Assessment of the Anthelmintic Efficacy of Albendazole in School Children in Seven Countries Where Soil-Transmitted Helminths Are Endemic

BackgroundThe three major soil-transmitted helminths (STH) Ascaris lumbricoides, Trichuris trichiura and Necator americanus/Ancylostoma duodenale are among the most widespread parasites worldwide. Despite the global expansion of preventive anthelmintic treatment, standard operating procedures to monitor anthelmintic drug efficacy are lacking. The objective of this study, therefore, was to define the efficacy of a single 400 milligram dose of albendazole (ALB) against these three STH using a standardized protocol. Methodology/Principal FindingsSeven trials were undertaken among school children in Brazil, Cameroon, Cambodia, Ethiopia, India, Tanzania and Vietnam. Efficacy was assessed by the Cure Rate (CR) and the Fecal Egg Count Reduction (FECR) using the McMaster egg counting technique to determine fecal egg counts (FEC). Overall, the highest CRs were observed for A. lumbricoides (98.2%) followed by hookworms (87.8%) and T. trichiura (46.6%). There was considerable variation in the CR for the three parasites across trials (country), by age or the pre-intervention FEC (pre-treatment). The latter is probably the most important as it had a considerable effect on the CR of all three STH. Therapeutic efficacies, as reflected by the FECRs, were very high for A. lumbricoides (99.5%) and hookworms (94.8%) but significantly lower for T. trichiura (50.8%), and were affected to different extents among the 3 species by the pre-intervention FEC counts and trial (country), but not by sex or age. Conclusions/SignificanceOur findings suggest that a FECR (based on arithmetic means) of >95% for A. lumbricoides and >90% for hookworms should be the expected minimum in all future surveys, and that therapeutic efficacy below this level following a single dose of ALB should be viewed with concern in light of potential drug resistance. A standard threshold for efficacy against T. trichiura has yet to be established, as a single-dose of ALB is unlikely to be satisfactory for this parasite. Trial RegistrationClinicalTrials.gov NCT01087099

研究背景：似蚓蛔线虫（Ascaris lumbricoides，即蛔虫）、毛首鞭形线虫（Trichuris trichiura，即鞭虫）以及美洲钩虫/十二指肠钩虫（Necator americanus/Ancylostoma duodenale）这三种土源性蠕虫（soil-transmitted helminths, STH），均属于全球范围内分布最为广泛的寄生虫之列。尽管预防性驱虫治疗在全球范围内得到推广，但目前仍缺乏监测驱虫药物疗效的标准操作规程。为此，本研究旨在通过标准化方案，评估单剂400mg阿苯达唑（albendazole, ALB）对上述三种土源性蠕虫的治疗效果。
研究方法与主要结果：研究团队在巴西、喀麦隆、柬埔寨、埃塞俄比亚、印度、坦桑尼亚及越南的学龄儿童中开展了7项临床试验。疗效通过转阴率（Cure Rate, CR）与粪便虫卵减少率（Fecal Egg Count Reduction, FECR）进行评估，采用麦克马斯特虫卵计数法测定粪便虫卵数（fecal egg counts, FEC）。总体而言，蛔虫的转阴率最高（98.2%），其次为钩虫（87.8%）与鞭虫（46.6%）。三种寄生虫的转阴率在不同试验（国家）、不同年龄组及干预前粪便虫卵数（治疗前）层面均存在显著差异，其中干预前虫卵数或许是最为关键的影响因素，其对三种土源性蠕虫的转阴率均存在显著影响。粪便虫卵减少率所反映的治疗疗效方面，蛔虫（99.5%）与钩虫（94.8%）的疗效极高，而鞭虫（50.8%）的疗效则显著偏低；三种寄生虫的疗效均受干预前虫卵数与试验（国家）的不同程度影响，但不受性别与年龄的影响。
结论与意义：本研究结果提示，在未来所有相关调查中，以算术均值计算的粪便虫卵减少率阈值应设定为：蛔虫＞95%、钩虫＞90%；若单剂阿苯达唑治疗后的疗效低于该阈值，则应警惕潜在的药物耐药性问题。目前尚无针对鞭虫的疗效标准阈值，因为单剂阿苯达唑对该寄生虫的治疗效果并不理想。
临床试验注册：ClinicalTrials.gov NCT01087099