Analysis of the immunological biomarker profile during acute Zika virus infection reveals the overexpression of CXCL10, a chemokine linked to neuronal damage.

BACKGROUND: Infection with Zika virus (ZIKV) manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications and little is known about Zika immunopathogenesis. OBJECTIVES: To define the immunologic biomarkers that correlate with acute ZIKV infection. METHODS: We characterized the levels of circulating cytokines, chemokines, and growth factors in 54 infected patients of both genders at five different time points after symptom onset using microbeads multiplex immunoassay; comparison to 100 age-matched controls was performed for statistical analysis and data mining. FINDINGS: ZIKV-infected patients present a striking systemic inflammatory response with high levels of pro-inflammatory mediators. Despite the strong inflammatory pattern, IL-1Ra and IL-4 are also induced during the acute infection. Interestingly, the inflammatory cytokines IL-1β, IL-13, IL-17, TNF-α, and IFN-γ; chemokines CXCL8, CCL2, CCL5; and the growth factor G-CSF, displayed a bimodal distribution accompanying viremia. While this is the first manuscript to document bimodal distributions of viremia in ZIKV infection, this has been documented in other viral infections, with a primary viremia peak during mild systemic disease and a secondary peak associated with distribution of the virus to organs and tissues. MAIN CONCLUSIONS: Biomarker network analysis demonstrated distinct dynamics in concurrence with the bimodal viremia profiles at different time points during ZIKV infection. Such a robust cytokine and chemokine response has been associated with blood-brain barrier permeability and neuroinvasiveness in other flaviviral infections. High-dimensional data analysis further identified CXCL10, a chemokine involved in foetal neuron apoptosis and Guillain-Barré syndrome, as the most promising biomarker of acute ZIKV infection for potential clinical application

Analysis of the immunological biomarker profile during acute zika virus infection reveals the overexpression of CXCL10, a chemokine linked to neuronal damage

BACKGROUND Infection with Zika virus (ZIKV) manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications and little is known about Zika immunopathogenesis. OBJECTIVES To define the immunologic biomarkers that correlate with acute ZIKV infection. METHODS We characterized the levels of circulating cytokines, chemokines, and growth factors in 54 infected patients of both genders at five different time points after symptom onset using microbeads multiplex immunoassay; comparison to 100 age-matched controls was performed for statistical analysis and data mining. FINDINGS ZIKV-infected patients present a striking systemic inflammatory response with high levels of pro-inflammatory mediators. Despite the strong inflammatory pattern, IL-1Ra and IL-4 are also induced during the acute infection. Interestingly, the inflammatory cytokines IL-1β, IL-13, IL-17, TNF-α, and IFN-γ; chemokines CXCL8, CCL2, CCL5; and the growth factor G-CSF, displayed a bimodal distribution accompanying viremia. While this is the first manuscript to document bimodal distributions of viremia in ZIKV infection, this has been documented in other viral infections, with a primary viremia peak during mild systemic disease and a secondary peak associated with distribution of the virus to organs and tissues. MAIN CONCLUSIONS Biomarker network analysis demonstrated distinct dynamics in concurrence with the bimodal viremia profiles at different time points during ZIKV infection. Such a robust cytokine and chemokine response has been associated with blood-brain barrier permeability and neuroinvasiveness in other flaviviral infections. High-dimensional data analysis further identified CXCL10, a chemokine involved in foetal neuron apoptosis and Guillain-Barré syndrome, as the most promising biomarker of acute ZIKV infection for potential clinical application. © 2018, Fundacao Oswaldo Cruz. All rights reserved

Evidence of vertical transmission of Zika virus in field-collected eggs of Aedes aegypti in the Brazilian Amazon

