Chagas disease or american trypanosomiasis is a zoonosis caused by the protozoan parasite Trypanosoma cruzi. Its major manifestations involve the gastrointestinal and cardiac systems. It is currently the most common cause of non-ischemic cardiomyopathy in South America.
Presentation
Acute phase: There is an incubation period of approximately two weeks after which the acute phase begins. The acute phase is characterized by non-specific symptoms such as fever and malaise. The acute phase may last eight to twelve weeks. Less than 10% of individuals get diagnosed during this phase. In a few, a chagoma may form. Inoculation via the conjunctiva causes unilateral swelling of the eyelids classically known as Romana’s sign.
Severe acute disease may occur in very few patients which presents with acute myocarditis which is clinically similar to myocarditis caused by viruses. It may also present with meningoencephalitis. Severe disease is associated with significant mortality [6].
Chronic phase: After 8-12 weeks, the patients enter the chronic phase; the intermediate phase of which is usually asymptomatic and may persist for decades. Later on, such patients progress to overt disease either in the gastrointestinal system, cardiac system or both.
Chronic Chagas cardiomyopathy: Patients that eventually develop this complication may be asymptomatic but eventually present with features of heart failure such as exertional dyspnea, palpitations and edema. They present with biventricular failure but the first presentation may be a stroke, thromboembolism or cardiac arrhythmia.
Gastrointestinal Chagas disease: This may present with esophageal manifestations such as motility disorders to mild achalasia to the most severe form being mega-esophagus. The most common symptom is dysphagia. There may also be severe regurgitation of food with risk of aspiration. Food may also lodge with the esophagus and cause local ulceration. There is an increased risk of esophageal cancer.
Colonic Chagas disease: The most common manifestation is slowly progressive constipation associated with bloating, abdominal distention and pain. There is also risk for developing intestinal obstruction due to volvulus.
Immune System
- Generalized Lymphadenopathy
Patients present initially with fever, swelling at the site of inoculation of triatomine feces, and generalized lymphadenopathy. [amboss.com]
Read more Symptoms The disease has two clinical stages: – Acute (in which 5% of children die) characterized by fever, malaise, facial oedema, generalized lymphadenopathy, and hepatosplenomegaly – often spontaneously resolves in four to six weeks– Chronic [dndi.org]
Symptoms after a Triatominae bite typically begin with a skin lesion or unilateral periorbital edema, then progress to fever, malaise, generalized lymphadenopathy, and hepatosplenomegaly; years later, some patients develop chronic cardiomyopathy, megaesophagus [merckmanuals.com]
Symptoms after a Triatominae bite typically begin with a skin lesion or unilateral periorbital edema, then progress to fever, malaise, generalized lymphadenopathy, and hepatosplenomegaly; years later, 20 to 30% of infected patients develop arrhythmias [msdmanuals.com]
- Splenomegaly
[…] unilateral purplish orbital oedema (Romaña’s sign) with local lymphadenopathy and fever over several weeks More general symptoms include: headache pallor myalgia dyspnoea oedema in inferior limbs or face abdominal pain cough hepatomegaly rash painful nodules splenomegaly [gov.uk]
On days 14 and 21, all three strains continued to develop increasing splenomegaly, but the Jα18 −/− spleens appeared the largest (Fig. 2C ). [dx.doi.org]
Hepatomegaly and splenomegaly may occur in children with acute Chagas disease, often accompanied by generalized lymphadenopathy. Varying degrees of generalized edema may occur in acutely infected persons, particularly children. [web.archive.org]
CD1d-restricted NKT cells contribute to malarial splenomegaly and enhance parasite-specific antibody responses. Eur. J. Immunol. 33 : 2588-2598. [ PubMed ] [ Google Scholar ] 35. Hesse, M., C. A. Piccirillo, Y. Belkaid, J. Prufer, M. [ncbi.nlm.nih.gov]
However, symptomatic manifestations of the acute phase—such as prolonged fever, headache, myalgia, lymphadenitis, hepatomegaly, and splenomegaly—usually cease within 60 days even without the use of etiological drugs (54). [frontiersin.org]
Entire Body System
- Fever
It is characterized by an acute and chronic phase; in the acute phase patients may have fever, malaise, and swelling at the site of the insect bite. [icd10data.com]
