ESTER CERDEIRA SABINO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
LIM/46 - Laboratório de Parasitologia Médica, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/46 - Laboratório de Parasitologia Médica, Hospital das Clínicas, Faculdade de Medicina - Líder
186 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 186
- Different Transcriptomic Response to T. cruzi Infection in hiPSC-Derived Cardiomyocytes From Chagas Disease Patients With and Without Chronic Cardiomyopathy(2022) OLIVEIRA, Theo G. M.; VENTURINI, Gabriela; ALVIM, Juliana M.; FEIJO, Larissa L.; DINARDO, Carla L.; SABINO, Ester C.; SEIDMAN, Jonathan G.; SEIDMAN, Christine E.; KRIEGER, Jose E.; PEREIRA, Alexandre C.Chagas disease is a tropical zoonosis caused by Trypanosoma cruzi. After infection, the host present an acute phase, usually asymptomatic, in which an extensive parasite proliferation and intense innate immune activity occurs, followed by a chronic phase, characterized by low parasitemia and development of specific immunity. Most individuals in the chronic phase remain without symptoms or organ damage, a state called indeterminate IND form. However, 20 to 40% of individuals develop cardiac or gastrointestinal complications at any time in life. Cardiomyocytes have an important role in the development of Chronic Chagas Cardiomyopathy (CCC) due to transcriptional and metabolic alterations that are crucial for the parasite survival and replication. However, it still not clear why some infected individuals progress to a cardiomyopathy phase, while others remain asymptomatic. In this work, we used hiPSCs-derived cardiomyocytes (hiPSC-CM) to investigate patterns of infection, proliferation and transcriptional response in IND and CCC patients. Our data show that T. cruzi infection and proliferation efficiency do not differ significantly in PBMCs and hiPSC-CM from both groups. However, RNA-seq analysis in hiPSC-CM infected for 24 hours showed a significantly different transcriptional response to the parasite in cells from IND or CCC patients. Cardiomyocytes from IND showed significant differences in the expression of genes related to antigen processing and presentation, as well as, immune co-stimulatory molecules. Furthermore, the downregulation of collagen production genes and extracellular matrix components was significantly different in these cells. Cardiomyocytes from CCC, in turn, showed increased expression of mTORC1 pathway and unfolded protein response genes, both associated to increased intracellular ROS production. These data point to a differential pattern of response, determined by baseline genetic differences between groups, which may have an impact on the development of a chronic outcome with or without the presentation of cardiac symptoms.
- Diversity of RH and transfusion support in Brazilian sickle cell disease patients with unexplained Rh antibodies(2019) DINARDO, Carla L.; KELLY, Shannon; DEZAN, Marcia R.; RIBEIRO, Ingrid H.; CASTILHO, Shirley L.; SCHIMIDT, Luciana C.; VALGUEIRO, Maria do C.; PREISS, Liliana R.; CUSTER, Brian; SABINO, Ester C.; WESTHOFF, Connie M.BACKGROUND Genetic diversity in the RH genes among sickle cell disease (SCD) patients is well described but not yet extensively explored in populations of racially diverse origin. Transfusion support is complicated in patients who develop unexpected Rh antibodies. Our goal was to describe RH variation in a large cohort of Brazilian SCD patients exhibiting unexpected Rh antibodies (antibodies against RH antigens to which the patient is phenotypically positive) and to evaluate the impact of using the patient's RH genotype to guide transfusion support. STUDY DESIGN AND METHODS Patients within the Recipient Epidemiology and Evaluation Donor Study (REDS)-III Brazil SCD cohort with unexpected Rh antibodies were selected for study. RHD and RHCE exons and flanking introns were sequenced by targeted next-generation sequencing. RESULTS Fifty-four patients with 64 unexplained Rh antibodies were studied. The majority could not be definitively classified as auto- or alloantibodies using serologic methods. The most common altered RH were RHD*DIIIa and RHD*DAR (RHD locus) and RHCE*ce48C, RHCE*ce733G, and RHCE*ceS (RHCE locus). In 53.1% of the cases (34/64), patients demonstrated only conventional alleles encoding the target antigen: five of 12 anti-D (41.7%), 10 of 12 anti-C (83.3%), 18 of 38 anti-e (47.4%), and one of one anti-E (100%). CONCLUSION RHD variation in this SCD cohort differs from that reported for African Americans, with increased prevalence of RHD*DAR and underrepresentation of the DAU cluster. Many unexplained Rh antibodies were found in patients with conventional RH allele(s) only. RH genotyping was useful to guide transfusion to determine which patients could potentially benefit from receiving RH genotyped donor units.
