INTRODUCTION
Parasitic infections previously seen only in developing countries are now diagnosed anywhere in the world due to better tourism marketing, immigration, immunosuppression, increasing numbers of HIV/acquired immunodeficiency syndrome, organ transplantation, and blood transfusion. Parasitic infection of the heart is highly associated with significant morbidity and mortality, especially in high endemic zone.[1] Therefore, clinicians anywhere around the world must be aware of the potential cardiac manifestations of parasitic infections. In this review, we aim to highlight some important cardiac manifestations of commonly identified parasites.
CLASSIFICATION
Cardiac manifestation of parasitic infection can be broadly classified into two major groups, depending upon affected layers of the heart [Table 1] and the class of parasites [Table 2].
;)
Table 1: Classification based on preferentially involved layer
Table 2: Classification based on class of parasite
ETIOPATHOGENESIS OF PARASITIC DISEASES OF THE HEART
The pathophysiology of structural damage to the heart by parasites may vary depending upon the etiology and hence the exact mechanism remains poorly understood in certain species. However, it has been elucidated that generally the parasites affect various structures of the heart, such as the myocardium, pericardium, and pulmonary vasculature directly or by indirect mechanisms such as by their presence elsewhere in the human host or by producing immune reactions.[1]
African trypanosomiasis, toxoplasmosis, trichinellosis, amoebiasis, and many other parasitic diseases may produce direct damage to the myocardium, leading to myocarditis and cardiomyopathy, while echinococcosis and cysticercosis affect the pericardium and associated with pericarditis, pericardial effusions, constrictive pericarditis, or cardiac tamponade due to rupture of cyst.[3] Certain species like Schistosoma damage the heart by indirect mechanisms in the form of their presence elsewhere in the human host such as pulmonary hypertension (PH) associated with hepatosplenic schistosomiasis. High-output cardiac failure may develop due to severe anemia following intestinal parasitic infestations (Ancylostoma duodenale or Necator americanus), malaria, or visceral leishmaniasis.[1]
Parasites like Trypanosoma cruzi (Chagas disease) may cause immune-mediated inflammatory reactions. The recruitment and migration processes of inflammatory cells to the myocardium during infection involve pro-inflammatory cytokines, adhesion molecules, and extracellular matrix interactions. These inflammatory reactions may result in myocardial damage, which can manifest clinically as congestive heart failure, arrhythmias, sudden cardiac death, and thromboembolic events.[3] Therefore, parasitic infections can produce a wide spectrum of cardiac manifestations depending upon the etiopathogenesis and this is demonstrated in Figure 1.
Figure 1: Pathogenesis and cardiac manifestations of parasitic infection
CARDIAC MANIFESTATION OF SPECIFIC SPECIES
Protozoa
There are many protozoans known to affect the heart, as mentioned in Table 2; their clinical manifestations may widely vary depending upon the species. Only the most common identified protozoans involving the heart are discussed below:
Chagas disease (American trypanosomiasis)
Chagas disease also known as American trypanosomiasis is a tropical parasitic disease caused by T. cruzi [Figure 2]. Majority of the cases were previously reported from rural areas of Central and South America. But now, it has become a global health problem due to various reasons such as tourism, immigration, and immunosuppression.[4] Chagas disease remains one of the most common causes of nonischemic cardiomyopathy throughout the world, especially in Latin America, although the incidence is changing. Vector-borne transmission by triatomine bugs is the major route of infection in endemic areas but can also occur through blood transfusion, organ transplantation, vertically from mother to infant, and more rarely by consumption of contaminated food with T. cruzi.[5] The exact pathogenesis of myocarditis and subsequent myocardial dysfunction in Chagas disease is still undetermined. Nevertheless, it well known that Chagas disease has two different clinical phases. The incubation period following exposure to the vector bug is 1–2 weeks, after the acute phase begins. The initial phase of infection with T. cruzi lasts for around 4–8 weeks and then the chronic phase follows throughout life. Most affected patients are either asymptomatic or have only a mild febrile illness in acute phase. Severe complications occur in <1% of patients which clinically manifested as myocarditis and pericarditis. On investigations, nonspecific electrocardiogram (ECG) changes, atrioventricular block, and cardiomegaly on chest X-ray are usual findings. Approximately 90% of the affected patients recover spontaneously and mortality occurs in <5%–10%, which are mostly due to cardiac and neurological complications.[6]
Figure 2: (a) Two-dimensional echocardiography at the apical four-chamber view showing a small left ventricular apical aneurysm with a thrombus (arrow). (b) Macroscopic four-chamber frontal view of Chagas heart disease showing a typical apical aneurysm with thrombus. LA: Left atrium, LV: Left ventricle, RA: Right atrium, RV: Right ventricular. (Courtesy Dr. Maria Carmo P Nunes, Hospital das Clinicas, School of Medicine, Federal University of Minas Gerais)
About 20%–40% of patients with acute phase may progress to chronic phase of Chagas disease. The chronic phase is generally preceded by long period of asymptomatic phase called indeterminate form, which lasts for the first one to three decades. The indeterminate form is characterized by the presence of antibodies against T. cruzi in serum but no signs and symptoms of T. cruzi infection. Rassi et al. reported that despite ongoing disease at cellular level, 50%–90% of patients with chronic phase of Chagas disease may remain asymptomatic clinically.[7] The major clinical manifestations of determinate form of chronic Chagas disease include heart failure, cardiac arrhythmias, systemic and pulmonary thromboembolism, and chest pain syndrome. The major pathophysiologic mechanisms responsible for this phase are primarily due to myocardial fibrosis, destruction of the conduction system, ventricular dilation, thinning of the apex of the heart, and formation of a thrombus in the apex of the heart [Figure 3].
