The Trypanosoma cruzi pleiotropic protein P21 orchestrates the intracellular retention and in-vivo parasitism control of virulent Y strain parasites.

P21 is a protein secreted by all forms of Trypanosoma cruzi (T. cruzi) with recognized biological activities determined in studies using the recombinant form of the protein. In our recent study, we found that the ablation of P21 gene decreased Y strain axenic epimastigotes multiplication and increased intracellular replication of amastigotes in HeLa cells infected with metacyclic trypomastigotes. In the present study, we investigated the effect of P21 in vitro using C2C12 cell lines infected with tissue culture-derived trypomastigotes (TCT) of wild-type and P21 knockout (TcP21-/-) Y strain, and in vivo using an experimental model of T. cruzi infection in BALB/c mice. Our in-vitro results showed a significant decrease in the host cell invasion rate by TcP21-/- parasites as measured by Giemsa staining and cell count in bright light microscope. Quantitative polymerase chain reaction (qPCR) analysis showed that TcP21-/- parasites multiplied intracellularly to a higher extent than the scrambled parasites at 72h post-infection. In addition, we observed a higher egress of TcP21-/- trypomastigotes from C2C12 cells at 144h and 168h post-infection. Mice infected with Y strain TcP21-/- trypomastigotes displayed higher systemic parasitemia, heart tissue parasite burden, and several histopathological alterations in heart tissues compared to control animals infected with scrambled parasites. Therewith, we propose that P21 is important in the host-pathogen interaction during invasion, cell multiplication, and egress, and may be part of the mechanism that controls parasitism and promotes chronic infection without patent systemic parasitemia.

Arrhythmogenic Manifestations of Chagas Disease: Perspectives From the Bench to Bedside.

Chagas cardiomyopathy caused by infection with the intracellular parasite Trypanosoma cruzi is the most common and severe expression of human Chagas disease. Heart failure, systemic and pulmonary thromboembolism, arrhythmia, and sudden cardiac death are the principal clinical manifestations of Chagas cardiomyopathy. Ventricular arrhythmias contribute significantly to morbidity and mortality and are the major cause of sudden cardiac death. Significant gaps still exist in the understanding of the pathogenesis mechanisms underlying the arrhythmogenic manifestations of Chagas cardiomyopathy. This article will review the data from experimental studies and translate those findings to draw hypotheses about clinical observations. Human- and animal-based studies at molecular, cellular, tissue, and organ levels suggest 5 main pillars of remodeling caused by the interaction of host and parasite: immunologic, electrical, autonomic, microvascular, and contractile. Integrating these 5 remodeling processes will bring insights into the current knowledge in the field, highlighting some key features for future management of this arrhythmogenic disease.

Hydroxymethylnitrofurazone (NFOH) decreases parasitaemia, parasitism and tissue lesion caused by infection with the Bolivia Trypanosoma cruzi type I strain in Swiss and C57BL/6 mice

Abstract The chemical hydroxymethylation of the antimicrobial nitrofurazone leads to the prodrug NFOH, also increases the anti-T. cruzi activities (in vitro and in vivo), as well as showed non-genotoxic (Ames and micronucleus assays). In the present study, we assessed the anti-T. cruzi effect of the NFOH In vivo - in acute Swiss and C57Bl/6 experimental Chagas models. The treatment started at 5 days post-infection during 20 consecutive days (orally, once day, 150mg/kg), and the parasitaemia as well as histopathology analysis were performed. In both experimental murine models, NFOH was able to reduce parasitemia blood avoiding parasitic reactivation, during immunosuppression period (dexamethasone 5mg/kg, 14 days), in 100% of the mice, and decrease tissue parasite nests, demonstrating absence of amastigote forms in all organs (100%) analyzed, data similar to benznidazole (BZN). Therefore, the results shown here pointing to the NFOH as promising compound for further preclinical studies, being a high potential drug to effective and safe chemotherapy to Chagas disease.

The B-blocker carvedilol and the benznidazole modulate the cardiac immune response in the acute infection induced by Colombian strain of the Trypanosoma cruzi

BACKGROUND The infection led by Trypanosoma cruzi persists in mammalian tissues causing an inflammatory imbalance. Carvedilol (Cv), a non-selective beta blocker drug indicated to treat heart failure and antihypertensive has shown to promote antioxidant and immunomodulatory properties which might improve the inflammation induced by T. cruzi. OBJECTIVES Evaluate the role of Cv on the inflammatory response of C57BL/6 mice acutely infected with the Colombian strain of T. cruzi. METHODS Animals were infected with the Colombian strain of T. cruzi and treated with Cv (25 mg/kg/day), benznidazole (Bz) (100 mg/kg/day) or their combination. On the 28th day of infection and 23 days of treatment, the euthanasia occurred, and the heart preserved for histopathological, oxidative stress (SOD, catalase, TBARs, carbonylated proteins) and plasma (CCL2, CCL5, TNF, IL-10) analyses. Parasitaemia and survival were assessed along the infection. FINDINGS Cv decreased TBARs, but increased the mortality rate, the parasitaemia and the levels of CCL2, CCL5, catalase and the inflammatory infiltrate in the cardiac tissue. Bz led the reduction of the inflammatory infiltrate and circulating levels of oxidative stress and inflammatory mediators in the infected mice. MAIN CONCLUSIONS Our data suggest that Cv, in this experimental model using the Colombian strain of T. cruzi, caused damage to the host.

