The international and intercontinental spread and expansion of antimicrobial-resistant Salmonella Typhi: a genomic epidemiology study

Silva, Késia Esther da; Tanmoy, Arif Mohammad; Pragasam, Agila Kumari; Iqbal, Junaid; Sajib, Mohammad Saiful Islam; Mutreja, Ankur; Veeraraghavan, Balaji; Tamrakar, Dipesh; Qamar, Farah Naz; Dougan, Gordon; Bogoch, Isaac I.; Seidman, Jessica C.; Shakya, Jivan; Vaidya, Krista; Carey, Megan E; Shrestha, Rajeev; Irfan, Seema; Baker, Stephen; Luby, Steve P.; Cao, Yanjia; Dyson, Zoe A.; Garrett, Denise O; John, Jacob; Kang, Gagandeep; Hooda, Yogesh; Saha, Samir K.; Saha, Senjuti; Andrews, Jason R

doi:10.1016/s2666-5247(22)00093-3

Cited by 63 publications

(89 citation statements)

References 39 publications

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“…Typhi genotype 4.3.1.1 isolates from Zimbabwe formed a discrete cluster within a subclade designated genotype 4.3.1.1EA1, composed entirely of isolates from east and southern African, or travel to this region (47). 4.3.1.1EA1 was in turn rooted within isolates from Southern Asia consistent with initial introduction from Southern Asia into Kenya and Tanzania and subsequent spread south into Malawi, as reported previously (44, 48). Our analyses confirm further transmission of this clone to Zimbabwe.…”

Section: Discussionsupporting

confidence: 86%

“…Typhi is normally associated with mutations in the quinolone resistance determining region (QRDR) of GyrA and ParC. A previous study reported that QRDR mutations emerged independently on at least 94 occasions globally but almost exclusively in South Asia (48). We detected at least four independent acquisitions of QRDR mutations in the gyrA gene.…”

Section: Discussionmentioning

confidence: 99%

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Population structure and evolution of Salmonella enterica serotype Typhi in Zimbabwe before a typhoid conjugate vaccine immunization campaign

Thilliez

Mashe

Chaibva

et al. 2022

Preprint

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Background: The continued emergence of Salmonella enterica serovar Typhi (S. Typhi) with ever increasing antimicrobial resistance (AMR), necessitates the use of vaccines in endemic countries. A typhoid fever outbreak in Harare, Zimbabwe in 2018 from a multidrug resistant S. Typhi with additional resistance to ciprofloxacin was the catalyst for the introduction of a typhoid conjugate vaccine program. To investigate the historic emergence and evolution of AMR of endemic S. Typhi in Zimbabwe and determined the population structure, gene flux and sequence polymorphisms of strains isolated prior to mass typhoid vaccination to provide a baseline for future evaluation of the effect of the vaccination program. Methods: We determined the population structure, gene flux and sequence polymorphisms and reconstructed the evolution of AMR. The S. Typhi population structure was investigated in the context the genome sequence of 1904 strains isolated from 65 countries to reconstruct spread of endemic strains into Zimbabwe. Findings: The population structure of S. Typhi in Zimbabwe is dominated by multidrug resistant genotype 4.3.1.1 (H58) that spread to Zimbabwe from neighboring countries around 2009. Evolution of AMR within Zimbabwe included acquisition of an IncN plasmid carrying a qnrS gene and a mutation in the quinolone resistance determining region of gyrA gene, both implicated in resistance to quinolone antibiotics. A minority population of antimicrobial susceptible S. Typhi genotype 3.3.1 strains was detected in typhoid cases. Interpretation: The currently dominant S. Typhi population is genotype 4.3.1.1 that spread to Zimbabwe and acquired additional AMR though acquisition of a plasmid and mutation of the gyrA gene. This study provides a baseline for future evaluation of the impact of the Typhoid Conjugate Vaccine program in Harare.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Population structure and evolution of Salmonella enterica serotype Typhi in Zimbabwe before a typhoid conjugate vaccine immunization campaign

