ID	title	abstract	authors	journal
231	Treatment of severe infectious purpura in children with human plasma from donors immunized with Escherichia coli J5: a prospective double-blind study. J5 study Group	To evaluate the efficacy of anti-J5 serum in the treatment of severe infectious purpura, 73 children were randomized to receive either anti-J5 (40) or control (33) plasma. Age, blood pressure, and biologic risk factors were similar in both groups. At admission, however, tumor necrosis factor serum concentrations were 974 +/- 173 pg/ml compared with 473 +/- 85 pg/ml (P = .023) and interleukin-6 serum concentrations were 129 +/- 45 compared with 19 +/- 5 ng/ml (P = .005) in the control and treated groups, respectively. The duration of shock and the occurrence of complications were similar in both groups. The mortality rate was 36% in the control group and 25% in the treated group (P = .317; odds ratio, 0.76; 95% confidence interval, 0.46-1.26). This trend disappeared after correction for unbalances in risk factors at randomization using a logistic regression model. These results suggest that anti-j5 plasma did not affect the course or mortality of severe infectious purpura in children.		The Journal of infectious diseases
341	Long-acting chloramphenicol for bacterial meningitis			Bulletin of the World Health Organization
379	Combined administration of meningococcal serogroup B outer membrane vesicle vaccine and conjugated serogroup C vaccine indicated for prevention of meningococcal disease is safe and immunogenic	MenBvac and Menjugate are safe and efficacious vaccines. The purpose of this study was to evaluate safety and immunogenicity of the combination (MenB/C) of the lyophilized active components of the conjugated group C vaccine Menjugate when reconstituted with the full liquid group B outer membrane vesicle vaccine MenBvac compared to MenBvac and Menjugate given separately. At 6-week intervals, healthy adults were given one dose of MenB/C followed by two doses of MenBvac (MenB/C group), three doses of MenBvac (MenB group), or one dose of Menjugate and two doses of placebo (MenC group). Injection site reactions were frequent in all groups. However, most reactions were short lasting and mild or moderate in intensity, and the vaccines were found to be well tolerated, with no vaccine-related serious adverse events. MenB/C was immunogenic with regard to both serogroup B and C meningococci. Both the serum bactericidal assay and the enzyme-linked immunosorbent assay analyses showed that the immune responses of the combination vaccine were similar to the immune responses of its separate components MenBvac and Menjugate for both serogroup B and C. In conclusion, the combined MenB/C vaccine is safe and immunogenic. The two vaccines do not interact negatively with each other and can easily be administered in the same syringe. The induced immune responses suggest that the combined vaccine is likely to confer protection against systemic group B disease caused by the vaccine strain as well as against group C meningococcal disease. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	I. S. Aaberge, P. Oster, O. S. Helland, A. C. Kristoffersen, E. Ypma, E. A. Hoiby, B. Feiring and H. Nokleby	Clinical & Diagnostic Laboratory Immunology
16	Comparison of functional immune responses in humans after intranasal and intramuscular immunisations with outer membrane vesicle vaccines against group B meningococcal disease	A serogroup B meningococcal outer membrane vesicle (OMV) vaccine was delivered either intranasally or intramuscularly to 12 and 10 volunteers, respectively. The mucosal vaccine was given as four weekly doses followed by a fifth dose after 5 months; each dose consisted of OMVs equivalent to 250 microg of protein. The intramuscular (i.m.) vaccine, consisting of the same OMVs but adsorbed to Al(OH)(3), was administered as three doses each of 25 microg of protein, with 6 weeks interval between first and second doses and the third dose after 10 months. Both groups of vaccinees demonstrated significant immune responses when measured as specific IgG antibodies against live meningococci, as serum bactericidal activity (SBA) and as opsonophagocytic activity. Two weeks after the last dose, the anti-meningococcal IgG concentrations were significantly higher in the i.m. group (median IgG concentration: 43.1 microg/ml) than in the intranasal group (10.6 microg/ml) (P=0.001). The corresponding opsonophagocytic activity was 7.0 and 3.0 (median log(2) titre) (P=0.001), and the SBA was 5.0 and 2.0 (median log(2) titre) (P=0.005), for the i.m. and intranasal groups, respectively. The last immunisation induced an enhanced immune response in the i.m. group, whereas the intranasal group showed no significant booster response. Accordingly, affinity maturation of anti-OMV-specific IgG antibodies was seen only after i.m. vaccination. The IgG1 subclass dominated the responses in both groups, whereas the significant IgG3 responses observed in the i.m. group were absent in the intranasal group. Although the intranasal OMV vaccination schedule used here induced functional immune responses relevant to protection, an improved vaccine formulation and/or a modified mucosal immunisation regimen may be needed to achieve a systemic effect comparable to that seen after three doses of intramuscular vaccination.	A. Aase, L. M. Naess, R. H. Sandin, T. K. Herstad, F. Oftung, J. Holst, I. L. Haugen, E. A. Høiby and T. E. Michaelsen	Vaccine
211	Adverse events following vaccine or placebo injection in an efficacy trial of an outer membrane vesicle vaccine against group B meningococcal disease in Norwegian secondary schools 1988-1991		P. Aavitsland, G. Bjune, S. Aasen and S. Halvorsen	NIPH annals
626	Profile of enterovirus disease in the first two weeks of life	We studied 57 infants < or = 14 days of age referred for possible enterovirus (EV) infection to assess the accuracy of that clinical diagnosis and describe the natural history of neonatal EV infection. Twenty-nine neonates proved to have EV infection, 23 had illnesses compatible with (but not proven to be) EV infection, and 5 had alternative diagnoses: bacterial infections (2); herpes simplex virus infection (1); and metabolic disorders (2). Neonates with proved EV infection were generally full term and had uncomplicated immediate postnatal periods but high percentages of ill contacts. Neonatal symptoms and signs included fever, irritability, anorexia, lethargy, hypoperfusion, rash, jaundice and respiratory findings. Laboratory abnormalities included cerebrospinal fluid (CSF) pleocytosis, chest radiograph infiltrates, abnormal urinalyses and elevated transaminases. EVs were most commonly isolated from CSF and rectum/stool but also frequently from serum and urine. Five EV-infected patients had severe multisystem disease (pneumonitis, hepatitis, thrombocytopenia, bleeding and meningitis), requiring supportive care and lengthy hospitalizations. All survived, 2 with residual hepatic dysfunction. Markers of severe disease included: early age of illness onset (especially Day 1 of life); maternal viral symptoms at delivery; absence of fever and irritability; tachypnea; lethargy; abdominal distension; hepatomegaly; and positive serum viral culture. These data support conservative management of ill infants < or = 2 weeks of age and suggest that antiviral therapy for neonatal EV infection would be optimally targeted at infants with early onset illness, multisystem disease and/or viremia.	M. J. Abzug, M. J. Levin and H. A. Rotbart	The Pediatric infectious disease journal
540	Adult tuberculous meningitis: comparative study of different chemotherapeutic regimens		V. N. Acharya, B. T. Kudva, V. J. Retnam and P. J. Mehta	Journal of the Association of Physicians of India
376	Antigenuria in Gambian infants following immunization with a Haemophilus influenzae type b polyribosylribitol phosphate-tetanus toxoid protein conjugate (PRP-T) vaccine	During a Haemophilus influenzae type b (Hib)-conjugate vaccine trial, the prevalence and duration of antigenuria after vaccination was studied in 102 Gambian infants aged 51 to 175 days. Urine samples were collected at 0, 1, 3, 7, 14, 21 and 28 days postvaccination and tested for Hib antigen by latex agglutination using Biomérieux and Directigen reagent kits. Biomérieux positive reactions were found in 6 of 247 (2.4%) samples from vaccinated children and in 8 of 199 (4.0%) from nonvaccinated children (chi 2 = 0.47; 1 df; p = 0.5). In contrast, Directigen positive reactions were obtained with 86/242 samples (35.5%) from vaccinated children and from 28/190 (14.7%) from non-vaccinated children (chi 2 = 22.7; 1 df; p < 0.0001). The highest rate of antigenuria was detected in samples collected on Day 7 after vaccination when 24 of 30 (80%) were positive. Antigenuria following vaccination was frequent and may complicate the use of this test as a means of diagnosing invasive Hib disease in vaccinated children.	R. A. Adegbola, A. Leach, K. Mulholland, S. Hilton, E. Demba, S. Jaffar and B. M. Greenwood	Diagnostic microbiology and infectious disease
210	First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children	BACKGROUND: An ongoing phase 3 study of the efficacy, safety, and immunogenicity of candidate malaria vaccine RTS,S/AS01 is being conducted in seven African countries. METHODS: From March 2009 through January 2011, we enrolled 15,460 children in two age categories--6 to 12 weeks of age and 5 to 17 months of age--for vaccination with either RTS,S/AS01 or a non-malaria comparator vaccine. The primary end point of the analysis was vaccine efficacy against clinical malaria during the 12 months after vaccination in the first 6000 children 5 to 17 months of age at enrollment who received all three doses of vaccine according to protocol. After 250 children had an episode of severe malaria, we evaluated vaccine efficacy against severe malaria in both age categories. RESULTS: In the 14 months after the first dose of vaccine, the incidence of first episodes of clinical malaria in the first 6000 children in the older age category was 0.32 episodes per person-year in the RTS,S/AS01 group and 0.55 episodes per person-year in the control group, for an efficacy of 50.4% (95% confidence interval [CI], 45.8 to 54.6) in the intention-to-treat population and 55.8% (97.5% CI, 50.6 to 60.4) in the per-protocol population. Vaccine efficacy against severe malaria was 45.1% (95% CI, 23.8 to 60.5) in the intention-to-treat population and 47.3% (95% CI, 22.4 to 64.2) in the per-protocol population. Vaccine efficacy against severe malaria in the combined age categories was 34.8% (95% CI, 16.2 to 49.2) in the per-protocol population during an average follow-up of 11 months. Serious adverse events occurred with a similar frequency in the two study groups. Among children in the older age category, the rate of generalized convulsive seizures after RTS,S/AS01 vaccination was 1.04 per 1000 doses (95% CI, 0.62 to 1.64). CONCLUSIONS: The RTS,S/AS01 vaccine provided protection against both clinical and severe malaria in African children. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619 .).	S. T. Agnandji, B. Lell, S. S. Soulanoudjingar, J. F. Fernandes, B. P. Abossolo, C. Conzelmann, B. G. Methogo, Y. Doucka, A. Flamen, B. Mordmüller, S. Issifou, P. G. Kremsner, J. Sacarlal, P. Aide, M. Lanaspa, J. J. Aponte, A. Nhamuave, D. Quelhas, Q. Bassat, S. Mandjate, E. Macete, P. Alonso, S. Abdulla, N. Salim, O. Juma, M. Shomari, K. Shubis, F. Machera, A. S. Hamad, R. Minja, A. Mtoro, A. Sykes, S. Ahmed, A. M. Urassa, A. M. Ali, G. Mwangoka, M. Tanner, H. Tinto, U. D'Alessandro, H. Sorgho, I. Valea, M. C. Tahita, W. Kaboré, S. Ouédraogo, Y. Sandrine, R. T. Guiguemdé, J. B. Ouédraogo, M. J. Hamel, S. Kariuki, C. Odero, M. Oneko, K. Otieno, N. Awino, J. Omoto, J. Williamson, V. Muturi-Kioi, K. F. Laserson, L. Slutsker, W. Otieno, L. Otieno, O. Nekoye, S. Gondi, A. Otieno, B. Ogutu, R. Wasuna, V. Owira, D. Jones, A. A. Onyango, P. Njuguna, R. Chilengi, P. Akoo, C. Kerubo, J. Gitaka, C. Maingi, T. Lang, A. Olotu, B. Tsofa, P. Bejon, N. Peshu, K. Marsh, S. Owusu-Agyei, K. P. Asante, K. Osei-Kwakye, O. Boahen, S. Ayamba, K. Kayan, R. Owusu-Ofori, D. Dosoo, I. Asante, G. Adjei, G. Adjei, D. Chandramohan, B. Greenwood, J. Lusingu, S. Gesase, A. Malabeja, O. Abdul, H. Kilavo, C. Mahende, E. Liheluka, M. Lemnge, T. Theander, C. Drakeley, D. Ansong, T. Agbenyega, S. Adjei, H. O. Boateng, T. Rettig, J. Bawa, J. Sylverken, D. Sambian, A. Agyekum, L. Owusu, F. Martinson, I. Hoffman, T. Mvalo, P. Kamthunzi, R. Nkomo, A. Msika, A. Jumbe, N. Chome, D. Nyakuipa, J. Chintedza, W. R. Ballou, M. Bruls, J. Cohen, Y. Guerra, E. Jongert, D. Lapierre, A. Leach, M. Lievens, O. Ofori-Anyinam, J. Vekemans, T. Carter, D. Leboulleux, C. Loucq, A. Radford, B. Savarese, D. Schellenberg, M. Sillman, P. Vansadia and Rts	The New England journal of medicine
