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Sökning: WFRF:(Falconar Andrew K.)

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1.
  • Wilder-Smith, Annelies, et al. (författare)
  • ZikaPLAN : addressing the knowledge gaps and working towards a research preparedness network in the Americas
  • 2019
  • Ingår i: Global Health Action. - : Taylor & Francis. - 1654-9716 .- 1654-9880. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Zika Preparedness Latin American Network (ZikaPLAN) is a research consortium funded by the European Commission to address the research gaps in combating Zika and to establish a sustainable network with research capacity building in the Americas. Here we present a report on ZikaPLAN`s mid-term achievements since its initiation in October 2016 to June 2019, illustrating the research objectives of the 15 work packages ranging from virology, diagnostics, entomology and vector control, modelling to clinical cohort studies in pregnant women and neonates, as well as studies on the neurological complications of Zika infections in adolescents and adults. For example, the Neuroviruses Emerging in the Americas Study (NEAS) has set up more than 10 clinical sites in Colombia. Through the Butantan Phase 3 dengue vaccine trial, we have access to samples of 17,000 subjects in 14 different geographic locations in Brazil. To address the lack of access to clinical samples for diagnostic evaluation, ZikaPLAN set up a network of quality sites with access to well-characterized clinical specimens and capacity for independent evaluations. The International Committee for Congenital Anomaly Surveillance Tools was formed with global representation from regional networks conducting birth defects surveillance. We have collated a comprehensive inventory of resources and tools for birth defects surveillance, and developed an App for low resource regions facilitating the coding and description of all major externally visible congenital anomalies including congenital Zika syndrome. Research Capacity Network (REDe) is a shared and open resource centre where researchers and health workers can access tools, resources and support, enabling better and more research in the region. Addressing the gap in research capacity in LMICs is pivotal in ensuring broad-based systems to be prepared for the next outbreak. Our shared and open research space through REDe will be used to maximize the transfer of research into practice by summarizing the research output and by hosting the tools, resources, guidance and recommendations generated by these studies. Leveraging on the research from this consortium, we are working towards a research preparedness network.
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2.
  • Boeras, Debi, et al. (författare)
  • Evaluation of Zika rapid tests as aids for clinical diagnosis and epidemic preparedness
  • 2022
  • Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 49
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Development and evaluation of diagnostics for diseases of epidemic potential are often funded during epidemics, but not afterwards, leaving countries unprepared for the next epidemic. United Nations Children's Emergency Fund (UNICEF) partnered with the United States Agency for International Development (USAID) to address this important gap by investing in an advance purchase commitment (APC) mechanism to accelerate the development and evaluation of Zika rapid diagnostic tests (RDTs) for case detection and surveillance. This paper describes the performance evaluation of five Zika RDTs eligible for procurement.Methods: A network of European Union-funded ZikaPLAN sites in Africa, Asia, Latin America with access to relevant serum specimens were selected to evaluate RDTs developed for the UNICEF APC mechanism. A standardised protocol and evaluation panels were developed and a call for specimens for the evaluation panels issued to different sites. Each site contributed specimens to the evaluation from their biobank. Data were collated, analysed and presented to the UNICEF Procurement Review Group for review.Findings: Three RDTs met the criteria for UNICEF procurement of sensitivity and specificity of 85% against a refence standard. The sensitivity/specificity of the ChemBio anti-Zika Virus (ZIKV) immunoglobulin M (IgM) test was 86.4 %/86.7% and the ChemBio ZCD system for anti-ZIKV IgM was 79.0%/97.1%, anti-dengue virus (DENV) IgM 90.0%/89.2%, anti-Chikungunya virus (CHIKV) IgM 90.6%/97.2%. The sensitivity/specificity of the SD Biosensor anti-ZIKV IgM was 96.8 %/90.8%, anti-DENV IgM 71.8%/83.5%, the DENV nonstructural protein 1 (NS1) glycoprotein 90.0%/90.2%, anti- yellow fever virus (YFV) IgM 84.6%/92.4%, anti-CHIKV IgM 86.3%/97.5%.Interpretation: Three RDTs fulfilled the performance thresholds set by WHO and were eligible for UNICEF procurement. These tests will improve the diagnosis of ZIKV and other arboviral infections as well as providing countries with better tools for surveillance and response to future epidemics.
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3.