Figure 3: Trypanosoma cruzi amastigotes (arrow) in the myocardium of Chagas cardiomyopathy. (Courtesy Dr. Carlos Franco-Paredes, Division of Infectious Diseases, Emory University School of Medicine)
One serious complication associated with T. cruzi is Chagas cardiomyopathy. Clinical manifestations of Chagas cardiomyopathy depend on the severity of myocardial dysfunction, damage to the conduction system, and presence of thromboembolic events. The most common ECG abnormalities are right bundle branch blocks with or without left anterior and/or atrioventricular blocks.[8] The most distinct feature of Chagas cardiomyopathy is presence of fibrosis that typically involves the posterior and apical regions of the left ventricle (LV). In addition, the clinical progression and outcomes of Chagas cardiomyopathy are significantly poorer than those with noninflammatory forms of dilated cardiomyopathy. On echocardiogram, diastolic dysfunction generally precedes systolic dysfunction, thus providing a clue to early detection of cardiac involvement in Chagas disease.[9] Other echocardiographic features include apical aneurysms, segmental left ventricular (LV) regional wall motion abnormality (particularly posteroinferior wall); and reduced LV systolic function [Figure 3].
Accurate diagnosis of acute Chagas myocarditis relies on identification of the parasite and/or IgM antibodies against anti-T. cruzi in background of true epidemiological and clinical picture. Endomyocardial biopsy is generally not required to establish the diagnosis of Chagas myocarditis except in cardiac transplantation when the distinction between acute Chagas myocarditis and implant rejection is crucial. However, it must be emphasized that since Chagas cardiomyopathy usually presents many years after the initial infection, and therefore, patients who migrated to nonendemic areas are still at risk of developing cardiomyopathy.[10]
The goal of treatment in all forms of Chagas disease is to eradicate the parasite. Antitrypanosomal treatment is strongly recommended for all patients with acute, congenital, and reactivated infections. However, antiparasite treatment generally is not indicated in patients with advanced heart failure from Chagas disease. Therapeutic management of Chagas disease involves parasite-specific therapy (nifurtimox or benznidazole) and standard treatment strategy for heart failure with reduced ejection fraction, arrhythmias, and thromboembolic events. Implantable cardioverter-defibrillators should be considered to prevent sudden cardiac death in high-risk patients, and heart transplantation is the treatment of choice for patients with refractory end-stage heart failure.[11]
African trypanosomiasis
African trypanosomiasis, also known as sleeping sickness, is caused by Trypanosoma species. There are two forms of the disease: the West and East African trypanosomiasis that are caused by Trypanosoma bruceigambiense and T. bruceirhodesiense, respectively. They are transmitted by the bite of tsetse flies, which are found mainly in the west and central part of Africa. The morphological appearances of both species are similar but cause distinct diseases that differ in their clinical presentation and prognosis.
