Chagas Disease: Epidemiology, Diagnosis, and Treatment.

PURPOSE OF REVIEW: This review seeks to describe the updates in the literature - particularly with regards to the epidemiology and diagnosis of Chagas disease. Additionally, this paper describes updates to the antiparasitic treatment for Chagas disease. RECENT FINDINGS: With regards to changing epidemiology, autochthonous cases are being found within the USA in addition to Latin America. Additionally, there appears to be more intermixing of discrete typing units-meaning, they are not confined to specific geographic regions. Screening for Chagas disease is recommended in persons who lived in areas with endemic Chagas, persons wtih family member diagnosed with Chagas Disease, persons who have lived in homes of natural material in Latin America, and persons with history of kissing bug bites. Treatment for the parasitic infection remains limited to benznidazole and nifurtimox, and the role of these treatments in Chagas cardiomyopathy has not yet been definitively defined. Finally, indications for and management of heart transplant in the setting of Chagas disease are discussed. FUTURE RESEARCH: Use of antiparasitics during chronic chagas disease should be further explored. Additionally, future research identifying other markers of infection would be valuable to defining cure from infection.

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.

Association of left ventricular abnormalities with incident cerebrovascular events and sources of thromboembolism in patients with chronic Chagas cardiomyopathy.

BACKGROUND: Although Chagas cardiomyopathy is related to thromboembolic stroke, data on risk factors for cerebrovascular events in Chagas disease is limited. Thus, we assessed the relationship between left ventricular (LV) impairment and cerebrovascular events and sources of thromboembolism in patients with Chagas cardiomyopathy. METHODS: This retrospective cohort included patients with chronic Chagas cardiomyopathy who underwent cardiovascular magnetic resonance (CMR). CMR was performed with a 1.5 T scanner to provide LV volumes, mass, ejection fraction (LVEF), and myocardial fibrosis. The primary outcome was a composite of incident ischemic cerebrovascular events (stroke or transient ischemic attack-TIA) and potential thromboembolic sources (atrial fibrillation (AF), atrial flutter, or intracavitary thrombus) during the follow-up. RESULTS: A total of 113 patients were included. Median age was 56 years (IQR: 45-67), and 58 (51%) were women. The median LVEF was 53% (IQR: 41-62). LV aneurysms and LV fibrosis were present in 38 (34%) and 76 (67%) individuals, respectively. The median follow-up time was 6.9 years, with 29 events: 11 cerebrovascular events, 16 had AF or atrial flutter, and two had LV apical thrombosis. In the multivariable model, only lower LVEF remained significantly associated with the outcomes (HR: 0.96, 95% CI: 0.93-0.99). Patients with reduced LVEF lower than 40% had a much higher risk of cerebrovascular events and thromboembolic sources (HR: 3.16 95% CI: 1.38-7.25) than those with normal LVEF. The combined incidence rate of the combined events in chronic Chagas cardiomyopathy patients with reduced LVEF was 13.9 new cases per 100 persons-year. CONCLUSIONS: LV systolic dysfunction is an independent predictor of adverse cerebrovascular events and potential sources of thromboembolism in patients with chronic Chagas cardiomyopathy.

Screening of at-risk blood donors for Chagas disease in non-endemic countries: Lessons from a 2-year experience in Tuscany, Italy.

BACKGROUND: Chagas disease (CD) is caused by the protozoan parasite Trypanosoma cruzi and is transmitted by blood-sucking triatomine insects in endemic areas of Latin America. Transmission can also occur via blood transfusion and is a major cause of CD in non-endemic areas. OBJECTIVES: The aim of the study was to assess the prevalence of anti-T. cruzi antibodies in blood donors at risk of infection in Tuscany, Italy, following the introduction of blood safety Italian legislation. MATERIAL AND METHODS: Donors (N = 1985) were tested in 2016 to 2018 for anti-T. cruzi IgG using an immunochromatographic test (ICT). Chemiluminescent immunoassay (CLIA) was performed on ICT-positive donors to exclude CD, whereas enzyme-linked immunosorbent assay and western blot were performed in case of discordant results. All assays were performed on CD patients (N = 10) for validation. RESULTS: Ten blood donors had a positive ICT result, with a resulting T. cruzi seroprevalence of 0.5% but demonstrated negative results to CLIA, as well as to the other serological assays. The comparison of serological assays suggested a lower relative sensitivity of ICT. CONCLUSION: The results of this study confirm the significance of serological testing in the screening strategy for CD. However, they provide evidence for discontinuing the use of ICT as a screening test and suggest that a sensitive, specific and multi-sample format assay should be used at the national level for uniformity of results.

