Eastern Mediterranean Health Journal La Revue De Santé De La Méditerranée Orientale

Contents

Editorial

Novel coronavirus infection: time to stay ahead of the curve...... S3 Perspective

Emergence of novel coronavirus: global context...... S5 Country experiences

Saudi Arabia and the emergence of a novel coronavirus...... S7 Novel coronavirus infections in Jordan, April 2012: epidemiological findings from a Eastern Mediterranean retrospective investigation...... S12 Health Journal Reviews

The early response to a novel coronavirus in the Middle East...... S19 Supplement on Novel Coronavirus Novel coronavirus: the challenge of communicating about a virus which one knows little about...... S26 Guest Editors La Revue de Santé de Volume 19 Ziad A Memish, MD Novel coronavirus infection in the Eastern Mediterranean Region: time to act...... S31 Jaouad Mahjour, MD, MPH la Méditerranée orientale Infection prevention and control measures for acute respiratory infections in healthcare settings: an update...... S39 Emerging respiratory and novel coronavirus 2012 infections and mass gatherings...... S48 Supplement 1 2013 Short communications Coronavirus particles Enhanced surveillance and investigation of coronavirus: what is required?...... S55 With the emergence of a novel coronavirus in 2012, WHO Public health investigations required for protecting the population against novel coronaviruses...... S61 convened a meeting of experts in January 2013 to address this new public health threat. This supplement presents papers arising out Meeting report of the meeting.

Highlights and conclusions from the technical consultative meeting on novel coronavirus infection, Cairo, Egypt, 14–16 January 2013...... S68

املجلد التاسع عرش Volume 19 العدد اإلضايف Supplement 1 / Supplément 1 2013 1

Cover 19 Supplement.indd 1 5/16/2013 1:30:57 PM Members of the WHO Regional Committee for the Eastern Mediterranean املجلة الصحية لرشق املتوسط Afghanistan . Bahrain . Djibouti . Egypt . Islamic Republic of Iran . Iraq . Jordan . Kuwait . Lebanon هى املجلة الرسمية التى تصدر عن املكتب اإلقليمى لرشق املتوسط بمنظمة الصحة العاملية. وهى منرب لتقديم Libya . Morocco . Oman . Pakistan . Palestine . Qatar . Saudi Arabia . Somalia . South Sudan السياسات واملبادرات اجلديدة ىف اخلدمات الصحية والرتويج هلا، ولتبادل اآلراء واملفاهيم واملعطيات الوبائية Sudan . Syrian Arab Republic . Tunisia . United Arab Emirates . Yemen ونتائج األبحاث وغري ذلك من املعلومات، وخاصة ما يتعلق منها بإقليم رشق املتوسط. وهى موجهة إىل كل أعضاء املهن الصحية، والكليات الطبية وسائر املعاهد التعليمية، وكذا املنظامت غري احلكومية املعنية، واملراكز املتعاونة مع منظمة الصحة العاملية واألفراد املهتمني بالصحة ىف اإلقليم وخارجه.

EASTERN MEDITERRANEAN HEALTH JOURNAL البلدان أعضاء اللجنة اإلقليمية ملنظمة الصحة العاملية لرشق املتوسط IS the official health journal published by the Eastern Mediterranean Regional Office of the World Health Organization. It is a forum for the presentation and promotion of new policies and initiatives in health services; and for the exchange of ideas, con‑ cepts, epidemiological data, research findings and other information, with special reference to the Eastern Mediterranean Region. األردن . أفغانستان . اإلمارات العربية املتحدة . باكستان . البحرين . تونس . ليبيا . مجهورية إيران اإلسالمية It addresses all members of the health profession, medical and other health educational institutes, interested NGOs, WHO Col‑ ...... اجلمهورية العربية السورية اليمن جنوب السودان جيبويت السودان الصومال العراق عُ ام ن فلسطني قطر الكويت لبنان مرص .laborating Centres and individuals within and outside the Region املغرب . اململكة العربية السعودية LA REVUE DE SANTÉ DE LA MÉDITERRANÉE ORIENTALE EST une revue de santé officielle publiée par le Bureau régional de l’Organisation mondiale de la Santé pour la Méditerranée orientale. Elle offre une tribune pour la présentation et la promotion de nouvelles politiques et initiatives dans le domaine des ser‑vices de santé ainsi qu’à l’échange d’idées, de concepts, de données épidémiologiques, de résultats de recherches et d’autres Membres du Comité régional de l’OMS pour la Méditerranée orientale informations, se rapportant plus particulièrement à la Région de la Méditerranée orientale. Elle s’adresse à tous les professionnels de la santé, aux membres des instituts médicaux et autres instituts de formation médico-sanitaire, aux ONG, Centres collabora‑ Afghanistan . Arabie saoudite . Bahreïn . Djibouti . Égypte . Émirats arabes unis . République islamique d’Iran teurs de l’OMS et personnes concernés au sein et hors de la Région. Iraq . Libye . Jordanie . Koweït . Liban . Maroc . Oman . Pakistan . Palestine . Qatar . République arabe syrienne Somalie . Soudan . Soudan du Sud . Tunisie . Yémen

EMHJ is a trilingual, peer reviewed, open access journal and the full contents are freely available at its website: http://www/emro.who.int/emhj.htm EMHJ information for Authors is available at its website: http://www.emro.who.int/emh-journal/authors/

EMHJ is abstracted/indexed in the Index Medicus and MEDLINE (Medical Literature Analysis and Retrieval Systems on Line) and the ExtraMed-Full text on CD-ROM, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), CAB International, Lexis Nexis, Scopus and the Index Medicus for the WHO Eastern Mediterranean Region (IMEMR). Correspondence

Disclaimer Nasr City, Cairo 11371 The designations employed and the presentation of the material in this publication do not imply the expression of any opinion Egypt whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of Tel: (+202) 2276 5000 its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border Fax: (+202) 2670 2492/(+202) 2670 2494 lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products Email: [email protected] does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either express or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. The named authors alone are responsible for the views expressed in this publication. Subscriptions and Distribution Enquiries regarding subscriptions and distribution of the print edition of EMHJ should be addressed to: Printing and Marketing of Publications at: email: [email protected]; ISSN 1020-3397 tel: (+202) 2276 5000; fax: (+202) 2670 2492 or 2670 2494

Permissions Requests for permission to reproduce or translate articles, whether for sale or Cover designed by Diana Tawadros non-commercial distribution should be addressed to Cover photograph: Dr Linda Stannard, UCT/Science Photo Library EMHJ at: [email protected] Internal layout designed by Emad Marji and Diana Tawadros Printed by WHO Regional Office for the Eastern Mediterranean

