TY - JOUR TI - Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya AU - Kariuki, Samuel AU - Dyson, Zoe A AU - Mbae, Cecilia AU - Ngetich, Ronald AU - Kavai, Susan M AU - Wairimu, Celestine AU - Anyona, Stephen AU - Gitau, Naomi AU - Onsare, Robert Sanaya AU - Ongandi, Beatrice AU - Duchene, Sebastian AU - Ali, Mohamed AU - Clemens, John David AU - Holt, Kathryn E AU - Dougan, Gordon A2 - Lewnard, Joseph A2 - Kana, Bavesh D A2 - Cowley, Lauren A2 - Senghore, Madikay VL - 10 PY - 2021 DA - 2021/09/13 SP - e67852 C1 - eLife 2021;10:e67852 DO - 10.7554/eLife.67852 UR - https://doi.org/10.7554/eLife.67852 AB - 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). KW - typhoid KW - children KW - carriage KW - multidrug-resistant KW - H58 lineages KW - Kenya JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -