Dipyridamole potentiated the trypanocidal effect of nifurtimox and improved the cardiac function in NMRI mice with acute chagasic myocarditis.

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.

Dipyridamole potentiated the trypanocidal effect of nifurtimox and improved the cardiac function in NMRI mice with acute chagasic myocarditis

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.

ADENOSINE DEAMINASE ACTIVITY AND SERUM C-REACTIVE PROTEIN AS PROGNOSTIC MARKERS OF CHAGAS DISEASE SEVERITY.

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.

ADENOSINE DEAMINASE ACTIVITY AND SERUM C-REACTIVE PROTEIN AS PROGNOSTIC MARKERS OF CHAGAS DISEASE SEVERITY / Atividade da adenosina deaminase e níveis de proteina C reativa sérica como marcadores de gravidade na doença de Chagas

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.

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.

[Risk factors associated with the diagnosis of chronic Chagasic miocardiopathy in seropositive individuals from Barinas state, Venezuela]. / Factores de riesgo asociados con el diagnóstico de miocardiopatía chagásica crónica en individuos seropositivos del estado Barinas, Venezuela.

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%; CI 95% = 66.4-74.4) had criteria for CChM, of which 74 (64.4%; IC 95% = 60.2-68.6) were in phase II; while 34 (29.6%; IC 95% = 25.5-33.5) were in phase I of the disease and 7 (6.1%; IC 95% = 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.

Factores de riesgo asociados con el diagnóstico de miocardiopatía chagásica crónica en individuos seropositivos del estado Barinas, Venezuela / Risk factors associated with the diagnosis of chronic chagasic miocardiopathy in seropositive individuals from Barinas state, Venezuela

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.

Electrophysiological and pharmacological evaluation of the nicotinic cholinergic system in chagasic rats.

BACKGROUND: Two theories attempt to explain the changes observed in the nicotinic acetylcholine receptors (nAChRs) in chagasic cardiomyopathy. The neurogenic theory proposes that receptor changes are due to loss of intracardiac ganglia parasympathetic neurons. The immunogenic theory proposes that the nAChRs changes are the result of autoantibodies against these receptors. Both theories agreed that nAChRs functional expression could be impaired in Chagas disease. METHODS: We evaluated nAChRs functional integrity in 54 Sprague Dawley rats, divided in two groups: healthy and chronic chagasic rats. Rats were subjected to electrocardiographic studies in the whole animal under pentobarbital anesthesia, by isolation and stimulation of vagus nerves and in isolated beating hearts (Langendorff's preparation). RESULTS: Nicotine, 10 µM, induced a significant bradycardia in both groups. However, rats that had previously received reserpine did not respond to nicotine stimulation. ß-adrenergic stimulation, followed by nicotine treatment, induced tachycardia in chagasic rats; while inducing bradycardia in healthy rats. Bilateral vagus nerve stimulation induced a significantly higher level of bradycardia in healthy rats, compared to chagasic rats; physostigmine potentiated the bradycardic response to vagal stimulation in both experimental groups. Electric stimulation (e.g., ≥ 2 Hz), in the presence of physostigmine, produced a comparable vagal response in both groups. In isolated beating-heart preparations 1 µM nicotine induced sustained bradycardia in healthy hearts while inducing tachycardia in chagasic hearts. Higher nicotine doses (e.g.,10 - 100 uM) promoted the characteristic biphasic response (i.e., bradycardia followed by tachycardia) in both groups. 10 nM DHßE antagonized the effect of 10 µM nicotine, unmasking the cholinergic bradycardic effect in healthy rats only. 1 nM α-BGT alone induced bradycardia in healthy hearts but antagonized the 10 µM nicotine-induced tachycardia in chagasic rats. In healthy but not in chagasic hearts, 10 µM nicotine shortened PQ and PR interval, an effect counteracted by MA, DHßE and αBGT CONCLUSION: Our results suggest that cholinergic function is impaired in chronic Chagas disease in rats, a phenomena that could be related to alteration on the nAChR expression.

Electrocardiography repolarization abnormalities are characteristic signs of acute chagasic cardiomyopathy / Los trastornos de la repolarización ventricular son signos característicos de la cardiomiopatía chagásica aguda

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 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.

Electrocardiography repolarization abnormalities are characteristic signs of acute chagasic cardiomyopathy.

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.

Prevalence of Trypanosoma cruzi antibodies and inflammatory markers in uncompensated heart failure / Prevalência de anticorpos anti-Trypanosoma cruzi e marcadores inflamatórios em pacientes com insuficiência cardíaca descompensada

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 percent and 40.1 percent 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 percent, 48 percent, 17.8 percent, 13.7 percent, and 6.9 percent 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.

