The Molecular and Spatial Epidemiology of Typhoid Fever in Rural Cambodia

Duy Pham Thanh,Stephen Baker,Soeng Sona,Derek Pickard,Catrin Moore,Guy E Thwaites,Sun Sopheary,Nga Tran Vu Thieu,Lalith Wijedoru,Nicholas Day,Paul Turner,Vanessa Wong,Varun Kumar,Maia A Rabaa,Gordon Dougan,Corinne N Thompson,Christopher M Parry,Kathryn E Holt,Edward T Ryan

doi:10.1371/journal.pntd.0004785

Abstract

Typhoid fever, caused by the bacterium Salmonella Typhi, is an endemic cause of febrile disease in Cambodia. The aim of this study was to better understand the epidemiology of pediatric typhoid fever in Cambodia. We accessed routine blood culture data from Angkor Hospital for Children (AHC) in Siem Reap province between 2007 and 2014, and performed whole genome sequencing (WGS) on the isolated bacteria to characterize the S. Typhi population. The resulting phylogenetic information was combined with conventional epidemiological approaches to investigate the spatiotemporal distribution of S. Typhi and population-level risk factors for reported disease. During the study period, there were 262 cases of typhoid within a 100 km radius of AHC, with a median patient age of 8.2 years (IQR: 5.1–11.5 years). The majority of infections occurred during the rainy season, and commune incidences as high as 11.36/1,000 in children aged <15 years were observed over the study period. A population-based risk factor analysis found that access to water within households and increasing distance from Tonle Sap Lake were protective. Spatial mapping and WGS provided additional resolution for these findings, and confirmed that proximity to the lake was associated with discrete spatiotemporal disease clusters. We confirmed the dominance of MDR H58 S. Typhi in this population, and found substantial evidence of diversification (at least seven sublineages) within this single lineage. We conclude that there is a substantial burden of pediatric typhoid fever in rural communes in Cambodia. Our data provide a platform for additional population-based typhoid fever studies in this location, and suggest that this would be a suitable setting in which to introduce a school-based vaccination programme with Vi conjugate vaccines.

Highlights

IntroductionTyphi) is the cause of the human infection typhoid fever, a systemic disease predominantly diagnosed in children and young adults in low-income settings [1]
Typhoid fever is an infectious disease caused by the bacterium Salmonella Typhi
Typhoid fever is a common cause of fever requiring hospital treatment in Cambodia, but limited data is available on the epidemiology of the disease

Summary

Introduction

Typhi) is the cause of the human infection typhoid fever, a systemic disease predominantly diagnosed in children and young adults in low-income settings [1]. S. Typhi is primarily contracted via ingestion of food or water contaminated with human feces from patients excreting the organism, and typhoid fever remains a major public health issue in areas with poor sanitation and limited access to safe water [2]. The control of typhoid fever is largely dependent on improving the availability of clean water, hygienic food preparation and access to adequate sanitation, but such interventions are substantial challenges in many locations where typhoid remains endemic [3]. Active case detection and appropriate antimicrobial therapy are currently the principal methods for controlling this disease in endemic locations. The lack of rapid and reliable diagnostics and the emergence of antimicrobial resistance (AMR) reduce the effectiveness of these strategies [4,5]

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