Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
PLoS Negl Trop Dis. 2021 Mar 17;15(3):e0009144. doi: 10.1371/journal.pntd.0009144. eCollection 2021 Mar.
Oral ivermectin is a safe broad spectrum anthelminthic used for treating several neglected tropical diseases (NTDs). Currently, ivermectin use is contraindicated in children weighing less than 15 kg, restricting access to this drug for the treatment of NTDs. Here we provide an updated systematic review of the literature and we conducted an individual-level patient data (IPD) meta-analysis describing the safety of ivermectin in children weighing less than 15 kg.
METHODOLOGY/PRINCIPAL FINDINGS: A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) for IPD guidelines by searching MEDLINE via PubMed, Web of Science, Ovid Embase, LILACS, Cochrane Database of Systematic Reviews, TOXLINE for all clinical trials, case series, case reports, and database entries for reports on the use of ivermectin in children weighing less than 15 kg that were published between 1 January 1980 to 25 October 2019. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42017056515. A total of 3,730 publications were identified, 97 were selected for potential inclusion, but only 17 sources describing 15 studies met the minimum criteria which consisted of known weights of children less than 15 kg linked to possible adverse events, and provided comprehensive IPD. A total of 1,088 children weighing less than 15 kg were administered oral ivermectin for one of the following indications: scabies, mass drug administration for scabies control, crusted scabies, cutaneous larva migrans, myiasis, pthiriasis, strongyloidiasis, trichuriasis, and parasitic disease of unknown origin. Overall a total of 1.4% (15/1,088) of children experienced 18 adverse events all of which were mild and self-limiting. No serious adverse events were reported.
CONCLUSIONS/SIGNIFICANCE: Existing limited data suggest that oral ivermectin in children weighing less than 15 kilograms is safe. Data from well-designed clinical trials are needed to provide further assurance.
口服伊维菌素是一种安全的广谱驱虫药，用于治疗几种被忽视的热带病（NTD）。目前，伊维菌素的使用禁忌是体重小于 15 公斤的儿童，这限制了该药物用于治疗 NTD。在这里，我们提供了对文献的最新系统评价，并进行了个体水平患者数据（IPD）荟萃分析，描述了体重小于 15 公斤的儿童使用伊维菌素的安全性。
方法/主要发现：使用循证医学系统评价和荟萃分析（PRISMA）的首选报告项目和 IPD 指南，通过在 PubMed 中搜索 MEDLINE、Web of Science、Ovid Embase、LILACS、Cochrane 系统评价数据库、TOXLINE，对 1980 年 1 月 1 日至 2019 年 10 月 25 日期间发表的所有临床试验、病例系列、病例报告和数据库条目进行检索，以检索关于体重小于 15 公斤的儿童使用伊维菌素的报告。该方案在国际前瞻性系统评价登记处（PROSPERO）中进行了注册：CRD42017056515。共确定了 3730 篇出版物，有 97 篇被选为潜在纳入的对象，但只有 17 篇来源描述了 15 项研究符合最低标准，这些标准包括与可能的不良反应相关的体重小于 15 公斤的儿童已知体重，并提供了全面的 IPD。共有 1088 名体重小于 15 公斤的儿童接受了口服伊维菌素治疗，以下列一种适应证：疥疮、疥疮大规模药物治疗、结痂性疥疮、皮肤幼虫移行症、蝇蛆病、头虱病、旋毛虫病、鞭虫病和寄生虫病未知来源。总的来说，共有 1.4%（15/1088）的儿童出现了 18 种不良反应，所有不良反应均为轻度且自限性的。没有报告严重的不良反应。
结论/意义：现有的有限数据表明，体重小于 15 公斤的儿童口服伊维菌素是安全的。需要有良好设计的临床试验提供进一步的保证。
