Antígeno nativo y no nativo para determinar la seroprevalencia de Trypanosoma cruzi en mujeres embarazadas en el estado de Morelos, México / Native and non-native antigen to determine the seroprevalence of Trypanosoma cruzi in pregnant women from the state of Morelos, Mexico

INTRODUCCIÓN: La enfermedad de Chagas es una infección parasitaria crónica sistémica, de importancia global, causada por Trypanosoma cruzi. OBJETIVO: Determinar la prevalencia de anticuerpos contra T cruzi en mujeres embarazadas en el estado de Morelos, México. MATERIALES Y MÉTODOS: Se analizaron 1.620 sueros de mujeres embarazadas mediante dos pruebas serológicas: ELISAc (antígeno crudo nativo) y ELISAr (antígeno recombinante, no nativo). Las muestras reactivas se analizaron posteriormente mediante hemaglutinación indirecta (HAI). Se utilizaron dos enfoques de detección, en paralelo (son positivas las muestras reactivas por cualquier método) y en serie (son positivas las muestras confirmadas por HAI). Se evaluaron factores sociodemográficos y de salud asociados a la presencia de anticuerpos contra T. cruzi mediante razones de momios al 95%. RESULTADOS: Se obtuvo una seroprevalencia de 4,87% con el diagnóstico en paralelo y de 0,43% en serie. A partir de los resultados en paralelo las mujeres que fueron atendidas en los hospitales generales de Tetecala y Jojutla tuvieron, respectivamente, 2,2 y 2,0 veces mayor posibilidad de presentar anticuerpos contra T cruzi con respecto a las mujeres que fueron atendidas en el Hospital General de Cuautla. CONCLUSIÓN: La prevalencia de anticuerpos contra T cruzi en mujeres embarazadas en el estado de Morelos fluctuó entre 0,43 y 4,87%, según el antígeno y el abordaje utilizado. Es necesario continuar con la vigilancia de la seroprevalencia de anticuerpos contra T cruzi en mujeres embarazadas en el estado de Morelos, México, con las técnicas de mayor sensibilidad y especificidad disponibles.

BACKGROUND: Chagas disease is a globally important chronic systemic parasitic infection caused by Trypanosoma cruzi. AIM: To determine the prevalence of antibodies against T cruzi in pregnant women from the state of Morelos, México. METHODS: 1,620 sera from pregnant women were analyzed using two serological tests: ELISAc (native crude antigen) and ELISAr (recombinant, non-native antigen). Reactive samples were subsequently analyzed by indirect hemagglutination (IHA). Two detection approaches were used, in parallel (reactive samples by any method are positive) and serial (samples confirmed by IHA are positive). Sociodemographic and health factors associated with the presence of antibodies against T cruzi were evaluated using 95% odds ratios. RESULTS: A seroprevalence of 4.87% was obtained with parallel diagnosis and 0.43% in series. From the parallel results, the women who were attended at the general hospitals of Tetecala and Jojutla had respectively 2.2 and 2.0 times greater chance of presenting antibodies against T cruzi compared to the women who were attended at the General Hospital of Cuautla. CONCLUSION: The prevalence of antibodies against T cruzi in pregnant women from the state of Morelos fluctuated between 0.43 and 4.87%, depending on the antigen and the approach used. It is necessary to continue with the surveillance of the seroprevalence of antibodies against T cruzi in pregnant women from the state of Morelos, Mexico, using the techniques with the highest sensitivity and specificity available.

Infección por trypanosoma cruzi y bloqueo cardíaco del nodo auriculoventricular en el salvador / Trypanosoma cruzi infection and atrioventricular-nodal heart block in El Salvador

