Drug screening and development cascade for Chagas disease: an update of in vitro and in vivo experimental models.

Chagas disease is a tropical neglected disease that affects millions of people worldwide, still demanding a more effective and safer therapy, especially in its chronic phase which lacks a treatment that promotes substantial parasitological cure. The technical note of Romanha and collaborators published in 2010 aimed establish a guideline with the set of minimum criteria and decision gates for the development of new agents against Trypanosoma cruzi with the focus on developing new antichagasic drugs. In this sense, the present review aims to update this technical note, bringing the state of the art and new advances on this topic in recent years.

Autonomic denervation, myocardial hypoperfusion and fibrosis may predict ventricular arrhythmia in the early stages of Chagas cardiomyopathy.

BACKGROUND: Sudden cardiac death (SCD) can be the first clinical event of Chagas heart disease (CHD). However, current guidelines contain no clear recommendation for early cardioverter-defibrillator implantation. Using imaging modalities, we evaluated associations among autonomic denervation, myocardial hypoperfusion, fibrosis and ventricular arrhythmia in CHD. METHODS AND RESULTS: Twenty-nine patients with CHD and preserved left ventricular function underwent 123I-metaiodobenzylguanidine (MIBG) scintigraphy, 99mTc-methoxyisobutylisonitrile (MIBI) myocardial perfusion and cardiac magnetic resonance imaging (MRI). They were divided into arrhythmic (≥ 6 ventricular premature complexes/h and/or non-sustained ventricular tachycardia on 24-hour Holter, n = 15) and non-arrhythmic (< 6 ventricular premature complexes/h and no ventricular tachycardia; n = 14) groups. The arrhythmic group had higher denervation scores from MIBG imaging (23.2 ± 18.7 vs 5.6 ± 4.9; P < .01), hypoperfusion scores from MIBI SPECT (4.7 ± 6.8 vs 0.29 ± 0.6: P = .02), innervation/perfusion mismatch scores (18.5 ± 17.5 vs 5.4 ± 4.8; P = .01) and fibrosis by late gadolinium enhancement on MRI (14.3% ± 13.5% vs 4.0% ± 2.9%; P = .04) than the non-arrhythmic group. CONCLUSION: These imaging parameters were associated with ventricular arrhythmia in early CHD and may enable risk stratification and the implementation of primary preventive strategies for SCD.

Benznidazole treatment safety: the Médecins Sans Frontières experience in a large cohort of Bolivian patients with Chagas' disease.

Background: Up to half of patients with Chagas' disease under benznidazole treatment present adverse drug reactions (ADRs) and up to one-third do not complete standard treatment. Objectives: To verify the incidence and possible factors associated with the suspension of benznidazole treatment in a large cohort of patients. Methods: We included 2075 patients treated with benznidazole during the projects managed by the medical humanitarian organization Doctors Without Borders (Médecins Sans Frontières) in Bolivia from 2009 to 2013. Benznidazole treatment was provided two or three times per day for ∼60 days at 5-7.5 mg/kg/day. A multiple logistic regression model was developed to evaluate the factors associated with permanent suspension of benznidazole treatment. Results: Permanent benznidazole treatment suspension occurred in 211 patients (10.2%) and the average time until permanent treatment suspension was 23 days. Multifactorial analysis revealed that female sex (adjusted OR = 1.70), moderate ADRs (adjusted OR = 10.57), mild ADRs (adjusted OR = 1.69) and skin disorders (adjusted OR = 4.18) were significantly associated with the permanent suspension of benznidazole treatment. Women with mild or moderate skin ADRs presented a probability of treatment interruption of 18.6% and 59.0%, respectively. Conclusions: Benznidazole treatment was safe and a large proportion of patients were able to complete a full course of benznidazole treatment under close treatment surveillance. Female sex, skin disorders and mild and moderate ADRs were independently associated with the permanent suspension of benznidazole treatment. In particular, women with moderate skin ADRs had the highest risk of benznidazole treatment interruption.

Omega-3 supplementation on inflammatory markers in patients with chronic Chagas cardiomyopathy: a randomized clinical study.

