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      An Intranasal Exposure Model of Lethal Nipah Virus Infection in African Green Monkeys

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          Abstract

          Due to the difficulty in conducting clinical trials for vaccines and treatments against Nipah virus (NiV), licensure will likely require animal models, most importantly non-human primates (NHPs). The NHP models of infection have primarily relied on intratracheal instillation or small particle aerosolization of NiV. However, neither of these routes adequately models natural mucosal exposure to NiV. To develop a more natural NHP model, we challenged African green monkeys with the Bangladesh strain of NiV by the intranasal route using the laryngeal mask airway (LMA) mucosal atomization device (MAD). LMA MAD exposure resulted in uniformly lethal disease that accurately reflected the human condition.

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          Exhaled droplets due to talking and coughing.

          Respiratory infections can be spread via 'contact' with droplets from expiratory activities such as talking, coughing and sneezing, and also from aerosol-generating clinical procedures. Droplet sizes predominately determine the times they can remain airborne, the possibility of spread of infectious diseases and thus the strategies for controlling the infections. While significant inconsistencies exist between the existing measured data on respiratory droplets generated during expiratory activities, a food dye was used in the mouth during measurements of large droplets, which made the expiratory activities 'unnatural'. We carried out a series of experiments using glass slides and a microscope as well as an aerosol spectrometer to measure the number and size of respiratory droplets produced from the mouth of healthy individuals during talking and coughing with and without a food dye. The total mass of respiratory droplets was measured using a mask, plastic bag with tissue and an electronic balance with a high precision. Considerable subject variability was observed and the average size of droplets captured using glass slides and microscope was about 50-100 microm. Smaller droplets were also detected by the aerosol spectrometer. More droplets seemed to be generated when a food dye was used.
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            Genetic Characterization of Nipah Virus, Bangladesh, 2004

            Until 2004, identification of Nipah virus (NV)-like outbreaks in Bangladesh was based on serology. We describe the genetic characterization of a new strain of NV isolated during outbreaks in Bangladesh (NV-B) in 2004, which confirms that NV was the etiologic agent responsible for these outbreaks.
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              Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge

              Nipah virus is an emerging pathogen in the Paramyxoviridae family. Upon transmission of Nipah virus from its natural reservoir, Pteropus spp. fruit bats, to humans, it causes respiratory and neurological disease with a case-fatality rate about 70%. Human-to-human transmission has been observed during Nipah virus outbreaks in Bangladesh and India. A therapeutic treatment for Nipah virus disease is urgently needed. Here, we tested the efficacy of remdesivir (GS-5734), a broad-acting antiviral nucleotide prodrug, against Nipah virus Bangladesh genotype in African green monkeys. Animals were inoculated with a lethal dose of Nipah virus, and a once-daily intravenous remdesivir treatment was initiated 24 hours later and continued for 12 days. Mild respiratory signs were observed in two of four treated animals, whereas all control animals developed severe respiratory disease signs. In contrast to control animals, which all succumbed to the infection, all remsdesivir-treated animals survived the lethal challenge, indicating that remdesivir represents a promising antiviral treatment for Nipah virus infection.
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                Author and article information

                Journal
                J Infect Dis
                J. Infect. Dis
                jid
                The Journal of Infectious Diseases
                Oxford University Press (US )
                0022-1899
                1537-6613
                01 May 2020
                30 October 2019
                30 October 2019
                : 221
                : Suppl 4 , Twenty Years of Nipah Virus Research
                : S414-S418
                Affiliations
                [1 ] Galveston National Laboratory , Galveston
                [2 ] Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston
                Author notes
                Correspondence: T. W. Geisbert, PhD, University of Texas Medical Branch at Galveston, Galveston National Laboratory, 301 University Blvd., Galveston, TX 77550-0610 ( twgeisbe@ 123456utmb.edu ).
                Article
                jiz391
                10.1093/infdis/jiz391
                7213566
                31665362
                cc0829fa-73ad-4182-94ad-5e3ce05d498f
                © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 30 October 2019
                Page count
                Pages: 9
                Categories
                Supplement Articles
                AcademicSubjects/MED00860
                AcademicSubjects/MED00290

                Infectious disease & Microbiology
                animal model,henipavirus,nipah virus,pathogenesis,primate
                Infectious disease & Microbiology
                animal model, henipavirus, nipah virus, pathogenesis, primate

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