JAC Advance Access published online on July 29, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg357
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Institute of Medical Microbiology and Hygiene, Johannes
Gutenberg-University, Augustusplatz/Hochhaus,
D-55101 Mainz, Germany
* Corresponding author. E-mail: fpetry{at}mail.uni-mainz.de.
Received 19 December 2002
; 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
Effect of antiretroviral protease inhibitors alone,
and in combination with paromomycin, on the excystation, invasion
and in vitro development of Cryptosporidium
parvum
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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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