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Imatinib augments standard malaria combination therapy without added toxicity

To egress from its erythrocyte host, the malaria parasite, Plasmodium falciparum, must destabilize the erythrocyte membrane by activating an erythrocyte tyrosine kinase. Because imatinib inhibits erythrocyte tyrosine kinases and because imatinib has a good safety profile, we elected to determine whe...

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Autores principales: Chien, Huynh Dinh, Pantaleo, Antonella, Kesely, Kristina R., Noomuna, Panae, Putt, Karson S., Tuan, Tran Anh, Low, Philip S., Turrini, Francesco M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404470/
https://www.ncbi.nlm.nih.gov/pubmed/34436509
http://dx.doi.org/10.1084/jem.20210724
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author Chien, Huynh Dinh
Pantaleo, Antonella
Kesely, Kristina R.
Noomuna, Panae
Putt, Karson S.
Tuan, Tran Anh
Low, Philip S.
Turrini, Francesco M.
author_facet Chien, Huynh Dinh
Pantaleo, Antonella
Kesely, Kristina R.
Noomuna, Panae
Putt, Karson S.
Tuan, Tran Anh
Low, Philip S.
Turrini, Francesco M.
author_sort Chien, Huynh Dinh
collection PubMed
description To egress from its erythrocyte host, the malaria parasite, Plasmodium falciparum, must destabilize the erythrocyte membrane by activating an erythrocyte tyrosine kinase. 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’s SOC (40 mg dihydroartemisinin + 320 mg piperaquine/d) or imatinib (400 mg/d) + SOC. Imatinib + SOC–treated 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.
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spelling pubmed-84044702022-04-04 Imatinib augments standard malaria combination therapy without added toxicity Chien, Huynh Dinh Pantaleo, Antonella Kesely, Kristina R. Noomuna, Panae Putt, Karson S. Tuan, Tran Anh Low, Philip S. Turrini, Francesco M. J Exp Med Brief Definitive Report To egress from its erythrocyte host, the malaria parasite, Plasmodium falciparum, must destabilize the erythrocyte membrane by activating an erythrocyte tyrosine kinase. 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’s SOC (40 mg dihydroartemisinin + 320 mg piperaquine/d) or imatinib (400 mg/d) + SOC. Imatinib + SOC–treated 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. Rockefeller University Press 2021-08-26 /pmc/articles/PMC8404470/ /pubmed/34436509 http://dx.doi.org/10.1084/jem.20210724 Text en © 2021 Chien et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Brief Definitive Report
Chien, Huynh Dinh
Pantaleo, Antonella
Kesely, Kristina R.
Noomuna, Panae
Putt, Karson S.
Tuan, Tran Anh
Low, Philip S.
Turrini, Francesco M.
Imatinib augments standard malaria combination therapy without added toxicity
title Imatinib augments standard malaria combination therapy without added toxicity
title_full Imatinib augments standard malaria combination therapy without added toxicity
title_fullStr Imatinib augments standard malaria combination therapy without added toxicity
title_full_unstemmed Imatinib augments standard malaria combination therapy without added toxicity
title_short Imatinib augments standard malaria combination therapy without added toxicity
title_sort imatinib augments standard malaria combination therapy without added toxicity
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404470/
https://www.ncbi.nlm.nih.gov/pubmed/34436509
http://dx.doi.org/10.1084/jem.20210724
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