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
BCG;
Diphtheria-tetanus-pertussis vaccine;
DTP;
Non-specific effects of vaccines;
Sex-differential effects;
Strategic Advisory Group of Experts on Immunization (SAGE);
VITAMIN-A SUPPLEMENTATION;
BIRTH-WEIGHT CHILDREN;
ROUTINE VACCINATIONS;
CHILDHOOD MORTALITY;
GUINEA-BISSAU;
MEASLES-VACCINE;
RANDOMIZED-TRIAL;
BCG VACCINATION;
PEDIATRIC WARD;
RURAL AREA;
D O I:
10.1093/trstmh/trw073
中图分类号:
R1 [预防医学、卫生学];
学科分类号:
1004 ;
120402 ;
摘要:
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.