Background
American trypanosomiasis, also known as Chagas disease, affects millions of people throughout the Americas. [1] Carlos Chagas first described this disease in 1911 when he discovered the parasite in the blood of a Brazilian child with fever, lymphadenopathy, and anemia. [2] Trypanosoma cruzi, a protozoan hemoflagellate, is the parasite that causes this disease. When humans are infected, the parasite can cause acute illness; however, the infection is generally asymptomatic. In some cases, usually many years after initial infection, the affected individual can have clinical signs and symptoms from damage to the heart or GI tract. The disease is the leading cause of non-ischemic congestive heart failure worldwide and notably in Latin America where it is endemic.
A rare form of trypanosomiasis, caused by Trypanosoma lewisi, has been reported in 8 individuals. [3]
This review does not include discussion of African trypanosomiasis (sleeping sickness) because that disease in infants and children is indistinguishable from disease in adults. For information, see African Trypanosomiasis (Sleeping Sickness).
Pathophysiology
When T cruzi enters the human host, it produces an acute local inflammatory reaction and a nodular swelling or chagoma can develop at the site of entry. This area becomes infiltrated with macrophages surrounded by lymphocytes, eosinophils, and polymorphonuclear neutrophils. Lymphatic spread then carries the organism to regional lymph nodes. When the histiocytes or other inflammatory cells ingest the parasites, they transform into amastigotes. In the amastigote form, parasites can multiply in the cells of virtually every organ and tissue.
After local multiplication, the organisms can assume the trypomastigote form and invade the bloodstream, carrying the infection to all parts of the body. Cells of the reticuloendothelial system; cardiac, skeletal, and smooth muscles; and neural cells are preferentially parasitized. A marked host inflammatory reaction characterized by local accumulation of polymorphonuclear leukocytes, lymphocytes, and plasma cells is associated with these areas of cellular destruction.
During the acute phase of illness, the parasite is believed to directly destroy host cells. The pathogenesis of the cardiac and GI alterations typical of the chronic phase is not as well characterized. One theory suggests that ganglionic neurons and nerve fibers are lost. Another theory implicates the inflammatory reaction from an allergic response to parasitic antigens. Yet another theory points to an autoimmune mechanism, as suggested by the findings of monoclonal antibodies with cross-reactivity between T cruzi and mammalian nervous tissue. [4]
In the acute phase, the heart is the main target organ. The severity of the acute infection widely varies, ranging from asymptomatic infection to severe tissue destruction. In all cases, the parasites have successfully entered various cells of the body and formed pseudocysts, each containing hundreds to thousands of amastigotes. Persons who recover from the acute illness carry these intracellular parasites for the remainder of their lives. The myocardium develops focal myonecrosis, contraction band necrosis, interstitial fibrosis, and lymphocytic infiltration. Interspersed among the degenerating fibers is a marked mixed inflammatory cell exudate, which becomes primarily mononuclear with time.
During the chronic phase, the ganglion cells are progressively destroyed; the affected organs widely vary in their tolerance to denervation. The myocardium often has diffuse fibrosis, with a small number of mononuclear cells scattered throughout. Cardiac function becomes compromised when approximately 20% of the neurons are destroyed, whereas esophageal function remains normal even when 80% of the neurons are nonfunctioning.
Early in the chronic stage of infection, the heart size may be normal or only slightly enlarged, although massive enlargement can occur later. The heart becomes dilated, with a thin muscular wall, especially in the right atrium. In more than one half of cases, an aneurysm is present at the apex of the left ventricle, which rarely ruptures. This is pathognomonic of chronic chagasic cardiopathy. Mural thrombosis develops in the right atrium, left atrium, and left ventricle, especially in the presence of atrial fibrillation. This mural thrombus increases the risk of embolization, especially to the brain, lungs, spleen, and kidneys. The right bundle branch is the most damaged part of the system and alterations in the atrioventricular conduction system are frequent.
