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The present study aimed to verify the impact of etiological treatment on the genotype-specific serological diagnosis of chronic Chagas disease patients (CH), using the Chagas-Flow ATE IgG1 methodology. For this purpose, a total of 92 serum samples from CH, categorized as Not Treated (NT, n = 32) and Benznidazole-Treated (Bz-T, n = 60), were tested at Study Baseline and 5Years Follow-up. At Study Baseline, all patients have the diagnosis of Chagas disease confirmed by Chagas-Flow ATE IgG1, using the set of attributes ("antigen/serum dilution/cut-off"; "EVI/250/30%"). The genotype-specific serodiagnosis at Study Baseline demonstrated that 96% of patients (44/46) presented a serological profile compatible with TcII genotype infection. At 5Years Follow-up monitoring, NT and Bz-T presented no changes in anti-EVI IgG1 reactivity. However, significant differences were detected in the genotype-specific IgG1 reactivity for Bz-T. The most outstanding shift comprised the anti-amastigote TcVI/(AVI), anti-amastigote TcII/(AII) and anti-epimastigote TcVI/(EVI) reactivities. Regardless no changes in the genotype-specific serology of NT (TcI = 6%; TcII = 94%), distinct T. cruzi genotype-specific sero-classification was detected for Bz-T samples at 5Years Follow-up (TcII = 100%) as compared to Baseline (TcII = 97%; TcVI = 3%). The anti-trypomastigote TcI/(TI) was the attribute accountable for the change in genotype-specific sero-classification. In conclusion, our findings of dissimilar T. cruzi genotype-specific serology upon Bz-treatment re-emphasize the relevance of accomplishing the genotype-specific serodiagnosis during clinical pos-therapeutic management of chronic Chagas disease patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Alessio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: New technologies and inadequate management of work might have negative impact on the mental health of workers., Objective: To investigate factors associated with the prevalence of burnout and levels of job satisfaction among emergency department and intensive care providers in a large public hospital., Methods: Cross-sectional study with 91 healthcare workers, who were administered the self-report questionnaires Maslach Burnout Inventory - Human Services Survey (MBI-HSS) and Job Satisfaction Scale (JSS20/23)., Results: The sample was predominantly composed of women (58.2%), married workers or with a stable partner (52.8%), having attended graduate studies (75.8%) and with average age 37 years old. Twenty-five percent of the participants exhibited emotional exhaustion and dissatisfaction with the work environment and hierarchical relationships, and 66% had already thought of leaving the profession. Allocation to intensive care unit, lack of professional growth opportunities, dissatisfaction with hierarchical relationships, nursing profession, and having thought of leaving the profession explained 55% of the prevalence of emotional exhaustion., Conclusion: Positive correlation between emotional exhaustion and job dissatisfaction was the earliest identifiable indicator of burnout. Periodic evaluations for early detection and prevention are important to reduce occupational disorders, and consequently improve the quality and safety of care delivery.

Child abuse is a complex, multi-faceted and controversial topic. A retrospective cohort study aimed to characterize the profile of children victims of domestic violence and their aggressors and to evaluate the efficiency of judicial interventions. Ninety-eight cases lodged with the Infancy and Childhood Court involving 179 children and 121 perpetrators were analyzed. Negligence/abandonment (62%) and physical violence (30%) were the most frequent violations. Mothers were identified as the most frequent aggressor; monthly income of up to one minimum wage and history of alcohol use have been associated with violence. Seventy-one percent of victims were enrolled in educational institutions. In 25% of the cases the severity of the abuse required the removal of the child from the family. A third of the children were enrolled in official programs designed to provide the family with support, orientation and follow-up. This protective judicial intervention was successful in reducing abuse in 93% of the cases within 2 years. Prevention of child abuse requires the involvement of professionals of multiple fields at an early stage. The promotion and safeguarding of children's rights must come primarily from the implementation of public policy not judicial intervention.

Chagas disease is a neglected chronic condition with a high burden of morbidity and mortality. It has considerable psychological, social, and economic impacts. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on the articulation and strategic contribution of renowned Brazilian experts with knowledge and experience on various aspects of the disease. It is the result of a close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. It is hoped that this document will strengthen the development of integrated actions against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research .

Chagas disease is a neglected chronic condition that presents high morbidity and mortality burden, with considerable psychological, social, and economic impact. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on collaboration and contribution of renowned Brazilian experts with vast knowledge and experience on various aspects of the disease. It is the result of close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. This document shall strengthen the development of integrated control measures against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research.

