Benznidazole, itraconazole, and their combination for the treatment of chronic experimental Chagas disease in dogs.

Treatment for Chagas disease has limited efficacy in the chronic phase. We evaluated benznidazole (BZ) and itraconazole (ITZ) individually and in association in dogs 16 months after infection with a BZ-resistant Trypanosoma cruzi strain. Four study groups (20 animals) were evaluated and treated for 60 days with BZ, ITZ, or BZ + ITZ, and maintained in parallel to control group infected and not treated (INT). All dogs were evaluated in the first, sixth, 12th, 18th and 24th months of study. Polymerase chain reaction (PCR) was negative in 2 of 3 animals in the BZ + ITZ group, 2 of 5 in the BZ group, and 4 of 5 in the ITZ group. Hemoculture performed in the 24th month was negative in all groups. Enzyme-linked immunoassay remained reactive in all treated animals. Echocardiography differentiated treated animals from control animals. Quantitative PCR analysis of cardiac tissue was negative in the BZ + ITZ and BZ groups, positive in 2 of 5 dogs in the ITZ group and in 2 of 3 dogs in the control group, but negative in colon tissue in all groups. Inflammation was significantly reduced in the right atrium and left ventricle of dogs treated with BZ + ITZ and BZ compared with those receiving ITZ alone. Fibrosis was absent in most dogs treated with BZ + ITZ, mild in those treated with BZ or ITZ alone, and intense in the control group. Parasitological and histopathological evaluations showed that BZ + ITZ treatment improved or stabilized the clinical condition of the dogs.

Prognosis of chronic Chagas heart disease and other pending clinical challenges.

In this chapter, the main prognostic markers of Chagas heart disease are addressed, with an emphasis on the most recent findings and questions, establishing the basis for a broad discussion of recommendations and new approaches to managing Chagas cardiopathy. The main biological and genetic markers and the contribution of the electrocardiogram, echocardiogram and cardiac magnetic resonance are presented. We also discuss the most recent therapeutic proposals for heart failure, thromboembolism and arrhythmias, as well as current experience in heart transplantation in patients suffering from severe Chagas cardiomyopathy. The clinical and epidemiological challenges introduced by acute Chagas disease due to oral contamination are discussed. In addition, we highlight the importance of ageing and comorbidities in influencing the outcome of chronic Chagas heart disease. Finally, we discuss the importance of public policies, the vital role of funding agencies, universities, the scientific community and health professionals, and the application of new technologies in finding solutions for better management of Chagas heart disease.

Evaluation of parasite and host genetics in two generations of a family with Chagas disease.

Chagas disease, caused by the protozoan Trypanosoma cruzi, is considered to be a multifactorial disease associated with host and parasite genetics, which influence clinical aspects of the disease and other host conditions. In order to understand better the evolution of the disease, this study intended to evaluation of parasite and host genetics in two generations of a family with Chagas disease from the Alto Paranaiba region, Minas Gerais, Brazil, comprising a mother and her five daughters. Several features were evaluated, including the characterization of T. cruzi directly from the blood of patients, host polymorphisms of genes related to cardiomyopathy (TNF, WISP1, CCR5, and TGF-ß1) and clinical aspects of the patients. To verify the intraspecific variability of the parasite, the characterization was done directly from human blood using the PCR-LSSP technique and analyzed based on Dice coefficient and unweighted pair group analysis (UPGMA). The host polymorphism was evaluated by PCR-RFLP. The global results showed low variability of the parasites characterized from blood of patients, through Shannon index (0.492) and mean heterozygosity value per locus (0.322). All six patients presented the same genetic polymorphism profile for TNF, WISP1, and TGF-ß1, and only one patient was homozygous to CCR5, which suggests that there is no association between the clinical aspects of the patients and their genetic profiles. In conclusion, the findings confirm that the understanding of the clinical evolution of Chagas disease goes beyond the genetic aspects of the parasite and the host.

Myocardial scars correlate with eletrocardiographic changes in chronic Trypanosoma cruzi infection for dogs treated with Benznidazole.