Resumen La enfermedad de Chagas es endémica en América Latina y sigue siendo un problema regional a pesar de que su frecuencia ha disminuido gracias a importantes avances en salud ambiental. Para determinar su frecuencia en pacientes con enfermedades miocárdicas de El Salvador, se llevó a cabo una in vestigación observacional retrospectiva en nuestro hospital que es un centro de referencia de nivel nacional. Se revisó el registro del Laboratorio de Chagas en el período 2013-2015 para conocer cuántos individuos internados en la Unidad Cardiológica eran positivos por serología para infección chagásica y cuáles fueron sus diagnósticos. Se realizó un total de 1472 pruebas a pacientes individuales durante los 36 meses del período de estudio. De los 557 pacientes con serología positiva para Chagas, 97 (17.4%) fueron eventualmente hospitalizados en la Unidad Cardiológica. A su vez, estos 97 pacientes representaron el 33.7% de los 288 pacientes con cardiopatías. Entre los 97 con cardiopatía chagásica, 40 (41.2%) cumplieron criterios para colocación de marcapaso permanente, mientras que solo 13 de 191 (6.8%) enfermos con cardiopatías no chagásicas cumplieron esos criterios. La frecuencia de bloqueos auriculoventriculares asociados a infección por Trypanosoma cruzi resultó mucho mayor que las publicadas en estudios previos realizados en Sudamérica.

Abstract Chagas disease is endemic in Latin America and remains a regional problem despite improvements in en vironmental health conditions that have helped to control its transmission. To know more about its prevalence in heart disease patients, we carried out a survey in our national (El Salvador) reference hospital. We reviewed the Chagas Lab´s records 2013-2015 to find out how many of the patients admitted to the Hospital´s Heart Unit were serologically positives for Trypanosoma cruzi infection and which the associated diagnoses were. A total of 1472 patients were tested along the 36-month study period. Out of 557 (37.8%) patients with positive serology for Chagas infection, 97 (17.4%) were eventually admitted to the Heart Unit. Among these 97 Chagas infected patients with heart disease, 40 (41.2%) met the criteria for permanent pacemaker placement, while only 13 of 191 (6.8%) patients with non-chagasic heart disease met these criteria. The frequency of heart atrioventricular block associated with Trypanosoma cruzi infection was higher than frequencies reported in South American studies.

Evaluación del UMELISA CHAGAS® con la incorporación de nuevos péptidos monoméricos y quiméricos representativos de diferentes regiones de Trypanosoma cruzi / Evaluation of UMELISA CHAGAS™ with the incorporation of new monomeric and chimeric peptides representative of different regions of Trypanosoma cruzi

Resumen | Introducción. La mayoría de las personas con enfermedad de Chagas desarrolla anticuerpos específicos contra Trypanosoma cruzi. En la infección temprana se producen anticuerpos IgM contra T. cruzi que son reemplazados por IgG durante el curso de la enfermedad. Los primeros síntomas de la enfermedad suelen ser muy leves y atípicos, por lo que a menudo no se detecta en la fase aguda. Objetivos. Evaluar la sensibilidad y la especificidad clínica y analítica, la precisión y la eficacia del UMELISA CHAGAS® con la incorporación de nuevos péptidos sintéticos en la fase sólida representativos de la proteína SAPA (Shed Acute Phase Antigen) y del antígeno TSA (Trypomastigote Surface Antigen). Materiales y métodos. Se evaluó un panel de desempeño de título mixto anti-I cruzi y uno de seroconversión de Chagas, así como muestras de suero positivas y negativas provenientes de zonas endémicas de la enfermedad y muestras positivas de otras enfermedades que podían interferir con la prueba. Las pruebas Bioelisa CHAGAS, Chagatest ELISA recombinante v. 4.0, Chagatest HAI y SD BIOLINE CHAGAS Ab Rapid, se emplearon como referencia. Resultados. Los porcentajes de sensibilidad y especificidad clínica fueron de 97,73 % (IC95% 96,23-99,24) y 99,33 % (IC95% 98,88-99,78), respectivamente. Se obtuvo un 98,96 % de eficacia y una buena precisión. Conclusiones. Los resultados demuestran que la nueva fase sólida del UMELISA CHAGAS® puede utilizarse para el inmunodiagnóstico, la certificación de sangre y la vigilancia epidemiológica en países endémicos y no endémicos con población de alto riesgo.