This study analyzes the profile of deaths from road traffic accidents in Belo Horizonte, Minas Gerais State, Brazil, by linking two public databases, the Information System of the Urban Transportation and Transit Company (BH10) and the Mortality Information System (SIM). The linked database (n = 306) identified a 24% under-recording rate for deaths and differed in the age distribution from the BH10 database and in roadway user category when compared to the mortality database. The mortality rate for road traffic accidents within the city limits was 10.2 per 100,000 thousand, and was higher among men, young adults, and the elderly. Poisson multivariate regression showed a higher mean death rate for motorcycle occupants (rate ratio - RR: 1.81); pedestrians (RR: 1.32); males (RR: 1.24); single/divorced (RR: 1.27); young adults 18-29 years of age (RR: 1.75); elderly (RR: 1.59); and deaths at the crash site (RR: 1.39) when compared to the reference categories. The study unveils the city's traffic violence, expressed by the large proportion of deaths at the crash site and within the first 24 hours, and confirms the relevance of database linkage for characterizing vulnerable groups and traffic accident mortality in the urban setting.

The identification of predictors for the progression of chronic Chagas cardiomyopathy (CCC) is essential to ensure adequate patient management. This study looked into a non-concurrent cohort of 165 CCC patients between 1985 and 2010 for independent predictors for CCC progression. The outcomes were worsening of the CCC scores and the onset of left ventricular dysfunction assessed by means of echo-Doppler cardiography. Patients were analyzed for social, demographic, epidemiologic, clinical and workup-related variables. A descriptive analysis was conducted, followed by survival curves based on univariate (Kaplan-Meier and Cox's univariate model) and multivariate (Cox regression model) analysis. Patients were followed from two to 20 years (mean: 8.2). Their mean age was 44.8 years (20-77). Comparing both iterations of the study, in the second there was a statistically significant increase in the PR interval and in the QRS duration, despite a reduction in heart rates (Wilcoxon < 0.01). The predictors for CCC progression in the final regression model were male gender (HR = 2.81), Holter monitoring showing pauses equal to or greater than two seconds (HR = 3.02) increased cardiothoracic ratio (HR = 7.87) and time of use of digitalis (HR = 1.41). Patients with multiple predictive factors require stricter follow-up and treatment.

Objective: To analyze the contribution of three data sources in the description of traffic accidents in the city of Belo Horizonte, Brazil., Methods: Exploratory study of databases: BHTRANS (metropolitan traffic and transportation authority), Hospital Admissions and Mortality Information Systems, with estimation of proportions, coefficients and odds ratios., Results: Incomplete data was observed in the three sources, especially regarding alcohol consumption by drivers and use of safety equipment. The victim profile among the sources was consistent: young adults, males, motorcycle riders and pedestrians. In addition to the high mortality rate (19.4 per 100.000 inhabitants), an increase in the number of non-fatal accidents was observed. An increase of 34% in hospital admissions and of 53% in hospital costs was evidenced. The motorcycle accident rate is higher than expected given the fleet composition. Male drivers have the highest risk of injury or death; relative to drivers, passengers or pedestrians have a 1,8 times higher risk of death. There was a 12% increase in the number of deaths at the site of the accident, 55% of which showed positive evidence of alcohol use and 50% higher risk of fatal accidents on weekends., Conclusions: Despite some incomplete record keeping and non-specific death registry codes, it was possible to characterize the main factors associated with accidents: elderly pedestrians, motorcycle riders, alcohol consumption and speeding. The study demonstrated the complementarity of the three data sources, with their different goals, and revealed important features of the traffic accident event-chain and victim profile, providing key data for the development of mitigation strategies.

Objective: Patients with chronic hepatitis C (CHC) have a poorer quality of life than those with other chronic liver diseases. However, some of the factors that determine health-related quality of life (HRQOL) in these patients, such as the degree of liver fibrosis, are still controversial. Therefore, the aim of the present study was to investigate the impact of CHC on HRQOL by conducting clinical, psychiatric, and sociodemographic evaluations., Methods: One hundred and twenty-four consecutive patients attending a referral center for hepatitis were evaluated using the Mini-International Neuropsychiatry Interview, the Hamilton Depression Rating Scale, the Hospital Anxiety and Depression Scale, and the Medical Outcomes Study 36-Item Short-Form Health Survey. Multiple linear regression analyses were used to quantify independent associations between HRQOL and the clinical, psychiatric, and sociodemographic variables of interest., Results: Reduced HRQOL was independently associated with major depressive disorder (MDD) and with elevated levels of alanine aminotransferase, but was not associated with hepatic cirrhosis., Conclusions: MDD rather than the grade of liver fibrosis was strongly associated with HRQOL impairment in patients with CHC. These findings highlight that, in patients with CHC, the psychological effects of the disease deserve more attention and the implementation of integrated medical, psychiatric, and psychological care may be helpful.

