Protection by BCG vaccine against tuberculosis: A systematic review of randomized controlled trials

Punam Mangtani; Ibrahim Abubakar; Cono Ariti; Rebecca Beynon; Laura Pimpin; Paul E.M. Fine; Laura C. Rodrigues; Peter G. Smith; Marc Lipman; Penny F. Whiting; Jonathan A. Sterne

doi:10.1093/cid/cit790

Protection by BCG vaccine against tuberculosis: A systematic review of randomized controlled trials

Punam Mangtani^*, Ibrahim Abubakar, Cono Ariti, Rebecca Beynon, Laura Pimpin, Paul E.M. Fine, Laura C. Rodrigues, Peter G. Smith, Marc Lipman, Penny F. Whiting, Jonathan A. Sterne

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

710 Citations (Scopus)

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.

Original language	English
Pages (from-to)	470-480
Number of pages	11
Journal	Clinical Infectious Diseases
Volume	58
Issue number	4
DOIs	https://doi.org/10.1093/cid/cit790
Publication status	Published - 15 Feb 2014

Bibliographical note

Funding Information:
Financial support. This work was supported by the UK National Institute for Health Research Evaluation, Trials and Studies Coordinating Centre (http://www.netscc.ac.uk/about/; grant number 08/16/01). Potential conflicts of interest. All authors: No reported conflicts.

Keywords

BCG vaccine
meta-analysis
meta-regression
trials
vaccine efficacy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/cid/cit790

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@article{7169860a56854f32a150c515137ced78,

title = "Protection by BCG vaccine against tuberculosis: A systematic review of randomized controlled trials",

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.",

keywords = "BCG vaccine, meta-analysis, meta-regression, trials, vaccine efficacy",

author = "Punam Mangtani and Ibrahim Abubakar and Cono Ariti and Rebecca Beynon and Laura Pimpin and Fine, {Paul E.M.} and Rodrigues, {Laura C.} and Smith, {Peter G.} and Marc Lipman and Whiting, {Penny F.} and Sterne, {Jonathan A.}",

note = "Funding Information: Financial support. This work was supported by the UK National Institute for Health Research Evaluation, Trials and Studies Coordinating Centre (http://www.netscc.ac.uk/about/; grant number 08/16/01). Potential conflicts of interest. All authors: No reported conflicts.",

year = "2014",

month = feb,

day = "15",

doi = "10.1093/cid/cit790",

language = "English",

volume = "58",

pages = "470--480",

journal = "Clinical Infectious Diseases",

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T1 - Protection by BCG vaccine against tuberculosis

T2 - A systematic review of randomized controlled trials

AU - Mangtani, Punam

AU - Abubakar, Ibrahim

AU - Ariti, Cono

AU - Beynon, Rebecca

AU - Pimpin, Laura

AU - Fine, Paul E.M.

AU - Rodrigues, Laura C.

AU - Smith, Peter G.

AU - Lipman, Marc

AU - Whiting, Penny F.

AU - Sterne, Jonathan A.

N1 - Funding Information: Financial support. This work was supported by the UK National Institute for Health Research Evaluation, Trials and Studies Coordinating Centre (http://www.netscc.ac.uk/about/; grant number 08/16/01). Potential conflicts of interest. All authors: No reported conflicts.

PY - 2014/2/15

Y1 - 2014/2/15

N2 - 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.

AB - 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.

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KW - meta-regression

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Protection by BCG vaccine against tuberculosis: A systematic review of randomized controlled trials

Abstract

Bibliographical note

Keywords

UN SDGs

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