Cover 19 Supplement.indd 2 5/16/2013 1:30:58 PM Eastern Mediterranean La Revue de Santé de Health Journal la Méditerranée orientale

املجلد التاسع عرش العدد اإلضايف Vol. 19 Supplement 1 •2013• 1

Supplement on Novel Coronavirus

Contents

Editorial Novel coronavirus infection: time to stay ahead of the curve Ala Alwan, Jaouad Mahjour and Ziad A. Memish...... S3 Perspective Emergence of novel coronavirus: global context Keiji Fukuda...... S5 Country experiences Saudi Arabia and the emergence of a novel coronavirus Z.A. Memish, R. Alhakeem and G.M. Stephens...... S7 Novel coronavirus infections in Jordan, April 2012: epidemiological findings from a retrospective investigation B. Hijawi, M. Abdallat A. Sayaydeh, S. Alqasrawi, A. Haddadin, N. Jaarour, S. Alsheikh and T. Alsanouri...... S12 Reviews The early response to a novel coronavirus in the Middle East A. Mounts, S. De La Rocque, J. Fitzner, E. Garcia, H.L. Thomas, D. Brown, H. Schuster, K. Vandemaele, H. Esmat, S. Eremin and A. Mafi...... S19 Novel coronavirus: the challenge of communicating about a virus which one knows little about G. Härtl...... S26 Novel coronavirus infection in the Eastern Mediterranean Region: time to act M.R. Malik, A.R. Mafi , J. Mahjour, M. Opoka, M. Elhakim and M.O. Muntasir...... S31 Infection prevention and control measures for acute respiratory infections in healthcare settings: an update W.H. Seto, J.M. Conly, C.L. Pessoa-Silva, M. Malik and S. Eremin...... S39 Emerging respiratory and novel coronavirus 2012 infections and mass gatherings J.A. Al-Tawfiq, C.A.H. Smallwood, K.G. Arbuthnott, M.S.K. Malik, M. Barbeschi and Z.A. Memish...... S48 Short communications Enhanced surveillance and investigation of coronavirus: what is required? R.G. Pebody, A. Nicoll, U. Buchholz, M. Zambon and A. Mounts...... S55 Public health investigations required for protecting the population against novel coronaviruses A. Nicoll...... S61 Meeting report Highlights and conclusions from the technical consultative meeting on novel coronavirus infection, Cairo, Egypt, 14–16 January 2013 C. Joseph, M.R. Malik, A.W. Mounts, A.R. Mafi, S. Briand, Z.A. Memish and the technical working group for the meeting on novel coronavirus...... S68

Book 19 Supplement.indb 1 5/16/2013 2:27:22 PM Dr Ala Alwan, Editor-in-chief Editorial Board Professor Zulfiqar Bhutta Professor Mahmoud Fahmy Fathalla Professor Rita Giacaman Dr Ziad Memish Dr Sameen Siddiqi Professor Huda Zurayk International Advisory Panel Dr Mansour M. Al-Nozha Professor Fereidoun Azizi Professor Rafik Boukhris Professor Majid Ezzati Dr Zuhair Hallaj Professor Hans V. Hogerzeil Professor Mohamed A. Ghoneim Professor Alan Lopez Dr Hossein Malekafzali Professor El-Sheikh Mahgoub Professor Ahmed Mandil Dr Hooman Momen Dr Sania Nishtar Dr Hikmat Shaarbaf Dr Salman Rawaf Editors Fiona Curlet, Guy Penet Eva Abdin, Alison Bichard, Marie-France Roux Graphics Suhaib Al Asbahi, Hany Mahrous, Diana Tawadros Administration Nadia Abu-Saleh, Yasmine El Sakhawy, Yasmeen Sedky

Book 19 Supplement.indb 398 5/16/2013 2:27:22 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

Editorial Novel coronavirus infection: time to stay ahead of the curve Ala Alwan,1 Jaouad Mahjour 2 and Ziad A. Memish 3

In 2003, the World Health Organiza- of the UK provided the first convincing Our experience with novel corona- tion (WHO) steered an unprecedented evidence of person-to-person transmis- virus infection reinforces the benefits of global response to successfully control sion [6]. regional engagement amongst WHO severe acute respiratory syndrome The origin of this virus remains Member States. It also highlights the (SARS), a new disease caused by a unknown. Early scientific evidence cooperation that is necessary to suc- previously unknown coronavirus. This suggests that the virus might already cessfully combat international health became the first major international be widespread in animals [7] but threats within the spirit and framework health emergency in the 21st century much about this virus remains to be of International Health Regulations [1]. Almost 10 years later in June 2012, understood. Important questions to (2005) [8]. WHO and international the discovery of another novel strain be answered include the origins of the scientific communities have benefitted of SARS-like coronavirus [2] sparked outbreak, how widespread it is in na- from the willingness of countries in our similar alarm. This virus belongs to the ture, whether it is a zoonotic infection, region to share viruses and information same family of viruses that caused SARS and how it emerged in humans as a immediately. This has allowed timely in 2003. It also causes unusually severe virulent pathogen. Most important of sequencing studies and the rapid devel- pneumonia and death in a majority of all is whether infection can be sustained opment of diagnostic tests. patients [3]. Because a significant pro- through human-to-human transmis- Ten years after the world success- portion of cases have been acquired sion. Its risk to global health will be fully fully contained SARS, critical questions in our region, it has had a significant understood once the scale and evolu- remain. How safe is the international impact on the countries of the Eastern tion of this virus is known. Geographic community? Are we prepared for an- Mediterranean. monitoring is a priority, particularly other global event like SARS? There are By April 2013, as the number of fa- mapping across jurisdictions. mounting concerns over a succession of talities from the Eastern Mediterranean In January this year, experts from new pathogens identified since the turn region rose to 9 and with 14 confirmed WHO and other international health of the century [9]. The world has already cases [4], the situation raised some bodies assembled in Cairo to discuss experienced the century’s first influenza pressing questions. This virus had not what is currently known about this pandemic. This event was preceded by been detected in humans or animals virus. Efforts to answer important another outbreak of global importance previously [5], and although most cases questions have been made as shown – avian influenza caused by H5N1 virus. were sporadic, recent evidence of limited by Angus Nicoll, Anthony Mounts and Lessons from avian influenza, pandemic person-to-person transmission from in- colleagues in this issue of the EMHJ. influenza, the recent emergence of novel dex case to family members heightened Articles from Richard Pebody, Bassam coronavirus infection in the Middle East concerns. The latest cluster involved a Hijawi and others have also contrib- and influenza A(H7N9) virus in China United Kingdom (UK) resident who uted important new data. The papers [10] demonstrate that all these diseases seemed to have acquired his infection published in this issue of the Journal have in common “known unknowns”. in south Asia or the Middle East. Two provide a convincing demonstration New pandemic diseases will emerge family members who became ill on his of the global health community work- again in the future. Novel microbes that return were subsequently diagnosed ing together to build the evidence base are sustained in nature will eventually with novel coronavirus infection. The that will guide and inform public health spill over again to infect human popu- fact that neither had travelled outside decisions. lations. When this happens, another

1Regional Director, World Health Organization Regional Office for Eastern Mediterranean, Cairo, Egypt. 2Director, Department of Communicable Disease Prevention and Control, World Health Organization Regional Office for Eastern Mediterranean, Cairo, Egypt. 3Deputy Minister of Health for Public Health, Ministry of Health, Riyadh; Professor, College of Medicine, Al Faisal University, Riyadh, Kingdom of Saudi Arabia (Correspondence to Ziad A. Memish: [email protected]).

