An inflammatory lesion called a chagoma often develops at the site where T. cruzi gains entry into a new host (Santos-Buch, 1979; Andrade
Fig. 14b.3 T. cruzi trypomastigote in human blood (Giemsa stain, x 625). Courtesy of Dr Maria Shikanai Yasuda, Sao Paulo, Brazil and Andrade, 1979). Local histologic changes include lymphocytic infiltration, intracellular parasitism of muscle and other subcutaneous tissues, interstitial edema, and reactive hyper-plasia of the lymph nodes that drain the area of the lesion. Trypomastigotes released when host cells rupture frequently can be seen by microscopic examination of fresh blood. After the organisms spread systemically, muscles, including the myocardium, are the most heavily parasitized tissues. Myocarditis may involve
Fig. 14b.4 T. cruzi in heart muscle of a Texan child who died of acute Chagas' disease. The several dozen amastigotes shown are inside a cardiomyocyte. Arrowheads point to the nucleus (N) and kinetoplast (K) of one amastigote. The kinetoplast is the organelle that characterizes the order Kinetoplastida patchy areas of infected cells, infiltration of mononuclear cells and necrosis (Ochs et al., 1996; Parada et al., 1997). The pseudocysts often seen in sections of infected tissues in patients with acute T. cruzi infection are intracellular aggregates of amastigotes (Figure 14b.4). A lympho-cytosis accompanies the high parasitemias of the acute disease, and mild elevation of transaminases may be present. In some acutely infected patients, organisms may be found in the cere-brospinal fluid (Hoff et al., 1978).
In chronic Chagas' disease the heart is the organ most commonly affected. Gross examination of the hearts of chronic chagasic patients who died of congestive heart failure often shows marked bilateral ventricular enlargement, typically involving the right side of the heart more than the left. The ventricular walls are often thin, and mural thrombi and apical aneurysms may be present. Widespread lymphocytic infiltration can be present, accompanied by diffuse interstitial fibrosis and atrophy of myocardial cells. Parasites are rarely seen in stained sections of such myocardial tissue, but recent studies using poly-merase chain reaction (PCR) assays have demonstrated an association between the presence of parasite DNA and focal inflammation (Jones et al., 1993).
Pathologic changes are frequently found in the conduction systems of chronic chagasic hearts and often correlate with pre-mortem rhythm disturbances (Andrade et al., 1978). Dense fibrosis and chronic inflammatory lesions often involve the left anterior branch and right branch of the bundle of His, but similar lesions are found in other parts of the conduction system as well.
The striking feature apparent on gross examination of the colon or esophagus of a patient with chronic Chagas' disease of the digestive tract (megadisease) is the enormous dilatation of the affected organs (Tanowitz et al., 1992). Focal inflammatory lesions with lymphocytic infiltration may be seen on microscopic examination. The number of neurons in the myenteric plexus is markedly reduced, and peri- and intraganglion fibrosis in the presence of Schwann cell proliferation and lymphocytosis is found. Quantitative evaluations of this process have shown that in severely affected persons as many as 85% of the neurons in the esophagus and 50% of those in the colon may be lost (Koberle, 1968). In most patients the clinical effects of this parasympa-thetic denervation is confined to the colon and/or the esophagus, but similar lesions have been observed in the stomach, ureters, biliary tree and other hollow viscera. Decreased acid secretion, hypotonia, hypoperistalsis and delayed emptying of the stomach have been described in patients with megaesophagus, but dilatation of the stomach is not found frequently (Troncon et al., 1993). The factors that underlie the variable rate and pattern of neuronal destruction are unknown.
The pathogenesis of the cardiac and gastrointestinal lesions of chronic Chagas' disease is poorly understood and has been debated for many years. Some investigators argue that tissue injury occurring during the acute phase of T. cruzi infection constitutes the fundamental pathogenic insult, which results, many years later, in lesions of the chronic phase (Koberle, 1968). Others hold the view that autoimmune mechanisms cause the chronic pathology (Cossio et al., 1974; Teixeira and Santos-Buch, 1975). Considerable laboratory work has been done in attempts to resolve the issue. Several studies have shown that mammalian nerve and cardiac cells have epitopes that cross-react with T. cruzi epitopes (Cunha-Neto et al., 1995; Van Voorhis et al., 1991; Wood et al., 1982), suggesting that autoimmunity plays the major role in the pathogenesis of chronic Chagas' disease. On the other hand, a small number of studies have provided evidence supporting the concept that a low-level presence of parasites in chronically affected cardiac tissue, detectable with recently developed PCR assays, stimulates a chronic inflammatory response that, over time, is the basis of the pathogenesis (Buckner et al., 1997; Jones et al., 1993). The issue remains unresolved, and it is certainly possible that both mechanisms play a role in the development of the lesions associated with chronic T. cruzi infection.
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