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.

[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.

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.

The cholinergic system in cyclophosphamide-induced Chagas dilated myocardiopathy in Trypanosoma-cruzi-infected rats: an electrocardiographic study.

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.

[Epidemiology of Chagas disease in Andrés Eloy Blanco, Lara, Venezuela: triatomine infestation and human seroprevalence]. / Epidemiología de la enfermedad de Chagas en el municipio Andrés Eloy Blanco, Lara, Venezuela: infestación triatomínica y seroprevalencia en humanos.

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 > or = 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.

[C-reactive protein and interleukin-6 serum levels increase as Chagas disease progresses towards cardiac failure]. / Las concentraciones séricas de interleucina-6 y proteína C reactiva se incrementan a medida que la enfermedad de Chagas evoluciona hacia el deterioro de la función cardíaca.

INTRODUCTION AND OBJECTIVES: Chagas disease is the most common cause of myocarditis in Latin America, including Venezuela. Some 25% of patients progress to chronic chagasic cardiomyopathy, which is characterized by heart failure and arrhythmias. The serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6) have prognostic value in non-chagasic cardiopathy. The goal of this study was to investigate the relationship between the serum levels of CRP and IL-6 and the developmental stage of Chagas disease. PATIENTS AND METHOD: The study included 64 Chagas disease patients (34 female and 30 male; age 62.2 [1.7] years) and 20 healthy individuals (10 of each sex; age 50.4 [2.7] years). Clinical investigations included echocardiography and measurement of CRP and IL-6 serum levels using ELISAs. Chagas disease patients were graded according to Carrasco et al 1994 classification. Patients with ischemic cardiopathy, liver disease, autoimmune disease, a systemic inflammatory condition, immunosuppression, cancer, pericarditis, or endocarditis were excluded. RESULTS: Multiple regression analysis demonstrated an association between Chagas disease developmental stage and the serum IL-6 level. The serum CRP level increased during only the most advanced phase of the disease. In addition, a high left ventricular mass index was associated with a high IL-6 level and male sex. CONCLUSIONS: IL-6 and CRP serum levels could be of prognostic value in assessing Chagas disease progression because there are significant correlations between elevated levels and the deterioration of cardiac function.

[Patients suffering dilated chagasic cardiopathy or non chagasic cardiopathy show an increased levels of tumor necrosis factor alpha]. / Pacientes con cardiomiopatía dilatada chagásica y cardiopatia no chagásica presentan niveles elevados del factor de necrosis tumoral alpha.

Chagas' disease is a public health problem in Venezuela, affecting people living in rural areas. 30% of the patients evolve to a Chronic Chagasic Myocardiopathy (CCM) characterized by heart failure, arrhythmias, incapacity to work and sudden death. There are not predictive factors to determine the evolution from the indeterminate form of the disease (asymptomatic form) to CCM. In the present paper we have studied 115 patients enrolled in the Cardiology unit at the Baudilio Lara Hospital in Quibor (Lara State, Venezuela) and 12 healthy patients coming from the same area. Patients were evaluated by means of clinical history; echocardiography, electrocardiography and radiology. The presence of anti-T. cruzi antibodies and levels of Tumor Necrosis Factor alpha (TNFalpha) were determined in serum samples. Chagas' disease patients were classified in 3 groups: I (asymptomatic), II (asymptomatic with normal left ventricular ejection fraction (LVEF) and electrocardiographic alterations) and and III (symptomatic, electrocardiographic alterations and LVEF < 70%). The results showed that 33.04% of the patients had anti-T. cruzi antibodies in their serum; we also observed a significant increase in the serum levels of TNFalpha in groups I and III of Chagas' disease patients as compared with the control healthy group. Chagas' disease patients belonging to Group II displayed similar TNFalpha levels as controls. We observed a statistically significant (p < 0.05) negative correlation between serum TNFalpha values and LVEF. Patients suffering of non-chagasic myocardiopathy had a significant increase of TNFalpha as compared with control patients and similar levels to those observed in Chagas' disease group III patients. These results confirm that the elevation of TNFalpha serum levels could be a immunopathogenic mechanism in the evolution of myocardiopathies.

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.

Genotypically distinct Leishmania colombiensis isolates from Venezuela cause both cutaneous and visceral leishmaniasis in humans.

Cutaneous leishmaniasis in Venezuela has been associated with different Leishmania species and the visceral form is frequently related to L. chagasi. However, in this study we have characterized as L. colombiensis by molecular techniques some isolates of Leishmania from patients presenting either cutaneous or visceral leishmaniasis. Three different molecular markers (two DNA and one protein) were used to investigate the diversity among the L. colombiensis isolates. The analysis revealed the isolates to be similar although distinct from the reference strain of L. colombiensis. Slight variation among the isolates could not be correlated with any epidemiological features of the samples however the visceral isolates were observed to cluster on a phenetic tree derived from one DNA marker. The results confirm previous findings that L. colombiensis can cause both the cutaneous and visceral forms of the disease and that there exists at least two distinct etiological agents of American visceral leishmaniasis (AVL). The report also shows the necessity of careful differentiation of leishmanial isolates in any clinical or epidemiological study of human leishmaniasis.

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.

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.

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.

[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.

[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.

[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.

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.

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.

[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.

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.

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.