title: The Molecular and Spatial Epidemiology of Typhoid Fever in Rural Cambodia.
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.
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Duy
authors.initials: D
authors.lastname: Pham Thanh
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine, Oxford University, Oxford, United Kingdom.|The London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Corinne N
authors.initials: CN
authors.lastname: Thompson
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine, Oxford University, Oxford, United Kingdom.
authors.forename: Maia A
authors.initials: MA
authors.lastname: Rabaa
authors.affiliation: Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia.
authors.forename: Soeng
authors.initials: S
authors.lastname: Sona
authors.affiliation: Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia.
authors.forename: Sun
authors.initials: S
authors.lastname: Sopheary
authors.affiliation: Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia.
authors.forename: Varun
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia.
authors.forename: Catrin
authors.initials: C
authors.lastname: Moore
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Nga
authors.initials: N
authors.lastname: Tran Vu Thieu
authors.affiliation: Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia.
authors.forename: Lalith
authors.initials: L
authors.lastname: Wijedoru
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Holt
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom.|The Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Wong
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom.
authors.forename: Derek
authors.initials: D
authors.lastname: Pickard
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine, Oxford University, Oxford, United Kingdom.
authors.forename: Guy E
authors.initials: GE
authors.lastname: Thwaites
authors.affiliation: Centre for Tropical Medicine, Oxford University, Oxford, United Kingdom.|Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Day
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom.|The Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.affiliation: Centre for Tropical Medicine, Oxford University, Oxford, United Kingdom.|Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia.
authors.forename: Paul
authors.initials: P
authors.lastname: Turner
authors.affiliation: The London School of Hygiene and Tropical Medicine, London, United Kingdom.|Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia.|School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Parry
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine, Oxford University, Oxford, United Kingdom.|The London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Baker
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002160:Cambodia / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D006239:Haplotypes; D006801:Humans; D017720:Molecular Epidemiology; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012424:Rural Population; D012485:Salmonella typhi / Q000235:genetics*; D012621:Seasons; D013997:Time Factors; D014435:Typhoid Fever / Q000453:epidemiology* / Q000382:microbiology*
chemical_list: D001426:Bacterial Proteins