Trypanosomiasis 

Updated: Mar 16, 2016
Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Russell W Steele, MD 

Overview

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

Frequency

United States

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]

International

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[16, 17] , Central America, and South America.[18] Human disease is most prevalent in Brazil, Argentina, and Venezuela.[19] 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.[20]

Mortality/Morbidity

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.

Race

No racial predilection is observed.

Sex

No gender predilection has been reported.

Age

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.

 

Presentation

History

The early phase of trypanosomiasis is typically asymptomatic, as only about one-third of patients have symptoms of acute Chagas disease. A minority of patients have severe clinical disease. About 10% of patients die in the early stage of the disease due to severe myocarditis or meningoencephalitis. The vast majority of people who have clinical symptoms include the following: infants, those who are defenseless in warding off the triatomid bite, and children aged 10 years or younger. Symptoms of the acute phase disappear within 4-8 weeks in most individuals.

The incubation period for Chagas disease is 7-14 d (1-2 weeks). In transfusion-acquired disease, the incubation period is longer (20-40 d). Chronic manifestations do not appear for years after infection. 

Symptoms of parasitic infection and proliferation include the following:

  • The first symptom is a bug bite by a reduviid or triatomine insect, typically on or near the face.

  • After 1-3 weeks, the organism proliferates, producing a red nodule known as a chagoma, which develops at the site of the original inoculation. The chagoma is usually located on the face or arms and can be painful. The surrounding skin becomes indurated and, later, hypopigmented.

  • A few days after proliferation, the parasites can spread throughout the body, infecting many tissues in particular the heart, skeletal muscles, and nervous system. This spread heralds the acute phase of the illness. During this stage, the infected patient may develop a flulike illness. Symptoms include a high temperature, chills, headache, irritability, tiredness, anorexia, malaise, myalgias, lymphadenopathy, and splenomegaly. The fever can be continuous, intermittent, or remitting and may last as long as 5 weeks. Epistaxis is common in young children.

  • Cardiac symptoms are observed in almost all patients, shortly after proliferation of the parasite begins.

In chronic disease, involvement of the GI system is common. Symptoms include dysphagia, regurgitation, hiccups, constipation, and abdominal pain. Disturbances in swallowing are common. These symptoms may develop weeks to years after the initial infection and subsequent progression is typically slow.

  • Symptoms specifically of esophageal involvement include dysphagia, regurgitation, heartburn, hiccups, odynophagia, and coughing. These symptoms generally develop insidiously. Less common symptoms of megaesophagus are severe malnutrition and aspiration with bronchitis and pneumonia. Hypertrophy of the salivary glands, especially the parotids, is present in 25% of patients with chagasic megaesophagus. These patients have an excessive response to salivary stimuli and the increased volume of saliva can lead to drooling.
  • Second to the esophagus, the colon is the most frequently affected portion of the GI tract in patients with chronic Chagas disease. The rectum and sigmoid colon are affected most often. The primary symptom is slowly progressive constipation. Most patients with megacolon have a bowel movement every 10 days. Impaction, caused by a firm mass of stool or a true fecaloma, develops in a minority of cases. Symptoms can range from vague abdominal pain and rectal fullness to symptoms of large bowel distention. Other symptoms include obstipation and meteorism.
  • Megaduodenum is usually asymptomatic but can lead to nonspecific dyspepsia, prolonged nausea and vomiting, and, rarely, malnutrition.

Neurologic symptoms are present in few patients with chronic disease. Involvement of the central, peripheral, or autonomic nervous systems can occur. Symptoms include paresis, cerebellar disturbance, convulsions, alterations in the dorsal root ganglia, and polyneuritis.[21]

Physical

If the bite occurs near the eye, unilateral periorbital edema of the eyelids, known as Romaña sign, develops. This edematous eyelid skin has a violaceous coloring. Conjunctivitis and enlargement of the ipsilateral preauricular lymph node is observed. Unilateral ocular and facial edema that involves the ipsilateral preauricular lymph node is known as oculoglandular syndrome. The preauricular region can markedly swell, causing an initial impression of parotitis, such as that caused by the mumps virus. In a small number of infected individuals, the facial edema may be generalized and mistaken for nephrotic syndrome. 

