Chagas disease is caused by infection with the protozoan Trypanosoma cruzi and affects over 8 million people worldwide. In spite of a powerful innate and adaptive immune response in acute infection, the parasite evades eradication, leading to a chronic persistent infection with low parasitism. Chronically infected subjects display differential patterns of disease progression. While 30% develop chronic Chagas disease cardiomyopathy (CCC)—a severe inflammatory dilated cardiomyopathy—decades after infection, 60% of the patients remain disease-free, in the asymptomatic/indeterminate (ASY) form, and 10% develop gastrointestinal disease. Infection of genetically deficient mice provided a map of genes relevant for resistance to T. cruzi infection, leading to the identification of multiple genes linked to survival to infection. These include pathogen resistance genes (PRG) needed for intracellular parasite destruction, and genes involved in disease tolerance (protection against tissue damage and acute phase death—DTG). All identified DTGs were found to directly or indirectly inhibit IFN-γ production or Th1 differentiation. We hypothesize that the absolute need for DTG to control potentially lethal IFN-γ PRG activity leads to T. cruzi persistence and establishment of chronic infection. IFN-γ production is higher in CCC than ASY patients, and is the most highly expressed cytokine in CCC hearts. Key DTGs that downmodulate IFN-γ, like IL-10, and Ebi3/IL27p28, are higher in ASY patients. Polymorphisms in PRG and DTG are associated with differential disease progression. We thus hypothesize that ASY patients are disease tolerant, while an imbalance of DTG and IFN-γ PRG activity leads to the inflammatory heart damage of CCC.

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Summary The adequate choice of Trypanosoma cruzi strains as antigen source for the diagnosis of Chagas disease is still controversial due to differences in terms of accuracy reported between different diagnostic tests. In this study was determined if the genetic variability between different genotypes of T. cruzi (TcI, TcII and TcIV) affect the final diagnosis of Chagas disease. The sensitivity and specificity index of in‐house ELISA tests prepared with different T. cruzi strains were evaluated with chagasic and non‐chagasic control sera and using the TESA‐blot as a reference test. The results of this study revealed that the sensitivity index did not vary, with percentages of 100% for all strains in both tests. However, the specificity index for ELISA tests showed differences between 92% and 98%, but were reduced to 78%‐89% when Leishmania‐positive sera were included. All ELISAs and TESA‐blot prepared with different antigens and the recombinant Wiener test were challenged in an endemic community for Chagas disease in Panama. Both ELISAs and TESA‐blot recognized the same positive sera, corroborating the sensitivity indexes (100%) found with the control sera. The TESA‐blot maintained the specificity index of 100% and did not display false positives. However, the recombinant Wiener test decreased its sensitivity to 81.25%.