BACKGROUND: Several studies have been focusing on the effect of omega-3 polyunsaturated fatty acids on modulation of inflammatory markers in several cardiopathies. Although immunoregulatory dysfunction has been associated to the chronic cardiac involvement in Chagas disease, there is no study examining the effects of omega-3 supplementation in these patients. We investigated the effects of omega-3 PUFAs on markers of inflammation and lipid profile in chronic Chagas cardiomyopathy patients. METHODS: The present study was a single-center double-blind clinical trial including patients with chronic Chagas cardiomyopathy. Patients were randomly assigned to receive omega-3 PUFAs capsules (1.8g EPA and 1.2g DHA) or placebo (corn oil) during an 8-week period. Cytokines, fasting glucose, lipid, and anthropometric profiles were evaluated. RESULTS: Forty-two patients (23 women and 19 men) were included in the study and there were only two losses to follow-up during the 8-week period. Most of sociodemographic and clinical characteristics were similar between the groups at baseline, except for the cytokines IL-1ß, IL-6, IL-8, IL-10, IL-17α, and IFNγ. The omega-3 PUFAs group demonstrated greater improvements in serum triglycerides (-21.1 vs. -4.1; p = 0.05) and IL-10 levels (-10.6 vs. -35.7; p = 0.01) in comparison to controls after 8 weeks of intervention. No further differences were observed between groups. CONCLUSION: Omega-3 PUFAs supplementation may favorably affect lipid and inflammatory profile in chronic Chagas cardiomyopathy patients, demonstrated by a decrease in triglycerides and improvements on IL-10 concentration. Further studies examining the clinical effects of omega-3 fatty acids supplementation in chronic Chagas cardiomyopathy are necessary. TRIAL REGISTRATION: NCT01863576.

Autochthonous transmission of Chagas disease in Rio de Janeiro State, Brazil: a clinical and eco-epidemiological study.

BACKGROUND: After the control of the main modes of Chagas disease (CD) transmission in most endemic countries, it is important to identify the participation of native sylvatic vectors in CD transmission. Although CD is not considered endemic in Rio de Janeiro State (RJ), Brazil, we identified patients with CD born in RJ and investigated the possible autochthonous transmission in the state. METHODS: Patients born in RJ and followed in our institution between 1986 and 2011 were retrospectively analyzed. The cases identified as autochthonous transmission were submitted to epidemiological, clinical, serological, parasitological and molecular studies. Sectional field study with serological survey, research of sylvatic reservoirs and vectors was conducted in rural areas where patients were born. RESULTS: Among 1963 patients, 69 (3.5%) were born in RJ. From these, 15 (21.7%) were considered to have acquired the infection by autochthonous transmission. Cardiac form was the commonest form of presentation (60%). In rural areas in RJ northern region, sylvatic cycles of Trypanosoma cruzi and domestic invasion by Triatoma vitticeps were identified, and CD prevalence among inhabitants was 0.74%.TcI genotype was identified in sylvatic reservoirs and vectors. The genotype (mixed infection TcI/TcVI) could be identified in one of the autochthonous cases. CONCLUSIONS: The autochthonous vectorial transmission of CD occurs in RJ, probably due to wild cycles of T. cruzi and sylvatic vectors, such as T. vitticeps. Therefore, the health authorities should evaluate if RJ should be included in the original endemic area of CD and CD should be included in the diagnostic work out of cardiomyopathy of patients born in RJ. Moreover, control and educational measures should be put into place in the risk areas.

Matrix metalloproteinases 2 and 9 are differentially expressed in patients with indeterminate and cardiac clinical forms of Chagas disease.

Dilated chronic cardiomyopathy (DCC) from Chagas disease is associated with myocardial remodeling and interstitial fibrosis, resulting in extracellular matrix (ECM) changes. In this study, we characterized for the first time the serum matrix metalloproteinase 2 (MMP-2) and MMP-9 levels, as well as their main cell sources in peripheral blood mononuclear cells from patients presenting with the indeterminate (IND) or cardiac (CARD) clinical form of Chagas disease. Our results showed that serum levels of MMP-9 are associated with the severity of Chagas disease. The analysis of MMP production by T lymphocytes showed that CD8(+) T cells are the main mononuclear leukocyte source of both MMP-2 and MMP-9 molecules. Using a new 3-dimensional model of fibrosis, we observed that sera from patients with Chagas disease induced an increase in the extracellular matrix components in cardiac spheroids. Furthermore, MMP-2 and MMP-9 showed different correlations with matrix proteins and inflammatory cytokines in patients with Chagas disease. Our results suggest that MMP-2 and MMP-9 show distinct activities in Chagas disease pathogenesis. While MMP-9 seems to be involved in the inflammation and cardiac remodeling of Chagas disease, MMP-2 does not correlate with inflammatory molecules.

