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Dyson, Zoe A, Ashton, Philip M, Khanam, Farhana, Chunga Chirambo, Angeziwa, Shakya, Mila, Meiring, James E, Tonks, Susan, Karkey, Abhilasha, Msefula, Chisomo, Clemens, John D, Dunstan, Sarah J, Baker, Stephen, Dougan, Gordon, Pitzer, Virginia E, Basnyat, Buddha, Qadri, Firdausi, Heyderman, Robert S, Gordon, Melita, Pollard, Andrew J and Holt, Kathryn E (2024) 'Pathogen diversity and antimicrobial resistance transmission of Salmonella enterica serovars Typhi and Paratyphi A in Bangladesh, Nepal, and Malawi: a genomic epidemiological study.'. Lancet Microbe, Vol 5, Issue 8, p. 100841.
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Abstract
Background
Enteric fever is a serious public health concern. The causative agents, Salmonella enterica serovars Typhi and Paratyphi A, frequently have antimicrobial resistance (AMR), leading to limited treatment options and poorer clinical outcomes. We investigated the genomic epidemiology, resistance mechanisms, and transmission dynamics of these pathogens at three urban sites in Africa and Asia.
Methods
S Typhi and S Paratyphi A bacteria isolated from blood cultures of febrile children and adults at study sites in Dhaka (Bangladesh), Kathmandu (Nepal), and Blantyre (Malawi) during STRATAA surveillance were sequenced. Isolates were charactered in terms of their serotypes, genotypes (according to GenoTyphi and Paratype), molecular determinants of AMR, and population structure. We used phylogenomic analyses incorporating globally representative genomic data from previously published surveillance studies and ancestral state reconstruction to differentiate locally circulating from imported pathogen AMR variants. Clusters of sequences without any single-nucleotide variants in their core genome were identified and used to explore spatiotemporal patterns and transmission dynamics.
Findings
We sequenced 731 genomes from isolates obtained during surveillance across the three sites between Oct 1, 2016, and Aug 31, 2019 (24 months in Dhaka and Kathmandu and 34 months in Blantyre). S Paratyphi A was present in Dhaka and Kathmandu but not Blantyre. S Typhi genotype 4.3.1 (H58) was common in all sites, but with different dominant variants (4.3.1.1.EA1 in Blantyre, 4.3.1.1 in Dhaka, and 4.3.1.2 in Kathmandu). Multidrug resistance (ie, resistance to chloramphenicol, co-trimoxazole, and ampicillin) was common in Blantyre (138 [98%] of 141 cases) and Dhaka (143 [32%] of 452), but absent from Kathmandu. Quinolone-resistance mutations were common in Dhaka (451 [>99%] of 452) and Kathmandu (123 [89%] of 138), but not in Blantyre (three [2%] of 141). Azithromycin-resistance mutations in acrB were rare, appearing only in Dhaka (five [1%] of 452). Phylogenetic analyses showed that most cases derived from pre-existing, locally established pathogen variants; 702 (98%) of 713 drug-resistant infections resulted from local circulation of AMR variants, not imported variants or recent de novo emergence; and pathogen variants circulated across age groups. 479 (66%) of 731 cases clustered with others that were indistinguishable by point mutations; individual clusters included multiple age groups and persisted for up to 2·3 years, and AMR determinants were invariant within clusters.
Interpretation
Enteric fever was associated with locally established pathogen variants that circulate across age groups. AMR infections resulted from local transmission of resistant strains. These results form a baseline against which to monitor the impacts of control measures.
| Item Type: | Article |
|---|---|
| Corporate Authors: | STRATAA Study Group |
| Subjects: | QW Microbiology and Immunology > QW 4 General works. Classify here works on microbiology as a whole. QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified. WC Communicable Diseases > Infection. Bacterial Infections > Enteric Infections > WC 260 Enterobacteriaceae and other enteric infections WC Communicable Diseases > Infection. Bacterial Infections > Enteric Infections > WC 266 Paratyphoid fevers WC Communicable Diseases > Infection. Bacterial Infections > Enteric Infections > WC 269 Salmonella infections |
| Faculty: Department: | Clinical Sciences & International Health > Clinical Sciences Department |
| Digital Object Identifer (DOI): | https://doi.org/10.1016/S2666-5247(24)00047-8 |
| SWORD Depositor: | JISC Pubrouter |
| Depositing User: | JISC Pubrouter |
| Date Deposited: | 07 Aug 2024 14:01 |
| Last Modified: | 07 Aug 2024 14:01 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/25007 |
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