Glycemic Control, Cardiac Autoimmunity, and Long-Term Risk of Cardiovascular Disease in Type 1 Diabetes Mellitus.

BACKGROUND: Poor glycemic control is associated with increased risk of cardiovascular disease (CVD) in type 1 diabetes mellitus (T1DM); however, little is known about mechanisms specific to T1DM. In T1DM, myocardial injury can induce persistent cardiac autoimmunity. Chronic hyperglycemia causes myocardial injury, raising the possibility that hyperglycemia-induced cardiac autoimmunity could contribute to long-term CVD complications in T1DM. METHODS: We measured the prevalence and profiles of cardiac autoantibodies (AAbs) in longitudinal samples from the DCCT (Diabetes Control and Complications Trial) in participants with mean hemoglobin A1c (HbA1c) ≥9.0% (n=83) and ≤7.0% (n=83) during DCCT. We assessed subsequent coronary artery calcification (measured once during years 7-9 in the post-DCCT EDIC [Epidemiology of Diabetes Interventions and Complications] observational study), high-sensitivity C-reactive protein (measured during EDIC years 4-6), and CVD events (defined as nonfatal myocardial infarction, stroke, death resulting from CVD, heart failure, or coronary artery bypass graft) over a 26-year median follow-up. Cardiac AAbs were also measured in matched patients with type 2 diabetes mellitus with HbA1c ≥9.0% (n=70) and ≤7.0% (n=140) and, as a control for cardiac autoimmunity, patients with Chagas cardiomyopathy (n=51). RESULTS: Apart from HbA1c levels, the DCCT groups shared similar CVD risk factors at the beginning and end of DCCT. The DCCT HbA1c ≥9.0% group showed markedly higher cardiac AAb levels than the HbA1c ≤7.0% group during DCCT, with a progressive increase and decrease in AAb levels over time in the 2 groups, respectively ( P<0.001). In the HbA1c ≥9.0% group, 46%, 22%, and 11% tested positive for ≥1, ≥2, and ≥3 different cardiac AAb types, respectively, similar to patients with Chagas cardiomyopathy, compared with 2%, 1%, and 0% in the HbA1c ≤7.0% group. Glycemic control was not associated with AAb prevalence in type 2 diabetes mellitus. Positivity for ≥2 AAbs during DCCT was associated with increased risk of CVD events (4 of 6; hazard ratio, 16.1; 95% CI, 3.0-88.2) and, in multivariable analyses, with detectable coronary artery calcification (13 of 31; odds ratio, 60.1; 95% CI, 8.4-410.0). Patients with ≥2 AAbs subsequently also showed elevated high-sensitivity C-reactive protein levels (6.0 mg/L versus 1.4 mg/L in patients with ≤1 AAbs; P=0.003). CONCLUSIONS: Poor glycemic control is associated with cardiac autoimmunity in T1DM. Furthermore, cardiac AAb positivity is associated with an increased risk of CVD decades later, suggesting a role for autoimmune mechanisms in the development of CVD in T1DM, possibly through inflammatory pathways.

Chagas Cardiomyopathy: An Update of Current Clinical Knowledge and Management: A Scientific Statement From the American Heart Association.

BACKGROUND: Chagas disease, resulting from the protozoan Trypanosoma cruzi, is an important cause of heart failure, stroke, arrhythmia, and sudden death. Traditionally regarded as a tropical disease found only in Central America and South America, Chagas disease now affects at least 300 000 residents of the United States and is growing in prevalence in other traditionally nonendemic areas. Healthcare providers and health systems outside of Latin America need to be equipped to recognize, diagnose, and treat Chagas disease and to prevent further disease transmission. METHODS AND RESULTS: The American Heart Association and the Inter-American Society of Cardiology commissioned this statement to increase global awareness among providers who may encounter patients with Chagas disease outside of traditionally endemic environments. In this document, we summarize the most updated information on diagnosis, screening, and treatment of T cruzi infection, focusing primarily on its cardiovascular aspects. This document also provides quick reference tables, highlighting salient considerations for a patient with suspected or confirmed Chagas disease. CONCLUSIONS: This statement provides a broad summary of current knowledge and practice in the diagnosis and management of Chagas cardiomyopathy. It is our intent that this document will serve to increase the recognition of Chagas cardiomyopathy in low-prevalence areas and to improve care for patients with Chagas heart disease around the world.

