Resumo Fundamento: Os níveis plasmáticos de peptídeos natriuréticos cerebrais têm melhor precisão diagnóstica em comparação com a avaliação clínico-radiológica para insuficiência cardíaca aguda. Nas síndromes coronárias agudas (SCA), o valor prognóstico da insuficiência cardíaca aguda é incorporado nos modelos preditivos através da classificação de Killip. Não está estabelecido se o NT-proBNP poderia aumentar a previsão prognóstica. Objetivo: Avaliar se o NT-proBNP, como medida da disfunção ventricular esquerda, melhora o valor prognóstico intra-hospitalar do escore GRACE na SCA. Métodos: Foram incluídos no estudo pacientes admitidos por dor torácica aguda, com eletrocardiograma e/ou critérios de troponina para SCA. O nível plasmático de NT-proBNP foi medido no momento da admissão hospitalar e o desfecho primário foi definido como morte cardiovascular durante a hospitalização. Foi considerado significativo o valor de p < 0,05. Resultados: A mortalidade cardiovascular entre os 352 pacientes estudados foi de 4,8%. O valor preditivo do NT-proBNP para morte cardiovascular foi mostrado por uma estatística C de 0,78 (IC 95% = 0,65-0,90). Após o ajuste para o modelo GRACE subtraído pela variável Killip, o NT-proBNP permaneceu independentemente associado à morte cardiovascular (p = 0,015). No entanto, a discriminação pelo modelo logístico GRACE-BNP (estatística C = 0,83; IC 95% = 0,69-0,97) não foi superior ao escore GRACE tradicional com Killip (estatística C = 0,82; IC 95% = 0,68-0,97). O modelo GRACE-BNP não proporcionou melhora na classificação dos pacientes de alto risco pelo Escore GRACE (índice líquido de reclassificação = - 0,15; p = 0,14). Conclusão: Apesar da associação estatística com a morte cardiovascular, não houve evidências de que o NT-proBNP aumente o valor prognóstico do escore GRACE na SCA.

Abstract Background: Plasma levels of brain natriuretic peptides have better diagnostic accuracy compared to clinical-radiologic judgment for acute heart failure. In acute coronary syndromes (ACS), the prognostic value of acute heart failure is incorporated into predictive models through Killip classification. It is not established whether NT-proBNP could increment prognostic prediction. Objective: To evaluate whether NT-proBNP, as a measure of left ventricular dysfunction, improves the in-hospital prognostic value of the GRACE score in ACS. Methods: Patients admitted due to acute chest pain, with electrocardiogram and/or troponin criteria for ACS were included in the study. The plasma level of NT-proBNP was measured at hospital admission and the primary endpoint was defined as cardiovascular death during hospitalization. P-value < 0.05 was considered as significant. Results: Among 352 patients studied, cardiovascular mortality was 4.8%. The predictive value of NT-proBNP for cardiovascular death was shown by a C-statistic of 0.78 (95% CI = 0.65-0.90). After adjustment for the GRACE model subtracted by Killip variable, NT-proBNP remained independently associated with cardiovascular death (p = 0.015). However, discrimination by the GRACE-BNP logistic model (C-statistics = 0.83; 95%CI = 0.69-0.97) was not superior to the traditional GRACE Score with Killip (C-statistic = 0.82; 95%CI = 0.68-0.97). The GRACE-BNP model did not provide improvement in the classification of patients to high risk by the GRACE Score (net reclassification index = - 0.15; p = 0.14). Conclusion: Despite the statistical association with cardiovascular death, there was no evidence that NT-proBNP increments the prognostic value of GRACE score in ACS.

