Trypanosoma cruzi burden, genotypes, and clinical evaluation of Chilean patients with chronic Chagas cardiopathy.

There are currently no biomarkers to assess which patients with chronic indeterminate Chagas disease will develop heart disease and which will spend their entire life in this state. We hypothetize that the parasite burden and Trypanosoma cruzi genotypes are related to the presence of heart disease in patients with Chagas disease. This study is aimed to investigate the parasite burden and T. cruzi genotypes in chagasic cardiopaths versus chagasic individuals without cardiac involvement according to the New York Heart Association. Patients with chronic Chagas disease, 50 with and 50 without cardiopathy (controls), groups A and B, respectively, were submitted to anamnesis, physical examination, and electrocardiogram. Echo-Doppler was performed for group A; all important known causes of cardiopathy were discarded. Xenodiagnosis, conventional PCR, and quantitative PCR were performed on patients of both groups. T. cruzi genotyping was done for 25 patients of group A and 20 of group B. The 50 cardiopaths had 80 electrocardiographic alterations, most of them in grade II of the New York Heart Association classification; 49 were classified in grade I by Echo-Doppler, and only one patient was in grade III. The difference in average parasitemia in patients of groups A and B was not significant. The most frequent T. cruzi DTU found was TcV. The parasite burden and genotype of the groups with and without cardiopathy were similar. Graphical abstract Imagen 1 Chronic chagas cardiopathy chest X-ray heart enlargement Figure 2 Chronic Chagas cardiopathy microaneurism of left ventricle. Cineangiography.

Treatment of Chagas' disease with itraconazole: electrocardiographic and parasitological conditions after 20 years of follow-up.

OBJECTIVES: To evaluate cases of chronic Chagas' disease for the long-term effects of treatment with itraconazole on Trypanosoma cruzi infections and the regression or development of ECG abnormalities. METHODS: In March 1992, we treated 46 patients with chronic Chagas' disease with 6 mg/kg/day of itraconazole for 120 days in a blind evaluation. The patients came from an area of Chile where the disease was endemic and were checked for ECG abnormalities and with xenodiagnosis (XD) or real-time XD-quantitative PCR (XD-qPCR) for Trypanosoma cruzi infection before treatment and once a year for 20 years. RESULTS: Twenty-one patients proved to be uninfected after 20 years and 15 of the patients had a normal ECG. Of the latter cases, 32.6% could be considered cured, although all of them had positive serology. Itraconazole prevents the development of ECG abnormalities, because after 20 years of treatment only 10.86% of patients developed ECG abnormalities (Z = 1.70, P = 0.046). XD-qPCR performed on 16 patients demonstrated 10 cases with <1.42 parasites/mL: eight with <1 parasite/mL, one with 1.42 parasites/mL and one with 1.01 parasites/mL. Five patients had more than 11.75 parasites/mL, all of them with a positive XD; these cases correspond to therapy failure, since re-infection was ruled out. In one case, XD-qPCR did not present amplification. CONCLUSIONS: Itraconazole is useful in the treatment of chronic Chagas' disease as it prevented the development of ECG abnormalities and cured 32.6% of patients.

Clinical, electrocardiographic and echocardiographic evolution of chronic Chagas disease treated with nifurtimox on prolonged follow-up in Chile: observational study.

OBJECTIVES: This study aimed to describe the electrocardiographic and echocardiographic status of chronic Chagas disease (cChD) patients treated with nifurtimox. METHODS: An observational study was performed in 146 cChD patients followed over a mean of 7.9 years. RESULTS: Of the 146 patients, 41 (28.1%) with normal electrocardiogram (ECG) at baseline maintained this condition, 34 (23.3%) with altered ECG at baseline normalised the alterations, and 46 (31.5%) with ECG abnormalities at baseline maintained this condition [23 (15.8%) with small alterations]. Finally, 25 cases (17.1%) in indeterminate phase altered the ECG. Differences before and after follow-up (P < 0.001) were found. The percentage of beneficial treatment was different than expected by chance (Z = 4.8; P < 0.001) and the annual percentage of cases that developed ECG alterations was lower than that of a historical cohort of untreated patients (P < 0.001). An echocardiogram was performed in 68 patients with baseline ECG alterations. The ejection fraction (EF) was normal in 57 (83.8%) and abnormal in 11 (16.2%). In 38 patients with ECG abnormalities that did not progress after treatment, EF and segmental motility (SM) were normal in 31 (81.6%) and 26 (68.4%), respectively. In 17 patients with ECG abnormalities, EF and SM were normal in 15 (88.2%) and 14 (82.4%) cases, respectively. CONCLUSION: Less progression to cardiomyopathy compared with a historical untreated cohort as well as the EF/SM results in patients with abnormal ECG that did not progress and in indeterminate cChD that altered the ECG suggests a beneficial effect of nifurtimox.

Microsatellite marker analysis shows differentiation among Trypanosoma cruzi populations of peripheral blood and dejections of Triatoma infestans fed on the same chronic chagasic patients : microsatellite marker analysis and T. cruzi.