The spleen and liver are palpable but, in general, are not greatly enlarged. The disease is often not recognized at this stage and is accurately diagnosed in only a minority of patients.

The younger the patient, the more severe the clinical manifestations. Occasionally, the illness is fatal, especially in children younger than 2 years old. Generalized lymphadenopathy, moderate hepatosplenomegaly, anasarca, vomiting, and diarrhea are common in infants. Meningoencephalitis is also more common in young infants. [22]  If dermatological findings are seen, they can vary from a generalized maculopapular or morbilliform rash to urticaria.

In the acute phase, tachycardia is present and may not be related to fever; rather, it may result from destruction of the heart's parasympathetic innervation. As many as 30% of patients have cardiovascular abnormalities, which include cardiac enlargement, functional murmurs, and conduction blocks. Evidence of myocarditis is almost always found. Myocarditis is mild in the majority of cases. Biventricular heart failure rarely develops. Death from acute myocarditis occurs in 2-3% of patients. Prognosis is poor with early development of premature ventricular contractions, atrial fibrillation, heart block, or congestive heart failure.

The manifestations of the acute phase of Chagas disease generally last 2-4 weeks. In those who survive, the disease progresses to the indeterminate, or asymptomatic, phase. A low level of parasitemia is present. This phase can persist for years or even for the rest of the patient's life. As many as 30% of persons with disease in the indeterminate phase have cardiac, GI, or neurologic damage 10-20 years after infection. 

Clinical manifestations of chronic disease can develop years after the initial acute infection. During the chronic phase, the most serious aspect of Chagas disease is the delayed damage that it can inflict on the heart and GI system. Serious sequelae can be cardiomyopathy, heart failure, megaesophagus, and megacolon. 

  • Cardiac abnormalities are the most frequent manifestations of chronic Chagas disease.
  • Cardiac disease is the most serious cause of morbidity and mortality.
  • Chagas cardiomyopathy develops in 30% of patients. 

Congestive heart failure is the first sign of chagasic heart disease. Once heart failure occurs, it usually is intractable and difficult to control. Signs of right-sided heart failure are more common than signs of left-sided heart failure. Heart sounds may be distant, and functional murmurs of mitral and tricuspid insufficiency can develop. Other signs and symptoms include dyspnea upon exertion, peripheral edema, ascites, hepatomegaly, chest pain, and palpitations.

Patients with cardiac abnormalities typically do not have acute pulmonary edema. Orthopnea is also uncommon. The most important complications are systemic and pulmonary embolism and sudden death. Sudden death frequently occurs from a fatal dysrhythmia, such as ventricular fibrillation, or, less frequently, from a third-degree heart block or an embolism.  

In advanced cases of cardiac disease, the typical aneurysm develops at the apex of the left ventricle. Predictors for poor prognosis include impaired left ventricular function, New York Heart Association class III/IV, cardiomegaly observed on radiographs, left ventricular systolic dysfunction observed on echocardiographs, nonsustained ventricular tachycardia on 24-hour Holter monitoring findings, low QRS voltage on electrocardiography findings, apical aneurysms, and male sex.  QT interval dispersion, a marker of inhomogeneous myocardial repolarization, has been shown to be an independent predictor of sudden cardiac death in patients with Chagas disease.

Abnormalities in the GI system are the second most common manifestation of chronic Chagas disease. These occur in 8-10% of patients and vary from minor changes in motility to severe dilatation of the esophagus or colon.

  • Esophageal disease is the most common cause of symptoms in chronic disease. Most patients have symptoms at age 20-40 years, and the rate of progression widely varies.
  • Less commonly involved organs include the stomach and duodenum; rarely, the gallbladder and biliary tree. Involvement of the stomach leads to hypotonia, hypoperistalsis, delayed emptying and decreased acid secretion; and, rarely, dilatation.
  • Abdominal examinations reveal abdominal distention and tympanism.

Other rare findings ascribed to Chagas disease include bronchiectasia, hemosiderosis, and dilatation of the ureter or urinary bladder.

