Predictors of Trypanosoma cruzi PCR positivity in patients with chronic Chagas disease

BACKGROUND A positive Trypanosoma cruzi polymerase chain reaction (PCR) is associated with a worse prognosis in patients with chronic Chagas disease (CD). OBJECTIVES To study the association of clinical, electrocardiographic, and echocardiographic characteristics and biomarker blood levels with positive T. cruzi PCR in chronic CD. METHODS This is a single-centre observational cross-sectional study. Positive T. cruzi PCR association with clinical, electrocardiographic, and echocardiographic characteristics, and biomarker blood levels were studied by logistic regression analysis. p values < 0.05 were considered significant. FINDINGS Among 333 patients with chronic CD (56.4% men; 62 ± 10 years), T. cruzi PCR was positive in 41.1%. Stepwise multivariate logistic regression showed an independent association between positive T. cruzi PCR and diabetes mellitus {odds ratio (OR) 0.53 [95% confidence interval (CI) 0.30-0.93]; p = 0.03}, right bundle branch block [OR 1.78 (95% CI 1.09-2.89); p = 0.02], and history of trypanocidal treatment [OR 0.13 (95% CI 0.04-0.38); p = 0.0002]. Among patients with a history of trypanocidal treatment (n = 39), only four (10%) patients had a positive T. cruzi PCR. MAIN CONCLUSIONS Among several studied parameters, only diabetes mellitus, right bundle branch block, and history of trypanocidal treatment showed an independent association with positive T. cruzi PCR. History of trypanocidal treatment was a strong protective factor against a positive T. cruzi PCR.

Exploring the Historical Background and Clinical Implications of Electrocardiogram in the Context of Chagas Disease Research

ABSTRACT Chagas disease (CD) remains one of the most significant endemic diseases in Latin America. Approximately 30% of individuals with CD develop the cardiac form, the main determinant of morbidity and mortality, which is characterized by typical electrocardiogram (ECG) changes caused by chronic chagasic cardiopathy (CCC). This review accentuates to how crucial it is for research teams and reference centers that treat patients with CD to standardize ECG in CCC. This was a non-systematic review of the literature. ECG is the most widely used examination in the diagnosis and evaluation of CCC, and it is also employed in epidemiological surveys, risk stratification for cardiovascular events and death, and monitoring the clinical progression of the disease. Carlos Chagas and Eurico Villela published the first work addressing CCC in 1922. Other works followed, including the study by Evandro Chagas' which was the first to perform ECG in CD, culminating in Francisco Laranja's seminal work in 1956. Since the 1980s, standardizations and ECG reading codes for CD have been established. This standardization aimed to code complex arrhythmias and characteristic ventricular conduction disorders and standardize ECG readings for clinical and epidemiological studies in CD. Nearly all existing electrocardiographic abnormalities can be found in CD, with a predominance of abnormalities in the formation and conduction of cardiac stimuli. The complex and heterogeneous substrate of CD with varied electrocardiographic manifestations poses a significant challenge when comparing studies involving patients with CCC, emphasizing the need for ECG standardization in CD.

Inspiratory Muscle Strength in Chagas Cardiomyopathy: A Systematic Scoping Review

ABSTRACT The increase in inflammatory markers associated with persistent chronic fibrosing myocarditis, a characteristic of chronic Chagas disease, can result in a reduction in inspiratory muscle strength (IMS) in Chagas cardiomyopathy (CC). However, literature in this field is still scarce. This review aimed to map and summarize the evidence regarding IMS in patients with CC. The inclusion criteria included reports with adult participants with a CC diagnosis, with or without heart failure (HF). The core concept examined was the maximum inspiratory pressure evaluated in the untrained and trained groups in the pre-training period. The context was open, including but not limited to hospitals and health centers. Two authors independently identified eligible studies and extracted the data. Descriptive synthesis was used as the primary strategy for analyzing the results. Nine studies (five clinical trials, three cross-sectional, and one cohort) were included. The CC classification differed among the studies, with no mention of HF in five and no CC staging specification in six. IMS was assessed using a manovacuometer, and only six studies analyzed and interpreted the data concerning the predicted values. The CC population with HF appeared to have impaired IMS. All studies involved only Brazilian volunteers. In conclusion, randomized clinical trials evaluating IMS and the effects of inspiratory muscle training need to be conducted to better understand the prevalence and risk of inspiratory muscle weakness in the CC population, as well as the effects of training. Such studies should be conducted at different stages of CC in different populations and countries.