OBJECTIVES: The cardiac form of Chagas disease is evidenced by a progressive cardiac inflammation that leads to myocarditis, fibrosis and electrocardiographic (ECG) conduction abnormalities. Considering these characteristics, the aim of this study was to prospectively evaluate the early ECG changes in dogs that were experimentally inoculated with Benznidazole (Bz)-susceptibly (Berenice-78) and Bz-resistant (VL-10, and AAS) Trypanosoma cruzi strains and, later, evaluate the efficacy of Bz treatment for preventing these ECG alterations. METHODS: Electrocardiographic changes of treated and untreated animals were prospectively evaluated for up to 270 days after infection, at which point collagen (right atrium) quantification was performed. RESULTS: All infected dogs had a high intensity of heart fibrosis (4616.00 ± 1715.82 collagen/74931 µm(2) in dogs infected with Berenice-78 strain, 5839.2 ± 1423.49 collagen/74931 µm(2) in infected by AAS and 6294.40 ± 896.04 collagen/74931 µm(2) in animals infected with VL-10 strain), while 78.57% of all infected dogs showed ECG alterations. Bz Therapy reduced or prevented fibrosis in Bz-susceptible Berenice-78 (2813.00 ± 607.13 collagen/74931 µm(2) ) and Bz-resistant AAS strains (4024 ± 1272.44 collagen/74931 µm(2) ), coincident with only 10% de ECG alterations at 270 days. However, in those animals infected with a Bz-resistant VL-10 strain, specific treatment did not alter collagen deposition (6749.5 ± 1596.35 collagen/74931 µm(2) ) and there was first atrioventricular block and chamber overload at 120 and 270 days after infection, with 75% abnormal ECG exams. CONCLUSIONS: These findings indicate that an effective antiparasitic treatment in the early stage of Chagas disease can lead to a significant reduction in the frequency and severity of the parasite-induced cardiac disease, even if parasites are not completely eliminated.

A serological, parasitological and clinical evaluation of untreated Chagas disease patients and those treated with benznidazole before and thirteen years after intervention.

The etiological treatment of Chagas disease is recommended for all patients with acute or recent chronic infection, but controversies remain regarding the benefit of chemotherapy and interpretations of the parasitological cure after etiological treatment. This study compares the laboratory and clinical evaluations of Chagas disease patients who were diagnosed 13 years earlier. Fifty-eight Chagas disease patients (29 treated with benznidazole and 29 untreated) were matched at the time of treatment based on several variables. Conventional serology revealed the absence of seroconversion in all patients. However, lower serological titres were verified in the treated group, primarily among patients who had the indeterminate form of the disease. Haemoculture performed 13 years after the intervention was positive for 6.9% and 27.6% of the treated and untreated patients, respectively. Polymerase chain reaction tests were positive for 44.8% and 13.8% of the treated and untreated patients, respectively. Patients who presented with the indeterminate form of the disease at the beginning of the study exhibited less clinical progression (17.4%) compared with the untreated group (56.5%). Therefore, this global analysis revealed that etiological treatment with benznidazole may benefit patients with respect to the clinical progression of Chagas disease and the prognosis, particularly when administered to patients with the indeterminate form of the disease.

COVID-19: Distance learning to empower educators and health assistants in rural areas.

BACKGROUND: Educators and health assistants can act as key players in controlling the pandemic. In general, they are respected by the community, especially in rural areas, and can help guide and raise the population's awareness of preventive measures. The objective of this paper is to evaluate the results in knowledge progress of an e-learning course offered to educators and health assistants by a public university and to analyze the profile and satisfaction of the participants. MATERIALS AND METHODS: A single group pre- and post-test design based on a questionnaire, interventional, study was conducted in the period from April 20th to June 20th. All participants of the course answered sociodemographic and satisfaction questionnaire and a pre- and post-test. Data were descriptively arranged and regarding the distribution and comparison of means and frequency, paired t-test for group comparisons. P < 0.05 was statistically significant. Data were collected from the Moodle® teaching platform, without identifying the participants. RESULTS: A total of 674 participants were enrolled in the five groups, and 583 concluded the course (86.5%). The reasons for those who did not access the entire course (n = 47) were: Lack of time, difficulty in accessing the internet, and lack of experience with distance learning courses. On the evaluation of the course platform, from the tutors in general and the degree of satisfaction in several questions, participants marked maximum grades. The comparison between pre- and post-proficiency scores showed increased proficiency of the enrolled groups (P < 0.0001). CONCLUSIONS: The course contributed to the training of health assistants and educators, preparing them to act in a participatory way in the prevention and control of the pandemic. The course was well evaluated and there was a progression of knowledge by the participants.