[…] transmitted chiefly by blood-sucking insects (genus Triatoma, Rhodnius, and Panstrongylus) and that occurs in both an acute and chronic form Note: The acute form of Chagas disease lasts for several weeks to months and is marked by mild symptoms (such as fever [merriam-webster.com]
[…] trypanosomiasis (sleeping sickness), Buruli ulcer, Chagas' disease, dengue, gastrointestinal helminths, infantile diarrhoea, leishmaniasis (Kala Azar), leprosy, lymphatic filariasis (elephantiasis), onchocerciasis (river blindness), schistosomiasis (snail fever [bg.glosbe.com]
Vimentin is mimicked by some bacterial proteins and anti-vimentin antibodies occur in autoimmune cardiac disease, as rheumatic fever. [ncbi.nlm.nih.gov]
- Asymptomatic
Paradoxically, they were relatively infrequent in asymptomatic (25%) infected patients, which had a clearly positive serological reaction to parasite antigens, but had low frequency of anti-vimentin antibodies, similar to controls (2,5%). [ncbi.nlm.nih.gov]
The majority of people infected will remain asymptomatic in the chronic phase. [utsouthwestern.edu]
Chronic phase: After 8-12 weeks, the patients enter the chronic phase; the intermediate phase of which is usually asymptomatic and may persist for decades. [symptoma.com]
Normal ECG Asymptomatic from rural Brazilian community. [dx.doi.org]
- Fatigue
[…] chiefly by blood-sucking insects (genus Triatoma, Rhodnius, and Panstrongylus) and that occurs in both an acute and chronic form Note: The acute form of Chagas disease lasts for several weeks to months and is marked by mild symptoms (such as fever, fatigue [merriam-webster.com]
When signs and symptoms do occur, they are usually mild and may include: Swelling at the infection site Fever Fatigue Rash Body aches Eyelid swelling Headache Loss of appetite Nausea, diarrhea or vomiting Swollen glands Enlargement of your liver or spleen [mayoclinic.org]
Caused by the organism Trypanosoma cruzi and spread by the feces of insects commonly called “kissing bugs,” Chagas disease may initially produce an array of vague signs, including headache, fatigue and swollen lymph nodes. [equusmagazine.com]
Some people do get mild symptoms, such as Fever Fatigue Body aches Headache Loss of appetite Diarrhea Vomiting A rash A swollen eyelid These early symptoms usually go away. However, if you don't treat the infection, it stays in your body. [nlm.nih.gov]
Trypanosoma cruzi infection in El Salvador WHO and Sanofi sign new agreement to sustain specific efforts to eliminate NTDs Better understanding of hybrid parasite strains could improve Chagas disease diagnosis Other symptoms that may manifest include fatigue [news-medical.net]
- Congestive Heart Failure
� This stage occurs years after the exposure and may include abnormal enlargement of the esophagus or colon and congestive heart failure.� Persons with weakened immune systems may have more severe symptoms. [ok.gov]
Our Markov model structure had a 1 year cycle length and consisted of five states: acute disease, indeterminate disease, cardiomyopathy with or without congestive heart failure, megaviscera, and death. [ncbi.nlm.nih.gov]
[…] discriminating factors are ECG status and presence or absence of congestive heart failure. [doi.org]
[…] factors are ECG status and presence or absence of congestive heart failure. [jamanetwork.com]
Respiratoric
- Dyspnea
Snapshot A 58-year-old man presents to the clinic with a 2 month history of cough, dyspnea on exertion, palpitations, and orthopnea. He immigrated from rural Bolivia when he was 25 years of age and visits Bolivia regularly. [medbullets.com]
The manifestations included sudden fever, myalgia, dyspnea and signs of heart failure. Diagnosis was confirmed by specific exams, especially QBC (Quantitative Buffy Coat) and natural xenodiagnosis. [ncbi.nlm.nih.gov]
These include: Dyspnea (shortness of breath). [verywellhealth.com]
Chronic Chagas cardiomyopathy: Patients that eventually develop this complication may be asymptomatic but eventually present with features of heart failure such as exertional dyspnea, palpitations and edema. [symptoma.com]
Gastrointestinal
- Nausea
When signs and symptoms do occur, they are usually mild and may include: Swelling at the infection site Fever Fatigue Rash Body aches Eyelid swelling Headache Loss of appetite Nausea, diarrhea or vomiting Swollen glands Enlargement of your liver or spleen [mayoclinic.org]
