ALEXANDER ROBERTO PRECIOSO

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Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina

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  • article 2 Citação(ões) na Scopus
    Plasmablast Expansion Following the Tetravalent, Live-Attenuated Dengue Vaccine Butantan-DV in DENV-Naive and DENV-Exposed Individuals in a Brazilian Cohort
    (2022) SILVEIRA, Cassia G. T.; MAGNANI, Diogo M.; COSTA, Priscilla R.; AVELINO-SILVA, Vivian I.; RICCIARDI, Michael J.; TIMENETSKY, Maria do Carmo S. T.; GOULART, Raphaella; CORREIA, Carolina A.; MARMORATO, Mariana P.; FERRARI, Lilian; NAKAGAWA, Zelinda B.; TOMIYAMA, Claudia; TOMIYAMA, Helena; KALIL, Jorge; PALACIOS, Ricardo; PRECIOSO, Alexander R.; WATKINS, David I.; KALLAS, Esper G.
    An effective vaccine against the dengue virus (DENV) should induce a balanced, long-lasting antibody (Ab) response against all four viral serotypes. The burst of plasmablasts in the peripheral blood after vaccination may reflect enriched vaccine-specific Ab secreting cells. Here we characterize the acute plasmablast responses from naive and DENV-exposed individuals following immunization with the live attenuated tetravalent (LAT) Butantan DENV vaccine (Butantan-DV). The frequency of circulating plasmablasts was determined by flow cytometric analysis of fresh whole blood specimens collected from 40 participants enrolled in the Phase II Butantan-DV clinical trial (NCT01696422) before and after (days 6, 12, 15 and 22) vaccination. We observed a peak in the number of circulating plasmablast at day 15 after vaccination in both the DENV naive and the DENV-exposed vaccinees. DENV-exposed vaccinees experienced a significantly higher plasmablast expansion. In the DENV-naive vaccinees, plasmablasts persisted for approximately three weeks longer than among DENV-exposed volunteers. Our findings indicate that the Butantan-DV can induce plasmablast responses in both DENV-naive and DENV-exposed individuals and demonstrate the influence of pre-existing DENV immunity on Butantan DV-induced B-cell responses.
  • article 20 Citação(ões) na Scopus
    Pulmonary Surfactant in Respiratory Syncytial Virus Bronchiolitis: The Role in Pathogenesis and Clinical Implications
    (2011) BARREIRA, Eliane Roseli; PRECIOSO, Alexander Roberto; BOUSSO, Albert
    Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of lower respiratory tract infection, and the most frequent reason for hospitalization among infants throughout the world. In addition to the acute consequences of the disease, RSV bronchiolitis in early childhood is related to further development of recurrent wheezing and asthma. Despite the medical and economic burden of the disease, therapeutic options are limited to supportive measures, and mechanical ventilation in severe cases. Growing evidence suggests an important role of changes in pulmonary surfactant content and composition in the pathogenesis of severe RSV bronchiolitis. Besides the well-known importance of pulmonary surfactant in maintenance of pulmonary homeostasis and lung mechanics, the surfactant proteins SP-A and SP-D are essential components of the pulmonary innate immune system. Deficiencies of such proteins, which develop in severe RSV bronchiolitis, may be related to impairment in viral clearance, and exacerbated inflammatory response. A comprehensive understanding of the role of the pulmonary surfactant in the pathogenesis of the disease may help the development of new treatment strategies. We conducted a review of the literature to analyze the evidences of pulmonary surfactant changes in the pathogenesis of severe RSV bronchiolitis, its relation to the inflammatory and immune response, and the possible role of pulmonary surfactant replacement in the treatment of the disease. Pediatr Pulmonol. 2011; 46:415-420. (c) 2010 Wiley-Liss, Inc.
