WILTON SANTOS FREIRE

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Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina

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  • article 7 Citação(ões) na Scopus
    Prospective study of human herpesvirus 8 oral shedding, viremia, and serological status among human immunodeficiency virus seropositive and seronegative individuals in Sao Paulo, Brazil
    (2017) BRAZ-SILVA, Paulo H.; TOZETTO-MENDOZA, Tania R.; SUMITA, Laura M.; FREIRE, Wilton; PALMIERI, Michelle; CANTO, Alan M. do; AVELINO-SILVA, Vivian I.; GALLOTTINI, Marina; MAYAUD, Philippe; PANNUTI, Claudio S.
    Human herpesvirus 8 (HHV-8) is a gamma-herpesvirus and etiological agent of all forms of Kaposi sarcoma (KS). Saliva may play an important role in HHV-8 transmission in specific populations. Little is known about HHV-8 oral shedding pattern and the possible correlation with the HHV-8 serological profile and viremia. A prospective study was conducted of HHV-8 salivary excretion among human immunodeficiency virus HIV-seronegative (n = 47) and -seropositive (n = 44) homosexual men and HIV-seropositive women (n = 32) over a 6-month period with monthly HHV-8 serologies (immunofluorescence assays to identify antibodies to latent and lytic HHV-8 viral proteins, and a whole-virus HHV-8 enzyme-linked immunosorbent assay [ELISA]), monthly HHV-8 DNA serum/plasma detection, and daily self-collected oral rinses for HHV-8-DNA detection using real-time polymerase chain reaction. HHV-8 seropositivity was 51.1%, 63.6%, and 37.5%, in the three studied groups. There was no case of HHV-8 DNA detection in serum/plasma. Intermittent detection of oral HHV-8 DNA was observed during 5.1% (110/2,160) of visits among 28% (18/64) of HHV-8-seropositive individuals, all of whom were males and HHV-8 ELISA seropositive. In immunologically controlled populations of Brazil, HHV-8 oral shedding was limited to HHV-8-seropositive men, occurred infrequently and intermittently, and was not linked to HHV-8 viremia, suggesting a limited potential for oral or blood transmission.
  • article 12 Citação(ões) na Scopus
    Fatal Human herpesvirus 1 (HHV-1) infection in captive marmosets (Callithrix jacchus and Callithrix penicillata) in Brazil: clinical and pathological characterization
    (2014) CASAGRANDE, Renata A.; PANNUTI, Claudio S.; KANAMURA, Cristina; FREIRE, Wilton S.; GRESPAN, Andre; MATUSHIMA, Eliana R.
    Fatal Human herpesvirus 1 (HHV-1) was diagnosed in 12 captive marmosets (Callithrix jacchus and Callithrix penicillata) from metropolitan region of Sao Paulo, Sao Paulo State. Clinical signs were variable among the cases, but most affected marmosets presented signs associated with viral epithelial replication: oral, lingual and facial skin ulcers and hypersalivation, and viral replication in the central nervous system: prostration, seizure and aggressive behavior. Consistent microscopic findings were diffuse mild to severe nonsuppurative necrotizing meningoencephalitis with gliosis, vasculitis and neuronal necrosis. Additionally, in the brain, oral cavity, skin, adrenal gland and myoenteric plexus intranuclear inclusion bodies were present. Immunohistochemistry confirmed the presence of the HHV-1 antigen in association with lesions in the brain, oral and lingual mucosa, facial skin, adrenal gland and myoenteric plexus. HHV-1-specific polymerase chain reaction (PCR) analysis of the brain was carried out and the virus was detected in 7/8 infected marmosets. It is concluded that HHV-1 causes widespread fatal infection in marmosets.
  • 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.
  • article 11 Citação(ões) na Scopus
    Torquetenovirus in saliva: A potential biomarker for SARS-CoV-2 infection?
    (2021) MENDES-CORREA, Maria C.; TOZETTO-MENDOZA, Tania Regina; FREIRE, Wilton S.; PAIAO, Heuder G. O.; FERRAZ, Andrea B. C.; MAMANA, Ana C.; FERREIRA, Noely E.; V, Anderson de Paula; FELIX, Alvina C.; ROMANO, Camila M.; BRAZ-SILVA, Paulo H.; LEAL, Fabio E.; GRESPAN, Regina M. Z.; SABINO, Ester C.; COSTA, Silvia F.; WITKIN, Steven S.
