Parasite DNA and Markers of Decreased Immune Activation Associate Prospectively with Cardiac Functional Decline over 10 Years among Trypanosoma cruzi Seropositive Individuals in Brazil.

Parasitemia and inflammatory markers are cross-sectionally associated with chronic Chagas cardiomyopathy (CCC) among patients with Trypanosoma cruzi. However, the prospective association of the parasite load and host immune response-related characteristics with CCC (that is, progressors) among T. cruzi seropositive individuals has only been partially defined. In a cohort of T. cruzi seropositive patients in Montes Claros and São Paulo, Brazil who were followed over 10 years, we identified the association of a baseline T. cruzi parasite load and systemic markers of inflammation with a decline in cardiac function and/or the presence of cardiac congestion 10 years later. The progressors (n = 21) were individuals with a significant decline in the left ventricular ejection fraction and/or elevated markers of cardiac congestion after 10 years. The controls (n = 31) had normal markers of cardiac function and congestion at the baseline and at the follow-up. They were matched with the progressors on age, sex, and genetic ancestry. The progressors had higher mean parasite loads at the baseline than the controls (18.3 vs. 0.605 DNA parasite equivalents/20 mL, p < 0.05). Of the 384 inflammation-related proteins analyzed, 47 differed significantly at a false discovery rate- (FDR-) corrected p < 0.05 between the groups. There were 44 of these 47 proteins that were significantly higher in the controls compared to in the progressors, including the immune activation markers CCL21, CXCL12, and HCLS1 and several of the tumor necrosis factor superfamily of proteins. Among the individuals who were seropositive for T. cruzi at the baseline and who were followed over 10 years, those with incident CCC at the 10-year marker had a comparatively higher baseline of T. cruzi parasitemia and lower baseline markers of immune activation and chemotaxis. These findings generate the hypothesis that the early impairment of pathogen-killing immune responses predisposes individuals to CCC, which merits further study.

Incidence and Predictors of Progression to Chagas Cardiomyopathy: Long-Term Follow-Up of Trypanosoma cruzi-Seropositive Individuals.

BACKGROUND: There are few contemporary cohorts of Trypanosoma cruzi-seropositive individuals, and the basic clinical epidemiology of Chagas disease is poorly understood. Herein, we report the incidence of cardiomyopathy and death associated with T. cruzi seropositivity. METHODS: Participants were selected in blood banks at 2 Brazilian centers. Cases were defined as T. cruzi-seropositive blood donors. T. cruzi-seronegative controls were matched for age, sex, and period of donation. Patients with established Chagas cardiomyopathy were recruited from a tertiary outpatient service. Participants underwent medical examination, blood collection, ECG, and echocardiogram at enrollment (2008-2010) and at follow-up (2018-2019). The primary outcomes were all-cause mortality and development of cardiomyopathy, defined as the presence of a left ventricular ejection fraction <50% or QRS complex duration ≥120 ms, or both. To handle loss to follow-up, a sensitivity analysis was performed using inverse probability weights for selection. RESULTS: We enrolled 499 T. cruzi-seropositive donors (age 48±10 years, 52% male), 488 T. cruzi-seronegative donors (age 49±10 years, 49% male), and 101 patients with established Chagas cardiomyopathy (age 48±8 years, 59% male). The mortality in patients with established cardiomyopathy was 80.9 deaths/1000 person-years (py) (54/101, 53%) and 15.1 deaths/1000 py (17/114, 15%) in T. cruzi-seropositive donors with cardiomyopathy at baseline. Among T. cruzi-seropositive donors without cardiomyopathy at baseline, mortality was 3.7 events/1000 py (15/385, 4%), which was no different from T. cruzi-seronegative donors with 3.6 deaths/1000 py (17/488, 3%). The incidence of cardiomyopathy in T. cruzi-seropositive donors was 13.8 (95% CI, 9.5-19.6) events/1000 py (32/262, 12%) compared with 4.6 (95% CI, 2.3-8.3) events/1000 py (11/277, 4%) in seronegative controls, with an absolute incidence difference associated with T. cruzi seropositivity of 9.2 (95% CI, 3.6-15.0) events/1000 py. T. cruzi antibody level at baseline was associated with development of cardiomyopathy (adjusted odds ratio, 1.4 [95% CI, 1.1-1.8]). CONCLUSIONS: We present a comprehensive description of the natural history of T. cruzi seropositivity in a contemporary patient population. The results highlight the central importance of anti-T. cruzi antibody titer as a marker of Chagas disease activity and risk of progression.

