Humans; Africa South of the Sahara/epidemiology; Drug Resistance, Microbial; Genomics; Salmonella Infections/epidemiology; Salmonella typhimurium/genetics; Africa South of the Sahara; Salmonella Infections; Salmonella typhimurium; Chemistry (all); Biochemistry, Genetics and Molecular Biology (all); Physics and Astronomy (all); General Physics and Astronomy; General Biochemistry, Genetics and Molecular Biology; General Chemistry; Multidisciplinary
Abstract :
[en] Invasive non-typhoidal Salmonella (iNTS) disease manifesting as bloodstream infection with high mortality is responsible for a huge public health burden in sub-Saharan Africa. Salmonella enterica serovar Typhimurium (S. Typhimurium) is the main cause of iNTS disease in Africa. By analysing whole genome sequence data from 1303 S. Typhimurium isolates originating from 19 African countries and isolated between 1979 and 2017, here we show a thorough scaled appraisal of the population structure of iNTS disease caused by S. Typhimurium across many of Africa's most impacted countries. At least six invasive S. Typhimurium clades have already emerged, with ST313 lineage 2 or ST313-L2 driving the current pandemic. ST313-L2 likely emerged in the Democratic Republic of Congo around 1980 and further spread in the mid 1990s. We observed plasmid-borne as well as chromosomally encoded fluoroquinolone resistance underlying emergences of extensive-drug and pan-drug resistance. Our work provides an overview of the evolution of invasive S. Typhimurium disease, and can be exploited to target control measures.
Disciplines :
Immunology & infectious disease
Author, co-author :
Van Puyvelde, Sandra ; Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, CB2 0AW, UK. sandra.vanpuyvelde@uantwerpen.be ; Parasites and Microbes Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK. sandra.vanpuyvelde@uantwerpen.be ; Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium. sandra.vanpuyvelde@uantwerpen.be
de Block, Tessa; Institute of Tropical Medicine, Antwerp, Belgium
Sridhar, Sushmita ; Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, CB2 0AW, UK ; Parasites and Microbes Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK ; Division of Infectious Disease, Massachusetts General Hospital, Boston, MA, USA ; Department of Medicine, Harvard Medical School, Boston, MA, USA
Bawn, Matt ; Quadram Institute Bioscience, Norwich, UK ; Earlham Institute, Norwich, UK ; Faculty of Biological Sciences, University of Leeds, Leeds, UK
Kingsley, Robert A ; Quadram Institute Bioscience, Norwich, UK ; School of Biological Science, University of East Anglia, Norwich, UK
Ingelbeen, Brecht ; Institute of Tropical Medicine, Antwerp, Belgium ; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Beale, Mathew A ; Parasites and Microbes Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK
Barbé, Barbara ; Institute of Tropical Medicine, Antwerp, Belgium
Jeon, Hyon Jin; Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, CB2 0AW, UK ; International Vaccine Institute, 1 Gwanak-ro, Seoul, 08826, Republic of Korea ; Madagascar Institute for Vaccine Research, University of Antananarivo, Antananarivo, Madagascar
Mbuyi-Kalonji, Lisette ; Department of Medical Biology, University Teaching Hospital of Kinshasa, Kinshasa, Democratic Republic of the Congo ; National Institute for Biomedical Research, Kinshasa, Democratic Republic of the Congo
Phoba, Marie-France; Department of Medical Biology, University Teaching Hospital of Kinshasa, Kinshasa, Democratic Republic of the Congo ; National Institute for Biomedical Research, Kinshasa, Democratic Republic of the Congo
Falay, Dadi; Department of Pediatrics, University Hospital of Kisangani, Kisangani, Democratic Republic of the Congo
Martiny, Delphine ; Université de Mons - UMONS > Faculté de Médecine et de Pharmac > Service du Doyen de la Faculté de Médecine et Pharmacie ; Department of Microbiology, Laboratoire Hospitalier Universitaire de Bruxelles-Universitair Laboratorium Brussel (LHUB-ULB), Université Libre de Bruxelles (ULB), 1000, Brussels, Belgium
Vandenberg, Olivier ; Department of Microbiology, Laboratoire Hospitalier Universitaire de Bruxelles-Universitair Laboratorium Brussel (LHUB-ULB), Université Libre de Bruxelles (ULB), 1000, Brussels, Belgium ; Division of Infection and Immunity, Faculty of Medical Sciences, University College London, London, UK
Affolabi, Dissou; Centre National Hospitalier Universitaire Hubert Koutoukou Maga, Cotonou, Benin
