In the present work, three series of cinnamic (1), p-coumaric (2) and ferulic (3) esters containing different side-chains such as ethyl (1a-3a), n-propyl (1b-3b), n-butyl (1c-3c), n-pentyl (1d-3d), n-hexyl (1e-3e), and n-heptyl (1f-3f) were prepared, tested for activity against trypomastigote forms of the parasite Trypanosoma cruzi and toxicity against NCTC cells. Obtained results indicated that the presence of p-coumaric or ferulic moieties associated with C4-C7 linear side-chains play an important role in the bioactivity against T. cruzi since compounds 2c-2f and 3d-3f were found to be the most active derivatives with a half maximal effective concentration (EC50) value ranging from 12.8 to 1.7 μM, superior to that determined for the positive control benznidazole (EC50 = 16.4 μM). Additionally, machine learning and multivariate statistical analyses identified molecular features correlated with biological activity, emphasizing the importance of side-chain length and lipophilicity, highlighting the significance of the molecular structure of phenylpropanoid derivatives in the activity against T. cruzi. work 1, 1 , (1) pcoumaric p coumaric 2 (2 3 (3 sidechains side chains 1a3a, 1a3a aa 1a 3a (1a-3a) npropyl n propyl 1b3b, 1b3b bb 1b 3b b (1b-3b) nbutyl butyl 1c3c, 1c3c cc 1c 3c c (1c-3c) npentyl pentyl 1d3d, 1d3d dd 1d 3d d (1d-3d) nhexyl hexyl 1e3e, 1e3e ee 1e 3e e (1e-3e) nheptyl heptyl 1f3f ff 1f 3f f (1f-3f prepared cells C4C7 CC C4 C7 C C4-C T 2c2f cf 2c 2f 3d3f df EC50 EC 128 12 8 12. 17 7 1. μM (EC5 164 16 4 16. μM. . μM) Additionally sidechain chain lipophilicity (1 ( (1a-3a (1b-3b (1c-3c (1d-3d (1e-3e C4C EC5 (EC

Abstract (Objective) Trypanosoma cruzi, a causal agent of Chagas’ disease, is a parasite whose life cycle alternates between an invertebrate (triatomine) and a vertebrate (mammal) host. Various studies have shown that in T. cruzi, HSP83 (a homolog of HSP90) is essential for cell division and control of the response to thermal stress. This investigation focused on studying the cloning, bioinformatic characterization, and expression of the heat shock protein HSP83 T. cruzi gene for further cell signaling studies. (Methodology) RNA was extracted from T. cruzi epimastigotes (EPm6 clone, MHOM/VE/2007/ 6c) using a commercial kit. The cDNA encoding HSP83 was determined using RT-PCR on extracted mRNA, for which the primers were designed based on the HSP83 sequence of T. cruzi strain CL Brener. Cloning was performed using pGEM®T-Easy and subcloned into the expression vector pQE30. Sequence and bioinformatic characterization were performed. The gene was expressed, and the recombinant protein was purified using affinity chromatography and identified through immunoblotting. (Results) Sequence analysis showed similarity to the gene encoding HSP83 from Trypanosoma cruzi, and HSP domains and B epitopes in the sequence were also observed. After 3 hours of induction with IPTG, a recombinant protein with an approximate weight of 83 kDa was obtained. The immunoblotting reaction with hyperimmune anti-T. cruzi epimastigote serum helped detect a single band with a molecular weight of nearly 83 kDa. (Conclusions) All results indicate that the cloning and characterization of HSP83 from Trypanosoma cruzi was achieved.

Resumo (Objetivo) O Tryapanosoma cruzi, agente causador da doença de Chagas, é um parasita que apresenta uma alternância em seu ciclo de vida entre um hospedeiro invertebrado triatomíneo) e um vertebrado(mamífero). Vários estudos demonstraram que, no T. cruzi, a HSP83 (homóloga da HSP90) é essencial para a divisão celular e o controle da resposta ao estresse térmico. Esta pesquisa concentrou-se no estudo da clonagem, caracterização bioinformática e expressão do gene da proteína de choque térmico HSP83 do T. cruzi para estudos adicionais de sinalização. (Metodologia) O RNA foi extraído de epimastigotas de T. cruzi (clone EPm6/MOHM/VE/2007/ 6c) usando um kit comercial. O cDNA que codifica a HSP83 foi obtido por meio de RT-PCR a partir do mRNA extraído, para o qual os primers foram projetados com base na sequência da HSP83 da cepa T. cruzi CL Brener. A clonagem foi realizada com o pGEM®T-Easy e subclonada no vetor de expressão pQE30. Foi realizada a caracterização bioinformática e de sequência. O gene foi expresso e a proteína recombinante foi purificada por cromatografia de afinidade e identificada por imunotransferência. (Resultados) A análise da sequência mostrou similaridade com o gene HSP83 do Trypanosoma cruzi e os domínios HSP, bem como os epítopos B, foram observados na sequência. Após 3 horas de indução com IPTG, foi obtida uma proteína recombinante com peso aproximado de 83 kDa. A imunotransferência com soro hiperimune antiepimastigota de T. cruzi permitiu a detecção de uma única banda com peso molecular de aproximadamente 83 kDa. (Conclusões) Todos os resultados indicam que a clonagem e a caracterização da HSP83 do Trypanosoma cruzi foram alcançadas.

