LEA CAMPOS DE OLIVEIRA
Projetos de Pesquisa
Unidades Organizacionais
LIM/46 - Laboratório de Parasitologia Médica, Hospital das Clínicas, Faculdade de Medicina
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
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Resultados de Busca
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- Incremental Prognostic Value of Echocardiography to Brain Natriuretic Peptide in Patients with Chagas Cardiomyopathy from Endemic Areas(2022) MAIA, Marcelo Alves; SABINO, Ester Cerdeira; OLIVEIRA, Lea Campos de; OLIVEIRA, Claudia Di Lorenzo; CARDOSO, Clareci S.; MAIA, Ana Isabel Nobre; VERSIANI, Fellipe Colares P. G.; SILVA, Jose Luiz Padilha da; FERREIRA, Ariela Mota; RIBEIRO, Antonio Luiz P.; NUNES, Maria Carmo P.
- Hospitalizations due to gastrointestinal Chagas disease: National registry(2022) BIERRENBACH, Ana Luiza; QUINTINO, Nayara Dornela; MOREIRA, Carlos Henrique Valente; DAMASCENO, Renata Fiuza; NUNES, Maria do Carmo Pereira; BALDONI, Nayara Ragi; SILVA, Lea Campos de Oliveira da; FERREIRA, Ariela Mota; CARDOSO, Clareci Silva; HAIKAL, Desiree Sant'Ana; SABINO, Ester Cerdeira; RIBEIRO, Antonio Luiz Pinho; OLIVEIRA, Claudia Di LorenzoObjectives Analyze the hospitalizations of patients admitted for Chagas disease with gastro-intestinal involvement (CD-GI) in the Brazilian Unified Health System, describe the epidemiological profile, mortality and costs. Methods This is an observational study that uses secondary data from the National Hospital Information System (SIH-SUS) for the years 2017-2019. CD-GI admissions were defined by specific ICD-10 codes that identify the main diagnosis. Results From 2017 to 2019, there were 4,407 hospitalizations for CD-GI in Brazil, considering only public hospitals and those associated with the SUS. This corresponds to an average of 1,470 hospitalizations per year, or 0.6 per 100,000 inhabitants, with significant regional variation. Hospitalizations increased with age and were slightly higher in men. More than 60% were emergencies and in 50% the procedure performed was surgical. The most used code was the one for megaesophagus followed by megacolon. In-hospital mortality was 5.8% and 17.2% went to intensive care units. The median cost was USD$ 553.15 per hospitalization, and an overall cost of USD$ 812,579.98 per year to the SUS budget. Conclusion The numbers, rates and costs presented here are possibly underestimated but they give us an idea of the overall profile of hospitalizations due to CD-GI, which are not rare and are related to significant in-hospital mortality. CD-GI is a neglected manifestation of a neglected disease.
- A refined genome phage display methodology delineates the human antibody response in patients with Chagas disease(2021) TEIXEIRA, Andre Azevedo Reis; CARNERO, Luis Rodriguez; KURAMOTO, Andreia; TANG, Fenny Hui Fen; GOMES, Carlos Hernique; PEREIRA, Natalia Bueno; OLIVEIRA, Lea Campos de; GARRINI, Regina; MONTEIRO, Jhonatas Sirino; SETUBAL, Joao Carlos; SABINO, Ester Cerdeira; PASQUALINI, Renata; COLLI, Walter; ARAP, Wadih; ALVES, Maria Julia Manso; CUNHA-NETO, Edecio; GIORDANO, Ricardo JoseLarge-scale mapping of antigens and epitopes is pivotal for developing immunotherapies but challenging, especially for eukaryotic pathogens, owing to their large genomes. Here, we developed an integrated platform for genome phage display (gPhage) to show that unbiased libraries of the eukaryotic parasite Trypanosoma cruzi enable the identification of thousands of antigens recognized by serum samples from patients with Chagas disease. Because most of these antigens are hypothetical proteins, gPhage provides evidence of their expression during infection. We built and validated a comprehensive map of Chagas disease antibody response to show howlinear and putative conformation epitopes, many rich in repetitive elements, allow the parasite to evade a buildup of neutralizing antibodies directed against protein domains that mediate infection pathogenesis. Thus, the gPhage platform is a reproducible and effective tool for rapid simultaneous identification of epitopes and antigens, not only in Chagas disease but perhaps also in globally emerging/reemerging acute pathogens.