Abstract | Introduction: Most people with Chagas disease develop specific antibodies against Trypanosoma cruzi. In early infection, IgM antibodies against T. cruzi are produced and later replaced for IgG antibodies during the course of the disease. The first symptoms of the infection may be very mild and atypical, which is why the disease is often not detected in the acute phase. Objectives: To evaluate the clinical and analytical sensitivity, and specificity, accuracy, and efficacy of UMELISA CHAGAS™ with the addition of new synthetic peptides in the solid phase representative of the shed acute phase antigen protein (SAPA) and the trypomastigote surface antigen (TSA). Materials and methods: We evaluated a mixed anti-T. cruzi titer performance panel and a Chagas seroconversion one, as well as positive and negative serum samples from endemic areas of the disease and positive samples for other diseases that may interfere with the assay. The Bioelisa CHAGAS assay, Chaga test recombinant ELISA v.4.0, Chagatest HAI, and SD BIOLINE CHAGAS Ab Rapid were used as reference tests. Results: The sensitivity of the assay was 97.73% (95% CI: 96,23-99,24) and the clinical specificity, 99.33% (95% CI: 98,88-99,78) while the efficacy and the accuracy were 98.96%. Conclusions: Our results show that the new solid phase of UMELISA CHAGAS® can be used for immunodiagnostic, blood certification, and epidemiological surveillance in endemic and non-endemic countries with high-risk populations.

Indeterminate form of Chagas disease: historical, conceptual, clinical, and prognostic aspects

Abstract Chagas disease (CD) remains a serious endemic disease in Latin America and a major public health problem. Because of globalization, the disease has spread to non-endemic areas in the northern hemisphere. In the chronic phase of the disease, most patients present with the indeterminate form (IF), characterized by positive serology for Trypanosoma cruzi, absence of clinical findings, and normal findings in electrocardiogram (ECG). IF was not recognized as a clinical entity until decades after the discovery of the disease, and only in the 1940-50s, it was categorized as a form of CD, and its conceptual definition was ratified in the 1980s. Children, adolescents, and young adults with the IF benefit from etiological treatment and tend to have less progression to heart disease in the long term than the untreated ones. IF patients have an essentially benign clinical condition, and their prognosis can be compared to that of healthy individuals with normal ECG findings. Currently, because of aging, patients with the IF have comorbidities that require attention in health services.

Case report of Chagas disease reactivation: new diagnosis tool by direct microscopic observation of biopsy specimen and its preservation fluid

Abstract Chagas Disease is caused by Trypanosoma cruzi. This infection is endemic in the Americas region. Neurological Chagas reactivation is diagnosed through the visualization of the parasite in the cerebrospinal fluid, blood, or tissue samples. Herein, we report the visualization of trypomastigotes by direct microscopic observation of a brain biopsy specimen and its preservation fluid (PF) in a paitient infected with VIH and T. cruzi. This easy and simple diagnostic method coupled with quantitative polymerase chain reaction can be used in all tissue biopsies and PF of T. cruzi seropositive patients, suspected of Chagas disease reactivation.

Temporal changes in the clinical-epidemiological profile of patients with Chagas disease at a referral center in Brazil

Abstract INTRODUCTION We aimed to describe the sociodemographic, epidemiological, and clinical characteristics of patients with chronic Chagas disease (CD) at an infectious disease referral center. Changes in patient profiles over time were also evaluated. METHODS This retrospective study included patients with CD from November 1986-December 2019. All patients underwent an evaluation protocol that included sociodemographic profile; epidemiological history; anamnesis; and physical, cardiologic, and digestive examinations. Trend differences for each 5-year period from 1986 to 2019 were tested using a nonparametric trend test for continuous and generalized linear models with binomial distribution for categorical variables. RESULTS A total of 2,168 patients (52.2% women) were included, with a mean age of 47.8 years old. White patients with low levels of education predominated. The reported transmission mode was vectorial in 90.2% of cases. The majority came from areas with a high prevalence (52.2%) and morbidity (67.8%) of CD. The most common clinical presentation was the indeterminate form (44.9%). The number of patients referred gradually decreased and the age at admission increased during the study period, as did the patients' levels of education. CONCLUSIONS The clinical profile of CD is characterized by a predominance of the indeterminate form of the disease. Regarding the patients who were followed up at the referral center, there was a progressive increase in the mean age and a concomitant decrease in the number of new patients. This reflects the successful control of vector and transfusion transmission in Brazil as well as the aging population of patients with CD.

