Multiple myeloma and Chagas disease: qPCR as a marker for preemptive antiparasitic therapy: a case reports series and review

ABSTRACT Multiple myeloma (MM) associated with Chagas disease is rarely described. This disease and its therapy suppress T cell and macrophage functions and increase regulatory T cell function, allowing the increase of parasitemia and the risk of Chagas Disease Reactivation (CDR). We aimed to analyze the role of conventional (cPCR) and quantitative Polymerase Chain Reaction (qPCR) for prospective monitoring of T. cruzi parasitemia, searching for markers of preemptive antiparasitic therapy in MM patients with Chagas disease. Moreover, we investigated the incidence and management of hematological diseases and CDR both inside and outside the transplant setting in the MEDLINE database. We found 293 studies and included 31 of them. Around 1.9-2.0% of patients with Chagas disease were reported in patients undergoing Stem Cell Transplantation. One case of CDR was described in eight cases of MM and Chagas disease. We monitored nine MM and Chagas disease patients, seven under Autologous Stem Cell Transplantation (ASCT), during 44.56±32.10 months (mean±SD) using parasitological methods, cPCR, and qPCR. From these patients, three had parasitemia. In the first, up to 256 par Eq/mL were detected, starting from 28 months after ASCT. The second patient dropped out and died soon after the detection of 161.0 par Eq/mL. The third patient had a positive blood culture. Benznidazole induced fast negativity in two cases; followed by notably lower levels in one of them. Increased T. cruzi parasitemia was related to the severity of the underlying disease. We recommend parasitemia monitoring by qPCR for early introduction of preemptive antiparasitic therapy to avoid CDR.

Spatial distribution of acute cases of Chagas disease reported from 2010 to 2020 in the State of Amazonas / Distribuição espacial dos casos agudos de doença de Chagas notificados de 2010 a 2020 no Estado da Amazônia / Distribución espacial de los casos agudos de enfermedad de Chagas notificados de 2010 a 2020 en el Estado Amazónico

This study aimed to investigate the epidemiology of acute cases of Chagas disease notified in the State of Amazonas between the period from 2010 to 2020. Data were obtained from the portal of the Sistema de Informação de Agravos de Notificação- SINAN, considering the number of cases per municipality of notification. 140 cases of Acute Chagas Disease were notified, distributed in 23 of the 62 municipalities of the State of Amazonas, 82 (59%) were male individuals, with a greater predominance in the age group of 20-39 years old, having 45 (32.1%) cases. As for the race/color variable, the highest number was among brown people with 101 (72.1%) notifications. The oral route prevailed as the main form of disease transmission with 93 (66.4%) records. Infection by the oral route of T. cruzi is the most important route of transmission of CD in the State of Amazonas, the occurrence of transmission is associated in most cases with the consumption of foods such as açaí juice and has been reported frequently over the years between municipalities.

este estudo se propôs a investigar a epidemiologia dos casos agudos de Doença de Chagas notificados no Estado do Amazonas no período de 2010 a 2020. Os dados foram obtidos no portal do Sistema de Informação de Agravos de Notificação - SINAN, considerando o número de casos por município de notificação. Foram notificados 140 casos de Doença de Chagas Aguda, distribuídos em 23 dos 62 municípios do Estado do Amazonas, 82 (59%) eram indivíduos do sexo masculino, com maior predominância na faixa etária de 20-39 anos de idade com 45 (32,1%) casos. Quanto a variável raça/cor, a maior registro foi entre pardos com 101(72,1%) notificações. A via oral, prevaleceu como a principal forma de transmissão da patologia com 93 (66,4%) registros. A infecção pela via oral do T. cruzi, é a mais importante via de transmissão de DC no Estado do Amazonas, a ocorrência da transmissão está associada na maioria das vezes ao consumo de alimentos como o suco de açaí, e tem sido reportada com frequência ao longo dos anos entre os municípios.

Este estudio tuvo como objetivo investigar la epidemiología de los casos agudos de la enfermedad de Chagas notificados en el Estado de Amazonas en el período de 2010 a 2020. Los datos fueron obtenidos del portal del Sistema de Información de Enfermedades de Notificación - SINAN, considerando el número de casos por municipio de notificación. Se notificaron 140 casos de Enfermedad de Chagas Aguda, distribuidos en 23 de los 62 municipios del Estado de Amazonas, 82 (59%) fueron individuos del sexo masculino, con mayor predominio en el grupo etario de 20 a 39 años con 45 (32,1%) casos. En cuanto a la variable raza/color, el mayor número fue entre los morenos con 101 (72,1%) notificaciones. La vía oral predominó como principal vía de transmisión de la enfermedad con 93 (66,4%) registros. La infección por vía oral de T. cruzi es la vía de transmisión más importante de la EC en el Estado de Amazonas, la ocurrencia de la transmisión está mayoritariamente asociada al consumo de alimentos como el jugo de açaí, y ha sido reportada con frecuencia a lo largo de los años entre municipios.