Busca por inibidores seletivos de Sirtuína 2 de T. cruzi empregando técnicas de planejamento de fármacos baseadona estrutura do receptor / Search for selective inhibitors of T. cruzi Sirtuin 2 employing drug design techniques based on receptor structure

A doença de Chagas, causada pelo parasita Trypanosoma cruzi, acomete entre 6 a 8 milhões de pessoas em todo o mundo. Conhecida como tripanossomíase americana, por ter sido considerada endêmica apenas na América Latina, esta doença, se espalhou para outros continentes devido aos movimentos migratórios se tornando um problema de sáude mundial. Estima-se que 56.000 novos casos e cerca de 12.000 mortes por complicações relacionadas à doença de Chagas anualmente. A quimioterapia disponível para o tratamento é composta apenas por dois fármacos, nifurtimox e benznidazol, no entanto são pouco eficazes na fase crônica da doença. Estes fármacos apresentarem, ainda, efeitos adversos graves e resistência por parte de algumas cepas do parasita. Diante deste panorama, é iminente a necessidade da busca de novos fármacos contra T. cruzi. Para a busca racional de novos quimiterapicos antiparasitários é fundamental a identificação e caracterização de vias metabólicas essenciais à sobrevivência dos parasitas. Assim, a enzima sirtuína 2 - Silent Information Regulator 2 (Sir2), tem importante papel para a infecção por T. cruzi, pois está totalmente envolvida no seu ciclo celular do parasita. Esta é uma enzima NAD+ dependente da classe III histona desacetilases, e se mostra como um interessante alvo bioquímico para o desenvolvimento de antichagásicos. A disponibilidade do sequenciamento genômico da Sir2 nos permite utilizar estratégias de planejamento de fármaco baseado no receptor (SBDD - Structure Based Drug Design) na identificação de candidatos a fármacos para essa doença. Entre as técnicas modernas de SBDD utilizadas, a triagem virtual possibilita identificar e selecionar inibidores enzimáticos potentes e seletivos para o alvo escolhido. Assim, neste trabalho, foi construído por meio da técnica de modelagem comparativa o modelo da enzima Sir2 de T. cruzi. Uma simulação por dinâmica molecular de 200ns, foi realizada para averiguar a estabilidade do modelo obtido. Diante da estabilização do modelo a partir de 100ns, o mesmo foi validado utilizando análise de clusters, RMSD (Root-mean-square Deviation) e análises de frequência de ligações de hidrogênio com o Cofator (NAD+) e os aminoácidos do sítio de catálise foram observadas, estes passos de simulação e validação foram realizados no programa DESMOND. Com o modelo robusto, os campos de interações moleculares (MIFs) foram gerados no programa GRID (Molecular Discovery v2.1) com o intuito de elucidar as regiões favoráveis a interação com a enzima em relação a propriedades físico-químicas da Sir2. A partir dos MIFs favoráveis a Sir2 de T. cruzi foi possível a construção de dois modelos farmacofóricos, o qual se baseou nas interações do Cofator (NAD+) e o sítio de catálise (Nicotinamida). O mesmo foi apliacdo como filtro para Triagem Virtual no programa UNITY da plataforma SYBYL X 2.0, utilizando os bancos de dados ZINC15 e GSK. A triagem resultou na seleção de 8 compostos candidatos a inibidores. Destes foram adquiridos 6 compostos por serem considerados mais promissores devido a complementariedade molecular. Estes foram testados contra a enzima de T. cruzi Sri2. Após o ensaio foi possível avaliar a potência de 4 compostos, sendo o composto CDMS-01 (IC50 = 39,9uM) o mais promissor que será submetido à processos de otimização molecular