Submitted by Sandra Infurna ([email protected]) on 2019-01-30T13:19:42Z No. of bitstreams: 1 JosebentoP_lima_etal_IOC_2018.pdf: 2186937 bytes, checksum: 1bcfe5efb7efff29cb5e91310e411791 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-01-30T13:43:48Z (GMT) No. of bitstreams: 1 JosebentoP_lima_etal_IOC_2018.pdf: 2186937 bytes, checksum: 1bcfe5efb7efff29cb5e91310e411791 (MD5)Made available in DSpace on 2019-01-30T13:43:48Z (GMT). No. of bitstreams: 1 JosebentoP_lima_etal_IOC_2018.pdf: 2186937 bytes, checksum: 1bcfe5efb7efff29cb5e91310e411791 (MD5) Previous issue date: 2018Fundação Estadual de Vigilância em Saúde do Amazonas. Departamento de Vigilância Ambiental. Manaus, AM. Brasil.Fiocruz Amazônia. Instituto Leônidas e Maria Deane. Laboratório de Ecologia de Doenças Transmissíveis da Amazônia. Manaus, AM, Brasil / Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane. Programa de Iniciação Científica. Manaus, AM. Brasil.Fiocruz Amazônia. Instituto Leônidas e Maria Deane. Laboratório de Ecologia de Doenças Transmissíveis da Amazônia. Manaus, AM, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Programa de Pós-Graduação em Biologia Celular e Molecular. Rio de Janeiro, RJ, Brasil.Fiocruz Amazônia. Instituto Leônidas e Maria Deane. Laboratório de Ecologia de Doenças Transmissíveis da Amazônia. Manaus, AM, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Programa de Pós-Graduação em Biologia Celular e Molecular. Rio de Janeiro, RJ, Brasil.Fiocruz Amazônia. Instituto Leônidas e Maria Deane. Laboratório de Ecologia de Doenças Transmissíveis da Amazônia. Manaus, AM, Brasil / Universidade Federal do Amazonas. Programa de Pós-Graduação em Imunologia Básica e Aplicada. Manaus, AM, Brasil.Fundação Estadual de Vigilância em Saúde do Amazonas. Departamento de Vigilância Ambiental. Manaus, AM. Brasil.Fundação Estadual de Vigilância em Saúde do Amazonas. Departamento de Vigilância Ambiental. Manaus, AM. Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Fisiologia e Controle de Artrópodes Vetores. Rio de Janeiro, RJ, Brasil.Fundação Estadual de Vigilância em Saúde do Amazonas. Departamento de Vigilância Ambiental. Manaus, AM. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Fisiologia e Controle de Artrópodes Vetores. Rio de Janeiro, RJ, Brasil.Fiocruz Amazônia. Instituto Leônidas e Maria Deane. Laboratório de Ecologia de Doenças Transmissíveis da Amazônia. Manaus, AM, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Programa de Pós-Graduação em Biologia Celular e Molecular. Rio de Janeiro, RJ, Brasil / Fiocruz Amazônia. Instituto Leônidas e Maria Deane. Programa de Pós-Graduação em Biologia da Interação Patógeno-Hospedeiro. Manaus, AM, Brasil.Arboviruses are viruses transmitted to humans and other animals by the bite of hematophagous arthropods. Infections caused by chikungunya virus (CHIKV), dengue virus (DENV), Zika virus (ZIKV), and the deadlier yellow fever virus (YFV) are current public health problems in several countries, mainly those located in tropical and subtropical regions. One of the main prevention strategies continues to be vector control, with the elimination of breeding sites and surveillance of infested areas. The use of ovitraps for Aedes mosquitos monitoring has already demonstrated promising results, and maybe be also useful for arboviral surveillance

