Chagas disease affects the human placental barrier's turnover dynamics during pregnancy

BACKGROUND Trypanosoma cruzi crosses the placental barrier and produces the congenital transmission of Chagas disease (CD). Structural alterations of the chorionic villi by this parasite have been described in vitro, but little is known about trophoblast turnover in placentas from women with CD. OBJECTIVE To analyze the proliferation and fusion processes in placentas from women with CD. METHODS Archived human term placenta paraffin-embedded blocks were used, from women with CD (CDP), and no pathology (NP). Immunohistochemistry tests were performed for Ki67 to calculate the proliferation index (PI) of cytotrophoblast (CTB) and Syncytin-1, a fusion marker of syncytiotrophoblast (STB). Hematoxylin/Eosin stained sections were employed to analyze STB percentages, STB detachment areas and syncytial knots quantity. Non parametric Student's t-tests were performed (p < 0.05). RESULTS Syncytial knots and STB detachment significantly increased in placental villi from the CDP group. STB percentage was significantly lower in the CDP group as well as the PI and Syncytin-1 expression significantly decreased in these placentas, compared with control (NP). CONCLUSION Dynamic of trophoblast turnover is altered in placentas from women with CD. These changes may lead into a gap in the placental barrier possibly allowing the parasite entry into the chorionic villi.

Diagnostico de Chagas Congénito en el Hospital de Niños "Sor María Ludovica" / Diagnosis of Congenital Chagas in the Children's Hospital "Sor María Ludovica"

Introducción:La transmisión congénita de Trypanosoma cruzi constituye, en la actualidad, la vía que genera mayor cantidad de nuevos casos de infección aguda. El diagnóstico y tratamiento temprano aseguran una elevada probabilidad de cura parasitológica. El objetivo del trabajo fue evaluar el seguimiento de potenciales casos de Chagas Congénito, estimar la tasa de transmisión materno-fetal y la capacidad diagnóstica del microhematocrito. Materiales y métodos: Se realizó un estudio descriptivo transversal sobre hijos de mujeres con Chagas, que concurrieron al Laboratorio Central del H.I.A.E.P. Sor María Ludovica durante abril 2013-febrero 2019. Los niños fueron estudiados por microhematocrito y pruebas serológicas. Los resultados se obtuvieron del Sistema Informático de Laboratorio de Wiener®. Resultados: En el período de tiempo evaluado, fueron estudiados por microhematocrito un total de 268 niños (edad promedio= 2,35 meses), obteniéndose 16 resultados positivos. De los 252 niños con microhematocrito negativo, 58 fueron seguidos por pruebas serológicas hasta el año de vida, obteniéndose 3 resultados positivos. Se evidenció una pérdida de seguimiento serológico del 77%. La tasa de transmisión congénita estimada fue del 6,9% y el porcentaje de detección diagnóstica de la técnica directa, del 84,2%. Conclusión: La búsqueda de infección congénita en hijos de mujeres con Chagas, y su seguimiento hasta el año de vida, resulta esencial para lograr la detección y tratamiento temprano de nuevos casos. Sin embargo, la pérdida de seguimiento de potenciales casos de Chagas Congénito resulta alarmante. Esto enfatiza la necesidad de plantear estrategias sólidas para mejorar la aplicación del algoritmo diagnóstico