Chagas disease, caused by the parasite Trypanosoma cruzi, affects between 6 and 8 million people worldwide. Also known as American trypanosomiasis, because it is considered endemic only in Latin America, but has spread to other continents due to migratory movements. It is estimated that 56,000 new cases and about 12,000 deaths from complications related to Chagas disease annually. The chemotherapy available for treatment consists of only two drugs, nifurtimox and benznidazole, however these are poorly effective in the chronic phase. These drugs also have serious adverse effects and resistance from strains of the parasite. Faced with this scenario, the need to search for new drugs against T. cruzi is imminent. For the drug planning for new antiparasitic chemotherapics, the identification and characterization of metabolic pathways essential to the survival of parasites is fundamental. Therewith, the sirtuin 2 - Silent Information Regulator 2 (Sir2) enzyme has an important role for T. cruzi infection, since Sir2 in the parasite is totally involved in its cell cycle. This is an NAD+-dependent enzyme of class III histone deacetylases, and it shows an interesting biochemical target for the development of antichagasic. The availability of Sir2 genomic sequencing allows us to use SBDD (Structure Based Drug Design) strategies in identifying drug candidates for this disease. Among the modern techniques of SBDD used, virtual screening makes it possible to identify and select potent and selective enzyme inhibitors for the chosen target. The model of the T. cruzi Sir2 enzyme was constructed using the comparative modeling technique. A molecular dynamics simulation of 200ns was performed to ascertain the stability of the obtained model. Considering the stabilization of the model from 100ns, it was validated using cluster analysis, Root-mean-square Deviation (RMSD) and hydrogen bond frequency analyzes with Cofator (NAD+) and the amino acids of the catalysis site were observed, these simulation and validation steps were performed in the DESMOND program. With the robust model, the molecular interaction fields (MIFs) were generated in the GRID program (Molecular Discovery v2.1) in order to elucidate the regions favorable to the interaction with the enzyme in relation to the physicalchemical properties of Sir2. From the MIFs favorable to Sir2 of T. cruzi it was possible to construct two pharmacophoric models, which was based on the interactions of Cofator (NAD+) and the catalysis site (Nicotinamide). It was also applied as a Virtual screening filter in the UNITY program of the SYBYL X 2.0 platform, using the ZINC15 and GSK databases. Screening resulted in the selection of 8 inhibitor candidate compounds. Six compounds were obtained from the screening, because they were considered more promising, and were tested against T. cruzi Sri2 enzyme. After the assay it was possible to evaluate the potency of 4 compounds, the most promising compound being CDMS-01 (IC50 = 39.9 µM) that will be submitted to molecular optimization processes

Compromiso gastrointestinal por Triypanosoma cruzi: ¿cuándo buscar y cuándo tratar? / Digestive involvement by Trypanosoma cruzi: when to look for it and when to treat

Chagas disease is an endemic zoonosis that can cause chronic medical complications in a third of those infected, usually decades after infection. It mainly affects the peripheral nervous system of heart, esophagus and colon. At digestive level, motor dysfunction leads to the development of megaesophagus and megacolon whose predominant symptoms are dysphagia and constipation. It should be suspected in patients with epidemiological history and compatible symptoms. In the chronic phase it is confirmed with the detection of specific antibodies. The etiological treatment is effective in early stages after infection. In the chronic stage the management is symptomatic, medical and/or surgical.

La enfermedad de Chagas es una zoonosis endémica que puede producir complicaciones médicas crónicas en un tercio de los infectados, habitualmente décadas luego de la infección. Afecta principalmente el sistema nervioso periférico de corazón, esófago y colon. A nivel digestivo la disfunción motora lleva a la formación de megaesófago y megacolon cuyos síntomas predominantes son disfagia y constipación. Debe sospecharse en pacientes con antecedentes epidemiológicos y síntomas compatibles. En la fase crónica se confirma con la detección de anticuerpos específicos. El tratamiento etiológico es efectivo en las fases tempranas post-contagio. En la etapa crónica el manejo es sintomático, médico y/o quirúrgico.

Cribado in situ de la enfermedad de Chagas con una intervención comunitaria: ¿puede mejorar la accesibilidad al diagnóstico y al tratamiento? / On site-screening for Chagas disease supported by a community intervention: can it improve accessibility for diagnosis and treatment?

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Sympatry influence in the interaction of Trypanosoma cruzi with triatomine