Conocimientos, actitudes y prácticas sobre la enfermedad de Chagas en una zona endémica de Boyacá, Colombia

Introducción: Los instrumentos para la obtención de información sobre los conocimientos, actitudes y prácticas de diversas enfermedades son ampliamente utilizados, ya que permiten obtener información clara y detallada de cada uno de los aspectos a indagar. Objetivo: Determinar conocimientos, actitudes y prácticas de la enfermedad de Chagas en una zona endémica de Boyacá, Colombia. Metodología: Estudio transversal que consistió en aplicar un instrumento validado que abordaba datos sociodemográficos, factores epidemiológicos, conocimientos, actitudes y prácticas de la enfermedad de Chagas en un integrante mayor de edad de 341 familias de Miraflores, Boyacá. Se emplearon escalas, óptimo, bueno, regular y malo; para el análisis bivariado se determinó el nivel de conocimientos, actitudes y prácticas con escala favorable y desfavorable. Se determinaron diferencias significativas de factores de riesgo, conocimientos, actitudes y prácticas de la enfermedad entre el grupo de hombres y mujeres encuestados. Resultados: El 68,6 % de la población nació en Miraflores, con un 48 % de escolaridad primaria y pertenecientes a la zona rural en su mayoría (57,2 %); en las mujeres predomina la ocupación de ama de casa, mientras que en los hombres es más frecuente la agricultura. Se identificaron conocimientos (48,1 %) y actitudes (82,1 %) óptimas sobre la enfermedad de Chagas que minimizan el riesgo de contraer la infección por T. cruzi; paradójicamente, se encontraron malas prácticas (61,9 %) en el hogar que no previenen la enfermedad. Se observó relación entre el nivel de escolaridad bajo, sexo femenino, ser menor de 49 años, vivir en zona urbana y actividades del hogar y un conocimiento favorable acerca de la enfermedad de Chagas, aunque sin evidencia estadística. Conclusiones: Se hace necesario incorporar programas que garanticen el aprendizaje y la implementación de actitudes y prácticas favorables contra la enfermedad en habitantes de zonas endémicas.

Introduction: The use of measurement tools to obtain information about knowledge, attitudes and practices of various diseases are widely used, since they allow to collect clear and detailed information of every aspect needing examination. Objective: Determine knowledge, attitudes and practices regarding Chagas disease in an endemic zone in Boyaca, Colombia. Methods: Cross-sectional study that consisted of applying a validated instrument that addressed sociodemographic data, epidemiological factors, knowledge, attitudes and practices of the Chagas disease in an adult member of 341 families from Miraflores, Boyaca. The scale categories used were optimal, good, regular and bad; for the bivariate analysis, the level of knowledge, attitudes and practices was determined with a favorable and unfavorable scale. Significant differences in risk factors, knowledge, attitudes and practices of the disease were determined between the group of men and women surveyed. Results: Sixty-eight percent of the population were born in Miraflores, 48% had primary education and most belonged to the rural area (57.2%); in women the occupation of housewife predominated, in men agriculture was more frequent. Optimal knowledge (48.1%) and attitudes (82.1%) about the Chagas disease that minimize the risk of contracting T. cruzi infection were identified. Paradoxically, bad practices that did not prevent the disease were found at home (61,9%). significant regarding the low level of schooling, female gender, being under 49 years of age, living in an urban area and household activities, all of the above allows a favorable knowledge about Chagas disease, although without statistical evidence. Conclusion: It is necessary to incorporate programs that guarantee learning and implementation of favorable attitudes and practices against the disease in inhabitants of endemic areas.

Contribuições para a mobilização social, comunicação e educação em saúde sobre a doença de Chagas no YouTube ­ percurso e notas sobre o canal Falamos de Chagas / Contributions to social mobilization, communication and health education on Chagas disease on YouTube ­ route and notes on the channel Falamos de Chagas / Aportes a la movilización social, comunicación y educación en salud sobre la enfermedad de Chagas en YouTube ­ trayectoria y notas en el canal Falamos de Chagas

