eMedicine Specialties > Pediatrics: General Medicine > Parasitology

Trypanosomiasis

Author: Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Coauthor(s): Antonio Muñiz, MD, Associate Professor of Emergency Medicine and Pediatrics, University of Texas Medical School at Houston; Medical Director of the Pediatric Emergency Department, Children's Memorial Hermann Hospital
Contributor Information and Disclosures

Updated: Jan 27, 2009

Introduction

Background

American trypanosomiasis, also known as Chagas disease, affects millions of people throughout the Americas. 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. 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 has clinical signs and symptoms from damage to the heart or GI tract. The disease is the leading cause of congestive heart failure in areas of Latin America where it is endemic.

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

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 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.

A nodular swelling or chagoma develops at the site of entry. This area becomes infiltrated with macrophages surrounded by lymphocytes, eosinophils, and polymorphonuclear neutrophils. When T cruzi enters the human host, it produces an acute local inflammatory reaction. 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.

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.

Frequency

United States

Trypanosomiasis is extremely rare but has been reported in Texas,1 Oklahoma, and California. As many as 5% of immigrants in Washington, DC, were found to carry trypanosomes and as many as 50,000-100,000 immigrants are thought to be infected. Transfusion-related cases, although rare, are increasingly recognized. Small mammals in the southern and southwestern United States can harbor T cruzi. Infected Triatoma protracta have been found in California, Arizona, and New Mexico.

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, Central America, and South America. Human disease is most prevalent in Brazil, Argentina, and Venezuela.2 Approximately 25% (90 million) of people in Latin America live in an area with endemic disease and are at risk of acquiring the infection. 

Mortality/Morbidity

The overall mortality during the acute phase of Chagas disease is 5%. More than 70,000 people die from this disease annually. The disease is the leading cause of congestive heart failure in areas of Latin America where it is endemic and is responsible for one quarter of all deaths in persons aged 25-44 years in such areas. By far the most common cause of death is cardiac abnormalities. The 5-year mortality rate in patients with chronic Chagas disease and cardiac dysfunction is reportedly more 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 megadisease 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 sex predilection has been reported.

Age

This disease occurs in people of all ages. The most severe form occurs in children younger than 5 years, in whom CNS involvement may predominate.

Clinical

History

The early phase of trypanosomiasis is asymptomatic, and only about one third of patients have symptoms of acute Chagas disease. A small minority of patients have severe clinical disease, including heart failure or meningoencephalitis. As many as 10% of patients die in the early stage of severe myocarditis or meningoencephalitis. The vast majority of those who have clinical symptoms include infants, those who are rather defenseless in warding off the triatomid bite, and children aged 10 years or younger. However, the symptoms of the acute phase disappear within 4-8 weeks in most individuals.

  • The incubation period for Chagas disease is 1-2 weeks. Chronic manifestations do not appear for years after infection. The incubation period is longer (20-40 d) in transfusion-acquired disease.
  • Symptoms of parasitic infection and proliferation include the following:
    • The first symptom is a bug bite on 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, particularly 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. Initial 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 the most common manifestations. Symptoms may develop weeks to years after the initial infection and subsequent progression is typically slow.
    • Symptoms 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 result in 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 significant minority of cases. Symptoms 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, with involvement of the central, peripheral, or autonomic nervous systems, are present in few patients. Symptoms include paresis, cerebellar disturbance, convulsions, alterations in the dorsal root ganglia, and polyneuritis.