- Development of a Novel Multiplex Immunoassay Multi-cruzi for the Serological Confirmation of Chagas Disease(2016) GRANJON, Elodie; DICHTEL-DANJOY, Marie-Laure; SABA, Esber; SABINO, Ester; OLIVEIRA, Lea Campos de; ZREIN, MaanBackground Chagas disease is due to the parasite Trypanosoma cruzi, a protist disseminated by a Triatome vector. This disease is endemic to Latin America and considered by WHO as one of the 17 world's neglected diseases. In Europe and in North America, imported cases are also detected, due to migration of population outside of the endemic region. Diagnosis of T. cruzi infection is usually made indirectly by the detection of specific antibodies to T. cruzi antigens. Following initial diagnostic evaluation or screening test (qualifying or discarding blood donation), a confirmation test is performed for samples initially reactive. The test presented in this study aims at the confirmation/refutation of the infectious status of human blood samples and will permit taking appropriate clinical measures. Methodology/Principal Findings We designed a novel array of twelve antigens and printed these antigens onto 96-well plates. We tested 248 positive samples T. cruzi, 94 unscreened blood donors' samples from non-endemic area, 49 seronegative blood donors, 7 false-positive and 3 doubtful samples. The observed reactivities were analyzed to propose a decision-tree algorithm that correctly classifies all the samples, with the potential to discriminate false-positive results and sticky samples. We observed that antibodies levels (Sum of all antigens) was significantly higher for PCR positive than for PCR negative samples in all studied groups with Multi-cruzi. Conclusion/Significance The results described in this study indicate that the Multi-cruzi improves the serological confirmation of Chagas disease. Moreover the ""sum of all antigens"" detected by Multi-cruzi could reflect parasitemia level in patients-like PCR signals does-and could serve as an indicator of parasite clearance in longitudinal follow-ups. Validation of this assay is still required on an independent large collection of well characterized samples including typical false-reactive samples such as Leishmaniasis.
- Genome-wide association study for Chagas Cardiomyopathy identify a new risk locus on chromosome 18 associated with an immune-related protein and transcriptional signature(2022) SABINO, Ester Cerdeira; FRANCO, Lucas Augusto Moyses; VENTURINI, Gabriela; RODRIGUES, Mariliza Velho; MARQUES, Emanuelle; SILVA, Lea Campos de Oliveira-da; MARTINS, Larissa Natany Almeida; FERREIRA, Ariela Mota; ALMEIDA, Paulo Emilio Clementino; SILVA, Felipe Dias Da; LEITE, Samara Fernandes; NUNES, Maria do Carmo Pereira; HAIKAL, Desiree Sant'Ana; OLIVEIRA, Claudia Di Lorenzo; CARDOSO, Clareci Silva; SEIDMAN, Jonathan G.; SEIDMAN, Christine E.; CASAS, Juan P.; RIBEIRO, Antonio Luiz Pinho; KRIEGER, Jose E.; PEREIRA, Alexandre C.Background Chronic Chagas Cardiomyopathy (CCC) usually develops between 10 and 20 years after the first parasitic infection and is one of the leading causes of end-stage heart failure in Latin America. Despite the great inter-individual variability in CCC susceptibility (only 30% of infected individuals ever present CCC), there are no known predictors for disease development in those chronically infected. Methodology/Principal findings We describe a new susceptibility locus for CCC through a GWAS analysis in the SaMi-Trop cohort, a population-based study conducted in a Chagas endemic region from Brazil. This locus was also associated with CCC in the REDS II Study. The newly identified locus (rs34238187, OR 0.73, p-value 2.03 x 10(-9)) spans a haplotype of approximately 30Kb on chromosome 18 (chr18: 5028302-5057621) and is also associated with 80 different traits, most of them blood protein traits significantly enriched for immune-related biological pathways. Hi-C data show that the newly associated locus is able to interact with chromatin sites as far as 10Mb on chromosome 18 in a number of different cell types and tissues. Finally, we were able to confirm, at the tissue transcriptional level, the immune-associated blood protein signature using a multi-tissue differential gene expression and enrichment analysis. Conclusions/Significance We suggest that the newly identified locus impacts CCC risk among T cruzi infected individuals through the modulation of a downstream transcriptional and protein signature associated with host-parasite immune response. Functional characterization of the novel risk locus is warranted.
- Failure to use health services by people with Chagas disease: Multilevel analysis of endemic area in Brazil(2022) DAMASCENO, Renata Fiuza; SABINO, Ester Cerdeira; RIBEIRO, Antonio Luiz Pinho; FERREIRA, Ariela Mota; SILVA, Lea Campos de Oliveira-da; OLIVEIRA, Claudia Di Lorenzo; CARDOSO, Clareci Silva; VIEIRA, Thallyta Maria; HAIKAL, Desiree Sant' AnaThis study aimed to assess the prevalence of non-use of health services in the last year by people with Chagas disease (CD) in an endemic area in Brazil and the contextual and individual factors associated with this non-use. This is a multilevel study that considered contextual and individual data. Contextual data were collected from official publicly accessible databases of the Brazilian government, at the municipal level. The individual data came from the first follow-up of a Brazilian cohort that assessed patients with CD in 21 municipalities in endemic area for the disease. The sample consisted of 1,160 individuals with CD. The dependent variable ""use of health services in the last year"" was categorized as yes vs. no. The analysis was performed using Poisson regression with robust variance. The prevalence of non-use of health services in the last year was 23.5% (IC95%: 21.1-25.9). The contextual factor ""larger population"" (PR: 1.6; 95% CI = 1.2-2.0) and individual factors related to the lower severity of the disease as a functional class without limitations (PR: 1.6; 95% CI = 1.2-2.1) and unaltered N-terminal pro b-type natriuretic peptide levels (PR: 2.2; 95% CI = 1.3-3.6) increased the prevalence of non-use of the health service in the last year by people with CD. The results of this study showed that individual determinants are not isolated protagonists of the non-use of health services in the last year by people with CD, which reinforces the need for public policies that consider the contextual determinants of the use of health services by populations affected by the disease.