Resumo Fundamento: Dados prévios têm demonstrado que pacientes na forma indeterminada podem apresentar fibrose miocárdica à ressonância magnética (RM). No entanto, são poucas as informações disponíveis quanto ao grau de fibrose miocárdica apresentada por esses indivíduos, o que guardaria relação com o potencial dessa variável na predição de evolução para a forma cardíaca da doença de Chagas. Objetivos: Descrever a frequência e extensão da fibrose miocárdica avaliada por RM em pacientes da forma indeterminada, comparando com as outras formas da doença. Métodos: Pacientes consecutivamente admitidos tiveram história clínica colhida e foram submetidos à realização de exames laboratoriais e RM. Resultados: Foram estudados 61 pacientes portadores da doença de Chagas, com média de idade de 58 ± 9 anos, sendo 17 pacientes na forma indeterminada, 16 na forma cardíaca sem disfunção do ventrículo esquerdo (VE) e 28 na forma com disfunção do VE. Foi considerado estatisticamente significante p < 0,05. Realce tardio foi detectado em 37 pacientes (64%). Foi identificada fibrose miocárdica em 6 indivíduos na forma indeterminada (41%; IC95% 23 - 66), proporção semelhante à observada na forma cardíaca sem disfunção do VE (44%); p = 1,0. Entre os indivíduos com fibrose, a área total do miocárdio acometida foi de 4,1% (IIQ: 2,1 - 10,7) na forma indeterminada versus 2,3% (IIQ: 1 - 5) na forma cardíaca sem disfunção do VE (p = 0,18). A fração de ejeção do ventrículo esquerdo nos indivíduos na forma indeterminada foi semelhante aos portadores da forma cardíaca sem disfunção ventricular (p = 0,09). Conclusão: A presença de fibrose na forma indeterminada da doença de Chagas tem frequência e extensão semelhante à forma cardíaca sem disfunção, o que sugere que a primeira faz parte de um espectro de doença subclínica, em vez da ausência de acometimento cardíaco.

Abstract Background: Previous data has shown that patients in the indeterminate form of Chagas disease may present myocardial fibrosis as shown on through magnetic resonance imaging (MRI). However, there is little information available regarding the degree of severity of myocardial fibrosis in these individuals. This variable has the potential to predict the evolution of Chagas’ disease into its cardiac form. Objectives: To describe the frequency and extent of myocardial fibrosis evaluated using an MRI in patients in the indeterminate form, and to compare it with other forms of the disease. Methods: Patients were admitted one after another. Their clinical history was collected and they were submitted to laboratory exams and an MRI. Results: Sixty-one patients with Chagas’ disease, with an average age of 58 ± 9 years old, 17 patients in the indeterminate form, 16 in the cardiac form without left ventricular (LV) dysfunction and 28 in the cardiac form with LV dysfunction were studied. P <0.05 was considered to be statistically significant. Late enhancement was detected in 37 patients (64%). Myocardial fibrosis was identified in 6 individuals in indeterminate form (41%; 95% CI 23-66) in a proportion similar to that observed in cardiac form without LV dysfunction (44%); p = 1.0. Among the individuals with fibrosis, the total area of the affected myocardium was 4.1% (IIQ: 2.1 - 10.7) in the indeterminate form versus 2.3% (IIQ: 1-5) in the cardiac form without LV (p = 0.18). The left ventricular fraction ejection in subjects in the indeterminate form was similar to that of the individuals in the cardiac form without ventricular dysfunction (p = 0.09). Conclusion: The presence of fibrosis in the indeterminate form of Chagas’ disease has a frequency and extension similar to that of in the cardiac form without dysfunction, suggesting that the former is part of a subclinical disease spectrum, rather than lacking cardiac involvement.

We have previously confirmed the presence of common antigens between Schistosoma mansoni and its vector, Biomphalaria glabrata. Cross-reactive antigens may be important as possible candidates for vaccine and diagnosis of schistosomiasis. Sera from outbred mice immunized with a soluble Biomphalaria glabrata antigen (SBgA) of non-infected B. glabrata snails recognized molecules of SBgA itself and S. mansoni AWA by Western blot. Recognition of several molecules of the SBgA were inhibited by pre-incubation with AWA (16, 30, 36, 60 and 155 kDa). The only specific molecule of AWA, inhibited by SBgA, was a 120 kDa protein. In order to determine which epitopes of SBgA were glycoproteins, the antigen was treated with sodium metaperiodate and compared with non-treated antigen. Molecules of 140, 60 and 24 kDa in the SBgA appear to be glycoproteins. Possible protective effects of the SBgA were evaluated immunizing outbred mice in two different experiments using Freund's Adjuvant. In the first one (12 mice/group), we obtained a significant level of protection (46%) in the total worm load, with a high variability in worm recovery. In the second experiment (22 mice/group), no significant protection was observed, neither in worm load nor in egg production per female. Our results suggest that SBgA constitutes a rich source of candidate antigens for diagnosis and prophylactic studies.

