BACKGROUND As chronic Chagas disease does not have a definitive treatment, the development of alternative therapeutic protocols is a priority. Dipyridamole (DPY) is an alternative to counteract the pathophysiological phenomena involved in Chagas cardiomyopathy. OBJECTIVE To evaluate the therapeutic efficacy of DPY associated with nifurtimox (Nfx) in epimastigote axenic cultures and in mice with acute Chagas disease. METHODS NMRI adult male mice were divided into nine groups: three healthy and six Trypanosoma cruzi-infected groups. Mice received vehicle, Nfx or DPY, alone or combined. The doses assayed were Nfx 10 and 40 mg/kg and DPY 30 mg/kg. The treatment efficacy was evaluated by clinical, electrocardiographic, parasitological, biochemical and histopathological methods. FINDINGS In vitro, DPY and Nfx had a trypanocidal effect with IC50 values of 372 ± 52 and 21.53 ± 2.13 µM, respectively; DPY potentiated the Nfx effect. In vivo, Nfx (40 mg/kg) with or without DPY had a therapeutic effect, which was reflected in the 84-92% survival rate and elimination of parasitaemia and heart tissue amastigotes. Nfx (10 mg/kg) had a subtherapeutic effect with no survival and persistence of amastigotes, inflammation and fibrosis in heart tissue; adding DPY increased the survival rate to 85%, and all tested parameters were significantly improved. MAIN CONCLUSION DPY has a trypanocidal effect in vitro and enhances the Nfx therapeutic effect in an in vivo murine model.

Resumo Fundamento: A doença de Chagas é um problema de saúde global, sendo necessário o desenvolvimento de novos protocolos terapêuticos. Nosso grupo demonstrou recentemente que o nifurtimox associado ao dipiridamol tem efeitos curativos em camundongos com doença de Chagas aguda. Neste estudo, avaliamos o efeito deste protocolo terapêutico em camundongos chagásicos com insuficiência cardíaca. Objetivo: Avaliar se o nifurtimox e o dipiridamol são úteis no tratamento de resgate em camundongos com miocardite chagásica aguda com insuficiência cardíaca. Métodos: Foram divididos em três grupos 42 camundongos com miocardite chagásica aguda e insuficiência cardíaca congestiva: Controle Chagas (n = 11); Nif-Dip, tratados com nifurtimox e dipiridamol (n = 14); e Nif-Dip-Insuficiência Cardíaca, tratados com nifurtimox e dipiridamol, associados com digoxina, furosemida e captopril (n = 17). As doses de nifurtimox e dipiridamol foram de 40 e 30 mg/kg/dia, respectivamente, durante 6 semanas. Os camundongos foram submetidos a avaliações clínicas, eletrocardiográficas, hemoparasitológicas e histopatológicas. Resultados: Observou-se menor mortalidade no Grupo Nif-Dip (n = 4; 28,57%) em relação ao Controle Chagas (n = 6; 54,54%) e ao Nif-Dip-Insuficiência Cardíaca (n = 9; 52,9%). Clinicamente, os camundongos tratados com nifurtimox e dipiridamol aumentaram o peso corporal e melhoraram a insuficiência cardíaca, sem mostrar esplenomegalia. Nestes grupos, foram erradicadas as parasitemias e os parasitas teciduais; a fibrose, a miocitólise, o infiltrado de células inflamatórias e os mastócitos diminuíram. Os distúrbios de repolarização, os intervalos QRS e o QT prolongados, o aumento da amplitude da onda S e a dissociação atrioventricular foram revertidos pelo tratamento. Conclusão: O tratamento com nifurtimox e dipiridamol pode ser usado no resgate em camundongos com doença chagásica aguda grave, já que o nifurtimox teve atividade tripanocida, e o dipiridamole potenciou seu efeito. O dipiridamol seria útil na insuficiência cardíaca chagásica.

Abstract Background: Chagas disease is a global health problem; therefore, the development of new therapeutic protocols is necessary. Our group recently demonstrated that nifurtimox associated with dipyridamole has curative effects in mice with acute Chagas disease. In this study, we assess the effect of this therapeutic protocol in chagasic mice with heart failure. Objective: To evaluate whether nifurtimox and dipyridamole are useful to rescue mice with severe acute chagasic myocarditis with heart failure. Methods: 42 mice with acute chagasic myocarditis and congestive heart failure were divided into three groups: control chagas (n = 11), Nif-Dip treated with nifurtimox and dipyridamole (n = 14) and Nif-Dip-heart failure treated with nifurtimox and dipyridamole associated with digoxin, furosemide, and captopril (n = 17). Nifurtimox and dipyridamole doses were 40 and 30 mg/kg/day, respectively, for 6 weeks. Mice underwent clinical, electrocardiographic, hemoparasitological and histopathological assessments. Results: Lower mortality in Nif-Dip (28.57%; n = 4) compared to control chagas (54.54%; n = 6) and Nif-Dip-heart failure (52.9%; n = 9) was observed. Clinically, nifurtimox and dipyridamole-treated mice increased body weight and improved heart failure without splenomegaly. In these groups, parasitemia and tissue parasites were eradicated; fibrosis, myocytolysis, inflammatory cell infiltrate and mast cells decreased. Repolarization disorders, prolonged QRS and QT intervals, increase of S wave amplitude and atrioventricular dissociation were reversed by the treatment. Conclusion: Nifurtimox with dipyridamole can rescue NMRI mice from severe acute chagas disease, as nifurtimox showed trypanocidal activity and dipyridamole potentiated its effect. Dipyridamole would be useful in chagasic heart failure.

