JORGE SIMAO DO ROSARIO CASSEB

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Departamento de Dermatologia, Faculdade de Medicina - Docente
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina - Líder

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Autor: OLIVEIRA, Augusto Cesar Penalva de ×

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  • article 8 Citação(ões) na Scopus
    Economic analysis of antenatal screening for human T-cell lymphotropic virus type 1 in Brazil: an open access cost-utility model
    (2023) ROSADAS, Carolina; SENNA, Katia; COSTA, Milene da; ASSONE, Tatiane; CASSEB, Jorge; NUKUI, Youko; COOK, Lucy; MARIANO, Livia; CASTRO, Bernardo Galvao; GRASSI, Maria Fernanda Rios; OLIVEIRA, Augusto Cesar Penalva de; CATERINO-DE-ARAUJO, Adele; MALIK, Bassit; BOA-SORTE, Ney; PEIXOTO, Paula; PUCCIONI-SOHLER, Marzia; SANTOS, Marisa; TAYLOR, Graham Philip
    Background Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes severe diseases, such as aggressive cancer or progressive neurological disease. HTLV-1 affects mainly people in areas with low human development index and can be transmitted from mother to child, primarily through breastfeeding. Refraining from breastfeeding is an effective intervention to reduce the risk of infection in infants. However, HTLV-1 antenatal screening is not offered globally. According to WHO, the scarcity of cost-effectiveness studies is considered one of the major barriers to the implementation of policies to prevent HTLV-1 infection. Therefore, this study aimed to assess the cost-effectiveness of antenatal screening and postnatal interventions to prevent HTLV-1 mother-to-child transmission in Brazil and to develop an open-access, editable, mathematical model that can be used by other countries and regions to assess different scenarios. Methods In this cost-utility analysis, we constructed a decision tree and a Markov model to assess the cost-effectiveness of HTLV-1 antenatal screening and postnatal interventions (ie, avoidance of breastfeeding, by suppression of lactation with cabergoline, and provision of formula feed) to reduce transmission. For our model, we used data from Brazil and we took the perspective of the public health-care system to estimate costs. Findings The implementation of both screening and interventions would result in the prevention of 1039 infections in infants every year in Brazil with an incremental cost-effectiveness ratio (ICER) of US$11 415 per quality-adjusted lifeyear (QALY). 88% of all probabilistic sensitivity analysis simulations had ICER values lower than the Brazilian costeffectiveness threshold ($18 107 center dot 74 per QALY). HTLV-1 prevalence in pregnant women, the risk of HTLV-1 transmission when breastfeeding lasts for 6 months or more, and the cost of screening tests were the variables with the largest effect on ICER. Interpretation HTLV-1 antenatal screening is cost-effective in Brazil. An open-access model was developed, and this tool could be used to assess the cost-effectiveness of such policy globally, favouring the implementation of interventions to prevent HTLV-1 mother-to-child transmission worldwide.