Blood culture positivity rate for Trypanosoma cruzi in patients with chronic Chagas disease differs among different clinical forms.

BACKGROUND: The purpose of this research was to compare the clinical and epidemiological characteristics of patients with chronic Chagas disease with and without positive blood cultures for Trypanosoma cruzi. METHODS: This was a retrospective longitudinal study that included 139 patients with chronic Chagas disease who underwent blood culture for T. cruzi. Blood cultures were performed using Novy-MacNeal-Nicolle medium enriched with Schneider's medium. Multivariate Cox proportional hazards regression analysis adjusting for age and sex was performed to identify if positive blood culture for T. cruzi was associated with all-cause mortality. RESULTS: The blood culture positivity rate was 30.9%. Most patients were born in the Northeast and Southeast regions of Brazil. Patients with positive blood cultures were older (52±13 vs 45±13 y; p=0.0009) and more frequently women (72.1% vs. 53.1%; p=0.03) than patients with negative blood cultures. The frequency of patients with cardiac or cardiodigestive forms was higher among patients with positive vs negative blood cultures (74.4% vs 54.1%; p=0.02). A total of 28 patients died during a mean follow-up time of 6.6±4.1 y. A positive blood culture was associated with all-cause mortality (hazard ratio 2.26 [95% confidence interval 1.02 to 5.01], p=0.045). CONCLUSIONS: We found a higher proportion of patients with Chagas heart disease among patients with T. cruzi-positive blood cultures. A positive blood culture was associated with an increased risk of all-cause mortality. Therefore T. cruzi persistence may influence Chagas disease pathogenesis and prognosis.

Temporal changes in the clinical-epidemiological profile of patients with Chagas disease at a referral center in Brazil.

INTRODUCTION: We aimed to describe the sociodemographic, epidemiological, and clinical characteristics of patients with chronic Chagas disease (CD) at an infectious disease referral center. Changes in patient profiles over time were also evaluated. METHODS: This retrospective study included patients with CD from November 1986-December 2019. All patients underwent an evaluation protocol that included sociodemographic profile; epidemiological history; anamnesis; and physical, cardiologic, and digestive examinations. Trend differences for each 5-year period from 1986 to 2019 were tested using a nonparametric trend test for continuous and generalized linear models with binomial distribution for categorical variables. RESULTS: A total of 2,168 patients (52.2% women) were included, with a mean age of 47.8 years old. White patients with low levels of education predominated. The reported transmission mode was vectorial in 90.2% of cases. The majority came from areas with a high prevalence (52.2%) and morbidity (67.8%) of CD. The most common clinical presentation was the indeterminate form (44.9%). The number of patients referred gradually decreased and the age at admission increased during the study period, as did the patients' levels of education. CONCLUSIONS: The clinical profile of CD is characterized by a predominance of the indeterminate form of the disease. Regarding the patients who were followed up at the referral center, there was a progressive increase in the mean age and a concomitant decrease in the number of new patients. This reflects the successful control of vector and transfusion transmission in Brazil as well as the aging population of patients with CD.

Prevalence of metabolic syndrome and associated factors among patients with chronic Chagas disease.

The increase in life expectancy and the migration of individuals with Chagas disease (ChD) from rural to urban centers exposes them to the development of chronic-degenerative abnormalities that may increase the prevalence of metabolic syndrome (MetS). The present study aimed to identify the prevalence of MetS and its components in individuals with chronic ChD. This is a cross-sectional study with 361 patients of both sexes, aging >18 years, followed at a national reference center (Rio de Janeiro, Brazil). MetS diagnosis followed the International Diabetes Federation 2005 criteria. The association between the variables was determined through logistic regression models. The mean age was and 60.7±10.8 years. About half (56.2%) were female and the majority self-reported their race as mulatto (59.8%). The percentage of individuals with MetS was 40.4%. The variables independently associated with MetS were age (OR 1.06; 95%CI 1.04-1.09), high education levels (OR 0.36; 95%CI 0.17-0.79) and cardiac form with heart failure (OR 0.34; 95%CI 0.17-0.68). Therefore, a high prevalence of MetS was found in this Brazilian chronic ChD cohort. The identification of the associated factors can facilitate the development of effective approaches for preventing and managing MetS in ChD patients.

Association between Trypanosoma cruzi DTU TcII and chronic Chagas disease clinical presentation and outcome in an urban cohort in Brazil.

