This project deals with both laboratory and clinical aspects of infection caused by the intestinal nematode, Strongyloides stercoralis. The laboratory research involves analysis and characterization of parasite antigens, including recombinant proteins prepared with a cDNA library from infective (L3) larvae of the parasite. The clinical studies focus upon the immune response of infected individuals and factors that influence the immune response. The diagnosis of chronic strongyloides infection is often difficult because larval excretion is often scanty and intermittent. Therefore, a serologic test (ELISA) is useful in identifying individuals who harbor the parasite. An immediate hypersensitivity skin test which demonstrates parasite-specific IgE antibodies is also under investigation for immunodiagnosis. One of the conditions that has been found to influence likelihood of disease and impaired response to therapy of strongyloidiasis is presence of co- infection with HTLV-1 retrovirus. The immunologic mechanism by which HTLV-1 infection leads to complications of concommitant strongyloidiasis appears to be the consequence of down-regulation of Th2 cytokines, especially IL-4, by in vivo activation of interferon- gamma. Another result of the IL-4 downregulation by INF-gamma is reduction in levels of serum IgE which may be important in control of strongyloides infection. This is being studied in an area of Brazil where both HTLV-1 and S. stercoralis infections are quite common. Peripheral blood mononuclear cells are cultured for assay of spontaneous, mitogen and antigen-stimulated cytokines and preparation of frozen cells for analysis of intracellular cytokines. - Strongyloides, recombinant antigens, HTLV-1, TH1 and TH2 cytokines, interferon gamma (INF-gamma) - Human Subjects

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000257-18
Application #
6288814
Study Section
Special Emphasis Panel (LPD)
Project Start
Project End
Budget Start
Budget End
Support Year
18
Fiscal Year
1999
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Mitre, Edward; Thompson, Robert W; Carvalho, Edgar M et al. (2003) Majority of interferon-gamma-producing CD4+ cells in patients infected with human T cell lymphotrophic virus do not express tax protein. J Infect Dis 188:428-32
Tarr, Philip E; Miele, Peter S; Peregoy, Kenneth S et al. (2003) Case report: Rectal adminstration of ivermectin to a patient with Strongyloides hyperinfection syndrome. Am J Trop Med Hyg 68:453-5
Ravi, Varatharajalu; Ramachandran, Srinivasan; Thompson, Robert W et al. (2002) Characterization of a recombinant immunodiagnostic antigen (NIE) from Strongyloides stercoralis L3-stage larvae. Mol Biochem Parasitol 125:73-81
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Porto, A F; Neva, F A; Bittencourt, H et al. (2001) HTLV-1 decreases Th2 type of immune response in patients with strongyloidiasis. Parasite Immunol 23:503-7