A simple risk score was developed to predict death in Chagas' heart disease and was validated in an independent cohort.

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Background-QT interval parameters are potential prognostic markers of arrhythmogenicity risk and cardiovascular mortality and have never been evaluated in Chagas' disease. Methods and Results-Outpatients (738) in the chronic phase of Chagas' disease were enrolled in a long-term follow-up study. Maximal heart rate-corrected QT (QTc) and T-wave peak-to-end (TpTe) intervals and QRS, QT, JT, QTapex, and TpTe dispersions and variation coefficients were measured manually and calculated from 12-lead ECGs obtained on admission. Clinical, radiological, and 2-dimensional echocardiographic data were also recorded. Primary end points were all-cause, Chagas' disease-related, and sudden cardiac mortalities. During a follow-up of 58Ϯ39 months, 62 patients died, 54 of Chagas' disease-related causes and 40 suddenly. Multivariate Cox survival analysis revealed that the QT-interval dispersion (QTd) (hazard ratio, 1.45; 95% confidence interval, 1.29 to 1.63; PϽ0.001, for 10-ms increments) and left ventricular (LV) end-systolic dimension (hazard ratio, 1.36; 95% confidence interval, 1.21 to 1.53; PϽ0.001, for 5-mm increments) were the strongest independent predictors for all end points. The maximum QTc interval (QTcmax) could substitute for QTd with a worse predictive performance. Other predictors were heart rate, presence of pathological Q waves, frequent premature ventricular contractions (PVCs), and isolated left anterior fascicular block (LAFB) on the ECGs. Kaplan-Meier survival curves demonstrated that a QTd Ն65 ms or a QTcmax Ն465 ms 1/2 discriminated the 2 groups with significantly different prognoses. Conclusions-Electrocardiographic QTd and echocardiographic LV end-systolic dimension were the most important mortality predictors in patients with Chagas' disease. Heart rate, the presence on ECG of pathological Q waves, frequent PVCs, and isolated LAFB refined the mortality risk stratification. (Circulation. 2003;108:305-312.)

BackgroundMost current guidelines recommend two serological tests to diagnose chronic Chagas disease. When serological tests are persistently inconclusive, some guidelines recommend molecular tests. The aim of this investigation was to review chronic Chagas disease diagnosis literature and to summarize results of ELISA and PCR performance.MethodsA systematic review was conducted searching remote databases (MEDLINE, LILACS, EMBASE, SCOPUS and ISIWeb) and full texts bibliography for relevant abstracts. In addition, manufacturers of commercial tests were contacted. Original investigations were eligible if they estimated sensitivity and specificity, or reliability -or if their calculation was possible - of ELISA or PCR tests, for chronic Chagas disease.ResultsHeterogeneity was high within each test (ELISA and PCR) and threshold effect was detected only in a particular subgroup. Reference standard blinding partially explained heterogeneity in ELISA studies, and pooled sensitivity and specificity were 97.7% [96.7%-98.5%] and 96.3% [94.6%-97.6%] respectively. Commercial ELISA with recombinant antigens studied in phase three investigations partially explained heterogeneity, and pooled sensitivity and specificity were 99.3% [97.9%-99.9%] and 97.5% [88.5%-99.5%] respectively. ELISA's reliability was seldom studied but was considered acceptable. PCR heterogeneity was not explained, but a threshold effect was detected in three groups created by using guanidine and boiling the sample before DNA extraction. PCR sensitivity is likely to be between 50% and 90%, while its specificity is close to 100%. PCR reliability was never studied.ConclusionsBoth conventional and recombinant based ELISA give useful information, however there are commercial tests without technical reports and therefore were not included in this review. Physicians need to have access to technical reports to understand if these serological tests are similar to those included in this review and therefore correctly order and interpret test results. Currently, PCR should not be used in clinical practice for chronic Chagas disease diagnosis and there is no PCR test commercially available for this purpose. Tests limitations and directions for future research are discussed.

Trypanosoma cruzi specific sequences were amplified by the polymerase chain reaction from total blood of human chagasic patients and normal individuals. A 330 bp fragment originating from kinetoplast DNA was specifically detected in most chagasic individuals. We tested the sensitivity and specificity of this method in normal and affected individuals attending the Evandro Chagas Hospital, Rio de Janeiro. The results of these tests were compared with serological diagnosis performed using standard techniques, and in some cases with xenodiagnosis. We found that none of the serologically negative individuals gave any specific amplification product, whereas 55 out of 61 patients previously serodiagnosed as chagasic were positive using the PCR method (sensitivity: 90%). Xenodiagnosis, which is currently considered to be the most sensitive parasitological technique for Chagas' disease diagnosis, detected only 12 out of 28 serologically positive patients (sensitivity: 43%). The usefulness of the PCR method was further investigated with chagasic patients who had received anti-parasite treatment with benznidazole. It has always been difficult to evaluate the incidence of cure in such cases by serology, since a humoral response against T. cruzi antigens may remain for years even in the absence of the parasite. We observed a positive amplification result in only 9 out of 32 treated patients who remained reactive when tested using classical serology. These observations suggest that PCR is the most sensitive technique available for direct detection of T. cruzi in chagasic patients and that it can be a very useful instrument for the follow-up of patients after specific treatment.

Cardiac dysfunction with progressive fibrosis is a hallmark of Chagas disease. To evaluate the involvement of transforming growth factor (TGF)-beta1 in this disease, TGF-beta1 levels in patients were measured at 3 stages: asymptomatic indeterminate (IND), cardiac with no or slight heart dysfunction (Card 1), and cardiac with moderate or severe heart dysfunction (Card 2). All patients had significantly higher circulating levels of TGF-beta1 than did healthy persons, and 27% of patients in the Card 1 group had higher TGF-beta1 levels than did patients in the IND group. Immunohistochemical analysis of cardiac biopsy specimens showed strong fibronectin staining in the extracellular matrix and staining for phosphorylated Smad 2 (activation of the TGF-beta1 signaling pathway) in cell nuclei. The higher levels of latent TGF-beta1 observed in patients with myocardiopathy, together with intracellular activation of the TGF-beta1 pathway and tissue fibrosis, suggest that TGF-beta1 plays an important role in Chagas disease. TGF-beta1 may represent a new target for preventive and curative treatments of Chagas disease.

The Naranjo algorithm was a useful tool to reduce the underreporting of ADRs. Events were common, but were associated with low morbidity and were reversible upon discontinuation of drug treatment. Moreover, there were no fatal events; therefore, benznidazole treatment was considered safe.

Chagas disease is a neglected chronic condition that presents high morbidity and mortality burden, with considerable psychological, social, and economic impact. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on collaboration and contribution of renowned Brazilian experts with vast knowledge and experience on various aspects of the disease. It is the result of close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. This document shall strengthen the development of integrated control measures against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research.