JOSE EDUARDO LEVI
Projetos de Pesquisa
Unidades Organizacionais
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
32 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 32
- Microbial Translocation Is Associated with Extensive Immune Activation in Dengue Virus Infected Patients with Severe Disease(2013) WEG, Cornelia A. M. van de; PANNUTI, Claudio S.; ARAUJO, Evaldo S. A. de; HAM, Henk-Jan van den; ANDEWEG, Arno C.; BOAS, Lucy S. V.; FELIX, Alvina C.; CARVALHO, Karina I.; MATOS, Andreia M. de; LEVI, Jose E.; ROMANO, Camila M.; CENTRONE, Cristiane C.; RODRIGUES, Celia L. de Lima; LUNA, Expedito; GORP, Eric C. M. van; OSTERHAUS, Albert D. M. E.; MARTINA, Byron E. E.; KALLAS, Esper G.Background: Severe dengue virus (DENV) disease is associated with extensive immune activation, characterized by a cytokine storm. Previously, elevated lipopolysaccharide (LPS) levels in dengue were found to correlate with clinical disease severity. In the present cross-sectional study we identified markers of microbial translocation and immune activation, which are associated with severe manifestations of DENV infection. Methods: Serum samples from DENV-infected patients were collected during the outbreak in 2010 in the State of Sao Paulo, Brazil. Levels of LPS, lipopolysaccharide binding protein (LBP), soluble CD14 (sCD14) and IgM and IgG endotoxin core antibodies were determined by ELISA. Thirty cytokines were quantified using a multiplex luminex system. Patients were classified according to the 2009 WHO classification and the occurrence of plasma leakage/shock and hemorrhage. Moreover, a (non-supervised) cluster analysis based on the expression of the quantified cytokines was applied to identify groups of patients with similar cytokine profiles. Markers of microbial translocation were linked to groups with similar clinical disease severity and clusters with similar cytokine profiles. Results: Cluster analysis indicated that LPS levels were significantly increased in patients with a profound pro-inflammatory cytokine profile. LBP and sCD14 showed significantly increased levels in patients with severe disease in the clinical classification and in patients with severe inflammation in the cluster analysis. With both the clinical classification and the cluster analysis, levels of IL-6, IL-8, sIL-2R, MCP-1, RANTES, HGF, G-CSF and EGF were associated with severe disease. Conclusions: The present study provides evidence that both microbial translocation and extensive immune activation occur during severe DENV infection and may play an important role in the pathogenesis.
- An autopsy-based study of Trypanosoma cruzi persistence in organs of chronic chagasic patients and its relevance for transplantation(2017) BENVENUTI, Luiz A.; ROGGERIO, Alessandra; CAVALCANTI, Marta M.; NISHIYA, Anna S.; LEVI, Jose E.BackgroundChagas' disease (CD) is caused by infection with the protozoan Trypanosoma cruzi. The disease can affect the heart and/or the gastrointestinal (GI) tract, but around 70% of infected individuals remain asymptomatic in the chronic form. Organ transplantation from T.cruzi-infected donors is often avoided because of the risk of disease transmission, previously reported after heart, kidney, or liver transplantation. MethodsWe investigated by histology, immunohistochemistry, and polymerase chain reaction (PCR) the persistence of T.cruzi in samples of the heart, lung, liver, kidney, pancreas, adrenal gland, esophagus, and GI tract of 21 chronic chagasic patients. ResultsParasite persistence was detected in 12/21 (57.1%) heart samples, mainly by PCR-based assays. T.cruzi parasites were detected by histology and immunohistochemistry in smooth muscle cells of the central vein from 1/21 (4.8%) adrenal gland samples. No samples of the lung, liver, kidney, pancreas, esophagus, or GI tract were found to have parasites by histology, immunohistochemistry, or PCR. ConclusionsWe concluded that, aside from the heart, the other solid organs of T.cruzi-infected donors can be used for transplantation with a lot of caution. Such organs are not safe in the view of previous reports of CD transmission, but seem to present a low T.cruzi load compared to the heart.
