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Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis

Doenhoff, Michael Ja; Cioli, Donatob; Utzinger, Jürgc

Current Opinion in Infectious Diseases: December 2008 - Volume 21 - Issue 6 - p 659–667
doi: 10.1097/QCO.0b013e328318978f
Antimicrobials: Edited by Tania C. Sorrell and Deenan Pillay
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Purpose of review Praziquantel (PZQ) is the only drug being used to treat human schistosomiasis on a large scale. This review focuses on current knowledge about the mechanisms of action of PZQ, prospects for PZQ resistance, possible future alternative drugs and on exhortations that control of schistosomiasis and other so-called neglected tropical diseases becomes more integrated.

Recent findings Schistosome calcium ion (Ca2+) channels are the only moiety so far identified as the molecular target of PZQ, but the evidence remains indirect. In the presence of cytochalasin D worms survive high concentrations of PZQ and experiments with cytochalasin D also indicated that PZQ induced worm death and Ca2+ influx are not correlated. Despite PZQ being widely used, there is no clinically relevant evidence for resistance to date, but worryingly low-cure rates have been recorded in some studies in Africa. Artemisinins and the related 1,2,4-trioxolanes are new promising antischistosomal compounds, as are inhibitors of a schistosome-specific bifunctional enzyme, thioredoxin-glutathione reductase.

Summary Use of PZQ will increase in the foreseeable future, whether given alone or coadministered with other anthelminthics in integrated control programmes. PZQ resistance remains a threat and its prevention requires adequate monitoring of current mass drug administration programmes and development of new schistosomicides.

aSchool of Biology, University of Nottingham, University Park, Nottingham, UK

bInstitute of Cell Biology, CNR, 32 Via Ramarini, 00015 Monterotondo, Rome, Italy

cDepartment of Public Health and Epidemiology, Swiss Tropical Institute, Basel, Switzerland

Correspondence to Michael J. Doenhoff, School of Biology, University of Nottingham, University Park, Nottingham NG7 2RD, UK Tel: +44 115 951 3304; fax: +44 115 951 3251; e-mail: mike.doenhoff@nottingham.ac.uk

© 2008 Lippincott Williams & Wilkins, Inc.