A doença de Chagas crônica afeta seis milhões de pessoas em regiões endêmicas, com 30 mil novos casos anuais ­ logo, espaços de divulgação científica são muito importantes para ofertar informações de qualidade à população. As iniciativas envolvendo o controle da doença de Chagas não podem se limitar às pesquisas com enfoque biológico. Este estudo objetiva apresentar um panorama sobre o processo de construção do canal Falamos de Chagas, no YouTube, sua importância para a comunicação, a informação, a educação em saúde e a mobilização social, bem como refletir sobre a qualidade de uma subamostra de vídeos do canal. Trata-se de um estudo qualitativo, dividido em duas fases: criação do canal e análise qualitativa dos vídeos sobre a doença disponíveis no YouTube. Observamos que existe potencial nas redes sociais, enquanto recurso de comunicação, contudo é preciso cautela, uma vez que se faz necessária a certificação da qualidade do material

Chronic Chagas disease affects six million people in endemic regions, with 30,000 new infected cases an-nually ­ thus, initiatives involving science diffusion are relevant to offer qualified information to the people. Chagas disease control initiatives cannot be limited to the level of biological focused research. This study aims to present an overview of the construction process of the YouTube channel Falando de Chagas, its importance for communication, information, health education and social mobilization, as well as to reflect on the quality of a subsample of videos present in the channel. Qualitative in nature, the study was divided into two stages: construction of the channel and qualitative analysis of videos about the disease available on YouTube. We observed that there is potential for social networks as communication resources, but caution is needed in their use, since the quality of the material needs certification

La enfermedad de Chagas crónica afecta seis millones de personas en regiones endémicas, con 30.000 nuevos casos anuales ­ los espacios de divulgación científica son muy importantes para ofrecer información a la población. Las iniciativas de control de la enfermedad de Chagas no pueden limitarse al nivel de investigación con enfoque biológico. El estudio tiene como objetivo presentar un panorama del proceso de construcción del canal Falando de Chagas, en YouTube, su importancia para la comunicación, información, educación en salud y movilización social, así como reflexionar sobre la calidad de una submuestra de videos presentes en la canal. De naturaleza cualitativa, el estudio se dividió en dos fases: construcción del canal y análisis cualitativo de videos sobre la enfermedad disponibles en YouTube. Observamos que existe potencial para las redes sociales como recurso de comunicación, sin embargo, se requiere cautela en su uso, ya que se requiere certificar la calidad del material

Prevalência de comorbidades em pacientes com megaesôfago chagásico / Prevalence of comorbidities in patients with chagasic megaesophagus

ABSTRACT Objective: This study aimed to evaluate the prevalence of some epidemiologically important comorbidities in patients with Chagas megaoesophagus in relation to the population without megaoesophagus, and whether this condition would be a protective or a risk factor for the conditions analysed. Methods: This observational descriptive study collected data from the medical records of patients with a previous diagnosis of megaoesophagus (timing: from 2005 to 2020). The patients were divided by age into a general (all ages) and an older group (aged 60 years or more). Associations were searched for four main areas/systems/involvements: cardiovascular, respiratory, endocrine and neurological. Results: The general group included 546 patients and the older group included 248 patients. As for the prevalence of comorbidities in the general group, the three most prevalent diseases were hypertension, with 44.3% (CI95%: 40.21-48.51%); dyslipidaemia, with 17.8% (CI95%: 14.79-21.19%); and heart failure, with 15.2% (CI95%: 12.43-18.45%). Similar to that in the general group, the most prevalent comorbidities in the group of older patients were hypertension, dyslipidaemia, and heart failure. Conclusion: Systemic arterial hypertension, dyslipidaemia, and heart failure were the most prevalent comorbidities in this population. The lower prevalence of diabetes mellitus and Alzheimer's disease suggests the association of enteric nervous system denervation and requires further investigation.

RESUMO Objetivo: Este estudo teve como objetivo avaliar a prevalência de algumas comorbidades epidemiologicamente importantes em pacientes com megaesôfago chagásico em relação à população sem o megaesôfago e se essa condição seria um fator protetor ou de risco para as condições analisadas. Métodos: Este estudo descritivo observacional coletou dados de prontuários de pacientes com diagnóstico prévio de megaesôfago (período: de 2005 a 2020). Os pacientes foram divididos por idade em um grupo geral (todas as idades) e um grupo idoso (60 anos ou mais). Foram pesquisadas associações para quatro áreas/sistemas/envolvimentos principais: cardiovascular, respiratório, endócrino e neurológico. Resultados: O grupo geral incluiu 546 pacientes e o grupo idosos incluiu 248 pacientes. Quanto à prevalência de comorbidades no grupo geral, as três doenças mais prevalentes foram hipertensão, com 44,3% (IC95%: 40,21-48,51%); dislipidemia, com 17,8% (IC95%: 14,79-21,19%); e insuficiência cardíaca, com 15,2% (IC95%: 12,43-18,45%). Assim como no grupo geral, as comorbidades mais prevalentes no grupo de idosos foram hipertensão, dislipidemia e insuficiência cardíaca. Conclusão: Hipertensão arterial sistêmica, dislipidemia e insuficiência cardíaca foram as comorbidades mais prevalentes nessa população. A menor prevalência de diabetes mellitus e doença de Alzheimer sugere uma associação de denervação do sistema nervoso entérico e requer mais investigação.

