Triple drug therapy could be game changer for lymphatic filariasis

Almost one billion people are at risk of contracting one of the major tropical diseases that permanently damage bodies and quality of life. But a new treatment regimen has researchers hopeful that one of these life-altering illnesses might be eliminated faster than originally anticipated.

Hundreds of millions of people are infected with lymphatic filariasis (LF), a parasitic infection that damages the lymphatic system and—if left  untreated—can lead to swelling of the scrotum or legs, or elephantiasis, known in some parts of the world as “big foot syndrome.” These painful conditions lead to disability and alienation for those they affect.  

The only tool public health officials have for slowing the spread of this disabling and disfiguring disease is mass drug administration, or MDA. This means fanning out across vast areas and using medical personnel and community volunteers to distribute medicines to entire communities.

“Rapid reduction (of disease) is easy, but elimination is difficult,” said Gary Weil, principal investigator of DOLF, the Death to Onchocerciasis and Lymphatic Filariasis project, at the 2016 COR-NTD meeting.  One purpose of DOLF’s ongoing work is to find the best way to eliminate LF from selected populations.

Current LF treatment relies on a two-drug cocktail, usually albendazole (ALB) combined with either diethylcarbamazine (DEC) or ivermectin (IVM). This treatment is relatively effective, but communities must use it for several years to be free of disease. That strict treatment calendar can prove problematic for people in the developing world, according to Catherine Bjerum, an infectious disease physician at the Global Health Center at Case Western Reserve University.

But an experimental regimen that appears to work faster and more effectively generated considerable excitement when NTD researchers gathered in Atlanta in November. An early clinical trial indicates that a three-drug combination can clear almost all the LF parasites from the blood of infected people within a few weeks, which would take years using a two-drug regimen.

The new approach is called IDA for the three standard treatments it packs into one, ivermectin, diethylcarbamazine and albendazole.

In clinical trials in Papua New Guinea and Cote d’Ivoire, patients treated with IDA were almost completely cleared of the parasites by the one-year mark while the ALB with DEC or IVM combination only cleared about a third of participants, reported Bjerum, who was a field investigator for the Cote d’Ivoire trials. The Papua New Guinea trials were overseen by Christopher King, a DOLF collaborator and a professor of international health, medicine and pathology at Case Western Reserve University.

“What we’ve shown in Papua New Guinea and Cote d’Ivoire is that it’s very effective,” Bjerum said, referring to the triple therapy. “It clears the microfilariae (larval filarial parasites in blood) almost completely; it also appears to kill most of the adult worms that we can see by ultrasound, and it’s safe.”

The standard two-drug treatment for LF constitutes the largest mass drug administration program in history. More than six billion treatments have been given since 2000, said Weil. Although the approach has prevented the disease in tens of millions of people, researchers doubt programs will meet the World Health Organization’s goal of eliminating LF by 2020 on their current course.

“We have 29 countries that under the current strategy will not be able to stop MDA nationally by 2020, so we need alternate strategies or we need more time,” said Jonathan King, a World Health Organization scientist and a DOLF technical advisor.

IDA is the “potential game changer” for accelerating to the finish line, Weil said.

Using IDA in disease-plagued countries could save roughly $200 million in under five years, King said.

Even when clinical trials show dramatic results, it often takes 10 to 20 years for new knowledge to help the people most in need. Where LF is concerned, “that’s not acceptable,” said Julie Jacobson, senior program officer for global health at the Bill & Melinda Gates Foundation and DOLF technical advisor. “What we’re trying to do is take that 15-20 years and bring it down to 15-18 months.”

Researchers are currently testing IDA in communities in five countries, confirming safety and efficacy. So far, the results are promising. We hope that the World Health Organization will be able to endorse IDA as a new option for filariasis elimination programs, Weil said. However, it will be important for programs to ensure high compliance with the new treatment. After all, “the new drug combination won’t work unless people swallow the pills.”