Book 19 Supplement.indb 3 5/16/2013 2:27:22 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

major international health crisis will be surveillance and targeted response cornerstone for WHO’s vision of global announced [11]. systems across all countries. Such sys- health security. It will also be a test of the The emergence two human patho- tems should be designed to optimize global public health community’s col- gens, novel coronavirus and influenza disease intelligence and to improve risk lective response to this new infectious A(H7N9) virus, within the past few forecasting. The current priority is to disease. months reminds us that global health monitor coronavirus infections for evi- The global public health community is not yet safe. Although these events dence of sustained human-to-human must attempt to understand the public could not be predicted, we can still transmission. While it is important to health risk associated with this virus. No gain if we are better prepared through weigh the evolving risk on a prospective one knows how far the disease might shared and joint defences. This will basis, we must stay ahead of the curve. spread and its ultimate ramifications for require constant vigilance, proactive Expecting the unexpected will be the the region and also the world.

References

1. Heyman DL, Mackenzie JS, Peiris M. SARS Legacy: out- 6. Update: Severe respiratory illness associated with a novel break reporting is expected and respected. Lancet, 2013, coronavirus-worldwide, 2012–2013. MMWR Morbidity and 381:779−781. Mortality Weekly Report, 2013, 62(10):194–195. 2. ProMED-mail. Novel coronavirus − Saudi Arabia: human isolate. 7. Müller MA et al. Human coronavirus EMC does not require Archive number: 20120920.1302733. 20 September 2012 the SARS-coronavirus receptor and maintains broad replica- (http://www.promedmail.org/?p=2400:1000, accessed 4 tive capability in mammalian cell lines. mBio, 2012, 3e00515-12 October, 2012). (http://mbio.asm.org/content/3/6/e00515-12.long, accessed 2 May 2013). 3. Nuttall I, Dye C. The SARS wake-up call. Science, 2013, 339:1287–1288. 8. International Health Regulations, 2005, 2nd ed. Geneva, World Health Organization, 2008. 4. World Health Organization. Global alert and response (GAR). Novel coronavirus infection − update. 26 March 2013 [webpage]. 9. Lightfoot N, Rweyemamu M, Heymann DL. Preparing for the (http://www.who.int/csr/don/2013_03_26/en/index.html, next pandemic. BMJ (Clinical Research ed), 2013, 346:f364. accessed 10 April, 2013). 10. Uyeki TM, Cox JN. Global concerns regarding novel influenza 5. Corman VM et al. Detection of a novel human coronavirus A (H7N9) virus infection. New England Journal of Medicine, by real-time reverse-transcription polymerase chain reac- 2013, DoI: 10.1056/NEJMp1304661 (http://www.nejm.org/ tion. Eurosurveillance, 2012, 17(39):pii 20285 (http://www. doi/full/10.1056/NEJMp1304661, accessed 2 May 2013). eurosurveillance.org/ViewArticle.aspx?ArticleId=20285, ac- 11. Morse SS et al. Prediction and prevention of the next pan- cessed 2 May 2013). demic zoonosis. Lancet, 2012, 380:1956–1965.

Book 19 Supplement.indb 4 5/16/2013 2:27:22 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

Perspective Emergence of novel coronavirus: global context Keiji Fukuda 1

In the past four decades, the emergence the International Health Regulations the full implementation of this Frame- of new infectious diseases has shaped (IHR) and to adopt a revision in 2005. work, similar to the IHR, will take time. not only medical concepts, but also The regulations, which came into force Nonetheless, both frameworks clearly those of science and public health; in 2007, are an acknowledgement that all point to the directions that the world affected political responses at global, countries are at risk from certain threats, will need to move if such new diseases regional and national levels; had seri- such as a new infectious disease with and other risks to global health security ous economic impact; and influenced the potential for international spread are to be optimally addressed. the anxieties and expectations of the [3]. The IHR also stress the need for a The 2009 H1N1 influenza pandem- public. The novel coronavirus (nCoV) proactive approach by affected coun- ic demonstrated that a global outbreak discovered in 2012 adds another such tries and the need for transparency in of even a relatively mild disease could disease [1] and its potential impact may reporting. This approach encompasses overwhelm the capacity of many coun- best be understood in such a historic prevention, containment, investigation tries to respond and raised a number and global context. and timely reporting of findings. of issues. At the beginning of the pan- In the 1980s, the emergence of In 2011, a new fundamental public demic, the naming of the virus raised HIV/AIDS had an enormous impact health agreement called the Pandemic concerns with respect to fairness and on medicine, science, politics and soci- Influenza Preparedness (PIP) Frame- stigmatization. The naming issue, along ety—an impact that is still unfolding. work was adopted after more than with the rapid pace of developments The concerns raised by HIV/AIDS four years of formal negotiations. This and enormous amounts of information changed the relationship of patients to Framework was catalysed by the spread and misinformation, aided in particular their disease, treatment and physicians of H5N1, which sharply demonstrated by social media and the Internet, cre- and provided the clearest example to the need for equity among countries ated significant levels of distrust and date that a disease has the capacity to [4]. In a strict sense, the PIP Framework anxiety among countries, the media, the become a globally transforming politi- pertains only to potential pandemic public, individuals and organizations. cal issue, affecting national and interna- influenza viruses but reflects the larger The pandemic eventually underscored tional relations [2]. concerns of Member States of the that countries are better prepared than The decade from 2000 to 2010 was World Health Organization (WHO). in the past but they still have much to do an active one for emerging infectious Under the PIP Framework, coun- to be adequately prepared. diseases. The emergence of severe acute tries have agreed that the sharing of With the emergence of a novel coro- respiratory syndrome (SARS) demon- potential pandemic influenza viruses navirus in 2012, we are once again in a strated the speed at which an infectious as well as the benefits resulting from situation both familiar and uncertain. disease, in this globalized world, can this sharing, such as diagnostic tests, This novel virus is capable of causing move beyond its local origins to be- vaccines and medicines, are of equal severe disease and death. Evidence come a global crisis affecting the health importance. The discussions preceding suggests that limited human-to-human of people and economies by reducing adoption of the Framework highlighted transmission has occurred but its pros- international travel and trade. The emer- other problematic issues around ac- pects for sustained or easy transmission gence of other infectious-disease agents, tivities, such as research, publications, remain unresolved. In addition, the such as avian influenza A(H5N1) and material transfer agreements, and source – presumably an animal – is still Nipah virus, further emphasized the in- patents and other intellectual prop- unknown, complicating efforts to limit extricable links between human health, erty claims. These issues can become exposure. In short, the future course is agriculture and the environment. potential impediments to the sharing uncertain but it is clear that early deci- SARS and H5N1 became the of critical information, materials and sions and actions could have profound driving forces for countries to reshape technology. Moreover, it is clear that and global effects.