Due to the scarcity of evidence of sexuality in Trypanosoma cruzi, the causative agent of Chagas disease, it has been general accepted that the parasite reproduction is essentially clonal with infrequent genetic recombination. This assumption is mainly supported by indirect evidence, such as Hardy-Weinberg imbalances, linkage disequilibrium and a strong correlation between independent sets of genetic markers of T. cruzi populations. However, because the analyzed populations are usually isolated from different geographic regions, the possibility of population substructuring as generating these genetic marker imbalances cannot be eliminated. To investigate this possibility, we firstly compared the allele frequencies and haplotype networks using seven different polymorphic loci (two from mitochondrial and five from different nuclear chromosomes) in two groups of TcII strains: one including isolates obtained from different regions in Latin America and the other including isolates obtained only from patients of the Minas Gerais State in Brazil. Our hypothesis was that if the population structure is essentially clonal, Hardy-Weinberg disequilibrium and a sharp association between the clusters generated by analyzing independent markers should be observed in both strain groups, independent of the geographic origin of the samples. The results demonstrated that the number of microsatellite loci in linkage disequilibrium decreased from 4 to 1 when only strains from Minas Gerais were analyzed. Moreover, we did not observed any correlation between the clusters when analyzing the nuclear and mitochondrial loci, suggesting independent inheritance of these markers among the Minas Gerais strains. Besides, using a second subset of five physically linked microsatellite loci and the Minas Gerais strains, we could also demonstrate evidence of homologous recombination roughly proportional to the relative distance among them. Taken together, our results do not support a clonal population structure for T. cruzi, particularly in TcII, which coexists in the same geographical area, suggesting that genetic exchanges among these strains may occur more frequently than initially expected., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Introduction: The aim of this study was to assess the epidemiological characteristics of Trypanosoma cruzi-infected mothers and the live birth conditions of neonates., Methods: A serological survey with IgG-specific tests was conducted using dried blood samples from newborn infants in the State of Minas Gerais. T. cruzi infection was confirmed in mothers through positive serology in two different tests, and infected mothers were required to have their infants serologically tested after the age of 6 months. The birth conditions of the neonates were obtained from the System of Information on Live Births database., Results: The study included 407 children born to T. cruzi-infected mothers and 407 children born to uninfected mothers. The average age of seropositive mothers was 32 years (CI95% 31.3-32.6), which was greater than the average age of seronegative mothers - 25 years (CI95% 24.8-25.2). The mothers' level of education was higher among uninfected mothers (41% had 8 or more years of education, versus 22% between the infected mothers). Vaginal delivery was more frequent among infected mothers. There was no evidence of inter-group differences with respect to the child's sex, gestational age, birth weight or Appearance, pulse, grimace, activity and respiration (APGAR) scores at 1 and 5 minutes., Conclusions: The level of education and the greater number of previous pregnancies and cases of vaginal delivery reflect the lower socioeconomical conditions of the infected mothers. In the absence of vertical transmission, neonates had similar health status irrespective of the infection status of their mothers.

Background: Benznidazole (Bz)-chemotherapy is recommended to prevent Chagas disease progression, despite its limited efficacy during chronic disease. However, the host mechanisms underlying these benefits still remain to be elucidated., Methods: In this study, we have used short-term whole blood cultures to describe the cytokine profile of Bz-treated Indeterminate Chagas disease patients-(INDt) as compared to untreated patients-(IND)., Results: Our findings showed that IND presented increased levels of IL-10+neutrophils, IL-12⁺ and IL-10⁺ monocytes and IFN-γ⁺NK-cells. Moreover, IND showed slight increase of IL-4⁺CD4⁺T-cells and enhanced levels of IL-10⁺CD8⁺T-cells and B-cells. Additional analysis of cytokine Low and High producers also highlighted the presence of High cytokine producers within IND, including IL-10 from CD4⁺ T-cells and IFN-γ from CD8⁺ T-cells, as compared to NI. The Bz-treatment lead to an overall cytokine down-regulation in the innate and adaptive compartments, including low levels of IL-12⁺ and IL-10⁺ neutrophils and monocytes, IFN-γ⁺NK-cells, IL-12⁺, TNF-α⁺, IFN-γ⁺ and IL-5⁺CD4⁺T-cells and IL-10⁺B-cells, along with basal levels of cytokine-expressing CD8⁺T-cells in INDt as compared to IND. The in vitro antigen stimulation shifted the cytokine profile toward a type 1-modulated profile, with increased levels of IL-12⁺ and IL-10⁺ monocytes, IFN-γ⁺ and IL-4⁺NK-cells along with TNF-α⁺ and IFN-γ⁺CD8⁺T-cells. Analysis of Low and High cytokine producers, upon in vitro antigen stimulation, further confirm these data., Conclusion: Together, our findings showed that the Bz treatment of Indeterminate Chagas' disease patients shifts the cytokine patterns of peripheral blood monocytes, NK-cells and CD8⁺ T-cells towards a long-lasting Type-1-modulated profile that could be important to the maintenance of a non-deleterious immunological microenvironment.

