BCG-scarring and improved child survival: A combined analysis of studies of BCG-scarring.

INTRODUCTION: Bacillus Calmette-Guerin (BCG) vaccine against tuberculosis (TB) is recommended given at birth in TB-endemic areas. Currently, BCG vaccination programs use "BCG vaccination coverage by 12 months of age" as the performance indicator. Previous studies suggest that BCG-vaccinated children, who develop a scar, have better overall survival compared with BCG-vaccinated children, who do not develop a scar. We summarised the available studies of BCG-scarring and child survival. METHODS: A structured literature search for studies with original data and analysis of BCG-scarring and mortality. Combined analyses on effect of BCG-scarring on overall mortality. RESULTS: We identified six studies covering seven cohorts, all from Guinea-Bissau, West Africa, with evaluation of BCG-scarring among BCG-vaccinated children and follow-up for mortality. Determinants for BCG-scarring were BCG strain, intra-dermal injection route, size of injection wheal, and co-administered vaccines and micronutrients. In a combined analysis, having a BCG scar vs. no BCG scar was associated with a mortality rate ratio (MRR) of 0.61 (95% CI: 0.51-0.74). The proportion with a BCG scar varied from 52-93%; the estimated effect of a BCG scar was not associated with the scar prevalence. The effect was strongest in the first (MRR=0.48 (0.37-0.62)) and second (MRR=0.63 (0.44-0.92)) year of life, and in children BCG-vaccinated in the neonatal period (MRR=0.45 (0.36-0.55). The effect was not explained by protection against TB. CONCLUSION: Confounding and genetic factors are unlikely to explain the strong association between BCG-scarring and subsequent survival. Including "BCG scar prevalence" as a BCG vaccination program performance indicator should be considered. The effect of revaccinating scar-negative children should be studied.