- A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus(2017) MAGNANI, Diogo M.; SILVEIRA, Cassia G. T.; ROSEN, Brandon C.; RICCIARDI, Michael J.; PEDRENO-LOPEZ, Nuria; GUTMAN, Martin J.; BAILEY, Varian K.; MAXWELL, Helen S.; DOMINGUES, Aline; GONZALEZ-NIETO, Lucas; AVELINO-SILVA, Vivian I.; TRINDADE, Mateus; NOGUEIRA, Juliana; OLIVEIRA, Consuelo S.; MAESTRI, Alvino; FELIX, Alvina Clara; LEVI, Jose Eduardo; NOGUEIRA, Mauricio L.; MARTINS, Mauricio A.; MARTINEZ-NAVIO, Jose M.; FUCHS, Sebastian P.; WHITEHEAD, Stephen S.; BURTON, Dennis R.; DESROSIERS, Ronald C.; KALLAS, Esper G.; WATKINS, David I.The isolation of neutralizing monoclonal antibodies (nmAbs) against the Zika virus (ZIKV) might lead to novel preventative strategies for infections in at-risk individuals, primarily pregnant women. Here we describe the characterization of human mAbs from the plasmablasts of an acutely infected patient. One of the 18 mAbs had the unusual feature of binding to and neutralizing ZIKV despite not appearing to have been diversified by affinity maturation. This mAb neutralized ZIKV (Neut(50) similar to 2 mu g/ml) but did not react with any of the four dengue virus serotypes. Except for the expected junctional diversity created by the joining of the V-(D)-J genes, there was no deviation from immunoglobulin germline genes. This is a rare example of a human mAb with neutralizing activity in the absence of detectable somatic hypermutation. Importantly, binding of this mAb to ZIKV was specifically inhibited by human plasma from ZIKV-exposed individuals, suggesting that it may be of value in a diagnostic setting.
- Transplant-Associated and Blood Transfusion-Associated Tropical and Parasitic Infections(2012) MACHADO, Clarisse Martins; LEVI, Jose EduardoBlood transfusion and transplantation may represent efficient mechanisms of spreading infectious agents to naive populations. In the developed countries, as a consequence of globalization, several factors such as international commerce, tourism, and immigration have acted as important features for the emergence or reemergence of infectious diseases previously referred to as tropical. This article reviews the relevant bacterial, protozoan and viral infections that are more frequently associated with blood transfusion and/or solid organ or marrow transplantation and may affect susceptible populations worldwide.
- Dengue Virus and Blood Transfusion(2016) LEVI, Jose Eduardo
- CD8+T Lymphocyte Expansion, Proliferation and Activation in Dengue Fever(2015) MATOS, Andreia Manso de; CARVALHO, Karina Inacio; ROSA, Daniela Santoro; VILLAS-BOAS, Lucy Santos; SILVA, Wanessa Cardoso da; RODRIGUES, Celia Luiza de Lima; OLIVEIRA, Olimpia Massae Nakasone Peel Furtado; LEVI, Jose Eduardo; ARAUJO, Evaldo Stanislau Affonso; PANNUTI, Claudio Sergio; LUNA, Expedito Jose Albuquerque; KALLAS, Esper GeorgeDengue fever induces a robust immune response, including massive T cell activation. The level of T cell activation may, however, be associated with more severe disease. In this study, we explored the level of CD8+ T lymphocyte activation in the first six days after onset of symptoms during a DENV2 outbreak in early 2010 on the coast of Sao Paulo State, Brazil. Using flow cytometry we detected a progressive increase in the percentage of CD8+ T cells in 74 dengue fever cases. Peripheral blood mononuclear cells from 30 cases were thawed and evaluated using expanded phenotyping. The expansion of the CD8+ T cells was coupled with increased Ki67 expression. Cell activation was observed later in the course of disease, as determined by the expression of the activation markers CD38 and HLA-DR. This increased CD8+ T lymphocyte activation was observed in all memory subsets, but was more pronounced in the effector memory subset, as defined by higher CD38 expression. Our results show that most CD8+ T cell subsets are expanded during DENV2 infection and that the effector memory subset is the predominantly affected sub population.