Treatment success of chronically infected Chagas disease patients is laborious and a positive prognosis often is made only after repetitive serological and/or parasitological examinations with continuous negative results. Recently, we have developed a non-conventional flow-cytometric method in order to detect immunoglobulin G antibodies against live trypomastigote forms of Trypanosoma cruzi and showed its usefulness in the prognosis of treatment success. In the present study, we investigated the performance of flow-cytometric anti-live trypomastigote IgG antibodies (FC-ALTA) and flow-cytometric anti-fixed epimastigote IgG antibodies (FC-AFEA), as well as conventional serological methods, for early monitoring of benznidazole treated Chagas disease patients, e.g. 5years after treatment. The analysis of individual FC-ALTA reactivity along the titration curve before and after treatment, we were able to show, that between 4% and 13% of treated patients under evaluation presented with reduced serological reactivity and segregated from the other patient groups. Similar results were obtained with semi-quantitative, conventional indirect hemagglutination or indirect immunofluorescence. Our data therefore suggest that the combined use of conventional and non-conventional serological methods could provide more suitable cure criteria in early post-therapeutic prognosis of Chagas disease., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Therapeutic failure of benznidazole (BZ) is widely documented in Chagas disease and has been primarily associated with variations in the drug susceptibility of Trypanosoma cruzi strains. In humans, therapeutic success has been assessed by the negativation of anti-T. cruzi antibodies, a process that may take up to 10 years. A protocol for early screening of the drug resistance of infective strains would be valuable for orienting physicians towards alternative therapies, with a combination of existing drugs or new anti-T. cruzi agents. We developed a procedure that couples the isolation of parasites by haemoculture with quantification of BZ susceptibility in the resultant epimastigote forms. BZ activity was standardized with reference strains, which showed IC₅₀ to BZ between 7.6-32 µM. The assay was then applied to isolates from seven chronic patients prior to administration of BZ therapy. The IC₅₀ of the strains varied from 15.6 ± 3-51.4 ± 1 µM. Comparison of BZ susceptibility of the pre-treatment isolates of patients considered cured by several criteria and of non-cured patients indicates that the assay does not predict therapeutic outcome. A two-fold increase in BZ resistance in the post-treatment isolates of two patients was verified. Based on the profile of nine microsatellite loci, sub-population selection in non-cured patients was ruled out.

This anthropological study addresses the cultural perceptions of a group of residents in the city of Bambuí, Minas Gerais State, Brazil, in relation to experience with Chagas disease and the impact of health measures on social life. The ethnographic study was based on open interviews, seeking to identify individual perceptions among 35 inhabitants of Bambuí (with and without Chagas disease) living in the region since the 1940s, when Chagas disease control activities were launched. Within a broad analysis of social perceptions concerning the effect of these health measures, the study sought to observe the cultural representations of the illness process. The study is intended to contribute to comprehensive work in health interventions, including the target population's socio-cultural characteristics. The cultural perspective plays an important role in preventing social distress.

The majority of individuals in the chronic phase of Chagas disease are asymptomatic (indeterminate form, IF). Each year, approximately 3% of them develop lesions in the heart or gastrointestinal tract. Cardiomyopathy (CCHD) is the most severe manifestation of Chagas disease. The factors that determine the outcome of the infection are unknown, but certainly depend on complex interactions amongst the genetic make-up of the parasite, the host immunogenetic background and environment. In a previous study we verified that the maxicircle gene NADH dehydrogenase (mitochondrial complex I) subunit 7 (ND7) from IF isolates had a 455 bp deletion compared with the wild type (WT) ND7 gene from CCHD strains. We proposed that ND7 could constitute a valuable target for PCR assays in the differential diagnosis of the infective strain. In the present study we evaluated this hypothesis by examination of ND7 structure in parasites from 75 patients with defined pathologies, from Southeast Brazil. We also analysed the structure of additional mitochondrial genes (ND4/CR4, COIII and COII) since the maxicircle is used for clustering Trypanosoma cruzi strains into three clades/haplogroups. We conclude that maxicircle genes do not discriminate parasite populations which induce IF or CCHD forms. Interestingly, the great majority of the analysed isolates belong to T. cruzi II (discrete typing unit, (DTU) IIb) genotype. This scenario is at variance with the prevalence of hybrid (DTU IId) human isolates in Bolivia, Chile and Argentina. The distribution of WT and deleted ND7 and ND4 genes in T. cruzi strains suggests that mutations in the two genes occurred in different ancestrals in the T. cruzi II cluster, allowing the identification of at least three mitochondrial sub-lineages within this group. The observation that T. cruzi strains accumulate mutations in several genes coding for complex I subunits favours the hypothesis that complex I may have a limited activity in this parasite.

