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

  1. Samuel Kariuki  Is a corresponding author
  2. Zoe A Dyson
  3. Cecilia Mbae
  4. Ronald Ngetich
  5. Susan M Kavai
  6. Celestine Wairimu
  7. Stephen Anyona
  8. Naomi Gitau
  9. Robert Sanaya Onsare
  10. Beatrice Ongandi
  11. Sebastian Duchene
  12. Mohamed Ali
  13. John David Clemens
  14. Kathryn E Holt
  15. Gordon Dougan
  1. Kenya Medical Research Institute, Kenya
  2. Monash University, Australia
  3. The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Australia
  4. John Hopkins University, United States
  5. International Diarrheal Diseases Research Centre, Bangladesh
  6. 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

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Samuel Kariuki

    Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya
    For correspondence
    samkariuki2@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3209-9503
  2. Zoe A Dyson

    Department of Infectious Diseases, Monash University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  3. Cecilia Mbae

    Microbiology, Kenya Medical Research Institute, Nairobi, Kenya
    Competing interests
    The authors declare that no competing interests exist.
  4. Ronald Ngetich

    Microbiology, Kenya Medical Research Institute, Nairobi, Kenya
    Competing interests
    The authors declare that no competing interests exist.
  5. Susan M Kavai

    Microbiology, Kenya Medical Research Institute, Nairobi, Kenya
    Competing interests
    The authors declare that no competing interests exist.
  6. Celestine Wairimu

    Microbiology, Kenya Medical Research Institute, Nairobi, Kenya
    Competing interests
    The authors declare that no competing interests exist.
  7. Stephen Anyona

    Microbiology, Kenya Medical Research Institute, Nairobi, Kenya
    Competing interests
    The authors declare that no competing interests exist.
  8. Naomi Gitau

    Microbiology, Kenya Medical Research Institute, Nairobi, Kenya
    Competing interests
    The authors declare that no competing interests exist.
  9. Robert Sanaya Onsare

    Microbiology, Kenya Medical Research Institute, Nairobi, Kenya
    Competing interests
    The authors declare that no competing interests exist.
  10. Beatrice Ongandi

    Microbiology, Kenya Medical Research Institute, Nairobi, Kenya
    Competing interests
    The authors declare that no competing interests exist.
  11. Sebastian Duchene

    Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  12. Mohamed Ali

    Department of International Health, John Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. John David Clemens

    International Diarrheal Diseases Research Centre, Dhaka, Bangladesh
    Competing interests
    The authors declare that no competing interests exist.
  14. Kathryn E Holt

    Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  15. Gordon Dougan

    Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

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.

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.

Reviewing Editor

  1. Joseph Lewnard, University of California Berkeley, United States

Publication history

  1. Received: February 24, 2021
  2. Preprint posted: March 10, 2021 (view preprint)
  3. Accepted: September 8, 2021
  4. Accepted Manuscript published: September 13, 2021 (version 1)
  5. Accepted Manuscript updated: September 15, 2021 (version 2)
  6. Accepted Manuscript updated: September 17, 2021 (version 3)
  7. 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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  1. Samuel Kariuki
  2. Zoe A Dyson
  3. Cecilia Mbae
  4. Ronald Ngetich
  5. Susan M Kavai
  6. Celestine Wairimu
  7. Stephen Anyona
  8. Naomi Gitau
  9. Robert Sanaya Onsare
  10. Beatrice Ongandi
  11. Sebastian Duchene
  12. Mohamed Ali
  13. John David Clemens
  14. Kathryn E Holt
  15. Gordon Dougan
(2021)
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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