Diagnóstico de la Enfermedad de Chagas congénito: Aspectos relevantes

Introducción: El presente artículo describe aspectos relevantes entorno de la Enfermedad de Chagas congénita, tales como epidemiología, sintomatología, revisión de casos clínicos y las técnicas diagnósticas. Métodos: Se realizó una revisión de la literatura por medio de bases de datos bibliográficas como PubMed, Science direct, Scopus, Plos One, SciELO, teniendo como criterio de inclusión las publicaciones artículos o comprendidos entre enero de 2013 y enero del año 2022 en idioma español e inglés. Resultados: Se determinó que la prevalencia de la Enfermedad de Chagas congénita aún es un problema de salud pública en áreas endémicas y no endémicas, siendo la serología materna indispensable para dar seguimiento oportuno a los casos. Conclusiones: Los seguimientos diagnósticos actuales difieren en los países endémicos y se están aplicando tamizajes en zonas no endémicas donde migran mujeres procedentes de áreas de trasmisión activa de la Enfermedad Chagásica.

Introduction: This article describes relevant aspects of congenital Chagas disease, such as epidemiology, symptoms, review of clinical cases, and diagnostic techniques. Methods: A review of the literature was carried out through bibliographic databases such as PubMed, Science direct, Scopus, Plos One, SciELO, having as inclusion criteria articles or publications between January 2013 and January 2022 in Spanish and English. Results: It was determined that the prevalence of congenital Chagas disease is still a public health problem in endemic and non-endemic areas, and maternal serology is essential for timely monitoring of cases. Conclusions: Current diagnostic follow-ups differ in endemic countries and screening is being applied in non-endemic areas where women from areas of active transmission of Chagasic disease migrate.

The Role of MicroRNAs in the Pathogenesis of Chagas Disease

Abstract Chagas disease (CD) is caused by the protozoan Trypanosoma cruzi and affects about six to seven million individuals worldwide. The distribution of cases is concentrated mainly throughout Latin America, especially in rural areas. This study aims to evaluate microRNAs (miRNAs) as indicators in CD diagnosis for possible contributions to its management. This is a literature review study, carried out in the PubMed, SciELO, Bireme Library, NCBI, Science Direct, and Embase databases, through which a total of 12 articles were included for qualitative analysis. The discussion of this review was based on the thematic axes regarding the modulation of T. cruzi in the immune system and the expression of miRNAs, their production and action, the modulation mechanism of host gene expression, how they act as biomarkers, the importance of miRNAs in the diagnosis of CD, and how their regulation occurs in Chronic Chagas Cardiomyopathy (CCC). Moreover, T. cruzi infection is associated with the downregulation of several miRNAs, which directly related to the findings of hypertrophy and fibrosis. When quantified, these could be used as consistent indicators for CD to support the diagnosis of patients with CD complications, as well as a possible therapeutic target. However, the need for clinical studies that evaluate the usefulness of this biomarker in humans is emphasized, considering that in the present study, only experimental in vitro studies were evaluated, reflecting a lack of studies with practical applicability.

Doença de chagas aguda: Um relato de experiência no município de crateús / Acute chagas disease: An experience report in the municipality of crateús

Objective: To report the experience of analyzing the epidemiological profile of patients with Acute Chagas disease in the municipality of Crateús-Ceará. Method: This is an experience report. The technical visit to the health department was in September 2022. The compulsory notification form of the patient diagnosed with Acute Chagas Disease was analyzed. Results: The epidemiological profile of the patient diagnosed with Acute Chagas Disease was identified, being: male, 42 years old, born in the rural area of Crateús - Ceará, unknown race, agricultural worker, arrived at the health unit with suspicions of acute symptoms of Chagas disease according to the notification form of injuries, made on August 02, 2022. Conclusion: Acute Chagas disease is considered a neglected disease, since it demonstrates human poverty, presenting a high morbidity and mortality rate in the endemic region.(AU)

