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Sera and peripheral blood mononuclear cells (PBMC) from patients displaying different clinical symptoms as well as from normal uninfected individuals (NI) were used to evaluate the humoral and cellular responses of Chagas' disease patients to Trypanosoma cruzi-derived paraflagellar rod proteins (PFR). Our results show that sera from both asymptomatic Chagas' disease patients (ACP) and cardiac Chagas' disease patients (CCP) have higher levels of antibodies to PFR than sera from NI. Immunoglobulin G1 (IgG1) and IgG3 were the main Ig isotypes that recognized PFR. We also tested three recombinant forms of PFR, named rPAR-1, rPAR-2, and rPAR-3, by Western blot analysis. Sera from seven out of eight patients with Chagas' disease recognized one of the three rPAR forms. Sera from 75, 50, and 37.5% of Chagas' disease patients tested recognized rPAR-3, rPAR-2, and rPAR-1, respectively. PFR induced proliferation of 100 and 70% of PBMC from ACP and CCP, respectively. Further, stimulation of cells from Chagas' disease patients with PFR enhanced the frequencies of both small and large CD4(+) CD25(+) and CD4(+) CD69(+) lymphocytes, as well as that of small CD8(+) CD25(+) lymphocytes. Finally, we evaluated the ability of PFR to elicit the production of gamma interferon (IFN-gamma) by PBMC from patients with Chagas' disease. Fifty percent of the PBMC from ACP as well as CCP produced IFN-gamma upon stimulation with PFR. PFR enhanced the percentages of IFN-gamma-producing cells in both CD3(+) and CD3(-) populations. Within the T-cell population, large CD4(+) T lymphocytes were the main source of IFN-gamma.

A análise epidemiológica da malária em Minas Gerais mostra a necessidade de divulgação permanente da situação da transmissão da doença, de forma a contribuir para a suspeita clínica em casos febris e para o diagnóstico precoce. A divulgação das informações técnicas sobre a malária visa ao melhor desempenho dos serviços de saúde locais, a fim de controlar os casos detectados e diminuir as taxas de morbi-mortalidade. Considera-se ser importante a manutenção de sistema organizado e ativo de vigilância epidemiológica de malária, mesmo em áreas endêmicas.

To verify the association between Human Activity Profile and functional capacity, functional class and systolic function of the patients with Chagas heart disease (CHD). Sixty-two patients with CHD were evaluated by echocardiography, maximal exercise testing and Human Activity Profile questionnaire. The sample was stratified, according to the values of peak oxygen uptake (low or normal), functional class (symptomatic or asymptomatic), and left ventricular ejection fraction (preserved or systolic dysfunction). Linear regression and two-group comparisons analyses were used. Receiver-operating characteristic analysis was used to determine different cutoff values of the Human Activity Profile for low peak oxygen uptake prediction. Peak oxygen uptake was an independent predictor of Human Activity Profile (R2-adjusted = 0.27). Patients with low peak oxygen uptake had lower scores in Human Activity Profile [difference of 6.9 (95%CI 2.5–11.4)] than those with normal peak oxygen uptake. Symptomatic patients also showed lower scores when compared to the asymptomatic [difference of 6.2 (95%CI 1.7–10.8)]. There was no difference between left ventricular ejection fraction classes. The Human Activity Profile score of 76.5 was the optimal cut point value in predicting low peak oxygen uptake (sensitivity = 66.0% and specificity = 71.8%). The Human Activity Profile questionnaire is associated with functional capacity of patients with CHD and is able to identify individuals with low peak oxygen uptake. Functional impairment is one of the most common clinical findings in all stages and is an important predictor of poor prognosis of the Chagas heart disease; A patient-derived measure of functional capacity is potentially useful in the setting of the Chagas heart disease; The Human Activity Profile questionnaire is effective in the identification of patients with Chagas heart disease with functional impairment and may be a valid method for functional evaluation. [ABSTRACT FROM AUTHOR]

