Genomic Signature of Multidrug-Resistant Salmonella enterica Serovar Typhi Isolates Related to a Massive Outbreak in Zambia between 2010 and 2012

Abstract

dRetrospectively, we investigated the epidemiology of a massive Salmonella enterica serovar Typhi outbreak in Zambia during 2010 to 2012. Ninety-four isolates were susceptibility tested by MIC determinations. Whole-genome sequence typing (WGST) of 33 isolates and bioinformatic analysis identified the multilocus sequence type (MLST), haplotype, plasmid replicon, antimicrobial resistance genes, and genetic relatedness by single nucleotide polymorphism (SNP) analysis and genomic deletions. The outbreak affected 2,040 patients, with a fatality rate of 0.5%. Most (83.0%) isolates were multidrug resistant (MDR). The isolates belonged to MLST ST1 and a new variant of the haplotype, H58B. Most isolates contained a chromosomally translocated region containing seven antimicrobial resistance genes, catA1, bla TEM-1 , dfrA7, sul1, sul2, strA, and strB, and fragments of the incompatibility group Q1 (IncQ1) plasmid replicon, the class 1 integron, and the mer operon. The genomic analysis revealed 415 SNP differences overall and 35 deletions among 33 of the isolates subjected to whole-genome sequencing. In comparison with other genomes of H58, the Zambian isolates separated from genomes from Central Africa and India by 34 and 52 SNPs, respectively. The phylogenetic analysis indicates that 32 of the 33 isolates sequenced belonged to a tight clonal group distinct from other H58 genomes included in the study. The small numbers of SNPs identified within this group are consistent with the short-term transmission that can be expected over a period of 2 years. The phylogenetic analysis and deletions suggest that a single MDR clone was responsible for the outbreak, during which occasional other S. Typhi lineages, including sensitive ones, continued to cocirculate. The common view is that the emerging global S. Typhi haplotype, H58B, containing the MDR IncHI1 plasmid is responsible for the majority of typhoid infections in Asia and sub-Saharan Africa; we found that a new variant of the haplotype harboring a chromosomally translocated region containing the MDR islands of IncHI1 plasmid has emerged in Zambia. This could change the perception of the term "classical MDR typhoid" currently being solely associated with the IncHI1 plasmid. It might be more common than presently thought that S. Typhi haplotype H58B harbors the IncHI1 plasmid or a chromosomally translocated MDR region or both.

Typhoid fever outbreak investigation in Ofla Woreda, Southern Zone of Tigray Region, Ethiopia, 2016: An unmatched 1:2 case-control

“…This outbreak investigation revealed that CFR was 1% which is in line with investigations in Zambia (Hendriksen et al, 2015) which indicates early detection of the outbreak and management of cases. Typhoid fever suspected cases were higher in females than males.…”

“…Thus, there was the higher likelihood of spreading the disease if appropriate hygiene practices were poorly observed and also exposure through household activities including preparation of food. However, it is in contrast with a study done in Zambia (Hendriksen et al, 2015).…”

Antimicrobial resistance and management of invasive Salmonella disease

“…In one study over five Asian countries the incidence ranged from 15 to 450/100,000 population/year [69]. The burden in Africa has been more difficult to determine as estimates, based on a handful of studies may have overestimated the number of cases [70]. Indeed in the 2010 study [8] advises caution in interpreting its estimates as one Kenyan study contributes disproportionately [10].…”

Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events

“…Since the 1990s, alternative treatment options have included fluoroquinolones, third-generation cephalosporins (such as ceftriaxone) and the azalide azithromycin 1 . The early emergence of MDR S. Typhi was driven in large part by the acquisition of IncHI1 plasmids carrying antibiotic resistance genes 12 and, more recently, by chromosomal mutations associated with resistance to fluoroquinolones, and MDR strains have been reported across Asia and Africa 13–16 .…”