Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, United Kingdom
Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, United Kingdom; Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, United Kingdom; London School of Hygiene & Tropical Medicine, London, United Kingdom; Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Australia
Cecilia Mbae
Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya
Ronald Ngetich
Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya
Susan M Kavai
Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya
Celestine Wairimu
Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya
Stephen Anyona
Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya
Naomi Gitau
Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya
Robert Sanaya Onsare
Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya
Beatrice Ongandi
Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya
Sebastian Duchene
Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
Mohamed Ali
Department of International Health, John’s Hopkins University, Baltimore, United States
John David Clemens
International Diarrheal Diseases Research Centre, Dhaka, Bangladesh
Kathryn E Holt
London School of Hygiene & Tropical Medicine, London, United Kingdom; Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Australia
Gordon Dougan
Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, United Kingdom
Background: Understanding the dynamics of infection and carriage of typhoid in endemic settings is critical to finding solutions to prevention and control. Methods: In a 3-year case-control study, we investigated typhoid among children aged <16 years (4670 febrile cases and 8549 age matched controls) living in an informal settlement, Nairobi, Kenya. Results: 148 S. Typhi isolates from cases and 95 from controls (stool culture) were identified; a carriage frequency of 1 %. Whole-genome sequencing showed 97% of cases and 88% of controls were genotype 4.3.1 (Haplotype 58), with the majority of each (76% and 88%) being multidrug-resistant strains in three sublineages of the H58 genotype (East Africa 1 (EA1), EA2, and EA3), with sequences from cases and carriers intermingled. Conclusions: The high rate of multidrug-resistant H58 S. Typhi, and the close phylogenetic relationships between cases and controls, provides evidence for the role of carriers as a reservoir for the community spread of typhoid in this setting. Funding: National Institutes of Health (R01AI099525); Wellcome Trust (106158/Z/14/Z); European Commission (TyphiNET No 845681); National Institute for Health Research (NIHR); Bill and Melinda Gates Foundation (OPP1175797).
