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

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. CLINICAL TRIALS REGISTRATION: NCT01975441.

Fatal Outcome of Disseminated Strongyloidiasis despite Detectable Plasma and Cerebrospinal Levels of Orally Administered Ivermectin.

Strongyloides stercoralis affects over 100 million people worldwide. Those people most susceptible to infection are those with an immunocompromising condition, such as cancer or human immunodeficiency virus (HIV). Local disease may spread throughout the body of the host, causing a condition termed disseminated strongyloidiasis. Standard treatment for Strongyloides stercoralis infection is oral ivermectin. We describe a patient with chronic lymphocytic leukemia diagnosed with disseminated strongyloidiasis two weeks after initial presentation. After repeated dosing of oral ivermectin with no clinical response, serum and cerebral spinal fluid (CSF) concentrations of ivermectin were measured to assess absorption. The peak serum concentration of 49.3 ng/mL correlated with a CSF concentration of 0.14 ng/mL. Despite these concentrations, the patient eventually succumbed to multi-system organ failure. We discuss the reasons for treatment failure and explore the utility of measuring ivermectin concentrations.