Current Progress in the Development and Use of Artemether for Chemoprophylaxis of Major Human Schistosome Parasites

Abstract

Human schistosomiasis, a chronic and debilitating parasitic disease of the tropics, is ranked second after malaria in terms of public health importance. At present, there is no vaccine available, and chemotherapy is the cornerstone of schistosomiasis control. Praziquantel is the drug of choice. Oxamniquine has become difficult to obtain and metrifonate has recently been withdrawn from the market. Rapid re-infection following treatment and concern about praziquantel resistance called for the search of novel drugs for prevention and cure of schistosomiasis. Significant progress has been made with artemether, the methyl ether of dihydroartemisinin, already widely used for the treatment of malaria. The present article reviews the literature that led to the development of artemether for chemoprophylaxis in schistosomiasis, and it summarises the experiences so far obtained with its use to control schistosomiasis in different endemic settings. Topics covered include an overview of the global burden of schis tosomiasis and approaches for its control; the nature and features of artemisinin and related derivatives, initially discovered as antimalarials, other bioactivities, and their recent discovery of antischistosomal properties a historic account disclosing the antischistosomal activity of artemether in vivo assessment of drug susceptibility of different developmental stages of schistosome parasites; artemether-induced pathology evidenced by scanning and transmission electron microscopy; the possible mechanism of action; in vivo studies with combination therapy of artemether and praziquantel results of randomised controlled clinical trials of oral artemether for the prevention of patent infection and morbidity and, ultimately the translation of this knowledge into public health action in different endemic settings towards a more integrated approach of schistosomiasis control.