WR-238605, CHLOROQUINE, AND THEIR COMBINATIONS AS BLOOD SCHIZONTICIDES AGAINST A CHLOROQUINE-RESISTANT STRAIN OF PLASMODIUM-VIVAX IN AOTUS MONKEYS

The compound WR 238605 is a primaquine analog being developed by the U .S. Army as an antimalarial drug. Currently, there is no established t reatment for Plasmodium vivax parasitemias that are not cured by chlor oquine. This study tested WR 238605, chloroquine, and their combinatio ns against a chloroquine-resistant strain of P. vivax (AMRU 1) in Aotu s monkeys. A total dose of 3 mg/kg of WR 238605 given at a dosage of 1 mg/kg/day for three days cleared patent parasites in all eight monkey s but recrudescence of parasitemia occurred 15-25 days after initiatio n of treatment. A total dose of 9 mg/kg of WR 238605 over a three-day period cured all three monkeys of their infections. A total dose of 30 mg/kg of chloroquine did not clear patent infections in three monkeys , whereas a total dose of 60 mg/kg generally (two of three) cleared pa tent parasitemia but did not cure. Whereas total doses of 30 mg/kg of chloroquine or 3 mg/kg of WR 238605 given alone failed to cure, both d rugs given in combination at these dosages cured two of three infectio ns. These results indicate that WR 238605 may be an alternative treatm ent for chloroquine-resistant vivax malaria.