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Meta-Analysis
. 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
Meta-Analysis

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/).

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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

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Fig 1 Study selection for systematic review of BCG vaccination against mycobacterium tuberculosis infection in children
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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
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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
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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)
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Fig 5 Funnel plot (with pseudo confidence intervals) of studies investigating association between BCG vaccination and result of interferon γ release assay
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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)
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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
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Comment in

References

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