title: Isonicotinic acid hydrazide: an anti-tuberculosis drug inhibits malarial transmission in the mosquito gut.
abstract: We studied the transmission-blocking effect of isonicotinic acid hydrazide (INH), a widely used anti-tuberculosis drug, against Plasmodium gallinaceum and Plasmodium berghei. INH-treatment of infected animals did not inhibit parasite development in the blood of the vertebrate host, but did inhibit exflagellation, ookinete formation, and oocyst development in the mosquito. Oocyst development was inhibited in a dose-dependent manner. The ED(50) in the P. gallinaceum/chicken/Aedes aegypti model and P. berghei/mouse/Anopheles stephensi model was 72 and 109 mg/kg, respectively. In marked contrast, in vitro exflagellation and ookinete development were not directly affected by physiological concentrations of INH. We suggest that INH exerts its inhibitory effects on the mosquito stages of the malaria parasite by an indirect, and at present undefined mechanism. Further elucidation of the mechanism how INH inhibits parasite development specifically on mosquito stages may allow us to identify new targets for malaria control strategy.
authors.affiliation: Department of Biological Sciences, Imperial College of Science, Technology, and Medicine, London SW7 2AZ, UK. marai@ms.jichi.ac.jp
authors.forename: Meiji
authors.initials: M
authors.lastname: Arai
authors.forename: Yasmene I H
authors.initials: YI
authors.lastname: Alavi
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Mendoza
authors.forename: Oliver
authors.initials: O
authors.lastname: Billker
authors.forename: Robert E
authors.initials: RE
authors.lastname: Sinden
mesh_terms: D000330:Aedes / Q000469:parasitology*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D000995:Antitubercular Agents / Q000494:pharmacology; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D005260:Female; D007303:Insect Vectors / Q000469:parasitology*; D007538:Isoniazid / Q000494:pharmacology*; D008288:Malaria / Q000517:prevention & control* / Q000635:transmission; D051379:Mice; D018512:Parasitemia / Q000469:parasitology / Q000517:prevention & control; D010962:Plasmodium berghei / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D010964:Plasmodium gallinaceum / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology
chemical_list: D000962:Antimalarials; D000995:Antitubercular Agents; D007538:Isoniazid