649	Have cranio-vertebral junction anomalies been overlooked as a cause of vertebro-basilar insufficiency?	STUDY DESIGN: A prospective controlled study using single photon emission computed tomography (SPECT) to assess cerebellar perfusion in a cohort of 19 patients with congenital cranio-vertebral junction (CVJ) anomalies, with or without vertebro-basilar insufficiency (VBI). OBJECTIVE: To correlate symptoms of VBI with the presence of posterior circulation ischemia in patients with congenital CVJ anomalies, using technetium 99m ethylene cystine dimer SPECT. SUMMARY OF BACKGROUND DATA: Patients with VBI are rarely investigated for CVJ anomalies, despite the fact that a significant number of patients with congenital CVJ anomalies has VBI. There are also no studies quantifying outcome of surgical interventions, such as like occipito-cervical fusion, in patients with VBI and CVJ anomalies. METHODS: There were 19 consecutive patients with congenital CVJ anomalies who were scheduled for combined transoral odontoidectomy and occipito-cervical fusion were included in the study. Technetium 99m ethylene cystine dimer brain SPECT and clinical assessment of all patients was performed in the preoperative period and at 4 weeks after surgery. Before surgery, patients were divided into 2 groups depending on the clinical findings: (1) symptomatic group, consisting of 12 patients having features suggestive of VBI (drop attacks, episodic vertigo, visual disturbances and dysarthria); and (2) control group, consisting of 7 patients without symptoms of VBI. RESULTS: SPECT showed decreased cerebellar perfusion in 75% (n = 9) of patients in the symptomatic group compared to 14% (n = 1) in the control group before surgery (Fisher exact 2-tailed test, P = 0.019). Following surgery, 8 patients (88.9%) in the symptomatic group and none in the control group had improvement in cerebellar perfusion. Two patients in the symptomatic group who had meningitis develop during the postoperative period had a decrease in cerebellar perfusion on follow-up SPECT. Clinically, all patients with improvement in cerebellar perfusion had improvement in the symptoms of VBI at 1 month of follow-up. CONCLUSIONS: A significant number of patients with congenital CVJ anomalies who have symptoms of VBI develop have decreased cerebellar perfusion shown by SPECT. Rigid internal fixation of the CVJ may alleviate symptoms and improve posterior circulation in some of these patients.	D. Agrawal, N. K. Gowda, C. S. Bal, S. S. Kale and A. K. Mahapatra	Spine
427	Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate) (PedvaxHIB): clinical evaluation	Although systemic infections caused by Haemophilus influenzae type b occur worldwide, detailed epidemiologic data are available in but a few countries. The public health impact of morbidity, mortality, and serious sequelae from disease caused by H influenzae type b has stimulated the search for control strategies. In the United States now, active immunoprophylaxis is largely favored over treatment of prophylaxis with antibiotics. This preference stems from three major observations: that high mortality and morbidity persist despite the availability of potent antimicrobial agents, that antibiotic-resistant strains of H influenzae type b have emerged, and that implementation of antimicrobial prophylaxis on a large scale has been unsatisfactory. Moreover, universal vaccination has been projected as offering a higher economic benefit than other control strategies. A matter of more proximate importance, however, is the search for H influenzae type b vaccines that will confer protection to all age groups, including infants younger than 18 months of age and subpopulations specifically at risk for invasive disease caused by H influenzae type b. Haemophilus b conjugate vaccine (meningococcal protein conjugate), PedvaxHIB (PRP-OMPC), is a conjugate H influenzae type b vaccine developed at Merck Sharp & Dohme Research Laboratories that now is undergoing extensive clinical evaluation to assess its prospects for disease control when first administered in early infancy. This is an interim report of results obtained in studies conducted in diverse locations throughout the United States.	V. I. Ahonkhai, L. J. Lukacs, L. C. Jonas, H. Matthews, P. P. Vella, R. W. Ellis, J. M. Staub, K. T. Dolan, C. M. Rusk and G. B. Calandra	Pediatrics
519	Human antibody responses to the meningococcal factor H binding protein (LP2086) during invasive disease, colonization and carriage		D. A. Ala'aldeen, M. Flint, N. J. Oldfield, S. A. Omer, L. K. McNeil, Q. Jiang, E. Murphy, P. C. Giardina, E. G. Novikova, I. L. Dodge-Scully, C. D. Bayliss, D. P. Turner, K. R. Neal, S. K. Hoiseth, K. U. Jansen and A. S. Anderson	Vaccine
382	Meningococcal carrier rate before and after hajj pilgrimage: effect of single dose ciprofloxacin on carriage	We determined the carriage rate of Neisseria meningitidis before and after haij pilgrimage among a group (1) of 674 randomly selected Iranian pilgrims, and the effect of 500 mg of ciprofloxacin given 24 hours before return on the reduction of meningococcal carriers among another group (2) of 123 randomly selected Iranian pilgrims. Throat specimens taken 1 hour before departure on the haji and immediately on return were cultured. Carriage rates of N. meningitidis in group 1 were 5.2% before and 4.6% after pilgrimage (P = 0.65); 3 new serogroups (Z, Z and A) were identified on return. In group 2, the carriage rate decreased from 8.1 % to zero before and after pilgrimage. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	A. Alborzi, S. Oskoee, B. Pourabbas, S. Alborzi, B. Astaneh, M. M. Gooya and M. J. Kaviani	Eastern Mediterranean Health Journal
32	Reactogenicity and safety of meningococcal A and C vaccine in Saudi children	During an outbreak caused by group A Neisseria meningitidis in March 1992, groups A and C meningococcal polysaccharide vaccine was administered to 1,168 children aged from 2 to 18 years. Parents were surveyed to ascertain reactions of children to the vaccine and development of invasive group A meningococcal disease after immunization. The most common reactions were mild local pain (21.9%), erythema (12.2%), and swelling at the injection site (7.2%). Only 1.7% of the children experienced fever and 3.7% displayed irritability. The vaccine was well tolerated and all adverse reactions disappeared within 24-48 hours of immunization. No cases of meningitis or sepsis caused by group A meningococci were seen in the 1st 12 months of observation among the vaccinated children.	Y. A. al-Eissa	Annals of tropical paediatrics
35	Serologic responses to ACYW135 polysaccharide meningococcal vaccine in Saudi children under 5 years of age	An immunization campaign with meningococcal ACYW135 polysaccharide vaccine was conducted in 2003 by the Saudi Arabian Ministry of Health and included a study to evaluate the immune responses in children under 5 years of age in the Al Qassim region of Saudi Arabia. Children who were >/=24 months old were given one dose of tetravalent polysaccharide vaccine, while younger children were given two doses with an interval of 2 to 3 months. Blood samples were collected prevaccination and 1 month after the second dose for children younger than 24 months old and 1 month after the single dose for older children. Serogroup-specific antibody responses were determined by serum bactericidal antibody (SBA) assays and a tetraplex immunoglobulin G (IgG) bead assay. Significant increases in the proportions of individuals who were >/=24 months old with SBA titers of >/=8 were observed pre- to postvaccination for all serogroups. Age-dependent increases in the percentage of individuals with SBA titers of >/=8 1 month postvaccination were observed for each serogroup. Age-dependent increases in postvaccination IgG levels were observed for serogroup A (menA), serogroup W135 (menW), and serogroup Y (menY) but not for serogroup C (menC). Two doses of tetravalent polysaccharide vaccine in individuals who were </=18 months old were poorly immunogenic for menC, menW, and menY. However, for menA, 42% of the children who were 18 months old were putatively protected with SBA titers of >/=8. A high percentage of subjects who were >/=2 years of age were putatively protected for menA; a similar level was observed for menY for children who were 4 years of age but not for younger children. However, for menC and menW poor levels of putative protection were still evident at 4 years of age.	Y. Al-Mazrou, M. Khalil, R. Borrow, P. Balmer, J. Bramwell, G. Lal, N. Andrews and M. Al-Jeffri	Infection and immunity
168	Immunogenicity and safety of a meningococcal quadrivalent conjugate vaccine in Saudi Arabian adolescents previously vaccinated with one dose of bivalent and quadrivalent meningococcal polysaccharide vaccines: a phase III, controlled, randomized, and modified blind-observer study	Reduced immune responses to repeated polysaccharide vaccination have been previously reported, but there are limited immunogenicity data on the use of meningococcal polysaccharide vaccine (PSV) followed by meningococcal conjugate vaccine. Saudi Arabian adolescents (aged 16 to 19 years) who had previously been vaccinated with ?1 dose of bivalent meningococcal polysaccharide vaccine and 1 dose of quadrivalent meningococcal polysaccharide (MPSV4) were enrolled in a controlled, randomized, and modified observer-blind study (collectively termed the PSV-exposed group). The PSV-exposed group was randomized to receive either quadrivalent meningococcal conjugate vaccine (MCV4) (n = 145 PSV-exposed/MCV4 group) or MPSV4 (n = 142 PSV-exposed/MPSV4 group), and a PSV-naïve group received MCV4 (n = 163). Serum samples collected prevaccination and 28 days postvaccination were measured by baby rabbit serum bactericidal antibody (rSBA) assay, and vaccine tolerability and safety were also evaluated. For each serogroup, the postvaccination geometric mean titers (GMTs) were significantly higher in the PSV-naïve group than in either group comprised of the PSV-exposed participants. The postvaccination serogroup C rSBA GMT was significantly higher in the PSV-MCV4 group than in the PSV-MPSV4 group after adjusting for prevaccination GMTs. Although not statistically significant, similar differences were observed for serogroups A, Y, and W-135. No worrisome safety signals were detected. This study demonstrated MCV4 to be safe and immunogenic in those who had previously received polysaccharide vaccination, and it suggests that conjugate vaccine can partially compensate for the hyporesponsiveness seen with repeated doses of polysaccharide vaccine.	Y. Al-Mazrou, M. Khalil, H. Findlow, H. Chadha, V. Bosch Castells, D. R. Johnson and R. Borrow	Clinical and vaccine immunology : CVI
242	[Absence of meningitis caused by Haemophilus influenzae type b in The Netherlands following twofold vaccination]	OBJECTIVE: To determine the two-year results of nationwide vaccination with Haemophilus influenzae type b (Hib) vaccine on the occurrence of Hib meningitis in the Netherlands.DESIGN: Retrospective controlled study.SETTING: The Netherlands.METHOD: Children born since April 1, 1993 are vaccinated at the age of 3, 4, 5 and 11 months to protect them from infections with Hib. The number of Hib meningitis patients in the period 1 April, 1993 to 1 April, 1995, among infants born in this period who were offered the Hib vaccine (study group), was compared with the number of Hib meningitis patients in the period 1 April, 1991 to 1 April, 1993 among children born in last-mentioned period (control group).RESULTS: Twenty-one cases of meningitis by Hib were observed in the study group. Twelve children who, as a consequence of their age, had only been vaccinated once or not at all; 7 children were not vaccinated for several reasons. In addition one patient was infected by H. influenzae type f strain and one by a non-typable strain. In the control group 185 cases of Hib meningitis occurred.CONCLUSION: Hib meningitis was not observed among infants who had been vaccinated at least twice.	L. Alphen, L. Spanjaard, A. Ende and J. Dankert	Nederlands tijdschrift voor geneeskunde