Chagas disease mortality during the coronavirus disease 2019 pandemic: A Brazilian referral center experience

ABSTRACT Background We investigated the mortality rates of patients with Chagas disease (CD) during the coronavirus disease 2019 (COVID-19) pandemic and assessed the association between this mortality and CD clinical presentation and comorbidities. Methods: This was an observational retrospective study with clinical data retrieved from medical records. Results: Comorbidities were more prevalent among patients who died from COVID-19 than those who died from other causes. The proportion of patients according to CD clinical presentation was similar between the two groups. Conclusions: The prevalence of comorbidities seems to be related to a poorer prognosis in CD and COVID-19.

Epidemiological-clinical profile and mortality in patients coinfected with Trypanosoma cruzi/HIV: experience from a Brazilian reference center

ABSTRACT Background: The recent urbanization of Chagas disease (CD) has contributed to a greater risk of coexistence with human immunodeficiency virus (HIV) and AIDS. Methods: This retrospective observational study included patients who were followed at INI-Fiocruz between July 1986 and October 2021. All patients underwent an assessment protocol that included sociodemographic profile, epidemiological history, and clinical evaluation. Descriptive data analyses included reports of the medians and frequencies of variables of interest. Differences in medians between groups were tested using the Mann-Whitney U test. Differences in frequency were tested using Fisher's exact test. Results: Among 2201 patients, 11 (0.5%) were identified with Trypanosoma cruzi/HIV coinfection. Of these, 63.6% were women with a median age of 51.0 years old. Two patients had the indeterminate form of CD, six had the cardiac form, two had the digestive form and one had the cardio-digestive form. Half of the patients were undergoing antiretroviral treatment at the time of coinfection diagnosis with a median CD4+ count of 350 cells/μL and a viral load of 1500 copies/μL. Four patients underwent a xenodiagnosis test at coinfection diagnosis, which all yielded positive results; two of them presented high parasitemia under the risk of reactivation. Prophylaxis for CD reactivation was administered to four patients; two with ketoconazole and two with benznidazole. Six patients died after a median follow-up of 22.5 months, with AIDS being the most common cause of death. Only one case of reactivation was observed. Conclusions: Early diagnosis and prompt treatment of CD reactivation dramatically reduced mortality. Identification of Trypanosoma cruzi/HIV co-infection is crucial to planning a close follow-up of coinfected patients.

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.

Indeterminate form of Chagas disease: historical, conceptual, clinical, and prognostic aspects

Abstract Chagas disease (CD) remains a serious endemic disease in Latin America and a major public health problem. Because of globalization, the disease has spread to non-endemic areas in the northern hemisphere. In the chronic phase of the disease, most patients present with the indeterminate form (IF), characterized by positive serology for Trypanosoma cruzi, absence of clinical findings, and normal findings in electrocardiogram (ECG). IF was not recognized as a clinical entity until decades after the discovery of the disease, and only in the 1940-50s, it was categorized as a form of CD, and its conceptual definition was ratified in the 1980s. Children, adolescents, and young adults with the IF benefit from etiological treatment and tend to have less progression to heart disease in the long term than the untreated ones. IF patients have an essentially benign clinical condition, and their prognosis can be compared to that of healthy individuals with normal ECG findings. Currently, because of aging, patients with the IF have comorbidities that require attention in health services.