Lobular panniculitis of the thigh as the only cutaneous manifestation of reactivation of Chagas disease in a renal transplant patient: a case report

Abstract Reactivation of chronic Trypanosoma cruzi infection in solid organ transplant recipients (SOTRs) has been reported. The patient presented with a 2-week history of two painful erythematous, infiltrated plaques with central ulceration and necrotic crust on the left thigh. She had a history of chronic indeterminate Chagas disease (CD) and had received a kidney transplant before 2 months. Skin biopsies revealed lobular panniculitis with intracellular amastigote forms of T. cruzi. The patient was diagnosed with CD reactivation. Treatment with benznidazole significantly improved her condition. CD reactivation should be suspected in SOTRs living in endemic areas with clinical polymorphism of skin lesions.

Trypanosoma cruzi discrete typing unit TcIV implicated in a case of acute Chagas disease in a domiciliated dog in the western Amazon

Abstract Chagas disease is caused by the protozoan Trypanosoma cruzi. Seven lineages have been identified based on different molecular markers, namely TcI, TcII, TcIII, TcIV, TcV, TcVI, and TcBat. Dogs play the role of epidemiological sentinels being domestic reservoirs of T. cruzi. The aim of the current study was to report the first case of CD in a domestic dog in Manaus, Amazonas, Brazil, infected with T. cruzi DTU TcIV. We hope our report encourages veterinarians and surveillance professionals to a take a deeper look at T. cruzi infection in domestic animals.

Evaluation of the Autonomic Nervous System in Chronic Chagasic Cardiopathy: A Systematic Review of the Literature

Abstract Background The importance of regional sympathetic denervation in the pathophysiology and prognosis of Chagas disease has been recognized. Objective To conduct a review of studies that have assessed dysautonomia in chronic Chagas heart disease. Methods The search was performed on the Medline, Pubmed, Lilacs and SciELO databases. The inclusion criteria were: original articles published in full; studies on individuals with Chagas disease, that used diagnostic methods for chagasic cardiomyopathy, and had clear inclusion and exclusion criteria. Duplicate studies, studies including children (0 to 10 years old), studies involving animals, in vitro experiments, case reports, editorials, theses, and dissertations were excluded. Results A total of 281 articles were retrieved, and 10 met the inclusion criteria and were analyzed. There was great heterogeneity as to the technique for assessing dysautonomia, groups of patients studied and classification of Chagas disease. The methods used for studying the autonomic system was immunohistochemistry (n=1), Valsalva and tilt-test (n=1), scintigraphy (n=6) and Holter monitoring (n=2). The results indicated dysautonomia in the indeterminate, digestive and cardiac forms of Chagas disease, and sympathetic denervation in the indeterminate and cardiac forms of the disease. There was agreement between areas of denervation, hypoperfusion and fibrosis, but areas of denervation were larger than those of hypoperfusion. The frequency of denervation and its extension increased from the indeterminate to the cardiac form. There was an association between extension of denervation and previous history of malignant ventricular arrhythmia. Conclusions The evidence presented in this review supports that an early diagnosis of autonomic denervation in chronic Chagas' disease allows the identification of patients with an increased risk of sudden death. Int J Cardiovasc Sci. 2020; [online].ahead print, PP.0-0

Prevalência da Infecção pelo Trypanosoma cruzi em Doadores de Sangue / Prevalence of Trypanosoma Cruzi Infection in Blood Donors

