Clinical Forms Of Chagas Disease Research Articles

Immunopathology of Chagas disease.

The main clinical forms of Chagas disease (acute, indeterminate and chronic cardiac) present strong evidences for the participation of the immune system on pathogenesis. Although parasite multiplication is evident during acute infection, the intense acute myocarditis of this phase exhibits clear ultrastructural signs of cell-mediated immune damage, inflicted to parasitized and non-parasitized myocardiocytes and to the endothelium of myocardial capillaries (microangiopathy). Inflammation subsides almost completely when immunity decreases parasite load and suppressor factors modulate host reaction, but inflammation does not disappear when the disease enters the indeterminate phase. Inflammation becomes mild and focal and undergoes cyclic changes leading to complete resolution. However, the process is maintained because the disappearance of old focal lesions is balanced by the upsurge of new ones. This equilibrium allows for prolonged host survival in the absence of symptoms or signs of disease. The chronic cardiac form is represented by a delayed-type, cell-mediated diffuse myocarditis, that probably ensues when the suppressive mechanisms, operative during the indeterminate phase, become defaulted. The mechanism responsible for the transition from the indeterminate to the cardiac form, is poorly understood.

Evolution on the immunopathology of Chagas disease.

The pathogenesis of Chagas disease is still con-troversial. The lesions that occur in the acute phaseof infection are initially due to rupture of the heartfibers by the Trypanosoma cruzi. When the para-site antigens sensitize the immune system, the in-flammatory process is due to a sum of the trau-matic mechanism and the immune reaction againstthe parasite.After the acute phase and the development ofthe specific immune response occur an equilibriumbetween the host and the parasite which can lastfor all the life of the host. The T. cruzi as a trueparasite do not kills the host and the immune sys-tem of the host do not kills all the parasites. De-spite it can be detected specific humoral and cellu-lar immune response against the T. cruzi, this para-site evades the immune response mainly penetrat-ing and proliferating in host cells. The equilib-rium phase is called indeterminate phase whenoccur a clearance of parasites from bloodstreamand tissues. Patients present positive serology toT. cruzi antigens but do not present signs and symp-toms of disease.At about 10 to 15% of infected individuals de-velop a chronic heart disease characterized bychronic diffuse and fibrosing myocarditis with ab-sence or very few parasites. Different mechanismshave been proposed to explain that aggressivemyocarditis similar to a rejection of an allogeneicheart transplant. It has been suggested that the le-sions result from gradual destruction of the heartfibers by parasites or by a mechanism of cellularhypersensitivity directed to parasite antigens whichaffect also the heart tissue. Another mechanismproposed is the autoimmune mechanism.Soares and Ribeiro dos Santos presented re-sults of several experiments about immunopathol-ogy of cardiomyopathy in experimental Chagasdisease that indicate autoimmune mechanism as anstrong candidate to explain the pathogenesis ofchagasic myocardiopathy. They show an elegantexperiment where mice chronically infected withT. cruzi reject syngeneic heart grafts. Hearts graftedinto normal or T. cruzi immunized syngeneic re-cipients are not rejected. The study shows that onlyCD4 and not CD8 T cells from chronically infectedmice were able to promote rejection. Mice chroni-cally infected with T. cruzi were treated with anti-CD4 and anti-CD8 monoclonal antibodies beforetransplantation. The in vivo depletion of CD4 cells,but not CD8 cells abrogates rejection.In another experiment it was shown that chroni-cally infected mice treated with anti-CD4 mono-clonal antibodies presented tolerance with abolish-ment of the chronic carditis. The opposite occurredwhen animals were treated with anti-CD8 or anti-Thy1. Tolerant animals presented low mortality andnegative parasitemia. I can not understand whyanimals that had T-CD4 cells destroyed had a nega-tive parasitemia. The expectance was to haveimmunodeficience similar to Aids with a high para-sitemia. The phenotype of cells present in chagasicmyocarditis has been controversial as in mice as inhumans. Some authors refer predominance of CD4cells and others predominance of CD8 cells. In ourexperience with material of necropsy of humanswho died with Chagas disease (Castro-Silva &Sadigursky) we had in 80% of patients predomi-nance of CD4 cells, 10% with predominance ofCD8 cells and 10% with predominance of mac-rophages. Macrophages were seen in variable num-ber in all the cases.Other experiments with lines of autoreactiveCD4 cells from mice chronically infected with T.cruzi reinforce the hypothesis of autoimmunity inchronic Chagas disease.Correa-Oliveira et al. presented “The role ofthe immune response on the development of hu-man severe clinical forms of Chagas disease”. Thesecretion of IFN γ can be correlated with the se-vere cardiac form of Chagas disease. The oppositewas observed for in vitro secretion of IL10. Thestudies indicated that as the cardiac function wors-ens, IFN γ secretion by PBMC increases with aparallel decrease on secretion of IL10. They con-clude that IFN γ secretion can be correlated withthe development of severe cardiac form of the dis-ease. I believe that the high level of IFN γ secre-

Subspecific kDNA probes for major clones of Trypanosoma cruzi

The relationship among genetic diversity of Trypanosoma cruzi and clinical forms of Chagas disease remain elusive. In order to assess the possible association between different T. cruzi Discrete Typing Units (DTUs) and the clinical pictures of the disease, 205 chronic patients from Salta province, Argentina, were analysed. One hundred and twenty-two of these patients were clinically categorized as: cardiac 38.5% (47/122), digestive 15% (18/122), cardio-digestive 16% (20/122) and asymptomatic 30% (37/122). From each patient, blood samples were taken for both, Polymerase Chain Reaction (PCR) targeting kDNA and blood culture analyses. The presence of T. cruzi kDNA was detected in 43% (88/205) of the patients. T. cruzi DTUs were identified in 74% (65/88) of the kDNA positive patients by PCR-hybridization using specific probes. We detected the presence of DTUs TcI, TcII, TcV and TcVI. Single infections (i.e. presence of only one DTU in the sample) were detected in 38.64% of the samples (34/88), while mixed infections were 35.23% (31/88). TcV was the most prevalent DTU (60.3%- 53/88). The association analyses showed, for the first time to the best of our knowledge, that TcV and TcVI were associated with the digestive form of Chagas Disease (Fisher p = .0001).