Rare Pathogenic Variants in Mitochondrial and Inflammation-Associated Genes May Lead to Inflammatory Cardiomyopathy in Chagas Disease.

Cardiomyopathies are an important cause of heart failure and sudden cardiac death. Little is known about the role of rare genetic variants in inflammatory cardiomyopathy. Chronic Chagas disease cardiomyopathy (CCC) is an inflammatory cardiomyopathy prevalent in Latin America, developing in 30% of the 6 million patients chronically infected by the protozoan Trypanosoma cruzi, while 60% remain free of heart disease (asymptomatic (ASY)). The cytokine interferon-γ and mitochondrial dysfunction are known to play a major pathogenetic role. Chagas disease provides a unique model to probe for genetic variants involved in inflammatory cardiomyopathy. METHODS: We used whole exome sequencing to study nuclear families containing multiple cases of Chagas disease. We searched for rare pathogenic variants shared by all family members with CCC but absent in infected ASY siblings and in unrelated ASY. RESULTS: We identified heterozygous, pathogenic variants linked to CCC in all tested families on 22 distinct genes, from which 20 were mitochondrial or inflammation-related - most of the latter involved in proinflammatory cytokine production. Significantly, incubation with IFN-γ on a human cardiomyocyte line treated with an inhibitor of dihydroorotate dehydrogenase brequinar (enzyme showing a loss-of-function variant in one family) markedly reduced mitochondrial membrane potential (ΔψM), indicating mitochondrial dysfunction. CONCLUSION: Mitochondrial dysfunction and inflammation may be genetically determined in CCC, driven by rare genetic variants. We hypothesize that CCC-linked genetic variants increase mitochondrial susceptibility to IFN-γ-induced damage in the myocardium, leading to the cardiomyopathy phenotype in Chagas disease. This mechanism may also be operative in other inflammatory cardiomyopathies.

Association between typical electrocardiographic abnormalities and NT-proBNP elevation in a large cohort of patients with Chagas disease from endemic area.

Chagas cardiomyopathy is the most harmful complication of Chagas disease. The electrocardiogram is a well-studied exam and has been considered an important tool for detection and evaluation of Chagas cardiomyopathy since the first years of its description. Many of its abnormalities have been described as associated with a worse prognosis. Serum BNP levels were described as inversely related to the left ventricular ejection fraction and as an independent predictor of death. It was not reported how electrocardiographic alterations correlate to NT-proBNP and its analog. The present study aims to describe the baseline electrocardiograms of a large cohort of patients with Chagas disease from endemic area and to establish an association between the number of electrocardiogram alterations and high levels of NT-ProBNP in Chagas disease patients. This study selected 1959 Chagas disease patients in 21 municipalities within a limited region in the northern part of the State of Minas Gerais (Brazil), 1084 of them had Chagas cardiomyopathy. NT-proBNP levels were suggestive of heart failure in 11.7% of this population. One or more electrocardiographic alterations have an Odds Ratio of 9.12 (CI 95% 5.62-14.80) to have NT-proBNP elevation. Considering the association between the number of 1, 2, and 3 or more alterations in electrocardiogram and NT-proBNP elevation, the ORs were 7.11 (CI 95% 4.33-11.67); 16.04 (CI 95% 9.27-27.77) and 47.82 (CI 95% 17.98-127.20), respectively. The presence and the number of typical electrocardiographic alterations of Chagas disease are independently associated with the severity of the cardiomyopathy.

Gastrointestinal Manifestations of Chagas Disease: A Systematic Review with Meta-Analysis.