Adverse drug events and the associated factors in patients with chronic Chagas disease

Abstract INTRODUCTION: Herein, we aimed to identify the factors associated with adverse drug events (ADEs) in chronic Chagas disease (CD) patients. METHODS: We analyzed 320 medical notes from 295 patients. The Naranjo algorithm was applied to determine the cause of ADEs. Mixed effects logistic regression was performed to evaluate the factors associated with ADEs. RESULTS: ADEs were described in 102 medical notes (31.9%). Captopril was most frequently associated with ADEs. Age (RR 0.96; 95%CI 0.94-0.99) and cardiac C/D stages (RR 3.24; 95%CI 1.30-4.58) were the most important clinical factors associated with ADEs. CONCLUSIONS: Close follow-up is warranted for CD patients.

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

Abstract 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.

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

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

Trypanosoma cruzi I genotype among isolates from patients with chronic Chagas disease followed at the Evandro Chagas National Institute of Infectious Diseases (FIOCRUZ, Brazil)

ABSTRACT INTRODUCTION: Trypanosoma cruzi is the etiologic agent of Chagas disease in humans, mainly in Latin America. Trypanosome stocks were isolated by hemoculture from patients followed at Evandro Chagas National Institute of Infectious Diseases (FIOCRUZ) and studied using different approaches. METHODS: For species and genotype identification, the stocks were analyzed by parasitological techniques, polymerase chain reaction assays targeted to specific DNA sequences, isoenzyme patterns, besides sequencing of a polymorphic locus of TcSC5D gene (one stock). RESULTS: The isolates presented typical T. cruzi morphology and usually grew well in routine culture media. Metacyclic trypomastigotes were found in cultures or experimentally infected Triatoma infestans. All isolates were pure T. cruzi cultures, presenting typical 330-bp products from kinetoplast DNA minicircles, and 250 or 200-bp amplicons from the mini-exon non-transcribed spacer. Their genetic type assignment was resolved by their isoenzyme profiles. The finding of TcI in one asymptomatic patient from Paraíba was confirmed by the sequencing assay. TcVI was found in two asymptomatic individuals from Bahia and Rio Grande do Sul. TcII was identified in six patients from Pernambuco, Bahia and Minas Gerais, who presented different clinical forms: cardiac (2), digestive with megaesophagus (1), and indeterminate (3). CONCLUSIONS: The main T. cruzi genotypes found in Brazilian chronic patients were identified in this work, including TcI, which is less frequent and usually causes asymptomatic disease, unlike that in other American countries. This study emphasizes the importance of T. cruzi genotyping for possible correlations between the parasite and patient’ responses to therapeutic treatment or disease clinical manifestations.

II Consenso Brasileiro em Doença de Chagas, 2015 / Brazilian Consensus on Chagas Disease, 2015

A doença de Chagas é uma condição crônica negligenciada com elevada carga de morbimortalidade e impacto dos pontos de vista psicológico, social e econômico. Representa um importante problema de saúde pública no Brasil, com diferentes cenários regionais. Este documento traduz a sistematização das evidências que compõe o Consenso Brasileiro de Doença de Chagas. O objetivo foi sistematizar estratégias de diagnóstico, tratamento, prevenção e controle da doença de Chagas no país, de modo a refletir as evidências científicas disponíveis. Sua construção fundamentou-se na articulação e contribuição estratégica de especialistas brasileiros com conhecimento, experiência e atualização sobre diferentes aspectos da doença. Representa o resultado da estreita colaboração entre a Sociedade Brasileira de Medicina Tropical e o Ministério da Saúde. Espera-se com este documento fortalecer o desenvolvimento de ações integradas para enfrentamento da doença no país com foco em epidemiologia, gestão, atenção integral (incluindo famílias e comunidades), comunicação, informação, educação e pesquisas.

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

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

Abstract: 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.

