Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya


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


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).

Keywords: S. enterica serovar typhi; epidemiology; global health; infectious disease; microbiology

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