Our research aimed to characterize the genetic profiles of 102 Trypanosoma cruzi isolates recently obtained from 44 chronic chagasic patients from different regions of the states of Minas Gerais and Goiás in Brazil. At least two isolates were obtained from each patient at different times in order to study the parasite population dynamics during disease progression in the chronic phase. The isolates were characterized molecularly by genotyping the 3' region of the 24S alpha rRNA, the mitochondrial cytochrome oxidase subunit 2 (COII) gene, and the intergenic region of the spliced leader intergenic region (SL-IR) gene. Seventy-seven isolates were analyzed for nine microsatellite loci. The data presented here show a strong correlation between the T. cruzi lineage II (T. cruzi II) and human infection in these regions of Brazil. Interestingly, isolates from two patients were initially characterized (by rRNA genotyping) as T. cruzi I and hybrid strains, but subsequent analyses of the COII and SL-IR genes confirmed that those isolates belonged to T. cruzi III and a hybrid group, respectively. Our results confirm the risk of misclassifying T. cruzi isolates on the basis of analysis of a single molecular marker. The microsatellite profiles showed that different isolates obtained from the same patient were genetically identical and monoclonal. Exceptions were observed for T. cruzi isolates from two patients who presented differences for the SCLE11 locus and also from two other patients who showed amplification of three peaks for a microsatellite locus (TcAAAT6), implying that they were multiclonal. On the basis of the findings of the studies described here, we were not able to establish a correlation between the clinical forms of Chagas' disease and the genetic profiles of the T. cruzi isolates.

The immune response is crucial for protection against disease; however, immunological imbalances can lead to heart and digestive tract lesions in chagasic patients. Several studies have evaluated the cellular and humoral immune responses in chagasic patients in an attempt to correlate immunological findings with clinical forms of Chagas disease. Moreover, immunoglobulins and cytokines are important for parasitic control and are involved in lesion genesis. Here, cytokine and IgG isotype production were studied, using total epimastigote antigen on sera of chagasic patients with indeterminate (IND, n = 27) and cardiac (CARD, n = 16) forms of the disease. Samples from normal,uninfected individuals (NI, n = 30) were use as controls. The results showed that sera from both IND and CARD patients contained higher levels of Trypanosoma cruzi-specific IgG1 (IgG1) antibodies than sera from NI. No difference in IgG2 production levels was observed between NI, IND and CARD patients, nor was a difference in IL-10 and IFN-gamma production detected in the sera of IND, CARD and NI patients. However, IND patients displayed a positive correlation between IL-10 and IFN-gamma levels in serum, while CARD patients showed no such correlation, indicating an uncontrolled inflammatory response in CARD patients. These findings support the hypothesis that a lack of efficient regulation between IFN-gamma and IL-10 productions in CARD patients may lead to cardiac immunopathology.

The present study had the aim of evaluating conventional serum tests that are used in neonatal screening for Chagas disease, with a discussion on the statistical methods available. A random sample among 23,308 newborns who were screened for congenital Chagas disease was studied using the following three tests: enzyme immunoassay, indirect immunofluorescence and indirect hemagglutination. The data were analyzed by different statistical methodologies: latent class analysis, Kappa test and relative sensitivity analysis. Using latent class analysis, enzyme immunoassay had the highest sensitivity (48.6%), followed by indirect immunofluorescence (39.8%) and indirect hemagglutination (23.2%). The kappa value was 0.496. The ratio between the sensitivities of enzyme immunoassays and indirect immunofluorescence tests was 92% [0.74;1.13]. Latent class analysis was not found to be adequate for sensitivity and specificity determination, but it provided important data about the equivalence of the tests, corroborated by relative sensitivity analysis. The results showed that enzyme immunoassaying of dry blood samples can be used as safely as the indirect immunofluorescence test.

