12 research outputs found

    Importation and early local transmission of COVID-19 in Brazil, 2020

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    We conducted the genome sequencing and analysis of the first confirmed COVID-19 infections in Brazil. Rapid sequencing coupled with phylogenetic analyses in the context of travel history corroborate multiple independent importations from Italy and local spread during the initial stage of COVID-19 transmission in Brazil

    Pathogenesis of leptospirosis pulmonary hemorrhage syndrome in human

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    A leptospirose é uma zoonose de alta morbidade em humanos e um importante problema de saúde pública. Causada por bactérias do gênero Leptospira, a doença apresenta diversas formas clínicas e é especialmente importante em países em desenvolvimento. Síndrome pulmonar hemorrágica é a maior causa de óbito em pacientes com formas severas da doença. Os mecanismos patogênicos relacionados à síndrome pulmonar hemorrágica na leptospirose humana são desconhecidos. Com o objetivo de avaliar estes mecanismos patogênicos, 30 necrópsias (tecido pulmonar) de pacientes com síndrome pulmonar hemorrágica na leptospirose e 7 controles foram avaliados. Para determinar a participação os mecanismos patogênicos envolvidos, experimentos de histologia e imunohistoquímica (IgM, IgG, IgA, and C3) foram realizados em amostras de tecidos pulmonares, bem como dosagem sérica de auto-anticorpos específicos (anticardiolipina e anti-membrana basal) de amostras pareadas de soros de pacientes com leptospirose com e sem síndrome hemorrágica pulmonar e de indivíduos doadores de banco de sangue. Nos achados patológicos, os pacientes com síndrome hemorrágica pulmonar na leptospirose diferem dos controles com hemorragia pulmonar em alguns aspectos: moderada ou intensa presença de macrófagos na luz alveolar (97% versus 29%, respectivamente; p < 0.01); presença de membrana hialina na superficie alveolar (100% versus 0% respectivamente; p < 0.01); intensa necrose e regeneração de pneumócitos II (100% versus 0%, respectivamente; p < 0.01); e presença de plasmócitos no septo aveolar (80% versus 29%; p < 0.02). Nenhuma diferença estatisticamente significativa foi observada em relação ao número de outras células no septo alveolar. Leptospiras intactas foram raramente observadas. A detecção de antígeno de leptospira não foi correlacionada com a intensidade de hemorragia pulmonar. Em nenhum dos tecidos pulmonares estudados foi evidenciado alterações microscópicas sugestivas de coagulação intravascular disseminada. Deposição de imunoglobulina foi detectada na superfície alveolar de 18 de 30 pacientes com síndrome pulmonar hemorrágica na leptospirose. Três padrões de marcação de imunoglobulina e complemento foram observados em tecido pulmonar de pacientes com hemorragia pulmonar e leptospirose: (A) marcação linear delicada, como uma membrana, recobrindo a superfície luminal alveolar de pneumócitos I e II; (MF) marcação multifocal, aleatória ao longo do septo; e (I) marcação fraca granular, focal, intra-alveolar. Não houve diferenças significativas na concentração de auto-anticorpos contra membrana basal nos diferentes grupos estudados. Observamos diferenças significativas nos títulos de anticorpos IgM anticardiolipina entre a primeira e segunda amostra, nos pacientes com e sem hemorragia pulmonar (p<0.01 e p=0.04, respectivamente). Aumento significativo nos títulos de anticorpos anti-cardiolipina da classe IgG, bem como na relação IgG/IgM, foi observado apenas nos pacientes com hemorragia pulmonar (p=0.01 e p=0.01). Nós concluímos que o comprometimento pulmonar na leptospirose humana grave ocorre principalmente sob a forma de uma pneumopatia hemorrágica com