362	Changes in the distribution of Haemophilus influenzae type b clones associated with widespread infant vaccination in Finland	Isolates from 646 consecutive Finnish Haemophilus influenzae type b (Hib) patients with systemic disease, collected before and during large-scale vaccinations with Hib conjugate vaccines, were analyzed by major outer membrane protein (OMP) subtyping, lipopolysaccharide (LPS) serotyping, and biotyping (BT). Strains with OMP-BT-LPS combinations (clones) 1-I-1 and 1c-I-1 disappeared at the same rate as the disease they were associated with. A preferential decrease in the number of isolates of clone 1-II-1 was recorded, whereas the reduction in disease caused by strains of clone 1-II-9 occurred at a lower rate than expected. The latter clone occurred mainly in the most densely populated area of Finland. Strains belonging to all the common Hib clones were isolated from the 16 infants who acquired Hib disease despite being (partially) vaccinated. Thus, Hib clones disappeared during mass vaccination with conjugate vaccines, although at different rates.	L. Alphen, A. K. Takala, L. Geelen-van den Broek, J. Dankert and J. Eskola	The Journal of infectious diseases
505	Effect of chemoprophylaxis on the meningococcal carrier state after systemic infection		F. Alvez, A. Aguilera, A. Garcia-Zabarte and M. Castro-Gago	Pediatric Infectious Disease Journal
381	Passive immunization against disease due to Haemophilus influenzae type b: concentrations of antibody to capsular polysaccharide in high-risk children	From the pooled plasma of 54 adult donors immunized with Haemophilus influenzae type b capsular polysaccharide (CP), a human hyperimmune globulin termed bacterial polysaccharide immune globulin (BPIG) was prepared. The pharmacokinetics of antibody to H. influenzae type b CP in high-risk children was compared after BPIG and conventional immune serum globulin (ISG) were administered intramuscularly at a dose of 0.5-0.6 ml/kg. The increase in antibody level four to seven days after injection was ninefold higher with BPIG than with ISG and remained higher throughout the three-month follow-up period. The mean half-life of antibody to H. influenzae type b CP was similar after BPIG (27 days) and ISG (29 days). Antibody levels returned to baseline one to two months after ISG but remained significantly above baseline three months after BPIG (mean concentration, 385 ng/ml). Based on the assumption that 150 ng of IgG antibody to H. influenzae type b CP/ml is the minimal protective level, it is concluded that a single intramuscular dose of 0.5 ml of BPIG/kg will protect children for four months.	D. M. Ambrosino, S. H. Landesman, C. C. Gorham and G. R. Siber	The Journal of infectious diseases
344	Accurate diagnosis of tuberculosis meningitis using polymerase chain reaction		A. G. Amin, A. K. Garg, K. Chopra and P. Khandekar	International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association
352	[The late results of intensive chemotherapy (9 months) in severe forms of tuberculosis in children]	The short-course chemotherapy (9 months) in the severe forms of tuberculosis in children is a very modern item. It was very few approached on an international level and relatively short time ago in our country. There were applied the following therapeutical regimens: 3 HRZ2 6 HR2 (in the experimental group) and 3 HR/3 HR2/6 H2 (in the control group). In the granulias and the caseous forms the late results, at 5 years after treatment end, were very good in 100% of cases in both groups. In meningitis clinical very good results (without sequellae) presented a proportion of 70.1% in the experimental group and of 68.2% in the control group (difference statistically non significant). The main advantage of the intensive short course regimens (9 months) comparatively with the "classical" ones (of at least 12 months) consists in reaching finally the same good results but in at least 3 months shorter time interval.	C. Anastasatu, O. Anastasatu, G. Murgoci and M. Dobre	Pneumoftiziologia : revista Societ?tii Române de Pneumoftiziologie / [Societatea Român? de Pneumoftiziologie]
183	Immunogenicity of heptavalent pneumococcal conjugate vaccine in infants	OBJECTIVE: To evaluate the safety, immunogenicity, and immunologic memory in young infants of a seven-valent (6B, 14, 19F, 23F, 18C, 4, 9V) pneumococcal vaccine conjugated to the outer membrane protein complex of Neisseria meningitidis. VACCINEES: Healthy 2-month-old infants 12- to 15-month-old control infants were recruited from participating private practices. METHODS: Infants (n = 25) were vaccinated at 2, 4, and 6 months of age with the conjugated pneumococcal vaccine, followed by a single dose of licensed pneumococcal polysaccharide vaccine (n = 20) at 12 to 15 months of age. Thirteen infants who had not received the investigational pneumococcal conjugate vaccine served as control subjects and were given a single dose of the licensed pneumococcal polysaccharide vaccine at 12 to 15 months of age. RESULTS: The investigational pneumococcal conjugate vaccine was well tolerated by infants. The vaccine was highly immunogenic in young infants, with significant increases in antibody to all seven serotypes after either two or three injections. At 12 to 15 months of age, infants who had been primed with the investigational pneumococcal conjugate vaccine had a brisk immunologic response to the booster injection of the licensed pneumococcal polysaccharide vaccine. Control infants, who received a single primary injection of the licensed pneumococcal polysaccharide vaccine, had negligible immunologic responses to four of the seven serotypes and low responses to the other three types. CONCLUSION: The investigational seven-valent pneumococcal conjugate vaccine administered to young infants was well tolerated and highly immunogenic and provided immunologic memory to an injection of the licensed pneumococcal polysaccharide vaccine.	E. L. Anderson, D. J. Kennedy, K. M. Geldmacher, J. Donnelly and P. M. Mendelman	The Journal of pediatrics
539	Chemotherapy of tuberculosis meningitis with isoniazid plus rifampicin- interim findings in a trial in children [abstract]	Summaries of the papers presented at the 34th National confernece on tuberculosis & Chest diseases at Jaipur from 28th to 31st October. 1979- A coâ?"operative study in which 6 orthopaedic surgeons of Madras are participating is in progress to assess the efficacy of short-course chemotherapy with or without surgery in tuberculosis of the spine. Nearly 60 patients were admitted to each of the 3 groups. One group was given Rifampicin and INK for 6 months with radical surgery. The second group was given Rifampicin and INH for 6 months without surgery and the third group was given the Same drugs for 9 months without surgery. Surgery consisted of excision of diseased vertebrae and bridging of the resultant gap with bone grafting and was usually performed within a month of admission to the study in the first group. The three groups were comparable in respect of number of vertebra involved, abscess formation and nervous involvement. 65, of the patients had 2 vertebrae involved, 34% had 3 or more vertebrae involved. 2l% had clinical evidence of abscess and/or sinus. 54% had mediastinal or paoas abscess shadows in the xâ?"rays. 85% had kyphosis and 95% had limitation of spinal movements. 17 patients had neurological involvement. 92% of the patients in the surgery group as against 62% in the other two groups showed resolution of the abscess within 3 months. By 9 months resolution bad occurred in all but one patient belonging to the third group. All the patients with nervous involvement recovered completely except that 3 patients in the non surgery group had to undergo surgery for neurological relief. There were 3 post-operative deaths in the surgery group. l4% of the patients had jaundice in the entire series. There is a suggestion that jaundice was more frequent in the surgery group. 56% in group 1, 8% in group 2 and 2% in group 3 had unfavourable response at 18 months. On the available evidence at present the 2 non-surgery groups have behaved practically as well as the surgery group. It is not possible to say at this stage whether the surgery group derived the three benefits of radical surgery (more frequent and early bony union, less kyphosis and more rapid resolution of the abscess) or not.	Anon	Indian Journal of Tuberculosis
633	Early neurologic complications following allogeneic bone marrow transplant for leukemia: a prospective study	BACKGROUND: Bone marrow transplant (BMT) is used for both neoplastic and nonneoplastic diseases. Following BMT, particularly during the first 3 months, patients have a number of neurologic complications. We evaluated the early neurologic complications following BMT and their influence on survival. METHODS: We prospectively followed 115 consecutive patients having BMT for leukemia, for a median period of 90 days after transplantation. RESULTS: Sixty-four patients (56%) had neurologic complications. Sixteen developed more than one complication. Twenty-seven patients (25%) had major neurologic complications: metabolic encephalopathy (8), seizures (8), psychiatric symptoms (3), cerebral hemorrhage (1), cerebral abscess (1), leukemic meningitis (1), peripheral neuropathies (5), and myopathies (2). Forty patients (35%) had minor complications, including headache (16) and tremor (31). Major neurologic complications occurred after engraftment in most patients. Metabolic encephalopathy correlated with graft-versus-host disease (GVHD) (p < 0.03). Seven percent of patients had generalized seizures that occurred without signs of structural cerebral lesions. Probability of survival at day 90 was lower in patients with than in those without major central nervous system complications (63% versus 87.5%, p < 0.01). CONCLUSIONS: Neurologic complications are frequent during the first 3 months following BMT and affect patient survival. Drug neurotoxicity and acute GVHD are the main factors influencing their occurrence.	G. Antonini, V. Ceschin, S. Morino, M. Fiorelli, F. Gragnani, A. Mengarelli, A. P. Iori and W. Arcese	Neurology
550	(Antibiotics for bacterial meningitis in children - results of a Finnish multicentre trial)		M. Anttila, I. Anttolainen, J. Ellmén, J. Eskola, T. Joki, L. Kaartinen, U. Kaski and M. Kataja	Duodecim
353	[Antibiotic treatment of bacterial meningitis in children--results from a Finnish multicenter study]		M. Anttila, I. Anttolainen, J. Ellmén, J. Eskola, T. Joki, L. Kaartinen, U. Kaski, M. Kataja, N. Kojo and M. Korppi	Duodecim; lääketieteellinen aikakauskirja
571	Differences in the avidity of antibodies evoked by four different pneumococcal conjugate vaccines in early childhood	Avidity of antibodies to Streptococcus pneumoniae type 6B, 14, 19F and 23F polysaccharides (PS) evoked by four different pneumococcal conjugate vaccines was compared. Infants were primed with pneumococcal PS conjugated to the variant diphtheria toxin CRM197 (PncCRM), diphtheria toxoid (PncD), tetanus toxoid (PncT) or meningococcal protein complex (PncOMPC) and boosted with the homologous conjugate or PS vaccine. No booster was given to children in the PncOMPC group. Relative antibody avidity was measured by thiocyanate EIA. No vaccine specific differences were found in avidity of anti-14 or -19F antibodies. By contrast, antibody avidity to 6B and 23F differed significantly between the vaccine groups, PncCRM and PncT inducing antibodies of highest avidity.	M. Anttila, J. Eskola, H. Ahman and H. Käyhty	Vaccine
