Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Aug 5:349:g4643.
doi: 10.1136/bmj.g4643.

Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis

A Roy  1 , M Eisenhut  2 , R J Harris  1 , L C Rodrigues  3 , S Sridhar  4 , S Habermann  2 , L Snell  2 , P Mangtani  3 , I Adetifa  5 , A Lalvani  4 , I Abubakar  6
Affiliations
Review

Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis

A Roy et al. BMJ. .

Abstract

Objectives: To determine whether BCG vaccination protects against Mycobacterium tuberculosis infection as assessed by interferon γ release assays (IGRA) in children.

Design: Systematic review and meta-analysis. Searches of electronic databases 1950 to November 2013, checking of reference lists, hand searching of journals, and contact with experts.

Setting: Community congregate settings and households.

Inclusion criteria: Vaccinated and unvaccinated children aged under 16 with known recent exposure to patients with pulmonary tuberculosis. Children were screened for infection with M tuberculosis with interferon γ release assays.

Data extraction: Study results relating to diagnostic accuracy were extracted and risk estimates were combined with random effects meta-analysis.

Results: The primary analysis included 14 studies and 3855 participants. The estimated overall risk ratio was 0.81 (95% confidence interval 0.71 to 0.92), indicating a protective efficacy of 19% against infection among vaccinated children after exposure compared with unvaccinated children. The observed protection was similar when estimated with the two types of interferon γ release assays (ELISpot or QuantiFERON). Restriction of the analysis to the six studies (n=1745) with information on progression to active tuberculosis at the time of screening showed protection against infection of 27% (risk ratio 0.73, 0.61 to 0.87) compared with 71% (0.29, 0.15 to 0.58) against active tuberculosis. Among those infected, protection against progression to disease was 58% (0.42, 0.23 to 0.77).

Conclusions: BCG protects against M tuberculosis infection as well as progression from infection to disease.Trial registration PROSPERO registration No CRD42011001698 (www.crd.york.ac.uk/prospero/).

PubMed Disclaimer

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; AL is inventor for several patents underpinning T cell based diagnosis. The ESAT-6/CFP-10 IFN-gamma ELISpot was commercialised by an Oxford University spin-out company (T-SPOT.TB, Oxford Immunotec, Abingdon, UK), in which Oxford University and AL have minority shares of equity and entitlement to royalties.

Figures

None
Fig 1 Study selection for systematic review of BCG vaccination against mycobacterium tuberculosis infection in children
None
Fig 2 Protection against Mycobacterium tuberculosis infection (TB) as determined by interferon γ release assay (QuantiFERON) in children vaccinated with BCG. D+L=DerSimonian and Laird method; M-H=Mantel-Haenszel method. One test was used per paper and in cases where both ELISpot and QuantiFERON data were available data from QuantiFERON testing were used
None
Fig 3 Protection against Mycobacterium tuberculosis infection (TB) as determined by interferon γ release assay (ELISpot v QuantiFERON) in children vaccinated with BCG. D+L=DerSimonian and Laird; M-H=Mantel-Haenszel
None
Fig 4 Subgroup analyses of protection in children by BCG vaccination against Mycobacterium tuberculosis infection (TB) in children vaccinated with BCG, as determined by type of interferon γ release assay, latitude, study quality, and age at vaccination policy comparing areas with (A) and without (B) policy to vaccinate infants at birth; and separate analysis of protection against active disease and against progression from infection to disease in subset of studies (DerSimonian and Laird method)
None
Fig 5 Funnel plot (with pseudo confidence intervals) of studies investigating association between BCG vaccination and result of interferon γ release assay
None
Fig 6 Schematic representation of protective effect of BCG immunisation against Mycobacterium tuberculosis infection, active tuberculosis, and progression to active tuberculosis from infection during screening from subset of six articles with data on active tuberculosis (vaccine efficacy (VE) and 95% confidence intervals)
None
Fig 7 Types of protection against Mycobacterium tuberculosis (TB) in children vaccinated with BCG: protection against infection (irrespective of whether they went on to develop active TB); overall protection against active TB; protection against progression from infection to active TB during screening. D+L=DerSimonian and Laird method; M-H=Mantel-Haenszel method
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Rodrigues LC, Mangtani P, Abubakar I. How does the level of BCG vaccine protection against tuberculosis fall over time? BMJ 2011;343:d5974. - PubMed
    1. Trunz BB, Fine P, Dye C. Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness. Lancet 2006;367:1173-80. - PubMed
    1. Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV et al. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA 1994;271:698-702. - PubMed
    1. Lienhardt C, Zumla A. BCG: the story continues. Lancet 2005;366:1414-6. - PubMed
    1. Zodpey SP, Shrikhande SN. The geographic location (latitude) of studies evaluating protective effect of BCG vaccine and it’s efficacy/effectiveness against tuberculosis. Indian J Public Health 2007;51:205-10. - PubMed