Severe schistosomiasis is a rare event in Venezuela nowadays, after a successful national campaign by the Schistosomiasis Control Program. Unfortunately, this program has practically disappeared, and snail surveillance in field is not a priority, anymore. Thus, schistosomiasis has become a neglected disease in this country. However, surveys in different populations from the endemic area have shown particular epidemiological features described herein. In five communities we evaluated 2,175 persons and searched for the presence of Biomphalaria glabrata snails. Some markers were used for classifying schistosomiasis foci: mean age of the persons with Schistosoma mansoni eggs in the stools, serological tests, presence of B. glabrata snails, and intensity of infection. Places without B. glabrata snails and with few schistosomiasis cases were defined as "past transmission sites"; a site with abundant snails but few cases was defined as "potential risk"; "new transmission" foci were characterized by the presence of infected snails and young people passing eggs in the stools. A "re-emergent" focus has shared these last features, showing in addition a place where schistosomiasis had been reported before. Recent evidences of active transmission with the increasing dispersion of B. glabrata snails, point out the necessity for the re-establishment of the Schistosomiasis Control Program in Venezuela.

Schistosomiasis control seems to be different in countries were low parasitic burden and asymptomatic clinical patients are the features of majority of cases. Immunological methods must substitute the traditional coprologic techniques used for some decades in the Control Program. Circumoval Precipitin Test (COPT), intradermal test and ELISA with soluble egg antigen (SEA) are evaluated for using as tools for seroepidemiologic studies. COPT and ELISA were performed after treatment to known their utility when impact of chemotherapy must be assessed. One hundred sixty five persons were followed up 3, 6, 9 and 12 months after treatment. The mean sensitivity of CPT studied by age groups was 95.6% which is very important considering that 88.4% of the studied population excreted less than 100 egg/gr of feces, while sensitivity of intradermal test was 58.2%. Children showed the highest ractivity to COPT. When treatment is effective, COPT reactivity progressively disminish until become negative one year later. In the non cure group, the COPT reactivity disminished but never below 20%. ELISA-SEA did not modify one year after treatment. Effort should be made to isolate fractions of eggs Schistosoma mansoni whose antibodies disappear after treatment.

Dezesseis doentes infectados e não tratados com S. mansoni (5 com infecção recente e 11 com doença crônica), foram submetidos à avaliação de atividade de células exterminadoras na turais (NK) "in vitro" frente a células alvo de linhagem K562. Os níveis de atividade das céluIas NK em 9 de 11 doentes (827r) com a infecção crônica foram significativamente menores (média = 15 ± 6%) quando comparados aos pacientes com infecção recente (média =41 ± 9%, p < 0,001) e aos indivíduos do grupo controle (média = 38 ± 13%, p < 0,001). Porém, tanto nos doentes como nos controles, a atividade de céluIas NK foi estimulada pelo antígeno solúvel do parasito adulto (SAWA), indicando que as céluIas NK, mesmo na fase crônica da infecção, têm capacidade de responder ao antígeno dos parasitos. Estes resultados sugerem a possível participação das células NK no mecanismo efetor de defesa contra o S. mansoni.

