Un caso de Chagas agudo en edad pediátrica / Acute Vector-transmitted Chagas in Pediatric Age. A Case Reportt

Presentación del caso. Se trata una niña de siete años de edad, originaria de una zona rural del departamento de San Miguel, quién consultó por presentar fiebre y edema bipalpebral derecho indoloro, de seis semanas de evolución, sin otros síntomas acompañantes. El estudio para el diagnóstico de enfermedad de Chagas fue realizado en una clínica privada; la Inmunoglobulina M para Chagas tuvo un resultado positivo, luego, se realizó la microscopía directa mediante gota al fresco y técnica de Strout con resultado negativo. En las intervenciones comunitarias se identificó la presencia del vector y la positividad del mismo, así como el diagnóstico de un caso crónico en otro miembro de la familia. Intervención terapéutica. Se indicó tratamiento con nifurtimox 150 mg cada ocho horas por 60 días y se realizó el seguimiento clínico de la evolución y control de efectos secundarios del tratamiento y exámenes de laboratorio. Evolución clínica. Evolucionó con leve disminución del apetito, se manejó con protectores gástricos. El concentrado de Strout y la gota al fresco resultaron negativos y los demás exámenes de laboratorio se mantenían en los rangos normales.

Case presentation. A seven-year-old female patient, with no previous medical history, originally from a rural area of the department of San Miguel, who presented febrile process plus long-term right bipalpebral edema of six weeks of evolution, without accompanying symptoms. Immunoglobulin M for Chagas was positive, direct microscopy by fresh drop and Strout technique was performed with negative results. In community interventions, the presence of the vector and its positivity were identified, as well as the diagnosis of a chronic case in another family member. Treatment. The patient was treated with nifurtimox 150 mg every eight hours for 60 days, subsequent controls were performed to investigate side effects of the treatment, and control tests. Outcome. With the treatment, the patient evolved with a slight decrease in appetite, and was managed with gastric protectors. Strout's concentrate and fresh gout were negative and the other laboratory tests were within normal ranges.

Efectos de la infección del Trypanosoma cruzi en ratones de las cepas Balb/c y NIH / Effects of Trypanosoma cruzi infection in Balb/c and NIH mouse strains

La enfermedad de Chagas es una infección causada por el parásito Trypanosoma cruzi y transmitida por el vector Triatoma dimidiata, conocido en El Salvador como «chinche picuda¼. Esta enfermedad siempre ha sido de interés científico en modelos animales. Objetivo. Identificar el efecto de la infección por Trypanosoma cruzi en ratones de diferentes cepas (BALB/c y NIH) y sexo. Metodología. Se establecieron ocho grupos: cuatro infectados con Trypanosoma cruzi y cuatro grupos no infectados, distribuidos por cepa y sexo, con cinco ratones por grupo. Durante seis semanas se registró el peso corporal de los ratones. Además, se prepararon muestras de sangre de los grupos infectados en láminas para realizar los conteos de parasitemia. Al final del estudio, se extrajeron el bazo y el corazón de ambos grupos para los análisis estadísticos. Resultados. Los grupos infectados mostraron un incremento de peso en comparación a sus grupos controles. En la cepa NIH, las hembras presentaron una mayor parasitemia, mientras que en la cepa BALB/c fueron los machos los de mayor parasitemia. Los órganos de los grupos infectados fueron significativamente más grandes comparados a los de los grupos de control, excepto en el corazón de la cepa BALB/c. Respecto al peso de los órganos, se observaron diferencias significativas únicamente en el corazón de los machos de la cepa BALB/c, mientras que en el bazo ocurrió lo contrario. Conclusión. Los machos de la cepa BALB/c son más susceptibles al Trypanosoma cruzi, presentando niveles de parasitemia más altos entre los grupos estudiados

Chagas disease is an infection caused by the parasite Trypanosoma cruzi and transmitted by the vector Triatoma dimidiata, known in El Salvador as "chinche picuda". This disease has always been of scientific interest in animal models. Objective. Identify the effect of Trypanozoma cruzi infection in mice of different strains (BALB/c and NIH) and sex. Methodology. Eight groups were established: four infected with Trypanosoma cruzi and four uninfected groups, distributed by strain and sex, with five mice per group. The body weight of the mice was recorded for six weeks. In addition, blood samples from the infected groups were prepared on slides for parasitemia counts. At the end of the study, the spleen and heart were extracted from both groups for statistical analyses. Results. The infected groups showed an increase in weight compared to their control groups. In the NIH strain, females had higher parasitemia, whereas in the BALB/c strain, males had higher parasitemia. The organs of the infected groups were significantly larger compared to those of the control groups, except in the heart of the BALB/c strain. Regarding organ weight, significant differences were observed only in the heart of the male BALB/c strain, while the opposite was true for the spleen. Conclusion. Males of the BALB/c strain are more susceptible to Trypanosoma cruzi, presenting higher levels of parasitemia among the groups studied.

