A leucoencefalopatia multifocal progressiva (LEMP) é uma doença desmielinizante causada pelo vírus JC, que acomete principalmente pessoas que vivem com HIV/Aids (PVHA). A frequência e mortalidade da LEMP diminuiu após a introdução do tratamento antirretroviral combinado em países de renda alta, mas existe pouca informação sobre a LEMP em países de baixa e meia renda, incluindo o Brasil. (i) descrever as principais características clínicas, laboratoriais, radiológicas e evolutivas de PVHA com LEMP; e (ii) identificar as taxas de mortalidade intrahospitalar e um ano após o diagnóstico de LEMP dessa população. Estudo observacional de coorte retrospectiva, o qual incluiu PVHA com diagnostico de LEMP, internados no IIER, entre 2011 e 2022. O diagnóstico de LEMP consistiu na presença de manifestações neurológicas e neuroradiológicas associada à identificação de DNA do vírus JC em amostras de líquor. Foram revisados os prontuários eletrônicos e físicos dos pacientes, assim como bases de dados laboratoriais e de neuroimagens. O estudo foi aprovado pelo Comité de Ética do IIER. Foram incluídos 93 casos, 59 (63,4%) dos quais foram homens. A mediana (intervalo interquartílico -IIQ-) da idade foi 44 (35 - 49) anos. Diagnósticos prévios de infecção por HIV e de doença definidora de aids foram identificados em 89,2% e 49,5% dos casos, respectivamente. As manifestações clínicas mais comuns foram déficits motores (55,9%), alteração de linguagem (43%), e alteração de marcha (41,9%). LEMP clássica e LEMP IRIS foram identificadas em 88,2% e 11,8% dos casos, respectivamente. A mediana (IIQ) da contagem de CD4+ foi 86,5 (22-101) células/mL. Na ressonância magnética, 89,2% dos casos apresentaram múltiplas imagens com hipersinal em T2/FLAIR e 83,8% dos casos tiveram, concomitantemente, lesões infra e supratentoriais. As taxas de letalidade intrahospitalar e um ano após o diagnóstico de LEMP foram de 24,7% e 52,7%, respectivamente. Neste estudo, a maioria de PVHIV foi homem e tinha diagnóstico prévio de infecção pelo HIV, mas em aproximadamente a metade dos pacientes, a LEMP foi a doença definidora de aids. A maioria apresentou déficits focais, teve LEMP clássica e lesões múltiplas nas neuroimagens. Aproximadamente um de cada quatro pacientes com LEMP faleceu durante a internação e um de cada dois pacientes faleceu um após o diagnóstico dessa doença oportunista, similar ao descrito em países de renda alta
Background:The aim of this study was to evaluate the frequency, spectrum, in-hospital mortality rate, and factors associated with death in people living with HIV/AIDS (PLWHA) presenting with neurological diseases from a middle-income country, as well as estimate its one-year global death rate.Methods:This prospective observational cohort study was conducted at a Brazilian tertiary health center between January and July 2017. HIV-infected patients above 18 years of age who were admitted due to neurological complaints were consecutively included. A standardized neurological examination and patient and/or medical assistant interviews were performed weekly until the patient's discharge or death. The diagnostic and therapeutic management of the included cases followed institutional routines.Results:A total of 105 (13.2%) patients were included among the 791 hospitalized PLWHA. The median age was 42.8 [34-51] years, and 61% were men. The median CD4+ lymphocyte cell count was 70 (27-160) cells/mm3, and 90% of patients were experienced in combined antiretroviral therapy. The main diseases were cerebral toxoplasmosis (36%), cryptococcal meningitis (14%), and tuberculous meningitis (8%). Cytomegalovirus causing encephalitis, polyradiculopathy, and/or retinitis was the third most frequent pathogen (12%). Moreover, concomitant neurological infections occurred in 14% of the patients, and immune reconstitution inflammatory syndrome-related diseases occurred in 6% of them. In-hospital mortality rate was 12%, and multivariate analysis showed that altered level of consciousness (P = 0.04; OR: 22.7, CI 95%: 2.6-195.1) and intensive care unit (ICU) admission (P = 0.014; OR: 6.2, CI 95%: 1.4-26.7) were associated with death. The one-year global mortality rate was 31%.Conclusion:In this study, opportunistic neurological diseases were predominant. Cytomegalovirus was a frequent etiological agent, and neurological concomitant diseases were common. ICU admission and altered levels of consciousness were associated with death. Although in-hospital mortality was relatively low, the one-year global death rate was higher.
