Long-lasting anticryptosporidial activity of nitazoxanide in an immunosuppressed rat model.
Cryptosporidium parvum, Tyzzer, 1912 is identified as a common cause of diarrhoea in immunocompetent individuals. In immunocompromised, especially HIV-infected subjects, cryptosporidiosis causes severe chronic diarrhoea. In this study, nitazoxanide (NTZ) was compared for curative activity with sinefungin (SNF) and paromomycin (PRM) in immunosuppressed rats, a screening model for anticryptosporidial agents. NTZ at either 50 mg/kg/day, 100 mg/kg/day or 200 mg/kg/day resulted in seven days in a dose-dependent inhibition of oocyst shedding similar to that obtained with SNF (10 mg/kg/day) and PRM (100 mg/kg/day). Further discontinuation of SNF or PRM 100 mg/kg/day therapy resulted in early relapse of oocyst shedding which reached the pre-treatment levels in 2-4 days. In contrast, seven days after discontinuation of therapy, shedding inhibition was unchanged in NTZ-treated rats. Data prompt further assessment of the activity of NTZ on sequestered C. parvum.
Laboratoire de Parasitologie, Faculté de Médecine-Pharmacie, and ADEN, UPRES-EA 3234, 76138 Rouen, France.
Xunde
X
Li
Philippe
P
Brasseur
Patrice
P
Agnamey
Denis
D
Leméteil
Loïc
L
Favennec
Jean-Jacques
JJ
Ballet
Jean-François
JF
Rossignol
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D003457:Cryptosporidiosis / Q000188:drug therapy* / Q000276:immunology; D016785:Cryptosporidium parvum / Q000254:growth & development*; D004195:Disease Models, Animal; D005243:Feces / Q000469:parasitology; D016867:Immunocompromised Host; D008297:Male; D009574:Nitro Compounds; D010270:Parasite Egg Count; D010303:Paromomycin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000494:pharmacology*
D000981:Antiprotozoal Agents; D009574:Nitro Compounds; D013844:Thiazoles; D010303:Paromomycin; D000241:Adenosine; C041747:nitazoxanide; C006235:sinefungin