18	Precise quantification of fever in childhood bacterial meningitis	Precise quantity of fever was determined in 191 cases of childhood bacterial meningitis by calculating the areas between the line indicating 37.8 degrees C or 39.5 degrees C temperature and the line connecting all individual temperature values. Temperature measurements were performed rectally one to four times a day throughout the hospitalization. The obtained areas under the curves (AUC), expressed as degree-hours, proved to be a sensitive index for delineating each individual fever pattern and reflected the magnitude of fever more precisely than the traditional fever curves. Children under five had significantly (p less than 0.05) greater AUC than those at five to 15 years; similarly, patients with Haemophilus influenzae meningitis showed greater AUC (i.e., had more fever) than those with meningococcal disease (p less than 0.05). The overall rates of secondary (14%), persistent (16%), and prolonged fever (8%) were virtually identical to previous reports; no drug fever was reported in this study. In cases with prolonged fever, a significantly higher rate (40%) of neurological complications was found compared to those who became afebrile earlier. This method is potentially utilizable in other diseases and conditions where precise measurement of fever is of clinical or scientific relevance.	M. Anttila, J. J. Himberg and H. Peltola	Clinical pediatrics
165	The investigational meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate vaccine (ACWY-TT) and the seasonal influenza virus vaccine are immunogenic and well-tolerated when co-administered in adults	Co-administration of meningococcal serogroups A, C, W-135 and Y conjugate vaccine (ACWY-TT) with seasonal influenza vaccine was investigated in a subset of adults enrolled in a larger study evaluating lot-to-lot consistency of ACWY-TT and non-inferiority to licensed tetravalent meningococcal polysaccharide vaccine (MenPS). Subjects in this sub-study were randomized (3:1:1) to receive ACWY-TT alone (ACWY-TT group) or with seasonal influenza vaccine (Coad), or licensed MenPS alone. Serum bactericidal antibodies (rSBA) and serum haemagglutination-inhibition (HI) antibody titers were measured pre- and 1 mo post-vaccination. Non-inferiority of the Coad group compared with ACWY-TT group was demonstrated in terms of rSBA geometric mean antibody titers (GMTs) to serogroups A, W-135 and Y. For serogroup C the pre-defined non-inferiority limit was marginally exceeded. Post-vaccination rSBA GMTs were significantly higher (exploratory analysis) in the Coad group compared with the MenPS group for serogroups A, W-135, and Y and were similar to the MenPS group for serogroup C. Overall, > 97% of subjects achieved rSBA titers ? 1:128 for all serogroups. The Coad group met all criteria defined by the Committee on Human Medicinal Products (CHMP) for seroprotection, seroconversion and seroconversion factor for HI antibodies for all three influenza strains. Grade 3 solicited local/general symptoms were reported by ? 1.9% of subjects in any group. These data support the co-administration of ACWY-TT with seasonal influenza vaccine when protection is needed against both diseases. This study is registered at clinicaltrials.gov NCT00453986.	M. R. Aplasca-De Los Reyes, E. Dimaano, N. Macalalad, G. Dbaibo, V. Bianco, Y. Baine and J. Miller	Human vaccines & immunotherapeutics
567	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
651	Intrathecally administered baclofen for treatment of children with spasticity of cerebral origin	Management of severe spasticity in children is often a difficult problem. Orally administered medications generally offer limited benefits. This study examines the value of intrathecally administered baclofen in the treatment of 19 children with severe spasticity of cerebral origin: eight of whom sustained brain injury associated with trauma, near drowning, or cardiac arrest; 10 with cerebral palsy (spastic quadriplegia); and one child with Leigh's disease. At the time of entry into the study, patients ranged from 4 to 19 years of age, and all were completely dependent on caretakers for activities of daily living. Children who responded positively to a trial dose of intrathecal baclofen underwent insertion of a drug delivery system for continuous infusion. This was followed by a double-blind trial of baclofen or placebo and follow-up review at 3 and 6 months, and yearly thereafter. Seven children did not undergo pump implantation because of excess sedation or poor response. The 12 remaining children have been followed for a period of 1 to 5 years. Favorable responses were present in all 12 children as determined by the Ashworth Scale, with the greatest benefit being reduction of lower limb tone. Except in the case of one child who had reduction in lower limb tone that resulted in difficulty with transfers, the caretakers all reported significant benefits from intrathecal baclofen, with improvement in muscle tone, behavior, sitting, and general ease of care being most commonly noted. Central side effects were seen in some children who received continuous intrathecal baclofen infusion and included hypotension (two patients), bradycardia (two), apnea or respiratory depression (two), and sedation (one). During a total of 568 months of pump operation there were 10 mechanical complications, including two related to pump or side port failure and eight related to catheter kinks, extrusions, or dislodgment. Pump pocket effusion occurred in five children and a cerebrospinal fluid fistula was seen in one child. Local infection occurred in three children and meningitis in two children. The results demonstrate the potential value of continuous intrathecal baclofen infusion for treatment of severe spasticity of cerebral origin. However, this treatment can result in significant complications and more experience is required before the long-term benefits can be determined.	R. W. Armstrong, P. Steinbok, D. D. Cochrane, S. D. Kube, S. E. Fife and K. Farrell	Journal of neurosurgery
47	Acute respiratory disease and meningococcal infection in army recruits		M. S. Artenstein, J. H. Rust, D. H. Hunter, T. H. Lamson and E. L. Buescher	JAMA : the journal of the American Medical Association
236	Long-term valacyclovir suppressive treatment after herpes simplex virus type 2 meningitis: a double-blind, randomized controlled trial	BACKGROUND: Herpes simplex virus type 2 (HSV-2) is a common cause of acute and recurrent aseptic meningitis. Our aim was to determine the impact of antiviral suppression on recurrence of meningitis and to delineate the full spectrum of neurological complications. METHODS: One hundred and one patients with acute primary or recurrent HSV-2 meningitis were assigned to placebo (n = 51) or 0.5 g of valacyclovir twice daily (n = 50) for 1 year after initial treatment with 1 g of valacyclovir 3 times daily for 1 week in a prospective, placebo-controlled, multicenter trial. The primary outcome was time until recurrence of meningitis. The patients were followed up for 2 years. RESULTS: The first year, no significant difference was found between the valacyclovir and placebo groups. The second year, without study drugs, the risk of recurrence of verified and probable HSV-2 meningitis was significantly higher among patients exposed to valacyclovir (hazard ratio, 3.29 [95% confidence interval, 10.06-10.21]). One-third of the patients experienced 1-4 meningitis episodes during the study period. A considerable morbidity rate, comprising symptoms from the central, peripheral, and autonomous nervous system, was found in both groups. CONCLUSIONS: Suppressive treatment with 0.5 g of valacyclovir twice daily was not shown to prohibit recurrent meningitis and cannot be recommended for this purpose after HSV meningitis in general. Protection against mucocutaneous lesions was observed, but the dosage was probably inappropriate for the prevention of HSV activation in the central nervous system. The higher frequency of meningitis, after cessation of active drug, could be interpreted as a rebound phenomenon.	E. Aurelius, E. Franzen-Röhl, M. Glimåker, O. Akre, L. Grillner, C. Jorup-Rönström and M. Studahl	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
527	Reduction of cerebrospinal fluid rhinorrhea after vestibular schwannoma surgery by reconstruction of the drilled porus acusticus with hydroxyapatite bone cement	OBJECT: Cerebrospinal fluid (CSF) rhinorrhea remains a significant cause of morbidity after resection of vestibular schwannomas (VSs), with rates of rhinorrhea after this procedure reported to range between 0 and 27%. The authors investigated whether reconstruction of the drilled posterior wall of the porus acusticus with hydroxyapatite cement (HAC) would decrease the incidence of postoperative CSF rhinorrhea. METHODS: A prospective observational study of 130 consecutive patients who underwent surgery for reconstruction of the posterior wall of the drilled porus acusticus with HAC was conducted between October 2002 and September 2005. All patients underwent a retrosigmoid transmeatal approach for VS resection and were followed up to document cases of CSF rhinorrhea, incisional CSF leak, meningitis, or rhinorrhea-associated meningitis. A cohort of 150 patients with VSs who were treated with the same surgical approach but without HAC reconstruction served as a control group. RESULTS: The authors found that HAC reconstruction of the porus acusticus wall significantly reduced the rate of postoperative CSF rhinorrhea in their patients. In the patients treated with HAC, rhinorrhea developed in only three patients (2.3%) compared with 18 patients (12%) in the control group. This was a statistically significant finding (p = 0.002, odds ratio = 5.8). CONCLUSIONS: The use of HAC in the reconstruction of the drilled posterior wall of the porus acusticus, occluding exposed air cells, greatly reduces the risk of CSF rhinorrhea.	C. J. Baird, A. Hdeib, I. Suk, H. W. Francis, M. J. Holliday, R. J. Tamargo, H. Brem and D. M. Long	Journal of neurosurgery
471	Effect of home-based neonatal care and management of sepsis on neonatal mortality: field trial in rural India	BACKGROUND: Neonatal care is not available to most neonates in developing countries because hospitals are inaccessible and costly. We developed a package of home- based neonatal care, including management of sepsis (septicaemia, meningitis, pneumonia), and tested it in the field, with the hypothesis that it would reduce the neonatal mortality rate by at least 25% in 3 years. METHODS: We chose 39 intervention and 47 control villages in the Gadchiroli district in India, collected baseline data for 2 years (1993-95), and then introduced neonatal care in the intervention villages (1995-98). Village health workers trained in neonatal care made home visits and managed birth asphyxia, premature birth or low birthweight, hypothermia, and breast-feeding problems. They diagnosed and treated neonatal sepsis. Assistance by trained traditional birth attendants, health education, and fortnightly supervisory visits were also provided. Other workers recorded all births and deaths in the intervention and the control area (1993-98) to estimate mortality rates. FINDINGS: Population characteristics in the intervention and control areas, and the baseline mortality rates (1993-95) were similar. Baseline (1993-95) neonatal mortality rate in the intervention and the control areas was 62 and 58 per 1000 live births, respectively. In the third year of intervention 93% of neonates received home-based care. Neonatal, infant, and perinatal mortality rates in the intervention area (net percentage reduction) compared with the control area, were 25.5 (62.2%), 38.8 (45.7%), and 47.8 (71.0%), respectively (p<0.001). Case fatality in neonatal sepsis declined from 16.6% (163 cases) before treatment, to 2.8% (71 cases) after treatment by village health workers (p<0.01) . Home-based neonatal care cost US$5.3 per neonate, and in 1997-98 such care averted one death (fetal or neonatal) per 18 neonates cared for. INTERPRETATION: Home-based neonatal care, including management of sepsis, is acceptable, feasible, and reduced neonatal and infant mortality by nearly 50% among our malnourished, illiterate, rural study population. Our approach could reduce neonatal mortality substantially in developing countries.	A. T. Bang, R. A. Bang, S. B. Baitule and M. H. Reddy	Lancet
