Prevalence of antibodies to equine alphaviruses in the State of Pará, Brazil

ABSTRACT: The State of Pará comprises 26% of Brazilian Amazon region, where a large diversity of arboviruses has been described. This study sought to assess the prevalence and distribution of hemagglutination inhibition (HI) antibodies against antigens of four alphaviruses (Togaviridae: Alphavirus ) from the species: Eastern equine encephalitis (EEEV), Western equine encephalitis (WEEV), Mayaro virus (MAYV), and Mucambo virus (MUCV) in 753 serum samples of horses in Pará State, Brazil. All investigated arboviruses were detected and indicate that horses are susceptible to these alphaviruses, and show evidences of their active circulation in farm animals in the Brazilian Amazon

Emergence of New Immunopathogenic Factors in Human Yellow Fever: Polarisation of the M1/M2 Macrophage Response in the Renal Parenchyma

Macrophages in the kidney play a pathogenic role in inflammation and fibrosis. Our study aimed to understand the polarisation of the M1 and M2 phenotypic profiles of macrophages in injured kidney tissue retrieved from fatal cases of yellow fever virus (YFV). A total of 11 renal tissue biopsies obtained from patients who died of yellow fever (YF) were analysed. To detect antibodies that promote the classical and alternative pathways of macrophage activation, immunohistochemical analysis was performed to detect CD163, CD68, inducible nitric oxide synthase (iNOS), arginase 1, interleukin (IL)-4, IL-10, interferon (IFN)-γ, IFN-β, tumour necrosis factor (TNF)-α, IL-13, and transforming growth factor (TGF)-β. There was a difference in the marker expression between fatal cases of YFV and control samples, with increased expression in the cortical region of the renal parenchyma. The immunoexpression of CD68 and CD163 receptors suggests the presence of activated macrophages migrating to infectious foci. The rise in IL-10, IL-4, and IL-13 indicated their potential role in the inactivation of the inflammatory macrophage response and phenotypic modulation of M2 macrophages. The altered expression of IFN-γ and IFN-β demonstrates the importance of the innate immune response in combating microorganisms. Our findings indicate that the polarisation of M1 and M2 macrophages plays a vital role in the renal immune response to YFV

New Insights into the Mechanism of Immune-Mediated Tissue Injury in Yellow Fever: The Role of Immunopathological and Endothelial Alterations in the Human Lung Parenchyma

Yellow fever (YF) may cause lesions in different organs. There are no studies regarding the in situ immune response in the human lung and investigating immunopathological aspects in fatal cases can help to better understand the evolution of the infection. Lung tissue samples were collected from 10 fatal cases of human yellow fever and three flavivirus-negative controls who died of other causes and whose lung parenchymal architecture was preserved. In YFV-positive fatal cases, the main histopathological changes included the massive presence of diffuse alveolar inflammatory infiltrate, in addition to congestion and severe hemorrhage. The immunohistochemical analysis of tissues in the lung parenchyma showed significantly higher expression of E-selectin, P-selectin, ICAM-1, VCAM-1 in addition to cytokines such as IL-4, IL-10, IL-13, TNF- α, IFN-γ and TGF-β compared to the negative control. The increase in immunoglobulins ICAM-1 and VCAM-1 results in strengthening of tissue transmigration signaling. E-selectin and P-selectin actively participate in this process of cell migration and formation of the inflammatory infiltrate. IFN-γ and TNF-α participate in the process of cell injury and viral clearance. The cytokines IL-4 and TGF-β, acting in synergism, participate in the process of tissue regeneration and breakdown. The anti-inflammatory cytokines IL-4, IL-10 and IL-13 also act in the reduction of inflammation and tissue repair. Our study indicates that the activation of the endothelium aggravates the inflammatory response by inducing the expression of adhesion molecules and cytokines that contribute to the rolling, recruitment, migration and eliciting of the inflammatory process in the lung parenchyma, contributing to the fatal outcome of the disease

