Alejandro Marcel Hasslocher-Moreno

ELISA versus PCR for diagnosis of chronic Chagas disease: systematic review and meta-analysis

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. ELISAs 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.

Implication of Transforming Growth Factor–β1 in Chagas Disease Myocardiopathy

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.

II Consenso Brasileiro em Doença de Chagas, 2015

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.

2 nd Brazilian Consensus on Chagas Disease, 2015

Chagas disease is a neglected chronic condition with a high burden of morbidity and mortality. It has considerable psychological, social, and economic impacts. 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 the articulation and strategic contribution of renowned Brazilian experts with knowledge and experience on various aspects of the disease. It is the result of a close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. It is hoped that this document will strengthen the development of integrated actions against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research .

Dealing with initial inconclusive serological results for chronic Chagas disease in clinical practice

Most guidelines for Chagas disease recommend the performance of two serological tests in order to detect it. However, inconclusive results may arise from this strategy. The aim was to describe whether serological follow-up together with the patient’s clinical characteristics could clarify the outcome of patients with initial inconclusive test results. In this retrospective case series, all results of Chagas disease serological tests and outpatient visits recorded from 2004 to 2008 were screened for inclusion. The inclusion criterion was clinical suspicion of chronic Chagas disease and the exclusion criteria were previous diagnosis of Chagas disease, suspicion of acute Chagas disease, and serological tests with no corresponding medical evaluation. A total of 1,732 patients were analyzed. Chronic Chagas disease prevalence was 21.1%. After the initial set of serological tests, 2.9% of patients had inconclusive test results. Most of these patients had definite diagnosis after clinical follow-up and the repetition of serological tests in a new blood sample. Loss to follow-up while partaking in the diagnostic investigation reached 17.7%. The prevalence of initial inconclusive serological tests for chronic Chagas disease is low. Clinical evaluations and follow-up clarify the definite diagnosis. Noncompliance to follow-up is a frequent problem. Strategies to reduce inconclusive results and noncompliance are discussed.

Impact of pharmaceutical care on the quality of life of patients with Chagas disease and heart failure: randomized clinical trial

BackgroundPharmaceutical care is the direct interaction between pharmacist and patient, in order to improve therapeutic compliance, promote adequate pharmacotherapeutic follow-up, and improve quality of life. Pharmaceutical care may be effective in reducing complications and in improving the quality of life of patients with chronic diseases, like Chagas heart disease, while bringing a positive impact on health system costs. The morbidity and mortality indexes for patients with Chagas heart disease are high, especially if this heart disease is complicated by heart failure. In this setting, we hypothesize that pharmaceutical care might be an important tool for the clinical management of these patients by improving their quality of life, as a better compliance to their treatment and the avoidance and prompt correction of drug-related problems will minimize their symptoms, improve their functional class, and decrease the number of hospital admissions. Therefore, the aim of this trial is to evaluate the contribution of pharmaceutical care to clinical treatment of patients with Chagas heart disease complicated by heart failure.Methods/designA prospective, single-center randomized clinical trial will be conducted in patients with Chagas heart disease complicated by heart failure. A total of 88 patients will be randomly assigned into two parallel groups: an intervention group will receive standard care and pharmaceutical care, and a control group will receive only standard care. Both groups will be subjected to a follow-up period of 12 months. The primary outcome of this trial is the evaluation of quality of life, measured by the 36-item short-form and the Minnesota Living with Heart Failure Questionnaire. Secondary outcomes include drug-related problems, exercise tolerance as measured by the standard six-minute-walk test, and compliance.DiscussionPatients with Chagas heart disease complicated by heart failure under pharmaceutical care are expected to improve their quality of life, present with a lower incidence of drug-related problems, improve their functional capacity, and improve in their compliance to treatment.Trial registrationClinicalTrials.gov Identifier: NCT01566617

Predictive value of transforming growth factor-β1in Chagas disease: towards a biomarker surrogate of clinical outcome