conferenceObject Symptoms and Outcomes of Dengue Among Transfusion Recipients in Brazil Who Were RNA plus or Who Received an RNA plus unit Compared to RNA- Recipients(2014) SABINO, E. C.; OLIVEIRA, C. D.; LOUREIRO, P.; LOPES, M.; CAPUANI, L. D.; MCCLURE, C.; CHOWDHURY, D.; KLEINMAN, S.; BUSCH, M.; CUSTER, B.conferenceObject Genetic variation in HLA genes: impact on transplant compatibility in a Brazilian admixed population(2023) ANDRADE, Heloisa S.; SILVA, Marcio; NUNES, Kelly; PASSOS, Carlos Henrique; SENA, Alexandre C.; CASTELLI, Erick C.; DINARDO, Carla; SABINO, Ester C.; TEIXEIRA, Carolina M.; TELES, Dahra; AMORIM, Luiz; CUSTER, Brian; KELLY, Shannon; PORTO, Luis Cristovao; MEYER, DiogoconferenceObject Changes in Gene Expression in Response to Red Blood Cell Transfusions in Chronically Transfused Sickle Cell Disease Patients(2019) KELLY, Shannon; DINARDO, Carla; DENG, Xutao; BELISARIO, Andre; PROIETTI, Anna Carneiro; LOUREIRO, Paula; MOTA, Rosimere Afonso; FLOR-PARK, Miriam V.; MAXIMO, Claudia; SABINO, Ester; CUSTER, Brian- Interpreting HIV diagnostic histories into infection time estimates: analytical framework and online tool(2019) GREBE, Eduard; FACENTE, Shelley N.; BINGHAM, Jeremy; PILCHER, Christopher D.; POWRIE, Andrew; GERBER, Jarryd; PRIEDE, Gareth; CHIBAWARA, Trust; BUSCH, Michael P.; MURPHY, Gary; KASSANJEE, Reshma; WELTE, Alex; WELTE, Alex; SEMPA, Joseph; MATTEN, David; BRAND, Hilmarie; CHIBAWARA, Trust; MURPHY, Gary; HALL, Jake; MCKINNEY, Elaine; BUSCH, Michael P.; GREBE, Eduard; FACENTE, Shelley; HAMPTON, Dylan; KEATING, Sheila; LEBEDEVA, Mila; PILCHER, Christopher D.; MARSON, Kara; KASSANJEE, Reshma; LAEYENDECKER, Oliver; QUINN, Thomas; BURNS, David; LITTLE, Susan; SANDS, Anita; HALLETT, Tim; OWEN, Sherry Michele; PAREKH, Bharat; SEXTON, Connie; PRICE, Matthew; KAMALI, Anatoli; LOEB, Lisa; MARTIN, Jeffrey; DEEKS, Steven G.; HOH, Rebecca; BARTOLOMEI, Zelinda; SANTOS, Breno; ZABTOSKI, Kellin; LIRA, Rita de Cassia Alves; SPERHACKE, Rosa Dea; MOTTA, Leonardo R.; PAGANELLA, Machline; KALLAS, Esper; TOMIYAMA, Helena; TOMIYAMA, Claudia; COSTA, Priscilla; NUNES, Maria A.; REIS, Gisele; SAUER, Mariana M.; CERQUEIRA, Natalia; NAKAGAWA, Zelinda; FERRARI, Lilian; AMARAL, Ana P.; MILANI, Karine; KARIM, Salim S. Abdool; KARIM, Quarraisha Abdool; NDUNGU, Thumbi; MAJOLA, Nelisile; SAMSUNDER, Natasha; NANICHE, Denise; MANDOMANDO, Inacio; MACETE, Eusebio V.; SANCHEZ, Jorge; LAMA, Javier; DUERR, Ann; CAPOBIANCHI, Maria R.; SULIGOI, Barbara; STRAMER, Susan; WILLIAMSON, Phillip; VERMEULEN, Marion; SABINO, EsterBackground It is frequently of epidemiological and/or clinical interest to estimate the date of HIV infection or time-since-infection of individuals. Yet, for over 15 years, the only widely-referenced infection dating algorithm that utilises diagnostic testing data to estimate time-since-infection has been the 'Fiebig staging' system. This defines a number of stages of early HIV infection through various standard combinations of contemporaneous discordant diagnostic results using tests of different sensitivity. To develop a new, more nuanced infection dating algorithm, we generalised the Fiebig approach to accommodate positive and negative diagnostic results generated on the same or different dates, and arbitrary current or future tests - as long as the test sensitivity is known. For this purpose, test sensitivity is the probability of a positive result as a function of time since infection. Methods The present work outlines the analytical framework for infection date estimation using subject-level diagnostic testing histories, and data on test sensitivity. We introduce a publicly-available online HIV infection dating tool that implements this estimation method, bringing together 1) curatorship of HIV test performance data, and 2) infection date estimation functionality, to calculate plausible intervals within which infection likely became detectable for each individual. The midpoints of these intervals are interpreted as infection time 'point estimates' and referred to as Estimated Dates of