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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  • article 18 Citação(ões) na Scopus
    High risk of heterosexual transmission of human T-cell lymphotropic virus type 1 infection in Brazil
    (2017) PAIVA, Arthur; SMID, Jerusa; HAZIOT, Michel E. J.; ASSONE, Tatiane; PINHEIRO, Samara; FONSECA, Luiz A. M.; OLIVEIRA, Augusto C. Penalva de; CASSEB, Jorge
    Human T-cell lymphotropic virus type 1 is transmitted primarily either through sexual intercourse or from mother to child. The current study investigated sexual transmission and compared the HTLV-1 proviral load between seroconcordant and serodiscordant couples by examining both men and women among the index partners without using subjective criteria to establish the direction of sexual transmission. Between January 2013 and May 2015, 178 HTLV-1-positive patients had spouses, 107 of which had tested partners, thus increasing the initial sample size (46 men and 61 women). Individuals co-infected with HTLV-2 or human immunodeficiency virus were not included in the analysis. From among the included participants, 26 men and 26 women were paired with each other, resulting in 26 seroconcordant couples; 12 seroconcordant couples were formed from another four men and eight women. Forty-three serodiscordant couples were formed from 16 men and 27 women. The rate of seroconcordance was 46.9%. The HTLV-1 proviral load was compared between 19 and 37 seroconcordant and serodiscondant couples, respectively, and the concordant couples showed higher proviral loads (P = 0.03). There were no differences between the groups according to age, relationship length, having a mother or sibling with HTLV-1, race, ethnicity, nationality, education, history of blood transfusion, HAM/TSP, ALT, or hepatitis C virus status. In multivariate analysis, relationship time was shown associated with ocurrence of seroconcordance status. The apparent association between high circulating levels of provirus and seroconcordance rate among couples suggests that proviral loads contribute markedly to the risk of sexual transmission, regardless of gender index.
  • conferenceObject
    In vitro basal T-cell proliferation and HTLV-1 proviral load among HTLV-1 subjects co-infected with Hepatitis C and/or HIV-1
    (2015) ASSONE, Tatiane; MITIKO, Tatiana; GOMES, Samara P. C.; PAIVA, Arthur; HAZIOT, Michel; SMID, Jerusa; OLIVEIRA, Augusto Penalva de; NORRIS, Philip J.; CASSEB, Jorge
  • 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.
  • bookPart
    Manifestações neurológicas virais primárias do sistema nervoso central, do sistema nervoso periférico e neuromusculares associadas à infeccao pelo HIV
    (2013) OLIVEIRA, Augusto César Penalva de; SMID, Jerusa; CASSEB, Jorge; ANNES, Marcelo; BERMúDEZ, José Ernesto Vidal
  • article 0 Citação(ões) na Scopus
    Evaluation of the New Multi-HTLV Serological Assay: Improvement for HTLV-2 Detection
    (2024) FOLGOSI, Victor Angelo; KONMINAKIS, Shirley Vasconcelos; SILVA, Felipe Dias da; LEITE JUNIOR, Pedro Domingos; HAZIOT, Michel Elyas Jung; OLIVEIRA, Augusto C. P.; SMID, Jerusa; ZREIN, Maan; SALVADOR, Florent; CASSEB, Jorge
    Despite the accuracy of confirmatory tests for the diagnosis of human T cell lymphotropic virus (HTLV), inconclusive or false-negative results still occur when diagnosing human T cell lymphotropic virus type 2 (HTLV-2)-positive patients. The goal of this study was to evaluate the sensitivity and accuracy of a confirmatory immunoassay, the Multi-HTLV assay. A total of 246 plasma samples were tested by real-time polymerase chain reaction (qPCR) and used to calculate the sensitivity and typing accuracy of the Multi-HTLV assay. Of the 246 plasma samples, 127 were positive for human T cell lymphotropic virus type 1 (HTLV-1), 112 were positive for HTLV-2, and 7 were positive for both HTLV-1 and HTLV-2. Thereafter, the nonparametric Mann-Whitney U test was used to calculate the concordance between the qPCR test and Multi-HTLV assay in 12 samples with discrepant and inconclusive qPCR results. The Multi-HTLV assay showed high performance in identifying HTLV-1 and HTLV-2 with sensitivities of 97% [95% confidence interval (CI): 0.92-0.98] and 94% (0.87-0.96), respectively. However, due to typing performance (98% for HTLV-1 and 94% for HTLV-2), it had 95% agreement with positive HTLV-1 qPCR results (95% CI: 90.07-97.81) and 86% (78.04-91.01) of HTLV-2 qPCR results were positive. Moreover, this test was able to recognize 80% of indeterminate samples and all HTLV-2 positive samples that showed false-negative qPCR results. Our findings, derived from a substantial number of HTLV-positive samples, underscore the inherent reliability and feasibility of the Multi-HTLV assay, regardless of the molecular testing facilities. Furthermore, the distinctive multiparametric nature of this assay, combined with its straightforward procedural execution, introduces novel perspectives for analyzing specific serological profiles in each patient, as well as the potential for immunological monitoring of disease progression.
  • 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 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
    Could Cesarean Delivery Help Prevent Mother-to-Child Transmission of Human T-Lymphotropic Virus Type 1?
    (2023) PRATES, Gabriela; PAIVA, Arthur; HAZIOT, Michel E.; FONSECA, Luiz Augusto M.; SMID, Jerusa; MARCUSSO, Rosa Maria do N.; ASSONE, Tatiane; OLIVEIRA, Augusto. C. P. de; CASSEB, Jorge
    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.
  • article 3 Citação(ões) na Scopus
    Memory impairment: an intermediate clinical syndrome symptom in HTLV-1-infected patients?
    (2019) GASCON, Maria Rita; HAZIOT, Michel E.; ASSONE, Tatiane; FONSECA, Luiz Augusto M.; SMID, Jerusa; OLIVEIRA, Augusto Cesar Penalva de; CASSEB, Jorge
    Background: Although classical human T-cell lymphocyte virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis syndrome is the most frequent HTLV-1-associated neurological disorder, some ""minor"" neurological disorders can be seen in ""asymptomatic"" carriers. These disorders, including cognitive alterations already described in clinical cases and studies, may constitute an intermediate syndrome (IMS) between the asymptomatic state and myelopathy. The aim of this study was to investigate the presence of cognitive deficits in patients with HTLV-1 virus, who usually are diagnosed as asymptomatic. Methods: A total of 54 HTLV-1-infected patients were evaluated, 35 asymptomatic and 19 with minor neurological alterations (evaluated by a neurologist); 25 HTLV-1-seronegative individuals served as controls. The instruments used were: Beck's Depression Inventory, Lawton's Daily Life Activity Scale, and a complete neuropsychological battery. The application of these evaluation instruments was performed blindly, with the evaluator neuropsychologist not knowing the clinical condition of the patient. Results: Most of the participants in this cohort, including seronegative controls, were female (n = 57, 72.21%), their mean age was 52.34 years (SD = 14.29) and their average schooling was 9.70 years (SD = 4.11). Discussion: Participants classified with IMS had lower gross scores when compared with both the patients classified as asymptomatic and with the control group, and when tested for auditory episodic memory of immediate (p < 0.01), and late (p = 0.01), recall. Conclusion: Patients with IMS presented with memory impairment when compared with asymptomatic patients and seronegative individuals; this is one of the symptoms that aids in the classification of the syndrome.