Resumen (Objetivo) Tryapanosoma cruzi, un agente causal de la enfermedad de Chagas, es un parásito que presenta una alternancia en su ciclo de vida entre un hospedador invertebrado (triatomino) y uno vertebrado (mamífero). Varios estudios han demostrado que en T. cruzi, HSP83 (homólogo de HSP90) es esencial para la división celular y el control de la respuesta al estrés térmico. Esta investigación se concentró en el estudio de la clonación, la caracterización bioinformática y la expresión del gen de la proteína de choque térmico HSP83 de T. cruzi para estudios posteriores sobre señalización. (Metodología) El ARN fue extraído de epimagostigotes T. cruci (clon EPm6/MOHM/VE/2007/ 6c), utilizando un kit comercial. El ADNc que codifica HSP83 se obtuvo utilizando RT-PCR, a partir del ARNm extraído, para lo cual se diseñaron los cebadores con base en la secuencia HSP83 de la cepa T. cruzi CL Brener. La clonación se realizó usando pGEM®T-Easy y se subclonó en el vector de expresión pQE30. Se efectuó la caracterización bioinformática y de secuencias. El gen se expresó y la proteína recombinante se purificó por cromatografía de afinidad, igual que se identificó por inmunotransferencia. (Resultados) El análisis de secuencia mostró similitud con el gen HSP83 de Trypanosoma cruzi y se observaron dominios HSP, así como epítopos B en la secuencia. Después de 3 horas de inducción con IPTG, se obtuvo una proteína recombinante con un peso aproximado de 83 kDa. La reacción de inmunotransferencia con suero hiperinmune anti-epimastigote de T. cruzi permitió la detección de una sola banda con un peso molecular de aproximadamente 83 kDa. (Conclusiones) Todos los resultados indican que se logró la clonación y caracterización de HSP83 de Trypanosoma cruzi.

Abstract Introduction: Chagas disease is caused by a hemoflagellate parasite called Trypanosoma cruzi, distributed mainly in Latin America. Countries like Mexico are affected by this parasite, and it is estimated that one million people carry the disease. Currently, the treatment focuses on benznidazole and nifurtimox, which, when applied in the acute phase, is effective but not in the chronic phase and is difficult to access. Therefore, alternatives that can provide new treatments are sought; one option is plants, since they produce secondary metabolites with various biological activities, including antiparasitic. Objective: To evaluate the trypanocidal potential of methanolic extracts collected in some Mexican states from various Latin American plants. Methods: The five plant species under study were obtained in Mexico from the states of Jalisco, Aguascalientes, and Nuevo León; the samples were dried, and the methanolic extracts were obtained. Two strains of T. cruzi were used to evaluate its trypanocidal activity; the Ninoa strain and a wild strain obtained in Calvillo, Aguascalientes. Concentrations of the extracts from 1 000 to 10 ppm were evaluated using a microdilution method. Results: The extracts showed an inhibitory concentration between 1 418.74 ± 6 ppm and 14.1 ± 5 ppm; the extract that presented the best activity was the Arctostaphylos pungens (pinguica) leaf. Conclusions: A. pungens is a plant used in traditional Mexican medicine, and this study has shown that it is a source of compounds against T. cruzi. Future studies could determine its toxicity and cytotoxicity to be applied as a possible treatment for Chagas disease.