Objetivo: Relatar a experiência de análise do perfil epidemiológico dos pacientes com doença de Chagas Aguda no município de Crateús-Ceará. Método: Trata-se de um relato de experiência. A visita técnica à secretaria de saúde ocorreu em setembro de 2022. Foi analisada a ficha de notificação compulsória do paciente diagnosticado com Doença de Chagas Aguda. Resultados: Identificou-se o perfil epidemiológico do paciente diagnosticado com Doença de Chagas Aguda, sendo: sexo masculino, 42 anos, natural da zona rural de Crateús - Ceará, raça desconhecida, trabalhador rural, chegou à unidade de saúde com suspeita de sintomas agudos da doença de Chagas conforme ficha de notificação de agravos, realizada em 02 de agosto de 2022. Conclusão: A doença de Chagas aguda é considerada uma doença negligenciada, pois demonstra pobreza humana, apresentando alto índice de morbimortalidade na região endêmica.(AU)

Research progress of Triatoma rubrofasciata, the vector of Chagas disease / 中华地方病学杂志

Chagas disease (also known as American trypanosomiasis) is a zoonotic disease caused by Trypanosoma cruzi. It has a long incubation period and low diagnosis rate. At present, there is no vaccine to prevent it, and there is no specific drug at the late stage of the disease. Therefore, some scholars call it "new AIDS". In the past two decades, Chagas disease has spread from the main epidemic area of Latin America to other non-epidemic countries. At the same time, Triatoma rubrofasciata, one of its main vectors, is widely distributed in the world, including some humid and warm southern areas of China. Therefore, in this paper, the distribution characteristics, biology and molecular biology of Triatoma rubrofasciata are comprehensively reviewed, in order to provide reference for the prevention and control of imported Chagas disease in China.

Epoxy-α-lapachone(2,2-Dimethyl-3,4-dihydro-spiro[2H-naphtho[2,3-b]pyran-10,2′-oxirane]-5(10H)-one): a promising molecule to control infections caused by protozoan parasites

ABSTRACT Natural products and their derivatives have been sources of search and research for new drugs for the treatment of neglected diseases. Naphthoquinones, a special group of quinones, are products of natural metabolites with a wide spectrum of biological activities and represent a group of interesting molecules for new therapeutic propositions. Among these compounds, lapachol stands out as a molecule from the heartwood of Tabebuia sp. whose structural changes resulted in compounds considered promising, such as epoxy-a-lapachone (ELAP). The biological activity of ELAP has been demonstrated, so far, for parasitic protozoa such as Leishmania spp., Trypanosoma cruzi and Plasmodium spp., species causing diseases needing new drug development and adequate health policy. This work gathers in vitro and in vivo studies on these parasites, as well as the toxicity profile, and the probable mechanisms of action elucidated until then. The potential of ELAP-based technology alternatives for a further drug is discussed here.

Anxiety, depression, and memory loss in Chagas disease: a puzzle far beyond neuroinflammation to be unpicked and solved*

Mental disorders such as anxiety, depression, and memory loss have been described in patients with chronic Chagas disease (CD), a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. Social, psychological, and biological stressors may take part in these processes. There is a consensus on the recognition of an acute nervous form of CD. In chronic CD patients, a neurological form is associated with immunosuppression and neurobehavioural changes as sequelae of stroke. The chronic nervous form of CD has been refuted, based on the absence of histopathological lesions and neuroinflammation; however, computed tomography shows brain atrophy. Overall, in preclinical models of chronic T. cruzi infection in the absence of neuroinflammation, behavioural disorders such as anxiety and depression, and memory loss are related to brain atrophy, parasite persistence, oxidative stress, and cytokine production in the central nervous system. Interferon-gamma (IFNγ)-bearing microglial cells are colocalised with astrocytes carrying T. cruzi amastigote forms. In vitro studies suggest that IFNγ fuels astrocyte infection by T. cruzi and implicate IFNγ-stimulated infected astrocytes as sources of TNF and nitric oxide, which may also contribute to parasite persistence in the brain tissue and promote behavioural and neurocognitive changes. Preclinical trials in chronically infected mice targeting the TNF pathway or the parasite opened paths for therapeutic approaches with a beneficial impact on depression and memory loss. Despite the path taken, replicating aspects of the chronic CD and testing therapeutic schemes in preclinical models, these findings may get lost in translation as the chronic nervous form of CD does not fulfil biomedical model requirements, as the presence of neuroinflammation, to be recognised. It is hoped that brain atrophy and behavioural and neurocognitive changes are sufficient traits to bring the attention of researchers to study the biological and molecular basis of the central nervous system commitment in chronic CD.

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

ABSTRACT 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.

