Non-specific effects of rabies vaccine on the incidence of self-reported common infectious disease episodes : a randomized controlled trial

Abstract

Vaccines may affect recipients’ immune systems in ways that change morbidity or mortality rates to unrelated infections in vaccinated populations. It has been proposed that these non-specific effects differ by type of vaccine and by sex, with non-live vaccines enhancing susceptibility of females to unrelated infections, and live vaccines enhancing resistance in both sexes. Rabies vaccine–a non-live vaccine–has been associated with protection against unrelated central nervous system infections. Data from randomized controlled trials are needed to assess this effect against other illnesses. This phase IV, single-site, participant-blinded, randomized, placebo-controlled trial in a population of veterinary students on the rabies-free island of St. Kitts assessed the effect of a primary course of rabies vaccine on the incidence rate of weekly self-reported new episodes of common infectious disease (CID) syndromes, defined as a new episode of any one of the following syndromes in a particular week: upper respiratory illness (URI), influenza-like illness (ILI), diarrheal illness (DIA) or undifferentiated febrile illness (UFI). As a secondary objective, we tested for modification of the effect of rabies vaccine on study outcomes by sex. 546 participants were randomized (274 to rabies vaccine and 272 to placebo). No statistically significant differences between groups were observed for any study outcomes: CID incidence rate ratio (IRR) 0.95 (95% CI 0.77–1.18); URI IRR 1.15 (95% CI 0.86–1.54); ILI IRR 0.83 (95% CI 0.54–1.27); DIA IRR 0.93 (95% CI 0.70–1.24) and UFI IRR 1.09 (95% CI 0.48–2.44). In a secondary analysis, there was little evidence that sex modified the effect of vaccination on any of the evaluated outcomes, although the power to detect this was low. In conclusion, rabies vaccine did not provide protection against mild self-reported illness among a young and healthy group of adults attending veterinary school.