Resumen Introducción: La enfermedad de Chagas es causada por un parásito hemoflagelado llamado Trypanosoma cruzi, distribuido principalmente en América Latina. Países como México se ven afectados por este parásito, y se estima que un millón de personas padecen la enfermedad. Actualmente, el tratamiento se centra en el benznidazol y el nifurtimox, que, cuando se aplican en la fase aguda, son efectivos, pero no en la fase crónica y son de difícil acceso. Por lo tanto, se buscan alternativas que puedan proporcionar nuevos tratamientos; una opción son las plantas, ya que producen metabolitos secundarios con diversas actividades biológicas, incluida la actividad antiparasitaria. Objetivo: Evaluar el potencial tripanocida de extractos metanólicos recolectados en algunos estados mexicanos de diversas plantas latinoamericanas. Métodos: Las cinco especies de plantas estudiadas fueron obtenidas en México de los estados de Jalisco, Aguascalientes y Nuevo León; las muestras fueron secadas y se obtuvieron los extractos metanólicos. Se utilizaron dos cepas de T. cruzi para evaluar su actividad tripanocida; la cepa Ninoa y una cepa silvestre obtenida en Calvillo, Aguascalientes. Se evaluaron las concentraciones de los extractos de 1 000 a 10 ppm utilizando un método de microdilución. Resultados: Los extractos mostraron una concentración inhibitoria entre 1 418.74 ± 6 ppm y 14.1 ± 5 ppm; el extracto que presentó la mejor actividad fue la hoja de Arctostaphylos pungens (pinguica). Conclusiones: A. pungens es una planta utilizada en la medicina tradicional mexicana, y este estudio ha demostrado que es una fuente de compuestos contra T. cruzi. Estudios futuros podrían determinar su toxicidad y citotoxicidad para ser aplicados como un posible tratamiento para la enfermedad de Chagas.

ABSTRACT Background: Chagasic cardiomyopathy (CC) differs from other heart failure causes in multiple aspects, highlighting the risk of systemic embolisms. However, few studies have evaluated the risk of embolic events in anticoagulated patients with CC compared with other cardiomyopathies. Objective: We aimed to analyze the incidence of systemic embolisms in a cohort of anticoagulated patients diagnosed with atrial fibrillation (AF) with and without CC. Methods: A retrospective cohort study was carried out at a fourth level hospital in Colombia during the period 2014-2020. All patients diagnosed with cardiomyopathy of any etiology and AF, who were on an anticoagulation regimen were included. The primary outcome was the incidence of embolic events. A survival analysis was performed using adjusted Cox proportional hazard models. A p-value <0.05 was considered significant. All statistical tests were two-tailed. Results: A total of 149 anticoagulated patients with cardiomyopathy were evaluated (median age: 71 years; women: 30.20%). The cumulative incidence of embolic events was significantly higher in patients with CC (17.50%) compared with those presenting other cardiomyopathies (4.95%), despite that the latter had a significantly higher CHA2DS2-VASc score (p=0.013). After multivariate analysis, patients with CC had a significantly higher risk of embolic events regardless of the CHA2DS2-VASc score and the type of anticoagulant prescribed (HR 5.65; 95% CI 1.46-21.83; p=0.012). Conclusions: Chagasic cardiomyopathy was associated with a significantly higher risk of embolic events, despite anticoagulation therapy in both groups. More research is required to understand the origin of the risk observed in order to translate this knowledge into specific indications for anticoagulation in patients with CC.

RESUMEN Introducción: La miocardiopatía chagásica (MC) difiere de otras causas de insuficiencia cardíaca en múltiples aspectos, destacándose el riesgo de embolias sistémicas. Sin embargo, pocos estudios han evaluado el riesgo de eventos embólicos en pacientes anticoagulados con MC en comparación con otras miocardiopatías. Objetivo: Nuestro objetivo fue analizar la incidencia de embolias sistémicas en una cohorte de pacientes anticoagulados con diagnóstico de fibrilación auricular (FA) con y sin MC. Material y métodos: Se realizó un estudio de cohorte retrospectivo en hospital de cuarto nivel en Colombia durante el periodo 2014-2020. Se incluyeron todos los pacientes con diagnóstico de miocardiopatía de cualquier etiología y FA que estuvieran en régimen de anticoagulación. El resultado primario fue la incidencia de eventos embólicos. Se realizó un análisis de supervivencia mediante modelos de riesgos proporcionales de Cox ajustados. Un valor de p <0,05 se consideró significativo. Todas las pruebas estadísticas fueron de dos colas. Resultados: Se evaluaron 149 pacientes anticoagulados con miocardiopatía (mediana de edad: 71 años; mujeres: 30,20%). La incidencia acumulada de eventos embólicos fue significativamente mayor en los pacientes con MC (17,50%) en comparación con aquellos con otras miocardiopatías (4,95%), a pesar de que estos últimos tenían una puntuación CHA2DS2-VASc significativamente mayor (p=0,013). Tras el análisis multivariado, los pacientes con MC tuvieron un riesgo significativamente mayor de eventos embólicos independientemente de la puntuación CHA2DS2-VASc y del tipo de anticoagulante prescrito (HR 5,65; IC 95% 1,46-21,83; p=0,012). Conclusiones: La MC se asoció con un riesgo significativamente mayor de eventos embólicos, a pesar del tratamiento anticoagulante en ambos grupos. Se requiere más investigación para comprender el origen de este riesgo observado y traducir este conocimiento en indicaciones específicas de anticoagulación para pacientes con MC.