Intrauterine infection can cause spontaneous abortion or premature delivery. In its acute stage, congenital Chagas disease often resembles the acquired disease. The onset might be at birth or a few months later.[23]

  • The affected infant has a low birth weight, hepatosplenomegaly, jaundice, anemia, fever, and edema.
  • Neurologic involvement includes meningoencephalitis with convulsions, hypotonia, hyporeflexia, and tremors.
  • Some patients have metastatic hemorrhagic chagomas in the skin or mucous membranes.
  • Intracranial calcifications and ocular lesions have been described.
  • Cardiac involvement is rare.
  • GI abnormalities from megaesophagus present as dysphagia and cause death by aspiration. 
  • Death frequently occurs within the first few weeks of life. Those who survive have severe neurologic sequelae with mental deficiency or behavioral and learning disabilities.

The differential diagnosis of intrauterine infection includes erythroblastosis fetalis, congenital toxoplasmosis, cytomegalovirus, parvovirus B19, lymphocytic choriomeningitis virus, and herpes simplex infections. A positive serologic result for specific immunoglobulin G (IgG) at 6-12 months for Chagas disease is an indication for treatment. Transmission of this infection through infected mother's milk has been observed in breastfed babies.

Immunosuppression as a result of organ transplantation or human immunodeficiency virus (HIV) infection can lead to reactivation of the infection. Severe myocarditis and neurologic disease with brain abscesses, meningoencephalitis, and seizures caused by T cruzi have been major findings in patients infected with HIV. Clinical findings of neurologic involvement are nuchal rigidity, convulsions, paralysis, and coma.[22]  

 

 

Causes

T cruzi, a protozoan hemoflagellate, causes American trypanosomiasis. T cruzi belongs to the order Kinetoplastida, suborder Trypanosomatina, genus Trypanosoma, and subgenus Schizotrypanum.

These organisms undergo an obligatory developmental and reproductive cycle in the alimentary tract of a reduviid or triatomine insect. The reduviid or triatomine insects commonly are called assassins, cone-nose, or kissing bugs because of their predilection for biting the victim's face while he or she is sleeping. The insects are large (2-3 cm in length), obligate hematophages that hide in crevices in mud walls, windows, door frames, and dark corners of poorly constructed adobe-style huts. These insects come out at night to feed on the blood of sleeping humans. They require blood to grow and mature.

The vector (ie, reduviid or triatomine insect) becomes infected by ingesting trypomastigotes present in the bloodstream of an infected mammal. Infection lasts for the life of the vector, which can be as long as 2 years.

The developmental cycle of T cruzi includes 3 morphologic forms: epimastigotes, trypomastigotes, amastigotes. The entire cycle takes place in the insect gut lumen over 6-15 days.

  • Within a few hours after the ingestion of infected blood, short, spindle-shaped forms lacking a free flagellum can be found in the insect's foregut. These develop into small epimastigote forms that divide and elongate, resulting in large (35-40 µm long) epimastigotes.
  • By the third or fourth day, the epimastigotes attach to the rectal epithelium.
  • By the fifth day, the epimastigotes become rounded, short trypomastigotes, which then elongate.
  • By the seventh and eighth days, they become infective metacyclic trypomastigotes that are long (17-22 µm), slender, and spindle shaped. They have a large kinetoplast posterior to the nucleus and a flagellum. 

Human transmission occurs through contact with infected insect excreta. These insects defecate while ingesting human blood, thereby excreting the infective trypanosomes. Each microliter of insect excreta may contain 3000-4000 organisms. The person who is bitten is inoculated by inadvertently rubbing the insect's feces into the site of the bite. The organism can also enter through abraded skin or intact mucous membranes of the mouth, nose, and conjunctiva. T cruzi invades cells near the inoculum. Once inside the cell, the infective metacyclic trypomastigote moves from the digestive vacuole to the cytosol. Next, they transform into intracellular amastigote forms and multiply by binary fission.

