Efficacy, safety, and pharmacokinetics of coadministered diethylcarbamazine, albendazole, and ivermectin for treatment of bancroftian filariasis

Edward K. Thomsen, Nelly Sanuku, Manasseh Baea, Samson Satofan, Elit Maki, Bart Lombore, Mark S. Schmidt, Peter M. Siba, Gary J. Weil, James W. Kazura, Lawrence L. Fleckenstein, Christopher L. King

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

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.

Original languageEnglish
Pages (from-to)334-341
Number of pages8
JournalClinical Infectious Diseases
Volume62
Issue number3
DOIs
StatePublished - Feb 1 2016

Keywords

  • albendazole
  • chemotherapy
  • diethylcarbamazine
  • ivermectin
  • lymphatic filariasis

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