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Imatinib augments standard malaria combination therapy without added toxicity.

ABSTRACT: 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.

SUBMITTER: Chien HD

PROVIDER: S-EPMC8404470 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Imatinib augments standard malaria combination therapy without added toxicity.

Chien Huynh Dinh HD Pantaleo Antonella A Kesely Kristina R KR Noomuna Panae P Putt Karson S KS Tuan Tran Anh TA Low Philip S PS Turrini Francesco M FM

The Journal of experimental medicine 20210826 10

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 ...[more]

PMID: 34436509

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Imatinib augments standard malaria combination therapy without added toxicity.

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Imatinib augments standard malaria combination therapy without added toxicity.

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