An immunosuppressed rat model for evaluation of anti-Cryptosporidium activity of sinefungin.
Cryptosporidium parvum causes life-threatening diarrhoea in immunocompromised, especially AIDS patients and the efficiency of proposed anti-cryptosporidial therapies is limited or doubtful. An immunosuppressed adult rat model of C. parvum infection was developed for screening molecules candidate for curative and preventive activity in human cryptosporidiosis. Among 31 drugs tested, lasalocid (2-10 mg/kg/24 h), and sinefungin (2-10 mg/kg/24 h), exhibited some activity against C. parvum infection. Oral sinefungin therapy resulted in a dose related suppression of oocysts shedding, which correlated with oocyst disappearance from ileum sections and was also efficient in preventing infection. Relapses were observed after discontinuation of curative sinefungin therapy, which suggests that the biliary tract, a major location and parasite reservoir which sustains persisting infection, was not cleared of parasites by the drug. Improved therapeutic procedures with sinefungin (or analogues) will result from current pharmacological studies.
Brasseur
P
P
Department of Parasitology, Hôpital Charles Nicolle, Rouen, France.
Favennec
L
L
Leméteil
D
D
Roussel
F
F
Ballet
J J
JJ
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D003049:Coccidiostats / Q000494:pharmacology / Q000627:therapeutic use*; D003457:Cryptosporidiosis / Q000188:drug therapy* / Q000517:prevention & control; D016785:Cryptosporidium parvum / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005243:Feces / Q000469:parasitology; D016867:Immunocompromised Host; D007832:Lasalocid / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D003049:Coccidiostats; D000241:Adenosine; C006235:sinefungin; D007832:Lasalocid