Trypanosomes are single-celled protozoan parasites that have an amazingly wide distribution in nature. They are found in both cold- and warmblooded vertebrates, and also in many invertebrate species that often act as vectors. Broadly stated, if an animal has blood, it is likely to be a host for these creatures. Trypanosomes were first observed in 1841 by Gabriel Valentin who saw the motile organisms while examining the blood of a trout under a microscope. Similar organisms were seen in the blood of a toad 2 years later by David Gruby, who provided an elegant description of their undulating membranes. Trypanosomes were first noted in mammals in 1878 by Timothy Lewis, who saw them while examining blood from rats. Shortly thereafter, Griffith Evans, a veterinarian working in the Punjab, observed trypanosomes in the blood of horses, mules and camels that were affected with an often fatal febrile illness called 'surra'. Evans demonstrated the relationship between the try-panosomes and surra by passing the infection from a sick animal to a previously healthy dog and horse and observing the development of the disease (Paredes-Espinoza and Paredes-Casillas, 1996).
Towards the end of the nineteenth century, major observations relating to trypanosomes were made in Africa. In 1894, David Bruce concluded that the trypanosomes he saw in the blood of animals afflicted with a disease called 'nagana' were the cause of that illness. Nagana had been a major killer of cattle and horses since early colonial times, and the parasite he observed was later designated Trypanosoma brucei. Bruce also established that the 'tsetse disease' that had been a persistent problem in domestic animals during the colonial period was caused by the same organism. It fell to Robert Koch (1906) to propose that T. brucei was cycling through tsetse flies and in this way was transmitted from one mammalian host to another (Duggan, 1970).
The first human trypanosome infection noted was in an English boat captain who was travelling up the Gambia River shortly after the turn of the century. An alert physician searching the patient's blood for Plasmodium encountered trypanosomes, which were later designated Trypanosoma gambiense by J. Everett Dutton, who reported the case after the patient's death. A second case was reported by Patrick Manson shortly thereafter, and within a few years it was suggested by Maxwell Adams and confirmed by cerebrospinal fluid studies by Aldo Castellani that sleeping sickness, which had killed hundreds of thousands of people in epidemics in many areas of Africa, was also caused by trypano-somes.
Principles and Practice of Clinical Parasitology
Edited by Stephen Gillespie and Richard D. Pearson © 2001 John Wiley & Sons Ltd
The history of the discovery of Trypanosoma cruzi and its role as the cause of Chagas' disease was quite different in that one person, the Brazilian physician Carlos Chagas, discovered the organism, vector, domestic and sylvatic reservoirs, and described the clinical manifestations of the disease in humans. In 1908 Chagas was sent as a public health official to the interior of the Brazilian state of Minas Gerais to control malaria among railroad construction workers. At that time he already was familiar with trypanosomes, having previously discovered, in a monkey, an organism he called Trypanosoma minasense. Local residents of the area in which Chagas was working pointed out some blood-sucking bugs that Chagas thought were the species Conorhinus megistus. When he examined their intestinal contents in his makeshift laboratory, he encountered flagellated organisms. He then sent infected insects to Oswaldo Cruz, his mentor and employer in Rio de Janeiro, who succeeded in passing the infection from the insects to monkeys. The trypanosomes observed in the blood of the infected monkeys had a morphology distinct from T. minasense. Shortly thereafter, Chagas established that this new trypanosome, which he called Trypanosoma cruzi in honor of his mentor, could be passed experimentally to dogs, cats and rabbits, and also that it could be grown on blood agar. With this knowledge of the infectivity of T. cruzi in hand, Chagas soon set out to find the parasite in mammals in the community in which he was working. He soon found trypa-nosomes in a cat, and shortly thereafter found similar organisms in the blood of a 2 year-old febrile child. In 1910, at the age of 29, in recognition of his discovery of the new disease, he was made an 'Extraordinary Tenured Member of the Brazilian National Academy of Medicine'. In subsequent work, spanning many years, Chagas described other natural mammalian reservoirs, most notably the armadillo, Dasypus novemcintus, and other species of triatomine vectors. He also described in detail the clinical syndromes of acute and chronic Chagas' disease, and published his findings in prestigious medical journals in Portuguese, English, French and German (Prata, 1981; Chagas, 1909, 1916).
Trypanosoma cruzi belongs to the genus Trypa-nosoma, which consists of approximately 20 species of protozoans. Only T. cruzi and two African trypanosome subspecies, T. brucei gam-biense and T. brucei rhodesiense, cause disease in humans (Levine et al., 1980). Broadly defined, the organisms in this genus are protozoan flagellates that belong to the family Trypanoso-matidae, order Kinetoplastida, that pass through different morphologic stages (tryptomastigote, amastigote and epimastigote) in their invertebrate and vertebrate hosts. The order Kinetoplastida is characterized by an organelle called the kinetoplast that is located in each cell's single, large mitochondrion. The kinetoplast contains many thousands of circular DNAs called minicircles and maxicircles, which play roles in the synthesis of mitochondrial proteins (see p. 346).
T. cruzi has a complex life-cycle involving insect vectors as well as mammalian hosts (Figure 14b.1). The vectors, often called triatomines or kissing bugs (Figure 14b.2), become infected when they ingest blood from mammals that have circulating trypomastigotes, which are non-dividing but infective forms of the parasite (Figure 14b.3). Once inside the midgut of a triatomine host, the parasites differentiate into epimastigotes, which are flagellates having a distinct morphology, and these organisms then multiply extracellularly. After migration to the hindgut, epimastigotes become non-dividing metacyclic trypomastigotes which are then discharged with the feces around the time of a subsequent blood meal. Transmission to a second mammalian host occurs when mucous membranes, breaks in the skin, or conjunctivas are contaminated with insect feces containing infective metacyclic forms. Once inside the new host, these parasites enter a variety of host cell types and, after differentiating into amastigotes, multiply intracellularly. When proliferating amasti-gotes fill the host cell, they differentiate into
trypomastigotes, which are released as the cell ruptures. The parasites released invade adjacent tissues and spread via the bloodstream and lymphatics to distant sites where they initiate further cycles of intracellular multiplication. By cycling asynchronously in this manner they maintain a parasitemia infective for vectors. T. cruzi can also be transmitted by transfusion of blood donated by infected persons (Schmunis, 1991), in laboratory accidents (Herwaldt, 2000)
and from mother to fetus (Bettencourt, 1976; Freilij and Altcheh, 1995).
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