Antibody cross-reactivity and evidence of susceptibility to emerging Flaviviruses in the dengue-endemic Brazilian Amazon

Objectives: Several Flaviviruses can co-circulate. Pre-existing immunity to one virus can modulate the response to a heterologous virus; however, the serological cross-reaction between these emerging viruses in dengue virus (DENV)-endemic regions are poorly understood. Methods: A cross-sectional study was performed among the residents of Manaus city in the state of Amazonas, Brazil. The serological response was assessed by hemagglutination inhibition assay (HIA), enzyme-linked immunosorbent assay, and neutralization assay. Results: A total of 74.52% of the participants were immunoglobulin G-positive (310/416), as estimated by lateral flow tests. Overall, 93.7% of the participants were seropositive (419/447) for at least one DENV serotype, and the DENV seropositivity ranged between 84.8% and 91.0%, as determined by HIA. About 93% had antiyellow fever virus 17D-reactive antibodies, whereas 80.5% reacted to wild-type yellow fever virus. Zika virus (ZIKV) had the lowest seropositivity percentage (52.6%) compared with other Flaviviruses. Individuals who were DENV-positive with high antibody titers by HIA or envelope protein domain III enzyme-linked immunosorbent assay reacted strongly with ZIKV, whereas individuals with low anti-DENV antibody titers reacted poorly toward ZIKV. Live virus neutralization assay with ZIKV confirmed that dengue serogroup and ZIKV-spondweni serogroup are far apart; hence, individuals who are DENV-positive do not cross-neutralize ZIKV efficiently. Conclusion: Taken together, we observed a high prevalence of DENV in the Manaus-Amazon region and a varying degree of cross-reactivity against emerging and endemic Flaviviruses. Epidemiological and exposure conditions in Manaus make its population susceptible to emerging and endemic arboviruses

First isolation of West Nile virus in Brazil

BACKGROUND Serological evidence of West Nile virus (WNV) infection has been reported in different regions of Brazil from equine and human hosts but the virus had never been isolated in the country. OBJECTIVES We sought to identify the viral etiology of equine encephalitis in Espírito Santo state. METHODS We performed viral culture in C6/36 cells, molecular detection of WNV genome, histopathology and immunohistochemistry from horse cerebral tissue. We also carried out sequencing, phylogenetic analysis and molecular clock. FINDINGS Histopathologic analysis from horse cerebral tissue showed injury related to encephalitis and WNV infection was confirmed by immunohistochemistry. The virus was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) from brain tissue and subsequently isolated in C6/36 cells. WNV full-length genome was sequenced showing the isolated strain belongs to lineage 1a. The molecular clock indicated that Brazilian WNV strain share the same common ancestor that were circulating in US during 2002-2005. MAIN CONCLUSIONS Here we report the first isolation of WNV in Brazil from a horse with neurologic disease, which was clustered into lineage 1a with others US WNV strains isolated in beginning of 2000’s decade

