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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 sixminute 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., 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.

Background The implications of the gut microbial communities in the immune response against parasites and gut motility could explain the differences in clinical manifestations and treatment responses found in patients with chronic Chagas disease. Methodology/Principal findings In this pilot prospective cross-sectional study, we included 80 participants: 29 with indeterminate CD (ICD), 16 with cardiac CD (CCD), 15 with digestive CD (DCD), and 20 controls without CD. Stool was collected at the baseline visit and faecal microbial community structure DNA was analyzed by whole genome sequencing. We also performed a comprehensive dietary analysis. Ninety per cent (72/80) of subjects were of Bolivian origin with a median age of 47 years (IQR 39–54) and 48.3% (29/60) had received benznidazole treatment. There were no substantial differences in dietary habits between patients with CD and controls. We identified that the presence or absence of CD explained 5% of the observed microbiota variability. Subjects with CD exhibited consistent enrichment of Parabacteroides spp, while for Enterococcus hirae, Lactobacillus buchneri and Megamonas spp, the effect was less clear once excluded the outliers values. Sex, type of visceral involvement and previous treatment with benznidazole did not appear to have a confounding effect on gut microbiota structure. We also found that patients with DCD showed consistent Prevotella spp enrichment. Conclusions We found a detectable effect of Chagas disease on overall microbiota structure with several potential disease biomarkers, which warrants further research in this field. The analysis of bacterial diversity could prove to be a viable target to improve the prognosis of this prevalent and neglected disease., Unión Europea-NextGeneration EU to JAPM, CIBER -Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Depto. de Nutrición y Ciencia de los Alimentos, Fac. de Farmacia, TRUE, pub

Objective: To analyse acute ChObjective: To analyse acute Chagas disease (CD) outbreaks through a qualitative systematic review and discuss the determinants for its prevention and control. Methods: Review of studies in which clinical cases of oral transmission were confirmed by parasitological and/or serological tests that included an epidemiological investigation of sources of infection, vectors and reservoirs. Results: Thirty-two outbreaks (1965-2022) were analysed. The main foods involved in oral transmission outbreaks are homemade fruit juices. Different species of vectors were identified. Reservoirs were mainly dogs, rodents and large American opossums (didelphids). Conclusion: Under a One Health approach, environmental changes are one of the factors responsible of the rise of oral transmission of CD. Entomological surveillance of vectors and control of the changes in wild and domestic reservoirs and reinforcement of hygiene measures around food in domestic and commercial sites are needed., Depto. de Farmacología y Toxicología, Fac. de Veterinaria, TRUE, pub

The objective of this article is to evaluate the effectiveness of preventive measures for the control of vectors (bedbugs) of Chagas disease in Madriz, Nicaragua, 2013-2021. For this purpose, a longitudinal study was conducted, whose universe consisted of 458 patients sampled positive for Chagas disease. The databases of the epidemiological monitoring system were reviewed, clinical records were reviewed, and the departmental epidemiologist was interviewed. Data tabulation and analysis was performed by the researcher in February-March 2023. Among the results, it was found that the most affected age range was 20-34 years with 28.1%, the least affected was 28 days-11 months with 0.43%. The female sex predominated with 57.6%. The most affected municipalities were Somoto with 39.7%, Totogalpa with 29% and San Lucas with 7.6% and the least affected was Las Sabanas with 1.3%. The main actions aimed at diagnosed patients were the correct management of patients according to regulation 111 and the indication of the Chagas test to all patients exposed to the vector, cardiac patients and pregnant women; likewise, preventive measures for vector control were: training of the community network in vector recognition and capture, referral of suspected cases to health posts, home control of positive patients in the first 24 hours with insecticide spraying, conducting an entomological survey, permanent monitoring of the local infestation rate and house-to-house educational visits. It is concluded that the main preventive measures applied for vector control by the Ministry of Health in Madriz Nicaragua, period 2013-2021 were: massive insecticide spraying days in the most affected municipalities, entomological surveys, bedbug capture by the population and health personnel, and house-to-house educational visits., El presente artículo, tiene como objetivo evaluar la efectividad de las medidas preventivas para el control de los vectores (Chinches) de la enfermedad de Chagas en Madriz, Nicaragua, 2013-2021. Para ello, se realizó un estudio longitudinal, cuyo universo estuvo constituido por 458 pacientes muestreados positivos para enfermedad de Chagas. Se realizó revisión de bases de datos del sistema de vigilancia epidemiológica, revisión de expedientes clínicos y entrevista a epidemióloga departamental. La tabulación y análisis de datos fue realizado por el investigador en los meses febrero-marzo 2023. Dentro de los resultados, se encontró que el rango de edad más afectada fue de 20-34 años con 28.1%, el menos afectado de 28 dias-11 meses con 0.43%. El sexo femenino predominó con el 57.6%. Los municipios más afectados fueron Somoto con 39.7%, Totogalpa con 29% y San Lucas con 7.6% y el menos afectado Las Sabanas con 1.3 %. Las principales acciones dirigidas a los pacientes diagnosticados fueron el manejo correcto de pacientes según la normativa 111 y la indicación del Test de Chagas a todo paciente expuesto al vector, pacientes cardíacos y embarazadas; así mismo, las medidas preventivas para el control de los vectores fueron: capacitación a la red comunitaria en reconocimiento y captura de vectores, referencia de casos sospechosos a puestos de salud, control de foco en casa de pacientes positivos en las primeras 24 horas con rociado de insecticida, realización de encuesta entomológica, monitoreo permanente del índice de infestación local y visitas educativas casa a casa. Se concluye que las principales medidas preventivas aplicadas para el control de los vectores por el ministerio de salud en Madriz Nicaragua, período 2013-2021 fueron: Jornadas masivas de rociado de insecticida en los municipios más afectados, encuestas entomológicas, captura de chinches por la población y personal de salud y las visitas educativas casa a casa.

Background:Current therapeutic agents, including nifurtimox and benznidazole, are not sufficiently effective in the chronic phase of Trypanosoma cruzi infection and are accompanied by various side effects. In this study, 120 kinds of extracts from medicinal herbs used for Kampo formulations and 94 kinds of compounds isolated from medicinal herbs for Kampo formulations were screened for anti-T. cruzi activity in vitro and in vivo. Methods:As an experimental method, a recombinant protozoan cloned strain expressing luciferase, namely Luc2-Tulahuen, was used in the experiments. The in vitro anti-T. cruzi activity on epimastigote, trypomastigote, and amastigote forms was assessed by measuring luminescence intensity after treatment with the Kampo extracts or compounds. In addition, the cytotoxicity of compounds was tested using mouse and human feeder cell lines. The in vivo anti-T. cruzi activity was measured by a murine acute infection model using intraperitoneal injection of trypomastigotes followed by live bioluminescence imaging. Results:As a result, three protoberberine-type alkaloids, namely coptisine chloride, dehydrocorydaline nitrate, and palmatine chloride, showed strong anti-T. cruzi activities with low cytotoxicity. The IC50 values of these compounds differed depending on the side chain, and the most effective compound, coptisine chloride, showed a significant effect in the acute infection model. Conclusions:For these reasons, coptisine chloride is a hit compound that can be a potential candidate for anti-Chagas disease drugs. In addition, it was expected that there would be room for further improvement by modifying the side chains of the basic skeleton., Tropical Medicine and Health, 51(1), art. no. 12; 2023

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 Boyacá, 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, Boyacá. 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., 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.

Chagas disease affects approximately 300,000 patients in the United States. We evaluated a multicenter U.S.-based network to obtain clinical characteristics and outcomes of chronic Chagas disease by disease forms. This was a U.S.-based, multicenter, population-based, retrospective cohort study. We queried TriNetX, a global research network, to identify patients with dual-positive IgG serology for Trypanosoma cruzi. We captured outcomes of interest for up to 5 years. We found 429 patients with evidence of dual-positive T. cruzi IgG out of 19,831 patients with an available test result from 31 U.S. medical centers. The positive proportion for those tested was 2.2%, up to 4.6% among Hispanics. We found a prevalence of a positive Chagas serology of 0.02% among Hispanics. Cardiomyopathy risk reached an annual rate of 1.3% during the initial 5 years of follow-up among patients with the indeterminate form. We found no new events for pulmonary embolism, sudden death, or left ventricular aneurysms at 5 years. Annual risks for arrhythmias and stroke for chronic Chagas cardiomyopathy (CCC) were 1.6% and 0.8%, respectively. The yearly mortality and hospitalization rates for CCC were 2.7% and 17.1%, respectively. Only 13 patients had a documented antitrypanosomal therapy course within 6 months after diagnosis. Of those receiving treatment, 10 patients received benznidazole and three nifurtimox. Chagas disease screening in patients from endemic areas living in the United States remains crucial. Chronic Chagas cardiomyopathy carries a considerable disease burden, translating into increased morbidity and mortality and an enlarging medical health service utilization.