Abstract Background Echocardiography is essential for the assessment of patients with heart transplants. However, normal values in such individuals are not clearly defined. Objectives To compare conventional echocardiographic and speckle tracking variables between patients with unrejected heart transplants and healthy individuals. Methods : A prospective study was conducted with adult patients having undergone heart transplantation at least one year earlier and submitted to endomyocardial biopsy followed by transthoracic echocardiogram (TTE). Conventional TTE measures and mechanical heart strain assessments using speckle tracking were performed and the results were compared to those of a group of healthy volunteers. Statistical significance was set at 5% (p < 0.05). Results Thirty-six transplant patients without rejection were analyzed and compared to 30 healthy individuals. Chagas disease was the main reason for transplantation. Lower left ventricular global longitudinal strain expressed in absolute values was found (11.99% in transplant patients vs. 20.60% in controls; p <0.0001), right ventricular free wall longitudinal strain (16.67% in transplant patients vs. 25.50% in controls; p <0.0001) and myocardial work indices (p < 0.0001) as well as a larger size of the left atrium (38.17 ml/m2 in transplant patients vs. 18.98 ml/m2 in controls; p <0.0001) and greater mass and relative wall thickness (p <0.0001). Conclusion Stable patients having undergone heart transplants without rejection have differences concerning echocardiographic variables compared to healthy individuals. These findings indicate that conventional echocardiographic measures and heart mechanics are altered in transplant patients even in the absence of rejection. Such findings are relevant to the clinical context and follow-up of the patient. However defined TTE. . (TTE) volunteers 5 0.05. 005 0.05 0 05 0.05) Thirtysix Thirty six 3 11.99% 1199 11 99 (11.99 vs 2060 20 60 20.60 controls <0.0001, 00001 <0.0001 , 0001 16.67% 1667 16 67 (16.67 2550 25 50 25.50 0.0001 38.17 3817 38 17 (38.1 mlm2 mlm ml m2 m ml/m 1898 18 98 18.9 <0.0001. followup follow up patient (TTE 00 0.0 11.99 119 1 9 (11.9 206 2 6 20.6 0000 <0.000 000 16.67 166 (16.6 255 25.5 0.000 38.1 381 (38. 189 18. 0. 11.9 (11. 20. <0.00 16.6 (16. 25. 0.00 38. (38 11. (11 <0.0 16. (16 (3 (1 <0. ( <0

Resumo Fundamento A ecocardiografia é essencial para avaliação do coração transplantado. No entanto, os valores de normalidade no transplante cardíaco (TC) não estão claramente definidos. Objetivos: Comparar parâmetros ecocardiográficos convencionais e pela técnica de Speckle Tracking entre pacientes transplantados cardíacos sem rejeição e uma população de indivíduos saudáveis. Métodos Foram estudados prospectivamente pacientes adultos, com menos de 1 ano de TC, que realizaram biópsia endomiocárdica de vigilância seguido de ecocardiograma transtorácico (ETT). Medidas convencionais de ETT acrescidas da avaliação de mecânica cardíaca por meio do Strain pelo Speckle Tracking foram realizadas e comparadas com um grupo de voluntários saudáveis. A significância estatística adotada para o estudo foi de 5%. Resultados Avaliou-se 36 pacientes transplantados sem rejeição, os quais foram comparados com 30 indivíduos saudáveis. Observou-se redução nos valores de Strain Global Longitudinal de Ventrículo Esquerdo em valor absoluto (11,99% transplantados, 20,60% controle, p<0,0001), Strain de parede livre de Ventrículo Direito (transplantados 16,67%, controle 25,50%, p<0,0001) e dos índices de trabalho miocárdico (p<0,0001), maior tamanho do átrio esquerdo (38,17 ml/m2 transplantados, controle 18,98 ml/m2, p<0,0001), maior índice de massa e espessura relativa das paredes (p<0,0001) e a presença da Doença de Chagas como principal etiologia para o transplante. Conclusão Os transplantados cardíacos estáveis e sem rejeição apresentaram diferenças com relação aos parâmetros ecocardiográficos comparados com indivíduos saudáveis. Estes achados indicam que medidas ecocardiográficas convencionais e de mecânica cardíaca são alteradas em transplantados mesmo na ausência de rejeição e podem ser relevantes para o contexto clínico e acompanhamento dos pacientes. transplantado entanto TC (TC definidos Objetivos saudáveis adultos ETT. . (ETT) 5 5% Avaliouse Avaliou se 3 Observouse Observou 11,99% 1199 11 99 (11,99 2060 20 60 20,60 p<0,0001, p00001 p p<0,0001 , 0 0001 1667 16 67 16,67% 2550 25 50 25,50% 38,17 3817 38 17 (38,1 mlm2 mlm ml m2 m ml/m 1898 18 98 18,9 (p<0,0001 (ETT 11,99 119 9 (11,9 206 2 6 20,6 p0000 p<0,000 000 166 16,67 255 25,50 38,1 381 (38, 189 18, (p<0,000 11,9 (11, 20, p000 p<0,00 00 16,6 25,5 38, (38 (p<0,00 11, (11 p00 p<0,0 16, 25, (3 (p<0,0 (1 p0 p<0, ( (p<0, p<0 (p<0 p< (p< (p

