TRYPANOSOMA CRUZI

General Concepts

Classification

Trypanosoma cruzi, the causative agent of Chagas’ disease or American trypanosomiasis, is classified in the domain Eukarya, kingdom Protista, Phylum Sarcomastigophora, subphylum Zoomastigophora, Class Zoomastogophorea. As a member of this subphylum and class they are animal-like (or non-photosynthetic) flagellates that locomote using whiplike flagella, and feed by pinocytosis or phagocytosis.  Trypansosoma spp. (and Leishmania spp.) is placed in the Order Kinetoplastida, Family Trypanosomatidae, that is, they have a single flagellum (free or attached by means of an undulating membrane), and a kinetoplast--- a self-replicating DNA-containing organelle connected to the mitochondrion. Because at some time in the life cycle trypanosomes invade the blood they are commonly referred to as hemoflagellates

Life Cycle and Transmission

Metacyclic trypomastigotes in the reduviid bug’s feces enter the skin at the site of the bite or through contaminated mucous membranes. There is local multiplication in the tissues in the form of amastigotes; these differentiate into trypomastigotes, which are released from the ruptured cell, circulate in the blood stream, and may penetrate many different kinds of cells where they differentiate into dividing amastigotes. Reduviid bugs become infected by ingesting trypomastigotes during blood feeding. These develop into epimastigotes, which multiply in the hindgut, and then they differentiate into metacyclic trypomastigotes, which are deposited in the bug’s feces.

Pathogenesis

Acute disease is common in children below the age of 10. Infections in this age group may have minimal symptoms, but may manifest many years later as chronic disease. When older children or adults acquire the infection the acute disease is more severe. Romana’s sign (unilateral periorbital edema) represents local multiplication of parasites rubbed into the conjunctiva. Parasites introduced into the bite wound by contamination may develop into a local inflammatory lesion called a chagoma. This is followed by trypomastigotes in the blood, fever, hepatosplenomegaly, and myocarditis. Chronic Chagas’ disease nay develop many years after the initial infection and is characterized by cardiomyopathy with congestive heart failure, arrhythmias, as well as mega-syndrome--- impaired function and dilation of the esophagus or colon.

Diagnosis

Examination of blood smears during the acute disease usually shows trypomastigotes. Recovery of flagellates is enhanced by examination of the buffy coat after centrifugation of blood.  PCR of kDNA may also be used. Xenodiagnosis is performed by having” clean” i.e. uninfected bugs bite the patient and examination one month later of the bug’s gut contents or feces for flagellates. In chronic infection serologic tests are most useful.

Epidemiology

Chagas’ disease exists only in the Americas and is mainly a disease of countries with substandard housing with dirt floors, mud walls and thatched roofs that allows infection with the reduviid vectors. It occurs principally in Mexico, Central and South America with isolated cases in Texas and California.

Control

Transmission control of vectors can be effected by use of insecticides and construction of bug-proof houses, and serologic screening and treatment of blood can prevent post-transfusion infections.

Treatment

There is no completely effective treatment for Chagas’ disease. Nifurtimox and benznidazole may control the parasitemias in the acute phase of the disease, but long-term follow-up of treated patients often reveals positive xenodiagnostic tests. Treatment of chronic complications such as cardimyopathy and megasyndrome is symptomatic.

Immunity

Antibodies generated in the acute phase may help to control the infection but they do not clear the parasites, which remain hidden from the immune response within muscle cells. The host immune response may result in the production of autoantibodies cross-reacting with parasites and host tissues leading to organ dysfunction.