Pathology of Chronic Disease

Chronic manifestations usually take three formsin order of prevalence: cardiac, colonic, and esophagealand more than half of the patients with Chagas’ disease reveal abnormal electrocardiograms. Up to 30 percent of people with the indeterminate or inapparent form of the infection suffer from cardiac, digestive, or neurological damage ten to twenty years after having contracted the disease, while the remainder never exhibit any manifest organ involvement (WHO 1991; see Figure 8). Symptoms of chagasic heart disease progress from barely decipherable indicators, such as fever, anemia, and hypertension, to serious pathologies.[35]Cardiomegaly results in the heart enlarging five or six times its normal size; but it is not found in all chronic patients, such as Bertha, whose symptoms of Chagas’ disease were expressed by ventricular arrhythmias, which frequently cause death sooner than does cardiomegaly.[36]Heart disease illustrates how widespread the damage of Chagas’s disease can be and how difficult it is to diagnose this disease by means of only a specific set of symptoms.

The pathology of the chronic stage of Chagas’ disease is related to denervation within the nervous system of the colonized organ (Brener 1994). Degeneration of neurons in the heart’s parasympathetic ganglia is common in chagasic patients with heart ailments. With megacolon and megaesophagus, lesions of the colon and esophagus are caused by destruction of nerve cells. These lesions are jointly caused by the parasite (intracellular invasion of the trypomastigotes, encystation of amastigotes, and bursting of cells) and by the autoimmune response of the host. Increasing evidence indicates that the pathogenesis of Chagas’ disease is related to the parasite’s ability to manipulate the host’s immune system.[37]It has been found that people die from chronic manifestations in which lesions are left from T. cruzi but the parasite is not present, perhaps being lysed at an earlier stage. This has led scientists to suspect that the traces or lesions left from the parasite mimic human antigens. The immune system mistakes these human cells as epitopes from T cruzi and attacks them (discussed in Appendix ii). This is similar to rheumatic fever, where people die from the disease long after the pathogen has been removed.

During the acute phase, inflammation, fevers, and cell damage are related to overactivity of the lymphocytes (see Appendix 9). This polyclonal stimulation is triggered by macrophages devouring trypomastigotes. Results include violent onslaughts on the parasites that drive them into central nervous system cells, lysing cells encapsulated with parasites that release toxins into the body, ineffective destruction of antigens, and eventual weakening of immune response. In short, damage from acute Chagas’ disease is more a result of overactivity of the immune system than damage due directly to T. cruzi.

The cardiopathy of chronic Chagas’ disease is an issue of considerable debate, with several lines of evidence to account for, including the inability to consistently find parasites in damaged areas (Torres 1930). The passive transfer of heart lesions by CD4⁺ T cells from T. cruzi ‑infected mice to uninfected mice indicates that inflammatory heart lesions could be of an autoimmune nature (Andrade 1958, Ribeiro‑dos‑Santos et al. 1992). (In simpler terms, the T cells from infected mice were encoded with self‑destructive tendencies, and when these T cells were placed in uninfected mice, they caused damage as if the sterile mice had the parasites.)

Referred to as the antigenic mimicry hypothesis, lymphocytes in the heart recognize and mount delayed‑type hypersensitivity responses toward a tissue‑specific heart component bearing structural similarities to a given T. cruzi antigen.[38]A recent study indicates that heart‑tissue destruction in chronic Chagas’ disease may be caused by autoimmune recognition of heart tissue by a mononuclear cell infiltrate decades after T. cruzi infection (Cunha‑Neto et al. 1995). Indirect evidence suggests that there are antigenic cross‑reactions between T. cruzi and heart tissue. Myosin heavy chain (myosin HC) is the most abundant heart protein–50 percent of total protein by weight–and is recognized in heart‑specific autoimmunity in rheumatic heart disease (Neu, Beisel, et al. 1987). Research indicates the involvement of cross‑reactions between cardiac myosin and a recombinant T. cruzi protein (B13) as targets for attack by the victim’s T cells (Cunha‑Neto et al. 1995).[39]

The immune response is also impaired in the chronic stage of Chagas’ disease (see Appendix II: Immune Response). An improper response of the cellular immune system results in tissue damage, which might lead to the autoimmune cardiac and neural damage of chronic T. cruzi infection (Botasso et al. 1994). Trypanosoma cruzi infection impairs immunity to many antigens and mitogens.[40]Chagasic patients have a reduced cellular immune response to common mycobacteria antigens, such as those of tuberculosis and leprosy (Bottasso et al. 1994).[41]T. cruzi causes loss of the TH1 response to mycobacterial antigens.

HIV patients are also unresponsive to mycobacterial antigens (Khoo et al. 1993). The progression from HIV seropositivity to AIDS is accompanied by a shift in T‑helper (TH) cells from TH1 to TH2 and selective loss of the response to mycobacterial antigens. Significantly, chagasic patients are predisposed to the establishment of HIV infection and its rapid progression to AIDS (Botasso et al. 1994).

In conclusion, the rapid spread and progression of HIV infection in Latin America is related to the frequency of infection of Chagas’ disease. The rapid spread and progression of tuberculosis and other acute respiratory infections in Bolivia is also related to Chagas’ disease. Bolivian public policy makers often object to the fact that AIDS and tuberculosis take medical priority to Chagas’ disease, when the fact is that Chagas’ disease is also related to the epidemiology of other diseases by the nature of the autoimmune response to it that predisposes its victims to these diseases.