Current progress in the development and use of artemether for chemoprophylaxis of major human schistosome parasites

Human schistosomiasis, a chronic and debilitating parasitic disease of the tropics, is ranked second after malaria in terms of public health importanc e. At present, there is no vaccine available, and chemotherapy is the corne rstone of schistosomiasis control. Praziquantel is the drug of choice. Oxam niquine has become difficult to obtain and metrifonate has recently been wi thdrawn from the market. Rapid re-infection following treatment and concern about praziquantel resistance called for the search of novel drugs for pre vention and cure of schistosomiasis. Significant progress has been made wit h artemether, the methyl ether of dihydroartemisinin, already widely used f or the treatment of malaria. The present article reviews the literature tha t led to the development of artemether for chemoprophylaxis in schistosomia sis, and it summarises the experiences so far obtained with its use to cont rol schistosomiasis in different endemic settings. Topics covered include a n overview of the global burden of schistosomiasis and approaches for its c ontrol; the nature and features of artemisinin and related derivatives, ini tially discovered as antimalarials, other bioactivities, and their recent d iscovery of antischistosomal properties; a historic account disclosing the antischistosomal activity of artemether; in vivo assessment of drug suscept ibility of different developmental stages of schistosome parasites; artemet her-induced pathology evidenced by scanning and transmission electron micro scopy; the possible mechanism of action; in vivo studies with combination t herapy of artemether and praziquantel; results of randomised controlled cli nical trials of oral artemether for the prevention of patent infection and morbidity; and, ultimately the translation of this knowledge into public he alth action in different endemic settings towards a more integrated approac h of schistosomiasis control.