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
17 resultados
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- 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.
- TGFB1 and IL8 gene polymorphisms and susceptibility to visceral leishmaniasis(2011) FRADE, Amanda Farage; OLIVEIRA, Lea Campos de; COSTA, Dorcas Lamounier; COSTA, Carlos Henrique Nery; AQUINO, Dorlene; WEYENBERGH, Johan Van; BARRAL-NETTO, Manoel; BARRAL, Aldina; KALIL, Jorge; GOLDBERG, Anna CarlaVisceral leishmaniasis (VL) or Kala-azar is a serious protozoan infectious disease caused by an obligate intracellular parasite. Cytokines have a major role in determining progression and severity of clinical manifestations in VL. We investigated polymorphisms in the TGFB1 and IL8 genes, which are cytokines known to have a role in onset and severity of the disease. Polymorphisms at TGFB1 -509 C/T and +869 T/C, and IL8 -251 A/T were analyzed by a PCR-RFLP technique, in 198 patients with VL, 98 individuals with asymptomatic infection positive for a delayed-type hypersensitivity test (DTH+) and in 101 individuals with no evidence of infection (DTH-). The presence of the T allele in position -509 of the TGFB1 gene conferred a two-fold risk to develop infection both when including those with clinical symptoms (DTH+ and VL, grouped) or when considering DTH+ only, respectively p = 0.007, OR = 1.9 [1.19-3.02] and p = 0.012, OR = 2.01 [1.17-3.79], when compared with DTH- individuals. In addition, occurrence of hemorrhage was associated with TGFB1 -509 T allele. We suggest that the -509 T allele of the TGFB1 gene, a cytokine with a biologically relevant role in the natural history of the disease, may contribute to overall susceptibility to infection by Leishmania and to severity of the clinical disease.
- Transfusion-Transmitted Dengue and Associated Clinical Symptoms During the 2012 Epidemic in Brazil(2016) SABINO, Ester C.; LOUREIRO, Paula; LOPES, Maria Esther; CAPUANI, Ligia; MCCLURE, Christopher; CHOWDHURY, Dhuly; DI-LORENZO-OLIVEIRA, Claudia; OLIVEIRA, Lea C.; LINNEN, Jeffrey M.; LEE, Tzong-Hae; GONCALEZ, Thelma; BRAMBILLA, Donald; KLEINMAN, Steve; BUSCH, Michael P.; CUSTER, BrianBackground. A linked donor-recipient study was conducted during epidemics in 2 cities in Brazil to investigate transfusion-transmitted (TT) dengue virus (DENV) by DENV RNA-positive donations. Methods. During February-June 2012, samples were collected from donors and recipients and retrospectively tested for DENV RNA by transcription-mediated amplification. Recipient chart review, using a case (DENV positive)-control (DENV negative and not known to be exposed) design, was conducted to assess symptoms. Results. Of 39 134 recruited blood donors, DENV-4 viremia was confirmed in 0.51% of donations from subjects in Rio de Janeiro and 0.80% of subjects in Recife. Overall, 42 DENV RNA-positive units were transfused into 35 recipients. Of these, 16 RNA-positive units transfused into 16 susceptible recipients were identified as informative: 5 cases were considered probable TT cases, 1 possible TT case, and 10 nontransmissions. The TT rate was 37.5% (95% confidence interval [CI], 15.2%-64.6%), significantly higher than the viremia rate of 0.93% (95% CI, .11%-3.34%) in nonexposed recipients (P < .0001). Chart review did not find significant differences between cases and controls in symptoms or mortality. Conclusions. During a large epidemic of DENV-4 infection in Brazil, >0.5% of donations were RNA positive, and approximately one third of components resulted in TT. However, no significant clinical differences were evident between RNA-positive and RNA-negative recipients.
- 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.
- SARS-CoV-2 and the COVID-19 disease: a mini review on diagnostic methods(2020) OLIVEIRA, Beatriz Araujo; OLIVEIRA, Lea Campos de; SABINO, Ester Cerdeira; OKAY, Thelma SuelyCoronavirus disease 2019 (COVID-19) is an infectious disease initially reported in China and currently worldwide dispersed caused by a new coronavirus (SARS-CoV-2 or 2019-nCoV) affecting more than seven million people around the world causing more than 400 thousand deaths (on June 8th, 2020). The diagnosis of COVID-19 is based on the clinical and epidemiological history of the patient. However, the gold standard for COVID-19 diagnosis is the viral detection through the amplification of nucleic acids. Although the quantitative Reverse-Transcription Polymerase Chain Reaction (RT-PCR) has been described as the gold standard for diagnosing COVID-19, there are several difficulties involving its use. Here we comment on RT-PCR and describe alternative tests developed for the diagnosis of COVID-19.