The aims of this study were to estimate the prevalence of gastrointestinal manifestations among individuals with positive serology for Chagas disease (ChD) and to describe the clinical gastrointestinal manifestations of the disease. A systematic review with meta-analysis was conducted based on the criteria and recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The PubMed, Scopus, Virtual Health Library, Web of Science, and Embase databases were used to search for evidence. Two reviewers independently selected eligible articles and extracted data. RStudio® software was used for the meta-analysis. For subgroup analysis, the studies were divided according to the origin of the individuals included: 1) individuals from health units were included in the health care service prevalence analysis, and 2) individuals from the general population were included in the population prevalence analysis. A total of 2,570 articles were identified, but after removal of duplicates and application of inclusion criteria, 24 articles were included and 21 were part of the meta-analysis. Most of the studies were conducted in Brazil. Radiological diagnosis was the most frequent method used to identify the gastrointestinal clinical form. The combined effect of meta-analysis studies showed a prevalence of gastrointestinal manifestations in individuals with ChD of 12% (95% CI, 8.0-17.0%). In subgroup analysis, the prevalence for studies involving health care services was 16% (95% CI, 11.0-23.0%), while the prevalence for population-based studies was 9% (95% CI, 5.0-15.0%). Megaesophagus and megacolon were the main forms of ChD presentation in the gastrointestinal form. The prevalence of gastrointestinal manifestations of ChD was 12%. Knowing the prevalence of ChD in its gastrointestinal form is an important step in planning health actions for these patients.

Evaluation of the properties of WHODAS-12 measurements in individuals with Chagas disease in Brazil.

Numerous tests employed to predict cardiac and functional status are expensive and not widely accessible for a considerable number of patients, particularly those diagnosed with Chagas disease (CD) residing in remote and endemic regions. To date, there is no knowledge of studies that have validated instruments that address functionality in an expanded way, including the biopsychosocial factors in patients with CD. This study aims to evaluate the psychometric properties of the World Health Organization Disability Assessment Schedule (WHODAS 2.0), in its 12-item shortened version (WHODAS-12) when applied to patients with CD. This is a cross-sectional study of a prospective cohort that follows individuals with CD (SaMi-Trop). Data collection took place between October 2019 and March 2020. In the interviews, sociodemographic information, life habits, clinical information, and indicators of disability measured by WHODAS-12 were collected. Descriptive analysis, internal consistency and construct validity of the instrument were performed. A total of 628 patients with CD were interviewed, most were women (69.5%), their mean age was of 57 years, and most declared an average self-perception of health (43.4%). The 12 items of WHODAS-12 were distributed into three factors, which together account for 61% of the variance. The Kaiser-Meyer-Olkin (KMO) index was 0.90, indicating adequacy of the sample for factor analysis. The internal consistency of the global scale showed alpha = 0.87. The percentage of incapacity was 16.05%, indicating mild incapacity for the evaluated patients. WHODAS-12 is a valid and reliable measure to assess the disability of the Brazilian population with CD.

Chagas disease and perceived quality of life: a cross-sectional study.

BACKGROUND: Chagas disease (ChD) is a neglected tropical disease that is caused by the protozoan parasite Trypanosoma cruzi and can negatively impact quality of life (QoL). This study aimed to assess and compare QoL between individuals with and without ChD. METHODS: This cross-sectional study was performed within a concurrent cohort study (REDS). The participants were derived from two blood donation centers: São Paulo capital and Montes Claros, Minas Gerais, Brazil. Participants with ChD were identified in blood donations by serological diagnosis between 2008 and 2010, and those without ChD were donors with negative serology identified during the same period. QoL was assessed using the World Health Organization Quality of Life-BREF questionnaire. Logistic regression was used to compare sociodemographic and clinical characteristics between the groups, and mean, standard deviation, and beta regression were used to compare QoL. RESULTS: In total, 611 individuals participated in the study (328 with ChD and 283 without ChD). Participants with ChD had lower QoL in the physical (p=0.02) and psychological (p<0.01) domains than did individuals without CD. CONCLUSIONS: Individuals with ChD had worse QoL perceptions. These results provide a comprehensive understanding of the impact of ChD on individuals' QoL, while also highlighting potential opportunities for improving the care and treatment of those affected.