BACKGROUND Transforming growth factor-β1 (TGF-β1) may be implicated in the development of Chagas heart disease. However, the clinical value of TGF-β1 measurement is yet to be determined. METHODS We retrospectively analyzed the outcome of 54 Chagas disease patients without heart failure and with left ventricular (LV) ejection fraction >45% whose TGF-β1 serum values were determined between January 1998 and December 1999. Primary end point was all-cause mortality and secondary end point was the combination of all-cause mortality or hospitalization due to worsening heart failure or cardiac arrhythmias. RESULTS TGF-β1 was independently associated with the occurrence of the primary and secondary end points. The optimal cutoff for TGF-β1 to identify the primary end point was 12.9 ng/ml (area under the curve = 0.82, p = 0.004, sensitivity 100%, and specificity 57%) and to identify the secondary end point was 30.8 ng/ml (area under the curve = 0.72, p = 0.03, sensitivity 60%, and specificity 86%). LV ejection fraction and LV end-diastolic diameter were also independent predictors of the primary and secondary endpoints, respectively. CONCLUSION The described association between TGF-β1 and clinical outcome provides evidence towards the clinical value of TGF-β1 in Chagas disease.

Cardiac rehabilitation program in patients with Chagas heart failure: a single-arm pilot study

INTRODUCTION The benefit of a cardiac rehabilitation (CR) program for patients with Chagas heart failure (CHF) remains unclear. Therefore, we aimed to investigate the effects of CR for CHF patients. METHODS A single-arm pilot study, including 12 patients with CHF, was performed. Patients participated in an 8-month physical exercise intervention, comprising aerobic, strength, and stretching exercises (3 times per week, 60 minutes per session). Nutritional and pharmaceutical counseling were also performed. Functional capacity (cardiopulmonary exercise test), muscle respiratory strength (manovacuometry), and body composition (anthropometry and skinfolds) were evaluated at baseline, and after 4 and 8 months of intervention. Cardiac function (echocardiography), biomarkers (lipid profile, glucose, and glycated hemoglobin) and quality of life (Minnesota Living with Heart Failure Questionnaire) were assessed at baseline and at the end of the intervention. RESULTS Seven of 12 patients included in the study completed the 8-month follow-up period. Only 2 moderate adverse events occurred during the exercise training. Functional capacity improved after 4 months of CR, while left ventricular ejection fraction (LVEF) and respiratory strength improved after 8 months. Patients with right ventricular (RV) dysfunction at baseline exhibited an improvement in functional capacity after 4 months, and improvements in left ventricular (LV) diastolic pressure, respiratory strength, and quality of life at the end of follow-up. Conversely, those with normal baseline RV function demonstrated LVEF increases that were not observed in patients with RV dysfunction. CONCLUSIONS CR was feasible, safe, and has important clinical benefits for patients with CHF, specifically for cardiac function and muscle respiratory strength.

Reassessment of quality of life domains in patients with compensated Chagas heart failure after participating in a cardiac rehabilitation program

INTRODUCTION: We evaluated the effects of a cardiac rehabilitation program on quality of life. METHODS This secondary analysis of a single-arm study included 12 patients with Chagas heart failure. The cardiac rehabilitation program comprised exercise training and nutritional and pharmaceutical counseling. Quality of life was assessed using the SF-36 questionnaire. RESULTS: The program promoted improved physical functioning (β= +5.7; p=0.003), role-physical (β= +1.9; p=0.03), and bodily pain (β= +3.5; p=0.02) scores. Moreover, the summary physical health score (β= +1.4; p=0.001) improved. CONCLUSION: The cardiac rehabilitation program significantly improved the physical quality of life of patients with Chagas heart failure.

Atenção integral e eficiência no Laboratório de Pesquisa Clínica em Doenças de Chagas do Instituto de Pesquisa Clínica Evandro Chagas, 2009-2011

Objective: to characterize the level of procedure diversiication required by the Integral Health Care Model for Chagas’ disease treatment and assess it with respect to eficient use of resources. Methods: a microcosts survey, as well as Activity-Based Costing (ABC) and Data Envelopment Analysis (DEA) models, were used to calculate annual expenditure and actual unit costs of procedures for a case study assessing the performance of the Chagas’ Disease Clinic Research Laboratory/Evandro Chagas Clinical Research Institute/Fiocruz health care model. Results: diversiication and pro-eficiency motivation were conirmed by the identiication of 291 procedures types in 2009 and 19% eficiency gain in the period 2009-2011. Conclusion: eficiency Analysis reveals explanatory power over decision-making in multipurpose public health organizations and demonstrated the eficiency of the model in Chagas’ disease treatment and its potential contribution to effective care actions in the Brazilian Uniied Health System.