Zika virus in the Americas: Early epidemiological and genetic findings

Submitted by sandra infurna ([email protected]) on 2016-06-21T16:53:42Z No. of bitstreams: 1 gonzalo2_bello_etal_IOC_2016.pdf: 1066180 bytes, checksum: d43c1cf1b828de79e634ed276cc62178 (MD5)Approved for entry into archive by sandra infurna ([email protected]) on 2016-06-21T17:27:43Z (GMT) No. of bitstreams: 1 gonzalo2_bello_etal_IOC_2016.pdf: 1066180 bytes, checksum: d43c1cf1b828de79e634ed276cc62178 (MD5)Made available in DSpace on 2016-06-21T17:27:43Z (GMT). No. of bitstreams: 1 gonzalo2_bello_etal_IOC_2016.pdf: 1066180 bytes, checksum: d43c1cf1b828de79e634ed276cc62178 (MD5) Previous issue date: 2016Submitted by Angelo Silva ([email protected]) on 2016-07-07T11:16:45Z No. of bitstreams: 3 gonzalo2_bello_etal_IOC_2016.pdf.txt: 51037 bytes, checksum: bebf604bcb5623ddff92fec2bebc02a5 (MD5) gonzalo2_bello_etal_IOC_2016.pdf: 1066180 bytes, checksum: d43c1cf1b828de79e634ed276cc62178 (MD5) license.txt: 2991 bytes, checksum: 5a560609d32a3863062d77ff32785d58 (MD5)Approved for entry into archive by sandra infurna ([email protected]) on 2016-07-07T11:43:23Z (GMT) No. of bitstreams: 3 license.txt: 2991 bytes, checksum: 5a560609d32a3863062d77ff32785d58 (MD5) gonzalo2_bello_etal_IOC_2016.pdf: 1066180 bytes, checksum: d43c1cf1b828de79e634ed276cc62178 (MD5) gonzalo2_bello_etal_IOC_2016.pdf.txt: 51037 bytes, checksum: bebf604bcb5623ddff92fec2bebc02a5 (MD5)Made available in DSpace on 2016-07-07T11:43:23Z (GMT). No. of bitstreams: 3 license.txt: 2991 bytes, checksum: 5a560609d32a3863062d77ff32785d58 (MD5) gonzalo2_bello_etal_IOC_2016.pdf: 1066180 bytes, checksum: d43c1cf1b828de79e634ed276cc62178 (MD5) gonzalo2_bello_etal_IOC_2016.pdf.txt: 51037 bytes, checksum: bebf604bcb5623ddff92fec2bebc02a5 (MD5) Previous issue date: 2016Ministério da Saúde. Instituto Evandro Chagas, Centro de Inovação tecnológica. Ananindeua, PA, Brasil / University of Oxford. Department of Zoology. Oxford, UK.Ministério da Saúde. Instituto Evandro Chagas. Departamento de Arbovirologia e Febres Hemorrágicas. Ananindeua, PA, Brasil.University of Oxford. Department of Zoology. Oxford, UK.Universidade de São Paulo. Instituto Adolfo Lutz. São Paulo, SP, Brasil.Universidade de São Paulo. Instituto Adolfo Lutz. São Paulo, SP, Brasil.University of Oxford. Department of Zoology. Oxford, UK.University of Oxford. Department of Zoology. Oxford, UK.University of Oxford. Department of Zoology. Oxford, UK.University of Oxford. Wellcome Trust Centre for Human Genetics. Oxford, UK.University of Oxford. Wellcome Trust Centre for Human Genetics. Oxford, UK.Universidade de São Paulo. Instituto Adolfo Lutz. São Paulo, SP, Brasil.Universidade de São Paulo. Instituto Adolfo Lutz. São Paulo, SP, Brasil.Universidade de São Paulo. Instituto Adolfo Lutz. São Paulo, SP, Brasil.Universidade de São Paulo. Instituto Adolfo Lutz. São Paulo, SP, Brasil.Universidade de São Paulo. Instituto Adolfo Lutz. São Paulo, SP, Brasil.Universidade de São Paulo. Instituto Adolfo Lutz. São Paulo, SP, Brasil.Ministério da Saúde. Instituto Evandro Chagas. Departamento de Arbovirologia e Febres Hemorrágicas. Ananindeua, PA, Brasil.Ministério da Saúde. Instituto Evandro Chagas. Departamento de Arbovirologia e Febres Hemorrágicas. Ananindeua, PA, Brasil.Ministério da Saúde. Instituto Evandro Chagas. Departamento de Arbovirologia e Febres Hemorrágicas. Ananindeua, PA, Brasil.Ministério da Saúde. Instituto Evandro Chagas. Departamento de Arbovirologia e Febres Hemorrágicas. Ananindeua, PA, Brasil.Ministério da Saúde. Instituto Evandro Chagas. Departamento de Arbovirologia e Febres Hemorrágicas. Ananindeua, PA, Brasil.Ministério da Saúde. Instituto Evandro Chagas. Departamento de Arbovirologia e Febres Hemorrágicas. Ananindeua, PA, Brasil.Ministério da Saúde. Instituto Evandro Chagas. Departamento de Arbovirologia e Febres Hemorrágicas. Ananindeua, PA, Brasil.Ministério da Saúde. Instituto Evandro Chagas. Departamento de Arbovirologia e Febres Hemorrágicas. Ananindeua, PA, Brasil.Ministério da Saúde. Instituto Evandro Chagas. Departamento de Arbovirologia e Febres Hemorrágicas. Ananindeua, PA, Brasil.Ministério da Saúde. Instituto Evandro Chagas. Departamento de Arbovirologia e Febres Hemorrágicas. Ananindeua, PA, Brasil.Ministério da Saúde. Instituto Evandro Chagas. Departamento de Arbovirologia e Febres Hemorrágicas. Ananindeua, PA, Brasil.Ministério