Herein we have employed an alternative strategy to assess the cytokine patterns of circulating leukocytes and correlate dominant cytokine profiles with indeterminate-IND and cardiac-CARD clinical forms of Chagas disease. We have first calculated median percentages of cytokine-positive leukocytes of our study sample to establish, for each cytokine-positive cell population, the cut-off edge that would segregate 'low' and 'high' cytokine producers to build colour diagrams and draw a panoramic cytokine chart. Using this approach we demonstrated that most IND individuals presented a dominant regulatory cytokine profile, whereas CARD individuals displayed a dominant inflammatory cytokine pattern. In addition, radar chart analysis confirmed the dichotomic cytokine balance between IND and CARD groups and further allowed the identification of the relative contribution of each cell population for the global cytokine pattern. Data analysis demonstrated that CD4+ T cells were the major cell population defining the regulatory profile in IND, whereas monocytes and CD4+ T cells determined the inflammatory cytokine pattern in CARD individuals. Interestingly, in vitro stimulation with trypomastigote Trypanosoma cruzi antigen was able to invert the cytokine balances in IND and CARD groups. Upon antigenic stimulation, changes in the frequencies of IL-10-producing CD4+ T cells and monocytes drove IND individuals towards an inflammatory pattern and CARD towards a regulatory cytokine profile. A similar inversion could be found after in vivo treatment of IND and CARD individuals with benzonidazole. Altogether, these findings shed some light into the complex cytokine network underlying the immunopathogenesis of Chagas disease and provide putative immunological biomarkers of disease severity and therapeutic response.

A case-control study on chronic Chagas heart disease (CCHD) was carried out between 1997 and 2005. Ninety patients over 50 years of age were examined for factors related to (CCHD). Fourty-six patients (51.1%) with Chagas heart disease (anomalous ECG) were assigned to the case group and 44 (48.9%) were included in the control group as carriers of undetermined forms of chronic disease. Social, demographic (age, gender, skin color, area of origin), epidemiological (permanence within an endemic zone, family history of Chagas heart disease or sudden death, physical strain, alcoholism, and smoking), and clinical (systemic hypertension) variables were analyzed. The data set was assessed through single-variable and multivariate analysis. The two factors independently associated with heart disease were age--presence of heart disease being three times higher in patients over 60 years of age (odds ratio, OR: 2.89; confidence interval of 95%: 1.09-7.61)--and family history of Chagas heart disease (OR: 2.833, CI 95%: 1.11-7.23). Systemic hypertension and gender did not prove to hold any association with heart disease, as neither did skin color, but this variable showed low statistical power due to reduced sample size.

This anthropological study aimed to evaluate the incorporation of pacemakers into the lives of individuals with Chagas disease. An ethnographic methodology was used, based on an open interview focusing on the personal perceptions of 15 patients with chronic Chagas cardiopathy who had required pacemaker implants at the Federal University Hospital in Belo Horizonte, Minas Gerais State, Brazil. As part of a broader quality of life analysis, the study investigated the cultural, physical, and psychological resources used by patients to confront, explain, and accept the disease process, including mental representations on the cultural perception of the illness and definition of social relations. The study was intended to contribute to comprehensive patient care by health professionals, including psychosocial aspects. Decoded and integrated orientation in the cultural sphere assumes an important role in order to prevent disinformation from perpetuating the dissemination of popular myths as active elements in patient stigmatization.

Objective: To describe the profile of notified tuberculosis cases and analyze the factors associated with treatment dropout., Methods: A total of 178 cases of tuberculosis notified in the western region of Belo Horizonte (Southeastern Brazil) in 2001 and 2002 and recorded in the National System for Notifiable Diseases were described. An unmatched case-control study was conducted, with data collected by means of interviews, to compare patients who dropped out of treatment with those who achieved cure. The following variables were analyzed: sociodemographic and behavioral characteristics, associations with AIDS, side effects, information on the disease and interest in treatment. Univariate analysis and unconditional logistic regression for multivariate analysis were used. Adjusted odds ratios with 95% confidence limits were used as the measurement for associations., Results: The coefficient of incidence was 56.6/100,000 inhabitants. There was predominance of men aged 30 to 49 years and of the pulmonary form (76.4%) and bacillary form (72.5%). Among the notified cases, 65.2% achieved cure, 12.4% dropped out of treatment and 9.6% died. Treatment location had no influence on the results. In the case-control study, there was no difference regarding gender, color, schooling, income, occupation, family support, association with AIDS and alcohol consumption. The use of drugs, interest in treatment and information about the disease were shown to be independently associated with dropout., Conclusions: Adherence to treatment is a challenge in controlling tuberculosis. The protection factors (interest in treatment and information about the disease) and recognition that drug use is a risk factor must form part of the strategies for patient care in order to reduce dropout rates and restore health.

