We propose to develop more sensitive and specific methods for diagnosis of acute toxoplasmosis in pregnant women, congenitally infected newborns, acute ocular toxoplasmosis and immunocompromised patients. To achieve this, we will attempt to identify antigens/epitopes recognized by Ig subclasses during the acute infection in adults and by those produced in the congenitally infected fetus/newborn. Recombinant antigens and selected synthetic peptides derived from surface and secreted antigens of T.gondii will be studies. To identify genes that encode antigens recognized by antibodies early during infection, tachyzoite cDNA expression libraries will be screened with purified IgM, IgA and IgE antibodies from sera of acutely infected patients and with antibodies raised against the unique acute phase AC antigen. To identify linear and conformational epitopes recognized by acute phase antibodies, we will attempt to identify peptides that mimic epitopes from T.gondii acute phase antigens using a phage-display random peptide library. Our observation of unique antigens recognized by the fetus but not by their mothers will be further examined to improve diagnosis of congenital toxoplasmosis. A new model of toxoplasmosis in mice genetically resistant to development of toxoplasmic encephalitis (TE) that more nearly resembles the natural resistance of humans to T. gondii (in humans, life threatening TE only develops when the immune system is severely impaired), will be used to study the role of alpha beta, gamma/delta, CD4+ and CD8+T cells (using adoptive transfer), cytokines and the major surface antigen SAG1 in resistance against and the histopathology of TE. Previous models were in mice genetically susceptible to development of TE> Cytokine production by and cytotoxic activity of gamma/delta and alpha/beta cells from brains of mice will be examined following infection. We will attempt to quantify parasites in the brain using transgenetic tachyzoites that express beta-galactosidase. We recently demonstrated for the first time that a clinical manifestation of toxoplasmosis, (TE in AIDS), may be under genetic regulation. We propose to determine whether toxoplasmic lymphadenopathy is also under genetic regulation since only approximately 10% of acutely infected, immunocompetent individuals develop this clinical manifestation. We propose to continue seeking more active and less toxic therapies for toxoplasmosis. We will identify the most satisfactory in vitro method for this purpose by comparing 3 methods now in use. Drugs will be tested alone or in combination with other drugs and/or cytokines in vitro and in mouse models of acute toxoplasmosis or TE. Drug activity against the cyst form will also be studied.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Tropical Medicine and Parasitology Study Section (TMP)
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Wali, Tonu M
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Palo Alto Medical Foundation Research Institute
Palo Alto
United States
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Montoya, Jose G; Huffman, Heather B; Remington, J S (2004) Evaluation of the immunoglobulin G avidity test for diagnosis of toxoplasmic lymphadenopathy. J Clin Microbiol 42:4627-31
Remington, Jack S; Thulliez, Philippe; Montoya, Jose G (2004) Recent developments for diagnosis of toxoplasmosis. J Clin Microbiol 42:941-5
Araujo, F; Slifer, T; Li, S et al. (2004) Gemifloxacin inhibits cytokine secretion by lipopolysaccharide stimulated human monocytes at the post-transcriptional level. Clin Microbiol Infect 10:213-9
Wang, Xisheng; Kang, Hoil; Kikuchi, Takane et al. (2004) Gamma interferon production, but not perforin-mediated cytolytic activity, of T cells is required for prevention of toxoplasmic encephalitis in BALB/c mice genetically resistant to the disease. Infect Immun 72:4432-8
Araujo, Fausto G; Slifer, Teri (2003) Different strains of Toxoplasma gondii induce different cytokine responses in CBA/Ca mice. Infect Immun 71:4171-4
Kang, Hoil; Liesenfeld, Oliver; Remington, Jack S et al. (2003) TCR V beta 8+ T cells prevent development of toxoplasmic encephalitis in BALB/c mice genetically resistant to the disease. J Immunol 170:4254-9
Yardley, Vanessa; Khan, Anis A; Martin, Michael B et al. (2002) In vivo activities of farnesyl pyrophosphate synthase inhibitors against Leishmania donovani and Toxoplasma gondii. Antimicrob Agents Chemother 46:929-31
Parmley, Stephen; Slifer, Teri; Araujo, Fausto (2002) Protective effects of immunization with a recombinant cyst antigen in mouse models of infection with Toxoplasma gondii tissue cysts. J Infect Dis 185 Suppl 1:S90-5
Suzuki, Yasuhiro (2002) Host resistance in the brain against Toxoplasma gondii. J Infect Dis 185 Suppl 1:S58-65
Montoya, Jose G; Liesenfeld, Oliver; Kinney, Sandra et al. (2002) VIDAS test for avidity of Toxoplasma-specific immunoglobulin G for confirmatory testing of pregnant women. J Clin Microbiol 40:2504-8

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