da Saúde. Instituto Evandro Chagas. Departamento de Arbovirologia e Febres Hemorrágicas. Ananindeua, PA, Brasil.Ministério da Saúde. Instituto Evandro Chagas. Departamento de Arbovirologia e Febres Hemorrágicas. Ananindeua, PA, Brasil.Ministério da Saúde. Instituto Evandro Chagas. Departamento de Arbovirologia e Febres Hemorrágicas. Ananindeua, PA, Brasil.University of Oxford. Department of Zoology. Oxford, UK / Metabiota. San Francisco, CA 94104, USA.University of Oxford. Department of Zoology. Oxford, UK.University of Oxford. Department of Zoology. Oxford, UK.Fundação Oswaldo Cruz. Salvador, BA, Brasil.Universidade Estadual de Feira de Santana, Feira de Santana. Departamento de Saúde. Centro de Pós-Graduação em Saúde Coletiva. Feira de Santana, BA, Brasil.Fundação Oswaldo Cruz. Salvador, BA, Brasil.University of Washington. Institute for Health Metrics and Evaluation,. Seattle, WA, USA / University of Oxford. Wellcome Trust Centre for Human Genetics. Oxford, UK.Ministério da Saúde. Instituto Evandro Chagas, Centro de Inovação tecnológica. Ananindeua, PA, Brasil.Ministério da Saúde. Instituto Evandro Chagas, Centro de Inovação tecnológica. Ananindeua, PA, BrasilMinistério da Saúde. Instituto Evandro Chagas, Centro de Inovação tecnológica. Ananindeua, PA, BrasilMinistério da Saúde. Instituto Evandro Chagas, Centro de Inovação tecnológica. Ananindeua, PA, BrasilMinistério da Saúde. Instituto Evandro Chagas, Centro de Inovação tecnológica. Ananindeua, PA, BrasilMinistério da Saúde. Instituto Evandro Chagas, Centro de Inovação tecnológica. Ananindeua, PA, BrasilMinistério da Saúde. Instituto Evandro Chagas, Centro de Inovação tecnológica. Ananindeua, PA, BrasilMinistério da Saúde. Instituto Evandro Chagas, Centro de Inovação tecnológica. Ananindeua, PA, BrasilMinistério da Saúde. Instituto Evandro Chagas, Centro de Inovação tecnológica. Ananindeua, PA, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.Li Ka Shing Knowledge Institute. St. Michael’s Hospital. Toronto, Canada / University of Toronto. Department of Medicine. Division of Infectious Diseases. Toronto, Canada.University of Toronto.Dalla Lana School of Public Health. Toronto, Canada;Brasil. Ministério da Saúde. Brasília, DF, Brasil.Brasil. Ministério da Saúde. Brasília, DF, Brasil.University of Texas Medical Branch. Department of Pathology. Galveston, TX, USA.University of Oxford. Department of Zoology. Oxford, UK / Metabiota. San Francisco, CA 94104, USA.Ministério da Saúde. Instituto Evandro Chagas, Centro de Inovação tecnológica. Ananindeua, PA, Brasil / University of Texas Medical Branch. Department of Pathology. Galveston, TX, USA.Ministério da Saúde. Instituto Evandro Chagas. Departamento de Arbovirologia e Febres Hemorrágicas. Ananindeua, PA, Brasil.Brazil has experienced an unprecedented epidemic of Zika virus (ZIKV), with ~30,000 cases reported to date. ZIKV was first detected in Brazil in May 2015 and cases of microcephaly potentially associated with ZIKV infection were identified in November 2015. Using next generation sequencing we generated seven Brazilian ZIKV genomes, sampled from four self-limited cases, one blood donor, one fatal adult case, and one newborn with microcephaly and congenital malformations. Phylogenetic and molecular clock analyses show a single introduction of ZIKV into the Americas, estimated to have occurred between May-Dec 2013, more than 12 months prior to the detection of ZIKV in Brazil. The estimated date of origin coincides with an increase in air passengers to Brazil from ZIKV endemic areas, and with reported outbreaks in Pacific Islands. ZIKV genomes from Brazil are phylogenetically interspersed with those from other South American and Caribbean countries. Mapping mutations onto existing structural models revealed the context of viral amino acid changes present in the outbreak lineage; however no shared amino acid changes were found among the three currently available virus genomes from microcephaly cases. Municipality-level incidence data indicate that reports of suspected microcephaly in Brazil best correlate with ZIKV incidence around week 17 of pregnancy, although this does not demonstrate causation. Our genetic description and analysis of ZIKV isolates in Brazil provide a baseline for future studies of the evolution and molecular epidemiology in the Americas of this emerging virus

