Isonicotinic acid hydrazide : an anti-tuberculosis drug inhibits malarial transmission in the mosquito gut

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

Aedes/*parasitology

Animals

Antimalarials/pharmacology

Antitubercular Agents/pharmacology

Chickens

Dose-Response Relationship

Drug

Female

Insect Vectors/*parasitology

Isoniazid/*pharmacology

Malaria/*prevention & control/transmission

Mice

Parasitemia/parasitology/prevention & control

Plasmodium berghei/*drug effects/growth & development/physiology

Plasmodium gallinaceum/*drug effects/growth & development/physiology

Publikations- och innehållstyp

ref (ämneskategori)

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