Rutanga, Jean Pierre; Institute of Tropical Medicine, Antwerp, Belgium ; College of Science and Technology, University of Rwanda, Kigali, Rwanda
Ceyssens, Pieter-Jan; National Reference Center for Salmonella, Unit of Human Bacterial Diseases, Sciensano, J. Wytsmanstraat 14, B-1050, Brussels, Belgium
Mattheus, Wesley; National Reference Center for Salmonella, Unit of Human Bacterial Diseases, Sciensano, J. Wytsmanstraat 14, B-1050, Brussels, Belgium
Cuypers, Wim L ; Institute of Tropical Medicine, Antwerp, Belgium ; Department of Computer Science, University of Antwerp, Antwerp, Belgium
van der Sande, Marianne A B ; Institute of Tropical Medicine, Antwerp, Belgium ; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Park, Se Eun ; International Vaccine Institute, 1 Gwanak-ro, Seoul, 08826, Republic of Korea ; Yonsei University Graduate School of Public Health, Seodaemun-gu, Seoul, 03722, Republic of Korea
Kariuki, Simon; Kenya Medical Research Institute/Centre for Global Health Research, Kisumu, Kenya
Otieno, Kephas; Kenya Medical Research Institute/Centre for Global Health Research, Kisumu, Kenya
Lusingu, John P A; National Institute for Medical Research, Tanga, Tanzania ; Center for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, København, Denmark
Mbwana, Joyce R ; National Institute for Medical Research, Tanga, Tanzania
Adjei, Samuel; University of Health & Allied Sciences, Ho, Volta Region, Ghana
Sarfo, Anima; University of Health & Allied Sciences, Ho, Volta Region, Ghana
Agyei, Seth O; University of Health & Allied Sciences, Ho, Volta Region, Ghana
Asante, Kwaku P; Kintampo Health Research Centre, Research and Development Division, Ghana Health Service, Kintampo North Municipality, Ho, Volta Region, Ghana
Otieno, Walter; KEMRI/Walter Reed Project, Kombewa, Kenya
Otieno, Lucas; KEMRI/Walter Reed Project, Kombewa, Kenya
Tahita, Marc C ; Institut de Recherche en Science de la Santé, Direction Régionale du Centre-Ouest/ClinicalResearch Unit of Nanoro, Nanoro, Burkina Faso
Lompo, Palpouguini; Institut de Recherche en Science de la Santé, Direction Régionale du Centre-Ouest/ClinicalResearch Unit of Nanoro, Nanoro, Burkina Faso
Hoffman, Irving F; University of North Carolina Project, Lilongwe, Malawi
Mvalo, Tisungane ; University of North Carolina Project, Lilongwe, Malawi ; Department of Pediatrics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Msefula, Chisomo; Malawi Liverpool Wellcome Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi
Hassan-Hanga, Fatimah; Department of Paediatrics, Bayero University, Kano, Nigeria ; Aminu Kano Teaching Hospital, Kano, Nigeria
Obaro, Stephen; University of Nebraska Medical Center, Omaha, NE, USA ; International Foundation Against Infectious Diseases in Nigeria (IFAIN), Abuja, Nigeria
Mackenzie, Grant; Medical Research Council Unit The Gambia at London School of Hygiene & Tropical Medicine, Fajara, The Gambia ; London School of Hygiene and Tropical Medicine, Keppel St, Bloomsbury, London, WC1E 7HT, UK ; Murdoch Children's Research Institute, Melbourne, VIC, Australia
Deborggraeve, Stijn; Institute of Tropical Medicine, Antwerp, Belgium
Feasey, Nicholas ; University of North Carolina Project, Lilongwe, Malawi ; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK
Marks, Florian ; Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, CB2 0AW, UK ; International Vaccine Institute, 1 Gwanak-ro, Seoul, 08826, Republic of Korea ; Madagascar Institute for Vaccine Research, University of Antananarivo, Antananarivo, Madagascar ; Heidelberg Institute of Global Health, University of Heidelberg, Heidelberg, Germany
MacLennan, Calman A ; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK ; Enteric and Diarrheal Diseases, Global Health, Bill & Melinda Gates Foundation, Seattle, WA, USA
Thomson, Nicholas R ; Parasites and Microbes Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK ; London School of Hygiene and Tropical Medicine, Keppel St, Bloomsbury, London, WC1E 7HT, UK
Jacobs, Jan ; Institute of Tropical Medicine, Antwerp, Belgium ; Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
Dougan, Gordon; Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, CB2 0AW, UK
Kariuki, Samuel ; Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya
Lunguya, Octavie; Department of Medical Biology, University Teaching Hospital of Kinshasa, Kinshasa, Democratic Republic of the Congo ; National Institute for Biomedical Research, Kinshasa, Democratic Republic of the Congo
