STEVEN SOL WITKIN
Projetos de Pesquisa
Unidades Organizacionais
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
40 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 40
- Prevalence and clinical consequences of Hepatitis C virus infection in patients undergoing hematopoietic stem cell transplantation(2024) DIAZ, Ana Claudia Marques Barbosa; WITKIN, Steven Sol; ALMEIDA-NETO, Cesar de; MENDRONE-JUNIOR, Alfredo; ROCHA, Vanderson; COSTA, Silvia Figueiredo; RAMOS, Jessica Fernandes; MENDES-CORREA, Maria CassiaHepatitis C virus (HCV) infection is a significant cause of morbidity and mortality among hematopoietic stem cell transplant (HCT) recipients. In Brazil, its occurrence in HCT recipients remains undetermined. We now report on HCV prevalence in HCT recipients and its clinical consequences. The medical records of all HCT recipients seen at Hospital das Clinicas, Sao Paulo University Medical School, from January 2010 to January 2020 were reviewed to determine HCV serostatus. A retrospective analysis of medical charts was undertaken on all seropositive cases to determine HCV genotype, presence of liver fibrosis, co-infections with other viruses, previous treatments, and clinical evolution of liver pathology after HCT. Of the 1,293 HCT recipients included in the study, seven (0.54%) were HCV antibody-positive and five (0.39%) were also viremic for HCV-RNA. Four of these individuals had moderate to severe liver fibrosis (METAVIR F2/F3) and one was cirrhotic. Two of the viremic patients developed acute liver dysfunction following transplantation. All patients had their acute episode of liver dysfunction resolved with no further complications. Four of the viremic patients were treated for HCV infection with direct acting agents (DAA). Information regarding HCV treatment was lacking for one of the viremic HCV patients due to loss of follow up. Sustained anti-virologic responses were observed in three cases after the use of DAA. The detection of HCV in hematological adults undergoing HCT and its successful treatment with DAA highlight the necessity of testing for HCV both prior to and following transplantation.
- Torquetenovirus: predictive biomarker or innocent bystander in pathogenesis(2023) TOZETTO-MENDOZA, Tania Regina; BRAZ-SILVA, Paulo Henrique; GIANNECCHINI, Simone; WITKIN, Steven S.
- The Torque Teno Virus Titer in Saliva Reflects the Level of Circulating CD4(+) T Lymphocytes and HIV in Individuals Undergoing Antiretroviral Maintenance Therapy(2022) HONORATO, Layla; WITKIN, Steven S.; MENDES-CORREA, Maria Cassia; TOSCANO, Ana Luiza Castro Conde; LINHARES, Iara Moreno; PAULA, Anderson Vicente de; PAIAO, Heuder Gustavo Oliveira; PAULA, Vanessa Salete de; LOPES, Amanda de Oliveira; LIMA, Silvia Helena; RAYMUNDI, Vanessa de Cassia; FERREIRA, Noely Evangelista; SILVA JUNIOR, Almir Ribeiro da; ABRAHIM, Karim Yaqub; BRAZ-SILVA, Paulo Henrique; TOZETTO-MENDOZA, Tania ReginaIntroductionTorque teno virus (TTV) is a non-pathogenic virus present in body fluids. Its titer in the circulation increases in association with immune suppression, such as in HIV-infected individuals. We evaluated if the TTV titer in saliva from HIV-positive individuals undergoing antiretroviral therapy (ART) was related to the circulating CD4+ T lymphocyte concentration and the HIV titer. MethodsSaliva was collected from 276 asymptomatic individuals undergoing ART, and an additional 48 individuals positive for AIDS-associated Kaposi's Sarcoma (AIDS-KS). The salivary TTV titer was measured by gene amplification analysis. The circulating CD4+ T lymphocyte and HIV levels were obtained by chart review. ResultsTTV was detectable in saliva from 80% of the asymptomatic subjects and 87% of those with AIDS-KS. In the asymptomatic group the median log(10) TTV titer/ml was 3.3 in 200 males vs. 2.4 in 76 females (p < 0.0001). TTV titer/ml was 3.7 when HIV was acquired by intravenous drug usage, 3.2 when by sexual acquisition and 2.4 when blood transfusion acquired. The salivary TTV titer was inversely correlated with the circulating CD4+ T lymphocyte level (p < 0.0001) and positively correlated with the circulating HIV concentration (p = 0.0005). The median salivary TTV titer and circulating HIV titer were higher, and the CD4+ count was lower, in individuals positive for AIDS-KS than in the asymptomatic subjects (p < 0.0001). ConclusionThe TTV titer in saliva is a potential biomarker for monitoring immune status in individuals undergoing ART.
