Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya
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 (4670 febrile cases and 8549 age matched c...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-09-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/67852 |
| _version_ | 1811199408603136000 |
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| author | Samuel Kariuki Zoe A Dyson Cecilia Mbae Ronald Ngetich Susan M Kavai Celestine Wairimu Stephen Anyona Naomi Gitau Robert Sanaya Onsare Beatrice Ongandi Sebastian Duchene Mohamed Ali John David Clemens Kathryn E Holt Gordon Dougan |
| author_facet | Samuel Kariuki Zoe A Dyson Cecilia Mbae Ronald Ngetich Susan M Kavai Celestine Wairimu Stephen Anyona Naomi Gitau Robert Sanaya Onsare Beatrice Ongandi Sebastian Duchene Mohamed Ali John David Clemens Kathryn E Holt Gordon Dougan |
| author_sort | Samuel Kariuki |
| collection | DOAJ |
| description | 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 (4670 febrile cases and 8549 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 three sublineages of the 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). |
| first_indexed | 2024-04-12T01:48:29Z |
| format | Article |
| id | doaj.art-87e1ad6489f44d1985757fb13d9b6c62 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:48:29Z |
| publishDate | 2021-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-87e1ad6489f44d1985757fb13d9b6c622022-12-22T03:53:01ZengeLife Sciences Publications LtdeLife2050-084X2021-09-011010.7554/eLife.67852Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, KenyaSamuel Kariuki0https://orcid.org/0000-0003-3209-9503Zoe A Dyson1https://orcid.org/0000-0002-8887-3492Cecilia Mbae2Ronald Ngetich3Susan M Kavai4Celestine Wairimu5Stephen Anyona6Naomi Gitau7Robert Sanaya Onsare8Beatrice Ongandi9Sebastian Duchene10Mohamed Ali11John David Clemens12Kathryn E Holt13Gordon Dougan14Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, United KingdomWellcome Sanger Institute, Wellcome Genome Campus, Cambridge, United Kingdom; Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, United Kingdom; London School of Hygiene & Tropical Medicine, London, United Kingdom; Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, AustraliaCentre for Microbiology Research, Kenya Medical Research Institute, Nairobi, KenyaCentre for Microbiology Research, Kenya Medical Research Institute, Nairobi, KenyaCentre for Microbiology Research, Kenya Medical Research Institute, Nairobi, KenyaCentre for Microbiology Research, Kenya Medical Research Institute, Nairobi, KenyaCentre for Microbiology Research, Kenya Medical Research Institute, Nairobi, KenyaCentre for Microbiology Research, Kenya Medical Research Institute, Nairobi, KenyaCentre for Microbiology Research, Kenya Medical Research Institute, Nairobi, KenyaCentre for Microbiology Research, Kenya Medical Research Institute, Nairobi, KenyaDepartment of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, AustraliaDepartment of International Health, John’s Hopkins University, Baltimore, United StatesInternational Diarrheal Diseases Research Centre, Dhaka, BangladeshLondon School of Hygiene & Tropical Medicine, London, United Kingdom; Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, AustraliaCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, United KingdomBackground: 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 (4670 febrile cases and 8549 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 three sublineages of the 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).https://elifesciences.org/articles/67852typhoidchildrencarriagemultidrug-resistantH58 lineagesKenya |
| spellingShingle | Samuel Kariuki Zoe A Dyson Cecilia Mbae Ronald Ngetich Susan M Kavai Celestine Wairimu Stephen Anyona Naomi Gitau Robert Sanaya Onsare Beatrice Ongandi Sebastian Duchene Mohamed Ali John David Clemens Kathryn E Holt Gordon Dougan Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya eLife typhoid children carriage multidrug-resistant H58 lineages Kenya |
| title | Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya |
| title_full | Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya |
| title_fullStr | Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya |
| title_full_unstemmed | Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya |
| title_short | Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya |
| title_sort | multiple introductions of multidrug resistant typhoid associated with acute infection and asymptomatic carriage kenya |
| topic | typhoid children carriage multidrug-resistant H58 lineages Kenya |
| url | https://elifesciences.org/articles/67852 |
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