Abstract Background Chagas disease (CD) is a serious public health problem in Latin America. Benznidazole (BNZ) is used for the treatment of CD and, despite its wide use, little information is available about its toxicity and mechanisms of adverse drug reactions (ADR). Objectives To identify and classify clinical and laboratory adverse reactions caused by BNZ in terms of causality and severity. Methods Prospective cohort study from January 2018 to December 2021. Treatment follow-up included visits and biochemical tests (complete blood count, liver and kidney function tests) before, during and after treatment. ADR were classified according to causality and severity. In the statistical analysis, the significance level was set at p<0.05. Results Forty patients with chronic CD were included. A high prevalence of ADR was observed 161 ADR in 30 patients [90%]; of these, 104 (64.6%) were classified as possible and 57 (35.4%) as probable. The ADR were classified as moderate and mild. Of the 40 patients, nine (22.5%) discontinued treatment. ADR associated with treatment discontinuation and interventions were those that affected the dermatological system, central and peripheral nervous system and sense organs such as ageusia. Mild hematological and biochemical changes such as lymphopenia were observed after 30 days of treatment. Conclusion Many patients were able to complete the treatment even with ADR, which can be attributed to the successful follow-up strategy with symptomatic treatment and counseling, leading to patient’s awareness of symptoms and treatment adherence. (CD America (BNZ use ADR. . (ADR) severity 201 2021 followup follow up count before analysis p005 p 0 05 p<0.05 16 3 90% 90 [90%] these 10 64.6% 646 64 6 (64.6% 5 35.4% 354 35 4 (35.4% probable mild 22.5% 225 22 (22.5% ageusia counseling patient s adherence (ADR 20 202 p00 p<0.0 1 9 [90% 64.6 (64.6 35.4 (35.4 22.5 2 (22.5 p0 p<0. [90 64. (64. 35. (35. 22. (22. p<0 [9 (64 (35 (22 p< [ (6 (3 (2 (

Resumo Fundamento A Doença de Chagas (DC) representa um grave problema de saúde pública na América Latina. O Benznidazol (BNZ) é utilizado para o tratamento DC e, apesar do seu amplo uso, poucas informações estão disponíveis sobre sua toxicidade e mecanismos das Reações Adversas ao Medicamento (RAM). Objetivos Identificar e classificar as reações adversas clínicas e laboratoriais ocasionadas pelo uso do BNZ quanto à sua causalidade e gravidade. Métodos Estudo de coorte prospectivo realizado no período de janeiro de 2018 a dezembro de 2021. O acompanhamento do tratamento incluiu consultas e análises laboratoriais antes, 30 e 60 dias após o início do tratamento. As RAM foram classificadas quanto à causalidade e gravidade. Na análise estatística o nível de significância adotado foi p<0,05. Resultados Participaram do estudo 40 pacientes com DC crônica, observou-se alta prevalência de RAM com um total de 161 em 30 (90%) pacientes. Destas, 104 (64,6%) foram classificadas como possíveis e 57 (35,4%) como prováveis. As reações foram classificadas em moderadas e leves. Dos 40 pacientes, nove (22,5%) suspenderam o tratamento. As RAM associadas à interrupção e intervenções foram as que afetaram o sistema dermatológico, sistema nervoso central e periférico ou que culminaram em ageusia. Após 30 dias de tratamento, alterações hematológicas e bioquímicas leves foram observadas como linfopenia. Conclusão Apesar do elevado percentual de RAM, muitos pacientes foram capazes de completar o tratamento, o que se atribui ao êxito da estratégia de acompanhamento com intervenções de tratamento sintomático juntamente ao aconselhamento, levando à compreensão da sintomatologia e manutenção do tratamento. (DC Latina (BNZ RAM. . (RAM) gravidade 201 2021 antes 3 6 p005 p 0 05 p<0,05 4 crônica observouse observou 16 90% 90 (90% Destas 10 64,6% 646 64 (64,6% 5 35,4% 354 35 (35,4% prováveis 22,5% 225 22 (22,5% dermatológico ageusia linfopenia aconselhamento (RAM 20 202 p00 p<0,0 1 9 (90 64,6 (64,6 35,4 (35,4 22,5 2 (22,5 p0 p<0, (9 64, (64, 35, (35, 22, (22, p<0 ( (64 (35 (22 p< (6 (3 (2

