Department of Medical Microbiology, University of Pretoria, Pretoria, South Africa.
National Microbiology Reference Laboratory, Harare, Zimbabwe.
J Antimicrob Chemother. 2021 Apr 13;76(5):1160-1167. doi: 10.1093/jac/dkaa519.
Typhoid fever, caused by S. enterica ser. Typhi, continues to be a substantial health burden in developing countries. Little is known of the genotypic diversity of S. enterica ser. Typhi in Zimbabwe, but this is key for understanding the emergence and spread of this pathogen and devising interventions for its control.
To report the molecular epidemiology of S. enterica ser. Typhi outbreak strains circulating from 2012 to 2019 in Zimbabwe, using comparative genomics.
A review of typhoid cases records from 2012 to 2019 in Zimbabwe was performed. The phylogenetic relationship of outbreak isolates from 2012 to 2019 and emergence of antibiotic resistance was investigated by whole-genome sequence analysis.
A total 22 479 suspected typhoid cases, 760 confirmed cases were reported from 2012 to 2019 and 29 isolates were sequenced. The majority of the sequenced isolates were predicted to confer resistance to aminoglycosides, β-lactams, phenicols, sulphonamides, tetracycline and fluoroquinolones (including qnrS detection). The qnrS1 gene was associated with an IncN (subtype PST3) plasmid in 79% of the isolates. Whole-genome SNP analysis, SNP-based haplotyping and resistance determinant analysis showed that 93% of the isolates belonged to a single clade represented by multidrug-resistant H58 lineage I (4.3.1.1), with a maximum pair-wise distance of 22 SNPs.
This study has provided detailed genotypic characterization of the outbreak strain, identified as S. Typhi 4.3.1.1 (H58). The strain has reduced susceptibility to ciprofloxacin due to qnrS carried by an IncN (subtype PST3) plasmid resulting from ongoing evolution to full resistance.
伤寒,由 S. enterica 血清型 Typhi 引起,在发展中国家仍是一个重大的健康负担。对津巴布韦 S. enterica 血清型 Typhi 的基因型多样性知之甚少,但这对于了解该病原体的出现和传播以及制定控制措施至关重要。
使用比较基因组学报告 2012 年至 2019 年津巴布韦流行的 S. enterica 血清型 Typhi 爆发菌株的分子流行病学。
对 2012 年至 2019 年津巴布韦的伤寒病例记录进行了回顾。通过全基因组序列分析,研究了 2012 年至 2019 年爆发分离株的系统发育关系和抗生素耐药性的出现。
2012 年至 2019 年共报告了 22479 例疑似伤寒病例,确诊病例 760 例,共测序 29 株。测序的大多数分离株被预测对氨基糖苷类、β-内酰胺类、酚类、磺胺类、四环素类和氟喹诺酮类(包括 qnrS 检测)具有耐药性。qnrS1 基因与 79%的分离株中的 IncN(亚型 PST3)质粒有关。全基因组 SNP 分析、SNP 基于单倍型和耐药决定因子分析表明,93%的分离株属于多药耐药 H58 谱系 I(4.3.1.1)的单一分支,最大的 SNP 对为 22 个。
本研究对爆发菌株进行了详细的基因特征分析,确定为 S. Typhi 4.3.1.1(H58)。由于 IncN(亚型 PST3)质粒携带 qnrS,导致对环丙沙星的敏感性降低,该质粒是由于对完全耐药的不断进化而产生的。