172	Idiopathic hypertrophic pachymeningeal lesions: correlation between clinical patterns and neuroimaging characteristics	Nine patients with intracranial pachymeningeal thickening and enhancement on magnetic resonance imaging (MRI) completed a short-term clinical and MRI follow-up study. Based on clinical pictures, 4 of them were found to have spontaneous intracranial hypotension (SIH) and the remaining 5 had idiopathic intracranial pachymeningitis (IIP). Both groups were compared regarding their clinical and MRI characteristics. In 4 patients with SIH, gadolinium-enhanced T1-weighted images (WI) showed a diffuse and even enhancement of the entire intracranial and spinal dura mater. These thickened dura was slightly hyperintense on T2-WI. They had a favorable prognosis. In 2 patients with IIP, MRI demonstrated a relatively focal and even thickening and enhancement of the intracranial dura which was slightly hyperintense with a central hypointense area on T2-WI. These patients showed a very favorable course with or without steroid pulse therapy. In the remaining 3 patients with IIP, MRI depicted a focal, uneven enhancement of the intracranial dura which was relatively hypointense on T2-WI. Two of them with prolonged symptoms had a remitting and relapsing course, and 1 had a favorable outcome. In spite of current limitations in identifying the underlying causes of idiopathic pachymeningeal abnormalities, MRI can characterize the different patterns of pachymeningeal thickening. These findings may also correlate with the clinical picture and may be useful in predicting the response to treatment and prognosis.	O. Y. Bang, D. I. Kim, S. R. Yoon and I. S. Choi	European neurology
131	Controlled clinical trial of IV cyclophosphamide versus IV methylprednisolone in severe neurological manifestations in systemic lupus erythematosus	BACKGROUND: Severe neurological involvement in systemic lupus erythematosus (NPSLE) is one of the most dreadful complications of the disease. OBJECTIVE: To identify the best drug, dose, and treatment. PATIENTS AND METHODS: The study was a controlled clinical trial at two tertiary care centres of patients with SLE according to the ACR criteria, with incident (no more than 15 days) onset of severe NP manifestations such as seizures, optic neuritis, peripheral or cranial neuropathy, coma, brainstem disease, or transverse myelitis. Induction treatment with 3 g of IV methylprednisolone (MP) followed by either IV monthly cyclophosphamide (Cy) versus IV MP bimonthly every 4 months for 1 year and then IV Cy or IV MP every 3 months for another year. The primary end point was response to treatment: at least 20% improvement from basal conditions on clinical, laboratory, or specific neurological testing variables. RESULTS: Overall, a response rate of 75% was observed. Of the 32 patients studied, 18/19 receiving Cy and 7/13 receiving MP responded to treatment (p<0.03). CONCLUSIONS: Cy seems to be more effective than MP in the treatment of acute, severe NPSLE.	L. Barile-Fabris, R. Ariza-Andraca, L. Olguín-Ortega, L. J. Jara, A. Fraga-Mouret, J. M. Miranda-Limón, J. Fuentes de la Mata, P. Clark, F. Vargas and J. Alocer-Varela	Annals of the rheumatic diseases
452	Cefuroxime versus ceftriaxone for bacterial meningitis (I)	Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	J. W. Bass, D. A. Person and R. J. Fonseca	Journal of Pediatrics
238	Antimicrobial treatment of occult bacteremia: a multicenter cooperative study	This prospective multicenter study was conducted to define more clearly clinical and laboratory criteria that predict a strong probability of occult bacteremia and to evaluate the effect of empiric broad spectrum antimicrobial treatment of these children. Children 3 to 36 months old with fever > or = 40 degrees C (104 degrees F) or, > or = 39.5 degrees C (103 degrees F) with white blood cells (WBC) > or = 15 x 10(9)/liter, and no focus of infection had blood cultures obtained and were randomized to treatment with oral amoxicillin/potassium clavulanate or intramuscular ceftriaxone. Sixty of 519 (11.6%) study patients had positive blood cultures: Streptococcus pneumoniae, 51; Haemophilus influenzae b, 6; Neisseria meningitidis, 2; and Group B Streptococcus, 1. Subgroups of high risk were identified as fever > or = 39.5 degrees C and WBC > or = 15 x 10(9)/liter, 55 of 331 or 16.6% positive with increasing incidence of positive culture with increasing increments of degrees of leukocytosis to WBC > or = 30 x 10(9)/liter where 9 of 21 or 42.9% were positive. Subgroups of significantly lower risk were identified as fever > or = 39.5 degrees C and WBC < 15 x 10(9)/liter, 5 of 182 or 2.7% positive and those with WBC < 10 x 10(9)/liter, 0 of 99 or 0.0% positive. Children with positive cultures who received ceftriaxone were nearly all afebrile after 24 hours whereas a significant number who received amoxicillin/potassium clavulanate remained febrile. In the 459 culture-negative children more amoxicillin/potassium clavulanate-treated children developed diarrhea and had less improvement in clinical scores after 24 hours than ceftriaxone-treated children.(ABSTRACT TRUNCATED AT 250 WORDS)	J. W. Bass, R. W. Steele, R. R. Wittler, M. E. Weisse, V. Bell, A. H. Heisser, J. H. Brien, J. E. Fajardo, G. M. Wasserman and J. M. Vincent	The Pediatric infectious disease journal
449	Results of treatment of meningococcal meningitis in children with a single dose of Sulphanilamido-Dimethoxy-Pyrimidin (Fanasil-Roche)		O. Bedir, O. Ilter and B. Tumay	Monatsschrift fur Kinderheilkunde
442	Comparison of ceftriaxone and cefotaxime in severe pediatric bacterial infection: A multicentric study: <ORIGINAL> EVALUATION DE LA CEFTRIAXONE ET DU CEFOTAXIME DANS L'INFECTION BACTERIENNE SEVERE EN PEDIATRIE: ETUDE MULTICENTRIQUE	319 children with clinical data indicating a probably severe bacterial infection were randomly studied during 9 months in 33 French center. They were treated either with a single daily injection of ceftriaxone at 50 mg/kg/d (100 mg/kg/d for meningitis or typhoid fever) or with 3 to 4 injections of cefotaxime at 100 to 200 mg/kg/d. An aminoglycoside or an imidazole compound could be used as associated therapy according to the severity of infection as well as ampicillin in neonates. The clinical severity criteria and the biological parameters (PCR) were assessed before antibiotic treatment. 233 cases were selected for the comparative study: 22 new-borns, 117 infants, 94 children. 118 were given ceftriaxone and 115 cefotaxime. The infections were documented for 221/233 patients (95%): E. coli (54%), H. influenzae (14%), N. meningitidis (6%), Proteus mirabilis (3.5%), S. pneumoniae (6%), Streptococci (2.6%), Pseudomonas (2.2%), Enterobacter (1.7%), Salmonella typhi (6.7%), miscellaneous (3.3%). The infections treated were pyelonephritis (131), meningitis (36), septic fever (35), and other infections (31). The groups were comparable in age and sex. Results showed no difference for efficacity or bacterial eradication, in any pathology. Tolerance was excellent for the two groups, adverse reactions were rare: 9 for the ceftriaxone group, 10 for the cefotaxime group (no significant difference). The total dose (mg/kg x days of treatment) of cefotaxime was three time higher than the total dose of ceftriaxone used. This trial stressed the easier management and the potential lower cost of ceftriaxone, thanks to a single daily administration. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	P. Begue, J. Astruc, P. Francois and D. Floret	Medecine Et Maladies Infectieuses
615	Safety and pharmacokinetics of single intravenous dose of MGAWN1, a novel monoclonal antibody to West Nile virus	West Nile Virus (WNV) is a neurotropic flavivirus that can cause debilitating diseases, such as encephalitis, meningitis, or flaccid paralysis. We report the safety, pharmacokinetics, and immunogenicity of a recombinant humanized monoclonal antibody (MGAWN1) targeting the E protein of WNV in a phase 1 study, the first to be performed on humans. A single intravenous infusion of saline or of MGAWN1 at escalating doses (0.3, 1, 3, 10, or 30 mg/kg of body weight) was administered to 40 healthy volunteers (30 receiving MGAWN1; 10 receiving placebo). Subjects were evaluated on days 0, 1, 3, 7, 14, 21, 28, 42, 56, 91, 120, and 180 by clinical assessments, clinical laboratory studies, electrocardiograms (ECGs), and pharmacokinetic and immunogenicity assays. All 40 subjects tolerated the infusion of the study drug, and 39 subjects completed the study. One serious adverse event of schizophrenia occurred in the 0.3-mg/kg cohort. One grade 3 neutropenia occurred in the 3-mg/kg cohort. Six MGAWN1-treated subjects experienced 11 drug-related adverse events, including diarrhea (1 subject), chest discomfort (1), oral herpes (1), rhinitis (1), neutropenia (2), leukopenia (1), dizziness (1), headache (2), and somnolence (1). In the 30-mg/kg cohort, MGAWN1 had a half-life of 26.7 days and a maximum concentration in serum (C(max)) of 953 microg/ml. This study suggests that single infusions of MGAWN1 up to 30 mg/kg appear to be safe and well tolerated in healthy subjects. The C(max) of 953 microg/ml exceeds the target level in serum estimated from hamster studies by 28-fold and should provide excess WNV neutralizing activity and penetration into the brain and cerebrospinal fluid (CSF). Further evaluation of MGAWN1 for the treatment of West Nile virus infections is warranted.	J. H. Beigel, J. L. Nordstrom, S. R. Pillemer, C. Roncal, D. R. Goldwater, H. Li, P. C. Holland, S. Johnson, K. Stein and S. Koenig	Antimicrobial agents and chemotherapy
164	A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptoccal meningitis	We compared amphotericin B therapy for cryptococcal meningitis with a newer regimen containing both amphotericin B and flucytosine. In 50 patients with 51 courses of therapy adherent to the protocol, 27 courses were with amphotericin B and 24 with the combination. Even though the combination regimen was given for only six weeks and amphotericin B for 10 weeks, the combination cured or improved more patients (16 vs 11), produced fewer failures or relapses (three vs. 11), more rapid sterilization of the cerebrospinal fluid (P less than 0.001) and less nephrotoxicity (P less than 0.05) than did amphotericin B alone. The number of deaths was the same (five) with each regimen. Adverse reactions to flucytosine occurred in 11 of 34 patients but were not life threatening. We conclude that combined flucytosine-amphoericin B therapy is the regimen of choice in cryptococcal meningitis.	J. E. Bennett, W. E. Dismukes, R. J. Duma, G. Medoff, M. A. Sande, H. Gallis, J. Leonard, B. T. Fields, M. Bradshaw, H. Haywood, Z. A. McGee, T. R. Cate, C. G. Cobbs, J. F. Warner and D. W. Alling	The New England journal of medicine
262	Beta-glucuronidase in the diagnosis of bacterial meningitis and response to treatment	AIM: Beta-glucuronidase activity is increased in the cerebrospinal fluid (CSF) of patients with bacterial meningitis. The aim of this study was to investigate the beta-glucuronidase activity in the cell-free CSF of bacterial meningitis and its course during treatment, and compare it with other CSF parameters. METHODS: The beta-glucuronidase activity, cell number, protein concentration and CSF/blood glucose ratio were measured in 43 consecutive infants and children with bacterial meningitis, and 97 control subjects. Patients had one or two follow-up lumbar punctures. RESULTS: The beta-glucuronidase activity was increased early in bacterial meningitis, even when the other CSF parameters were undisturbed. Before treatment, the median activity in affected children was 136 micromoles 4-methylumbelliferone l(-1) h(-1) (range 44-826) and in controls 14 (7-23). In all patients who improved, the activity was lower in the follow-up CSF samples. Six to 12 h after starting treatment, the median activity was already reduced by 59%. The other CSF parameters showed a variability during the first 24 h of treatment independently of the course of the disease. Multiple comparisons of the CSF parameters in 17 patients who had two follow-up punctures showed that the beta-glucuronidase activity was the best prognostic index. CONCLUSION: Beta-glucuronidase activity in the CSF is a reliable indicator of bacterial meningitis, which can identify the response to treatment early in the course of illness. The enzyme activity is increased early in the disease, even when the other laboratory parameters from the CSF remain normal.	N. G. Beratis, M. I. Eliopoulou and G. A. Syrogiannopoulos	Acta paediatrica (Oslo, Norway : 1992)