Screening for Chagas disease from the electrocardiogram using a deep neural network.

BACKGROUND: Worldwide, it is estimated that over 6 million people are infected with Chagas disease (ChD). It is a neglected disease that can lead to severe heart conditions in its chronic phase. While early treatment can avoid complications, the early-stage detection rate is low. We explore the use of deep neural networks to detect ChD from electrocardiograms (ECGs) to aid in the early detection of the disease. METHODS: We employ a convolutional neural network model that uses 12-lead ECG data to compute the probability of a ChD diagnosis. Our model is developed using two datasets which jointly comprise over two million entries from Brazilian patients: The SaMi-Trop study focusing on ChD patients, enriched with data from the CODE study from the general population. The model's performance is evaluated on two external datasets: the REDS-II, a study focused on ChD with 631 patients, and the ELSA-Brasil study, with 13,739 civil servant patients. FINDINGS: Evaluating our model, we obtain an AUC-ROC of 0.80 (CI 95% 0.79-0.82) for the validation set (samples from CODE and SaMi-Trop), and in external validation datasets: 0.68 (CI 95% 0.63-0.71) for REDS-II and 0.59 (CI 95% 0.56-0.63) for ELSA-Brasil. In the latter, we report a sensitivity of 0.52 (CI 95% 0.47-0.57) and 0.36 (CI 95% 0.30-0.42) and a specificity of 0.77 (CI 95% 0.72-0.81) and 0.76 (CI 95% 0.75-0.77), respectively. Additionally, when considering only patients with Chagas cardiomyopathy as positive, the model achieved an AUC-ROC of 0.82 (CI 95% 0.77-0.86) for REDS-II and 0.77 (CI 95% 0.68-0.85) for ELSA-Brasil. INTERPRETATION: The neural network detects chronic Chagas cardiomyopathy (CCC) from ECG-with weaker performance for early-stage cases. Future work should focus on curating large higher-quality datasets. The CODE dataset, our largest development dataset includes self-reported and therefore less reliable labels, limiting performance for non-CCC patients. Our findings can improve ChD detection and treatment, particularly in high-prevalence areas.

Failure to use health services by people with Chagas disease: Multilevel analysis of endemic area in Brazil.

This study aimed to assess the prevalence of non-use of health services in the last year by people with Chagas disease (CD) in an endemic area in Brazil and the contextual and individual factors associated with this non-use. This is a multilevel study that considered contextual and individual data. Contextual data were collected from official publicly accessible databases of the Brazilian government, at the municipal level. The individual data came from the first follow-up of a Brazilian cohort that assessed patients with CD in 21 municipalities in endemic area for the disease. The sample consisted of 1,160 individuals with CD. The dependent variable "use of health services in the last year" was categorized as yes vs. no. The analysis was performed using Poisson regression with robust variance. The prevalence of non-use of health services in the last year was 23.5% (IC95%: 21.1-25.9). The contextual factor "larger population" (PR: 1.6; 95% CI = 1.2-2.0) and individual factors related to the lower severity of the disease as a functional class without limitations (PR: 1.6; 95% CI = 1.2-2.1) and unaltered N-terminal pro b-type natriuretic peptide levels (PR: 2.2; 95% CI = 1.3-3.6) increased the prevalence of non-use of the health service in the last year by people with CD. The results of this study showed that individual determinants are not isolated protagonists of the non-use of health services in the last year by people with CD, which reinforces the need for public policies that consider the contextual determinants of the use of health services by populations affected by the disease.

Contextual influence on poor self-rated health in patients with Chagas disease: multilevel study.

Chagas disease (CD) is recognized by the World Health Organization as one of the thirteen most neglected tropical diseases in the world. Self-perceived health is considered a better predictor of mortality than objective measures of health status, and the context in which one lives influences this predictor. This study aimed to evaluate the prevalence and individual and contextual factors associated with poor self-rated health among CD patients from an endemic region in Brazil. It is a multilevel cross-sectional study. The individual data come from a cross-section of a cohort study named SaMi-Trop. Contextual data was collected from publicly accessible institutional information systems and platforms. The dependent variable was self-perceived health. The analysis was performed using multilevel binary logistic regression. The study included 1,513 patients with CD, where 335 (22.1%) had Poor self-rated health. This study revealed the influence of the organization/offer of the Brazilian public health service and of individual characteristics on the self-perceived health of patients with CD.

