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Meta-Analysis
. 2012 Apr 18;2012(4):CD005530.
doi: 10.1002/14651858.CD005530.pub3.

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)

Edna S Bar-On  1 , Elad Goldberg, Sarah Hellmann, Leonard Leibovici
Affiliations
Meta-Analysis

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)

Edna S Bar-On et al. Cochrane Database Syst Rev. .

Abstract

Background: Advantages to combining childhood vaccines include reducing the number of visits, injections and patient discomfort, increasing compliance and optimising prevention. The World Health Organization (WHO) recommends that routine infant immunisation programmes include a vaccination against Haemophilus influenzae (H. influenzae) type B (HIB) in the combined diphtheria-tetanus-pertussis (DTP)-hepatitis B virus (HBV) vaccination. The effectiveness and safety of the combined vaccine should be carefully and systematically assessed to ensure its acceptability by the community.

Objectives: To compare the effectiveness of combined DTP-HBV-HIB vaccines versus combined DTP-HBV and separate HIB vaccinations.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (January 1966 to week 1, November 2011), EMBASE (January 1990 to November 2011) and www.clinicaltrials.gov (up to April 2011).

Selection criteria: Randomised controlled trials (RCTs) or quasi-RCTs comparing vaccination with any combined DTP-HBV-HIB vaccine, with or without three types of inactivated polio virus (IPV) or concomitant oral polio vaccine (OPV) in any dose, preparation or time schedule, compared with separate vaccines or placebo, administered to infants up to two years old.

Data collection and analysis: 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.

Main results: Data for the primary outcome (prevention of disease) were lacking. We performed a meta-analysis to pool the results of 20 studies with 5874 participants in an immunogenicity analysis and 5232 participants in the reactogenicity analysis. There were no data on clinical outcomes for the primary outcome (prevention of disease) and all studies used immunogenicity and reactogenicity (adverse events). The number of vaccine doses differed significantly between the studies. Heterogeneous interventions, study location, healthcare environment and combining research across disparate geographical locations, may have lead to bias. The risk of bias was unclear across most of the included studies. Comparisons found little heterogeneity. In two immunological responses the combined vaccine achieved lower responses than the separate vaccines for HIB and tetanus. No significant differences in immunogenicity were found for pertussis, diphtheria, polio and hepatitis B. Serious adverse events were comparable with mainly hospitalisation and acute bronchiolitis cases. Minor adverse events such as pain and redness were more common in children given the combined vaccine. Overall, the direction shown by the results is in favour of the DTPw (diptheria-tetanus-whole cell pertussis)-HBV-HIB vaccine rather than the DTPa (diptheria-tetanus-acellular pertussis)-HBV-HIB vaccine when compared to the separate vaccines (size of effect: risk ratio (RR) 1.43; 95% confidence interval (CI) 0.98 to 2.10, for 5269 participants).

Authors' conclusions: We could not conclude that the immune responses elicited by the combined vaccine were different from or equivalent to the separate vaccines. There was significantly less immunological response for HIB and tetanus 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 (ITT) 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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Conflict of interest statement

None to declare.

Figures

1
1
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Funnel plot of comparison: 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, outcome: 1.1 Anti‐PRP titres below the assay cut‐off 0.15 µg/ml.
4
4
Funnel plot of comparison: 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, outcome: 1.2 Anti‐PRP titres below the assay cut‐off 1.0 µg/ml.
1.1
1.1. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 1 Anti‐PRP titres below the assay cut‐off 0.15 µg/ml.
1.2
1.2. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 2 Anti‐PRP titres below the assay cut‐off 1.0 µg/ml.
1.3
1.3. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 3 Anti‐FHA (Filamentous haemagglutinin).
1.4
1.4. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 4 Anti‐PRN (Pertactin).
1.5
1.5. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 5 Anti‐HBV (Hepatitis B).
1.6
1.6. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 6 Anti‐BPT (Pertussis).
1.7
1.7. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 7 Anti‐D (Diphtheria).
1.8
1.8. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 8 Anti‐T (Tetanus).
1.9
1.9. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 9 DTPa Anti‐polio type 1 below the assay cut‐off 1:8 IU/mL.
1.10
1.10. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 10 DTPa Anti‐polio type 2 below the assay cut‐off 1:8 IU/mL.
1.11
1.11. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 11 DTPa Anti‐polio type 3 below the assay cut‐off 1:8 IU/mL.
1.12
1.12. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 12 Serious adverse events.
1.13
1.13. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 13 Pain.
1.14
1.14. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 14 Redness.
1.15
1.15. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 15 Swelling.
1.16
1.16. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 16 Fever.
1.17
1.17. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 17 Fussiness or restlessness.
1.18
1.18. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 18 Drowsiness.
1.19
1.19. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 19 Irritability or tenderness.
1.20
1.20. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 20 Poor appetite.
1.21
1.21. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 21 Vomiting.
1.22
1.22. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 22 Diarrhoea.
1.23
1.23. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 23 Unusual crying.
1.24
1.24. Analysis
Comparison 1 DTP‐HBV‐HIB vaccine versus separately administered DTP‐HBV and HIB vaccines, Outcome 24 Sleeping more than usual.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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References to studies excluded from this review

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Lagos 2005 {published data only}
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Lopez 2002 {published data only}
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Meriste 2006 {published data only}
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Nolan 2004 {published data only}
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Pichichero 1999 {published data only}
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Pichichero 2007 {published data only}
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Saenger 2005 {published data only}
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Scheifele 2006 {published data only}
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References to ongoing studies

Sanofi‐Aventis 2011 {published data only (unpublished sought but not used)}
    1. Sanofi‐Aventis ICMJE Investigators. Study of PENTAXIM™ Vaccine Versus TETRAXIM™ Vaccine Given With ACTHIB™ Vaccine in South Korean Infants. www.clinicaltrials.gov First Received on October 1, 2010. Last Updated on April 4, 2011.

Additional references

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References to other published versions of this review

Bar‐On 2009
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