Resumo Fundamento A doença de Chagas (DC) é considerada um problema de saúde pública na América Latina. A região nordeste, principalmente o estado do Ceará, ainda representa grande preocupação em termos de risco de transmissão da doença. Objetivo Estimar a prevalência de T. cruzi em doadores de sangue do estado do Ceará. Métodos Trata-se um de estudo retrospectivo descritivo realizado no período de 2010 a 2015, a partir de dados registrados no sistema informatizado do Centro de Hematologia e Hemoterapia do Ceará (HEMOCE). Resultados Dos 763.731 potenciais doadores de sangue, 14.159 foram considerados impedidos de fazer a doação devido à sorologia, sendo que 1.982 (0,33%) o foram devido à positividade/inconclusão para doença de Chagas. Compareceram à Hemorrede para a repetição 425 indivíduos, sendo confirmados 28,2% (120/425) como impedidos de doar devido a DC. Conclusão Não houve redução significativa das sorologias positivas/inconclusivas no período entre 2010-2015, porém foi observada redução em relação a 1996/1997 no estado. A determinação da prevalência da doença de Chagas em bancos de sangue pode ser relevante como indicador do risco de transmissão transfusional em determinada região. Novos testes sorológicos para triagem com melhor acurácia são necessários, reduzindo o descarte desnecessário de bolsas de sangue, os custos para o Sistema Único de Saúde e a insegurança para os pacientes e familiares. (Arq Bras Cardiol. 2020; 115(6):1082-1091)

Abstract Background Chagas disease (CD) is considered a public health problem in Latin America. The northeastern region, especially the state of Ceará, still represents a major concern in terms of the risk of transmission of CD. Objective To estimate the prevalence of T. cruzi in blood donors from the state of Ceará. Methods This is a retrospective descriptive study that was performed in the period from 2010 to 2015 from data recorded in the computerized system of the Hematology and Hemotherapy Center of Ceará (HEMOCE in Portuguese). Results Of the 763,731 potential blood donors, 14,159 were serologically ineligible; 1,982 (0.33%) were serologically ineligible due to positive / inconclusive diagnosis for CD. A total of 425 individuals came to the HEMOCE to repeat the test, with 28.2% (120/425) declared ineligible for donations due to CD. Conclusion No significant reduction of positive / inconclusive serology was observed in the period between 2010 and 2015, but a reduction was observed when compared to 1996/1997 in the state. The determination of the prevalence of CD in blood banks may be relevant as an indicator of the risk of CD transmission through blood transfusions in a given region. New serological tests for triage with better accuracy in screening are needed, in an attempt to reduce the unnecessary disposal of blood bags, reduce costs for the Brazilian Unified Health System, and diminish insecurity for the patient and family members. (Arq Bras Cardiol. 2020; 115(6):1082-1091)

La investigación biomédica y su relación con el control de la enfermedad de Chagas / Biomedical research and its relationship with the control of Chagas disease

En la Enfermedad de Chagas la investigación biomédica ha hecho avances importantes en áreas del conocimiento del parásito, vectores e interrelación hospedero/ parásito. El nuevo contexto epidemiolólogicomuestra una reducción de casos de la enfermedad de Chagas en el continente americano, sin embargo sigue siendo un problema de salud pública. El estudio del genoma de Trypanosoma cruzi deja como desafío el desarrollo de nuevos medicamentos, vacunas y estudios de proteomica en el futuro inmediato. Por otra parte el estudio del genoma de Rhodnius prolixus abre camino para controlar el vector y hallar nuevas maneras de prevenir la transmisión de la enfermedad. La demostración correcta del agente patógeno o de sus productos en tejidos o fluidos conlleva al diagnóstico acertado, en el caso del T. cruzi, esta detección no siempre es posible debido a la baja presencia del parásito en sangre, por esto los métodos de diagnóstico serológicos (indirectos) han sido los más desarrollados y utilizados. Los métodos de detección directa como la PCR y la qPCR presentan alternativas diagnósticas. Recientes estudios sobre la variabilidad genética del parásito han dado nuevas luces sobre los diferentes escenarios de los ciclos de transmisión de la enfermedad, patogénesis en humanos, ciclo zoonótico y aspectos co-evolutivos. Benzonidazol y Nifurtimox son las únicas drogas que se utilizan para el tratamiento. Las actividades de minería, explotación petrolera y siembra de cultivos agroindustriales en América Latina han ocasionado profundas modificaciones en los ecosistemas con la consecuente alteración del ciclo zoonótico de la enfermedad de Chagas. omo conclusión se requiere continuar con los esfuerzos en el desarrollo de nuevos medicamentos y la búsqueda de biomarcadores de eficacia terapéutica en pacientes que reciben los actuales medicamentos y que también permitan el pronóstico de la patogénesis(AU)