  • article 3 Citação(ões) na Scopus
    Safety assessment of seasonal trivalent influenza vaccine produced by Instituto Butantan from 2013 to 2017
    (2019) GATTAS, Vera Lucia; BRAGA, Patricia Emilia; KOIKE, Marcelo Eiji; LUCCHESI, Maria Beatriz Bastos; OLIVEIRA, Mayra Martho Moura de; PIORELLI, Roberta de Oliveira; QUEIROZ, Vivian; PRECIOSO, Alexander Roberto
    Vaccination has been a successful strategy in influenza prevention. However, despite the safety and efficacy of the vaccines, they can cause adverse events following immunization (AEFI). Moreover, due to the vaccination success, most of vaccine-preventable diseases (VPD) have become rare, and public attention has been shifted from VPD to the AEFI associated with vaccination. This manuscript describes the safety of Instituto Butantan (IB) seasonal trivalent influenza vaccine (TIV) from 2013 to 2017. AEFI data were received by the Department of Pharmacovigilance of IB (PV-IB), from January the 1st 2013 to December the 31st 2017, and were recorded in an electronic database (OpenClinica (c)). PV-IB received 1,415 Individual Case Safety Reports (ICSR) associated with the TIV; 1,253 ICSR with at least one AEFI were analyzed and 4,140 AEFI were identified. The other 162 (11.4%) cases did not present any symptom. Among the total of AEFI, 405 (9.8%) were classified as serious. AEFI with the highest incidence rates per 100,000 doses of TIV were: ""local pain"" (0.28), ""local erythema"" (0.23), ""local warmth"" (0.22), ""local swelling"" (0.20) and ""fever"" (0.19). PV-IB received 175 (4.2%) occurrences of SAE of special interest, of which 75 (1.8%) anaphylaxis/anaphylactic reactions, 56 (1.4%) neurological syndromes (including seven Guillain-Barre Syndrome) and 44 (1.1%) convulsion/febrile convulsion. The results of this manuscript suggested that Instituto Butantan trivalent influenza vaccine (IB-TIV) is safe, as most of the reported AEFI were classified as non-serious. AEFI described for the IB-TIV are in agreement with the ones described in the literature for similar vaccines.
  • article 2 Citação(ões) na Scopus
    Dose-sparing effect of two adjuvant formulations with a pandemic influenza A/H7N9 vaccine: A randomized, double-blind, placebo-controlled, phase 1 clinical trial
    (2022) VANNI, Tazio; THOME, Beatriz C.; SPARROW, Erin; FRIEDE, Martin; FOX, Christopher B.; BECKMANN, Anna Marie; HUYNH, Chuong; MONDINI, Gabriella; SILVEIRA, Daniela H.; VISCONDI, Juliana Y. K.; BRAGA, Patricia Emilia; SILVA, Anderson da; SALOMAO, Maria da Graca; PIORELLI, Roberta O.; SANTOS, Joane P.; GATTAS, Vera Lucia; LUCCHESI, Maria Beatriz B.; OLIVEIRA, Mayra M. M. de; KOIKE, Marcelo E.; KALLAS, Esper G.; CAMPOS, Lucia M. A.; COELHO, Eduardo B.; SIQUEIRA, Marilda A. M.; GARCIA, Cristiana C.; MIRANDA, Milene Dias; PAIVA, Terezinha M.; TIMENETSKY, Maria do Carmo S. T.; ADAMI, Eduardo A.; AKAMATSU, Milena A.; HO, Paulo Lee; PRECIOSO, Alexander R.
    The emergence of potentially pandemic viruses has resulted in preparedness efforts to develop candidate vaccines and adjuvant formulations. We evaluated the dose-sparing effect and safety of two distinct squalene-based oil-in-water adjuvant emulsion formulations (IB160 and SE) with influenza A/H7N9 antigen. This phase I, randomized, double-blind, placebo-controlled, dose-finding trial (NCT03330899), enrolled 432 healthy volunteers aged 18 to 59. Participants were randomly allocated to 8 groups: 1A) IB160 + 15 mu g H7N9, 1B) IB160 + 7.5 mu g H7N9, 1C) IB160 + 3.75 mu g H7N9, 2A) SE + 15 mu g H7N9, 2B) SE + 7.5 mu g H7N9, 2C) SE + 3.75 mu g H7N9, 3) unadjuvanted vaccine 15 mu g H7N9 and 4) placebo. Immunogenicity was evaluated through haemagglutination inhibition (HI) and microneutralization (MN) tests. Safety was evaluated by monitoring local and systemic, solicited and unsolicited adverse events (AE) and reactions (AR) 7 and 28 days after each study injection, respectively, whereas serious adverse events (SAE) were monitored up to 194 days post-second dose. A greater increase in antibody geometric mean titers (GMT) was observed in groups receiving adjuvanted vaccines. Vaccinees receiving IB160-adjuvanted formulations showed the greatest response in group 1B, which induced an HI GMT increase of 4.7 times, HI titers >= 40 in 45.2% of participants (MN titers >= 40 in 80.8%). Vaccinees receiving SE-adjuvanted vaccines showed the greatest response in group 2A, with an HI GMT increase of 2.5 times, HI titers >= 40 in 22.9% of participants (MN titers >= 40 in 65.7%). Frequencies of AE and AR were similar among groups. Pain at the administration site and headache were the most frequent local and systemic solicited ARs. The vaccine candidates were safe and the adjuvanted formulations have a potential dose-sparing effect on immunogenicity against influenza A/H7N9. The magnitude of this effect could be further explored.