Prognosis of chronic Chagas heart disease and other pending clinical challenges

In this chapter, the main prognostic markers of Chagas heart disease are addressed, with an emphasis on the most recent findings and questions, establishing the basis for a broad discussion of recommendations and new approaches to managing Chagas cardiopathy. The main biological and genetic markers and the contribution of the electrocardiogram, echocardiogram and cardiac magnetic resonance are presented. We also discuss the most recent therapeutic proposals for heart failure, thromboembolism and arrhythmias, as well as current experience in heart transplantation in patients suffering from severe Chagas cardiomyopathy. The clinical and epidemiological challenges introduced by acute Chagas disease due to oral contamination are discussed. In addition, we highlight the importance of ageing and comorbidities in influencing the outcome of chronic Chagas heart disease. Finally, we discuss the importance of public policies, the vital role of funding agencies, universities, the scientific community and health professionals, and the application of new technologies in finding solutions for better management of Chagas heart disease.

Seroprevalence of Chagas disease in schoolchildren from two municipalities of Jequitinhonha Valley, Minas Gerais, Brazil; six years following the onset of epidemiological surveillance.

Six years after the beginning of the epidemiological surveillance of Chagas disease in Berilo and José Gonçalves de Minas, Jequitinhonha Valley, MG, Brazil, a serological inquiry was performed to observe whether the transmission of this endemy was occurring in this area. A randomized sample of 1,412 children seven to 14 years old, was screened. Six asymptomatic children were found to be positive, leading to 0.4% of prevalence. Hemoculture confirmed infection in five out of the six positive cases. Additional epidemiological investigation revealed important antecedents, such as disease reports in relatives and predisposing ecological and housing conditions. Our results demonstrated similar seroprevalence (0.4%) in schoolchildren, ranging from seven to 14 years old, and that were observed six years ago (0.2%) for children 0-9 year-old. Thus, considering the constant presence of Panstrogylus megistus in the peridomicile these findings emphasize the need of continuous improved epidemiological surveillance of Chagas disease in this region.

Covid-19: e-Learning as a tool for improving the knowledge / Covid-19: e-learning como ferramenta para melhoria do conhecimento

Abstract: Introduction: Preventing and fighting COVID-19 are of the utmost importance. In this context, the importance of using telemedicine tools has grown, including teleconsultations, epidemiological telemonitoring, remote diagnosis, support, and training of health professionals. Objective: This article aims to report the results of a distance-training course on SARS-CoV-2 and COVID-19. We analyze the course adherence, the students' profile, pre, and post-test proficiency index and satisfaction with the course. Methods: This is a cross-sectional study that evaluated data from the course on SARS-CoV-2 and COVID-19. The data were analyzed in terms of distribution and comparisons of means and frequencies. A paired t-test was used to compare the pre and post-test grades. A p-value <0.05 was considered significant. Data were collected from the Moodle teaching platform, without identifying the participants. Results: From March 23 to May 14, the course was offered to 1,008 medical students and health care providers. Most were from the state of Minas Gerais, some from other Brazilian states, and Mozambique. The majority completed the course, with an 89.8% adherence. The evaluations related to the course, the tutors, the degree of satisfaction, and the security for the professional performance after the course obtained maximum scores. The comparison between the pre and post grades showed proficiency gain (p<0.0001). Conclusion: The course has contributed to the training of medical students and health professionals from Brazil and Mozambique. The organizing committee was able to prepare students and provide knowledge to professionals with difficulty to access good technical and evidence-based information. After the training, the students were selected to work on university projects aiming at supporting city halls, health departments, and the community.

