Divergent female-male mortality ratios associated with different routine vaccinations among female-male twin pairs

Int J Epidemiol. 2004 Apr;33(2):367-73. doi: 10.1093/ije/dyh004.


Background: Observational studies have suggested that vaccinations have non-specific effects that differ by sex. In the absence of randomized trials, studies of female-male twin pairs would allow us to investigate whether an intervention had sex-specific effects on survival. We therefore examined mortality patterns among female-male twin pairs according to vaccination status. Design We identified female-male twin pairs using the population registers from one urban district and three rural studies from Guinea-Bissau and Senegal and examined the female-male mortality ratio (MR) according to the last vaccine received among pairs in which a death occurred before 18 months of age. As background information, we examined sex- and age-specific mortality patterns in the pre-vaccination era. Subjects In all, 626 female-male twin pairs identified between 1978 and 2000.

Results: There was no sex difference in mortality for boys and girls in the pre-vaccination era. In the combined analysis of all studies, the female-male MR was 0.25 (95% CI: 0.05, 0.93) for pairs having received Bacille Calmette-Guerin (BCG) as the last vaccine, 7.33 (95% CI: 2.20, 38.3) for pairs having received diphtheria, tetanus, pertussis (DTP) as the last vaccine, and 0.40 (95% CI: 0.04, 2.44) for pairs having received measles vaccine as the last vaccine. The female-male MR varied significantly for BCG compared with DTP (exact test of homogeneity, P < 0.001) and for DTP compared with measles vaccine (exact test of homogeneity, P = 0.001).

Conclusion: Non-specific effects of routine vaccinations are likely to be important and influence sex-specific mortality patterns in areas with high mortality. The effects of vaccines need to be considered in the planning of immunization programmes for low-income countries.

Publication types

  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • BCG Vaccine
  • Developing Countries
  • Diphtheria-Tetanus-Pertussis Vaccine
  • Female
  • Guinea-Bissau / epidemiology
  • Humans
  • Immunization Schedule
  • Infant
  • Infant Mortality*
  • Male
  • Measles Vaccine
  • Risk Factors
  • Rural Health / statistics & numerical data
  • Senegal / epidemiology
  • Sex Factors
  • Urban Health / statistics & numerical data
  • Vaccination / statistics & numerical data*


  • BCG Vaccine
  • Diphtheria-Tetanus-Pertussis Vaccine
  • Measles Vaccine