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

Elife. 2021 Sep 13:10:e67852. doi: 10.7554/eLife.67852.

Abstract

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).

Keywords: H58 lineages; Kenya; S. enterica serovar typhi; carriage; children; epidemiology; global health; infectious disease; microbiology; multidrug-resistant; typhoid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anti-Bacterial Agents / pharmacology*
  • Carrier State / microbiology*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Drug Resistance, Multiple, Bacterial*
  • Female
  • Humans
  • Infant
  • Kenya / epidemiology
  • Male
  • Phylogeny
  • Salmonella typhi / classification
  • Salmonella typhi / drug effects*
  • Salmonella typhi / genetics
  • Salmonella typhi / isolation & purification
  • Typhoid Fever / drug therapy
  • Typhoid Fever / epidemiology
  • Typhoid Fever / microbiology*

Substances

  • Anti-Bacterial Agents