International Journal of Infectious Diseases 29 (2014) 299–300

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Editorial

Health-care associate transmission of Middle East Respiratory Syndrome Corona virus, MERS-CoV, in the Kingdom of Saudi Arabia

In a paper by Saad and co-workers in this issue of the International Journal of Infections Diseases reporting on seventy consecutive patients with MERS-CoV in the Kingdom of Saudi Arabia, KSA, 55% (39/70) were defined as health care associated. Only one of the seventy had contact with camels within two weeks of onset of symptoms. The authors write that ‘‘Healthcare exposure to infection was the most important risk factor to develop MERSCoV infection’’. Also in this issue Memish and co-workers report that MERS-CoV shedding in inpatients is much longer compared to MERS-CoV patients managed outside hospitals. This may not be surprising as the most severe cases are admitted, but again underline high risk of infection in hospitals from severe MERS-CoV infections. Clearly health care workers are more exposed compared to household contacts of milder cases managed at home. The report by Abaidani and co-workers of two fatal cases in the Sultanate of Oman admitted to intensive care and treated in ventilators resulted in no secondary cases. As of 30 September 2014 there had been a global total of 887 laboratory confirmed cases of MERS-CoV infection reported, including 352 deaths (CFR 39.7%), with 97.5% (865/887) of cases occurring in the Middle East (Saudi Arabia, United Arab Emirates, Qatar, Jordan, Oman, Kuwait, Egypt, Yemen, Lebanon and Iran).1 Of these, 85.0% (754) were reported by Saudi Arabia.2 A cluster of nosocomial MERS-CoV infections was reported in April – May 2013 from eastern Saudi Arabia, where 21 out of 23 patients were infected in the hospital. An additional five clusters arising from these patients were found, of whom two were in health care workers.3 A report of seven secondary cases in health care workers found that two were asymptomatic carriers of MERSCoV, one had only a runny nose, and four reported mild symptoms. They did not require treatment, recovered fully within a week, and remained healthy on follow-up.4 Nosocomial transmission of MERS-CoV between two immunosuppressed patients was reported early in the outbreak outside of the Middle East.5 In September 2013, the CDC has determined that federal isolation and quarantine were authorized for MERS-CoV.6 A screening study of 5,065 patients and contacts found 99 MERS-CoV infected cases of which 70 were hospitalized and 19 (19.2%) were health care workers.7 An update from the 25th of April 2014 by the European Center for Disease Control, ECDC, concluded that ‘‘Recent MERS-CoV cases comprise a significant proportion of healthcare workers and asymptomatic cases or cases presenting with mild symptoms’’ and

commented on the April outbreak in hospitals in Jeddah that ‘‘it is unclear if the recent hospital clusters in SA and UAE resulted from a failure to adhere to these recommendations, or from the failure of these measures themselves!’’.8 An analysis of the 2012 outbreak in Jordan, the first known cases of MERS-CoV infection, found an attack rate of 10% among potentially exposed hospital personnel,9 compared to a study of secondary transmission in the home which found an attack rate of 5%.10 A review of 95 cases showed that 63.2% were healthcare associated and 13.7% took place in family contacts.11 In a recent update by the WHO, it was noted that the number of laboratory-confirmed MERSCoV cases increased sharply at the beginning of mid-March 2014, in KSA and UAE, and was related to the occurrence of healthcareassociated outbreaks.12 Transmission on commercial aircraft and other public transportation has not been reported and appears to be rare or nonexistent among airline passengers who traveled with two well-publicized infected and symptomatic passengers to the USA despite the conduct of an extensive investigation.13 The paper by Saad and co-workers in this issue of the International Journal of Infections Diseases defined health care associated infection as onset of illness more than 48 hours after admission or within 14 days after discharge from the hospital. This clearly does not entirely exclude infection occurring outside the health care facility since incubation periods of up to two weeks have been described (although more commonly less than one week). MERS-CoV appears to have a relatively low R0,14,10 yet the major seasonal increases of MERS-CoV activity observed in April 2012,8 April/May/June 2013,1 August/September 201315 and April/May/ June 201416 all included nosocomial outbreaks, urging the need to further investigate in-hospital risk factors for exposure and transmission. The paper by Saad and co-workers presented a cluster of 15 cases related to exposure in the Emergency Room where 10 cases were apparently infected by a single patient. A follow-up case-control study involving these cases with controls being other patients treated in the same emergency room on the same day might greatly enhance our knowledge on risk factors for transmission of MERS-CoV in the hospital environment. Likewise, going forward, case control studies are needed to better define risk factors for MERS-CoV transmission both in the community as well as in the healthcare environment. Nevertheless, the study highlights that transmission in health care facilities may be a major driver of the infection in the Kingdom of Saudi Arabia. The fact that there were 10 healthcare workers with MERS-CoV infection in the Prince Sultan Military Medical

http://dx.doi.org/10.1016/j.ijid.2014.10.001 1201-9712/ß 2014 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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Editorial / International Journal of Infectious Diseases 29 (2014) 299–300

