Non-specific effects of rabies vaccine on the incidence of common infectious disease episodes: study protocol for a randomized controlled trial

Abstract

Background: Vaccines may cause non-specific effects (NSEs) on morbidity and mortality through immune-mediated mechanisms that are not explained by the prevention of the targeted disease. Much of the evidence for NSEs comes from observational studies with a high risk of bias, and there is a clear need for new data from randomized controlled trials. Recently, it was proposed that rabies vaccine has protective NSEs in people and in animals. The aim of the proposed study is to determine whether rabies vaccine reduces the incidence rate of episodes of common infectious disease syndromes in a population of veterinary students on the island of St. Kitts. Methods: The trial design is a single-site, two-arm, parallel-group, participant-blinded, randomized, placebo-controlled, two-sided comparative study, with an internal pilot study for blinded sample size re-estimation. Allocation to study arm is by block randomization stratified by sex within cohort with a 1:1 allocation ratio. The primary study outcome is the number of new weekly episodes of common infectious diseases including respiratory, diarrheal and febrile illnesses. A vaccine immunogenicity ancillary study is planned. Discussion: Demonstration of a non-specific protective effect of rabies vaccine against unrelated respiratory, gastrointestinal and febrile illnesses would provide supportive evidence for the design of similar studies in children in populations with a high burden of these illnesses.

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

“…Average length of participation, event rate for control group and negative binomial dispersion parameter were estimated from data collected over 7 weeks of a pilot study of rates of CID episodes in 90 RUSVM students from 21 May to 8 July 2018. The planned blinded sample size re-estimation was conducted on 22 November 2019, based on data from the first three cohorts to complete the study (n = 351), and resulted in a recalculated target sample size of 584 29 . The increase in sample size was largely due to a lower-than-expected rate of new episodes of CID.…”