1Assistant-Director General, Health Security and Environment, World Health Organization, Geneva, Switzerland ([email protected]).

Book 19 Supplement.indb 5 5/16/2013 2:27:22 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

When new threats to human health embodied in both the IHR and the PIP those who need to know to address arise, anxiety, needs and expectations are Framework. the critical questions related to the high. Policy-makers require information Just as events such as the emer- novel pathogen is critical for inform- quickly that will inform risk assessments gence of a novel pathogen have inter- ing control efforts. The IHR provide and potential countermeasures. The national consequences, successfully both a useful mechanism for report- public, likewise, demand transparency ing and sharing information through responding to them requires interna- and trust and assurance that the actions WHO, and a framework for making tional cooperation. This includes in- taken by all of those involved, including decisions about what to report. As has WHO and its Member States, scientific formation sharing and cooperation been seen in SARS, H5N1, Nipah and and public health organizations, and between animal and human health countless other emerging pathogens, the research community, are guided sectors, between ministries of health in WHO serves a critical coordinating by overarching concerns about global affected countries and between those function, providing a platform for this health and security and commitment conducting research and those on the coordination and collaboration, and to the highest ideals of science, fairness front lines. Bringing diverse expertise synthesizing information into useful and equity. In short, the principles and moving information quickly to guidance for Member States.

References

1. Zaki AM et al. Isolation of a novel coronavirus from a man with 3. International Health Regulations, 2005, 2nd ed. Geneva, World pneumonia in Saudi Arabia. New England Journal of Medicine, Health Organization, 2008. 2012, 367:1814−1820. 4. Pandemic influenza preparedness framework for the sharing of 2. De Cock KM et al. Reflections on 30 years of AIDS. Emerging influenza viruses and access to vaccines and other benefits. Ge- Infectious Diseases, 2011, 17(6):1044−1048. neva: World Health Organization, 2011.

Book 19 Supplement.indb 6 5/16/2013 2:27:22 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

Country experience Saudi Arabia and the emergence of a novel coronavirus Z.A. Memish,1 R. Alhakeem 1 and G.M. Stephens 1

اململكة العربية السعودية وظهور الفريوس التاجي اجلديد زياد ميمش، رأفت احلكيم، غوين ستيفنس اخلالصـة: إن فاشية املرض الناجم عن الفريوس التاجي Coronavirus اجلديد التي حدثت يف اململكة العربية السعودية يف عام 2012 أصابت أكثر 2012 ما أصابت الذكور ومن يعيشون يف املناطق احلرضية، فمنذ أيلول/سبتمرب وترشين األول/أكتوبر ، حينام نرشت املعلومات عن أول َحالت نْي، بلغ جمموع احلاالت َّاملؤكدة التي أبلغ عنها مخس عرشة حالة. وباستثناء َحالت نْي َاثنت نْي، فإن مجيع احلاالت قد ارتبطت ببلدان شبه اجلزيرة العربية، نْإذ كان معظم احلاالت من مواطني اململكة العربية السعودية )8 حاالت(، وكان من بينها أنثى واحدة، وأصيب سبعة مرىض بالتهاب رئوي وخيم، ونجا منهم اثنان، واحد منهم كان ًمصابا بمرض طفيف، وواحد آخر بمرض دفيذي شأن. وعىل الرغم من االشتباه برساية الفريوس إىل العاملي يف الرعاية الصحية يف الفاشية التي وقعت يف األردن يف نيسان/أبريل 2012، فإنه مل تظهر جمموعات عنقودية مشاهبة يف مستشفيات اململكة العربية السعودية، ومل تكتشف حاالت إضافية من خالل التعقب االستعادي للعاملي املعرضي يف الرعاية الصحية. وقد كشفت جمموعتان عنقوديتان عائليتان، واحدة منهام يف الرياض وواحدة أخرى يف مانشسرت، إنكلرتا. ويتواصل يف الوقت احلارض استقصاء جمموعة عنقودية عائلية ثانية يف الرياض.

ABSTRACT The novel coronavirus disease outbreak in Saudi Arabia in 2012 predominately affected males and those living in urban areas. Since September and October 2012, when the first 2 cases were published, a total of 15 confirmed cases have been reported. All but 2 have been linked to countries of the Arabian peninsula; Saudi Arabian nationals accounted for a majority, 8 in all, and only 1 case was female. Seven patients had severe pneumonia; 2 survived—1 with mild disease and 1 with significant underlying illness. Although transmission of the virus to health-care workers was suspected in Jordan’s April 2012 outbreak, similar clusters have not been found in Saudi Arabia’s hospitals, nor have additional cases been identified through retrospective tracing of exposed health-care workers. Two family clusters have been identified, 1 in Riyadh and 1 in Manchester, England. A second Riyadh family cluster is being investigated.

Emergence d'un nouveau coronavirus en Arabie saoudite

RÉSUMÉ La flambée d'une infection par le nouveau coronavirus en Arabie saoudite en 2012 a principalement affecté des hommes et des résidents urbains. Depuis septembre et octobre 2012, lorsque les deux premiers cas ont été rendus public, 15 cas confirmés au total ont été notifiés. Tous les cas sauf deux avaient des liens avec des pays de la Péninsule arabique ; les citoyens saoudiens étaient majoritaires avec huit cas et un seul cas de sexe féminin a été observé. Sept patients ont souffert d'une pneumonie sévère ; deux ont survécu, le premier cas étant atteint d'une forme légère de la maladie et le deuxième cas étant porteur d'une maladie sous-jacente importante. Si la transmission du virus aux agents de soins de santé a été suspectée pendant la flambée d'avril 2012 en Jordanie, aucun groupe similaire n'a été observé dans les hôpitaux en Arabie saoudite ; aucun cas supplémentaire n'a été dépisté après le suivi rétrospectif des agents de soins de santé exposés. Deux groupes familiaux ont été identifiés, un à Riyad et un autre à Manchester (Angleterre). Un deuxième groupe familial fait l'objet d'analyses à Riyad.

