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May 13, 2020
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Three-drug regimen sterilizes adult filarial worms for at least 5 years

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A three-drug regimen of ivermectin, diethylcarbamazine and albendazole given as a single dose sterilizes adult filarial worms for at least 5 years, according to a letter to the editor in The New England Journal of Medicine, though this regimen may fail to clear circulating filarial antigen.

“We wanted to see if triple-drug therapy permanently sterilized adult worms, since their reproductive life span is about 5 years,” Christopher L. King, MD, PhD, professor in the department of pathology and associate professor in the department of medicine at Case Western Reserve University School of Medicine, told Healio. “This is a follow-up of a paper we published in The New England Journal of Medicine in 2018 showing the results at 3 years.”

King and colleagues re-examined 36 of the original trial participants approximately 5 years after they were treated with a single dose of the three-drug treatment — and 2 years after completion of the clinical trial — using the same parasitologic methods from the original study. The results showed that a single dose of triple drug therapy, if given to enough people in a community, will be sufficient to interrupt transmission and therefore eliminate lymphatic filariasis (LF), King said.

According to the letter, 35 of the 36 re-examined participants had no microfilariae in 2 mL of venous blood collected at night, which is when circulating microfilariae are present. One person had a single microfilaria in 2 mL of blood, which researchers say is most likely less than the concentration needed for transmission by local mosquitoes. Only nine of the 36 trial participants (25%) who were re-examined had negative filarial antigen tests at 5 years.

King noted that this treatment can help accelerate global eradication of LF though mass drug treatment and is also effective in reducing the burden of soil-transmitted helminths, particularly Strongyloides, Trichuris and hookworm and is also highly effective against scabies. Mass drug administration, as well as distribution of insecticide-treated bed nets in the study area, could explain the lack of reinfection among trial participants in the 5 years following treatment with the combination, according to the letter.

“Mass drug treatment for LF is probably one of the largest programs ever to try to achieve global eradication for any infection. Over the last 20 years, well over 7 billion doses of treatment have been given, but included only two drugs and required at least five rounds of annual treatment to interrupt transmission,” King concluded. “This has been accomplished by donation of drugs from Merck, GSK and now Eisai. The triple-drug treatment is now being rolled out to an estimated 68 million people this year and probably up to 100 million next year and may require only one or two rounds of mass drug treatment.”