603	Polymerase chain reaction for diagnosis of varicella zoster virus central nervous system infections without skin manifestations	Varicella zoster virus (VZV) can cause disease in the central nervous system (CNS) during both primary infection and reactivation. Rapid and adequate diagnosis of VZV have previously been hampered by the shortcomings of standard virological methods, such as isolation and serology. Earlier reported cases of CNS manifestations of VZV infection have, therefore, mostly been noted in connection with, or shortly after, onset of vesicular rash. Several studies have recently been described of cases of VZV-induced CNS disease occurring as the only sign of viral reactivation, with the diagnosis aided by polymerase chain reaction (PCR) amplification and other methods of genome detection. A prospective study was performed using PCR on cerebrospinal fluid (CSF) and brain samples received for routine diagnosis of possible VZV infection during a 2-year period. Samples from 8 (7 from CSF, 1 from brain) of the 260 patients investigated (3.1%) were found to be positive for VZV-DNA. All 8 had a presumed reactivated VZV infection according to serological and clinical analysis. Their CNS manifestations ranged from meningitis to severe encephalitis, and only in 3 of these patients was a vesicular rash present. Thus, VZV-DNA detection in the CSF was an unexpected finding for the clinician and, in 2 cases, antiviral treatment with aciclovir was initiated only because of the PCR evidence of CNS infection. VZV should be considered as a possible causative agent of infection in patients with CNS disease of suspected viral origin, even in the absence of skin manifestations. Rapid diagnosis by PCR amplification of VZV-DNA from CSF might allow for early and adequate antiviral treatment.	T. Bergström	Scandinavian journal of infectious diseases. Supplementum
135	Safety and immunogenicity of a tetravalent meningococcal serogroups A, C, W-135 and Y conjugate vaccine in adolescents and adults	The highest incidence of invasive meningococcal disease is in young children, with a second peak in adolescents/young adults. All five major disease-causing serogroups (A, B, C, W-135 and Y) have been described in Asia. Immunogenicity and safety of the investigational meningococcal ACWY-tetanus toxoid conjugate vaccine (ACWY-TT, GlaxoSmithKline Biologicals) was evaluated in healthy, meningococcal conjugate vaccine-naïve adolescents in the Philippines, India and Taiwan. 1025 adolescents were randomized (3:1) to receive one dose of ACWY-TT or tetravalent ACWY polysaccharide vaccine (Mencevax?, Men-PS). Serum bactericidal activity using rabbit complement (rSBA) was measured. Local and systemic adverse reactions were recorded for 4 days. Safety data were pooled with results from a second, similarly designed study in adults for evaluation of grade 3 systemic events. The pre-specified immunogenicity criterion for non-inferiority to Men-PS was met. One month post-vaccination, ?85.4%-97.1% had a vaccine response (post-titre ?1:8 in initially seronegative and ?4-fold increase in seropositive), versus 78.0%-96.6% after Men-PS, against each vaccine serogroup. Exploratory comparisons showed statistically significantly higher post-vaccination rSBA geometric mean titres against all serogroups following ACWY-TT versus Men-PS. Exploratory analysis showed no statistically significant differences between groups in grade 3 general symptoms; however, the statistical criterion for non-inferiority between pooled treatment groups in terms of the ratio of incidences of grade 3 general symptoms was not demonstrated. No SAEs were related to vaccination. ACWY-TT was immunogenic in Asian adolescents with a reactogenicity profile that was clinically acceptable and similar to that of licensed Men-PS. The results of this study indicate that ACWY-TT could be used as a third conjugate vaccine in the protection of adolescents against meningococcal disease.	N. Bermal, L. M. Huang, A. P. Dubey, H. Jain, A. Bavdekar, T. Y. Lin, V. Bianco, Y. Baine and J. M. Miller	Human vaccines
498	[Ceftriaxone for the treatment of bacterial meningitis in children]	in English (page 42) - prospective blind comparative study	L. Bernadino and N. Marques	Acta Medica Angolana
574	Measles vaccination in the presence of maternal antibodies primes for a balanced humoral and cellular response to revaccination	Early or low dose antigen exposure can prime the immune system for subsequent responses; the so-called "prime-boost" effect. In the context of a Sudanese measles vaccine trial, we assessed whether or not such early exposure could influence the response to revaccination. Children received either Connaught high titer vaccine (CN: n = 53; 10(4.7)pfu) or meningococcal A + C vaccine as a placebo (MEN: n = 58) at 5 months of age. At 9 months of age, all received standard titer Schwarz vaccine (SCH: 10(3.9)pfu). Neutralizing antibodies were measured before initial vaccination and at 9 months of age (plaque reduction neutralization assay (PRN)) and again at 5 years of age (syncytium inhibition assay (SIA)). Lymphoproliferative responses to measles virus (MV) antigens were evaluated at 5 years of age. Eleven of the 53 CN-SCH children (21%) had sub-protective neutralizing antibody titers prior to revaccination (log PRN 1.5 +/- 0.03 versus 2.9 +/- 0.07 in the remaining 42 children; P < 0.004). Maternal antibody titers at the time of initial vaccination in these 11 were high (PRN 2.44 +/- 0.12 versus 1.9 +/- 0.04; P < 0.0001). At 5 years of age, neutralizing antibodies were comparable in the 11 CN-SCH poor responders (log SIA 2.1 +/- 0.09), the remaining CN-SCH children (2.2 +/- 0.06) and the MEN-SCH group vaccinated only once at 9 months of age (2.25 +/- 0.06). In contrast, 7/11 of the CN-SCH poor responders (64%) had stimulation indices (SI) > 3 in response to MV antigens at 5 years of age (SI 3.1 +/- 0.6) compared with only 14% in the remaining children of the CN-SCH group (2.0 +/- 0.3; P = 0.05) and 8% in the MEN-SCH group (1.4 +/- 0.2; P < 0.0003). These data suggest that early measles vaccination in the presence of maternal antibodies can sometimes prime for a balanced humoral and cellular immune response to subsequent revaccination.	F. M. Bertley, S. A. Ibrahim, M. Libman and B. J. Ward	Vaccine
276	Use of intrathecal hyaluronidase in the management of tuberculous meningitis with hydrocephalus	A preliminary study to evaluate the efficacy of intrathecal hyaluronidase was carried out in nine children suffering from tuberculous meningitis with communicating hydrocephalus. This was followed by a randomized trial in which five cases were treated with intrathecal hyaluronidase, while six cases were treated by the insertion of a ventriculoperitoneal shunt. No untoward reaction of any significance was noted. The results were judged in terms of improvement in the sensorium and mentation, in specific neurological deficit (e.g., visual impairment and hemiparesis), and in overall functional performance. Although most of the patients receiving hyaluronidase showed some improvement in the sensorium, only one of the nine preliminary cases and one of the five cases in the randomized trial showed a total recovery of function. Two of the six shunted patients, however, showed complete recovery. Shunt insertion led to further improvement in two of the nine preliminary cases who had failed to respond to treatment with hyaluronidase. This preliminary study shows that intrathecal hyaluronidase does, in most cases, lead to an improvement in the sensorium but does not offer any particular advantage over shunt insertion in terms of regression of specific neurological deficit or overall functional improvement.	S. N. Bhagwati and K. George	Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery
478	Pathways to infant mortality in urban slums of Delhi, India: implications for improving the quality of community- and hospital-based programmes	The study aimed at obtaining insights into the processes underlying infant deaths to help identify preventive interventions which may bring down infant mortality rates further. Verbal autopsies were performed on 162 deaths of liveborn infants that occurred in a birth cohort in two urban slums of Delhi, India, between February 1995 and August 1996. A structured verbal autopsy form was used for ascertaining the cause of death. The narratives of caretakers on seeking of care and treatment received for illness were reviewed to identify the actions and behaviours that might have contributed to death. Seeking of care was less common (57%) for illnesses that led to death in the first week of life than at later ages. The first-week deaths commonly (61%) occurred within 24 hours of recognition of illness which might have been too a short time for effective interventions by care providers. Only six of 45 neonates who had features of sepsis, pneumonia or meningitis, major congenital malformations, birth asphyxia, or prematurity were advised by primary care providers for hospitalization. Similarly, only 25 (41%) of 61 older infants who had severe malnutrition and sepsis or meningitis, diarrhoea or pneumonia, or other illnesses were referred to hospital. Parenteral antibiotics were prescribed less often than warranted. Only two of 16 neonates with serious bacterial infections and eight of 19 postneonates with features of sepsis or meningitis received parenteral antibiotics. Inappropriate healthcare practices were common among the practitioners of modern and indigenous systems of medicine and registered medical practitioners. Forty percent of the neonates and a little over half of the older infants, advised for hospitalization, were taken to hospital. Fifteen percent of the infants taken to hospital were refused admission. Of 21 hospitalized infants discharged alive, five (23%) died within 48 hours and 13 (62%) within a week of returning home. A major effort is required to improve skills of healthcare providers of the biomedical and indigenous systems of medicine in caring for neonates and infants. Development of home-based treatment regimens for young infants and objective criteria for their hospitalization and discharge should receive a high priority.	N. Bhandari, R. Bahl, S. Taneja, J. Martines and M. K. Bhan	Journal of health, population, and nutrition
538	Role of dexamethasone as adjunctive therapy in acute bacterial meningitis in adults		S. Bhaumik and M. Behari	Neurology India
318	High-dose amphotericin B with flucytosine for the treatment of cryptococcal meningitis in HIV-infected patients: a randomized trial	BACKGROUND: The standard therapy for human immunodeficiency virus (HIV)-associated cryptococcal meningitis of amphotericin B (AmB; 0.7 mg/kg per day) plus flucytosine frequently takes >2 weeks to sterilize the cerebral spinal fluid, and acute mortality remains high. A dosage range for AmB of 0.7-1 mg/kg per day is noted in current guidelines, but there are no data comparing 0.7 mg/kg per day with 1 mg/kg per day. METHODS: Sixty-four HIV-seropositive, antiretroviral therapy-naive patients in Cape Town, South Africa, who experienced their first episode of cryptococcal meningitis during the period May 2005-June 2006 were randomized to receive either (1) AmB, 0.7 mg/kg per day, plus flucytosine, 25 mg/kg 4 times per day (group 1; 30 patients); or (2) AmB, 1 mg/kg per day, plus flucytosine, 25 mg/kg 4 times per day (group 2; 34 patients). Regimens were given for 2 weeks, followed by treatment with oral fluconazole. The primary outcome measure was early fungicidal activity, as determined by results of serial, quantitative cerebral spinal fluid cryptococcal cultures. Secondary outcome measures were safety and mortality. The median duration of follow-up was 1 year. RESULTS: Early fungicidal activity was significantly greater for group 2 than for group 1 (mean +/- SD, -0.56 +/- 0.24 vs. -0.45 +/- 0.16 log cfu/mL of cerebral spinal fluid per day; P = .02). The incidence of renal impairment did not significantly differ between the 2 groups. Anemia was associated with female sex and, less strongly, with membership in group 2. Renal impairment and anemia reversed after the regimen was switched to fluconazole. Two- and 10-week mortality rates were 6% and 24%, respectively, with no difference between groups. CONCLUSIONS: AmB, 1 mg/kg per day, plus flucytosine is more rapidly fungicidal than is standard-dose AmB plus flucytosine. Because of its size, this study provides limited data on any difference in toxicity between the regimens, but toxicities were manageable and reversible. CLINICAL TRIALS REGISTRATION NUMBER: ISRCTN68133435 (http://www.controlled-trials.com).	T. Bicanic, R. Wood, G. Meintjes, K. Rebe, A. Brouwer, A. Loyse, L. G. Bekker, S. Jaffar and T. Harrison	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
