Protection Against Recurrent Typhoid Fever Conferred by a Prior Episode: Evidence from a Large Cohort Study in Dhaka, Bangladesh.

BACKGROUND: Understanding the extent of protection against typhoid fever conferred by naturally occurring typhoid is essential for transmission modeling and vaccine policy development. However, data on the level of protection from natural typhoid against recurrent typhoid episodes are sparse. METHODS: We analyzed data from a cluster-randomized trial of a typhoid conjugate vaccine conducted in Dhaka, Bangladesh. A cohort of blood culture-confirmed typhoid patients (index cases) and matched controls (1:4 ratio) from the community who had not received the typhoid vaccine were followed for up to six years to identify recurrent typhoid episodes. A recurrent typhoid episode was defined as one occurring more than 30 days after the onset of the initial episode and/or involving a strain with a different antimicrobial resistance profile. Febrile patients who tested negative for Salmonella Typhi through passive surveillance were also evaluated as facility-based controls. Stratified Cox proportional hazards models were used to estimate hazard ratios (HRs) for recurrent typhoid episodes. RESULTS: We identified 13 recurrent episodes among 940 index cases and 12 episodes among 3,760 community-based controls, yielding incidence rates of 741 and 158 per 100,000 person-years, respectively, with an adjusted hazard ratio (aHR) of 3.7; 95%CI: 1.8, 7.9; p<0.001. However, when using facility-based controls to prevent healthcare utilization bias, there was no statistically significant difference between groups (aHR: 1.5, 95%CI: 0.8, 2.8; p=0.160). CONCLUSION: In this typhoid-endemic population comprising both children and adults, we found no evidence that natural typhoid fever confers protection against recurrent typhoid episodes.