A recent study has found that the Bacille Calmette-Guérin (BCG) vaccination at birth provides significant protection against tuberculosis, but only among children under five-years-old – despite having been used in TB prevention for 100 years, and given to at least 100m people annually.
TB affects at least 10m people a year across the world, and researchers have always questioned the effectiveness of the BCG vaccine, reports News24.
The latest study, by Boston University School of Public Health and published in The Lancet Global Health, analysed data from the past 10 years from high-burden settings in 17 countries, including South Africa, China, Vietnam, Indonesia, Uganda, The Gambia and Brazil.
The researchers analysed individual-level data from 26 longitudinal studies, including nearly 70 000 participants exposed to TB from 1998 to 2018. The analysis examined variability across the studies, including skin and blood TB infection tests, and accounted for potentially confounding factors, such as HIV, exposure status and history of prior TB.
It found the overall effectiveness of BCG vaccination against all forms of tuberculosis was 18%. When stratified by age, BCG vaccination only significantly protected against all TB in children younger than five.
Among the subset of 14 cohorts reporting specific forms of TB, researchers found evidence of a small, significant reduction in the rate of pulmonary TB with vaccination (19% effectiveness).
“For both of these outcomes, protection was concentrated in young children. Whether BCG vaccination protects them from pulmonary tuberculosis is controversial and previous results have been heterogeneous,” the paper states.
They also found protection from death among BCG-vaccinated children in the study. This persisted until participants were aged 14.
“Unlike many of the mRNA COVID-19 vaccines, which we know are highly effective, there is widespread debate on the BCG vaccine’s effectiveness and duration of protection, as well as whether the vaccine works only in selective settings.
“Our findings indicate that BCG vaccination is effective at preventing tuberculosis in young children, and as TB in children is a highly debilitating and severe disease, vaccination should continue to be used,” said the study’s lead author, Leonardo Martinez, an assistant professor of epidemiology.
The paper suggests a booster shot be administered after childhood.
“Boosting immunoprotection is needed for older populations. Novel vaccines are urgently needed to supplement BCG vaccination in high-burden settings,” Martinez said.
Study details
Infant BCG vaccination and risk of pulmonary and extrapulmonary tuberculosis throughout the life course: a systematic review and individual participant data meta-analysis
Leonardo Martinez, Olivia Cords, Qiao Liu, Carlos Acuna-Villaorduna, Maryline Bonnet, Greg Fox, et al.
Published in The Lancet Global Health on 1 September 2022
Summary
Background
BCG vaccines are given to more than 100 million children every year, but there is considerable debate regarding the effectiveness of BCG vaccination in preventing tuberculosis and death, particularly among older children and adults. We therefore aimed to investigate the age-specific impact of infant BCG vaccination on tuberculosis (pulmonary and extrapulmonary) development and mortality.
Methods
In this systematic review and individual participant data meta-analysis, we searched MEDLINE, Web of Science, BIOSIS, and Embase without language restrictions for case-contact cohort studies of tuberculosis contacts published between Jan 1, 1998, and April 7, 2018. Search terms included “mycobacterium tuberculosis”, “TB”, “tuberculosis”, and “contact”. We excluded cohort studies that did not provide information on BCG vaccination or were done in countries that did not recommend BCG vaccination at birth. Individual-level participant data for a prespecified list of variables, including the characteristics of the exposed participant (contact), the index case, and the environment, were requested from authors of all eligible studies. Our primary outcome was a composite of prevalent (diagnosed at or within 90 days of baseline) and incident (diagnosed more than 90 days after baseline) tuberculosis in contacts exposed to tuberculosis. Secondary outcomes were pulmonary tuberculosis, extrapulmonary tuberculosis, and mortality. We derived adjusted odds ratios (aORs) using mixed-effects, binary, multivariable logistic regression analyses with study-level random effects, adjusting for the variable of interest, baseline age, sex, previous tuberculosis, and whether data were collected prospectively or retrospectively. We stratified our results by contact age and Mycobacterium tuberculosis infection status.
Findings
We identified 14 927 original records from our database searches. We included participant-level data from 26 cohort studies done in 17 countries in our meta-analysis. Among 68 552 participants, 1782 (2·6%) developed tuberculosis (1309 [2·6%] of 49 686 BCG-vaccinated participants vs 473 [2·5%] of 18 866 unvaccinated participants). The overall effectiveness of BCG vaccination against all tuberculosis was 18% (aOR 0·82, 95% CI 0·74–0·91). When stratified by age, BCG vaccination only significantly protected against all tuberculosis in children younger than 5 years (aOR 0·63, 95% CI 0·49–0·81). Among contacts with a positive tuberculin skin test or IFNγ release assay, BCG vaccination significantly protected against tuberculosis among all participants (aOR 0·81, 95% CI 0·69–0·96), participants younger than 5 years (0·68, 0·47–0·97), and participants aged 5–9 years (0·62, 0·38–0·99). There was no protective effect among those with negative tests, unless they were younger than 5 years (0·54, 0·32–0·90). 14 cohorts reported on whether tuberculosis was pulmonary or extrapulmonary (n=57 421). BCG vaccination significantly protected against pulmonary tuberculosis among all participants (916 [2·2%] in 41 119 vaccinated participants vs 334 [2·1%] in 16 161 unvaccinated participants; aOR 0·81, 0·70–0·94) but not against extrapulmonary tuberculosis (106 [0·3%] in 40 318 vaccinated participants vs 38 [0·2%] in 15 865 unvaccinated participants; 0·96, 0·65–1·41). In the four studies with mortality data, BCG vaccination was significantly protective against death (0·25, 0·13–0·49).
Interpretation
Our results suggest that BCG vaccination at birth is effective at preventing tuberculosis in young children but is ineffective in adolescents and adults. Immunoprotection therefore needs to be boosted in older populations.
News24 article – BCG vaccine prevents TB in young children, but not adults – new study (Open access)
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