BCG scar and positive tuberculin reaction associated with reduced child mortality in West Africa: a non-specific beneficial effect of BCG?

ML Garly, CL Martins, C Balé, MA Baldé… - Vaccine, 2003 - Elsevier
ML Garly, CL Martins, C Balé, MA Baldé, KL Hedegaard, P Gustafson, IM Lisse, HC Whittle…
Vaccine, 2003Elsevier
Previous studies have suggested that the bacille Calmette–Guérin (BCG) vaccine may have
a non-specific beneficial effect on childhood survival in areas with high mortality. We
examined whether BCG-vaccinated children with a BCG scar or a positive tuberculin
reaction had better survival than children without such reactions. As part of an ongoing two-
dose measles vaccine trial for which children were recruited at 6 months of age, we
examined 1813 children for BCG scar at 6 months of age and 813 BCG-vaccinated children …
Previous studies have suggested that the bacille Calmette–Guérin (BCG) vaccine may have a non-specific beneficial effect on childhood survival in areas with high mortality. We examined whether BCG-vaccinated children with a BCG scar or a positive tuberculin reaction had better survival than children without such reactions. As part of an ongoing two-dose measles vaccine trial for which children were recruited at 6 months of age, we examined 1813 children for BCG scar at 6 months of age and 813 BCG-vaccinated children were skin-tested for delayed hypersensitivity to tuberculin, tetanus and diphtheria. We found that BCG-vaccinated children with a BCG scar had significantly lower mortality compared with BCG scar-negative children, the mortality ratio in the first 12 months of follow-up being 0.41 (0.25–0.67). BCG-vaccinated children with a positive tuberculin test had a mortality ratio of 0.45 (0.24–0.85) compared with tuberculin negative children. These results were unchanged by control for potential confounders or using different cut-off points for a tuberculin-positive response. Exclusion of dead children who had HIV antibodies did not modify the estimate (mortality rate (MR)=0.46 (0.23–0.94)). After censoring for tuberculosis (TB) exposure at home, the mortality ratios for having a scar and being tuberculin-positive were 0.46 (0.27–0.79) or 0.42 (0.21–0.84), respectively. Children positive to tetanus or diphtheria in the skin test had the same mortality as children not responding to these vaccine-related antigens. Thus, BCG scar and a positive tuberculin reaction were associated with better survival in early childhood in an area with high mortality. Since nothing similar was found for responders to diphtheria–tetanus–pertussis (DTP) vaccine, and the effect could not be explained by protection against tuberculosis, the effect of BCG vaccination could be due to non-specific immune-stimulation protecting against other infections.
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