**2. Biology and life cycle of** *T. cruzi*

**1. Introduction**

216 Cardiomyopathies - Types and Treatments

in **Figure 1**.

countries.

The pathogenic protozoan *Trypanosoma cruzi* (*T. cruzi*) is the causative agent of Chagas' disease, and more than 150 species of mammals are affected by this unicellular parasite, including humans. The parasite was discovered in 1909 by the Brazilian physician Carlos Chagas, while dissecting assassin bugs (*Reduviidae*) from the subfamily *Triatominae* that act as vectors and hosts for the parasite, and was later named after Chagas' scientific mentor Oswaldo Cruz [1]. Chagas' disease, also termed American trypanosomiasis, causes the third largest disease burden of the tropics after malaria and schistosomiasis [2] and is responsible for higher morbidity and mortality than any other parasitic infection in America [3]. According to surveys of the World Health Organization (WHO) from 2014, six to seven million people worldwide are estimated to be infected with *T. cruzi*, while around 14,000 patients die annually as a result of the parasitosis. An overview of the geographic distribution of Chagas' disease is presented

The link between poverty and dissemination of Chagas' disease is striking, as it particularly affects people living in simple huts made of mud and wood with roofs of straw or palm leaves in rural areas of Latin America, where the predatory bugs have easy access. In the most important endemic areas, vectors include *Panstrongylus megistus, Triatoma infestans, T. dimidiata, T. pallidipennis*, and *Rhodnius prolixus* [4] (**Figure 2**). Non-vectorial transmission, such as the ingestion of *T. cruzi*-contaminated food and congenital transmission from the mother to the fetus [5] as well as blood transfusion and organ transplantation, increase the number of people at risk, estimated at 100 million worldwide. Owing to international migration, isolated

cases of Chagas' disease in nonendemic countries are increasingly being recognized.

**Figure 1.** Geographical distribution of Chagas' disease. Dark blue indicates endemic countries and light blue nonendemic

Assassin bugs infected with *T. cruzi* preferably sting sleeping victims and usually suck their blood unnoticed. After the blood meal, the pressure in the bug's gastrointestinal tract increases and the insect defecates on the skin near the wound. This behavior of *Triatominae* is crucial for their ability to act as a vector for *T. cruzi*, since infective stages of *T. cruzi* reach the stab wound only when the bugs defecate during food intake. The assassin bug transmits the parasites to the definitive host, by spreading excrement on the wound while escaping. When the pathogencontaining feces are rubbed into the fresh puncture wound by the victim or when the pathogen penetrates into uninjured mucosa, especially those of the eye, highly infectious and very motile metacyclic trypomastigotes of *T. cruzi* are transmitted into the blood flow of the host [6, 7] (**Figure 3**). The trypomastigotes are then disseminated successively into the organism of the host, and preferably infect cells of the reticuloendothelial and mononuclear phagocytic system [8]. A parasitophorous vacuole is formed only briefly during the life cycle of *T. cruzi*, while the intracellular parasites multiply in the cytoplasm of the host cell by binary division [9, 10].

*T. cruzi* can infect any nucleated cell but predominantly replicates in cardiac muscle cells as well as in cells of the nervous system, gonads, intestinal mucosa, and placenta [11]. After penetration into the cytoplasm of the host cell, the morphology of the metacyclic trypomastigotes

**Figure 3.** *Trypanosoma cruzi* metacyclic trypomastigotes on a peripheral blood smear shown by Giemsa staining.

changes to intracellular amastigotes with diameters of 3–5 µm, when they lose their undulating membrane which is a characteristic feature of mobile trypomastigotes [9, 12] (**Figure 4**). Intracellular amastigotes undergo several rounds of division and are then transformed into trypomastigotes, approximately 20-µm long, which leave the host cell and spread further into the organism to infect new host cells [13]. Unlike the African sleeping sickness caused by *T. brucei*, intracellular replication of *T. cruzi* in host cells is mandatory, since the pathogenic agent of American trypanosomiasis is not able to divide in the blood. For this reason, the intracellular amastigote form of *T. cruzi* is always present and can be histopathologically detected in tissue samples from spleen, liver, brain, and heart muscle. The life cycle of *T. cruzi* continues when the bug takes a blood meal from an infected host, and the parasites transform in the

**Figure 4.** Intracytoplasmic localization of *T. cruzi* amastigotes in cultured fibroblasts stained with Giemsa at low (left) and high (right) magnification. Arrows mark intracellular amastigotes, and the arrow head (left) indicates an extracellular trypomastigote.

bug´s midgut to epimastigote forms and multiply by binary fission. Finally, the highly infectious metacyclic trypomastigotes develop in the rectum of the bug, and will be passed again with the feces during a subsequent second blood meal [14].
