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Efficacy, Safety, and Pharmacokinetics of Coadministered Diethylcarbamazine, Albendazole, and Ivermectin for Treatment of Bancroftian Filariasis

Thomsen, Edward ORCID: https://orcid.org/0000-0003-1136-6430, Sanuku, Nelly, Baea, Manasseh, Satofan, Samson, Maki, Elit, Lombore, Bart, Schmidt, Mark S, Siba, Peter M, Weil, Gary J, Kazura, James W, Fleckenstein, Lawrence L and King, Christopher L (2015) 'Efficacy, Safety, and Pharmacokinetics of Coadministered Diethylcarbamazine, Albendazole, and Ivermectin for Treatment of Bancroftian Filariasis'. Clinical Infectious Diseases, Vol 62, Issue 3, pp. 334-341.

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Abstract

Background
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.

Methods
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.

Results
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.

Conclusions
Triple-drug therapy is safe and more effective than DEC + ALB for Bancroftian filariasis and has the potential to accelerate elimination of lymphatic filariasis.

Item Type: Article
Subjects: QV Pharmacology > QV 38 Drug action.
QX Parasitology > Helminths. Annelida > QX 301 Filarioidea
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 880 Filariasis and related conditions (General)
WF Respiratory System > Tuberculosis > WF 360 Drug therapy
Faculty: Department: Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI): https://doi.org/10.1093/cid/civ882
Depositing User: Jessica Jones
Date Deposited: 19 Feb 2016 16:10
Last Modified: 15 Jun 2018 14:42
URI: http://archive.lstmed.ac.uk/id/eprint/5687

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