Amastigotes have a short flagellum, are spherical or oval, and 2-4 µm in diameter. After a period of multiplication, amastigotes transform back into trypomastigotes; rupture the cell; enter the bloodstream; and invade other cells, predominantly reticuloendothelial, cardiac, skeletal and smooth muscle, and neuroglial cells.

The parasite can be transmitted congenitally, [24, 25, 26]  transmitted through organ transplantation[27] , via infected breast milk, via blood transfusion,[28] or accidentally in the laboratory. As much as 6.5% of blood stored in some blood banks in Latin America is contaminated by T cruzi. In highly endemic areas, this figure can be as high as 20%. Transplacental transmission occurs in 2-10.5% of infected mothers.[29]

Natural infection occurs in a wide variety of animals, including guinea pigs, opossums, foxes, squirrels, armadillos, anteaters, porcupines, rats, mice, bats, and monkeys. After humans, birds are the most important blood sources; however, birds are not susceptible to infection. Domestic cats and dogs are the most important domestic reservoirs for human infection.

The parasite can also be transmitted orally.[30, 31, 32, 33]

  • Ingestion of food contaminated by triatomine feces or entire insects

  • Consumption of raw or undercooked blood and/or meat of reservoir hosts

  • Eating food contaminated by the anal gland secretions of the common opossum

 

DDx

 

Workup

Laboratory Studies

During the acute phase of trypanosomiasis, the CBC count may reveal leukocytosis with relative lymphocytosis, and transaminase levels are often elevated.

During acute illness (ie, the first 6-12 wk), parasites are frequently seen in blood smears[34] , using either Giemsa staining or direct wet-mount preparations (in which motile parasites may be seen). Sensitivity is 80-90%. Thickly-stained and thinly-smeared blood can allow morphologic characterization of the parasite and differentiation from other trypanosomes, but these preparations are less sensitive (60%). Concentration using centrifugation after red-cell lysis, or clotting and examination of the buffy coat increases detection to 90-100%. Following the acute infectious period, low levels of parasitemia are present; therefore, blood smear results are often negative. 

Serologic confirmation of diagnosis requires that the parasites are cultured on a special medium or identified by means of xenodiagnosis. Blood cultures have positive results in 100% of patients with acute-phase illness, but only 40-50% in those with chronic illness. Xenodiagnosis is the best method for parasitologic diagnosis in the latent or chronic phases. It consists of allowing laboratory-reared reduviid nymphs to feed on blood from an infected patient. The feces and intestines of the nymphs are examined 20-60 days later for the presence of parasites. Test results are positive in approximately 50% of individuals.

Serologic tests for anti– T cruzi immunoglobulin M (IgM) play a limited role in the diagnosis because these tests are not widely available or standardized. In recent human infections, antibodies of the IgM class appear in the blood stream 15 days after infection, peak 17-45 days after infection, and persist for years. Antibodies of the IgM isotype predominate during the acute phase. Later, in the latent and chronic stages, antibodies are primarily from the IgG and IgA classes. 

Serologic tests include complement fixation (CF), indirect immunofluorescence (IFAT) and enzyme-linked immunosorbent assay (ELISA). 

  • The CF test, or Machado-Guerreiro test, is considered the most reliable immunodiagnostic method for diagnosis.
  • The indirect fluorescent antibody test (IFAT) is rapid and easy to perform, has a high sensitivity, and can be used to differentiate IgM antibodies from IgG antibodies. IFAT reveals the earliest positive results for IgM antibodies after initial infection.
  • Enzyme-linked immunosorbent assay (ELISA) is as sensitive as the IFAT and can also be used to differentiate IgM antibodies from IgG antibodies.

In the United States, CF and IFAT are available from the Centers for Disease Control and Prevention (CDC). In addition, the Food and Drug Administration (FDA) has approved assays based on the ELISA format for use in clinical testing; these are performed at Abbott Laboratories in Illinois and Gull Laboratories in Utah.

Several agglutination tests have been developed that detect the presence of antibodies against T cruzi, such as indirect hemagglutination (IHA), direct agglutination (DA), latex agglutination (LA), and flocculation tests. After initial infection, IFAT reveals the earliest positive results for IgM antibodies; also confirmed early-on by the DA method. All of these tests have been reported to provide positive results in more than 95% of the sera from infected humans.