Does my patient have chronic Chagas disease? Development and temporal validation of a diagnostic risk score

Abstract: INTRODUCTION With the globalization of Chagas disease, unexperienced health care providers may have difficulties in identifying which patients should be examined for this condition. This study aimed to develop and validate a diagnostic clinical prediction model for chronic Chagas disease. METHODS This diagnostic cohort study included consecutive volunteers suspected to have chronic Chagas disease. The clinical information was blindly compared to serological tests results, and a logistic regression model was fit and validated. RESULTS The development cohort included 602 patients, and the validation cohort included 138 patients. The Chagas disease prevalence was 19.9%. Sex, age, referral from blood bank, history of living in a rural area, recognizing the kissing bug, systemic hypertension, number of siblings with Chagas disease, number of relatives with a history of stroke, ECG with low voltage, anterosuperior divisional block, pathologic Q wave, right bundle branch block, and any kind of extrasystole were included in the final model. Calibration and discrimination in the development and validation cohorts (ROC AUC 0.904 and 0.912, respectively) were good. Sensitivity and specificity analyses showed that specificity reaches at least 95% above the predicted 43% risk, while sensitivity is at least 95% below the predicted 7% risk. Net benefit decision curves favor the model across all thresholds. CONCLUSIONS: A nomogram and an online calculator (available at http://shiny.ipec.fiocruz.br:3838/pedrobrasil/chronic_chagas_disease_prediction/) were developed to aid in individual risk estimation.

First report of acute Chagas disease by vector transmission in Rio de Janeiro State, Brazil / Primeiro relato de doença de Chagas aguda por transmissão vetorial no Estado do Rio de Janeiro, Brasil

SUMMARYChagas 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.

RESUMOA doença de Chagas é antropozoonose endêmica na América Latina que tem como principal mecanismo de transmissão humana o contato da pele lesada ou da mucosa com as fezes de triatomíneos infectados por Trypanosoma cruzi. Neste artigo descrevemos o primeiro caso de doença de Chagas aguda adquirida no Estado do Rio de Janeiro por transmissão vetorial com confirmação parasitológica, sorológica e pela PCR. O paciente apresentou miocardite aguda e derrame pericárdico de evolução benigna. Juntamente com as manifestações sistêmicas da fase aguda, foi notada pápula eritematosa de três cm de diâmetro compatível com chagoma em punho esquerdo. Este relato de caso chama a atenção para a possibilidade de transmissão da doença de Chagas por vetores nativos não domiciliados e em áreas consideradas indenes. Portanto, a doença de Chagas aguda deve ser incluída entre os diagnósticos diferenciais de doenças febris e miopericardites agudas no Rio de Janeiro.

Atenção integral e eficiência no Laboratório de Pesquisa Clínica em Doenças de Chagas do Instituto de Pesquisa Clínica Evandro Chagas, 2009-2011 / Integrated health care and efficiency in the Chagas’ Disease Clinic Research Laboratory, Evandro Chagas Clinical Research Institute/Fiocruz, 2009-2011

Objetivo: caracterizar o grau de diversificação dos procedimentos requeridos do Modelo de Atenção Integral no tratamento da doença de Chagas e analisá-lo quanto à eficiência no uso de recursos em 2009-2011. Métodos: levantamento de microcustos e modelos de Custeio Baseado em Atividades e Análise Envoltória de Dados, no cálculo das despesas e custos unitários efetivos dos procedimentos para um estudo de caso de avaliação do desempenho do modelo de atenção do Laboratório de Pesquisa Clínica em Doença de Chagas/Instituto de Pesquisa Clínica Evandro Chagas/Fiocruz. Resultados: o grau de diversificação e a motivação pró-eficiência foram confirmados – 291 tipos de procedimentos em 2009, e ganho de eficiência de 19 por cento no período 2009-2011. Conclusão: a análise de eficiência revela poder explicativo sobre a tomada de decisão nas organizações públicas multipropósito de saúde, evidenciando a eficiência do modelo no tratamento da doença de Chagas e sua contribuição potencial para ações efetivas do Sistema Único de Saúde brasileiro (SUS).

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