To investigate whether Trypanosoma cruzi populations found in chagasic cardiopathic and non-cardiopathic patients are genetically differentiated, three molecular microsatellite markers were analysed. This analysis was also applied to compare T. cruzi samples from peripheral blood or dejections of Triatoma infestans fed on the blood of the same patients. In order to obtain the first objective, analyses of predominant T. cruzi genotypes were conducted using three approaches: a locus-by-locus analysis; a Fisher method across three loci; and analysis of molecular variance by Genepop and Arlequin programs. Only with one locus and on the blood samples was a significant differentiation detected among non-cardiopathic and cardiopathic groups, which was not confirmed by the other two methods. On the contrary, with the three approaches, it was found that T. cruzi clones present in the blood of patients are genetically differentiated from those detected in dejections of T. infestans fed on the same patients. Our results showed that the most frequent lineage both in blood as well as in triatomine dejection samples was TcI. No significant difference in T. cruzi lineage distribution was observed among chagasic cardiopathic and non-cardiopathic patients. The majority of the samples (50-60%) had only one T. cruzi clone (uniclonal) either in blood or dejection samples.

Chronic Chagas cardiopathy in Chile. Importance of Trypanosoma cruzi burden and clinical evaluation.

Currently there are no biological markers to indicate which individuals with chronic indeterminate period of Chagas disease develop heart disease and who will remain all his life in this phase. The aim of this survey was to determine if Trypanosoma cruzi burden is related to the presence of heart disease in patients with chronic Chagas disease. 200 patients who had not been treated, 100 with cardiopathy and 100 without, groups A and B respectively, were submitted to clinical study and electrocardiogram, Echo-Doppler was performed for group A in which all important known causes of cardiopathy were discarded. In both groups xenodiagnosis, conventional PCR and quantitative PCR were undertaken. The 100 cardiopaths had 133 electrocardiographic alterations most of them in grade II of the New York Heart Association classification. 98 cardiopaths were classified in grade I by Echo-Doppler and only 2 cases were in grade III due to low ejection fraction. The difference in average parasitemia in patients of group A and B was not significant and no statistically differences were observed between average parasitemia of cardiopaths grade II versus grade I of NYHA. This results allow to characterize same clinical, electrocardiographical and parasitological features in chagasic cardiopaths of Chile.

Differential distribution of Trypanosoma cruzi clones in human chronic chagasic cardiopathic and non-cardiopathic individuals.

PCR and Southern blot hybridization were used to determine the distribution of Trypanosoma cruzi clones in 37 chronic chagasic cardiopathic and non-cardiopathic patients. Parasite DNA amplified from peripheral blood or dejections of Triatoma infestans fed on patient blood was hybridized with probes containing hypervariable minicircle nucleotide sequences capable of detecting three sublineages of T. cruzi. Probes Z-I and Z-IIb detect unique sequences in lineages TcI and TcIIb, respectively. Probe Z-hybrid detects sequences of lineages TcIId and TcIIe. T. cruzi clones of the Z-I sublineage were detected in 62.2% of T. infestans dejections and 5.4% of peripheral blood samples. Clones of Z-IIb and Z-hybrid sublineages had similar distribution in blood and dejection samples. Interestingly, clones of the Z-IIb sublineage were significantly lower in cardiopathic than in non-cardiopathic patients (23.5% versus 75%; P=0.0006). Clones of the Z-hybrid sublineage were found in 29.4% of cardiopathic and 75% of non-cardiopathic patients, respectively (P=0.0051). By contrast, clones of sublineage Z-I were similarly distributed in both groups of patients. The low frequency of Z-IIb and Z-hybrid sublineage clones detected in cardiopathic patients suggests that the immunological mechanisms involved in controlling and eliminating these T. cruzi parasites may be detrimental to the host, leading to the development of chagasic cardiomyopathy.

[No association between persistence of the parasite and electrocardiographic evolution in treated patients with Chagas disease]. / La mejoría electrocardiográfica con el tratamiento de la enfermedad de Chagas crónica, es independiente de la persistencia de Trypanosoma cruzi.

BACKGROUND: At the present time the assessment of results of treatment of Chagas disease is mainly parasitological. Anti Trypanosoma cruzi IgGs remain positive practically lifelong and electrocardiographic tracings are not usually used as criteria of improvement. AIM: To determine, in a long term follow up, if electrocardiographic evolution is associated with the persistence of the parasite in treated patients with chronic Chagas disease. MATERIAL AND METHODS: Thirty patients with chronic Chagas disease that participated in a randomized trial of treatment with itraconazole or allopurinol, were studied. Seven years after treatment, patients were classified in group I if they had a positive xenodiagnosis test, polymerase chain reaction and hybridization in blood or in group II if they had negative tests. A 12 lead electrocardiogram (EKG) was performed each year to all patients. RESULTS: Seventeen patients were classified in group I and 13 in group II. At baseline 10 patients in group I and 8 in group II had a normal EKG. Six years after treatment 13 patients in group I and 10 in group II had a normal tracing. Of those with a normal tracing at baseline, only one patient in each group presented alterations after six years. A regression of abnormal tracings was observed in four and three patients of groups I and II respectively. CONCLUSIONS: There is no association between the persistence of the parasite in treated patients with Chagas disease and the evolution of electrocardiographic tracings.

