Trypanosoma cruzi

Trypanosoma cruzi is a parasitic kinetoplastid protozoan and the cause of Chagas disease. Like other trypanosomes, it bores into host tissues and feeds mainly on blood, also consuming lymph. This feeding behavior can lead to disease—Chagas disease and sleeping sickness in humans, dourine and surra in horses, and a brucellosis-like illness in cattle. The parasite requires a host body and is primarily transmitted by haematophagous triatomine insects, known as assassin bugs, cone-nose bugs, or kissing bugs. These bugs shelter in the nests of vertebrate animals, where they bite and feed on blood. When a triatomine infected with protozoa from prior animal contact takes a blood meal, it deposits feces containing the parasite on the host’s skin. Scratching the bite area then helps the infected feces penetrate the skin.

The species name *cruzi* honors Brazilian scientist Oswaldo Cruz, who was the teacher of the parasite’s discoverer, Carlos Chagas.

The life cycle begins in an animal reservoir, usually wild or domestic mammals, including humans. A triatomine bug acts as the vector. While feeding on an infected host, it ingests *T. cruzi*. Inside the bug—the main species transmitting the parasite to humans is *Triatoma infestans*—the parasite becomes an epimastigote, which can reproduce by binary fission. These epimastigotes then move to the rectal cell wall of the bug, where they become infectious metacyclic trypomastigotes. When the bug takes another blood meal, it defecates, releasing these infectious stages. According to Trumper and Gorla (1991), transmission success depends heavily on the bug’s defecation behavior. Alternatively, infection can occur through oral ingestion of parasites, often due to inadequate disinfection of contaminated food in human cases.

The trypomastigotes in the feces use their flagella—a swimming tail typical of euglenoid protists—to swim into host cells. They enter through the bite wound or across mucous membranes. Host cells have surface macromolecules such as laminin, thrombospondin, heparin sulphate, and fibronectin, which are essential for adhesion and invasion. The trypomastigotes must cross a network of proteins lining the host cell exterior to make contact and invade. Molecules and proteins on the host cell’s cytoskeleton also bind to the parasite’s surface, initiating invasion.

*T. cruzi* has three major morphological forms: epimastigote, trypomastigote, and amastigote. The epimastigote develops and multiplies in the triatomine’s midgut; it is elongated and flagellated, dividing by binary fission. Toward the end of the insect phase, epimastigotes migrate to the hindgut and become metacyclic trypomastigotes, the infective, non-dividing form excreted in feces. After entering a mammalian host, metacyclic trypomastigotes invade cells and transform into amastigotes—intracellular, rounded forms with a short flagellum that multiply in the cytoplasm by binary fission. After several replication cycles, they differentiate into cell-derived trypomastigotes (bloodstream trypomastigotes), which are released when the host cell ruptures. These circulate in the blood, infecting new cells or being ingested by another triatomine, where they revert to epimastigotes, completing the cycle.

In human trypanosomiasis, the parasite develops into trypomastigotes in the blood and amastigotes in tissues. As infection progresses, the number of infected cells and the number of amastigotes per infected cell (APC) increase. An APC near one indicates a recent infection; a higher APC means amastigotes have begun replicating. The acute form is often unnoticed but may cause localized swelling at the entry site, elevated parasitism, myocarditis, and changes in myocardial gene expression. The chronic form can appear 30 to 40 years later, affecting the heart, esophagus, colon, and peripheral nervous system. Affected people may die from heart failure and severe heart lesions. Acute cases are treated with nifurtimox and benznidazole, but no effective therapy for chronic cases is known.

Cardiac manifestations follow processes common to all cardiomyopathies: first an inflammatory response, then cellular damage, and finally fibrosis as the body attempts repair. Another cardiomyopathy in nearly all chronic Chagas disease cases is thromboembolic syndrome—thrombosis (clot formation) and its complication, embolism (clot blockage of a distal vessel). This contributes to death through arrhythmias.