A method for screening drugs against the liver stages of malaria using Plasmodium gallinaceum and Aedes mosquitos.
1. The radical cure of human malaria caused by Plasmodium vivax requires two drugs, i.e., a blood schizontocide such as chloroquine to clear the circulating parasites, and primaquine aimed at the liver stages (hyponozoites) responsible for the late relapses of this parasite. Primaquine is unique as a radical curative drug but is highly toxic. The only useful model currently available for screening drugs to replace primaquine is Plasmodium cynomolgi-induced malaria in Rhesus monkeys. Because of the limited availability and cost of these animals, the development of non-primate models for such screening would be of considerable value. 2. We used a drug-screening assay for the liver stage malaria parasite based on the ability of such drugs to stop development of gametocytes in the mosquito vector. The inhibition of the sporogonic cycle of malaria in the mosquito by primaquine (15 mg/kg) was confirmed here and used for re-evaluation of the gametocyte method. 3. We observed that the level of parasitemia in the untreated control chicken used to infect mosquitos was a crucial factor affecting the subsequent development of sporogony. Thus, parasitemia was carefully controlled in the studies involving oocyst development. Parasitemias lower than 6% at the beginning of the experiment and increasing were found to be most appropriate for the production of the infectious gametocytes during a period of 8 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Carvalho
L H
LH
Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil.
Ferrari
W M
WM
Krettli
A U
AU
D000330:Aedes / Q000469:parasitology; D000818:Animals; D001938:Brazil; D002645:Chickens / Q000469:parasitology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D008099:Liver / Q000469:parasitology; D016780:Malaria, Vivax / Q000188:drug therapy*; D009285:Naphthoquinones / Q000494:pharmacology* / Q000627:therapeutic use*; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use*; D010946:Plants, Medicinal; D010964:Plasmodium gallinaceum / Q000187:drug effects* / Q000254:growth & development
D009285:Naphthoquinones; D010936:Plant Extracts