The most common adverse reactions in patients taking benznidazole were stomach pain, rash, decreased weight, headache, nausea, vomiting, abnormal white blood cell count, urticaria (hives), pruritus (itching) and decreased appetite. [fda.gov]
[…] infection in El Salvador WHO and Sanofi sign new agreement to sustain specific efforts to eliminate NTDs Better understanding of hybrid parasite strains could improve Chagas disease diagnosis Other symptoms that may manifest include fatigue, rash, headache, nausea [news-medical.net]
The predominant symptoms were: rash (37.9%), itching (33.7%), epigastric pain (26.4%), abdominal bloating (24.2%) and nausea (22.1%). ADRs were mild (57.4%), moderate (35.5%) and severe (7.3%). [ncbi.nlm.nih.gov]
- Constipation
Chagas' disease often goes undiagnosed because its symptoms are associated with heart disease, volulus, achlasia, and constipation. Laboratory tests are necessary to detect the presence of T. cruzi. [uta.edu]
Patients who have parasitic infection of the colon may experience abdominal pain and constipation. Death is usually caused by heart disease. [web.archive.org]
[…] the flagellate protozoan Trypanosoma cruzi, causing chagasic megacolon Essential features Infection most commonly involves the heart and GI tract (esophagus is most frequent site, followed by colon) Patients with chagasic megacolon suffer from chronic constipation [pathologyoutlines.com]
Megacolon occurs when your colon becomes abnormally dilated, causing abdominal pain, distention and severe constipation. [mayoclinic.org]
The large intestine (colon) may enlarge, and severe constipation may develop. [msdmanuals.com]
- Dysphagia
Chagas megaesophagus manifests as dysphagia and may lead to pulmonary infections caused by aspiration or to severe undernutrition. Megacolon may result in long periods of obstipation and intestinal volvulus. [merckmanuals.com]
Non-operative treatment provides only temporary relief of dysphagia. Cardiomyotomy with partial fundoplication is indicated in the non-advanced variant of achalasia and provides relief of dysphagia. [link.springer.com]
The most common symptom is dysphagia. There may also be severe regurgitation of food with risk of aspiration. Food may also lodge with the esophagus and cause local ulceration. There is an increased risk of esophageal cancer. [symptoma.com]
[…] orthopnea, and jugular venous distension), arrhythmias ( e.g., palpitations, weakness, and syncope), stroke ( e.g., focal neurological deficit secondary to thromboembolism formation in dilated cardiac chambers) gastrointestinal megaesophagus progressive dysphagia [medbullets.com]
- Abdominal Pain
Patients who have parasitic infection of the colon may experience abdominal pain and constipation. Death is usually caused by heart disease. [web.archive.org]
pain; in severe cases, there may be several weeks between bowel movements Histology shows ganglionitis with neuronal cell depopulation Terminology Also known as American trypanosomiasis ICD coding B57.3 Chagas disease (chronic) with digestive system [pathologyoutlines.com]
Megacolon occurs when your colon becomes abnormally dilated, causing abdominal pain, distention and severe constipation. [mayoclinic.org]
pain, and bloating Studies Blood smear trypomastigote (motile, flagellated form) in blood smear Polyermase chain reaction (PCR) Serology enzyme-linked immunosorbent assay (ELISA) Differential Alcohol-induced dilated caridiomyopathy differentiating factor [medbullets.com]
These changes can result in weakness, difficulty swallowing, abdominal pain, and death. Other organs may also malfunction (ureters, bile duct, for example). What research is being done for Chagas disease? Research is progressing on Chagas disease. [medicinenet.com]
- Intestinal Disease
Megacolon may result in long periods of obstipation and intestinal volvulus. [merckmanuals.com]
Cardiovascular
- Heart Failure
Levosimendan is a positive inotropic drug with vasodilatory properties that is indicated for acute heart failure. [ncbi.nlm.nih.gov]
It may take more than 20 years from the time of the original infection to develop heart or digestive problems. Abnormal heart rhythms may cause sudden death. Once heart failure develops, death usually occurs within several years. [medlineplus.gov]
Once heart failure develops, death usually occurs within several years. [web.archive.org]
The symptoms of this later phase include: Irregular heartbeat that may lead to sudden cardiac arrest or sudden death Heart failure Enlarged heart that is unable to pump blood efficiently Stroke Problems with the digestive system such as enlargement of [news-medical.net]