A persistent problem with these tests is false-positive reactions. These have been observed with leishmaniasis, malaria, syphilis, infectious mononucleosis, tuberculosis, leprosy, and collagen vascular disease. The use of a minimum of 2 different, independently performed serologic tests is recommended to confirm infection. A Western blot confirmatory test has been described, to address the concern for serologic cross-reactivity.[35]

T cruzi kinetoplast DNA has been observed using polymerase chain reaction (PCR) amplification,[36, 37] which can be used to identify as few as 1 parasite in 20 mL of blood with a sensitivity of 96-100%. PCR has also been used to detect T cruzi in congenital trypanosomiasis and to follow the efficacy of patients treated for Chagas disease.[38]

Blood banks in areas of endemic disease use either the IHA or LA tests for disease detection. Recent studies involving the use of ELISA for the detection of antibodies to T cruzi and a radioimmunoprecipitation assay had a sensitivity and specificity of 100%.

In congenital Chagas disease, an indirect immunofluorescence test with anti-IgM has been introduced recently and it is effective in confirming acute congenital disease. Test infants of seropositive mothers as soon as possible for the presence of circulating parasites and specific IgM antibody, recognizing that these tests are not optimally sensitive.[39] Additionally, an ELISA using shed acute phase antigen (SAPA) for newborns has been described.[40, 41]

Atrial natriuretic factor is a sensitive marker capable of detecting gradual impairments in cardiac function and suggests poor survival in patients with Chagasic cardiomyopathy. N -terminal proBNP has been shown to be a marker of impaired left ventricular dysfunction. [42]  Brain natriuretic peptide has also been shown to be a marker for severity of disease in Chagas disease. Mass spectroscopy has been used to measure serum biomarkers of disease.[43]

In people who are immunosuppressed and thought to have Chagas disease, examine other specimens, such as lymph node aspirates, bone marrow, cerebrospinal fluid, and pericardial fluid, if the presence of T cruzi cannot be confirmed in the blood.

Imaging Studies

See the list below:

  • In patients with cardiac involvement, chest radiography may reveal cardiac enlargement with clear lung fields.

    • Electrocardiography (ECG) may be useful. The most common electrocardiographic abnormalities in acute infection include sinus tachycardia, prolongation of the PR interval, S-T segment depression and T-wave inversion, low voltage of the QRS complex, and prolongation of the QT interval.[44]  The most common electrocardiographic manifestations in chronic disease are intraventricular blocks (right bundle branch block and left anterior hemiblock), sinus bradycardia, atrioventricular (AV) block (first degree, second degree, complete), sinoatrial block, atrial fibrillation, and premature ventricular beats.

    • Echocardiography is used to assess for evidence of acute chagasic myocarditis or chronic Chagas cardiomyopathy.[45]  In the acute setting, echocardiography may reveal pleural effusions, apical or anterior dyskinesis, and left ventricular dilatation. In patients with chronic disease, echocardiography may reveal left ventricular aneurysm, segmental wall abnormalities, left ventricular dilatation, decreased left ventricular ejection fraction, diastolic dysfunction, tricuspid, and mitral regurgitation.

    • Thallium stress-redistribution myocardial perfusion scintigraphy may reveal reversible and irreversible perfusion defects in chronic Chagas cardiomyopathy. The perfusion defects occur in the presence of normal epicardial coronary arteries and probably represent myocardial fibrosis, coronary microvasculature abnormalities, or extensive impairment of cardiac sympathetic function.

    • Cardiac MRI has been shown to be the most accurate method to detect myocardial fibrosis in patients with Chagas disease. CMR offers a wide variety of imaging tools to evaluate morphology, function, and other tissue characterization abilities, such as edema and fat.

  • In patients with advanced esophageal involvement, chest radiography may reveal a tubular mass along the aorta and air-fluid level, which reflects the retention of swallowed material in the esophagus.

    • Fluoroscopic esophagrams obtained with barium often show the absence of mucosal irregularities and a variably dilated esophagus with a narrow, conical segment at its lower end that represents the nonrelaxing sphincter (bird-beak appearance). In advanced disease, the diameter is grossly enlarged, causing it to fold over the diaphragm.

