Department of Virology, Parasitology and Immunology, Ghent University, Merelbeke, Belgium.
Center for Tropical Diseases, Sacro Cuore Don Calabria Hospital, Negrar, Italy.
PLoS Negl Trop Dis. 2019 Aug 1;13(8):e0007471. doi: 10.1371/journal.pntd.0007471. eCollection 2019 Aug.
Preventive 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.
An 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.
The 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.
ClinicalTrials.gov NCT03465488.
苯并咪唑类药物的预防性化疗(PC)是土壤传播性蠕虫(STH)控制项目的核心。在过去的十年中,药物覆盖率有所增加,随之而来的是产生驱虫耐药性的可能性。因此,监测药物疗效至关重要。目前,有多种新型诊断方法,但尚不清楚它们是否可用于监测药物疗效。在这项研究中,我们通过头对头比较,比较了不同诊断方法测量的阿苯达唑(ALB)的疗效,与推荐的单个加藤加藤法进行比较。
在三个不同的 STH 流行国家(埃塞俄比亚、老挝人民民主共和国和坦桑尼亚)进行了 ALB 疗效试验,每个国家都有不同的 PC 历史。在这些试验中,使用加藤加藤(单份和双份)、Mini-FLOTAC、FECPAKG2 和 qPCR 评估粪便样本。计算平均每克粪便中的卵数(ERR)和平均基因组当量/ml 提取的 DNA (GERR)的减少率,以估计药物疗效。
疗效试验的结果表明,在所评估的诊断方法中,没有一种方法能够为所有 STH 提供与单个加藤加藤相当的降低率。然而,尽管临床敏感性和卵计数存在差异,但它们在根据世界卫生组织(WHO)指南分类疗效方面是一致的。这表明,用于评估药物疗效的诊断方法应根据其预期用途进行验证,并且其他因素,如用户友好性和成本,可能是推动诊断选择的重要因素。此外,在 PC 历史较长的地点,ALB 对 STH 感染的疗效较低。然而,需要进一步研究以确定导致这种发现的因素,并验证疗效降低是否与先前与驱虫耐药性相关的β-微管蛋白基因的突变有关。
ClinicalTrials.gov NCT03465488。