Sex-differential effects on mortality of BCG and diphtheria-tetanus-pertussis vaccines in a rural area with high vaccination coverage: observational study from Senegal

Abstract

Diphtheria-tetanus-pertussis (DTP) may be associated with increased female mortality; the effect of co-administration with BCG is not known. Between 1989 and 1997, we examined female and male mortality rates in rural Senegal where 7824 infants received the first dose of DTP and inactivated polio vaccine (DTP-IPV) with BCG. Subsequent doses of DTP-IPV were administered alone. We analysed mortality according to sex and number of doses of DTP-IPV vaccine. BCG and DTP-IPV1 simultaneously reduced mortality from 60/1000 person-years in unvaccinated girls to 35/1000 person-years, but mortality increased with subsequent doses of DTP-IPV to 45/1000 person-years. Among boys, BCG and DTP-IPV1 simultaneously reduced mortality from 72/1000 person-years to 60/1000 person-years and mortality decreased further with subsequent doses of DTP-IPV to 34/1000 person-years. In age-adjusted analyses, female-male mortality rate ratios were 0.83(95% CI 0.50-1.40) among unvaccinated children and 0.58 (95% CI 0.35-0.96) among children vaccinated simultaneously with BCG and DTP-IPV1, but increased to 1.17 (95% CI 0.67-2.03) after DTP-IPV2, and 1.63 (95% CI 0.86-3.10) after DTP-IPV3. Difference in vaccination coverage could not explain these sex-differential patterns; girls had significantly better weight-for-age than boys so nutritional status did not explain the increase in female mortality after DTP-IPV3. Whereas BCG co-administered with DTP-IPV was associated with lower female than male mortality, subsequent DTP-IPV vaccinations were associated with an increase in female mortality relative to male mortality.