características peculiares, cujo quadro morfológico difere de outras hemorragias pulmonares. Caracteriza-se pela deposição linear de imunoglobulina (IgM, IgG e IgA) e complemento(C3) na superfície luminal alveolar de pneumócitos I e II e multifocal nos septos alveolares. Associa-se à intensa necrose de pneumócitos I e II, regeneração de pneumócitos II, além de inflamação septal e alveolarLeptospirosis is a zoonotic disease that is a cause of high morbidity and mortality in humans and is an important public health problem. Caused by bacteria of Leptospira genus, this disease presents diverse clinical manifestations and is especially important in developing countries. Leptospirosis pulmonary hemorrhage syndrome is the major cause of death in patients with the severe form of leptospirosis. The pathogenic mechanisms of this syndrome are unknown. With the purpose of identifying these pathogenic mechanisms, 30 necropsies (pulmonary samples) from patients with leptospirosis pulmonary hemorrhage syndrome and seven controls were evaluated. . To determine whether the immune system is involved, histology and immunohistochemistry (IgM, IgG, IgA, and C3) experiments were performed on lung tissue samples, as well sera measurements of autoantibodies (against the basal membrane and anti-cardiolipin) were performed in leptospirosis patients with and without pulmonary hemorrhage syndrome (in paired samples) and in healthy donors from a blood bank. We found that patients with leptospirosis pulmonary hemorrhage syndrome differed from control pulmonary hemorrhage patients in several features: the presence of moderate to high levels of macrophages in the alveolar space (77% versus 29%, respectively; p = 0.02), the presence of the focal hyaline membrane on alveolar surface (100% versus 0%; p < 0.01), extensive necrosis and regeneration of pneumocyte II cells (100% versus 0%; p < 0.01) and the presence of plasma cells in the alveolar septum (77% versus 29%, respectively; p =0.02). No statistically significant differences were observed in the number of others cells in the alveolar septae. Intact leptospires were rarely detected. Leptospiral antigen was not correlated with the intensity of the lesions. None of the patients showed microscopic evidence for disseminated intravascular coagulation. Immunoglobulin deposits were detected on the alveolar surface of 18/30 leptospirosis patients with pulmonary hemorrhage. Three staining patterns were observed for the immunoglobulins and C3 in the lung tissues of leptospirosis patients with pulmonary hemorrhage syndrom: (A) delicate linear staining adjacent to the alveolar surface, like a membrane covering the luminal surface of type I and II pneumocyte cells; (MF) random, multifocal staining along the alveolar septum; and (I) weak, focal intra-alveolar granular staining.. We were not able to show any significant difference in autoantibodies concentration in the different groups. We found significant difference between the titles of anticardiolipin IgM antibodies in the first and second sera sample from leptospirosis patients with and without pulmonary hemorrhage (p<0.01 e p=0.04, respectively). The increased in the titles of anti-cardiolipin IgG antibodies, as well IgG/IgM ratio was observed only in patients with pulmonary hemorrhage(p=0.01 and p=0.01). We concluded that the pulmonary involvement on severe human leptospirosis have particular characteristics, which the morphologic aspect differ from the others causes of lung hemorrhage. It was distinguished by linear deposition of immunoglobulin and complement (C3C) on the luminal alveolar surface of pneumocyte I and II cells. This event was associated with pneumocyte I and II cells necrosis, pneumocyte II regeneration and septal and alveolar inflammatio