    Torquetenovirus (TTV) is present in biological fluids from healthy individuals and measurement of its titer is used to assess immune status in individuals with chronic infections and after transplants. We assessed if the titer of TTV in saliva varied with the presence of SARS-CoV-2 in the nasopharynx and could be a marker of COVID-19 status. Saliva from 91 individuals positive for SARS-CoV-2 in nasal-oropharyngeal samples, and from 126 individuals who were SARS-CoV-2-negative, all with mild respiratory symptoms, were analyzed. Both groups were similar in age, gender, symptom duration and time after symptom initiation when saliva was collected. Titers of TTV and SARS-CoV-2 were assessed by gene amplification. Loss of smell (p = 0.0001) and fever (p = 0.0186) were more prevalent in SARS-CoV-2-positive individuals, while sore throat (p = 0.0001), fatigue (p = 0.0037) and diarrhea (p = 0.0475) were more frequent in the SARS-CoV-2 negative group. The saliva TTV and nasal-oropharyngeal SARS-CoV-2 titers were correlated (p = 0.0085). The TTV level decreased as symptoms resolved in the SARS-CoV-2 infected group (p = 0.0285) but remained unchanged in the SARS-CoV-2 negative controls. In SARS-CoV-2 positive subjects who provided 2-4 saliva samples and in which TTV was initially present, the TTV titer always decreased over time as symptoms resolved. We propose that sequential TTV measurement in saliva is potentially useful to assess the likelihood of symptom resolution in SARS-CoV-2-positive individuals and to predict prognosis.
  • article 16 Citação(ões) na Scopus
    Transmission of Human Herpesvirus Type 8 Infection Within Families in American Indigenous Populations From the Brazilian Amazon
    (2012) BORGES, Jaila D.; SOUZA, Vanda A. U. F.; GIAMBARTOLOMEI, Claudia; DUDBRIDGE, Frank; FREIRE, Wilton S.; GREGORIO, Shinai Arriel; TORREZ, Pasesa Pascuala Quispe; QUIROGA, Mariana; MAYAUD, Philippe; PANNUTI, Claudio S.; NASCIMENTO, Maria Claudia
    Background. The intrafamilial dynamics of endemic infection with human herpesvirus type 8 (HHV-8) in Amerindian populations is unknown. Methods. Serum samples were obtained from 517 Amerindians and tested for HHV-8 anti-latent nuclear antigen (anti-LANA) and antilytic antibodies by immunofluorescence assays. Logistic regression and mixed logistic models were used to estimate the odds of being HHV-8 seropositive among intrafamilial pairs. Results. HHV-8 seroprevalence by either assay was 75.4% (95% confidence interval [CI]: 71.5%-79.1%), and it was age-dependent (P-trend<.001). Familial dependence in HHV-8 seroprevalence by either assay was found between mother-offspring (odds ratio [OR], 5.44; 95% CI: 1.62-18.28) and siblings aged >= 10 years (OR 4.42, 95% CI: 1.70-11.45) or siblings in close age range (<5 years difference) (OR 3.37, 95% CI: 1.21-9.40), or in families with large (>4) number of siblings (OR, 3.20, 95% CI: 1.33-7.67). In separate analyses by serological assay, there was strong dependence in mother-offspring (OR 8.94, 95% CI: 2.94-27.23) and sibling pairs aged >= 10 years (OR, 11.91, 95% CI: 2.23-63.64) measured by LANA but not lytic antibodies. Conclusions. This pattern of familial dependence suggests that, in this endemic population, HHV-8 transmission mainly occurs from mother to offspring and between close siblings during early childhood, probably via saliva. The mother to offspring dependence was derived chiefly from anti-LANA antibodies.
  • article 15 Citação(ões) na Scopus
    Non-Detection of Human Herpesvirus 8 (HHV-8) DNA in HHV-8-Seropositive Blood Donors from Three Brazilian Regions
    (2011) LEVI, Jose Eduardo; NASCIMENTO, Maria Claudia; SUMITA, Laura Masami; SOUZA, Vanda Akico Ueda Fick de; FREIRE, Wilton S.; MAYAUD, Philippe; PANNUTI, Claudio S.
    Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), is the etiologic agent of all forms of Kaposi's sarcoma, primary effusion lymphoma and the plasmablastic cell variant of multicentric Castleman disease. In endemic areas of sub-Saharan Africa, blood transfusions have been associated with a substantial risk of HHV-8 transmission. By contrast, several studies among healthy blood donors from North America have failed to detect HHV-8 DNA in samples of seropositive individuals. In this study, using a real-time PCR assay, we investigated the presence of HHV-8 DNA in whole-blood samples of 803 HHV-8 blood donors from three Brazilian states (Sao Paulo, Amazon, Bahia) who tested positive for HHV-8 antibodies, in a previous multicenter study. HHV-8 DNA was not detected in any sample. Our findings do not support the introduction of routine HHV-8 screening among healthy blood donors in Brazil. (WC = 140).
  • article 12 Citação(ões) na Scopus
    Torquetenovirus Titer in Vaginal Secretions from Pregnant and Postpartum Women: Association with Absence ofLactobacillus crispatusand Levels of Lactic Acid and Matrix Metalloproteinase-8
    (2020) TOZETTO-MENDOZA, Tania R.; BONGIOVANNI, Ann Marie; MINIS, Evelyn; LINHARES, Iara M.; BOESTER, Allison; FREIRE, Wilton S.; LIMA, Silvia H.; OLIVEIRA, Natan P. G. de; MENDES-CORREA, Maria C.; FORNEY, Larry J.; WITKIN, Steven S.
