Clinical Question: Does exposure to multiple-antigen vaccine or aggregated vaccine increase the risk of infectious disease hospitalization?

Setting: Population-based

Study Design: Cohort (prospective)

Synopsis: Many physicians and laypersons are concerned that vaccination with multiple-antigen vaccines or cumulative vaccines could cause immune dysfunction secondary to an “overload” mechanism, resulting in an increased risk of subsequent infectious disease. The investigators monitored all children born in Denmark from January 1, 1990, through December 31, 2001. Individuals living in Denmark are given a unique identification number at birth, allowing accurate linkage to information on childhood vaccinations, infectious disease hospitalizations, and potential confounding factors. Vaccines routinely given during this time included the Haemophilus influenzae type B (Hib), diphtheriatetanus-inactivated pertussis, inactivated poliovirus, live attenuated oral polio virus, and mumps-measles-rubella. The effect of vaccination was evaluated in three different periods:within 14 days, 14 days through three months, and more than three months after vaccination. Appropriate statistical analyses accounted for potential confounders including sex, place of birth, birth weight, month of birth, and mother’s age at birth.

In the 805,206 children born during the study period, the investigators identified 84,317 cases of hospitalization because of infectious disease. Adequate monitoring occurred for more than 98 precent of the children. The only adverse association occurred between exposure to the Hib vaccine and subsequent hospitalization for acute upper respiratory tract infection more than three months after exposure (relative risk = 1.05; 95% confidence interval [CI], 1.01 to 1.08; number needed to treat to harm = 31,250; 95% CI, 19,531 to 156,250). Given that the authors tested 42 possible associations, it was likely that they would find a significant difference in one by chance alone. In addition, there was no temporal or dose-response relationship between Hib vaccination and hospitalization for acute upper respiratory tract infection, arguing against a causal relationship. No association was found between cumulative vaccine exposure and infectious diseases.

Bottom Line: There is no evidence of an increased risk of hospitalizations caused by infectious disease in children receiving multiple-antigen vaccines or aggregated vaccines. (Level of Evidence: 1b)