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.

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.

La reinfestación por vectores secundarios es un problema emergente para la transmisión de la enfermedad de Chagas. Objetivo: Realizar un análisis comparativo para determinar los factores de riesgo asociados a la seropositividad en humanos. Materiales y Métodos: Estudio ecoentomológico y seroepidemiológico realizado en dos comunidades del Estado Lara, infestadas por Triatoma maculata o Panstrongylus geniculatus. Resultados: Guariquito (bosque húmedo tropical templado intervenido para actividad agrícola) mostró una seroprevalencia (SP) canina del 33,33 % y humana del 6,81 % asociada a: menores de 40 años, vector en vivienda anterior, comer animales de caza, migración rural, reconocimiento y contacto con el vector, siendo factores protectores conocimiento del vector y haber vivido en ranchos; infestación 20,45 %, colonización 0 % e infección 18,75 %; ninfas capturadas en cuevas de Xenarthra, los cuales se encontraron infectados (20 %), al igual que Rodentias (25 %). Cauderales (región semidesértica): SP humana del 11,56 % asociada a: mayores de 40 años, vector en vivienda anterior tipo rancho, comer animales de caza, migración rural, reconocimiento y contacto con el vector, siendo factor protector presencia de caninos en la vivienda, los cuales fueron seronegativos; infestación 5,51 %, colonización 0 % e infección-vivienda 0 %; ninfas y Chiropteras no infectadas fueron capturadas en Cactáceas. Conclusión: Panstrongylus geniculatus es responsable de la transmisión reciente en regiones intervenidas de bosque tropical húmedo y con reservorios de los géneros Xenarthra y Rodentia; Tm tiene capacidad vectorial limitada debido a bajos índices de infección producto de sus fuentes de alimento.

Reinfestation by secondary vectors is an emerging problem for h g ’ i e e smission. Objective: To make a comparative analysis and to identify risk factors associated with human seropositivity. Methods: We have done and ecoentomological and seroepidemiologic study in two communities in Lara state, infested by Triatoma maculata or Panstrongylus geniculatus. Results: Guariquito (temperate rainforest, human intervened for agricultural activity) showed 33,33 % og’ e op ev le ce (SP) 6,81 % hum SP associated with: individuals under 40 years, vector infestation of previous house, eating hunting animals, rural migration, vector recognition or contact; protective factors were: knowledge about vectors and used to live in dwellings; 20,45 % infestation, 0% colonization and 18,75 % infection; nymphs were capture in Xenarthra caves, which were found infected (20 %), as well as Rodentias (25 %). Cauderales (semi-desert region) showed 11,56 % human SP associated with: individuals older than 40 years, vector presence in dwellings, eating wild animals, rural migration, recognition and vector contact; as protective factors presence of dogs in the house, which were seronegative; 5,51 % infestation, 0 % colonization or infection indexes; non-infected Chiropteras and Tm nymphs were captured in Cactaceae. Conclusion: Panstrongylus geniculatus is the vector responsible for recent transmission of Chagas disease in tropical rain forest regions, where human intervention is in evolution and reservoirs of genera Xenarthra and Rodentia are present, while Tm has a limited vector capacity because of their low rates of infection as consequence of their food sources.

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.

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

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. 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. 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.

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.

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% y en cánidos de 6,36%. De los 545 triatominos capturados 97,98% fueron T. maculata, 1,65% Eratyrus mucronatus y 0,37% Panstrongylus geniculatus; con índices vectoriales de infección 0,36%, infestación 16,4%, colonización 39,1%, coinfestación 8,6% y dispersión 100%. 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% 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.

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% y en cánidos de 6,36%. De los 545 triatominos capturados 97,98% fueron T. maculata, 1,65% Eratyrus mucronatus y 0,37% Panstrongylus geniculatus; con índices vectoriales de infección 0,36%, infestación 16,4%, colonización 39,1%, coinfestación 8,6% y dispersión 100%. 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.

La Miocardiopatía Chagásica Crónica (MCC) se relaciona con el sistema colinérgico por las teorías neurogénica y autoinmune. La teoría neurogénica explica la MCC como resultado de la denervación parasimpática. La ciclofosfamida (CF) facilita el desarrollo de enfermedades autoinmunes por una depleción selectiva de las células T supresoras. En este estudio caracterizamos el reflejo vasovagal inducido por fenilefrina usando drogas colinérgicos, en dos modelos animales: ratas infectadas con Trypanosoma cruzi (TC) y ratas con MCC inducida por ciclofosfamida. 90 ratas Sprague Dawley fueron divididas en 4 grupos: Control (C), CF, TC y TCCF; los grupos TC y TCCF fueron inoculadas con 1000 tripomastigotes/g; los grupos CF y TCCF fueron tratados con CF 20 mg/kg dos veces por semana por 5 veces. Después de 6 meses de evolución de la infección, las ratas fueron sometidas a estudios electrocardiográficos (EKG), radiológicos (Rx) e histopatológicos (HP). La integridad vagal fue evaluada mediante fenilefrina y tacrina, la funcionalidad colinérgica mediante antagonistas muscarínicos selectivos. Los resultados mostraron que las ratas del grupo TCCF presentaron mayor frecuencia de trastornos electrocardiográficos, radiológicos e histopatológicos. Las ratas de los grupos TC y TCCF mostraron una respuesta disminuida a: fenilefrina que induce bradicardia refleja; metoctramina, 4-DAMP y tropicamida que inducen taquicardia; metoctramina que induce acortamiento del complejo QRS; y tropicamida que induce un alargamiento del intervalo QT. En conclusión, CF facilita el desarrollo de MCC en ratas infectadas con TC, promoviendo trastornos parasimpáticos que aparecen como consecuencia de alteraciones en la distribución de los receptores muscarínicos a diferentes niveles de integración neural.