Resumo: Introdução: A prevenção e o combate da Covid-19 são de extrema importância. Nesse contexto, a importância do uso de ferramentas de telemedicina tem crescido, incluindo teleconsultas, telemonitoramento epidemiológico, diagnóstico remoto, suporte e treinamento de profissionais de saúde. Objetivo: Este trabalho tem como objetivo relatar os resultados de um curso de treinamento a distância que abordou aspectos relacionados ao Sars-CoV-2 e à Covid-19. Método: Analisaram-se os seguintes aspectos: adesão ao curso, perfil dos alunos, índice de proficiência pré e pós-teste e satisfação com o curso.Trata-se de um estudo transversal que avaliou os dados do curso sobre o Sars-CoV-2 e a Covid-19. Os dados foram analisados em termos de distribuição e comparação de médias e frequências. Um teste t pareado foi usado para comparar as notas do pré e do pós-teste. O valor de p < 0,05 foi considerado significativo.Coletaram-se os dados na plataforma de ensino Moodle, sem identificação dos participantes. Resultado: De 23 de março a 14 de maio de 2020, o curso foi oferecido a 1.008 estudantes de Medicina e profissionais de saúde. A maioria era de Minas Gerais, alguns de outros estados brasileiros e de Moçambique. A maioria concluiu o curso com 89,8% de adesão. As avaliações referentes ao curso, aos tutores, ao grau de satisfação e à segurança para o desempenho profissional após o curso obtiveram pontuação máxima. A comparação entre as séries pré e pós-teste mostrou ganho de proficiência (p < 0,0001). Conclusão: O curso tem contribuído para a formação de estudantes de Medicina e profissionais de saúde do Brasil e de Moçambique. A comissão organizadora conseguiu capacitar alunos e profissionais de saúde com dificuldade de acesso a boas informações técnicas e baseadas em evidências. Após a capacitação, os alunos foram selecionados para atuar em projetos universitários com o objetivo de apoiar prefeituras, secretarias de saúde e comunidade.

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

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

2 nd Brazilian Consensus on Chagas Disease, 2015.

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

Prevalence of rheumatic heart disease in a public school of Belo Horizonte.

BACKGROUND: Previous studies indicate that compared with physical examination, Doppler echocardiography identifies a larger number of cases of rheumatic heart disease in apparently healthy individuals. OBJECTIVES: To determine the prevalence of rheumatic heart disease among students in a public school of Belo Horizonte by clinical evaluation and Doppler echocardiography. METHODS: This was a cross-sectional study conducted with 267 randomly selected school students aged between 6 and 16 years. students underwent anamnesis and physical examination with the purpose of establishing criteria for the diagnosis of rheumatic fever. They were all subjected to Doppler echocardiography using a portable machine. Those who exhibited nonphysiological mitral regurgitation (MR) and/or aortic regurgitation (AR) were referred to the Doppler echocardiography laboratory of the Hospital das Clínicas of the Universidade Federal of Minas Gerais (HC-UFMG) to undergo a second Doppler echocardiography examination. According to the findings, the cases of rheumatic heart disease were classified as definitive, probable, or possible. RESULTS: Of the 267 students, 1 (0.37%) had a clinical history compatible with the diagnosis of acute rheumatic fever (ARF) and portable Doppler echocardiography indicated nonphysiological MR and/or AR in 25 (9.4%). Of these, 16 (6%) underwent Doppler echocardiography at HC-UFMG. The results showed definitive rheumatic heart disease in 1 student, probable rheumatic heart disease in 3 students, and possible rheumatic heart disease in 1 student. CONCLUSION: In the population under study, the prevalence of cases compatible with rheumatic involvement was 5 times higher on Doppler echocardiography (18.7/1000; 95% CI 6.9/1000-41.0/1000) than on clinical evaluation (3.7/1000-95% CI).

P-wave dispersion and left atrial volume index as predictors in heart failure.

BACKGROUND: Studies have shown that P-wave dispersion (PWD) and left atrial volume index (LAVi) are predictors of cardiovascular events (CE). OBJECTIVE: To verify the prognostic value of PWD and LAVi for the occurrence of CE in patients with heart failure (HF). METHODS: This was a longitudinal prospective study of 78 consecutive patients with a mean age of 47.2 years, of which 52 were males. Patients had stable HF and underwent clinical evaluation, electrocardiogram and echocardiogram assessments, with a follow-up of 26.5 months. RESULTS: The means of the variables were: 50 ms for PWD and 35.5 mL/m² for LAVi. Considering PWD > 40 ms and, as reference, LAVi > 28 mL/m², the positive predictive value of PWD was 87.5% and the negative predictive value was 76.9%. During follow-up, 21 patients had CE. There was an association between left atrial measurements, left ventricular volumes, ejection fraction and CE. There was no association between PWD and CE. At the multivariate analysis, the left atrium and LAVi were predictors of events (p = 0.00 and 0.02). Through the operating characteristic curve for the variable stable CE, areas of 0.80 and 0.69 were obtained for LAVi (p = 0.00) and LAVi > 28 mL/m² (p = 0.01). Survival curves (Kaplan-Meier) free of those events for LAVi > 28 mL/m² and for Chagas disease etiology showed an odds ratio of 14.4 (p = 0.00) and 3.2 (p = 0.03). There was no difference in outcome between patients with ischemic and nonischemic heart failure. CONCLUSION: PWD was not correlated to CE. LAVi was an independent predictor of CE, and chagasic patients showed worse outcomes.