- Palpitations
Snapshot A 58-year-old man presents to the clinic with a 2 month history of cough, dyspnea on exertion, palpitations, and orthopnea. He immigrated from rural Bolivia when he was 25 years of age and visits Bolivia regularly. [medbullets.com]
Chronic Chagas cardiomyopathy: Patients that eventually develop this complication may be asymptomatic but eventually present with features of heart failure such as exertional dyspnea, palpitations and edema. [symptoma.com]
When the heart or digestive tract are affected, the most common symptoms are: dizziness fainting spells palpitations chest pain fatigue constipation difficulty swallowing Most children and adults who have Chagas disease do not know when they were infected [infochagas.org]
Palpitations. The cardiac arrhythmias commonly associated with heart failure often produce palpitations. Syncope. Loss of consciousness may result from dangerous cardiac arrhythmias. Stroke. [verywellhealth.com]
Chronic-phase symptoms and signs of Chagas disease may be irregular heartbeats, EKG changes, palpitations, fainting (syncope), cardiomyopathy, congestive heart failure, shortness of breath (dyspnea), emphysema, stroke, sudden death, chronic abdominal [medicinenet.com]
- Cardiomegaly
Chest X-ray may reveal cardiomegaly. In the latent and chronic phases, serology is required. [patient.info]
Detection of IgG antibodies to T. cruzi can be used to demonstrate chronic infections.[5] A chest x-ray may show heart involvement with cardiomegaly. [ncbi.nlm.nih.gov]
There are bibasilar crackles on chest exam and a chest radiograph shows cardiomegaly. Echocardiogram revealed biventricular dilatation with an EF of 25%. Serological testing was positive for Trypanosoma cruzi. [medbullets.com]
- Hypotension
The next day after the surgery (4th postoperative day) the patient presented a decreased level of consciousness (Glasgow coma scale = 8), hypotension and hypoxemia. In two samples of blood cultures there was growth of Leuconostoc mesenteroides. [ncbi.nlm.nih.gov]
- S3 Gallop
Cardiovascular exam reveals an elevated JVD, S3 gallop, and pitting edema of both ankles. There are bibasilar crackles on chest exam and a chest radiograph shows cardiomegaly. Echocardiogram revealed biventricular dilatation with an EF of 25%. [medbullets.com]
Jaw & Teeth
Liver, Gall & Pancreas
- Hepatosplenomegaly
In the chronic phase patients develop hepatosplenomegaly, lymphadenopathy, cardiomyopathy and arrhythmias. Chagas disease is caused by a parasite. It is common in latin america but not in the United States. [icd10data.com]
In October 1986, 7 to 22 days after a meeting at a farm in Paraíba state, 26 individuals presented with a febrile illness associated with bilateral eyelid and lower limb edema, mild hepatosplenomegaly, lymphadenopathy and, occasionally a skin rash. [ncbi.nlm.nih.gov]
Read more Symptoms The disease has two clinical stages: Acute (in which 5% of children die) - characterised by fever, malaise, facial oedema, generalised lymphadenopathy, and hepatosplenomegaly – often spontaneously resolves in four to six weeks Chronic [web.archive.org]
Read more Symptoms The disease has two clinical stages: – Acute (in which 5% of children die) characterized by fever, malaise, facial oedema, generalized lymphadenopathy, and hepatosplenomegaly – often spontaneously resolves in four to six weeks– Chronic [dndi.org]
- Hepatomegaly
In the hospital admission, physical examination showed tachycardia, hepatomegaly, bipalpebral edema and anasarca. Trypanosoma cruzi trypomastigotes were found in microscopy during blood cell count. [ncbi.nlm.nih.gov]
[…] a skin chancre (chagoma) unilateral purplish orbital oedema (Romaña’s sign) with local lymphadenopathy and fever over several weeks More general symptoms include: headache pallor myalgia dyspnoea oedema in inferior limbs or face abdominal pain cough hepatomegaly [gov.uk]
Hepatomegaly and splenomegaly may occur in children with acute Chagas disease, often accompanied by generalized lymphadenopathy. Varying degrees of generalized edema may occur in acutely infected persons, particularly children. [web.archive.org]
However, symptomatic manifestations of the acute phase—such as prolonged fever, headache, myalgia, lymphadenitis, hepatomegaly, and splenomegaly—usually cease within 60 days even without the use of etiological drugs (54). [frontiersin.org]
Face, Head & Neck
- Facial Edema
