Folia Parasitologica 50[1] 19-22 (2003) | DOI: 10.14411/fp.2003.003

Long-lasting anticryptosporidial activity of nitazoxanide in an immunosuppressed rat model

Xunde Li1, Philippe Brasseur1, Patrice Agnamey1, Denis Leméteil1, Loïc Favennec1, Jean-Jacques Ballet2, Jean-François Rossignol3
1 Laboratoire de Parasitologie, Faculté de Médecine-Pharmacie, and ADEN, UPRES-EA 3234, 76138 Rouen, France
2 Laboratoire d'Immunologie et Immunopathologie, CHU Clemenceau, 14033 Caen Cedex, France
3 Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK

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.

Keywords: Cryptosporidium parvum, nitazoxanide, immunosuppressed rat model

Received: June 10, 2002; Accepted: October 2, 2002; Published: March 1, 2003  Show citation

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Li, X., Brasseur, P., Agnamey, P., Leméteil, D., Favennec, L., Ballet, J., & Rossignol, J. (2003). Long-lasting anticryptosporidial activity of nitazoxanide in an immunosuppressed rat model. Folia Parasitologica50(1), 19-22. doi: 10.14411/fp.2003.003
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References

  1. BICART-SEE A., MASSIP P., LINAS M.D., DATRY A. 2000: Successful treatment with nitazoxanide of Enterocytozoon bieneusi microsporidiosis in a patient with AIDS. Antimicrob. Agents Chemother. 44: 167-168 Go to original source... Go to PubMed...
  2. BLAGBURN B.L., DRAIN K.L., LAND T.M., KINARD R.G., MOORE P.H., LINDSAY D.S., PATRICK D.A., BOYKIN D.W., TIDWELL R.R. 1998: Comparative efficacy evaluation of dicationic carbazole compounds, nitazoxanide, and paromomycin against Cryptosporidium parvum infections in a neonatal mouse model. Antimicrob. Agents Chemother. 42: 2877-2882 Go to original source... Go to PubMed...
  3. BLAGBURN B.L., SOAVE R. 1997: Prophylaxis and chemotherapy: human and animal. In: R. Fayer (Ed.), Cryptosporidium and Cryptosporidiosis. CRC Press, Boca Raton, pp. 111-128
  4. BRASSEUR P., FAVENNEC L., LEMETEIL D., ROUSSEL F., BALLET J.J. 1994: An immunosuppressed rat model for evaluation of anti-Cryptosporidium activity of sinefungin. Folia Parasitol. 41: 13-16 Go to PubMed...
  5. BRASSEUR P., LEMETEIL D., BALLET J.J. 1988: Rat model for human cryptosporidiosis. J. Clin. Microbiol. 26: 1037-1039 Go to original source... Go to PubMed...
  6. DAVIS L.J., SOAVE R., DUDLEY R.E., FESSEL J.W., FAULKNER S., MAMAKOS J.P. 2000: Nitazoxanide (NTZ) for AIDS-related cryptosporidial diarrhea (CD): an open-label safety, efficacy and pharmacokinetic study. In: Abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C., abstract LM50, p. 289
  7. DOUMBO O., ROSSIGNOL J.F., PICHARD E., TRAORE H.A., DEMBELE T.M., DIAKITE M., TRAORE F., DIALLO D.A. 1997: Nitazoxanide in treatment of cryptosporidial diarrhea and other intestinal parasitic infections associated with acquired immunodeficiency syndrome in tropical Africa. Am. J. Trop. Med. Hyg. 56: 637-639 Go to original source... Go to PubMed...
  8. DUBREUIL L., HOUCKE I., MOUTON Y., ROSSIGNOL J.F. 1996: In vitro evaluation of activities of nitazoxanide and tizoxanide against anaerobes and aerobic organisms. Antimicrob. Agents Chemother. 40: 2260-2270 Go to original source...
  9. GRIFFITHS J.L. 1998: Human cryptosporidiosis: epidemiology, transmission, clinical disease, treatment and diagnosis. Adv. Parasitol. 40: 37-85 Go to original source... Go to PubMed...
