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Does Changas' disease exist as an undiagnosed form of cardiomyopathy in the United States?
EDITORIALS
Does Chagas’ disease exist as an undiagnosed form of cardiomyopathy United States?
in the
Jose Milei, MD, Branco Mautner, MD, Ruben Storino, MD, Julian A. Sanchez, MD,” and Victor J. Ferrans, MD, PhD.a Buenos Aires, Argentina, and Bethesda, Md.
Chagas’ disease (American trypanosomiasis), a chronic illness caused by the flagellate parasite Trypanosoma cruzi, was first described in 1909 by the Brazilian physician Carlos Chagas. The insect vectors of the disease are present throughout most of South and Central America, and their zone of distribution extends across the southern United States, where at least some of these vectors are infected with Trypanosoma.’ Several animal species in this zone are affected by the disease in their natural habitats. Many believe that Chagas’ disease was first transmitted to humans after the Incas brought infected wild animals to raise near their homes.2 Chagas’ disease is considered to be an “exotic” disease in the United States, where it is rarely detected.3, 4 The infection is characterized by an acute symptomatic phase with high parasitemia, and is followed by a lifelong indeterminate phase in which low numbers of parasites are sequestered in tissues5; however, the acute phase often is clinically silent. Chronic progressive Chagas’ disease develops in 10 5% to 20 % of previously asymptomatic, infected individuals. It is manifested by a chronic, diffuse, progressive, fibrosing myocarditis that involves not only the working myocardium but also the atridventricular conduction system.6, 7 This leads to cardiomegaly, cardiac failure, arrhythmias, thromboembolic phenomena, and death.6 Megacolon and megaesophagus may also occur.
From the Centro de Enfermedad de Chagas, Division Fernandez, Buenos Aires; and BPathology Branch, and Blood Institute, National Institutes of Health, This study Organization Received Reprint Buenos
for publication
Oct. 31, 1991;
requests: Jose Milei, Aires, Argentina.
411136476
1732
was partially supported with (T80/181/11/ID 870343).
a grant accepted
MD, CARDIOPSIS,
Cardiologia, Hospital National Heart, Lung, Bethesda.
from Dec.
TDR,
World
Health
16, 1991.
Tucuman
2163 4” B, 1050
Myocardial biopsy studies83 g of the chronic form of Chagas’ disease have revealed myocyte hypertrophy and degeneration, focal lymphocytic infiltration, and interstitial fibrosis. In addition to these nonspecific changes, these studies have shown marked thickening of the basement membranes of the cardiac myocytes and capil1aries.s It has not yet been determined to what extent these changes may help in the differential diagnosis of Chagas’ disease from other cardiomyopathies. It is well established that intracellular parasites are found in cardiac myocytes only during the acute phase. At the present time the diagnosis of chronic chagasic cardiomyopathy cannot be made only on the basis of microscopic study of the heart. The left ventricular apical aneurysms found in patients with the chronic form of chagasic cardiomyopathy constitute a highly interesting and clinically important feature of this disorder. A recent study” established morphologic-electrophysiologic correlations in these lesions. Chronic recurrent ventricular tachyardia occurred in three patients with chagasic aneuryms and intraoperative ventricular mapping studies indicated that these arrythmias originated in regions adjacent to the aneurysms. The edges of the surgically resected aneurysms showed hypertrophy of myocytes and partial or complete loss of myofibrils, mitochondrial swelling, accumulation of lipofuscin granules, intracellular edema, and thickening of the basement membrane of the myocytes and vascular endothelial cells and smooth muscle cells. The interlaced fronts of healthy (fast conducting) and “early” damaged (slow conducting) myocytes were considered to have the configuration of ideal reentry circuits. Further evidence that the arrythmias originated in these regions was their abolition by aneurysm resection. Prevalence of Chagas’ disease in Latin America. In Latin America, 16 to 18 million people are thought to have Chagas’ diseaseand 90 million are considered to
Volume Number
123 6
