Anti-parasitic drug could accelerate the elimination of infection endemic to Africa

Tens of millions of people in Africa are infected by parasitic worms that cause lymphatic filariasis (also called elephantiasis), a disease that leads to severe swelling and deformities of the limbs and genitals. Despite widespread treatment programs that have successfully reduced the risk of contracting lymphatic filariasis, hundreds of millions of people remain vulnerable to the infection.

A small clinical trial in Cote d'Ivoire, led by researchers at Washington University School of Medicine in St. Louis, shows that the anti-parasitic drug moxidectin – currently approved to treat river blindness, another tropical disease caused by parasitic worms – is also more effective for lymphatic filariasis than the current gold standard, ivermectin. Moreover, because moxidectin has a persistent effect in most treated individuals, it may need fewer rounds of treatment, compared with annual treatment for at least five years for ivermectin, pointing to the possibility of accelerating the elimination of the infection in Africa.

This study appears May 6 in The Lancet Infectious Diseases.

Moxidectin really works much better than the drugs that we're currently using against lymphatic filariasis. The fact is, in most of Africa, lymphatic filariasis and onchocerciasis, or river blindness, are co-endemic and you really need a drug that is going to work well for both of them."

Philip Budge, MD, PhD, associate professor of medicine in the Division of Infectious Diseases at WashU Medicine and senior author of the study

The trial was conducted in collaboration with the Centre Suisse de Recherches Scientifique in Côte d'Ivoire. Lymphatic filariasis is endemic to many African countries, and more than 26 million people are estimated to be at risk for infection in Cote d'Ivoire alone. The parasite that causes the disease, Wuchereria bancrofti, is spread by mosquitoes.

River blindness, which causes itching, rashes, skin nodules and vision impairment (which, left untreated, can lead to permanent blindness) is endemic in many of the same countries as lymphatic filariasis. Both diseases have been targeted for elimination by global programs enacted by the World Health Organization (WHO). For lymphatic filariasis, the administration of anti-parasitic medications to nearly 1 billion people so far represents the largest mass drug administration initiative for any infectious disease. In addition to limb swelling, lymphatic filariasis may increase the risks of patients contracting other diseases such as malaria, tuberculosis and HIV/AIDS.

Typically, people must receive annual doses of ivermectin and another anti-parasitic drug, albendazole, for five years to fully clear the infection. The aim of this study was to determine whether moxidectin, a new medicine for river blindness, shown to be superior to ivermectin in combatting that disease, could be a better option in combination therapies for treating lymphatic filariasis.

Participants in the trial – all adults ages 18 to 70 – had high blood concentrations of microfilaria, the larvae of adult worms. Those with high concentrations are considered infectious, contributing to the continued spread of this disease.

The study involved four treatment groups, each of which received combinations of either moxidectin or ivermectin with one or two other drugs commonly used to treat parasitic worm infections.

After 12 months, 18 out of 19 participants in the group that received moxidectin and another drug (albendazole) had cleared their infections, compared to 8 out of 25 in the ivermectin plus albendazole group. At 24 months, 14 out of 16 participants in the moxidectin group continued to remain microfilaria-free.

Among participants who received either ivermectin or moxidectin in combination with two other drugs, 21 out of 23 people in the moxidectin group were parasite-free after 24 months while 20 out of 22 participants in the ivermectin group cleared their infections over that same time period. The finding suggests that one dose of moxidectin and another drug is just as effective as moxidectin or ivermectin combined with two other drugs.

"If you treat someone with moxidectin, they are more likely to clear their parasites for longer," said Budge. "With ivermectin, people must be treated multiple times. So, maybe the right place for moxidectin in the global elimination program is in people who are hard to reach repeatedly."

Budge explained that many people who are missed by mass drug administration programs are difficult to re-dose because they live in remote villages.

Medicines Development for Global Health, a not-for-profit pharmaceutical company in collaboration with the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) developed moxidectin for human use.

"The best possible outcome for this work long-term would be for moxidectin to be used in mass drug administration programs," Budge said. "That would shorten the number of years we need to achieve lymphatic filariasis elimination. There are hundreds of millions of people who won't have this disease in the future if we can eliminate it, and moxidectin may be able to help accelerate that process."