Activity of azithromycin as a blood schizonticide against rodent and human plasmodia in vivo.
We compared the efficacy of azithromycin to the clinical antimalarial doxycycline in Plasmodium berghei-infected mice and in P. falciparum-infected Aotus monkeys. When mice were administered drug orally twice a day for three days, the minimum total dose of azithromycin that cured all mice was 768 mg/kg. Doxycycline at a dose of 1,536 mg/kg cured no mice. The efficacy of fast-acting blood schizonticides (quinine, halofantrine, artemisinin) against P. berghei was augmented by azithromycin. In monkey experiments in which there were two animals per experimental group, azithromycin (100 mg/kg/day for seven days) eliminated parasitemia; azithromycin (30 mg/kg/day) initially cleared 99.8-100% of the parasites with recrudescence in the one completely cleared case. Doxycycline (30 mg/kg/day) cleared 100% of the parasites with recrudescence in both cleared cases. Since azithromycin can be clinically administered at a somewhat higher daily dosage than doxycycline, the data suggest that it may be possible to replace drugs of the tetracycline class with azithromycin in combination with fast-acting blood schizonticides for the treatment of P. falciparum infection.
Andersen
S L
SL
Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, District of Columbia.
Ager
A
A
McGreevy
P
P
Schuster
B G
BG
Wesche
D
D
Kuschner
R
R
Ohrt
C
C
Ellis
W
W
Rossan
R
R
Berman
J
J
D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use; D001029:Aotus trivirgatus; D037621:Artemisinins; D017963:Azithromycin / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004318:Doxycycline / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D007279:Injections, Subcutaneous; D008288:Malaria / Q000188:drug therapy*; D016778:Malaria, Falciparum / Q000188:drug therapy*; D051379:Mice; D018512:Parasitemia / Q000188:drug therapy; D010616:Phenanthrenes / Q000008:administration & dosage / Q000627:therapeutic use; D010962:Plasmodium berghei; D011803:Quinine / Q000008:administration & dosage / Q000627:therapeutic use; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000627:therapeutic use
D000962:Antimalarials; D037621:Artemisinins; D010616:Phenanthrenes; D012717:Sesquiterpenes; D017963:Azithromycin; C031327:artemisinin; D011803:Quinine; D004318:Doxycycline; C023768:halofantrine