BACKGROUND: The specific roles of parasite characteristics and immunological factors of the host in Chagas disease progression and prognosis are still under debate. Trypanosoma cruzi genotype may be an important determinant of the clinical chronic Chagas disease form and prognosis. This study aimed to identify the potential association between T. cruzi genotypes and the clinical presentations of chronic Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: This is a retrospective study using T. cruzi isolated from blood culture samples of 43 patients with chronic Chagas disease. From 43 patients, 42 were born in Brazil, mainly in Southeast and Northeast Brazilian regions, and one patient was born in Bolivia. Their mean age at the time of blood collection was 52.4±13.2 years. The clinical presentation was as follows 51.1% cardiac form, 25.6% indeterminate form, and 23.3% cardiodigestive form. Discrete typing unit (DTU) was determined by multilocus conventional PCR. TcII (n = 40) and TcVI (n = 2) were the DTUs identified. DTU was unidentifiable in one patient. The average follow-up time after blood culture was 5.7±4.4 years. A total of 14 patients (32.5%) died and one patient underwent heart transplantation. The cause of death was sudden cardiac arrest in six patients, heart failure in five patients, not related to Chagas disease in one patient, and ignored in two patients. A total of 8 patients (18.6%) progressed, all of them within the cardiac or cardiodigestive forms. CONCLUSIONS/SIGNIFICANCE: TcII was the main T. cruzi DTU identified in chronic Chagas disease Brazilian patients (92.9%) with either cardiac, indeterminate or cardiodigestive forms, born at Southeast and Northeast regions. Other DTU found in much less frequency was TcVI (4.8%). TcII was also associated to patients that evolved with heart failure or sudden cardiac arrest, the two most common and ominous consequences of the cardiac form of Chagas disease.

Associations between Cardiac Magnetic Resonance T1 Mapping Parameters and Ventricular Arrhythmia in Patients with Chagas Disease.

Chronic Chagas disease can progress to myocardial involvement with intense fibrosis, which may predispose patients to sudden cardiac death through ventricular arrhythmia. The associations of myocardial fibrosis detected by cardiac magnetic resonance (CMR) parameters with non-sustained ventricular tachycardia (NSVT) were evaluated. This cross-sectional study included patients in early stages of Chagas disease (n = 47) and a control group (n = 15). Patients underwent cardiac evaluation, including CMR examination. Myocardial fibrosis assessment by CMR with measurement of late gadolinium enhancement (LGE), native T1, and extracellular volume (ECV) was performed. There was an increase in myocardial fibrosis CMR parameters and ventricular arrhythmias among different stages of Chagas disease, combined with a decrease in the left ventricular ejection fraction (LVEF) by CMR and also in the right ventricular systolic function by S' wave on tissue Doppler. Fibrosis mass and ECV were associated with the Rassi score, ventricular extrasystole, and E/e' ratio in a logistic regression model adjusted for age and gender. The ECV maintained an association with the presence of NSVT, even after adjustments for fibrosis mass and LVEF assessed by CMR. The receiver-operating characteristic area under the curve for global ECV (0.85; 95% CI: 0.71-0.99) and NSVT was greater than that for fibrosis mass (0.75; 95% CI: 0.54-0.96), although this difference was not statistically significant. Extracellular volume could be an early marker of increased risk of ventricular arrhythmia in Chagas disease, presenting an independent association with NSVT in the initial stages of chronic Chagas cardiomyopathy, even after adjustment for fibrosis mass and LVEF.

Progression Rate from the Indeterminate Form to the Cardiac Form in Patients with Chronic Chagas Disease: Twenty-Two-Year Follow-Up in a Brazilian Urban Cohort.

Most patients with chronic Chagas disease (CD) present the indeterminate form and are at risk to develop the cardiac form. However, the actual rate of progression to the cardiac form is still unknown. METHODS: In total, 550 patients with the indeterminate CD form were followed by means of annual electrocardiogram at our outpatient clinic. The studied endpoint was progression to cardiac form defined by the appearance of electrocardiographic changes typical of CD. The progression rate was calculated as the cumulative progression rate and the incidence progression rate per 100 patient years. RESULTS: Thirty-seven patients progressed to the CD cardiac form within a mean of 73 ± 4 8 months of follow-up, which resulted in a 6.9% cumulative progression rate and incidence rate of 1.48 cases/100 patient years. Patients who progressed were older (mean age 47.8 ± 12.2 years), had a higher prevalence of associated heart diseases (p < 0.0001), positive xenodiagnosis (p = 0.007), and were born in the most endemic Brazilian states (p = 0.018). Previous co-morbidities remained the only variable associated with CD progression after multivariate Cox proportional hazards regression analysis (p = 0.002). CONCLUSION: The progression rate to chronic CD cardiac form is low and inferior to rates previously reported in other studies.

