SUZETE CLEUSA FERREIRA SPINA LOMBARDI
Projetos de Pesquisa
Unidades Organizacionais
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
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- Detection and analysis of blood donors seropositive for syphilis(2021) ATTIE, Adriana; ALMEIDA-NETO, Cesar de; WITKIN, Steven S.; DERRIGA, Juliana; NISHIYA, Anna S.; FERREIRA, Jerenice E.; COSTA, Natalia de Souza Xavier; SALLES, Nanci Alves; FACINCANI, Tila; LEVI, Jose E.; SABINO, Ester C.; ROCHA, Vanderson; MENDRONE-JR, Alfredo; FERREIRA, Suzete C.Background The increasing incidence of syphilis worldwide has called attention to the risk of transmission by transfusion. Aims To determine the prevalence of active syphilis in blood donors and characterise the serological profile of syphilis-positive donors. Methods Samples positive for Treponema pallidum using the chemiluminescent microparticle immunoassay (CMIA) during blood donor screening from 2017 to 2018 were tested by the Venereal Disease Research Laboratory (VDRL) non-treponemal test and for anti-T. pallidum IgM by ELISA (Immunoassay Enzyme test for detection of IgM antibodies). The INNO-LIA Syphilis test (Line Immuno Assay solid test for confirmation antibodies to Treponema pallidum) was performed as a confirmatory test on samples that were positive on ELISA-IgM but negative on VDRL. ELISA-IgM (+) samples were also tested for T. pallidum DNA in sera by real-time polymerase chain reaction (PCR). Results Of 248 542 samples screened, 1679 (0.67%) were positive for syphilis by CMIA. Further analysis was performed on 1144 (68.1%) of these samples. Of those tested, 16% were ELISA IgM(+)/VDRL(+), 16.5% were ELISA IgM(-)/VDRL(+), 4.1% were ELISA IgM(+)/VDRL(-), and 63.4% were ELISA IgM (-)/VDRL(-). The INNO-LIA Syphilis test results were 33 (3%) positive, 2 (0.2%) undetermined and 12 (1%) negative. Of the 230 EIA-IgM(+) samples (20.1%), 5 (2.2%) were PCR positive. The prevalence of active syphilis in 2017 and 2018 was 0.1% and 0.07%, respectively, and overall prevalence of serologic markers for syphilis was highest among male, unmarried, 25-34-year-olds with a high school education and who were first-time donors. Conclusion There is a risk of transfusion-transmitted syphilis in blood banks that exclusively use the VDRL test for donor screening, as is currently the situation in some Brazilian blood centres, as well as in other blood centres around the world.
- Epstein-Barr Viral Load is Associated to Response in AIDS-Related Lymphomas(2014) TANAKA, Paula Yurie; OHSHIMA, Kouichi; MATSUOKA, Masao; SABINO, Ester Cerdeira; FERREIRA, Suzete Cleusa; NISHYA, Anna Shoko; COSTA, Renata de Oliveira; CALORE, Edenilson Eduardo; PEREZ, Nilda Maria; PEREIRA, JulianaAIDS-related lymphoma (ARL) development is associated to immunodeficiency state with proliferation of B-cells driven by HIV itself and EBV infection. However, Epstein-Barr DNA is not detected in malignant cells of all ARL subtypes. A prospective and controlled study to analyze EBV viral load (VL) in plasma and peripheral blood mononuclear cells (PBMC) of ARL patients was performed to analyze if Epstein-Barr VL could be related to response in these patients. Fifteen patients with ARL were included in this study with measurement of EBV VL at three different periods of time: at lymphoma diagnosis, upon completion of chemotherapy, and 3 months after. Two control groups composed by HIV-negative and HIV-positive patients were also evaluated for EBV VL comparison. In situ hybridization for EBER was performed on diagnostic samples of all ARL patients. Median EBV VL in PBMC and plasma had a significant decrease (p = 0.022 and p = 0.003, respectively) after ARL treatment. EBER was positive in 7 (46.7 %) cases. Median EBV VL in PBMC before lymphoma treatment in patients positive for EBER was significantly higher compared to EBER negative cases (p = 0.041). Reduction of EBV viral load during treatment of lymphoma could be predictive of response. EBER expression was associated to advanced stages of disease and worse immune status. Our study suggests that measurement of EBV VL during ARL treatment could be used as a marker for response, but further studies are needed to validate this association.