Human T-lymphotropic virus type 1 (HTLV-1)–associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a slowly progressive spinal cord disorder with no effective treatment. There is much of interest in developing potential biomarkers for predicting the pathogenesis of HAM/TSP disorder. This study used Illumina massive parallel sequencing (MPS) technology to assess the cellular global noncoding RNAome expression profile in HAM/TSP patients (n = 10), asymptomatic HTLV-1 infected carriers (ASP, n = 8), and a second group of healthy controls (n = 5). Using various bioinformatics tools, the sRNA MPS reads were aligned, annotated, and profiled. There were 251 known and 50 potential novel sRNAs among the 402 detected sRNAs in the HAM and ASP groups versus the HC group. Sixty-eight known sRNAs were found to be significantly different between the ASP and HAM groups. In HAM vs ASP subjects, 88 mature miRNAs were downregulated. Three of these miRs (hsa-miR-185-5p, 32-5p, and 192-5p) have the potential to be used as biomarkers for predicting the pathogenesis of HAM/TSP. The top seven deregulated miRS target genes were linked to a variety of biological processes and molecular functions. Relevant reactome pathways to our findings provide a rich source of data and an opportunity to further understand sRNA regulation and function in HTLV-1 pathophysiology.
Abstract Background Mother-to-child transmission (MTCT) of human T-lymphotropic virus type 1 (HTLV-1) is an important route of transmission that can cause lifelong infection. There is high morbidity and mortality due to adult T-cell leukemia/lymphoma, HTLV-1–associated myelopathy (HAM), and other inflammatory disorders. These conditions develop in nearly 10% of people with HTLV-1 infection, with a higher risk if infection occurs early in life. Identification of risk factors can inform targeted measures to reduce HTLV-1 MTCT. This study aimed to investigate the potential of cesarean delivery to prevent HTLV-1 MTCT. Methods We performed a review of the cases of women and their offspring under regular follow-up at the HTLV-1 outpatient clinic at the Institute of Infectious Diseases Emilio Ribas. Results A total of 177 HTLV-1–infected women and 369 adult offspring were investigated. Overall, 15% of the children were positive for HTLV-1 and 85% were negative. Regarding vertical transmission, we found that a breastfeeding duration of >6 months was associated with MTCT. Moreover, maternal proviral load was not associated with transmission, but high educational level and cesarean delivery were identified as protective factors. Conclusions HTLV-1 MTCT was associated with mother's age at delivery of >25 years, low educational level, prolonged breastfeeding, and vaginal delivery.
The human T cell lymphotropic virus type 1 (HTLV-1) is the first human retrovirus discovered. Since then, it has spread worldwide and is mainly associated with adult T cell leukemia/lymphoma (ATLL) and HTLV1-associated myelopathy (HAM). Its relationship, however, with other types of cancer is controversial. We describe the case of a patient presenting with small cells lung epidermoid carcinoma who had recently developed HAM, and a review of the literature related to these conditions. This is the first case of this type of lung cancer, the same of the first description in the literature, associated with HAM outside Japan.