Chronic Chagasic Cardiomyopathy (CCC) has been related to the cholinergic system by the neurogenic and autoimmune theories. The neurogenic theory explains cardiomyopathy as a result of post-ganglionic parasympathetic denervation. Cyclophosphamide (CP) facilitates the development of autoimmune disease because of a selective depletion of suppressor T cells. In this study we characterized the phenylephrine-induced vasovagal reflex using selective cholinergic drugs, in two rat models: Trypanosoma cruzi (TC) infected animals and CCC CP-treated rat model. To achieve this goal, 3 week old-90 Sprague Dawley rats were divided into four groups: Control (C), CP, TC and TCCP; TC and TCCP were inoculated with 1000 trypomastigotes/g; CP and TCCP were treated with CP 20 mg/Kg twice a week for five times. After 6 months, the studied animals underwent electrocardiographic (EKG), radiographic (Rx) and histopathological (HP) assesments. The vagal integrity was evaluated by application of phenylephrine (PE) plus tacrine, while the muscarinic cholinergic function was evaluated using selective M1, M2, M3 and M4 muscarinic antagonists. Our data show show that TCCP rats displayed the highest frequency of EKG, Rx and HP disturbances. TC and TCCP rats exhibited a decreased response to: 1) phenylephrine-induced vagal baroreflex bradycardia; 2) methoctramine-, 4-DAMP- and tropicamide-induced tachycardia; 3) methoctramine-induced QRS shortening, and 4) tropicamide-induced QT prolongation. In conclusion, CP facilitates the development of CCC in Trypanosoma cruzi infected rats, by promoting parasympathetic disturbances that appear as consequence of alterations on the muscarinic receptor distribution at different neural integration levels.

Mediante morfometría geométrica de las alas se estudió Triatoma maculata procedente de ambientes domiciliarios y peridomiciliarios en la localidad de Cauderales, estado Lara, en el Centro Occidente de Venezuela. Se colectaron 74 ejemplares, 34 domiciliarios y 40 peridomiciliarios, entre Noviembre de 2002 y Noviembre de 2003. No se encontraron diferencias significativas de la variable tamaño ni de la conformación de las alas entre individuos machos y hembras del domicilio y peridomicilio, lo que sugiere que los ejemplares de T. maculata colectados forman parte de una misma población, y por tanto no se evidencia que esta especie esté desarrollando mecanismos adaptativos al domicilio.

Wing geometric morphometrics was used to study the spatial structuring of populations of Triatoma maculata from different ecotopes within a village in western Venezuela. A total of 74 T. maculata collected from peridomestic and domestic ecotopes from November 2002 to November 2003 were analyzed. No statistically significant differences were found between males and females from domestic and peridomestic ecotopes, which suggests that the triatomines collected form part of the same population and therefore non-adaptative strategies are being developed by T. maculata to human dwellings in this locality.

A seroepidemiological survey and vector captures were performed in four rural communities in Andrés Eloy Blanco, Lara State, Venezuela. Systematic random sampling was based on family clusters, with samples drawn from 869 individuals to determine anti-Trypanosoma cruzi and anti-Leishmania sp. antibodies by indirect immunofluorescence. Positive individuals were defined as > 1:32 for anti-T. cruzi antibody and non-reactive to Leishmania sp. antigen, revealing an antibody frequency of 6.9% (n = 60), of whom 46.66% were females and 53.33% males and 60% were over 39 years of age. Some 5 (8.33%) seropositive individuals were under 10 years of age and 10 (16.66%) under 20 years. Rhodnius prolixus and Panstrongylus geniculatus were the triatomines captured, with infestation rates of 1.9% and 10.54%, colonization index of 0% and 18.18% in infested houses, and a T. cruzi infection index of 20% and 5.07%, respectively. The results suggest active Chagas disease transmission in Andrés Eloy Blanco in the last two decades and that P. geniculatus is replacing R. prolixus as the Chagas disease vector.

Se realizó un despistaje serológico y recolección de vectores en cuatro comunidades rurales del municipio Andrés Eloy Blanco, Estado Lara, Venezuela. La muestra fue escogida en forma sistemática y aleatoria basada en conglomerados familiares. Se muestrearon 869 habitantes para determinar anticuerpos anti-Trypanosoma cruzi y anti-Leishmania sp. por inmunofluorescencia indirecta, aceptando como positivo diluciones > a 1:32 para anticuerpos anti-T. cruzi no reactivos para antígenos de Leishmania sp., obteniendo una frecuencia de anticuerpos en la muestra de 6,9% (n = 60); de los cuales 46,66% son femeninos, 53,33% masculinos y 60% mayores de 40 años. Se observó que 5 (8,33%) de los seropositivos eran menores de 10 años y 10 (16,66%) menores de 20 años. Rhodnius prolixus y Panstrongylus geniculatus fueron los triatominos capturados, con índice de infestación de 1,9 y 10,54%, índice de colonización, del 0 y 18,18% en las viviendas infestadas e índice de infección a T. cruzi del 20 y 5,07%, respectivamente. Los resultados sugieren que existe una transmisión activa de la enfermedad de Chagas en el Municipio Andrés Eloy Blanco en las últimas dos décadas y que P. geniculatus está substituyendo a R. prolixus como vector de la enfermedad de Chagas.