Biomarkers of severity and chronification in chikungunya fever: a systematic review and meta-analysis

Currently, there are no biomarkers for Chikungunya fever (CHIK) in clinical practice that can accurately predict the severity or chronification of the disease. The aim of this study is to evaluate the existing literature on biomarkers related to the severity and chronification of CHIK. In this sense, a systematic review was conducted based on the PRISMA Statement guideline. Articles that described the association of biomarkers with the evolution of the disease (severity or chronification), published until August 20th 2019 were considered eligible. The search was carried out in the PubMed, Scopus, Virtual Health Library (VHL) and Science Direct databases. After searching the databases, 17 articles were added to the review, and after analyzing the articles, several biomarkers were associated with severity, such as increased levels of IL-6, IP-10, IL-1b, MIG, MCP-1, and reduced levels of RANTES and IL-8 or chronification, such as increased levels of IL-6, TNF-α, MCP-1, IL-12, INF-α, IL-13, INF-γ, GM-CSF, CRP, IL-1a, IL-15, Factor VII, IP-10, IL-10, IL-4, IL-1RA, IL-8, MIP-1α, MIP-1β, ferritin, MIG, ESR, NO, malondialdehyde, and reduced levels of RANTES, ferritin, eotaxin, HGF, IL-27, IL-17A, IL-29, TGF-β, IL-10, and thiols. IL-6, CRP and TNF-α were included in the meta-analysis to assess the relationship with chronification, although they did not reach statistical significance. It was concluded that several biomarkers showed a relationship with severity and chronification of CHIK; the search for these biomarkers can reveal prognostic factors and important therapeutic targets for the treatment of the disease

Longitudinal study of patients with chronic Chagas cardiomyopathy in Brazil (SaMi-Trop project): a cohort profile.

PurposeWe have established a prospective cohort of 1959 patients with chronic Chagas cardiomyopathy to evaluate if a clinical prediction rule based on ECG, brain natriuretic peptide (BNP) levels, and other biomarkers can be useful in clinical practice. This paper outlines the study and baseline characteristics of the participants.ParticipantsThe study is being conducted in 21 municipalities of the northern part of Minas Gerais State in Brazil, and includes a follow-up of 2 years. The baseline evaluation included collection of sociodemographic information, social determinants of health, health-related behaviours, comorbidities, medicines in use, history of previous treatment for Chagas disease, functional class, quality of life, blood sample collection, and ECG. Patients were mostly female, aged 50-74 years, with low family income and educational level, with known Chagas disease for >10 years; 46% presented with functional class >II. Previous use of benznidazole was reported by 25.2% and permanent use of pacemaker by 6.2%. Almost half of the patients presented with high blood cholesterol and hypertension, and one-third of them had diabetes mellitus. N-terminal of the prohormone BNP (NT-ProBNP) level was >300 pg/mL in 30% of the sample.Findings to dateClinical and laboratory markers predictive of severe and progressive Chagas disease were identified as high NT-ProBNP levels, as well as symptoms of advanced heart failure. These results confirm the important residual morbidity of Chagas disease in the remote areas, thus supporting political decisions that should prioritise in addition to epidemiological surveillance the medical treatment of chronic Chagas cardiomyopathy in the coming years. The São Paulo-Minas Gerais Tropical Medicine Research Center (SaMi-Trop) represents a major challenge for focused research in neglected diseases, with knowledge that can be applied in primary healthcare.Future plansWe will continue following this patients' cohort to provide relevant information about the development and progression of Chagas disease in remotes areas, with social and economic inequalities.Trial registration numberNCT02646943; Pre-results

Quality of life in patients with Chagas disease and the instrument used: an integrative review

Chagas disease (CD) is a neglected tropical highly morbid disease that can have a negative impact on the quality of life (QoL). The purpose of this study was to conduct an integrative review to analyze the QoL of patients with CD in the chronic phase of the disease, as well as the instruments used and the effect of different interventions. The review was carried out based on the criteria and recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes guideline (PRISMA) using the PubMed, Scopus, Web of Science and Science Direct databases. An analysis of the reference list of the included articles was also carried out. Publications in all languages have been included. Two independent reviewers selected the eligible articles and extracted the data. A total of 1,479 articles were identified, and after applying the inclusion criteria 18 articles were included. Four different instruments were used to assess QoL and the most used was the Minnesota Living with Heart Failure Questionnaire (MLWHFQ) [33.3% (n = 6)]. Investigations involving intervention showed a positive impact on the patients’ QoL, and the Environment domain had the lowest score. Heterogeneity of instruments and lack of methodology standardization for assessing QoL was observed. QoL proved to be an important indicator for the planning and monitoring of patients with CD, however it is suggested that the instruments for its assessment should be the ones recommended by the validation studies. This process will allow the comparison of data between investigations

HCV Genotypes, Characterization of Mutations Conferring Drug Resistance to Protease Inhibitors, and Risk Factors among Blood Donors in São Paulo, Brazil