be at risk of infection.ri In its usual mode of transmission, the disease is spread by the insect vectors, usually members of the Reduviidae family (kissing bug). These insects puncture the skin of the host to suck blood. They carry T. cruzi in their gastrointestinal tract; they defecate as they suck blood, and the excreted T. cruzi then penetrates into the host through the punctured skin. Because of regional variations in the biologic behavior of insects that can serve as T. cruzi vectors and because of the nature of the living conditions of the local human populations, vector transmission of Chagas’ disease is extremely unlikely to occur in the U.S. Asymptomatic patients with the chronic phase of Chagas’ disease can have a low degree of parasitemia and blood transfusions are the second most frequent mode of transmission of Chagas’ disease. I2 The congenital form, transmitted through the placenta, is also relatively frequent.3 The prevalence of Chagas’ disease is expected to be increased in cities in which there is heavy migration of individuals from the countryside, where infection is more prevalent, than in large urban centers. The incidence of infection with T. cruzi in some urban centers in Latin America is extremely high. For example, the cities of Goiana (Brazil), Tegucigalpa (Honduras), and Santa Cruz (Bolivia) are known to have a 25.8 % , 28%, and 63 % , respectively, prevalence of infection.t2 For Brazil’s Federal District (Brasilia), which had 1 million inhabitants, vital statistics in 1977/78 indicated that 4.3% of all deaths were attributed to Chagas’ disease.13 If we consider all the Latin American countries, an overall prevalence of 7.4 % may be calculated.14 Therefore it is not surprising that transfusions are an important source of transmission. Data from Brazil point out that a mean of 7% of blood donors have positive serologic tests for T. cruzi .I3 The estimated risk for transmission is 13% to 23 % for each unit of contaminated blood transfused. l5 SchmuniP has estimated that the attack rate after transfusion of seropositive blood products ranges from 12% to 50%. In 1988, it was estimated that as many as 20,000 individuals per year became infected with T. cruzi through blood transfusions in Brazil.13 In one department of Bolivia the rate of infection of T, cruzi among blood donors in a blood bank was found to be 51% in 1989.t6 The United States seemed spared by the disease, but recently blood banks in the United States have faced the problem of transfusion-associated Chagas’ disease 4,17-19 Acute Chagas’ disease in the United States. Chagas’ disease has been limited to the New World tropics and has never been endemic in the United States.20-22 In spite of the presence of T. cruzi-infected insects in
Chagas’ disease in the USA
1733
many parts of the southern and southwestern United States, only a few cases of acute Chagas’ disease resulting from vector transmission have been described in the U.S.21j 22 A case of Chagas’ disease transmitted by an insect in northern California was diagnosed in 1982, the first such case reported since 1955, when two infants in Texas were diagnosed with domestically acquired Chagas’ disease.22 In the last 20 years, six laboratory-acquired infections and nine imported cases of acute Chagas’ disease have been reported”; however, the number of vector-related and imported cases of acute T. cruzi infection that go unrecognized may be several times the number reported. Chagas’
disease
in Latin
American
immigrants.
According to the Immigration and Naturalization Service,23 from 1961 to 1987 almost 5 million immigrants from Latin America settled in the United States. The prevalence of chagasic infection in these immigrants has not been assessed. Only two studies have been made of the incidence of positive serologic reactions for T. cruzi among Latin American immigrants in the United States: one in Washington, D.C.24 and one in Los Angeles, California.25 Most of the participants in both surveys were from Central American countries, and it is not possible to estimate from the published data how representative they were of the immigrant population derived either from their countries or from all of Latin America. From August 1989 to June 1990,3492 prospective donors at the Los Angeles County-University of Southern California Medical Center met all standards for donating blood; 72 were deferred because they might be infected with T. cruzi. Forty-five of this number agreed to be serologically tested and positive results were obtained in two of them (4.4%).25 These findings were interpreted as suggesting that there may be upwards of 50,000 T. cruzi-infected Central American immigrants in the United States.* The estimates, cited above, of 5 million Latin Americans migrating into the U.S. from 1961 to 1987, and an overall 7.4% incidence of Chagas’ disease in Latin American, served as the basis for calculating that the number of persons infected with T. cruzi and living in the U.S. is 370,000. As a consequence, the estimate of 35,000 to 100,000 Central American immigrants4 regarded as being infected and residing in the United States may be transformed into 500,000 to 675,000 individuals when overall immigration from Latin America is considered. A conservative estimate of the evolution toward chronic cardiomyopathy in this population (approximately 20 % ) is around 75,000 persons. Most of these individuals probably are either undiagnosed or misdiagnosed as having either idiopathic (dilated)
1734
Milei et al.
