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

肯尼亚多次引入耐多药伤寒,伴有急性感染和无症状携带

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作者: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.

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).

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).

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