Bill and Melinda Gates Foundation DH | National Institute for Health Research
Funding text :
We are grateful to Jacqueline Keane, Christoph Puethe and the Pathogen Informatics team (Wellcome Sanger Institute, Hinxton, Cambridge, United Kingdom) for the support. The work by S.V.P. and G.D. is funded in part by a grant from the Bill & Melinda Gates Foundation (OPP1151153). R.K. and M.B. were supported by research grants BB/N007964/1 and BB/M025489/1, and by the BBSRC Institute Strategic Programme Microbes in the Food Chain BB/R012504/1 and its constituent projects BBS/E/F/000PR10348 and BBS/E/F/000PR10349. W.L.C. was supported by the Research Foundation—Flanders (FWO SB PhD fellowship 1S40018N); J.P.R. was financially supported by the Belgian Directorate General for Development Cooperation (DGD). M.A.B. and N.R.T. were supported by Wellcome funding to the Sanger Institute (#206194). The work done in Benin, Burkina Faso and DRC by B.B., L.M.-K., M.-F.P., D.F., D.A., J.J. and O.L. was funded by the Belgian Directorate of Development Cooperation (DGD) through the Multi-Year Programme (2012–2016) between the Belgian DGD and the Institute of Tropical Medicine, Belgium and (for DRC) by the Baillet-Latour find and the Flemish Interuniversity Council (VLIR-UOS). The isolates from Malawi were generated by Malawi Liverpool Wellcome Research Programme bacteraemia service, supported by Asia and Africa Programme Grant 206545/Z/17/Z to NF. The work in The Gambia was supported by the Bill & Melinda Gates Foundation (OPP1020327); GAVI The Vaccine Alliance’s Accelerated Development and Introduction Plan (PneumoADIP), Medical Research Council (UK) to GM. Salmonella isolates obtained through the RTS,S study was funded by the Bill & Melinda Gates Foundation to CAM. Salmonella isolates obtained through the TSAP study were funded by the Bill & Melinda Gates Foundation to IVI (OPPGH5231) to F.M., H.J.J. and S.E.P. This research by S.V.P., S.S. and G.D. was funded by the National Institute for Health Research [Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust]. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. This research was funded in whole, or in part, by the Wellcome Trust (#206194).We are grateful to Jacqueline Keane, Christoph Puethe and the Pathogen Informatics team (Wellcome Sanger Institute, Hinxton, Cambridge, United Kingdom) for the support. The work by S.V.P. and G.D. is funded in part by a grant from the Bill & Melinda Gates Foundation (OPP1151153). R.K. and M.B. were supported by research grants BB/N007964/1 and BB/M025489/1, and by the BBSRC Institute Strategic Programme Microbes in the Food Chain BB/R012504/1 and its constituent projects BBS/E/F/000PR10348 and BBS/E/F/000PR10349. W.L.C. was supported by the Research Foundation—Flanders (FWO SB PhD fellowship 1S40018N); J.P.R. was financially supported by the Belgian Directorate General for Development Cooperation (DGD). M.A.B. and N.R.T. were supported by Wellcome funding to the Sanger Institute (#206194). The work done in Benin, Burkina Faso and DRC by B.B., L.M.-K., M.-F.P., D.F., D.A., J.J. and O.L. was funded by the Belgian Directorate of Development Cooperation (DGD) through the Multi-Year Programme (2012–2016) between the Belgian DGD and the Institute of Tropical Medicine, Belgium and (for DRC) by the Baillet-Latour find and the Flemish Interuniversity Council (VLIR-UOS). The isolates from Malawi were generated by Malawi Liverpool Wellcome Research Programme bacteraemia service, supported by Asia and Africa Programme Grant 206545/Z/17/Z to NF. The work in The Gambia was supported by the Bill & Melinda Gates Foundation (OPP1020327); GAVI The Vaccine Alliance’s Accelerated Development and Introduction Plan (PneumoADIP), Medical Research Council (UK) to GM. Salmonella isolates obtained through the RTS,S study was funded by the Bill & Melinda Gates Foundation to CAM. Salmonella isolates obtained through the TSAP study were funded by the Bill & Melinda Gates Foundation to IVI (OPPGH5231) to F.M., H.J.J. and S.E.P. This research by S.V.P., S.S. and G.D. was funded by the National Institute for Health Research [Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust]. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. This research was funded in whole, or in part, by the Wellcome Trust (#206194).
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