Introdução e objetivo . A Doença de Chagas é um problema de saúde pública mundial. A disponibilidade de ferramentas diagnósticas para prever o desenvolvimento de miocardiopatia chagásica crônica é fundamental para reduzir a morbidade e a mortalidade. Aqui estudamos o valor prognóstico da atividade sérica da adenosina deaminase (ADA) e dos níveis de proteína C reativa (PCR) em indivíduos chagásicos. Métodos : 110 indivíduos: 28 saudáveis e 82 pacientes chagásicos foram divididos de acordo com a gravidade da doença em fase I (n = 35), II (n = 29) e III (n = 18). Para cada indivíduo foram feitos uma história médica, eletrocardiograma, radiografia de tórax e ecocardiografía transtorácica. O diagnóstico de Chagas foi confirmado por ELISA e MABA utilizando antígenos recombinantes, a atividade sérica da enzima ADA foi determinada por espectrofotometria, e os níveis séricos de PCR por ELISA. Resultados : os níveis de PCR e da atividade da ADA aumentaram linearmente em relação à fase da doença, sendo a PCR significativamente maior na fase III, e a ADA em todas as fases. Além disso, PCR e ADA foram correlacionados positivamente com parâmetros ecocardiográficos de remodelamento cardíaco e alterações eletrocardiográficas, e negativamente com a fração de ejeção. PCR e ADA foram mais elevadas em pacientes com índice cardiotorácico ≥ 50%, enquanto que a ADA foi maior em pacientes com alterações da repolarização ventricular. Finalmente, os níveis de PCR foram correlacionados positivamente com a atividade da ADA. Conclusão : ADA e PCR são marcadores prognósticos de disfunção e remodelamento cardíaco na Doença de Chagas, e devem ser incluídos na avaliação e acompanhamento dos pacientes.

SUMMARY Chagas disease is a public health problem worldwide. The availability of diagnostic tools to predict the development of chronic Chagas cardiomyopathy is crucial to reduce morbidity and mortality. Here we analyze the prognostic value of adenosine deaminase serum activity (ADA) and C-reactive protein serum levels (CRP) in chagasic individuals. One hundred and ten individuals, 28 healthy and 82 chagasic patients were divided according to disease severity in phase I (n = 35), II (n = 29), and III (n = 18). A complete medical history, 12-lead electrocardiogram, chest X-ray, and M-mode echocardiogram were performed on each individual. Diagnosis of Chagas disease was confirmed by ELISA and MABA using recombinant antigens; ADA was determined spectrophotometrically and CRP by ELISA. The results have shown that CRP and ADA increased linearly in relation to disease phase, CRP being significantly higher in phase III and ADA at all phases. Also, CRP and ADA were positively correlated with echocardiographic parameters of cardiac remodeling and with electrocardiographic abnormalities, and negatively with ejection fraction. CRP and ADA were higher in patients with cardiothoracic index ≥ 50%, while ADA was higher in patients with ventricular repolarization disturbances. Finally, CRP was positively correlated with ADA. In conclusion, ADA and CRP are prognostic markers of cardiac dysfunction and remodeling in Chagas disease.