Influence of sexual hormones on Chagas disease / Influencia de las hormonas sexuales en la enfermedad de Chagas

Abstract Objective: Analyze sex hormone's influence during Chagas disease. Methods: Male and female BALB/c mice were divided into six groups, four experimental (sham, orchiectomized, orchiectomized and supplemented with estradiol, orchiectomized supplemented with testosterone, oophorectomized, oophorectomized and supplemented with estradiol, and oophorectomized and supplemented with testosterone), and two control (healthy and intraperitoneally with T. cruzi strain NINOA infected). Clinical data were recorded daily, parasitemia was evaluated using a Neubauer chamber during the infection, and heart histopathological analysis was performed using the paraffin embedding technique. To analyze parasitemia curves and the area under the parametric curves, two-way ANOVA test was performed to correlate groups' data. P-values < 0.05 were considered statistically significant. Results: Higher mortality rates, cardiomegaly, hepatomegaly, ascites, edema, higher parasitemia levels, more amastigote nests, and more severe inflammatory infiltrate were found in higher testosterone concentration mice, whereas in higher estradiol concentration groups, paresia, prostration, edema, and necrosis were found. Conclusions: Our results showed that testosterone increased infection severity, whereas estradiol had the opposite effect. This research improves the understanding of sex hormones´ infuence upon this infection to contribute with the handling of Chagas´ disease.

Resumen Objetivo: Analizar la influencia de las hormonas durante la enfermedad de Chagas. Métodos: Se separaron grupos de ratones macho y hembras BALB/c, todos infectados con T. cruzi (cepa NINOA), 4 grupos experimentales de machos (Sham, orquidectamizados, orquidectimezados y suplementados con estradiol, orquidectamizaos y suplementados con testosterona). 4 grupos experimentales de hembras (oforectomizadas, oforectomizadas y suplementadas con estradiol, oforectomizadas y suplementadas con testosterona y sham), and y dos grupos control para cada sexo (sin infección e infectados intraperitonealmente con T. cruzi (cepa NINOA). Los datos clínicos fueron registrados diariamente, la parasitemia fue evaluada durante toda la infección utilizando una cámara de Neubauer y el análisis histopatológico del corazón fue realizada con la técnica de inclusión en parafina. Para el análisis de las curvas de parasitemia y el área bajo la curva, se realizó una prueba de ANOVA de dos vías, p < 0.05 fueron considerados estadísticamente diferentes. Resultados: Las mayores tasas de mortalidad, cardiomegalia, hepatomegalia y mayor infiltrado inflamatorio, se encontró en los ratones con una mayor concentración de testosterona. En contraste los ratones con mayor concentración de estradiol presentaron paresia, postración edema y necrosis. Conclusiones: Nuestros resultados ponen en manifiesto que la testosterona incrementa la severidad del curso de la enfermedad de Chagas, mientras que el estradiol tuvo el efecto opuesto. Este trabajo mejora el entendimiento del rol que juegan las hormonas sexuales en esta infección para contribuir en un mejor manejo de la enfermedad de Chagas.