Purpose: This study was designed to evaluate the association of non-genetic factors and polymorphisms CYP2C9*2 (rs1799853), CYP2C9*3 (rs1075910), and VKORC1-G1639A (rs9923231) with time in therapeutic range (TTR), and to build a regression model to predict the quality of oral anticoagulation control in a sample of Brazilian patients. Methods: This is a retrospective cohort study developed at an anticoagulation clinic of a university hospital. Overall, 312 patients were included. The quality of oral anticoagulation control was evaluated by TTR. TTR was dichotomized for analysis, using two cutoff points for classification as inadequate (TTR ≤ 60.0%) and optimal (TTR ≥ 75.0%) control. Results: The average age was 60.4 ± 13.5 years, with a predominance of women (187; 59.9%). The -G1639A polymorphism of the VKORC1 gene, when evaluated, based on the recessive inheritance pattern [AA × (GA + GG)], patients with AA genotype exhibited a higher TTR (68.2% versus 62.8%, p = 0.017). TTR ≤ 60.0% was associated with number of drugs in chronic use, assistance for warfarin administration, reports of not taking warfarin, absenteeism, sex (female), and target INR (International Normalized Ratio; 2.00–3.00). TTR ≥ 75.0% was associated with sex (male), target INR (2.00–3.00), assistance for warfarin administration, reports of not taking warfarin, and absenteeism. The two algorithms proposed showed adequate ability to predict TTR presenting good sensitivity and specificity. Conclusions: Our findings provided useful information for risk stratification depending on TTR level and for future investigations on the quality of oral anticoagulation control in Brazilian anticoagulation clinics. [ABSTRACT FROM AUTHOR]

Interleukin 17A (IL-17A) has been associated with protective rather than pathogenic response in Chagas disease (ChD). However, it is not established whether or not IL-17A-mediated immune response is correlated with patient’s left ventricular (LV) function in ChD. To address this question we have gathered cardiac functional parameters from ChD patients and analysed the possible relationship between their plasma IL-17A levels and LV function. Plasma IL-17A levels were measured by BD Cytometric Bead Array (CBA) in 240 patients with positive specific serology for Trypanosoma cruzi (T. cruzi) grouped as indeterminate (IND) and Chagas cardiomyopathy (CARD) forms. The levels of IL-17A in ChD patients were compared with 32 healthy individuals, mean age of 39 years, 50% male, that were also included as a control group (non-infected [NI]). The overall mean age of ChD patients was 46 years and 52% were male. The IND group included 95 asymptomatic patients, with ages ranging from 27 to 69 years (mean of 43 years), and 42.1% of them were male. The CARD group included 145 patients, which 58.6% were male, with ages ranging from 23 to 67 years (mean of 49). The IND group presented substantially higher levels of IL-17A, median of 26.16 (3.66–48.33) as compared to both the CARD group, median of 13.89 (3.87–34.54) (P <0.0001), and the NI group, median of 10.78 (6.23–22.26) (P <0.0001). The data analysis demonstrated that the IND group comprises a significantly greater proportion (P <0.001) of high IL-17A producers (52.6%, 50 of 95 subjects) than do the other groups. A significant direct correlation was verified between IL-17A levels and cardiac function expressed by LV ejection fraction (LVEF), LV diastolic diameter (LVDd), and body surface area (BSA)-indexed LVDd as well as ratio of the early diastolic transmitral flow velocity to early diastolic mitral annular velocity (E/e’) in both groups. We demonstrated that plasma IL-17A levels has an accurate sensitivity and specificity to predict heart failure in serology-positive patients and might be a useful parameter to distinguish patients with or without cardiac impairment. This study indicates a consistent relationship between high expression of IL-17A and better LV in human chronic ChD. Our data raise the possibility that IL-17A plays an important immunomodulatory role in the chronic phase of ChD and might be involved in protection against myocardial damage. [ABSTRACT FROM AUTHOR]