Introduction:Congenital Trypanosoma cruzi transmission is currently the route that generates the largest number of new cases of acute infection. Early diagnosis and treatment ensure a high probability of parasitological cure. The aim of this article was to evaluate the follow-up of possible cases of Congenital Chagas, to estimate the maternal-fetal transmission rate and the diagnostic capacity of microhematocrit. Materials and methods: A cross-sectional descriptive study was carried out on children born from Chagasic women, who attended the Central Laboratory of the H.I.A.E.P Sor María Ludovica during April 2013-February 2019. The children were studied by microhematocrit and serological tests. The results were obtained from the Wiener® Laboratory Information System. Results: In the evaluated time period, a total of 268 children (mean age = 2.35 months) were studied by microhematocrit, obtaining 16 positive results. Among the 252 children with negative microhematocrit, 58 were followed by serological tests up to one year of life, obtaining 3 positive results. A 77% loss of serological follow-up was evidenced. The estimated congenital transmission rate was 6.9% and the percentage of diagnostic detection of the direct technique was 84.2%. Conclusion: The search for congenital infection in children born from Chagasic women, and its follow-up until one year of life, is essential to achieve the early detection and treatment of new cases. However, the loss of follow-up of potential cases of Congenital Chagas is alarming. This emphasizes the need to propose solid strategies to improve the application of the diagnostic algorithm

Higher congenital transmission rate of Trypanosoma cruzi associated with family history of congenital transmission

Abstract INTRODUCTION: Congenital transmission (CT) of Trypanosoma cruzi has led to globalization of Chagas disease and its growing relevance as a public health problem. Although the occurrence of CT has been associated with several factors, its mechanisms are still unknown. This study aimed to analyze the geographical and familiar variables of mothers and their association with CT of Chagas disease in a population living in non-endemic areas of Argentina for the last decades. METHODS: We developed a retrospective cohort study in a sample of 2120 mother-child pairs who attended three reference centers in the cities of Buenos Aires, Santa Fe, and Salta between 2002 and 2015. RESULTS: The highest CT rates were observed in children born to Argentinean mothers (10.7%) and in children born to mothers from Buenos Aires (11.7%). Considering the areas of origin of the mothers, those from areas of null-low risk for vector-borne infection had higher CT rates than those from areas of medium-high risk (11.1% vs 8.2%). We also observed a significant intra-familiar "cluster effect," with CT rates of 35.9% in children with an infected sibling, compared to 8.2% in children without infected siblings (RR=4.4 95% CI 2.3-8.4). CONCLUSIONS: The associations observed suggest a higher CT rate in children born to mothers who acquired the infection congenitally, with familiar antecedents, and from areas without the presence of vectors. These observations are considered new epidemiological evidence about Chagas disease in a contemporary urban population, which may contribute to the study of CT and may also be an interesting finding for healthcare professionals.

Investigation of Chagas disease within the same family: case study / Investigação da doença de Chagas em um mesmo núcleo familiar: estudo de caso

ABSTRACT Chagas disease (CD) is a neglected endemic disease. Its classic form of transmission occurs through hematophagous triatomine insects. Its classic form of transmission occurs through hematophagous triatomine insects. There are cases of the disease in non-endemic regions that occur through alternative transmissions, as this possibility also exists. The aim of this study was to report a case among members of a same family (born and resident in Taquarituba, São Paulo, Brazil) diagnosed with CD. The family matriarch lived in a mud house in the countryside and reported contact with the triatomine during childhood. Two grown-up children are also seroreactive; both reported not having contact with the insect as children. Medical record analyzes and new laboratory tests were performed. Clinical history and recent tests have confirmed positivity for CD in the matriarch and her grown-up children. Parasitological techniques have shown negative results, evidencing that they are in the chronic form of the disease. Congenital transmission may have occurred between them, as well as the possibility of vector transmission by secondary species cannot be ruled out, since the patients come from a municipality considered endemic for CD in the past.

