title: Unraveling the drivers of MERS-CoV transmission.
abstract: With more than 1,700 laboratory-confirmed infections, Middle East respiratory syndrome coronavirus (MERS-CoV) remains a significant threat for public health. However, the lack of detailed data on modes of transmission from the animal reservoir and between humans means that the drivers of MERS-CoV epidemics remain poorly characterized. Here, we develop a statistical framework to provide a comprehensive analysis of the transmission patterns underlying the 681 MERS-CoV cases detected in the Kingdom of Saudi Arabia (KSA) between January 2013 and July 2014. We assess how infections from the animal reservoir, the different levels of mixing, and heterogeneities in transmission have contributed to the buildup of MERS-CoV epidemics in KSA. We estimate that 12% [95% credible interval (CI): 9%, 15%] of cases were infected from the reservoir, the rest via human-to-human transmission in clusters (60%; CI: 57%, 63%), within (23%; CI: 20%, 27%), or between (5%; CI: 2%, 8%) regions. The reproduction number at the start of a cluster was 0.45 (CI: 0.33, 0.58) on average, but with large SD (0.53; CI: 0.35, 0.78). It was >1 in 12% (CI: 6%, 18%) of clusters but fell by approximately one-half (47% CI: 34%, 63%) its original value after 10 cases on average. The ongoing exposure of humans to MERS-CoV from the reservoir is of major concern, given the continued risk of substantial outbreaks in health care systems. The approach we present allows the study of infectious disease transmission when data linking cases to each other remain limited and uncertain.
authors.affiliation: Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, 75015 Paris, France; Centre National de la Recherche Scientifique, Unité de Recherche Associée 3012, 75015 Paris, France; Center of Bioinformatics, Biostatistics and Integrative Biology, Institut Pasteur, 75015 Paris, France;
authors.forename: Simon
authors.initials: S
authors.lastname: Cauchemez
authors.affiliation: Medical Research Council Centre for Outbreak Analysis and Modelling, Imperial College London, Faculty of Medicine, London W2 1PG, United Kingdom;
authors.forename: Pierre
authors.initials: P
authors.lastname: Nouvellet
authors.affiliation: Medical Research Council Centre for Outbreak Analysis and Modelling, Imperial College London, Faculty of Medicine, London W2 1PG, United Kingdom;
authors.forename: Anne
authors.initials: A
authors.lastname: Cori
authors.affiliation: Medical Research Council Centre for Outbreak Analysis and Modelling, Imperial College London, Faculty of Medicine, London W2 1PG, United Kingdom;
authors.forename: Thibaut
authors.initials: T
authors.lastname: Jombart
authors.affiliation: Medical Research Council Centre for Outbreak Analysis and Modelling, Imperial College London, Faculty of Medicine, London W2 1PG, United Kingdom;
authors.forename: Tini
authors.identifier: 0000-0002-8952-4710
authors.initials: T
authors.lastname: Garske
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205;
authors.forename: Hannah
authors.initials: H
authors.lastname: Clapham
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205;
authors.forename: Sean
authors.initials: S
authors.lastname: Moore
authors.affiliation: Medical Research Council Centre for Outbreak Analysis and Modelling, Imperial College London, Faculty of Medicine, London W2 1PG, United Kingdom;
authors.forename: Harriet Linden
authors.initials: HL
authors.lastname: Mills
authors.affiliation: Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, 75015 Paris, France; Centre National de la Recherche Scientifique, Unité de Recherche Associée 3012, 75015 Paris, France; Center of Bioinformatics, Biostatistics and Integrative Biology, Institut Pasteur, 75015 Paris, France; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205;
authors.forename: Henrik
authors.initials: H
authors.lastname: Salje
authors.affiliation: Medical Research Council Centre for Outbreak Analysis and Modelling, Imperial College London, Faculty of Medicine, London W2 1PG, United Kingdom;
authors.forename: Caitlin
authors.initials: C
authors.lastname: Collins
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205;
authors.forename: Isabel
authors.initials: I
authors.lastname: Rodriquez-Barraquer
authors.affiliation: Medical Research Council Centre for Outbreak Analysis and Modelling, Imperial College London, Faculty of Medicine, London W2 1PG, United Kingdom;
authors.forename: Steven
authors.initials: S
authors.lastname: Riley
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205;
authors.forename: Shaun
authors.initials: S
authors.lastname: Truelove
authors.affiliation: Ministry of Health, Riyadh 12234, Kingdom of Saudi Arabia;
authors.forename: Homoud
authors.initials: H
authors.lastname: Algarni
authors.affiliation: Ministry of Health, Riyadh 12234, Kingdom of Saudi Arabia;
authors.forename: Rafat
authors.initials: R
authors.lastname: Alhakeem
authors.affiliation: Ministry of Health, Riyadh 12234, Kingdom of Saudi Arabia;
authors.forename: Khalid
authors.initials: K
authors.lastname: AlHarbi
authors.affiliation: Ministry of Health, Riyadh 12234, Kingdom of Saudi Arabia;
authors.forename: Abdulhafiz
authors.initials: A
authors.lastname: Turkistani
authors.affiliation: Medical Research Council Centre for Outbreak Analysis and Modelling, Imperial College London, Faculty of Medicine, London W2 1PG, United Kingdom;
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Aguas
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205; Department of Biology, University of Florida, Gainesville, FL 32610; Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610;
authors.forename: Derek A T
authors.initials: DA
authors.lastname: Cummings
authors.affiliation: Medical Research Council Centre for Outbreak Analysis and Modelling, Imperial College London, Faculty of Medicine, London W2 1PG, United Kingdom; Outbreak Investigation Task Force, Center for Global Health, Institut Pasteur, 75015 Paris, France.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Van Kerkhove
authors.affiliation: Medical Research Council Centre for Outbreak Analysis and Modelling, Imperial College London, Faculty of Medicine, London W2 1PG, United Kingdom;
authors.forename: Christl A
authors.initials: CA
authors.lastname: Donnelly
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205;
authors.forename: Justin
authors.initials: J
authors.lastname: Lessler
authors.affiliation: Medical Research Council Centre for Outbreak Analysis and Modelling, Imperial College London, Faculty of Medicine, London W2 1PG, United Kingdom;
authors.forename: Christophe
authors.initials: C
authors.lastname: Fraser
authors.affiliation: Ministry of Health, Riyadh 12234, Kingdom of Saudi Arabia; neil.ferguson@imperial.ac.uk ambarrak@moh.gov.sa.
authors.forename: Ali
authors.initials: A
authors.lastname: Al-Barrak
authors.affiliation: Medical Research Council Centre for Outbreak Analysis and Modelling, Imperial College London, Faculty of Medicine, London W2 1PG, United Kingdom; neil.ferguson@imperial.ac.uk ambarrak@moh.gov.sa.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Ferguson
mesh_terms: D000818:Animals; D018352:Coronavirus Infections / Q000635:transmission*; D004197:Disease Reservoirs; D006801:Humans; D015047:Zoonoses / Q000635:transmission
keywords: animal reservoir; epidemic dynamics; mathematical modeling; outbreaks; zoonotic virus