Evaluación del alopurinol en la enfermedad de Chagas crónica humana en Chile / Evaluation of allopurinol in the treatment of human chronic disease in Chile

Se evaluó el tratamiento con alopurinol en 51 personas con enfermedad de Chagas crónica y xenodiagnóstico positivo, 30 de ellas infectadas asintomáticas y 21 con cardiopatía chagásica. Se utilizó como criterio de éxito de la terapia los aspectos clínicos, electrocardiográficos y la parasitemia detectada mediante xenodiagnóstico. En general la eficacia del alopurinol fué de 27%. La droga fué muy bien tolerada, no observándose efectos adversos. Por éste motivo, éste fármaco podría ser considerado como terapia alternativa en casos seleccionados de enfermedad de Chagas crónica

Estudio de las arritmias de la cardiopatía chagásica en zona endémica mediante Holter de 1 hora / Arrhythmias of chagasic myocardiopathy: field study in endemic rural zones with a 1-hour Holter

Se estudia una casuística de 142 cardiópatas chagásicos y un grupo control de 64 chagásicos sin cardiopatía, en zonas endémicas mediante ECG y Holter de 1 hora en sistema de minicassette para detectar arritmias. Se encuentra que con el ECG hubo arritmias en el 21,8% de los casos con cardiopatía en tanto que con el Holter de 1 hora la frecuencia fué de 64,8% de éstos pacientes (p<0,005). La especificidad de los métodos para comprobar presencia de arritmia fué de 89,1% para el ECG y de 92,2% para el Holter. Se conclutye que el método del Holter de 1 hora es útil y representa un aporte no invasivo al estudio de las arritmias de la Enfermedad de Chagas en el tereno, de fácil empleo, fidedigno y muy económico. El estudio permitió, además, verificar que las arritmias comprometieron sobre el 50% de la casuística estudiada, a diferentes edades, y aparecieron más precozmente en las mujeres que en los hombres

Evolución de la cardiopatía chagásica durante un período de cuatro años en un grupo de pacientes chilenos / Course of chagas' cardiopathy during a 4 year follow-up in a group of chilean patients

En 1977, los autores emprendieron una investigación a largo plazo de la epidemiología de la enfermedad de Chagas y sus repercusiones cardíacas en Chile. En un grupo de 2 938 personas que residían en localidades rurales del norte de ese país se efectuaron exámenes clínicos, pruebas serológicas y electrocardiogramas; esto se volvió a repetir cuatro años después con 481 sujetos que seguían residiendo en la región. El presente informe da a conocer los resultados del estudio complementario efectuado a los cuatro años. Inicialmente, los sujetos estudiados se dividieron en tres grupos específicos: los que padecían cardiopatía (a juzgar por un ECG anormal) pero no tenían indicios de enfermedad de Chagas formaron el grupo A; los que presentaban prueba serológica positiva y cardiopatía chagásica constituyeron el grupo B; y 67 personas escogiadas al azar entre las que tenían prueba serológica positiva para enfermedad de Chagas y ECG normal formaron el grupo C. En el momento del estudio complementario, 216 sujetos quedaban en el grupo A y 198 en el grupo B. La comparación de los datos iniciales y finales de los grupos A y B arrojó varios resultados que parecen significativos. Se observó una mortalidad cuatro veces mayor entre los sujetos infectados y la cardiopatía chagásica mostró tendencia a afectar a una población mucho más joven de la que es afectada por otras cardiopatías. Asimismo, la cardiopatía se presentó en los sujetos infectados del grupo C con una tasa aproximada de 9,7% al año, o sea con rapidez considerablemente mayor que la señalada en un estudio longitudinal anterior. Además los resultados ponen de relieve la capacidad del ECG para identificar la cardiopatía chagásica en evolución, lo cual hace pensar que esta prueba podría resultar útil para seleccionar a los pacientes que deben recibir tratamiento. Los resultados también indican que el cuadro clínico de la enfermedad de Chagas en Chile difiere del observado en otras partes de América, pues los síntomas francos son escasos a pesar de que la enfermedad tiene todo el aspecto de estar ocasionando daños graves...

Seguimiento de marcapasos, antiarritmia y acelerados por espacio QT / Follow-up of antiarrhythmic and accelerated by QT time pacemakers

Se revisa una casuística de 10 pacientes en los que se empleó un marcapaso con módulo antiarrítmico en 6 portadores de enfermedad del nódulo y un marcapaso acelerado por espacio QT en 4 portadores de bloqueo A-V de 2- y 3- grado. En 5 casos se empleó un módulo flywheel que normalizó el ritmo en todos. En un caso se empleó un módulo overdrive para controlar una fibrilación auricular caótica. Dos casos fallecieron en el período de observación que varió de 27 a 57 meses. Se revisa las indicaciones del marcapaso DPG y TX. Se puntualiza que este tipo de marcapasos tienen indicaciones limitadas y lógicas de implante y que presentan evidentes ventajas sobre la estimulación VVI