RESUMEN La enfermedadde Chagas (EC) es una infección endémica que ha sido descuidada. Su forma clásica de transmisión ocurre mediante insectos triatominos hematófagos. Hay casos de la enfermedad en regiones no endémicas que ocurrieron por vías alternativas de transmisión, puesto que también hay esa posibilidad. El objetivo de este estudio fue reportar un caso de miembros de una misma familia diagnosticados con EC. La matriarca de la familia vivía en una casa hecha de barro en la zona ruraly reportó contacto con el triatomino en su infancia. Dos hijosson también sero-reactivos, pero no reportaron contacto con el insecto cuando eran ninos. Se hicieron análisis de historial médico y nuevaspruebas de laboratorio. El histórico clínico y laspruebas recientes confirmaran la positividad para EC, tanto en la madre como en los hijos. Las técnicasparasitológicas demostraron resultados negativos, comprobando la forma crónica de la enfermedad. Transmisión congénitapuede haber ocurrido entre ellos, así como no se puede descartar la posibilidad de ocurrencia de transmisión vectorial por especies secundarias, ya que los pacientes proceden de un municipio que fue considerado endémico para EC en el pasado.

RESUMO A doença de Chagas (DC) é uma enfermidade endêmica negligenciada. Sua forma clássica de transmissão ocorre por meio de insetos triatomíneos hematófagos. Há casos da doença em regiões não endêmicas ocorridos por transmissões alternativas, uma vez que também existe essa possibilidade. O objetivo deste estudo foi relatar um caso de membros da mesma família (natural e residente em Taquarituba, São Paulo, Brasil) diagnosticados com DC. A matriarca da família morava em uma casa de barro na zona rural e relatou contato com o triatomíneo na infância. Dois filhos também são sororreagentes; ambos relataram não terem tido contato com o inseto quando crianças. Análises de prontuário e novos testes laboratoriais foram feitos. O histórico clínico e os recentes exames confirmaram a positividade para DC, tanto na mãe quanto nos filhos. As técnicas parasitológicas demonstraram resultados negativos, constatando forma crônica da doença. Transmissão congênita pode ter ocorrido entre eles, assim como também não se pode descartar a possibilidade de ocorrência de transmissão vetorial por espécies secundárias, visto que os pacientes são oriundos de um município considerado endêmico para DC no passado.

Congenital Chagas disease: alert of research negligence

Abstract INTRODUCTION: Chagas disease (CD), a neglected endemic disease in Latin America, has acquired new epidemiological characteristics with an increase in the importance of alternative transmission routes such as congenital transmission. We evaluated the scientific research on this subject. METHODS: We searched the Scielo, BVS, and PubMed databases from 2006 to 2017. RESULTS: We identified a small number of published articles, mostly in journals with an impact factor less than 3.0. Studies on human congenital transmission of CD were carried out in only seven different countries. CONCLUSIONS: Our data highlight the lack of research on congenital CD.

Congenital Chagas disease: an update

Congenital infection with Trypanosoma cruzi is a global problem, occurring on average in 5% of children born from chronically infected mothers in endemic areas, with variations depending on the region. This presentation aims to focus on and update epidemiological data, research methods, involved factors, control strategy and possible prevention of congenital infection with T. cruzi. Considering that etiological treatment of the child is always effective if performed before one year of age, the diagnosis of infection in pregnant women and their newborns has to become the standard of care and integrated into the surveillance programs of syphilis and human immunodeficiency virus. In addition to the standard tests, polymerase chain reaction performed on blood of neonates of infected mothers one month after birth might improve the diagnosis of congenital infection. Recent data bring out that its transmission can be prevented through treatment of infected women before they become pregnant. The role of parasite genotypes and host genetic factors in parasite transmission and development of infection in foetuses/neonates has to be more investigated in order to better estimate the risk factors and impact on health of congenital infection with T. cruzi.