- Immunogenicity and safety of primary fractional-dose yellow fever vaccine in autoimmune rheumatic diseases(2021) TONACIO, Adriana Coracini; PEDROSA, Tatiana do Nascimento; BORBA, Eduardo Ferreira; AIKAWA, Nadia Emi; PASOTO, Sandra Gofinet; FERREIRA FILHO, Julio Cesar Rente; BARROS, Marilia Mantovani Sampaio; LEON, Elaine Pires; LOMBARDI, Suzete Cleusa Ferreira Spina; MENDRONE JUNIOR, Alfredo; AZEVEDO, Adriana de Souza; SCHWARCZ, Waleska Dias; FULLER, Ricardo; YUKI, Emily Figueiredo Neves; LOPES, Michelle Remiao Ugolini; PEREIRA, Rosa Maria Rodrigues; BARROS, Percival Degrava Sampaio; ANDRADE, Danieli Castro Oliveira de; MEDEIROS-RIBEIRO, Ana Cristina de; MORAES, Julio Cesar Bertacini de; SHINJO, Samuel Katsuyuki; MIOSSI, Renata; DUARTE, Alberto Jose da Silva; LOPES, Marta Heloisa; KALLAS, Esper Georges; SILVA, Clovis Artur Almeida da; BONFA, EloisaBackground Brazil faced a yellow fever(YF) outbreak in 2016-2018 and vaccination was considered for autoimmune rheumatic disease patients(ARD) with low immunosuppression due to YF high mortality. Objective This study aimed to evaluate, prospectively for the first time, the short-term immunogenicity of the fractional YF vaccine(YFV) immunization in ARD patients with low immunossupression. Methods and Results A total of 318 participants(159 ARD and 159 age- and sex-matched healthy controls) were vaccinated with the fractional-dose(one fifth) of 17DD-YFV. All subjects were evaluated at entry(D0), D5, D10, and D30 post-vaccination for clinical/laboratory and disease activity parameters for ARD patients. Post-vaccination seroconversion rate(83.7%vs.96.6%, p = 0.0006) and geometric mean titers(GMT) of neutralizing antibodies[1143.7 (95%CI 1012.3-1292.2) vs.731 (95%CI 593.6-900.2), p< 0.001] were significantly lower in ARD compared to controls. A lower positivity rate of viremia was also identified for ARD patients compared to controls at D5 (53%vs.70%, p = 0.005) and the levels persisted in D10 for patients and reduced for controls(51%vs.19%, p = 0.0001). The viremia was the only variable associated with seroconvertion. No serious adverse events were reported. ARD disease activity parameters remained stable at D30(p>0.05). Conclusion Fractional-dose 17DD-YF vaccine in ARD patients resulted in a high rate of seroconversion rate(> 80%) but lower than controls, with a longer but less intense viremia. This vaccine was immunogenic, safe and did not induce flares in ARD under low immunosuppression and may be indicated in YF outbreak situations and for patients who live or travel to endemic areas.
