title: An observational, laboratory-based study of outbreaks of middle East respiratory syndrome coronavirus in Jeddah and Riyadh, kingdom of Saudi Arabia, 2014.
abstract: BACKGROUND
  In spring 2014, a sudden rise in the number of notified Middle East respiratory syndrome coronavirus (MERS-CoV) infections occurred across Saudi Arabia with a focus in Jeddah. Hypotheses to explain the outbreak pattern include increased surveillance, increased zoonotic transmission, nosocomial transmission, and changes in viral transmissibility, as well as diagnostic laboratory artifacts.
  
  
  METHODS
  Diagnostic results from Jeddah Regional Laboratory were analyzed. Viruses from the Jeddah outbreak and viruses occurring during the same time in Riyadh, Al-Kharj, and Madinah were fully or partially sequenced. A set of 4 single-nucleotide polymorphisms distinctive to the Jeddah outbreak were determined from additional viruses. Viruses from Riyadh and Jeddah were isolated and studied in cell culture.
  
  
  RESULTS
  Up to 481 samples were received per day for reverse transcription polymerase chain reaction (RT-PCR) testing. A laboratory proficiency assessment suggested positive and negative results to be reliable. Forty-nine percent of 168 positive-testing samples during the Jeddah outbreak stemmed from King Fahd Hospital. All viruses from Jeddah were monophyletic and similar, whereas viruses from Riyadh were paraphyletic and diverse. A hospital-associated transmission cluster, to which cases in Indiana (United States) and the Netherlands belonged, was discovered in Riyadh. One Jeddah-type virus was found in Riyadh, with matching travel history to Jeddah. Virus isolates representing outbreaks in Jeddah and Riyadh were not different from MERS-CoV EMC/2012 in replication, escape of interferon response, or serum neutralization.
  
  
  CONCLUSIONS
  Virus shedding and virus functions did not change significantly during the outbreak in Jeddah. These results suggest the outbreaks to have been caused by biologically unchanged viruses in connection with nosocomial transmission.
authors.affiliation: Institute of Virology, University of Bonn Medical Centre German Centre for Infection Research, Hannover, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Drosten
authors.affiliation: Institute of Virology, University of Bonn Medical Centre.
authors.forename: Doreen
authors.initials: D
authors.lastname: Muth
authors.affiliation: Institute of Virology, University of Bonn Medical Centre German Centre for Infection Research, Hannover, Germany.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Corman
authors.affiliation: Jeddah Regional Laboratory.
authors.forename: Raheela
authors.initials: R
authors.lastname: Hussain
authors.affiliation: Global Centre for Mass Gatherings Medicine.
authors.forename: Malaki
authors.initials: M
authors.lastname: Al Masri
authors.affiliation: Regional Laboratory, Ministry of Health, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Waleed
authors.initials: W
authors.lastname: HajOmar
authors.affiliation: Tib-Molbiol, Berlin, Germany.
authors.forename: Olfert
authors.initials: O
authors.lastname: Landt
authors.affiliation: Global Centre for Mass Gatherings Medicine.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Assiri
authors.affiliation: Institute of Virology, University of Bonn Medical Centre.
authors.forename: Isabella
authors.initials: I
authors.lastname: Eckerle
authors.affiliation: Regional Laboratory, Ministry of Health, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Ali
authors.initials: A
authors.lastname: Al Shangiti
authors.affiliation: Johns Hopkins Aramco Healthcare, Saudi Aramco, Dhahran, Kingdom of Saudi Arabia Indiana University School of Medicine, Indianapolis.
authors.forename: Jaffar A
authors.initials: JA
authors.lastname: Al-Tawfiq
authors.affiliation: Prince Sultan Military Medical City, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Ali
authors.initials: A
authors.lastname: Albarrak
authors.affiliation: Global Centre for Mass Gatherings Medicine Division of Infection and Immunity, University College London National Institute for Health Research Biomedical Research Centre, University College London Hospitals National Health Service Foundation Trust.
authors.forename: Alimuddin
authors.initials: A
authors.lastname: Zumla
authors.affiliation: Institute of Evolutionary Biology, University of Edinburgh, Centre for Infection, Immunity and Evolution, University of Edinburgh, United Kingdom Fogarty International Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Andrew
authors.initials: A
authors.lastname: Rambaut
authors.affiliation: Global Centre for Mass Gatherings Medicine Alfaisal University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Memish
mesh_terms: D001483:Base Sequence; D018352:Coronavirus Infections / Q000453:epidemiology*; D003428:Cross Infection; D004196:Disease Outbreaks; D006801:Humans; D065207:Middle East Respiratory Syndrome Coronavirus / Q000235:genetics; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D012529:Saudi Arabia
keywords: MERS-coronavirus; nosocomial transmission; outbreak; transmission infection control; virus isolation