This project deals with both the laboratory and clinical aspects of infection caused by the intestinal nematode, Strongyloides stercoralis. The laboratory research involves analysis and characterization of parasite antigens. The clinical studies focus upon the immune response of infected individuals, and factors that influence the immune response. For certain purposes experimental infections are carried out in the jird (Meriones unguiculaius). The diagnosis of chronic strongyloides infection is often difficult because excretion of larvae is scanty and intermittent. Therefore, an Elisa type of serologic test is useful in identifying individuals who harbor the parasite. But this serologic test is available only in specialized laboratories and availability of the antigen is limited. For these reasons, a cDNA library was prepared from infective (L3) larvae of the parasite, and several recombinant clones were identified by screening the library with immune serum of patients. It appears that some of the clones, alone or in combination, can be used as diagnostic antigens in an Elisa test. Since some of the recombinant antigens are reactive with parasite-specific serum IgE, it may be possible to use them in an immediate hypersensitivity skin test. Further analysis was carried out of the cytokine responses of peripheral blood mononuclear cells (PBMCs) of Brazilian patients with different combinations of infection with HTLV-1 retrovirus and S. stercoralis. A significant inverse correlation between spontaneous INF-gamma production by PBMCs and total serum IgE levels was found when these values in individual patients were examined. A similar trend, but without statistical significance, was evident between spontaneous INF-gamma and parasite-specific serum IgE. Additional evidence that HTLV-1 infection in individuals also infected with S. stercoralis impairs a Th-2 cytokine response was found in reduced IL-5 levels when PBMCs were stimulated with strongyloides antigen.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000257-16
Application #
6160571
Study Section
Special Emphasis Panel (LPD)
Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
1997
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
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
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
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
Neva, F A; Gam, A A; Maxwell, C et al. (2001) Skin test antigens for immediate hypersensitivity prepared from infective larvae of Strongyloides stercoralis. Am J Trop Med Hyg 65:567-72
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Porto, A F; Oliveira Filho, J; Neva, F A et al. (2001) Influence of human T-cell lymphocytotropic virus type 1 infection on serologic and skin tests for strongyloidiasis. Am J Trop Med Hyg 65:610-3
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