- Detection of bacterial contamination in platelet concentrates from Brazilian donors by molecular amplification of the ribosomal 16S gene(2018) VIANA, J. D.; FERREIRA, S. C.; MATANA, S. R.; ROSSI, F.; PATEL, P.; GARSON, J. A.; ROCHA, V.; TEDDER, R.; MENDRONE-JUNIOR, A.; LEVI, J. E.Objective The aim of our work was to establish a semi-automated high-throughput DNA amplification method for the universal screening of bacteria in platelet concentrates (PCs). Background Among cases of transfusion transmission of infectious agents, bacterial contamination ranks first in the number of events, morbidity and mortality. Transmission occurs mainly by transfused PCs. Automated culture is adopted by some blood banks for screening of bacterial contamination, but this procedure is expensive and has a relatively long turnaround time. Methods PCs were spiked with suspensions of five different bacterial species in a final concentration of 1 and 10 colony-forming units (CFU) per millilitre. After incubation, the presence of bacteria was investigated by real-time polymerase chain reaction (PCR) and by the Enhanced Bacterial Detection System (eBDS, Pall) assay as a reference method. Real-time PCR amplification was performed with a set of universal primers and probes targeting the 16S rRNA gene. Co-amplification of human mitochondrial DNA served as an internal control. Results Using the real-time PCR method, it was possible to detect the presence of all bacterial species tested with an initial concentration of 10 CFU mL(-1) 24 h after contamination, except for Staphylococcus hominis. The PCR assay also detected, at 24 h, the presence of Serratia marcescens and Enterobacter cloacae with an initial concentration of 1 CFU mL(-1). Conclusions The real-time PCR assay may be a reliable alternative to conventional culture methods in the screening of bacterial contamination of PCs, enabling bacterial detection even with a low initial concentration of microorganisms.
- SARS-CoV-2 antibody dynamics in blood donors and COVID-19 epidemiology in eight Brazilian state capitals: A serial cross-sectional study(2022) PRETE JR., Carlos A.; BUSS, Lewis F.; WHITTAKER, Charles; SALOMON, Tassila; OIKAWA, Marcio K.; PEREIRA, Rafael H. M.; MOURA, Isabel C. G.; DELERINO, Lucas; BARRAL-NETTO, Manoel; TAVARES, Natalia M.; FRANCA, Rafael F. O.; BOAVENTURA, Viviane S.; MIYAJIMA, Fabio; MENDRONE-JUNIOR, Alfredo; ALMEIDA-NETO, Cesar De; SALLES, Nanci A.; FERREIRA, Suzete C.; FLADZINSKI, Karine A.; SOUZA, Luana M. de; SCHIER, Luciane K.; INOUE, Patricia M.; XABREGAS, Lilyane A.; CRISPIM, Myuki A. E.; FRAIJI, Nelson; V, Fernando L. Araujo; CARLOS, Luciana M. B.; PESSOA, Veridiana; RIBEIRO, Maisa A.; SOUZA, Rosenvaldo E. de; SILVA, Sonia M. N. da; CAVALCANTE, Anna F.; VALENCA, Maria I. B.; V, Maria da Silva; LOPES, Esther; FILHO, Luiz A.; MATEOS, Sheila O. G.; NUNES, Gabrielle T.; SILVA-JUNIOR, Alexander L.; BUSCH, Michael P.; CASTRO, Marcia C.; DYE, Christopher; RATMANN, Oliver; FARIA, Nuno R.; NASCIMENTO, Vitor H.; SABINO, Ester C.Background: The COVID-19 situation in Brazil is complex due to large differences in the shape and size of regional epidemics. Understanding these patterns is crucial to understand future outbreaks of SARS-CoV-2 or other respiratory pathogens in the country. Methods: We tested 97,950 blood donation samples for IgG antibodies from March 2020 to March 2021 in 8 of Brazil's most populous cities. Residential postal codes were used to obtain representative samples. Weekly age- and sex-specific seroprevalence were estimated by correcting the crude seroprevalence by test sensitivity, specificity, and antibody waning. Results: The inferred attack rate of SARS-CoV-2 in December 2020, before the Gamma variant of concern (VOC) was dominant, ranged from 19.3% (95% credible interval [CrI] 17.5-21.2%) in Curitiba to 75.0% (95% CrI 70.8-80.3%) in Manaus. Seroprevalence was consistently smaller in women and donors older than 55 years. The age-specific infection fatality rate (IFR) differed between cities and consistently increased with age. The infection hospitalisation rate increased significantly during the Gamma-dominated second wave in Manaus, suggesting increased morbidity of the Gamma VOC compared to previous variants circulating in Manaus. The higher disease penetrance associated with the health system's collapse increased the overall IFR by a minimum factor of 2.91 (95% CrI 2.43-3.53). Conclusions: These results highlight the utility of blood donor serosurveillance to track epidemic maturity and demonstrate demographic and spatial heterogeneity in SARS-CoV-2 spread.
