Basic info Trypanosoma cruzi
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protozoan parasite (unicellular eukaryotic organism)
causative agent of Chagas disease, which is common in Central and South America
Class: Kinetoplastida characterized by the presence of a kinetoplast
What are the three life stages of T. cruzi
Epimastigote stage Multiplies in the insects midgut
Amastigote stage Multiplies intracellularly in vertebrate host cells Trypomastigote stage Extracellular, non-replicative form, circulates throughout the body and infects host cells
What does the choosing of the model depent on?
the host strain
the parasite strain
the route of inoculation
the size of the inoculum
What animals have been used to investigate T. cruzi?
Mice
hamster
dogs
rats
rabbits
monkeys
What parasites have been used to investigate T. cruzi?
Y: isolated from a human acute phase
CL: isolated from a reduviid bug
Ernane: isolated from a patient with cardiac form and megaesophagus
Benedito: isolated through xenodiagnosis
Vicentina: isolated through xenodiagnosis from a patient with the chronic cardiac form
What charateristics would the ideal model for Chagas disease have?
survive the acute phase of infection
support a long lasting subclinical parasitemia which can be detected by xenodiagnoses and/or hemoculture and serology develop the cardiac and digestive forms of the disease with typical histopathologic lesions
develop the disease in a manner which is more or less independent of the age and sex of the infected animal
be available at a reasonable cost
What mouse strains are used for Chagas disease?
◦ C57BL/6, C57BL/10: relatively resistant
◦ C3H: susceptible
◦ BALB/c: intermediate
◦ Nude mice: highly susceptible (immunodeficient)
What three phases of the infection in Chagas disease are observed?
Acute phase: high parasitemia, acute myocarditis
Intermediate phase with no heart inflammation
Five month after infection: chronic heart inflammation
What are the most common inoculation routes?
-Intraperitoneal
-conjunctival
-subcutaneous
-oral
How is inoculation archived?
-Through blood trypomastigote (mouse) --> higher parasitemia
- metacyclic trypomastigote (bug)
What are key parameters to monitor infection?
Determination of mortality
Determination of parasitemia
Determination of tissue parasitism
Determination of pathology
Determination of immune responses
Determination of parasitemia in the chronic phase?
Xenodiagnosis
Hemoculture
How to determine the liver pathology?
AST (Aspartate transminase)
ALT (Alanine transaminase)
What are ways to study in vitro?
Studying the killing of parasites by macrophages