T. bruceigambiense usually causes endemic disease with chronic manifestations, while T. bruceirhodesiense is an acute epidemic disease. The disease is manifested in three stages: the first stage is characterized by a painful chancre at the site of the inoculation, followed by hemolymphatic stage in which a systemic febrile illness develops as the parasites disseminate and circulate throughout the body via the bloodstream and lymphatic system. The last stage, meningoencephalitic stage, is characterized by the development of various neurological complications.[2]
Cardiac involvement is more frequently observed in T. bruceigambiense infection, during the hemolymphatic stage. It is characterized by acute, severe febrile disease with myocarditis or pancarditis. The pathophysiology of cardiac involvement in African trypanosomiasis is due to infiltration of perivascular structure by the parasite and lymphocytes leading to endarteritis and myocardial fibrosis. The most common abnormal findings in ECG include low voltage, P-R segment depression, and repolarization changes and QT interval prolongation. Remarkably, conduction defect is not a prominent feature of cardiac complication in sleeping sickness.
The definitive diagnosis is made by identification of the trypanosomes in blood, chancre fluid, lymph node aspirates, or cerebrospinal fluid. Serologic testing is useful for screening in control programs and untreated disease is almost invariably fatal. The treatment regimen of African trypanosomiasis depends upon the species and the clinical stage of infection. In the hemolymphatic stage, suramin is recommended for T. bruceirhodesiense while pentamidine or suramin (as an alternative) is recommended for T. brucei gambiense.[12]
Leishmaniasis
Leishmaniasis refers to a heterogeneous group of vector-borne diseases caused by protozoa of the genus Leishmania and is transmitted by sand fly vectors. Cardiac involvement in leishmaniasis infection is rare and limited to case reports of myocarditis and pericarditis.[13] However, certain drugs administered for treating the disease such as sodium stibogluconate and meglumine antimoniate can cause serious cardiotoxicity which may even lead to death. Toxicity of the drugs is usually related to the cumulative dose. Antimony can lead to nonspecific ECG changes, including flattening or inversion of the T waves, prolongation of QT interval to >0.5 s, or development of T wave inversion with concave ST segments. Arrhythmias, such as premature atrial and ventricular contraction, and torsades de pointes occur especially with dosage higher than 20 mg of pentavalent antimonial/kg/day. Any preexisting cardiac disease is thought to increase the risk of cardiotoxicity and antimonial drugs should be used cautiously in such patients. Cardiac dysfunction due to leishmaniasis often resolved spontaneously after elimination of the causative parasite.[14]
Toxoplasmosis
Toxoplasmosis is caused by Toxoplasma gondii, a parasite of members of the cat family, and humans serve as intermediate hosts. Humans acquire infection by consumption of undercooked meat and contaminated water, fecal-oral transmission from feline feces, vertically through transplacental transmission, blood transfusion, and transplantation. The clinical expression of toxoplasmosis depends on the level of immunity in the human host. In immunocompetent persons, primary infection is most often asymptomatic but rarely may present as acute undifferentiated febrile illness. Cardiac complications such as myocarditis, pericardial effusion, constrictive pericarditis, arrhythmias, and congestive heart failure have been described even among immunocompetent patients with toxoplasmosis.[15] In patients with acquired immunodeficiency syndrome, the heart is the second most commonly affected organ after the brain. The exact prevalence of cardiac toxoplasmosis is uncertain because cardiac involvement is usually clinically silent in most cases and usually dominated by CNS manifestations. Toxoplasmosis is the most commonly identified parasitic infection among patients with heart transplantation and it may mimic organ rejection.[16] The definitive diagnosis of cardiac toxoplasmosis relies on serology or identification of the bradyzoites in myocardial tissue. The treatment of choice is based on a combination of pyrimethamine and sulfadiazine or pyrimethamine and clindamycin.[17]
Amoebiasis
Amoebiasis is caused by a protozoan Entamoeba histolytica, which is mainly transmitted by the feco-oral route. Extraintestinal amoebic disease mainly affects the liver, but more rare manifestations such as pulmonary, cardiac, and brain involvement have been reported.[18] When cardiac involvement occurs, it usually results from rupture of a liver abscess into the pericardium, particularly from abscesses involving the left lobe of the liver, and it is considered a serious complication of amoebiasis.[18] Rarely, rupture of an amoebic abscess from liver, lungs, or pleura into the pericardium may cause acute cardiac tamponade, chest pain, or heart failure.[19] The diagnosis is usually established by serology. Treatment of pericardial amoebiasis requires a combination of surgical drainage and metronidazole.
Helminths
The helminths that involve the human heart comprise a variety of species such as the trematodes (schistosomes and other flukes), the cestodes (tapeworms), and the nematodes (intestinal and tissue roundworms). These helminths affect the heart directly or indirectly in their various forms – worms, larval forms, or eggs form, thereby causing different cardiac diseases. Only a few helminths which commonly cause cardiac diseases will be discussed below.
