부산대학교 도서관

Summary Background Cases of human monkeypox are rarely seen outside of west and central Africa. There are few data regarding viral kinetics or the duration of viral shedding and no licensed treatments. Two oral drugs, brincidofovir and tecovirimat, have been approved for treatment of smallpox and have demonstrated efficacy against monkeypox in animals. Our aim was to describe the longitudinal clinical course of monkeypox in a high-income setting, coupled with viral dynamics, and any adverse events related to novel antiviral therapies. Methods In this retrospective observational study, we report the clinical features, longitudinal virological findings, and response to off-label antivirals in seven patients with monkeypox who were diagnosed in the UK between 2018 and 2021, identified through retrospective case-note review. This study included all patients who were managed in dedicated high consequence infectious diseases (HCID) centres in Liverpool, London, and Newcastle, coordinated via a national HCID network. Findings We reviewed all cases since the inception of the HCID (airborne) network between Aug 15, 2018, and Sept 10, 2021, identifying seven patients. Of the seven patients, four were men and three were women. Three acquired monkeypox in the UK: one patient was a health-care worker who acquired the virus nosocomially, and one patient who acquired the virus abroad transmitted it to an adult and child within their household cluster. Notable disease features included viraemia, prolonged monkeypox virus DNA detection in upper respiratory tract swabs, reactive low mood, and one patient had a monkeypox virus PCR-positive deep tissue abscess. Five patients spent more than 3 weeks (range 22--39 days) in isolation due to prolonged PCR positivity. Three patients were treated with brincidofovir (200 mg once a week orally), all of whom developed elevated liver enzymes resulting in cessation of therapy. One patient was treated with tecovirimat (600 mg twice daily for 2 weeks orally), experienced no adverse effects, and had a shorter duration of viral shedding and illness (10 days hospitalisation) compared with the other six patients. One patient experienced a mild relapse 6 weeks after hospital discharge. Interpretation Human monkeypox poses unique challenges, even to well resourced health-care systems with HCID networks. Prolonged upper respiratory tract viral DNA shedding after skin lesion resolution challenged current infection prevention and control guidance. There is an urgent need for prospective studies of antivirals for this disease. Funding None. Author Affiliation: (a) Tropical and Infectious Disease Unit, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK (b) Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK (c) Directorate of Infection, Guy's & St Thomas' NHS Foundation Trust, London, UK (d) Department of Paediatric Infectious Diseases, Alder Hey Children's NHS Foundation Trust, Liverpool, UK (e) Respiratory Unit, Alder Hey Children's NHS Foundation Trust, Liverpool, UK (f) Rare and Imported Pathogens Laboratory, UK Health Security Agency, Porton Down, Salisbury, UK (g) University College London, London, UK (h) Department of Infection and Tropical Medicine, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle, UK (i) Translational and Clinical Research Institute, Immunity and Inflammation Theme, Newcastle University, Newcastle Upon Tyne, UK (j) Department of Infectious Diseases, Royal Free London NHS Foundation Trust, London, UK (k) Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK (l) National Infection Service, UK Health Security Agency, London, UK (m) Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK (n) NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK (o) Royal Devon and Exeter NHS Foundation Trust, Exeter, UK (p) Department of Infectious Diseases, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Sheffield (q) World Health Organization Collaborating Centre on Tuberculosis and Social Medicine, Department of Global Public Health, Karolinska Institute, Stockholm, Sweden * Correspondence to: Dr Nicholas M Price, Directorate of Infection, Guy's & St Thomas' NHS Foundation Trust, Westminster Bridge Road, London SE1 7EH, UK (footnote)* Contributed equally (footnote)[Dagger] Members are listed in the appendix Byline: Hugh Adler, PhD (a,b), Susan Gould, MRCP (a,b), Paul Hine, MRCP (a,b), Luke B Snell, MRCP (c), Waison Wong, MRCPCH (d), Catherine F Houlihan, PhD (f,g), Jane C Osborne, PhD (f), Tommy Rampling, DPhil (f,g), Mike BJ Beadsworth, MD (a,b), Christopher JA Duncan, DPHil (h,i), Jake Dunning, PhD (j,k,l), Tom E Fletcher, PhD (a,b), Ewan R Hunter, PhD (h), Michael Jacobs, PhD (g,j), Prof Saye H Khoo, MD (a,m), William Newsholme, FRCP (c), David Porter, PhD (d), Robert J Porter, FRCPath (o), Libuse Ratcliffe, MRCP (a), Matthias L Schmid, MD (h), Prof Malcolm G Semple, PhD (e,n), Anne J Tunbridge, FRCP (p), Tom Wingfield, PhD (a,b,q), Nicholas M Price, PhD [nicholas.price@gstt.nhs.uk] (c), Mike Abouyannis, Asma Al-Balushi, Stephen Aston, Robert Ball, Nicholas J Beeching, Thomas J Blanchard, Ffion Carlin, Geraint Davies, Angela Gillespie, Scott R Hicks, Marie-Claire Hoyle, Chinenye Ilozue, Luke Mair, Suzanne Marshall, Anne Neary, Emmanuel Nsutebu, Samantha Parker, Hannah Ryan, Lance Turtle, Chris Smith, Jon van Aartsen, Naomi F Walker, Stephen Woolley, Anu Chawla, Ian Hart, Anna Smielewska, Elizabeth Joekes, Cathryn Benson, Cheryl Brindley, Urmi Das, Chin K Eyton-Chong, Claire Gnanalingham, Clare Halfhide, Beatriz Larru, Sarah Mayell, Joanna McBride, Claire Oliver, Princy Paul, Andrew Riordan, Lekha Sridhar, Megan Storey, Audrey Abdul, Jennifer Abrahamsen, Breda Athan, Sanjay Bhagani, Colin S Brown, Oliver Carpenter, Ian Cropley, Kerrie Frost, Susan Hopkins, Jessica Joyce, Lucy Lamb, Adrian Lyons, Tabitha Mahungu, Stephen Mepham, Edina Mukwaira, Alison Rodger, Caroline Taylor, Simon Warren, Alan Williams, Debbie Levitt, Denise Allen, Jill Dixon, Adam Evans, Pauline McNicholas, Brendan Payne, D Ashley Price, Uli Schwab, Allison Sykes, Yusri Taha, Margaret Ward, Marieke Emonts, Stephen Owens, Alina Botgros, Sam T Douthwaite, Anna Goodman, Akish Luintel, Eithne MacMahon, Gaia Nebbia, Geraldine O'Hara, Joseph Parsons, Ashwin Sen, Daniel Stevenson, Tadgh Sullivan, Usman Taj, Claire van Nipsen tot Pannerden, Helen Winslow, Ewa Zatyka, Ekene Alozie-Otuka, Csaba Beviz, Yusupha Ceesay, Latchmin Gargee, Morloh Kabia, Hannah Mitchell, Shona Perkins, Mingaile Sasson, Kamal Sehmbey, Federico Tabios, Neil Wigglesworth, Emma J Aarons, Tim Brooks, Matthew Dryden, Jenna Furneaux, Barry Gibney, Jennifer Small, Elizabeth Truelove, Clare E Warrell, Richard Firth, Gemma Hobson, Christopher Johnson, Alison Dewynter, Sebastian Nixon, Oliver Spence, Joachim J Bugert, Dennis E Hruby