Triple-Drug Therapy Superior to Two Drugs for Treating Lymphatic Filariasis
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Researchers randomized 182 adults (1:1:1) in Papua New Guinea with Wuchereria bancrofti microfilaremia to receive a single dose of a three-drug regimen, a single dose of a two-drug regimen, or a two-drug regimen yearly for 3 years. The two-drug regimen included diethylcarbamazine (6 mg/kg) and albendazole (400 mg). The three-drug regimen added ivermectin (200 μg/kg). All drugs were given orally under direct observation.
After the three-drug regimen, 96% of participants were clear of microfilaremia at 12 months; the same rate of clearance was found at 24 and 36 months. Clearance was significantly better than with the single dose, two-drug regimen (32%, 56%, and 83% clearance at 12, 24, and 36 months). Clearance at 36 months with triple-drug therapy was not inferior to clearance with two-drug therapy once yearly for 3 years (98% at 36 months). No serious adverse events were noted; moderate adverse events were more common for three-drug than two-drug recipients (27% vs. 5%). Participants with higher baseline microfilarial counts had more-severe and more frequent adverse events.
Rapidity of microfilarial clearance is relevant because blood microfilariae are a source of onward transmission via mosquitoes. Although three doses of the two-drug regimen was not inferior at 3 years, repeat dosing is a barrier to successful implementation. The advantage of the three-drug regimen is that a single encounter can clear microfilariae for most. The WHO has now recommended the triple-drug regimen for selected regions. As an editorialist observes, triple-drug treatment is not recommended for parts of Africa because of potential adverse effects in areas where loiasis or onchocerciasis is co-endemic, but potential added benefits from including ivermectin, where possible, are reduced transmission of scabies and intestinal helminths.
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