  • conferenceObject
    Ventilatory Practices And Adjunctive Therapies In Children With Ards: A Prospective Observational Study
    (2014) BARREIRA, E. R.; SHIEH, H. H.; SUZUKI, A. S.; DEGASPARE, N. V.; CAVALHEIRO, P. O.; MUNOZ, G. O. C.; MARTINES, J. A. D. S.; LANE, C.; CARVALHO, W. B.; GILIO, A. E.; PRECIOSO, A. R.
  • article 15 Citação(ões) na Scopus
    Pandemic unadjuvanted influenza A (H1N1) vaccine in dermatomyositis and polymyositis: Immunogenicity independent of therapy and no harmful effect in disease
    (2012) SHINJO, Samuel Katsuyuki; MORAES, Julio Cesar Bertacini de; LEVY-NETO, Mauricio; AIKAWA, Nadia Emi; RIBEIRO, Ana Cristina de Medeiros; SAAD, Carla Goncalves Schahin; PRECIOSO, Alexander; SILVA, Clovis Artur; BONFA, Eloisa
    The goal of the present study was to evaluate the influence of the influenza A H1N1/2009 vaccine on dermatomyositis/polymyositis (DM/PM) disease parameters and the potential deleterious effect of therapy on immune response. Thirty-seven DM and 21 PM patients (Bohan and Peter's criteria) were gender- and age-matched to 116 healthy controls. Seroprotection, seroconversion, the geometric mean titers (GMTs) and the factor increase (FI) in the GMTs were calculated. Disease safety was determined from a muscle enzyme analysis and the DM/PM scores [patient's visual analog scale (VAS), physician's VAS, manual muscle strength (MMT-8)] evaluated pre- and post-vaccination. The mean age (43.1 +/- 9.9 vs. 43.8 +/- 8.4 years, p = 0.607) and gender distribution (p = 1.00) were comparable between the patients and controls. After 21 days, seroconversion (p = 0.394), seroprotection (p = 0.08), GMT (p = 0.573) and the FI in the GMT (p = 0.496) were similar in both groups. The disease and muscle parameters remained stable throughout the study, including the creatine kinase (p = 0.20) and aldolase levels (p = 0.98), the physicians' VAS (p = 1.00), the patients' VAS (p = 1.00) and the MMT-8 (p = 1.00). Regarding the influence of treatment, the seroconversion rates were comparable between the controls and patients undergoing treatment with glucocorticoid (GC) (p = 0.969), GC >0.5 mg/kg/day (p = 0.395) and GC + immunosuppressors (p = 0.285). Vaccine-related adverse events were mild and similar in the DM/PM and control groups (p > 0.05). Our data support the administration of the pandemic influenza A H1N1/2009 vaccination in DM/PM, as we found no short-term harmful effects related to the disease itself and adequate immunogenicity in spite of therapy. Further studies are necessary to identify any long-term adverse effects in patients with these diseases.(c) 2012 Elsevier Ltd. All rights reserved.
  • article 1 Citação(ões) na Scopus
    Seroconversion in asymptomatic COVID-19 pediatric patients with rheumatic diseases of one tertiary referral hospital
    (2022) SIMON, Juliana R.; PEREIRA, Maria F. B.; MARQUES, Heloisa H.; ELIAS, Adriana M.; SAKITA, Neusa K.; FERREIRA, Juliana C. O. A.; PRECIOSO, Alexander Roberto; GRISI, Sandra J. F. E.; FERRER, Ana Paula S.; BAIN, Vera; SILVA, Clovis A.; CAMPOS, Lucia M. A.
