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

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.

Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes

“…Here, we found that at the region level, 4.3.1.1.EA1 dominated (78%, [95% CI 75.1–80.8%] n=647/830; see Figure 1a ). However, there were country-level differences, with 4.3.1.1.EA1 dominating in Malawi (94%; n=524/558), Tanzania (83%; n=15/18), Zimbabwe (80%; n=20/25), and earlier years in Kenya (59%, n=86/145 in 2012–2016), and 4.3.1.2.EA3 dominating in Rwanda (85%, n=23/27) ( Rutanga et al, 2023 ) and Uganda (97%, n=35/36) ( Figure 1b and Figure 1—figure supplement 3 ). Although the specific periods of sampling differ for these countries, the prevalence of H58 was consistently high across the available time frames for all countries, with no change in dominant genotypes (see Figure 1b and Figure 1—figure supplement 3 ; note the apparent shift to 4.3.1.2.EA3 in Kenya is based on n=4 isolates only so requires confirmation).…”