Diversos agentes infecciosos interfieren en la progresión del cáncer. En esta investigación se estudió el efecto de la infección o inmunización con Trypanosoma cruzi (Tc) sobre el desarrollo del melanoma maligno. Se utilizaron 258 ratones machos C57BL/6 divididos en 5 grupos melanoma: melanoma control, melanoma Tc inmunizado, melanoma Tc agudo, melanoma Tc crónico y melanoma Tc infectado; 3 grupos controles: control sano, control Tc agudo, control Tc crónico. 100.000 células de melanoma B16-BL6 fueron inoculados vía intramuscular a los grupos melanoma; 3 ó 20 tripomastigotes/g de peso fueron inoculados vía intraperitoneal a los grupos Tc crónicos o Tc agudos previo a la inoculación del melanoma, respectivamente, el grupo melanoma Tc inmunizado fue inoculado con 30.000 epimastigotes fijados en formol y suspendidos en adyuvante completo de Freund, y el grupo melanoma Tc infectado fue inoculado con células de melanoma obtenidas de ratones melanoma Tc agudo. Se evaluó volumen tumoral, supervivencia, parasitemia e histopatología tumoral. Los grupos melanoma Tc: agudo, crónico y melanoma infectado, respectivamente, mostraron una disminución significativa del desarrollo tumoral y de la supervivencia al ser comparados con los grupos melanoma control e inmunizado. Los estudios histopatológicos mostraron áreas de necrosis asociadas con depósitos de melanina, degeneración citopática tumoral y amastigotes intracelulares contenidos en vacuolas parasitofóricas. En conclusión, Tc inhibe el desarrollo tumoral del melanoma maligno y aumenta la supervivencia de ratones C57BL/6, fenómeno que podría estar relacionado con la capacidad invasiva tumoral del parásito y a la respuesta inmune generada.

Some infectious pathogens have the capacity to affect cancer progression. In the present paper we studied the effect of infection or immunization with Trypanosoma cruzi (Tc) against malignant melanoma development. We worked on 258 C57BL/6 male mice divided in five melanoma groups: control melanoma, melanoma Tc acutely infected, melanoma Tc chronically infected, melanoma Tc immunized and infected melanoma; and three control groups: healthy, Tc acutely infected and Tc chronically infected. 100.000 B16-BL6 melanoma cells were inoculated in the thigh of melanoma groups; 3 or 20 trypomastigotes/g were inoculated intraperitoneally in chronic or acute Tc groups, before the melanoma injection, respectively; melanoma Tc immunized were subcutaneously inoculated with 30.000 formaldehide-fixed epimastigotes diluted in complete Freund´s adjuvant and the infected melanoma group was inoculated with melanoma cells obtained from melanoma Tc acutely infected mice. We evaluated survival, parasitemia, tumor volume and tumor histopathology. Results showed that in mice infected with Tc, the tumor development and survival were significantly lower as compared with control melanoma and melanoma Tc immunized. Histopathologically, the tumor displayed necrosis areas with melanin deposits, cytopathic degeneration and amastigotes in parasitophorous vacuoles. In conclusion, Tc inhibits the development of malignant melanoma, increasing C57BL/6 survival, a phenomena that could be related to the parasite tumoral invasive capacity, its ability to produce melanoma cell lysis and to induce a robust immune response.

Es cada vez mayor la evidencia experimental y clínica de que el sistema inmune interviene activamente en la patogénesis y el control de la progresión tumoral. Una respuesta antitumoral efectiva depende de la correcta interacción de diversos componentes del sistema inmune, como las células presentadoras de antígeno y diferentes sub-poblaciones de células T. Sin embargo, los tumores malignos desarrollan numerosos mecanismos para evadir su reconocimiento y eliminación. Diversos estudios reportan que estructuras asociadas a tumor tales como los antígenos Tn y sialil-Tn se expresan en algunos parásitos protozoarios y helmintos, planteando numerosas interrogantes a nivel de la interacción parásito-hospedador. Considerando que existe una correlación negativa entre ciertas infecciones parasitarias y el desarrollo de cáncer, los antígenos de O-glicosilación incompleta obtenidos de parásitos podrían ser potenciales estructuras miméticas para la inducción de respuestas cruzadas contra antígenos tumorales. Actualmente, el área de la glicobiología del cáncer tiene muchas expectativas para encontrar solución a uno de los grandes problemas de salud que afecta a la población tanto desde el punto de vista económico como social.

There is increasing experimental and clinical evidence that the immune system plays an active role in the pathogenesis and control of tumor progression. An effective antitumor response depends on the correct interaction of the various components of the immune system, such as antigen presenting cells and sub-populations of T cells. However, malignant tumors develop numerous mechanisms to evade recognition and elimination. Several studies report that structures associated with tumors such as Tn and sialyl-Tn antigens are expressed in some protozoan parasites and helminths, thus raising many questions regarding parasite-host interactions. The negative correlation between certain parasite infections and cancer development suggests that antigens from incomplete O-glycosylation obtained from parasites could represent potential mimetic structures for inducing cross responses against tumor antigens. Currently, cancer glycobiology is a promising area in the search for a solution to one of the major health problems affecting the population both from an economic and a social perspective.