Chagas disease (CD) is a tropical and potentially fatal infection caused by Trypanosoma cruzi. Although CD was limited to Latin America as a silent disease, CD has become widespread as a result of globalization. Currently, 6-8 million people are infected worldwide, and no effective treatment is available. Here, we identify new effective agents against T. cruzi. In short, 16 aryl polyamines were screened in vitro against different T. cruzi strains, and lead compounds were evaluated in vivo after oral administration in both the acute and chronic infections. The mode of action was also evaluated at the energetic level, and its high activity profile could be ascribed to a mitochondria-dependent bioenergetic collapse and redox stress by inhibition of the Fe-SOD enzyme. We present compound 15 as a potential compound that provides a step forward for the development of new agents to combat CD.

Due to the lack of specific vaccines, management of the trypanosomatid-caused neglected tropical diseases (sleeping sickness, Chagas disease and leishmaniasis) relies exclusively on pharmacological treatments. Current drugs against them are scarce, old and exhibit disadvantages, such as adverse effects, parenteral administration, chemical instability and high costs which are often unaffordable for endemic low-income countries. Discoveries of new pharmacological entities for the treatment of these diseases are scarce, since most of the big pharmaceutical companies find this market unattractive. In order to fill the pipeline of compounds and replace existing ones, highly translatable drug screening platforms have been developed in the last two decades. Thousands of molecules have been tested, including nitroheterocyclic compounds, such as benznidazole and nifurtimox, which had already provided potent and effective effects against Chagas disease. More recently, fexinidazole has been added as a new drug against African trypanosomiasis. Despite the success of nitroheterocycles, they had been discarded from drug discovery campaigns due to their mutagenic potential, but now they represent a promising source of inspiration for oral drugs that can replace those currently on the market. The examples provided by the trypanocidal activity of fexinidazole and the promising efficacy of the derivative DNDi-0690 against leishmaniasis seem to open a new window of opportunity for these compounds that were discovered in the 1960s. In this review, we show the current uses of nitroheterocycles and the novel derived molecules that are being synthesized against these neglected diseases.

Infectious diseases represent a serious global public health problem. They have the potential to kill millions of people, whether they emerge naturally as outbreaks or pandemics, or deliberately through bioterrorism. Some examples of diseases caused by emerging pathogens are the Bubonic Plague, Toxoplasmosis, African Sleeping Sickness, and Chagas Disease. Each day, infectious disease scientists serve on the front lines protecting us from such threats. In this course students will learn how to design and critique experiments through the discussion of primary research articles that explore the molecular basis of disease caused by emerging pathogens. This course is one of many Advanced Undergraduate Seminars offered by the Biology Department at MIT. These seminars are tailored for students with an interest in using primary research literature to discuss and learn about current biological research in a highly interactive setting. Many instructors of the Advanced Undergraduate Seminars are postdoctoral scientists with a strong interest in teaching.

Introduction: Among the main diseases associated with the social determinants of health, lifestyles and healthy environments, is Chagas disease, which is linked to poverty and infrastructures whose conditions promote the permanence of the vector. Therefore, the objective of this article was to carry out an exploratory ecological analysis of the social determinants of health related to the prevention and control of Chagas disease, for the generation of relevant epidemiological knowledge and the formulation of public policy guidelines, which help to improve the approach to this public health problem and fulfill the national commitment to eliminate this neglected disease. Methodology: an ecological and geographical study was designed considering social determinants to the prevention and the regulation of the Chagas disease. To this end, this study is based on primary data by the Ministerio de Salud (MINSA) and the Instituto de Estadística y Censos (INEC), the information was analyzed by generating maps using GIS, in addition to a negative binomial linear regression and a spatial neighborhood analysis by calculating the Moran Index. Results: From the sample analyzes, it can be drawn that the most influential factors regarding the contagion rate for Chagas disease are the percentage of canton-level urban slums, the percentage of poor homes, and the percentage goods and services missing. Conclusions: The results obtained imply a relationship between Chagas disease and the social determinants of health, especially linked to inequity and inequality, which is why this document proposes public policy guidelines that allow the recording of information related to social determinants of health. that facilitate the surveillance of the disease and that lead to the identification or elimination of a possible underreporting of cases derived from the lack of analysis of indicators of social determinants of health., Introducción: la enfermedad de Chagas es una de las principales afecciones asociadas con los determinantes sociales de la salud, los estilos de vida y los ambientes saludables, donde las condiciones de pobreza e infraestructura promueven la permanencia del vector. El presente artículo tiene por objetivo analizar los determinantes sociales de la salud relacionados con la prevención y el control de la enfermedad de Chagas para el aporte de conocimiento epidemiológico relevante y la propuesta de políticas públicas que permitan mejorar el abordaje y la atención de este problema sanitario, en favor del compromiso nacional de eliminarlo. Metodología: se desarrolló un estudio, de tipo ecológico-exploratorio con fundamento espacial, de los determinantes sociales de la salud vinculados con la prevención y el control de la enfermedad de Chagas. Para ello, como fuentes de información primaria, se tomaron datos generados por el Ministerio de Salud (MINSA) y el Instituto Nacional de Estadística y Censos (INEC), los cuales se cartografiaron usando SIG; de seguido, se analizaron los patrones espaciales mediante el Índice de Moran. Se diseñó un modelo de regresión lineal binomial negativa. Resultados: de acuerdo con el mejor modelo obtenido, las variables que más explicaron la variación en la probabilidad de enfermar de Chagas fueron el porcentaje de tugurios por cantón, el porcentaje de hogares afectados por la pobreza y el porcentaje de carencias de otros bienes y servicios. El porcentaje de varianza en la probabilidad de enfermar de Chagas, conforme a los determinantes sociales de la salud incluidos en el modelo de regresión, fue del 38 %. Conclusiones: los resultados obtenidos implican una relación entre la enfermedad de Chagas y los determinantes sociales de la salud, especialmente, aquellos ligados a la inequidad y desigualdad. Por tanto, se plantean lineamientos en torno a un registro de información que facilite la vigilancia de la enfermedad. Esto conlleva una identificació

Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020216072, identifier: CRD42020216072., Chronic chagasic cardiomyopathy (CCC) is the most important complication of patients with Chagas disease (CD). The role of persistent detection of DNA in peripheral blood and its association to CCC is unknown. We performed a systematic review up to July 2021, including studies that reported ratios of CCC and PCR positivity among non-treated adult patients. We identified 749 records and selected 12 for inclusion corresponding to 1,686 patients. Eight studies were performed in endemic countries and 4 in non-endemic countries. Only two studies showed an association between CCC and Trypanosoma cruzi parasitemia by means of PCR detection. Six studies reported greater positive PCR ratios among patients with CCC than in the patients with indeterminate chagas disease (ICD) with no statistical significance. A significant risk of bias has been detected among most of the studies. Therefore, while we performed a meta-analysis, wide inter-study heterogeneity impeded its interpretation. Conclusions: With the available information, we could not establish a correlation between PCR-detectable parasitemia and CCC.