Data from: Zika virus in the Americas: early epidemiological and genetic findings

Brazil has experienced an unprecedented epidemic of Zika virus (ZIKV), with ~30,000 cases reported to date. ZIKV was first detected in Brazil in May 2015 and cases of microcephaly potentially associated with ZIKV infection were identified in November 2015. Using next generation sequencing we generated seven Brazilian ZIKV genomes, sampled from four self-limited cases, one blood donor, one fatal adult case, and one newborn with microcephaly and congenital malformations. Phylogenetic and molecular clock analyses show a single introduction of ZIKV into the Americas, estimated to have occurred between May-Dec 2013, more than 12 months prior to the detection of ZIKV in Brazil. The estimated date of origin coincides with an increase in air passengers to Brazil from ZIKV endemic areas, and with reported outbreaks in Pacific Islands. ZIKV genomes from Brazil are phylogenetically interspersed with those from other South American and Caribbean countries. Mapping mutations onto existing structural models revealed the context of viral amino acid changes present in the outbreak lineage; however no shared amino acid changes were found among the three currently available virus genomes from microcephaly cases. Municipality-level incidence data indicate that reports of suspected microcephaly in Brazil best correlate with ZIKV incidence around week 17 of pregnancy, although this does not demonstrate causation. Our genetic description and analysis of ZIKV isolates in Brazil provide a baseline for future studies of the evolution and molecular epidemiology in the Americas of this emerging virus

Epidemiological Data: Numbers of suspected ZIKV cases and suspected microcephaly cases per state and per epidemiological week.

Contains 1) CSV file with number suspected ZIKV cases from January 2015 to the end of December 2015; 2) CSV file with number of suspected microcephaly cases from January 2015 to the first week of January 2016. Numbers correspond to suspected microcephaly cases at week 20 of pregnancy; 3) CSV file with codes of state of residence and municipality of residence in Brazil; and 4) R scripts for correlation analysis described in SI Section 1.5

Sequence data details and alignments for dataset A and B.

Contains (1) table with accession numbers, isolate names, cell passage history, publication details, country/location of sampling, sampling dates and (2) Fasta format sequence alignments of datasets A and B

BEAST XML input file used for genetic analysis.

BEAST XML input file used to generate Figure 3 under a strict clock model, a Bayesian skyline coalescent prior and a CTMC prior on the clock rate