Se determinaron los factores de riesgo asociados al diagnóstico de miocardiopatía chagásica crónica (MChC) en 115 individuos seropositivos para anticuerpos anti-Trypanosoma cruzi, en el Estado Barinas, Venezuela. La seropositividad fue determinada mediante ELISA y MABA (Multiple Antigen Blot Assay) y el diagnóstico de MChC fue establecido mediante electrocardiografía y ecocardiografía. A cada individuo se le realizó una historia clínica completa que incluyó antecedentes epidemiológicos, antecedentes patológicos personales y familiares, y hábitos psicobiológicos; además se realizó una encuesta donde se interrogó acerca de factores de riesgo socioeconómicos, psicosociales y de hábitos alimentarios. Los factores de riesgo fueron establecidos mediante una regresión logística binaria. Los resultados mostraron que 81 (70,4%; IC95% = 66,4-74,4) pacientes reunían criterios para el diagnóstico de MChC, de los cuales 74 (64,4%; IC95% = 60,2-68,6) estaban en Fase II (6,1%; IC95% = 4,0-8,2) y 7 en Fase III, mientras que 34 (29,6%; IC95% = 25,5-33,5) estaban en Fase I. En el periodo de 1 año murieron 2 individuos en Fase III. El diagnóstico de MChC estuvo asociado con la práctica de la caza de animales silvestres, el consumo de chimó, antecedentes maternos de cardiopatía, antecedentes personales de hipertensión arterial y un ápex visible, como factores de riesgo, mientras que: el consumo de alimentos preservados y enlatados constituyó un factor de protección. En conclusión, el diagnóstico de MChC tiene una alta frecuencia en individuos seropositivos del estado Barinas y la prevención del desarrollo de insuficiencia cardíaca debe basarse en la atención médica precoz y en medidas educativas para controlar los factores de riesgo.

This study evaluates the risk factors associated with the diagnosis of chronic chagasic miocardiopathy (CChM) in 115 seropositive individuals to anti-Trypanosoma cruzi antibodies, in Barinas state, Venezuela. Serology was performed with ELISA and MABA; while the CChM diagnosis was established by electrocardiography and echocardiography. A complete clinical history including epidemiological, personal/familiar antecedents and psychobiological habits, plus socioeconomic, psychosocial and alimentary habits interviews were performed for each individual. Risk factors were determined through binary logistic regression. Results showed that 81 patients (70,4%; CI95% = 66.4-74.4) had criteria for CChM, of which 74 (64.4%; IC95% = 60.2-68.6) were in phase II; while 34 (29.6%; IC95% = 25.5-33.5) were in phase I of the disease and 7 (6.1%; IC95% = 4.0-8.2) in phase III. In a one year period, two patients in phase III died of heart failure. The diagnosis of CChM was associated with hunting practice, maternal history of cardiopathies, chewing chimó, medical history of hypertension and apex beat visible; it was negatively associated with canned and preserved foods ingest. In conclusion the CChM diagnosis has high frequency in seropositive individuals in Barinas and heart failure prevention must be based on an early medical attention and educative strategies in order to control risk factors.

Durante la carcinogénesis ocurren modificaciones importantes en la glicosilación, entre ellas la elongación incompleta de las cadenas sacarídicas con uniones de tipo O y la exposición de antígenos que en condiciones normales estaban ocultos, los cuales son reconocidos por componentes de la respuesta inmune que promueven o limitan el crecimiento tumoral. Diversos estudios reportan que estructuras asociadas a tumor tales como los antígenos Tn y sialil-Tn se expresan en algunos parásitos protozoarios y helmintos, planteando numerosas interrogantes a nivel de la interacción parásito-hospedador. Considerando que existe una correlación negativa entre ciertas infecciones parasitarias y el desarrollo de cáncer, los antígenos de O-glicosilación incompleta obtenidos de parásitos podrían ser potenciales blancos en la inmunoterapia del cáncer.

During carcinogenesis important modifications in glycosylation occur, among them incomplete elongation of the saccharide chains with type O bonds and the exposure of antigens that were hidden under normal conditions, which are recognized by components of the immune system which promote or limit tumor growth. Several studies report that tumor-associated structures, such as Tn and sialil-Tn, are expressed in some parasites protozoa and helminths, and pose many questions regarding parasite-host interaction. Considering the negative correlation between certain parasite infections and cancer development, antigens from incomplete O-glycosylation obtained from parasites could be potential targets in cancer immunotherapy.

