Epidemiology and Pathology

This multiplication occurs rapidly at the site of inoculation, causing a severe localized inflammatory reaction consisting of neutrophils, eosinophils, interstitial edema and focal lymphangitis (a chagoma). This is followed by lymphatic spread to regional lymph nodes to produce a primary complex in the first or second week of infection. Amastigotes multiply within the cells over a 5 day period, and evolve into highly motile trypanosomes, rupture the cell membranes and disperse to either enter a new cell or return to the blood. The fact that T. cruzi multiplies within the host cell cytoplasm and not in the bloodstream makes Chagas' disease especially difficult to treat.

This parasitemia results in dissemination of the disease and invasion of multiple host tissues. Amastigotes can be found in virtually any organ or tissue but there is a distinct predilection for smooth and striated muscle (especially cardiac muscle), and glial and nerve cells. In heavy infections, where many amastigotes are released, there may be destruction of other cells, such as myofibers, liver cells and adipose cells. This occurs primarily in the acute phase of the disease, when the parasitemia and invasion of tissues is most pronounced and before specific immunity has developed.

With progression of the disease and development of partial immunity, the acute inflammatory process abates and is followed by a chronic inflammatory reaction consisting of histiocytes, lymphocytes, plasma cells and, later, epithelioid and multinucleated giant cells. The lesions become more localized with occasional development of distinct granulomas. Adjacent non-parasitized cells may exhibit hyaline degeneration with partial or complete disappearance of cross-striations and necrobiosis. Marked degeneration and lysis of ganglia cells occurs in the tissues surrounding ruptured pseudocysts, especially in the heart and brain. As the amastigotes degenerate, the ganglia cells in their immediate vicinity rapidly disappear without cellular reaction. Köberle believed that destruction of the ganglia cells is due neither to parasitism of the nerve cells themselves nor to the marked inflammatory reaction, but rather to cytotoxic and necrolytic substances (i.e., a toxin or enzyme liberated or elaborated after disintegration of the amastigote forms outside the ruptured pseudocyst). However, no such substance has yet been found, and the etiology of the extensive nerve cell destruction seen in Chagas' disease remains a mystery.

This is the basic pathological process during the acute and subacute phases, but the pathogenesis of Chagas' disease involves at least three distinct phases, each with its own pathological processes. Once defense mechanisms have developed, the disease passes into a latent phase for many years, usually several decades, during which the parasites are difficult to demonstrate, both in the blood-stream and in body tissues.

The third or chronic (late) stage of the disease provides the Chagas' syndromes which are the end result of the destruction of ganglion cells in the central or peripheral nervous system. The lesions may be widespread, but are most severe in the heart, muscles, nervous system, and gastrointestinal tract, particularly the esophagus and colon.

The three stages of the disease, although of one etiology, are clinically and radiologically distinct. The middle latent period is clinically silent; the acute and late stages can be severe and dramatic.