- Three-quarters attack rate of SARS-CoV-2 in the Brazilian Amazon during a largely unmitigated epidemic(2021) BUSS, Lewis F.; JR, Carlos A. Prete; ABRAHIM, Claudia M. M.; JR, Alfredo Mendrone; SALOMON, Tassila; ALMEIDA-NETO, Cesar de; FRANCA, Rafael F. O.; BELOTTI, Maria C.; CARVALHO, Maria P. S. S.; COSTA, Allyson G.; CRISPIM, Myuki A. E.; FERREIRA, Suzete C.; FRAIJI, Nelson A.; GURZENDA, Susie; WHITTAKER, Charles; KAMAURA, Leonardo T.; TAKECIAN, Pedro L.; PEIXOTO, Pedro da Silva; OIKAWA, Marcio K.; NISHIYA, Anna S.; ROCHA, Vanderson; SALLES, Nanci A.; SANTOS, Andreza Aruska de Souza; SILVA, Martirene A. da; CUSTER, Brian; V, Kris Parag; BARRAL-NETTO, Manoel; KRAEMER, Moritz U. G.; PEREIRA, Rafael H. M.; PYBUS, Oliver G.; BUSCH, Michael P.; CASTRO, Marcia C.; DYE, Christopher; NASCIMENTO, Vitor H.; FARIA, Nuno R.; SABINO, Ester C.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly in Manaus, the capital of Amazonas state in northern Brazil. The attack rate there is an estimate of the final size of the largely unmitigated epidemic that occurred in Manaus. We use a convenience sample of blood donors to show that by June 2020, 1 month after the epidemic peak in Manaus, 44% of the population had detectable immunoglobulin G (IgG) antibodies. Correcting for cases without a detectable antibody response and for antibody waning, we estimate a 66% attack rate in June, rising to 76% in October. This is higher than in Sao Paulo, in southeastern Brazil, where the estimated attack rate in October was 29%. These results confirm that when poorly controlled, COVID-19 can infect a large proportion of the population, causing high mortality.
- Predicting SARS-CoV-2 Variant Spread in a Completely Seropositive Population Using Semi-Quantitative Antibody Measurements in Blood Donors(2022) BUSS, Lewis; PRETE, Carlos A.; WHITTAKER, Charles; SALOMON, Tassila; OIKAWA, Marcio K.; PEREIRA, Rafael H. M.; MOURA, Isabel C. G.; DELERINO, Lucas; FRANCA, Rafael F. O.; MIYAJIMA, Fabio; JR, Alfredo Mendrone; ALMEIDA-NETO, Cesar; SALLES, Nanci A.; FERREIRA, Suzete C.; FLADZINSKI, Karine A.; SOUZA, Luana M. de; SCHIER, Luciane K.; INOUE, Patricia M.; XABREGAS, Lilyane A.; CRISPIM, Myuki A. E.; FRAIJI, Nelson; CARLOS, Luciana M. B.; PESSOA, Veridiana; RIBEIRO, Maisa A.; SOUZA, Rosenvaldo E. de; CAVALCANTE, Anna F.; VALENCA, Maria I. B.; V, Maria da Silva; LOPES, Esther; FILHO, Luiz A.; MATEOS, Sheila O. G.; NUNES, Gabrielle T.; SCHLESINGER, David; SILVA, Sonia Mara Nunes da; SILVA-JUNIOR, Alexander L.; CASTRO, Marcia C.; NASCIMENTO, Vitor H.; DYE, Christopher; BUSCH, Michael P.; FARIA, Nuno R.; SABINO, Ester C.SARS-CoV-2 serologic surveys estimate the proportion of the population with antibodies against historical variants, which nears 100% in many settings. New approaches are required to fully exploit serosurvey data. Using a SARS-CoV-2 anti-Spike (S) protein chemiluminescent microparticle assay, we attained a semi-quantitative measurement of population IgG titers in serial cross-sectional monthly samples of blood donations across seven Brazilian state capitals (March 2021-November 2021). Using an ecological analysis, we assessed the contributions of prior attack rate and vaccination to antibody titer. We compared anti-S titer across the seven cities during the growth phase of the Delta variant and used this to predict the resulting age-standardized incidence of severe COVID-19 cases. We tested similar to 780 samples per month, per location. Seroprevalence rose to >95% across all seven capitals by November 2021. Driven by vaccination, mean antibody titer increased 16-fold over the study, with the greatest increases occurring in cities with the highest prior attack rates. Mean anti-S IgG was strongly correlated (adjusted R2 = 0.89) with the number of severe cases caused by Delta. Semi-quantitative anti-S antibody titers are informative about prior exposure and vaccination coverage and may also indicate the potential impact of future SARS-CoV-2 variants.
