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

Abstract

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 MERS-CoV 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).1European Centre for Disease Prevention and Control (ECDC). Epidemiological update: Middle East respiratory syndrome coronavirus (MERS-CoV); 1 Oct 2014 <http://ecdc.europa.eu/en/press/news/_layouts/forms/News_DispForm.aspx?List=8db7286c-fe2d-476c-9133-18ff4cb1b568&ID=1074>Google Scholar Of these, 85.0% (754) were reported by Saudi Arabia.2Ministry of Health, Saudi Arabia, Command & Control Center. 1 new Confirmed Corona Case, 30 Sep 2014 <http://www.moh.gov.sa/en/CCC/PressReleases/Pages/Statistics-2014-09-30-001.aspx>Google Scholar 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.3Assiri A. McGeer A. Perl T.M. Price C.S. Al Rabeeah A.A. Cummings D.A. et al.Hospital outbreak of Middle East respiratory syndrome coronavirus.N Engl J Med. 2013; 369: 407-416Google Scholar A report of seven secondary cases in health care workers found that two were asymptomatic carriers of MERS-CoV, 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.4Memish Z.A. Zumla A.I. Assiri A. Middle East respiratory syndrome coronavirus infections in health care workers.N Engl J Med. 2013; 369: 884-886Google Scholar Nosocomial transmission of MERS-CoV between two immunosuppressed patients was reported early in the outbreak outside of the Middle East.5Guery B. Poissy J. el Mansouf L. Séjourné C. Ettahar N. Lemaire X. et al.MERS-CoV study groupClinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission.Lancet. 2013; 381 (Erratum in: Lancet. 2013;381:2254): 2265-2272Google Scholar In September 2013, the CDC has determined that federal isolation and quarantine were authorized for MERS-CoV.6Centers 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: 793-796Google Scholar 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.7Memish ZA1 Al-Tawfiq J.A. Makhdoom H.Q. Al-Rabeeah A.A. Assiri A. Alhakeem R.F. 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: 469-474Google Scholar 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!”.8Sprenger M. Coulombier D. Middle East Respiratory Syndrome coronavirus – two years into the epidemic.Eurosurveillance. 2014; 19 (24 April 2014)Google Scholar 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,9Al-Abdallat M.M. Payne D.C. Alqasrawi S. Rha B. Tohme R.A. Abedi G.R. et al.for the Jordan MERS-CoV Investigation TeamHospital-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])Google Scholar compared to a study of secondary transmission in the home which found an attack rate of 5%.10Drosten C. Meyer B. Müller M.A. Corman V.M. Al-Masri M. Hossain R. et al.Transmission of MERS-coronavirus in household contacts.N Engl J Med. 2014; 371: 828-835Google Scholar A review of 95 cases showed that 63.2% were healthcare associated and 13.7% took place in family contacts.11The WHO MERS-CoV Research GroupState of knowledge and data gaps of Middle East respiratory syndrome coronavirus (MERSCoV) in humans.PLoS Curr. 2013 Nov 12; 5 (pii: ecurrents.outbreaks.0bf719e352e7478f8ad85fa30127ddb8)Google Scholar In a recent update by the WHO, it was noted that the number of laboratory-confirmed MERS-CoV cases increased sharply at the beginning of mid-March 2014, in KSA and UAE, and was related to the occurrence of healthcare-associated outbreaks.12WHO. Global Alert and Response (GAR). Middle East respiratory syndrome coronavirus (MERS-CoV) – update http://www.who.int/csr/don/2014_05_28_mers/en/Google Scholar 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.13Bialek S.R. 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: 431-436Google Scholar 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 R0,14Memish Z.A. 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: 51-53Google Scholar, 10Drosten C. Meyer B. Müller M.A. Corman V.M. Al-Masri M. Hossain R. et al.Transmission of MERS-coronavirus in household contacts.N Engl J Med. 2014; 371: 828-835Google Scholar yet the major seasonal increases of MERS-CoV activity observed in April 2012,8Sprenger M. Coulombier D. Middle East Respiratory Syndrome coronavirus – two years into the epidemic.Eurosurveillance. 2014; 19 (24 April 2014)Google Scholar April/May/June 2013,1European Centre for Disease Prevention and Control (ECDC). Epidemiological update: Middle East respiratory syndrome coronavirus (MERS-CoV); 1 Oct 2014 <http://ecdc.europa.eu/en/press/news/_layouts/forms/News_DispForm.aspx?List=8db7286c-fe2d-476c-9133-18ff4cb1b568&ID=1074>Google Scholar August/September 201315WHO. Global Alert and Response (GAR): MERS-CoV Update 11, 20 Sep 2014 <http://who.int/csr/disease/coronavirus_infections/update_20130920/en/>Google Scholar and April/May/June 201416WHO. 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>Google Scholar 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 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,14Memish Z.A. 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: 51-53Google Scholar 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 0.5.14Memish Z.A. 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: 51-53Google Scholar, 10Drosten C. Meyer B. Müller M.A. Corman V.M. Al-Masri M. Hossain R. et al.Transmission of MERS-coronavirus in household contacts.N Engl J Med. 2014; 371: 828-835Google Scholar 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.