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.

Resumen La Enfermedad de Chagas (EC) es endémica en el Ecuador, con una notable prevalencia en la provincia de Manabí. Específicamente, el cantón Olmedo destaca como uno de los más afectados por esta enfermedad. El objetivo del presente estudio es caracterizar clínica y epidemiológicamente los casos de EC, diagnosticados desde enero 2019 a diciembre 2022 en el Cantón Olmedo, Manabí, Ecuador. Se realizó un estudio observacional, descriptivo, de registro de 14 casos confirmados por infección de Trypanosoma cruzi. Las variables estudiadas fueron, el número de casos presentados por año, sexo, grupos de edades, diagnóstico de laboratorio, tipo de vigilancia. Se identificaron un total 14 casos reactivo; mayormente representada por el sexo masculino; con predominio de personas mayores de 65 años. La vigilancia activa contribuyó al mayor número de notificaciones. El total de casos correspondieron a Chagas crónicos. Las comunidades San Roque y el barrio Divino Niño, presentaron el mayor número de notificaciones de casos confirmados. En conclusión, se plantea que la Enfermedad de Chagas representa un problema de salud silente en el Cantón Olmedo. La vigilancia activa a través de búsqueda de casos, así como los test de anticuerpos son claves en el diagnóstico.

Abstract Chagas Disease (CD) is endemic in Ecuador, with a notable prevalence in the province of Manabí. Specifically, the Olmedo canton stands out as one of the most affected by this disease. The objective of the present study is to clinically and epidemiologically characterize the cases of CD, diagnosed from January 2019 to December 2022 in the Olmedo Canton, Manabí, Ecuador. An observational, descriptive study was carried out, registering 14 confirmed cases of Trypanosoma cruzi infection. The variables studied were the number of cases presented per year, sex, age groups, laboratory diagnosis, type of surveillance. A total of 14 reactive cases were identified; mostly represented by the male sex; with a predominance of people over 65 years of age. Active surveillance contributed to the highest number of notifications. The total number of cases corresponded to chronic Chagas disease. The communities of San Roque and the Divino Niño neighborhood presented the highest number of notifications of confirmed cases. In conclusion, it is proposed that Chagas Disease represents a silent health problem in the Olmedo Canton. Active surveillance through case search, as well as antibody tests, are key in diagnosis.

ABSTRACT We present a case of acute phase Chagas disease in a 40-year-old male patient from Vereda Buenos Aires, Municipality of Miraflores, Department of Guaviare. The patient attended the emergency department with fever, headache, asthenia, adynamia and dysuria. The blood smear and urinalysis were positive for symptomatic urinary tract infection, but negative for malaria. Five days later the diagnosis of acute phase Chagas disease was confirmed after a positive result for Trypanosoma cruzi. The patient was treated with nifurtimox and benznidazole, his contacts and risk areas were investigated, an active entomological community and institutional search was carried out, as well as in the reservoirs, finally, laboratory surveillance for possible cases of infection in the community was conducted. Five cases with similar symptoms were identified, but parasitological tests were negative. Health education measures were implemented to prevent the spread of the disease.

RESUMEN Se presenta un caso de enfermedad de Chagas en fase aguda en un paciente masculino de 40 años, procedente de la Vereda Buenos Aires, Municipio de Miraflores, Departamento del Guaviare. El paciente acudió a urgencias con fiebre, cefalea, astenia, adinamia y disuria. Se realizó un frotis de sangre y un análisis de orina, con resultados positivos para infección urinaria sintomática, pero negativos para malaria. Cinco días más tarde se confirmó el diagnóstico de enfermedad de Chagas en fase aguda tras recibir un resultado positivo para Trypanosoma cruzi. El paciente recibió tratamiento con nifurtimox y benznidazol, y se llevó a cabo una investigación de contactos y zonas de riesgo, búsqueda activa comunitaria e institucional, entomológica y de reservorios, y una vigilancia de laboratorio para detectar posibles casos de infección en la comunidad. Se identificaron cinco casos con síntomas similares, pero las pruebas parasitológicas fueron negativas. Se aplicaron medidas de educación sanitaria para prevenir la propagación de la enfermedad.

