Selection of Increased Quinine Resistance in Plasmodium Falciparum in Aotus Monkeys

Abstract

Although partial resistance (RI) of Plasmodium falciparum to quinine is common in some areas of the world, failure to obtain an initial response (RII or RIII) is unusual. Furthermore, emergence of quinine resistance during therapy of malaria infections in humans and animals is uncommon. In the current study, exposure of the Panama II strain of P. falciparum in Aotus monkeys to subcurative quinine therapy during six serial passages over 6 months resulted in a shift in the quinine responsiveness of the strain from mild insensitivity to quinine to uniform resistance of a marked degree. Treatment with quinine for 14 days of infections in 12 monkeys with the original isolate resulted in cure in 8 monkeys and RI resistance in 4. Infections with the resistant isolate (selected under quinine pressure) were uniformly resistant to cure by 14 days of quinine; resistance to quinine was RIII in 4 of 12 monkeys and was RII in 5. These results suggest that extensive usage of quinine or related drugs (e.g., mefloquine) in the field may result in decreasing sensitivity of falciparum malaria to quinine.