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个体疗效和伊维菌素、乙胺嗪和阿苯达唑群体药物治疗在斐济控制淋巴丝虫病的社区影响:一项集群随机试验。

Individual Efficacy and Community Impact of Ivermectin, Diethylcarbamazine, and Albendazole Mass Drug Administration for Lymphatic Filariasis Control in Fiji: A Cluster Randomized Trial.

机构信息

Tropical Diseases Research Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.

Department of Paediatrics, University of Melbourne, ,Melbourne, Victoria, Australia.

出版信息

Clin Infect Dis. 2021 Sep 15;73(6):994-1002. doi: 10.1093/cid/ciab202.

Abstract

BACKGROUND

Bancroftian filariasis remains endemic in Fiji despite >10 years of mass drug administration (MDA) using diethylcarbamazine and albendazole (DA). The addition of ivermectin to this combination (IDA) has improved efficacy of microfilarial clearance at 12 months in individually randomized trials in nocturnal transmission settings, but impact in a setting of diurnally subperiodic filarial transmission has not been evaluated.

METHODS

This cluster randomized study compared the individual efficacy and community impact of IDA vs DA as MDA for lymphatic filariasis in 35 villages on 2 islands of Fiji. Participants were tested at enrollment for circulating filarial antigen and, if positive, for microfilariae. Weight-dosed treatment was offered according to village randomization. Communities were visited at 12 months and retested for lymphatic filariasis. Infected individuals from Rotuma were retested at 24 months.

RESULTS

A total of 3816 participants were enrolled and 3616 were treated. At 12 months, microfilariae clearance was achieved in 72 of 111 participants detected with infection at baseline, with no difference in efficacy between treatment groups: DA, 69.2% (95% confidence interval [CI], 57.2%-79.1%) vs IDA, 62.5% (95% CI, 43.6%-78.2%); risk difference, 11.3 % (95% CI, -10% to 32.7%); P = .30. There was no difference between treatment groups in community prevalence of microfilariae at 12 months or individual clearance at 24 months.

CONCLUSIONS

We found no difference between IDA and DA in individual clearance or community prevalence of lymphatic filariasis at 12 months, and no improved efficacy following a second annual round of IDA. Possible explanations for the apparent lack of benefit of IDA compared to DA include drug and parasite factors affecting clearance, and higher than expected reinfection rates. Clinical Trials Registration: NCT03177993 and Australian New Zealand Clinical Trial Registry: N12617000738325.

摘要

背景

尽管在斐济已经进行了超过 10 年的大规模药物治疗(MDA),使用乙胺嗪和阿苯达唑(DA),班克罗夫特氏丝虫病仍然流行。在夜间传播环境中进行的个体随机试验中,伊维菌素的加入(IDA)已提高了微丝蚴清除的效果,在 12 个月时,但在日间亚周期性丝虫传播的环境中,其影响尚未得到评估。

方法

这项在斐济两个岛屿的 35 个村庄进行的集群随机研究比较了 IDA 与 DA 作为淋巴丝虫病 MDA 的个体疗效和社区影响。参与者在入组时接受循环丝虫抗原检测,如果呈阳性,则接受微丝蚴检测。根据村庄随机化进行体重剂量治疗。在 12 个月时访问社区并重新检测淋巴丝虫病。来自罗图马的感染者在 24 个月时接受重新检测。

结果

共有 3816 名参与者入组,3616 名接受了治疗。在 12 个月时,在基线时检测到感染的 111 名参与者中有 72 名实现了微丝蚴清除,两组之间的疗效没有差异:DA 组为 69.2%(95%置信区间[CI],57.2%-79.1%),IDA 组为 62.5%(95% CI,43.6%-78.2%);风险差异为 11.3%(95% CI,-10%至 32.7%);P=.30。在 12 个月时,两组之间社区微丝蚴的流行率或个体清除率没有差异,在 24 个月时也没有差异。

结论

我们发现 IDA 与 DA 在 12 个月时个体清除率或社区淋巴丝虫病的流行率没有差异,并且在进行第二轮年度 IDA 后没有提高疗效。与 DA 相比,IDA 似乎没有益处的可能解释包括影响清除的药物和寄生虫因素,以及高于预期的再感染率。临床试验注册:NCT03177993 和澳大利亚新西兰临床试验注册:N12617000738325。

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