Host Response to Infection and Treatment in Filarial Diseases

This study will evaluate and treat patients with filarial infections to explore in depth the immunology of the disease, including susceptibility to infection, disease development, and response to treatment. Filarial infections are caused by parasitic worms. The immature worm (larva) is transmitted to a person through a mosquito bite and grows in the human body to 2 to 4 inches in length. Although many of these infections do not produce symptoms, especially in the early stages of infection, others can have serious consequences, including swelling of the limbs or genitalia, allergic-lung problems, skin rash, eye inflammation that can lead to blindness, and heart disease. This protocol does not involve any experimental diagnostic procedures or treatments, and will use only procedures employed in the standard practice of medicine.

Persons between 1 and 75 years of age diagnosed with or suspected of infection with Wuchereria bancrofti, Bugia malayi, Onchocerca volvulus, Loa loa, or other parasitic worms may be eligible for this study.

Participants will have routine tests to determine the specific type of filarial infection. These may include special tests of the lungs, skin or heart, depending on the type of parasite suspected. Patients with skin reactions may have a "punch biopsy" to examine a small piece of affected skin. For this procedure, an area of skin is numbed with an anesthetic and a small circular area, about 1/3-inch in diameter and 1/2-inch thick, is removed using a sharp cookie cutter-type instrument. Some patients may require bronchoalveolar lavage. For this procedure, the mouth and throat are numbed with lidocaine jelly and spray and, if needed, a sedative is given for comfort. A small plastic tube is placed in a vein to give medications. A pencil-thin tube is then passed through the nose or mouth into the lung airways to examine the airways. Salt water is injected through the bronchoscope into the air passage, acting as a rinse. A sample of the fluid is then withdrawn and examined for infection, inflammatory cells and inflammatory chemicals. (Bronchoalveolar lavage is done only if medically necessary and only on patients 21 years or older.) Once the diagnosis is established, standard treatment will be instituted with either diethylcarbamazine or ivermectin, depending on the type of infection.

Additional procedures for research purposes include:

• Extra blood draws to study immune cells and other immune substances. (This is the only research procedure that will be done in - More frequent and extensive follow-up evaluations than usual for routine care. They will include physical examination and blood studies.
• Urine collections at specified periods, possibly including 24-hour collections.
• Skin tests to examine the body's reaction to allergens-common environmental substances, such as cat dander or pollen-that cause an allergic reaction. The test is done in one of two ways: either the skin is lightly scratched and an allergen extract is placed over the just-broken skin, or a very fine needle is used to inject a small amount of allergen under the skin. In both methods, the site is monitored for swelling or hives in the next 48 hours.
• Leukapheresis (only on patients 21 or older ) to collect quantities of white blood cells. Whole blood is collected through a needle in an arm vein, similar to donating blood. The blood circulates through a machine that separates it into its components, and the white cells are removed. The rest of the blood is returned to the body, either through the same needle or through another needle in the other arm.

Patients admitted on this protocol will have, or be suspected of having, one of the filarial infections affecting humans. After routine clinical evaluation they will be studied in depth immunologically, and their blood cells and/or serum will be collected to provide reagents (eg., specific antibodies, T-cell clones, etc.) that will be used in the laboratory to address the broader questions of diagnosis, immunoregulation, pathology and immunoprophylaxis. Careful observations of the patients' clinical and immunologic responses to therapy will be made, as well as long-term follow-up of these changes. It is anticipated both that the patients will receive optimal clinical care for their infections and that the specimens collected from them will prove to be valuable reagents for the laboratory studies of the immunologic responses unique to filarial or other related helminth infections.

• Filariasis
• Helminthiasis
• Loiasis
• Mansonelliasis
• Onchocerciasis

• Elson LH, Shaw S, Van Lier RA, Nutman TB. T cell subpopulation phenotypes in filarial infections: CD27 negativity defines a population greatly enriched for Th2 cells. Int Immunol. 1994 Jul;6(7):1003-9.
• Zimmerman PA, Guderian RH, Aruajo E, Elson L, Phadke P, Kubofcik J, Nutman TB. Polymerase chain reaction-based diagnosis of Onchocerca volvulus infection: improved detection of patients with onchocerciasis. J Infect Dis. 1994 Mar;169(3):686-9.
• Klion AD, Ottesen EA, Nutman TB. Effectiveness of diethylcarbamazine in treating loiasis acquired by expatriate visitors to endemic regions: long-term follow-up. J Infect Dis. 1994 Mar;169(3):604-10.

• INCLUSION CRITERIA:

Age 1-100 years.

Access to a primary medical care provider outside of the NIH.

Ability to give informed consent.

Clinical evidence suggestive of a filarial infection

Therapeutic plasmapheresis or leukapheresis:

• individuals 18 years of age or older
• greater than 55 kgs with the objective of decreasing their filarial burden prior to treatment.

Research plasmapheresis or leukapheresis

• 18 years of age or older
• greater than 55 kgs.

EXCLUSION CRITERIA:

Pregnant or nursing women will be excluded from the treatment arm of the study.

Less than 1 year of age; greater than 100 years of age.

For research pheresis:

• No clinical contraindications to the procedure
• severe anemia
• cardiovascular disease
• coagulopathy