Ahead of Print -Molecular Epidemiology of Hospital Outbreak of Middle East Respiratory Syndrome, Riyadh, Saudi Arabia, 2014 - Volume 21, Number 11—November 2015 - Emerging Infectious Disease journal - CDC

full-text ►

Ahead of Print -Molecular Epidemiology of Hospital Outbreak of Middle East Respiratory Syndrome, Riyadh, Saudi Arabia, 2014 - Volume 21, Number 11—November 2015 - Emerging Infectious Disease journal - CDC

Volume 21, Number 11—November 2015

Research

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

On This Page

• Materials and Methods
• Results
• Discussion
• Suggested Citation

Figures

• Figure 1
• Figure 2
• Figure 3

Tables

• Table

Technical Appendicies

Downloads

• RIS[TXT - 2 KB]

Shamsudeen F. Fagbo1, Leila Skakni1, Daniel K.W. Chu1, Musa A. Garbati, Mercy Joseph, Malik Peiris, and Ahmed M. Hakawi

Author affiliations: King Fahad Medical City, Riyadh, Saudi Arabia (S.F. Fagbo, L. Skakni, M.A. Gabrati, M. Joseph, A.M. Hakawi); The University of Hong Kong, Hong Kong, China (D.K.W. Chu, M. Peiris)

Suggested citation for this article

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.

Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) was first recognized as a cause of severe human respiratory disease in 2012 (1). As of June 19, 2015, a total of 1,338 confirmed cases of MERS and at least 475 MERS-associated deaths had been reported (2). Human zoonotic infections have largely been acquired in the Middle East. Imported cases in Europe, North America, Africa, and Asia have been linked to travel to the Middle East, occasionally with local secondary transmission (2).

Although human infections are zoonotic in origin, clusters of human-to-human transmission have been reported, particularly within households or health care settings (3–6). In an outbreak in Jeddah, Saudi Arabia, in 2014 involving multiple health care facilities, 255 laboratory-confirmed MERS cases were documented during a 2-month period, but intensified infection prevention measures in hospitals terminated that outbreak (6,7). Available genetic data for these patients showed that they were clustered, which suggested widespread transmission of related viruses (6). Of 191 symptomatic patients, 40 were health care workers (HCWs). For the remaining patients for whom data were available, most had some form of contact with a health care facility or patients with suspected MERS. Investigation of outbreaks in health care settings also identified asymptomatic and milder cases, especially in healthy young adults and HCWs with no underlying illnesses (7). Dromedary camels have been proposed as a source of human infection; however, the possibility of other reservoirs and intermediate hosts has not been excluded (2,8).

Molecular epidemiologic analysis of transmission was attempted for a 2013 MERS outbreak at multiple health care facilities in the eastern region of Saudi Arabia (5). Combined analysis of genomic and epidemiologic data provided insights into transmission chains that would otherwise not have been apparent. The study on the 2014 Jeddah outbreak included analysis of viral sequences from 2 hospitals in Riyadh and identified a cluster of infections at the Prince Sultan Military Medical City (PSMMC) during March–April 2014 (6). In this study, we analyzed viral genetic data for patients and HCWs with MERS at King Fahad Medical City (KFMC), Riyadh, Saudi Arabia, during February 1–May 31, 2014, and available epidemiologic data to better understand transmission within the hospital and place the outbreak in KFMC in the context of contemporaneous MERS outbreaks in other hospitals in Riyadh.

Dr Fagbo is an epidemiologist at the Clinical and Applied Research Department, King Fahad Medical City, Riyadh, Saudi Arabia. His research interests are emerging viral infections and zoonoses at the animal human interface.

Acknowledgments

We thank Abdulwahid Al Dehaimi, Rami Hassan, Abdulrahman Mohammed Al Rashaid, Angelita Des Santos, Trevor Wyngaard, Rizalina Espanola, Rhoda Medina, Tariq Wani, and Noorazlina Abdulhamid for support and assistance with laboratory, clinical, and epidemiologic data collection and analysis; and H.Y.E. Lau, B.J. Cowling, and T.T.Y. Lam for advice on statistical and phylogenetic analysis..

