1. Epidemiology and Global Health
  2. Microbiology and Infectious Disease
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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
Research Article
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Cite this article as: eLife 2021;10:e67852 doi: 10.7554/eLife.67852

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. Accepted: September 8, 2021
  3. Accepted Manuscript published: September 13, 2021 (version 1)
  4. Accepted Manuscript updated: September 15, 2021 (version 2)
  5. Accepted Manuscript updated: September 17, 2021 (version 3)

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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    The virus SARS-CoV-2 can exploit biological vulnerabilities (e.g. host proteins) in susceptible hosts that predispose to the development of severe COVID-19.

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    Our work provides a prioritised list of host targets potentially exploited by SARS-CoV-2 and is a precursor for further research on CD209 and FAS as therapeutically tractable targets for COVID-19.

    Funding:

    MAK, JSc, JH, AB, DO, MC, EMM, MG, ID were funded by Open Targets. J.Z. and T.R.G were funded by the UK Medical Research Council Integrative Epidemiology Unit (MC_UU_00011/4). JSh and GJW were funded by the Wellcome Trust Grant 206194. This research was funded in part by the Wellcome Trust [Grant 206194]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.

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    Background:

    Lack of early infection-exposure has been associated with increased allergy-related disease (ARD) susceptibility. In tropical Africa, little is known about which infections contribute to development of ARDs, and at which time.

    Methods:

    We used latent class analysis to characterise the early infection-exposure of participants in a Ugandan birth cohort and assessed ARDs in later childhood.

    Results:

    Of 2345 live births, 2115 children (90%) had data on infections within the first year of life while 1179 (50%) had outcome data at 9 years. We identified two latent classes of children based on first-year infection-exposure. Class 1 (32% membership), characterised by higher probabilities for malaria (80%), diarrhoea (76%), and lower respiratory tract infections (LRTI) (22%), was associated with lower prevalence of wheeze, eczema, rhinitis, and Dermatophagoides skin prick test (SPT) positivity at 9 years. Based on 5-year cumulative infection experience, class 1 (31% membership), characterised by higher probabilities for helminths (92%), malaria (79%), and LRTI (45%), was associated with lower probabilities of SPT positivity at 9 years.

    Conclusions:

    In this Ugandan birth cohort, early childhood infection-exposure, notably to malaria, helminths, LRTI, and diarrhoea, is associated with lower prevalence of atopy and ARDs in later childhood.

    Funding:

    This work was supported by several funding sources. The Entebbe Mother and Baby Study (EMaBS) was supported by the Wellcome Trust, UK, senior fellowships for AME (grant numbers 064693, 079110, 95778) with additional support from the UK Medical Research Council. LL is supported by a PhD fellowship through the DELTAS Africa Initiative SSACAB (grant number 107754). ELW received funding from MRC Grant Reference MR/K012126/1. SAL was supported by the PANDORA-ID-NET Consortium (EDCTP Reg/Grant RIA2016E-1609). HM was supported by the Wellcome’s Institutional Strategic Support Fund (grant number 204928/Z/16/Z).