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Am J Trop Med Hyg. 2009 Oct;81(4):587-94. doi: 10.4269/ajtmh.2009.08-0445.

Adaptation of a Thai multidrug-resistant C2A clone of Plasmodium falciparum to Aotus monkeys and its preliminary in vivo antimalarial drug efficacy-resistance profile.

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  • 1Malaria Drug and Vaccine Evaluation Center, Tropical Medicine Research, Panama City, Republic of Panama. nobaldia@gorgas.gob.pa

Abstract

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.

PMID:
19815871
DOI:
10.4269/ajtmh.2009.08-0445
[PubMed - indexed for MEDLINE]
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