cardiomyopathy or coronary artery disease, since Chagas’ disease is largely unrecognized and blood screening is rarely performed. Chronic immigrants
chagasic cardiomyopathy in Latin American in the United States. Only one series of pa-
tients with chronic chagasic cardiomyopathy has been reported from the United States,26 although individual case reports have been published previous1y.27-32Very recently, Hagar and Rahimtoola26 described 25 patients in whom this diagnosis was established on the basis of the appropriate serologic and cardiologic findings. The patients mainly presented with atrioventricular block, congestive heart failure, angina1 chest pain, sudden death averted by resuscitation, or sustained ventricular tachycardia. Eighteen patients had been treated for coronary artery diseaseor idiopathic dilated cardiomyopathy for up to 108 months before the diagnosis of Chagas’ disease was considered. The electrocardiograms frequently suggested coronary artery disease. Six of the seven patients who had exercise thallium perfusion scans had abnormalities suggesting ischemia or infarction. A left ventricular aneurysm was found in 14 patients, segmental akinesia or hypokinesia was found in five, and diffuse hypokinesia was seen in three. Programmed ventricular stimulation performed in 13 patients induced sustained ventricular tachycardia in nine and nonsustained ventricular tachycardia in two. Actuarial survival (mean * SE) after 4 years for the entire group was 56 + 1256; it was 32 f 16% among those with global left ventricular dysfunction, and 78 2 14% among those without such dysfunction. The authors concluded that in the United States, Chagas’ heart disease commonly mimics coronary artery disease or idiopathic dilated cardiomyopathy, and that the prognosis is poor for patients with heart failure or left ventricular aneurysm or dysfunction. Transmission of Chagas’ disease by blood transfusion in the U.S. The transmission of T. cruzi infection
by transfusion of blood has now been unequivocally documented in the United States.25>i7, 33 Grant et a1.17and Nickerson et al.is described two cases of acute Chagas’ disease that occurred in the United States and Canada in immunocompromised patients as a result of transfusion of blood donated by asymptomatic immigrants. Fatal myocarditis developed in a 17-year-old boy who received a blood transfusion from his father, an immigrant from southeast Mexico; this patient had also traveled to endemic areas. The second case was that of an ll-year-old girl who was being treated for Hodgkin’s disease and who developed pericarditis after receiving blood from a
American
June 1992 Heart Journal
woman from Bolivia; she recovered from the acute infection. After the Canadian case, one additional, unconfirmed case was reported to have occurred in Texas.34 Transfusion-induced infection must be distinguished from immunosuppression-associated reactivation of preexisting Chagas’ disease, as reported in a patient with acute lymphocytic leukemia.35 It is possible that other, more clinically benign cases of transfusion-induced acute Chagas’ disease may have occurred in the United States. Given the nonspecific symptoms and the generally self-limited course followed by the acute phase of Chagas’ disease in most patients, it is very unlikely that it would be recognized as such in the United States. Regardless of the route of transmission, most patients with acute Chagas’ disease are expected to follow a benign course and then enter into the indeterminate phase.36 Conversely, fulminant courses are expected in immunosuppressed or immunocompromised patients, as documented in several reports.17, I8236-38 The two most important public health questions relating to the presence of T. cruzi-infected immigrants in the United States are: (1) the prevention of transmission of the parasite by transfusion of blood and (2) the detection and medical care of patients with chronic chagasic cardiomyopathy. In the patients in whom chronic Chagas’ diseasedevelops, the cardiac lesions are the most frequent abnormalities found. As mentioned above, these lesions must be distinguished from those attributed to idiopathic dilated cardiomyopathy and coronary artery disease. However, current emphasis on the management of Chagas’ disease is on prevention, because of the lack of a chemotherapeutic agent capable of eradicating the parasite in the chronic stage of the disease. Some United States blood banks have adopted a deferral policy by which blood donations are not accepted from individuals considered to be at high