Schistosomiasis
Schistosomiasis is a tropical helminth infection caused by trematode flatworms of the genus Schistosoma. The parasites that cause schistosomiasis live in certain types of freshwater snails. Schistosome infections are classified into acute and chronic phases. The acute phase is usually manifest in people who live in nonendemic areas like travelers, because these individuals have not yet developed immunity. In contrast, the chronic phase is observed among individuals living in an endemic area with ongoing exposure to the parasite.[20] Involvement of the heart by Schistosoma species is considered a rare event and is usually caused by the host immune response to the migrating eggs leading to an eosinophilic granulomatous reaction. The most prominent cardiopulmonary complication of chronic schistosomiasis is cor-pulmonale secondary to pulmonary arterial hypertension (PAH). In fact, schistosomiasis-associated PAH is one of the most common causes of PAH in an endemic area. PAH due to schistosomiasis is commonly observed among hepatosplenic form of Schistosoma mansoni, Schistosoma japonicum, or Schistosoma haematobium infection. The exact pathogenesis of schistosomiasis-associated PAH remains unknown, but the speculated mechanisms include mechanical obstruction of lung vasculature by the eggs and pulmonary vascular inflammation with remodeling and carry a grave prognosis and usually represents end-stage disease which is irreversible.[21] Echocardiography is a useful screening tool for PH in patients with hepatosplenic schistosomiasis. The diagnostic of schistosomiasis-associated PAH is warranted for patients presenting with PH in the setting of appropriate epidemiologic exposure. Praziquantel is the treatment of choice for all species of schistosome. Treatment of schistosomiasis-associated PAH is still a matter of debate, and it has been reported that antihelminth agent does not provide clinical and mortality benefits in such patients.[22]
Echinococcosis (hydatid cyst)
Echinococcosis is caused by infection with the tapeworm Echinococcus, and cystic echinococcosis caused by Echinococcus granulosus is the most common form encountered in humans. The usual host of E. granulosus is dog, but humans may serve as intermediate hosts if they accidentally ingest ova from contaminated dog feces. The formation of hydatid cysts may take over months to years and may remain asymptomatic in most cases. Cysts are mostly found in the liver and the lung, but when the heart is involved, it is usually univesicular, located intramyocardially in the interventricular septum or left ventricular free wall. Most cases of pericardial echinococcosis may be due to spread from an initial location at the liver dome. Cyst rupture may lead to cardiac tamponade and can even mimic ST-segment elevation myocardial infarction upon electrocardiography. Rarely, acute pericarditis following rupture may even progress to chronic constrictive pericarditis. The diagnosis relies on positive serologic test, and echocardiography is an important screening tool for cardiac involvement. The drug of choice for the treatment of echinococcosis is albendazole, mebendazole, and/or praziquantel. When feasible, surgical removal is recommended even in asymptomatic cases as rupture of cyst can cause catastrophic complications.[23]
Cysticercosis
Cysticercosis is caused by the larval stage (metacestode) of the pork tapeworm Taenia solium. While cerebral cysticercosis is the most common and serious complication, it may also involve a wide range of extraneural tissues such as occular, spinal, cutaneous, muscular, or cardiac muscle. Clinical manifestations usually develop at the time of cyst degeneration, but the trigger for this event is unknown. Cardiac cysticercosis is extremely rare and often asymptomatic, and they are usually discovered during cardiac surgery or at autopsy. One autopsy report has shown the prevalence of 20%–25% in patients with concomitant documented neurocysticercosis.[24] Cardiac cysticercosis is usually multiple and may affect all layers of the heart. The most common cardiac manifestations are arrhythmias and conduction abnormalities, due to the formation of granuloma and myocardial fibrosis in response to local inflammatory reaction. The diagnosis is mainly based on serological test in the context of true epidemiology. Echocardiography plays an important role in identifying cardiac cysts and occasionally identifies cardiac cysts in routine screening for other purposes. The role of antihelminths such as albendazole and praziquantel or surgery in cardiac cysticercosis remains elusive and has not been properly investigated yet.[25]
Trichinellosis
