Journal article
Treatment failure in a UK malaria patient harbouring genetically variant Plasmodium falciparum from Uganda with reduced in vitro susceptibility to artemisinin and lumefantrine
- Abstract:
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Background: Recent cases of clinical failure in UK malaria patients treated with artemether-lumefantrine have implications for malaria chemotherapy worldwide.
Methods: Parasites were isolated from an index case of confirmed Plasmodium falciparum treatment failure after standard treatment, and from comparable travel-acquired UK malaria cases. Drug susceptibility in vitro and genotypes at six resistance-associated loci were determined for all parasite isolates and compared with clinical outcomes for each parasite donor.
Results: A traveller, who returned to the UK from Uganda in 2022 with Plasmodium falciparum malaria, twice failed treatment with full courses of artemether-lumefantrine. Parasites from the patient exhibited significantly reduced susceptibility to artemisinin (ring-stage survival 17.3%; 95% C.I. 13.6 - 21.1 %; P<0.0001) and lumefantrine (EC50 259.4nM; 95% C.I. 130.6 388.2nM; P=0.001). Parasite genotyping identified an allele of pfk13 encoding both the A675V variant in the Pfk13 propeller domain and a novel L145V non-propeller variant. In vitro susceptibility testing of six other P. falciparum lines of Ugandan origin identified reduced susceptibility to artemisinin and lumefantrine in one additional line, also from a 2022 treatment failure case. These parasites did not harbour a pfk13 propeller domain variant but rather the novel non-propeller variant T349I. Variant alleles of pfubp1, pfap2mu and pfcoronin were also identified among the seven parasite lines.
Conclusions: We confirm, in a documented case of artemether-lumefantrine treatment failure imported from Uganda, the presence of pfk13 mutations encoding L145V and A675V. Parasites with reduced susceptibility to both artemisinin and lumefantrine may be emerging in Uganda.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 664.0KB, Terms of use)
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- Publisher copy:
- 10.1093/cid/ciad724
Authors
- Publisher:
- Oxford University Press
- Journal:
- Clinical Infectious Diseases More from this journal
- Volume:
- 78
- Issue:
- 2
- Pages:
- 445–452
- Publication date:
- 2023-11-29
- Acceptance date:
- 2023-11-23
- DOI:
- EISSN:
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1537-6591
- ISSN:
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1058-4838
- Language:
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English
- Keywords:
- Pubs id:
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1569794
- Local pid:
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pubs:1569794
- Deposit date:
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2023-11-23
- ARK identifier:
Terms of use
- Copyright holder:
- van Schalkwyk et al
- Copyright date:
- 2023
- Rights statement:
- © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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