Thilliez

Mashe

Chaibva

et al. 2022

Preprint

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“…Notably, unlike the extent global population of S . Typhi, which is largely dominated by a single lineage, 14,35 this historic population exhibited considerable genetic diversity, with 37 genotypes represented (Figure 1a). The majority of isolates belonged to primary clade 2 (194/463), of which clade 2.0 was most common (36%, 69/194) followed by subclades 2.3.3 (14%, 28/194) and 2.2.2 (13%, 25/194).…”

Section: Resultsmentioning

confidence: 99%

“…[19][20][21][22] We continue to observe a pattern in which drug-resistant variants emerge in South Asia and spread radially, with H58 being the only major genotype to do so to date. 14,35,[46][47][48][49] H58 S. Typhi was first isolated in Kenya shortly after its estimated emergence in 1988, further illustrating the potential for rapid spread of this lineage. 48 This suggests that prioritization of widespread use of TCVs in South Asia can not only prevent significant morbidity in the region but should limit the continued emergence and spread of drug-resistant organisms elsewhere, which could expand the useful lifespan of existing therapeutic options in some parts of the world until TCVs become more widely available.…”

Section: Discussionmentioning

confidence: 99%

“…We inferred a maximum likelihood phylogenetic tree from the sequencing data to examine the population structure of this historic (1980 -1995) collection of global S. Typhi sequences (Figure 1). Notably, unlike the extent global population of S. Typhi, which is largely dominated by a single lineage, 14,35 this historic population exhibited considerable genetic diversity, with 37 genotypes represented (Figure 1a). The majority of isolates belonged to primary clade 2 (194/463), of which clade 2.0 was most common (36%, 69/194) followed by subclades 2.3.3 (14%, 28/194) and 2.2.2 (13%, 25/194).…”

Section: Typhimentioning

confidence: 96%

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The origins of haplotype 58 (H58) Salmonella enterica serovar Typhi

Carey

Nguyen

Nhu

et al. 2022

Preprint

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Antimicrobial resistance (AMR) poses a serious threat to the clinical management of typhoid fever. AMR in Salmonella Typhi (S. Typhi) is associated with the H58 lineage, which arose comparatively recently before becoming globally disseminated. To better understand when and how this lineage emerged and became dominant, we performed detailed phylogenetic and phylodynamic analyses on contemporary genome sequences from S. Typhi isolated in the period spanning the emergence. Our dataset, which contains the earliest described H58 S. Typhi, indicates that the prototype H58 organisms were multi-drug resistant (MDR). These organisms emerged spontaneously in India in 1987 and became radially distributed throughout South Asia and then globally in the ensuing years. These early organisms were associated with a single long branch, possessing mutations associated with increased bile tolerance, suggesting that the first H58 organism was generated during chronic carriage. The subsequent use of fluoroquinolones led to several independent mutations in gyrA. The ability of H58 to acquire and maintain AMR genes continues to pose a threat, as extensively drug-resistant (XDR; MDR plus resistance to ciprofloxacin and third generation cephalosporins) variants, have emerged recently in this lineage. Understanding where and how H58 S. Typhi originated and became successful is key to understand how AMR drives successful lineages of bacterial pathogens. Additionally, these data can inform optimal targeting of typhoid conjugate vaccines (TCVs) for reducing the potential for emergence and the impact of new drug-resistant variants. Emphasis should also be placed upon the prospective identification and treatment of chronic carriers to prevent the emergence of new drug resistant variants with the ability to spread efficiently.

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Methods for Genomic Epidemiology of Bacterial Pathogens: Example Salmonella

Sanderson,

White

2024

Methods in Molecular Biology

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The international and intercontinental spread and expansion of antimicrobial-resistant Salmonella Typhi: a genomic epidemiology study

Cited by 63 publications

References 39 publications

Population structure and evolution of Salmonella enterica serotype Typhi in Zimbabwe before a typhoid conjugate vaccine immunization campaign

Population structure and evolution of Salmonella enterica serotype Typhi in Zimbabwe before a typhoid conjugate vaccine immunization campaign

The origins of haplotype 58 (H58) Salmonella enterica serovar Typhi

Methods for Genomic Epidemiology of Bacterial Pathogens: Example Salmonella

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