Molecular Epidemiology of Hospital Outbreak of Middle East Respiratory Syndrome, Riyadh, Saudi Arabia, 2014

Abstract

We investigated an outbreak of Middle East respiratory syndrome (MERS) at King Fahad Medical City (KFMC), Riyadh, Saudi Arabia, during March 29-May 21, 2014. This outbreak involved 45 patients: 8 infected outside KFMC, 13 long-term patients at KFMC, 23 health care workers, and 1 who had an indeterminate source of infection. Sequences of full-length MERS coronavirus (MERS-CoV) from 10 patients and a partial sequence of MERS-CoV from another patient, when compared with other MERS-CoV sequences, demonstrated that this outbreak was part of a larger outbreak that affected multiple health care facilities in Riyadh and possibly arose from a single zoonotic transmission event that occurred in December 2013 (95% highest posterior density interval November 8, 2013-February 10, 2014). This finding suggested continued health care-associated transmission for 5 months. Molecular epidemiology documented multiple external introductions in a seemingly contiguous outbreak and helped support or refute transmission pathways suspected through epidemiologic investigation.

Keywords: MERS; MERS-CoV; Middle East respiratory syndrome; Middle East respiratory syndrome coronavirus; Saudi Arabia; coronavirus; health care workers; molecular epidemiology; mutation; nosocomial infection; phylogeny; respiratory infections; transmission; viruses; zoonoses.

Figure 1

Date of symptom onset for patients with confirmed Middle East respiratory syndrome coronavirus (MERS-CoV) infection hospitalized at King Fahad Medical City, Riyadh, Saudi Arabia, 2014. For 4 asymptomatic health care workers (HCWs) detected by screening, date of virus detection, rather than symptom onset, is indicated.

Figure 2

Time-resolved phylogenetic tree of Middle East respiratory syndrome coronavirus (MERS-CoV) genomes, Saudi Arabia, 2014, constructed by using BEAST version 1.8 (http://beast.bio.ed.ac.uk/). Upper scale bar indicates nucleotide substitutions per site. Lower scale bar indicates years in reference to sample KFMC-6 (collected May 18, 2014). Genomes sequenced in this study are indicated in bold. *Indicates major nodes with posterior probabilities >0.95. Estimated median dates for nodes A, B, C, D, and E (95% highest posterior density intervals) are A) Dec 31, 2013 (Nov 8, 2013–Feb 10, 2014), B) Jan 28, 2014 (Dec 16, 2013–Feb 27, 2014), C) Feb 15, 2014 (Jan 10, 2014–Mar 16, 2014), D) Feb 26,2014 (Jan 23, 2014–Mar 25, 2014), E) Apr 4, 2014 (Mar 9, 2014–Apr 25, 2014). KKUH, King Khalid University Hospital; KFMC, King Fahd Medical City.

Figure 3

Nucleotide differences from consensus ancestral sequences of Middle East respiratory syndrome coronavirus (MERS-CoV), Saudi Arabia, 2014, estimated at nodes C and E in a time-resolved phylogenetic tree (Figure 2). The region of the genome sequenced is indicated by the length of each box. Exact genome polymorphic nucleotide positions, sampling date, and nucleotide substitutions is shown in Technical Appendix 2. Nucleotide changes are indicated by red (A), orange (T), blue (C), and green (G) vertical bars. ORF, open reading frame; KKUH, King Khalid University Hospital; KFMC, King Fahad Medical City; KSA, Kingdom of Saudi Arabia.