Enteric fever cluster identification in South Africa using genomic surveillance of Salmonella enterica serovar Typhi

Abstract

The National Institute for Communicable Diseases in South Africa participates in national laboratory-based surveillance for human isolates of Salmonella species. Laboratory analysis includes whole-genome sequencing (WGS) of isolates. We report on WGS-based surveillance of Salmonella enterica serovar Typhi ( Salmonella Typhi) in South Africa from 2020 through 2021. We describe how WGS analysis identified clusters of enteric fever in the Western Cape Province of South Africa and describe the epidemiological investigations associated with these clusters. A total of 206 Salmonella Typhi isolates were received for analysis. Genomic DNA was isolated from bacteria and WGS was performed using Illumina NextSeq technology. WGS data were investigated using multiple bioinformatics tools, including those available at the Centre for Genomic Epidemiology, EnteroBase and Pathogenwatch. Core-genome multilocus sequence typing was used to investigate the phylogeny of isolates and identify clusters. Three major clusters of enteric fever were identified in the Western Cape Province; cluster one (n=11 isolates), cluster two (n=13 isolates), and cluster three (n=14 isolates). To date, no likely source has been identified for any of the clusters. All isolates associated with the clusters, showed the same genotype (4.3.1.1.EA1) and resistome (antimicrobial resistance genes: bla TEM-1B, catA1, sul1, sul2, dfrA7). The implementation of genomic surveillance of Salmonella Typhi in South Africa has enabled rapid detection of clusters indicative of possible outbreaks. Cluster identification allows for targeted epidemiological investigations and a timely, coordinated public health response.

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

“…Overall, there were 36 countries with ≥20 genomes (total n=12,409 genomes, 95.7%) and 21 countries with ≥100 genomes (n=11,761 genomes, 90.7%) (see Supplementary file 4 ). Countries with the most genomes available (n≥100 each) were mainly those where local surveillance studies have utilised WGS for isolate characterisation: India ( Britto et al, 2020 ; da Silva et al, 2022 ), Bangladesh ( Rahman et al, 2020 ; da Silva et al, 2022 ), Nepal ( Britto et al, 2018 ; da Silva et al, 2022 ; Pham Thanh et al, 2016a ), Pakistan ( da Silva et al, 2022 ), Cambodia ( Kuijpers et al, 2017 ; Pham Thanh et al, 2016b ), Laos ( Wong et al, 2015 ), Vietnam ( Holt et al, 2011a ), Kenya ( Kariuki et al, 2021 ; Kariuki et al, 2010 ), Malawi ( Feasey et al, 2015 ), Zimbabwe ( Mashe et al, 2021 ; Thilliez et al, 2022 ), Ghana ( Park et al, 2018 ), Nigeria ( Ikhimiukor et al, 2022a ; Wong et al, 2016b ), Chile ( Maes et al, 2022 ), Samoa Sikorski et al, 2022 ; plus South Africa ( Smith et al, 2023 ), the Philippines ( Lagrada et al, 2022 ), United Kingdom, and United States, where Typhi isolates are sequenced as part of national surveillance programmes.…”

“…The majority of Typhi from Southern Africa were isolated in South Africa between 2017 and 2020 (92%; n=262/285), via routine sequencing at the National Institute for Communicable Diseases reference laboratory ( Smith et al, 2023 ). H58 prevalence in South Africa was high (69.5%, [95% CI, 63.9–75.1%]; n=182/262) during this time period (mostly 4.3.1.1.EA1, 64%; n=168/262), but was much lower (25% [95% CI, 4–46%]) among the smaller sampling of earlier years (n=4/16 for 2010–2012) (see Figure 1b ).…”

“…The 3.3 QRDR triple-mutant accounted for 3.8% of CipR genomes in India, and was also found in neighbouring Nepal (n=4, 3% of CipR). CipR genomes were identified from Zimbabwe (4.3.1.1.EA1 with gyrA S83 F + qnrS , associated with recent CipR outbreaks; Thilliez et al, 2022 ) and South Africa (five different genotypes, totalling 3.5%; see Figure 2—figure supplement 5 ; Smith et al, 2023 ), but were otherwise absent from African Typhi genomes.…”