Primer consenso colombiano sobre Chagas congénito y orientación clínica a mujeres en edad fértil con diagnóstico de Chagas / First Colombian consensus on congenital Chagas and clinical approach to women of fertile age diagnosed with Chagas

La transmisión congénita de la enfermedad de Chagas ha sido poco estudiada en Colombia y existen pocos procedimientos rutinarios en el sistema de salud para el manejo de esta enfermedad. Por ello se desarrolló un consenso de expertos dirigido a generar recomendaciones de diagnóstico y tratamiento de Chagas congénito y orientación a mujeres en edad fértil. Con ese propósito se realizó una búsqueda extensiva de la literatura, empleando una combinación de términos MeSH (Chagas, Chagas congénito, prevención, control, diagnóstico, tratamiento y embarazo) para reflejar el estado del arte en cada tema de interés. Después de ello, se leyeron los resúmenes y aquellos seleccionados para análisis del texto completo. La literatura relevante se sintetizó, clasificó y organizó en tablas y se presentó al panel de expertos, el cual estaba constituido por 30 profesionales en diferentes áreas. Mediante la metodología Delphi se realizaron 2 rondas de cuestionarios virtuales y una reunión presencial en los cuales se evaluaron los niveles de acuerdo entre los participantes. Los puntos con falta de consenso durante las 2 rondas virtuales se expusieron durante las mesas de discusión en la ronda presencial. La evidencia utilizada se adaptó a las particularidades nacionales según el caso y se aprobó el contenido del documento final. Se propone que estas recomendaciones sean usadas por profesionales de la salud en Colombia.

Congenital transmission of Chagas disease has not been extensively studied in Colombia, and there are no standardized processes in the health system regarding the specific diagnosis, treatment and follow-up of this disease. In order to generate recommendations on congenital Chagas disease and Chagas in women of childbearing age in Colombia, a consensus of experts was developed. An extensive literature search through the Medline database was carried out using the MeSH terms: " Chagas disease/congenital " , " prevention and control " , " diagnosis " , " therapeutics " and " pregnancy " . Appropriate abstracts were selected and the full texts were analyzed. The relevant information was synthesized, classified, and organized into tables and figures and was presented to a panel of experts, which was composed of 30 professionals from various fields. Based on the Delphi methodology, three rounds of consultation were conducted. The first and second rounds were based on electronic questionnaires that measured the level of consensus of each question among the participants. The third round was based on a face-toface discussion focusing on those questions without consensus in the previous consultations. The evidence was adapted to national circumstances on a case-by-case basis, and the content the final document was approved. These recommendations are proposed for use in routine medical practice by health professionals in Colombia.

Doença de Chagas congênita com manifestações pleomórficas: relato de caso / Congenital Chagas disease in adolescent with pleomorphic manifestations: case report

JUSTIFICATIVA E OBJETIVOS: A doença de Chagas é uma infecção parasitária, endêmica, em várias regiões do Brasil. Nas últimas décadas, a via de transmissão predominante foi modificada de vetorial para congênita, devido ao êxodo rural e aos métodos mais eficazes de combate aos vetores. Alguns pacientes jovens apresentam manifestações crônicas e intensas, consequentes da transmissão congênita. O objetivo deste estudo foi relatar um caso de uma paciente com doença de Chagas de transmissão vertical com manifestações variadas da doença. Ressalta-se a importância de se conhecer diversas formas de transmissão e, ademais, enfatiza-se a importância de realizar adequado pré-natal em áreas endêmicas para possível diagnóstico, tratamento precoce e acompanhamento clínico. RELATO DO CASO: Paciente do sexo feminino, 20 anos, solteira, apresentando há 8 meses dispneia aos mínimos esforços, precordialgia, epigastralgia e tosse seca, evoluindo com disfagia, confirmando-se o diagnóstico de insuficiência cardíaca com exames complementares. A investigação prosseguiu com provas sorológicas, eletrocardiograma, radiografia do coração e vasos da base (RCVB), Ecodopplercardiograma, confirmando-se: IgG positivo para Chagas em dois testes sorológicos (hemaglutinação indireta e imunofluorescência para T. Cruzi), alterações eletrocardiográficas difusas, megaesôfago grau II, cardiomegalia grau III. Foi realizado tratamento etiológico com benzonidazol (Rochagan®) para doença de Chagas crônica de início recente. Apesar da dificuldade na obtenção dos exames complementares,objetivando maior acurácia no diagnóstico e melhor acompanhamento do tratamento, concluiu-se que era um caso de doença de Chagas congênita, uma vez que a história familiar era positiva e a paciente não teve contato com triatomídeos (morou sempre na área urbana) e a transmissão vetorial está diminuindo devido às campanhas de erradicação dos vetores...