    Vaginal samples from women with term deliveries were tested for torquetenovirus (TTV) by gene amplification, matrix metalloproteinase (MMP)-8 and D- and L-lactic acid by ELISA, and microbiome composition by analysis of the bacterial 16S ribosomal RNA gene. TTV was detected in 43.2%, 31.5%, and 41.4% of first trimester, third trimester, and postpartum samples, respectively. The viral titer was higher in postpartum than in the first (p = 0.0018) or third (p = 0.0013) trimester. The mean gestational age at delivery was lower in women positive for TTV in their first trimester (p = 0.0358). In the first and third trimester, the MMP-8 level was higher if TTV was also present (p < 0.0091). The D-lactic acid level was lower in first trimester samples if TTV was present (p = 0.0334).Lactobacillus crispatusdominance in first and third trimester samples was higher when TTV was absent (p < 0.0033). We conclude that TTV is present in the vagina in many women with normal pregnancy outcomes and that its occurrence is associated with a lack ofL. crispatusdominance, an increase in vaginal MMP-8 and a decrease in D-lactic acid.
  • article 0 Citação(ões) na Scopus
    Influenza A and B in a cohort of outpatient children and adolescent with influenza like-illness during two consecutive influenza seasons
    (2020) MACHADO, Clarisse M.; SOUZA, Ana Carolina Mamana Fernandes de; ROMANO, Camila Malta; FREIRE, Wilton dos Santos; COSTA, Angela Aparecida; FIGUEIREDO, Walter Manso; PANNUTI, Claudio S.; LUNA, Expedito J. A.
    Introduction: Influenza is an important cause of morbimortality worldwide. Although people at the extremes of age have a greater risk of complications, influenza has been more frequently investigated in the elderly than in children, and inpatients than outpatients. Yearly vaccination with trivalent or quadrivalent vaccines is the main strategy to control influenza. Objectives: Determine the clinical and molecular characteristics of influenza A and B infections in children and adolescents with influenza-like illness (ILI). Methods: A cohort of outpatient children and adolescents with ILI was followed for 20 months. Influenza was diagnosed with commercial multiplex PCR platforms. Results: 179 patients had 277 episodes of ILI, being 79 episodes of influenza A and 20 episodes of influenza B. Influenza A and B cases were mild and had similar presentation. Phylogenetic tree of influenza B viruses showed that 91.6% belonged to the B/Yamagata lineage, which is not included in trivalent vaccines. Conclusions: Influenza A and B are often detected in children and adolescents with ILI episodes, with similar and mild presentation in outpatients. The mismatch between the circulating influenza viruses and the trivalent vaccine offered in Brazil may have contributed to the high frequency of influenza A and B in this population. (C) 2020 Sociedade Brasileira de Infectologia.
  • article 0 Citação(ões) na Scopus
    Characterization of Torquetenovirus in amniotic fluid at the time of in utero fetal surgery: correlation with early premature delivery and respiratory distress
    (2023) TOZETTO-MENDOZA, Tania Regina; DA-COSTA, A. Charlys; MORON, Antonio F.; LEAL, Elcio; LIMA, Silvia Helena; FERREIRA, Noely Evangelista; HONORATO, Layla; PAIAO, Heuder Gustavo Oliveira; FREIRE, Wilton Santos; MENDES-CORREA, Maria Cassia; WITKIN, Steven S.
    Torquetenovirus (TTV) is a commensal virus present in many healthy individuals. Although considered to be non-pathogenic, its presence and titer have been shown to be indicative of altered immune status in individuals with chronic infections or following allogeneic transplantations. We evaluated if TTV was present in amniotic fluid (AF) at the time of in utero surgery to correct a fetal neurological defect, and whether its detection was predictive of adverse post-surgical parameters. AF was collected from 27 women by needle aspiration prior to a uterine incision. TTV titer in the AF was measured by isolation of viral DNA followed by gene amplification and analysis. The TTV genomes were further characterized and sequenced by metagenomics. Pregnancy outcome parameters were subsequently obtained by chart review. Three of the AFs (11.1%) were positive for TTV at 3.36, 4.16, and 4.19 log(10) copies/mL. Analysis of their genomes revealed DNA sequences similar to previously identified TTV isolates. Mean gestational age at delivery was >2 weeks earlier (32.5 vs. 34.6 weeks) and the prevalence of respiratory distress was greater (100% vs. 20.8%) in the TTV-positive pregnancies. TTV detection in AF prior to intrauterine surgery may indicate elevated post-surgical risk for earlier delivery and newborn respiratory distress.