- Evaluation of eleven immunochromatographic assays for SARS-CoV-2 detection: investigating the dengue cross-reaction(2022) OLIVEIRA, Beatriz Araujo; OLIVEIRA, Lea Campos de; OLIVEIRA, Franciane Mendes de; PEREIRA, Geovana Maria; SOUZA, Regina Maia de; MANULI, Erika Regina; MARCHINI, Fabricio Klerynton; ESPINOZA, Evelyn Patricia Sanchez; PARK, Marcelo; TANIGUCHI, Leandro; MENDES, Pedro Vitale; FRANCO, Lucas Augusto Moyses; NASTRI, Ana Catharina; OLIVEIRA, Maura Salaroli de; VIEIRA JUNIOR, Jose Mauro; KALLAS, Esper Georges; LEVIN, Anna Sara; SABINO, Ester Cerdeira; COSTA, Silvia FigueiredoCOVID-19 disease is spread worldwide and diagnostic techniques have been studied in order to contain the pandemic. Immunochromatographic (IC) assays are feasible and a low-cost alternative especially in low and middle-income countries, which lack structure to perform certain diagnostic techniques. Here we evaluate the sensitivity and specificity of eleven different IC tests in 145 serum samples from confirmed cases of COVID-19 using RT-PCR and 100 negative serum samples from blood donors collected in February 2019. We also evaluated the cross-reactivity with dengue using 20 serum samples from patients with confirmed diagnosis for dengue collected in early 2019 through four different tests. We found high sensitivity (92%), specificity (100%) and an almost perfect agreement (Kappa 0.92) of IC assay, especially when we evaluated IgG and IgM combined after 10 days from the onset of symptoms with RT-PCR. However, we detected cross-reactivity between dengue and COVID-19 mainly with IgM antibodies (5 to 20% of cross-reaction) and demonstrated the need for better studies about diagnostic techniques for these diseases.
- 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.
- Beneficial effects of benznidazole in Chagas disease: NIH SaMi-Trop cohort study(2018) CARDOSO, Clareci Silva; RIBEIRO, Antonio Luiz P.; OLIVEIRA, Claudia Di Lorenzo; OLIVEIRA, Lea Campos; FERREIRA, Ariela Mota; BIERRENBACH, Ana Luiza; LUIZ, Jose; SILVA, Padilha; COLOSIMO, Enrico Antonio; FERREIRA, Joao Eduardo; LEE, Tzong-Hae; BUSCH, Michael P.; REINGOLD, Arthur Lawrence; SABINO, Ester CerdeiraBackground The effectiveness of anti-parasite treatment with benznidazole in the chronic Chagas disease (ChD) remains uncertain. We evaluated, using data from the NIH-sponsored SaMi-Trop prospective cohort study, if previous treatment with benznidazole is associated with lower mortality, less advanced cardiac disease and lower parasitemia in patients with chronic ChD. Methods The study enrolled 1,959 ChD patients and abnormal electrocardiogram (ECG) from in 21 remote towns in Brazil. A total of 1,813 patients were evaluated at baseline and after two years of follow-up. Those who received at least one course of benznidazole were classified as treated group (TrG = 493) and those who were never treated as control group (CG = 1,320). The primary outcome was death after two-year follow-up; the secondary outcomes were presence at the baseline of major ChD-associated ECG abnormalities, NT-ProBNP levels suggestive of heart failure, and PCR positivity. Results Mortality after two years was 6.3%; it was lower in the TrG (2.8%) than the CG (7.6%); adjusted OR: 0.37 (95% CI: 0.21; 0.63). The ECG abnormalities typical for ChD and high age-adjusted NT-ProBNP levels suggestive of heart failure were lower in the TrG than the CG, OR: 0.35 [CI: 0.23; 0.53]. The TrG had significantly lower rates of PCR positivity, OR: 0.35 [CI: 0.27; 0.45]. Conclusion Patients previously treated with benznidazole had significantly reduced parasitemia, a lower prevalence of markers of severe cardiomyopathy, and lower mortality after two years of follow-up. If used in the early phases, benznidazole treatment may improve clinical and parasitological outcomes in patients with chronic ChD.