Integrating environmental and clinical surveillance for typhoid: insights from a prospective wastewater surveillance study in urban India.

Abstract

Wastewater surveillance can be used to monitor Salmonella enterica serovar Typhi (S Typhi) transmission in the community, allowing early outbreak detection and vaccine effect evaluation. This study aims to establish the baseline detection rate of S Typhi in wastewater and to evaluate its relationship with the clinical burden of typhoid before typhoid conjugate vaccine (TCV) introduction in an endemic urban context. We conducted wastewater surveillance for S Typhi in Vellore, Tamil Nadu, India, from Dec 12, 2022, to June 30, 2023, before implementing a cluster-randomised trial of a TCV. 723 grab and 723 Moore swabs were collected from 50 sampling locations and concentrated using Nanotrap A beads for grab samples and Moore swabs as a passive sampler. S Typhi was detected using multiplex quantitative PCR targeting ttr, staG, and tviB genes. Blood culture-confirmed cases of typhoid fever were recorded through hospital-based surveillance established as a part of an independent ongoing VeVact study, an observer-blinded, cluster-randomised trial of a TCV (TyphiBEV). We calculated proportions of typhoid positivity in wastewater sampling sites and the incidence rates of blood culture-confirmed typhoid cases. Spatial analysis was performed to detect statistically significant hotspots for typhoid fever cases in the study area. Bayesian inference using the integrated nested Laplace approximation and mixed-effects spatiotemporal regression quantified associations between wastewater S Typhi detection and typhoid incidence. S Typhi was detected in 80 (5·5%) of 1446 wastewater samples, higher in grab samples (60 [8·3%] of 723) than in Moore swabs (20 [2·8%] of 723). 207 typhoid cases were recorded, with cases peaking between March and May, 2023. Spatial clustering of typhoid cases corresponded with higher wastewater S Typhi detection. The proportion of wastewater samples that were positive over the study period correlated with typhoid incidence when analysed across the 60 vaccine trial clusters (Spearman's ρ=0·32; p=0·014) or the non-overlapping wastewater site catchment areas (ρ=0·57; p<0·0001). Mixed-effects logistic regression adjusting for spatiotemporal random effects, levels of human faecal contamination, rainfall, and laboratory processing method, gave a 2·43 (95% CI 1·38-4·27) times higher odds of detecting S Typhi in wastewater samples for each 10-fold increase in typhoid fever incidence. Wastewater surveillance data correlate with clinical disease incidence in an endemic setting and could be used to monitor targeted interventions, including TCV introduction. The Gates Foundation.