risk of having become infected with T. cruzi because of their having resided in areas where this parasite is endemic. This decision has been made considering that the applicability of a currently available serologic test for T. cruzi is uncertain for screening purposes.2” There may be approximately 75,000 nondiagnosed or misdiagnosed cases of chronic chagasic cardiomyopathy in the United States, where transfusion-associated transmission of the disease also can cause significant clinical disease, especially among immunosuppressed and immunocompromised patients. However, the dimensions of this problem are far smaller than those of the public health catastrophe that has occurred in Latin America. Conclusion. In Latin America, 16 to 18 million individuals are thought to have Chagas’ disease and 90
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123 6
million are considered to be at risk of infection. In the United States, the occurrence of Chagas’ disease is virtually limited to individuals who have resided in Latin America and who then have migrated to this country. Data on the prevalence of positive serologic reactions for Trypanosoma cruzi serve to indicate that a total of up to 74,000 Latin Americans residing in the U.S. have the chronic form of chagasic cardiomyopathy. The vast majority of these individuals are either undiagnosed or misdiagnosed as having idiopathic dilated cardiomyopathy or coronary artery disease. Vector transmission of T. cruzi infection is very unlikely to occur in the U.S. because of variations in the biologic behavior of local species of insect vectors and because of changes in human living conditions. Transfusion of blood from infected asymptomatic individuals is considered the most important mechanism of transmission of this disorder in the United States. REFERENCES
1. UNDP/World Bank WHO. Special program for research and training in tropical diseases. VI. Programme reports 1-7. December 31. 1982. 2. Anonymous. Latin America’s plague. Derwin’s disease. The Economist, May 5, 1990. 3. Marsden PD. American trypanosomiasis. Br Med J 1989; 299:969-70. 4. Kirchhoff LV. Is Trypanosoma cruzi a new threat to our blood sur~ulv? Ann Intern Med 1989:111:773-5. 5. Brener Z. Biology of Trypanosbma cruzi. Ann Rev Microbial 1973;27:347-82. 6. Andrade ZA. A patologia da doenca de Chagas no honen. Ann Sot Belg Med Trop 1985;65(suppl 1):15-30. 7. Milei J, Storino RA, Beigelman G, et al. Histopathology of specialized and ordinary myocardium and nerves in chronic Chagas’ disease, with a morphometric study of inflammation and fibrosis. Cardiologia 1991;36:107-15. 8. Ferrans VJ, Milei J, Tomita Y, Storino RA. Basement membrane thickening in cardiac myocytes and capillaries in chronic Chagas’ disease. Am J Cardiol 1988;61:1137-40. 9. Carrasco Guerra HA, Palacios-Pru E, Dagert de Scorza C, Molina C. Inalessis G. Mendoza RV. Clinical. histochemical. and ultrastructural correlation in septal endomyocardial bi: opsies from chronic chagasic patients: detection of early myocardial damage. AM HEART J 1987;113:716-24. 10. Milei J, Pesce R, Valero E, Muratore C, Beigelman R, Ferrans VJ. Electrophysiologic-structural study in chagasic aneurysms causing malignant arrhythmias. Int J Cardiol 1991; 32:65-73. 11. UNDR/World Bank/WHO. Special programme for research and training in tropical diseases. TDR News No. 34, December 1990. 12. Schmunis GA. Chagas’ diseases and blood transfusion. In: Dodd RY, Barker LF, eds. Infection, immunity and blood transfusion. New York: Alan R Liss. 1984:127-47. 13. Neto VA. Doence de Chagas pos-transfusional. Rev Hosp Clin Fat Med Sao Paulo 1988;43:135-7. 14. Hayes RJ, Schofield CJ. Estimation de las tasas de incidencia de infecciones y parasitosis cronicas a partir de la prevalencia: la enfermedad de Chagas en America latina. Bol Of Sanit Panam 1990;108:308-16. 15. Neto VA, Molineri HE, Siqueire AP, Lucas RS. Analise, per
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maio de reacao de fixacao de complemento, do riaco do aquiaicao de Chagas etravco de hemoterapie, por parte de pacientes politrenafundidos. Rev Goiana Med 197%21:1-g. 16. Carrasco R, Miguez H, Camacho C, Echalar L, Revollo S, Ampuero T, Dedet JP. Prevalence of Trypanosoma cruzi infection in blood banks of seven departments of Bolivia. Mem Inst Oswald0 Cruz 1990;85:69-73. 17. Grant IH, Gold JW, Wittner M, Tanowitz HB, Nathan C, Mayer K, Reich L, Wollner N, Steinherz L, Ghavimi F, Richard J, G’Reilly MD, Armstrong D. Transfusion-associated acute Chagas” disease acquired in the U.S.A. Ann Intern Med 1989;111:849-51.
