A Trial of a Triple-Drug Treatment for Lymphatic Filariasis.
A Trial of a Triple-Drug Treatment for Lymphatic Filariasis.
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DOI：
10.1056/nejmoa1706854
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发表时间：
2018-11-08
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影响因子：
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通讯作者：
Kazura JW
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作者：
King CL;Suamani J;Sanuku N;Cheng YC;Satofan S;Mancuso B;Goss CW;Robinson LJ;Siba PM;Weil GJ;Kazura JW
在撒哈拉以南非洲以外地区消除淋巴丝虫病的推荐药物方案是单剂量乙胺嗪（DEC）加阿苯达唑（ALB）。消除需要每年多次治疗，因为该方案不能持续将血液微丝蚴（Mf）计数降低到中断传播所需的阈值以下。本研究测试了单剂量伊维菌素（IVM）联合DEC/ALB的疗效。我们进行了一项开放标签、随机临床试验，其中巴布亚新几内亚班氏丝虫感染的成人被分配至DEC/ALB治疗一次（n=61）、DEC/ALB治疗两次（n = 61，基线，12个月）和IVM/DEC/ALB治疗一次（n=60）。主要结局是24个月时血液Mf完全清除。在24个月时，96%接受IVM/DEC/ALB治疗的受试者为无微丝蚴血症，而单次给药DEC/ALB后为56%（Mf+的相对风险= 0.08 [0.02-0.34，95%CI]，p<0.001），在每年两次DEC/ALB给药后为75%（Mf+的相对风险= 0.15 [0.03-0.62，95% CI]，p=0.009）。丝虫抗原水平显着下降，并与所有3个方案治疗后的相似程度。三联治疗组的中度不良事件发生率高于双药治疗组（27% vs. 5%，p<0.001）。未发生严重不良事件。单剂量IVM/DEC/ALB治疗清除Mf上级单剂量或每年两次DEC/ALB治疗。无重大安全性问题。广泛应用IVM/DEC/ALB可大大加速消灭淋巴丝虫病。（ClinicalTrials.gov，NCT 01978771）
The recommended drug regimen for elimination of lymphatic filariasis outside sub-Saharan Africa is single dose of diethylcarbamazine (DEC) plus albendazole (ALB). Multiple annual treatments are required for elimination since this regimen does not sustainably reduce blood microfilaria (Mf) counts below the threshold required to interrupt transmission. This study tested the efficacy of a single dose of ivermectin (IVM) combined with DEC/ALB. We conducted an open label, randomized clinical trial in which Wuchereria bancrofti-infected adults in Papua New Guinea were assigned to treatment with DEC/ALB once (n=61), DEC/ALB twice (n=61, baseline, 12 months) and IVM/DEC/ALB once (n=60). The primary outcome was complete clearance of blood Mf at 24 months. At 24 months 96% of participants treated with IVM/DEC/ALB were amicrofilaremic compared to 56% after single dose DEC/ALB (relative risk for Mf+ = 0.08 [0.02-0.34, 95% CI], p<0.001) and 75% after two annual doses of DEC/ALB (relative risk for Mf+ = 0.15 [0.03-0.62, 95% CI], p=0.009). Filarial antigen levels decreased markedly and to a similar degree after treatment with all 3 regimens. Moderate adverse events were more common after the triple than the two-drug regimen (27% vs. 5%, p<0.001). There were no serious adverse events. Treatment with a single dose of IVM/DEC/ALB was superior to a single dose or two annual doses of DEC/ALB for clearing Mf. There were no significant safety concerns. Widespread use of IVM/DEC/ALB could greatly accelerate elimination of lymphatic filariasis. (ClinicalTrials.gov, NCT01978771)