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Int J Infect Dis. MERS-CoV. Conclusions from the 2nd Scientific Advisory Board Meeting of the WHO Collaborating Center for Mass Gathering Medicine, Riyadh. [OA]

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  • Int J Infect Dis. MERS-CoV. Conclusions from the 2nd Scientific Advisory Board Meeting of the WHO Collaborating Center for Mass Gathering Medicine, Riyadh. [OA]

    [Source: Science Direct, full PDF document: (LINK). [OA], edited.]
    Accepted Manuscript


    Title: 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.

    Author: Ziad A Memish, Jaffar Al-Tawfiq, Christian Drosten, Abdullah Assiri, Rafaat Alhakeem, Ali Albarrak, Saber Yezli, Malak Almasri, Alimuddin Zumla, Eskild Petersen

    PII: S1201-9712(14)01491-X / DOI: http://dx.doi.org/doi:10.1016/j.ijid.2014.05.001 / Reference: IJID 1969

    To appear in: International Journal of Infectious Diseases

    Please cite this article as: Memish ZA, Al-Tawfiq J, Drosten C, Assiri A, Alhakeem R, Albarrak A, Yezli S, Almasri M, Zumla A, Petersen E, 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., International Journal of Infectious Diseases (2014), http://dx.doi.org/10.1016/j.ijid.2014.05.001

    This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.


    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.

    Ziad A Memish, Jaffar Al-Tawfiq, Christian Drosten, Abdullah Assiri, Rafaat Alhakeem, Ali Albarrak, Saber Yezli, Malak Almasri, Alimuddin Zumla, Eskild Petersen

    Global Centre for Mass Gatherings Medicine (GCMGM), Ministry of Health, Riyadh, Kingdom of Saudi Arabia: Ziad A. Memish, Abdullah Assiri, Raafat F. Alhakeem, Ali Albarrak, Alimuddin I. Zumla, Saber Yezli, Malak Almasri Saudi Aramco Medical Services Organization, Saudi Aramco, Dhahran, Kingdom of Saudi Arabia and Indiana University School of Medicine, Indianapolis, IN (USA): Jaffar A. Al-Tawfiq. Institute of Virology, University of Bonn Medical Centre, 53127 Bonn, Germany: Christian Drosten

    Saudi CDC, Ministry of Health, Riyadh, KSA: Ali Albarrak Division of Infection and Immunity, University College London, and UCL Hospitals NHS Foundation Trust, London, United Kingdom: Alimuddin I Zumla Institute of Clinical Medicine, Departments of Infectious Diseases and Clinical Microbiology, Aarhus University Hospital, Denmark: Eskild Petersen

    Corresponding author: Ziad A. Memish MD,FRCP(Can),FRCP(Edin),FRCP(Lond),FACP, Deputy Minister for Public Health, and Director WHO Collaborating Center for Mass Gathering Medicine Ministry of Health, and Professor, Al-Faisal University, Riyadh 11176, KSA. Email: zmemish@yahoo.com
    _____

    The 2nd Scientific Advisory Board Meeting of the Global Center for Mass Gathering Medicine, Ministry of Health, Riyadh, Kingdom of Saudi Arabia, met April 28 ? 29 in Riyadh to discuss risk of infectious diseases and research and surveillance during Hajj. Due to the on-going outbreak of MERSCoV and especially the recent increase in case detection in Jeddah, (138 MERS cases were reported from Jeddah between 11 to 26 April 2014), the agenda for the second day was focused on MERS-CoV, both in relation to the risk it presents for the forthcoming Ramadan and Hajj, but also in the Kingdom of Saudi Arabia and the Middle East in general. The Ministry of Health used the opportunity to ask the Scientific Advisory Board to review the MERS-CoV situation globally with specific attention to MERS in the country and review case definition, infection control guidelines and risk assessment to nationals, health care workers, family contacts, camel owners, and travelers to KSA, and the future control.


    Background

    MERS-CoV is a new Coronavirus initially isolated from a patient from Saudi Arabia in 2012.1 Phylogenetic analyses showed that the virus was close to the SARS Coronavirus, and the epidemiology and clinical presentation of infection with the two viruses has been compared.2

    As of May 1st 2014, the total number of laboratory confirmed MERS-CoV infections reported were 371, including 107 deaths.3 Countries in the Middle East reporting cases are KSA, Qatar, Jordan, Oman, Kuwait and United Arab Emirates . Secondary cases has been reported in several European (United Kingdom, France, Germany, Italy, Greece), Asian (Malaysia and Phillipines) and MEA (Egypt) countries, and the potential for a pandemic as for SARS has been discussed.4,5 The cases outside the Arabian peninsula and Middle East have either been infected in the Middle East or been in close contact with a MERS-CoV cases. Only secondary cases linked to index cases infected in the Middle East have been reported and no further human to human transmission has occurred. The US Centers for Diseases Control and Prevention (CDC) announced on Friday May 2nd, 2014, the first case of MERS-CoV in a travelerto the United States from Riyadh, KSA.6


    The Virus

    Corona virus is found in all mammalian and avian species. The origin of the MERS-CoV has been much discussed and bats were early mentioned due to close phylogeny between certain bat CoV?s and MERS-CoV.1 The phylogeny of Coronaviruses has been extensively reviewed.7 Recently three entire MERS-CoV genomes from Jeddah outbreak have been sequenced and the data was presented at the Scientific Advisory Board Meeting of the WHO Collaborating Center for Mass Gathering Medicine, Ministry of Health, Riyadh, Kingdom of Saudi Arabia, April 28 ? 29 (Drosten C unpublished).

