Innovative chemotherapeutical treatment options for alveolar and cystic echinococcosis

Abstract

Echinococcus granulosus and Echinococcus multilocularis are cestode parasites, of which the metacestode (larval) stages cause the diseases cystic echinococcosis (CE) and alveolar echinococcosis (AE), respectively. Albendazole and mebendazole are presently used for chemotherapeutical treatment. However, these benzimidazoles do not appear to be parasiticidal in vivo against AE. In addition, failures in drug treatments as well as the occurrence of side-effects have been reported. New drugs are needed to cure AE and CE, which are considered to be neglected diseases. Strategies currently being implemented to identify novel chemotherapeutical treatment options include (i) conventional primary in vitro testing of broad-spectrum anti-infective drugs, either in parallel with, or followed by, animal experimentation ; (ii) studies of drugs which interfere with the proliferation of cancer cells and of Echinococcus metacestodes ; (iii) exploitation of the similarities between the parasite and mammalian signalling machineries, with a special focus on targeting specific signalling receptors ; (iv) in silico approaches, employing the current Echinococcus genomic database information to search for suitable targets for compounds with known modes of action. In the present article, we review the efforts toward obtaining better anti-parasitic compounds which have been undertaken to improve chemotherapeutical treatment of echinococcosis, and summarize the achievements in the field of host-parasite interactions which may also lead to new immuno-therapeutical options.

In Vitro and In Vivo Treatments of Echinococcus Protoscoleces and Metacestodes with Artemisinin and Artemisinin Derivatives

“…Surgery is accompanied by chemotherapy, and in inoperable cases, chemotherapy is the only option. Albendazole and mebendazole are currently used (8,10). For alveolar echinococcosis, these compounds were shown to act parasitostatically rather than parasitocidally, with high recurrence rates after interruption of therapy.…”

“…For alveolar echinococcosis, these compounds were shown to act parasitostatically rather than parasitocidally, with high recurrence rates after interruption of therapy. Improved drug treatments are needed (8,24).Most countries to which malaria is endemic have now adopted artemisinin-based combination therapy as a first-line treatment for Plasmodium falciparum infection (34), and activities of artemisinins against other protozoans have been reported (1, 12). Trematodes, including schistosomes (31) and others, have proven susceptible to artemisinins and semisynthetic derivatives (13)(14)(15)(16)26), and antitumor activities of artemisinins have been reported (11,18,35).…”

“…For alveolar echinococcosis, these compounds were shown to act parasitostatically rather than parasitocidally, with high recurrence rates after interruption of therapy. Improved drug treatments are needed (8,24).…”

Efficacy of Cyperus Rotundus Rhizomes-Tubers Extracts Against Protoscoleces of Echinococcus Granulosus

“…[15] Puncture, aspiration, injection, re-aspiration(PAIR) is a technique that was introduced in the mid-eighties and includes percutaneous puncture of the cyst under ultrasonic guidance, aspiration of substantial amounts of cyst fluid, injection of protoscolicidal substance (eg.95% ethanol)and re-aspiration of fluid after 5-20 min. [16] Treatment of cystic echinococcosis has been developed after a series of animal studies, both albendazole and mebendazole are considered to be equally effective [5] but other researcher concluded that albendazole is more effective than mebendazole in the treatment of hydatid cyst caused by E.granulosus and that both the intensity and the frequency of the usually mild adverse effects are comparable which including raised transaminases, abdominal pain, headache, vertigo, urticaria, jaundice. [17] Furthermore, Horton [18] mentioned that albendazole has a relatively benign safety profile with three principle areas affected (liver functions, bone marrow and hair).…”

Echinococcusmetacestodes as laboratory models for the screening of drugs against cestodes and trematodes

“…Thus benzimidazoles only prevent parasite growth, and the recurrence rates after interruption of therapy are high. Nevertheless, clinical studies have shown that chemotherapy has significantly increased the 10-year survival rate of inoperable or non-radically operated AE patients from 6-25 % to 80-83 % (Hemphill et al 2007).…”