  • article 2 Citação(ões) na Scopus
    Rapid and Sensitive Qualitative Duoplex Real-Time PCR Method for Discriminatory and Confirmatory Diagnosis of HTLV-1 and HTLV-2 Infections: Brazilian Multicentric Study
    (2022) ROCHA-JUNIOR, Mauricio Cristiano; RODRIGUES, Evandra Strazza; SLAVOV, Svetoslav Nanev; ASSONE, Tatiane; PEDRESCHI, Maira; ROQUE, Debora Glenda Lima de la; SOUSA, Maisa; OLAVARRIA, Viviana; GALVAO-CASTRO, Bernardo; FONSECA, Benedito Antonio Lopes da; OLIVEIRA, Augusto Cesar Penalva de; SMID, Jerusa; TAKAYANAGUI, Oswaldo Massaiti; CASSEB, Jorge; COVAS, Dimas Tadeu; KASHIMA, Simone
    Human T cell lymphotropic virus (HTLV) is the caustive agent of two main conditions i. e., the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and the adult T-cell leukemia/lymphoma (ATLL). HTLV diagnosis is based on serological and molecular approaches; however, an accurate and validated method is still needed. The objective of this study was to establish a rapid and sensitive molecular test to confirm and discriminate HTLV 1/2 types. The test validation was performed as a multicentric study involving HTLV confirmation centers throughout Brazil. Proviral DNA was extracted from whole blood and the amplification was performed using in-house designed primer and probe sets targeting the pol genomic region. An internal control to validate the extraction and amplification was also included. The limit of detection (LoD) of the assay was four copies/reaction for HTLV-1 and 10.9 copies/reaction for HTLV-2. The diagnostic sensitivity of the platform was 94.6% for HTLV-1, 78.6% for HTLV-2, and the specificity was 100% for both viruses. Cross-reactions of the test with human viruses including HAV, HBV, HCV, HIV-1/2, and parvovirus B19 were not observed. During the multicentric validation, the test was used to screen a total of 692 blood samples obtained from previously confirmed HTLV-positive individuals. From these, 91.1% tested positive being concordant with the previously obtained results. In conclusion, our duoplex-RT-PCR-HTLV1 /2 presented adequate efficiency for HTLV-1/2 differentiation showing high sensitivity and specificity. Therefore, it can be a suitable tool for confirmation of suspected and inconclusive HTLV cases, prenatal and pre-transplant diagnosis, in Brazil and in other countries HTLV-endemic countries.
  • article 0 Citação(ões) na Scopus
    Neuropsychological profile of patients with infectious disease: characterization and comparison of patients with HIV, HTLV, and HCV
    (2023) GASCON, Maria Rita Polo; OLIVEIRA, Giovana S. de; LAURENCE, Paulo Guirro; GUALQUI, Carolina Fernandes; OLIVEIRA, Augusto Cesar Penalva de; SMID, Jerusa; FONSECA, Luiz A. M.; CASSEB, Jorge; MACEDO, Elizeu Coutinho
    Understanding the effect of the HIV, HTLV-1, and HCV viruses on cognitive aspects can help in the better characterization of dementia, as well as the best conducts to be suitable for rehabilitation. Thus, the present study aimed to characterize and compare the neuropsychological profile of 3 groups of patients with infectious diseases: HIV, HTLV, and HCV. The results of neuropsychological assessments and depression assessment of 325 people treated at a referral hospital for infectious dis-eases were analyzed, being 120 HIV carriers (74 (61.7%) men) with an average age of 47.5 years (SD = 10.3), 65 patients with HTLV-1 (16 (24.6%) men) with a mean age of 49.9 years (SD = 12.9), and 87 HCV patients (47 (54%) men) with a mean age of 55.5 years (SD = 11.2). In addition, 54 people (26 (48.1%) men) with negative serology who made up the con-trol group were evaluated. The results of the statistical evaluation of the sociodemographic factors of the four groups (HIV, HTLV-1, HCV, and control) showed that in addition to age, schooling was a significant factor among them and may have a strong influence on the performance of cognitive tests. The HTLV-1 group had the lowest neurocognitive performance and also the highest rate of depressive symptoms.