Agreement between upper endoscopy and esophagography in the diagnosis of megaesophagus in Chagas disease.

INTRODUCTION: The diagnosis and classification of megaesophagus can be challenging in patients with Chagas disease. The present study aimed to evaluate the agreement between upper endoscopies and esophagographies for the diagnosis and classification of megaesophagus in Chagas disease. METHODS: A cross-sectional study of 50 patients with Chagas disease with upper digestive symptoms was undertaken. Esophagography and upper endoscopy exams were performed to compare diagnoses. Statistical analysis included sensitivity and specificity used to evaluate the diagnostic accuracy of upper endoscopies, and measures of agreement: linearly weighted Kappa (κw) and Cohen`s classical Kappa (κ) coefficients with 95% confidence intervals (95% CI). RESULTS: Twenty-three patients (46%) were diagnosed with megaesophagus by esophagography. The upper endoscopy sensitivity and specificity for megaesophagus diagnosis were 100% and 33.3%, respectively. Regarding megaesophagus classifications, there was a substantial agreement between the two exams (κw = 0.622; 95% CI: 0.498 to 0.746). Within megaesophagus groups, agreement for group I was slight (κ = 0.096; 95% CI: 0.000 to 0.403); for group II, substantial (κ = 0.703; 95% CI: 0.456 to 0.950); and for groups III and IV, inconclusive (κ = 0.457; 95% CI: 0.000 to 0.967; κ = 0.540; 95% CI: 0.035 to 1.000, respectively). CONCLUSIONS: Upper endoscopy has a high sensitivity, but a low specificity to diagnose megaesophagus. Agreement between the two exams varies depending on the megaesophagus grade. Thus, upper endoscopy can be used in the diagnostic workup of a possible Chagas disease megaesophagus, but all identified cases should undergo esophagography.

Ageing with Chagas disease: an overview of an urban Brazilian cohort in Rio de Janeiro.

BACKGROUND: Chagas disease control programmes have decreased the prevalence of Chagas disease in Latin America. Together with migration to urban areas and increase in life expectancy, a new scenario for Chagas disease has emerged in Brazil with most patients currently elderly individuals living in urban areas. However, acute Chagas disease cases still occur due to vector transmission by sylvatic vectors and oral transmission by contaminated food. Therefore, we characterized the clinical and epidemiological profile of the patients followed at Evandro Chagas National Institute of Infectious Diseases in Rio de Janeiro, Brazil. We aimed to identify the clinical forms, associated co-morbidities, and geographical areas where younger patients originate from. This will aid in the identification of potential challenges to be currently faced. RESULTS: This is a cross-sectional study. Adult patients with chronic Chagas disease were recruited between March 2013 and April 2016. Clinical and epidemiological data were obtained from electronic medical records and interviews. The clinical form of the Chagas disease presented by the patients was determined following the Brazilian Consensus on Chagas disease. Six hundred and nineteen patients (mean age 60 ± 12 years; 56.9% women) were included in this study. Patients' clinical forms were classified as follows: indeterminate 29.1%; cardiac 55.4%; digestive 5.5%; and mixed 10.0%. Patients aged over 65 years comprised 38% of the population. Hypertension was present in 347 (56%) patients, dyslipidemia in 261 patients (42%) and diabetes mellitus in 185 patients (30%). There were no differences regarding gender, race, comorbidities frequency or place of origin across Chagas disease clinical forms. Most of the elderly population originated from Bahia, Minas Gerais and Pernambuco states, while most of the younger patients were born in Ceará, Paraíba and Rio de Janeiro states. CONCLUSIONS: We described a great proportion of elderly patients in the composition of an urban Brazilian Chagas disease patient cohort with a high prevalence of comorbidities. We also identified a change in the pattern of the place of origin among younger patients.

A protocol update for the Selenium Treatment and Chagasic Cardiomyopathy (STCC) trial.

