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Cochrane Database Syst Rev. 2009 Jul 8;(3):CD005530. doi: 10.1002/14651858.CD005530.pub2.

Combined DTP-HBV-HIB vaccine versus separately administered DTP-HBV and HIB vaccines for primary prevention of diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae B (HIB).

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Department of Medicine E, Beilinson Campus, Rabin Medical Center, 39 Jabotinsky Street, Petah-Tiqva, Israel, 49100.



Advantages to combining childhood vaccines include reducing the number of visits, injections and patient discomfort, increasing compliance, and optimizing prevention. The World Health Organization recommends that routine infant immunization programs include a vaccination against Haemophilus influenza type B (HIB) in the combined diphtheria, tetanus, pertussis (DTP)-hepatitis B (HBV) vaccination. The effectiveness and safety of the combined vaccine should be carefully and systematically assessed to ensure their acceptability by the community.


To compare the effectiveness of combined DTP-HBV-HIB vaccine with DTP-HBV and HIB vaccinations.


We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 1) which contains the Acute Respiratory Infection Group's Specialized Register; MEDLINE (January 1966 to March 2009) and EMBASE (January 1990 to March 2009).


Randomized or quasi-randomized controlled trials comparing vaccination with any combined DTP-HBV-HIB vaccine, with or without three types of inactivated poliovirus (IPV) or concomitant oral polio vaccine (OPV) in any dose, preparation or time schedule, compared with separate vaccines or placebo, administered to infants aged up to two years.


Two review authors independently inspected references identified by the searches and evaluated them against the inclusion criteria, extracted data and assessed the methodological quality of included trials.


Meta-analysis was performed to pool the results of 18 studies. There were no data on clinical outcomes for the primary outcome and all studies used immunogenicity and reactogenicity (adverse events). In two immunological responses the combined vaccine achieved lower responses than the separate vaccines for HIB and HBV. Comparison found little heterogeneity. No significant differences in immunogenicity were found for pertussis, diphtheria, polio and tetanus. Serious adverse events were comparable. Minor adverse events were more common in children given the combined vaccine.


We could not conclude that the immune responses elicited by the combined vaccine were different from, or equivalent to, the separate vaccines. Data for the primary outcome (prevention of disease) were lacking. There was significantly less immunological response for HIB and HBV, and more local reactions in the combined injections. However, these differences rely mostly on one study each. Studies did not use an intention-to-treat analysis and we were uncertain about the risk of bias in many of the studies. These results are therefore inconclusive. Studies addressing clinical end-points whenever possible, using correct methodology and a large enough sample size should be conducted.

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