Clinical findings such as facial edema, gingivitis, and dry cough are probably the consequence of the penetration of the parasite throughout the oral cavity, lips or pharyngeal mucosa. [doi.org]
The most frequent symptoms are fever, dyspnea, myalgias, and generalized and facial edema; ECG changes are also common. [dx.doi.org]
Neurologic
- Headache
In the early stage, symptoms are typically either not present or mild, and may include fever, swollen lymph nodes, headaches, or local swelling at the site of the bite. [dbpedia.org]
If symptoms are present, they may include headache, fever, muscle pain, difficulty breathing, and abdominal or chest pain. During the second or “chronic” phase, the parasites are concentrated mainly in the heart and digestive tissue. [unhco.org]
Caused by the organism Trypanosoma cruzi and spread by the feces of insects commonly called “kissing bugs,” Chagas disease may initially produce an array of vague signs, including headache, fatigue and swollen lymph nodes. [equusmagazine.com]
The most common adverse reactions in patients taking benznidazole were stomach pain, rash, decreased weight, headache, nausea, vomiting, abnormal white blood cell count, urticaria (hives), pruritus (itching) and decreased appetite. [fda.gov]
- Stroke
Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved. [ncbi.nlm.nih.gov]
[…] form cardiac acute myopericarditis chronic fibrosing myocarditis dilated cardiomyopathy symptoms of heart failure ( e.g., paroxysmal nocturnal dyspnea, orthopnea, and jugular venous distension), arrhythmias ( e.g., palpitations, weakness, and syncope), stroke [medbullets.com]
Workup
- Acute phase: During the acute phase, the level of parasitemia is high and the parasites are visible on fresh preparations of blood (anti-coagulated or buffy coat). The level of parasitemia decreases with the next two months. Polymerase chain reaction is very sensitive for detecting infection even before the parasites circulate into the blood.
- Chronic phase: Usually serological methods are used to detect immunoglobulins towards the parasite. Methods used include enzyme-linked immunosorbent assay and immunofluorescent antibody assay. There is no gold standard test for the chronic phase as all the currently available test are not sensitive enough to detect infection [7].
- Imaging: Echocardiography is used to assess the structure and function of the heart in patients with chronic Chagas cardiomyopathy. Electrocardiogram is also indicated to assess for conduction abnormalities. For gastrointestinal disease, barium swallows and enemas are used to assess the extent of disease [8].
X-Ray
- Cardiomegaly on Chest X-ray
[…] at chest X-Ray, 15 with abnormal ECG but normal chest X-Ray, and 11 with abnormalities in the ECG and in the chest X-Ray. [ncbi.nlm.nih.gov]
Microbiology
- Trypanosoma Cruzi
American trypanosomiasis infection due to Trypanosoma cruzi Clinical Information A parasitic infection caused by trypanosoma cruzi. It is transmitted by insect bites. [icd10data.com]
Overview Chagas disease, a serious and potentially fatal infection, is caused by Trypanosoma cruzi, a blood-borne parasite. [aabb.org]
KEYWORDS: Chagas' disease; Heart disease; History of medicine; Thyroid; Trypanosoma cruzi [ncbi.nlm.nih.gov]
Microscopically, T. cruzi can be confused with Trypanosoma rangeli, which is not known to be pathogenic in humans. [en.wikipedia.org]
Chagas disease or american trypanosomiasis is a zoonosis caused by the protozoan parasite Trypanosoma cruzi. Its major manifestations involve the gastrointestinal and cardiac systems. [symptoma.com]
Blocks
- Right Bundle Branch Block
The most common disorders include right bundle branch block alone or in association with left anterior fascicular block. We present an unusual case of a patient with Chagas' cardiomyopathy in association with a preexcitation syndrome. [ncbi.nlm.nih.gov]
bundle branch block (RBBB) Biventricular dilative cardiomyopathy; → heart failure Mural thrombi → stroke Gastrointestinal tract Damage to the submucosal and myenteric plexus → inability to relax lower esophageal sphincter and impaired gut motility → [amboss.com]
Treatment
Acute and indeterminate disease: Antitrypanosomal therapy is recommended to treat acute Chagas disease. The drugs include benznidazole and nifurtimox. These are the only drug that have been shown to be efficacious in humans [9].
Chronic disease: There is no role of antitrypanosomal drugs in treating chronic disease since such therapy will not reverse existing pathology. Focus is on supportive management of cardiac or gastrointestinal disease.