BACKGROUND AND OBJECTIVES: Chagas disease is a parasitic infection, endemic in several regions of Brazil. In recent decades the predominant route of transmission changed from vectorial to congenital, due to rural exodus and more effective methods for fighting the vectors. Some young patients have chronic and severe manifestations due to congenital transmission. The aim of this study was to report a case of a young adult patient with Chagas disease vertical transmission, with varied clinical manifestations of the disease. The importance of knowing the various forms of transmission was emphasized and also of the importance of prenatal assistance in endemic areas for possible early diagnosis, treatment and clinical follow up. CASE REPORT: Female patient, 20 years old, single, has presented experiencing, for the previous 8 months, dyspnea on exertion, constrictive chest pain, epigastric pain, and dry cough associated with progressive dysphagia; the diagnosis of heart failure was confirmed by complementary tests. The investigation progressed with serological tests, electrocardiogram, chest teleradiograph, echodopplercardiogram, confirming: IgG positive for Chagas disease, in two different serological tests (indirect hemagglutination assay and immunofluorescence for T cruzi), diffuse electrocardiographic changes, grade II megaesophagus, grade III cardiomegaly. Etiological treatment was conducted with benzonidazol (Rochagan®) for chronic Chagas disease of recent onset. Despite the difficulty in obtaining additional tests, aiming greater accuracy in the diagnosis and better monitoring of the treatment, it was concluded that it was a case of congenital Chagas disease, since family history is positive and the patient denied having contact with triatomids (hematophagus bugs) as she has always lived in urban areas, and because vectorial transmission is declining due to campaigns for eradication of the vectors...

Vertical transmission of Trypanosoma cruzi in the Province of Choapa, IV Region, Chile: Preliminary Report (2005-2008)

Congenital Chagas disease acquired special importance in Chile after the certification of the control of Triatoma infestans and transmission by blood donors affected with Trypanosoma cruzi. In order to establish adequate protocols for intervention and control in infected mother-neonate pairs in endemic zones of Chagas disease, we present partial results (2005-2008) of a pilot project which is being carried out in the Province of Choapa, IV Region, Chile, whose objectives are: determine the current prevalence of the disease in pregnant women, estimate the incidence of vertical transmission of T. cruzi to newborns, determine the lineages of the parasite present in mothers who do and do not transmit the disease, determine the prevalence of Chagas disease in maternal grandmothers of neonates and study placental histopathology. Preliminary results indicated that in this study period, 3.7 percent of the women who gave birth in the Province have Chagas disease and 2.5 percent of their newborns were infected. The most frequent T. cruzi genotypes found in mothers studied during pregnancy were TCI and TCIId, either alone or in mixed infections. A high percentage (74.3 percent) of the grandmothers studied was infected with the parasite. In 29 placentas from mothers with Chagas disease we observed edema, necrosis, fibrinoid deposits and slight lymphoplasmocyte infiltration. In three placentas we found erythroblastosis and in one of them amastigote forms of T. cruzi; this was one of the cases of congenital infection. The evaluation of the diagnostic and control protocols generated will allow us to determine if it has been possible to modify the natural history of vertical transmission of T. cruzi in Chile.

Infection and invasion mechanisms of Trypanosoma cruzi in the congenital transmission of Chagas' disease: A proposal

Chagas' disease is produced by the haemophlagelated protozoan Trypanosoma cruzi and transmitted by haematophages insects such as Triatoma infestans (vinchuca). Due to vector control, congenital transmission gains importance and is responsible for the presence and expansion of this disease in non-endemic areas. The mechanisms of congenital infection are uncertain. It has been suggested that the parasite reaches the fetus through the bloodstream by crossing the placental barrier, and that congenital Chagas' disease is the result of complex interactions between the immune response, placental factors, and the parasite's characteristics. We review the cellular and molecular mechanisms of infection and invasion of the parasite and how immune and placental factors may modulate this process. Finally, we propose a possible model for the vertical transmission of Chagas' disease.

