Rodent systems (Plasmodium berghei-Anopheles Stephensi) for screening compounds for potential causal prophylaxis.

An in vivo screening system is described in which drugs administered to rats or mice and challenged with sporozoites are evaluated for their antimalarial properties (causal prophylaxis, suppression, therapy) by the presence or absence of exoerythrocytic forms and parasitemia. The system is composed of A/J mice, Sprague-Dawley rats, Plasmodium berghei, and Anopheles stephensi. Good correlation has been found between test results and practical application.

Sporozoite-induced infections of Plasmodium berghei administered by the oral route.

Administration of suspensions of Plasmodium berghei sporozoites by the oral route to groups of susceptible animals (A/J mice, young rats, hamsters, and Thamnomys) resulted in high rates of infection (66 to 100 percent). Control animals each given a suspension of 200,000 to 500,000 erythrocytes infected with P. berghei by the same oral route did not develop parasitemia. Direct intubation of sporozoite suspensions into the stomach failed to produce parasitemia. In vitro studies showed that sporozoites kept in medium M 199 acidified to pH 3.6 (the acid environment of the rat stomach) for 5 to 15 mtinutes lost their viability and infectivity. We believe that sporozoites of P. berghei find their way to the bloodstream during their brief sojourn in the esophagus.