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Overview:American trypanosomiasis, or Chagas' disease (named after Carlos Chagas who discovered the infectious agent in the early 1900's (Fig. 1), is the most common cause of congestive heart failure in the world. This condition results from infection with Trypanosoma cruzi and is endemic to rural South and Central America (Fig. 2 and (Fig. 3). The infection leads to cardiac disease including CHF, heart block, and arrhythmia. Also, illness of the autonomic ganglia of the gastrointestinal tract is another frequent finding of T. cruzi infection, leading to megacolon and megaesophagus.
Life cycle: Humans are merely unfortunate hosts whose involvement in the cycle of transmission is not necessary for the perpetuation of the parasite in nature. T. cruzi (seen by EM in Fig. 4) is transmitted by various species of bloodsucking reduviid insects, or kissing bugs. The kissing bug (Fig. 5 and Fig. 6) is a large 2-3 cm winged insect that takes up residence in the cracks and holes of primitive wood, mud, and stone houses. Vector transmission in humans occurs only in areas where reduviid species that defecate during or immediately after blood meals are present. These vectors are found in large numbers in the wild, where the parasite is transmitted among many mammalian species (more than 150 species identified) that constitute the parasite's natural reservoir. The insects become infected by sucking blood from an infected animal that has circulating trypomastigotes (Fig. 7). The ingested parasites multiply in the midgut of the insects as epimasigotes that are discharged with the feces at the time of subsequent blood meals. Transmission to a second vertebrate host occurs when mucous membranes, conjunctiva, or breaks in the skin are contaminated with bug feces containing the infective parasite. These epimastigotes then multiple in the cytoplasm after they transform into amastigotes (seen in heart muscle Fig. 8). Cell rupture and release into the circulation occurs as the amastigotes mature into trypomastigotes (life cycle, Fig. 9).
Epidemiology: Worldwide, 16-18 million people are infected with T. Cruzi and up to 50,000 persons die each year of Chagas disease. In some small villages in Brazil (Fig. 10), chagasic cardiac disease was found to be the leading cause of death in adults. The mean age of infection is thought to be around 4 years of age. Although 50-100,000 T. cruzi infected immigrants may reside in the United States, only four cases of Chagas' disease have been reported where the patient was infected in this country. In California blood banks, it was found that 1:500-1000 Hispanic donors were infected. It was also found that by screening out donors from this population the blood supply was only decreased 2%.
Acute infection: The first signs of illness occur at least 1 week after invasion by the parasites. The inflammatory lesion caused by T. cruzi at the site of entry is called a chagoma. Local histologic changes include intracellular parasitism of muscle, interstitial edema, lymphocytic infiltration, and reactive hyperplasia of adjacent lymph nodes. Romana sign (unilateral periorbital edema) is the classic sign of acute Chagas' disease. It consists of painless edema of the palpebrae and periocular tissues. This sign follows fever, malaise, anorexia, and edema of the face and lower extremities. Trypomastigotes released when host cells rupture often can be detected by microscopic examination of fresh blood.
Chronic Chagas' disease: The classical onset of symptoms in chronic Chagas occurs about 35-45 years after the primary infection. Heart failure is the most common feature. Bilateral ventricular enlargement, often involving the right heart more than the left. Thinning of the ventricular walls is common, as are apical aneurysms and mural thrombi. Pathological changes are also common in the conduction system of chronic chagasic hearts and often correlates with rhythm disturbances.
Diagnosis: The diagnosis of the acute disease is made by detecting parasites in fresh blood, and serologic tests for anti-T. cruzi IgM. The diagnosis of the chronic form is by detecting IgG antibodies that bind specifically to parasite antigens. Several sensitive serologic tests are used widely in Latin America. These tests often show cross-reactivity with illnesses such as malaria, leishmaniasis, and syphilis among others. In the United States samples can be sent to the CDC or to Gull Laboratories in SLC, Utah which has been approved by the FDA for clinical testing. PCR-based tests are currently under development.
Treatment: Unfortunately, T. cruzi is not generally susceptible to most of the long list of drugs tested for activity over the past several decades. Nitrofurtimox is the only drug available in the U.S. for therapy of Chagas. It markedly reduces the duration, severity, and mortality of the illness. However, parasitologic cure results in only about 50% of treated patients. Nifurtimox should be administered if the disease has not previously been treated and may be used as a prophylaxis if there is a high likelihood of recurrence such as following immunosuppressive therapy. Benznidazole is a second agent that has undergone trials in Latin America. It is not available in the United States, but physicians should be aware of it as an alternate agent for patients who do not tolerate Nifurtimox. Chronically infected individuals should have EKGs done periodically as complete heart block can be benifited by a pacemaker.
