Immunogenicity and serotype-specific efficacy of a 9-valent pneumococcal conjugate vaccine (PCV-9) determined during an efficacy trial in The Gambia.

This study aimed to determine the immunogenicity of a 9-valent pneumococcal conjugate vaccine (PCV-9) in a subgroup of Gambian children enrolled in a large vaccine efficacy trial. To place the antibody results in context, in this paper we also report previously unpublished data on serotype-specific clinical vaccine efficacy from the main trial. In the sub-study, a single 2-4 ml venous blood specimen was collected from 212 Gambian children 4-6 weeks after the administration of a third dose of PCV-9 or placebo. IgG antibodies to pneumococcal serotype 1, 4, 5, 6B, 9V, 14, 18C, 19F and 23F polysaccharides were measured by ELISA. The proportions of infants with antibody concentrations above 0.2, 0.35 and 1.0 microg/ml, and the geometric mean concentrations (GMCs) of anti-pneumococcal polysaccharide antibodies were substantially higher for each serotype in children who received three doses of PCV-9 than those in the placebo group. Among PCV-9 recipients, GMCs ranged between 2.61 and 11.09 microg/ml with the highest being against serotype 14 and the lowest against 9V polysaccharide. The estimated overall protective antibody level for all nine serotypes, based on the vaccine efficacy against vaccine-type invasive pneumococcal disease (IPD) of 77% (95% CI: 51, 90) observed in the trial, was 2.3 microg/ml (95% CI: 1.0, 5.0). The PCV-9 studied was immunogenic in a Gambian population where it was also found to be efficacious.

Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial.

BACKGROUND: Pneumonia is estimated to cause 2 million deaths every year in children. Streptococcus pneumoniae is the most important cause of severe pneumonia. We aimed to assess the efficacy of a nine-valent pneumococcal conjugate vaccine in children. METHODS: We undertook a randomised, placebo-controlled, double-blind trial in eastern Gambia. Children age 6-51 weeks were randomly allocated three doses of either pneumococcal conjugate vaccine (n=8718) or placebo (8719), with intervals of at least 25 days between doses. Our primary outcome was first episode of radiological pneumonia. Secondary endpoints were clinical or severe clinical pneumonia, invasive pneumococcal disease, and all-cause admissions. Analyses were per protocol and intention to treat. FINDINGS: 529 children assigned vaccine and 568 allocated placebo were not included in the per-protocol analysis. Results of per-protocol and intention-to-treat analyses were similar. By per-protocol analysis, 333 of 8189 children given vaccine had an episode of radiological pneumonia compared with 513 of 8151 who received placebo. Pneumococcal vaccine efficacy was 37% (95% CI 27-45) against first episode of radiological pneumonia. First episodes of clinical pneumonia were reduced overall by 7% (95% CI 1-12). Efficacy of the conjugate vaccine was 77% (51-90) against invasive pneumococcal disease caused by vaccine serotypes, 50% (21-69) against disease caused by all serotypes, and 15% (7-21) against all-cause admissions. We also found an efficacy of 16% (3-28) against mortality. 110 serious adverse events arose in children given the pneumococcal vaccine compared with 131 in those who received placebo. INTERPRETATION: In this rural African setting, pneumococcal conjugate vaccine has high efficacy against radiological pneumonia and invasive pneumococcal disease, and can substantially reduce admissions and improve child survival. Pneumococcal conjugate vaccines should be made available to African infants.

Evaluation of Binax now Streptococcus pneumoniae urinary antigen test in children in a community with a high carriage rate of pneumococcus.

Pneumococcal antigen was present in urine from 49 of 102 well Gambian children. Eighty-nine of the 102 were nasopharyngeal carriers of pneumococci. The positive predictive value for carriage was 96%, and the negative predictive value was 22%. The test is not useful for predicting etiology of disease in populations with a high rate of nasopharyngeal carriage of pneumococci.

Screening of human corneas for herpes simplex virus by tissue culture and polymerase chain reaction.

Superficial eye infections by herpes simplex virus (HSV) constitute a major cause of corneal disease, necessitating the need for corneal transplantation in many patients. Eighty-three corneas from 46 post-mortem donors received from the David Lucas Eye Bank in Manchester were analyzed by Vero cell culture and the polymerase chain reaction (PCR) technique to detect HSV. There was no evidence of a characteristic cytopathic effect in any of the cultures. A 350-bp PCR product corresponding to the HSV thymidine kinase (TK) was detected by southern blotting in only 2.4% (2/83) of samples. In contrast, approximately 70% of samples yielded a 758-bp PCR product. Although this low prevalence of HSV in corneas may be encouraging, it is high for the actual transplantation program if the viral DNAs maintain their abilities to replicate.

Detection of herpes simplex virus DNA in donor cornea culture medium by polymerase chain reaction.

AIMS/BACKGROUND: Herpes simplex virus (HSV) may establish latent infection in the cornea and therefore be transmissible by corneal transplantation. Monitoring of donor cornea culture medium was evaluated for HSV infection. METHODS: HSV was sought using virus isolation in cell culture, and its DNA was amplified to detectable levels using the polymerase chain reaction (PCR). RESULTS: Virus isolation in cell culture was negative on neat, cell pellet, and cell free supernatant prepared from the spent culture media of 80 corneas. Three cell pellets (3.8%) were positive for HSV DNA. The PCR positive culture negative results might have reflected latent rather than active HSV infection of the cornea. Post transplant follow up of the three recipients of corneas with HSV PCR positive organ culture media revealed no evidence of HSV induced eye disease or primary graft failure. CONCLUSION: Screening of corneal culture medium for HSV by virus culture or for HSV DNA by PCR could not be recommended.