    Objectives: To evaluate seroconverted asymptomatic COVID-19 in pediatric Autoimmune Rheumatic Diseases (ARDs) patients and to identify the risk factors related to contagion.Methods: A cross-sectional study was conducted in March 2021, before vaccination of children and adolescents in Brazil, including 77 pediatric ARDs patients, followed at a tertiary hospital and 45 healthy controls, all of them without a previous diagnosis of COVID-19. Data was obtained by a questionnaire with demographic data, symp-toms compatible with COVID-19 over the previous year, and contact with people with confirmed COVID-19. Patient's medical records were reviewed to access data regarding disease and current medications. A qualitative immunochromatographic SARS-CoV-2 test was performed on all participants.Results: Patients and controls were similar in terms of female gender (70.1% vs. 57.8%, p = 0.173), age (14 vs. 13 years, p = 0.269) and SARS-CoV-2 positive serology (22% vs. 15.5%, p = 0.481). 80.5% of rheumatic patients were in use of immunosuppressive drugs: 27.3% of them used corticosteroids (33.3% in high doses), and 7.8% on immunobiologicals. No statistical differences were found between positive (n = 17) and negative serol-ogy (n = 60) patients regarding demographic/socioeconomic data, contact with people with confirmed COVID-19, use and number of immunosuppressive drugs, use and dose of corticosteroids, use of hydroxychloroquine and immunobiological drugs (p > 0.05).Conclusions: Pediatric rheumatic disease patients were infected at the same rate as healthy ones. Neither the underlying pathology nor its immunosuppressive treatment seemed to interfere with contagion risk.
  • article 30 Citação(ões) na Scopus
    Short and long-term effects of pandemic unadjuvanted influenza A(H1N1)pdm09 vaccine on clinical manifestations and autoantibody profile in primary Sjogren's syndrome
    (2013) PASOTO, Sandra Gofinet; RIBEIRO, Ana Cristina; VIANA, Vilma Santos Trindade; LEON, Elaine Pires; BUENO, Cleonice; LEVY NETO, Mauricio; PRECIOSO, Alexander Roberto; TIMENETSKY, Maria do Carmo Sampaio Tavares; BONFA, Eloisa
    Despite WHO recommendations about the A/Califomia/7/2009/H1N1-like virus vaccination, studies evaluating its possible influence on clinical manifestations and autoantibody profile in primary Sjogren's syndrome (SS) are scarce. The aim of this study was to evaluate the possible influence of the unadjuvanted A/Califomia/7/2009/H1N1-like virus vaccination on clinical manifestations and autoantibody profile in SS in the short/long-term. Thirty-six SS patients (The American-European Consensus Group Criteria, 2002) and 36 healthy controls with comparable mean age and gender were evaluated before and 21-days after this vaccination regarding seroprotection/seroconversion, factor increase in geometric mean titer (FI-GMT) and side effects. New onset of disease flares and autoantibody profile [antinuclear antibodies, anti-dsDNA, anti-Ro(SSA)/La(SSB), anti-RNP/anti-Sm, rheumatoid factor, anti-alpha-fodrin, anticardiolipin and anti-beta2-glycoprotein-I] were assessed before, 21-days and 1-year after vaccination. Patients and controls had similar rates of seroconversion (77.8 vs. 69.4%, p = 0.42), seroprotection (83.3 vs. 72.2%, p = 0.26) and FI-GMT (p = 0.85). Disease duration, prednisone (2.1 +/- 4.9 mg/day), methotrexate and azathioprine did not affect seroconversion (p > 0.05). Regarding short-term, no change in the frequency or levels of autoantibodies was observed (p > 0.05) and only mild side effects were reported in comparable rates to controls (p > 0.05). During 1-year follow-up, the frequency of new disease flares was similar to the previous year (11 vs. 19%, p = 0.51), and four patients developed positivity to one of the following specificities: anti-Ro(SSA)/anti-La/(SSB), anti-alpha-fodrin, or IgM anticardiolipin. None developed specific lupus autoantibodies. Of note, a significant increase in the mean levels of anti-Ro/SSA (p = 0.0001) and anti-La/SSB (p = 0.002) was detected after 1-year with no change in the other autoantibodies. This is the first study indicating that influenza A(H1N1)pdm09 vaccine induces long-term changes in autoantibody profile restricted to SS spectrum without a deleterious effect in disease course.