The majority of individuals in the chronic phase of Chagas disease are asymptomatic (indeterminate form). Every year 2-3% of these individuals develop severe clinical manifestations (cardiac and digestive forms). In this study a Trypanosoma cruzi DNA microarray was used to compare the transcript profiles of six human isolates: three from asymptomatic and three from cardiac patients. Seven signals were expressed differentially between the two classes of isolates, including tryparedoxin, surface protease GP63, cyclophilin, some hypothetical proteins and the pre-edited maxicircle gene NADH dehydrogenase subunit 7 (ND7). The approximately 30-fold greater signal in cardiac strains for ND7 was the most pronounced of the group, and differential levels of pre-edited ND7 transcript confirmed the microarray analysis. The ND7 gene from asymptomatic isolates showed a deletion of 455bp from nt 222 to nt 677 relative to ND7 of the CL Brener reference strain. The ND7 gene structure correlated with disease manifestation for 20 isolates from clinically characterised, chronic phase patients. The ND7 lesion produces a truncated product that could impair the function of mitochondrial complex I. Possible links between the integrity of the electron transport chain and symptom presentation are discussed. We propose that ND7 and other genes of the pathway constitute valuable targets for PCR assays in the differential diagnosis of the infective T. cruzi strain. While this hypothesis requires validation by the examination of additional recent parasite isolates from patients with defined pathologies, the identification of specific molecular markers represents a promising advance in the association between parasite genetics and disease pathology.

The genetic variability of 61 Trypanosoma cruzi isolates from 47 chronic chagasic patients of Minas Gerais state was analyzed by random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) using M13-40, lambdagt11-F, and L15996 primers. Cluster analysis by unweighted pair group method analysis was applied to RAPD profiles, and cluster analysis used to verify a possible correlation among different clinical forms of the disease from these patients. The T. cruzi isolates showed distinct grouping on tree topology, with the isolates not being possible to establish a correlation to the clinical forms of Chagas' disease. These data showed that the T. cruzi isolates from these patients would compose a group of populations well correlated genetically.

One of the greatest concerns in Chagas' disease is the absence of reliable methods for the evaluation of chemotherapy efficacy in treated patients. The tests available to evaluate cure after the specific treatment are the complement-mediated lysis (CoML) and flow cytometry tests, but they are not feasible for routine clinical use. In this study, we evaluated an enzyme-linked immunosorbent assay (ELISA) based on the recombinant Trypanosoma cruzi complement regulatory protein (rCRP) as a method to determine parasite clearance in comparison to the CoML and other methods such as conventional serology, hemoculture, and PCR in serum samples of 31 patients collected before and after the treatment, monitored for an average of 27.7 months after chemotherapy. The results showed that the percentage of patient samples that were positive by rCRP ELISA was reduced from 100 to 70.3, 62.5, 71.4, and 33.4% in the first, second, third, and fourth years after treatment, respectively, while the samples positive by CoML were reduced to 85.2, 81.2, 71.4, and 33.4% during the same period, demonstrating the same significant tendency in the reduction of positive samples. On the other hand, the conventional serology (CS) tests did not present this reduction. The percentage of samples positive by PCR was initially 77.4% and decreased to 55.5, 68.7, 47.7, and 50.0% at the fourth year after treatment, confirming the drastic clearance of circulating parasites after treatment. Our results strongly suggest that the rCRP ELISA was capable of detecting the early therapeutic efficacy in treated patients and confirmed its superiority over the CS tests and parasitologic methods.

Currently, diagnosis of Chagas' disease is based on serological methods, but due to the high occurrence of inconclusive results, more reliable methods are needed. The use of recombinant antigens for serodiagnosis of Chagas' disease is recommended in order to increase the sensitivity and specificity of the serological tests. The Trypanosoma cruzi complement regulatory protein (CRP) is a surface glycoprotein present on the trypomastigote forms of the parasite, and the recombinant CRP (rCRP) was cloned in a mammalian expression system and purified by affinity chromatography. The purified recombinant protein was used as an antigen in an enzyme-linked immunosorbent assay (rCRP ELISA) in order to verify its sensitivity and specificity compared with other established methods. In this evaluation, a panel of 184 serum samples distributed among chronic chagasic patients (n = 65), blood bank donors (n = 100), and patients infected with Leishmania spp. (n = 19) was used. The sensitivity and specificity of the rCRP ELISA were 100% when compared to conventional serology and complement-mediated lysis tests from these groups. When hemoculture and PCR tests were evaluated for diagnosis of chronic chagasic patients, using the rCRP ELISA as a reference test, the positivities were found to be 64.62 and 81.54%, respectively, showing a higher degree of sensitivity of the test. The data demonstrate that rCRP ELISA was able to discriminate between chronic chagasic patients and nonchagasic individuals, such as blood donors and patients with leishmaniasis. Thus, the rCRP is an excellent antigen for use in Chagas' disease diagnosis, due to the absence of false-negative or false-positive results.