18. Nickerson H, Orr P, Schroeder ML, Sekia L, Johnston JB. Transfusion-associated Trypanosoma cruzi infection. Ann Intern Med 1989;111:851-3. 19. Kirchhoff LV, Gam AA, Gilliam FC. American trypanosomiasis (Chagas’ disease) in Central American immigrants. Am J Med 1987;82:915-20. 20. Wood SF. An additional California locality for Trypanosoma cruzi. Chagas’ in the western cone-nosed buck, Triatoma protracte (Uhler). J Parasitol 1944;30:199. 21. SchifIler RJ, Mansur GP, Navin TR. Indigenous Chagas’ disease (American trypanosomiasis) in California. JAMA 1984; 251:2983-4. 22. U.S. Congress, Office of Technology Assessment. Status of biomedical research and related technology for tropical diseases. OTA-K-258. Washington, DC: U.S. Government Printing Office, September 1989. 23. Tabulation of immigrants admitted by country of birth, 19611987. Immigration and Naturalization Service. Washington, DC: U.S. Department of State, 1987. 24. Kirchhoff LV, Neva FA. Chagas’ disease in Latin American immigrants. JAMA 1985;254:3058-60. 25. Skolnick A. Deferral aims to defer Chagas’ parasite. JAMA 1991;265:173. 26. Hagar JM, Rahimtoola SH. Chagas’ heart disease in the United States. N Engl J Med 1991;325:763-8. 27. Massumi RA, Gooch A. Chagas’ myocarditis. Arch Intern Med 1965;116:531-6.
28. Edmiston WA, Yokoyama T, Kay J, Bilitch M, Lau FY. Ventricular tachycardia in a young adult with an apical aneurysm. West J Med 1978;128:248-53. 29. Pearlman JD. Chagas’ disease in northern California: no longer an edemic diagnosis. Am J Med 1983;75:1057-60. 30. Feit A, El-Sherif N, Korostoff S. Chagas’ disease masquerading as coronary artery disease. Arch Intern Med 1983;75:105760. 31. Lorenzana R. Chronic Chagas’ myocarditis: report of a case. Am J Clin Path01 1967;48:39-43. 32. Shafi A. Chagas’ disease with cardiopathy and hemiplegia. N Y State J Med 1977;77:418-9. 33. Geiaaler PJ, Ito JI, Kerndt PR, et al. Fulminant Chagas’ disease (CD) in bone marrow transplantation (BMT). Abstract of the 1987 Interscience Conference of Antimicrobial Agents and Chemotherapy. 169. 34. Skolnick A. Does influx from endemic areas mean more transfusion-associated Chagas’ disease? JAMA 1989;262:1433. 35. Kohl S, Pickering LK, Frankel LS, Yaeger RG. Reactivation of Chagas’ disease during therapy of acute lymphocytic leukemia. Cancer 1982;50:827-8. 36. Storino R, Milei J, Miocardiopatia chagasica cronica. Un enfoque para el clinic0 general. Buenos Aires Club Estudio, 1986. 37. Thambo S, Passalacqua W, Van Cauwelaert R. Lazcano F. Chagas’ disease in patients’ with renal transplantation. Rev Med Chil 1989;117:18-22. 38. Leiguarda R, Roncoroni A, Taratuto AL, Jost L, Berthier M, Nogues M, Freilij H. Acute CNS infection by Trypanosoma cruzi (Chagas’ disease) in immunosuppressed patients. Neurology 1990;40:850-1.
Does Chagas’ disease exist as an undiagnosed form of cardiomyopathy United States?
in the
Jose Milei, MD, Branco Mautner, MD, Ruben Storino, MD, Julian A. Sanchez, MD,” and Victor J. Ferrans, MD, PhD.a Buenos Aires, Argentina, and Bethesda, Md.