Trichinellosis is caused by nematodes (roundworms) of the genus Trichinella and has a worldwide distribution. Consumption of raw or undercooked meat (e.g., pork) is the major route of infection. The clinical manifestation of trichinellosis is directly correlated with the number of larvae ingested. Although cardiac involvement is rare, it represents the most severe form of the disease and life-threatening cardiac arrhythmias are considered the most common cause of death in trichinellosis.[26] The pathophysiology of cardiac manifestation in trichinellosis is not caused by the direct formation of cyst within the myocardium, but is due to an eosinophilic-enriched inflammatory response resulting in myocarditis, similar to the pathogenic process as observed in tropical endomyocardial fibrosis (EMF). Nonspecific ST-T wave change is the most frequently observed abnormality in ECG. The diagnosis of trichinellosis is usually based on the typical clinical presentation in the presence of eosinophilia, and confirmation is based on serology and tissue biopsy. Systemic symptoms are treated with antiparasitic drugs such as albendazole or mebendazole and steroids should be reserved for severe cases like myocarditis.[27]
Tropical endomyocardial fibrosis
EMF is typically a disease of young, characterized by fibrosis of the apical endocardium of the right ventricle, left ventricle, or both, leading to restrictive physiology. Accurate epidemiologic data are unknown, but are considered one of the most common causes of restrictive cardiomyopathy, especially in resource constraint countries.[28] The exact pathogenesis of this entity remains unclear. Due to pathological similarities with the Loffler syndrome, chronic hypereosinophilia is considered the primary initiating factor for EMF.[29] Helminths, especially filariae, are the most common tropical infection found associated with chronic eosinophilia and EMF. The clinical presentations of tropical EMF are similar to restrictive cardiomyopathy and sometimes complicated by mural thrombus formation, arrhythmias, and pericardial effusion. Echocardiographic criteria are utilized to diagnose EMF, and magnetic resonance imaging plays an emerging role. Patients are medically managed with standard heart failure therapy and surgical resection of significant apical obliteration shows promising result in experienced centers.[30]
CONCLUSION
All over the world, the prevalence of parasitic infection leading to cardiac complications is on the rise due to increased immigration, immunocompromised status, and better diagnostic facilities. The clinical manifestations may vary from asymptomatic cases to severe complications like fulminant myocarditis, which depend upon the virulence of parasite and involved layer of the heart. Table 3 summarizes the important characteristics of the most frequently identified parasites with cardiac involvement. Due to scarcity of this entity in nonendemic area, diagnosis requires a high index of suspicion along with appropriate investigations. It remains a public health challenge due to lack of awareness, effective chemoprophylaxis, and vaccine. Therefore, the treating physician must consider parasites as a possible etiology while dealing with various cardiac diseases and more research is needed in future for better management of parasitic infection complicated by cardiac diseases.
Table 3: Important clinical features commonly identified parasites that affect the heart
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
REFERENCES
1. Franco-Paredes C, Rouphael N, Méndez J, Folch E, RodrÃguez-Morales AJ, Santos JI, et al. Cardiac manifestations of parasitic infections part 1:Overview and immunopathogenesis. Clin Cardiol 2007;30:195–9.
2. Bennett JE, Dolin R, Blaser MJ. Bennett's Principles and Practice of Infectious Diseases Philadelphia, PA Elsevier Churchill Livingstone 2014.
3. Rocha A, de Meneses AC, da Silva AM, Ferreira MS, Nishioka SA, Burgarelli MK, et al. Pathology of patients with Chagas'disease and acquired immunodeficiency syndrome. Am J Trop Med Hyg 1994;50:261–8.
4. World Health Organization. Chagas disease in Latin America:an epidemiological update based on 2010 estimates. Wkly Epidemiol Rec 2015;90:33–43.
5. Magill AJ, Reed SG. American Trypanosomiasis Strickland GT. Hunter's Tropical Medicine and Emerging Diseases 8th ed Philadelphia, PA W. B. Saunders Company 2000 653–664.
6. Dias E, Laranja FS, Miranda A, Nobrega G. Chagas'disease;a clinical, epidemiologic, and pathologic study. Circulation 1956;14:1035–60.
7. Rassi A Jr, Rassi A, Marin-Neto JA. Chagas disease. Lancet 2010;375:1388–402.
8. Rocha MO, Ribeiro AL, Teixeira MM. Clinical management of chronic Chagas
cardiomyopathy. Front Biosci 2003;8:e44–54.
9. Migliore RA, Guerrero FT, Armenti A, Fernandez C, Adaniya ME, Iannariello J, et al. Diastolic function in Chagas disease. Medicina (B Aires) 1990;50:537–42.
