Meta-analysis of 14 studies indicated that BCG vaccination protects against Mycobacterium tuberculosis infection in children under 16 years old, while a six-study analysis determined that the vaccine protects and against progression from infection to active disease.
Individual trials indicate that BCG vaccination has 60% to 80% protective efficacy against severe TB in children. The recently developed T-cell-based interferon γ release assay can detect M tuberculosis infection and thus determine whether the vaccine protects against infection, not just disease. TB remains the leading cause of death in HIV-infected people in many parts of Africa.
Researchers scoured electronic databases from 1950 to November 2013, looking for articles on vaccinated and unvaccinated children under 16 years old with known recent exposure to pulmonary TB. The investigators also searched reference lists, hand-searched journals, and consulted experts.
All children in candidate studies were tested for M tuberculosis with an interferon γ release assay, and the researchers analyzed protection against M tuberculosis infection by interferon γ release assay results. They used random effects meta-analysis to combine risk estimates from individual studies.
The analysis included 14 studies of 3855 children. Estimated overall protective efficacy against infection in vaccinated versus unvaccinated children was 19% (risk ratio [RR] 0.81, 95% confidence interval [CI] 0.71 to 0.92). Protection was similar when the analysis focused individually on two types of interferon γ release assay, ELISpot or QuantiFERON.
Next the researchers analyzed six studies that assessed progression from TB infection to active disease. In these six studies protection against infection in all children (regardless of whether they later developed disease) was 27% (RR 0.73, 95% CI 0.61 to 0.87), while protection against active TB was 71% (RR 0.29, 95% CI 0.15 to 0.58). In infected children, BCG vaccination protection against progression from infection to active disease was 58% (RR 0.42, 95% CI 0.23 to 0.77).
The researchers believe their findings “support a paradigm shift in the understanding of how antimycobacterial vaccines (new and old) can work, from the view that BCG protects against disease but not against infection to one that it protects against infection itself.”
“Given the incomplete control of tuberculosis, especially in high burden countries,” the authors propose, “optimization of use of BCG is sensible. Our analysis supports vaccinating children as soon as possible after birth to prevent infection and disease.”
Source: A. Roy, M. Eisenhut, R.J. Harris, L.C. Rodrigues, S. Sridhar, S. Habermann, L. Snell, P. Mangtani, I. Adetifa, A. Lalvani, I. Abubakar. Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis. BMJ. 2014; 349: g4643.