In 1909, Carlos Justiniano Chagas first described the clinical manifestations of Chagas disease. The hemoflagellate parasite Trypanosoma cruzi (agent) is characterized by the presence of a flagellum and of a cytostome, glycosomes, reservosomes, and a nucleus in its cytoplasm. The life cycle of T. cruzi begins when a vector defecates on the skin of a host; the feces contain metacyclic trypomastigotes, which infect vertebrate cells. The vectors of this disease are members of the subfamily Triatominae, nocturnal, hematophagous insects capable of locating hosts by heat detection. T. cruzi infection has effects on the biology of the triatomine insect, its behavior, gut function, immune system, and associated microbiota. In the mammalian host, the parasite activates innate immune responses, and host cytokines are key to either control the infection or progress to chronicity. T. cruzi exhibits a wide genetic diversity, and while it has been proved under laboratory conditions to show varying degrees if virulence and organ tropism, no clear association has been found between specific strains and the clinical picture of the disease. This review addresses the history of the discovery of Chagas disease and discusses recent aspects of T. cruzi biology that provide insight into the dynamics of transmission., En 1909, Carlos Justiniano Chagas describió por primera vez las manifestaciones clínicas de la enfermedad de Chagas. El parásito hemoflagelado Trypanosoma cruzi (agente) se caracteriza por la presencia de un flagelo, y en su citoplasma presenta organelos como el citostoma, los glicosomas, los reservosomas y un núcleo. El ciclo de vida de T. cruzi se inicia cuando el vector defeca sobre la piel del hospedero sus heces contienen tripomastigotes metacíclicos, que infectan las células del vertebrado. Los vectores de esta enfermedad pertenecen a la Subfamilia Triatominae, insectos hematófagos, nocturnos y con la capacidad de localizar a sus hospederos mediante la detección del calor. T. cruzi tiene efectos en la biología del insecto triatomino, en su comportamiento, en el funcionamiento del intestino, su sistema inmunológico y la microbiota asociada. En el hospedero mamífero, el parásito activa la respuesta inmune innata, y las citocinas tienen un papel clave para controlar la infección o bien evolucionar a la cronicidad. T. cruzi presenta una amplia diversidad genética, y bajo condiciones de laboratorio se han demostrado sus diferentes grados de virulencia y tropismo hacia los órganos blanco; sin embargo, no existe una asociación clara entre las cepas y el comportamiento clínico de la enfermedad. Esta revisión aborda la historia del descubrimiento de la enfermedad de Chagas y discute aspectos recientes sobre la biología de T. cruzi para comprender la dinámica de su transmisión.

BackgroundChagas disease is an endemic protozoan disease with high prevalence in Latin America. Of those infected, 20-30% will develop chronic Chagas cardiomyopathy (CCC) however, prediction using existing clinical criteria remains poor. In this study, we investigated the utility of left ventricular (LV) echocardiographic speckle-tracking global longitudinal strain (GLS) for early detection of CCC.Methods and results139 asymptomatic T. cruzi seropositive subjects with normal heart size and normal LV ejection fraction (EF) (stage A or B) were enrolled in this prospective observational study and underwent paired echocardiograms at baseline and 1-year follow-up. Progressors were participants classified as stage C or D at follow-up due to development of symptoms of heart failure, cardiomegaly, or decrease in LVEF. LV GLS was calculated as the average peak systolic strain of 16 LV segments. Measurements were compared between participants who progressed and did not progress by two-sample t-test, and the odds of progression assessed by multivariable logistic regression. Of the 139 participants, 69.8% were female, mean age 55.8 ± 12.5 years, with 12 (8.6%) progressing to Stage C or D at follow-up. Progressors tended to be older, male, with wider QRS duration. LV GLS was -19.0% in progressors vs. -22.4% in non-progressors at baseline, with 71% higher odds of progression per +1% of GLS (adjusted OR 1.71, 95% CI 1.20-2.44, p = 0.003).ConclusionBaseline LV GLS in participants with CCC stage A or B was predictive of progression within 1-year and may guide timing of clinical follow-up and promote early detection or treatment.

Introduction. Chagas’s disease a neglected and debilitating tropical illness, caused by Trypanosoma cruzi-infection, afflicts millions of people in most Latin-American countries. In the same region, frequent and severe viral infection cases have been reported due to SARS-CoV-2, the causative agent of COVID-19, deemed as the worst global pandemic in the 21st century. Objective. To investigate the Chagas diseaseCOVID-19-relationship, and the comorbidity effect on chagasic patients living in communities where SARS-CoV-2 have circulated during the last two years causing severe cases and deaths. Material and methods. Randomly selected chagasic patients (N=50) from rural localities of western Venezuela, where COVID-19 has occurred, were evaluated in order to know whether they had suffered SARS-CoV-2- infection. COVID-infected chagasic patients were clinically compared with non-chagasic individuals (N=22) who had suffered the viruses in the same localities. Results. SARS-CoV-2-infection caused significantly less aggressive effects in chagasic patients than in nonchagasic patients, evidenced by the short-lasting scarce mild symptoms and the attenuated clinical profile (p<0.05), without further complications. Comparison revealed COVID-19 detection in 10% of chagasic patients, showing all of them mild clinical pattern and few symptoms, while non-chagasic COVID-infected control individuals, showed 45% and 13% severe and fatal cases, respectively. Conclusion. Chagasic patients suffering from COVID-19 comorbidity seem to express a robust immune response (Th1/Th2/Th17), which associated with anti-T. cruzi-glycoproteins circulating antibodies, directed to certain SARS-CoV-2 glycoproteins (membrane/spike), may induce a short lasting and milder clinical profile. More investigations in populations where Chagas disease is endemic, is recommended., Introducción. La enfermedad de Chagas es una dolencia desatendida y debilitante, causada por la infección con Trypanosoma cruzi que afecta millones de pobladores humanos en los países de América latina. En la misma región han sido registrados, durante los últimos años, frecuentes y severos casos de infección viral causados por SARS-CoV-2, agente etiológico de COVID-19, considerada la peor pandemia global del siglo XXI. Objetivo. Investigar la relación enfermedad de Chagas-COVID-19, y el efecto de la comorbilidad en pacientes chagásicos en comunidades donde SARS-CoV-2 ha circulado durante los dos últimos años, causando casos severos y muertes en la población. Materiales y métodos. Un grupo de 50 pacientes chagásicos provenientes de localidades rurales del occidente de Venezuela, afectadas por la pandemia de COVID-19, seleccionados al azar, fueron evaluados con el propósito de saber si habían sufrido la infección por SARS-Cov-2. Los pacientes chagásicos fueron comparados clínicamente con individuos no-chagásicos (N=22) quienes habían sufrido COVID-19 en las mismas comunidades. Resultados. La infección por SARS-CoV-2 en pacientes chagásicos provocó efectos significativamente menos agresivos que en pacientes no-chagásicos (p<0.05). Mientras que en pacientes chagásicos el COVID-19 cursó con atenuados perfiles clínicos de escasos y leves síntomas de corta duración, sin complicaciones posteriores, en controles no-chagásicos infectados con COVID-19 fueron detectados 45% y 13% de casos severos y fatales, respectivamente. Conclusión. En pacientes chagásicos con comorbilidad por COVID-19, pareciera expresarse una robusta respuesta inmune (Th1/Th2/Th17), la cual en combinación con la acción de anticuerpos circulantes anti-glicoproteinas de T. cruzi dirigidas contra ciertas glicoproteínas de membrana y/o de espículas de SARS-CoV-2, podría inducir perfiles clínicos de leve sintomatología y corta duración. Se recomiendan más investigaciones en poblaciones donde la enfermedad de Ch

Trypanosoma cruzi is a unicellular protistan parasitic species that is comprised of strains and isolates exhibiting high levels of genetic and metabolic variability. In the insect vector, it is known to be highly responsive to starvation, a signal for progression to a life stage in which it can infect mammalian cells. Most mRNAs encoded in its mitochondrion require the targeted insertion and deletion of uridines to become translatable transcripts. This study defined differences in uridineinsertion/ deletion RNA editing among three strains and established the mechanism whereby abundances of edited (and, thus, translatable) mitochondrial gene products increase during starvation. Our approach utilized our custom T-Aligner toolkit to describe transcriptome-wide editing events and reconstruct editing products from high-throughput sequencing data. We found that the relative abundance of mitochondrial transcripts and the proportion of mRNAs that are edited varies greatly between analyzed strains, a characteristic that could potentially impact metabolic capacity. Starvation typically led to an increase in overall editing activity rather than affecting a specific step in the process. We also determined that transcripts CR3, CR4, and ND3 produce multiple open reading frames that, if translated, would generate different proteins. Finally, we quantitated the inherent flexibility of editing in T. cruzi and found it to be higher relative to that in a related trypanosomatid lineage. Over time, new editing domains or patterns could prove advantageous to the organism and become more widespread within individual transcriptomes or among strains.

Chagas disease (CD) is a parasitic, systemic, chronic, and often fatal illness caused by infection with the protozoan Trypanosoma cruzi. The World Health Organization classifies CD as the most prevalent of poverty-promoting neglected tropical diseases, the most important parasitic one, and the third most infectious disease in Latin America. Currently, CD is a global public health issue that affects 6-8 million people. However, the current approved treatments are limited to two nitroheterocyclic drugs developed more than 50 years ago. Many efforts have been made in recent decades to find new therapies, but our limited understanding of the infection process, pathology development, and long-term nature of this disease has made it impossible to develop new drugs, effective treatment, or vaccines. This Review aims to provide a comprehensive update on our understanding of the current life cycle, new morphological forms, and genetic diversity of T. cruzi, as well as identify intervention points in the life cycle where new drugs and treatments could achieve a parasitic cure.