1Ministry of Health, Public Health Directorate, Riyadh, Saudi Arabia (Correspondence to Z.A. Memish: [email protected]).

Book 19 Supplement.indb 7 5/16/2013 2:27:22 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

Introduction human coronavirus that emerged in for influenza surveillance were screened southern China during the winter of for nCoV. Hospital laboratories were Novel coronavirus (nCoV) was first iso- 2002 that would highlight the inher- also required to add nCoV to routine lated in June 2012 from the respiratory ent weaknesses of solitary national investigations of respiratory illness cas- secretions of a businessman in the Bisha efforts. Before SARS disappeared the es. Specimens found to be positive by area of Saudi Arabia, who subsequently following summer, it had made more initial testing at MOH laboratories were died of pneumonia and renal failure [1]. than 8000 people ill and killed 774 in forwarded for confirmation to the Unit- This discovery, published in September some 30 countries. It had also disrupted ed Kingdom (UK) Health Protection 2012 [2], was accompanied by a full international trade and compromised Agency laboratories in Birmingham and genome sequence deposit and develop- the economies of more than a dozen Colindale, England, where they were ment of commercial laboratory tests for affected jurisdictions, in developed and assayed for coinfecting viruses (influ- diagnosing acute cases [3]. Confirma- developing countries alike. The World enza A and B virus, parainfluenza virus, tion of more cases of nCoV infection Health Organization (WHO) follow- respiratory syncytial virus, adenovirus, followed, including the case of a Qatari up response included an update of its human metapneumovirus and seasonal national who had been transported to 1969 International Health Regulations in coronaviruses). nCoV confirmation London for treatment of severe pneu- 2005 [6], modifications of treaty obliga- was done by molecular amplification monia [4], and another Saudi Arabian tions that would improve member state of 3 nCoV genes. Confirmation results case, a middle-aged teacher in Riyadh, accountability and a reorganization were reported to the MOH and by the who was the first to survive the infection that prioritized global surveillance and country’s focal point to WHO. [5]. The sequencing alignments for the reporting through the Global Outbreak 2 viral genes from these first 3 cases were Alert and Response network. The emer- Chart reviews identical, and confirmed the outbreak gence of another nCoV in the Eastern Chart reviews were done for each case of a virulent new coronavirus in the Mediterranean Region is about to test to identify clinical features, evaluate Arabian peninsula [5]. Although there these systems. comorbidities and risk factors and track was no immediate evidence of similar the case response to treatment. illness in the hospital contacts or family Family investigations contacts of any of these confirmed cases, Cases and laboratory the clinical presentations were similar investigations Epidemiologists investigated cases and to that of severe acute respiratory syn- associated households within their drome (SARS) pneumonia, prompt- The public health directorate of the Min- respective administrative jurisdictions. ing the Saudi Arabian government istry of Health (MOH) in Saudi Arabia Investigations included a survey of the to convene a session of its National is charged with policy and planning for immediate premises, household inter- Scientific Council to address this new communicable diseases prevention and views and evaluations of close contacts, communicable disease risk both for the control. In September 2012 its surveil- in particular family caregivers. Swabs local population and for inbound Hajj lance and investigation mandates were and sera were collected and coded for pilgrims, who were already arriving by expanded to identify nCoV cases as a each family member. the tens of thousands at King Abdulaziz priority, assess transmission to close Infection control international airport and other Saudi contacts and investigate the possibility investigations Arabian ports of entry. that this was a new zoonotic infectious disease with an animal reservoir on the Hospitals and medical cities conducted Arabian peninsula. retrospective investigations according Background to institutional protocols. Swabs and Case finding sera were collected by infection control The 2003 SARS epidemic had galva- Acutely ill individuals who met Saudi personnel, coded and referred to the nized global efforts to improve and Arabia’s case definition (Table 1) were MOH laboratories. modernize communicable disease identified through physician, infection surveillance, and to identify and contain control and other institutional reports Animal studies outbreaks of serious respiratory disease to the MOH communicable diseases Surveillance of immediate and neigh- as a first priority. Although influenza office. Hospitals and medical cities were bouring premises was done for each preparedness programmes had been required to identify patients on ventila- case, along with investigations of ad- updated in many jurisdictions by the tion to the MOH and submit speci- joining areas and locales such as rest year 2000, it was a previously unknown mens for testing. Specimens submitted houses (istirahat) and farms that had

Book 19 Supplement.indb 8 5/16/2013 2:27:23 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

Table 1 Saudi Arabian case definitions of novel coronavirus Term Saudi Arabian criteria Suspected case • Acute respiratory illness; • Onset includes high fever ≥ 38 °C, cough; • Requires hospitalization; • Evidence of lung parenchymal involvement; • Not explained by other etiology. Probable case • May or may not require hospitalization but otherwise fits criteria for suspected case; • Specimens are not available for testing or patient is not available for testing; • Not explained by other etiology. Confirmed case • Laboratory confirmed. Close contact • Anyone who provided care for the patient; • May include health-care worker or family member; • Anyone who stayed in the same place as a probable or confirmed case while case was symptomatic. Hajj case definition • Meets criteria for suspected, probable or confirmed case; • Symptom onset during Hajj, or 10 days before or 10 days after Hajj; • Located in or near Mecca or Medina cities. Secondary case • Contact with a suspected, probable or confirmed case; • Disease onset within 10 days of index case.

been visited by cases. This was used to Suspected cases each gathering involves the work of 24 guide specimen collections that were In addition to the 8 confirmed cases, supervising committees that coordi- forwarded to reference laboratories for Saudi Arabia to date has had 2 suspect- nate with the Saudi Arabian MOH as sequencing studies. ed cases, both residents of Riyadh. The the agency with primary oversight of first was a 16-year-old male, grandson preventive medicine and public health of case 7, son of case 8 and nephew of matters. Pilgrims are provided with free Summary of findings case 9. All were members of the same health care in 141 centres in or near Hajj venues. This includes 25 hospitals Confirmed cases household. A second suspected case was the brother of case 15 and the likely and a total of 4457 beds including 500 Table 2 summarizes the chronology index case for his household. Case 10, a critical care and 500 emergency care and clinical picture of cases linked to 60-year-old UK resident with a history of beds. Around 20 000 specialized health- Saudi Arabia. To date, Saudi Arabia travel to Pakistan and Saudi Arabia, was care workers are deployed to work in has had a total of 8 confirmed cases, reported by the UK Health Protection these various facilities in a typical year. including 2 survivors—1 who did not Agency on 7 February 2013. This case Ports of entry are managed by public progress to respiratory failure and 1 who was also associated with subsequent health officers to ensure compliance survived despite underlying disease and transmission of novel coronavirus to 2 with MOH regulations. There are addi- respiratory and renal failure. Only 1 family members, neither of whom had tional public health teams, including 21 confirmed case was female, the others travelled outside the UK [7]. mobile teams, located in various areas of were males between the ages of 31 and the Hajj. King Abdulaziz international 70 years. The 5 sporadic cases outnum- airport terminal in Jeddah is the port of bered the 3 cases in clusters, although a Surveillance before, entry for more than 80% of pilgrims and second family cluster linked to case 15 during and after Hajj the site of initial health screening for the was identified. All but 2 cases lived in vast majority who will enter the holy urban Riyadh: case 1 resided in Bisha, Background sites within hours to days of arriving in an agricultural community located in The Hajj pilgrimage draws 2.5 to 3 Saudi Arabia. Public health teams based south-western Asir province, and case million visitors to Saudi Arabia each at the airport and throughout Hajj ven- 14 lived in Burayda, a city in Al Qassim year, more than half of whom come ues report to a central unit on 9 types of province, north of Riyadh (Figure 1). from overseas countries. Planning for communicable disease: influenza and