  • article 9 Citação(ões) na Scopus
    Global expression of noncoding RNome reveals dysregulation of small RNAs in patients with HTLV-1-associated adult T-cell leukemia: a pilot study
    (2021) NASCIMENTO, Andrezza; SOUZA, Daniela Raguer Valadao de; PESSOA, Rodrigo; PIETROBON, Anna Julia; NUKUI, Youko; PEREIRA, Juliana; CASSEB, Jorge; OLIVEIRA, Augusto Cesar Penalva de; LOUREIRO, Paula; DUARTE, Alberto Jose da Silva; CLISSA, Patricia Bianca; SANABANI, Sabri Saeed
    Background Adult T cell lymphoma/leukemia (ATLL) is a peripheral T-cell neoplasm caused by human T-cell lymphotropic virus-1 (HTLV-1). Small RNAs (sRNAs), including microRNAs (miRNAs), play a pivotal role in the initiation and development of hematological malignancies and may represent potential therapeutic target molecules. However, little is known about how these molecules impact the pathogenesis of ATLL. In this study, we aimed to identify sRNA expression signatures associated with ATLL and to investigate their potential implication in the pathophysiology of the disease. Methods Small-RNAseq analysis was performed in peripheral blood mononuclear cells from HTLV-1- associated ATLL (n = 10) in comparison to asymptomatic carriers (n = 8) and healthy controls (n = 5). Sequencing was carried out using the Illumina MiSeq platform, and the deregulation of selected miRNAs was validated by real-time PCR. Pathway analyses of most deregulated miRNA were performed and their global profiling was combined with transcriptome data in ATLL. Results The sequencing identified specific sRNAs signatures associated with ATLL patients that target pathways relevant in ATLL, such as the transforming growth factor-(beta TGF-beta), Wnt, p53, apoptosis, and mitogen-activated protein kinase (MAPK) signaling cascades. Network analysis revealed several miRNAs regulating highly connected genes within the ATLL transcriptome. miR-451-3p was the most downregulated miRNA in active patients. Conclusions Our findings shed light on the expression of specific sRNAs in HTLV-1 associated ATLL, which may represent promising candidates as biomarkers that help monitor the disease activity.
  • article 0 Citação(ões) na Scopus
    Small RNA Profiling in an HTLV-1-Infected Patient with Acute Adult T-Cell Leukemia-Lymphoma at Diagnosis and after Maintenance Therapy: A Case Study
    (2023) PESSOA, Rodrigo; SOUZA, Daniela Raguer Valadao de; NUKUI, Youko; PEREIRA, Juliana; FERNANDES, Lorena Abreu; MARCUSSO, Rosa Nascimento; OLIVEIRA, Augusto Cesar Penalva de; CASSEB, Jorge; DUARTE, Alberto Jose da Silva; SANABANI, Sabri Saeed
    Small RNAs (sRNAs) are epigenetic regulators of essential biological processes associated with the development and progression of leukemias, including adult T-cell leukemia/lymphoma (ATLL) caused by human T-cell lymphotropic virus type 1 (HTLV-1), an oncogenic human retrovirus originally discovered in a patient with adult T-cell leukemia/lymphoma. Here, we describe the sRNA profile of a 30-year-old woman with ATLL at the time of diagnosis and after maintenance therapy with the aim of correlating expression levels with response to therapy.
  • article 8 Citação(ões) na Scopus
    Prevalence of Sjogren's syndrome in Brazilian patients infected with human T-cell lymphotropic virus
    (2017) VALE, Daniela Assis do; CASSEB, Jorge; OLIVEIRA, Augusto Cesar Penalva de; BUSSOLOTI FILHO, Ivo; SOUSA, Suzana Cantanhede Orsini Machado de; ORTEGA, Karem Lopez
    BackgroundHuman T-lymphotropic virus type I (HTLV-I) is known to be associated with neoplastic and neurodegenerative changes, and it is believed to be associated with various systemic inflammatory diseases, including Sjogren's syndrome (SS). Although HTLV-I infection is endemic in Brazil, there is no information regarding the association between HTLV-I infection and SS in the Brazilian population. The objective of this study was to determine the prevalence of SS in HTLV-I-infected individuals and the prevalence of HTLV-I infection in individuals diagnosed with SS. MethodsSerology for HTLV-I was performed in 50 patients presenting with complaints consistent with SS (the SS group). The HTLV-I group comprised 129 HTLV-I-infected patients who were screened for SS. ResultsNone of the patients in the SS group tested positive for HTLV-I. Of the 129 patients in the HTLV-I group, 46 (35.7%) had xerostomia, 18 (13.95%) had xerophthalmia, eight (6.2%) had hyposalivation, two (1.55%) showed impaired tear secretion, and one (0.77%) was positive for autoantibodies (anti-SSB). In addition, six underwent minor salivary gland biopsy, and the histopathological findings were consistent with SS. Only two (1.55%) met the diagnostic criteria for SS. ConclusionsThe prevalence of SS was found to be three times as high in HTLV-I-infected individuals as it was in those without HTLV-I infection. However, given the small number of HTLV-seropositive patients with SS, it is impossible to state that HTLV acts as an immune-activating pathogen for SS.