Chagas disease, caused by the protozoa Trypanosoma cruzi, is a potentially life-threatening parasitic zoonosis infecting 6–7 million people worldwide, mainly in Latin America. Due to the limited numbers of drugs available against this neglected disease and their frequent adverse effects, novel anti-chagasic agents are urgently needed. Cichorium intybus L. (chicory) is a bioactive plant with potent activity against parasitic nematodes, but its effects on protozoans are poorly known and no studies have explored its trypanocidal potential. Here, we investigated the activity of C. intybus against extracellular and intracellular stages of T. cruzi, including the prediction of trypanocidal compounds by metabolomic analyses and bioactivity-based molecular networking. Purified C. intybus extracts were prepared from leaves and roots of five C. intybus cultivars (cv. ‘Benulite’, ‘Goldine’, ‘Larigot’, ‘Maestoso’ and ‘Spadona’). All C. intybus extracts induced concentration-dependent effects against T. cruzi trypomastigotes. C. intybus leaf extracts had higher trypanocidal selectivity and lower cytotoxicity on mammalian cells than root extracts. The leaf extract of C. intybus cv. Goldine also significantly reduced the number of mammalian cells infected with T. cruzi amastigotes. Metabolomic and bioactivity-based molecular networking analyses revealed 11 compounds in C. intybus leaves strongly linked with activity against trypomastigotes, including the sesquiterpene lactone lactucin, and flavonoid- and fatty acid-derivatives. Furthermore, seven distinct C. intybus molecules (including two sesquiterpene lactone-derivatives) were predicted to be involved in reducing the number of mammalian cells infected with amastigotes. This is the first report of the anti-protozoal activity of C. intybus against trypanosomatid parasites and expands our understanding of the anti-parasitic effects of this plant and its bioactive metabolites. Further studies to elucidate the anti-protozoal comp

The objective of the work is to review the published studies that deal directly or indirectly with the social, cultural and economic aspects of the Chagas problem in Mexico for discussion and as a starting point to propose new lines of work towards the multidimensional opening of the subject. A systematic review approach was used. Among the most relevant findings was that the literature found was scarce and came mainly on the subject of socioeconomic risk factors that make up two thirds of the articles reviewed. Most of the studies were located in rural contexts, they were unevenly distributed in the country and their location was associated with the presence of state or regional biomedical research centers. The review allows to conclude that it is necessary to advance in sociocultural, economic and political research from the social sciences that reflects the complexity of Chagas as a socio-environmental problem in both rural and urban contexts, of multiple dimensions, as ubiquitous in the Mexican territory and that affects the Mexican population even beyond our borders. In this sense, a list of priorities of lines of work is proposed., El objetivo del trabajo es revisar los estudios publicados que tratan directa o indirectamente sobre los aspectos sociales, culturales y económicos de la problemática del Chagas en México para su discusión y como punto de partida para proponer nuevas líneas de trabajo hacia la apertura multidimensional del tema. Se utilizó un enfoque de revisión sistemática. Entre los hallazgos más relevantes fue que la literatura encontrada fue escasa y dos terceras partes de los artículos revisados son estudios de factores socioeconómicos del riesgo. La mayoría de los estudios se ubicaron en contextos rurales, se distribuyeron de manera desigual en el país y su localización estuvo asociada a la presencia de centros de investigación biomédica estatales o regionales. La revisión permite concluir que se requiere avanzar en la investigación sociocultural, económica y política desde las ciencias sociales que refleje la complejidad del Chagas como una problemática sanitaria y socio-ambiental tanto en contextos rurales como urbanos, de múltiples dimensiones, como ubicua en el territorio mexicano y que afecta a población mexicana incluso más allá de nuestras fronteras. En este sentido, se propone un listado de prioridades de líneas de trabajo.

Understanding the development of Trypanosoma cruzi within the triatomine vector at the molecular level should provide novel targets for interrupting parasitic life cycle and affect vectorial competence. The aim of the current study is to provide new insights into triatomines immunology through the characterization of the hemolymph proteome of Rhodnius prolixus, a major Chagas disease vector, in order to gain an overview of its immune physiology. Surprisingly, proteomics investigation of the immunomodulation of T. cruzi-infected blood reveals that the parasite triggers an early systemic response in the hemolymph. The analysis of the expression profiles of hemolymph proteins from 6 h to 24 h allowed the identification of a broad range of immune proteins expressed already in the early hours post-blood-feeding regardless of the presence of the parasite, ready to mount a rapid response exemplified by the significant phenol oxidase activation. Nevertheless, we have also observed a remarkable induction of the immune response triggered by an rpPGRP-LC and the overexpression of defensins 6 h post-T. cruzi infection. Moreover, we have identified novel proteins with immune properties such as the putative c1q-like protein and the immunoglobulin I-set domain-containing protein, which have never been described in triatomines and could play a role in T. cruzi recognition. Twelve proteins with unknown function are modulated by the presence of T. cruzi in the hemolymph. Determining the function of these parasite-induced proteins represents an exciting challenge for increasing our knowledge about the diversity of the immune response from the universal one studied in holometabolous insects. This will provide us with clear answers for misunderstood mechanisms in host–parasite interaction, leading to the development of new generation strategies to control vector populations and pathogen transmission., SCOPUS: ar.j, info:eu-repo/semantics/published

In this study, a new series of eleven 5-nitroindazole derivatives (10−20) and a related 6-nitroquinazoline (21) was synthesized and tested in vitro against different forms of the kinetoplastid parasite Trypanosoma cruzi, etiological agent of Chagas disease. Among these compounds, derivatives 11−14 and 17 showed trypanocidal profiles on epimastigotes (IC50 = 1.00−8.75 µM) considerably better than that of the reference drug benznidazole, BZ (IC50 = 25.22 µM). Furthermore, the lack of cytotoxicity observed for compounds 11, 12, 14, 17 and 18 over L929 fibroblasts, led to a notable selectivity (SI) on the extracellular replicative form of the parasite: SIEPI > 12.41 to > 256 µM. Since these five derivatives overpassed the cut-off value established by BZ (SIEPI ≥ 10), they were moved to a more specific assay against the intracellular and replicative form of T. cruzi, i.e, amastigotes. These molecules were not as active as BZ (IC50 = 0.57 µM) against this parasite form; however, all of them showed remarkable IC50 values lower than 7 µM. Special mention deserve compounds 12 and 17, whose SIAMA were > 246.15 and > 188.23, respectively. The results compiled in the present work, point to a positive impact over the trypanocidal activity of the electron withdrawing substituents introduced at position 2 of the N-2 benzyl moiety of these compounds, especially fluorine, i.e., derivatives 12 and 17. These outcomes, supported by the in silico prediction of good oral bioavailability and suitable risk profile, reinforce the 5-nitroindazole scaffold as an adequate template for preparing potential antichagasic agents.

Drawing on observation-based ethnography, interviews of health personnel and document review, this article describes and examines how, in clinical handling of Chagas disease, infection is treated as latent risk. It suggests that how this risk is managed has enabled a clinical practice to be conducted among people classified as at the indeterminate stage, by adding a dimension of possibility (Is it going to happen?) and potentiality (When and where?). This allows measures to be taken, including administration of medication or permanent monitoring. The reification of latent risk as a phenomenon that is manageable through a process of medicalisation engages, in turn, with other conceptions and specific experiences of risk among the affected groups. Framing the clinical practices deployed to address this risk as objects of study is a first step towards being able to describe and include them concretely in health system organisation.

Currently, Chagas disease is a complex global health problem with local and global implications. In the present article, we approach this complexity from the perspective of human mobility and its effects on people’s health in places of origin and in transit and destination. We raise key concepts such as human mobility-understood as a possible socio-structural and economic determination of health-, the associated social and institutional barriers and the processes of social exclusion related to Chagas disease. We also propose what we identify as emerging opportunities from the perspective of health as a right. Finally, we propose strategies aimed at addressing Chagas disease from a multidimensional and intersectional perspective in complex, diverse and interconnected territories through migration. © 2021, Fundacao Oswaldo Cruz. All rights reserved.

