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Three-drug regimen more effective for treatment of lymphatic filariasis
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A three-drug regimen including ivermectin, diethylcarbamazine and albendazole is more effective for the treatment of lymphatic filariasis than the standard two-drug regimen of diethylcarbamazine plus albendazole that is used outside of sub-Saharan Africa, according to findings published in The New England Journal of Medicine.
“Lymphatic filariasis caused by mosquito-borne nematode parasites is usually characterized by lymphedema of the arms and legs (‘elephantiasis’), hydrocele, and long-term disability,” Christopher L. King, MD, PhD, professor of international health, medicine and pathology at Case Western Reserve University School of Medicine, and colleagues wrote. “The life cycle of the parasite requires the uptake of microfilariae by mosquitoes during a blood meal and further development of the microfilariae into infective larvae, which are transmitted by the mosquitoes to initiate new infections in humans.”
According to King and colleagues, more than 100 million people in 52 countries have been infected by the parasitic roundworms that cause lymphatic filariasis — mostly the species Wuchereria bancrofti — and an additional 856 million people are at risk for infection. WHO has set goal for the global elimination of lymphatic filariasis by 2020 via mass drug administration.
In a randomized, controlled trial, King and colleagues compared the effectiveness of a single dose of the three-drug regimen with a single dose of the two-drug regimen to clear microfilaremia from the blood of patients infected with W. bancrofti. They also comparted the three-drug regimen administered once compared with the two-drug regimen administered once a year for 3 years.
Between June 11 and Dec. 13, 2014, King and colleagues enrolled 182 adults from Papua New Guinea with W. bancrofti microfilaremia. Eligible participants were aged 18 to 65 years, had a count higher than 50 microfilariae (mf)/mL of blood, had no recent history of illness, were not pregnant, had not received previous treatment with diethylcarbamazine or albendazole, had no clinically significant biochemical or hematologic abnormalities and had no clinically significant proteinuria, hematuria or glucosuria, the researchers said.
They randomly assigned 60 participants to receive a single dose of the three-drug regimen, 61 to receive a single dose of the two-drug regimen and 61 to receive the two-drug regimen once a year for 3 years. At 36 months the groups consisted of 54, 52 and 52 participants, respectively. King and colleagues measured participants’ blood for microfilariae clearance at months 12, 24 and 36. The primary outcome was complete clearance of microfilaremia 36 months after trial initiation.
King and colleagues observed that the three-drug regimen cleared microfilaremia in 96% of remaining participants at 12, 28 and 36 months. Among participants who received a single dose of the two-drug regimen, microfilaremia clearance was observed in 32% of participants at 12 months, 56% of participants at 24 months and 83% of participants at 36 months (P = .02). Among participants who received the two-drug regimen administered once a year for 3 years, the clearance rate was 34% at 12 months, 75% at 24 months and 98% at 36 months (P = .004).
According to study findings, moderate adverse events were more common in the three-drug regimen arm compared with the two groups that received the two-drug regimen, 27% vs. 5%, and no serious adverse events were observed in any patients.
“Collectively, these findings indicate that the three-drug regimen produces sustained clearance of microfilaremia in almost all persons who receive the treatment,” they wrote. “By contrast, treatment with the two-drug regimen administered either once or once a year for 3 years produces a slower reduction and clearance of microfilaremia. Incomplete or delayed clearance of microfilaremia can contribute to continued transmission.” – by Marley Ghizzone
Disclosures: King reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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Through mass drug administration, we have the potential to eliminate the ancient scourge of lymphatic filariasis. The new report from The New England Journal of Medicine finds that we can accelerate global elimination efforts by moving from a two-drug to a three-drug regimen. It is an important and timely advance. We now need to evaluate the potential impact of the three-drug regimen on additional and coendemic infections, including soil-transmitted helminth infection and possibly some ectoparasitic conditions.
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