International Severe Acute Respiratory and Emerging Infection Consortium, Pandemic Sciences Institute, University of Oxford, Oxford, United Kingdom.
Centre of Competence for Methodology and Statistics, Luxembourg Institute of Health, Strassen, Luxembourg.
PLoS Negl Trop Dis. 2022 Aug 2;16(8):e0010593. doi: 10.1371/journal.pntd.0010593. eCollection 2022 Aug.
Periodic administration of anthelmintic drugs is a cost-effective intervention for morbidity control of soil-transmitted helminth (STH) infections. However, with programs expanding, drug pressure potentially selecting for drug-resistant parasites increases. While monitoring anthelmintic drug efficacy is crucial to inform country control program strategies, different factors must be taken into consideration that influence drug efficacy and make it difficult to standardize treatment outcome measures. We aimed to identify suitable approaches to assess and compare the efficacy of different anthelmintic treatments.
We built an individual participant-level database from 11 randomized controlled trials and two observational studies in which subjects received single-agent or combination therapy, or placebo. Eggs per gram of stool were calculated from egg counts at baseline and post-treatment. Egg reduction rates (ERR; based on mean group egg counts) and individual-patient ERR (iERR) were utilized to express drug efficacy and analyzed after log-transformation with a linear mixed effect model. The analyses were separated by follow-up duration (14-21 and 22-45 days) after drug administration.
The 13 studies enrolled 5,759 STH stool-positive individuals; 5,688 received active medication or placebo contributing a total of 11,103 STH infections (65% had two or three concurrent infections), of whom 3,904 (8,503 infections) and 1,784 (2,550 infections) had efficacy assessed at 14-21 days and 22-45 days post-treatment, respectively. Neither the number of helminth co-infections nor duration of follow-up affected ERR for any helminth species. The number of participants treated with single-dose albendazole was 689 (18%), with single-dose mebendazole 658 (17%), and with albendazole-based co-administrations 775 (23%). The overall mean ERR assessed by day 14-21 for albendazole and mebendazole was 94.5% and 87.4%, respectively on Ascaris lumbricoides, 86.8% and 40.8% on hookworm, and 44.9% and 23.8% on Trichuris trichiura. The World Health Organization (WHO) recommended criteria for efficacy were met in 50%, 62%, and 33% studies of albendazole for A. lumbricoides, T. trichiura, and hookworm, respectively and 25% of mebendazole studies. iERR analyses showed similar results, with cure achieved in 92% of A. lumbricoides-infected subjects treated with albendazole and 93% with mebendazole; corresponding figures for hookworm were 70% and 17%, and for T. trichiura 22% and 20%.
CONCLUSIONS/SIGNIFICANCE: Combining the traditional efficacy assessment using group averages with individual responses provides a more complete picture of how anthelmintic treatments perform. Most treatments analyzed fail to meet the WHO minimal criteria for efficacy based on group means. Drug combinations (i.e., albendazole-ivermectin and albendazole-oxantel pamoate) are promising treatments for STH infections.
定期给予驱虫药是控制土壤传播性蠕虫（STH）感染发病率的一种具有成本效益的干预措施。然而，随着项目的扩展，药物压力可能会选择具有耐药性的寄生虫。虽然监测驱虫药的疗效对于为国家控制规划战略提供信息至关重要，但必须考虑到不同的因素，这些因素会影响药物疗效，并使治疗结果的衡量标准难以标准化。我们旨在确定评估和比较不同驱虫治疗效果的合适方法。
我们从 11 项随机对照试验和 2 项观察性研究中建立了一个个体参与者水平的数据库，这些研究中受试者接受了单一药物或联合治疗或安慰剂治疗。根据基线和治疗后粪便中的虫卵计数计算每克粪便中的虫卵数。采用基于平均组虫卵计数的虫卵减少率（ERR）和个体患者虫卵减少率（iERR）来表示药物疗效，并在对数转换后使用线性混合效应模型进行分析。分析分为药物治疗后 14-21 天和 22-45 天两个时间段。
这 13 项研究共纳入了 5759 例 STH 粪便阳性个体；5688 人接受了活性药物或安慰剂治疗，共涉及 11103 例 STH 感染（65%的人有两种或三种同时感染），其中 3904 人（8503 例感染）和 1784 人（2550 例感染）在治疗后 14-21 天和 22-45 天分别进行了疗效评估。任何蠕虫物种的 ERR 均不受合并寄生虫感染数量或随访时间的影响。接受单次剂量阿苯达唑治疗的参与者有 689 人（18%），单次剂量甲苯达唑治疗的参与者有 658 人（17%），接受阿苯达唑联合治疗的参与者有 775 人（23%）。阿苯达唑和甲苯达唑在治疗后 14-21 天的总体平均 ERR 分别为蛔虫的 94.5%和 87.4%，钩虫的 86.8%和 40.8%，以及鞭虫的 44.9%和 23.8%。世界卫生组织（WHO）推荐的疗效标准在阿苯达唑治疗蛔虫、鞭虫和钩虫的 50%、62%和 33%的研究中得到满足，甲苯达唑研究中有 25%符合标准。iERR 分析显示了类似的结果，接受阿苯达唑治疗的蛔虫感染患者中 92%得到治愈，接受甲苯达唑治疗的患者中 93%得到治愈；钩虫的相应数字为 70%和 17%，鞭虫为 22%和 20%。
结论/意义：将使用群体平均值的传统疗效评估与个体反应相结合，更全面地了解驱虫治疗的效果。基于群体平均值，大多数分析的治疗方法都未能达到世界卫生组织的最低疗效标准。药物联合治疗（即阿苯达唑-伊维菌素和阿苯达唑-奥沙苯达唑）是治疗 STH 感染的有前途的治疗方法。
