Adaptation of a Thai multidrug-resistant C2A clone of Plasmodium falciparum to Aotus monkeys and its preliminary in vivo antimalarial drug efficacy-resistance profile.
A multidrug-resistant (MDR) clone of Plasmodium falciparum (C2A) from Thailand was adapted through serial passage to Aotus monkeys. During adaptation, the parasite showed resistance to a single 20 or 40 mg/kg oral dose of mefloquine (MQ). Infection was only cured when MQ was administered orally at 40 mg/kg once in combination with intravenous artesunic acid at 20 mg/kg for 3 days. Similarly, the parasite clone was found to be resistant to quinine, failing at 20 mg/kg orally for 5 days in combination with an experimental dihydrofolate reductase (DHFR) inhibitor (WR297608) at 10, 20, or 40 mg/kg orally for 3 days, and with atovaquone/proguanil at 25 mg/kg for 3 days. This new model will allow in vivo testing of new antimalarial compounds or their combinations against a currently circulating MDR P. falciparum strain.
Obaldía
Nicanor
N
Malaria Drug and Vaccine Evaluation Center, Tropical Medicine Research, Panama City, Republic of Panama. nobaldia@gorgas.gob.pa
Milhous
Wilbur
W
Kyle
Dennis
D
D000222:Adaptation, Physiological; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D016645:Aotidae; D018432:Drug Resistance, Multiple; D005260:Female; D016778:Malaria, Falciparum / Q000469:parasitology; D008297:Male; D018512:Parasitemia; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000502:physiology*; D013785:Thailand; D013997:Time Factors
D000962:Antimalarials