STEVEN SOL WITKIN

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12
Projetos de Pesquisa
Unidades Organizacionais
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina

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Agora exibindo 1 - 10 de 26
  • article 0 Citação(ões) na Scopus
    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 Cassia
    Hepatitis 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.
  • article 5 Citação(ões) na Scopus
    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 Regina
    IntroductionTorque 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.
  • article 0 Citação(ões) na Scopus
    Association between torquetenovirus in vaginal secretions and infertility: An exploratory metagenomic analysis
    (2023) COSTA, A. Charlys Da; BORTOLETTO, Pietro; SPANDORFER, Steven D.; TOZETTO-MENDOZA, Tania Regina; LINHARES, Iara M.; MENDES-CORREA, Maria Cassia; WITKIN, Steven S.
    ProblemThe association of viruses with infertility remains incompletely evaluated.Method of studyVaginal secretions from 46 women seeking treatment in the Center for Reproductive Medicine and Infertility at Weill Cornell Medicine were tested for viruses by metagenomic analysis by lab personnel blinded to all clinical data.ResultsTorquetenovirus (TTV) was identified in 16 women, alphapapillomavirus in seven women and most were positive for bacteriophages. Twelve of the subjects were fertile and sought to freeze their oocytes for future implantation. These women were all negative for TTV. In contrast, 16 of the 34 women (47.1%) being treated for infertility were TTV-positive (p = .0035). Evaluating the women by cause of infertility, five of nine women (55.6%) whose male partner had inadequate sperm parameters and six of 14 women (42.9%) with defective ovulation were TTV positive (p = .0062 and p = .0171, respectively, vs. the fertile women). Alphapapillomavirus was identified in one (8.3%) fertile woman, five (35.7%) women with ovulation deficiency, and one (11.1%) woman with male factor infertility. These differences were not statistically significant. There were no differences in bacteriophage families or the presence of Lactobacillus phages between fertile or infertile women or between different causes of infertility. There was a negative association between TTV detection and Lactobacillus crispatus dominance in the vaginal microbiota (p = .0184), but no association between TTV detection and the presence of alphapapillomavirus or Candida species.ConclusionDetection of TTV in the vagina might be a biomarker for specific causes of infertility.
  • article 10 Citação(ões) na Scopus
    Identification of bacteriophages in the vagina of pregnant women: a descriptive study
    (2021) COSTA, A. C. da; MORON, A. F.; FORNEY, L. J.; LINHARES, I. M.; SABINO, E.; COSTA, S. F.; MENDES-CORREA, M. C.; WITKIN, S. S.
    Objective To determine the presence and identity of extracellular bacteriophage (phage) families, genera and species in the vagina of pregnant women. Design Descriptive, observational cohort study. Setting Sao Paulo, Brazil. Population Pregnant women at 21-24 weeks' gestation. Methods Vaginal samples from 107 women whose vaginal microbiome and pregnancy outcomes were previously determined were analysed for phages by metagenomic sequencing. Main outcome measures Identification of phage families, genera and species. Results Phages were detected in 96 (89.7%) of the samples. Six different phage families were identified: Siphoviridae in 69.2%, Myoviridae in 49.5%, Microviridae in 37.4%, Podoviridae in 20.6%, Herelleviridae in 10.3% and Inviridae in 1.9% of the women. Four different phage families were present in 14 women (13.1%), three families in 20 women (18.7%), two families in 31 women (29.1%) and one family in 31 women (29.1%). The most common phage species detected wereBacillusphages in 48 (43.6%),Escherichiaphages in 45 (40.9%),Staphylococcusphages in 40 (36.4%),Gokushovirusin 33 (30.0%) andLactobacillusphages in 29 (26.4%) women. In a preliminary exploratory analysis, there were no associations between a particular phage family, the number of phage families present in the vagina or any particular phage species and either gestational age at delivery or the bacterial community state type present in the vagina. Conclusions Multiple phages are present in the vagina of most mid-trimester pregnant women. Tweetable abstract Bacteriophages are present in the vagina of most pregnant women.