An anthropological approach was employed to investigate the universe of representations (ways of thinking) and behaviors (ways of acting) associated with Chagas disease in a group of public service workers in Belo Horizonte (both infected and not infected with Trypanosoma cruzi). An attempt was also made to evaluate the repercussions of this universe of representations and behaviors on the lives of the infected individuals. The collection and analysis of the data followed the "systems of signs, meanings, and actions" model developed by Corin et al. (1989, 1992). Sixteen seropositive and 12 seronegative workers were interviewed to compare their ways of thinking and acting towards the disease. Data analysis allowed identification of diverse elements within a context that maximized the limitations imposed by Chagas disease. These should be taken into account in the planning of educational campaigns and elaboration of health care models for Chagas patients.

Infection of humans with Trypanosoma cruzi leads to either a lifelong asymptomatic infection or to symptomatic presentations such as cardiomyopathy, mega-syndromes, or both. The reasons for the different clinical manifestations are not understood. We have previously studied a group of chronically infected individuals with different clinical forms of Chagas' disease and found that the levels of some anti-T. cruzi antibody isotypes, analyzed by enzyme-linked immunosorbent assay, differed among patients with different clinical presentations. We have expanded these studies to examine the antigen specificity of these patients' IgG1, 2, 3, IgM, and IgA by western blot. We observed that binding of particular antigens by some antibody isotypes were more prevalent in some clinical groups as compared to others. For example, IgG3 from 13 of 19 (68%) individuals with digestive manifestations bound a 68-kDa antigen, but only 3 of 31 (9%) individuals with cardiac involvement detected this same moiety. We also found that, regardless of the clinical group, the profiles of antigens recognized by each antibody isotype differs dramatically from the profiles recognized by each other isotype. Together with our previous observations demonstrating that the levels of anti-parasite antibody isotypes correlates with the clinical form, these data suggest that overall anti-T. cruzi antibody reactivities may indeed be skewed toward different antigens in individuals with different clinical presentations.

Chagas' disease results from infection with the protozoan hemoflagellate Trypanosoma cruzi. Patients in the chronic phase of infection can be categorized into four groups based on the presence of cardiac abnormalities (CARD), gastrointestinal involvement (DIGEST), a combination of both presentations (BOTH), or indeterminate (IND) if Chagas' related pathology is not apparent. Previous studies have indicated that parasite-specific antibody production is important in both resistance to and pathogenesis of disease. The anti-T. cruzi epimastigote stage antibody isotype profiles in the sera of Brazilian patients from each clinical category, as well as from uninfected individuals (UNINF) from the same endemic area were analyzed. Anti-epimastigote immunoglobulin G (IgG)1 and IgG3 levels were strikingly high with titers > or = 1:100,000. Sera from patients in the CARD group had higher levels of IgM than either UNINF or IND individuals, which is consistent with the theory that autoimmunity may contribute to chagasic cardiomyopathy. The IgA levels were higher in sera from patients with gastrointestinal involvement when compared with individuals from any of the other clinical categories as well as from uninfected controls. Interestingly, patients with both digestive and cardiac involvement did not express high serum levels of IgA. However, like patients with cardiac involvement alone, persons with both clinical manifestations produced elevated levels of IgG2 compared with the IND or UNINF groups. These data suggest the presence of complex immunoregulatory processes, most likely related to differential cytokine involvement, which can influence the expression of antibody isotypes and possibly the course of disease.

A case-control study to analyse clinical and epidemiological data of 842 patientes seen in an outpatient ward reference center for chagas disease in Belo Horizonte, Brazil, from 1985 to 1992. It was verified that these patients were in a average age of 37.78 years; lower literacy regardless of race, and, performed activities that demanded greater muscle effort (p < 0.05). The main mechanism for disease transmission proved to be the vectorial route. Disease-especific complaints prevailed in the above mentioned patients (p < 0.05). The most important abnormalities found in clinical examination were with cardiac sounds (OR: 2.96 95% CI: 1.29-4.09) and the presence of extrasystole (OR: 7.16 95% CI: 1.59-45.07). Imunofluorescence Test was more sensitive (94%) and specific (96%). It also had a PPV of 99% and e NPV of 83%. ELISA test carried out in 43 patientes did not yield false results. Indeterminate chronic phase (56%) or early stages of the disease prevailed. The findings of normal EKGs and abnormalities in 30% of the Holter tests, 41% of the exercise tests, 33% of the ECO tests and, 48% of normal chest x-ray with abnormal ECO, high lights the importance of caring out more detailed exams in specific situations. We hereby propose a care model for the Chagas disease patient, integrated to our State Health Plan stressing serologic tests, and training capable human resources committed to the development of integrated health care and the optimization of our referral and counter-referral system, thus issuing total care to the Chagas disease patient.