antibody responses; those fed on the adapted formula had a high but temporary response; and those fed on low-protein cow's milk or the soy-based formula had poor responses.	G. Zoppi, R. Gasparini, F. Mantovanelli, L. Gobio-Casali, R. Astolfi and P. Crovari	Lancet
451	Response to RIT 4237 oral rotavirus vaccine in human milk, adapted-and soy-formula fed infants	During the first month of life 28 full-term newborns were breast-fed (18 males and 11 females). Thereafter 8 infants continued breast-feeding while the remainder were randomly fed on either an adapted milk formula (n=13) or a soy-formula (n=7). At five months, after an oral dose of RIT 4237 rotavirus vaccine of bovine origin was given, growth and IgM/IgG type antibodies against rotavirus were measured. Weight gain was similar in all infants. There were 2 IgM and 1 IgG responders out of 7 soy fed infants, compared with 4 out of 8 human milk fed (both IgM and IgG) and 7 out of 13 IgM and 6/12 IgG formula fed infants responding to vaccination. This observation confirms previous results obtained with polio, diphtheria tetanus and pertussis vaccines indicating that soy-protein formulas may interfere with immunization processes.	G. Zoppi, F. Mantovanelli, K. Pittschieler, A. Delem and D. E. Teuwen	Acta paediatrica Scandinavica
84	Immunogenicity of a whole-cell pertussis vaccine with low lipopolysaccharide content in infants	The lack of a clear correlation between the levels of antibody to pertussis antigens and protection against disease lends credence to the possibility that cell-mediated immunity provides primary protection against disease. This phase I comparative trial had the aim of comparing the in vitro cellular immune response and anti-pertussis toxin (anti-PT) immunoglobulin G (IgG) titers induced by a cellular pertussis vaccine with low lipopolysaccharide (LPS) content (wP(low) vaccine) with those induced by the conventional whole-cell pertussis (wP) vaccine. A total of 234 infants were vaccinated at 2, 4, and 6 months with the conventional wP vaccine or the wP(low) vaccine. Proliferation of CD3(+) T cells was evaluated by flow cytometry after 6 days of peripheral blood mononuclear cell culture with stimulation with heat-killed Bordetella pertussis or phytohemagglutinin (PHA). CD3(+), CD4(+), CD8(+), and T-cell receptor gammadelta-positive (gammadelta(+)) cells were identified in the gate of blast lymphocytes. Gamma interferon, tumor necrosis factor alpha, interleukin-4 (IL-4), and IL-10 levels in supernatants and serum anti-PT IgG levels were determined using enzyme-linked immunosorbent assay (ELISA). The net percentage of CD3(+) blasts in cultures with B. pertussis in the group vaccinated with wP was higher than that in the group vaccinated with the wP(low) vaccine (medians of 6.2% for the wP vaccine and 3.9% for the wP(low) vaccine; P = 0.029). The frequencies of proliferating CD4(+), CD8(+), and gammadelta(+) cells, cytokine concentrations in supernatants, and the geometric mean titers of anti-PT IgG were similar for the two vaccination groups. There was a significant difference between the T-cell subpopulations for B. pertussis and PHA cultures, with a higher percentage of gammadelta(+) cells in the B. pertussis cultures (P < 0.001). The overall data did suggest that wP vaccination resulted in modestly better specific CD3(+) cell proliferation, and gammadelta(+) cell expansions were similar with the two vaccines.	T. Q. Zorzeto, H. G. Higashi, M. T. Silva, F. Carniel Ede, W. O. Dias, V. D. Ramalho, T. N. Mazzola, S. C. Lima, A. M. Morcillo, M. A. Stephano, M. A. Antonio, L. Zanolli Mde, I. Raw and M. M. Vilela	Clinical and vaccine immunology : CVI
