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Chagas disease, or American trypanosomiasis, which is caused by the protozoan parasite Trypanosoma cruzi, is primarily a vector disease endemic in 21 Latin American countries, including Mexico. Although many vector control programs have been implemented, T. cruzi has not been eradicated. The development of an anti-T. cruzi vaccine for prophylactic and therapeutic purposes may significantly contribute to the transmission control of Chagas disease. Immune protection against experimental infection with T. cruzi has been studied since the second decade of the last century, and many types of immunogens have been used subsequently, such as killed or attenuated parasites and new DNA vaccines. This primary prevention strategy appears feasible, effective, safe, and inexpensive, although problems remain. The objective of this review is to summarize the research efforts about the development of vaccines against Chagas disease worldwide. A thorough literature review was conducted by searching PubMed with the terms "Chagas disease" and "American trypanosomiasis" together with "vaccines" or "immunization". In addition, reports and journals not cited in PubMed were identified. Publications in English, Spanish, and Portuguese were reviewed.

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UNLABELLED: Northern Veracruz has conditions, biotic and abiotic, to support Triatomine bugs and vectorial transmission of Trypanosoma cruzi to human beings. Therefore we explore seroprevalence of antibodies to this parasite and the presence of Chronic Chagasic Cardiopathy (CCC) at Cardiology ward in a General Hospital serving North of Veracruz State, and neighbord states Hidalgo, Puebla San Luis Potosi and Tamaulipas. MATERIAL AND METHODS: We search for consecutive adult patients attending outpatient and beds assigned to Cardiology between March through September, 2003. An epidemiology questionnaire, clinical work up, chest roentgenogram, 12 lead peripheral EKG and transthoracic echocardiogram were performed in 240 female/males patients. All of them were bled to blindly search for T. cruzi antibodies. RESULTS: Seroprevalence was 8%, 49 cases of dilated cardiomyopathy were diagnosed 23 attributed to chronic diseases such as systemic hypertension diabetes mellitus or ischemic heart disease 12 with idiopathic disease and 14 (29%) had CCC. The latter accumulated epidemiologic features suggestive of vectorial infection. Four additional individuals without CCC but having specific antibodies were considered indeterminate Chagasic cases. DISCUSSION AND CONCLUSIONS: This case series identify American Trypanosomiasis among 19 people attending a Cardiology Service, and 14 of them had a severe heart disease linked to progressive and fatal course. This observation points out that Chagas disease could be a regional public health problem in Northern Veracruz.

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Northern Veracruz has conditions, biotic and abiotic, to support Triatomine bugs and vectorial transmission of Trypanosoma cruzi to human beings. Therefore we explore seroprevalence of antibodies to this parasite and the presence of Chronic Chagasic Cardiopathy (CCC) at Cardiology ward in a General Hospital serving North of Veracruz State, and neighbord states Hidalgo, Puebla San Luis Potosi and Tamaulipas. MATERIAL AND METHODS: We search for consecutive adult patients attending outpatient and beds assigned to Cardiology between March through September, 2003. An epidemiology questionnaire, clinical work up, chest roentgenogram, 12 lead peripheral EKG and transthoracic echocardiogram were performed in 240 female/males patients. All of them were bled to blindly search for T. cruzi antibodies. RESULTS: Seroprevalence was 8%, 49 cases of dilated cardiomyopathy were diagnosed 23 attributed to chronic diseases such as systemic hypertension diabetes mellitus or ischemic heart disease 12 with idiopathic disease and 14 (29%) had CCC. The latter accumulated epidemiologic features suggestive of vectorial infection. Four additional individuals without CCC but having specific antibodies were considered indeterminate Chagasic cases. DISCUSSION AND CONCLUSIONS: This case series identify American Trypanosomiasis among 19 people attending a Cardiology Service, and 14 of them had a severe heart disease linked to progressive and fatal course. This observation points out that Chagas disease could be a regional public health problem in Northern Veracruz.

