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JAC Advance Access originally published online on July 29, 2003
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Journal of Antimicrobial Chemotherapy (2003) 52, 359-364
© 2003 The British Society for Antimicrobial Chemotherapy

Effect of antiretroviral protease inhibitors alone, and in combination with paromomycin, on the excystation, invasion and in vitro development of Cryptosporidium parvum

Vera Hommer, Jutta Eichholz and Franz Petry*

Institute of Medical Microbiology and Hygiene, Johannes Gutenberg-University, Augustusplatz/Hochhaus, D-55101 Mainz, Germany

Received 19 December 2002; returned 7 March 2003; revised 17 April 2003; accepted 4 June 2003

With the spread of the human immunodeficiency virus in the early 1980s, cryptosporidiosis was regarded as an AIDS-defining disease. As an opportunistic pathogen, the intestinal parasite Cryptosporidium parvum became an important cause of chronic diarrhoea, leading to high morbidity and mortality in immunocompromised patients. To date, no effective chemotherapy is available. With the introduction of protease inhibitors (PIs) in highly active antiretroviral therapy (HAART), the incidence of cryptosporidiosis in AIDS patients has declined substantially in western countries. We have therefore tested the effect of five PIs used in HAART on the excystation, invasion and development of the parasite in a cell culture system. The human ileocaecal adenocarcinoma cell line HCT-8 served as a host cell. None of the substances had an effect on the excystation rate, and only nelfinavir moderately, but statistically significantly, inhibited the host cell invasion over a period of 2 h. There were more pronounced inhibitory effects when PIs were present over the total time of intracellular development (48 h). Indinavir, nelfinavir and ritonavir inhibited parasite development significantly. The inhibitory effect was increased when the aminoglycoside paromomycin was combined with the PIs indinavir, ritonavir, and to a lesser extent saquinavir, compared to the PIs alone.

Keywords: highly active antiretroviral therapy, HAART, AIDS, Apicomplexa, HCT-8

* Corresponding author. Tel: +49-6131-393-3139; Fax: +49-6131-393-3439; E-mail: fpetry{at}mail.uni-mainz.de


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 J Antimicrob ChemotherHome page
G. A. Dugue
Comment on: Effect of antiretroviral protease inhibitors alone, and in combination with paromomycin, on the excystation, invasion and in vitro development of Cryptosporidium parvum
J. Antimicrob. Chemother., February 1, 2004; 53(2): 403 - 403.
[Full Text] [PDF]

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 J Antimicrob ChemotherHome page
F. Petry, V. Hommer, and J. Eichholz
Reply
J. Antimicrob. Chemother., February 1, 2004; 53(2): 403 - 403.
[Full Text] [PDF]


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