Inflammatory Cardiomyopathic Syndromes.

Inflammatory activation occurs in nearly all forms of myocardial injury. In contrast, inflammatory cardiomyopathies refer to a diverse group of disorders in which inflammation of the heart (or myocarditis) is the proximate cause of myocardial dysfunction, causing injury that can range from a fully recoverable syndrome to one that leads to chronic remodeling and dilated cardiomyopathy. The most common cause of inflammatory cardiomyopathies in developed countries is lymphocytic myocarditis most commonly caused by a viral pathogenesis. In Latin America, cardiomyopathy caused by Chagas disease is endemic. The true incidence of myocarditis is unknown to the limited utilization and the poor sensitivity of endomyocardial biopsies (especially for patchy diseases such as lymphocytic myocarditis and sarcoidosis) using the gold-standard Dallas criteria. Emerging immunohistochemistry criteria and molecular diagnostic techniques are being developed that will improve diagnostic yield, provide additional clues into the pathophysiology, and offer an application of precision medicine to these important syndromes. Immunosuppression is recommended for patients with cardiac sarcoidosis, giant cell myocarditis, and myocarditis associated with connective tissue disorders and may be beneficial in chronic viral myocarditis once virus is cleared. Further trials of immunosuppression, antiviral, and immunomodulating therapies are needed. Together, with new molecular-based diagnostics and therapies tailored to specific pathogeneses, the outcome of patients with these disorders may improve.

Lower urinary tract dysfunction in chronic Chagas disease: clinical and urodynamic presentation.

PURPOSE: To describe and give an estimation of the prevalence of urinary disorders in chronic Chagas disease, since most clinical research has been centered on the description of the cardiac and digestive forms. METHODS: To explore this topic, a cross-sectional study was conducted in 137 Bolivian adults of both sexes suffering from symptomatic chronic Chagas disease. All patients presenting confirmed chagasic cardiomyopathy, megacolon or both underwent a urologic symptom questionnaire, uroflowmetry, urinary tract ultrasonography and a creatinine assay. When urinary abnormality was detected, a complete urodynamic study was proposed including cystometry, pressure-flow studies and urethral pressure profile. RESULTS: Out of all study patients, 35 (26%) had a Chagas cardiomyopathy, 81 (59%) a megacolon, and 21 (15%) a megacolon associated with cardiomyopathy. In all, 63% presented urinary disorders defined by IPSS > 7 and/or ICIQ SF > 1. Among them, 62% were incontinent, mainly by bladder overactivity, and 45% presented grade 2 or 3 renal insufficiency. Of 49 patients, the urodynamic study identified 34 patients with detrusor overactivity (69%), mostly in those with Chagas megacolon. Median bladder functional capacity, urethral closure pressure and bladder compliance had normal values. Moreover, 36% of these patients presented moderate hypocontractility, without significant post-void residual. CONCLUSIONS: This study evidenced lower urinary tract dysfunction in a majority of chronic chagasic patients; those presenting megacolon were more likely to suffer from urinary incontinence. These results strongly suggest including routine urological clinical investigation in chronic Chagas patients, as urinary incontinence due to overactive bladder is frequently observed in this population.

Reactivation of Chagas disease among heart transplant recipients in the United States, 2012-2016.

