Conjugate vaccines for preventing Haemophilus influenzae type b infections.
BACKGROUND
Haemophilus influenzae (H. influenzae) is an important cause of meningitis and pneumonia in children, causing an estimated three million cases of serious disease and hundreds of thousands of deaths annually worldwide. The introduction of H. influenzae type b (Hib) vaccines into routine immunisation schedules in developed countries has been followed by a rapid decline in disease occurrence, but vaccine cost is a significant barrier to use in developing countries. There is a need to determine the size of the effects of the vaccine, to enable cost-effectiveness comparisons with competing priorities in developing countries.


OBJECTIVE
1. To determine the effects of conjugate Hib vaccine in preventing Hib disease or death in children under five years.2. To determine any serious adverse outcomes.


METHODS
Searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (issue 1, 2003); MEDLINE (January 1966 to April 2003), EMBASE (1990 to April 2003); and scanning of reference lists and contacting of authors of trial reports. Reports in all languages were considered.


METHODS
All randomised controlled trials or quasi-randomised trials 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.


METHODS
Two investigators independently selected eligible studies and extracted data. Differences were resolved by discussion.


RESULTS
Five studies were included in the review, and four in meta-analyses. The overall quality of the trials was good. The relative risk for invasive Hib disease was 0.20 (95% confidence interval 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 found in the trials did not appear to differ consistently with different vaccine types, the number of vaccine doses, age at first vaccination or use in developed vs developing countries, but the confidence intervals for the effect estimates were wide.Hib-related mortality data showed a non-significant trend towards benefit (relative risk was 0.29; 95% confidence interval 0.07 to 1.20; random effects model). The relative risk for all cause mortality in the single trial from which data were available was 1.01 (95% confidence interval 0.38 to 2.67, random effects model). No serious adverse effects were reported in any of the trials, involving a total of 257,000 infants.


CONCLUSIONS
Hib vaccine is safe and effective. The size of the effect could plausibly be anywhere between a 46% and 93% reduction in Hib invasive disease, before the effect of herd immunity is taken into account. In resource-poor settings, decisions to use the vaccine will depend on its cost, the local burden of Hib disease and competing priorities. Insufficient evidence from randomised controlled trials was identified of the effects of Hib conjugate vaccine on either Hib-specific or on all-cause mortality.
School of Child and Adolescent Health, Red Cross Children's Hospital, Klipfontein Road, Rondebosch, Cape Town, South Africa, 7700.
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G
Swingler
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D
Fransman
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G
Hussey
D016667:Bacterial Capsules; D003906:Developing Countries; D006192:Haemophilus Infections / Q000517:prevention & control*; D018073:Haemophilus Vaccines / Q000627:therapeutic use*; D019741:Haemophilus influenzae type b; D006801:Humans; D011135:Polysaccharides, Bacterial / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018074:Vaccines, Conjugate / Q000627:therapeutic use
D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate