Is diphtheria-tetanus-pertussis (DTP) associated with increased female mortality? A meta-analysis testing the hypotheses of sex-differential non-specific effects of DTP vaccine.
BACKGROUND
Ten years ago, we formulated two hypotheses about whole-cell diphtheria-tetanus-pertussis (DTP) vaccination: first, when given after BCG, DTP increases mortality in girls and, second, following DTP there is an increase in the female/male mortality rate ratio (MRR). A recent review by WHO found no convincing evidence that DTP increases mortality in females.


METHODS
We used previous DTP reviews as well as the recent WHO review for assessing the hypotheses. As pre-specified we excluded studies with survival or frailty bias; if children had received BCG and DTP simultaneously; and if the children had received neonatal vitamin A.


RESULTS
In seven studies of BCG-vaccinated children, DTP vaccination was associated with a 2.54 (95% CI 1.68-3.86) increase in mortality in girls (with no increase in boys [ratio 0.96, 0.55-1.68]). In 10 studies of BCG-vaccinated children, the female-to-male mortality ratio was 2.45 (1.48-4.06) times higher after DTP than before DTP. In 15 studies of children who had received DTP after previous BCG vaccination, mortality was 1.53 (1.21-1.93) times higher in girls than boys. The findings were similar in studies conducted before and after formulation of the hypotheses.


CONCLUSIONS
The two hypotheses were confirmed in the studies that fulfilled pre-specified criteria.
['Aaby|Peter|P|', 'Ravn|Henrik|H|', 'Fisker|Ane B|AB|', 'Rodrigues|Amabelia|A|', 'Benn|Christine S|CS|']
D002675:Child, Preschool D015721:Diphtheria-Tetanus-Pertussis Vaccine D019317:Evidence-Based Medicine D005260:Female D006801:Humans D007223:Infant D008297:Male D064887:Observational Studies as Topic D016032:Randomized Controlled Trials as Topic D012727:Sex Characteristics D012737:Sex Factors D016019:Survival Analysis D014611:Vaccination
DTP BCG Diphtheria-tetanus-pertussis vaccine Non-specific effects of vaccines Sex-differential effects Strategic Advisory Group of Experts on Immunization (SAGE)