Protection by BCG Vaccine Against Tuberculosis: A Systematic Review of Randomized Controlled Trials
Punam Mangtani,Ibrahim Abubakar,Cono Ariti,R Beynon,Laura Pimpin,Paul E. M. Fine,Laura C. Rodrigues,Pete Smith,Marc Lipman,Marc Lipman,Penny Whiting,Jonathan A C Sterne +11 more
TLDR
Absence of prior M. tuberculosis infection or sensitization with environmental mycobacteria is associated with higher efficacy of BCG against pulmonary tuberculosis and possibly against miliary and meningeal tuberculosis.Abstract:
BACKGROUND: Randomized trials assessing BCG vaccine protection against tuberculosis have widely varying results, for reasons that are not well understood. METHODS: We examined associations of trial setting and design with BCG efficacy against pulmonary and miliary or meningeal tuberculosis by conducting a systematic review, meta-analyses, and meta-regression. RESULTS: We identified 18 trials reporting pulmonary tuberculosis and 6 reporting miliary or meningeal tuberculosis. Univariable meta-regression indicated efficacy against pulmonary tuberculosis varied according to 3 characteristics. Protection appeared greatest in children stringently tuberculin tested, to try to exclude prior infection with Mycobacterium tuberculosis or sensitization to environmental mycobacteria (rate ratio [RR], 0.26; 95% confidence interval [CI], .18-.37), or infants (RR, 0.41; 95% CI, .29-.58). Protection was weaker in children not stringently tested (RR, 0.59; 95% CI, .35-1.01) and older individuals stringently or not stringently tested (RR, 0.88; 95% CI, .59-1.31 and RR, 0.81; 95% CI, .55-1.22, respectively). Protection was higher in trials further from the equator where environmental mycobacteria are less and with lower risk of diagnostic detection bias. These associations were attenuated in a multivariable model, but each had an independent effect. There was no evidence that efficacy was associated with BCG strain. Protection against meningeal and miliary tuberculosis was also high in infants (RR, 0.1; 95% CI, .01-.77) and children stringently tuberculin tested (RR, 0.08; 95% CI, .03-.25). CONCLUSIONS: Absence of prior M. tuberculosis infection or sensitization with environmental mycobacteria is associated with higher efficacy of BCG against pulmonary tuberculosis and possibly against miliary and meningeal tuberculosis. Evaluations of new tuberculosis vaccines should account for the possibility that prior infection may mask or block their effects.read more
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Prevention of M. tuberculosis Infection with H4:IC31 Vaccine or BCG Revaccination
Elisa Nemes,Hennie Geldenhuys,Virginie Rozot,Kathryn Tucker Rutkowski,Frances Ratangee,Nicole Bilek,Simbarashe Mabwe,Lebohang Makhethe,Mzwandile Erasmus,Asma Toefy,Humphrey Mulenga,Willem A. Hanekom,Steven G. Self,Linda-Gail Bekker,Ryall Robert P,Sanjay Gurunathan,Carlos A. DiazGranados,Peter Andersen,Ingrid Kromann,Thomas J. Evans,Ruth D. Ellis,Bernard Landry,David A. Hokey,Robert Hopkins,Ann M. Ginsberg,Thomas J. Scriba,Mark Hatherill +26 more
TL;DR: The rate of sustained QFT conversion, which may reflect sustained M. tuberculosis infection, was reduced by vaccination in a high‐transmission setting, and this finding may inform clinical development of new vaccine candidates.
Journal ArticleDOI
Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis
Anjana Roy,Michael Eisenhut,Ross J Harris,Laura C. Rodrigues,Saranya Sridhar,S Habermann,Luke B Snell,Punam Mangtani,Ifedayo M. O. Adetifa,Ajit Lalvani,Ibrahim Abubakar,Ibrahim Abubakar +11 more
TL;DR: BCG protects against M tuberculosis infection as well as progression from infection to disease, and the observed protection was similar when estimated with the two types of interferon γ release assays (ELISpot or QuantiFERON).
Journal ArticleDOI
BCG vaccine protection from severe coronavirus disease 2019 (COVID-19).
TL;DR: Results fail to confirm the null hypothesis of no association between BCG vaccination and COVID-19 mortality, and suggest that BCG could have a protective effect, but public health implications of a plausible BCG cross-protection from severe COVID -19 are discussed.
Journal ArticleDOI
Non-specific effects of BCG vaccine on viral infections
TL;DR: Evidence for non-specific protection induced by BCG vaccination against viral infections, possible mechanisms of action, and implications for vaccination policies and vaccine discovery are reviewed.
Journal ArticleDOI
Prevention of tuberculosis in macaques after intravenous BCG immunization
Patricia A. Darrah,Joseph J. Zeppa,Pauline Maiello,Joshua A Hackney,Marc H. Wadsworth,Marc H. Wadsworth,Marc H. Wadsworth,Travis K. Hughes,Travis K. Hughes,Travis K. Hughes,Supriya Pokkali,Phillip A. Swanson,Nicole L. Grant,Mark Rodgers,Megha Kamath,Chelsea M Causgrove,Dominick Laddy,Aurelio Bonavia,Danilo R. Casimiro,Philana Ling Lin,Edwin Klein,Alexander G. White,Charles A. Scanga,Alex K. Shalek,Mario Roederer,JoAnne L. Flynn,Robert A. Seder +26 more
TL;DR: The finding that intravenous BCG prevents or substantially limits Mtb infection in highly susceptible rhesus macaques has important implications for vaccine delivery and clinical development, and provides a model for defining immune correlates and mechanisms of vaccine-elicited protection against tuberculosis.
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TL;DR: Evidence accumulated to date indicates that regional differences in environmental mycobacteria are responsible for much of the variation observed between populations in the efficacy of BCG against pulmonary tuberculosis.