Salmonella Typhi whole genome sequencing in Rwanda shows a diverse historical population with recent introduction of haplotype H58

PLoS Negl Trop Dis. 2023 Jun 16;17(6):e0011285. doi: 10.1371/journal.pntd.0011285. eCollection 2023 Jun.

Abstract

Salmonella enterica serovar Typhi (S. Typhi) is the cause of typhoid fever, presenting high rates of morbidity and mortality in low- and middle-income countries. The H58 haplotype shows high levels of antimicrobial resistance (AMR) and is the dominant S. Typhi haplotype in endemic areas of Asia and East sub-Saharan Africa. The situation in Rwanda is currently unknown and therefore to reveal the genetic diversity and AMR of S. Typhi in Rwanda, 25 historical (1984-1985) and 26 recent (2010-2018) isolates from Rwanda were analysed using whole genome sequencing (WGS). WGS was locally implemented using Illumina MiniSeq and web-based analysis tools, thereafter complemented with bioinformatic approaches for more in-depth analyses. Whereas historical S. Typhi isolates were found to be fully susceptible to antimicrobials and show a diversity of genotypes, i.e 2.2.2, 2.5, 3.3.1 and 4.1; the recent isolates showed high AMR rates and were predominantly associated with genotype 4.3.1.2 (H58, 22/26; 84,6%), possibly resulting from a single introduction in Rwanda from South Asia before 2010. We identified practical challenges for the use of WGS in endemic regions, including a high cost for shipment of molecular reagents and lack of high-end computational infrastructure for the analyses, but also identified WGS to be feasible in the studied setting and giving opportunity for synergy with other programs.

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Haplotypes
  • Humans
  • Microbial Sensitivity Tests
  • Rwanda
  • Salmonella typhi* / genetics
  • Typhoid Fever* / epidemiology
  • Whole Genome Sequencing

Substances

  • Anti-Bacterial Agents

Grants and funding

JPR was financially supported by the Belgian Directorate General for Development cooperation (DGD). SVP and GD were supported by Gates (TyVAC Consortium), WLC was supported by a personal fellowship from the Research Foundation Flanders (FWO). SD and SVP were supported by the ‘Bacterial Infections in the Tropics’ program from Baillet-Latour. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.