  • article 8 Citação(ões) na Scopus
    Polymorphisms in HLA-C and KIR alleles are not associated with HAM/TSP risk in HTLV-1-infected subjects
    (2018) ASSONE, Tatiane; MALTA, Fernanda M.; BAKKOUR, Sonia; MONTALVO, Leilani; PAIVA, Arthur M.; SMID, Jerusa; OLIVEIRA, Augusto Cesar Penalva de; GONCALVES, Fernanda de Toledo; LUIZ, Olinda do Carmo; FONSECA, Luiz Augusto M.; NORRIS, Philip J.; CASSEB, Jorge
    Introduction: Several genetic polymorphisms may be related to susceptibility or resistance to viral disease outcomes. Immunological or genetic factors may act as major triggers of the immune pathogenesis of HAM/TSP. This study investigated the association of immune related genetic polymorphisms with viral and immunological markers. Methods: 247 HTLV-1-infected volunteers, drawn from a larger group of HTLV-infected subjects followed at the Institute of Infectious Diseases ""Emilio Ribas"" (IIER) for up to 19 years, participated in this study, which ran from June 2011 to July 2016. The subjects were classified according to their neurological status into two groups: Group 1 (160 asymptomatic individuals) and Group 2 (87 HAM/TSP patients). Samples were tested for spontaneous lymphocyte proliferation (LPA) and HTLV-1 proviral load (PVL) and for IFN-lambda 4, HLA-C and KIR genotypes using qPCR. Results: We found associations between LPA (p = 0.0001) with HAM/TSP and confirmed the IFN-lambda 4 polymorphism rs8099917, allele GG, as a protective factor using a recessive model (OR = 3.22, CI = 1.10-9.47). Polymorphisms in HLA-C and KIR alleles were not associated with risk of developing HAM/TSP. Conclusion: We demonstrated that age, LPA and an IFN-lambda 4 polymorphism were associated with progression to HAM/TSP. Understanding HAM/TSP pathogenesis can provide important markers of prognostic value for clinical management, and contribute to the discovery of new therapeutic interventions in the future.
  • article 1 Citação(ões) na Scopus
    Differential modulation of IL-4, IL-10, IL-17, and IFN-? production mediated by IgG from Human T-lymphotropic virus-1 (HTLV-1) infected patients on healthy peripheral T (CD4+, CD8+, and ?d) and B cells
    (2023) MACHADO, Nicolle Rakanidis; FAGUNDES, Beatriz Oliveira; FERNANDES, Lorena Abreu; OLIVEIRA, Augusto Cesar Penalva de; NUKUI, Youko; CASSEB, Jorge; CUNHA, Fernando Roberto Machado; NALI, Luiz Henrique da Silva; SANABANI, Sabri Saeed; VICTOR, Jefferson Russo
    Human T-lymphotropic virus 1 (HTLV-1) infected individuals remain as asymptomatic carriers (ACs) or can develop the chronic neurological disorder HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP) or the adult T-cell leukemia/lymphoma (ATLL), and the immunological mechanisms involved in this pathologies need to be elucidated. Recently, it has been demonstrated that induced or naturally developed IgG repertoires obtained from different groups of donors, grouped by immune status, can modulate human T and B cell functions. Here we aimed to evaluate if the IgG obtained from HTLV-1-infected ACs, HAM/TSP, and ATLL patients can differentially modulate the production of cytokines by human T and B cells. With this purpose, we cultured PBMCs with IgG purified from ACs, HAM/TSP, or ATLL donors and evaluated the frequency and intracellular cytokine production by flow cytometry. Our results indicate that IgG from HAM/TSP patients could induce an augment of IL-17-producing CD4+ T cells, reduce the frequency of IL-4-producing CD4+ T cells, increase IFN-?-producing CD8+ T cells, and reduce IL-4-producing CD8+ T cells. IgG from ATLL could reduce the frequency of IL-4-producing CD4+ T cells, similarly to IgG from HAM/TSP /TSP, and could reduce the frequency of IFN-?-producing ?dT cells without influence on IL-17- and IL4-producing ?dT and could reduce the frequency of IL-10- producing B cells. Finally, IgG from both HAM/TSP and ATLL patients could reduce the frequency of IFN-? producing B cells. In conclusion, these results suggest that these preparations are active, partly overlapping in their effects, and able to elicit distinct effects on target populations.