- Prevalence and diagnostic accuracy of microcephaly in a pediatric cohort in Brazil: a retrospective cross-sectional study(2021) BERTOZZI, Ana Paula Antunes Pascalicchio; GAZETA, Rosa Estela; FAJARDO, Thamirys Cosmo Gillo; MORON, Antonio Fernandes; SORIANO-ARANDES, Antoni; ALARCON, Ana; GARCIA-ALIX, Alfredo; SILVA, Alify Bertoldo da; FLORENCE FILHO, Nemesio; SARMENTO, Stephanno Gomes Pereira; WITKIN, Steven S.; PASSOS, Saulo DuarteObjective: We sought to describe the prevalence of microcephaly and to compare the different cutoff points established by the Brazilian Ministry of Health at various times during a Zika virus epidemic. As a secondary aim, we investigated the possible etiology of the microcephaly. Method: This retrospective study utilized newborn participants in the Zika Cohort Study Jundiai. Newborns from the Zika Cohort Study Jundiai with an accurate gestational age determination and complete anthropometric data were analyzed, and microcephaly was diagnosed according to the INTERGROWTH-21st curve. At delivery, fluids were tested for specific antibodies and for viruses. Brain images were evaluated for microcephaly. Receiver Operating Characteristic curves were plotted to define the accuracy of different cutoff points for microcephaly diagnosis. Results: Of 462 eligible newborns, 19 (4.1%) were positive for microcephaly. Cutoff points corresponding to the curves of the World Health Organization yielded the best sensitivity and specificity. Three of the microcephaly cases (15.8%) were positive for Zika virus infections; nine (47.4%) had intrauterine growth restriction; one had intrauterine growth restriction and was exposed to Zika virus; three had a genetic syndrome (15.8%); and three had causes that had not been determined (15.8%). Conclusions: Microcephaly prevalence was 4.1% in this study. Cutoff values determined by the World Health Organization had the highest sensitivity and specificity in relation to the standard IG curve. The main reason for microcephaly was intrauterine growth restriction. All possible causes of microcephaly must be investigated to allow the best development of an affected baby. (C) 2020 Sociedade Brasileira de Pediatria.
- Detection of RNA-Dependent RNA Polymerase of Hubei Reo-Like Virus 7 by Next-Generation Sequencing in Aedes aegypti and Culex quinquefasciatus Mosquitoes from Brazil(2019) RIBEIRO, Geovani de Oliveira; MONTEIRO, Fred Julio Costa; REGO, Marlisson Octavio da S.; RIBEIRO, Edcelha Soares D'Athaide; CASTRO, Daniela Funayama de; CASEIRO, Marcos Montani; MARINHO, Robson dos Santos Souza; KOMNINAKIS, Shirley Vasconcelos; WITKIN, Steven S.; DENG, Xutao; DELWART, Eric; SABINO, Ester Cerdeira; COSTA, Antonio Charlys da; LEAL, ElcioAdvancements in next-generation sequencing and bioinformatics have expanded our knowledge of the diversity of viruses (pathogens and non-pathogens) harbored by mosquitoes. Hubei reo-like virus 7 (HRLV 7) was recently detected by the virome analysis of fecal samples from migratory birds in Australia. We now report the detection of RNA-dependent RNA polymerase sequences of HRLV 7 in pools of Aedes aegypti and Culex quinquefasciatus mosquitoes species from the Brazilian Amazon forest. Phylogenetic inferences indicated that all HRLV 7 strains fall within the same independent clade. In addition, HRLV 7 shared a close ancestral lineage with the Dinovernavirus genus of the Reoviridae family. Our findings indicate that HRLV 7 is present in two species of mosquitoes.
