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Oxygen Enhances the Antimalarial Activity of the Imidazoles^*

We have previously reported the antimalarial activity of imidazoles and amphotericin B against chloroquine-resistant Plasmodium falciparum. We now report the enhancement of imidazole activity in an atmosphere with 17–18% oxygen (the candle jar) vs. 3% or 0.3% oxygen. Based on both morphologic and radiometric testing, smaller amounts of the imidazoles were required to inhibit parasite growth by 50% in the candle jar vs. 3% or 0.3% oxygen. The use of older (more oxidant-sensitive) red cells also enhanced the antimalarial activity of ketoconazole. Neither increased concentrations of oxygen nor the use of older red cells affected the activity of amphotericin B. These results suggest that the imidazoles may exert their antimalarial effect by increasing the oxidant stress on the red cell-parasite complex.

Accepted for publication December 3, 1982.

^* Presented in part at the Annual Meeting of the American Society of Tropical Medicine and Hygiene, San Juan, Puerto Rico, November 1981.

Address reprint requests to: Dr. Donald J. Krogstad, Microbiology Laboratory, Barnes Hospital, St. Louis, Missouri 63110.

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