Therapeutic efficacy of albendazole against soil-transmitted helminthiasis in children measured by five diagnostic methods

BackgroundPreventive chemotherapy (PC) with benzimidazole drugs is the backbone of soil-transmitted helminth (STH) control programs. Over the past decade, drug coverage has increased and with it, the possibility of developing anthelmintic resistance. It is therefore of utmost importance to monitor drug efficacy. Currently, a variety of novel diagnostic methods are available, but it remains unclear whether they can be used to monitor drug efficacy. In this study, we compared the efficacy of albendazole (ALB) measured by different diagnostic methods in a head-to-head comparison to the recommended single Kato-Katz.MethodsAn ALB efficacy trial was performed in 3 different STH-endemic countries (Ethiopia, Lao PDR and Tanzania), each with a different PC-history. During these trials, stool samples were evaluated with Kato-Katz (single and duplicate), Mini-FLOTAC, FECPAKG2, and qPCR. The reduction rate in mean eggs per gram of stool (ERR) and mean genome equivalents / ml of DNA extract (GERR) were calculated to estimate drug efficacy.Principal findings and conclusionsThe results of the efficacy trials showed that none of the evaluated diagnostic methods could provide reduction rates that were equivalent to a single Kato-Katz for all STH. However, despite differences in clinical sensitivity and egg counts, they agreed in classifying efficacy according to World Health Organization (WHO) guidelines. This demonstrates that diagnostic methods for assessing drug efficacy should be validated with their intended-use in mind and that other factors like user-friendliness and costs will likely be important factors in driving the choice of diagnostics. In addition, ALB efficacy against STH infections was lower in sites with a longer history of PC. Yet, further research is needed to identify factors that contribute to this finding and to verify whether reduced efficacy can be associated with mutations in the β-tubulin gene that have previously been linked to anthelmintic resistance.Trial registrationClinicalTrials.gov NCT03465488.

背景 苯并咪唑类药物的预防性化疗（Preventive chemotherapy, PC）是土源性蠕虫（soil-transmitted helminth, STH）防控计划的核心支柱。近十年来，药物覆盖范围持续提升，与此同时，抗蠕虫药性（anthelmintic resistance）的出现风险也随之升高。因此，监测药物疗效显得至关重要。目前已有多种新型诊断方法问世，但尚不清楚这些方法能否用于药物疗效监测。本研究通过头对头（head-to-head）对照试验，将不同诊断方法测得的阿苯达唑（albendazole, ALB）的疗效与推荐的单份Kato-Katz法检测结果进行对比。
方法 本研究在3个土源性蠕虫流行国家（埃塞俄比亚、老挝人民民主共和国、坦桑尼亚）开展阿苯达唑疗效试验，各地区的预防性化疗（PC）史各不相同。试验期间，采用Kato-Katz法（单份、双份）、Mini-FLOTAC法、FECPAKG2法以及实时荧光定量PCR（qPCR）对粪便样本进行检测。通过计算每克粪便平均虫卵数减少率（eggs per gram reduction rate, ERR）与DNA提取物平均基因组当量减少率（genome equivalents reduction rate, GERR），以此评估药物疗效。
主要发现与结论 疗效试验结果显示，针对所有土源性蠕虫感染，所有被评估的诊断方法均无法得到与单份Kato-Katz法相当的虫卵减少率。尽管各类方法的临床灵敏度与虫卵计数结果存在差异，但依据世界卫生组织（World Health Organization, WHO）指南对疗效进行分类时，各方法的分类结果一致。这表明，评估药物疗效的诊断方法需结合其预期用途进行验证，而操作便捷性与检测成本等其他因素，或将成为诊断方法选择的关键考量因素。此外，预防性化疗（PC）史更长的地区，其阿苯达唑对抗土源性蠕虫感染的疗效更低。但仍需开展进一步研究以明确该现象的相关影响因素，并验证疗效降低是否与此前被证实与抗蠕虫药性相关的β-微管蛋白基因（β-tubulin gene）突变存在关联。
试验注册 ClinicalTrials.gov 注册号：NCT03465488。