Oropouche virus detection in saliva and urine

Submitted by Sandra Infurna ([email protected]) on 2020-03-20T18:14:45Z No. of bitstreams: 1 ValdineteA_Nascimento_etal_IOC_2020.pdf: 1633279 bytes, checksum: 6476856a2fea50dbc68fc042cca925c6 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2020-03-20T18:25:29Z (GMT) No. of bitstreams: 1 ValdineteA_Nascimento_etal_IOC_2020.pdf: 1633279 bytes, checksum: 6476856a2fea50dbc68fc042cca925c6 (MD5)Made available in DSpace on 2020-03-20T18:25:29Z (GMT). No. of bitstreams: 1 ValdineteA_Nascimento_etal_IOC_2020.pdf: 1633279 bytes, checksum: 6476856a2fea50dbc68fc042cca925c6 (MD5) Previous issue date: 2020Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane. Manaus, AM, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Programa de Pós-Graduação em Biologia Celular e Molecular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Amazonas. Manaus, AM, Brasil / Hospital Adventista de Manaus. Manaus, AM, Brasil.Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane. Manaus, AM, Brasil.Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane. Manaus, AM, Brasil / Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane; Programa de Pós-Graduação em Biologia da Interação Patógeno-Hospedeiro. Manaus, AM, Brasil.Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane. Manaus, AM, Brasil / Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane; Programa de Pós-Graduação em Biologia da Interação Patógeno-Hospedeiro. Manaus, AM, Brasil.Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane. Manaus, AM, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Programa de Pós-Graduação em Biologia Celular e Molecular. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Amazonas. Manaus, AM, Brasil.Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane. Manaus, AM, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Programa de Pós-Graduação em Biologia Celular e Molecular. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz-Fiocruz, Instituto Leônidas e Maria Deane, Programa de Pós-Graduação em Biologia da Interação Patógeno-Hospedeiro, Manaus, AM, Brasil.Oropouche virus (OROV) is an arthropod-borne virus of the Peribunyaviridae family, transmitted to humans primarily by Culicoides paraensis. It is one of the main arboviruses infecting humans in Brazil, primarily in the Amazon Region. Here, we report the detection of OROV in the saliva and urine of a patient whose samples were collected five days after the onset of symptoms. Nucleotide sequencing and phylogenetic analysis further confirmed the results. To our knowledge, this is the first study reporting the detection of OROV in the saliva and urine of an infected patient. In addition, the results of our study expand the current knowledge pertaining to the natural history of Oropouche fever

Map of the Itacoatiara city in the context of the Amazonas State, Brazil.

<p>The location of each ovitrap is represented by a black diamond. The red circles represent the location of positive arbovirus ovitraps. The red triangle represents the human Zika case.</p

Strand-specific amplification of ZIKV RNA from infected <i>Aedes aegypti</i> larvae.

<p>Strand-specific amplification of ZIKV RNA from infected <i>Aedes aegypti</i> larvae.</p

Molecular characterisation of the emerging measles virus from Roraima state, Brazil, 2018

Measles is a human infectious disease of global concern that is caused by the measles virus. In this study, we report the complete genome sequencing of one measles virus isolate, genotype D8, that was obtained directly from a urine sample in Boa Vista city, the capital of Roraima state in Brazil. Phylogenetic reconstruction grouped the genome described in this study with that of samples from Australia, South Korea, and Italy. To our knowledge, this is the first complete genome sequence of a wild-type measles virus reported from Latin America. Therefore, the present data strengthen the current knowledge on the molecular epidemiology of measles worldwide

A multi-country analysis of COVID-19 hospitalizations by vaccination status

Background: Individuals vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), when infected, can still develop disease&nbsp;that requires hospitalization. It remains unclear whether these patients differ from hospitalized unvaccinated patients with regard to presentation, coexisting comorbidities, and outcomes. Methods: Here, we use data from an international consortium to study this&nbsp;question and assess whether differences between these groups are&nbsp;context specific. Data from 83,163 hospitalized COVID-19 patients (34,843 vaccinated, 48,320 unvaccinated) from 38 countries were analyzed. Findings: While typical symptoms were more often reported in unvaccinated patients, comorbidities, including some associated with worse prognosis in previous studies, were more common in vaccinated patients. Considerable between-country variation in both in-hospital fatality risk and vaccinated-versus-unvaccinated difference in this outcome was observed. Conclusions: These findings will inform allocation of healthcare resources in future surges as well as design of longer-term international studies to characterize changes in clinical profile of hospitalized COVID-19 patients related to vaccination history. Funding: This work was made possible by the UK Foreign, Commonwealth and Development Office and Wellcome (215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z, and 220757/Z/20/Z); the Bill&nbsp;&amp; Melinda Gates&nbsp;Foundation (OPP1209135); and the philanthropic support of the donors&nbsp;to the University of Oxford's COVID-19 Research Response Fund (0009109). Additional funders are listed in the "acknowledgments" section

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research