Abstract
Chagas disease, also known as American trypanosomiasis, results from infection by the protozoan Trypanosoma cruzi, and is a major cause of cardiac disease worldwide. Until recently, Chagas disease was confined to those areas of South and Central America where Trypanosoma cruzi is endemic. With the migration of infected individuals, however, the disease has spread, and it is estimated that 6-7 million people worldwide are infected. In the US alone, more than 7 million people from Trypanosoma cruzi-endemic countries became legal US residents by the turn of the century, resulting in a surge of Chagas disease in this country. According to preliminary estimates, the US now ranks seventh in the Western Hemisphere in number of individuals infected with Trypanosoma cruzi, and the disease has become a major public health concern due to limited awareness in the medical community.
Keywords
Clinical Significance
- •Chagas disease was previously limited to Latin America, where it is the leading cause of nonischemic cardiomyopathy
- •With the migration of infected individuals from Latin America to the US, the US now ranks seventh in the Western Hemisphere in the number of individuals infected with Trypanosoma cruzi.
- •Chagas disease poses a major public health concern in the US because of its rising prevalence and limited awareness within the medical community.
Epidemiology
In Latin America, the triatomine bug thrives in poor housing conditions and commonly infects the rural populations that inhabit dilapidated residences. Transmission in this region most commonly occurs when Trypanosoma cruzi is excreted in the feces of an infected triatomine bug, and the parasites breach the dermis through excoriations in the human skin to gain systemic access. However, Chagas disease also can be transmitted through nonvectorial mechanisms, such as blood transfusion, or vertically from mother to infant. These mechanisms are the main forms of human infestation in urban zones and nonendemic countries and are, therefore, the major targets for reduction of spread.
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Clinical Manifestations
The acute phase of Chagas disease begins after a 1–2-week incubation period following inoculation. The acute phase of the disease then ensues, which is characterized by parasitemia and subsequent immune response. The level of parasitemia is high during this phase, and trypomastigotes are detectable on blood microscopy. Polymerase chain reaction also can be utilized for tissue diagnosis during the acute phase as it offers both a qualitative and quantitative assessment of Trypanosoma cruzi burden.
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The acute phase of Chagas disease has multiple clinical manifestations, most common of which are nonspecific viral-like signs and symptoms including fever, malaise, and lymphadenopathy. For this reason, many infected individuals are not identified, as they often do not seek medical care. Patients may manifest cardiac arrhythmias and transient electrocardiographic abnormalities during the acute phase. In <5% of cases, more severe illness, including myocarditis and meningoencephalitis, can occur.3
It is during this phase that treatment is most effective and can be curative.Following the acute phase, about 30% of patients directly enter the determinate (final) stage, but the majority proceeds to the indeterminate phase, which involves host-parasite equilibrium without progressive host damage. This phase generally carries an excellent prognosis, with survival rates similar to those of noninfected individuals.
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Twenty to thirty percent of infected individuals will progress from the indeterminate to the determinate phase of the disease, during which cardiac symptoms and signs arise. Diagnosis in this stage focuses on detection of serum antibodies to the parasite. Cardiac complications result from remodeling of the cardiac collagenous matrix and subsequent fibrosis, leading to increased myocardial stiffness, systolic and diastolic dysfunction, and ultimately, a severe, dilated cardiomyopathy associated with ventricular arrhythmias and the potential for sudden death, which is the leading cause of mortality in patients with Chagas heart disease.
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Chagas cardiomyopathy also is associated with an elevated risk of stroke. This complication is caused by embolization of intracardiac thrombi related to depressed left ventricular function or aneurysm with subsequent embolization. While the brain is affected most commonly, thrombi may also shower to other vital organs.3
Treatment
The treatment of Chagas disease focuses on anti-infective agents during the acute disease phase, and management of complications in the determinate stage. Two antiparasitic drugs are available for treatment of Chagas disease: benznidazole and nifurtimox. These agents are most effective in the acute phase of the disease, with rates of parasitological cure of 60%-80%.