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 por cento e 40,1 por cento 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 por cento 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.

Persistence of Chagas disease active transmission among dogs in Venezuela rural community / Persistencia de la enfermedad de Chagas y trasmisión activa entre perros en una comunidad rural de Venezuela

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.

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.

[Seroprevalence for Trypanosoma cruzi infection and associated factors in an endemic area of Venezuela]. / Seroprevalencia de la infección por Trypanosoma cruzi y factores asociados en un área endémica de Venezuela.

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.

Seroprevalencia de la infección por Trypanosoma cruzi y factores asociados en un área endémica de Venezuela / Seroprevalence for Trypanosoma cruzi infection and associated factors in an endemic area of Venezuela

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 percent in humans and 6.9 percent 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 por ciento y la canina 6,9 por ciento. 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.

Prevalence of Trypanosoma cruzi antibodies and inflammatory markers in uncompensated heart failure.

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, ILß1, 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.

[Viability and spatial structuring in a Triatoma maculata (Hemiptera: Reduviidae) laboratory colony fed with human blood]. / Evaluación de la estructura espacial de Triatoma maculata del centro-occidente de Venezuela y su viabilidad alimentado con sangre humana en condiciones de laboratorio.

INTRODUCTION: Immature and adult forms of Triatoma maculata have been captured repeatedly in and around the homes in the town of Xaguas, Venezuela. Because of its potential as a Chagas disease vector, a study was undertaken to evaluate the effect of human blood feeding on the viability and spatial structuring of a laboratory colony of this species. OBJECTIVE: The effect of human blood feeding was determined for the viability of a T. maculata laboratory colony, as well as its spatial structuring. MATERIAL AND METHODS: Insects were fed with human blood on artificial feeder. Spatial structuring was undertaken by the generalized analysis of by geometric morphometry. RESULTS: The average fecundity of 27.7 eggs/female/lifetime was found, with a mean time to oviposition of 32.7 days, and a female longevity of 39.2 days. The longest inter-molt period was at the fifth nymphal stage (45.9 days), whereas the shortest was at 18.4 days, during the first nymphal stage. The highest mortality of nymphs was observed at the fifth nymphal stage (77.8%). The lowest molting percentage was observed in the fifth nymphal stage (22.2%). No differences in the size of wings and heads were detectable; although differences in the head shape of individuals of the same sex from different environments were noted. Wing-shape differences were found only between the males of peridomestic and domestic ecotopes. CONCLUSIONS: Triatoma maculata may be entering human dwellings to feed on non-human animals, or alternatively, may be in an incipient state of adaptation to a domestic ecotope for feeding on human beings.

Adenosina induce arritmias ventriculares en corazones con miocardiopatía chagásica crónica / Adenosine induces ventricular arrythmias in hearts with chronic chagas cardiomyopathy

La adenosina liberada durante la isquemia y la hipoxia es capaz de inducir arritmias ventriculares, fenómenos también observados en la enfermedad de Chagas. En este trabajo caracterizamos farmacológicamente las propiedades arritmogénicas de la adenosina en ratas Sprague Dawley sanas (n = 14) y con miocarditis chagásica crónica (n = 14), que fueron sometidas a estudios electrocardiográficos y farmacológicos en preparaciones de corazón aislado tipo Langendorff. La adenosina incrementó las arritmias ventriculares en ambos grupos en forma dosis-dependiente, y en un 50% de las ratas chagásicas indujo fibrilación ventricular respecto a un 7,14% de las ratas sanas (p < 0,05). La fibrilación fue prevenida por antagonistas A1 (DPCPX) y A2a (8-CSC). Las arritmias se asociaron a un QT prolongado, a depolarizaciones tempranas, a fenómenos R sobre T y torsade de pointes. En conclusión, la adenosina es un fármaco proarrítmico capaz de inducir fibrilación ventricular en ratas chagásicas (AU)

Adenosine released during ischemia and hypoxia can induce ventricular arrhythmias. This phenomenon is also observed in Chagas disease. This study involved pharmacologic analysis of the arrhythmogenic properties of adenosine in healthy Sprague-Dawley rats (n=14) and in rats with chronic Chagas cardiomyopathy (n=14). Electrocardiographic and pharmacologic studies were performed on isolated hearts prepared using the Langendorff method. Adenosine increased ventricular arrhythmias in both groups of animals in a dose-dependent manner: 50% of chagasic rats developed ventricular fibrillation compared with 7.14% of healthy rats (P < .05). Fibrillation was prevented by A1 (i.e., DPCPX) and A2a (i.e., 8-CSC) receptor antagonists. Arrhythmia was associated with a prolonged QT interval, early depolarization, and the R-on-T and torsade de pointes phenomena. In conclusion, adenosine is a proarrythmic drug that is able to induce ventricular fibrillation in chagasic rat hearts (AU)

[Adenosine induces ventricular arrythmias in hearts with chronic chagas cardiomyopathy]. / Adenosina induce arritmias ventriculares en corazones con miocardiopatía chagásica crónica.

