دورية أكاديمية
Treatment Failure in a UK Malaria Patient Harboring Genetically Variant Plasmodium falciparum From Uganda With Reduced In Vitro Susceptibility to Artemisinin and Lumefantrine.
| العنوان: | Treatment Failure in a UK Malaria Patient Harboring Genetically Variant Plasmodium falciparum From Uganda With Reduced In Vitro Susceptibility to Artemisinin and Lumefantrine. |
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| المؤلفون: | van Schalkwyk DA; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom., Pratt S; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom., Nolder D; UK Health Security Agency Malaria Reference Laboratory, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom., Stewart LB; UK Health Security Agency Malaria Reference Laboratory, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom., Liddy H; UK Health Security Agency Malaria Reference Laboratory, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom., Muwanguzi-Karugaba J; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom., Beshir KB; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom., Britten D; UK Health Security Agency Malaria Reference Laboratory, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom., Victory E; UK Health Security Agency Malaria Reference Laboratory, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom., Rogers C; UK Health Security Agency Malaria Reference Laboratory, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom., Millard J; Hospital for Tropical Diseases, University College London Hospitals NHS Foundation Trust, London, United Kingdom., Brown M; Hospital for Tropical Diseases, University College London Hospitals NHS Foundation Trust, London, United Kingdom., Nabarro LE; Hospital for Tropical Diseases, University College London Hospitals NHS Foundation Trust, London, United Kingdom., Taylor A; Department of Infectious Diseases, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom., Young BC; Department of Infectious Diseases, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom., Chiodini PL; UK Health Security Agency Malaria Reference Laboratory, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom., Sutherland CJ; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.; UK Health Security Agency Malaria Reference Laboratory, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. |
| المصدر: | Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2024 Feb 17; Vol. 78 (2), pp. 445-452. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 9203213 Publication Model: Print Cited Medium: Internet ISSN: 1537-6591 (Electronic) Linking ISSN: 10584838 NLM ISO Abbreviation: Clin Infect Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Jan. 2011- : Oxford : Oxford University Press Original Publication: Chicago, IL : The University of Chicago Press, c1992- |
| مواضيع طبية MeSH: | Antimalarials*/pharmacology , Antimalarials*/therapeutic use , Artemisinins*/pharmacology , Artemisinins*/therapeutic use , Malaria*/drug therapy , Malaria, Falciparum*/drug therapy , Malaria, Falciparum*/parasitology, Humans ; Lumefantrine/pharmacology ; Lumefantrine/therapeutic use ; Plasmodium falciparum ; Artemether, Lumefantrine Drug Combination/pharmacology ; Artemether, Lumefantrine Drug Combination/therapeutic use ; Uganda ; Drug Resistance ; Artemether/pharmacology ; Artemether/therapeutic use ; Treatment Failure ; United Kingdom ; Protozoan Proteins/genetics |
| مستخلص: | Background: Recent cases of clinical failure in malaria patients in the United Kingdom (UK) 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 6 resistance-associated loci were determined for all parasite isolates and compared with clinical outcomes for each parasite donor. Results: A traveler, 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% confidence interval {CI}, 13.6%-21.1%]; P < .0001) and lumefantrine (effective concentration preventing 50% of growth = 259.4 nM [95% CI, 130.6-388.2 nM]; P = .001). Parasite genotyping identified an allele of pfk13 encoding both the A675V variant in the Pfk13 propeller domain and a novel L145V nonpropeller variant. In vitro susceptibility testing of 