Physical

  • If the bite occurs near the eye, unilateral periorbital edema of the eyelids, known as Romaña sign, develops. The edematous skin is violet, with conjunctivitis and enlargement of the ipsilateral preauricular lymph node. Unilateral ocular and facial edema that involves the ipsilateral preauricular lymph node is known as the oculoglandular syndrome. In a small number of infected individuals, the edema may be generalized and mistaken for nephrotic syndrome. The preauricular region can significantly swell, causing an initial impression of parotitis, such as that caused by the mumps virus.
  • 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. Generalized lymphadenopathy, moderate hepatosplenomegaly, anasarca, vomiting, and diarrhea, as well as signs of meningeal irritation, are common in infants. Skin lesions can vary from a generalized maculopapular or morbilliform rash to urticaria.
  • 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 vast majority of cases. Biventricular heart failure rarely develops. Death from acute myocarditis occurs in 2-3% of patients. The prognosis is poor with the early development of premature ventricular contractions, atrial fibrillation, heart block, or congestive heart failure.
  • Occasionally, meningoencephalitis can develop. This is more common in young infants and immunosuppressed patients. Death can occur in as many as 50% of these cases. Clinical manifestations include nuchal rigidity, convulsions, paralysis, and coma. Encephalitis can develop in patients who are immunosuppressed.
  • The manifestations of the acute phase of Chagas disease generally last 2-4 weeks. In individuals 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. In other individuals, the illness progresses to the chronic phase.
  • The most serious aspect of Chagas disease is the delayed damage that it can inflict on the heart and GI system during the chronic phase. Serious sequelae consist of cardiomyopathy, heart failure, megaesophagus, and megacolon. Clinical manifestations can develop years after the initial acute infection.
  • Cardiac abnormalities are the most frequent manifestations of chronic Chagas disease and are the most serious causes 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. If left ventricular failure is present, it usually causes mild symptoms.
    • Patients with cardiac abnormalities usually do not have acute pulmonary edema, and orthopnea is 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 many advanced cases, 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 when they are aged 20-40 years, and the rate of progression widely varies.
    • Less commonly involved organs include the duodenum; stomach; small intestine; and, 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.
  • 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.
  • 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.
    • The infant has a low birth weight, hepatosplenomegaly, jaundice, anemia, fever, edema, and 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 is an indication for treatment.
  • Transmission of this infection through infected mother's milk has been observed in breastfed babies.
  • Rare findings ascribed to Chagas disease include bronchiectasia, hemosiderosis, and dilatation of the ureter or urinary bladder.

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: amastigotes, trypomastigotes, and epimastigotes. 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, these organisms 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. Each microliter of insect excreta may contain 3000-4000 organisms.
  • Human transmission occurs through contact with infected insect excreta. These insects defecate while ingesting human blood, thereby excreting the infective trypanosomes. 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.
    • The amastigotes have a short flagellum and 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 parasites are transmitted through the feces of the insects of the triatomid or reduviid families. 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 be congenitally transmitted or transmitted through organ transplantation, via infected breast milk, by blood transfusion, or accidentally in the laboratory. As much as 1.9-6.5% of the blood 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.

More on Trypanosomiasis

Overview: Trypanosomiasis
Differential Diagnoses & Workup: Trypanosomiasis
Treatment & Medication: Trypanosomiasis
Follow-up: Trypanosomiasis
References
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Further Reading

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Keywords

trypanosomiasis, American trypanosomiasis, Chagas disease, Chagas' disease, chagasic heart disease, chagasic megaesophagus, chagoma, chronic Chagas disease, chronic chagasic cardiopathy, contraction band necrosis, dyspepsia, focal myonecrosis, interstitial fibrosis, Kinetoplastida, lymphocytic infiltration, megacolon, megaduodenum, megaesophagus, parasitemia, parasitic disease, Romaña sign, Romaña's sign, Schizotrypanum, triatomid, Trypanosoma cruzi, T cruzi, Trypanosomatina

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Contributor Information and Disclosures

Author

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Consulting; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; Novartis Honoraria Speaking and teaching; sanofi pasteur Grant/research funds Unrestricted research grant; sanofi pasteur  Consulting; sanofi pasteur Honoraria Speaking and teaching; Tap Honoraria Speaking and teaching; Baxter Healthcare Honoraria Speaking and teaching

Coauthor(s)

Antonio Muñiz, MD, Associate Professor of Emergency Medicine and Pediatrics, University of Texas Medical School at Houston; Medical Director of the Pediatric Emergency Department, Children's Memorial Hermann Hospital
Antonio Muñiz, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Pediatrics, American College of Emergency Physicians, American Heart Association, American Medical Association, Society for Academic Emergency Medicine, and Southern Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Ashir Kumar, MBBS, MD, FAAP, Professor, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University; Consulting Staff, Department of Pediatrics, EW Sparrow Hospital
Ashir Kumar, MBBS, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association of Physicians of Indian Origin, American Federation for Clinical Research, American Society for Microbiology, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Leslie L Barton, MD, Professor, Program Director, Department of Pediatrics, University of Arizona School of Medicine
Leslie L Barton, MD is a member of the following medical societies: American Academy of Pediatrics, Association of Pediatric Program Directors, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

CME Editor

Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine
Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine
Disclosure: Baxter Honoraria Consulting; Pfizer Honoraria Consulting

Chief Editor

Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None

 
 
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