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Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review.
BMJ. 2016 Oct 13; 355:i5170.BMJ

Abstract

OBJECTIVES

To evaluate the effects on non-specific and all cause mortality, in children under 5, of Bacillus Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP), and standard titre measles containing vaccines (MCV); to examine internal validity of the studies; and to examine any modifying effects of sex, age, vaccine sequence, and co-administration of vitamin A.

DESIGN

Systematic review, including assessment of risk of bias, and meta-analyses of similar studies.

STUDY ELIGIBILITY CRITERIA

Clinical trials, cohort studies, and case-control studies of the effects on mortality of BCG, whole cell DTP, and standard titre MCV in children under 5.

DATA SOURCES

Searches of Medline, Embase, Global Index Medicus, and the WHO International Clinical Trials Registry Platform, supplemented by contact with experts in the field. To avoid overlap in children studied across the included articles, findings from non-overlapping birth cohorts were identified.

RESULTS

Results from 34 birth cohorts were identified. Most evidence was from observational studies, with some from short term clinical trials. Most studies reported on all cause (rather than non-specific) mortality. Receipt of BCG vaccine was associated with a reduction in all cause mortality: the average relative risks were 0.70 (95% confidence interval 0.49 to 1.01) from five clinical trials and 0.47 (0.32 to 0.69) from nine observational studies at high risk of bias. Receipt of DTP (almost always with oral polio vaccine) was associated with a possible increase in all cause mortality on average (relative risk 1.38, 0.92 to 2.08) from 10 studies at high risk of bias; this effect seemed stronger in girls than in boys. Receipt of standard titre MCV was associated with a reduction in all cause mortality (relative risks 0.74 (0.51 to 1.07) from four clinical trials and 0.51 (0.42 to 0.63) from 18 observational studies at high risk of bias); this effect seemed stronger in girls than in boys. Seven observational studies, assessed as being at high risk of bias, have compared sequences of vaccines; results of a subset of these suggest that administering DTP with or after MCV may be associated with higher mortality than administering it before MCV.

CONCLUSIONS

Evidence suggests that receipt of BCG and MCV reduce overall mortality by more than would be expected through their effects on the diseases they prevent, and receipt of DTP may be associated with an increase in all cause mortality. Although efforts should be made to ensure that all children are immunised on schedule with BCG, DTP, and MCV, randomised trials are needed to compare the effects of different sequences.

Authors+Show Affiliations

School of Social and Community Medicine, University of Bristol, Bristol BS8 2PS, UK julian.higgins@bristol.ac.uk.Cochrane, St Albans House, London SW1Y 4QX, UK.School of Social and Community Medicine, University of Bristol, Bristol BS8 2PS, UK.Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.School of Social and Community Medicine, University of Bristol, Bristol BS8 2PS, UK.School of Social and Community Medicine, University of Bristol, Bristol BS8 2PS, UK.School of Social and Community Medicine, University of Bristol, Bristol BS8 2PS, UK Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.School of Social and Community Medicine, University of Bristol, Bristol BS8 2PS, UK.Division of Epidemiology, School of Public Health, University of California, Berkeley, CA 94720-7358, USA.

Pub Type(s)

Journal Article
Meta-Analysis
Review
Systematic Review

Language

eng

PubMed ID

27737834

Citation

Higgins, Julian P T., et al. "Association of BCG, DTP, and Measles Containing Vaccines With Childhood Mortality: Systematic Review." BMJ (Clinical Research Ed.), vol. 355, 2016, p. i5170.
Higgins JP, Soares-Weiser K, López-López JA, et al. Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review. BMJ. 2016;355:i5170.
Higgins, J. P., Soares-Weiser, K., López-López, J. A., Kakourou, A., Chaplin, K., Christensen, H., Martin, N. K., Sterne, J. A., & Reingold, A. L. (2016). Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review. BMJ (Clinical Research Ed.), 355, i5170. https://doi.org/10.1136/bmj.i5170
Higgins JP, et al. Association of BCG, DTP, and Measles Containing Vaccines With Childhood Mortality: Systematic Review. BMJ. 2016 Oct 13;355:i5170. PubMed PMID: 27737834.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review. AU - Higgins,Julian P T, AU - Soares-Weiser,Karla, AU - López-López,José A, AU - Kakourou,Artemisia, AU - Chaplin,Katherine, AU - Christensen,Hannah, AU - Martin,Natasha K, AU - Sterne,Jonathan A C, AU - Reingold,Arthur L, Y1 - 2016/10/13/ PY - 2016/10/15/entrez PY - 2016/10/16/pubmed PY - 2017/4/1/medline SP - i5170 EP - i5170 JF - BMJ (Clinical research ed.) JO - BMJ VL - 355 N2 - OBJECTIVES: To evaluate the effects on non-specific and all cause mortality, in children under 5, of Bacillus Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP), and standard titre measles containing vaccines (MCV); to examine internal validity of the studies; and to examine any modifying effects of sex, age, vaccine sequence, and co-administration of vitamin A. DESIGN: Systematic review, including assessment of risk of bias, and meta-analyses of similar studies. STUDY ELIGIBILITY CRITERIA: Clinical trials, cohort studies, and case-control studies of the effects on mortality of BCG, whole cell DTP, and standard titre MCV in children under 5. DATA SOURCES: Searches of Medline, Embase, Global Index Medicus, and the WHO International Clinical Trials Registry Platform, supplemented by contact with experts in the field. To avoid overlap in children studied across the included articles, findings from non-overlapping birth cohorts were identified. RESULTS: Results from 34 birth cohorts were identified. Most evidence was from observational studies, with some from short term clinical trials. Most studies reported on all cause (rather than non-specific) mortality. Receipt of BCG vaccine was associated with a reduction in all cause mortality: the average relative risks were 0.70 (95% confidence interval 0.49 to 1.01) from five clinical trials and 0.47 (0.32 to 0.69) from nine observational studies at high risk of bias. Receipt of DTP (almost always with oral polio vaccine) was associated with a possible increase in all cause mortality on average (relative risk 1.38, 0.92 to 2.08) from 10 studies at high risk of bias; this effect seemed stronger in girls than in boys. Receipt of standard titre MCV was associated with a reduction in all cause mortality (relative risks 0.74 (0.51 to 1.07) from four clinical trials and 0.51 (0.42 to 0.63) from 18 observational studies at high risk of bias); this effect seemed stronger in girls than in boys. Seven observational studies, assessed as being at high risk of bias, have compared sequences of vaccines; results of a subset of these suggest that administering DTP with or after MCV may be associated with higher mortality than administering it before MCV. CONCLUSIONS: Evidence suggests that receipt of BCG and MCV reduce overall mortality by more than would be expected through their effects on the diseases they prevent, and receipt of DTP may be associated with an increase in all cause mortality. Although efforts should be made to ensure that all children are immunised on schedule with BCG, DTP, and MCV, randomised trials are needed to compare the effects of different sequences. SN - 1756-1833 UR - https://www.unboundmedicine.com/medline/citation/27737834/full_citation L2 - http://www.bmj.com/cgi/pmidlookup?view=long&pmid=27737834 DB - PRIME DP - Unbound Medicine ER -