BACKGROUND: Heart transplantation has been shown to be a safe and effective intervention for progressive cardiomyopathy from chronic Chagas disease. However, in the presence of the immunosuppression required for heart transplantation, the likelihood of Chagas disease reactivation is significant. Reactivation may cause myocarditis resulting in allograft dysfunction and the rapid onset of congestive heart failure. Reactivation rates have been well documented in Latin America; however, there is a paucity of data regarding the risk in non-endemic countries. METHODS: We present our experience with 31 patients with chronic Chagas disease who underwent orthotopic heart transplantation in the United States from 2012 to 2016. Patients were monitored following a standard schedule. RESULTS: Of the 31 patients, 19 (61%) developed evidence of reactivation. Among the 19 patients, a majority (95%) were identified by laboratory monitoring using polymerase chain reaction testing. One patient was identified after the onset of clinical symptoms of reactivation. All subjects with evidence of reactivation were alive at follow-up (median: 60 weeks). CONCLUSIONS: Transplant programs in the United States are encouraged to implement a monitoring program for heart transplant recipients with Chagas disease. Our experience using a preemptive approach of monitoring for Chagas disease reactivation was effective at identifying reactivation before symptoms developed.

Diagnosis and Management of Chagas Cardiomyopathy in the United States.

PURPOSE OF REVIEW: Chagas cardiomyopathy is an emerging form of non-ischemic cardiomyopathy in the USA. This review aims to summarize current concepts in pathophysiology, disease transmission, medical therapy, and heart transplantation for patients with chronic Chagas cardiomyopathy. RECENT FINDINGS: The incidence of Chagas cardiomyopathy is increasing in the USA, driven mainly by immigration from countries where Chagas disease is endemic. Chagas cardiomyopathy is a chronic, progressive myocarditis, with hallmark features of biventricular dysfunction, ventricular arrhythmias, thromboembolic complications, and a high risk of mortality. Currently, there is no effective treatment for chronic Chagas cardiomyopathy. Heart transplantation is the only treatment for patients with end-stage Chagas cardiomyopathy, but is associated with unique challenges including risk of reactivation. As the prevalence of Chagas cardiomyopathy increases in the USA, practitioners must be aware of the unique challenges in diagnosis and management that Chagas cardiomyopathy presents.

Etiological Classification of Stroke in Patients with Chagas Disease Using TOAST, Causative Classification System TOAST, and ASCOD Phenotyping.

BACKGROUND: Cardioembolism is considered a major pathophysiological mechanism in patients with ischemic stroke (IS) and Chagas disease (CD). However, a previous study reported that other stroke subtypes are present in more than 40% of CD patients according to the TOAST classification. Therefore, the aim of our study was to evaluate the etiologic classification of stroke in patients with CD using the Causative Classification System (CCS), the ASCOD, and the TOAST classifications in a prospective cohort of patients. METHODS: Patients evaluated in our outpatient clinic from 2012 to 2015 with IS and CD were included and underwent full investigation for stroke etiology. TOAST, CCS TOAST, and the ASCOD classifications were compared. FINDINGS: We Included 32 patients (18 men; mean age 62.7 +/-10.1 years). A total of 93.8% had at least 1 vascular risk factor; the most frequent was hypertension (87.5%). According to TOAST, we defined 87.5% as having cardioembolic stroke, being 9.4% as large-artery atherosclerotic (LAA) and 3.1% as undetermined cause. Using the CCS TOAST, 62.5% were classified as cardioaortic embolism evident and 15.6% as possible, 6.3% as small artery occlusion evident and 3.1% as probable, and 12.5% as LAA evident. When ASCOD phenotyping was applied, atherosclerosis was present in 50.1% of patients (A1 = 6.3%, A3 = 43.8%), cardiac pathology in 84.4% (C1 = 62.5%, C2 = 15.6%, C3 = 6.3%), and small-vessel disease in 66% (S1 = 9.4%, S2 = 3.1%, S3 = 3.1%). FINDINGS: In conclusion, the use of the CCS and the ASCOD phenotyping in patients with CD confirmed a high frequency of cardioembolic IS but also showed that other etiologies are prevalent, such as large-artery atherosclerosis and small-vessel occlusion.

The Prevalence of Atrial Fibrillation and Conduction Abnormalities in Chagas' Disease: A Meta-Analysis.