    • Cine-esophagrams may show tertiary contractions and accumulation of the contrast material.

    • Manometry in patients with Chagas disease typically reveals loss of peristalsis upon deglutition and an abnormally elevated pressure in the lower esophageal sphincter, which fails to relax.

    • Scintigraphy is as sensitive as manometry in depicting esophageal dysmotility and it reveals patterns of transit similar to those described in idiopathic achalasia.

  • In colonic involvement, barium enema examination is the cornerstone for diagnosis. The sigmoid colon is frequently dilated and elongated in nearly all cases, and the rectum is dilated in 80% of cases.

 

Other Tests

See the list below:

  • Complex ventricular dysrhythmias during cardiac stress testing are a clinical marker for progressive cardiomyopathy in Chagas disease.

  • Lumbar puncture to assess for CNS involvement. Cerebral spinal fluid may show pleocytosis with a predominance of lymphocytes and elevated protein level; often, it reveals the presence of T cruzi.

  • Autonomic dysfunction may occur in infected children.[46]

Procedures

Endoscopy is not essential to diagnose chagasic achalasia. Its main value is to identify other disorders, such as gastric and esophageal cancer, which are more common in patients with chagasic megaesophagus.

Histologic Findings

See the list below:

  • The lesion at the parasite's portal of entry has a predominance of lymphocytic, monocytic, and eosinophilic infiltration, along with the presence of giant cells.

  • When the heart is invaded, myocardial fibers are often edematous and undergo various stages of focal necrosis, which primarily involves the contractile and conduction systems. Interspersed among the degenerating fibers is a markedly mixed inflammatory cell exudate consisting of granulocytes, lymphocytes, monocytes, mast cells, and plasma cells.

  • Diffuse inflammation of the myocardium is present, as well as dense foci of fibrosis in the interstitial spaces and invasion of lymphocytes, plasma cells, and macrophages. In two-thirds of cases, detection of parasites in the myocardium is difficult.

 

Treatment

Medical Care

The acute phase of trypanosomiasis (Chagas disease) is treated with nifurtimox or benznidazole.[47, 48, 49, 50] Cases of congenital Chagas disease have been successfully treated with either drug. A single case of successful treatment of an adult with posaconazole (after failure of therapy with benznidazole) has been reported.[51]

Management of chronic Chagas disease is supportive, although recent studies and some expert opinion suggest that therapy with benznidazole in chronic disease may be appropriate in certain circumstances.[52] Recommendations continue to evolve, as neither of the available drugs is well-tolerated, treatment failures have been reported ,[53] and alternatives are lacking.[54, 55]

Dysrhythmias usually respond to typical agents. Patients with bradydysrhythmias and atrial fibrillation with a slow ventricular response may require a permanent pacemaker, if they are symptomatic. In the management of heart failure, digitalis or vasoactive drugs are not well tolerated and must be cautiously administered. However, diuretics are effective. Transplantation is not without risk, as immunosuppression reactivates the chronic trypanosome infection.

Embolism or evidence of thrombosis may necessitate anticoagulant therapy.

Treatment of esophageal alterations in patients with Chagas disease is the same as in idiopathic achalasia. The focus is on facilitating the transit of food and liquids through the achalasic lower esophageal sphincter. Dietary measures, such as eating soft foods or administering anticholinergic drugs, are generally of little use. Nifedipine or sublingual isosorbide dinitrate taken prior to meals may provide some relief for those patients with a nondilated esophagus.

In most patients, symptomatic megaesophagus can benefit from pneumatic dilation of the lower esophageal sphincter. Relapse occurs in as many as 26% of patients, but good results have been achieved with second dilations. Surgical approaches for chagasic megaesophagus are reserved for use when repeat dilation fails and for the most severe cases with dolichomegaesophagus.

Patients with Chagas disease in the early stages of colonic dysfunction can be treated employing a high-fiber diet and increased fluid intake, as well as laxatives. These patients occasionally require enemas to evacuate the bowel.