Resumo A reativação da doença de Chagas crônica é condição rara e ocorre apenas em pacientes imunossuprimidos. O envolvimento da pele foi reportado em pacientes com doença de Chagas crônica e transplante hepático e cardíaco com reativação da tripanossomíase. Em todos os casos cutâneos foi detectada a forma amastigota do Trypanosoma cruzi. Nosso caso traz paciente feminina de 51 anos com história de transplante cardíaco devido à doença de Chagas e imunodepressão. A equipe dermatológica foi chamada devido ao aparecimento de nódulos eritematosos dolorosos, após 30 dias de hospitalização. Primeiramente, a biópsia de pele foi compatível com hipótese de leishmaniose cutânea. Depois da imuno-histoquímica, confirmou-se a presença de T. cruzi, sendo decidido tratar reativação da doença de Chagas. O desenvolvimento de paniculite não é usualmente associado à doença de Chagas. Assim, ressalta-se a importância de não excluir tal diagnóstico e refere a necessidade da análise anatomopatológica e imuno-histoquímica para complementação diagnóstica.

Abstract Reactivation of chronic Chagas disease is a rare condition, occurring solely in immunosuppressed patients. Skin involvement has been reported in patients with chronic Chagas disease and heart or kidney transplantation who reactivated the trypanosomiasis. In all cases involving the skin, amastigote forms of Trypanosoma cruzi are detected. Our case focuses on a 51-year-old female with a history of cardiac transplantation due to Chagas disease and immunodepression. The dermatology team was consulted due to the presence of painful erythematous nodules, after 30 days of hospitalization. Initially, a skin biopsy suggested cutaneous leishmaniasis as a hypothesis. However, subsequent immunohistochemistry confirmed the presence of T. cruzi, leading to the decision to treat for Chagas disease reactivation. The development of panniculitis is not commonly associated with Chagas disease. This case underscores the importance of not disregarding such possibilities and highlights the necessity for histopathological and immunohistochemical analyses to complement the diagnostic process.

Abstract Introduction. Although Chagas disease causes high levels of morbidity, the muscle function and tolerance to physical activity in Chagas disease patients are still not completely understood. Objective. To compare health-related fitness of patient groups with acute Chagas disease versus chronic Chagas disease. Materials and methods. We conducted a cross-sectional study involving 18 patients. The data were obtained from patient's records, and functional capacity was measured with the six-minute walk test, the peripheral muscle strength with handgrip strength, and respiratory muscle strength using the maximum inspiratory pressure and the maximum expiratory pressure. Results. The 18 patients were divided in two groups: acute Chagas disease (n=9) and chronic Chagas disease (n=9). The distance walked in the six-minute walk test was lower than the predicted distance walked in both groups (p < 0.0001). The maximum expiratory pressure was lower than the predicted one (p = 0.005), and statistically significant for chronic Chagas disease patients (p = 0.02). Heart rate increased faster in the chronic Chagas disease group within the first two minutes of the six-minute walk test (p = 0.04). The sixminute walk test in the acute Chagas disease group presented a strong correlation with peripheral muscle strength (p = 0.012) and maximum inspiratory pressure (p = 0.0142), while in the chronic Chagas disease group, only peripheral muscle strength and maximum inspiratory pressure were correlated (p = 0.0259). Conclusion. The results suggest lowered functional capacity and reduced respiratory and peripheral muscle strength in patients with Chagas disease, although no differences were observed between groups. The early increase in heart rate during exercise in the chronic Chagas disease group implies a greater myocardial overload.