BACKGROUND/OBJECTIVES: Chagas' disease (CD) has been associated with atrial fibrillation (AF) and electrocardiographic (ECG) conduction defects. However, prior studies have shown conflicting results. We performed a meta-analysis comparing the prevalence of AF and conduction abnormalities between CD and non-CD patients. METHODS: PubMed, EMBASE, Cochrane Central, and Latin American databases were searched for studies that directly compared the prevalence of AF and conduction defects in CD and non-CD patients. Odds ratios (OR) were computed using random-effects model due to anticipated heterogeneity. We further performed subanalyses limited to studies that included only patients with cardiomyopathy. RESULTS: A total of 17,238 patients from 30 studies were included, of whom 6,840 (40%) had a positive serology for CD. In the pooled data, AF was significantly more prevalent in the CD group (OR 1.62; 95%CI 1.21-2.15; P = 0.001). However, no significant difference was observed between groups when the analysis included only patients with cardiomyopathy (OR 1.21; 95%CI 0.97-1.50; P = 0.08) or heart failure (OR 1.09; 95%CI 0.81-1.47; P = 0.55). The combination of right bundle branch block (RBBB) and left anterior fascicular block (LAFB) had the highest OR for increased prevalence in patients with Chagas' cardiomyopathy compared to non-CD etiologies (OR 5.31; 95%CI 1.23-22.86; P = 0.03). CONCLUSIONS: Our meta-analysis suggests that the prevalence of AF in patients with Chagas' cardiomyopathy is not significantly different from non-CD cardiomyopathies. The pattern of RBBB and LAFB in patients with cardiomyopathy of unknown etiology and epidemiologic risk factors should raise the possibility of CD and prompt specific diagnostic testing.

Value of cardiac MRI for evaluation of chronic Chagas disease cardiomyopathy.

AIM: To determine whether cardiac magnetic resonance imaging (cMRI) is more sensitive than electrocardiogram (ECG) and echocardiogram (ECHO) for detecting myocardial involvement in a Latin American migrant population with untreated Chagas disease (CD) in the United States. MATERIALS AND METHODS: All untreated CD patients with ECG and ECHO examinations who underwent cMRI at Olive View-UCLA Medical Center from September 2010 to December 2013 (n=81) were analysed in three groups: Group 1, normal ECG and ECHO examinations (n=50); Group 2, abnormal ECG and normal ECHO examinations (n=10); and Group 3, abnormal ECHO examination (n=21). Frequencies of ECG, ECHO, and cMRI findings were compared across groups. RESULTS: Seventy percent (57/81) of the study population was female, with a mean age of 47 years (range, 17-77 years). Twenty-six percent (21/81) had delayed myocardial enhancement (DME), which was most commonly inferolateral in location (27%, 32/117 segments) and transmural in pattern (56%, 65/117 segments). Eight percent (4/50), 30% (3/10), and 67% (14/21) of Groups 1-3, respectively, had DME. Of these individuals with DME, 50% (2/4), 67% (2/3), and 100% (14/14) of Groups 1-3, respectively, also had wall motion abnormality (WMA) on cMRI. In addition to the highest percentages of DME and WMA, Group 3 also had significantly higher mean myocardial mass (p<0.01), mean left ventricular end-diastolic (p<0.01) and end-systolic volumes (p<0.0005), and significantly lower mean left ventricular ejection fraction (p<0.001). CONCLUSION: cMRI may detect myocardial involvement in untreated CD that is otherwise unrecognised on ECG and ECHO.

Chagas Disease in Mexico: Report of 14 Cases of Chagasic Cardiomyopathy in Children.

Chagas disease is a parasitic infection mainly found in Latin America; it is transmitted by a triatomine, also known as assassin bug or kissing bug. In humans, the parasite causes mostly cardiac disorders. Two-thirds of the Mexican territory are regarded as risk areas for vector transmission of Trypanosoma cruzi, the causal agent. The parasite can be found as a blood-borne trypomastigote or as an intracellular amastigote. The progression and severity of lesions could be due to frequent reinfections or to infection by highly virulent strains. A total of 3,327 individuals younger than 18 years old, living in risk areas for this disease in the rural setting of the States of Queretaro, San Luis Potosi, and Veracruz, underwent a seroepidemiological study. Among them, 37 subjects were seropositive for T. cruzi, and were studied to look for signs of cardiac pathology, which has only been reported in adults. A clinical record was prepared for all included individuals, and electrocardiography (ECG) and echocardiography (ECHO) studies were performed; 25 cases showed lesions compatible with the onset of Chagas cardiomyopathy. The other 12 patients showed either normal ECG and ECHO data or showed abnormal parameters that were not regarded as significant. Lesions found in the onset of Chagas cardiomyopathy in children are herein reported, along with 14 cases of cardiac pathology compatible with Chagas disease. Our results indicate that patients younger than 18 years can show a cardiac pathology similar to that observed in adults.

