Environmental surveillance for Salmonella Typhi as a tool to estimate the incidence of typhoid fever in low-income populations
Authors: Uzzell Christopher B. , Troman Catherine M. , Rigby Jonathan , Mohan Venkata Raghava , John Jacob , Abraham Dilip , Srinivasan Rajan , Nair Satheesh , Meschke John Scott , Elviss Nicola , Kang Gagandeep , Feasey Nicholas , Grassly Nicholas C. 
Published: May 2021

AbstractBackgroundThe World Health Organisation recommends prioritised use of recently prequalified typhoid conjugate vaccines in countries with the highest incidence of typhoid fever. However, representative typhoid surveillance data are lacking in many low-income countries because of the costs and challenges of diagnostic clinical microbiology. Environmental surveillance (ES) of Salmonella Typhi in sewage and wastewater using molecular methods may offer a low-cost alternative, but its performance in comparison with clinical surveillance has not been assessed.Methodology/Principal FindingsWe developed a harmonised protocol for typhoid ES and its implementation in communities in India and Malawi where it will be compared with findings from hospital-based surveillance for typhoid fever. The protocol includes methods for ES site selection based on geospatial analysis, grab and trap sample collection at sewage and wastewater sites, and laboratory methods for sample processing, concentration and quantitative PCR to detect Salmonella Typhi. The optimal locations for ES sites based on digital elevation models and mapping of sewage and river networks are described for each community and their suitability confirmed through field investigation. We will compare the prevalence and abundance of Salmonella Typhi in ES samples collected each month over a 12-month period to the incidence of blood culture confirmed typhoid estimated from cases recorded at referral hospitals serving the study areas and community surveys of healthcare seeking for individuals with fever.SignificanceIf environmental detection of Salmonella Typhi correlates with the incidence of typhoid fever estimated through clinical surveillance, typhoid ES may be a powerful and low-cost tool to estimate the local burden of typhoid fever and support the introduction of typhoid conjugate vaccines. Typhoid ES could also allow the impact of vaccination to be assessed and rapidly identify circulation of drug resistant strains.Author SummaryTyphoid fever is a bacterial enteric infection that remains a significant health burden to the 6.4 billion people living in low- and middle-income countries. The WHO recently prequalified highly immunogenic typhoid conjugate vaccines (TCVs) and recommended that the introduction of public vaccination programmes should be based on an understanding of the local epidemiology of infection. However, representative data on the community level describing incidence of microbiologically confirmed typhoid cases are limited, reflecting the costs and challenges of implementing blood culture for Salmonella Typhi (S. Typhi). Therefore, cost-effective alternative means of community surveillance are required to assess overall burden of disease.We developed a protocol for typhoid environmental surveillance, including methods for the identification of suitable sampling sites, sample collection and laboratory processing. The detection of S. Typhi in wastewater and sewage samples will be examined against the outcomes of hospital-based surveillance for typhoid fever with healthcare utilisation surveys to evaluate and validate the use of ES as an effective means of assessing community level incidence of typhoid. The findings of this study will inform potential wider implementation of ES for typhoid to support the introduction of TCVs and monitor their impact.