WITHDRAWN: Conjugate vaccines for preventing Haemophilus influenzae type B infections

Haemophilus influenzae (H. influenzae) is an important cause of meningitis and pneumonia in children. Vaccine cost is a significant barrier to use in low income countries. Determining the size of the effects of the vaccine will enable cost-effectiveness comparisons with competing priorities in low income countries.

1. To determine the effects of conjugate Hib vaccine in preventing Hib disease or death in children under five years of age. 2. To determine any variation in effect with type of vaccine, number of doses, age at first dose, in children with known HIV infection, or in high and low income countries. 3. To determine any serious adverse outcomes.

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2006, issue 4) which contains the Acute Respiratory Infections Group's specialized register; MEDLINE (January 1966 to December 2006); EMBASE (1990 to June 2006) and scanned reference lists and contacting of authors of trial reports.

All randomised controlled trials (RCTs) or quasi-RCTs of conjugate H. influenzae type b vaccines compared with placebo or no treatment in children who were followed until at least two years of age.

Two review authors independently selected eligible studies and extracted data.

Six studies were included in the review, and four in the meta-analyses. The overall quality of the trials was good. The relative risk for invasive Hib disease was 0.20 (95% confidence interval (CI) 0.07 to 0.54; random-effects model), but there was statistically significant unexplained variation (heterogeneity) in the effects of the four trials in the meta-analysis (P = 0.002). The size of the effects did not appear to differ consistently with different vaccine types, the number of vaccine doses, age at first vaccination or use in high income versus low income countries, but the CIs for the effect estimates were wide. Hib-related mortality data showed a non-significant trend towards benefit (relative risk was 0.29; 95% CI 0.07 to 1.20; random-effects model). The relative risk for all cause mortality in the two trials from which data were available were 1.01 (95% CI 0.38 to 2.67, random-effects model) and 0.97. No serious adverse effects were reported in any of the trials.

Hib vaccine is safe and effective. In resource-poor settings, decisions to use the vaccine will depend on its cost, the local burden of Hib disease and competing priorities.