- Anti-Trypanosoma cruzi antibody profiling in patients with Chagas disease treated with benznidazole assessed by genome phage display(2023) CARNERO, Luis Antonio Rodriguez; KURAMOTO, Andreia; OLIVEIRA, Lea Campos de; MONTEIRO, Jhonatas Sirino; SETUBAL, Joao Carlos; CUNHA-NETO, Edecio; SABINO, Ester Cerdeira; GIORDANO, Ricardo JoseBackgroundThere have been significant improvements in Chagas disease therapy and it is now widely accepted that most patients with chronic disease might benefit from therapy. However, there are challenges to monitor drug efficacy and cure for these patients, which are important impediments for current and future therapies. Trypanosoma cruzi-PCR is highly variable while IgG seroconversion takes decades yielding variable results depending on the antigen(s) used for the assay. Methods and resultsWe used the genomic phage display (gPhage) platform to perform a pairwise comparison of antigens and epitopes recognized by twenty individual patients with chronic Chagas disease before and after treatment with benznidazole. In total, we mapped 54,473 T. cruzi epitopes recognized by IgG from individual patients (N = 20) before benznidazole treatment. After treatment, the number of epitopes recognized by all patients was significantly smaller (21,254), a reduction consistent with a decrease in anti-T. cruzi antibodies. Most of these epitopes represent distinct fragments from the same protein and could, therefore, be grouped into 80 clusters of antigens. After three years of treatment with benznidazole, we observed a 64% reduction in the number of clusters of antigens recognized by patients (59 clusters before versus 21 clusters after treatment). The most abundant antigenic clusters recognized by patients correspond to the surface antigen CA-2 (B13) followed by the microtubule associated antigen, which highlights the value of these epitopes in Chagas disease diagnosis. Most importantly, quantitative pairwise comparison of gPhage data allowed for the prediction of patient response to treatment based on PCR status. Principal findingHere, we compiled a list of antigens and epitopes preferentially recognized by Chagas disease patients before and after benznidazole treatment. Next, we observed that gPhage data correlated with patient PCR-status and could, therefore, predict patient response to treatment. Moreover, gPhage results suggest that overall, independent of PCR status, treatment led to a reduction in the presence of T. cruzi-specific antibody levels and the number of antigens and epitopes recognized by these patients. ConclusionThe gPhage platform use of unbiased library of antigens, which is different from conventional serological assays that rely on predetermined antigens, is a contribution for the development of novel diagnostic tools for Chagas disease. Author summaryChagas disease, caused by the single-celled parasite Trypanosoma cruzi, can be a life-treating and debilitating illness. Because there is no vaccine and currently the only two available drugs are most effective if used during the early acute stage of the disease, treatment options for infected individuals are limited. Most individuals will only find out they have Chagas disease during a routine medical examination or in blood bank while donating blood, in which cases, they are already chronically infected. At this stage, treatment will not undo clinical mani-festations (i.e., cardiomyopathy) but may eliminate the parasite and prevent disease progression. Currently, polymerase chain reaction (PCR) and serological assays are the only diagnostic tools available, both with limi-tations in sensitivity and accuracy. The lack of effective molecular markers thus prevents physicians to deter-mine whether a patient is parasite free and cured from the disease. It also has important implications for the development of new drugs to treat Chagas disease. Here, we studied the reactivity of anti-T. cruzi antibodies in sera from a cohort of 20 patients that underwent treatment for Chagas disease using a new method developed by our group named gPhage. Using gPhage, we scanned all T. cruzi proteins to identify those that were reactive with the antibodies from each individual patient before and after treatment. In sum, gPhage data correlated with patient PCR-status and could, therefore, predict patient response to treatment. It also revealed a new set of T. cruzi proteins that could be useful for the development of future diagnostic methods.
