Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, P.O. Box 30, Giza 12411, Egypt
Expert Opin Drug Discov. 2007 Oct;2(s1):S35-40. doi: 10.1517/17460441.2.S1.S35.
Results from infected patients, not cured by multiple doses of praziquantel (PZQ), have been reported from different geographic locations, suggesting that resistance to the drug may be present. This has been coupled with several in vivo (e.g., studies on mice infected with 'resistant isolates') and in vitro tests (e.g., direct application and measurement of the effects of the drug on schistosomes maintained in culture) demonstrating a significant reduction in the drug's efficacy. Despite little field evidence that schistosomes are becoming less sensitive to the drug, 100% cure after PZQ is rarely achieved; meanwhile, the percentage of cure rates in endemic areas could be an overestimate if one accounts for the sensitivity of most egg counting methods coupled with the limited faecal sampling. To be proactive, the efficacy of PZQ has to be monitored on a systematic basis not only for cure, but also for the reduction of egg excretion complemented with periodical assessment for the susceptibility to the drug on local strains. Investigation of field isolates with confirmed diminished sensitivity to the drug will help in determining the frequency, epidemiology, genetic and physiologic basis for the observed resistance. Monitoring for changes in drug responsiveness in high transmission areas, where treatment failure as a result of immature or resistant parasites can not be differentiated, should be initiated. New chemotherapeutic alternatives and strategies in addition to a simple rapid, inexpensive test to detect resistance should be encouraged.
从不同地理位置报告了未被多次剂量吡喹酮(PZQ)治愈的感染患者,表明可能存在对该药物的耐药性。这与几项体内(例如,感染“耐药分离株”的小鼠研究)和体外测试(例如,直接应用和测量药物对培养中保持的血吸虫的作用)相结合,表明药物的功效显著降低。尽管几乎没有现场证据表明血吸虫对药物的敏感性降低,但 PZQ 后的 100%治愈率很少实现;同时,如果考虑到大多数卵计数方法的敏感性以及粪便采样的局限性,那么在流行地区的治愈率可能被高估。为了主动采取措施,不仅要监测 PZQ 的疗效以确保治愈,还要监测其减少卵排泄的效果,并定期评估当地菌株对药物的敏感性。对确证对药物敏感性降低的现场分离株进行调查,将有助于确定观察到的耐药性的频率、流行病学、遗传和生理基础。应在高传播地区启动对药物反应性变化的监测,因为在不成熟或耐药寄生虫的情况下,治疗失败无法区分。应鼓励除了简单、快速、廉价的耐药性检测方法外,还提供新的化疗替代方案和策略。