Book 19 Supplement.indb 9 5/16/2013 2:27:23 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

influenza-like illness, cholera and foodborne illness, menin- b gococcal disease, yellow fever, viral haemorrhagic fever, polio No No No No Yes Yes Yes Yes Family Family cluster and plague [8]. The WHO collaborating Centre for Mass Gatherings Medicine in Saudi Arabia is the repository for data from each Hajj event.

Alive Alive Novel coronavirus Outcome Deceased Deceased Deceased Deceased Deceased Deceased Hajj 2012 was scheduled to start on 24 October, a month after the first report of the discovery of nCoV. Infectious disease risks were updated and reviewed by the National Sci- entific Committee on 27 September 2012. Evidence of nCoV

– – – – – – prevalence in the region was then limited to 2 confirmed cases. Although both cases resembled SARS pneumonias—ful-

Diabetes mellitus, minant disease in previously healthy adults—there were no Past medical history Past cardiovascular disease disease cardiovascular Congestive health failure symptomatic secondary cases among 64 health-care workers

a exposed to case 2 in the UK [9] and none were identified at Jeddah or Bisha hospitals where there was exposure to the first No No No No No No No No Other agents case. Family members of both cases remained well. Neither the WHO nor the Saudi Arabian government found compelling reasons to restrict access to the Hajj based on concerns about

– – – – nCoV. Other diagnoses Renal failure Renal failure Renal failure Renal failure Hajj studies and collaborations To further evaluate the prevalence of nCoV in Saudi Arabia, enhanced surveillance was undertaken at the 2012 Hajj. Individuals who met the Hajj case definition for suspected infection (Table 1) were evaluated by health-care staff and swab specimens were collected and referred to a regional Pneumonia Acute diagnosis

Respiratory failure Respiratory failure Respiratory failure Respiratory failure Respiratory failure Respiratory failure Respiratory failure Respiratory MOH laboratory for testing. Public health staff also monitored

Congestive health failure; health-care facilities and all hospitals in the cities of Mecca and Medina for cases of severe respiratory infection. In addition, Saudi Arabia enabled other governments and nongovern- mental organizations to collect specimens and analyse data on Bisha Riyadh Riyadh Riyadh Riyadh Riyadh Riyadh Region pilgrims returning home. Bur Qassim Sample size continues to be an issue for studies of communicable disease risks at the Hajj; organizing investigations Family cluster = more than cluster = more Family within 1 case a household. b based on a representative selection of pilgrims is particularly challenging given the intensity of the event and a denominator Jan 2013 Jun 2012 Feb 2012 Feb 2012 Feb Oct 2012 Oct 2012 Nov 2012 Nov 2012 of 2.5 to 3 million people. Nonetheless, the Saudi Arabian

Date of onset MOH confirmed that admissions of respiratory cases to Hajj hospitals had been within the expected range for the 2012 Hajj. Respiratory tract swabs of hospitalized patients—190 Sex Male Male Male Male Male Male Male Female from Medina hospitals and another 86 from Mecca hospitals —tested negative for nCoV molecular targets, as did swabs from 154 pilgrims tested on return home to France [10]. More 31 61 37 39 65 49 70 60 recently the Saudi Arabian MOH, through its leadership of

Age (years) the newly established collaborating Centre for Mass Gather-

Description of confirmed cases of infection novel coronavirus to Saudi Arabia linked ings Medicine, will conduct cross-sectional and longitudinal studies on nCoV and other respiratory tract infections for Case no. Case 3 5 7 8 9 13 14 15 Other agents = other coinfecting viruses or bacterial pathogens; Table 2 Table a surveillance, prevention and control.

S10

Book 19 Supplement.indb 10 5/16/2013 2:27:23 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

compelled the first truly international effort aimed at containing an incipient virus pandemic. That legacy is evident now; scientific collaborations have produced full genome sequences, laboratory tests to quickly diagnose infection and a body of knowledge that supports a technology-driven search for an animal reservoir. Perhaps the most important legacy of SARS is the International Health Regulations 2005, with new rules to compel rapid, coordinated case reporting and enable an informed evaluation of global risks [6]. This information is now disseminated to a global audience in real time. Whether nCoV disappears suddenly, as did the SARS coronavirus in 2003, remains to be seen. To date, there is limited evidence to support a pandemic risk, although transmission to close contacts is now established Figure 1 Map of Saudi Arabia showing the location of cases with certainty. Whether we are watch- ing an epidemic in progress remains to be seen. Collaborations and partner- Summary global expertise focused on this agent ships with local disease experts have and on the countries of the Eastern been slow to evolve, yet they remain The first report of a virulent nCoV in Mediterranean Region that have been essential if we are to have a better un- September 2012 has been followed linked to it. Ten years ago it was anoth- derstanding of the epidemiology of by an extraordinary convergence of er virulent coronavirus—SARS—that nCoV.