Chagas’ disease (American trypanosomiasis), a chronic illness caused by the flagellate parasite Trypanosoma cruzi, was first described in 1909 by the Brazilian physician Carlos Chagas. The insect vectors of the disease are present throughout most of South and Central America, and their zone of distribution extends across the southern United States, where at least some of these vectors are infected with Trypanosoma.’ Several animal species in this zone are affected by the disease in their natural habitats. Many believe that Chagas’ disease was first transmitted to humans after the Incas brought infected wild animals to raise near their homes.2 Chagas’ disease is considered to be an “exotic” disease in the United States, where it is rarely detected.3, 4 The infection is characterized by an acute symptomatic phase with high parasitemia, and is followed by a lifelong indeterminate phase in which low numbers of parasites are sequestered in tissues5; however, the acute phase often is clinically silent. Chronic progressive Chagas’ disease develops in 10 5% to 20 % of previously asymptomatic, infected individuals. It is manifested by a chronic, diffuse, progressive, fibrosing myocarditis that involves not only the working myocardium but also the atridventricular conduction system.6, 7 This leads to cardiomegaly, cardiac failure, arrhythmias, thromboembolic phenomena, and death.6 Megacolon and megaesophagus may also occur.
From the Centro de Enfermedad de Chagas, Division Fernandez, Buenos Aires; and BPathology Branch, and Blood Institute, National Institutes of Health, This study Organization Received Reprint Buenos
for publication
Oct. 31, 1991;
requests: Jose Milei, Aires, Argentina.
411136476
1732
was partially supported with (T80/181/11/ID 870343).
a grant accepted
MD, CARDIOPSIS,
Cardiologia, Hospital National Heart, Lung, Bethesda.
from Dec.
TDR,
World
Health
16, 1991.
Tucuman
2163 4” B, 1050
Myocardial biopsy studies83 g of the chronic form of Chagas’ disease have revealed myocyte hypertrophy and degeneration, focal lymphocytic infiltration, and interstitial fibrosis. In addition to these nonspecific changes, these studies have shown marked thickening of the basement membranes of the cardiac myocytes and capil1aries.s It has not yet been determined to what extent these changes may help in the differential diagnosis of Chagas’ disease from other cardiomyopathies. It is well established that intracellular parasites are found in cardiac myocytes only during the acute phase. At the present time the diagnosis of chronic chagasic cardiomyopathy cannot be made only on the basis of microscopic study of the heart. The left ventricular apical aneurysms found in patients with the chronic form of chagasic cardiomyopathy constitute a highly interesting and clinically important feature of this disorder. A recent study” established morphologic-electrophysiologic correlations in these lesions. Chronic recurrent ventricular tachyardia occurred in three patients with chagasic aneuryms and intraoperative ventricular mapping studies indicated that these arrythmias originated in regions adjacent to the aneurysms. The edges of the surgically resected aneurysms showed hypertrophy of myocytes and partial or complete loss of myofibrils, mitochondrial swelling, accumulation of lipofuscin granules, intracellular edema, and thickening of the basement membrane of the myocytes and vascular endothelial cells and smooth muscle cells. The interlaced fronts of healthy (fast conducting) and “early” damaged (slow conducting) myocytes were considered to have the configuration of ideal reentry circuits. Further evidence that the arrythmias originated in these regions was their abolition by aneurysm resection. Prevalence of Chagas’ disease in Latin America. In Latin America, 16 to 18 million people are thought to have Chagas’ diseaseand 90 million are considered to
Volume Number
123 6
be at risk of infection.ri In its usual mode of transmission, the disease is spread by the insect vectors, usually members of the Reduviidae family (kissing bug). These insects puncture the skin of the host to suck blood. They carry T. cruzi in their gastrointestinal tract; they defecate as they suck blood, and the excreted T. cruzi then penetrates into the host through the punctured skin. Because of regional variations in the biologic behavior of insects that can serve as T. cruzi vectors and because of the nature of the living conditions of the local human populations, vector transmission of Chagas’ disease is extremely unlikely to occur in the U.S. Asymptomatic patients with the chronic phase of Chagas’ disease can have a low degree of parasitemia and blood transfusions are the second most frequent