Fecal impaction might occur as the disease progresses and requires manual disimpaction. Treat fecaloma with multiple mineral oil or saline enemas and colonic lavages with balanced salt solutions or tap water. In the most severe cases, manual emptying under general anesthesia may be necessary. Endoscopic emptying can be performed as the initial treatment in patients in whom no clinical, radiographic, or endoscopic signs of ischemia are present. Complicated cases require surgical decompression. Patients in whom conservative methods fail, as well as those with frequent fecal impaction or sigmoid volvulus, need surgical treatment.

Surgical Care

Surgical care for those with esophageal dysfunction

Surgical approaches for chagasic megaesophagus are reserved for disease that fails to respond to repeated dilatation and the most severe cases with dolichomegaesophagus. Laparoscopic transhiatal subtotal esophagectomy has been successful with fewer complications than a transthoracic approach.

Good results have been evidenced after performing a Thal operation with a wide esophagocardiomyotomy on the anterior gastroesophageal junction combined with a valvuloplasty to reduce reflux. Surgical complications include pleural effusions and fistulas at the site of anastomosis.

Future approaches might include laparoscopic myotomy, which is successful in patients with severe idiopathic achalasia.

Surgical care for those with colonic dysfunction

Patients with megacolon in whom conservative methods fail, as well as those with frequent fecal impaction or sigmoid volvulus, need surgical treatment.  Various surgical procedures have been used to treat advanced megacolon. These procedures include resection of the sigmoid colon as well as a portion of the rectum.

Resection of part of the rectum has been found necessary to prevent subsequent recurrences of megacolon in the portion brought down and sutured to the rectum. Resection of the rectum requires an abdominal-perineal approach; the Duhamel procedure, as modified by Haddad, has been used with considerable success; however, it is a 2-stage procedure. Another procedure, the Habr-Gama technique, consists of abdominal rectosigmoidectomy with immediate posterior colorectal end-to-end stapling and has positive reports of success.

Consultations

Consultations with an infectious diseases specialist, cardiologist, gastroenterologist, neurologist, and surgeon may be helpful; these specialists should be consulted as indicated by the patient's clinical condition.

Diet

Dietary measures are generally not effective, except for high-fiber and increased fluid intake for the treatment of mild colonic dysfunction.

 

Medication

Medication Summary

Current consensus recommendations strongly recommend treatment for patients diagnosed with acute, congenital, or with reactivation of infection. Children aged 18 years or younger with chronic infection should also be treated. Most of these consensus recommendations suggest offering treatment to adults with chronic infection, as well.[56]

The acute phase of Chagas disease is treated with nifurtimox or benznidazole.[56] Both agents reduce the duration and severity of acute and congenital Chagas disease. Treatment is also indicated in a patient with HIV who has reactivation trypanosomiasis. Both agents are available in the United States from the drug service of the CDC at the Parasite Drug Service, which can be reached at (770) 488-7775 during business hours and at (770) 488-7100 on evenings, weekends, and holidays. Questions regarding treatment of Chagas disease should be directed to CDC Parasitic Diseases Inquiries (404-718-4745; email chagas@cdc.gov) M-F 8:00am-4pm EST. For emergencies (for example, acute Chagas disease with severe manifestations, Chagas disease in a newborn, or Chagas disease in an immunocompromised person) outside of regular business hours, call the CDC Emergency Operations Center (770-488-7100) and ask to talk to the person on-call for Parasitic Diseases.

Nifurtimox has been reported to be 75-90% effective. In some areas, such as Brazil, it is not as effective. Benznidazole has similar efficacy and may be better tolerated than nifurtimox. PCR can be used to monitor treatment response.[57]  

A long-term follow-up study of patients with chronic disease treated with benznidazole revealed a significant decrease in the electrocardiographic changes, clinical deterioration, and rate of seropositivity. Allopurinol has been shown to be as effective as nifurtimox and benznidazole in suppressing parasitemia with fewer adverse effects.[58] However, the open and nonrandomized study structure and the lack of well-defined criteria for cure make interpretation of these findings difficult. In addition, allopurinol has recently been ineffective in eradicating T cruzi in patients from Brazil. In Chile, the use of itraconazole has been shown to decrease electrocardiographic abnormalities in some patients with chronic Chagas disease.[59]

Nifurtimox and recombinant interferon alfa successfully treated Chagas disease in a child who acquired the disease through transfusion and in a laboratory worker who accidentally was infected. Interferon alfa may improve the activation of macrophages that kill the organism.

