Differences in female-male mortality after high-titre measles vaccine and association with subsequent vaccination with diphtheria-tetanus-pertussis and inactivated poliovirus: reanalysis of West African studies

Background Females given high-titre measles vaccine (HTMV) have high mortality; diphtheria-tetanus-pertussis (DTP) vaccination might be associated with increased female mortality. We aimed to assess whether DTP or inactivated poliovirus (IPV) administered after HTMV was associated with increased female-male mortality ratio. Methods In three trials from West Africa, 2000 children were randomised to HTMV or control vaccine at 4–5 months of age; a second vaccination was given at age 9–10 months (standard measles vaccine). Children in high-titre groups were given IPV or DTP-IPV. Another 944 children received HTMV as routine vaccination in Senegal. Findings When we compared high-titre and control groups, no difference in mortality between the first and the second vaccination was noted. After the second vaccination, the female-male mortality ratio was 1•84 (95% CI 1•19–2•84) in children in the high-titre groups who received DTP-IPV or IPV, and 0•59 (0•34–1•04) in controls who received standard measles vaccine (p=0•007). Children who received HTMV but no additional DTP-IPV or IPV had a female-male mortality ratio of 0•83 (0•41–1•67). This ratio was 2•22 (1•04–4•71) for children who received DTP-IPV after routine HTMV and 1•00 (0•68–1•47) for those who did not. When we combined the results from all trials, the female-male mortality ratio was 1•93 (1•33–2•81) for those who received DTP or IPV after HTMV, and 0•96 (0•69–1•34) for those who did not (p=0•006). Interpretation A change in sequence of vaccinations, rather than HTMV itself, may have been the cause of increased female mortality in these trials.