The newborns of women infected with the parasite Trypanosoma cruzi (the agent of Chagas disease) can be infected either before birth (congenitally), or after birth (as e.g. by vector route). Congenital Chagas disease can induce high levels of neonatal morbidity and mortality. Parasite-infected pregnant women transmit antibodies to their fetus. Antibodies, by opsonizing parasites, can promote phagocytosis and killing of T. cruzi by cells expressing FcγR, on the mandatory condition that such cells are sufficiently activated in an inflammatory context. Antibody-dependent enhancement (ADE) is a mechanism well described in viral infections, by which antibodies enhance entry of infectious agents into host cells by exploiting the phagocytic FcγR pathway. Previously reported Chagas disease studies highlighted a severe reduction of the maternal-fetal/neonatal inflammatory context in parasite-transmitting pregnant women and their congenitally infected newborns. Otherwise, experimental observations brought to light ADE of T. cruzi infection (involving FcγR) in mouse pups displaying maternally transferred antibodies, out of an inflammatory context. Herein, based on such data, we discuss the previously unconsidered possibility of a role of ADE in the trans-placental parasite transmission, and/or the development of severe and mortal clinical forms of congenital/neonatal Chagas disease in newborns of T. cruzi-infected mothers., SCOPUS: ar.j, info:eu-repo/semantics/published

Research objective is to classify seropositive donors according to origin, age, sex and occupation and to determine the prevalence of infection. It was a descriptive, non-experimental, cross-sectional study. Data recorded from the Donors Book of the Blood Bank of the Red Cross of Guayaquil, during the years 2016-2018, were analyzed. Patient seropositivity was checked for IgG antibodies to Trypanosoma cruzi using Enzyme-Linked ImmunoSorbent Assay (ELISA), Indirect Hemagglutination (HAI) and Indirect Immunofluorescence (IFI). 315 seropositive donors with the highest prevalence for 2017, from the urban area (n = 105; 76.64%) were counted. In rural areas, the highest prevalence was recorded in 2016 (n = 34; 33.33%). The age group most compromised was the range of 18-22 years, corresponding to the male sex (n=68, 21,58%; n= 103, 32,69%; n= 53, 16,68%). The main occupation for 2018 corresponded to students (43.47%). For 2017, household chores (32.35%) and for 2016, elementary occupations (13.82%), such as selling goods on the streets, agriculture, fishing, construction of public works and manufacturing industries. The infection prevalence for 2016, 2017 and 2018 was 0.038%, 0.028% and 0.051% respectively, El objetivo de la investigación fue clasificar donantes seropositivos atendiendo a procedencia, edad, sexo y ocupación y determinar prevalencia de infección. Se trató de un estudio descriptivo, de campo, no experimental, de corte transversal. Se analizaron datos registrados del Libro de Donantes del Banco de Sangre de la Cruz Roja de Guayaquil, durante los años 2016-2018. Se comprobó seropositividad de pacientes para detectar anticuerpos IgG para Trypanosoma cruzi empleando Ensayo por inmunoabsorción ligado a enzimas (ELISA), Hemaglutinación Indirecta (HAI) e Inmunofluorescencia Indirecta (IFI). Se contabilizaron 315 donantes seropositivos con prevalencia mayor para 2017, procedentes del área urbana (n=105; 76,64%). En el área rural, se registró mayor prevalencia en 2016 (n=34; 33,33%). El grupo edad mayormente comprometido fue el rango de 18-22 años, correspondiente al sexo masculino (n=68, 21,58%; n= 103, 32,69%; n= 53, 16,68%). La ocupación principal para 2018, correspondió a estudiantes (43,47%). Para 2017, quehaceres del hogar (32,35%) y para 2016, ocupaciones elementales (13,82%), tales como vender mercancías en las calles, agricultura, pesca, construcción de obras públicas e industrias manufactureras. La prevalencia de infección para 2016, 2017 y 2018 fue 0,038%, 0,028% y 0,051% respectivamente

Research on vaccines against trypanosomatids, a family of protozoa that cause neglected tropical diseases, such as Chagas disease, leishmaniasis, and sleeping sickness, is a current need. Today, according to modern vaccinology, virus-like particle (VLP) technology is involved in many vaccines, including those undergoing studies related to COVID-19. The potential use of VLPs as vaccine adjuvants opens an opportunity for the use of protozoan antigens for the development of vaccines against diseases caused by Trypanosoma cruzi, Leishmania spp., and Trypanosoma brucei. In this context, it is important to consider the evasion mechanisms of these protozoa in the host and the antigens involved in the mechanisms of the parasite–host interaction. Thus, the immunostimulatory properties of VLPs can be part of an important strategy for the development and evaluation of new vaccines. This work aims to highlight the potential of VLPs as vaccine adjuvants for the development of immunity in complex diseases, specifically in the context of tropical diseases caused by trypanosomatids.

Chagas disease is endemic in Ecuador. Currently, cases have been confirmed in fifteen of its provinces, among which the province of Guayas stands out. Chagas disease is inflammatory and infectious and is caused by a parasite called Trypanosoma cruzi, which is found in the feces of the triatomine insect. It is estimated that in the world there are between 6 and 7 million people infected with Trypanosoma cruzi, most of them in Latin America. In Ecuador, the province of Guayas is one of the main endemic areas of the country. The objective of this research is to capture the epidemiological characterization of Chagas disease in the Guayas province of Ecuador. The research model is a bibliographic documentary type review. From the review carried out, it was found that the parasite T. cruzi, in the vector T. dimidiata, is found with high concentrations in the province of Guayas. Housing, as well as the presence of animals and bird nests, are predominant factors in the area. Likewise, it can be concluded that there is no significant difference that relates factors such as sex, age, educational level or occupation, with Chagas disease. The occupation of ranches, which determine the ideal niche for the colonization of triatomines, is another factor in this province that is related to the disease. Likewise, the existence of domestic pets in the peridomicile and / or domicile, constitutes an important risk factor. The study of these epidemiological factors of Chagas disease is essential for the development of preventive strategies and early diagnosis, which has an impact on the decrease in the rates currently present in the province of Guayas., La enfermedad de Chagas es endémica en el Ecuador. En la actualidad, se ha confirmado casos en quince de sus provincias, entre las que se destaca la provincia de Guayas. La enfermedad de Chagas es inflamatoria e infecciosa y la ocasiona un parásito llamado Trypanosoma cruzi, que se encuentra en las heces del insecto triatomino. Se calcula que en el mundo hay entre 6 y 7 millones de personas infectadas por el Trypanosoma cruzi, la mayoría de ellas en América Latina. En Ecuador, la provincia de Guayas es un de las principales zonas endémicas del país. El objetivo de la presente investigación consiste en plasmar la caracterización epidemiológica de la enfermedad de Chagas, en la provincia de Guayas del Ecuador. El modelo de investigación es una revisión de tipo documental bibliográfico. De la revisión realizada se encontró que el parásito T. cruzi, en el vector T. dimidiata, se encuentra con altas concentraciones en la provincia de Guayas. La vivienda, así como la presencia de animales y nidos de aves, son factores predominantes en la zona. Asimismo, se puede concluir que no existe diferencia significativa que relacionen factores tales como el sexo, la edad, el nivel educativo u ocupación, con la enfermedad de Chagas. La ocupación de ranchos, los cuales condicionan el nicho ideal para la colonización de triatominos, es otro de los factores en esta provincia que se relaciona con la enfermedad. Asimismo, la existencia de mascotas domésticas en el peridomicilio y/o domicilio, constituye un factor de riesgo importante. El estudio de estos factores epidemiológicos de la enfermedad de Chagas resulta fundamental para el desarrollo de estrategias preventivas y el diagnóstico temprano, que repercuta en la disminución de las tasas presentes actualmente en la provincia de Guayas.