References

1. Zaki AM et al. Isolation of a novel coronavirus from a man with 7. Novel coronavirus 2012 in the UK: situation as at 19 February pneumonia in Saudi Arabia. New England Journal of Medicine, 2013. Health Protection Report, 2013, 7(8). 2012, 367:1814–1820. 8. Al-Tawfiq JA, Memish ZA. The Hajj: updated health hazards 2. Novel coronavirus—Saudi Arabia: human isolate. ProMed, and current recommendations for 2012. Eurosurveillance, 2012, 2012, archive number 1302733:20. 17(41):pii 20295. 3. Corman VM et al. Detection of a novel human coronavirus 9. Pebody RG et al. The United Kingdom public health response by real-time reverse-transcription polymerase chain reaction. to an imported laboratory confirmed case of a novel coro- Eurosurveillance, 2012, 17(39):pii 20285. navirus in September 2012. Eurosurveillance, 2012, 17(40):pii 4. Bermingham A et al. Severe respiratory illness caused by a 20292. novel coronavirus, in a patient transferred to the United King- 10. Gautret P et al. Lack of nasal carriage of novel corona virus dom from the Middle East, September 2012. Eurosurveillance, (HCoV-EMC) in French Hajj pilgrims returning from the Hajj 2012, 17(40):pii 20290. 2012, despite a high rate of respiratory symptoms. Clinical 5. Albarrak AM et al. Recovery from severe novel coronavirus Microbiology and Infection, 2013, Feb 11 (doi: 10.1111/1469- infection. Saudi Medical Journal, 2012, 33:1265–1269. 0691.12174). 6. International health regulations (2005), 2nd ed. Geneva, World Health Organization, 2005.

S11

Book 19 Supplement.indb 11 5/16/2013 2:27:23 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

Country experience Novel coronavirus infections in Jordan, April 2012: epidemiological findings from a retrospective investigation B. Hijawi,1 M. Abdallat 2 A. Sayaydeh,2 S. Alqasrawi,2 A. Haddadin,3 N. Jaarour,2 S. Alsheikh 2 and T. Alsanouri 3

العدوى بالفريوس التاجي اجلديد يف األردن نيسان 2012: النتائج الوبائية للتقصيات االستعادية ِ بسام ح َّجاوي، حممد العبدالّت، أيوب صيايده، سلطان الكرساوي، أكثم حدادين، نجوى جعروري، سامح الشيخ، طارق السانوري 2012 اخلالصـة: يف نيسان/أبريل ، اندلعت فاشية من املرض التنفيس ّاحلاديف إحدى املستشفيات العمومية يف مدينة الزرقاء يف األردن، وأصيب خالهلا ثامنية من العاملي يف الرعاية الصحية من بي أحد عرش ًمصابا، ومات أحدهم بعد ذلك. ومل يكن سبب الفاشية ًمعروفا آنذاك، فالنتائج التي أسفرت عنها التقصيات الوبائية والتي َّتضمنت اختبارات خمتربية أجريت فور اندالع الفاشية مل تكن قاطعة. وبعد اكتشاف العدوى بالفريوس التاجي اجلديد يف اجلزيرة العربية يف أيلول/سبتمرب 2012، أجريت االختبارات ًجمدداعىل العينات التنفسية واملصلية التي تم ختزينها من املرىض يف تلك الفاشية، َّفتأكد تشخيص العدوى بالفريوس التاجي اجلديد لدى َمريض نْي َمتوفي نْي. وتصف هذه الدراسة النتائج الوبائية للتقصيات االستعادية التي أجريت يف ترشين الثاين/ 2012 نوفمرب ، ُوتلقي الضوء عىل احتامل رساية عدوى املستشفيات بالفريوس التاجي يف مواقع الرعاية الصحية. فقد تم كشف َحالت نْي َّمؤك َدت نْي ًخمتربيا وإحدى عرشة حالة حمتملة يف تلك الفاشية، وكان من بي املصابي هبا عرشة من العاملي يف الرعاية الصحية واثنان من أفراد ُأ َسر املصابي باحلاالت.

ABSTRACT In April 2012, an outbreak of acute respiratory illness occurred in a public hospital in Zarqa city, in Jordan; 8 health care workers were among the 11 people affected, 1 of who later died. The cause of the outbreak was unknown at the time and an epidemiological investigation including laboratory testing carried out immediately after the outbreak was inconclusive. Following the discovery of novel coronavirus infection (nCoV) in the Arabian peninsula in September 2012, stored respiratory and serum samples of patients from this outbreak were retested and the diagnosis of nCoV was confirmed in 2 deceased patients. This paper describes the epidemiological findings of retrospective investigation carried out in November 2012 and highlights the likelihood of nosocomial transmission of nCoV infection in a health-care setting. A total of 2 laboratory-confirmed and 11 probable cases were identified from this outbreak of whom 10 were HCWs and 2 were family members of cases.

Infections par le nouveau coronavirus en Jordanie, avril 2012 : résultats épidémiologiques d'une étude rétrospective

RÉSUMÉ En avril 2012, une flambée de maladies respiratoires aiguës a été observée dans un hôpital public de la ville de Zarqa (Jordanie) ; huit agents de soins de santé faisaient partie des onze personnes affectées, et l'un d'eux est décédé ultérieurement. La cause de cette flambée était inconnue à l'époque et l'étude épidémiologique menée immédiatement après la flambée, comprenant des analyses de laboratoire, n'a pas permis de tirer de conclusions. Après la découverte d'une infection par le nouveau coronavirus dans la péninsule arabique en septembre 2012, des échantillons respiratoires et sériques prélevés chez des patients de cette flambée, et qui avaient été conservés, ont été réanalysés et le diagnostic d'infection par le nouveau coronavirus a été confirmé chez deux patients décédés. Le présent article présente les résultats épidémiologiques de l'étude rétrospective menée en novembre 2012 et souligne la probabilité d'une transmission nosocomiale de l'infection par le nouveau coronavirus en milieu de soins. Au total, deux cas confirmés en laboratoire et onze cas probables ont été identifiés à partir de cette flambée ; dix de ces patients étaient des agents de soins de santé et deux patients des membres de la famille de cas.

1Primary Health Care Administration; 2Directorate of Communicable Diseases; 3Laboratory Directorate, Ministry of Health, Jordan (Correspondence to S. Alqasrawi: [email protected]).

S12

Book 19 Supplement.indb 12 5/16/2013 2:27:23 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