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UNLABELLED: Chagas disease is caused by the flagellate protozoan T: cruzi. Seroepidemiological surveys in Chiapas, Mexico have shown seropositive individuals, therefore, we searched for people affected by the chronic form of Chagas disease which involves the heart, causing a chronic, progressive and fatal disease called Chronic Chagasic Cardiopathy (CCC). MATERIAL AND METHODS: To establish the frequency of CCC we studied 28 patients seen at the Hospital General Regional "Dr. Rafael Pascacio Gamboa" during October 2002 through October 2003 in Tuxtla Gutierrez, Chiapas, the State capital city, with diagnosis of dilated cardiomyopathy (DC), a serological survey for antibodies against T. cruzi was done. This hospital cares for people from all parts of Chiapas, Mexico. Clinical diagnosis of DC was established there and blind serological studies were performed in Mexico City. RESULTS: Fifteen out of 28 DC patients (54%) had anti T. cruzi antibodies. All of them came from poor rural villages and they had heart failure and/or arrhythmia or heart blockade on EKG. CONCLUSIONS: This observation suggest that in Chiapas were Chagas disease is endemic, there are CCC patients. Any case with a clinical diagnosis of DC should be tested for antibodies against T. cruzi. The low socioeconomic status, culture and environment in this Mexican State favour the presence and transmission of this parasitic disease.

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OBJECTIVE: To compare the epidemiological and clinical characteristics of chronic Chagas' heart disease to other dilated cardiomyopathies. METHODS: A study comprising 128 patients from a heart disease center was carried out from 1993 to 2003. Of them, 51 (40%) were Trypasonoma cruzi positive. Epidemiological data was obtained through interviews and clinical and serological data from health services. Statistic analysis was conducted using the Chi-square, Fischer, Mann-Whitney or Students' t-test as well as multivariate analysis. RESULTS: Chronic Chagas' disease patients were older (55+/-10 years old) than those patients with cardiopathy (42+/-17 years old). Most of them were born in rural areas (90% vs 68%), lived in poor (75% vs 16%), crowded households (45% vs 20%), together with domestic animals (71% vs 61%) and were aware of the Chagas' vector (73% vs 25%). Rhythm and conduction ECG abnormalities as well as permanent pacemaker were common among Chagas' patients (84% vs 55%, 78% vs 64% and 24% vs 10%, respectively). Congestive heart failure was more frequent among cardiomiopathy patients (88% vs 71%). Both groups had abnormal myocardial perfusion with normal epicardial arteries. Comorbidities were more frequent in cardiomiopathy patients than in chronic Chagas' disease patient (two cases only). CONCLUSIONS: Chagas' disease is the most common cause of dilated cardiomiopathy in the study hospital. Due to its regional distribution in Mexico, it deserves special attention and control programs proven to be effective in other countries.

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OBJECTIVO: Comparar las características epidemiológicas y clínicas de la cardiopatía chagásica crónica con otras miocardiopatías dilatadas. MÉTODOS: Se incluyeron a 128 pacientes consecutivos en un hospital de espcialidad, de 1993 a 2003 con miocardiopatías dilatadas, donde 51 (40 por ciento) con anti Tripanosoma cruzi. Se recopiló información epidemiológica por entrevista directa, y datos clínicos en los servicios asistenciales. Se utilizaron la prueba de la Chi-cuadrado o prueba exacta de Fischer, prueba t de Student ó la prueba de U de Mann Whitney y análisis multivariado. RESULTADOS: Los pacientes con cardiopatía chagásica crónica, eran más viejos (55±10 años) que los pacientes con miocardiopatías (42±17 años), nacieron en zonas rurales (90 por ciento vs 68 por ciento), en viviendas precarias (75 por ciento vs 16 por ciento), con hacinamiento (45 por ciento vs 20 por ciento), convivencia con animales domésticos (71 por ciento vs 61 por ciento) y conocían al vector (73 por ciento vs 25 por ciento). Los trastornos del ritmo y de la conducción, así como la colocación de marcapaso definitivo fueron frecuentes en los pacientes con cardiopatía chagásica crónica (84 por ciento vs 55 por ciento, 78 por ciento vs 64 por ciento Y 24 por ciento vs 10 por ciento respectivamente). La insuficiencia cardiaca congestiva venosa fue más frecuente en los pacientes con miocardiopatía seronegativa (88 por ciento vs 71 por ciento) y la perfusión miocárdic anormal con arterias epicárdicas normales fue igual en ambos grupos. Con respecto a co-morbilidad, los pacientes con cardiopatía chagásica crónica tenían sólo dos padecimientos, mientras que en el otro grupo era más amplia. CONCLUSIONES: La enfermedad de Chagas causa la miocardiopatía dilatada específica más común. Debido a su distribución regional en la República Mexicana, merece atención y se recomienda a nivel público adoptar medidas de prevención que ya probaron eficacia en otros países.

