Timing of Mycobacterium tuberculosis exposure explains variation in BCG effectiveness: A systematic review and meta-analysis

Trauer, James M., Kawai, Andrew, Coussens, Anna K., Datta, Manjula, Williams, Bridget M., McBryde, Emma S., and Ragonnet, Romain (2021) Timing of Mycobacterium tuberculosis exposure explains variation in BCG effectiveness: A systematic review and meta-analysis. Thorax, 76 (11). pp. 1131-1141.

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Rationale The heterogeneity in efficacy observed in studies of BCG vaccination is not fully explained by currently accepted hypotheses, such as latitudinal gradient in non-tuberculous mycobacteria exposure. Methods We updated previous systematic reviews of the effectiveness of BCG vaccination to 31 December 2020. We employed an identical search strategy and inclusion/exclusion criteria to these earlier reviews, but reclassified several studies, developed an alternative classification system and considered study demography, diagnostic approach and tuberculosis (TB)-related epidemiological context. Main results Of 21 included trials, those recruiting neonates and children aged under 5 were consistent in demonstrating considerable protection against TB for several years. Trials in high-burden settings with shorter follow-up also showed considerable protection, as did most trials in settings of declining burden with longer follow-up. However, the few trials performed in high-burden settings with longer follow-up showed no protection, sometimes with higher case rates in the vaccinated than the controls in the later follow-up period. Conclusions The most plausible explanatory hypothesis for these results is that BCG protects against TB that results from exposure shortly after vaccination. However, we found no evidence of protection when exposure occurs later from vaccination, which would be of greater importance in trials in high-burden settings with longer follow-up. In settings of declining burden, most exposure occurs shortly following vaccination and the sustained protection observed for many years thereafter represents continued protection against this early exposure. By contrast, in settings of continued intense transmission, initial protection subsequently declines with repeated exposure to Mycobacterium tuberculosis or other pathogens.

Item ID: 70033
Item Type: Article (Research - C1)
ISSN: 1468-3296
Keywords: clinical epidemiology, respiratory infection, tuberculosis
Copyright Information: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC Early Career Fellowship (APP1142638)
Date Deposited: 26 Apr 2022 01:49
FoR Codes: 42 HEALTH SCIENCES > 4202 Epidemiology > 420205 Epidemiological modelling @ 70%
49 MATHEMATICAL SCIENCES > 4901 Applied mathematics > 490102 Biological mathematics @ 30%
SEO Codes: 20 HEALTH > 2004 Public health (excl. specific population health) > 200404 Disease distribution and transmission (incl. surveillance and response) @ 80%
20 HEALTH > 2002 Evaluation of health and support services > 200205 Health policy evaluation @ 20%
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