Detectable Infection (EDDIs). The tool is designed for easy bulk processing of information (as may be appropriate for research studies) but can also be used for individual patients (such as in clinical practice). Results In many settings, including most research studies, detailed diagnostic testing data are routinely recorded, and can provide reasonably precise estimates of the timing of HIV infection. We present a simple logic to the interpretation of diagnostic testing histories into infection time estimates, either as a point estimate (EDDI) or an interval (earliest plausible to latest plausible dates of detectable infection), along with a publicly-accessible online tool that supports wide application of this logic. Conclusions This tool, available at , is readily updatable as test technology evolves, given the simple architecture of the system and its nature as an open source project.
- A generalizable method for estimating duration of HIV infections using clinical testing history and HIV test results(2019) PILCHER, Christopher D.; PORCO, Travis C.; FACENTE, Shelley N.; GREBE, Eduard; DELANEY, Kevin P.; MASCIOTRA, Silvina; KASSANJEE, Reshma; BUSCH, Michael P.; MURPHY, Gary; OWEN, S. Michele; WELTE, Alex; MATTEN, David; BRAND, Hilmarie; CHIBAWARA, Trust; MCKINNEY, Elaine; HALL, Jake; BUSCH, Michael; KEATING, Sheila; LEBEDEVA, Mila; HAMPTON, Dylan; PILCHER, Christopher; FACENTE, Shelley; MARSON, Kara; LAEYENDECKER, Oliver; QUINN, Thomas; BURNS, David; LITTLE, Susan; SANDS, Anita; HALLETT, Tim; OWEN, Sherry Michele; PAREKH, Bharat; SEXTON, Connie; PRICE, Matthew; KAMALI, Anatoli; LOEB, Lisa; MARTIN, Jeffrey; DEEKS, Steven G.; HOH, Rebecca; BARTOLOMEI, Zelinda; CERQUEIRA, Natalia; SANTOS, Breno; ZABTOSKI, Kellin; LIRA, Rita de Cassia Alves; SPERHACKE, Rosa Dea; MOTTA, Leonardo R.; PAGANELLA, Machline; KALLAS, Esper; TOMIYAMA, Helena; TOMIYAMA, Claudia; COSTA, Priscilla; NUNES, Maria A.; REIS, Gisele; SAUER, Mariana M.; NAKAGAWA, Zelinda; FERRARI, Lilian; AMARAL, Ana P.; MILANI, Karine; KARIM, Salim S. Abdool; KARIM, Quarraisha Abdool; NDUNGU, Thumbi; MAJOLA, Nelisile; SAMSUNDER, Natasha; NANICHE, Denise; MANDOMANDO, Inicio; V, Eusebio Macete; SANCHEZ, Jorge; LAMA, Javier; DUERR, Ann; CAPOBIANCHI, Maria R.; SULIGOI, Barbara; STRAMER, Susan; WILLIAMSON, Phillip; VERMEULEN, Marion; SABINO, EsterObjective: To determine the precision of new and established methods for estimating duration of HIV infection. Design: A retrospective analysis of HIV testing results from serial samples in commercially available panels, taking advantage of extensive testing previously conducted on 53 seroconverters. Methods: We initially investigated four methods for estimating infection timing: method 1, 'Fiebig stages' based on test results from a single specimen; method 2, an updated '4th gen' method similar to Fiebig stages but using antigen/antibody tests in place of the p24 antigen test; method 3, modeling of 'viral ramp-up' dynamics using quantitative HIV-1 viral load data from antibody-negative specimens; and method 4, using detailed clinical testing history to define a plausible interval and best estimate of infection time. We then investigated a 'two-step method' using data from both methods 3 and 4, allowing for test results to have come from specimens collected on different days. Results: Fiebig and '4th gen' staging method estimates of time since detectable viremia had similar and modest correlation with observed data. Correlation of estimates from both new methods (3 and 4), and from a combination of these two ('two-step method') was markedly improved and variability significantly reduced when compared with Fiebig estimates on the same specimens. Conclusion: The new 'two-step' method more accurately estimates timing of infection and is intended to be generalizable to more situations in clinical medicine, research, and surveillance than previous methods. An online tool is now available that enables researchers/clinicians to input data related to method 4, and generate estimated dates of detectable infection.
