Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya

eLife

Gordon Dougan¹  Celestine Wairimu²  Stephen Anyona²  Susan M Kavai²  Cecilia Mbae²  Naomi Gitau²  Beatrice Ongandi²  Robert Sanaya Onsare²  Ronald Ngetich²  Samuel Kariuki³  Mohamed Ali⁴  Sebastian Duchene⁵  John David Clemens⁶  Kathryn E Holt⁷  Zoe A Dyson⁸ 

[1] Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, United Kingdom;Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya;Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya;Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, United Kingdom;Department of International Health, John’s Hopkins University, Baltimore, United States;Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia;International Diarrheal Diseases Research Centre, Dhaka, Bangladesh;London School of Hygiene & Tropical Medicine, London, United Kingdom;Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Australia;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;

关键词: typhoid;    children;    carriage;    multidrug-resistant;    H58 lineages;    Kenya;    S. enterica;   

DOI  :  10.7554/eLife.67852

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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).

【 授权许可】

CC BY