Adenosine released during ischemia and hypoxia can induce ventricular arrhythmias. This phenomenon is also observed in Chagas disease. This study involved pharmacologic analysis of the arrhythmogenic properties of adenosine in healthy Sprague-Dawley rats (n=14) and in rats with chronic Chagas cardiomyopathy (n=14). Electrocardiographic and pharmacologic studies were performed on isolated hearts prepared using the Langendorff method. Adenosine increased ventricular arrhythmias in both groups of animals in a dose-dependent manner: 50% of chagasic rats developed ventricular fibrillation compared with 7.14% of healthy rats (P< .05). Fibrillation was prevented by A1 (i.e., DPCPX) and A2a (i.e., 8-CSC) receptor antagonists. Arrhythmia was associated with a prolonged QT interval, early depolarization, and the R-on-T and torsade de pointes phenomena. In conclusion, adenosine is a proarrythmic drug that is able to induce ventricular fibrillation in chagasic rat hearts.

Evaluación de la estructura espacial de Triatoma maculata del centro-occidente de Venezuela y su viabilidad alimentado con sangre humana en condiciones de laboratorio / Viability and spatial structuring in a Triatoma maculata (Hemiptera: Reduviidae) laboratory colony fed with human blood

Introducción. Dado el reiterado hallazgo de adultos y formas inmaduras de Triatoma maculata capturados en domicilios y peridomicilios en la localidad de Xaguas (Venezuela), se analizó la viabilidad de una colonia de laboratorio de esta especie alimentada con sangre humana y su estructura espacial. Objetivos. Analizar la viabilidad del ciclo de T. maculata alimentado con sangre humana en condiciones de laboratorio y caracterizar la estructura espacial de una población de T. maculata proveniente de ambientes domiciliarios y peridomiciliarios del centro-occidente de Venezuela. Materiales y métodos. La alimentación con sangre humana se llevó a cabo en lotes por estadio, utilizando un alimentador artificial, y la estructura espacial de los insectos por sexo y ambiente fue analizada mediante morfometría geométrica. Resultados. Los hallazgos fueron: fecundidad promedio, 27,70 huevos/hembra/vida, tiempo promedio de postura de huevos, 32,74 días, y longevidad promedio de la hembra, 39,15 días; el mayor tiempo en V estadio fue de 45,9 días y el menor en I estadio, 18,41 días; la mayor mortalidad fue de 77,78% y el menor porcentaje de muda en V estadio, de 22,23%.No se encontraron diferencias en el tamaño de alas y cabezas; sí se encontraron diferencias de conformación entre las cabezas de un mismo sexo de diferentes hábitats; sólo se encontraron diferencias de conformación de alas entre los machos del domicilio y peridomicilio. Conclusiones. T. maculata de la localidad de Xaguas podría encontrarse en un estado de adaptación al domicilio con fuentes sanguíneas diferentes al humano y en un estado incipiente de adaptación al domicilio con la sangre humana como fuente de alimentación.

Introduction. Immature and adult forms of Triatoma maculata have been captured repeatedly in and around the homes in the town of Xaguas, Venezuela. Because of its potential as a Chagas disease vector, a study was undertaken to evaluate the effect of human blood feeding on the viability and spatial structuring of a laboratory colony of this species. Objective. The effect of human blood feeding was determined for the viability of a T. maculata laboratory colony, as well as its spatial structuring. Material and methods. Insects were fed with human blood on artificial feeder. Spatial structuring was undertaken by the generalized analysis of by geometric morphometry. Results. The average fecundity of 27.7 eggs/female/lifetime was found, with a mean time to oviposition of 32.7 days, and a female longevity of 39.2 days. The longest inter-molt period was at the fifth nymphal stage (45.9 days), whereas the shortest was at 18.4 days, during the first nymphal stage. The highest mortality of nymphs was observed at the fifth nymphal stage (77.8%). The lowest molting percentage was observed in the fifth nymphal stage (22.2%). No differences in the size of wings and heads were detectable; although differences in the head shape of individuals of the same sex from different environments were noted. Wing-shape differences were found only between the males of peridomestic and domestic ecotopes.