Seroprevalencia de Trypanosoma cruzi en niños de Veracruz, México: línea epidemiológica de base para un modelo de control fundamentado de la transmisión activa de la enfermedad de Chagas / Seroprevalence of Trypanosoma cruzi among children from Veracruz, Mexico: Epidemiological baseline for a control model based on Chagas disease active transmission

Resumen Introducción. En el 2021, la Secretaría de Salud de México y la Organización Panamericana de la Salud lanzaron una iniciativa para interrumpir la transmisión vectorial intradomiciliaria de Trypanosoma cruzi, fundamentada en la prevalencia de la enfermedad de Chagas en la población infantil. El estado mexicano de Veracruz fue el pionero de esta iniciativa. Objetivo. Estimar la seroprevalencia de infección por T. cruzi en menores de 15 años de localidades rurales de Veracruz, México. Materiales y métodos. Se identificaron ocho localidades prioritarias para la serología basal del municipio de Tempoal, Veracruz. Entre junio y agosto de 2017, se recolectaron muestras de sangre en papel filtro de 817 individuos para su tamizaje mediante un inmunoensayo enzimático de tercera generación. Los casos reactivos del tamizaje se confirmaron mediante pruebas de hemaglutinación indirecta, ensayo de inmunoabsorción ligado a enzimas e inmunofluorescencia indirecta en muestras de suero. Se calculó la seroprevalencia y su intervalo de confianza (IC) del 95 %. Resultados. En las localidades de Citlaltépetl, Cornizuelo, Cruz de Palma y Rancho Nuevo se confirmaron casos de la enfermedad de Chagas en menores de 15 años con una seroprevalencia de 1,9 % (IC 95 % = 1,12-3,16). Conclusiones. Los resultados indican que estas comunidades presentan transmisión reciente de T. cruzi y permiten establecer una línea epidemiológica de base para el diseño e implementación de un modelo dirigido a aquellas áreas geográficas con transmisión activa. Se espera que dicho modelo contribuya a la eliminación de la transmisión vectorial intradomiciliaria del tripanosomátido en México.

Abstract Introduction. In 2021, the Secretaría de Salud de México and the Pan American Health Organization launched an initiative to interrupt intra-domiciliary vector transmission of Trypanosoma cruzi based on the prevalence of Chagas disease in children. The Mexican State of Veracruz was leading this initiative. Objective. To estimate the seroprevalence of T. cruzi infection among children under 15 years of age from rural areas of Veracruz, México. Materials and methods. We identified eight localities of high priority from the Municipality of Tempoal, Veracruz, for baseline serology. Blood samples were collected on filter paper from 817 individuals between June and August 2017, for screening with a third-generation enzyme immunoassay. Reactive cases were confirmed by indirect hemagglutination, enzyme-linked immunosorbent assay, and indirect immunofluorescence tests on peripheral blood serum samples. We calculated seroprevalence and 95% confidence intervals (CI). Results. We confirmed Chagas disease cases in children under 15 years of age with a seroprevalence of 1,9% (95 % CI = 1,12-3,16) in the localities of Citlaltepetl, Cornizuelo, Cruz de Palma and Rancho Nuevo. Conclusions. These results indicate recent transmission of T. cruzi in these communities and allow to establish an epidemiological baseline for the design and implementation of a model focused on geographical areas with active transmission to advance toward the elimination of intra-domiciliary vector transmission of this parasite in Mexico.

GSK-3 kinase a putative therapeutic target in trypanosomatid parasites

ABSTRACT Trypanosomatids are an important group of parasites that predominate in tropical and subtropical areas of the planet, which cause diseases that are classified as forgotten and neglected by the world health organization. In this group of parasites, we find Trypanosoma cruzi, Trypanosoma brucei, Trypanosoma brucei rhodesiense and Leishmania spp, for which there is no vaccine available, and its control has focused mainly on pharmacological treatment. Due to the poverty situation where these diseases are found and the biological complexity of these parasites, there are multiple variables to control, including the diversity of species, the complexity of their life cycles, drug resistance, cytotoxicity, the limited use in pregnant women, the high costs of treatment and the little-known pharmacological mechanisms of action, among others. It is therefore necessary to find new strategies and approaches for the treatment of these parasitic diseases. Among these new approaches is the rational search for new targets based on the allosteric inhibition of protein kinases, which have been little studied in trypanosomatids. Among these kinases, we find Glycogen Synthase Kinase-3 (GSK-3), a kinase of great pharmacological interest, which is under intense basic and clinical research by pharmaceutical companies for the treatment of cancer. This kinase, highly studied in the PI3K/AKT/mTOR pathway signaling in humans, has an orthologous gene in these parasites (GSK-3 s), which has proven to be essential for them in response to different challenges; Therefore, it is notable to increase research in this kinase in order to achieve a broad structural and functional characterization in the different species of trypanosomatids.

