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

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.

• Authors: Nicanor Obaldía 3rd, Wilbur Milhous, Dennis Kyle
• Journal: The American journal of tropical medicine and hygiene (Am J Trop Med Hyg) Vol. 81 Issue 4 Pg. 587-94 (Oct 2009) ISSN: 1476-1645 [Electronic] United States
• PMID: 19815871 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antimalarials

Topics

• Adaptation, Physiological
• Animals
• Antimalarials (pharmacology)
• Aotidae
• Drug Resistance, Multiple
• Female
• Malaria, Falciparum (parasitology)
• Male
• Parasitemia
• Plasmodium falciparum (drug effects, physiology)
• Thailand
• Time Factors