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Because imatinib inhibits erythrocyte tyrosine kinases and because imatinib has a good safety profile, we elected to determine whether coadministration of imatinib with standard of care (SOC) might be both well tolerated and therapeutically efficacious in malaria patients. Patients with uncomplicated P. falciparum malaria from a region in Vietnam where one third of patients experience delayed parasite clearance (DPC; continued parasitemia after 3 d of therapy) were treated for 3 d with either the region\u2019s SOC (40 mg dihydroartemisinin + 320 mg piperaquine\/d) or imatinib (400 mg\/d) + SOC. Imatinib + SOC\u2013treated participants exhibited no increase in number or severity of adverse events, a significantly accelerated decline in parasite density and pyrexia, and no DPC. Surprisingly, these improvements were most pronounced in patients with the highest parasite density, where serious complications and death are most frequent. Imatinib therefore appears to improve SOC therapy, with no obvious drug-related toxicities.<\/jats:p>","DOI":"10.1084\/jem.20210724","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T14:14:48Z","timestamp":1629987288000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Imatinib augments standard malaria combination therapy without added toxicity"],"prefix":"10.1084","volume":"218","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8229-1889","authenticated-orcid":true,"given":"Huynh Dinh","family":"Chien","sequence":"first","affiliation":[{"name":"College of Health Science, Vin University, Hanoi, Vietnam 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2954-7053","authenticated-orcid":true,"given":"Antonella","family":"Pantaleo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Sassari, Sassari, Italy 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8828-7573","authenticated-orcid":true,"given":"Kristina R.","family":"Kesely","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Purdue University, West Lafayette, IN 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7696-4488","authenticated-orcid":true,"given":"Panae","family":"Noomuna","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Purdue University, West Lafayette, IN 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0619-2616","authenticated-orcid":true,"given":"Karson S.","family":"Putt","sequence":"additional","affiliation":[{"name":"Institute for Drug Discovery, Purdue University, West Lafayette, IN 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4923-5735","authenticated-orcid":true,"given":"Tran Anh","family":"Tuan","sequence":"additional","affiliation":[{"name":"Huong Hoa District Health Center, Quang Tri, Vietnam 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9042-5528","authenticated-orcid":true,"given":"Philip S.","family":"Low","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Purdue University, West Lafayette, IN 3"},{"name":"Institute for Drug Discovery, Purdue University, West Lafayette, IN 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1371-1082","authenticated-orcid":true,"given":"Francesco M.","family":"Turrini","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Turin, Turin, Italy 6"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2021,8,26]]},"reference":[{"key":"2023072622353635500_bib1","doi-asserted-by":"publisher","first-page":"55827","DOI":"10.1074\/jbc.M409792200","article-title":"A novel mode of Gleevec binding is revealed by the structure of spleen tyrosine kinase","volume":"279","author":"Atwell","year":"2004","journal-title":"J. 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