Open AccessImatinib augments standard malaria combination therapy without added toxicity
Author(s) -
Huynh Dinh Chien,
Antonella Pantaleo,
Kristina R. Kesely,
Panae Noomuna,
Karson S. Putt,
Trần Anh Tuấn,
Philip S. Low,
Francesco Michelangelo Turrini
Publication year - 2021
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20210724
Subject(s) - imatinib , parasitemia , pharmacology , plasmodium falciparum , malaria , medicine , artemisinin , tyrosine kinase inhibitor , dihydroartemisinin , adverse effect , immunology , cancer , myeloid leukemia
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.