Sporontocidal activity of the antimalarial WR-238605 against Plasmodium berghei ANKA in Anopheles stephensi

Abstract

The influence of WR-238605 (8-[(4-amino-1-methyl-butyl) amino]-2,6-dimethoxy-4-methyl-5-[3-tri-fluoromethylphenoxyl] quinoline succinate) on the sporogonic development of a Plasmodium berghei ANKA clone was determined. Anopheles stephensi were fed on P. berghei infected mice treated 90 min earlier with 25 or 50 mg WR-238605/kg body weight. Mosquitoes engorging on drug-treated mice produced the same number of ookinetes as did those fed on controls; drug-fed mosquitoes produced fewer oocysts/mosquito than did controls. These oocytes developed more slowly than did those in control-fed mosquitoes. Sporozoites did not invade the salivary glands of drug-fed mosquitoes, nor did these mosquitoes transmit P. berghei to mice. Uptake of WR-238605 6 or 12 days after mosquitoes were infected with P. berghei had no effect on the percentage of mosquitoes with oocysts or the mean number of oocysts produced per mosquito. Oocyst development was significantly retarded in mosquitoes ingesting drug on day 6 postinfection. Subsequent salivary gland sporozoite infections were lighter in mosquitoes drug-fed on day 6 or day 12 than in control mosquitoes or mosquitoes drug-fed on day 18. These data indicate that WR-238605 has significant sporontocidal activity.