La enfermedad de Chagas es una hemoparasitosis causada por Trypanosoma cruzi (T. cruzi), cuya re-emergencia como epidemias por contaminación oral es actualmente un problema de salud pública en Venezuela. La infección por T. cruzi causa miocarditis; que de acuerdo con la teoría microvascular deriva del daño del endotelio vascular, al inducir agregación plaquetaria e isquemia. Con el objetivo de demostrar que los trastornos de repolarización son signos propios de la miocarditis chagásica aguda (MChA) reproducibles en modelos animales, estudiamos 12 pacientes humanos con diagnostico bien documentado de MChA, basado en datos epidemiológicos, clínicos, parasitológicos y moleculares. A partir de la sangre de los pacientes obtuvimos los aislados de T cruzi, los caracterizamos molecularmente y los inoculamos en ratones albinos NMRI; paralelamente, aislados de T cruzi provenientes de otras regiones de Venezuela fueron también ensayados. Tanto en los pacientes humanos como en los ratones con Chagas agudo, se realizaron estudios electrocardiográficos en 12 derivaciones estándares y en configuración bipolar, respectivamente. En humanos observamos trastornos de la repolarización ventricular caracterizados por: onda T negativa, bimodal o bifásica; elevación o depresión del segmento ST y despolarizaciones tempranas. En ratones observamos incrementos en la amplitud de la onda T, aumento en la duración del intervalo QT y elevación o depresión del segmento ST. Estos hallazgos fueron evidenciados en todos los ratones infectados con los diferentes aislados, sugiriendo que los trastornos de repolarización, en un adecuado y bien documentado contexto epidemiológico y clínico, son signos que aumentan la sensibilidad para el diagnóstico de MChA

Chagas disease is a tropical parasitic disease caused by the protozoan Trypanosoma cruzi (T. cruzi), whose reemergence as oral outbreaks is currently a public health problem in Venezuela. T. cruzi infection induces myocardial damage; which according to the microvascular theory, is derived from parasite-mediated disruption of the endothelium, inducing platelet aggregation and ischemia. In order to determine whether ventricular repolarization disorders observed in human patients are characteristic signs of the disease that can be reproduced in NMRI mice; we studied 12 patients with a well documented diagnosis of acute Chagas disease, based on epidemiological, clinical, parasitological and molecular data. Also, T. cruzi isolates from the blood of human patients from other Venezuelan geographical regions were characterized and inoculated in albino NMRI mice. A standard 12-lead and bipolar electrocardiogram configuration were done in human patients during the acute phase of the disease and in mice, after three weeks of infection. Results in human showed repolarization disorders, characterized by: negative, bimodal or biphasic T waves, ST segment depression or elevation and early repolarization. In mice a significant increase in T wave amplitude, increased QT interval duration and elevation or depression of ST segment were observed. These findings were evidenced in all infected mice, suggesting that electrocardiographic repolarization abnormalities in a well documented clinical and epidemiological context are signs that increase the sensitivity for the diagnosis of acute Chagas´ disease

La Adenosin deaminasa es una enzima del metabolismo de las purinas cuya función es transformar la adenosina en inosina y la desoxiadenosina en desoxiinosina. La unión de ecto-ADA1 a la superficie celular a través de CD26 contribuye a la regulación de citocinas y estimula la proliferación de células T mediante la activación de CD45. La deficiencia de esta enzima genera el síndrome de inmunodeficiencia combinada severa, caracterizado por la acumulación de metabolitos de adenina y desoxiadenosina, los cuales tienen efectos tóxicos sobre los linfocitos, afectando así la síntesis de ADN y en consecuencia la expansión clonal. Un diagnóstico temprano de esta inmunodeficiencia es esencial ya que reduce notablemente la morbilidad y mortalidad asociada con infecciones recurrentes. Los avances recientes en biología molecular y genética han conducido a la identificación de los defectos genéticos de muchas de las inmunodeficiencias primarias y al desarrollo de herramientas de diagnóstico y tratamiento prometedoras

Adenosine deaminase is an enzyme of the purine metabolism whose function is to convert adenosine to inosine and deoxyadenosine to deoxyinosine. The ecto-ADA1 binding to the cell surface through CD26 contributes to the regulation of cytokines and stimulates the proliferation of T cells by activating CD45. The deficiency of this enzyme generates the severe combined immunodeficiency syndrome, characterized by the accumulation of deoxyadenosine and adenine metabolites, which have toxic effects on lymphocytes, affecting DNA synthesis and consequently, clonal expansion. Early diagnosis of this immunodeficiency is essential, as it significantly reduces morbidity and mortality associated with recurrent infections. Recent advances in molecular biology and genetics have led to the identification of genetic defects of many primary immunodeficiencies and the development of promising diagnostic tools and treatment

