Childhood vaccination and nontargeted infectious disease hospitalization

JAMA. 2005 Aug 10;294(6):699-705. doi: 10.1001/jama.294.6.699.


Context: It has been hypothesized that multiple-antigen vaccines, such as measles-mumps-rubella vaccine, or aggregated vaccine exposure could lead to immune dysfunction, resulting in nontargeted infectious diseases as a result of an "overload" mechanism.

Objective: To evaluate the relationship between routinely administered childhood vaccines (Haemophilus influenzae type b; diphtheria-tetanus-inactivated poliovirus; diphtheria-tetanus-acellular pertussis-inactivated poliovirus; whole-cell pertussis; measles-mumps-rubella; oral poliovirus) and hospitalization for nontargeted infectious diseases.

Design, setting, and participants: Population-based cohort comprising all children born in Denmark from 1990 through 2001 (N = 805 206). Longitudinal information was collected on type and number of vaccine doses received and hospitalization with infectious diseases, specifically acute upper respiratory tract infection, viral and bacterial pneumonia, septicemia, viral central nervous system infection, bacterial meningitis, and diarrhea.

Main outcome measures: Rate ratios for each type of infectious disease according to vaccination status.

Results: During 2,900,463 person-years of follow-up, 84,317 cases of infectious disease hospitalization were identified. Out of 42 possible associations (6 vaccines and 7 infectious disease categories), the only adverse association was for Haemophilus influenzae type b vaccine and acute upper respiratory tract infection (rate ratio, 1.05; 95% confidence interval, 1.01-1.08 comparing vaccinated participants with unvaccinated participants). This one adverse association of 42 possible outcomes was within the limits of what would be expected by chance alone and the effect was not temporal or dose-response. When considering aggregated vaccine exposure, we found no adverse associations between an increasing number of vaccinations and infectious diseases.

Conclusion: These results do not support the hypotheses that multiple-antigen vaccines or aggregated vaccine exposure increase the risk of nontargeted infectious disease hospitalization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Communicable Diseases / epidemiology*
  • Communicable Diseases / immunology
  • Confounding Factors, Epidemiologic
  • Denmark / epidemiology
  • Hospitalization / statistics & numerical data*
  • Humans
  • Risk
  • Vaccination / adverse effects
  • Vaccination / methods
  • Vaccination / statistics & numerical data*
  • Vaccines, Combined / adverse effects
  • Vaccines, Combined / immunology


  • Vaccines, Combined