16 year-old African boy with Elephantiasis.

Global Health Research: Eliminating Lymphatic Filariasis

Researchers at The Genome Institute and Washington University School of Medicine are working together on projects to help eliminate the tropical disease lymphatic filariasis and control other diseases caused by parasitic worms.

Lymphatic filariasis is a tropical disease that affects more than 100 million people in over 70 countries. Some 1.4 billion people live in areas where filariasis is transmitted. Mosquitoes transmit the thread-like worms that infect the body’s lymphatic system and cause the disease. Parasite larvae from mosquitoes migrate through the body’s tissues to the lymphatic system where they develop into adult worms over a period of months. Inflammatory responses to the worms damage the lymphatic vessels, and this can result in genital deformities and abnormally swollen legs - a condition known as elephantiasis - that causes pain and severe disability.

Three of the eight filarial worm species that infect humans can cause elephantiasis. One of the other species causes onchocerciasis, which is also known as “river blindness.” There are regional differences in the biological characteristics of filarial worms and the diseases that they cause, but little is known about genetic diversity within filarial species.

The largest global health program ever attempted based on mass treatment

The Global Program to Eliminate Lymphatic Filariasis (GPELF) is attempting to interrupt transmission of filariasis by providing mass drug administration (MDA) to all those who live in endemic areas. The drugs used for MDA (donated by Merck and by GlaxoSmithKline) do not completely cure infected individuals, but they clear parasites from the blood for prolonged periods of time, and this prevents mosquitoes from acquiring the parasites for transmission to others.

In the first 12 years of the MDA program, over 4 billion treatments were administered to more than 600 million people in 50 countries. “This is the largest public health program every attempted based on mass treatment,” says Dr. Gary Weil, professor of medicine and molecular microbiology at Washington University School of Medicine. The goal is to eradicate filariasis by 2020, though it will likely take longer than this, considering how long other eradication programs, such as polio, have taken.

“Because the disease is transmitted through a mosquito vector and reinfection does not occur as quickly as with soil transmitted parasitic worms (such as hookworm, ascaris or whipworm) there is a much better chance of completely eliminating the disease using mass treatment,” says Dr. Makedonka Mitreva, assistant professor of medicine and assistant director of The Genome Institute.

Dr. Weil is leading the DOLF (Death to Onchocerciasis and Lymphatic Filariasis) project which aims to eliminate filariasis in eight countries in Africa and Asia. DOLF’s funding comes from the Bill and Melinda Gates Foundation; the goal of the project is to conduct field studies and clinical trials to improve mass treatment programs needed for global elimination of lymphatic filariasis and river blindness. As part of that process Dr. Weil will be providing Dr. Mitreva with hundreds of clinical isolates of parasitic worms for sequencing. By sequencing these important parasite species, they hope to learn more how the species’ genomes vary. These variations may be related to how severe the disease is in different regions or how sensitive the parasites are to drug treatments.

Developing improved diagnostic tests

In order to better monitor treatment programs, Dr. Weil’s group is working to develop and evaluate improved diagnostic tests for parasite infections. The concept is similar to a pregnancy test in that it gives a ‘yes’ or ‘no’ answer. These tests include dipsticks or small cards that detect products of parasitic worms in the blood. Other tests detect human antibodies produced in response to infection.

Next-generation sequencing

Once Dr. Weil and his team collect the samples and isolate the parasitic DNA – both challenging tasks - Dr. Mitreva’s team at The Genome Institute will sequence the genomes of the parasites. They will use next-generation sequencing technology to generate much needed data on the genetic makeup of these clinical samples. Funding for the sequencing component is provided by the National Institute of Health’s National Human Genome Research Institute, while the National Institute of Allergy and Infectious Diseases is funding the data analysis.

The Genome Institute and others have already sequenced a number of parasitic worm species, but these have all been lab-based samples. These reference genomes are very important when researching the basic biology underlying the worms. But to understand what is going on in the field, it’s important to sequence parasites that have been isolated from people in their natural habitat.

The sequencing data and analysis generated by this project will help identify genetic markers for monitoring and managing the development of drug resistance and other indicators of disease spread, such as geographic diversity. The project will also provide the resources and tools necessary to lower costs and speed development of new treatments for these key parasitic diseases.

Parasitic Nematode Clinical Isolates Map

View Clinical Isolates of Parasitic Nematodes in a larger map