- Monitoring SARS-CoV-2 seroprevalence over time among pregnant women admitted to delivery units: Suitability for surveillance(2023) MIYADAHIRA, Mariana Yumi; BRIZOT, Maria de Lourdes; ALEXANDER, Neal; SABINO, Ester Cerdeira; SILVA, Lea Campos de Oliveira da; HOSHIDA, Mara Sandra; OLIVEIRA, Ana Maria da Silva Sousa; FARCHE, Ana Claudia Silva; FRANCISCO, Rossana Pulcineli Vieira; MAYAUD, PhilippeObjectivesTo determine SARS-CoV-2 seroprevalence over time and risk factors among pregnant women at delivery in Sao Paulo, Brazil; and to evaluate the suitability of pregnant women as a sentinel population for SARS-CoV-2 serosurveillance. MethodsUnselected consecutive pregnant women presenting at the labor ward of a single large hospital between July 20(th) 2020 to February 21(st) 2021 were enrolled and tested for SARS-CoV-2 serology using two assays: the rapid chromatic Wondfo One Step (for total IgA and IgG detection) and Roche Elecsys assay (detecting anti-nucleoprotein [N] IgG). SARS-CoV-2 seroprevalence was computed as smooth spline function over time with 95% confidence intervals (CI). Risk factors were evaluated for positivity by each assay. We compared timepoint seroprevalence by the two assays with four concomitant community household surveys (HHS), in which the Roche assay was used, to determine the sensitivity and relevance of the pregnant women population as sentinel population. ResultsOverall SARS-CoV-2 seroprevalence was 28.9% (221/763) by Roche and 17.9% (137/763) by Wondfo. Reported symptoms experienced during pregnancy were all significantly correlated with being SARS-CoV-2 seropositive at delivery with any assay (with odds-ratios ranging from 3.0 [95% CI: 2.1-4.3] for coryza to 22.8 [95% CI: 12.3-46.6] for ageusia). Seropositivity by either assay was high in women at delivery in the early period of the pandemic (June 2020), compared with seropositivity in women from the concomitant HHS: 44.1% (95% CI: 21.8-66.4) for Roche, 54.1% (30.9-78.5) for Wondfo, versus 11.4% (95% CI: 9.2-13.6) for HHS. For later periods (October 2020 and January 2021), the seropositivity in women at delivery measured by Roche corresponded well with the prevalence found among women in the HHS using the same assay, whilst prevalence measured by Wondfo dropped. ConclusionsWomen at delivery represent a highly exposed and readily accessible population for sentinel surveillance of emerging infections such as SARS-CoV-2.
- Parasite DNA and Markers of Decreased Immune Activation Associate Prospectively with Cardiac Functional Decline over 10 Years among Trypanosoma cruzi Seropositive Individuals in Brazil(2024) SUNDERRAJ, Ashwin; CUNHA, Luisa Marin; AVILA, Matheus; ALEXANDRIA, Shaina; FERREIRA, Ariela Mota; SILVA, Lea Campos de Oliveira-da; RIBEIRO, Antonio L. P.; NUNES, Maria do Carmo Pereira; SABINO, Ester C.; LANDAY, Alan; KALIL, Jorge; CHEVILLARD, Christophe; CUNHA-NETO, Edecio; FEINSTEIN, Matthew J.Parasitemia and inflammatory markers are cross-sectionally associated with chronic Chagas cardiomyopathy (CCC) among patients with Trypanosoma cruzi. However, the prospective association of the parasite load and host immune response-related characteristics with CCC (that is, progressors) among T. cruzi seropositive individuals has only been partially defined. In a cohort of T. cruzi seropositive patients in Montes Claros and Sao Paulo, Brazil who were followed over 10 years, we identified the association of a baseline T. cruzi parasite load and systemic markers of inflammation with a decline in cardiac function and/or the presence of cardiac congestion 10 years later. The progressors (n = 21) were individuals with a significant decline in the left ventricular ejection fraction and/or elevated markers of cardiac congestion after 10 years. The controls (n = 31) had normal markers of cardiac function and congestion at the baseline and at the follow-up. They were matched with the progressors on age, sex, and genetic ancestry. The progressors had higher mean parasite loads at the baseline than the controls (18.3 vs. 0.605 DNA parasite equivalents/20 mL, p < 0.05). Of the 384 inflammation-related proteins analyzed, 47 differed significantly at a false discovery rate- (FDR-) corrected p < 0.05 between the groups. There were 44 of these 47 proteins that were significantly higher in the controls compared to in the progressors, including the immune activation markers CCL21, CXCL12, and HCLS1 and several of the tumor necrosis factor superfamily of proteins. Among the individuals who were seropositive for T. cruzi at the baseline and who were followed over 10 years, those with incident CCC at the 10-year marker had a comparatively higher baseline of T. cruzi parasitemia and lower baseline markers of immune activation and chemotaxis. These findings generate the hypothesis that the early impairment of pathogen-killing immune responses predisposes individuals to CCC, which merits further study.