Improving in vitro screening compounds anti-Trypanosoma cruzi by GFP-expressing parasites

BACKGROUND Conventional microscopic counting is a widely utilised method for evaluating the trypanocidal effects of drugs on intracellular amastigotes. This is a low-cost approach, but it is time-consuming and reliant on the expertise of the microscopist. So, there is a pressing need for developing technologies to enhance the efficiency of low-cost anti-Trypanosoma cruzi drug screening. OBJECTIVES In our laboratory, we aimed to expedite the screening of anti-T. cruzi drugs by implementing a fluorescent method that correlates emitted fluorescence from green fluorescent protein (GFP)-expressing T. cruzi (Tc-GFP) with cellular viability. METHODS Epimastigotes (Y strain) were transfected with the pROCKGFPNeo plasmid, resulting in robust and sustained GFP expression across epimastigotes, trypomastigotes, and intracellular amastigotes. Tc-GFP epimastigotes and intracellular amastigotes were exposed to a serial dilution of benznidazole (Bz). Cell viability was assessed through a combination of microscopic counting, MTT, and fluorimetry. FINDINGS The fluorescence data indicated an underestimation of the activity of Bz against epimastigotes (IC50 75 µM x 14 µM). Conversely, for intracellular GFP-amastigotes, both fluorimetry and microscopy yielded identical IC50 values. Factors influencing the fluorimetry approach are discussed. MAIN CONCLUSIONS Our proposed fluorometric assessment is effective and can serve as a viable substitute for the time-consuming microscopic counting of intracellular amastigotes.

Diagnóstico de Chagas agudo: experiencia en un hospital pediátrico de tercer nivel de atención / Diagnosis of acute Chagas: experience in a tertiary care children's hospital / Diagnóstico de Chagas agudo: experiência em um hospital pediátrico de terceiro nível de atenção

Resumen Chagas es una infección causada por Trypanosoma cruzi. Actualmente la principal vía de transmisión en la Argentina es la vertical y es prioritario el diagnóstico oportuno. El objetivo de este trabajo fue analizar características epidemiológicas y de seguimiento de pacientes con sospecha de Chagas agudo. Se realizó un estudio observacional, descriptivo y retrospectivo, analizando las historias clínicas de pacientes con pedido de parasitemia entre 2015 y 2022. Se registró resultado, antecedentes epidemiológicos y si se completó el algoritmo diagnóstico. Se analizaron 254 pacientes con una mediana de edad de 6 meses. Veintidós fueron diagnosticados con Chagas; 17 fueron por transmisión vertical, 1 por transmisión vertical/trasplante y 4 por vertical/vectorial. En 126 pacientes se descartó la infección, mientras que en 99 no se completó el algoritmo diagnóstico. Siete pacientes fueron excluidos del estudio. Se diagnosticó Chagas en el 8,7% de los pacientes y se observó pérdida de seguimiento en un 36,2%.

Abstract Chagas is an infection caused by Trypanosoma cruzi. Nowadays, in Argentina vertical transmission is the main source of infection, which makes opportunistic diagnosis mandatory. The aim of this study was to analyse the epidemiological characteristics and follow-up of patients with suspected acute Chagas infection. An observational, descriptive, retrospective study was carried out. Medical records of patients with parasitemia test solicitude in the period between 2015 and 2022 were analysed, and results were registered, along with epidemiological background and if diagnosis algorithm were completed; 254 patients were analysed with a median age of 6 months: 22 patients were diagnosed with Chagas, 17 of whom had a vertical transmission, 1 was vertical/transplant transmission and there were 4 cases of vertical/vectorial transmission. Infection was ruled out in 126 patients, while in 99 children algorithm diagnosis was not completed. Seven patients were excluded from this study. Chagas was diagnosed in 8.7% of the patients studied and there was loss in follow-up in 36.2% of patients.

