Papua New Guinea Institute of Medical Research, Papua New Guinea.
Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Clin Infect Dis. 2016 Feb 1;62(3):334-341. doi: 10.1093/cid/civ882. Epub 2015 Oct 20.
Available treatments for lymphatic filariasis (LF) are limited in their longterm clearance of microfilaria from the blood. The safety and efficacy of a single-dose triple-drug therapy of the antifilarial drugs diethylcarbamazine (DEC), ivermectin (IVM), and albendazole (ALB) for LF are unknown.
We performed a pilot study to test the efficacy, safety, and pharmacokinetics of single-dose DEC, IVM, and ALB in Wuchereria bancrofti-infected Papua New Guineans. Adults were randomized into 2 treatment arms, DEC 6 mg/kg + ALB 400 mg (N = 12) or DEC 6 mg/kg + ALB 400 mg + IVM 200 μg/kg (N = 12), and monitored for microfilaria, parasite antigenemia, adverse events (AEs), and serum drug levels.
Triple-drug therapy induced >2-log reductions in microfilaria levels at 36 and 168 hours after treatment compared with approximately 1-log reduction with 2 drugs. All 12 individuals who received 3 drugs were microfilaria negative 1 year after treatment, whereas 11 of 12 individuals in the 2-drug regimen were microfilaria positive. In 6 participants followed 2 years after treatment, those who received 3 drugs remained microfilaria negative. AEs, particularly fever, myalgias, pruritus, and proteinuria/hematuria, occurred in 83% vs 50% of those receiving triple-drug compared to 2-drug treatment respectively (P = .021); all resolved within 7 days after treatment. No serious AEs were observed in either group. There was no significant effect of IVM on DEC or ALB drug levels.
Triple-drug therapy is safe and more effective than DEC + ALB for Bancroftian filariasis and has the potential to accelerate elimination of lymphatic filariasis.
NCT01975441.
目前可用于治疗淋巴丝虫病（LF）的方法在长期清除血液中的微丝蚴方面效果有限。尚未明确抗丝虫药物乙胺嗪（DEC）、伊维菌素（IVM）和阿苯达唑（ALB）三联疗法单次用药治疗 LF 的安全性和疗效。
我们开展了一项试点研究，以检测 DEC、IVM 和 ALB 三联疗法单次用药治疗感染班氏丝虫的巴布亚新几内亚成年人的疗效、安全性和药代动力学。将成年人随机分配到 2 个治疗组，即 DEC 6 mg/kg+ALB 400 mg（N=12）或 DEC 6 mg/kg+ALB 400 mg+IVM 200 μg/kg（N=12），并监测微丝蚴、寄生虫抗原血症、不良事件（AE）和血清药物水平。
与 2 种药物治疗相比，三联疗法在治疗后 36 和 168 小时可使微丝蚴水平降低>2 个对数级，而 2 种药物治疗仅使微丝蚴水平降低约 1 个对数级。接受 3 种药物治疗的 12 个人在治疗后 1 年均未检测到微丝蚴，而接受 2 种药物治疗的 12 个人中有 11 人微丝蚴阳性。在治疗后 2 年随访的 6 名参与者中，接受 3 种药物治疗的人仍未检测到微丝蚴。AE，尤其是发热、肌痛、瘙痒和蛋白尿/血尿，在接受三联疗法的参与者中分别有 83%和 50%发生（P=0.021），均在治疗后 7 天内缓解。两组均未观察到严重 AE。IVM 对 DEC 或 ALB 药物水平无显著影响。
与 DEC+ALB 相比，三联疗法治疗班氏丝虫病更安全、更有效，有可能加速淋巴丝虫病的消除。
NCT01975441。