- Higher risk of death from COVID-19 in low-income and non-White populations of SAo Paulo, Brazil(2021) LI, Sabrina L.; PEREIRA, Rafael H. M.; JR, Carlos A. Prete; ZAREBSKI, Alexander E.; EMANUEL, Lucas; ALVES, Pedro J. H.; PEIXOTO, Pedro S.; V, Carlos K. Braga; SANTOS, Andreza Aruska de Souza; SOUZA, William M. de; BARBOSA, Rogerio J.; BUSS, Lewis F.; MENDRONE, Alfredo; ALMEIDA-NETO, Cesar de; FERREIRA, Suzete C.; SALLES, Nanci A.; MARCILIO, Izabel; WU, Chieh-Hsi; GOUVEIA, Nelson; NASCIMENTO, Vitor H.; SABINO, Ester C.; FARIA, Nuno R.; MESSINA, Jane P.IntroductionLittle evidence exists on the differential health effects of COVID-19 on disadvantaged population groups. Here we characterise the differential risk of hospitalisation and death in SAo Paulo state, Brazil, and show how vulnerability to COVID-19 is shaped by socioeconomic inequalities.MethodsWe conducted a cross-sectional study using hospitalised severe acute respiratory infections notified from March to August 2020 in the Sistema de Monitoramento Inteligente de SAo Paulo database. We examined the risk of hospitalisation and death by race and socioeconomic status using multiple data sets for individual-level and spatiotemporal analyses. We explained these inequalities according to differences in daily mobility from mobile phone data, teleworking behaviour and comorbidities.ResultsThroughout the study period, patients living in the 40% poorest areas were more likely to die when compared with patients living in the 5% wealthiest areas (OR: 1.60, 95% CI 1.48 to 1.74) and were more likely to be hospitalised between April and July 2020 (OR: 1.08, 95% CI 1.04 to 1.12). Black and Pardo individuals were more likely to be hospitalised when compared with White individuals (OR: 1.41, 95% CI 1.37 to 1.46; OR: 1.26, 95% CI 1.23 to 1.28, respectively), and were more likely to die (OR: 1.13, 95% CI 1.07 to 1.19; 1.07, 95% CI 1.04 to 1.10, respectively) between April and July 2020. Once hospitalised, patients treated in public hospitals were more likely to die than patients in private hospitals (OR: 1.40%, 95% CI 1.34% to 1.46%). Black individuals and those with low education attainment were more likely to have one or more comorbidities, respectively (OR: 1.29, 95% CI 1.19 to 1.39; 1.36, 95% CI 1.27 to 1.45).ConclusionsLow-income and Black and Pardo communities are more likely to die with COVID-19. This is associated with differential access to quality healthcare, ability to self-isolate and the higher prevalence of comorbidities.
