Prevention of sporogony of Plasmodium falciparum and P. berghei in Anopheles stephensi mosquitoes by transmission-blocking antimalarials

Abstract

The sporontocidal activity of three 8-aminoquinolines, a 1,4-naphthoquinone, and three dihydroacridine-diones was determined against the ANKA clone of Plasmodium berghei and both chloroquine-sensitive (NF54) and chloroquine-resistant (7G8) P. falciparum. Anopheles stephensi mosquitoes previously fed on P. berghei--infected mice or P. falciparum--infected cultures were refed on uninfected mice treated previously with a given drug. Sporontocidal activity was determined by assessing both oocyst and sporozoite development. Neither primaquine nor menoctone exhibited sporontocidal activity against P. berghei or either strain of P. falciparum at a dose of 100 mg base drug/kg mouse body weight, whereas the other five compounds each effectively interrupted the sporogonic development of all three parasite strains at this dose. These data clearly demonstrate that experimental dihydroacridine-diones and 8-aminoquinolines are capable of interrupting the sporogonic development of P. berghei and chloroquine-sensitive and chloroquine-resistant P. falciparum. These data also suggest that the P. berghei model may be used to accurately predict sporontocidal activity against P. falciparum.