The study was supported by a research grant from the US National Institutes of Health (contract no. HHSN272201400006C), and a commissioned grant from the Health and Medical Research fund, Food and Health Bureau, Government of the Hong Kong Special Administrative Region.

References

1. Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.N Engl J Med. 2012;367:1814–20. DOIPubMed
2. World Health Organization. Middle East respiratory syndrome coronavirus (MERS-CoV): summary and risk assessment of current situation in the Republic of Korea and China as of 19 June 2015 [cited 2015 Jun 23]. http://www.who.int/emergencies/mers-cov/mers-cov-republic-of-korea-and-china-risk-assessment-19-june-2015.pdf?ua=1
3. Drosten C, Meyer B, Müller MA, Corman VM, Al-Masri M, Hossain R, Transmission of MERS-coronavirus in household contacts. N Engl J Med.2014;371:828–35. DOIPubMed
4. Assiri A, McGeer A, Perl TM, Price CS, Al Rabeeah AA, Cummings DA, Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med. 2013;369:407–16. DOIPubMed
5. Cotten M, Watson SJ, Kellam P, Al-Rabeeah AA, Makhdoom HQ, Assiri A, Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study. Lancet. 2013;382:1993–2002. DOIPubMed
6. Drosten C, Muth D, Corman VM, Hussain R, Al Masri M, HajOmar W, et al. An observational, laboratory-based study of outbreaks of Middle East respiratory syndrome coronavirus in Jeddah and Riyadh, Kingdom of Saudi Arabia, 2014. Clin Infect Dis. 2015;60:369–77. DOIPubMed
7. Oboho IK, Tomczyk SM, Al-Asmari AM, Banjar AA, Al-Mugti H, Aloraini MS, 2014 MERS-CoV outbreak in Jeddah—a link to health care facilities. N Engl J Med. 2015;372:846–54. DOIPubMed
8. Haagmans BL, Al Dhahiry SH, Reusken CB, Raj VS, Galiano M, Myers R, Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation. Lancet Infect Dis. 2014;14:140–5.DOIPubMed
9. US Centers for Disease Control and Prevention. MERS clinical features [cited 2015 May 30]. http://www.cdc.gov/coronavirus/mers/clinical-features.html
10. Anisimova M, Gil M, Dufayard JF, Dessimoz C, Gascuel O. Survey of branch support methods demonstrates accuracy, power, and robustness of fast likelihood-based approximation schemes. Syst Biol. 2011;60:685–99. DOIPubMed
11. Kapoor M, Pringle K, Kumar A, Dearth S, Liu L, Lovchik J, Clinical and laboratory findings of the first imported case of Middle East respiratory syndrome coronavirus to the United States. Clin Infect Dis. 2014;59:1511–8. DOIPubMed
12. Kraaij-Dirkzwager M, Timen A, Dirksen K, Gelinck L, Leyten E, Groeneveld P, MERS-CoV outbreak investigation team of the Netherlands. Middle East respiratory syndrome coronavirus (MERS-CoV) infections in two returning travelers in the Netherlands, May 2014. Euro Surveill.2014;19:20817.PubMed
13. Wang N, Shi X, Jiang L, Zhang S, Wang D, Tong P, Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4. Cell Res. 2013;23:986–93. DOIPubMed

Figures

• 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...
• 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....

Table

• Table. Characteristics of 21 patients tested for infection with MERS-CoV, King Fahad Medical City, Saudi Arabia, 2014

Technical Appendices

• . Additional information regarding molecular epidemiology of hospital outbreak of Middle East respiratory syndrome, Riyadh, Saudi Arabia, 2014.  460 KB
• . Nucleotide differences from consensus ancestral sequences of Middle East respiratory syndrome coronavirus, 2014, estimated at nodes C and E of the time-resolved phylogenetic tree (). Relevant nucleotides at each polymorphic... 16 KB

Suggested citation for this article: Fagbo SF, Skakni L, Chu DKW, Garbati MA, Joseph M, Peiris M, et al. Molecular epidemiology of hospital outbreak of Middle East respiratory syndrome, Riyadh, Saudi Arabia, 2014. Emerg Infect Dis. 2015 Nov [date cited]. http://dx.doi.org/10.3201/eid2111.150944

DOI: 10.3201/eid2111.150944

1These authors contributed equally to this article.