Trypanosoma cruzi

Overview: Trypanosoma cruzi is an intracellular protozoan that causes Chagas' disease or trypanosomiasis, a very serious problem in South and Central America (Figure 1). T. cruzi is transmitted to humans and various mammalian hosts by hematophagous reduviid bugs when T. cruzi trypomastigotes present in the insect's feces enter the human host through breaks in the skin (the insect bite) or mucous membranes and subsequently infect macrophages and other human cells. Chagas’ disease is potentially fatal in humans and widely prevalent in animals, both wild and domestic. Currently 16 to 18 million people are infected with the disease.


Figure 1. Trypanosoma cruzi trypomastigote in blood smear.

Morphology: T. cruzi is a single-celled organism that exists in three distinct forms, namely, the infectious trypomastigote found in the bloodstream, the intracellular amastigote found in tissues, and the reproductive epimastigote found in the reduviid insect. Each form has the same basic morphological characteristics, with slight variations in physiology. Each cell contains a nucleus containing its genetic material, and a single tubular mitochondrion, which houses its own DNA, cristae, and enzymes, located within the kinetoplast. The kinetoplast is a distinguishing features of this group of species and is composed of a fibrous network of DNA comprising 25% of the parasite's total DNA. In the trypomastigote stage, the kinetoplast is basket-shaped due to an odd arrangement of DNA loops, while in amastigotes it is rod-shaped. Infectious trypomastigotes found in blood grow to approximately 20 mm (millimetres) long and are very slender with a thin, irregular shaped outer membrane and central nucleus. The flagellum stems from the kinetoplast, which is located toward the posterior of the cell, and runs through the remainder of the organism to the flagellar pocket compartment before emerging from the cell. When viewed under light microscopy, trypomastigotes are usually seen in a ‘C’ or ‘U’ shape. The reproductive epimastigote stage is similar to the trypomastigote, but the kinetoplast is located anterior to the nucleus. In the intracellular amastigote stage, however, the cells are round instead of elongated, and the flagellum is almost unapparent.

Life Cycle and Pathogenicity: The life cycle of T. cruzi begins in an animal reservoir, usually mammalian, either wild or domestic, and includes humans. The vector of transmission is the reduviid bug, or assassin bug (Figure 2). While feeding on a host, the T. cruzi-infected bug defecates, discharging infective trypomastigotes in the feces. The trypomastigotes enter the bite wound, mucous membranes, or conjunctivae and infect a wide variety of cells. An indurated inflammatory lesion (chagoma) often appears at the site of the bit and parasite entry. Within host cells the trypomastigotes transform into amastigotes, replicating until the host cells rupture to release additional parasites. Trypomastigotes in the circulation can be ingested by reduviid bugs during a blood meal, thereby continuing the parasite life cycle. The life cycle of T. cruzi is summarized in Figure 3.

Figure 2. Triatoma infestans or the “Kissing Bug”, “Assassin Bug”, or “Cone-Nose Bug”, is a vector for Chagas' disease. 

Figure 3. This illustration depicts the life cycle of Trypanosoma cruziClick to enlarge.

Clinical Infection: Chagas' disease can also be transmitted by blood transfusion because of the stages in the bloodstream. Early in the disease, heavy infection of the cardiac muscle occasionally cause acute heart failure and sudden cardiac death (Figure 4). The pathogenesis of chronic Chagas' disease is not well understood, but myocardial inflammation, fibrosis, and atrophy can develop with few or no detectable parasites. In some patients, focal inflammation and destruction of the myenteric nerve plexus of the gut result in loss of peristalsis and enormous dilation of the esophagus or colon. Since T. cruzi antigens are processed via the endogenous antigen-presentation pathway involving MHC class I molecules (like viruses), a strong cytotoxic CD8+ response to infection is required to absolve an infected host from disease.

Figure 4. Trypanosoma cruzi in monkey heart. 

The acute phase of T. cruzi infection may result in a mild fever and swelling at the entry site, but often infection and the subsequent latency period are asymptomatic. Chronic infection can go unnoticed for decades and approximately 30% of those infected will suffer life threatening complications. T. cruzi goes to great lengths to avoid its host’s immune response, producing a protein called parasite-derived neurotrophic factor (PDNF) that activates anti-apoptotic molecules within infected cells. Chronic symptoms include megacolon, megaesophagus, conduction abnormalities (damaged nerves in the heart), epicardial lesions (reaction to chronic inflammation of the heart), cardiac manifestations (fibrosis of damaged cardiac tissue), and sudden death by heart failure.

Treatment: There are two approaches to treating Chagas' disease, namely, antiparasitic treatment, to kill the parasite and symptomatic treatment, to manage the symptoms and signs of infection. Antiparasitic treatment is most effective early in the course of infection, but is not limited to cases in the acute phase. Drugs of choice include azole or nitro derivatives such as benznidazole or nifurtimox. Both agents are limited in their capacity to effect parasitologic cure (a complete elimination of T. cruzi from the body), especially in chronically infected patients, and resistance to these drugs has been reported. Studies suggest that antiparasitic treatment leads to parasitological cure in about 60-85% of adults and more than 90% of infants treated in the first year of acute phase Chagas disease. Children (age 6 to 12 years) with chronic disease have a cure rate of about 60% with benznidazole. While the rate of cure declines the longer an adult has been infected with Chagas' disease, treatment with benznidazole has been shown to slow the onset of heart disease in adults with chronic Chagas infections.


Guedes, P. M., & Silva, J. S. (2009). The role of parasite persistence in pathogenesis of Chagas’ Heart Disease. Parasite Immunology, 31: 673-685. 

Hunter, C. A., Slifer, T., Kanaly, S., Fort, M, & Rennick, D. (1997). IL-10 is required to prevent immune hyperactivity during infection with Trypanosoma cruzi. The Journal of Immunology, 158: 3311-3316.

Pier, G.B., Lyczak, J.B., & Wetzler, L.M. (2004). Immunology, Infection, and Immunity. Washington: ASM Press.