Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya
- Kenya Medical Research Institute, Kenya
- Monash University, Australia
- The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Australia
- John Hopkins University, United States
- International Diarrheal Diseases Research Centre, Bangladesh
- University of Cambridge, United Kingdom
Abstract
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 (4,670 febrile cases and 8,549 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 3 sublineages of 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).
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.Raw Illumina sequence reads have been submitted to the European Nucleotide Archive (ENA) under accession PRJEB19289. Individual sequence accession numbers are listed in Table S1
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ARG-ANNOT, a new bioinformatic tool to discover antibiotic resistance genes in bacterial genomes.Antimicrob Agents Chemother 2014; 58: 212-20.
Article and author information
Author details
Funding
National Institutes of Health (R01AI099525)
- Samuel Kariuki
Wellcome Trust (106158/Z/14/Z)
- Zoe A Dyson
European Commission (TyphiNET No 845681)
- Zoe A Dyson
National Institute for Health Research (AMR Theme)
- Gordon Dougan
Bill and Melinda Gates Foundation (OPP1175797)
- Kathryn E Holt
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Joseph Lewnard, University of California Berkeley, United States
Ethics
Human subjects: The study was approved by the Scientific and Ethics Review Unit (SERU) of the Kenya Medical Research Institute (KEMRI) (Scientific Steering Committee No. 2076). All parents and/or guardians of participating children were informed of the study objectives and voluntary written consent was sought and obtained before inclusion.
Version history
- Received: February 24, 2021
- Preprint posted: March 10, 2021 (view preprint)
- Accepted: September 8, 2021
- Accepted Manuscript published: September 13, 2021 (version 1)
- Accepted Manuscript updated: September 15, 2021 (version 2)
- Accepted Manuscript updated: September 17, 2021 (version 3)
- Version of Record published: October 6, 2021 (version 4)
Copyright
© 2021, Kariuki et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya
eLife 10:e67852.
https://doi.org/10.7554/eLife.67852
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