Background: Hepatitis C virus (HCV) infection is a global health problem estimated to affect almost 200 million people worldwide. the aim of this study is to analyze the subtypes and existence of variants resistant to protease inhibitors and their association with potential HCV risk factors among blood donors in Brazil.Methods: Repeat anti-HCV reactive blood donors are systematically asked to return for retest, notification, and counseling in which they are interviewed for risk factors for transfusion-transmitted diseases. We analyzed 202 donors who returned for counseling from 2007 to 2010 and presented enzyme immunoassay-and immunoblot-reactive results. the HCV genotypes and resistance mutation analyses were determined by the direct sequencing of the NS5b and NS3 regions, respectively. the HCV viral load was determined using an in-house real-time PCR assay targeting the 5'-NCR.Results: HCV subtypes 1b, 1a, and 3a were found in 45.5%, 32.0%, and 18.0% of the donors, respectively. the mean viral load of genotype 1 was significantly higher than that of the genotype 3 isolates. Subtype 1a was more frequent among young donors and 3a was more frequent among older donors. Protease inhibitor-resistant variants were detected in 12.8% of the sequenced samples belonging to genotype 1, and a higher frequency was observed among subtype 1a (20%) in comparison to 1b (8%). There was no difference in the prevalence of HCV risk factors among the genotypes or drug-resistant variants.Conclusions: We found a predominance of subtype 1b, with an increase in the frequency of subtype 1a, in young subjects. Mutations conferring resistance to NS3 inhibitors were frequent in treatment-naive blood donors, particularly those infected with subtype 1a. These variants were detected in the major viral population of HCV quasispecies, have replicative capacities comparable to nonresistant strains, and could be important for predicting the response to antiviral triple therapy.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundacao Pro-Sangue/Hemocentro de São PauloFundacao Prosangue Hemoctr São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, Infect Dis Div DIPA, São Paulo, BrazilUniv São Paulo, Fac Med, Discipline Med Sci, São Paulo, BrazilHCFMUSP, Dept Pathol, LIM Lab Medice Lab 03, São Paulo, BrazilUniv Sao Joao del Rei, Divinopolis, MG, BrazilUniv São Paulo, Fac Med, Dept Infect Dis, São Paulo, BrazilUniversidade Federal de São Paulo, Infect Dis Div DIPA, São Paulo, BrazilWeb of Scienc

Serological screening for Chagas disease in an endemic region of Northern Minas Gerais, Brazil: the SaMi-Trop project

Chagas disease (CD) is still a neglected disease. Infected individuals are diagnosed late, being treated in worse clinical conditions. Thus, this study aimed to analyze the prevalence and the factors associated with new confirmed cases of CD identified by serological screening in an endemic region of Minas Gerais State, Brazil. This is an analytical cross-sectional study with data from a project of the Research Center in Tropical Medicine of Sao Paulo- Minas Gerais (SaMi-Trop) conducted in two municipalities. Data collection included a questionnaire with closed questions, a venous blood collection and an ELISA serological test for CD. A total of 2,038 individuals with no previous diagnosis of CD participated in the study. The result of the serological test for CD was adopted as the dependent variable. The independent variables addressed personal issues, health conditions and lifetime housing. A descriptive analysis of individual variables was performed. Subsequently, a bivariate analysis was performed using the Pearson’s chi-square test. Households sheltering individuals positive for CD were georeferenced, and the analysis of spatial distribution was performed using the quartic function to estimate the density of the nucleus. Among the participants, 188 (9.2 %) were positive for CD. The profile of participants with CD was associated with place of residence, age, relative/family member with CD and living conditions. It is noteworthy that there are still patients with CD who are unaware of their diagnosis in both, rural and urban areas

Prevalence of dementia subtypes in a developing country: a clinicopathological study

OBJECTIVES: To assess the distribution of dementia subtypes in Brazil using a population-based clinicopathological study. METHOD: Brains from deceased individuals aged ≥50 years old were collected after the next of kin signed an informed consent form and provided information through standardized questionnaires. Post-mortem clinical diagnoses were established in consensus meetings, and only cases with moderate or severe dementia or without cognitive impairment were included in the analysis. Immunohistochemical neuropathological examinations were performed following the universally accepted guidelines. A diagnosis of Alzheimer's disease was made when there were at least both a moderate density of neuritic plaques (Consortium to Establish a Register for Alzheimer's disease B or C) and Braak stage III for neurofibrillary tangle distribution. For the diagnosis of vascular dementia, at least three zones or strategic areas had to be affected by infarcts, lacunae, or microinfarcts. RESULTS: From 1,291 subjects, 113 cases were classified as having moderate or severe dementia, and 972 cases were free of cognitive impairment. The neuropathological diagnoses of the dementia sub-group were Alzheimer's disease (35.4%), vascular dementia (21.2%), Alzheimer's disease plus vascular dementia (13.3%), and other causes of dementia (30.1%). Small-vessel disease, which alone was not considered sufficient for a vascular dementia diagnosis, was present in 38.9% of all of the dementia cases and in 16.8% of the group without cognitive impairment (odds ratio = 2.91; 95% confidence interval, 1.53-5.51), adjusted for age, sex, and education. CONCLUSIONS: The relatively high frequencies of vascular dementia and small-vessel disease in the dementia sub-group constitute relevant findings for public health initiatives because control of vascular risk factors could decrease the prevalence of dementia in developing countries