    Sugar cane manufacturing is associated with tuberculosis in an indigenous population in Brazil

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    Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-12-15T12:21:09Z No. of bitstreams: 1 Sacchi EPC Sugar cane manufacturing....pdf: 183803 bytes, checksum: 654d7fe83d7b8a699f368a7f40c7a92a (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-12-15T12:38:09Z (GMT) No. of bitstreams: 1 Sacchi EPC Sugar cane manufacturing....pdf: 183803 bytes, checksum: 654d7fe83d7b8a699f368a7f40c7a92a (MD5)Made available in DSpace on 2015-12-15T12:38:09Z (GMT). No. of bitstreams: 1 Sacchi EPC Sugar cane manufacturing....pdf: 183803 bytes, checksum: 654d7fe83d7b8a699f368a7f40c7a92a (MD5) Previous issue date: 2013Federal University of Grande Dourados. University Hospital. Grande Dourados, MGS, Brasil / Federal University of Grande Dourados. Faculty of Health Sciences. Grande Dourados, MGS, BrasilFederal University of Grande Dourados. University Hospital. Grande Dourados, MGS, BrasilFederal University of Grande Dourados. Faculty of Health Sciences. Grande Dourados, MGS, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Yale School of Public Health. Epidemiology of Microbial Disease Division. New Haven, USAFederal University of Grande Dourados. Faculty of Health Sciences. Grande Dourados, MGS, BrasilBackground: Tuberculosis (TB) remains one of the leading causes of morbidity and mortality among indigenous peoples in Brazil, and identifying the risk factors for TB in this population secondary to specific epidemiological conditions is essential for recommending interventions aimed at disease control. Methods: This case-control study was conducted with an indigenous population between June 2009 and August 2011 in Dourados, Brazil. Tuberculosis cases reported to the national disease surveillance programme were paired with two control cases matched by age and geographic location. Results: There were 63 cases included in this study, and the annual incidence of TB in the indigenous communities examined was 222 (95% CI, 148–321) per 100 000 inhabitants. The multivariate analysis demonstrated that the variables associated with TB infection included male gender (OR 2.6; 95% CI 1.3–5.3), not owning a home (OR 3.4; 95% CI 1.2–10.1), illiteracy (OR 2.4; 95% CI 1.1–5.0), TB contact (OR 2.4; 95% CI 1.2–4.8) and work performed in a sugar cane factory (OR 6.8; 95% CI 1.2–36.9). Conclusion: There is a potential relationship between exposure to sugar cane manufacturing processes and tuberculosis infection among indigenous populations

    Monoclonal antibodies against LipL32, the major outer membrane protein of pathogenic Leptospira: production, characterization, and testing in diagnostic applications.

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    Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-11-10T13:36:14Z No. of bitstreams: 1 Fernandes CPH Monoclonal antibodies against....pdf: 2615824 bytes, checksum: 6323db4939230d4e82e18d306c86946c (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-11-10T14:00:35Z (GMT) No. of bitstreams: 1 Fernandes CPH Monoclonal antibodies against....pdf: 2615824 bytes, checksum: 6323db4939230d4e82e18d306c86946c (MD5)Made available in DSpace on 2015-11-10T14:00:35Z (GMT). No. of bitstreams: 1 Fernandes CPH Monoclonal antibodies against....pdf: 2615824 bytes, checksum: 6323db4939230d4e82e18d306c86946c (MD5) Previous issue date: 2007Centro de Biotecnologia. Pelotas, RS, Brasil / Universidade Federal de Pelotas. Faculdade de Medicina Veterinária. Pelotas, RS, BrasilCentro de Biotecnologia. Pelotas, RS, BrasilCentro de Biotecnologia. Pelotas, RS, BrasilCentro de Biotecnologia. Pelotas, RS, BrasilCentro de Biotecnologia. Pelotas, RS, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Cornell University. Weill Medical College. Division of International Medicine and Infectious Disease. New YorkCentro de Biotecnologia. Pelotas, RS, BrasilCentro de Biotecnologia. Pelotas, RS, BrasilPathogenic serovars of Leptospira have a wide antigenic diversity attributed mainly to the lipopolysaccharide present in the outer membrane. In contrast, antigens conserved among pathogenic serovars are mainly represented by outer membrane proteins. Surface exposure of a major and highly conserved outer membrane lipoprotein (LipL32) was recently demonstrated on pathogenic Leptospira. LipL32 in its recombinant form (rLipL32) was used to immunize BALB/c mice to develop murine monoclonal antibodies (MAbs). Three MAbs against rLipL32 were produced, isotyped, and evaluated for further use in diagnostic tests of leptospirosis using different approaches. MAbs were conjugated to peroxidase and evaluated in a native protein enzyme-linked immunosorbent assay (ELISA) with intact and heat-treated leptospiral cells, conjugated to fluorescein isothiocyanate (FITC) for indirect immunofluorescence with intact and methanol fixed cells and were used for LipL32 immunoprecipitation from leptospiral cells. rLipL32 MAbs conjugated to peroxidase or used as primary antibody bound to intact and heat-treated cells in ELISA, proving that they could be used in enzyme immunoassays for detection of the native protein. In immunofluorescence assay, MAbs labeled bacterial cells either intact or methanol fixed. Two MAbs were able to immunoprecipitate the native protein from live and motile leptospiral cells and, adsorbed onto magnetic beads, captured intact bacteria from artificially contaminated human sera for detection by polymerase chain reaction (PCR) amplification. Results of this study suggest that the MAbs produced can be useful for the development of diagnostic tests based on detection of LipL32 leptospiral antigen in biological fluids

