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- Title
Salmonella Typhi whole genome sequencing in Rwanda shows a diverse historical population with recent introduction of haplotype H58.
- Authors
Rutanga, Jean Pierre; de Block, Tessa; Cuypers, Wim L.; Cafmeyer, Josephine; Peeters, Marjan; Umumararungu, Esperance; Ngabonziza, Jean Claude S.; Rucogoza, Aniceth; Vandenberg, Olivier; Martiny, Delphine; Dusabe, Angélique; Nkubana, Théoneste; Dougan, Gordon; Muvunyi, Claude Mambo; Mwikarago, Ivan Emil; Jacobs, Jan; Deborggraeve, Stijn; Van Puyvelde, Sandra
- 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. Author summary: Typhoid fever, caused by S. Typhi, remains a public health threat in low- and middle-income countries in Asia and sub-Saharan Africa. Country data on antimicrobial susceptibility and genetic diversity of circulating S. Typhi is crucial for surveillance, treatment guidelines and prevention. Typhoid fever is endemic in Rwanda but there are no data on the diversity of S. Typhi genotypes, genetic evolution, or the association with antimicrobial resistance (AMR) in the country. Therefore, we conducted whole genome sequencing (WGS) of 25 S. Typhi historical (1984-1985) and 26 recent (2010-2018) isolates from Rwanda. Whereas the historical population is diverse and susceptible to antimicrobials, the recent S. Typhi population in Rwanda is dominated by genotype 4.3.1.2 (H58) which is associated with high AMR rates and is dominant in Asia and East Africa. Furthermore, we present a workflow for implementation of WGS to support typhoid surveillance and identified challenges of this workflow in endemic regions.
- Subjects
RWANDA; SUB-Saharan Africa; WHOLE genome sequencing; SALMONELLA typhi; HAPLOTYPES; SALMONELLA enterica serovar Typhi; TYPHOID fever
- Publication
PLoS Neglected Tropical Diseases, 2023, Vol 16, Issue 6, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0011285