Sixteen S. mansoni infected and untreated patients (5 with recent infection and 11 with chronic disease) were evaluated for their in vitro natural killer (NK) activity against the NK sensitive target K562 cell line. NK levels in 9 out of 11 patients (82%) with chronic disease were significantly lower (mean = 15 ± 6%),compared with patients recently infected (mean = 41 ± 9% p < 0.001) and with the control group (mean = 38 ± 13% p < 0.001). However, both patients and controls NK activity was stimulated by soluble adult worm antigens (SAWA), indicating that NK function even in the chronic stage of the infection is able to respond to the parasite antigens. These results suggest the possibility of NK cell participation as effector mechanism against S. mansoni.

A resposta imune celular foi estudada em pacientes com infecção recente ou crônica por Schistosoma mansoni. Células mononucleares do sangue periférico pré cultivadas reagiram significantemente a antígenos do verme adulto (SAWA) do S. mansoni quando comparadas à preparação contendo células frescas. A adição de soro autólogo às células pré-cultivadas resultou em inibição da reação frente a SAWA ou antígenos de memória; o mesmo efeito foi notado quando os soros de pacientes foram adicionados a culturas de células alogênicas obtidas de indivíduos normais. A subpopulação CD4 foi a principal população celular respondedora a SAWA, sendo que esta reatividade foi intensamente suprimida na presença de preparações purificadas contendo monócitos-macrófagos. Estes resultados sugerem a ação de fatores inibidores, tanto humorais como celulares, sobre a resposta imune celular específica ao S. mansoni.

Cell mediated immune response was studied in patients with recent and chronic Schistosoma mansoni infection. Precultured peripheral mononuclear cells showed significantly higher responses to S. mansoni adult worm antigen (SAWA) when compared to fresh cell preparations. The addition of each patient serum to the precultured cells reactions to SAWA or recall antigens demonstrated a strong inhibitory serum action, which was also noted on allogeneic cells derived from healthy subjects. The CD4 subset was the main responding cell to SAWA being this reactivity highly suppressed by the presence of the monocyte macrophage accessory cells. We stressed the simultaneous inhibitory action of humoral and cellular factors on the specific cell response to S. mansoni.

The number and pattern of argentophilic papillae (chaetotaxy) of Schistosoma mansoni cercariae, permits the differentiation between the male and the female of this larval stage, through the following criteria: - A greater homogenity in the male cercariae concerning the number of ventral and dorsal papillae on the body and tail (C.V.= 4.1%), than in the female cercariae (C.V.=18.3%) (p<0.001). - The presence in the 80% of the male cercariae of papillae on the inferior-right and left quadrant, respectively, on the ventral surface; while this criterion is only present in the 40% of the female cercariae (P<0.001). A significative statistical difference (P<0.001) between the average number of ventral body papillae in the female cercariae (X =11.9 ± 0.2) and the male cercariae (X = 11.1 ± 0.3). -A significative statistical difference (p<0.05) for the average of the major distance between the papillae AIL-AIIL for each cercariae in relation to the sex (men = 25.5 µm, women = 27.3 µm).

El número de papilas argirófilas superficiales y su modelo de disposición en el tegumento de las cercarias (quetotaxia) de Schistosoma mansoni nos permitió diferenciar los sexos a nivel del mencionado estadío larvario, mediante los siguientes critérios: - Mayor homogeneidad en las cercarias machos, en cuanto al número total de papilas ventrales y dorsales a nivel de cuerpo y cola cercarianos (C.V. = 4,1%), que en las cercarias hembras (C. V. = 18,3%) (P < 0,001). - Presencia en el 80% de las cercarias machos de cuatro papilas en los cuadrantes "C" ó "D" )inferior-izquierdo e inferior-derecho, respectivamente) ventrales, mientras que dicho caracter sólo está presente en el 40% de las cercarias hembras (P < 0,001). - Diferencia estadísticamente significativa (P < 0,001) entre el número total promedio de papilas corporales centrales de las cercarias hembras (X = 11,9 ± 0,2) y el de las cercarias machos (X = 11,1 ± 0,3). - Diferencia estadísticamente significativa (P < 0,05) para la mayor distancia promedio entre las papilas AIL y AIIL, de cada cercaria, en relación con el sexo (femenino = 25,5 µm ± 0,33; masculino = 27,3 µm ± 0,26).