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La enfermedad de Chagas es causada por el protozoario flagelado Trypanosoma cruzi. Encuestas seroepidemiológicas realizadas en Chiapas informan individuos seropositivos en comunidades rurales, y cabe la posibilidad de que la forma crónica de la enfermedad ocurra en el estado. La expresión clínica dominante en la enfermedad de Chagas crónica es cardíaca. Material y métodos: Con el objeto de conocer la frecuencia de cardiopatía chagásica crónica (CCC) se hizo una encuesta serológica a pacientes con miocardiopatía dilatada (MD) internados entre octubre de 2002 a octubre de 2003, en el Servicio de Cardiología del Hospital General Regional "Dr. Rafael Pascacio Gamboa" de Tuxtla Gutiérrez, Chiapas. El diagnóstico fue establecido en forma independiente y el estudio seroinmunológico fue ciego. Resultados: Quince (54%) de 28 sujetos con MD tenían anticuerpos a T. cruzi. Todos provenían de medio rural pobre, su cuadro clínico incluyó insuficiencia cardíaca y/o trastornos del ritmo o conducción. Conclusiones: Esta evidencia sugiere que en Chiapas, una zona endémica de enfermedad de Chagas, hay CCC. Dentro del estudio de la MD, la etiología chagásica, debe ser considerada, ya que las condiciones socioeconómicas, culturales y regionales favorecen su presencia.

Chagas disease is caused by the flagellate protozoan T. cruzi. Seroepidemiological surveys in Chiapas, Mexico have shown seropositive individuals, therefore, we searched for people affected by the chronic form of Chagas disease which involves the heart, causing a chronic, progressive and fatal disease called Chronic Chagasic Cardiopathy (CCC). Material and methods: To establish the frequency of CCC we studied 28 patients seen at the Hospital General Regional "Dr. Rafael Pascacio Gamboa" during October 2002 through October 2003 in Tuxtla Gutierrez, Chiapas, the State capital city, with diagnosis of dilated cardiomyopathy (DC), a serological survey for antibodies against T. cruzi was done. This hospital cares for people from all parts of Chiapas, Mexico. Clinical diagnosis of DC was established there and blind serological studies were performed in Mexico City. Results: Fifteen out of 28 DC patients (54%) had anti T. cruzi antibodies. All of them came from poor rural villages and they had heart failure and/or arrhythmia or heart blockade on EKG. Conclusions: This observation suggest that in Chiapas were Chagas disease is endemic, there are CCC patients. Any case with a clinical diagnosis of DC should be tested for antibodies against T. cruzi. The low socioeconomic status, culture and environment in this Mexican State favour the presence and transmission of this parasitic disease.

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Chagas' disease contributes significantly to cardiovascular morbidity and mortality in several Latin-American countries. Previous studies have reported the effect of the human leukocyte antigen (HLA) molecules in the immune response regulation of Trypanosoma cruzi infection, and the association of HLA antigens with heart damage. We studied the major histocompatibility complex (MHC) class I (HLA-A and HLA-B), and class II (HLA-DR) genes in a sample of 66 serologically positive individuals with and without cardiomyopathy, and in 127 healthy controls. The total group of seropositive individuals revealed increased frequencies of HLA-B39 (pc=4.3x10(-5), odds ratio [OR]=3.35) and DR4 (pc=1.8x10(-5), OR=2.91) when compared to healthy controls. Increased frequencies of HLA-A68 and HLA-B39 were found in asymptomatic individuals when compared to patients with cardiomyopathy (pc=0.014, OR=4.99 and pc=0.001, OR=4.46, respectively). Also, patients with cardiomyopathy exhibited increased frequency of HLA-B35 when compared to healthy controls (pc=0.048, OR=2.56). The HLA-DR16 frequency was increased in patients with cardiomyopathy compared with asymptomatic individuals (pc=0.05, OR=No determined) and healthy controls (pc=0.02, OR=5.0). The results suggest that MHC alleles might be associated with the development of chronic infection and with heart damage in Chagas' disease. HLA-DR4 and HLA-B39 could be associated directly with the infection by T. cruzi, whereas, HLA-DR16 could be marker of susceptibility to heart damage and HLA-A68 might confer protection to develop cardiomyopathy.