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Treatment is recommended for all cases of acute, reactivated, or congenitally transmitted infection, and also for children up to age 18 years old with chronic infection.1
Heart failure in Chagas disease is associated with neurohumoral activation similar to other etiologies of dilated cardiomyopathy, and the mainstay of therapy is in accordance with the American College of Cardiology/American Heart Association guidelines for management of patients with systolic heart failure.
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A caveat concerning this approach is the frequently lower blood pressure and higher incidence of bradyarrhythmias in these patients; therefore, they may not tolerate target doses of renin-angiotensin-aldosterone system inhibitors and beta-adrenergic blockers. Importantly, outcomes have been improved even at nontarget doses with these agents.6
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Cardiac resynchronization therapy can be considered for patients with severe systolic dysfunction (left ventricular ejection fraction <35%) and prolonged QRS complex. In this group, resynchronization therapy has improved New York Heart Association Functional Class significantly, increased left ventricular ejection fraction, and enhanced survival in patients with chronic Chagas cardiomyopathy.
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In those patients who fail maximal medical treatment for heart failure, a left ventricular assist device and, ultimately, cardiac transplantation may be considered.As previously noted, sudden cardiac death is the leading cause of mortality in these patients. The implantable cardioverter-defibrillator has been used to prevent sudden cardiac death in patients with Chagas cardiomyopathy.
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Some data also suggest that amiodarone can improve survival in patients who are at high risk of arrhythmic death; thus, amiodarone has been recommended as the treatment of choice for all patients with sustained ventricular tachycardia, and also for those with nonsustained ventricular tachycardia and myocardial dysfunction. Additionally, therapy with implantable cardioverter-defibrillator plus amiodarone was superior to amiodarone alone for secondary prevention of sudden death in patients with Chagasic cardiomyopathy.2
Patients with high-degree atrioventricular block or with symptomatic bradycardia warrant treatment with permanent cardiac pacing.10
These patients often require high pacing output and have an increased incidence of new-onset atrial fibrillation following device implantation.- Epstein A.
- DiMarco J.
- Ellenbogen K.
- et al.
ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons.
Circulation. 2008; 117: e350
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Conclusion
Chagas disease is increasing in importance in the US. In the past, this disease was primarily limited to regions in South America; however, with globalization it is now on the rise in this country. Diagnosis can be suspected based on clinical symptoms and confirmed with serologic testing. Treatment in the acute phase is highly effective, but oftentimes these patients do not present in this phase, and chronic infection ensues. The mainstay of treatment focuses on heart failure management and both medical and device therapy for arrhythmia treatment. The primary method of control is prevention of transmission. In Latin America, vector control strategies have been implemented by insecticide spraying campaigns to eradicate the triatomine bug. In the US, this goal is being approached by increasing awareness of Chagas disease to identify and treat patients, and by legal requirements to optimize the safety of blood supply.
References
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Malik L, Singh G, Amsterdam E. The epidemiology, clinical manifestations and management of Chagas heart disease. Clin Card. Currently in press.
- The Assasin: Chagas Cardiomyopathy.Am J Med. 2013; 126: 864-867
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- Clinical course of Chagas heart disease: a comparison with dilated cardiomyopathy.Int J cardiol. 1997; 60: 187-193
- Clinical and therapeutic aspects of heart failure due to Chagas disease.Arq Bras Cardiol. 2006; 86: 297-302
- Cardiac resynchronization therapy in patients with chronic Chagas cardiomyopathy: long-term follow up.Rev Bras Cir Cardiovasc. 2014; 29: 31-36
- Long-term follow-up of patients with chronic Chagas disease and implantable cardioverter-defibrillator.Pacing Clin Electrophysiol. 2014; 37: 751-756
- ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons.Circulation. 2008; 117: e350
- Permanent pacing in patients with Chagas’ disease.Pacing Clin Electrophysiol. 2012; 35: 1494-1497
Article info
Publication history
Published online: June 04, 2015
Footnotes
Funding: None.
Conflict of Interest: All authors have no conflict of interest.
Authorship: All authors had access to the data and a role in writing the manuscript.
Identification
Copyright
© 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