- Chlamydia trachomatis infection in women living in remote areas in Amazonas, Brazil-a self-collection screening experience(2019) ROCHA, Danielle A. P.; MORAES, Cassia de Oliveira; ARAUJO, Adriene F.; BELTRAO, Emille dos Santos; SANTOS, Lainara Castelo dos; MATA, Ligia Menezes da; XAVIER, Antonio N. N.; REIS, Renato dos Santos; SOARES, Silvia C. C.; TORRES, Katia L.; LEVI, Jose E.; MARINO, Josiane M.Chlamydia trachomatis infection is the most common sexually transmitted bacterial infection among women. In Brazil, there is no organized screening program for C. trachomatis, and the actual prevalence of infection is unknown. This study aimed to determine the prevalence of C. trachomatis infection in women living in riverside communities in the Amazon, using self-collection employing the Evalyn (R) Brush and polymerase chain reaction. A total of 299 riverine women aged 18-81 years, mean age 35.7 (+/- 12.8) years, predominantly agricultural workers, with low schooling and living with a partner, participated in this study. The prevalence of C. trachomatis infection was found to be 3.7% (95% CI 1.8-6.5), most of them being symptomatic. The mean age of the first sexual intercourse reported by women was 15.2 (+/- 2.3) years, and the majority reported having had none or only one partner in the last 12 months, with very low adherence to consistent condom use (15.4%). Most women (98.3%) reported having approved using the vaginal self-collecting brush, and only 4.7% reported having difficulty in handling the brush. We consider that a vaginal self-collecting device is adequate for diagnosing C. trachomatis infection in women living in remote, hard-to-reach areas.
- Predictors of mortality in patients with yellow fever: an observational cohort study(2019) KALLAS, Esper G.; ZANELLA, Luiz Gonzaga F. A. B. D'Elia; V, Carlos Henrique Moreira; BUCCHERI, Renata; DINIZ, Gabriela B. F.; CASTINEIRAS, Anna Carla P.; COSTA, Priscilla R.; DIAS, Juliana Z. C.; MARMORATO, Mariana P.; SONG, Alice T. W.; MAESTRI, Alvino; BORGES, Igor C.; JOELSONS, Daniel; CERQUEIRA, Natalia B.; SOUZA, Nathalia C. Santiago e; CLARO, Ingra Morales; SABINO, Ester C.; LEVI, Jose Eduardo; I, Vivian Avelino-Silva; HO, Yeh-LiBackground Yellow fever virus infection results in death in around 30% of symptomatic individuals. The aim of this study was to identify predictors of death measured at hospital admission in a cohort of patients admitted to hospital during the 2018 outbreak of yellow fever in the outskirts of Sao Paulo city, Brazil. Methods In this observational cohort study, we enrolled patients with yellow fever virus from two hospitals in Sao Paolo-the Hospital das Clinicas, University of Sao Paulo and the Infectious Diseases Institute ""Emilio Ribas"". Patients older than 18 years admitted to hospital with fever or myalgia, headache, arthralgia, oedema, rash, or conjunctivitis were consecutively screened for inclusion in the present study. Consenting patients were included if they had travelled to geographical areas in which yellow fever virus cases had been previously confirmed. Yellow fever infection was confirmed by real-time PCR in blood collected at admission or tissues at autopsy. We sequenced the complete genomes of yellow fever virus from infected individuals and evaluated demographic, clinical, and laboratory findings at admission and investigated whether any of these measurements correlated with patient outcome (death). Findings Between Jan 11, 2018, and May 10, 2018, 118 patients with suspected yellow fever were admitted to Hospital das Clinicas, and 113 patients with suspected yellow fever were admitted to Infectious Diseases Institute ""Emilio Ribas"". 95 patients with suspected yellow fever were included in the study, and 136 patients were excluded. Three (3%) of 95 patients with suspected yellow fever who were included in the study were excluded because they received a different diagnosis, and 16 patients with undetectable yellow fever virus RNA were excluded. Therefore, 76 patients with confirmed yellow fever virus infection, based on detectable yellow fever virus RNA in blood (74 patients) or yellow fever virus confirmed only at the autopsy report (two patients), were included in our analysis. 27 (36%) of 76 patients died during the 60 day period after hospital admission. We generated 14 complete yellow fever virus genomes from the first 15 viral load-detectable samples. The genomes belonged to a single monophyletic clade of the South America I genotype, sub-genotype E. Older age, male sex, higher leukocyte and neutrophil counts, higher alanine aminotransferase, aspartate transaminase (AST), bilirubin, and creatinine, prolonged prothrombin time, and higher yellow fever virus RNA plasma viral load were associated with higher mortality. In a multivariate regression model, older age, elevated neutrophil count, increased AST, and higher viral load remained independently associated with death. All 11 (100%) patients with neutrophil counts of 4000 cells per mL or greater and viral loads of 5.1 log(10) copies/mL or greater died (95% CI 72-100), compared with only three (11%) of 27 (95% CI 2-29) among patients with neutrophil counts of less than 4000 cells per mL and viral loads of less than 5.1 log(10) copies/mL. Interpretation We identified clinical and laboratory predictors of mortality at hospital admission that could aid in the care of patients with yellow fever virus. Identification of these prognostic markers in patients could help clinicians prioritise admission to the intensive care unit, as patients often deteriorate rapidly. Moreover, resource allocation could be improved to prioritise key laboratory examinations that might be more useful in determining whether a patient could have a better outcome. Our findings support the important role of the virus in disease pathogenesis, suggesting that an effective antiviral could alter the clinical course for patients with the most severe forms of yellow fever.