Abstract INTRODUCTION: Trypanosoma cruzi, the etiologic agent of Chagas disease, is widely distributed in nature, circulating between triatomine bugs and sylvatic mammals, and has large genetic diversity. Both the vector species and the genetic lineages of T. cruzi present a varied geographical distribution. This study aimed to verify the influence of sympatry in the interaction of T. cruzi with triatomines. Methods: The behavior of the strains PR2256 (T. cruzi II) and AM14 (T. cruzi IV) was studied in Triatoma sordida (TS) and Rhodnius robustus (RR). Eleven fifth-stage nymphs were fed by artificial xenodiagnosis with 5.6 × 103 blood trypomastigotes/0.1mL of each T. cruzi strain. Every 20 days, their excreta were examined for up to 100 days, and every 30 days, the intestinal content was examined for up to 120 days, by parasitological (fresh examination and differential count with Giemsa-stained smears) and molecular (PCR) methods. Rates of infectivity, metacyclogenesis and mortality, and mean number of parasites per insect and of excreted parasites were determined. RESULTS: Sympatric groups RR+AM14 and TS+PR2256 showed higher values of the four parameters, except for mortality rate, which was higher (27.3%) in the TS+AM14 group. General infectivity was 72.7%, which was mainly proven by PCR, showing the following decreasing order: RR+AM14 (100%), TS+PR2256 (81.8%), RR+PR2256 (72.7%) and TS+AM14 (36.4%). CONCLUSIONS: Our working hypothesis was confirmed once higher infectivity and vector capacity (flagellate production and elimination of infective metacyclic forms) were recorded in the groups that contained sympatric T. cruzi lineages and triatomine species.

Necesidad de cribado de enfermedad de Chagas y de infestación por Strongyloides previo a inicio de terapia biológica en países no endémicos / Need to screen for Chagas disease and Strongyloides infestation in non-endemic countries prior to treatment with biologics

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Complicaciones colónicas agudas en paciente con enfermedad de Chagas / Acute colonic complications in a patient with Chagas disease

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Asistolia momentánea por degenaración del sistema de conducción cardiaca / Momentary asystolia due to degeneration of the cardiac conduction system

Se presenta el caso de una persona de género masculino, de 38 años de edad, sin antecedentes médicos personales o familiares, originario de Jutiapa, residente de ciudad de Guatemala, con historia de síncope, a la evaluación inicial con Bloqueo de Rama Derecha, el monitoreo electrocardiográfico de Holter encontró pausa sinusal de 13 segundos y bradicardia. Encontramos anticuerpos para Trypanosoma Cruzi así como hallazgo incidental de Esclerosis Sistémica a través de reactividad de la proteína ribosomal (Rib-P) y SCL-70 aunque sin presentar cuadro clínico habitual...(AU)

This case report of man, 38 years old, without medical history, born in Jutiapa, resident in Guatemala City, consult for syncope, in the initial evaluation shown in electrocardiogram Right Bundle Branch Block, the Holter monitoring found pause of 13 seconds, and bradycardia. Aditional laboratory test found antibodies to Trypanosoma Cruzi, and incidental finding Systemic Sclerosis through reactivity of the ribosomal P and SCL-70 protein but without showing usual clinical sings or symptoms...(AU)

Actividad tripanocida de Piper solmsianum C. DC. sobre formas epimastigota y tripomastigota de Trypanosoma cruzi / Trypanocidal activity of Piper solmsianum C. DC. against epimastigote and trypomastigote forms of Trypanosoma cruzi

Introducción: la infección por Trypanosoma cruzi, conocida como enfermedad de Chagas, es un problema importante de salud pública en países de América Central y Sudamérica.Objetivo: evaluar la actividad de extractos crudos de acetato de etilo de plantas in vitro de 6-8 meses y 10-12 meses de edad, de tallos leñosos y hojas de plantas silvestres maduras y el lignano tetrahidrofurano grandisina, aislados de Piper solmsianum, sobre las formas epimastigota y tripomastigota de T. cruzi in vitro.Métodos: en la evaluación del efecto de diversos extractos crudos de acetato de etilo y grandisina de P. solmsianum, sobre la viabilidad de las formas epimastigota y tripomastigota de T. cruzi, se utilizó el método MTT (3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium bromuro).Resultados: en la forma epimastigota, el mejor resultado en la inhibición del crecimiento fue obtenido con 50 µg/mL de extracto de tallo y en la forma tripomastigota con 25 y 50 µg/mL de grandisina y plantas in vitro de 6-8 meses de edad, respectivamente. En todos los casos los valores de inhibición oscilaron entre 86 a 96 por ciento. Plantas in vitro de 6-8 meses de edad y grandisina fueron más activas sobre las formas epimastigota y tripomastigota de T. cruzi con valores de CI50 de 0,018 y 0,360 µg/mL, respectivamente.Conclusiones: se demuestra la actividad tripanocida de extractos de plantas silvestres y plantas in vitro de P. solmsianum(AU)

