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.