Thioridazine is a phenothiazine with high antitrypanothionine reductase activity that has been shown to be effective in preventing chagasic myocardiopathy in mice when used in the acute phase of infection.[60]

Anthelmintics

Class Summary

These are used to treat acute and congenital Chagas disease. Parasite biochemical pathways are different from the human host, thus toxicity is directed to the parasite, egg, or larvae. Mechanism of action varies within the drug class. Antiparasitic actions may include the following:

- Inhibition of microtubules causes irreversible block of glucose uptake

- Tubulin polymerization inhibition

- Depolarizing neuromuscular blockade

- Cholinesterase inhibition

- Increased cell membrane permeability, resulting in intracellular calcium loss

- Vacuolization of the schistosome tegument

- Increased cell membrane permeability to chloride ions via chloride channels alteration

Nifurtimox (Lampit)

Used to treat acute and congenital Chagas disease. It decreases the period of acute disease and decreases the mortality rate from myocarditis and meningoencephalitis. It interferes with the parasite's carbohydrate metabolism by inhibiting pyruvic acid synthesis. Available in the US via a compassionate IND from the CDC.

Benznidazole (Rochagan)

Imidazole that inhibits nucleic acid synthesis. Used for acute and congenital Chagas disease. More trypanocidal than nifurtimox. Not available in the US.

 

Follow-up

Further Outpatient Care

See the list below:

  • Observe infants born to seropositive mothers for at least 1 year.

Further Inpatient Care

See the list below:

  • The clinical condition of the patient with trypanosomiasis dictates further inpatient care.

Transfer

See the list below:

  • Transfer to another facility is appropriate when required specialists and services are unavailable locally.

Deterrence/Prevention

Educate people in areas with endemic disease about how trypanosomiasis is spread and methods of prevention.

Inspect homes for presence of vectors and for measures that prevent vectors from entrance. If reduviid or triatomine insects are found, a thorough disinfection with synthetic pyrethroid insecticides can help keep the home vector free for about 2 years. Screens on windows and doors exclude the vectors. Improving the home by covering crevices and cracks significantly reduces triatomid insect infestation. 

Screen blood donors in areas of endemic disease with serologic tests.

Blood recipients in areas of endemic disease can be protected by treating donated blood with gentian violet. Gentian violet (250 mg/L blood, dilution of 1:4000 for 24 h at 4°C), an amphophilic cationic agent that acts photodynamically, has been used to kill the parasite in blood. Photoradiation of blood that contains gentian violet and ascorbate generates ascorbyl radicals and superoxide anions, which are potent trypanocides. Other agents that can be added to the blood to treat the infection include mepacrine, an antimalarial agent, and maprotiline, an antidepressant.

A vaccine likely would prove cost-effective.[61]

Complications

See the list below:

  • Congestive heart failure

  • Myocarditis

  • Cardiomyopathy[62, 63]

  • Dysrhythmias

  • Sudden death

  • Meningoencephalitis

  • Megaesophagus: Esophagitis and esophageal cancer are the most common complications of megaesophagus.

  • Megacolon: Fecaloma and volvulus of redundant sigmoid complicate megacolon. Fecaloma-associated stercoral ulceration, overflow incontinence, and ischemic colitis have been described.

  • 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%).

  • Pregnancy: In addition to risk of congenital infection,[64] pregnancy may exacerbate chronic infection,[65] during which circulating parasites increase in number.

Prognosis

See the list below:

  • 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.

  • 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.

  • Right bundle branch block (RBBB) is an ominous sign in the acute phase.

  • The prognosis with the GI symptoms of the illness is generally good.

Patient Education

See the list below:

  • The use of proper preventive measures when one travels to endemic areas should be emphasized.