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

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 c...

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Autores principales: Samuel Kariuki, Zoe A Dyson, Cecilia Mbae, Ronald Ngetich, Susan M Kavai, Celestine Wairimu, Stephen Anyona, Naomi Gitau, Robert Sanaya Onsare, Beatrice Ongandi, Sebastian Duchene, Mohamed Ali, John David Clemens, Kathryn E Holt, Gordon Dougan
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spelling oai:doaj.org-article:87e1ad6489f44d1985757fb13d9b6c622021-11-15T06:04:03ZMultiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya10.7554/eLife.678522050-084Xe67852https://doaj.org/article/87e1ad6489f44d1985757fb13d9b6c622021-09-01T00:00:00Zhttps://elifesciences.org/articles/67852https://doaj.org/toc/2050-084XBackground: 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).Samuel KariukiZoe A DysonCecilia MbaeRonald NgetichSusan M KavaiCelestine WairimuStephen AnyonaNaomi GitauRobert Sanaya OnsareBeatrice OngandiSebastian DucheneMohamed AliJohn David ClemensKathryn E HoltGordon DouganeLife Sciences Publications Ltdarticletyphoidchildrencarriagemultidrug-resistantH58 lineagesKenyaMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution DOAJ
collection DOAJ
language EN
topic typhoid
children
carriage
multidrug-resistant
H58 lineages
Kenya
Medicine
R
Science
Q
Biology (General)
QH301-705.5
spellingShingle typhoid
children
carriage
multidrug-resistant
H58 lineages
Kenya
Medicine
R
Science
Q
Biology (General)
QH301-705.5
Samuel Kariuki
Zoe A Dyson
Cecilia Mbae
Ronald Ngetich
Susan M Kavai
Celestine Wairimu
Stephen Anyona
Naomi Gitau
Robert Sanaya Onsare
Beatrice Ongandi
Sebastian Duchene
Mohamed Ali
John David Clemens
Kathryn E Holt
Gordon Dougan
Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya
description 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).
format article
author Samuel Kariuki
Zoe A Dyson
Cecilia Mbae
Ronald Ngetich
Susan M Kavai
Celestine Wairimu
Stephen Anyona
Naomi Gitau
Robert Sanaya Onsare
Beatrice Ongandi
Sebastian Duchene
Mohamed Ali
John David Clemens
Kathryn E Holt
Gordon Dougan
author_facet Samuel Kariuki
Zoe A Dyson
Cecilia Mbae
Ronald Ngetich
Susan M Kavai
Celestine Wairimu
Stephen Anyona
Naomi Gitau
Robert Sanaya Onsare
Beatrice Ongandi
Sebastian Duchene
Mohamed Ali
John David Clemens
Kathryn E Holt
Gordon Dougan
author_sort Samuel Kariuki
title Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya
title_short Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya
title_full Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya
title_fullStr Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya
title_full_unstemmed Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya
title_sort multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, kenya
publisher eLife Sciences Publications Ltd
publishDate 2021
url https://doaj.org/article/87e1ad6489f44d1985757fb13d9b6c62
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