  • Gaunt, Michael W., et al. (författare)
  • Recombination of B- and T-cell epitope-rich loci from Aedes- and Culex-borne flaviviruses shapes Zika virus epidemiology
  • 2020
  • Ingår i: Antiviral Research. - : Elsevier. - 0166-3542 .- 1872-9096. ; 174
  • Tidskriftsartikel (refereegranskat)abstract
    • Sporadic human Zika virus (ZIKV) infections have been recorded in Africa and Asia since the 1950s. Major epidemics occurred only after ZIKV emerged in the Pacific islands and spread to the Americas. Specific biological determinants of the explosive epidemic nature of ZIKV have not been identified. Phylogenetic studies revealed incongruence in ZIKV placement in relation to Aedes-borne dengue viruses (DENV) and Cu/ex-borne flaviviruses. We hypothesized that this incongruence reflects interspecies recombination resulting in ZIKV evasion of cross-protective T-cell immunity. We investigated ZIKV phylogenetic incongruence in relation to: DENV T-cell epitope maps experimentally identified ex vivo, published B-cell epitope loci, and CD8(+) T-cell epitopes predicted in silico for mosquito-borne flaviviruses. Our findings demonstrate that the ZIKV proteome is a hybrid of Aedes-borne DENV proteins interspersed amongst Cu/ex-borne flavivirus proteins derived through independent interspecies recombination events. These analyses infer that DENV-associated proteins in the ZIKV hybrid proteome generated immunodominant human B-cell responses, whereas ZIKV recombinant derived Cu/ex-borne flavivirus-associated proteins generated immunodominant CD8(+) and/or CD4(+) T-cell responses. In silico CD8(+) T-cell epitope ZIKV cross-reactive prediction analyses verified this observation. We propose that by acquiring cytotoxic T-cell epitope-rich regions from Cu/ex-borne flaviviruses, ZIKV evaded DENV-generated T-cell immune cross-protection. Thus, Cu/ex-borne flaviviruses, including West Nile virus and Japanese encephalitis virus, might induce cross-protective T-cell responses against ZIKV. This would explain why explosive ZIKV epidemics occurred in DENV-endemic regions of Micronesia, Polynesia and the Americas where Cu/ex-borne flavivirus outbreaks are infrequent and why ZIKV did not cause major epidemics in Asia where Culex-borne flaviviruses are widespread.
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4.
  • Pettersson, John H. -O., et al. (författare)
  • How Did Zika Virus Emerge in the Pacific Islands and Latin America?
  • 2016
  • Ingår i: mBio. - 2161-2129 .- 2150-7511. ; 7:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The unexpected emergence of Zika virus (ZIKV) in the Pacific Islands and Latin America and its association with congenital Zika virus syndrome (CZVS) (which includes microcephaly) and Guillain-Barre syndrome (GBS) have stimulated wide-ranging research. High densities of susceptible Aedes spp., immunologically naive human populations, global population growth with increased urbanization, and escalation of global transportation of humans and commercial goods carrying vectors and ZIKV undoubtedly enhanced the emergence of ZIKV. However, flavivirus mutations accumulate with time, increasing the likelihood that genetic viral differences are determinants of change in viral phenotype. Based on comparative ZIKV complete genome phylogenetic analyses and temporal estimates, we identify amino acid substitutions that may be associated with increased viral epidemicity, CZVS, and GBS. Reverse genetics, vector competence, and seroepidemiological studies will test our hypothesis that these amino acid substitutions are determinants of epidemic and neurotropic ZIKV emergence.
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5.
  • Pettersson, John H.-O. 1981-, et al. (författare)
  • Re-visiting the evolution, dispersal and epidemiology of Zika virus in Asia
  • 2018
  • Ingår i: Emerging Microbes & Infections. - : Nature Publishing Group. - 2222-1751. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Based on serological evidence and viral isolation, Zika virus (ZIKV) has circulated for many years relatively benignly in a sylvatic cycle in Africa and an urban cycle in South East Asia (SEA). With the recent availability of limited but novel Indian ZIKV sequences to add to the plethora of SEA sequences, we traced the phylogenetic history and spatio-temporal dispersal pattern of ZIKV in Asia prior to its explosive emergence in the Pacific region and the Americas. These analyses demonstrated that the introduction and dispersal of ZIKV on the Pacific islands were preceded by an extended period of relatively silent transmission in SEA, enabling the virus to expand geographically and evolve adaptively before its unanticipated introduction to immunologically naive populations on the Pacific islands and in the Americas. Our findings reveal new features of the evolution and dispersal of this intriguing virus and may benefit future disease control strategies.
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