Triagem neonatal para infecção chagásica congênita: aplicação de análise de classe latente para avaliação dos testes diagnósticos / Neonatal screening for congenital Chagas infection: application of latent class analysis for diagnostic test evaluation

O presente estudo tem como objetivo avaliar os testes sorológicos convencionais usados na triagem neonatal para doença de Chagas, discutindo métodos estatísticos disponíveis. Estudou-se uma amostra aleatória dentre 23.308 recém-nascidos triados para doença de Chagas congênita por meio de três testes: imunoensaioenzimático, imunofluorescência indireta e hemoaglutinação indireta. Os dados obtidos foram analisados por diferentes metodologias estatísticas: a análise de classe latente, o teste Kappa e a análise de sensibilidade relativa. Utilizando a análise de classe latente, a maior sensibilidade foi do imunoensaioenzimático (48,6 por cento), seguido pela imunofluorescência indireta (39,8 por cento) e pela hemoaglutinação indireta (23,2 por cento). O valor Kappa foi 0,496. A razão entre as sensibilidades dos testes imunoensaioenzimático e imunofluorescência indireta foi de 92 por cento [0,74;1,13]. A análise de classe latente não se mostrou adequada para determinação de sensibilidade e especificidade, mas forneceu dados importantes sobre a equivalência dos testes, corroborados pela análise de sensibilidade relativa. Os resultados mostraram que o teste imunoensaioenzimático em sangue-seco pode ser utilizado com a mesma segurança do teste imunofluorescência indireta.

The present study had the aim of evaluating conventional serum tests that are used in neonatal screening for Chagas disease, with a discussion on the statistical methods available. A random sample among 23,308 newborns who were screened for congenital Chagas disease was studied using the following three tests: enzyme immunoassay, indirect immunofluorescence and indirect hemagglutination. The data were analyzed by different statistical methodologies: latent class analysis, Kappa test and relative sensitivity analysis. Using latent class analysis, enzyme immunoassay had the highest sensitivity (48.6 percent), followed by indirect immunofluorescence (39.8 percent) and indirect hemagglutination (23.2 percent). The kappa value was 0.496. The ratio between the sensitivities of enzyme immunoassays and indirect immunofluorescence tests was 92 percent [0.74;1.13]. Latent class analysis was not found to be adequate for sensitivity and specificity determination, but it provided important data about the equivalence of the tests, corroborated by relative sensitivity analysis. The results showed that enzyme immunoassaying of dry blood samples can be used as safely as the indirect immunofluorescence test.

Seqüência de transmissões não habituais da infecção chagásica em uma mesma família: transfusional para a mãe e congênita para o filho, de cepa de Trypanosoma cruzi resistente ao tratamento / Sequence of unusual Chagas infection transmissions in the same family: mother by blood transfusion and child congenitally, with a treatment-resistant strain of Trypanosoma cruzi

Os autores apresentam dois casos de transmissão não habitual da infecção chagásica em uma mesma família: a mãe, por transfusão sangüínea e seu segundo filho, via transplacentária. O diagnóstico da criança foi acidental e a resposta ao tratamento etiológico, em ambos, foi ineficaz em erradicar a parasitemia. Atualmente, mãe e filho permanecem em forma indeterminada da doença.

The authors present two cases of unusual transmission of Chagas infection in the same family: the mother by blood transfusion and her second child across the placenta. The child was diagnosed by chance and etiological treatment for both the mother and the child was ineffective in eradicating the parasitemia. At present, they continue to present the indeterminate form of the disease.