10. RamÃrez JD, Guhl F, Umezawa ES, Morillo CA, Rosas F, Marin-Neto JA, et al. Evaluation of adult chronic Chagas'heart disease diagnosis by molecular and serological methods. J Clin Microbiol 2009;47:3945–51.
11. Rodriguez H, Munoz M, Llamas G, Iturralde P, Medeiros A, Delgado L, et al. Automatic, implantable cardioverter-defibrillator in a patient with chronic Chagas cardiopathy and sustained ventricular tachycardia. Arch Inst Cardiol Mex 1998;68:391–9.
12. Drugs for parasitic infections. Med Lett 2007;5 Suppl e1–14.
13. Puerto-Alonso JL, Molina-Ruano FJ, Gómez-Soto F, Gómez-RodrÃguez F. Visceral leishmaniasis with cardiac affectation in an immunocompetent patient. Med Clin (Barc) 2006;127:519.
14. Herwaldt BL, Berman JD. Recommendations for treating leishmaniasis with sodium stibogluconate (Pentostam) and review of pertinent clinical studies. Am J Trop Med Hyg 1992;46:296–306.
15. Chandenier J, Jarry G, Nassif D, Douadi Y, Paris L, Thulliez P, et al. Congestive
heart failure and myocarditis after seroconversion for toxoplasmosis in two immunocompetent patients. Eur J Clin Microbiol Infect Dis 2000;19:375–9.
16. Adair OV, Randive N, Krasnow N. Isolated toxoplasma myocarditis in acquired immune deficiency syndrome. Am Heart J 1989;118:856–7.
17. Wreghitt TG, Gray JJ, Pavel P, Balfour A, Fabbri A, Sharples LD, et al. Efficacy of pyrimethamine for the prevention of donor-acquired
Toxoplasma gondii infection in heart and heart-lung transplant patients. Transpl Int 1992;5:197–200.
18. Ibarra-Pérez C. Thoracic complications of amebic abscess of the liver:Report of 501 cases. Chest 1981;79:672–7.
19. Samsuzzaman SM, Hashiguchi Y. Thoracic amebiasis. Clin Chest Med 2002;23:479–92.
20. Visser LG, Polderman AM, Stuiver PC. Outbreak of schistosomiasis among travelers returning from Mali, West Africa. Clin Infect Dis 1995;20:280–5.
21. Kumar R, Mickael C, Chabon J, Gebreab L, Rutebemberwa A, Garcia AR, et al. The causal role of IL-4 and IL-13 in
Schistosoma mansoni pulmonary hypertension. Am J Respir Crit Care Med 2015;192:998–1008.
22. Kolosionek E, Crosby A, Harhay MO, Morrell N, Butrous G. Pulmonary vascular disease associated with schistosomiasis. Expert Rev Anti Infect Ther 2010;8:1467–73 doi:10.1586/eri.10.124.
23. Guidelines for treatment of cystic and alveolar echinococcosis in humans. WHO Informal Working Group on Echinococcosis. Bull World Health Organ 1996;74:231–42.
24. Lino RS Jr, Reis MA, Teixeira VP. Occurrence of encephalic and cardiac cysticercosis (
Cysticercus cellulosae) in necropsy. Rev Saude Publica 1999;33:495–8.
25. Lino RD Jr, Ribeiro PM, Antonelli EJ, Faleiros AC, Terra SA, dos Reis MA, et al. Developmental characteristics of
Cysticercus cellulosae in the human brain and heart. Rev Soc Bras Med Trop 2002;35:617–22.
26. Siwak E, Droń D, Pancewicz S, Zajkowska J, Snarska I, Szpakowicz T, et al. Changes in ECG examination of patients with trichinosis. Wiad Lek 1994;47:499–502.
27. Moorhead A, Grunenwald PE, Dietz VJ, Schantz PM. Trichinellosis in the United States, 1991–1996:Declining but not gone. Am J Trop Med Hyg 1999;60:66–9.
28. Grimaldi A, Mocumbi AO, Freers J, Lachaud M, Mirabel M, Ferreira B, et al. Tropical endomyocardial fibrosis:Natural history, challenges, and perspectives. Circulation 2016;133:2503–15.
29. Weller PF, Bubley GJ. The idiopathic hypereosinophilic syndrome. Blood 1994;83:2759.
30. Schneider U, Jenni R, Turina J, Turina M, Hess OM. Long-term follow up of patients with endomyocardial fibrosis:Effects of surgery. Heart 1998;79:362–7.
