Sex-differential effects of diphtheria-tetanus-pertussis vaccine for the outcome of paediatric admissions? A hospital based observational study from Guinea-Bissau

Abstract

Background: In spite of protection against the targeted infections, a large volume of observational data indicates that diphtheria-tetanus-pertussis (DTP) vaccine may have a negative impact on overall childhood mortality in low-income countries, especially in girls.

Methods: In an observational study using data from Bandim Health Project's continuous registration of all admissions to the paediatric ward at the National Hospital Simão Mendes in Bissau, we investigated whether DTP was associated with higher female than male in-hospital mortality (female/male case fatality ratio (F/M CFR)) and whether the CFR comparing DTP-vaccinated and DTP-unvaccinated children differed by sex. We included children aged 6 weeks to 8 months (274 days) admitted to the paediatric ward with a vaccination card seen during admission.

Results: From May 2001 to January 2008, 4230 children aged 6 weeks to 8 months were admitted and 3450 (82%; 1997 boys, 1453 girls) presented a vaccination card. The proportion presenting a vaccination card and DTP coverage did not differ by sex. During admission, 16% (200/1250) of the girls and 13% (220/1694) of the boys who had received DTP died. The F/M CFR among the 2944 DTP-vaccinated children was 1.23 (1.03-1.46); while it was 0.95 (0.66-1.38) among the 506 children who had not received DTP. DTP-vaccinated children were older and had better socioeconomic status. Adjusted for age, BCG-vaccination, residence, and maternal education the CFR comparing DTP-vaccinated boys with DTP-unvaccinated boys was 0.84 (0.63-1.11), while the CFR comparing DTP-vaccinated girls with DTP-unvaccinated girls was 1.28 (0.90-1.83) (p = .07 for same effect in boys and girls).

Conclusion: Among DTP-vaccinated children, female in-hospital mortality was higher than male in-hospital mortality and DTP-vaccination tended to be associated with higher mortality in girls. The data are consistent with DTP having negative effects on mortality for girls. Further studies are necessary to design the optimal vaccination programme for both sexes.

Keywords: Child mortality; Diphtheria-tetanus-pertussis vaccine; Heterologous (non-specific) effects of vaccines; Immunisation; Sex-differences.