Two-year death prediction models among patients with Chagas Disease using machine learning-based methods.

Chagas disease (CD) is recognized by the World Health Organization as one of the thirteen most neglected tropical diseases. More than 80% of people affected by CD will not have access to diagnosis and continued treatment, which partly supports the high morbidity and mortality rate. Machine Learning (ML) can identify patterns in data that can be used to increase our understanding of a specific problem or make predictions about the future. Thus, the aim of this study was to evaluate different models of ML to predict death in two years of patients with CD. ML models were developed using different techniques and configurations. The techniques used were: Random Forests, Adaptive Boosting, Decision Tree, Support Vector Machine, and Artificial Neural Networks. The adopted settings considered only interview variables, only complementary exam variables, and finally, both mixed. Data from a cohort study with CD patients called SaMi-Trop were analyzed. The predictor variables came from the baseline; and the outcome, which was death, came from the first follow-up. All models were evaluated in terms of Sensitivity, Specificity and G-mean. Among the 1694 individuals with CD considered, 134 (7.9%) died within two years of follow-up. Using only the predictor variables from the interview, the different techniques achieved a maximum G-mean of 0.64 in predicting death. Using only the variables from complementary exams, the G-mean was up to 0.77. In this configuration, the protagonism of NT-proBNP was evident, where it was possible to observe that an ML model using only this single variable reached G-mean of 0.76. The configuration that mixed interview variables and complementary exams achieved G-mean of 0.75. ML can be used as a useful tool with the potential to contribute to the management of patients with CD, by identifying patients with the highest probability of death. Trial Registration: This trial is registered with ClinicalTrials.gov, Trial ID: NCT02646943.

Prevalence and factors associated with impaired left ventricular global longitudinal strain in patients with Chagas disease: SaMi-Trop cohort study.

Cardiomyopathy is a major cause of death in Chagas disease and early detection of cardiac involvement is essential. Myocardial strain is a reliable technique for assessment of subtle left ventricular (LV) contractility alterations. This study assessed LV global longitudinal strain (GLS) in a large Chagas disease population living in remote areas. Between 2015 and 2016, Chagas disease patients were selected in the northern of the Minas Gerais state. All patients underwent T. cruzi antibodies tests and those who had positive tests were included. A resting 12-lead ECG was recorded and classified using the Minnesota Code criteria. Echocardiography was performed at public health primary care units and speckle-tracking strain was analyzed offline. LV dysfunction was defined as ejection fraction (LVEF < 50%) and reduced GLS was defined as < 16% (absolute value). A total of 1387 patients were included, mean age of 60.0 ± 12.5 years, 68% were women, and 14% had LV dysfunction. Among patients with normal LVEF, 59% had impaired LV GLS. Overall, patients with impaired GLS were older, had more comorbidities and ECG abnormalities than those with normal GLS. The independent factors associated with reduced GLS were ST-T abnormalities (OR 1.954; 95% CI 1.027-3.718), QRS duration (OR 1.009; 95% CI 1.002-1.016), LVEF (OR 0.947; 95% CI 0.923-0.972), and E/e' ratio (OR 1.059; 95% CI 1.009-1.112). In a cohort of Chagas disease from endemic areas, impaired LV GLS was detected in a significant proportion of patients, despite normal ECG and preserved LVEF. The main determinants of reduced LV GLS were ST-T abnormalities, QRS duration, LVEF and E/e' ratio, adjusting for demographical and clinical data.

Occurrence and spatial distribution of triatomines (Hemiptera: Reduviidae) in the urban area of the municipality of Montes Claros, Northern Minas Gerais, Brazil.