Abstract Background: HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is an incapacitating neuroinflammatory disorder for which no disease-modifying therapy is available, but corticosteroids provide some clinical benefit. Although HAM/TSP pathogenesis is not fully elucidated, older age, female sex and higher proviral load are established risk factors. We investigated systemic cytokines and a novel chronic inflammatory marker, GlycA, as possible biomarkers of immunopathogenesis and therapeutic response in HAM/TSP, and examined their interaction with established risk factors. Patients and Methods: We recruited 110 People living with HTLV-1 (PLHTLV-1, 67 asymptomatic individuals and 43 HAM/TSP patients) with a total of 946 person-years of clinical follow-up. Plasma cytokine levels (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, TNF) and GlycA were quantified by Cytometric Bead Array and 1 NMR, respectively. Cytokine signaling and prednisolone response were validated in an independent cohort by nCounter digital transcriptomics. We used multivariable regression, machine learning algorithms and Bayesian network learning for biomarker identification. Results: We found that systemic IL-6 was positively correlated with both age (r=0.50, p<0.001) and GlycA (r=0.45, p=0.00049) in asymptomatics, revealing an ‘inflammaging” signature which was absent in HAM/TSP. GlycA levels were higher in women (p=0.0069), but cytokine levels did not differ between the sexes. IFN-γ (p=0.007) and IL-17A (p=0.0001) levels were increased in untreated HAM/TSP Multivariable logistic regression identified IL-17A and proviral load as independent determinants of clinical status, resulting in modest accuracy of predicting HAM/TSP status (64.1%), while a machine learning-derived decision tree classified HAM/TSP patients with 90.7% accuracy. Pre-treatment GlycA and TNF levels significantly predicted clinical worsening (measured by Osame Motor Disability Scale), independent of proviral load. In addition, a poor prednisolone response was significantly correlated with higher post-treatment IFN-γ levels. Likewise, a transcriptomic IFN signaling score, significantly correlated to previously proposed HAM/TSP biomarkers ( CASP5/CXCL10/FCGR1A/STAT1 ), was efficiently blunted by in vitro prednisolone treatment of PBMC from PLHTLV-1 and incident HAM/TSP. Conclusions: An age-related increase in systemic IL-6/GlycA levels reveals inflammaging in PLHTLV-1, in the absence of neurological disease. IFN-γ and IL-17A are biomarkers of untreated HAM/TSP, while pre-treatment GlycA and TNF predict therapeutic response to prednisolone pulse therapy, paving the way for a precision medicine approach in HAM/TSP.
In the context of megacities in an urban environment, air quality is an important issue, due to the direct correlation to population's health. The biomonitoring of pollutants can indicate subtle environmental alterations, for that, anemophilous fungi can be monitored for changes in atmospheric conditions related to pollution. In the present study, the concentration of fungi and bacteria in the atmosphere was measured during a specific vehicle fleet reduction in the city of São Paulo, Brazil, from May 24 to 30, 2018, using impactor air samplers. The number of isolated developed colonies was related to atmospheric conditions and the concentration of other air pollutants constantly monitored. Aspergillus, Curvularia, Penicillium, Neurospora, Rhizopus and Trichoderma were identified. The number of colony-forming units increased by approximately 80% during the sampling period in response to environmental changes favored by the fleet reduction. This result implies the relation between fuel emissions, concentration of atmospheric pollutants, and the presence of viable fungal spores in the urban environment, which highlights the importance of combined public policies for air quality in large cities.
Background The WHO established targets for 2030 to globally reduce new viral hepatitis B and C infections by 90% and deaths by 65% and recommends searching for coinfections that increase the progression of chronic liver infections towards cirrhosis and hepatocellular carcinoma. Aims and methodology This study aimed to add information concerning the influence of human T-lymphotropic virus type 1 (HTLV-1) and type 2 (HTLV-2) infections in hepatitis B and C, since in Brazil, these human retroviruses are endemic but neglected. Serum samples from 1,910 patients with hepatitis B and 1,315 with hepatitis C from São Paulo, southeast Brazil, that were previously tested and grouped for HIV and HTLV-1/-2 coinfections were analyzed for hepatitis B virus (HBV) and hepatitis C virus (HCV) loads measurements and subsequent clearance using data from laboratory records. Key results Briefly, the lowest HBV viral load (VL) was detected in HBV/HTLV-2 coinfected patients, regardless of whether they were infected with HIV (all comparisons p<0.05). In contrast, higher HCV VL was detected in HCV/HIV, HCV/HIV/HTLV-1/-2 coinfected patients (all p<0.05), and the lowest HCV VL was detected in HCV/HTLV-2 coinfected patients. Curiously, 61.1% of the patients with HBV/HTLV-2 coinfection had an undetectable HBV VL at the beginning of the study versus 21.4% in the patients with HBV/HTLV-1 coinfection. Although the percentages of undetectable HCV loads in HCV/HTLV-1 and HCV/HTLV-2 coinfected patients were quite similar, during follow-up, more HCV clearance was detected in patients with HCV/HTLV-2 coinfection [OR 2.65; 95% IC (1.17–5.99)]. Major conclusions HTLV-2 positively impacts HBV and HCV viral loads and HCV clearance, while HIV and/or HTLV-1 negatively impacts HCV viral load. Thus, the search for HTLV-1/-2 in viral hepatitis B and C infected patients has virological prognostic value, which is a strong reason to suggest including HTLV serology in the follow-up of patients.
The cause of oropharyngeal dysphagia in patients with coronavirus disease (COVID-19) can be multifactorial and may underly limitations in swallowing rehabilitation.
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