- MAIT cells are activated in acute Dengue virus infection and after in vitro Zika virus infection(2018) PAQUIN-PROULX, Dominic; AVELINO-SILVA, Vivian I.; SANTOS, Bianca A. N.; BARSOTTI, Nathalia Silveira; SIROMA, Fabiana; RAMOS, Jessica Fernandes; TONACIO, Adriana Coracini; SONG, Alice; MAESTRI, Alvino; CERQUEIRA, Natalia Barros; FELIX, Alvina Clara; LEVI, Jose Eduardo; GREENSPUN, Benjamin C.; ROUGVIE, Miguel de Mulder; ROSENBERG, Michael G.; NIXON, Douglas F.; KALLAS, Esper G.Dengue virus (DENV) and Zika virus (ZIKV) are members of the Flaviviridae and are pre-dominantly transmitted via mosquito bites. Both viruses are responsible for a growing number of infections in tropical and subtropical regions. DENV infection can cause lethargy with severe morbidity and dengue shock syndrome leading to death in some cases. ZIKV is now linked with Guillain-Barre A syndrome and fetal malformations including microcephaly and developmental disorders (congenital Zika syndrome). The protective and pathogenic roles played by the immune response in these infections is unknown. Mucosal-associated invariant T (MAIT) cells are a population of innate T cells with potent anti-bacterial activity. MAIT cells have also been postulated to play a role in the immune response to viral infections. In this study, we evaluated MAIT cell frequency, phenotype, and function in samples from subjects with acute and convalescent DENV infection. We found that in acute DENV infection, MAIT cells had elevated co-expression of the activation markers CD38 and HLA-DR and had a poor IFN gamma response following bacterial stimulation. Furthermore, we found that MAIT cells can produce IFN gamma in response to in vitro infection with ZIKV. This MAIT cell response was independent of MR1, but dependent on IL-12 and IL-18. Our results suggest that MAIT cells may play an important role in the immune response to Flavivirus infections.
- Unexpected detection of Plasmodium vivax and Plasmodium falciparum DNA in asymptomatic blood donors: fact or artifact?(2014) MENDRONE JR., Alfredo; CERUTTI JR., Crispim; LEVI, Jose Eduardo; BOULOS, Marcos; SANCHEZ, Maria Carmen Arroyo; MALAFRONTE, Rosely dos Santos; SANTI, Silvia Maria Di; ODONE JR., VicenteA study searching for Plasmodium vivax and Plasmodium falciparum DNA among blood donors from the non-endemic area in Brazil reported a rate of 7.41%. This number is at least three times higher than what has been observed in blood donors from the Amazon, an endemic area concentrating >99% of all malaria cases in Brazil. Moreover, the majority of the donors were supposedly infected by P. falciparum, a rare finding both in men and anophelines from the Atlantic forest. These findings shall be taken with caution since they disagree with several publications in the literature and possibly overestimate the actual risk of malaria transmission by blood transfusion in Sao Paulo city.