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

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/)