City, Riyadh, further demonstrates that transmission was ongoing in the hospital during the period covered by the study. The importance of transmission in health care facilities could be further supported by mapping patient routes within the facility, as well as where they were waiting and for how long they were in each location. History of exposure to laboratory confirmed cases of MERS-CoV infection within the hospital should be ascertained, with documentation of no prior contact between these individuals outside of the hospital environment. It is uncertain as yet whether MERS-CoV has pandemic or even epidemic potential. So far more than 90% of cases have been reported from KSA with few cases from neighboring countries. In the two years since the first report of the infection, it has not spread outside the region except for very limited secondary spread from an imported case to close family contacts. At a workshop held in Riyadh in April 2014, the epidemiology of MERS-CoV was discussed and from the data presented,14 the meeting concluded that the outbreak was the result of repeated introductions of the MERS-CoV into the human population resulting from contact with infected camels and that the actual R0 was below 1, and probably below 0.5.14,10 If this is true and if the results in this paper hypothesizing that over 50% of cases treated in one hospital were nosocomially transmitted, there is a large potential to reduce transmission through early identification of possible MERS-CoV infected patients thereby leading to early isolation of these patients – ideally at the arrival point in the hospital.

7. Memish ZA1, Al-Tawfiq JA, Makhdoom HQ, Al-Rabeeah AA, Assiri A, Alhakeem RF, et al. Screening for Middle East respiratory syndrome coronavirus infection in hospital patients and their healthcare worker and family contacts: a prospective descriptive study. Clin Microbiol Infect 2014;20:469–74. 8. Sprenger M, Coulombier D. Middle East Respiratory Syndrome coronavirus – two years into the epidemic. Eurosurveillance 2014;19. 24 April 2014. 9. Al-Abdallat MM, Payne DC, Alqasrawi S, Rha B, Tohme RA, Abedi GR, et al., for the Jordan MERS-CoV Investigation Team. Hospital-Associated Outbreak of Middle East Respiratory Syndrome Coronavirus: A Serologic, Epidemiologic, and Clinical Description. Clin Infect Dis 2014 May 14. pii: ciu359. [Epub ahead of print]. 10. Drosten C, Meyer B, Mu¨ller MA, Corman VM, Al-Masri M, Hossain R, et al. Transmission of MERS-coronavirus in household contacts. N Engl J Med 2014;371:828–35. 11. The WHO MERS-CoV Research Group. State of knowledge and data gaps of Middle East respiratory syndrome coronavirus (MERSCoV) in humans. PLoS Curr 2013 Nov 12;5. pii: ecurrents.outbreaks.0bf719e352e7478f8ad85fa30127ddb8. 12. WHO. Global Alert and Response (GAR). Middle East respiratory syndrome coronavirus (MERS-CoV) – update http://www.who.int/csr/don/2014_05_28_ mers/en/ 13. Bialek SR, Allen D, Alvarado-Ramy F, Arthur R, Balajee A, Bell D, et al., Centers for Disease Control and Prevention (CDC). First confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the United States, updated information on the epidemiology of MERS-CoV infection, and guidance for the public, clinicians, and public health authorities - May 2014. MMWR Morb Mortal Wkly Rep 2014 May 16;63(19):431–6. 14. Memish ZA, Assiri A, Alhakeem R, Yezli S, Almasri M, Zumla A, et al. Middle East respiratory syndrome corona virus, MERS-CoV. Conclusions from the 2nd Scientific Advisory Board Meeting of the WHO Collaborating Center for Mass Gathering Medicine, Riyadh. Int J Infect Dis 2014;24:51–3. 15. WHO. Global Alert and Response (GAR): MERS-CoV Update 11, 20 Sep 2014 16. WHO. Global Alert and Response (GAR). MERS-CoV Update 16, 11 Jun 2014 < http://who.int/csr/disease/coronavirus_infections/MERS-CoV_summary_update_20140611.pdf?ua=1>

References 1. European Centre for Disease Prevention and Control (ECDC). Epidemiological update: Middle East respiratory syndrome coronavirus (MERS-CoV); 1 Oct 2014 2. Ministry of Health, Saudi Arabia, Command & Control Center. 1 new Confirmed Corona Case, 30 Sep 2014 3. Assiri A, McGeer A, Perl TM, Price CS, Al Rabeeah AA, Cummings DA, et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med 2013;369:407–16. 4. Memish ZA, Zumla AI, Assiri A. Middle East respiratory syndrome coronavirus infections in health care workers. N Engl J Med 2013;369:884–6. 5. Guery B, Poissy J, el Mansouf L, Se´journe´ C, Ettahar N, Lemaire X, et al., MERSCoV study group. Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission. Lancet 2013;381:2265–72. Erratum in: Lancet. 2013;381:2254. 6. Centers for Disease Control and Prevention (CDC). Updated information on the epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) infection and guidance for the public, clinicians, and public health authorities, 2012–2013. Morb Mortal Wkly Rep 2013;62:793–6.

Eskild Petersena,* Marjorie M. Pollackb Lawrence C. Madoffc a Editor-in-Chief, International Journal of Infectious Diseases, Departments of Infectious Diseases and Clinical Microbiology, Aarhus University Hospital, Aarhus, Denmark b Deputy Editor, ProMED-mail, Consultant medical epidemiologist, New York City, New York, USA c Editor, ProMED-mail, Professor of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School Boston, Massachusetts, USA *Corresponding author E-mail address: [email protected] (E. Petersen).

Health-care associate transmission of Middle East Respiratory Syndrome Corona virus, MERS-CoV, in the Kingdom of Saudi Arabia.

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