Protection conferred by typhoid fever against recurrent typhoid fever in urban Kolkata.

Author summary Recurrent episodes of typhoid fever can occur in individuals, particularly those living in typhoid endemic regions. Natural typhoid infection should, in theory, offer a degree of protection against future typhoid, however, this protection has only been assessed in a limited number of studies, none of which were conducted recently nor in the context of a carefully controlled clinical trial. The findings from our study, which were based on data from a cluster-randomized trial of Vi polysaccharide vaccine in Kolkata, India, suggest that previous typhoid fever does not provide an appreciable level of protection against future typhoid disease. This finding is important for informing mathematical modelers who predict transmission dynamics within a population and influence the design of effective vaccine intervention strategies. We evaluated the protection conferred by a first documented visit for clinical care of typhoid fever against recurrent typhoid fever prompting a visit. This study takes advantage of multi-year follow-up of a population with endemic typhoid participating in a cluster-randomized control trial of Vi capsular polysaccharide typhoid vaccine in Kolkata, India. A population of 70,566 individuals, of whom 37,673 were vaccinated with one dose of either Vi vaccine or a control (Hepatitis A) vaccine, were observed for four years. Surveillance detected 315 first typhoid visits, among whom 4 developed subsequent typhoid, 3 due to reinfection, defined using genomic criteria and corresponding to -124% (95% CI: -599, 28) protection by the initial illness. Point estimates of protection conferred by an initial illness were negative or negligible in both vaccinated and non-vaccinated subjects, though confidence intervals around the point estimates were wide. These data provide little support for a protective immunizing effect of clinically treated typhoid illness, though modest levels of protection cannot be excluded.