Introduction: the infection by Trypanosoma cruzi, known as Chagas' disease, poses a major public health problem in Central and South America countries.Objective: to evaluate the activity of crude ethyl acetate extracts from in vitro plants of 6-8 and 10-12 months of age, stem barks and mature wild plant leaves and tetrahydrofuran lignin grandisin isolated from Piper solmsianum against the epimastigote and trypomastigote forms of T. cruzi in vitro.Methods: in the evaluation of the effect of various crude ethyl acetate extracts and grandisin from P. solmsianum on the viability of epimastigote and trypomastigote forms of T. cruzi, the MTT method (3-(4,5-dimethylthiazol-2-il)-2,5-diphenyltetrazolium bromide) was used.Results: in the epimastigote form, the best results in growth inhibition was obtained with 50 µg/mL of stem extract, and in the trypomastigote form, with 25 and 50 µg/mL of grandisin and 6-8 months-old in vitro plants, respectively. The inhibition values in all cases ranged from 86 to 96 percent. 6-8 months old in vitro plants and grandisin were found to be active against the epimastigote and trypomastigote forms of T. cruzi with IC50 of 0.018 µg/mL and 0.360 µg/mL, respectively.Conclusions: the trypanocidal activity of extracts from wild plants and in vitro plants of P. solmsianum was proved(AU)

Actualización en enfermedad de Chagas / Update Chagas diseas

Los constantes flujos migratorios han favorecido la presencia de personas con la enfermedad de Chagas en regiones clásicamente consideradas como no endémicas, como Estados Unidos, Europa, Asia y Oceanía. Este hecho ha obligado tanto a las autoridades sanitarias como a los profesionales a tener que actualizarse para poder dar respuesta a tal demanda asistencial. Los últimos años han supuesto un gran avance tanto en el campo del diagnóstico como del tratamiento de la enfermedad de Chagas, una de las enfermedades tropicales más olvidadas. Ensayos clínicos recientes están arrojando nuevas evidencias que hacen que el manejo de estos pacientes sea un desafío constante para los profesionales involucrados. Novedosas herramientas diagnósticas y esquemas terapéuticos hacen que veamos el futuro de la enfermedad de Chagas con optimismo

The constant migration flows have favored the presence of people with Chagas disease in regions traditionally regarded as non-endemic, such as North America, Europe, Asia and Oceania. This has forced both health authorities and professionals to be updated in order to respond to such a demand for assistance. Recent years have led to significant progress in the field of diagnosis and treatment of Chagas disease, one of the most neglected tropical diseases. Recent clinical trials are providing new evidence that makes the management of these patients, a constant challenge for the professionals involved. Innovative diagnostic tools and therapeutic regimens, allow us to face the future of Chagas disease with optimism

Papel da galectina-3 na patogênese no tratamento da miocardiopatia chagásica crônica / Role of galectin-3 in pathogenesis in the treatment of chronic chagasic cardiomyopathy

INTRODUÇÃO: A doença de Chagas é uma relevante causa de insuficiência cardíaca na América Latina, onde cerca de 30% dos indivíduos infectados por Trypanosoma cruzi desenvolvem a cardiopatia chagásica crônica (CCC). Fatores relacionados à interação parasito-hospedeiro, resposta imune, reparo e regeneração tecidual participam da fisiopatologia da doença. A identificação de novos alvos terapêuticos depende de um melhor entendimento destes processos. Anteriormente, demonstramos que a galectina-3 (Gal-3), uma lectina com capacidade de ligação a β-galactosídeos, é superexpressa no tecido cardíaco em um modelo experimental de CCC. OBJETIVOS: O objetivo deste estudo foi investigar o papel exercido pela Gal-3 na patogênese da CCC e seu potencial uso como alvo terapêutico. MATERIAIS E MÉTODOS: A expressão de Gal-3 foi avaliada no coração de camundongos C57Bl/6...

INTRODUCTION: Chagas disease is a relevant cause of heart failure in Latin America, where about 30% of individuals infected with Trypanosoma cruzi develop chronic Chagas' disease cardiomyopathy (CCC). Several factors related to host-parasite interactions, immune response, tissue repair and regeneration participate in the pathophysiology of the disease. The identification of novel therapeutic targets relies on a better understanding of these processes. Previously, we have demonstrated that the galectin-3 (Gal-3) - a β-galactoside binding lectin - is overexpressed in the cardiac tissue in an experimental model of CCC. AIM: The aim of this study was to investigate the role of Gal-3 in the pathogenesis of CCC and its potential use as a therapeutic target. MATERIALS AND METHODS: The expression of Gal-3 was assessed in the hearts of T. cruzi infected C57BL/6...