    The overall finding was announced the 26th April,8 and the conclusion is that overall the virus is stable and there is no sign of mutations indicating an adaptation to cause sustained human to human transmission.


    Animal reservoirs

    Dromedary camels have convincingly been shown to harbor the virus and be able to shed MERS CoV in high numbers in secretions from the upper respiratory tract.9 Studies of previous samples from 2005 found neutralizing antibodies to MERS-CoV in dromedars in Dubai, indicating that the virus is not new on the Arabian peninsula.10 It cannot be excluded that other animal reservoirs exist, but the fact that the MERS-CoV cases primarily is reported from the Middle East and in particular from the Arabian peninsula, suggest that dromedars and camels are the main animal reservoir and primary cases occur in areas where camel and dromedars are an important part of life. Unpasteurized camel milk is a possible route of transmission, but so far there is no data on excreting of MERS-CoV into camel milk.


    Human transmission

    The Scientific Advisory Board Meeting of the Global Center for Mass Gatherings Medicine discussed the reported cases and the risk factors for infection. The questions addressed were: 1) what were the reasons for the increased case detection rates in March and April as reported from Jeddah? 2) Was this due to seasonality or increased virulence? 3) Had the human-to-human transmission pattern changed and the basic reproductive rate increased? 4).Were optimal infection control procedures followed? 5) Had the clinical presentation of MERS-CoV changed? 6) What changes were required in current recommendations for infection control practices in the community or in hospitals? 7) What precautions should those in contact with camels follow? 8) What advice should be given to parents and schools? 9) What advice should be given to travelers to the Middle East and should travel restrictions be in place? 10) What options were available for treatment of MERS? 11) What were the research priorities?

    It is clear from previous reports that nosocomial infection is important.11,12,13,14 Household transmission is another important risk.15


    Management of inpatients with MERS

    Once in hospital with proved MERS-CoV treatment options are limited and patients are most often in intensive care with respiratory failure and may have multi-organ impairment especially renal failure.16

    It has been suggested looking at data from SARS-CoV that Ribavirin and Interferon beta or lopinavir combined with ritonavir may be used,17 but the experience so far is limited.18 The use of hyperimmune plasma from patients recovering from MERS-CoV may in theory also be an effective treatment as has been shown for influenza.19


    Conclusions
    1. Sequencing of MERS-CoV isolates from Jeddah patients who?s the virus seems stable, showing no signs so far of mutations which indicate an adaption to humans with increased risk of human to human infections.
    2. The primary animal reservoir is camels and dromedars. Transmission is thought to be due to close physical contact or due to consumption of camel products.
    3. The epidemiology since the virus was first found in 2012 is compatible with multiple introductions into humans from the animal reservoir, with no long-term sustained human-to-human transmission.
    4. There is no human reservoir of cases with few or no symptoms.
    5. The basic reproductive rate of the virus (R0) is definitely below 1 and probably below 0.5 clearly showing that the virus has no pandemic or even local epidemic potential.
    6. The incubation period was between 2 to 16 days? Period of infectivity was?
    7. Nosocomial infection is an important risk factor for human to human transmission. Thus infection prevention and control measures are crucial to prevent the possible spread of MERSCoV within health care facilities. Hospital infection control procedures needs to be emphazised and enforced. The Jeddah outbreak showed that it is not always possible to identify patients with MERS-CoV early because some have mild or unusual symptoms.It is important that health-care workers apply standard precautions consistently with all patients irrespective of the diagnosis. Droplet precautions should be undertaken when providing care to patients with symptoms of respiratory tract infection. Contact precautions including eye protection should be added when caring for suspected or confirmed cases of MERS-CoV infection. Airborne precautions should be taken when performing aerosol generating procedures
    8. In patients suspected of MERS-CoV, if initial tests using nasopharyngeal swab is negative, repeat testing should be performed, and other specimens from the lower respiratory tract should be obtained if possible.
    9. Awareness of MERS-CoV is important in countries where camels and dromedars are a common livestock.
    10. The importance of educational campaigns for educating health care workers, the general public, family contacts and travelers to the Middle East was emphasized. General hygiene measures such as regular hand washing, antiseptic before and after handling animals Owners of camels and dromedars should use gloves and mask when handling ill animals.
    11. There is no evidence that camel's milk tested positive for MERS, however, milk has the potential of transmitting other infections. Camel milk should be boiled before consumption. Unpasteurised milk should not be consumed
    12. There was no grounds for preventing children attending schools and closing schools
    13. For the forthcoming Hajj, camel sacrifice or contact with camels should be avoided.