  • conferenceObject
    IMPACT ON MORTALITY OF BEING SEROPOSITIVE FOR HEPATITIS C VIRUS ANTIBODIES AMONG BLOOD DONORS IN BRAZIL: A TWENTY YEAR STUDY
    (2019) SR., Helio Ranes de Menezes Filho; CAPUANI, Maria Ligia Damato; BIERRENBACH, Ana Luiza De Souza; MENDRONE JUNIOR, Alfredo; BENZAKEN, Adele Schwartz; MACHADO, Soraia Mafra; SAIVISH, Marielena Vogel; SABINO, Ester Cerdeira; WITKIN, Steven Sol; CORREA, Maria Cassia Mendes
  • article 0 Citação(ões) na Scopus
    Evaluation of enterovirus concentration, species identification, and cerebrospinal fluid parameters in patients of different ages with aseptic meningitis in Sao Paulo, Brazil
    (2024) HONORATO, Layla; FERREIRA, Noely Evangelista; DOMINGUES, Renan Barros; SENNE, Carlos; LEITE, Fernando Brunale Vilela de Moura; SANTOS, Marcio Vega dos; FERNANDES, Gustavo Bruniera Peres; PAIAO, Heuder Gustavo Oliveira; BOAS, Lucy Santos Vilas; COSTA, Antonio Charlys da; TOZETTO-MENDOZA, Tania Regina; WITKIN, Steven S.; MENDES-CORREA, Maria Cassia
    Human enteroviruses (EV) are the most common cause of aseptic meningitis worldwide. Data on EV viral load in cerebrospinal fluid (CSF) and related epidemiological studies are scarce in Brazil. This study investigated the influence of EV viral load on CSF parameters, as well as identifying the involved species. CSF samples were collected in 2018-2019 from 140 individuals at The Hospital das Clinicas, Sao Paulo. The EV viral load was determined using real-time quantitative polymerase chain reaction, while EV species were identified by 5 ' UTR region sequencing. Median viral load was 5.72 log10 copies/mL and did not differ by subjects' age and EV species. Pleocytosis was observed in 94.3% of cases, with the highest white blood cell (WBC) counts in younger individuals. Viral load and WBC count were correlated in children (p = 0.0172). Elevated lactate levels were observed in 60% of cases and correlated with the viral load in preteen-teenagers (p = 0.0120) and adults (p = 0.0184). Most individuals had normal total protein levels (70.7%), with higher in preteen-teenagers and adults (p < 0.0001). By sequencing, 8.2% were identified as EV species A and 91.8% as species B. Age-specific variations in CSF characteristics suggest distinct inflammatory responses in each group.
  • article 2 Citação(ões) na Scopus
    Factors Associated with Spontaneous Clearance of Recently Acquired Hepatitis C Virus among HIV-Positive Men in Brazil
    (2023) FERRUFINO, Rosario Quiroga; RODRIGUES, Camila; FIGUEIREDO, Gerusa Maria; GLEISON, Daniel; YAPURA, Silvia; MATOS, Maria Laura Mariano de; WITKIN, Steven S. S.; MENDES-CORREA, Maria Cassia
    Introduction: The objective of the present study was to describe the clinical and epidemiological aspects of recently acquired hepatitis C virus (HCV) infection and the frequency of its spontaneous clearance in a people living with the human immunodeficiency virus (PLWH) cohort. Methods: We reviewed the medical records from all PLWH at the human immunodeficiency virus (HIV) outpatient reference clinic affiliated with the University of Sao Paulo, Brazil, and identified, by immunoassays and RNA-PCR individuals who acquired HCV infection between January 2015 and December 2017. The factors associated with subsequent spontaneous clearance of the infection in this group were identified and analyzed. Results: Among 3143 PLWH individuals, 362 (11.5%) were coinfected with HCV. Forty-eight (13.2%) of these subjects first became HCV-positive between January 2015 and December 2017. Spontaneous HCV clearance was documented in 23 individuals (47.9%). The majority of this latter group were male (83.3%), and the median age was 31 years (23-39). The main risk group for HCV acquisition was men who had sex with men (MSM) (89.5%). In a multivariate analysis, only an elevated CD4+ T lymphocyte count at the time of seroconversion was found to be associated with subsequent HCV clearance (p = 0.025). Conclusions: In HIV-infected individuals in Sao Paulo, Brazil, most cases of recent HCV transmission were by sexual exposure. In PLWH, particularly in MSM, the individual's CD4+ T lymphocyte count is a determinant of whether an acquired HCV infection will be prolonged or will spontaneously clear.