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

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

Ten-year incidence of Chagas cardiomyopathy among asymptomatic Trypanosoma cruzi-seropositive former blood donors.

BACKGROUND: Very few studies have measured disease penetrance and prognostic factors of Chagas cardiomyopathy among asymptomatic Trypanosoma cruzi-infected persons. METHODS AND RESULTS: We performed a retrospective cohort study among initially healthy blood donors with an index T cruzi-seropositive donation and age-, sex-, and period-matched seronegatives in 1996 to 2002 in the Brazilian cities of São Paulo and Montes Claros. In 2008 to 2010, all subjects underwent medical history, physical examination, ECGs, and echocardiograms. ECG and echocardiogram results were classified by blinded core laboratories, and records with abnormal results were reviewed by a blinded panel of 3 cardiologists who adjudicated the outcome of Chagas cardiomyopathy. Associations with Chagas cardiomyopathy were tested with multivariate logistic regression. Mean follow-up time between index donation and outcome assessment was 10.5 years for the seropositives and 11.1 years for the seronegatives. Among 499 T cruzi seropositives, 120 (24%) had definite Chagas cardiomyopathy, and among 488 T cruzi seronegatives, 24 (5%) had cardiomyopathy, for an incidence difference of 1.85 per 100 person-years attributable to T cruzi infection. Of the 120 seropositives classified as having Chagas cardiomyopathy, only 31 (26%) presented with ejection fraction <50%, and only 11 (9%) were classified as New York Heart Association class II or higher. Chagas cardiomyopathy was associated (P<0.01) with male sex, a history of abnormal ECG, and the presence of an S3 heart sound. CONCLUSIONS: There is a substantial annual incidence of Chagas cardiomyopathy among initially asymptomatic T cruzi-seropositive blood donors, although disease was mild at diagnosis.

Chagas cardiomyopathy is associated with higher incidence of stroke: a meta-analysis of observational studies.

BACKGROUND: Chagas disease (CD) has been associated with an elevated risk of stroke, but current data are conflicting and prospective controlled studies are lacking. We performed a systematic review and meta-analysis examining the association between stroke and CD. METHODS: Pubmed, Embase, Cochrane Central, Latin American database, and unpublished data were searched with the use of the following terms: ("Chagas" OR "American trypanosomiasis") AND ("dilated" OR "ischemic" OR "idiopathic" OR "nonChagasic" OR "stroke" OR "cerebrovascular"). We included studies that reported prevalence or incidence of stroke in a CD group compared with a non-CD control group. Odds ratios (ORs) and their 95% confidence intervals (CIs) were computed with the use of a random-effects model. RESULTS: A total of 8 studies and 4,158 patients were included, of whom 1,528 (36.7%) had CD. Risk of stroke was elevated in the group of patients with CD (OR 2.10, 95% CI 1.17-3.78). Similar results were observed in a subanalysis of cardiomyopathy patients (OR 1.74, 95% CI 1.02-3.00) and in sensitivity analysis with removal of each individual study. Furthermore, exclusion of studies at higher risk for bias also yielded consistent results (OR 1.70, 95% CI 1.06-2.71). Subanalysis restricted to studies that included patients with the indeterminate form found no significant difference in the stroke prevalence between CD and non-CD patients (OR 3.10, 95% CI 0.89-10.77). CONCLUSIONS: CD is significantly associated with cerebrovascular events, particularly among patients with cardiomyopathy. These findings underline the need for prospective controlled studies in patients with Chagas cardiomyopathy to ascertain the prognostic significance of cerebrovascular events and to evaluate the role of therapeutic anticoagulation in primary prevention.

[Risk factors associated with the diagnosis of chronic Chagasic miocardiopathy in seropositive individuals from Barinas state, Venezuela]. / Factores de riesgo asociados con el diagnóstico de miocardiopatía chagásica crónica en individuos seropositivos del estado Barinas, Venezuela.