Sobrevida de Pacientes Transplantados Cardíacos com Doença de Chagas Sob Diferentes Regimes de Imunossupressores Antiproliferativos / Survival of Heart Transplant Patients with Chagas' Disease Under Different Antiproliferative Immunosuppressive Regimens

Resumo Fundamento A Doença de Chagas (DC) é uma causa importante de transplante cardíaco (TC). O principal obstáculo é a reativação da DC (RDC), normalmente associada a altas doses de imunossupressores. Estudos anteriores sugeriram uma associação do micofenolato de mofetila com aumento na RDC. No entanto, preditores de mortalidade são desconhecidos. Objetivos Identificar os fatores de risco de mortalidade em pacientes com DC após o TC e o impacto do regime antiproliferativo sobre a sobrevida. Métodos Estudo retrospectivo com pacientes chagásicos submetidos ao TC entre janeiro de 2004 e setembro de 2020, em protocolo de imunossupressão que priorizava o uso de azatioprina e sua mudança para micofenolato de mofetila em caso de rejeição. Realizamos regressão univariada para identificar preditores de mortalidade e comparamos sobrevida, rejeição, e evidência RDC entre os pacientes que usavam azatioprina, micofenolato de mofetila, e aqueles que mudaram de azatioprina para micofenolato (grupo "Mudança") após a alta. Um valor de p<0,05 foi considerado estatisticamente significativo. Resultados Foram incluídos 85 pacientes, 54,1% homens, idade mediana 49 (39-57) anos, e 91,8% com prioridade na lista de espera. Dezenove (22,4%) usavam azatioprina, 37 (43,5%) micofenolato de mofetila, e 29 (34,1%) trocaram a terapia; a sobrevida não foi diferente entre os grupos, 2,9 (1,6-5,0) x 2,9 (1,8-4,8) x 4,2 (2,0-5,0) anos, respectivamente; p=0,4. Não houve diferença na taxa de rejeição (42%, 73% e 59% respectivamente; p=0,08) ou de RDC (T. cruzi positiva na biópsia endomiocárdica 5% x 11% x 7%; p=0,7; uso benzonidazol 58% x 65% x 69%; p=0,8; PCR positiva para T. cruzi 20% x 68% x 42% respectivamente; p=0,1). Conclusões Este estudo retrospectivo com pacientes com DC e TC não mostrou diferença na sobrevida entre os diferentes regimes antiproliferativos. O uso de micofenolato de mofetila não foi associado com taxas significativamente mais altas de RDC ou rejeição do enxerto nesta coorte. Novos ensaios randomizados são necessários para abordar essa questão.

Abstract Background Chagas' disease (CD) is an important cause of heart transplantation (HT). The main obstacle is Chagas' disease reactivation (CDR), usually associated to high doses of immunosuppressants. Previous studies have suggested an association of mycophenolate mofetil with increased CDR. However, mortality predictors are unknown. Objectives To identify mortality risk factors in heart transplant patients with CD and the impact of antiproliferative regimen on survival. Methods Retrospective study with CD patients who underwent HT between January 2004 and September 2020, under immunosuppression protocol that prioritized azathioprine and change to mycophenolate mofetil in case of rejection. We performed univariate regression to identify mortality predictors; and compared survival, rejection and evidence of CDR between who received azathioprine, mycophenolate mofetil and those who changed from azathioprine to mycophenolate mofetil after discharge ("Change" group). A p-value < 0.05 was considered statistically significant. Results Eighty-five patients were included, 54.1% men, median age 49 (39-57) years, and 91.8% were given priority in waiting list. Nineteen (22.4%) used azathioprine, 37 (43.5%) mycophenolate mofetil and 29 (34.1%) switched therapy; survival was not different between groups, 2.9 (1.6-5.0) x 2.9 (1.8-4.8) x 4.2 (2.0-5.0) years, respectively; p=0.4. There was no difference in rejection (42%, 73% and 59% respectively; p=0.08) or in CDR (T. cruzi positive by endomyocardial biopsy 5% x 11% x 7%; p=0.7; benznidazole use 58% x 65% x 69%; p=0.8; positive PCR for T. cruzi 20% x 68% x 42% respectively; p=0.1) rates. Conclusions This retrospective study did not show difference in survival in heart transplant patients with CD receiving different antiproliferative regimens. Mycophenolate mofetil was not associated with statistically higher rates of CDR or graft rejection in this cohort. New randomized clinical trials are necessary to address this issue.

