Effectiveness of Haemophilus influenzae type b vaccines administered according to various schedules: systematic review and meta-analysis of observational data.

BACKGROUND: Conjugate vaccines against Haemophilus influenzae type b (Hib) are widely used. The full implications of Hib vaccination schedule for vaccine effectiveness (VE) are unclear. METHODS: We searched the literature for observational studies reporting the effectiveness of conjugate Hib vaccines administered according to different schedules. We summarized dose-specific VE estimates, where appropriate, using random effects meta-analysis. RESULTS: Thirty-one eligible articles (reporting 30 studies conducted in 17 countries) were identified. Meta-analysis of case-control studies using community controls produced VE estimates against Hib meningitis of 55% (95% confidence interval: 2-80%, based on 3 studies), 96% (86-99%, 3 studies) and 96% (86-99%, 4 studies) after 1, 2 and 3 doses of vaccines other than the polyribosyl ribitol phosphate outer membrane protein vaccine. Estimates were similar using hospital controls. VE against invasive Hib disease in case-control studies was estimated as 59% (30-76%, 3 studies) and 97% (87-99%, 3 studies) for 1 and 3 doses (insufficient data were identified to estimate 2-dose VE). Point estimates from 2 studies suggested VE>90% after 1 dose of the polyribosyl ribitol phosphate outer membrane protein vaccine, but meta-analysis was not possible. Using data from 4 cohort studies, 3-dose VE was estimated as 94% (88-97%). There was some evidence that Hib vaccine was less effective when administered with acellular (rather than whole cell) pertussis vaccine. Weak evidence from 2 studies suggested that a booster confers some additional protection following full primary vaccination and may compensate for an incomplete primary series. CONCLUSIONS: Observational data suggest that ≥2 doses of Hib vaccine are required for high effectiveness, but do not strongly favor any particular schedule.