{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T19:32:26Z","timestamp":1787686346535,"version":"build-2784847793"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T00:00:00Z","timestamp":1692662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"National Parasitology Reference Laboratory"},{"name":"Public Health Services"},{"name":"Ministry of Health, Israel"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Artemisinin-based combination therapies (ACTs) are recommended as first-line treatment against uncomplicated Plasmodium falciparum infection. Mutations in the PfKelch13 (PF3D7_1343700) gene led to resistance to artemisinin in Southeast Asia. Mutations in the Pfcoronin (PF3D7_1251200) gene confer reduced artemisinin susceptibility in vitro to an African Plasmodium strain, but their role in clinical resistance has not been established.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective observational study of Israeli travellers returning from sub-Saharan Africa with P. falciparum malaria, including patients with artemether\u2013lumefantrine (AL) failure. Blood samples from all malaria-positive patients are delivered to the national Parasitology Reference Laboratory along with personal information. Confirmation of malaria, species identification and comparative parasite load analysis were performed using real-time PCR. DNA extractions from stored leftover samples were analysed for the presence of mutations in Pfkelch13 and Pfcoronin. Age, weight, initial parasitaemia level and Pfcoronin status were compared in patients who failed treatment vs responders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>During 2009\u20132020, 338 patients had P. falciparum malaria acquired in Africa. Of those, 15 (24\u201369\u00a0years old, 14 males) failed treatment with AL. Four were still parasitemic at the end of treatment, and 11 had malaria recrudescence. Treatment failure rates were 0% during 2009\u20132012, 9.1% during 2013\u20132016 and 17.4% during 2017\u20132020. In all patients, the Pfkelch13 propeller domain had a wild-type sequence. We did find the P76S mutation in the propeller domain of Pfcoronin in 4\/15 (28.6%) of the treatment-failure cases compared to only 3\/56 (5.5%) in the successfully treated patients (P\u00a0=\u20090.027).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>AL treatment failure emergence was not associated with mutations in Pfkelch13. However, P76S mutation in the Pfcoronin gene was more frequently present in the treatment-failure group and merits further investigation. The increase of malaria incidence in sub-Saharan-Africa partly attributed to the COVID-19 pandemic might also reflect a wider spread of ACT resistance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jtm\/taad114","type":"journal-article","created":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T07:44:31Z","timestamp":1692690271000},"source":"Crossref","is-referenced-by-count":24,"title":["Emergence of artemisinin-based combination treatment failure in patients returning from sub-Saharan Africa with\n                    <i>P. falciparum<\/i>\n                    malaria"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6301-1696","authenticated-orcid":false,"given":"Tamar","family":"Grossman","sequence":"first","affiliation":[{"name":"Parasitology Reference Laboratory , Public Health Laboratories\u2013Jerusalem (PHL-J), , Jerusalem 9134302 , Israel"},{"name":"Public Health Services (PHS), Ministry of Health (MOH) , Public Health Laboratories\u2013Jerusalem (PHL-J), , Jerusalem 9134302 , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Vainer","sequence":"additional","affiliation":[{"name":"Parasitology Reference Laboratory , Public Health Laboratories\u2013Jerusalem (PHL-J), , Jerusalem 9134302 , Israel"},{"name":"Public Health Services (PHS), Ministry of Health (MOH) , Public Health Laboratories\u2013Jerusalem (PHL-J), , Jerusalem 9134302 , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Paran","sequence":"additional","affiliation":[{"name":"Infectious Disease Department, Tel Aviv Sourasky Medical Center , Tel Aviv 64239 , Israel"},{"name":"Faculty of Medicine, Tel Aviv University , Tel Aviv 69978 , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liora","family":"Studentsky","sequence":"additional","affiliation":[{"name":"Parasitology Reference Laboratory , Public Health Laboratories\u2013Jerusalem (PHL-J), , Jerusalem 9134302 , Israel"},{"name":"Public Health Services (PHS), Ministry of Health (MOH) , Public Health Laboratories\u2013Jerusalem (PHL-J), , Jerusalem 9134302 , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3912-6957","authenticated-orcid":false,"given":"Uri","family":"Manor","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Tel Aviv University , Tel Aviv 69978 , Israel"},{"name":"The Center for Geographic Medicine, Sheba Medical Center , Tel HaShomer 5262000 , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron","family":"Dzikowski","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Molecular Genetics , The Kuvin Center for the Study of Infectious and Tropical Diseases, IMRIC, , Jerusalem 91120 , Israel"},{"name":"The Hebrew University-Hadassah Medical School , The Kuvin Center for the Study of Infectious and Tropical Diseases, IMRIC, , Jerusalem 91120 , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Tel Aviv University , Tel Aviv 69978 , Israel"},{"name":"The Center for Geographic Medicine, Sheba Medical Center , Tel HaShomer 5262000 , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,8,22]]},"reference":[{"key":"2023122906165094700_ref1","volume-title":"World Malaria Report 2021","author":"WHO","year":"2021"},{"key":"2023122906165094700_ref2","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.ijpddr.2021.05.007","article-title":"Plasmodium falciparum resistance to ACTs: emergence, mechanisms, and outlook","volume":"16","author":"Siddiqui","year":"2021","journal-title":"Int J Parasitol Drugs Drug 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