    Pathogenic Leptospira species express surface-exposed proteins belonging to the bacterial immunoglobulin superfamily

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    Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-04-30T17:19:56Z No. of bitstreams: 1 Matsunaga J Pathogenic Leptospira....pdf: 1203467 bytes, checksum: 293db660c4d6910bda034909fe19bb75 (MD5)Made available in DSpace on 2014-04-30T17:19:56Z (GMT). No. of bitstreams: 1 Matsunaga J Pathogenic Leptospira....pdf: 1203467 bytes, checksum: 293db660c4d6910bda034909fe19bb75 (MD5) Previous issue date: 2003Veterans Affairs Greater Los Angeles Healthcare System. Los Angeles, CA, USA / Department of Medicine. UCLA School of Medicine. Los Angeles, CA, USA.Division of Infectious Diseases and Immunity. School of Public Health. University of California. Berkeley Berkeley, CA, USA.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil.Veterans Affairs Greater Los Angeles Healthcare System. Los Angeles, CA, USA.Veterans Affairs Greater Los Angeles Healthcare System. Los Angeles, CA, USA / Department of Medicine. UCLA School of Medicine. Los Angeles, CA, USA.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil.College of Veterinary Medicine. Michigan State University. East Lansing, MI, USA.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil.Division of Infectious Diseases and Immunity. School of Public Health. University of California. Berkeley Berkeley, CA, USA.Veterans Affairs Greater Los Angeles Healthcare System. Los Angeles, CA, USA / Department of Medicine. UCLA School of Medicine. Los Angeles, CA, USA.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Division of International Medicine and Infectious Diseases. Weill Medical College of Cornell University. New York, NY, USA.Proteins with bacterial immunoglobulin-like (Big) domains, such as the Yersinia pseudotuberculosis invasin and Escherichia coli intimin, are surface-expressed proteins that mediate host mammalian cell invasion or attachment. Here, we report the identification and characterization of a new family of Big domain proteins, referred to as Lig (leptospiral Ig-like) proteins, in pathogenic Leptospira. Screening of L. interrogans and L. kirschneri expression libraries with sera from leptospirosis patients identified 13 lambda phage clones that encode tandem repeats of the 90 amino acid Big domain. Two lig genes, designated ligA and ligB, and one pseudogene, ligC, were identified. The ligA and ligB genes encode amino-terminal lipoprotein signal peptides followed by 10 or 11 Big domain repeats and, in the case of ligB, a unique carboxy-terminal non-repeat domain. The organization of ligC is similar to that of ligB but contains mutations that disrupt the reading frame. The lig sequences are present in pathogenic but not saprophytic Leptospira species. LigA and LigB are expressed by a variety of virulent leptospiral strains. Loss of Lig protein and RNA transcript expression is correlated with the observed loss of virulence during culture attenuation of pathogenic strains. High-pressure freeze substitution followed by immunocytochemical electron microscopy confirmed that the Lig proteins were localized to the bacterial surface. Immunoblot studies with patient sera found that the Lig proteins are a major antigen recognized during the acute host infection. These observations demonstrate that the Lig proteins are a newly identified surface protein of pathogenic Leptospira, which by analogy to other bacterial immunoglobulin superfamily virulence factors, may play a role in host cell attachment and invasion during leptospiral pathogenesis

    The terminal portion of leptospiral immunoglobulin-like protein LigA confers protective immunity against lethal infection in the hamster model of leptospirosis (preprint)

