title: Plasmodium yoelii: activity of azithromycin in combination with pyrimethamine or sulfadoxine against blood and sporozoite induced infections in Swiss mice.
abstract: The efficacy of pyrimethamine or sulfadoxine administered in combination with azithromycin was examined in a rodent malaria model. Outbred Swiss mice infected with blood stage parasites were treated from day 0 to day 3 and efficacy of different regimens was monitored in terms of the curative response and the delay time to reach 2% parasitaemia (2% DT). Administration of azithromycin alone at 60 mg/kg/day produced curative response while lower doses showed marginally delayed 2% DT. A marked potentiation in activities of pyrimethamine (100-fold) or sulfadoxine (10-fold) was observed when administered at non-curative doses of 0.1 mg/kg/day in combination with azithromycin (30 mg/kg/day) against blood stage parasites. A combination of 10 mg/kg/day azithromycin with 0.3 mg/kg/day sulfadoxine was also curative. Likewise in the causal prophylactic test, a combination regimen comprising 1/16th and 1/3rd the individual curative doses of pyrimethamine and azithromycin, respectively, prevented the development of patent infection after Plasmodium yoelii sporozoite challenge. Our results suggest that a combination of azithromycin with the second line treatment regimen of fansidar may enhance the therapeutic efficacy of the latter and also provide better prophylaxis against Plasmodium falciparum malaria.
authors.affiliation: Division of Parasitology, Central Drug Research Institute, Lucknow 226001, India.
authors.forename: J
authors.initials: J
authors.lastname: Neerja
authors.forename: S K
authors.initials: SK
authors.lastname: Puri
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D017963:Azithromycin / Q000494:pharmacology / Q000627:therapeutic use*; D002738:Chloroquine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology / Q000517:prevention & control; D008297:Male; D051379:Mice; D018512:Parasitemia / Q000188:drug therapy / Q000469:parasitology / Q000517:prevention & control; D010967:Plasmodium yoelii / Q000187:drug effects*; D011739:Pyrimethamine / Q000494:pharmacology / Q000627:therapeutic use*; D034101:Sporozoites / Q000187:drug effects; D013413:Sulfadoxine / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000962:Antimalarials; D017963:Azithromycin; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine