Inhibitory Activity of the Anti-Malarial Atovaquone (566C80) against Ookinetes, Oocysts, and Sporozoites of Plasmodium berghei

• Published in: The Journal of parasitology Vol. 81; no. 3; pp. 452 - 458
• Main Authors: Fowler, R. E., Sinden, R. E., Pudney, M.
• Format: Journal Article
• Language: English
• Published: Lawrence, KS American Society of Parasitologists 01-06-1995
• Subjects: Animal feeding behavior; Animals; Anopheles - parasitology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimalarials - pharmacology; Antiparasitic agents; Atovaquone; Biological and medical sciences; Carcinoma, Hepatocellular; Culture Media; Ethanol; Flagella - physiology; Infections; Insect Vectors - parasitology; Liver Neoplasms; Medical sciences; Mice; Mosquitos; Naphthoquinones - pharmacology; Oocysts; Ookinetes; Parasites; Parasitology; Pharmacology. Drug treatments; Plasmodium berghei; Plasmodium berghei - drug effects; Plasmodium berghei - physiology; Sporozoites; Therapeutics-Diagnostics; Tumor Cells, Cultured; Protozoa; Antimalarial; Growth inhibitor; Protozoal disease; Malaria; Gametogenesis; Parasite; Sporozoit; Parasitosis; Infection; Plasmodium berghei; Pathogenic; Infectivity; Parasiticid; Development; Sporozoa; Vector
• ISSN: 0022-3395; 1937-2345
• DOI: 10.2307/3283831

Ookinete formation from mature Plasmodium berghei gametocytes in vitro was partially inhibited by 0.05-0.1 µM atovaquone and almost totally blocked at a concentration of 0.25 µM. Microgametocyte exflagellation was not affected by atovaquone at concentrations up to 300 µM. Ookinete formation was also inhibited in culture when addition of 0.20 µM atovaquone was delayed by 4 hr, by which time DNA replication was likely to have been completed. Inhibition of ookinete formation by atovaquone was not reversed by orotic acid. Plasmodium berghei-infected Anopheles stephensi mosquitoes were fed a second blood meal 4, 7, 14, and 20 days postinfection (p.i.) from mice that had been treated with atovaquone or control diluent 8 hr previously. Atovaquone blood feeds on day 4 reduced oocyst numbers on days 6-12, although sporozoite numbers in the thorax and abdomen on day 20 were not significantly reduced. Blood feeds on day 7 slowed oocyst growth, blood feeds on day 14 did not significantly reduce sporozoite numbers, and feeds to mosquitoes on day 20 p.i. had no effect on transmission to naive mice. Sporozoite invasion of human hepatoma cells was unaffected by the presence of atovaquone.