Resumo Chagas é uma infecção causada pelo Trypanosoma cruzi. Atualmente, na Argentina, a principal via de transmissão é a vertical e é prioritário o diagnóstico oportuno. O objetivo deste trabalho foi analisar as características epidemiológicas e de seguimento de pacientes com suspeita de Chagas agudo. Foi realizado um estudo observacional, descritivo e retrospectivo. Analisaram-se osprontuarios médicos dos pacientes com pedido de parasitemia entre 2015 e 2022. Foram registrados resultado e antecedentes epidemiológicos, e se completou o algoritmo diagnóstico. Analisaram-se 254 pacientes com uma mediana de idade de 6 meses: 22 foram diagnosticados com Chagas; 17 foram por transmissão vertical, 1 transmissão vertical/transplante, e 4 vertical/vetorial. Em 126 pacientes foi descartada a infecção, enquanto que em 99 não se completou o algoritmo diagnóstico. Sete pacientes foram excluídos do estudo. Foi diagnosticado Chagas em 8,7% dos pacientes e se observou perda de seguimento em 36,2%.

Synthesis of (-) - 6, 6'-dinitrohinokinin from hinokinin natural product and in silico and in vitro trypanocidal activity assessment

Chagas disease is a public health problem affecting approximately seven million people worldwide. Thus, there is a need to discover drugs for the adequate treatment of this disease because currently available drugs have serious side effects. Therefore, this study aimed to evaluate the in vitro trypanocidal activity of (-)-6,6'-dinitrohinokinin, obtained from the partial synthesis of (-)-hinokinin, on the trypomastigotes and amastigotes forms. For the trypomastigote assay, blood was collected from mice infected with Trypanosoma cruzi through cardiac puncture at the parasitemic peak. The results show that (-)-6,6'-dinitrohinokinin was effective against the trypomastigote forms, presenting an IC50 of 19.83 µM and lysis percentage values ​​of 78.4% and 69.4% at concentrations of 200 and 100 µM, respectively. Molecular docking calculations indicate that (-)-6,6'-dinitrohinokinin favorably interacts with the amino acids present in the active site of the protein trypanothione reductase, a typical target for anti-trypanosomal drug development. According to the results, the (-)-6,6'-dinitrohinokinin showed more significant trypanocidal activity with IC50 of 1.83 µM than benzonidazole positive control with IC50 of 53.2 µM, showing to be a prototype molecule promising for the development of a new antiparasitic drug.

Drug screening and development cascade for Chagas disease: an update of in vitro and in vivo experimental models

Chagas disease is a tropical neglected disease that affects millions of people worldwide, still demanding a more effective and safer therapy, especially in its chronic phase which lacks a treatment that promotes substantial parasitological cure. The technical note of Romanha and collaborators published in 2010 aimed establish a guideline with the set of minimum criteria and decision gates for the development of new agents against Trypanosoma cruzi with the focus on developing new antichagasic drugs. In this sense, the present review aims to update this technical note, bringing the state of the art and new advances on this topic in recent years.

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

Acute Chagas disease Diagnostic experience through an outbreak / Enfermedad de Chagas aguda Experiencia diagnóstica a través de un brote

Abstract Chagas disease is a public health problem in Latin America, with a tendency to globalize due to migration phenomena. The acute phase of the disease tends to be indolent, but a low percentage of patients have an ominous course, especially when the route of transmission is oral, presenting as a prolonged febrile syndrome in the form of an epidemic outbreak. Early detection of the disease will probably avoid morbid outcomes and, in some cases, death. In this case report we summarize a diagnostic approach by describing the index case in an epidemic outbreak. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2727).

Resumen La enfermedad de Chagas constituye un problema de salud pública en Latinoamérica con tendencia a la globalización, debido a los fenómenos de migración. La fase aguda de la enfermedad suele ser indolente, pero un bajo porcentaje de pacientes tienen un curso ominoso, especialmente cuando la ruta de transmisión es oral, presentándose como un síndrome febril prolongado en forma de brote epidémico. La detección temprana de la enfermedad probablemente evite desenlaces de morbilidad y en algunos casos la muerte. En este reporte de caso resumimos un enfoque diagnóstico a través de la descripción del caso índice de un brote epidémico. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2727).

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.