Trypanosoma cruzi -infected Triatoma gerstaeckeri (Hemiptera: Reduviidae) from Nuevo León, México, and pathogenicity of the regional strain / Triatoma gerstaeckeri (Hemiptera: Reduviidae) infectada con Trypanosoma cruzi en Nuevo León, México, y capacidad patógena de la cepa regional

Introduction: Four species of triatomines have been reported in Nuevo León, northeast (NE) México, but Triatoma gerstaeckeri has only been recorded from a peridomestic dwelling. Objectives: To assess the natural infection index (NII) of Trypanosoma cruzi in triatomines and the infestation index (II) of T. gerstaeckeri collected in a suburban locality, and to collect histopathological data to understand tissue tropism of the regional T. cruzi strain (strain NE) obtained from the vectors collected after an experimental inoculation in Mus musculus . Materials and methods: Triatomines were collected from 85 houses and peridomiciles in Allende, Nuevo León. Stool samples were obtained to determine the T. cruzi NII and were used in an experimental mice infection. Results: A total of 118 T . gerstaeckeri were captured, and 46 (adults and nymphs) were collected inside the same house (II=1.17%). Thirty-seven reduvids were infected with T. cruzi (NII=31.3%). Tissue tropism of the T. cruzi NE strain was progressive in skeletal muscle, myocardial, and adipose tissues and was characterized by the presence of intracellular amastigotes and destruction of cardiac myocells. Conclusions: The presence of naturally infected domiciliary vectors is an important risk factor for public health in the region considering that these vectors are the principal transmission mechanism of the parasite. The T. cruzi NE strain has similar virulence to that of other Mexican and Texan strains and caused chagasic infections in 11 of 12 mice.

Introducción. En Nuevo León, localizado en el noreste de México, existen cuatro especies de triatominos, de las cuales Triatoma gerstaeckeri ha sido la única reportada en peridomicilios. Objetivos. Evaluar el índice de infección natural de Trypanosoma cruzi en los triatominos y el índice de infestación de T. gerstaeckeri en una localidad suburbana, y obtener datos histopatológicos para comprender el tropismo tisular de la cepa regional (cepa NE) de T. cruzi obtenida de los vectores recolectados después de la infección experimental en Mus musculus. Materiales y métodos. La recolección de triatominos se llevó a cabo en 85 casas y peridomicilios de Allende, Nuevo León, México. Se obtuvieron muestras de las deyecciones para conocer el índice de infección natural por T. cruzi y, con estas, se hicieron inoculaciones experimentales en ratones. Resultados. Se capturaron 118 especímenes de T. gerstaeckeri , 46 (adultos y ninfas) en el mismo domicilio (índice de infestación=1,17 %). Treinta y siete redúvidos estaban infectados con T. cruzi (índice de infección natural, 31,3). El tropismo tisular de la cepa NE de T. cruzi fue progresivo en músculo esquelético, miocardio y tejido adiposo, y se caracterizó por la presencia de amastigotes intracelulares con destrucción de células cardiacas. Conclusiones. La presencia de vectores domiciliarios naturalmente infectados con T. cruzi , es un factor de riesgo importante para la salud pública de la región, considerando que este es el principal mecanismo de la transmisión del parásito y que la cepa NE de T. cruzi tiene una virulencia similar a la de otras cepas mexicanas y texanas, y causó infección chagásica en 11 de los 12 ratones inoculados.

Prevalence of Chagas disease in the Bolivian population of Majorca (Spain) / Prevalencia de la enfermedad de Chagas en población boliviana de Mallorca (España)

Objective: To establish the prevalence of Trypanosoma cruzi infection in Bolivian (Spain) participants. Methods: A cross sectional study was carried out in Majorca. Bolivian residents older than 18 years assigned to the family physicians of two primary care centers were randomly selected from the health card population database. Participants were invited to attend a serology test and an interview. T. cruzi infection was confirmed after two positive ELISA tests. If the result was positive or dubious, the serological test was sent to the National Microbiology Center for confirmation. Results: A total of 251 participants were included (response rate 36.3%). The overall seroprevalence of Chagas infection was 19.1% (95% CI: 14.06-24.19). Seroprevalence was higher in participants from highly endemic provinces, those from rural areas, those who had lived in mud houses, and in those whose mother or a family member had contracted this infection. Conclusion: This study demonstrates a high prevalence of T. cruzi in Bolivian residents, which was strongly associated with established risk factors (AU)

Objetivo: Este estudio pretende estimar la seroprevalencia de la infección por Tripanosoma cruzi en sujetos bolivianos. Métodos: Estudio descriptivo transversal en Mallorca (España), en el cual sujetos bolivianos mayores de 18 años, asignados a médicos de familia de dos centros de salud, fueron seleccionados aleatoriamente de la base de Tarjeta Sanitaria Individual. Se citaron en el centro de salud para prueba serológica y entrevista. Se confirma como caso dos pruebas de ELISA positivas. Los resultados positivos o dudosos se enviaron al Centro Nacional de Microbiología para su confirmación. Resultados: Se incluyeron 251 sujetos (tasa de respuesta 36,3%). La seroprevalencia fue del 19,1% (intervalo de confianza del 95%: 14,06-24,19). La seroprevalencia fue mayor en quienes vivían en provincias endémicas, áreas rurales, casas de adobe o cuya madre o algún familiar había sufrido la infección. Conclusión: Este trabajo evidencia una alta prevalencia en personas bolivianas residentes que se asocia con los factores de riesgo ya establecidos (AU)