The north of the Brazilian state of Minas Gerais is classified as an area of high risk of vectorial transmission of Chagas disease (CD) or of reestablishing transmission in the home, but the Chagas disease control programme is disjointed. The study evaluated the occurrence, natural infection and the spatial distribution of species of triatomines associated with climatic variations in the urban area of Montes Claros, a municipality endemic to CD in the north of Minas Gerais, Brazil. Triatomine data were obtained from passive entomological surveillance actions of the Chagas Disease Control Program (Programa de Controle de Doença de Chagas-PCDCh), registered by the Zoonosis Control Center (Centro de Controle de Zoonoses-CCZ) from 2009 to 2019. A total of 277 triatomines belonging to eight species were collected, and of these, 203 insects were examined. It was found that 46.2% of triatomines were captured inside the home and 8.3% around the home. The natural infection rate was 6.9%; 14 specimens showed natural infection by Trypanosoma cruzi (12 females and 2 males), and of these, 13 were found in the home and one in an uninformed location. The number of triatomine records collected was significantly higher in the month of September (p = .01), and there was an inverse correlation between the number of triatomines and the relative humidity of the air (p < .001). It was verified that the highest triatomine densities are located in transition areas between urban infrastructure (32.12%) and pasture (25.72%). The diversity of species of triatomines infected with T. cruzi in residential units in urban areas in the municipality of Montes Claros is worrying, as it suggests a potential risk of transmission of the parasite to domestic animals and humans.

Hospitalizations due to gastrointestinal Chagas disease: National registry.

OBJECTIVES: Analyze the hospitalizations of patients admitted for Chagas disease with gastro-intestinal involvement (CD-GI) in the Brazilian Unified Health System, describe the epidemiological profile, mortality and costs. METHODS: This is an observational study that uses secondary data from the National Hospital Information System (SIH-SUS) for the years 2017-2019. CD-GI admissions were defined by specific ICD-10 codes that identify the main diagnosis. RESULTS: From 2017 to 2019, there were 4,407 hospitalizations for CD-GI in Brazil, considering only public hospitals and those associated with the SUS. This corresponds to an average of 1,470 hospitalizations per year, or 0.6 per 100,000 inhabitants, with significant regional variation. Hospitalizations increased with age and were slightly higher in men. More than 60% were emergencies and in 50% the procedure performed was surgical. The most used code was the one for megaesophagus followed by megacolon. In-hospital mortality was 5.8% and 17.2% went to intensive care units. The median cost was USD$ 553.15 per hospitalization, and an overall cost of USD$ 812,579.98 per year to the SUS budget. CONCLUSION: The numbers, rates and costs presented here are possibly underestimated but they give us an idea of the overall profile of hospitalizations due to CD-GI, which are not rare and are related to significant in-hospital mortality. CD-GI is a neglected manifestation of a neglected disease.

Genome-wide association study for Chagas Cardiomyopathy identify a new risk locus on chromosome 18 associated with an immune-related protein and transcriptional signature.

BACKGROUND: Chronic Chagas Cardiomyopathy (CCC) usually develops between 10 and 20 years after the first parasitic infection and is one of the leading causes of end-stage heart failure in Latin America. Despite the great inter-individual variability in CCC susceptibility (only 30% of infected individuals ever present CCC), there are no known predictors for disease development in those chronically infected. METHODOLOGY/PRINCIPAL FINDINGS: We describe a new susceptibility locus for CCC through a GWAS analysis in the SaMi-Trop cohort, a population-based study conducted in a Chagas endemic region from Brazil. This locus was also associated with CCC in the REDS II Study. The newly identified locus (rs34238187, OR 0.73, p-value 2.03 x 10-9) spans a haplotype of approximately 30Kb on chromosome 18 (chr18: 5028302-5057621) and is also associated with 80 different traits, most of them blood protein traits significantly enriched for immune-related biological pathways. Hi-C data show that the newly associated locus is able to interact with chromatin sites as far as 10Mb on chromosome 18 in a number of different cell types and tissues. Finally, we were able to confirm, at the tissue transcriptional level, the immune-associated blood protein signature using a multi-tissue differential gene expression and enrichment analysis. CONCLUSIONS/SIGNIFICANCE: We suggest that the newly identified locus impacts CCC risk among T cruzi infected individuals through the modulation of a downstream transcriptional and protein signature associated with host-parasite immune response. Functional characterization of the novel risk locus is warranted.

