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Ashton, Philip M, Chunga Chirambo, Angeziwa, Meiring, James E, Patel, Priyanka D, Mbewe, Maurice, Silungwe, Niza, Chizani, Kenneth, Banda, Happy, Heyderman, Robert S, Dyson, Zoe A, MacPherson, Peter, Henrion, Marc, Holt, Kathryn E, Gordon, Melita A, Biswas, Prasanta Kumar, Bhuiyan, Md Amiruli Islam, Blohmke, Christoph, Darton, Thomas C, Dolecek, Christiane, Dongol, Sabina, Farooq, Yama, Hill, Jennifer, Hoang, Nhu Tran, Makhaza Jere, Tikhala, Msuku, Harrison, Nga, Tran Vu Thieu, Nkhata, Rose, Rahman, Sadia Isfat Ara, Rahman, Nazia, Saad, Neil J, Van Tan, Trinh, Thindwa, Deus, Voysey, Merryn, Wachepa, Richard and Pollard, Andrew (2024) 'Evaluating the relationship between ciprofloxacin prescription and non-susceptibility in Salmonella Typhi in Blantyre, Malawi: an observational study'. The Lancet Microbe, Vol 5, Issue 3, pp. 226-234.
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Abstract
Background
Ciprofloxacin is the first-line drug for treating typhoid fever in many countries in Africa with a high disease burden, but the emergence of non-susceptibility poses a challenge to public health programmes. Through enhanced surveillance as part of vaccine evaluation, we investigated the occurrence and potential determinants of ciprofloxacin non-susceptibility in Blantyre, Malawi.
Methods
We conducted systematic surveillance of typhoid fever cases and antibiotic prescription in two health centres in Blantyre, Malawi, between Oct 1, 2016, and Oct 31, 2019, as part of the STRATAA and TyVAC studies. In addition, blood cultures were taken from eligible patients presenting at Queen Elizabeth Central Hospital, Blantyre, as part of routine diagnosis. Inclusion criteria were measured or reported fever, or clinical suspicion of sepsis. Microbiologically, we identified Salmonella enterica serotype Typhi (S Typhi) isolates with a ciprofloxacin non-susceptible phenotype from blood cultures, and used whole-genome sequencing to identify drug-resistance mutations and phylogenetic relationships. We constructed generalised linear regression models to investigate associations between the number of ciprofloxacin prescriptions given per month to study participants and the proportion of S Typhi isolates with quinolone resistance-determining region (QRDR) mutations in the following month.
Findings
From 46 989 blood cultures from Queen Elizabeth Central Hospital, 502 S Typhi isolates were obtained, 30 (6%) of which had either decreased ciprofloxacin susceptibility, or ciprofloxacin resistance. From 11 295 blood cultures from STRATAA and TyVAC studies, 241 microbiologically confirmed cases of typhoid fever were identified, and 198 isolates from 195 participants sequenced (mean age 12·8 years [SD 10·2], 53% female, 47% male). Between Oct 1, 2016, and Aug 31, 2019, of 177 typhoid fever cases confirmed by whole-genome sequencing, four (2%) were caused by S Typhi with QRDR mutations, compared with six (33%) of 18 cases between Sept 1 and Oct 31, 2019. This increase was associated with a preceding spike in ciprofloxacin prescriptions. Every additional prescription of ciprofloxacin given to study participants in the preceding month was associated with a 4·2% increase (95% CI 1·8–7·0) in the relative risk of isolating S Typhi with a QRDR mutation (p=0·0008). Phylogenetic analysis showed that S Typhi isolates with QRDR mutations from September and October, 2019, belonged to two distinct subclades encoding two different QRDR mutations, and were closely related (4–10 single-nucleotide polymorphisms) to susceptible S Typhi endemic to Blantyre.
Interpretation
We postulate a causal relationship between increased ciprofloxacin prescriptions and an increase in fluoroquinolone non-susceptibility in S Typhi. Decreasing ciprofloxacin use by improving typhoid diagnostics, and reducing typhoid fever cases through the use of an efficacious vaccine, could help to limit the emergence of resistance.
| Item Type: | Article | ||||
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| Subjects: | WC Communicable Diseases > Infection. Bacterial Infections > Enteric Infections > WC 269 Salmonella infections WC Communicable Diseases > Infection. Bacterial Infections > Enteric Infections > WC 270 Typhoid fever |
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| Repository link: |
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| Faculty: Department: | Clinical Sciences & International Health > Clinical Sciences Department | ||||
| Digital Object Identifer (DOI): | https://doi.org/10.1016/s2666-5247(23)00327-0 | ||||
| SWORD Depositor: | JISC Pubrouter | ||||
| Depositing User: | JISC Pubrouter | ||||
| Date Deposited: | 29 Feb 2024 13:17 | ||||
| Last Modified: | 12 Mar 2024 15:58 | ||||
| URI: | https://archive.lstmed.ac.uk/id/eprint/24108 |
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