Chagas' disease (ChD), caused by the protozoa Trypanosoma cruzi (T. cruzi), was discovered and described by the Brazilian physician Carlos Chagas in 1909. After a century of original description, trypanosomiasis still brings much misery to humanity and is classified as a neglected tropical disease prevalent in underdeveloped countries, particularly in South America. It is an increasing worldwide problem due to the number of cases in endemic areas and the migration of infected subjects to more developed regions, mainly North America and Europe. Despite its importance, chronic chagas cardiomyopathy (CCC) pathophysiology is yet poorly understood, and independently of its social, clinical, and epidemiological importance, the therapeutic approach of CCC is still transposed from the knowledge acquired from other cardiomyopathies. Therefore, the objective of this review is to describe the treatment of Chagas cardiomyopathy with emphasis on its peculiarities. [ABSTRACT FROM AUTHOR]

Aims: The effects of exercise training in chronic heart failure are well established, however, they have not been evaluated in Chagas cardiomyopathy (ChC). We sought to determine the effects of exercise training on functional capacity, health-related quality of life (HQoL), and brain natriuretic peptide (BNP) levels in patients with ChC. [ABSTRACT FROM PUBLISHER]

Abstract: Aims: NT-proBNP levels are known to be elevated in systolic and diastolic dysfunction. Doppler indices of diastolic dysfunction (DD) have been shown to have prognostic value in patients with Chagas'' cardiomyopathy (CC). However, the additional value of NT-proBNP levels in further stratifying these patients according to DD has not been established. This study analyzed the correlation of N-terminal proBNP (NT-proBNP) levels with systolic and diastolic function in patients with CC. Methods and results: NT-proBNP levels were measured in 59 patients with dilated cardiomyopathy due to Chagas disease without other systemic illness that were studied by Doppler echocardiography, including left atrial volume (LAV) calculation and tissue Doppler evaluation of LV longitudinal function. Univariate analysis showed a strong correlation of NT-proBNP values with LVEF (r =−0.733, p <0.001) and a weak correlation with most Doppler echocardiographic parameters of diastolic function. On a multivariate analysis, LVEF and LAV volume emerged as correlating with elevated levels of the NT-proBNP. Patients with restrictive filling pattern (n =10), when compared to other patterns of DD, (n =49), showed a lower LVEF (25.4±6.4% vs. 39.8±9.4, p <0.001), a larger LAV (50.1±17.2 vs. 37.7±15.6ml/m2, p =0.004) and higher NT-proBNP levels (median±IQR: 3488±3056 vs. 492±700pg/dl, p <0.001). A marked elevated concentration of NT-proBNP (≥800pg/ml) had a sensitivity of 90.0%, specificity of 70.5%, positive predictive value of 40.9% and negative predictive value of 96.9% for detecting a restrictive filling pattern. Conclusion: In patients with CC, NT-proBNP augmentation is a marker of LV dysfunction, with higher levels correlating with the more severe forms of both systolic and diastolic dysfunction. [Copyright &y& Elsevier]

Leishmaniases are diseases caused by several Leishmania species. Leishmania (Viannia) braziliensis can cause localized cutaneous leishmaniasis (LCL), which heals spontaneously, or mucosal leishmaniasis (ML), characterized by chronic and intense inflammation and scanty parasitism. Annexin A1 (AnxA1) is a protein involved in modulation and resolution of inflammation through multiple mechanisms. In the present study, the role of AnxA1 was investigated in L. braziliensis-infected BALB/c mice. AnxA1 levels increased at the peak of tissue lesion and parasitism in infected mice. AnxA1 increased also after L. braziliensis infection of BALB/c (wild-type [WT]) bone marrow derived macrophages. Despite a lower parasite intake, parasite burden in bone marrow-derived macrophages from AnxA1-/- mice was similar to WT and associated with an early increase of TNF-α and, later, of IL-10. AnxA1-/- mice controlled tissue parasitism similarly to WT animals, but they developed significantly larger lesions at later stages of infection, with a more pronounced inflammatory infiltrate and increased specific production of IFN-γ, IL-4, and IL-10. AnxA1-/- mice also presented higher phosphorylation levels of ERK-1/2 and p65/RelA (NF-κB) and inducible NO synthase expression, suggesting that AnxA1 may be involved in modulation of inflammation in this model of experimental leishmaniasis. Finally, assessment of AnxA1 levels in sera from patients with LCL or ML revealed that ML patients had higher levels of serum AnxA1 than did LCL patients or control subjects. Collectively, these data indicate that AnxA1 is actively expressed during L. braziliensis infection. In the absence of AnxA1, mice are fully able to control parasite replication, but they present more intense inflammatory responses and delayed ability to resolve their lesion size. [ABSTRACT FROM AUTHOR]