- Epizootics due to Yellow Fever Virus in Sao Paulo State, Brazil: viral dissemination to new areas (2016-2017)(2019) CUNHA, Mariana Sequetin; COSTA, Antonio Charlys da; FERNANDES, Natalia Coelho Couto de Azevedo; GUERRA, Juliana Mariotti; SANTOS, Fabiana Cristina Pereira dos; NOGUEIRA, Juliana Silva; D'AGOSTINO, Leandro Guariglia; KOMNINAKIS, Shirley Vasconcelos; WITKIN, Steven S.; RESSIO, Rodrigo Albergaria; MAEDA, Adriana Yurika; VASAMI, Fernanda Gisele Silva; KAIGAWA, Ursula Mitsue Abreu; AZEVEDO, Lais Sampaio de; FACIOLI, Paloma Alana de Souza; MACEDO, Fernando Luiz Lima; SABINO, Ester Cerdeira; LEAL, Elcio; SOUZA, Renato Pereira deBeginning in late 2016 Brazil faced the worst outbreak of Yellow Fever in recent decades, mainly located in southeastern rural regions of the country. In the present study we characterize the Yellow Fever Virus (YFV) associated with this outbreak in Sao Paulo State, Brazil. Blood or tissues collected from 430 dead monkeys and 1030 pools containing a total of 5,518 mosquitoes were tested for YFV by quantitative RT-PCR, immunohistochemistry (IHC) and indirect immunofluorescence. A total of 67 monkeys were YFV-positive and 3 pools yielded YFV following culture in a C6/36 cell line. Analysis of five nearly full length genomes of YFV from collected samples was consistent with evidence that the virus associated with the Sao Paulo outbreak originated in Minas Gerais. The phylogenetic analysis also showed that strains involved in the 2016-2017 outbreak in distinct Brazilian states (i.e., Minas Gerais, Rio de Janeiro, Espirito Santo) intermingled in maximum-likelihood and Bayesian trees. Conversely, the strains detected in Sao Paulo formed a monophyletic cluster, suggesting that they were local-adapted. The finding of YFV by RT-PCR in five Callithrix monkeys who were all YFV-negative by histopathology or immunohistochemistry suggests that this YFV lineage circulating in Sao Paulo is associated with different outcomes in Callithrix when compared to other monkeys.
- Vaginal Biomarkers That Predict Cervical Length and Dominant Bacteria in the Vaginal Microbiomes of Pregnant Women(2019) WITKIN, Steven S.; MORON, Antonio F.; RIDENHOUR, Benjamin J.; MINIS, Evelyn; HATANAKA, Alan; SARMENTO, Stephanno G. P.; FRANCA, Marcelo S.; CARVALHO, Francisco H. C.; HAMAMOTO, Tatiana K.; MATTAR, Rosiane; SABINO, Ester; LINHARES, Iara M.; RUDGE, Marilza V. C.; FORNEY, Larry J.In many impoverished regions of the world, it may not be possible to assess two major risk factors for preterm birth: a short cervical length and the depletion of vaginal lactobacilli. We determined whether measuring specific compounds in vaginal fluid might be a simple, noninvasive, and cost-effective way to predict the bacteria that dominate the vaginal microbiome and indicate the presence of a shortened cervix (<25 mm). Vaginal fluid samples were prospectively collected from mid-trimester pregnant women, and the concentrations of D- and L-lactic acid, tissue inhibitor of matrix metalloproteinases TIMP-1 and TIMP-2, matrix metalloproteinases MMP-2 and MMP-8, the 70-kDa heat shock protein, a2 isoform of vacuolar ATPase, and sequestrome-1 were quantified by an enzyme-linked immunosorbent assay (ELISA). The compositions of vaginal microbiomes were assessed by analysis of the V1-V3 regions of 16S rRNA genes, while cervical length was determined by transvaginal ultrasonography. The vaginal microbiomes could be clustered into five community state types (CSTs), four of which were dominated by a single Lactobacillus species. The dominance of Lactobacillus crispatus or Lactobacillus jensenii in the vaginal microbiome predicted the level of D-lactic acid present. Several of the biomarkers, especially TIMP-1, in combination with the subject's age and race, were significantly associated with cervical length. Using piecewise structural equation modeling, we established a causal network that links CST to cervical length via biomarkers. We concluded that measuring levels of TIMP-1 and D-lactic acid in vaginal secretions might be a straightforward way to assess the risk for preterm birth due to a short cervix and microbiome composition. IMPORTANCE Premature birth and its complications are the largest contributors to infant death in the United States and globally. A short cervical length and the depletion of Lactobacillus species are known risk factors for preterm birth. However, in many resource-poor areas of the world, the technology to test for their occurrence is unavailable, and pregnant women with these risk factors are neither identified nor treated. In this study, we used path analysis to gain an unprecedented understanding of interactions between vaginal microbiome composition, the concentrations of various compounds in vaginal secretions, and cervical length. We identified low-cost point-of-care measures that might be used to identify pregnant women at risk for preterm birth. The use of these measures coupled with appropriate preventative or treatment strategies could reduce the incidence of preterm births in poor areas of the world that lack access to more sophisticated diagnostic methods.