Objetivo: Determinar la seroprevalencia humana y canina del índice entomológico y factores de riesgo para la transmisión de la enfermedad de Chagas en una comunidad rural. Materiales y Método: Se incluyeron 48 casas, 162 personas, y se tomaron muestras de 55 caninos. se determinaron anticuerpos séricos anti-Trypanosoma cruzi mediante técnicas de ELISA y MABA, utilizando antígenos recombinantes. La recolección de triatominos se llevó a cabo mediante búsqueda pasiva sistemática en la comunidad y casas. La infección por T. cruzi se determinó mediante microscopia directa. Resultados: El 2,47 % de los humanos y 18,18 % de los caninos fueron positivos al suero anti-T.cruzi. Los triatominos encontrados fueron T. maculata (98,24 %) y Eratyrus mucronatus (1,76%). No hubo infección vectorial, el 18,75 % de infestación intradomiciliaria, 25 % de infestación extradomiciliaria, no hubo colonización intradomiciliar, el 83,33 % de colonización extradomiciliar y el 4,16 % de infestación intradomiciliar. Se obtuvo una asociación entre infestación intradomiciliar por triatominos y la visualización de los animales en la casa. Discusión: No se observo transmisión vectorial de la enfermedad de Chagas en la comunidad, sin embargo, la alta prevalencia en perros está relacionada con sus hábitos biológicos y el comportamiento

Objective: To determine human and canine seroprevalence, entomologic indexes and risk factors for Chagas’ disease transmission in a rural community. Method: 48 houses, 162 people, and 55 canines were sampled. Serum anti-Trypanosoma cruzi antibodies were determined by means of ELISA and MABA techniques using recombinant antigens. Triatomine collection were carried out by passive search by community and an active/systematic house, T. cruzi infection was determined by direct microcopy. Results: 2,47% of the humans and 18.18% of the canines were positive to serum anti-T.cruzi antibodies. The triatomine bugs found was 98.24% and 1.76% Eratyrus mucronatus. Vector’s indexes were: 0 % vector infection, 18.75% indoor house infestation, 25% outdoor house infestation, 0% indoor house colonization, 83.33 % outdoor house colonization and 4.16% house co-infestation. We obtained an association between house triatomine infestation and visualization of wild animals in the house. Discussion: there are not vector transmission of Chagas disease in the community, however, high dog’s prevalence is related to their biological habits and behavior

INTRODUÇÃO: A insuficiência cardíaca (IC) representa o estágio final da cardiopatia chagásica crônica (CChC). O diagnóstico de CChC é baseado na demonstração de anticorpos anti-Trypanosoma cruzi (AgTc), dados clínicos e epidemiológicos. Na Venezuela, não há informação sobre a prevalência da IC chagásica. O objetivo deste estudo foi determinar fatores de risco epidemiológicos, clínicos e inflamatórios associados à IC chagásica. MÉTODOS: Realizamos um estudo prospectivo transversal em estados do centro-oeste da Venezuela em uma população rural saudável e em pacientes com IC descompensada. RESULTADOS: A soroprevalência de AgTc mostrou valores de 11,2% e 40,1% na população saudável e em pacientes com IC, respectivamente. A soropositividade de indivíduos sadios se associou com a idade, conhecimento de vetores e a observação de reservatórios silvestres na habitação. Em pacientes com IC, estavam relacionados ao contato com o vetor e ao diagnóstico clínico prévio de doença de Chagas. Em ambos os grupos juntos, a soropositividade foi associada com idade, conhecimento do vetor e com IC. Os pacientes soropositivos apresentavam prolongamento do intervalo QRS, fração de ejeção diminuída e magnésio sérico elevado. Aumento atrial esquerdo e hipertrofia ventricular foram as mais frequentemente observadas em pacientes com IC soronegativos. PCR, IL6, ILβ1, IL2 e FNTα foram elevados em 94,5, 48, 17,8, 13,7 e em 6,9% dos pacientes com IC, respectivamente; os níveis de IL-2 foram associados com IC chagásica. CONCLUSÕES: Uma alta prevalência de AgTc foi observada em pacientes com IC na região centro-oeste da Venezuela, cujos aspectos epidemiológicos, clínicos e inflamatórios são discretamente diferentes dos soronegativos.

INTRODUCTION: Heart failure (HF) represents the final stage of chronic chagasic cardiomyopathy (CChC). The diagnosis of CChC is based on the demonstration of anti-Trypanosoma cruzi antibodies (aTcAg) and clinical and epidemiological data. In Venezuela, there are no data about the prevalence of chagasic HF. The aim of this study was to determine the epidemiological, clinical, and inflammatory risk factors associated with seronegative or seropositive HF patients. METHODS: We performed a cross-sectional study in the Venezuelan central-west states among a healthy rural population and in patients admitted to the emergency room with uncompensated HF. RESULTS: The seroprevalence rates of Trypanosoma cruzi antibodies were 11.2% and 40.1% in the healthy population and in HF patients, respectively. Seropositivity in healthy individuals was associated with age, knowledge on triatomine vectors, and having seen wild reservoirs in the house; in HF patients, with contact with the vector and previous clinical diagnosis of Chagas' disease; and in both groups taken together, with age, knowledge on triatomines, and HF. Seropositive patients had prolonged QRS, decreased ejection fraction, and high serum magnesium, all significant as compared with HF seronegative cases. Left atrium enlargement and ventricular hypertrophy were most frequently observed in HF seronegative patients. CRP, IL6, ILβ1, IL2, and FNTα were elevated in 94.5%, 48%, 17.8%, 13.7%, and 6.9% of HF patients, respectively, but only IL2 levels were associated with chagasic HF. CONCLUSIONS: There is a high prevalence of aTcAg in HF patients from the central-west region of Venezuela, and their epidemiological, clinical, and inflammatory features are discreetly different as compared with those of seronegative cases.