Background: Trypanosoma cruzi has a high rate of biological and genetic variability, and its population structure is divided into seven distinct genetic groups (TcI-TcVI and Tcbat). Due to immigration, Chagas disease (ChD), caused by T. cruzi, has become a serious global health problem including in Europe. Therefore, the aim of this study was to evaluate the existence of genetic variability within discrete typing unit (DTU) TcV of T. cruzi in Bolivian patients with chronic ChD residing in Barcelona, Spain. Methods: The DNA was extracted from the peripheral blood of 27 patients infected with T. cruzi DTU TcV and the fragments of the genetic material were amplificated through the low stringency single primer-polymerase chain reaction (LSSP-PCR). The data generated after amplification were submitted to bioinformatics analysis. Results: Of the 27 patients evaluated in the study, 8/27 (29.6%) were male and 19/27 (70.4%) female, 17/27 (62.9%) were previously classified with the indeterminate clinical form of Chagas disease and 10/27 (37.1%) with Chagas cardiomyopathy. The LSSP-PCR detected 432 band fragments from 80 to 1,500 bp. The unweighted pair-group method analysis and principal coordinated analysis data demonstrated the existence of three distinct genetic groups with moderate-high rates of intraspecific genetic variability/diversity that had shared parasite's alleles in patients with the indeterminate and cardiomyopathy forms of ChD. Conclusions: This study demonstrated the existence of a moderate to high rate of intra-DTU TcV variability in T. cruzi. Certain alleles of the parasite were associated with the absence of clinical manifestations in patients harboring the indeterminate form of ChD. These results support the need to search for increasingly specific targets in the genome of T. cruzi to be correlated with its main biological properties and clinical features in patients with chronic ChD

As the development of new drugs for Chagas disease is not a priority due to its neglected disease status, an option for increasing treatment adherence is to explore alternative treatment regimens, which may decrease the incidence of side effects. Therefore, we evaluated the efficacy of different therapeutic schemes with benznidazole (BNZ) on the acute and chronic phases of the disease, using mice infected with strains that have different BNZ susceptibilities. Our results show that the groups of animals infected by VL-10 strain, when treated in the chronic phase with a lower dose of BNZ for a longer period of time (40 mg/kg/day for 40 days) presented better treatment efficacy than with the standard protocol (100 mg/kg/day for 20 days) although the best result in the treatment of the animals infected by the VL-10 strain was with100 mg/kg/day for 40 days. In the acute infection by the Y and VL-10 strains of T. cruzi, the treatment with a standard dose, but with a longer time of treatment (100 mg/kg/day for 40 days) presented the best results. Given these data, our results indicate that for BNZ, the theory of dose and time proportionality does not apply to the phases of infection

Background: To deeply understand the role of antibodies in the context of Trypanosoma cruzi infection, we decided to characterize A2R1, a parasite antibody selected from single-chain variable fragment (scFv) phage display libraries constructed from B cells of chronic Chagas heart disease patients. Methods: Immunoblot, ELISA, cytometry, immunofluorescence and immunohistochemical assays were used to characterize A2R1 reactivity. To identify the antibody target, we performed an immunoprecipitation and two-dimensional electrophoresis coupled to mass spectrometry and confirmed A2R1 specific interaction by producing the antigen in different expression systems. Based on these data, we carried out a comparative in silico analysis of the protein targets orthologues, focusing mainly on post-translational modifications. Findings: A2R1 recognizes a parasite protein of similar to 50 kDa present in all life cycle stages of T. cruzi, as well as in other members of the kinetoplastid family, showing a defined immunofluorescence labeling pattern consistent with the cytoskeleton. A2R1 binds to tubulin, but this interaction relies on its post-translational modifications. Interestingly, this antibody also targets mammalian tubulin only present in brain, staining in and around cell bodies of the human peripheral and central nervous system. Interpretation: Our findings demonstrate for the first time the existence of a human antibody against T. cruzi tubulin capable of cross-reacting with a human neural protein. This work re-emphasizes the role of molecular mimicry between host and parasitic antigens in the development of pathological manifestations of T. cruzi infection.

Confirmed diagnosis of chronic Chagas disease (CD) requires positive results by two different IgG serology tests. Variable sensitivity has been reported among tests and in different geographic regions. Inadequate specificity presents a particular challenge in low-prevalence settings such as the United States. This study provides a direct comparison of the latest-generation IgG serology assays with four previously assessed FDA-cleared tests. Seven hundred ten blood donor plasma specimens were evaluated by Wiener Lisado and Wiener v.4.0 enzyme-linked immunosorbent assays (ELISAs) and Abbott PRISM Chagas chemiluminescent assay (ChLIA). Sensitivity and specificity were assessed relative to infection status as determined by the original blood donation testing algorithm. All three latest-generation assays demonstrated 100% specificity (95% confidence interval [CI], 98.6 to 100.0). Wiener Lisado, Wiener v.4.0, and Abbott PRISM had sensitivities of 97.1% (95% CI, 95.1 to 98.4), 98.9% (95% CI, 97.4 to 99.6), and 95.5% (95% CI, 93.2 to 97.3), respectively. As with previously evaluated FDA-cleared tests, all three assays had the highest reactivity and sensitivity in samples from donors born in South America and lowest reactivity and sensitivity in specimens from those born in Mexico, with intermediate results in specimens from Central American donors. Wiener v.4.0 had the highest diagnostic sensitivity in all comparisons. Our findings suggest that the latest-generation CD serology tests could improve diagnostic sensitivity without affecting specificity.

Introduction: Chagas disease is a neglected tropical disease of interest to public health because of its social and economic burden. Identifying infected and sick people with Chagas disease constitutes the first step towards achieving World Health Ooganization’s goals for 2020.Objective: To evaluate the reproducibility with gold standard of a rapid diagnostic test for detection of antibodies to T. cruzi; and to propose a diagnostic algorithm for Chagas disease under the point-of-care concept in an area with limited access to health care coverage.Material and Methods: A cross-sectional study was performed to detect antibodies to T. cruzi in 151 indigenous volunteers belonging to three ethnic groups of the Sierra Nevada de Santa Marta, Colombia. Rapid tests-PDR SD BIOLINE Chagas Ab were implemented in the field versus confirmation in the laboratory using two standardized serological methods (ELISAs).Results: The results show that 19,2 % seroreactivity for T. cruzi was found among the entire population screening. The highest rate of human infection with T. cruzi was detected in the Wiwa community. No significant differences between rapid diagnostic test and the standard techniques (ELISAs) were found. Sensitivity, specificity and concordance for RDT were 100 % (Kappa: 1,0).Conclusions: The Sierra Nevada de Santa Marta continues to be a hyperendemic area for Chagas disease. The area is difficult to access and has low or no primary health care coverage, making the assessed rapid diagnostic test a useful tool for screening programs and defining treatment and control plans, which represents the first approach at establishing a point-of-care testing strategy for endemic countries for Chagas disease., Introducción: La enfermedad de Chagas es una enfermedad desatendida de interés en salud pública por su carga social y económica. Identificar personas infectadas y enfermas con el mal de Chagas constituye el primer paso para alcanzar los objetivos de la Organización Mundial de la Salud para el 2020.Objetivo: Evaluar la reproducibilidad de una prueba de diagnóstico rápida para la detección de anticuerpos contra T. cruzi; y proponer un algoritmo de diagnóstico para enfermedad de Chagas bajo el concepto de uso de tecnologías en el lugar de atención en áreas de acceso limitados a los servicios de salud.Materiales y métodos: Se realizó un estudio de corte transversal para la detección de anticuerpos para T. cruzi a 151 indígenas voluntarios pertenecientes a tres grupos étnicos de la Sierra Nevada de Santa Marta, Colombia. Se implementó pruebas rápidas-PDR SD BIOLINE Chagas Ab en campo versus la confirmación en el laboratorio mediante dos métodos serológicos estandarizados (ELISAs).Resultados: Se encontró el 19,2 % de seroreactividad para T. cruzi entre toda la población estudiada. La tasa más alta de infección humana por T. cruzi se detectó en la comunidad Wiwa. No hubo diferencias significativas entre la prueba de diagnóstico rápida y las técnicas estandarizadas (ELISAS). La sensibilidad, especificidad y concordancia para la PDR fue del 100 % (Kappa: 1,0).Conclusiones: La Sierra Nevada de Santa Marta continúa siendo un área hiperendémica para la enfermedad de Chagas. Dado que es un área de difícil acceso, con baja o nula cobertura en atención primaria en salud, la prueba de diagnóstico rápida evaluada se convierte en una herramienta útil como prueba de elección para programas de tamización y definir planes de acción de tratamiento y control, y representa el primer acercamiento de uso de tecnologías en el sitio de atención para el diagnóstico rápido en países endémicos para la enfermedad.

