Systematic Review of the Non-Specific Effects of Bacillus Calmette-Guérin Vaccine on Child Mortality

Abstract

Background: Until a different vaccine is given, BCG provides non-specific protection against diseases other than tuberculosis, mainly respiratory infections and sepsis. Methods: A systematic review was made using the databases Medline, Lilacs, Cochrane Library, Scopus and the WHO review of BCG, using the terms BCG, nonspecific effects, heterologous immunity, and child mortality. The objective was to quantify the effect of BCG on all-cause mortality until a different vaccine was given in children up to 5 years of age in low-income countries. Randomized trials and observational studies performed in low-income populations where all-cause mortality was reported were selected. Results: Fifty-nine articles were found. Nine studies had a low to moderate risk of bias; they consisted of two randomized trials, six cohort studies and one case-control study; they were performed in Guinea-Bissau, India, Benin, Malawi and Senegal. The effect estimates were homogeneous, with I2=0.0% (p=0.71). Meta-analysis of all nine studies using a random effects model yielded an effect estimate of 0.56 (95% CI 0.46-0.69). The combined estimate for the two randomized trials of BCG-Denmark that had a low risk of bias was 0. 52 (95% CI 0.33- 0.82). Conclusions: The two randomized trials and the seven observational studies suggests that, until a different vaccine is given, administration of the strains of BCG used in these studies approximately halved all-cause mortality in children under five years of age in these low-income countries.