Trypanosoma Cruzi and Chagas' Disease: Part 1 Lecture Notes
Key Words and Terms:
Trypanosome, Chagas’ disease, epimastigote, trypomastigote, amastigote, Southern Cone Initiative, Raduviid insects, disease vector, disease of poverty, blood born pathogen, protozoa
Trypanosoma cruzi is a protozoan parasite that causes Chagas’ disease in humans. It belongs to the genus Trypanosoma and the family Trypanosomatidae (along with the Leishmania genus). T. cruzi is also called the American Trypanosome because it is endemic to South and Central America with 16-18 million people currently infected (April 2007). There is another species of Trypanosoma that is called the African Trypanosome that causes African Sleeping Sickness.
Carlos Chagas, while working on Malaria transmission at a rural site in Brazil, first discovered T. cruzi, its insect vector, animal reservoirs, and the living conditions that contribute to transmission of the disease - mud huts infested with Raduviid insects. These insects feed at night on the blood of humans and animals. Chagas dissected some of these insects and found that they carried a large protozoan that appeared in two forms – a long skinny form and a smaller form with a flagellum. He sent some of these insects to Rio de Janeiro and they infected some monkeys and found that it caused an infection and that these parasites could be found circulating in the blood. At the same time, Chagas noticed that blood taken from infected children also contained a large number of parasites.
In the insect the parasite exists as the epimastigote form and lives in the digestive tract. It is shed in the feces in the trypomastigote form and can infect humans by contamination of a wound or a mucosal membrane (eye, nose, mouth, etc.). There are many cell types that can be infected in the host. When the parasite infects a cell, it transforms into the amastigote form. The epimastigote form is susceptible to complement – a part of the host immune system that functions to clear pathogens from the host – and the epimastigote is lysed by the membrane attack complex that is formed by some of the complement proteins. The trypomastigote form is resistant to complement – it isn’t lysed when it enters the host.
The parasite invades a host cell via an active process, which is distinct from phagocytosis. It involves the recruitment of intracellular membranes and eventually the parasite resides in inside a vacuole in the cytoplasm. Subsequently the vacuole is lysed and the parasite is released into the cytoplasm. At this point the parasite undergoes a transformation to the amastigote form and replicates via binary fission. During this time the host cell is still viable and continues to grow and divide – meaning that sometimes when an infected host cell divides, the daughter cell will also be infected with the parasite. The amastigote form undergoes approximately nine divisions, which takes 4-5 days, at which point the amastigotes change back to the trypomastigote form and the cell ruptures, releasing the parasite for another round of infection.
There are two different phases of the disease that are observed. The acute phase is characterized by localized swelling at the site of entry (the eye is very common), fever, enlarged spleen, and seizures and death are possible. Death in the acute phase is usually observed in children and adults that were not exposed to the parasite as a child.
The chronic phase is characterized by immunity from re-infection but the parasite is not cleared by the immune system and symptoms don’t develop until decades after the original infection. In the population that is chronically infected 40% are asymptomatic, 45% have cardiomyopathy – enlargement of the heart, and 11% have megasyndrome – enlargement of the esophagus and/or colon. The largest cause of sudden death in the chronically infected population is due to cardiomyopathy. Another very serious problem is that chronically infected people can transmit the infection through blood transfusions – especially in countries where blood is not screened.
Prevention of Human Infections
Housing improvements and insecticide spraying have proven effective in preventing human infections by controlling the vector. This has been known since the 1940s, but improvements did not occur until much later.
Even though T. cruzi is endemic in the southern United States and persists in a wild cycle (insects to wild animals to insects, etc.), it does not cause human infections because of superior housing. Because there are many different species of insect that are capable of transmitting the parasite and multiple vertebrate reservoirs, T. cruzi will never be eradicated from nature. Chagas’ disease is really a disease of poverty that can be effectively controlled by consistent programs of vector elimination.
The Southern Cone Initiative that was organized by the Pan-American Heath Organization (PAHO) and the World Health Organization (WHO) was started in 1991 and it is focused on vector control as the means of eliminating the transmission of T. cruzi. So far the reduction in the incidence of Chagas’ disease has been pretty dramatic in some countries - in Chile, Uruguay, and Brazil a 99% reduction has been observed. Controlling the transmission of T. cruzi is really a matter of political will and will be accomplished if the correct measures are taken. Even though T. cruzi will never be eliminated from nature, because of the large number of vertebrates that are hosts, Chagas’ disease can be prevented by improved social and economical conditions. The critical issues are effective and sustained surveillance and the development of new drugs that are less toxic that can be used to treat chronically infected populations.