Objectives: to identify the components of social stigma associated with a positive diagnosis of Chagas disease based on individual and family accounts. Methods: The study compiles the testimonies of 3 families through in-depth interviews that were recorded, the content of which was structured and then shared among the researchers through a process of triangulation. Results: different forms of social stigma, experienced, perceived, anticipated, as well as self-stigma, stigma by association and discriminatory behaviours were identified, leading to social isolation, reinforcing traditional fears associated with the disease, and causing intra-familial tensions. Social stigma and the silence that accompanies it are serious barriers to access to medical consultation and deworming treatment. Conclusions: It is important to take into account psycho-socio-cultural aspects in strategies for comprehensive care of Chagas disease, especially in information, education and communication (IEC) programmes and during the medical consultation. Also, to break the stigma and the silence surrounding it, it’s essential to integrate people affected by Chagas and other civil society actors into the conception of these programs., Objetivos: identificar a partir de relatos individuales y familiares los componentes del estigma social asociado a un diagnóstico de Chagas positivo. Métodos: el estudio recopila los testimonios de tres familias a través de entrevistas a profundidad que fueron grabadas, cuyo contenido fue estructurado y luego compartido entre los investigadores a través de un proceso de triangulación. Resultados: se identificaron las diferentes formas de estigma social, experimentado, percibido, anticipado, así como el autoestigma, el estigma por asociación y comportamientos de discriminación; lo que conlleva el aislamiento social, refuerza los miedos tradicionalmente relacionados a esta enfermedad, y provoca tensiones intrafamiliares. El estigma social y el silencio que lo acompaña son serias barreras de acceso a la consulta médica y al tratamiento antiparasitario Conclusiones: Es importante tomar en cuenta aspectos de tipo psico-socio-cultural en las estrategias de atención integral de Chagas, principalmente en los programas de información, educación, comunicación (IEC) y durante la consulta médica. Para romper el estigma y el silencio que lo acompaña, es indispensable integrar las personas afectadas por Chagas y otros actores de la sociedad civil en el diseño de esas estrategias.

Introduction: Chagas disease is a parasitic zoonosis caused by Trypanosoma cruzi , a vector-born protozoan that is transmitted to humans. Field studies predict that one-third of around 18 million T cruzi-infected humans will die of Chagas disease in Latin America.Objective: To determine the seroprevalence of the infection with Trypanosoma cruzi and to identify some risk factors associated with this condition in Cumaral, Meta, Colombia.Material and Methods: A descriptive, cross-sectional study was conducted. Blood samples were collected from subjects that had been living in urban and rural areas of Cumaral municipality for more than six months. An ELISA-IgG method with total extracts (first test) was used for the detection of Trypanosoma cruzy IgG. A recombinant-based ELISA was performed as a confirmatory test. Doubtful results were sent to the National Institute for Health for confirmation by indirect immunofluorescence assay. Prism 8 for MacOS (version 8.2.1) was used for statistical analysis.Results: In the screening for Chagas disease, 2,7 % of all the cases tested were positive. When comparing subjects with positive and negative results, differences between age, scholarship and materials used in the construction of house walls were evidenced.Conclusions: The results provide useful information about housing conditions and seroprevalence of the disease that help to evaluate the effectiveness of the arrangement that provides and strengthens the access to the diagnosis and treatment of the disease., Introducción: La Enfermedad de Chagas es una zoonosis parasitaria causada por Trypanosoma cruzi, un protozoario que se transmite principalmente de manera vectorial al ser humano. Estudios de campo predicen que un tercio de un estimado de 18 millones de personas infectadas en Latinoamérica morirán de Enfermedad de Chagas.Objetivo: El objetivo de este estudio fue determinar la seroprevalencia de la infección por Trypanosoma cruzi y factores asociados en población del municipio de Cumaral, Meta, Colombia.Material y Métodos: Se realizó un estudio descriptivo de tipo transversal, en el cual se recolectaron sueros de toda persona habitante del municipio de Cumaral por más de seis meses y que habitara en área urbana o rural. Se utilizó el método de ELISA de extractos totales (Primera prueba) para la detección de IgG antiTripanosoma cruzy; a los positivos se les realizó prueba confirmatoria por ELISA recombinante; los resultados dudosos fueron enviados al Instituto Nacional de Salud para su confirmación mediante la inmunofluorescencia indirecta. Para el análisis de la información se utilizó el paquete estadístico Prism versión 8.2.1 para MacOS.Resultados: En la tamización de la prueba para Chagas del presente estudio, resultó positivo 2,7 % de los evaluados; al contrastar los sujetos con resultado positivo con los negativos, se observaron diferencias en la edad, la escolaridad y el material de las paredes de sus viviendas.Conclusiones: Los resultados proporcionan información útil de condiciones de vivienda y seroprevalencia de la enfermedad, que ayudan a evaluar la efectividad del acuerdo que facilita y fortalece el acceso al diagnóstico y tratamiento de la enfermedad.

Trypanosoma cruzi has existed in humans for >9000 years 1. Parasite, vector and human disease were described by Carlos Chagas in 1909 2. Vectorial and congenital transmissions account for ~70% and 26% of new infections, respectively. The clinical course of Chagas Disease (CD) is generally presented with acute parasitemic phase, clinically asymptomatic indeterminate phase, and chronic phase when patients develop cardiac, colon, or neurological disorders. Heart failure is recognized as the major cause of death in CD patients. The global productivity gain by treating acute or chronic CD and preventing heart failure and death is estimated to be $8 billion US dollars in 2021-2030 3. Thus, just the economic benefits make a strong case for new investments in controlling this disease.

Introduction. Chagas disease is one of the main parasitosis worldwide, although it is distributed mainly in poor areas of Latin America. In the absence of an eff ective vaccine or prophylaxis, the active search for infected people and the implementation of prevention methods of the disease are the best strategies to fi ght it. Objective. The objective of this study was to analyze the prevalence of Trypanosoma cruzi infection and knowledge about Chagas disease in communities in the state of Chiapas, Mexico. Material and methods. The ELISA test was performed on inhabitants of two communities that had reports of the presence of triatomines. Knowledge about the disease and data on risk factors were determined through semi-structured surveys. Results. 317 samples were analyzed, six of them were reactive to infection by T. cruzi (1.89%). Less than half (39) of the people surveyed mentioned they knew the triatomine insect, however most of them know that it can transmit a life-threatening disease. Triatomines are commonly known as bed bugs or talage. Conclusions. Chagas disease is still active in endemic areas of the state of Chiapas. Lack of knowledge about the components of the disease is evident and it is necessary to carry out awareness campaigns to address this problem, Introducción. La enfermedad de Chagas es una de las principales parasitosis a nivel mundial, aunque se distribuye principalmente en zonas pobres de América Latina. Ante la falta de una vacuna efectiva o profilaxis, la búsqueda activa de personas infectadas y la prevención de la enfermedad son las mejores estrategias para combatirla. El objetivo de este estudio fue analizar la prevalencia de la infección por Trypanosoma cruzi y el conocimiento sobre la enfermedad de Chagas en comunidades del estado de Chiapas, México. Material y Métodos. Se realizó la prueba de ELISA a habitantes de dos comunidades que tenían reportes de la presencia de triatominos. A través de encuestas semiestructuradas se determinó el conocimiento sobre la enfermedad y datos de factores de riesgo. Resultados. Se analizaron 317 muestras, de las cuales seis resultaron reactivas a la infección por T. cruzi (1,89 %). Menos de la mitad (39) de los encuestados mencionaron conocer al insecto triatomino, pero de ellos la gran mayoría sabe que puede transmitir una enfermedad potencialmente mortal. Comúnmente conocen a los triatominos como chinches o talaje. Conclusiones. La enfermedad de Chagas sigue activa en zonas endémicas del estado de Chiapas. El desconocimiento sobre los componentes de la enfermedad es evidente y se hace necesario realizar campañas de concientización para atender este problema

The purpose of this article is to reflect on the conceptual dimensions and dispositives that are put in place in the structure of techno-scientific promises within peripheral societies and contexts. For this, the author brings in the case of Chagas disease and analyzes the original mode of construction of the question at the beginning of the 20th century; also, its most modern formulation: the T. cruzi Genome Sequencing Project (causal agent of Chagas disease), at the beginning of the 21st century. Finally, it analyzes the clarities and opacities within the development of techno-scientific promises in non-hegemonic contexts., Resumo O objeto deste artigo é refletir em torno das dimensões conceptuáis e os dispositivos que se colocam em andamento na estrutura das promessas tecnocientíficas em contextos de sociedades periféricas. Para isso, o autor considera o caso da enfermidade de Chagas ao longo de um século, analisando o modo de construção original da questão a começos do século XX, e sua formulação mais moderna a começos do século XXI: o Projeto Sequenciamento do Genoma do T. cruzi (agente causal da enfermidade de Chagas). Finalmente, analisa o que se mostra e o que se oculta no desenvolvimento das promessas tecnocientíficas em contextos não hegemônicos., Resumen El objeto de este artículo es reflexionar en torno a las dimensiones conceptuales y los dispositivos que se ponen en marcha en la estructura de las promesas tecnocientíficas en contextos de sociedades periféricas. Para ello, el autor considera el caso de la enfermedad de Chagas a lo largo de un siglo, analizando el modo de construcción original de la cuestión a comienzos del siglo XX, y luego su formulación más moderna a comienzos del siglo XXI: el Proyecto Secuen-ciamiento del Genoma del T. cruzi (agente causal de la enfermedad de Chagas). Finalmente, analiza lo que se muestra y lo que se oculta en el desarrollo de las promesas tecnocientíficas en contextos no hegemónicos.