Electrophysiological study in chagasics with syncope and conduction disorder

SUMMARY BACKGROUND: Investigation of syncope involves the use of electrophysiological study, particularly in patients with cardiac conduction disorder. There is conflicting evidence about the role of electrophysiological study in patients with Chagas disease. OBJECTIVE: The objective of this study was to evaluate the electrophysiological study findings in patients with Chagas disease and bundle branch block and/or divisional block presenting with syncope. METHODS: This is a retrospective study of patients with Chagas disease and cardiac conduction disorder who underwent electrophysiological study from 2017 to 2021 for the investigation of syncope in a tertiary hospital in São Paulo, Brazil. Those with non-interpretable ECG, known coronary artery disease, and/or other cardiomyopathies were excluded. HV interval and electrophysiological study-induced malignant ventricular arrhythmias data were analyzed. RESULTS: A total of 45 patients (60.2±11.29 years, 57.8% males) were included. The mean HV interval was 58.37 ms±10.68; 22.2% of the studied population presented an HV interval of ≥70 ms; and malignant ventricular arrhythmias were induced in 57.8% patients. The use of beta-blockers and amiodarone (p=0.002 and 0.036, respectively), NYHA functional class≥II (p=0.013), wide QRS (p=0.047), increased HV interval (p=0.02), Rassi score >6.5 (p=0.003), and reduced left ventricular ejection fraction (p=0.031) were associated with increased risk of inducible malignant ventricular arrhythmias. CONCLUSION: More than half of the patients with Chagas disease, syncope, and cardiac conduction disorder have inducible malignant ventricular arrhythmias. Prolonged HV interval was observed in only 20% of population. Wide QRS, prolonged HV, reduced ejection fraction, and higher Rassi score were associated with increased risk of malignant ventricular arrhythmias.

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

ABSTRACT 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.

Rattus norvegicus infectados com Trypanosoma cruzi: efeitos clínicos do tratamento com Lycopodium clavatun e phosphorus ultradiluídos / Rattus norvegicus infected with Trypanosoma cruzi: clinical effects of treatment with highly diluted Lycopodium clavatun and phosphorus / Rattus norvegicus infectado con Trypanosoma cruzi: efectos clínicos del tratamiento con Clavatun licopodio altamente diluido y fósforo

A doença de Chagas causada pelo parasita Trypanosoma cruzi acomete milhões de pessoas no mundo e não conta com um medicamento de ação efetiva para o seu tratamento etiológico. As drogas disponíveis, o nifurtimox e o benznidazol possuem índices de cura baixos com efeitos colaterais e toxidade que dificultam a adesão dos pacientes à terapia. Este fato impulsiona a busca por alternativas de tratamento que sejam mais efetivas e menos agressivas. Sendo assim, este trabalho teve como objetivo a avaliação dos efeitos clínicos apresentados por Rattus norvergicus infectados por T. cruzi e tratados com soluções ultradiluídas de Lycopodium clavatum ou Phosphorus. O estudo envolveu 93 ratos com quarenta e cinco dias de idade infectados intraperitonealmente com 5x106 formas tripomastigotas sanguíneos da cepa Y de T. cruzi, distribuídos nos grupos: Sadio SD (n=13) - controle não infectado e não tratado, grupo CI (n=27) - controle infectado e tratado com solução hidroalccólica 7% (etanol ­ água), grupo LY diluição 1:1x1026 (n=27) - infectado e tratado com Lycopodium, grupo PH diluição 1:1x1026 (n=26) - infectado e tratado com Phosphorum. Os animais foram avaliados clinicamente através dos parâmetros peso, temperatura, consumo de água e ração, quantidade de excretas, diâmetro e comprimento intestinal, aspecto da pelagem e consistência das fezes. Este estudo mostrou que os parâmetros utilizados foram importantes para a definição clínica da infecção de Rattus novergicus, linhagem Wistar pelo T. cruzi. Mostrou que os medicamentos LY e PH apresentam efeitos benéficos na evolução da clínica dos animais tratados. A utilização de Lycopodium clavatum e Phosphorus diluídos na proporção de 1:1x1026, apresentaram efeitos diferentes. Oito e seis parâmetros de quatorze analisados mostraram efeitos positivos para LY e PH, respectivamente. Os parâmetros consumo de água e ração, quantidade de excretas, diarreia, alopecia difusa e comprimento intestinal apresentaram diferenças significativas em relação ao controle infectado mostrando que mais estudos são necessários com o uso de medicamentos ultradiluídos na infecção pelo T. cruzi.

