This project deals with both laboratory and clinical aspects of infection caused by the intestinal nematode, Strongyloides stercoralis. The laboratory work is now focused upon preparation and purification of recombinant antigens from infective (L3) larvae of the parasite. The clinical studies involve assay and evaluation of immune responses in individuals infected with S. stercoralis. The diagnosis of chronic Strongyloides infection is often difficiult because larval excretion is scanty and intermittent. Therefore, a serologic test and other immunologic methods are useful in identifying infected individuals. Assay of antibodies of different isotypes, such as IgG, IgG4 and IgE, has been found useful in immunodiagnosis. An immediate hypersensitivity skin test mediated by parasite-specific IgE using crude parasite antigens continues to be studied. The effect of infection with the retrovirus, HTLV-1, upon individuals also infected with S. stercoralis was found to affect the likelihood of severe disease due to the parasite and efficacy of treatment. The immunologic mechanism for this was found to involve in-vitro activation of T cells with production of interferon-gamma (INF-gamma). This was associated with down-regulation of Th2 cytokines, as well as low serum IgE levels. This stimulus to INF-gamma production has been considered to be due to TAX protein, a product of HTLV-1 infected CD4 positive T cells. However, there may be other sources of INF-gamma since Mitre, et al. found that the majority of INF-gamma producing CD4 positive cells in patients with HTLV-1 infection do not express TAX protein. Since helminth infections are associated with Th2 cytokine responses we examined whether such infections would influence the pro-viral load in patients also infected with HTLV-1. No consistent pattern of either increase or decrease of pro-viral load was found in cells from 20 patients infected with S. mansoni and S. stercoralis. The homology of recombinant NiE antigen with allergen 5 of insect venoms did not interfere with immuno-diagnostic properties of NiE antigen.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000257-22
Application #
6807883
Study Section
(LPD)
Project Start
Project End
Budget Start
Budget End
Support Year
22
Fiscal Year
2003
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
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
Carvalho, E M; Bacellar, O; Porto, A F et al. (2001) Cytokine profile and immunomodulation in asymptomatic human T-lymphotropic virus type 1-infected blood donors. J Acquir Immune Defic Syndr 27:1-6
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