660	[Importance of the study of the minimal bactericidal time of serum in the choice of optimal treatment of neonatal septicemias]	Rapid eradication of bacteria in bloodstream is critical for the outcome in neonatal bacterial sepsis. Two groups of neonates with E. coli K1 sepsis without purulent meningitis were studied. Group I (n = 14) received cefotaxime IV (100 mg.kg-1 D-1) plus netilmicin (4 mg.kg-1 D-1); group II (n = 8) received amoxicillin/clavulanic acid IV (100/10 mg.kg-1 D-1) plus netilmicin (4 mg.kg-1 D-1). Both groups were identical. For all strains MICs of cefotaxime, amoxicillin/clavulanic acid, netilmicin were less than 0.2, 4 and 1 mg/l respectively. Serum bactericidal activity (SBA) was determined for each patient (peak sample). The SBA was defined as the greatest dilution in which 99,99% of the inoculum was killed. Time-kill curves were performed with 1:16 dilutions of peak serum samples to measure the kinetic of bacterial killing. The minimal bactericidal time of serum (MBTS) was defined as the minimal time required to observe a decrease of more than 4 log CFU/ml of the bacterial inoculum. Samples (10 microliters) were taken at 1 h intervals over a 6 h period and at 24 h for quantitative culture. All patients cured. Median SBA were respectively 1/128 and 1/64 for group I and II. However, mean MBTS for groups I and II were respectively 1.2 h +/- 0.8 and 3.9 h +/- 1.4. Killing was more rapid in group I (p less than 0.01). The MBTS may be a clinically useful adjunctive test when optimal therapy would be expected.	E. Bingen, N. Lambert-Zechovsky, E. Guihaire, P. Mariani, M. Coache, E. Jacqz, Y. Aujard and H. Mathieu	Pathologie-biologie
518	Early Versus Delayed Antiretroviral Therapy and Cerebrospinal Fluid Fungal Clearance in Adults With HIV and Cryptococcal Meningitis		G. P. Bisson, M. Molefi, S. Bellamy, R. Thakur, A. Steenhoff and N. Tamuhla	Clinical infectious diseases
415	Concentrations of ofloxacin in serum and cerebrospinal fluid of patients without meningitis receiving the drug intravenously and orally	The cerebrospinal fluid (CSF) penetration of ofloxacin given orally or intravenously was studied in cancer patients without meningitis. Each patient was assigned to a different sampling time to assess the relation between time and penetration. Ofloxacin was measured in serum and CSF by high-pressure liquid chromatography and bioassay. In addition, the bactericidal titers were measured in CSF and serum against a set of relevant bacteria. Concentrations measured by high-pressure liquid chromatography and bioassay were well correlated. Peak concentrations in CSF (0.4 to 1 mug/ml) were observed 2 to 4 h after infusion or oral administration. Peak concentrations in serum were observed just after infusion (2 to 3.5 mug/ml) or 1 to 2 h after oral administration (1.7 to 4 mug/ml). Measured bactericidal titers were well correlated with the titers expected from the MBC and concentration. High CSF bactericidal titers were observed against Neisseria meningitidis, Haemophilus influenzae, and Escherichia coli, whereas low or no bactericidal titers were obtained against Staphylococcus aureus, Listeria monocytogenes, and Streptococcus pneumoniae. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	N. Bitar, R. Claes and P. Auwera	Antimicrobial Agents & Chemotherapy
360	Assessing costs and cost effectiveness of pneumococcal disease and vaccination within Kaiser Permanente	Objective: To review studies of the costs of pneumococcal disease and the cost effectiveness of pneumococcal conjugate vaccination conducted in association with the Kaiser Permanente Pneumococcal conjugate Efficacy Trial. Results: for each birth cohort of 3.8 million infants, routine pneumococcal conjugate vaccination program for healthy infants would prevent more than 12000 (78% of potential) meningitis and bacteremia cases, 53000 (69% of potential) pneumonia cases, and 1 million (8% of potential) otitis media episodes. Before accounting for vaccine costs, the vaccination program would reduce the costs of pneumococcal disease by $342 million in medical and $415 million in work-loss and other costs. Vaccination of healthy infants would result in net savings for society if the vaccine cost less than $46 per dose, and net savings for the health care payer if the vaccine cost less than $18 per dose.	S. Black, T. A. Lieu, G. T. Ray, A. Capra and H. R. Shinefield	Vaccine
200	Safety and efficacy of the seven-valent pneumococcal conjugate vaccine: evidence from Northern California	UNLABELLED: Pneumococcal disease remains a significant cause of morbidity among young children. A large-scale efficacy trial in the Northern California Kaiser Permanente system (the KP trial) demonstrated that a seven-valent conjugate vaccine (PCV) is safe and immunogenic in young children and effective in preventing both invasive pneumococcal disease caused by vaccine serotypes (97.4% efficacy) and episodes of otitis media (7.0% efficacy). Since the publication of the results of the KP trial in 2000, we have performed an additional analysis on the safety, immunogenicity, and efficacy of the vaccine in low birth weight (LBW) and preterm (PT) infants, and have examined the efficacy of the vaccine during 1 year of wide-scale post-licensure use. The vaccine was at least as immunogenic in LBW and PT infants as in normal-weight, full-term infants and was 100% effective, although the LBW and PT infants had higher rates of adverse events such as redness and swelling. LBW and PT infants receiving pneumococcal vaccine also had higher rates of adverse events, such as hives, than those receiving control meningococcal vaccine, but these reactions were not severe. When the PCV was used in the general population, the efficacy remained high and there was no corresponding increase in disease caused by nonvaccine serotypes. There was also evidence that vaccine administration led to herd immunity. Febrile illness was the only adverse event seen more frequently after vaccine administration than during a control period. CONCLUSION: the seven-valent conjugate vaccine is safe and effective for use in the general population.	S. Black and H. Shinefield	European journal of pediatrics
457	Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children	Objective. To determine the efficacy, safety and immunogenicity of the heptavalent CRM197 pneumococcal conjugate vaccine against invasive disease caused by vaccine serotypes and to determine the effectiveness of this vaccine against clinical episodes of otitis media. Methods. The Wyeth Lederle Heptavalent CRM197 (PCV) was given to infants at 2, 4, 6 and 12 to 15 months of age in a double blind trial; 37 868 children were randomly assigned 1:1 to receive either the pneumococcal conjugate vaccine or meningococcus type C CRM197 conjugate. The primary study outcome was invasive disease caused by vaccine serotype. Other outcomes included overall impact on invasive disease regardless of serotype, effectiveness against clinical otitis media visits and episodes, impact against frequent and severe otitis media and ventilatory tube placement. In addition the serotype-specific efficacy against otitis media was estimated in an analysis of spontaneously draining ears. Results. In the interim analysis in August, 1998, 17 of the 17 cases of invasive disease caused by vaccine serotype in fully vaccinated children and 5 of 5 of partially vaccinated cases occurred in the control group for a vaccine efficacy of 100%. Blinded case ascertainment was continued until April, 1999. As of that time 40 fully vaccinated cases of invasive disease caused by vaccine serotype had been identified, all but 1 in controls for an efficacy of 97.4% (95% confidence interval, 82.7 to 99.9%), and 52 cases, all but 3 in controls in the intent-to-treat analysis for an efficacy of 93.9% (95% confidence interval, 79.6 to 98.5%). There was no evidence of any increase of disease caused by nonvaccine serotypes. Efficacy for otitis media against visits, episodes, frequent otitis and ventilatory tube placement was 8.9, 7.0, 9.3 and 20.1% with P < 0.04 for all. In the analysis of spontaneously draining ears, serotype-specific effectiveness was 66.7%. Conclusion. This heptavalent pneumococcal conjugate appears to be highly effective in preventing invasive disease in young children and to have a significant impact on otitis media. Number of References 24. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	S. Black, H. Shinefield, B. Fireman, E. Lewis, P. Ray, J. R. Hansen, L. Elvin, K. M. Ensor, J. Hackell, G. Siber, F. Malinoski, D. Madore, I. Chang, R. Kohberger, W. Watson, R. Austrian, K. Edwards, J. Aguilar, M. Bartlett, R. Bergen, M. Burman, S. Dorfman, W. Easter, A. Finkel, H. Froehlich, J. Glauber, A. Herz, D. Honeychurch, R. Kleinrock, I. Landaw, A. Lavetter, C. Le, S. McMurtry, P. Morozumi, P. Mullin, M. Rehbein, R. Rossin, G. Soe, I. Takahashi, G. Udkow and R. Whitson	Pediatric Infectious Disease Journal
89	The effect of rifampicin on meningococcal carriage in family contacts in northern Nigeria		I. S. Blakebrough and H. M. Gilles	The Journal of infection
77	Failure of meningococcal vaccination to stop the transmission of meningococci in Nigerian schoolboys	A combined group A and group C meningococcal polysaccharide vaccine was given to 438 Nigerian schoolboys shortly before an outbreak of group A meningococcal disease occurred in their school. Four months after vaccination the carriage rate of group A meningococci among vaccinated subjects (11%) was no different from that found among the controls (12%), although a good antibody response to both components of the vaccine was observed. One case of group A meningococcal disease was recorded amongst 438 vaccinated subjects while five cases occurred among 874 controls.	I. S. Blakebrough, B. M. Greenwood, H. C. Whittle, A. K. Bradley and H. M. Gilles	Annals of tropical medicine and parasitology
335	[The effect of antiinflammatory therapy with dexamethasone and dexamethasone with pentoxifylline on the course of bacterial meningitis]	Despite of antimicrobial therapy mortality rate in the bacterial meningitis (BM) is high. The aim of the study was to assess the influence of anti-inflammatory treatment with dexamethasone and dexamethasone with pentoxifylline on the course of this disease and concentration of proinflammatory cytokines TNF-alpha, IL-1 beta, II-8 in the cerebrospinal fluid (CSF). 42 patients with the BM were analysed. They were divided into three groups on the basis of applied therapy: A--treated only with antibiotics, A+D--treated with antibiotics and dexamethasone, A+D+P--treated with antibiotics, dexamethasone and pentoxifylline. Anti-inflammatory therapy did not have impact on the resolution of inflammation (pleocytosis, protein and glucose level) in the CSF. However, it was established that adjuvant treatment with dexa-methasone and pentoxifylline has beneficial effect on the course of the BM. In this group 61.5% of patients recovered, in comparison with 28.6% in the group A+D and 26.7% in the group A. Mortality rate was: in the group A--33%, A+D--21.4%, A+D+P--7.7% (p = 0.01). Correlation between the outcome of the BM in the investigated groups and cytokines concentration in CSF was observed. In the group A+D+P all patients responded to the therapy with decrease of cytokine concentration, and coefficients of variation were low (TNF-alpha--1%, IL-1 beta--23.6%, IL-8--18.9%). Also in the group A+D decrease of cytokines concentration in the CSF was observed, however was not such significant in all cases. In the group of patients treated only with antibiotics concentration of cytokines in the CSF varied, even increased in some of them. Our investigation indicates that inhibition of cytokines production in central nervous system (CNS) with dexamethasone and pentoxifylline improves the outcome of BM and is associated with the reduction of neurological sequels and deaths.	M. Bociaga-Jasik, A. Kalinowska-Nowak, A. Garlicki and T. Mach	Przegla?d lekarski
132	Immediate and longer term immunogenicity of a single dose of the combined haemophilus influenzae type B-Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine in primed toddlers 12 to 18 months of age	Hib-primed but MenC-naive toddlers (N = 433) were randomized to receive 1 dose of Hib-MenC-TT or separate Hib-TT and MenC-CRM197 vaccines. One month later, noninferiority was demonstrated for serum bactericidal anti-MenC antibodies (rSBA) and Hib antipolyribosylribitol phosphate (PRP) antibodies; >99% in both groups had rSBA titer ? 8 or anti-PRP concentration ? 0.15 ?g/mL. After 12 months, rSBA titer ? 8 persisted in 86.7% and 76.4%, and anti-PRP concentration ? 0.15 ?g/mL persisted in 98.8% and 100% of children, respectively.	R. Booy, P. Richmond, T. Nolan, J. McVernon, H. Marshall, M. Nissen, G. Reynolds, J. B. Ziegler, L. Heron, S. Lambert, M. Caubet, N. Mesaros and D. Boutriau	The Pediatric infectious disease journal