This study investigated risk factors associated with positive serological status for Trypanosoma cruzi antibodies in 26 rural communities including 905 households, 2,156 humans, and 333 dogs in Lara State, Venezuela. Serology was performed with ELISA and MABA. Data were obtained from entomological, demographic, and clinical surveys. Risk factors were determined through binary logistic regression. Seroprevalence was 7.24% in humans and 6.9% in canines. Positive serological status was positively associated with the Rhodnius prolixus vector, age, maternal history of Chagas disease, tobacco chewing, presence of mammals and birds in the household, household disarray, mud-and-wattle outbuildings, and animal nests and burrows in the peridomicile, and negatively associated with tobacco and alcohol consumption, history of cancer, and storage deposits in the peridomile. In conclusion, Chagas disease in this rural area is an old phenomenon transmitted by R. prolixus or by the transplacental route, associated with socio-cultural habits related to poverty, sylvatic surroundings, and the host's medical history.

Determinamos factores de riesgo asociados a la seropositividad para anticuerpos anti-Trypanosoma cruzi en 26 poblaciones rurales, 905 viviendas, 2.156 individuos y 333 caninos en el Estado Lara, Venezuela. La seropositividad fue determinada mediante ELISA y MABA. Los datos fueron obtenidos mediante encuestas entomológicas, demográficas y médicas. Los factores de riesgo fueron establecidos mediante regresión logística binaria. La seroprevalencia humana fue de 7,24% y la canina 6,9%. La seropositividad estuvo asociada positivamente al Rhodnius prolixus, la edad, madre con antecedentes de Chagas, consumo de chimó, presencia de mamíferos y aves en la vivienda, desorden en el domicilio, y anexos de bajareque, nidos y cuevas en el peridomicilio. Negativamente con hábitos de consumo de tabaco y alcohol, antecedentes de cáncer y a depósitos en el peridomicilio. En conclusión, la enfermedad de Chagas en el área rural estudiada es un fenómeno remoto transmitida por R. prolixus y vía transplacentaria, asociada a hábitos socioculturales relacionados con la pobreza, a entornos selváticos y antecedentes médicos del huésped.

This study investigated risk factors associated with positive serological status for Trypanosoma cruzi antibodies in 26 rural communities including 905 households, 2,156 humans, and 333 dogs in Lara State, Venezuela. Serology was performed with ELISA and MABA. Data were obtained from entomological, demographic, and clinical surveys. Risk factors were determined through binary logistic regression. Seroprevalence was 7.24% in humans and 6.9% in canines. Positive serological status was positively associated with the Rhodnius prolixus vector, age, maternal history of Chagas disease, tobacco chewing, presence of mammals and birds in the household, household disarray, mud-and-wattle outbuildings, and animal nests and burrows in the peridomicile, and negatively associated with tobacco and alcohol consumption, history of cancer, and storage deposits in the peridomile. In conclusion, Chagas disease in this rural area is an old phenomenon transmitted by R. prolixus or by the transplacental route, associated with socio-cultural habits related to poverty, sylvatic surroundings, and the host's medical history.

Determinamos factores de riesgo asociados a la seropositividad para anticuerpos anti-Trypanosoma cruzi en 26 poblaciones rurales, 905 viviendas, 2.156 individuos y 333 caninos en el Estado Lara, Venezuela. La seropositividad fue determinada mediante ELISA y MABA. Los datos fueron obtenidos mediante encuestas entomológicas, demográficas y médicas. Los factores de riesgo fueron establecidos mediante regresión logística binaria. La seroprevalencia humana fue de 7,24% y la canina 6,9%. La seropositividad estuvo asociada positivamente al Rhodnius prolixus, la edad, madre con antecedentes de Chagas, consumo de chimó, presencia de mamíferos y aves en la vivienda, desorden en el domicilio, y anexos de bajareque, nidos y cuevas en el peridomicilio. Negativamente con hábitos de consumo de tabaco y alcohol, antecedentes de cáncer y a depósitos en el peridomicilio. En conclusión, la enfermedad de Chagas en el área rural estudiada es un fenómeno remoto transmitida por R. prolixus y vía transplacentaria, asociada a hábitos socioculturales relacionados con la pobreza, a entornos selváticos y antecedentes médicos del huésped.