mode of transmission of Chagas’ disease. I2 The congenital form, transmitted through the placenta, is also relatively frequent.3 The prevalence of Chagas’ disease is expected to be increased in cities in which there is heavy migration of individuals from the countryside, where infection is more prevalent, than in large urban centers. The incidence of infection with T. cruzi in some urban centers in Latin America is extremely high. For example, the cities of Goiana (Brazil), Tegucigalpa (Honduras), and Santa Cruz (Bolivia) are known to have a 25.8 % , 28%, and 63 % , respectively, prevalence of infection.t2 For Brazil’s Federal District (Brasilia), which had 1 million inhabitants, vital statistics in 1977/78 indicated that 4.3% of all deaths were attributed to Chagas’ disease.13 If we consider all the Latin American countries, an overall prevalence of 7.4 % may be calculated.14 Therefore it is not surprising that transfusions are an important source of transmission. Data from Brazil point out that a mean of 7% of blood donors have positive serologic tests for T. cruzi .I3 The estimated risk for transmission is 13% to 23 % for each unit of contaminated blood transfused. l5 SchmuniP has estimated that the attack rate after transfusion of seropositive blood products ranges from 12% to 50%. In 1988, it was estimated that as many as 20,000 individuals per year became infected with T. cruzi through blood transfusions in Brazil.13 In one department of Bolivia the rate of infection of T, cruzi among blood donors in a blood bank was found to be 51% in 1989.t6 The United States seemed spared by the disease, but recently blood banks in the United States have faced the problem of transfusion-associated Chagas’ disease 4,17-19 Acute Chagas’ disease in the United States. Chagas’ disease has been limited to the New World tropics and has never been endemic in the United States.20-22 In spite of the presence of T. cruzi-infected insects in
Chagas’ disease in the USA
1733
many parts of the southern and southwestern United States, only a few cases of acute Chagas’ disease resulting from vector transmission have been described in the U.S.21j 22 A case of Chagas’ disease transmitted by an insect in northern California was diagnosed in 1982, the first such case reported since 1955, when two infants in Texas were diagnosed with domestically acquired Chagas’ disease.22 In the last 20 years, six laboratory-acquired infections and nine imported cases of acute Chagas’ disease have been reported”; however, the number of vector-related and imported cases of acute T. cruzi infection that go unrecognized may be several times the number reported. Chagas’
disease
in Latin
American
immigrants.
According to the Immigration and Naturalization Service,23 from 1961 to 1987 almost 5 million immigrants from Latin America settled in the United States. The prevalence of chagasic infection in these immigrants has not been assessed. Only two studies have been made of the incidence of positive serologic reactions for T. cruzi among Latin American immigrants in the United States: one in Washington, D.C.24 and one in Los Angeles, California.25 Most of the participants in both surveys were from Central American countries, and it is not possible to estimate from the published data how representative they were of the immigrant population derived either from their countries or from all of Latin America. From August 1989 to June 1990,3492 prospective donors at the Los Angeles County-University of Southern California Medical Center met all standards for donating blood; 72 were deferred because they might be infected with T. cruzi. Forty-five of this number agreed to be serologically tested and positive results were obtained in two of them (4.4%).25 These findings were interpreted as suggesting that there may be upwards of 50,000 T. cruzi-infected Central American immigrants in the United States.* The estimates, cited above, of 5 million Latin Americans migrating into the U.S. from 1961 to 1987, and an overall 7.4% incidence of Chagas’ disease in Latin American, served as the basis for calculating that the number of persons infected with T. cruzi and living in the U.S. is 370,000. As a consequence, the estimate of 35,000 to 100,000 Central American immigrants4 regarded as being infected and residing in the United States may be transformed into 500,000 to 675,000 individuals when overall immigration from Latin America is considered. A conservative estimate of the evolution toward chronic cardiomyopathy in this population (approximately 20 % ) is around 75,000 persons. Most of these individuals probably are either undiagnosed or misdiagnosed as having either idiopathic (dilated)
1734
Milei et al.
