Trypanosoma cruzi is a kinetoplastid, intracellular protozoan parasite that causes American trypanosomiasis, or Chagas disease. Chagas disease occurs rarely in the United States and Mexico but is more common in South America, particularly Brazil. T. cruzi parasites infect many animals, including cats, dogs, and rodents.
T. cruzi parasites are transmitted between animals and to humans by "kissing bugs" (triatomids), which hide in the cracks of loosely constructed houses, feed on the sleeping inhabitants, and pass infectious parasites in the feces; the infectious parasites enter the host through damaged skin or through mucous membranes. At the site of skin entry, there may be a transient, erythematous nodule called a chagoma.
Pathogenesis
T. cruzi has on its surface a homologue of the human complement regulatory protein decay-accelerating factor (DAF). Like human DAF, the parasite homologue is anchored by means of a glycosyl phosphatidylinositol linkage, binds C3b, and inhibits C3 convertase formation and alternative pathway complement activation.
While most intracellular pathogens avoid the toxic contents of lysosomes, T. cruzi actually requires brief exposure to the acidic phagolysosome to stimulate development of amastigotes, the intracellular stage of the parasite.
To gain exposure to lysosomes, T. cruzi trypomastigotes stimulate an increase in the concentration of cytoplasmic calcium in host cells, which promotes fusion of the phagosome and lysosome. In addition to stimulating amastigote development, the low pH of the lysosome activates hemolysins that disrupt the lysosomal membrane, releasing the parasite into the cell cytoplasm.
Parasites reproduce as rounded amastigotes in the cytoplasm of host cells and then develop flagella, burst host cells, enter the bloodstream, and penetrate smooth, skeletal, and heart muscles or infect kissing bugs when the insects take a blood meal.
In acute Chagas disease, which is mild in most individuals, cardiac damage results from direct invasion of myocardial cells by the organisms and from the consequent inflammatory changes. Rarely, acute Chagas disease patients present with high parasitemia, fever, or progressive cardiac dilation and failure, often with generalized lymphadenopathy or splenomegaly.
In chronic Chagas disease, which occurs in 20% of infected patients 5 to 15 years after initial infection, the mechanism of cardiac and digestive tract damage is controversial; it likely results from an immune response induced by T. cruzi parasites, which are still present in small numbers. The striking inflammatory infiltration of the myocardium may be induced by the scant organisms.
Alternatively, parasites may induce an autoimmune response, such that antibodies and T cells that react with parasite proteins cross-react with host myocardial and nerve cells and extracellular proteins such as laminin.
Damage to myocardial cells and to conductance pathways causes a dilated cardiomyopathy and cardiac arrhythmias, whereas damage to the myenteric plexus causes dilated colon (megacolon) and esophagus.
Morphology. In lethal acute myocarditis, the changes are diffusely distributed throughout the heart. Clusters of amastigotes cause swelling of individual myocardial fibers and create intracellular pseudocysts.
There is focal myocardial cell necrosis accompanied by extensive, dense, acute interstitial inflammatory infiltration throughout the myocardium, and there is often four-chamber cardiac dilation.
In chronic Chagas disease, the heart is typically dilated, rounded, and increased in size and weight. Often, there are mural thrombi that, in about half of autopsy cases, have given rise to pulmonary or systemic emboli or infarctions.
On histologic examination, interstitial and perivascular inflammatory infiltration is composed of lymphocytes, plasma cells, and monocytes and is heaviest in the right bundle branch of the cardiac conduction system.
There are scattered foci of myocardial cell necrosis and interstitial fibrosis, especially toward the apex of the left ventricle, which may undergo aneurysmal dilation and thinning.
In the Brazilian endemic foci, as many as half of the patients with lethal carditis also have dilation of the esophagus or colon, apparently related to damage to the intrinsic innervation of these organs. At the late stages, however, when such changes appear, parasites cannot be found within these ganglia. Chronic Chagas cardiomyopathy is often treated by cardiac transplantation.
Synopsis
cardiomyopathy
megacolon
megaesophagus
References
Campbell DA, Westenberger SJ, Sturm NR. The determinants of Chagas disease: connecting parasite and host genetics. Curr Mol Med. 2004 Sep;4(6):549-62. PMID: 15357207
Andrews NW. Lysosome recruitment during host cell invasion by Trypanosoma cruzi. Trends Cell Biol. 1995 Mar;5(3):133-7. PMID: 14732170