404	Effectiveness of rifampicin in the treatment of carriers of meningococcal infections	Los problemas presentados por las recientes epidemias de meningitis meningococica ocurridas en varios paises, junto a la importancia de los portadores de meningococo en tales epidemias, y la dificultad para encontrar terapias adecuadas, han hecho necesario investigar nuevas y efectivas formas de profilaxis Los autores investigan la eficacia e inocuidad de la Rifampicina(Rimactan) en 2.132 ninos entre 1 y 18 anos de edad que asistian a los jardines infantiles y escuelas basicas de Santiago de Chile. A ellos se les efectuo un frotis faringeo para investigar la condicion de portadores de meningococo. El 12% de ellos catalogados como portador de meningococo y tratados con Rifampicina o placebo de acuerdo con una seleccion aleatoria simple por metodo de doble ciego. Nuevos frotis fueron tomados a los tercero y decimo dias. El 92% de los individuos tratados con Rifampicina fueron negativos al tercer dia, y el 35% de los tratados con placebo presentaron igual situacion El 96% de los individuos tratados con Rifampicina que se negativizaron, mantienen esta condicion al decimo dia de tratamiento. No se observaron signos o sintomas atribuibles al medicamento. No se observo resistencia de las cepas a la Rifampicina.	D. J. Borgono and H. J. I. Rodriguez	Rev Chile Pediatr
167	Influence of prior meningococcal C polysaccharide vaccination on the response and generation of memory after meningococcal C conjugate vaccination in young children	To determine whether the immunological hyporesponsiveness induced by meningococcal AC polysaccharide (MACP) vaccines can be overcome by meningococcal C conjugate (MCC) vaccine in young children, serum bactericidal antibody (SBA) serogroup C-specific IgG and IgG avidity indices were measured in young children who received MACP vaccine, followed 7 months later by MCC vaccine, and their responses were compared with those in age-matched MACP-naive control children, who received a single dose of MCC vaccine. For children <1 year of age at MACP vaccination, the SBA geometric mean titer (GMT) after MCC vaccination was lower (P=.022) and proportions with SBA titers <8 (P=.0083) or <128 (P=.0091) were higher than those in the control children. For older children, there was no difference in the SBA GMTs between the study and control groups (P>.5) or in the proportion with SBA titers <8 (P=1.00) or <128 (P=.98). No increase in avidity occurred after MACP vaccination, whereas avidity increased significantly 1 month after MCC vaccination, with a further increase at 6 months, which indicates that the induction of immunological memory was not impaired.	R. Borrow, D. Goldblatt, N. Andrews, P. Richmond, J. Southern and E. Miller	The Journal of infectious diseases
58	Immunogenicity and safety of three doses of a bivalent (B:4:p1.19,15 and B:4:p1.7-2,4) meningococcal outer membrane vesicle vaccine in healthy adolescents	An experimental bivalent meningococcal outer membrane vesicle (OMV) vaccine (B:4:P1.19,15 and B:4:P1.7-2,4) has been developed to provide wide vaccine coverage particularly of the circulating strains in Europe. A randomized, controlled phase II study (study identification number, 710158/002; ClinicalTrials.gov identifier number, NCT00137917) to evaluate the immunogenicity and safety of three doses of the OMV vaccine when given to healthy 12- to 18-year-olds on a 0-2-4 month (n = 162) or 0-1-6 month schedule (n = 159). A control group received two doses of hepatitis A and one of conjugated meningococcal serogroup C vaccine on a 0-1-6 month schedule (n = 157). Immune response, defined as a fourfold increase in serum bactericidal titer using a range of vaccine-homologous or PorA-related and heterologous strains, was determined for samples taken before and 1 month after vaccination; assays were performed at two laboratories. As measured at the GlaxoSmithKline (GSK) laboratory, the OMV vaccine induced an immune response against homologous or PorA-related strains (in at least 51% of subjects against strains of serosubtype P1.19,15 and at least 66% against strains of serosubtype P1.7-2,4) and against a set of three heterologous strains (in 28% to 46% of subjects). Both laboratories showed consistent results for immune response rates. The OMV vaccine had a similar reactogenicity profile for each schedule. Pain preventing normal activities occurred in approximately one-fifth of the subjects; this was significantly higher than in the control group. The immune responses induced by the bivalent OMV vaccine demonstrated the induction of bactericidal antibodies against the vaccine-homologous/PorA-related strains but also against heterologous strains, indicating the presence of protective antigens in OMVs and confirming the potential of clinical cross-protection.	D. Boutriau, J. Poolman, R. Borrow, J. Findlow, J. D. Domingo, J. Puig-Barbera, J. M. Baldó, V. Planelles, A. Jubert, J. Colomer, A. Gil, K. Levie, A. D. Kervyn, V. Weynants, F. Dominguez, R. Barberá and F. Sotolongo	Clinical and vaccine immunology : CVI
169	A placebo-controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome. California Collaborative Treatment Group	BACKGROUND AND METHODS: In patients with the acquired immunodeficiency syndrome (AIDS), the rate of relapse after primary treatment for cryptococcal meningitis remains high. We conducted a controlled, double-blind trial to evaluate the efficacy of maintenance therapy with fluconazole. At entry into the study, all participants had sterile cultures of cerebrospinal fluid, blood, and urine after following a standardized course of therapy for culture-proved cryptococcal meningitis. The patients were randomly assigned to take either fluconazole or placebo as maintenance therapy. The dose of fluconazole was 100 mg daily in the first phase of study and 200 mg daily in the second phase. RESULTS: Of 84 patients initially enrolled, 16 (19 percent) were found to have silent, persistent infection on the basis of cultures that became positive after entry into the study; 7 other patients were lost to follow-up shortly after entry. Of the remaining 61 patients, 10 of 27 assigned to placebo (37 percent) and 1 of 34 assigned to fluconazole (3 percent) had a recurrence of cryptococcal infection at any site (difference in risk, 34 percent; 95 percent confidence interval, 15 to 53). Of the 11 recurrent infections, 7 were detected in urine obtained after prostatic massage. There were four recurrent meningeal infections in the patients taking placebo, but none in those taking fluconazole (mean duration of follow-up, 164 days) (P = 0.03). In multivariate analyses, the best predictors of recurrence-free survival were fluconazole treatment (P = 0.02; relative hazard, 13.2), a lower serum cryptococcal-antigen titer (P = 0.05; relative hazard, 1.2), and more prolonged primary therapy with flucytosine (P = 0.09; relative hazard, 1.1). Survival and toxicity were similar in the two maintenance-treatment groups. CONCLUSIONS: In patients with AIDS, silent persistent infection is common after clinically successful treatment for cryptococcal meningitis. Maintenance therapy with fluconazole is highly effective in preventing recurrent cryptococcal infection.	S. A. Bozzette, R. A. Larsen, J. Chiu, M. A. Leal, J. Jacobsen, P. Rothman, P. Robinson, G. Gilbert, J. A. McCutchan and J. Tilles	The New England journal of medicine
180	Malaria chemoprophylaxis with chloroquine in young Nigerian children. II. Effect on the immune response to vaccination	The immune response of 198 young Nigerian children protected against malaria by chemoprophylaxis with chloroquine to immunization with triple, poliomyelitis, measles, typhoid, meningococcal and BCG vaccines was compared with the immune response to vaccination of 185 control children. Good responses to triple, measles and BCG vaccines were shown by children in both groups; poorer responses were obtained to poliomyelitis, typhoid and meningococcal vaccines. The response to immunization of protected children was similar to that observed among control children for all the vaccines tested except for meningococcal polysaccharide vaccine. Protected children showed a significantly greater antibody response to both group A and group C meningococcal polysaccharides than control children. This finding supports the results of previous studies which have shown that the immune response to meningococcal polysaccharide vaccines is adversely affected both by acute malaria and by asymptomatic malaria parasitaemia.	A. M. Bradley-Moore, B. M. Greenwood, A. K. Bradley, A. Bartlett, D. E. Bidwell, A. Voller, J. Craske, B. R. Kirkwood and H. M. Gilles	Annals of tropical medicine and parasitology
162	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
69	Fc gamma receptor IIa (CD32) polymorphism in fulminant meningococcal septic shock in children	Antibodies are essential in host defense against Neisseria meningitidis. Therefore, interactions among IgG and Fc receptors (Fc gamma R) on phagocytes may be crucial. Genetic polymorphic forms of Fc gamma RIIa (CD32) express different functional activities. In a retrospective study, Fc gamma R polymorphisms were determined in 25 children who survived fulminant meningococcal septic shock: 11 had Fc gamma RIIa-R/R131, the poor IgG2-binding allotype, which is a significantly more frequent rate than found in a healthy white population (44% vs. 23%; P = .028; odds ratio = 2.67; 95% confidence interval, 1.09-6.53). The relevance of this finding was further supported by the fact that neutrophils with the Fc gamma RIIa-R/R131 allotype phagocytized N. meningitidis opsonized with polyclonal IgG2 antibodies less effectively than did IIa-H/H131 neutrophils. Our findings suggest an important role for anti-N. meningitidis IgG2 and the Fc gamma RIIa polymorphism in host defense against systemic meningococcal infections.	R. G. Bredius, B. H. Derkx, C. A. Fijen, T. P. Wit, M. Haas, R. S. Weening, J. G. Winkel and T. A. Out	The Journal of infectious diseases
329	Oral versus intravenous flucytosine in patients with human immunodeficiency virus-associated cryptococcal meningitis	In a randomized controlled trial of amphotericin B-based therapy for human immunodeficiency virus (HIV)-associated cryptococcal meningitis in Thailand, we also compared the mycological efficacy, toxicity, and pharmacokinetics of oral versus intravenous flucytosine at 100 mg/kg of body weight/day for the initial 2 weeks. Half of 32 patients assigned to the two arms containing flucytosine were randomized to oral and half to intravenous flucytosine. Early fungicidal activity was determined from serial quantitative cultures of cerebrospinal fluid (CSF), and toxicity was assessed by clinical and laboratory monitoring. Flucytosine and fluorouracil concentrations in plasma and CSF were measured by high-performance liquid chromatography. No significant bone marrow or hepatotoxicity was seen, there was no detectable difference in bone marrow toxicity between patients on intravenous and those on oral formulation, and no patients discontinued treatment. In patients receiving intravenous flucytosine, the median 24-h area under the concentration-time curve was significantly higher than in the oral group. Despite this difference, there was no difference in early fungicidal activity between patients on intravenous compared with patients on oral flucytosine. The results suggest that either formulation can be used safely at this dosage in a developing country setting, without drug concentration monitoring. The bioavailability of the oral formulation may be reduced in late-stage HIV-infected patients in Thailand. Concentrations of flucytosine with intravenous formulation at 100 mg/kg/day may be in excess of those required for maximal fungicidal activity.	A. E. Brouwer, H. J. Kan, E. Johnson, A. Rajanuwong, P. Teparrukkul, V. Wuthiekanun, W. Chierakul, N. Day and T. S. Harrison	Antimicrobial agents and chemotherapy