6 other P. falciparum lines of Ugandan origin identified reduced susceptibility to artemisinin and lumefantrine in 1 additional line, also from a 2022 treatment failure case. These parasites did not harbor a pfk13 propeller domain variant but rather the novel nonpropeller variant T349I. Variant alleles of pfubp1, pfap2mu, and pfcoronin were also identified among the 7 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. Competing Interests: Potential conflicts of interest. B. C. Y. reports a clinical lecturer starter grant paid via institution from Academy of Medical Sciences and funding to institution from the Oxford University National Institute for Health and Care Research Biomedical Research Centre grant. P. L. C. reports grants or contracts from the World Health Organization for the Molecular External Quality Assessment Scheme. J. M. reports grant to institution 203919/Z/16/Z from Wellcome Trust Clinical PhD and grant to institution from UCL Global Challenges, and participation as chair of a data and safety monitoring board for Triage Test for All Oral DR-TB Regimen (TRiAD Study). L. E. N. reports royalties or licenses paid to author from Peter’s Atlas of Tropical Medicine and Parasitology (Elsevier, author). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.) |
| References: | Int J Parasitol Drugs Drug Resist. 2019 Apr;9:93-99. (PMID: 30831468) Sci Rep. 2019 Mar 25;9(1):5107. (PMID: 30911048) Antimicrob Agents Chemother. 2015 May;59(5):2540-7. (PMID: 25691625) Nature. 2014 Jan 2;505(7481):50-5. (PMID: 24352242) Malar J. 2021 Dec 2;20(1):451. (PMID: 34856982) BMJ Glob Health. 2017 Aug 30;2(3):e000371. (PMID: 29082016) Lancet Microbe. 2021 Sep;2(9):e441-e449. (PMID: 34553183) Malar J. 2013 Sep 13;12:320. (PMID: 24028570) N Engl J Med. 2023 Aug 24;389(8):722-732. (PMID: 37611122) J Infect Dis. 2009 Mar 1;199(5):750-7. (PMID: 19210165) Lancet Infect Dis. 2021 Aug;21(8):1120-1128. (PMID: 33864801) Antimicrob Agents Chemother. 2011 Nov;55(11):5408-11. (PMID: 21896916) N Engl J Med. 2008 Dec 11;359(24):2619-20. (PMID: 19064625) Nat Med. 2020 Oct;26(10):1602-1608. (PMID: 32747827) N Engl J Med. 2017 Mar 9;376(10):991-3. (PMID: 28225668) N Engl J Med. 2023 Sep 28;389(13):1191-1202. (PMID: 37754284) Antimicrob Agents Chemother. 2019 Dec 20;64(1):. (PMID: 31636063) J Antimicrob Chemother. 2007 Jun;59(6):1197-9. (PMID: 17475629) J Infect Dis. 2014 Dec 15;210(12):2001-8. (PMID: 24994911) J Antimicrob Chemother. 2017 Nov 01;72(11):3051-3058. (PMID: 28961865) Science. 2015 Jan 23;347(6220):428-31. (PMID: 25502314) N Engl J Med. 2009 Jul 30;361(5):455-67. (PMID: 19641202) Clin Infect Dis. 2017 Jan 15;64(2):199-206. (PMID: 27986683) Nat Commun. 2022 Oct 26;13(1):6353. (PMID: 36289202) Int J Parasitol Drugs Drug Resist. 2019 Apr;9:23-26. (PMID: 30599390) Proc Natl Acad Sci U S A. 2018 Dec 11;115(50):12799-12804. (PMID: 30420498) N Engl J Med. 2016 Jun 23;374(25):2453-64. (PMID: 27332904) Antimicrob Agents Chemother. 2017 Feb 23;61(3):. (PMID: 28137810) Antimicrob Agents Chemother. 2007 Mar;51(3):991-7. (PMID: 17194834) Lancet Infect Dis. 2013 Dec;13(12):1043-9. (PMID: 24035558) Antimicrob Agents Chemother. 2014 Aug;58(8):4938-40. (PMID: 24867976) Antimicrob Agents Chemother. 2009 Aug;53(8):3405-10. (PMID: 19433569) J Infect Dis. 2005 Mar 15;191(6):1014-7. (PMID: 15717281) N Engl J Med. 2021 Sep 23;385(13):1163-1171. (PMID: 34551228) |
| معلومات مُعتمدة: | MR/T016124/1 United Kingdom MRC_ Medical Research Council |
| فهرسة مساهمة: | Keywords: Plasmodium falciparum; Uganda; drug susceptibility; travelers’ malaria; treatment failure |
| المشرفين على المادة: | F38R0JR742 (Lumefantrine) 0 (Antimalarials) 0 (Artemether, Lumefantrine Drug Combination) C7D6T3H22J (Artemether) 9RMU91N5K2 (artemisinin) 0 (Artemisinins) 0 (Protozoan Proteins) |
| تواريخ الأحداث: | Date Created: 20231129 Date Completed: 20240219 Latest Revision: 20240329 |
| رمز التحديث: | 20240330 |
| مُعرف محوري في PubMed: | PMC10874266 |
| DOI: | 10.1093/cid/ciad724 |
| PMID: | 38019958 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1537-6591 |
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| DOI: | 10.1093/cid/ciad724 |