Introducción. En años recientes se han encontrado P. geniculatus infectados con Trypanosoma cruzi en ambientes rurales y urbanos de Caracas, Venezuela, lo que indica adaptaciones de dicha especie, considerada históricamente como silvestre, a ambientes artificiales. Objetivo. Determinar la presencia de dimorfismo sexual como indicador de adaptación al domicilio. Materiales y métodos. Mediante análisis generalizado de Procrustes y análisis elíptico de Fourier, se analizaron el tamaño isométrico y la conformación de alas, cabezas y pronotos de P. geniculatus capturados activa y pasivamente en domicilios en sectores urbanos de Altagracia y Petare de Caracas, y provenientes de ambientes rurales o silvestres de Sanare en el municipio Andrés Eloy Blanco en el estado Lara. Resultados. Se observó dimorfismo sexual al considerar el tamaño de las alas en los especímenes capturados en Sanare, las cuales fueron mayores en las hembras que los machos. Asimismo, las alas y cabezas de las hembras capturadas en Caracas fueron más pequeñas comparadas con las de las hembras provenientes de Sanare. No se encontraron diferencias significativas en cuanto a la conformación del pronoto. Conclusiones. Con base en el supuesto de que, por dimorfismo sexual, el tamaño es más reducido en triatominos domiciliados que en los silvestres, se concluye que P. geniculatus de Caracas están adaptados al domicilio, lo que constituye un factor de riesgo en la transmisión de la enfermedad de Chagas en dicha ciudad.

Introduction. In recent years, the assassin bug, Panstrongylus geniculatus, has been found infected with Trypanosoma cruzi in rural and urban areas of Caracas, Venezuela. Although historically this insect has been considered a forest species, it has become adapted to more urban artificial environments. Objective. The presence of sexual dimorphism was determined as an indicator of adaptation to domicilies. Material and methods. By Generalized Procrustes Analysis (GPA) and Elliptical Fourier Analysis (EFA), the isometric size and shape of wings, head and pronotums of P. geniculatus was assessed for actively and passively captured specimens. These were collected within domiciles in urban areas of Petare and Altagracia in Caracas City, and from rural or wild environments of Sanare in Andres Eloy Blanco in the state of Lara. Results. Sexual dimorphism was observed in the Sanare specimens, with female wings consistently larger than male wings. Similarly, female wings and heads from bugs captured in Caracas were smaller than those of female bugs captured in Sanare. No significative differences in the conformation of the pronotum were found between male and female bugs. Conclusions. Based on the assumption that the sexual dimorphism of bugs is reflected by smaller size in domesticated triatomines than in wild bugs, the conclusion is that Caracas P. geniculatus has become adapted to living indoors. This represents an additional risk factor for the Chagas disease transmission in Caracas.

La adenosin deaminasa (ADA), es una enzima del metabolismo de las purinas que ha sido objeto de mucho interés debido a que el defecto congénito de esta enzima causa el síndrome de inmunodeficiencia combinada severa. Una de las tres isoformas de la enzima (ecto-ADA) es capaz de unirse a la glicoproteína CD26 y a los receptores de adenosina A1 y A2B. La interacción ADA-CD26 produce una señal coestimuladora en los eventos de activación de las células T y en la secreción de IFN-g, TNF-a e IL-6. Durante dicha activación la actividad de la enzima está regulada de manera positiva por IL-2 e IL-12 y negativamente por IL-4, basado en un mecanismo de translocación. Diversos estudios señalan que los niveles séricos y plasmáticos de ADA se elevan en algunas enfermedades causadas por microorganismos que infectan principalmente a los macrófagos; así como en trastornos hipertensivos, lo cual podría representar un mecanismo compensatorio como consecuencia de la elevación de los niveles de adenosina y la liberación de mediadores hormonales e inflamatorios estimulados por la hipoxia

Adenosine deaminase (ADA) is an enzyme of purine metabolism which has been the subject of much interest because the congenital defect of this enzyme causes severe combined immunodeficiency syndrome. One of the three isoforms of the enzyme (ecto-ADA) is capable of binding to the glycoprotein CD26 and adenosine receptors A1 and A2B. ADA-CD26 interaction produces a costimulatory signal in the events of T cell activation and secretion of IFN-g, TNF-a and IL-6. During this activation, the enzyme activity is regulated positively by IL-2 and IL-12 and negatively by IL-4, based on the mechanism of translocation. Diverse studies suggest that seric and plasmatic levels of ADA rise in some diseases caused by microorganisms infecting mainly the macrophages and in hypertensive disorders, which may represent a compensatory mechanism resulting from increased adenosine levels and the release of hormones and inflammatory mediators estimulated by hipoxia