In Chagas disease, biomedical research has made important advances in areas of knowledge of the parasite, vectors, and host / parasite interrelationship. The new epidemiological context shows a reduction in cases of Chagas disease in the American continent, however it continues to be a public health problem. The study of the Trypanosoma cruzi genome leaves as a challenge the development of new drugs, vaccines and proteomic studies in the immediate future. On the other hand, the study of the Rhodnius prolixus genome opens the way to control the vector and find new ways to prevent the transmission of the disease. Correct demonstration of the pathogen or its products in tissues or fluids leads to the correct diagnosis, in the case of T. cruzi, this detection is not always possible due to the low presence of the parasite in blood, for this reason serological diagnostic methods (indirect) have been the most developed and used. Direct detection methods such as PCR and qPCR present diagnostic alternatives. Recent studies on the genetic variability of the parasite have shed new light on the different scenarios of the disease transmission cycles, pathogenesis in humans, zoonotic cycle and co-evolutionary aspects. Benzonidazole and Nifurtimox are the only drugs that are used for treatment. The activities of mining, oil exploitation and planting of agro-industrial crops in Latin America have caused profound changes in ecosystems with the consequent alteration of the zoonotic cycle of Chagas disease. As a conclusion, it is necessary to continue with the efforts in the development of new drugs and the search for biomarkers of therapeutic efficacy in patients who receive the current drugs and that also allow the prognosis of the pathogenesis(AU)

Neurochagas: atualização clínica / Neurochagas: clinical update

A doença de Chagas ainda é uma doença tropical muito prevalente no Brasil. Pode apresentar duas fases (aguda e crônica) e exibe grandes repercussões, sobretudo as que envolvem o sistema nervoso periférico e/ou central. Com o aumento do número de pessoas vivendo em estado (transitório ou permanente) de imunossupressão, os casos de manifestações neurológicas por neurochagas aumentaram, e este tornou-se um importante diagnóstico diferencial com outras doenças oportunistas. Este artigo teve como objetivo revisar os principais aspectos clínicos e terapêuticos da doença de Chagas no sistema nervoso central.

Chagas disease is still a very prevalent tropical disease in Brazil. It can have two phases - acute and chronic ­ and shows major repercussions, especially those involving the peripheral and/ or central nervous system. With the increase in the number of people living in the (transient or permanent) state of immunosuppression the cases of neurological manifestations of Chagas disease increased and this became an important differential diagnosis with other opportunistic diseases. This article aimed to review the main clinical and therapeutic aspects of central nervous system Chagas disease

Application of WHO International Biological Reference Standards to evaluate commercial serological tests for chronic Chagas disease

BACKGROUND Chagas disease, resulting from Trypanosoma cruzi infections, continues to be a health concern mainly in Latin American countries where the parasite is endemic. The laboratory diagnosis of a chronic infection is determined through serological assays for antibodies against T. cruzi and several tests are available that differ in key components, formats and methodologies. To date, no single test meets the criteria of a gold standard. The situation is further complicated by the difficulties associated with performance comparisons between different immunoassays or methodologies executed at different times and geographical areas. OBJECTIVE To improve the diagnosis of Chagas disease, the WHO coordinated the development of two International Biological Reference Standards for antibodies against anti-T. cruzi: NIBSC 09/186 and NIBSC 09/188 that respectively represent geographical regions with the highest prevalence of TcII and TcI lineages of the parasite. METHODS The principle goal of this study was to verify the behavior of these standards when assayed by several commercially available serological tests that employ different methods to capture and detect human anti-T. cruzi antibodies. FINDINGS AND MAIN CONCLUSIONS The results reinforce the recommendation that these standards be considered for performance evaluations of commercialised immunoassays and should be an integral step in the development of new test components or assay paradigms.