conferenceObject DENGUE RNA AMONG BLOOD DONORS AND RECIPIENTS DURING LARGE EPIDEMICS OF DENV-4 IN RIO DE JANEIRO AND RECIFE, BRAZIL(2013) SABINO, E.; LOUREIRO, P.; LOPES, M.; CAPUANI, L.; OLIVEIRA, C.; OLIVEIRA, L.; LINNEN, J.; LEE, T-H; PRINCE, H.; MCCLURE, C.; CHOWDHURY, D.; GONCALEZ, T.; CUSTER, B.; BRAMBILLA, D.; BUSCH, M.- Lack of evidence of seronegative infection in an endemic area of Chagas disease(2019) OLIVEIRA, Lea Campos de; LEE, Tzong-Hae; FERREIRA, Ariela Mota; BIERRENBACH, Ana Luiza; SOUZA-BASQUEIRA, Marcela de; OLIVEIRA, Claudia Di Lorenzo; CARDOSO, Clareci Silva; MOREIRA, Carlos Henrique Valente; OIKAWA, Marcio K.; RIBEIRO, Antonio Luiz P.; BUSCH, Michael P.; SABINO, Ester CerdeiraThe diagnosis of Chagas disease is based on the detection of Trypanosoma cruzi (T. cruzi)-specific antibodies. Nonetheless, there is concern about the sensitivity of current serological assays due to reports of T. cruzi PCR positivity among seronegative individuals. The aim of this study was to evaluate if T. cruzi seronegative infections occur in endemic areas. We recruited 2,157 individuals that were identified as having Chagas disease in a public health system database of an endemic region in Brazil. All participants were interviewed and 2,091 had a sample collected for serological and PCR testing. From these, 149 (7.1%) had negative serological results. PCR was positive in 610 samples (31.4%) of the 1,942 seropositive samples but in none of the 149 samples from seronegative participants. True T. cruzi seronegative infections seem to be rare (95% CI 0-3.7) and should not be a concern for blood supply, which relies on antibody screening.
- Wuhan large pig roundworm virus identified in human feces in Brazil(2018) LUCHS, Adriana; LEAL, Elcio; KOMNINAKIS, Shirley Vasconcelos; MILAGRES, Flavio Augusto de Padua; BRUSTULIN, Rafael; TELES, Maria da Aparecida Rodrigues; GILL, Danielle Elise; DENG, Xutao; DELWART, Eric; SABINO, Ester Cerdeira; COSTA, Antonio Charlys daWe report here the complete genome sequence of a bipartite virus, herein denoted WLPRV/human/BRA/TO-34/201, from a sample collected in 2015 from a two-year-old child in Brazil presenting acute gastroenteritis. The virus has 98-99% identity (segments 2 and 1, respectively) with the Wuhan large pig roundworm virus (unclassified RNA virus) that was recently discovered in the stomachs of pigs from China. This is the first report of a Wuhan large pig roundworm virus detected in human specimens, and the second genome described worldwide. However, the generation of more sequence data and further functional studies are required to fully understand the ecology, epidemiology, and evolution of this new unclassified virus.