AUTHORS
Dilip Abraham, Lalithambigai Kathiresan, Midhun Sasikumar, Kristen Aiemjoy, Richelle C. Charles, Dilesh Kumar, Rajan Srinivasan, Catherine Troman, Elizabeth Gray, Christopher B. Uzzell, Jacob John, Balaji Veeraraghavan, Nicholas C. Grassly, Venkata Raghava Mohan
ABSTRACT
Background
Blood culture-based surveillance for typhoid fever has limited sensitivity, and operational challenges are encountered in resource-limited settings. Environmental surveillance targeting Salmonella Typhi (S. Typhi) shed in wastewater (WW), coupled with cross-sectional serosurveys of S. Typhi-specific antibodies estimating exposure to infection, emerges as a promising alternative.
Methods
We assessed the feasibility and effectiveness of wastewater (WW) and sero-surveillance for S. Typhi in Vellore, India, from May 2022 to April 2023. Monthly samples were collected from 40 sites in open drainage channels and processed using standardized protocols. DNA was extracted and analyzed via quantitative PCR for S. Typhi genes (ttr, tviB, staG) and the fecal biomarker HF183. Clinical cases of enteric fever were recorded from four major hospitals, and a cross-sectional serosurvey measured hemolysin E (HlyE) IgG levels in children under 15 years of age to estimate seroincidence.
Results
7.50% (39/520) of grab and 15.28% (79/517) Moore swabs were positive for all 3 S. Typhi genes. Moore swab positivity was significantly associated with HF183 (adjusted odds ratio (aOR): 3.08, 95% CI: 1.59–5.95) and upstream catchment population (aOR: 4.67, 1.97–11.04), and there was increased detection during monsoon season – membrane filtration (aOR: 2.99, 1.06–8.49), and Moore swab samples (aOR: 1.29, 0.60–2.79).
Only 11 blood culture-confirmed typhoid cases were documented over the study period. Estimated seroincidence was 10.4/100 person-years (py) (95% CI: 9.61 – 11.5/100 py). The number of S. Typhi positive samples at a site was associated with the estimated sero-incidence in the site catchment population (incidence rate ratios: 1.14 (1.07–1.23) and 1.10 (1.02–1.20) for grab and Moore swabs respectively.
Conclusions
These findings underscore the utility and effectiveness of alternate surveillance approaches to estimating the incidence of S. Typhi infection in resource-limited settings, offering valuable insights for public health interventions and disease monitoring strategies where conventional methods are challenging to implement.
Author summary
Our study explores the potential of detecting Salmonella Typhi in wastewater, informing public health strategies, guiding vaccination campaigns, and monitoring the effectiveness of interventions, contributing to better disease control and prevention policies. S. Typhi positivity rates of 7.50% and 15.30% were observed in grab samples and Moore swabs, respectively, and significant correlations were found between S. Typhi positivity in Moore swabs and fecal contamination marker levels in wastewater samples. The study also estimated that the community seroincidence for typhoid was 10.40/100 person-years and that S. Typhi detections in WW positively correlated with seroincidence. The study reveals significant associations between wastewater S. Typhi positivity and typhoid seroincidence, seasonal variations, and population dynamics, providing deeper insights into the epidemiology of typhoid fever. Findings from this study suggest that surveillance of pathogens from environmental sources like wastewater might serve as an alternative to direct estimation of disease burden in areas where traditional surveillance methods are either not feasible or not cost-effective.
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