- Study protocol to investigate biomolecular muscle profile as predictors of long-term urinary incontinence in women with gestational diabetes mellitus(2020) RUDGE, Marilza V. C.; SOUZA, Fatima P.; ABBADE, Joelcio F.; HALLUR, Raghavendra L. S.; MARCONDES, Joao Paulo C.; PICULO, Fernanda; MARINI, Gabriela; VESENTINI, Giovana; THABANE, Lehana; WITKIN, Steven S.; CALDERON, Iracema M. P.; BARBOSA, Angelica M. P.; RUDGE, M. V.; BARBOSA, A. M. P.; CALDERON, I. M. P.; SOUZA, F. P.; ABBADE, J. F.; HALLUR, L. S. R.; PICULO, F.; MARINI, G.; VESENTINI, G.; THABANE, L.; PALMA, M. S.; GRAEFF, C. F. O.; ARNI, R. K.; HERCULANO, R. D.; SALVADORI, D. F.; MATEUS, S.; SILVA, M. Dal Pai; MAGALHAES, C. G.; COSTA, R. A.; LIMA, S. A. M.; FELISBINO, S. L.; BARBOSA, W.; ATALLAH, A.; GIRAO, M. J. B.; BELLA, Z. Di; UCHOA, S. M.; PAYAO, S.; HIJAS, A.; BERGHMAN, B.; BIE, R. De; SOBREVIA, L.; JUNGINGER, B.; ALVES, F. C. B.; ROSSIGNOLI, P. S.; PRUDENCIO, C. B.; ORLANDI, M. I. G.; GONCALVES, M. I.; NUNES, S. K.; CATINELLI, B. B.; QUIROZ, S.; SARMENTO, B. V.; PINHEIRO, F. A.; SARTORAO, C. I.; LUCAS, R. R.; REYES, D. R. A.; QUIROZ, S. B. C. V.; ENRIQUEZ, E. M. A.; OLIVEIRA, R. G.; FLORIANO, J. F.; MARCONDES, J. P. C.; BARNEZE, S.; DANGIO, T. D.; PASCON, T.; ROSSIGNOLI, P.; FREITAS, J. V.; TAKANO, L.; REIS, F.; CALDEIRAO, T. D.; FERNANDES, J. N.; CARR, A. M.; GAITERO, M. V. C.; CORRENTE, J. E.; NUNES, H. R. C.; CANDIDO, A. F.; COSTA, S. M. B.; DANGIO, T. D.; PASCON, T.; MELO, J. V. F.; TAKANO, L.; REIS, F. V. D. S.; CALDEIRAO, T. D.; CARR, A. M.; GARCIA, G. A.; RABADAN, G. B.; BASSIN, H. C. M.; SUYAMA, K. S.; DAMASCENO, L. N.; TAKEMOTO, M. L. S.; MENEZES, M. D.; BUSSANELI, D. G.; NOGUEIRA, V. K. C.; LIMA, P. R.; LOURENCO, I. O.; SA, J. Marostica de; MEGID, R. A.; CARUSO, I. P.; RASMUSSEN, L. T.; PRATA, G. M.; PICULO, F.; VESENTINI, G.; ARANTES, M. A.; FERRAZ, G. A. R.; CAMARGO, L. P.; KRON, M. R.; CORRENTE, J. E.; NUNES, H. R. C.Background Pelvic floor muscles (PFM) and rectus abdominis muscles (RAM) of pregnant diabetic rats exhibit atrophy, co-localization of fast and slow fibers and an increased collagen type I/III ratio. However, the role of similar PFM or RAM hyperglycemic-related myopathy in women with gestational diabetes mellitus (GDM) remains poorly investigated. This study aims to assess the frequency of pelvic floor muscle disorders and pregnancy-specific urinary incontinence (PS-UI) 12 months after the Cesarean (C) section in women with GDM. Specifically, differences in PFM/RAM hyperglycemic myopathy will be evaluated. Methods The Diamater is an ongoing cohort study of four groups of 59 pregnant women each from the Perinatal Diabetes Research Centre (PDRC), Botucatu Medical School (FMB)-UNESP (Sao Paulo State University), Brazil. Diagnosis of GDM and PS-UI will be made at 24-26 weeks, with a follow-up at 34-38 weeks of gestation. Inclusion in the study will occur at the time of C-section, and patients will be followed at 24-48 h, 6 weeks and 6 and 12 months postpartum. Study groups will be classified as (1) GDM plus PS-UI; (2) GDM without PS-UI; (3) Non-GDM plus PS-UI; and (4) Non-GDM without PS-UI. We will analyze relationships between GDM, PS-UI and hyperglycemic myopathy at 12 months after C-section. The mediator variables to be evaluated include digital palpation, vaginal squeeze pressure, 3D pelvic floor ultrasound, and 3D RAM ultrasound. RAM samples obtained during C-section will be analyzed for ex-vivo contractility, morphological, molecular and OMICS