    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.
    2. Hui DS, Memish ZA, Zumla A.Severe acute respiratory syndrome vs. the Middle East respiratory syndrome. Curr Opin Pulm Med. 2014;20:233-41 
    3. ProMED. MERS-CoV - Eastern Mediterranean (45): Saudi Arabia. 20140430.2437089, Wed. 1st May, 2014
    4. Khan K1, Sears J, Hu VW, Brownstein JS, Hay S, Kossowsky D, Eckhardt R, Chim T, Berry I, Bogoch I, Cetron M. Potential for the international spread of Middle East Respiratory Syndrome in association with mass gatherings in Saudi Arabia. PLoS Curr. 2013 Jul 17;5.
    5. Breban R, Riou J, Fontanet A. Interhuman transmissibility of Middle East respiratory syndrome coronavirus: estimation of pandemic risk. Lancet. 2013;382:694-9.
    6. http://www.cdc.gov/media/releases/2014/p0502-US-MERS.html
    7. Drexler JF, Corman VM, Drosten C. Ecology, evolution and classification of bat coronaviruses in the aftermath of SARS. Antiviral Res. 2014;101:45-56.
    8. ProMED. MERS-CoV - Eastern Mediterranean (42): Saudi Arabia, genome sequencing, Jeddah. 20140426.2432140. Sat, 26 April 2014.
    9. Nowotny N, Kolodziejek J. Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in dromedary camels, Oman, 2013. Eurosurveillance 2014;19: 24 april 2014
    10. Alexandersen S, Kobinger GP, Soule G, Wernery U. Middle East respiratory syndrome coronavirus antibody reactors among camels in Dubai, United Arab Emirates, in 2005. Transbound Emerg Dis. 2014;61:105-8.
    11. Guery B, Poissy J, el Mansouf L, S?journ? C, Ettahar N, Lemaire X, Vuotto F, Goffard A, Behillil S, Enouf V, Caro V, Mailles A, Che D, Manuguerra JC, Mathieu D, Fontanet A, van der Werf S; MERS-CoV 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).
    12. Penttinen PM1, Kaasik-Aaslav K, Friaux A, Donachie A, Sudre B, Amato-Gauci AJ, Memish ZA, Coulombier D. Taking stock of the first 133 MERS coronavirus cases globally--Is the epidemic changing? Euro Surveill. 2013;18: 20596.
    13. Memish ZA1, Al-Tawfiq JA, Makhdoom HQ, Al-Rabeeah AA, Assiri A, Alhakeem RF, Alrabiah FA, Al Hajjar S, Albarrak A, Flemban H, Balkhy H, Barry M, Alhassan S, Alsubaie S, Zumla A. Screening for Middle East respiratory syndrome coronavirus infection in hospital patients and their healthcare worker and  family contacts: a prospective descriptive study. ClinMicrobiol Infect. 2014 Jan 24. doi: 10.1111/1469-0691.12562.
    14. Al-Tawfiq JA, Hinedi K, Ghandour J, Khairalla H, Musleh S, Ujayli A, Memish ZA. Middle East Respiratory Syndrome-Coronavirus (MERS-CoV): a case-controlstudy of hospitalized patients. Clin Infect Dis. 2014 Apr 9 [E-pub ahead of print]
    15. Omrani AS, Matin MA, Haddad Q, Al-Nakhli D, Memish ZA, Albarrak AM.A family cluster of Middle East Respiratory Syndrome Coronavirus infections related to a likely unrecognized asymptomatic or mild case. Int J Infect Dis. 2013;17:668-72.
    16. Arabi YM, Arifi AA, Balkhy HH, Najm H, Aldawood AS, Ghabashi A, Hawa H, Alothman A, Khaldi A, Al Raiy B. Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann Intern Med. 2014;160:389-97.
    17. Momattin H, Mohammed K, Zumla A, Memish ZA, Al-Tawfiq JA. Therapeutic options for Middle East respiratory syndrome coronavirus (MERS-CoV)--possible lessons from a systematic review of SARS-CoV therapy. Int J Infect Dis. 2013;17:792-8.
    18. Al-Tawfiq JA, Momattin H, Dib J, Memish ZA. Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study. Int J Infect Dis. 2014;20:42-6.
    19. **** IF, To KK, Lee CK, Lee KL, Yan WW, Chan K, Chan WM, Ngai CW, Law KI, Chow FL, Liu R, Lai KY, Lau CC, Liu SH, Chan KH, Lin CK, Yuen KY.Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection. Chest. 2013;144:464-73.

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