Humoral and cellular immune response of adults from northeastern Brazil with chronic Trypanosoma cruzi infection: depressed cellular immune response to T. cruzi antigen among Chagas' disease patients with symptomatic versus indeterminate infection.

Infection with Trypanosoma cruzi can cause chronic Chagas' disease manifestations (cardiac, gastrointestinal), although most persons with chronic infection have no ill effects (indeterminate form). Cell-mediated immunity (CMI) responses are believed to be intrinsically important in the containment of T. cruzi and in the pathogenesis of Chagas' disease. Humoral and CMI responses were investigated in 70 T. cruzi-infected persons from an endemic area in northeastern Brazil and in 30 uninfected controls. An epidemiologic survey, physical examination, and blood evaluation were conducted for each subject. The 70 chronically infected persons were subclassified into three clinical groups: indeterminate, cardiac, and gastrointestinal. Serum was tested for antibodies to T. cruzi by hemagglutination assay, indirect immunofluorescent assay, and enzyme-linked immunosorbent assay, and for autoantibodies to tubulin. Serum levels of soluble interleukin-2 receptor (sIL-2R), albumin, and C-reactive protein (CRP) were also measured to assess one parameter each of immunosuppression, nutritional status, and inflammation. The proliferative response of peripheral blood mononuclear cells (PBMC) to T. cruzi antigens, mitogen (phytohemagglutinin), and antigen-free controls was also assessed. Our data did not reveal any significant differences in serum levels of antibodies to T. cruzi, antibodies to tubulin, albumin, CRP, or sIL-2R among the subgroups of infected individuals. The data demonstrate differences in CMI responses. Trypanosoma cruzi trypomastigote lysate stimulated proliferation of PBMC from infected persons, but not uninfected controls. Patients with symptomatic Chagas' disease (cardiac and gastrointestinal groups) had decreased cellular responses to T. cruzi lysate (median proliferation index [PI] = 3), compared with those in the indeterminate group (median PI = 9; P < 0.005). Further investigations of the mechanism of this reduced CMI response in those with chronic disease may yield insights into the pathogenesis of Chagas' disease.

Evaluation of recombinant trypomastigote surface antigens of Trypanosoma cruzi in screening sera from a population in rural northeastern Brazil endemic for Chagas' disease.

A perfect serologic test for infection with Trypanosoma cruzi does not exist. This study uses recombinant T. cruzi surface proteins in the antibody capture enzyme linked immunoabsorption assay (ELISA); and compares this approach to the more standard immunofluorescence assay (IFA). Three recombinant antigens are studied: F1-160 corresponding to the 160 kDa flagellar associated surface protein of trypomastigotes (the motile form of T. cruzi in mammalian infections); and SA 85-1.1 and 1.2 corresponding to different members of the 85 kDa family of surface proteins expressed by trypomastigotes and amastigotes (the replicative, non-motile form of T. cruzi in mammalian infections). Each recombinant antigen is found to be highly specific (range 86-94%) but relatively insensitive (range 36-52%) when used to screen for antibodies to T. cruzi. Defining seropositivity as reactivity to any of the three recombinant antigens markedly increases the sensitivity (72%) with only a minor reduction in specificity (82%). Thus, employing recombinant T. cruzi antigens to screen for T. cruzi infection has promise, but improvements in sensitivity must be made before widespread utilization is recommended.