[An entomological and seroepidemiological study of Chagas' disease in an area in central-western Venezuela infested with Triatoma maculata (Erichson 1848)]. / Estudio seroepidemiológico y entomológico sobre la enfermedad de Chagas en un área infestada por Triatoma maculata (Erichson 1848) en el centro-occidente de Venezuela.

This article presents a study on seroepidemiological, entomologic, and risk factors for domiciliary infestation in a circumscribed area infested with Triatoma maculata in Parroquia Xaguas, Urdaneta Municipality, Lara State, Venezuela. One hundred and forty households, 509 persons, and 110 dogs were sampled. Serum anti-Trypanosoma cruzi antibodies were determined by means of ELISA and MABA techniques using recombinant antigens. Tr. cruzi infection in the triatomines was determined by direct microscopy and PCR. According to the results, 1.57% of humans and 6.36% of dogs were positive for serum anti-Tr. cruzi antibodies. Triatomine species were: 97.98% T. maculata, 1.65% Eratyrus mucronatus, and 0.37% Panstrongylus geniculatus. Vector indices were: 0.36% vector infection, 16.4% household infestation, 39.1% household colonization, 8.6% household co-infestation, and 100% vector dispersion. Domiciliary and peridomiciliary infestation was associated with the presence of chickens and disorderly goat corrals, chicken coops, and domiciliary distribution. The results strongly suggest that T. maculata is the predominant Tr. cruzi vector in the area and that due to its capacity to infest and colonize human dwellings, it could be involved in Chagas' disease transmission.

Estudio seroepidemiológico y entomológico sobre la enfermedad de Chagas en un área infestada por Triatoma maculata (Erichson 1848) en el centro-occidente de Venezuela / An entomological and seroepidemiological study of Chagas' disease in an area in central-western Venezuela infested with Triatoma maculata (Erichson 1848)

En el presente trabajo se realizó un estudio seroepidemiológico, entomológico y de factores de riesgo para la infestación de las viviendas en un área infestada por Triatoma maculata (Parroquia Xaguas, Municipio Urdaneta, Estado Lara, Venezuela). Se muestrearon 140 viviendas, 509 personas y 110 cánidos, a los cuales se les determinó anticuerpos séricos anti-Trypanosoma cruzi mediante ELISA y MABA, utilizando antígenos recombinantes. La infección por Tr. cruzi de los triatominos fue determinada por microscopía óptica y PCR. Los resultados mostraron una seroprevalencia en humanos de 1,57 por ciento y en cánidos de 6,36 por ciento. De los 545 triatominos capturados 97,98 por ciento fueron T. maculata, 1,65 por ciento Eratyrus mucronatus y 0,37 por ciento Panstrongylus geniculatus; con índices vectoriales de infección 0,36 por ciento, infestación 16,4 por ciento, colonización 39,1 por ciento, coinfestación 8,6 por ciento y dispersión 100 por ciento. La presencia de vectores en el domicilio y peridomicilio estuvo asociada a la presencia de gallinas, desorden en el peridomicilio, caprinos, gallineros y/o distribución del domicilio. Los resultados permiten concluir que T. maculata es el vector predominante en la región, con capacidad de infestar y colonizar el domicilio y estaría involucrado en la transmisión de la enfermedad de Chagas.

This article presents a study on seroepidemiological, entomologic, and risk factors for domiciliary infestation in a circumscribed area infested with Triatoma maculata in Parroquia Xaguas, Urdaneta Municipality, Lara State, Venezuela. One hundred and forty households, 509 persons, and 110 dogs were sampled. Serum anti-Trypanosoma cruzi antibodies were determined by means of ELISA and MABA techniques using recombinant antigens. Tr. cruzi infection in the triatomines was determined by direct microscopy and PCR. According to the results, 1.57 percent of humans and 6.36 percent of dogs were positive for serum anti-Tr. cruzi antibodies. Triatomine species were: 97.98 percent T. maculata, 1.65 percent Eratyrus mucronatus, and 0.37 percent Panstrongylus geniculatus. Vector indices were: 0.36 percent vector infection, 16.4 percent household infestation, 39.1 percent household colonization, 8.6 percent household co-infestation, and 100 percent vector dispersion. Domiciliary and peridomiciliary infestation was associated with the presence of chickens and disorderly goat corrals, chicken coops, and domiciliary distribution. The results strongly suggest that T. maculata is the predominant Tr. cruzi vector in the area and that due to its capacity to infest and colonize human dwellings, it could be involved in Chagas' disease transmission.