  • article 0 Citação(ões) na Scopus
    Detailed characterization of Redondovirus in saliva of SARS-CoV-2-infected individuals in Sao Paulo, Brazil
    (2023) COSTA, Antonio Charlys da; MENDES-CORREA, Maria C.; TOZETTO-MENDOZA, Tania Regina; VILLAS-BOAS, Lucy S.; PAULA, Anderson Vicente de; PAIAO, Heuder Gustavo Oliveira; LEAL, Fabio E.; FERREIRA, Noely E.; HONORATO, Layla; LEAL, Elcio; GRANDI, Giuliano; MORAIS, Vanessa dos Santos; MANULI, Erika R.; SABINO, Ester C.; WITKIN, Steven S.
    BackgroundRedondovirus (ReDoV) is a DNA virus present in the respiratory tract of many healthy individuals. Since SARS-CoV-2, the virus responsible for COVID-19, also primarily infects the same site, we evaluated whether ReDoV was present at increased frequency in patients with COVID-19 and influenced infection parameters.MethodsSaliva samples were collected weekly from 59 individuals with COVID-19 and from 132 controls. ReDoV was detected by polymerase chain reaction and the genotypes were identified by metagenomics. Torque Teno Virus (TTV) in these samples were previously reported.ResultsReDoV was detected in saliva more frequently from COVID-19 patients (72.9%) than from controls (50.0%) (p = 0.0015). There were no associations between ReDoV detection and either continuous or intermittent SARS-CoV-2 shedding, the duration of SARS-CoV-2 detection in saliva, patients' sex or if infection was by the B1 or Gamma strain. The two ReDoV strains, Brisavirus and Vientovirus, were present in equivalent frequencies in ReDoV-positive COVID-19 patients and controls. Phylogenetic analysis suggested that the two ReDoV strains in Brazil were similar to strains previously detected on other continents.ConclusionReDoV expression in saliva is increased in males and females in Brazil with mild COVID-19 but its presence does not appear to influence properties of the SARS-CoV-2 infection.