Left ventricular systolic dysfunction predicted by artificial intelligence using the electrocardiogram in Chagas disease patients-The SaMi-Trop cohort.

BACKGROUND: Left ventricular systolic dysfunction (LVSD) in Chagas disease (ChD) is relatively common and its treatment using low-cost drugs can improve symptoms and reduce mortality. Recently, an artificial intelligence (AI)-enabled ECG algorithm showed excellent accuracy to detect LVSD in a general population, but its accuracy in ChD has not been tested. OBJECTIVE: To analyze the ability of AI to recognize LVSD in patients with ChD, defined as a left ventricular ejection fraction determined by the Echocardiogram ≤ 40%. METHODOLOGY/PRINCIPAL FINDINGS: This is a cross-sectional study of ECG obtained from a large cohort of patients with ChD named São Paulo-Minas Gerais Tropical Medicine Research Center (SaMi-Trop) Study. The digital ECGs of the participants were submitted to the analysis of the trained machine to detect LVSD. The diagnostic performance of the AI-enabled ECG to detect LVSD was tested using an echocardiogram as the gold standard to detect LVSD, defined as an ejection fraction <40%. The model was enriched with NT-proBNP plasma levels, male sex, and QRS ≥ 120ms. Among the 1,304 participants of this study, 67% were women, median age of 60; there were 93 (7.1%) individuals with LVSD. Most patients had major ECG abnormalities (59.5%). The AI algorithm identified LVSD among ChD patients with an odds ratio of 63.3 (95% CI 32.3-128.9), a sensitivity of 73%, a specificity of 83%, an overall accuracy of 83%, and a negative predictive value of 97%; the AUC was 0.839. The model adjusted for the male sex and QRS ≥ 120ms improved the AUC to 0.859. The model adjusted for the male sex and elevated NT-proBNP had a higher accuracy of 0.89 and an AUC of 0.874. CONCLUSION: The AI analysis of the ECG of Chagas disease patients can be transformed into a powerful tool for the recognition of LVSD.

Accuracy and reliability of focused echocardiography in patients with Chagas disease from endemic areas: SaMi-Trop cohort study.

BACKGROUND: Chagas disease remains a major cause of cardiovascular death in endemic areas. Focused echocardiography (FoCUS) is a point-of-care means of assessing cardiac function which can be useful for the diagnosis of cardiac involvement. OBJECTIVE: This study aims evaluating the characteristics of validity and reliability of FoCUS applied on Chagas disease patients. METHODS: Patients with Chagas disease coming from an endemic area were selected from a large cohort (SaMi-Trop). A simplified echocardiogram with only three images was extracted from the conventional echocardiogram performed in this cohort. The images were evaluated by an observer who was blinded to the clinical and echocardiographic data, to determine the accuracy and reliability of FoCUS for cardiac assessment. The analysis constituted of 5 prespecified variables, dichotomized in absence or presence: left ventricular (LV) size and systolic function, right ventricular (RV) size and systolic function, and LV aneurysm. RESULTS: We included 725 patients with a mean age of 63.4 ± 12.3 years, 483 (67%) female. Abnormal electrocardiogram was observed in 81.5% of the patients. Left and right ventricular dysfunctions were found in 103 (14%) and 49 (7%) of the patients, respectively. Sensitivity, specificity, positive predictive value and negative predictive value were 84%, 94%, 70% and 97% for LV enlargement and 81%, 93%, 68% and 97% for LV systolic dysfunction, respectively, and 46%, 99%, 60% and 98% for RV dilatation, and 37%, 100%, 100% and 96% for RV dysfunction, respectively. Inter and intraobserver agreement were 61% and 87% for LV enlargement and 63% and 92% for LV dysfunction, respectively, and 50% and 49% for RV size and 46% and 79% for RV dysfunction, respectively. LV apical aneurysm was found in 45 patients (6.2%) with the lowest sensitivity of FoCUS study (11%; 95% CI 2-28%). CONCLUSIONS: FoCUS showed satisfactory values of validity and reliability for assessment of cardiac chambers in patients with Chagas disease, except for apical aneurysm. This tool can identify heart disease with potential impact on patient management in the limited-resource setting.