Benznidazole treatment decreases IL-6 levels in Trypanosoma cruzi-infected human adipocytes differentiated from adipose tissue-derived stem cells

BACKGROUND Trypanosoma cruzi, which causes Chagas disease (CD), is a versatile haemoparasite that uses several strategies to evade the host's immune response, including adipose tissue (AT), used as a reservoir of infection. As it is an effective barrier to parasite evasion, the effectiveness of the drug recommended for treating CD, Benznidazole (BZ), may be questionable. OBJECTIVE To this end, we evaluated the parasite load and immunomodulation caused by BZ treatment in the culture of adipocytes differentiated from human adipose tissue-derived stem cells (ADSC) infected with T. cruzi. METHODS The ADSC were subjected to adipogenic differentiation. We then carried out four cultures in which we infected the differentiated AT with trypomastigote forms of the Y strain of T. cruzi and treated them with BZ. After the incubation, the infected AT was subjected to quantitative polymerase chain reaction (qPCR) to quantify the parasite load and transmission electron microscopy (TEM) to verify the infection. The supernatant was collected to measure cytokines, chemokines, and adipokines. FINDINGS We found elevated secretion of IL-6, CXCL-10/IP-10, CCL2/MCP-1, CCL5/RANTES, and leptin in infected fat cells. However, treatment with BZ promoted a decrease in IL-6. MAIN CONCLUSION Therefore, we believe that BZ has a beneficial role as it reduces inflammation in infected fat cells.

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.

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.

Trypanosoma cruzi DTU II coinfection with bacteria producing prolonged cutaneous lesion in a healthy young male

ABSTRACT Chagas disease (CD) is a neglected tropical disease caused by Trypanosoma cruzi and is genetically classified in six discrete typing units (DTUs). The isolates reported in Mexico are generally associated with DTU I. We presented a case of a prolonged cutaneous lesion in a Mexican man, caused by DTU II in coinfection with Bacillus velezensis and Corynebacterium sp. The patient assessment included a complete clinical history, physical exam, laboratory tests, and a skin biopsy. In the facial tissues, intracellular parasites were revealed. The PCR tests were positive for T. cruzi in tissue and blood samples. DNA satellite sequencing was correlated with the DTU II. The initial serological tests reported negative results. However, four months later, two serological tests reported positive results. These exams were performed in different health centers. Mexico is considered an endemic area for CD; nevertheless, this is just the second cutaneous case associated with a DTU different from DTU-I noted in this country. From an ecological point of view, this fact suggests a geographical expansion of DTU II and an association with atypical skin manifestations. Further studies should be conducted to understand this exciting association between DTU-II and prolonged cutaneous expression in humans.

Tolerance and Adherence of Patients with Chronic Chagas Disease Treated with Benznidazole

ABSTRACT Background: Chagas disease (CD) treatment is commonly associated with a high incidence of adverse effects. It is crucial to study and update these adverse effects to improve the existing knowledge of which drugs to use and to clarify the information presented to patients. Methods: We analyzed the adverse effects of benznidazole in two cohorts of patients: a large retrospective study and a small prospective study. Results: This large retrospective study described the most and least common adverse effects in our area and characterized our Chagas disease population. This prospective study, along with a close follow-up of the treatment, detected more adverse effects and enhanced the patients' perception of the disease and treatment. Conclusions: This information is important for preventing non-medical-related withdrawals and for removing baseless fears. Better knowledge of patients could help us provide better care.

Epidemiological indicators of Chagas disease in the metropolitan region of Salvador, Bahia, Brazil

ABSTRACT Background: Chagas disease (CD) is caused by Trypanosoma cruzi and transmitted by triatomines. Historical information from the 20th century demonstrates T. cruzi records in the metropolitan region of Salvador (MRS), the third largest urban agglomeration in the Brazilian Northeast and the eighth largest in Brazil, an area with intense migratory activity from CD-endemic regions. Therefore, this study aimed to evaluate CD indicators (prevalence and mortality) in the MRS. Methods: A mixed ecological and descriptive study was conducted using secondary data. We analyzed data from 2008 to 2015: deaths due to CD, self-reported cases of CD, and blood donors that were non-negative for T. cruzi infection. Results: São Francisco do Conde was one of the municipalities with the highest mortality rates due to CD. The seroprevalence rates varied by year and municipality; those with the highest values were 2008: Vera Cruz, 2009: Mata de São João, 2010: Dias D'Ávila, 2011 and 2015: São Francisco do Conde, 2012: São Sebastião do Passé, and 2013 and 2014: Pojuca. Spatial correlations between the municipalities were not detected. Conclusions: We conclude that CD is present in the MRS. The indicators analyzed in the MRS are below-state-level data. Given the importance of indicator analysis for the surveillance and control of CD at the state and national levels, it is important to strengthen the surveillance program at the municipal level, including the regions classified as low risk for T. cruzi vector transmission.