Diagnóstico serológico de las infecciones congénitas y algoritmos para mejorar la eficacia diagnóstica / Serological diagnosis of congenital infections and algorithms to improve diagnostic efficacy

Puede ocurrir por vía transplacentaria o por contacto directo con el patógeno durante el parto o en el período posnatal. Se puede producir infección congénita tanto por virus (rubéola, citomegalovirus, herpes simple, varicela-zóster, hepatitis B y C, virus de la inmunodeficiencia humana, erythrovirus B19) como por bacterias (Treponema pallidum) y parásitos (Toxoplasma gondii y Trypanosoma cruzi). El diagnóstico serológico de la infección congénita se basa tanto en el conocimiento de la serología infecciosa en la madre, incluyendo el control serológico sistemático y aspectos del diagnóstico por determinación de IgM y métodos confirmatorios, como los ensayos de avidez de IgG o el establecimiento de perfiles de anticuerpos, como en el diagnóstico en el neonato. El diagnóstico serológico de la infección congénita en el recién nacido se basa fundamentalmente en la detección de IgM específica, generalmente mediante técnicas inmunoenzimáticas o de inmunoquimioluminiscencia; en ocasiones es de importancia realizar el seguimiento serológico del recién nacido para confirmar la infección congénita

Congenital infection is those transmitted by the mother to the fetus before delivery. It can occur transplacentally or by direct contact with the pathogen during birth or in the immediate postnatal period. Congenital infection can be due to viruses (rubella, cytomegalovirus, herpes simplex, varicella-zoster, hepatitis B and C virus, human inunodeficiencia, erythrovirus B19) as bacteria (Treponema pallidum) and parasites (Toxoplasma gondii and Trypanosoma cruzi). Serological diagnosis of congenital infection is based on both the knowledge of infectious serology in the mother, including the systematic serological screening and diagnostic aspects of the determination of IgM and confirmatory methods, IgG avidity tests, establishment of antibody profiles, and in the diagnosis the neonate. Serological diagnosis of congenital infection in the newborn is mainly based on the detection of specific IgM usually by immunoenzymatic assays or immunochemiluminescence techniques. In some instances it is important to perform the serological follow up of the newborn to confirm the congenital infection

¿Puede considerarse portadores asintomáticos a los donantes de sangre seropositivos para Trypanosoma cruzi?: un estudio de validación en el proyecto CHICAMOCHA / Can Seropositive Blood Donors be Considered Asymptomatic Carriers for Trypanosoma cruzi?: a validation study in CHICAMOCHA project / Poderiam ser considerados portadores assintomáticos os doadores de sangue soropositivos para Trypanosoma cruzi? um estudo de validação no projeto CHICAMOCHA

Identificar el deterioro clínico de individuos seropositivos para la enfermedad de Chagas requiere observar la evolución de personas con infección establecida por Trypanosoma cruzi (T.cruzi), libres de signos y síntomas de cardiomiopatía en una línea de base. Objetivo: Realizar una comparación entre donantes de bancos de sangre de Bucaramanga con serología positiva y negativa para T. cruzi. Metodología: La muestra consistio en donantes elegibles con pruebas de tamización positivas para T. cruzi, pero negativas para otros agentes infecciosos tamizados por los bancos de sangre. Estos registros fueron apareados con una muestra aleatoria 1:4 de donantes con pruebas negativas a todas las pruebas de tamizaci¾n. Los participantes fueron entrevistados para conocer aspectos sociodemográficos y de percepción de su estado de salud, se realizó examen físico y se tomaron muestras de sangre para examenes paraclínicos. Se reportaron las frecuencias y proporciones de los participantes. Se hicieron pruebas de hipótesis de no diferencias entre los dos grupos con la prueba Chi cuadrado, con un nivel alfa de significancia de 5%. Resultados: La muestra consistió en 2,132 donantes de sangre incluidos entre mayo de 2000 y marzo de 2004. Mediante prueba serológica se identificaron 488 (22.9%) seropositivos y 1644 (77.1%) seronegativos. Los seropositivos fueron mayores en edad, presentaron indicadores socioeconómicos menos favorables y menor afiliación a seguridad social con el régimen contributivo y tenÝan una mejor percepción de su salud en comparación con los seronegativos (p<0.05). No se observaron diferencias estadísticamente significativas en cuanto a la percepción del funcionamiento de los tres sistemas evaluados (cardiovascular, urinario y gastrointestinal) en ambos grupos.

