A single triple-drug treatment for lymphatic filariasis may prove to be more effective and potent than the current treatment of a double-drug regimen administered once every 3 years, according to a study recently published in The New England Journal of Medicine.
Caused by mosquito-borne nematode parasites, lymphatic filariasis typically presents as lymphedema (commonly known as elephantiasis) of the arms and legs and hydrocele and may also result in long-term disability. The life cycle of the parasite requires uptake by mosquitoes to allow development into infective larvae, which are then transmitted to humans by the mosquitoes. The World Health Organization hopes to achieve global elimination of lymphatic filariasis by 2020 through mass drug administration using 1 of 3 antifilarial drug regimens: diethylcarbamazine plus albendazole in countries where onchocerciasis and loiasis are not co-endemic, ivermectin plus albendazole in African countries where onchocerciasis is endemic, and albendazole alone in regions of Africa where loiasis and lymphatic filariasis are co-endemic.
However, a single dose of these therapy regimens does not completely eradicate adult filarial worms or reduce the number of microfilariae in the community to sufficiently low levels; therefore, multiple rounds of treatment are required to interrupt transmission. Although this approach has been successful, elimination could be greatly accelerated with a more effective treatment that requires a smaller number of doses and annual rounds. The current randomized, controlled trial (ClinicalTrials.gov identifier: NCT01975441) tested whether a single dose of a 3-drug regimen of ivermectin plus diethylcarbamazine and albendazole would result in a greater sustained clearance of microfilariae compared with a single dose of a 2-drug regimen. Administration of the 2-drug regimen is currently recommended once a year for 3 years.
A total of 182 adults, aged 18 to 65 years, from Papua, New Guinea, who were infected with Wuchereria bancrofti-microfilaremia with a microfilarial count >50 microfilariae/mL of blood were included in the cohort. Participants were randomly assigned (1:1:1) to receive either a single dose of the 3-drug regimen (n=60), a single dose of the 2-drug regimen (n=61), or the 2-drug regimen administered once a year for 3 years (n=61). Clearance of microfilariae from the blood was measured at 12, 24, and 36 months after trial initiation. The primary outcome was complete clearance of microfilaremia at 36 months after trial initiation.
Results showed that at 36 months, a single dose of a 3-drug regimen of ivermectin plus diethylcarbamazine and albendazole was more effective in clearing W bancrofti microfilaremia than a single dose of a 2-drug regimen of diethylcarbamazine plus albendazole: 96% vs 83%, respectively, P =.02. This is significant, as the 2-drug regimen is the standard therapy for mass drug administration for the elimination of lymphatic filariasis outside sub-Saharan Africa. This is significant because incomplete or delayed clearance of microfilaremia contributes to continued transmission of the parasite. Of note, the single dose of 3-drug regimen was noninferior to the 2-drug regimen administered once every 3 years. Further, both regimens were shown to have partial macrofilaricidal effects based on reductions in circulating filarial antigen levels at 36 months after initiation. Adverse events were more frequent with the 3-drug regimen compared with the 2-drug regimen. The researchers expected this because adverse events are believed to be triggered by microfilarial death.
Overall, the study authors concluded that, “Collectively, these findings indicate that the 3-drug regimen produces sustained clearance of microfilaremia in almost all persons who receive the treatment.”
King CL, Suamani J, Sanuku N, et al. A trial of triple-drug treatment for lymphatic filariasis. N Engl J Med. 2018;379(19):1801-1810.