- Graphene-based hybrid electrical-electrochemical point-of-care device for serologic COVID-19 diagnosis(2022) MATTIOLI, Isabela A.; CASTRO, Karla R.; MACEDO, Lucyano J. A.; SEDENHO, Graziela C.; OLIVEIRA, Mona N.; TODESCHINI, Iris; VITALE, Phelipe M.; FERREIRA, Suzete Cleusa; MANULI, Erika R.; PEREIRA, Geovana M.; SABINO, Ester C.; CRESPILHO, Frank N.The outbreak of COVID-19 pandemics highlighted the need of sensitive, selective, and easy-to-handle biosensing devices. In the contemporary scenario, point-of-care devices for mass testing and infection mapping within a population have proven themselves as of primordial importance. Here, we introduce a graphene-based Electrical-Electrochemical Vertical Device (EEVD) point-of-care biosensor, strategically engineered for serologic COVID-19 diagnosis. EEVD uses serologic IgG quantifications on SARS-CoV-2 Receptor Binding Domain (RBD) bioconjugate immobilized onto device surface. EEVD combines graphene basal plane with high charge carrier mobility, high conductivity, low intrinsic resistance, and interfacial sensitivity to capacitance alterations. EEVD application was carried out in real human serum samples. Since EEVD is a miniaturized device, it requires just 40 mu L of sample for a point-of-care COVID-19 infections detection. When compared to serologic assays such ELISA and other immunochromatographic methods, EEVD presents some advantages such as time of analyses (15 min), sample preparation, and a LOD of 1.0 pg mL(-1). We glimpse that EEVD meets the principles of robustness and accuracy, desirable analytic parameters for assays destined to pandemics control strategies.
- Overexpression of OCT-1 gene is a biomarker of adverse prognosis for diffuse large B-cell lymphoma (DLBCL): data from a retrospective cohort of 77 Brazilian patients(2020) GOUVEIA, Gisele R.; FERREIRA, Suzete C.; SIQUEIRA, Sheila A. C.; LAGE, Luis Alberto de Padua Covas; HALLACK NETO, Abrahao E.; COSTA, Renata de Oliveira; PEREIRA, JulianaBackgroundOCT-1 gene is a member of the POU-homeodomain family of transcriptional regulators of B-lymphocyte differentiation by controlling expression of B-cell specific genes. BCL-2 gene is a potent inhibitor of apoptosis and it is essential during B-cell differentiation into germinal center. These genes may be expressed in diffuse large B-cell lymphoma (DLBCL), but the role of BCL-2 in its prognosis has been contradictory, and OCT-1 has yet to be tested.MethodsIn this study, we aimed to investigate the prognostic impact of OCT-1 and BCL-2 expression in DLBCL treated in the real world with immunochemotherapy in a single center. BCL-2 and OCT-1 genes were available in 78.5% (77/98) DLBCL patients, and the RNA for quantitative real-time PCR was isolated from formalin-fixed paraffin-embedded samples. The values obtained for gene expression were transformed in categorical variable according to their median.ResultsCohort median age was 54.5years (15-84), 49 (50%) were male, 38/77 (49.4%) and 40/77 (51.9%) presented OCT-1 and BCL-2 expression >= median, respectively. The overall response rate (ORR) in all patients was 68.4% (67/98), 65,3% (64/98) of patients acquired complete response, and 3.1% (3/98) partial response, while 6.1% (6/98) were primary refractory. The median follow-up was 3.77years (95% CI: 3.2-4.1), with 5.43 (95% CI: 2.2-NR) of overall survival (OS) and 5.15years (95% CI: 2.9-NA) of progression free survival (PFS). OCT-1 >= median was associated with shorter OS at univariate analysis (p =0.013; [HR] 2.450, 95% CI: 1.21-4.96) and PFS (p =0.019; [HR] 2.270, 95%CI: 1.14-4.51) and BCL-2 gene overexpression presented worse PFS (p =0.043, [HR] 2.008, 95% CI: 1.02-3.95). At multivariate analysis, OCT-1 overexpression was associated with poor PFS (p =0.035, [HR] 2.22, 95% CI: 1.06-4.67).ConclusionIn this study, we showed that overexpression of OCT1 gene was an independent prognostic factor of adverse outcomes in DLBCL.