Several studies evaluating clinical forms of chronic Chagas disease show that about one-third of patients present cardiac involvement. Heart failure, sudden death and cardioembolic stroke are the main mechanisms of death in Chagas heart disease. The impact of specific etiologic treatment on the prognosis of patients with chronic Chagas heart disease is very limited regardless of the presence or absence of heart failure. Patients with symptomatic Chagas heart disease present serum selenium (Se) levels lower than patients without Chagas heart disease. Moreover, Se supplementation in animal models showed promising results. The aim of this trial is to estimate the effect of Se treatment on prevention of heart disease progression in patients with Chagas cardiomyopathy. However, we had to introduce some protocol modifications in order to keep trial feasibility, as follows: the primary outcome was restricted to left ventricular ejection fraction as a continuous variable, excluding disease progression; the follow-up period was decreased from 5 years to 1 year, an adjustment that might increase the participation rate of our study; the superior age limit was increased from 65 to 75 years; and diabetes mellitus was no longer considered an exclusion criterion. All of these protocol modifications were extensively debated by the research team enrolled in the design, recruitment and conduction of the clinical trial to guarantee a high scientific quality. TRIAL REGISTRATION: Clinical Trials.gov, NCT00875173 . Registered on 20 October 2008.

Chagas disease transmission by consumption of game meat: systematic review. / Transmissão da doença de Chagas por consumo de carne de caça: revisão sistemática.

OBJECTIVE:: To evaluate the influence of game meat consumption in Chagas disease (CD) transmission, the conditions under which it occurs and the frequency of reports in the literature. METHODS:: Through systematic review, databases PubMed, LILACS, MEDLINE, and SciELO were consulted, and articles written in Portuguese, English, and Spanish were included, with no limitation over publication date. We used the following descriptors: oral, transmission, meat, wild animals, hunt, carnivory, and Chagas disease. Articles that mentioned consumption of animal meat as a form of human transmission of CD were included. We used epidemiological, clinical, and laboratory evidence criteria to confirm cases. RESULTS:: Among the 298 articles identified, only six met the eligibility criteria. Only five episodes of oral transmission through wild animal meat or blood consumption were identified. However, in two of them, the possibility of vectorial transmission could not be ruled out. Most reports met the epidemiological, clinical, and laboratory evidence criteria established to support the transmission. CONCLUSION:: Though CD transmission is uncommon, hunting and consumption of wild mammals that serve as Trypanosoma cruzi reservoirs should be discouraged in endemic countries in light of the risks inherent to these practices.

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.

Temporal changes in the clinical-epidemiological profile of patients with Chagas disease at a referral center in Brazil

Abstract INTRODUCTION We aimed to describe the sociodemographic, epidemiological, and clinical characteristics of patients with chronic Chagas disease (CD) at an infectious disease referral center. Changes in patient profiles over time were also evaluated. METHODS This retrospective study included patients with CD from November 1986-December 2019. All patients underwent an evaluation protocol that included sociodemographic profile; epidemiological history; anamnesis; and physical, cardiologic, and digestive examinations. Trend differences for each 5-year period from 1986 to 2019 were tested using a nonparametric trend test for continuous and generalized linear models with binomial distribution for categorical variables. RESULTS A total of 2,168 patients (52.2% women) were included, with a mean age of 47.8 years old. White patients with low levels of education predominated. The reported transmission mode was vectorial in 90.2% of cases. The majority came from areas with a high prevalence (52.2%) and morbidity (67.8%) of CD. The most common clinical presentation was the indeterminate form (44.9%). The number of patients referred gradually decreased and the age at admission increased during the study period, as did the patients' levels of education. CONCLUSIONS The clinical profile of CD is characterized by a predominance of the indeterminate form of the disease. Regarding the patients who were followed up at the referral center, there was a progressive increase in the mean age and a concomitant decrease in the number of new patients. This reflects the successful control of vector and transfusion transmission in Brazil as well as the aging population of patients with CD.

FIRST REPORT OF ACUTE CHAGAS DISEASE BY VECTOR TRANSMISSION IN RIO DE JANEIRO STATE, BRAZIL.

Chagas disease (CD) is an endemic anthropozoonosis from Latin America of which the main means of transmission is the contact of skin lesions or mucosa with the feces of triatomine bugs infected by Trypanosoma cruzi. In this article, we describe the first acute CD case acquired by vector transmission in the Rio de Janeiro State and confirmed by parasitological, serological and PCR tests. The patient presented acute cardiomyopathy and pericardial effusion without cardiac tamponade. Together with fever and malaise, a 3 cm wide erythematous, non-pruritic, papule compatible with a "chagoma" was found on his left wrist. This case report draws attention to the possible transmission of CD by non-domiciled native vectors in non-endemic areas. Therefore, acute CD should be included in the diagnostic workout of febrile diseases and acute myopericarditis in Rio de Janeiro.