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Cardiomyopathies are a heterogenous group of heart ailments. Some of them are primary myocardial diseases and are classified as dilated, hypertrophic, restrictive and arryhithmogenic. Dilated cardiomyopathies (DCs) are the most common. Sometimes it is possible to identify an etiologic agent, in that case we talk about a specific dilated cardiomyopathy. Here in, we review one of these specific DCs, the so called Chronic Chagasic Cardiopathy (CCC) from the point of view of our personal experience at the Instituto Nacional de Cardiología "Ignacio Chávez". Chagas' disease is present in Mexico, therefore CCC is also present. We estimate that 5,000 people, suffer CCC with severe symptoms. In Mexico, Chagas' disease occurs below the Tropic of Cancer and between 2,000-2,500 m above sea level, in this area there is a real risk for vectorial infection, mainly in rural villages. Clinical diagnosis should be supported by epidemiological and seroepidemiological confirmatory data. There is not appropriate therapy yet for this condition.

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Background. American trypanosomiasis (Chagas' disease), an anthropozoonosis fairly common in rural Latin American, has become an urban disease due to continuous migration, intra- and internationally. Blood transfusion, the second important pathway for transmission, increases its impact. Recognition of seropositive subjects among blood donors is now recommended, and clinical and serological screening enforced. Maneuvers to inactivate or remove Trypanosoma cruzi present in collected blood are recommended. Methods. We surveyed voluntary donors at the National Institute of Cardiology in Mexico City in of anti-T. cruzi by indirect immunofluorescence, ELISA, and Western blot analysis. Seropositive donors were identified and tested for immunoglobulin. We used types and fractions of donated blood to extract DNA and perform the PCR technique using kinetoplast primers seeking parasite DNA in blood. Results. After 3,300 donors were screened, we identified 10 seropositive subjects (0.3 percent). These subjects were considered as indeterminate chagasic patients, came mainly from rural areas, and had IgG (100 percent) and IgA (30 percent) antibodies aginst a crude extract as well as a recombinant T. cruzi antigen. Identification of parasite DNA in red cell and platelet fraction was achieved from eight blood units. Conclusions. The present data provide evidence that blood donors at an urban hospital are seropositive for T. cruzi and at least 50 percent of donors carry the parasite potentially able to transmit T. cruzi in their cellular blood products. Serological screening should be included in routine blood-banking. It is also necessary to adopt measures to inactivate or eliminate organisms in donated blood

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Seven patients with diagnosis of dilated myocardiopathy, who fulfilled epidemiological, clinical, and serological criteria for chronic American Trypanosomosis, were submitted to hemoculture. Parasites were isolated in two patients (29 percent) confirming diagnosis and indicating and infection. Antibody titers did not show any relationship with the presence or absence of parasitemia nor were clinical differences noticed. Isolated Trypanosoma cruzi parasites belonged to biodeme III

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La enfermedad de Chagas (tripanosomiasis Americana) afecta a más de 20 millones de personas en América. El 30 por ciento de los infectados desarrollan enfermedad crónica, miocardiopatía dilatada, sin tratamiento efectivo. En México el 40 por ciento de los sujetos con miocardioatía dilatada tienen anticuerpos contra Trypanosoma cruzi. En la fase crónica la parasitemia es esporádica y escasa; no es posible detectar el parásito por métodos directos. Comunicamos un método capaz de detectar T. cruzi, sebsible y específico. Dos oligonucleótidos (KNs1 y KNS2), diseñados a partir de la secuencia de ADN de minicírculos de cinetoplasto, se usaron para amplificar la región hipervariable por el método de la reacción en cadena de la ADN polimerasa (PCR). Se logró detectar el equivalente de 0.8 a 1.5 moléculas de minicírculo o 1/12,000 de parásito. AI aplicar el método a muestras de ADN de tejidos de ratones infectados con parásito, se amplificó un producto reconocido por una sonda específica para minicírculos. Estos resultados se correlacionan con estudios inmunohistoquímicos que muestran la presencia tisular del parásito a varios tiempos estudiados. El método desarrollado puede tener aplicación en estudios clínicos, epidemiológicos de campo y de vigilancia en bancos de sangre.

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