Consenso Brasileño en Enfermedad 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.

Estilo de vida e intervenções não farmacológicas no tratamento e na prevenção das síndromes geriátricas: uma revisão integrativa / Lifestyle and non-pharmacological interventions in the treatment and prevention of geriatric syndromes: an integrative revision / Estilo de vida e intervenciones no farmacológicas en el tratamiento y la prevención de los síndromes geriátricos: una revisión integrativa

As grandes síndromes geriátricas ­ insuficiência cognitiva, instabilidade postural, incontinência urinária, iatrogenia e imobilidade ­ estão associadas ao declínio da capacidade funcional de importante parcela da população idosa. Esta revisão faz uma compilação e análise de estudos que abordam a importância do estilo de vida, da alimentação, de exercícios físicos, e de outras medidas não farmacológicas, na prevenção e no tratamento dos chamados "gigantes da geriatria", condições de alta prevalência e morbidade na população idosa.

The major geriatric syndromes ­ cognitive impairment, postural instability, urinary incontinence, iatrogeny and immobility ­ are associated with the decline in the functional capacity of significant part of the elderly population. This review assembles and analyzes studies, which show the importance of lifestyle, feeding, physical activity and other non-pharmacological interventions in prevention and treatment of the "geriatric giants", conditions of high prevalence and morbidity in that group.

Los grandes síndromes geriátricos - insuficiencia cognitiva, inestabilidad postural, incontinencia urinaria, iatrogenia e inmovilidad - están asociadas al declive de la capacidad funcional de importante parte de la población anciana. Esta revisión hace una compilación y análisis de estudios que abordan la importancia del estilo de vida, de la alimentación, de ejercicios físicos, y de otras medidas no farmacológicas, en la prevención y el tratamiento de los llamados "gigantes de la geriatría", condiciones de alta prevalencia y morbilidad población anciana.

In-house ELISA method to analyze anti-Trypanosoma cruzi IgG reactivity for differential diagnosis and evaluation of Chagas disease morbidity.

INTRODUCTION: The goal was to develop an in-house serological method with high specificity and sensitivity for diagnosis and monitoring of Chagas disease morbidity. METHODS: With this purpose, the reactivities of anti-T. cruzi IgG and subclasses were tested in successive serum dilutions of patients from Berilo municipality, Jequitinhonha Valley, Minas Gerais, Brazil. The performance of the in-house ELISA was also evaluated in samples from other relevant infectious diseases, including HIV, hepatitis C (HCV), syphilis (SYP), visceral leishmaniasis (VL), and American tegumentary leishmaniasis (ATL), and noninfected controls (NI). Further analysis was performed to evaluate the applicability of this in-house methodology for monitoring Chagas disease morbidity into three groups of patients: indeterminate (IND), cardiac (CARD), and digestive/mixed (DIG/Mix), based on their clinical status. RESULTS: The analysis of total IgG reactivity at serum dilution 1:40 was an excellent approach to Chagas disease diagnosis (100% sensitivity and specificity). The analysis of IgG subclasses showed cross-reactivity, mainly with NI, VL, and ATL, at all selected serum dilutions. Based on the data analysis, the IND group displayed higher IgG3 levels and the DIG/Mix group presented higher levels of total IgG as compared with the IND and CARD groups. CONCLUSIONS: These findings demonstrated that methodology presents promising applicability in the analysis of anti-T. cruzi IgG reactivity for the differential diagnosis and evaluation of Chagas disease morbidity.

II Consenso Brasileiro em Doença de Chagas, 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.