Research on vaccines against trypanosomatids, a family of protozoa that cause neglected tropical diseases, such as Chagas disease, leishmaniasis, and sleeping sickness, is a current need. Today, according to modern vaccinology, virus-like particle (VLP) technology is involved in many vaccines, including those undergoing studies related to COVID-19. The potential use of VLPs as vaccine adjuvants opens an opportunity for the use of protozoan antigens for the development of vaccines against diseases caused by Trypanosoma cruzi, Leishmania spp., and Trypanosoma brucei. In this context, it is important to consider the evasion mechanisms of these protozoa in the host and the antigens involved in the mechanisms of the parasite-host interaction. Thus, the immunostimulatory properties of VLPs can be part of an important strategy for the development and evaluation of new vaccines. This work aims to highlight the potential of VLPs as vaccine adjuvants for the development of immunity in complex diseases, specifically in the context of tropical diseases caused by trypanosomatids.

The infection caused by the protozoan Trypanosoma cruzi affects humans and is called as Chagas disease. Currently, the main measures available to reduce the incidence of this disease are drug treatment and vector control. Traditionally, the development of vaccines occurs mainly through the use of antigenic candidates of the etiologic agent in the form of a vaccine preparation. Virus-like particles (VLPs) are structures analogous to viral capsids composed essentially of structural proteins and are widely used in vaccination protocols because of their immunostimulatory properties. In this context, the objective of this study was to use strategies in a murine immunization model to characterize the immunostimulatory capacity of VLPs from Triatoma virus (TrV-VLPs), analysed in the presence or absence of the aluminium vaccine adjuvant. In parallel, to characterize the immunogenic behaviour of four T. cruzi chimeric recombinant proteins (mix-IBMP) associated with TrV-VLPs or aluminium vaccine adjuvant.

All trypanosomatid genomes are colonized by non-LTR retrotransposons which exhibit a highly conserved 77-nt sequence at their 5′ ends, known as the Pr77-hallmark (Pr77). The wide distribution of Pr77 is expected to be related to the gene regulation processes in these organisms as it has promoter and HDV-like ribozyme activities at the DNA and RNA levels, respectively. The identification of Pr77 hallmark-bearing retrotransposons and the study of the associations of mobile elements with relevant genes have been analyzed in the genomes of six strains of Trypanosoma cruzi belonging to different discrete typing units (DTUs) and with different geographical origins and host/vectors. The genomes have been sequenced, assembled and annotated. BUSCO analyses indicated a good quality for the assemblies that were used in comparative analyses. The results show differences among the six genomes in the copy number of genes related to virulence processes, the abundance of retrotransposons bearing the Pr77 sequence and the presence of the Pr77 hallmarks not associated with retroelements. The analyses also show frequent associations of Pr77-bearing retrotransposons and single Pr77 hallmarks with genes coding for trans-sialidases, RHS, MASP or hypothetical proteins, showing variable proportion depending on the type of retroelement, gene class and parasite strain. These differences in the genomic distribution of active retroelements and other Pr77-containing elements have shaped the genome architecture of these six strains and might be contributing to the phenotypic variability existing among them.

Chagas disease principally affects Latin-American people, but it currently has worldwide distribution due to migration. Death among those with Chagas disease can occur suddenly and without warning, even in those who may not have evidence of clinical or structural cardiac disease and who are younger than 60 years old. HCN4 channels, one of the principal elements responsible for pacemaker currents, are associated with cardiac fetal reprogramming and supraventricular and ventricular arrhythmias, but their role in chagasic arrhythmias is not clear. We found that a single-dose administration of ivabradine, which blocks HCN4, caused QTc and QRS enlargement and an increase in P-wave amplitude and was associated with ventricular and supraventricular arrhythmias in mice challenged with isoproterenol, a chronotropic/ionotropic positive agent. Continuous treatment with ivabradine did not alter the QTc interval, but P-wave morphology was deeply modified, generating supraventricular arrhythmias. In addition, we found that repolarization parameters improved with ivabradine treatment. These effects could have been caused by the high HCN4 expression observed in auricular and ventricular tissue in infected mice. Thus, we suggest, for the first time, that molecular remodeling by overexpression of HCN4 channels may be related to supraventricular arrhythmias in acute Chagas disease, causing ivabradine over-response. Thus, ivabradine treatment should be administered with caution, while HCN4 overexpression may be an indicator of heart failure and/or sudden death risk.

Introduction: Chagas’ disease is the leading cause of infectious myocarditis worldwide. This infection caused by Trypanosoma cruzi is usually life-long and asymptomatic; however, the third part of infected people can develop severe or even fatal cardiomyopathy. As the parasitemia in the chronic phase is both low-grade and intermittent, T. cruzi infection is principally detected by serology, although this method has sensitivity and specificity limitations.Objective: To determine the level of agreement between serologic and molecular tests in 658 voluntary blood donors from six provinces in the Colombian department of Santander.Materials and methods: We evaluated an array of diagnostic technologies by cross-section sampling performing a serological double diagnostic test for T. cruzi antibody detection (Chagas III ELISA™, BiosChile Group, and ARCHITECT Chagas CMIA™, Abbott), and DNA detection by polymerase chain reaction (PCR). We collected the demographic, clinical, and epidemiological information of participants. The sample size was calculated using Epidat™ and the statistical analysis was done with Stata 12.1™.Results: PCR was six times more sensitive in detecting T. cruzi infection than ELISA/CMIA with prevalence values of 1.8% (12/658) and 0.3% (2/658), respectively, and kappa=0.28 (95%CI: -0.03 - 0.59). In contrast, serology showed a sensitivity of 16.7% (95%CI: 2.09 - 48.4) and a specificity of 100% (95%CI: 99.4 - 100). All seropositive samples were found to be positive by PCR.Conclusions: The implementation of PCR as a complementary method for screening donors could reduce the probability of false negative and the consequent risk of transfusional-transmission of Chagas’ disease, especially in endemic regions., Introducción. La enfermedad de Chagas constituye la principal causa de miocarditis infecciosa en el mundo. Causada por Trypanosoma cruzi, la infección puede persistir toda la vida de manera asintomática y silenciosa, pero un tercio de los infectados desarrolla cardiomiopatía grave. Debido a que la parasitemia en la fase crónica es baja e intermitente, el diagnóstico se hace principalmente mediante la detección de anticuerpos (serología), método que tiene limitaciones de sensibilidad y especificidad.Objetivo. Determinar la concordancia entre el diagnóstico serológico y molecular de T. cruzi en 658 donantes voluntarios de sangre del departamento de Santander, Colombia.Materiales y métodos. Se hizo un estudio de evaluación de tecnologías diagnósticas con muestreo transversal, utilizando un doble diagnóstico serológico para la detección de anticuerpos anti-T. cruzi (Chagas III ELISA™, BiosChile Group, y ARCHITECT Chagas CMIA™, Abbott) y la de ADN por PCR. Se recolectó la información demográfica, clínica y epidemiológica de los participantes. El tamaño de la muestra se estimó utilizando Epidat™ y el análisis estadístico se hizo mediante Stata 12.1™.Resultados. La sensibilidad de la PCR fue seis veces mayor que la de las pruebas de ELISA/CMIA, con prevalencias de 1,8 % (12/658) y 0,3 % (2/658), respectivamente, y kappa de 0,28 (IC95% -0,03 - 0,59). La sensibilidad serológica fue de 16,7 % (IC95% 2,09 - 48,4) y la especificidad de 100 % (IC95% 99,4 - 100). Todas las muestras seropositivas fueron positivas también en la PCR.Conclusiones. El uso de la PCR como método complementario para la tamización de donantes podría reducir el riesgo de falsos negativos y disminuir los casos de transmisión transfusional de la enfermedad de Chagas, especialmente en regiones endémicas.