  • article 1 Citação(ões) na Scopus
    IMPACT OF THE COVID-19 PANDEMIC ON CERVICAL CANCER SCREENING IN SAOPAULO STATE, BRAZIL
    (2023) MARTINS, Toni Ricardo; WITKIN, Steven S.; MENDES-CORREA, Maria Cassia; GODOY, Amanda Scancella de; CURY, Lise; BALANCIN, Marcelo Luiz; AB'SABER, Alexandre Muxfeldt; PERES, Stela Verzinhasse; MESSIAS, Sandra; MENDONZA, Tania Regina Tozetto; LONGATTO-FILHO, Adhemar
    INTRODUCTION: The early identification of precursor lesions followed by appropriate treatment prevents development of cervical cancer and its consequences OBJECTIVE: The present study evaluated the influence of the Covid-19 pandemic on cervical cancer screening by comparing the quantity of tests to detect cervical cellular changes performed in Sao Paulo state in 2019, prior to the detection of SARS-CoV-2 in Brazil, to the first (2020) and second (2021) years following its appearance. MATERIALS AND METHODS: Data from Fundacao Oncocentro de Sao Paulo (FOSP), the agency that analyses approximately 220,000 Pap tests annually, was reviewed. RESULTS: A median of 1835 Papanicolaou (Pap) tests were performed in 55 municipalities in 2019. This was reduced to 815 tests in 2020, a 56% decrease (p = 0.0026). In 2021, the median number was 1745, a 53% increase over 2020 levels (p = 0.0233). The 26 municipalities with >1000 tests in 2020 had a median reduction from 4433 in 2019 to 2580 in 2020 (p = 0. 0046). The 29 municipalities with <1000 tests had a median reduction from 951 in 2019 to 554 in 2020 (p < 0.0001). There was a 44% reduction in the number of follow-up cytological evaluations from 2019 to 2020, followed by a 30% increase the following year. However, the percentage of women with a normal finding or with any abnormality remained unchanged. The findings from a histological evaluation of women in Sao Paulo city indicated that the percent of cases positive for CIN-1 (p<0.0410) and CIN-3 (p<0.0012) increased in 2020 and 2021 as compared to 2019 levels. CONCLUSION: A reduction in testing for cervical cancer in the first year of the Covid-19 pandemic, accompanied by an elevated incidence of precancerous lesions in each of the first two years following its initiation, may portend a subsequent increased occurrence of cervical cancer in Brazil.
  • article 2 Citação(ões) na Scopus
    SARS-CoV-2 Detection and Culture in Different Biological Specimens from Immunocompetent and Immunosuppressed COVID-19 Patients Infected with Two Different Viral Strains
    (2023) MENDES-CORREA, Maria Cassia; SALOMAO, Matias Chiarastelli; GHILARDI, Fabio; TOZETTO-MENDOZA, Tania Regina; VILLAS-BOAS, Lucy Santos; PAULA, Anderson Vicente de; PAIAO, Heuder Gustavo Oliveira; COSTA, Antonio Charlys da; LEAL, Fabio E.; FERRAZ, Andrea de Barros Coscelli; SALES, Flavia C. S.; CLARO, Ingra M.; FERREIRA, Noely E.; PEREIRA, Geovana M.; JR, Almir Ribeiro da Silva; FREIRE, Wilton; ESPINOZA, Evelyn Patricia Sanchez; MANULI, Erika R.; ROMANO, Camila M.; JESUS, Jaqueline G. de; SABINO, Ester C.; WITKIN, Steven S.
    Introduction-The dynamics of SARS-CoV-2 shedding and replication in humans remain incompletely understood. Methods-We analyzed SARS-CoV-2 shedding from multiple sites in individuals with an acute COVID-19 infection by weekly sampling for five weeks in 98 immunocompetent and 25 immunosuppressed individuals. Samples and culture supernatants were tested via RT-PCR for SARS-CoV-2 to determine viral clearance rates and in vitro replication. Results-A total of 2447 clinical specimens were evaluated, including 557 nasopharyngeal swabs, 527 saliva samples, 464 urine specimens, 437 anal swabs and 462 blood samples. The SARS-CoV-2 genome sequences at each site were classified as belonging to the B.1.128 (ancestral strain) or Gamma lineage. SARS-CoV-2 detection was highest in nasopharyngeal swabs regardless of the virus strain involved or the immune status of infected individuals. The duration of viral shedding varied between clinical specimens and individual patients. Prolonged shedding of potentially infectious virus varied from 10 days up to 191 days, and primarily occurred in immunosuppressed individuals. Virus was isolated in culture from 18 nasal swab or saliva samples collected 10 or more days after onset of disease. Conclusions-Our findings indicate that persistent SARS-CoV-2 shedding may occur in both competent or immunosuppressed individuals, at multiple clinical sites and in a minority of subjects is capable of in vitro replication.