  • article 17 Citação(ões) na Scopus
    A phase I clinical trial of a new 5-valent rotavirus vaccine
    (2013) LUNA, Expedito J. A.; FRAZATTI-GALLINA, Neuza M.; TIMENETSKY, Maria C. S. T.; CARDOSO, Maria R. A.; VERAS, Maria A. S. M.; MIRAGLIA, Joao L.; ESCOBAR, Ana M. U.; GRISI, Sandra J. F. E.; RAW, Isaias; PRECIOSO, Alexander R.
    We conducted a phase I, double-blind, placebo-controlled trial to evaluate a new 5-valent oral rotavirus vaccine's safety and immunogenicity profiles. Subjects were randomly assigned to receive 3 orally administered doses of a live-attenuated human-bovine (UK) reassortant rotavirus vaccine, containing five viral antigens (G1, G2, G3, G4 and G9), or a placebo. The frequency and severity of adverse events were assessed. Immunogenicity was evaluated by the titers of anti-rotavirus IgA and the presence of neutralizing antibodies anti-rotavirus. No severe adverse events were observed. There was no difference in the frequency of mild adverse events between experimental and control groups. The proportion of seroconversion was consistently higher in the vaccine group, for all serotypes, after each one of the doses. The 5-valent vaccine has shown a good profile of safety and immunogenicity in this small sample of adult volunteers.
  • article 29 Citação(ões) na Scopus
    Epidemiology and Outcomes of Acute Respiratory Distress Syndrome in Children According to the Berlin Definition: A Multicenter Prospective Study
    (2015) BARREIRA, Eliane R.; MUNOZ, Gabriela O. C.; CAVALHEIRO, Priscilla O.; SUZUKI, Adriana S.; DEGASPARE, Natalia V.; SHIEH, Huei H.; MARTINES, Joao A. D. S.; FERREIRA, Juliana C.; LANE, Christianne; CARVALHO, Werther B.; GILIO, Alfredo E.; PRECIOSO, Alexander R.
    Objectives: In 2012, a new acute respiratory distress syndrome definition was proposed for adult patients. It was later validated for infants and toddlers. Our objective was to evaluate the prevalence, outcomes, and risk factors associated with acute respiratory distress syndrome in children up to 15 years according to the Berlin definition. Design: A prospective, multicenter observational study from March to September 2013. Setting: Seventy-seven PICU beds in eight centers: two private hospitals and six public academic hospitals in Brazil. Patients: All children aged 1 month to 15 years admitted to the participating PICUs in the study period. Interventions: None. Measurements and Main Results: All children admitted to the PICUs were daily evaluated for the presence of acute respiratory distress syndrome according to the American-European - Consensus Conference and Berlin definitions. Of the 562 patients included, acute respiratory distress syndrome developed in 57 patients (10%) and 58 patients (10.3%) according to the Berlin definition and the American-European Consensus Conference definition, respectively. Among patients with acute respiratory distress syndrome according to the Berlin definition, nine patients (16%) were mild, 21 (37%) were moderate, and 27 (47%) were severe. Compared with patients without acute respiratory distress syndrome, patients with acute respiratory distress syndrome had significantly higher severity scores, longer PICU and hospital length of stay, longer duration of mechanical ventilation, and higher mortality (p < 0.001). The presence of two or more comorbidities and admission for medical reasons were associated with development of acute respiratory distress syndrome. Comparisons across the three the Berlin categories showed significant differences in the number of ventilator-free days (21, 20, and 5 d, p = 0.001) and mortality for severe acute respiratory distress syndrome (41%) in comparison with mild (0) and moderate (15%) acute respiratory distress syndrome(p = 0.02). No differences in PICU or hospital stay were observed across the groups. Conclusions: The Berlin definition can identify a subgroup of patients with distinctly worse outcomes, as shown by the increased mortality and reduced number of ventilator-free days in pediatric patients with severe acute respiratory distress syndrome.