cardiomyopathy or coronary artery disease, since Chagas’ disease is largely unrecognized and blood screening is rarely performed. Chronic immigrants
chagasic cardiomyopathy in Latin American in the United States. Only one series of pa-
tients with chronic chagasic cardiomyopathy has been reported from the United States,26 although individual case reports have been published previous1y.27-32Very recently, Hagar and Rahimtoola26 described 25 patients in whom this diagnosis was established on the basis of the appropriate serologic and cardiologic findings. The patients mainly presented with atrioventricular block, congestive heart failure, angina1 chest pain, sudden death averted by resuscitation, or sustained ventricular tachycardia. Eighteen patients had been treated for coronary artery diseaseor idiopathic dilated cardiomyopathy for up to 108 months before the diagnosis of Chagas’ disease was considered. The electrocardiograms frequently suggested coronary artery disease. Six of the seven patients who had exercise thallium perfusion scans had abnormalities suggesting ischemia or infarction. A left ventricular aneurysm was found in 14 patients, segmental akinesia or hypokinesia was found in five, and diffuse hypokinesia was seen in three. Programmed ventricular stimulation performed in 13 patients induced sustained ventricular tachycardia in nine and nonsustained ventricular tachycardia in two. Actuarial survival (mean * SE) after 4 years for the entire group was 56 + 1256; it was 32 f 16% among those with global left ventricular dysfunction, and 78 2 14% among those without such dysfunction. The authors concluded that in the United States, Chagas’ heart disease commonly mimics coronary artery disease or idiopathic dilated cardiomyopathy, and that the prognosis is poor for patients with heart failure or left ventricular aneurysm or dysfunction. Transmission of Chagas’ disease by blood transfusion in the U.S. The transmission of T. cruzi infection
by transfusion of blood has now been unequivocally documented in the United States.25>i7, 33 Grant et a1.17and Nickerson et al.is described two cases of acute Chagas’ disease that occurred in the United States and Canada in immunocompromised patients as a result of transfusion of blood donated by asymptomatic immigrants. Fatal myocarditis developed in a 17-year-old boy who received a blood transfusion from his father, an immigrant from southeast Mexico; this patient had also traveled to endemic areas. The second case was that of an ll-year-old girl who was being treated for Hodgkin’s disease and who developed pericarditis after receiving blood from a
American
June 1992 Heart Journal
woman from Bolivia; she recovered from the acute infection. After the Canadian case, one additional, unconfirmed case was reported to have occurred in Texas.34 Transfusion-induced infection must be distinguished from immunosuppression-associated reactivation of preexisting Chagas’ disease, as reported in a patient with acute lymphocytic leukemia.35 It is possible that other, more clinically benign cases of transfusion-induced acute Chagas’ disease may have occurred in the United States. Given the nonspecific symptoms and the generally self-limited course followed by the acute phase of Chagas’ disease in most patients, it is very unlikely that it would be recognized as such in the United States. Regardless of the route of transmission, most patients with acute Chagas’ disease are expected to follow a benign course and then enter into the indeterminate phase.36 Conversely, fulminant courses are expected in immunosuppressed or immunocompromised patients, as documented in several reports.17, I8236-38 The two most important public health questions relating to the presence of T. cruzi-infected immigrants in the United States are: (1) the prevention of transmission of the parasite by transfusion of blood and (2) the detection and medical care of patients with chronic chagasic cardiomyopathy. In the patients in whom chronic Chagas’ diseasedevelops, the cardiac lesions are the most frequent abnormalities found. As mentioned above, these lesions must be distinguished from those attributed to idiopathic dilated cardiomyopathy and coronary artery disease. However, current emphasis on the management of Chagas’ disease is on prevention, because of the lack of a chemotherapeutic agent capable of eradicating the parasite in the chronic stage of the disease. Some United States blood banks have adopted a deferral policy by which blood donations are not accepted from individuals considered to be at high risk of having become infected with T. cruzi because of their having resided in areas where this parasite is endemic. This decision has been made considering that the applicability of a currently available serologic test for T. cruzi is uncertain for screening purposes.2” There may be approximately 75,000 nondiagnosed or misdiagnosed cases of chronic chagasic cardiomyopathy in the United States, where transfusion-associated transmission of the disease also can cause significant clinical disease, especially among immunosuppressed and immunocompromised patients. However, the dimensions of this problem are far smaller than those of the public health catastrophe that has occurred in Latin America. Conclusion. In Latin America, 16 to 18 million individuals are thought to have Chagas’ disease and 90
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million are considered to be at risk of infection. In the United States, the occurrence of Chagas’ disease is virtually limited to individuals who have resided in Latin America and who then have migrated to this country. Data on the prevalence of positive serologic reactions for Trypanosoma cruzi serve to indicate that a total of up to 74,000 Latin Americans residing in the U.S. have the chronic form of chagasic cardiomyopathy. The vast majority of these individuals are either undiagnosed or misdiagnosed as having idiopathic dilated cardiomyopathy or coronary artery disease. Vector transmission of T. cruzi infection is very unlikely to occur in the U.S. because of variations in the biologic behavior of local species of insect vectors and because of changes in human living conditions. Transfusion of blood from infected asymptomatic individuals is considered the most important mechanism of transmission of this disorder in the United States. REFERENCES
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