Abstract

A highly invasive form of non-typhoidal Salmonella (iNTS) disease has recently been documented in many countries in sub-Saharan Africa. The most common Salmonella enterica serovar causing this disease is Typhimurium (Salmonella Typhimurium). We applied whole-genome sequence–based phylogenetic methods to define the population structure of sub-Saharan African invasive Salmonella Typhimurium isolates and compared these to global Salmonella Typhimurium populations. Notably, the vast majority of sub-Saharan invasive Salmonella Typhimurium isolates fell within two closely related, highly clustered phylogenetic lineages that we estimate emerged independently 52 and 35 years ago in close temporal association with the current HIV pandemic. Clonal replacement of isolates from lineage I by those from lineage II was potentially influenced by the use of chloramphenicol for the treatment of iNTS disease. Our analysis suggests that iNTS disease is in part an epidemic in sub-Saharan Africa caused by highly related Salmonella Typhimurium lineages that may have occupied new niches associated with a compromised human population and antibiotic treatment.

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Acknowledgements

We thank J. Cheesborough for providing the DRC isolates, M. Okong, N. French and the Medical Research Council, Uganda, for providing the Uganda isolates, S. Nair for providing the Health Protection Agency (HPA) isolates, L. Barquist for modeling the pre-1990 HIV prevalence data and the Sequencing team at the Wellcome Trust Sanger Institute. This work was funded by a Wellcome Trust grant (098051). C.A.M. was supported by a Tropical Research Fellowship from the Wellcome Trust and a Clinical Research Fellowship from GlaxoSmithKline.

Author information

Author notes

    • Chinyere K Okoro
    •  & Robert A Kingsley

    These authors contributed equally to this work.

Affiliations

  1. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.

    • Chinyere K Okoro
    • , Robert A Kingsley
    • , Thomas R Connor
    • , Simon R Harris
    • , Julian Parkhill
    •  & Gordon Dougan
  2. Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

    • Christopher M Parry
  3. Department of Clinical Infection, Microbiology and Immunology, Institute for Infection and Global Health, University of Liverpool, Liverpool, UK.

    • Christopher M Parry
    •  & Manar N Al-Mashhadani
  4. Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya.

    • Samuel Kariuki
  5. Malawi-Liverpool–Wellcome Trust Clinical Research Program, University of Malawi College of Medicine, Blantyre, Malawi.

    • Chisomo L Msefula
    •  & Robert S Heyderman
  6. Department of Microbiology, College of Medicine, University of Malawi, Blantyre, Malawi.

    • Chisomo L Msefula
  7. Department of Gastroenterology, Institute of Translational Medicine, Liverpool University, Liverpool, UK.

    • Melita A Gordon
  8. Health Protection Agency, Laboratory for Gastrointestinal Infections, Centre for Infections, London, UK.

    • Elizabeth de Pinna
    •  & John Wain
  9. Norwich Medical School, University of East Anglia, Norwich, UK.

    • John Wain
  10. School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.

    • Robert S Heyderman
  11. Division of Paediatric Infectious Diseases, Department of Paediatrics and Human Development, Michigan State University, East Lansing, Michigan, USA.

    • Stephen Obaro
  12. Pediatrics Department, National Hospital Abuja, Garki Abuja, Nigeria.

    • Stephen Obaro
  13. Barcelona Centre for International Health Research (CRESIB), Hospital Clínic–Universitat de Barcelona, Barcelona, Spain.

    • Pedro L Alonso
  14. Centro de Investigação em Saúde de Manhiça (CISM), Manhiça, Mozambique.

    • Pedro L Alonso
    •  & Inacio Mandomando
  15. Instituto Nacional de Saúde, Ministerio de Saúde, Maputo, Mozambique.

    • Inacio Mandomando
  16. Novartis Vaccines Institute for Global Health (NVGH), Siena, Italy.

    • Calman A MacLennan
  17. Medical Research Council (MRC) Centre for Immune Regulation, School of Immunity and Infection, College of Medicine and Dental Sciences, University of Birmingham, Birmingham, UK.

    • Calman A MacLennan
  18. Center for Vaccine Development, University of Maryland, Baltimore, Baltimore, Maryland, USA.

    • Milagritos D Tapia
    •  & Myron M Levine
  19. Department of Medicine, University of Maryland, Baltimore, Baltimore, Maryland, USA.

    • Myron M Levine
    •  & Sharon M Tennant

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Contributions

C.K.O. and R.A.K. contributed to collecting data and manuscript writing. C.K.O. analyzed sequence data and performed phylogenetic, BEAST and comparative genomics analyses. T.R.C. and S.R.H. wrote the coding scripts for phylogenetic and Bayesian statistical analyses and contributed to manuscript writing. C.M.P., M.N.A.-M., S.K., C.L.M., M.A.G., E.d.P., R.S.H., S.O., P.L.A., I.M., C.A.M., J.W., M.D.T., M.M.L. and S.M.T. contributed to studies from which isolates were drawn and to manuscript writing. G.D., J.P. and R.A.K. designed the study, and G.D. supervised the work.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Gordon Dougan.

Supplementary information

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    Supplementary Text and Figures

    Supplementary Figures 1–6 and Supplementary Note

Excel files

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    Supplementary Table 1

    Isolates used in study with mapping statistics and metadata (to be included as a separate file in Excel format)

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https://doi.org/10.1038/ng.2423

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