Prognosis
The prognosis in the non-severe acute phase is better as compared to the severe form that has a variable outcome. The chronic phase of the disease is potentially fatal if no intervention is instituted, with cardiac failure or fatal arrhythmias being the cause of mortality.
Etiology
The parasite Trypanosoma cruzi is transmitted into the human host by an insect vector known as reduviid bug.
Epidemiology
Chagas disease is only found in the American continent. It is found in wild animals from the Southern part of the United States to the southern parts of Argentina. Due to the nature of transmission by infected triatomines, it tends to be a disease of the poor. Most infections occur in childhood. The true incidence is difficult to determine because most cases remain undiagnosed [2]. Blood transfusion used to be a major source of transmission in endemic areas but this has dramatically declined after screening of donated blood was implemented [3].
Pathophysiology
Trypanosoma cruzi is transmitted to it hosts (mammals) by hematophagous triatomine insect better known as reduviid bug. The insect gets infected when it feeds on a blood meal from an infected mammal. The parasites mature in the insect's gut and the infective forms of the parasite are excreted in its droppings. The infective parasite usually gains access, through broken skin or mucous membranes like the conjunctiva. This usually occurs after blood meal of the reduviid bug [4]. The parasites may also be transmitted via blood transfusions and organ transplants or orally from contaminated utensils or food. They can also be transmitted from an infected mother to her unborn child.
The parasites then infect the cells of the nearby muscles and subcutaneous tissues. These infected cells soon rupture and the infection spreads systemically. The parasites may reach the cardiac muscles and infect them causing inflammation which is initially acute but eventually becomes chronic. Aggregates of amastigotes may be seen on histology of the heart muscles. The chronic manifestations are caused by a chronic inflammatory response that eventually leads to the pathologic changes observed microscopically and clinically as organ dysfunction [5].
Prevention
The best mode of prevention is breaking the transmission cycle and this may be done by using long lasting residual insecticides in the dwellings that are at risk and improving the living conditions for the inhabitants in endemic zones [10].
Summary
Chagas disease is a parasitic disease which is initially acute and treatable. If left untreated, the disease progresses into a chronic phase with primary damage to the heart and the gastrointestinal tract [1].
Patient Information
Chagas disease is caused by the parasite Trypanosoma cruzi that is transmitted by a bug. Chagas disease may either be acute or chronic; both of which have differet features and are managed differently. The disease can be prevented if proper measures are taken in the areas where the disease is endemic. The treatment for the acute phase is to kill the parasite by using specific medications; whereas in the chronic phase, the treatment is only supportive.
References
- Brun R, Blum J, Chappuis F, Burri C. Human African trypanosomiasis. Lancet 375:148, 2010
- Carabarin-Lima A, González-Vázquez MC, Rodríguez-Morales O, et al. Chagas disease (American trypanosomiasis) in Mexico: an update. Acta Trop. Aug 2013;127(2):126-35
- Kirchhoff LV, Paredes P, Lomelí-Guerrero A, et al. Transfusion-associated Chagas' disease (American trypanosomiasis) in Mexico: Implications for transfusion medicine in the United States. Transfusion 46:298, 2006
- Maguire JH. Trypanosoma. In: Infectious Diseases, 2nd ed, Gorbach S, Bartlett J, Blacklow N (Eds), Lippincott, Williams & Wilkins, Philadelphia 2004.
- Lent H, Wygodzinsky P. Revision of the Triatominae (Hemiptera, Reduviidae), and their significance as vectors of Chagas' disease. Bull Am Museum Natural History. 1979
- Secretaria de Vigilancia em Saude de Brasil. Doenca de Chagas Aguda. Nota Tecnica, 9 de outubro de 2007. Brasilia, Brasil, 2007.
- Bern C, Montgomery SP, Herwaldt BL, et al. Evaluation and treatment of chagas disease in the United States: a systematic review. JAMA 2007; 298:2171.
- Acquatella H. Echocardiography in Chagas heart disease. Circulation 2007; 115:1124.
- Rodriques Coura J, de Castro SL. A critical review on Chagas disease chemotherapy. Mem Inst Oswaldo Cruz 2002; 97:3.
- Moncayo A, Ortiz Yanine MI. An update on Chagas disease (human American trypanosomiasis). Ann Trop Med Parasitol 2006; 100:663.