一项在印度开展的伊维菌素、乙胺嗪加阿苯达唑联合用药与乙胺嗪加阿苯达唑单药治疗淋巴丝虫病的开放性标签、块随机、社区研究，评估联合用药的安全性和疗效。

An open label, block randomized, community study of the safety and efficacy of co-administered ivermectin, diethylcarbamazine plus albendazole vs. diethylcarbamazine plus albendazole for lymphatic filariasis in India.

机构信息

ICMR-Vector Control Research Centre, Puducherry, India.

Indian Council of Medical Research, New Delhi, India.

出版信息

PLoS Negl Trop Dis. 2021 Feb 16;15(2):e0009069. doi: 10.1371/journal.pntd.0009069. eCollection 2021 Feb.

BACKGROUND

Better drug regimens for mass drug administration (MDA) could accelerate the Global Programme to Eliminate Lymphatic Filariasis (LF). This community study was designed to compare the safety and efficacy of MDA with IDA (ivermectin, diethylcarbamazine and albendazole) or DA (diethylcarbamazine and albendazole) in India.

METHODOLOGY/PRINCIPAL FINDINGS: This two-armed, open-labelled, block randomised, community study was conducted in LF endemic villages in Yadgir district, Karnataka, India. Consenting participants ≥5 years of age were tested for circulating filarial antigenemia (CFA) and microfilaremia (Mf) before treatment with a single oral dose of IDA or DA. Adverse events (AEs) were monitored actively for two days and passively for five more days. Persons with positive CFA or Mf tests at baseline were retested 12-months post-treatment to assess treatment efficacy. Baseline CFA and Mf-rates were 26.4% and 6.9% in IDA and 24.5% and 6.4% in DA villages respectively. 4758 and 4160 participants received IDA and DA. Most AEs were mild after both treatments; fewer than 0.1% of participants experienced AEs with severity > grade 1. No serious AEs were observed. Fever, headache and dizziness were the most common AEs. AE rates were slightly higher after IDA than DA (8.3% vs. 6.4%, P<0.01). AEs were more frequent in females and Mf-positives after either treatment, but significantly more frequent after IDA (40.5% vs 20.2%, P < 0.001). IDA was more effective for clearing Mf than DA (84% vs. 61.8%, P < 0.001). Geometric mean Mf counts per 60μl in retested Mf-positives decreased by 96.4% from 11.8 after IDA and by 90.0% from 9.5 after DA. Neither treatment was effective for clearing CFA.

CONCLUSIONS/SIGNIFICANCE: IDA had an acceptable safety profile and was more effective for clearing Mf than DA. With adequate compliance and medical support to manage AEs, IDA has the potential to accelerate LF elimination in India.

TRIAL REGISTRATION

Clinical Trial Registry of India (CTRI No/2016/10/007399).

背景

更好的药物治疗方案用于大规模药物治疗（MDA）可以加速全球消灭淋巴丝虫病（LF）规划。本社区研究旨在比较在印度使用 IDA（伊维菌素、乙胺嗪和阿苯达唑）或 DA（乙胺嗪和阿苯达唑）进行 MDA 的安全性和疗效。

方法/主要发现：这是一项在印度卡纳塔克邦亚德吉尔区 LF 流行村庄进行的双臂、开放性、分组随机、社区研究。在接受单次口服伊维菌素、乙胺嗪和阿苯达唑（IDA）或乙胺嗪和阿苯达唑（DA）治疗之前，同意的参与者年龄≥5 岁，进行循环丝状抗原血症（CFA）和微丝蚴血症（Mf）检测。积极监测不良事件（AE）两天，再监测五天。基线时 CFA 和 Mf 检测呈阳性的人在治疗后 12 个月进行复测，以评估治疗效果。IDA 组和 DA 组的基线 CFA 和 Mf 率分别为 26.4%和 6.9%和 24.5%和 6.4%。IDA 组和 DA 组分别有 4758 名和 4160 名参与者接受了治疗。两种治疗后大多数 AE 均为轻度；不到 0.1%的参与者经历了严重程度>1 级的 AE。未观察到严重 AE。发热、头痛和头晕是最常见的 AE。IDA 组的 AE 发生率略高于 DA 组（8.3%比 6.4%，P<0.01）。女性和 Mf 阳性者在两种治疗后 AE 更常见，但 IDA 后更常见（40.5%比 20.2%，P < 0.001）。IDA 清除 Mf 的效果优于 DA（84%比 61.8%，P < 0.001）。复测的 Mf 阳性者中，每 60μl 几何均数 Mf 计数从 IDA 后的 11.8 下降 96.4%，从 DA 后的 9.5 下降 90.0%。两种治疗均不能清除 CFA。

结论/意义：IDA 具有可接受的安全性，并且清除 Mf 的效果优于 DA。如果依从性和医疗支持足够，以管理 AE，IDA 有可能加速印度 LF 的消除。