Resumen Introducción. Aunque la enfermedad de Chagas causa gran morbilidad, la función muscular y la tolerancia a la actividad física de estos pacientes aún no se comprenden por completo. Objetivos. Comparar el estado físico relacionado con la salud de pacientes con enfermedad de Chagas aguda versus crónica de Chagas. Materiales y métodos. Se hizo un estudio transversal que incluyó 18 pacientes. La información se obtuvo de los registros de los pacientes. La capacidad funcional se evaluó con la prueba de la caminata de seis minutos, se determinó la fuerza de prensión manual para evaluar los músculos periféricos y se estableció la fuerza de los músculos respiratorios mediante presión inspiratoria máxima y la presión espiratoria máxima. Resultados. Se evaluaron 18 pacientes, nueve con enfermedad de Chagas aguda y nueve con enfermedad de Chagas crónica. La distancia recorrida en la prueba de caminata de seis minutos fue menor que la distancia recorrida predicha en ambos grupos (p < 0,0001). La presión espiratoria máxima fue más baja de lo previsto (forma aguda: p = 0,005; forma crónica: p = 0,02). La frecuencia cardíaca aumentó más rápido en el grupo con enfermedad de Chagas crónica dentro de los primeros dos minutos de la caminata (p = 0,04). La distancia recorrida en el grupo con la forma aguda se correlacionó con la fuerza de prensión manual (p = 0,01) y la presión inspiratoria máxima (p = 0,01). En el grupo con la enfermedad crónica, solo hubo correlación entre la fuerza de presión manual y la presión inspiratoria máxima (p = 0,02). Conclusiones. Los resultados sugirieren disminución de la capacidad funcional y de la fuerza muscular respiratoria y periférica, aunque sin diferencias entre ambos grupos. El aumento de la frecuencia cardiaca en el grupo con enfermedad de Chagas crónica sugiere una mayor sobrecarga miocárdica.

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.

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 The teaching of human parasitology is essential for students of health sciences, especially medicine, because it is a major global public health problem―occurring with high frequency in low-income countries―and because of its presence in countries considered developed. In this sense, it is estimated that worldwide there are 2,800 million individuals infected with soil-transmitted helminths, 20 to 30% people infected with Toxoplasma gondii, 300 to 500 million new cases of malaria per year, and nearly 15 million Latin Americans with Chagas disease, an infection caused by Trypanosoma cruzi. This narrative review article analyzes information available in digital repositories on aspects of the traditional educational program of human or medical parasitology using descriptors or keywords closely related to the topic. The reviewed articles were mainly those published in peer-reviewed, indexed and prestigious scientific journals. Moreover, the traditional program of parasitology and the prevailing pedagogy are described with the purpose of encouraging discussion on the methods that lead to its learning. Also, given the dynamic nature of this process and the constant challenges that must be faced in this field, said information can help to explore new ways of teaching parasitology in answer to the demands of the context. In conclusion, parasitic diseases have affected humankind throughout history, causing illness, disability and death in millions of people. Therefore, among the measures to fight such a terrible scourge, the training of more and better professionals in the area is promoted due to their leading role in the design and execution of control programs. As a result, the need to describe in detail the characteristics of the traditional teaching of this branch of knowledge arises―as shown in this paper―in view of the new human teaching methods: participatory learning, problem-based learning and Internetassisted learning.

RESUMEN Es fundamental la enseñanza de la parasitología humana para los estudiantes de las carreras de ciencias de la salud, especialmente la médica, por ser un importante problema de salud pública con distribución mundial, con alta frecuencia en países de bajos recursos económicos y por su presencia en aquellos países considerados desarrollados. En este sentido, se estima que existen en el mundo 2800 millones de individuos infectados con geohelmintos, 20 % a 30 % de infectados con Toxoplasma gondii, 300 a 500 millones de casos nuevos de malaria al año y aproximadamente 15 millones de latinoamericanos con enfermedad de Chagas, una enfermedad causada por el Trypanosoma cruzi. En este artículo de revisión narrativa se analiza información disponible en repositorios digitales sobre aspectos del programa pedagógico tradicional de la parasitología humana o médica, para lo cual se emplearon descriptores o palabras clave en estrecha relación con el tema. Los artículos que se revisaron principalmente fueron aquellos publicados en revistas científicas arbitradas, indexadas y de reconocido prestigio. Asimismo, se describen el programa tradicional de parasitología y la pedagogía prevalente empleada, con el propósito de fomentar el debate sobre los métodos que conducen a su aprendizaje. Por otro lado, si se consideran el carácter dinámico que posee este proceso y los constantes desafíos que deben afrontarse en este campo, esta información puede ayudar a explorar nuevas formas de enseñar la parasitología en respuesta a las exigencias del contexto. En conclusión, las enfermedades parasitarias han afectado a la humanidad a lo largo de la historia, y han causado enfermedades, discapacidad y la muerte de millones de personas. Por tanto, entre las medidas para combatir tan terrible flagelo se señala la capacitación de más y mejores profesionales en el área, por su papel preponderante en el diseño y ejecución de los programas de control, de lo que se desprende la necesidad de describir en detalle las características de la enseñanza tradicional de esta rama del conocimiento ―como se muestra en el contenido de este escrito― en virtud de la existencia de nuevos métodos de enseñanza humana: la enseñanza participativa, aprendizaje basado en problemas y aprendizaje asistido por internet.