Chagas disease caused by the parasite Trypanosoma cruzi affects millions of people worldwide and does not have an effective drug for its etiological treatment. The available drugs, nifurtimox and benznidazole, have low cure rates with side effects and toxicity that make it difficult for patients to adhere to therapy. This fact drives the search for treatment alternatives that are more effective and less aggressive. Therefore, this work aimed to evaluate the clinical effects presented by Rattus norvergicus infected by T. cruzi and treated with ultradiluted solutions of Lycopodium clavatum or Phosphorus. The study involved 93 forty five day old rats intraperitoneally infected with 5x106 blood trypomastigotes forms of the Y strain of T. cruzi, distributed in the following groups: Healthy SD (n=13) - non-infected and untreated control, CI group (n =27) - infected control and treated with 7% hydroalcoholic solution (ethanol ­ water), LY group dilution 1:1x1026 (n=27) - infected and treated with Lycopodium, PH group dilution 1:1x1026 (n=26) - infected and treated with Phosphorum. The animals were clinically evaluated through the parameters weight, temperature, water and feed consumption, amount of excreta, intestinal diameter and length, coat appearance and feces consistency. This study showed that the parameters used were important for the clinical definition of infection of Rattus novergicus, Wistar lineage by T. cruzi. It showed that LY and PH drugs have beneficial effects on the clinical evolution of treated animals. The use of Lycopodium clavatum and Phosphorus diluted in the ratio of 1:1x1026, showed different effects. Eight and six parameters out of fourteen analyzed showed positive effects for LY and PH, respectively. The parameters water and feed consumption, amount of excreta, diarrhea, diffuse alopecia and intestinal length showed significant differences in relation to the infected control, showing that more studies are needed with the use of ultradiluted drugs in T. cruzi infection.

La enfermedad de Chagas causada por el parásito Trypanosoma cruzi afecta a millones de personas en todo el mundo y no cuenta con un fármaco eficaz para su tratamiento etiológico. Los fármacos disponibles, nifurtimox y benznidazol, presentan bajas tasas de curación con efectos secundarios y toxicidad que dificultan la adherencia terapéutica de los pacientes. Este hecho impulsa la búsqueda de alternativas de tratamiento más eficaces y menos agresivas. Por lo tanto, este trabajo tuvo como objetivo evaluar los efectos clínicos presentados por Rattus norvergicus infectados por T. cruzi y tratados con soluciones ultradiluidas de Lycopodium clavatum o Fósforo. En el estudio participaron 93 ratas de cuarenta y cinco días de edad infectadas intraperitonealmente con 5x106 formas tripomastigotes sanguíneas de la cepa Y de T. cruzi, distribuidos en los siguientes grupos: SD sano (n=13) - control no infectado y no tratado, grupo CI (n =27) - control infectado y tratado con solución hidroalcohólica al 7% (etanol - agua), grupo LY dilución 1:1x1026 (n=27) - infectado y tratado con Lycopodium, grupo PH dilución 1:1x1026 (n=26) - infectado y tratado con Phosphorum. Los animales fueron evaluados clínicamente mediante los parámetros peso, temperatura, consumo de agua y pienso, cantidad de excrementos, diámetro y longitud intestinal, aspecto del pelaje y consistencia de las heces. Este estudio demostró que los parámetros utilizados eran importantes para la definición clínica de la infección de Rattus novergicus, linaje Wistar por T. cruzi. Demostró que los fármacos LY y PH tienen efectos beneficiosos en la evolución clínica de los animales tratados. El uso de Lycopodium clavatum y Phosphorus diluidos en la proporción de 1:1x1026, mostró efectos diferentes. Ocho y seis parámetros de los catorce analizados mostraron efectos positivos para LY y PH, respectivamente. Los parámetros consumo de agua y pienso, cantidad de excretas, diarrea, alopecia difusa y longitud intestinal mostraron diferencias significativas en relación al control infectado, mostrando que son necesarios más estudios con el uso de fármacos ultradiluidos en la infección por

Detection of Trypanosoma cruzi DTUs TcI and TcIV in two outbreaks of orally-transmitted Chagas disease in the Northern region of Brazil

ABSTRACT This study describes the laboratory investigation of two acute Chagas disease outbreaks that occurred in the riverside communities of Marimarituba and Cachoeira do Arua, in the Santarem municipality, Para State, located in the Northern region of Brazil, and occurred in March 2016 and August 2017, respectively. The generation of data regarding the diversity of Trypanosoma cruzi parasites circulating in the Amazon region is key for understanding the emergence and expansion of Chagas disease. This study aimed to identify T. cruzi Discrete Typing Units (DTUs) involved in two outbreaks of acute Chagas disease (ACD) directly from the patient's biological sample. Nested and multiplex PCR targeting the 24Sα (rRNA) and mini-exon genes, respectively, were used to identify T. cruzi DTU in blood samples from patients diagnosed with ACD. The samples with positive cPCR were submitted for analysis for T. cruzi DTUs, which included 13 samples from the patients with ACD by oral transmission and two samples collected from two newborns of two women with ACD, from Marimarituba and Cachoeira do Arua. The samples were classified as T. cruzi TcIV, from Marimarituba's outbreak, and T. cruzi TcI, from Cachoeira do Arua's outbreak. The molecular identification of T. cruzi may increase understanding of the role of this parasite in Chagas disease's emergence within the Amazon region, contributing to the improvement of the management of this important, but also neglected, disease.