  • article 19 Citação(ões) na Scopus
    Detection of human T-cell lymphotropic virus type 1 in plasma samples
    (2012) CABRAL, Fabio; ARRUDA, Lia Barbara; ARAUJO, Marilia Ladeira de; MONTANHEIRO, Patricia; SMID, Jerusa; OLIVEIRA, Augusto Cesar Penalva de; DUARTE, Alberto J. S.; CASSEB, Jorge
    Human T-cell lymphotropic virus type 1 (HTLV-1) is-an RNA virus responsible for diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATL). Cell-to-cell contact and Tax-induced clonal expansion of infected cells are the main modes of virus replication, making virus detection during the viremic stage difficult. Consequently, the proviral load is the current virologic marker for disease monitoring, but the mechanisms of progression have not been established yet. Thus, this study investigated the presence of virus in plasma from asymptomatic HTLV-1 carriers and from HAM/TSP patients. Real-time PCR was performed on DNA from 150 plasma samples; 12(8%) had detectable DNA amplification, including 6(4%) asymptomatic HTLV-1 carriers and 14(26%) HAM/TSP patients (p < 0.005). Of the 33 samples submitted for nested PCR, six (18%, p = 0.02) were positive for HTLV-1 RNA in the plasma. Additionally, 26 plasma samples were treated with DNAse enzyme to eliminate any DNA contamination before RNA extraction. Two of them (8%) showed amplification for HTLV-1 (p = 0.5). Therefore, this study described for the first time the detection of free HTLV-1 RNA in plasma from HTLV-1-infected subjects, regardless of their clinical status. Thus, HTLV-1 viral replication does occur in plasma, and other transmission pathways for HTLV-1 should be investigated further.
  • article 0 Citação(ões) na Scopus
    Identification of miRnas with possible prognostic roles for HAM/TSP
    (2023) SOUZA, Daniela Raguer Valadao de; PESSOA, Rodrigo; NUKUI, Youko; PEREIRA, Juliana; MARCUSSO, Rosa Nascimento; OLIVEIRA, Augusto Cesar Penalva de; CASSEB, Jorge; DUARTE, Alberto Jose da Silva; CLISSA, Patricia Bianca; SANABANI, Sabri Saeed
    Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropic spastic paraparesis (HAM/TSP) is an insidiously progressive spinal cord disease for which there is no effective treatment. There is great interest in developing potential biomarkers to predict the pathogenesis of HAM/TSP disease. In this study, Illumina Massive Parallel Sequencing (MPS) technology was used to investigate 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). Various bioinformatics tools were used to align, annotate, and profile the sRNA-MPS reads. Among the 402 sRNAs detected, 251 were known and 50 were potentially novel sRNAs in the HAM and ASP groups compared with the HC group. Sixty-eight known sRNAs were significantly different between the ASP and HAM groups. Eighty-eight mature miRNAs were downregulated in subjects from HAM compared with ASP. 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 seven most deregulated miRs target genes have been associated with a variety of biological processes and molecular functions. The reactome pathways relevant to our findings provide a rich source of data and offer the opportunity to better understand sRNA regulation and function in HTLV-1 pathophysiology. To the best of our knowledge, this study is the first to demonstrate evaluates sRNAs in HTLV-1 patients with HAM/TSP.