Cohort profile update: the main and new findings from the SaMi-Trop Chagas cohort.

The SaMi-Trop project is a cohort study conducted in 21 municipalities of endemic areas of Chagas disease, including 1,959 patients with chronic Chagas cardiomyopathy. In this article we updated the results of the project, adding information from the second cohort visit. Trypanosoma cruzi-seropositive patients were enrolled from the primary care Telehealth service in Minas Gerais State, Brazil. The eligibility criterium for the second visit was the participation in the baseline evaluation. Of 1,959 participants at the baseline assessment, 1,585 (79.9%) returned after two years for the second evaluation. The mortality rate was 6.7%, but varied from 0.9% to 18.2% when it was stratified by certain clinical characteristics. A lower age-adjusted NT-Pro-BNP level (less than 300) and a prior benznidazole treatment were associated with lower mortality. There was an improvement in most quality of life domain scores. Participants have also reported fewer signs and symptoms and greater use of medication. The second follow-up visit will be complete in Oct 2021.

Serological screening for Chagas disease in an endemic region of Northern Minas Gerais, Brazil: the SaMi-Trop project.

Chagas disease (CD) is still a neglected disease. Infected individuals are diagnosed late, being treated in worse clinical conditions. Thus, this study aimed to analyze the prevalence and the factors associated with new confirmed cases of CD identified by serological screening in an endemic region of Minas Gerais State, Brazil. This is an analytical cross-sectional study with data from a project of the Research Center in Tropical Medicine of Sao Paulo- Minas Gerais (SaMi-Trop) conducted in two municipalities. Data collection included a questionnaire with closed questions, a venous blood collection and an ELISA serological test for CD. A total of 2,038 individuals with no previous diagnosis of CD participated in the study. The result of the serological test for CD was adopted as the dependent variable. The independent variables addressed personal issues, health conditions and lifetime housing. A descriptive analysis of individual variables was performed. Subsequently, a bivariate analysis was performed using the Pearson's chi-square test. Households sheltering individuals positive for CD were georeferenced, and the analysis of spatial distribution was performed using the quartic function to estimate the density of the nucleus. Among the participants, 188 (9.2 %) were positive for CD. The profile of participants with CD was associated with place of residence, age, relative/family member with CD and living conditions. It is noteworthy that there are still patients with CD who are unaware of their diagnosis in both, rural and urban areas.

Challenges in the care of patients with Chagas disease in the Brazilian public health system: A qualitative study with primary health care doctors.

BACKGROUND: Care to patients with Chagas disease (CD) is still a challenge for health systems in endemic and non-endemic countries. In the Brazilian public health system, the expansion of Primary Health Care (PHC) services to remote and disadvantaged areas has facilitated the access of patients with CD to medical care, however this is in a context where care gaps remain, with insufficient public funding and inadequate distribution of services. Considering the need for studies on care to patients with CD in different settings, this study explored the challenges of family doctors to provide care to patients with CD in an endemic region in Brazil with high coverage of public PHC services. METHODS AND FINDINGS: This is a qualitative study. A focus group with 15 family doctors was conducted in a municipality participating in a multicenter cohort that monitors almost two thousand patients with CD in an endemic region in Brazil. The data were analyzed using a thematic content analysis technique. The family doctors pointed out the following challenges for care to patients with CD: unsatisfactory medical training (academic education not suitable for the clinical management of the disease, and lack of training on CD in PHC); uncertainties regarding antiparasitic treatment in the chronic phase of the disease; difficulty in patients' access to specialized care when necessary, especially to the cardiologist; and trivialization of the disease by patients as a barrier to seeking care. CONCLUSION: The access of CD patients to adequate medical care, even in regions with high coverage of public PHC services, still represents an important challenge for health systems. The results of this study may contribute to the development of strategies to improve the clinical management of CD in PHC.