Chagas disease is a pleomorphic clinical entity that has several unique features. The aim of this study is to summarise some of the recent contributions from our research group to knowledge of the morbidity and prognostic factors in Chagas heart disease. A retrospective study suggested that ischaemic stroke associated with left ventricular (LV) apical thrombi is the first clinical manifestation of Chagas disease observed in a large proportion of patients. LV function and left atrial volume (LAV) are independent risk factors for ischaemic cerebrovascular events during follow-up of Chagas heart disease patients. Pulmonary congestion in Chagas-related dilated cardiomyopathy is common but usually mild. Although early right ventricular (RV) involvement has been described, we have shown by Doppler echocardiography that RV dysfunction is evident almost exclusively when it is associated with left ventricle dilatation and functional impairment. In addition, RV dysfunction is a powerful predictor of survival in patients with heart failure secondary to Chagas disease. We have also demonstrated that LAV provides incremental prognostic information independent of clinical data and conventional echocardiographic parameters that predict survival.

The potential impact of the hepatitis C virus (HCV) on clinical, immunological and virological responses to initial highly active antiretroviral therapy (HAART) of patients infected with human immunodeficiency virus (HIV) is important to evaluate due to the high prevalence of HIV-HCV coinfection. A historical cohort study was conducted among 824 HIV-infected patients starting HAART at a public referral service in Belo Horizonte, Brazil, to assess the impact of HCV seropositivity on appearance of a new AIDS-defining opportunistic illness, AIDS-related death, suppression of viral load, and an increase in CD4-cell count. A total of 76 patients (9.2%) had a positive HCV test, 26 of whom (34.2%) had a history of intravenous drug use. In multivariate analysis, HCV seropositivity was associated with a smaller CD4-cell recovery (RH=0.68; 95% CI [0.49-0.92], but not with progression to a new AIDS-defining opportunistic illness or to AIDS-related death (RH=1.08; 95% CI [0.66-1.77]), nor to suppression of HIV-1 viral load (RH=0.81; 95% CI [0.56-1.17]) after starting HAART. These results indicate that although associated with a blunted CD4-cell recovery, HCV coinfection did not affect the morbidity or mortality related to AIDS or the virological response to initial HAART.

Chemokines and chemokine receptors (CKRs) control the migration of leukocytes during the inflammatory process and are important immunological markers of type 1 (CCR5 and CXCR3) and type 2 (CCR3 and CCR4) responses. The coexpression of CKRs (CCR2, CCR3, CCR5, CXCR3, and CXCR4) and intracellular cytokines (interleukin-10 [IL-10], IL-4, tumor necrosis factor alpha [TNF-alpha], and gamma interferon [IFN-gamma]) on T CD4+ and CD8+ peripheral cells from individuals with indeterminate (IND) or cardiac (CARD) clinical forms of Chagas' disease after in vitro stimulation with Trypanosoma cruzi antigens, were evaluated in this study. The percentage of T CD4+ and CD8+ cells coexpressing CCR5 and IFN-gamma, CXCR3 and IFN-gamma, and CXCR3 and TNF-alpha were higher in CARD than in IND individuals; on the other hand, the percentage of T CD4+ or CD8+ cells coexpressing CCR3 and IL-10 or coexpressing CCR3 and IL-4 were lower in CARD individuals than in IND individuals. In addition, a significant positive correlation between the expression of CCR5 or CXCR3 and IFN-gamma was observed in CARD individuals contrasting with a significant positive correlation between the expression of CCR3 and IL-4 and of CCR3 and IL-10 in IND patients. These results reinforce the hypothesis that a T. cruzi-exacerbated specific type 1 immune response developed by CARD chagasic patients is associated with the development of heart pathology.