In order to identify the clinical deterioration of seropositive individuals for Chagas disease, it is necessary to observe the evolution of people infected by Trypanosoma cruzi (T. cruzi), who do not show signs and symptoms of cardiomyopathy on a baseline. Objective: To compare blood donors with positive and negative serology for Trypanosoma cruzi in the city of Bucaramanga. Methodology: The sample consisted of eligible donors with positive screening tests for T. cruzi, but negative for other infectious agents screened by blood banks. These records were matched with a random sample 1: 4 donors who showed negative results to all the screening tests. Participants were interviewed to know their socio-demographic aspects and to get a perception of their health status. Physical exams were performed and blood samples were taken for laboratory tests. Frequencies and proportions of participants were reported. Hypothesis testing of no differences between the two groups using the Chi square test was performed, showing a 5% level of alpha significance. Resultados: The sample included 2132 blood donors between May 2000 and March 2004. By using serological tests, it was identified that 488 (22.9%) were seropositive and 1644 (77.1%) were seronegative. Seropositive donors were older people who belonged to a low socio-economic level and had no health insurance. They also had a better perception of their health compared to seronegative donors (p <0.05). The perception of how the three evaluated systems worked (cardiovascular, urinary and gastrointestinal) showed no statistically significant differences between the two groups. Conclusions: The study findings allow us to infer that seropositive blood donors for T. cruzi could be considered as asymptomatic carriers without clinical evidence of cardiomyopathy.

Para identificar o deterioro clínico dos indivíduos soropositivos para a doença de Chagas Ú necessério acompanhar a evolução de indivíduos com infecção estabelecida pelo Trypanosoma cruzi (T. cruzi), livres de sinais e sintomas de cardiomiopatia numa linha de base. Objetivo: Fazer uma comparação entre os doadores dos bancos de sangue de Bucaramanga com sorologia positiva e negativa para T. cruzi. Metodologia: A amostra consistiu de doadores elegíveis com rastreamento positivo para T. cruzi, porém negativo para outros agentes infecciosos selecionados pelos bancos de sangue. Esses registros foram emparelhados com uma amostra aleatória de 1: 4 com testes negativos a todos os testes da triagem de doadores. Os participantes foram entrevistados para se conhecer aspectos sociodemográficos e perceber seus aspectos de saúde, foi realizado um exame físico e foram coletadas amostras de sangue para exames de laboratório. Relataram-se as frequéncias e proporções de participantes. Foi feito um teste de hipóteses de não diferenças entre os dois grupos com o teste do chi-quadrado, com um nível alfa de significãncia de 5%. Resultados: A mostra consistiu em 2132 doadores de sangue incluídos entre maio de 2000 e marþo de 2004. Pela prova sorol¾gica identificaram-se 488 (22.9%) soropositivos y 1644 (77.1%) soronegativos. Os Soropositivos foram maiores de 18 anos, tinham indicadores socioeconómicos menos favoróveis, menor inscrição no seguro social com o regime contributivo e melhor percepção da sua saúde em relação aos soronegativos (p <0,05). Estatisticamente não se observaram diferenças significativas quanto Ó percepção do funcionamento dos trés sistemas avaliados (cardiovascular, gastrointestinal e urinário) em ambos os grupos. Concluções: resultados do estudo permitem concluir que os doadores soropositivos para T. cruzi no sangue poderiam ser vistos como portadores assintomáticos, sem evidência clínica de cardiomiopatia.

Immunological response to re-infections with clones of the Colombian strain of Trypanosoma cruzi with different degrees of virulence: influence on pathological features during chronic infection in mice

Re-infections with Trypanosoma cruzi are an aggravating factor for Chagas disease morbidity. The Colombian strain of T. cruzi represents multiclonal populations formed by clonally propagating organisms with different tropisms and degrees of virulence. In the present study, the influence of successive inoculations with clones of the Colombian strain, exhibiting different degrees of virulence, on chronic myocarditis and the humoral and cellular immune responses (Col-C1 high virulence, Col-C8 medium virulence and Col-C5 low virulence) were demonstrated. Mice from three groups with a single infection were evaluated during the acute (14th-30th day) and chronic phases for 175 days. An immunofluorescence assay, ELISA and delayed type hypersensitivity (DTH) cutaneous test were also performed. Mice with a triple infection were studied on the 115th-175th days following first inoculation. The levels of IgM and IgG2a were higher in the animals with a triple infection. DTH showed a higher intensity in the inflammatory infiltrate based on the morphometric analysis during a 48 h period of the triple infection and at 24 h with a single infection. The histopathology of the heart demonstrated significant exacerbation of cardiac inflammatory lesions confirmed by the morphometric test. The humoral responses indicate a reaction to the triple infection, even with clones of the same strain.