This study evaluates the risk factors associated with the diagnosis of chronic chagasic miocardiopathy (CChM) in 115 seropositive individuals to anti-Trypanosoma cruzi antibodies, in Barinas state, Venezuela. Serology was performed with ELISA and MABA; while the CChM diagnosis was established by electrocardiography and echocardiography. A complete clinical history including epidemiological, personal/familiar antecedents and psychobiological habits, plus socioeconomic, psychosocial and alimentary habits interviews were performed for each individual. Risk factors were determined through binary logistic regression. Results showed that 81 patients (70,4%; CI 95% = 66.4-74.4) had criteria for CChM, of which 74 (64.4%; IC 95% = 60.2-68.6) were in phase II; while 34 (29.6%; IC 95% = 25.5-33.5) were in phase I of the disease and 7 (6.1%; IC 95% = 4.0-8.2) in phase III. In a one year period, two patients in phase III died of heart failure. The diagnosis of CChM was associated with hunting practice, maternal history of cardiopathies, chewing chimó, medical history of hypertension and apex beat visible; it was negatively associated with canned and preserved foods ingest. In conclusion the CChM diagnosis has high frequency in seropositive individuals in Barinas and heart failure prevention must be based on an early medical attention and educative strategies in order to control risk factors.

Exploring the latency period in Chagas disease: duration and determinants in a cohort from Colombia.

BACKGROUND: Chagas disease has a varying latency period, the time between infection and onset of cardiac symptoms, due to multiple factors. This study seeks to identify and understand these factors to enhance our knowledge of the disease. METHODS: A retrospective follow-up study was conducted in Colombia on patients with indeterminate chronic Chagas disease. Medical files were examined to evaluate the disease latency time using time ratios (TRs) and the AFT Weibull model. RESULTS: The study followed 578 patients, of whom 309 (53.5%) developed cardiac disease, with a median latency period of 18.5 (95% CI 16 to 20) y for the cohort. Those with the TcISyl genotype (TR 0.72; 95% CI 0.61 to 0.80), individuals who lived 5-15 y (TR 0.80; 95% CI 0.67 to 0.95), 15-30 y (TR 0.63; 95% CI 0.53 to 0.74) or >30 y (vs 5 y) in areas with high disease prevalence had shorter latency periods. On the other hand, undergoing treatment increased the latency period (TR: 1.74; 95% CI 1.52 to 1.87). CONCLUSIONS: The latency period of Chagas disease was found to be independently related to male gender, receipt of etiological treatment, length of time spent in an endemic area and the TcISyl genotype. The implications of these findings are discussed.

The Burden of Chagas Disease in the Contemporary World: The RAISE Study.

Chagas disease (ChD), a Neglected Tropical Disease, has witnessed a transformative epidemiological landscape characterized by a trend of reduction in prevalence, shifting modes of transmission, urbanization, and globalization. Historically a vector-borne disease in rural areas of Latin America, effective control measures have reduced the incidence in many countries, leading to a demographic shift where most affected individuals are now adults. However, challenges persist in regions like the Gran Chaco, and emerging oral transmission in the Amazon basin adds complexity. Urbanization and migration from rural to urban areas and to non-endemic countries, especially in Europe and the US, have redefined the disease's reach. These changing patterns contribute to uncertainties in estimating ChD prevalence, exacerbated by the lack of recent data, scarcity of surveys, and reliance on outdated models. Besides, ChD's lifelong natural history, marked by acute and chronic phases, introduces complexities in diagnosis, particularly in non-endemic regions where healthcare provider awareness is low. The temporal dissociation of infection and clinical manifestations, coupled with underreporting, has rendered ChD invisible in health statistics. Deaths attributed to ChD cardiomyopathy often go unrecognized, camouflaged under alternative causes. Understanding these challenges, the RAISE project aims to reassess the burden of ChD and ChD cardiomyopathy. The project is a collaborative effort of the World Heart Federation, Novartis Global Health, the University of Washington's Institute for Health Metrics and Evaluation, and a team of specialists coordinated by Brazil's Federal University of Minas Gerais. Employing a multidimensional strategy, the project seeks to refine estimates of ChD-related deaths, conduct systematic reviews on seroprevalence and prevalence of clinical forms, enhance existing modeling frameworks, and calculate the global economic burden, considering healthcare expenditures and service access. The RAISE project aspires to bridge knowledge gaps, raise awareness, and inform evidence-based health policies and research initiatives, positioning ChD prominently on the global health agenda.