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    Submitted by Martha Silveira Berbert ([email protected]) on 2012-11-15T02:21:11Z No. of bitstreams: 1 Silva Everton.pdf: 745194 bytes, checksum: 6f189173f7d221a3ffb0273d9674affd (MD5)Made available in DSpace on 2012-11-15T02:21:11Z (GMT). No. of bitstreams: 1 Silva Everton.pdf: 745194 bytes, checksum: 6f189173f7d221a3ffb0273d9674affd (MD5) Previous issue date: 2007-08Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Veterans Affairs Greater Los Angeles Healthcare System. Los Angeles, CA, United States of America.Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Universidade Federal de Pelotas. Centro de Biotecnologia. Pelotas, RGS, Brasil.Veterans Affairs Greater Los Angeles Healthcare System. Los Angeles, CA, USA.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Subunit vaccines are a potential intervention strategy against leptospirosis, which is a major public health problem in developing countries and a veterinary disease in livestock and companion animals worldwide. Leptospiral immunoglobulin-like (Lig) proteins are a family of surface-exposed determinants that have Ig-like repeat domains found in virulence factors such as intimin and invasin. We expressed fragments of the repeat domain regions of LigA and LigB from Leptospira interrogans serovar Copenhageni. Immunization of Golden Syrian hamsters with Lig fragments in Freund's adjuvant induced robust antibody responses against recombinant protein and native protein, as detected by ELISA and immunoblot, respectively. A single fragment, LigANI, which corresponds to the six carboxy-terminal Ig-like repeat domains of the LigA molecule, conferred immunoprotection against mortality (67-100%, P<0.05) in hamsters which received a lethal inoculum of L. interrogans serovar Copenhageni. However, immunization with this fragment did not confer sterilizing immunity. These findings indicate that the carboxy-terminal portion of LigA is an immunoprotective domain and may serve as a vaccine candidate for human and veterinary leptospirosis

    Potential immunomodulatory effects of plant lectins in Schistosoma mansoni infection

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    Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-03-13T18:51:27Z No. of bitstreams: 1 Reis E Potential Immunomodulatory....pdf: 727632 bytes, checksum: 4c436017589ebd87aa96d15e68b3d809 (MD5)Made available in DSpace on 2014-03-13T18:51:28Z (GMT). No. of bitstreams: 1 Reis E Potential Immunomodulatory....pdf: 727632 bytes, checksum: 4c436017589ebd87aa96d15e68b3d809 (MD5) Previous issue date: 2008Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal do Ceará. Departamento de Bioquímica e Biologia Molecular. Fortaleza, CE, BrasilUniversidade Federal de Ceará. Faculdade de Medicina. Sobral, CE, BrasilUniversidade Federal de Ceará. Faculdade de Medicina. Sobral, CE, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilHarvard School of Public Health. Department of Immunology and Infectious Diseases. Boston, USAFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilLectins are sugar-binding glycoproteins that can stimulate, in a non-antigen-specific fashion, lymphocytes, leading to proliferation and cytokine production. Some lectins are utilized as in vitro mitogenic lymphocyte stimulators and their use as immunomodulators against infectious diseases has been evaluated experimentally. In the experimental murine model, the immune response to schistosomiasis is Th1-like during the initial stage of infection, with a shift towards a Th2-like response after oviposition. We report the response of schistosomiasis patients' (n=37) peripheral blood mononuclear cells (PBMC) to stimulation by lectins, including newly isolated lectins from Brazilian flora, and by Schistosomamansoni soluble egg antigens (SEA). Cytokine production upon lectin stimulation ex vivo was assessed in PBMC supernatants, collected at 24 and 72 h, by sandwich ELISA to IL-5, IL-10, TNF-alpha and IFN-gamma. In PBMC from infected patients all but one of the lectins induced a Th2-like cytokine response, characterized by elevated IL-5 production that was higher than that induced by SEA stimulation alone. Our results show that the Th2 environment present during schistosomiasis is not affected and that it may be further stimulated by the presence of lectins
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