  10. HEALEY M.C., YANG S., RASMUSSEN K.R., JACKSON M.K., DU C. 1995: Therapeutic efficacy of paromomycin in immunosuppressed adult mice infected with Cryptosporidium parvum. J. Parasitol. 81: 114-116 Go to original source... Go to PubMed...
  11. HEINE J. 1982: Eine einfache Nachweismethode fuer Kryptosporidien im Kot. Zentralbl. Veterinaermed. 29: 324-327 Go to original source...
  12. LEMETEIL D., ROUSSEL F., FAVENNEC L., BALLET J.J., BRASSEUR P. 1993: Assessment of candidate anticryptosporidial agents in an immunosuppressed rat model. J. Infect. Dis. 167: 766-768 Go to original source... Go to PubMed...
  13. McVAY C.S., ROLFE R.D. 2000: In vitro and in vivo activities of nitazoxanide against Clostridium difficile. Antimicrob. Agents Chemother. 44: 2254-2258 Go to original source... Go to PubMed...
  14. MEGRAUD F., OCCHIALINI A., ROSSIGNOL J.F. 1998: Nitazoxanide, a potential drug to eradicate Helicobacter pylori with no cross resistance to metronidazole. Antimicrob. Agents Chemother. 42: 2836-2840 Go to original source... Go to PubMed...
  15. ROSSIGNOL J.F., AYOUB A., AYERS M.S. 2001: Treatment of diarrhea caused by Cryptosporidium parvum: a prospective randomized, double-blind, placebo-controlled study of nitazoxanide. J. Infect. Dis. 184: 103-106 Go to original source... Go to PubMed...
  16. ROSSIGNOL J.F., ABAZA H., FRIEDMAN H. 1998a: Successful treatment of human fascioliasis with nitazoxanide. Trans. R. Soc. Trop. Med. Hyg. 92: 103-104 Go to original source... Go to PubMed...
  17. ROSSIGNOL J.F., HIDALGO H., FEREGRINO M., HIGUERA F., GOMEZ W.H., ROMERO J.L., PADIERNA J., GEYNE A., AYERS M.S. 1998b: A double-blind placebo-controlled study of nitazoxanide in the treatment of cryptosporidial diarrhoea in AIDS patients in Mexico. Trans. R. Soc. Trop. Med. Hyg. 92: 663-666 Go to original source... Go to PubMed...
  18. ROSSIGNOL J.F., MAISONNEUVE H. 1984: Nitazoxanide in the treatment of Taenia saginata and Hymenolepis nana. Am. J. Trop. Med. Hyg. 33: 511-512 Go to original source... Go to PubMed...
  19. ROUSSEL F., FAVENNEC L., LEMETEIL D., TAYOT J., BALLET J.J., BRASSEUR P. 1996: Biliary tract cryptosporidiosis in an immunosuppressed rat model. Int. J. Parasitol. 26: 19-24 Go to original source... Go to PubMed...
  20. THEODOS C.M., GRIFFITHS J.K., D'ONFRO J., FAIRFIELD A., TZIPORI S. 1998: Efficacy of nitazoxanide against Cryptosporidium parvum in cell culture and in animal models. Antimicrob. Agents Chemother. 42: 1959-1965 Go to original source... Go to PubMed...
  21. TZIPORI S. 1998: Cryptosporidiosis: laboratory investigation and chemotherapy. Adv. Parasitol. 40: 187-221 Go to original source... Go to PubMed...
  22. TZIPORI S., RAND W., GRIFFITHS J., WIDMER G., CRABB J. 1994: Evaluation of an animal model system for cryptosporidiosis: therapeutic efficacy of paromomycin and hyperimmune bovine colostrum-immunoglobulin. Clin. Diagn. Lab. Immunol. 1: 450-463 Go to original source... Go to PubMed...
  23. VERDON R., POLIANSKI J., GAUDEBOUT C., MARCHE C., GARRY L., CARBON C., POCIDALO J.J. 1995: Evaluation of high-dose regimen of paromomycin against cryptosporidiosis in the dexamethasone-treated rat model. Antimicrob. Agents Chemother. 39: 2155-2157 Go to original source... Go to PubMed...