In the GI system, the 2 principal organs affected are the esophagus and colon. Damage to the autonomic nervous system of the heart parallels that of the Auerbach plexus in the walls of the digestive tract. Abnormalities of secretion, absorption, and motility are present. Denervation and fibrosis occurs in the submucosal (Meissner) and myenteric (Auerbach) plexuses. Dysfunction of peristalsis may lead to arrest of transit, extreme dilatation, and hypertrophy.
Epidemiology
United States statistics
Endemic trypanosomiasis is extremely rare but has been reported in Texas [5] , Oklahoma, Tennessee, Louisiana, and California. [6] Only 7 cases acquired in the United States have been reported since 1955. [7, 8] However, as many as 5% of immigrants in Washington DC were found to carry trypanosomes and potentially 300,000 immigrants are thought to be infected. [9] Based upon seroprevalence data from immigrants living in the United States, as many as 166-638 cases of congenital infection [10, 11] and 45,000 cases of cardiomyopathy annually could occur [9] .
Transfusion-related cases, although rare, are increasingly recognized. Imported disease in a traveler has been reported. [12]
Small mammals in the southern and southwestern United States can harbor T cruzi. Infected Triatoma protracta (an insect in the family Reduviidae, known as the western bloodsucking conenose) have been found in California, Arizona, and New Mexico. T rubida has been found in Arizona. [13, 14, 15] Triatoma sanguisuga (“kissing bug”), a vector that can transmit T cruzi, has been reported as far north as Delaware. [16]
International statistics
The World Health Organization (WHO) has estimated that approximately 16-18 million people are infected. The incidence has been estimated at 200,000 cases per year. The disease is limited to the Western Hemisphere, in temperate, subtropical, and tropical regions. It is prevalent in Mexico [17, 18] , Central America, and South America. [19] Human disease is most prevalent in Brazil, Argentina, and Venezuela. [20] Approximately 90 million, comparable to 25% of people in Latin America live in an area with endemic disease and are at risk of acquiring the infection. As reported in the United States, congenital infection in nonendemic regions is increasing. [21]
Race-, sex-, and age-related demographics
No racial predilection is observed.
No gender predilection has been reported.
This disease occurs in people of all ages. The most severe form occurs in children younger than 5 years old, in whom CNS involvement may predominate.
Prognosis
The prognosis depends on the clinical stage and the complications that develop.
The acute phase is most serious in children younger than 2 years, and the disease is almost always fatal if heart failure or meningoencephalitis develops. Right bundle branch block (RBBB) is an ominous sign in the acute phase.
In chronic disease with pronounced cardiac manifestations, the prognosis is poor. Death usually occurs within 5 years as a result of heart failure or pulmonary embolism.
The prognosis with the GI symptoms of the illness is generally good.
Morbidity/mortality
The overall mortality during the acute phase of Chagas disease is 5%. Annually, more than 70,000 people die from this disease. The disease is the leading cause of congestive heart failure in areas of Latin America where it is endemic. In these areas, Chagas disease is responsible for 25% of all deaths in persons aged 25-44 years. By far, the most common cause of death is cardiac abnormalities. The 5-year mortality rate in those patients with chronic Chagas disease and cardiac dysfunction is reportedly greater than 50%. In infants and children younger than 5 years, the mortality rate is increased because of their predilection for CNS involvement.
The relative prevalence of cardiac lesions versus mega disease among persons with chronic infection widely varies by location. In Brazil, GI involvement is as likely as cardiac alterations in persons with chronic infection. In contrast, neither megacolon nor megaesophagus has been associated with chronic trypanosomiasis infection in Colombia, Venezuela, Central America, or Mexico.
Complications
Complications are as follows:
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Congestive heart failure
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Myocarditis
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Dysrhythmias
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Sudden death
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Meningoencephalitis
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Megaesophagus: Esophagitis and esophageal cancer are the most common complications of megaesophagus.
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Megacolon: Fecaloma and volvulus of redundant sigmoid complicate megacolon. Fecaloma-associated stercoral ulceration, overflow incontinence, and ischemic colitis have been described.
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Embolic events (eg, cardioembolic stroke, small bowel infarction, splenic infarcts, kidney infarcts): Stroke has been found to be more frequent in patients with chagasic cardiomyopathy (15%) compared with other cardiomyopathies (6.3%).
