Development of antischistosomal drugs in China, with particular consideration to praziquantel and the artemisinins.
Remarkable achievements have been made in the control of schistosomiasis in China, with chemotherapy playing a seminal role. From the early 1950s through the early 1980s, Chinese scientists made considerable progress in discovery and development of compounds with antischistosomal properties, including antimonials, non-antimonials and various effective principles stemming from traditional herbs. However, only few compounds entered clinical testing, while others were abandoned mainly due to their toxicity and poor efficacy. The advent of praziquantel in the 1970s changed the landscape of research and development of drugs for treatment and morbidity control of schistosomiasis. The main Chinese contributions to enhance the understanding of the antischistosomal drug praziquantel are reviewed here, including issues of metabolism, antibody-dependency, host immune factors, stage-specific susceptibility and resistance. Over the past 25 years, researchers from China successfully developed artemether and artesunate, two derivatives from the antimalarial artemisinin, as promising drugs against Schistosoma japonicum. Laboratory investigations showed that the artemisinins display their highest activity against the juvenile stages of the parasite. These findings were consistently confirmed in randomised controlled trials; repeated oral administration of artemether or artesunate was safe and efficacious in the prevention of patent S. japonicum infections. The key findings are reviewed here, and emphasis is placed on how it stimulated research outside of China on other human schistosome species.
Xiao
Shu-Hua
SH
National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai 200025, China. shxiao1@yahoo.com
D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D000077549:Artemether; D037621:Artemisinins / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000077332:Artesunate; D002986:Clinical Trials as Topic; D015195:Drug Design; D004351:Drug Resistance; D006801:Humans; D011223:Praziquantel / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012549:Schistosoma japonicum / Q000187:drug effects / Q000378:metabolism; D012554:Schistosomiasis japonica / Q000188:drug therapy* / Q000276:immunology; D012556:Schistosomicides / Q000627:therapeutic use*; D012717:Sesquiterpenes / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013237:Stereoisomerism
D000909:Antibodies, Helminth; D037621:Artemisinins; D012556:Schistosomicides; D012717:Sesquiterpenes; D000077332:Artesunate; D011223:Praziquantel; D000077549:Artemether