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

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. 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. 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). A change in sequence of vaccinations, rather than HTMV itself, may have been the cause of increased female mortality in these trials.