profiles to further characterize the hyperglycemic myopathy. Additional variables to be evaluated include maternal age, socioeconomic status, educational level, ethnicity, body mass index, weight gain during pregnancy, quality of glycemic control and insulin therapy. Discussion To our knowledge, this will be the first study to provide data on the prevalence of PS-UI and RAM and PFM physical and biomolecular muscle profiles after C-section in mothers with GDM. The longitudinal design allows for the assessment of cause-effect relationships between GDM, PS-UI, and PFMs and RAMs myopathy. The findings may reveal previously undetermined consequences of GDM.
- A Novel Highly Divergent Strain of Cell Fusing Agent Virus (CFAV) in Mosquitoes from the Brazilian Amazon Region(2018) FERNANDES, Licia Natal; COLETTI, Thais de Moura; MONTEIRO, Fred Julio Costa; REGO, Marlisson Octavio da Silva; RIBEIRO, Edcelha Soares D'Athaide; RIBEIRO, Geovani de Oliveira; MARINHO, Robson dos Santos Souza; KOMNINAKIS, Shirley Vasconcelos; WITKIN, Steven S.; DENG, Xutao; DELWART, Eric; SABINO, Ester Cerdeira; LEAL, Elcio; COSTA, Antonio Charlys daClassical insect-specific flaviviruses (cISFs) have been widely detected in different countries in the last decades. Here, we characterize the near full-length genomes of two cISFs detected in mosquitoes collected in the city of Macapa, state of Amapa, Amazon region of Brazil. A total of 105 pools of female mosquitos were analyzed by next-generation sequencing (NGS). Comparative genomics and phylogenetic analysis identified three strains of cell fusing agent virus (CFAV) and two of Culex flavivirus (CxFV). All sequences were obtained from pools of Culex sp., except for one sequence of CFAV detected in a pool of Aedes aegypti. Both CxFV strains are phylogenetically related to a strain isolated in 2012 in the Southeast region of Brazil. The CFAV strains are the first of this species to be identified in Brazil and one of them is highly divergent from other strains of CFAV that have been detected worldwide. In conclusion, CFAV and CxFV, circulate in mosquitoes in Brazil. One strain of CFAV is highly divergent from others previously described, suggesting that a novel strain of CFAV is present in this region.
- Characterization of insect-specific Culex flavivirus (Flaviviridae) nucleotide sequences in mosquitoes from urban parks in Sao Paulo, Brazil(2022) COLETTI, Thais de Moura; ROMANO, Camila Malta; URBINATTI, Paulo Roberto; TEIXEIRA, Renildo Souza; PEDROSA, Leila Weiss de Almeida; NARDI, Marcello Schiavo; NATAL, Delsio; COSTA, Antonio Charlys da; JESUS, Jaqueline Goes de; CLARO, Ingra Morales; SABINO, Ester Cerdeira; WITKIN, Steven S.; MARRELLI, Mauro Toledo; FERNANDES, Licia NatalBackground: Despite their worldwide occurrence, the distribution and role of insect-specific flaviviruses (ISFs) remain unclear. Methods: We evaluated the presence of ISFs in mosquitoes collected in Sao Paulo, Brazil, using reverse transcription and semi-nested polymerase chain reaction (PCR). Some of the positive samples were subjected to nanopore sequencing. Results: Twelve mosquito pools (2.8%) tested positive for flavivirus infection. Nanopore sequencing was successfully performed on six samples. Phylogenetic analysis grouped these sequences into genotype 2 of Culex flavivirus (CxFV). Conclusions: The identification of CxFV genotype 2 at new locations in Sao Paulo highlights the importance of understanding the role of ISFs in mosquito vector competence.