Introduction conduct a retrospective investigation of some of the close contacts of both the this outbreak. This paper presents the laboratory-confirmed and probable In April 2012, an outbreak of acute epidemiological findings of this out- cases, and key epidemiological and respiratory illness was reported by the break investigation. clinical information were collected Ministry of Health (MOH) in Jordan including their history of contact with in an intensive care unit (ICU) of a other laboratory-confirmed cases. The hospital in Zarqa. Among the 11 people Methods investigation was targeted at potential affected were 7 nurses and 1 internist; modes of acquisition of the infection. Settings 1 of the nurses later died [1]. All cases The questionnaire contained questions were reported to have had high fever The field investigation was carried out about the early course of disease, social and acute lower respiratory symptoms. in Zarqa, which is the second largest city status, living conditions, profession, An epidemiological investigation, in- in Jordan with a population of about 1 hobbies and regular activities, exposure cluding laboratory tests carried out in million. The city is located 25 km north- to animals, eating habits and contact the immediate aftermath of this out- east of the capital, Amman. There are with individuals with respiratory ill- break, was inconclusive and the cause of 3 public and 3 private hospitals in the ness in the 10 days before the onset of this outbreak remained unknown. city, of which the Zarqa hospital is the illness. oldest and largest public hospital, with In September 2012, novel coronavi- Contact investigations rus (nCoV) infection was identified in a a capacity of 300 beds including 6 beds The family members of the 2 laboratory- patient from Saudi Arabia and later in a in the coronary care unit (CCU) and 6 confirmed cases could not be contacted patient from Qatar [2–4]. In October beds in the ICU. and no information was collected on 2012, after the discovery of the nCoV Epidemiological investigations the duration or frequency of contact and following reports of patients with with the laboratory-confirmed cases. nCoV infections presenting with similar Case definition acute lower respiratory symptoms, the For the purpose of retrospective in- Laboratory investigations Ministry of Health decided to retest the vestigation a probable case definition The hospital laboratory was searched samples from this outbreak for nCoV was developed, defined as “any case for availability of any other stored res- at the United States Naval Medical admitted in Zarqa hospital or their close piratory or blood samples from the ad- Research Unit-3 (US NAMRU-3) contacts, who complained of fever and ditional cases reported in this outbreak in Cairo, a World Health Organiza- dry cough with radiological evidence of in April 2012. No such samples were tion (WHO) collaborating centre for pneumonia during the period from 15 available. emerging infectious diseases. Samples March to 30 April [2012]”. For the pur- were tested by conventional universal pose of the investigation, a close contact pan-corona virus primers and specific was defined as “anyone who provided Results reverse transcription real-time polymer- care to a laboratory-confirmed case, ase chain reaction (RT-PCR) for the Epidemiological investigation including a HCW or family member, or of the initial cluster nCoV using reagents from the United who had other similarly close physical States Centers for Disease Control and contact”, as recommended in the WHO For the description of this outbreak, Prevention. Bronchioalveolar lavage interim surveillance recommendations all listed cases from the outbreak were and nasal swab extracts from a case, who for human infection with nCoV [6]. considered as probable if no laboratory was a health-care worker (HCW)—an conformation were available. A total of intensive care unit (ICU) nurse—and Patient interviews 13 cases were identified that matched a convalescent serum sample from a The team visited the Zarqa public the case definition developed for this second case, who was a student, tested hospital as well as 2 other hospitals to investigation. The total number of positive for nCoV by RT-PCR. Accord- which patients were referred during laboratory-confirmed cases was 2, while ingly 2 laboratory-confirmed cases of the outbreak in April 2012. Medical the remaining 11 cases were defined as nCoV infections were officially notified records were retrieved and reviewed probable. Of these 13 cases, 10 were to WHO by the Ministry of Health in for all patients with severe acute lower HCW in the CCU or ICU, medical or Jordan [5] respiratory infections admitted to ei- emergency ward in the Zarqa public Following these positive test re- ther the ICU or CCU in Zarqa hospital hospital (Table 1). The 3 non HCWs sults, the MOH Jordan, together with from 15 March to 30 April. During were a student, a brother of the de- WHO, fielded a team in Zarqa from the visit, interviews were conducted ceased female nurse and the mother of 28 November to 7 December 2012 to with all the probable cases, HCW and a male nurse.

S13

Book 19 Supplement.indb 13 5/16/2013 2:27:23 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

Table 1 Line list of confirmed and probable cases of novel coronavirus (nCoV) infection in Zarqa, Jordan, March to May 2012 Case no. Age Sex Date of Date of Date of Occupation Outcome Classification (years) onset admission discharge/ death 1 25 Male 21 Mar 4 Apr 25 Apr Student Deceased Confirmed case 2 30 Male 30 Mar 8 Apr 23 Apr Nurse Alive Probable case 3 40 Female 2 Apr 9 Apr 19 Apr Nurse Deceased Confirmed case Refused Physician, Alive Probable case 4 60 Male 2 Apr admission – internist 5 29 Male 11 Apr 15 Apr 21 Apr Nurse Alive Probable case 6 33 Male 12 Apr 14 Apr 21 Apr Nurse Alive Probable case 7 28 Male 13 Apr 17 Apr 21 Apr Nurse Alive Probable case 8 45 Male 14 Apr 17 Apr 24 Apr Road technician Alive Probable case (brother of case 3) 9 46 Male 15 Apr 16 Apr 21 Apr Nurse Alive Probable case 10 25 Male 15 Apr 18 Apr 21 Apr Nurse Alive Probable case Physician, Alive Probable case 11 53 Male 18 Apr 21 Apr 23 Apr internist 12 28 Female 19 Apr Refused Nurse Alive Probable case admission – 13 60 Female 26 Apr 1 May 5 May Housewife (mother Alive Probable case of case 2)

The investigation and the epidemic further treatment, where he was admit- of illness. It was reported that he was curve suggested 2 phases to the out- ted to the CCU and then to the ICU in direct contact with case 1 as he was break (Figure 1). The initial phase con- isolation room on the second day of his caring for him in the CCU; however, sisted of 4 cases: 2 laboratory-confirmed arrival and was intubated. His condi- it was not clear why his date of onset cases (who died) and 2 probable cases tion deteriorated and he eventually died of symptoms was 5 to 6 days before (who recovered from their illness). For on 25 April. The patient had no travel case 1 was admitted in the hospital. investigation purposes, emphasis was history and had no reported direct con- He was admitted to the CCU of Zarqa put on the initial phase in order to better tact with animals or with persons with hospital on 8 April with shortness of understand the potential origin of the severe respiratory illness in the 10 days breath and bilateral pneumonia. He disease. before the onset of his illness. A total of was transferred to the CCU of Islamic 3 close contacts of case 1 were identified hospital on 12 April and was discharged Case 1 and exposure history (1 household and 2 HCW contact). in good condition on 23 April. A total of Based on the reported date of onset The household contact, who was the 2 close contacts (household contacts) of symptoms case 1 was a 25-year-old patient’s mother, did not report any were identified for case 2. One was the university student who had onset of respiratory symptoms, while 2 HCW mother of case 2 (hereafter referred to symptoms on 21 March 2012. He was developed respiratory symptoms (here- as case 13) and developed respiratory among the 4 cases identified in the after referred as case 2 and case 3) that symptoms which required hospitaliza- initial phase of this outbreak. He had progressed to severe illness requiring tion. The other household contact, who cough for a week followed by fever and hospitalization. was a brother of case 3, had also cared for shortness of breath. He was admitted him but did not report any respiratory to the regular medical ward in Zarqa Case 2 and contacts symptoms in the 10 days post-exposure. public hospital on 4 April with an ini- Case 2 was a 30-year-old male CCU tial diagnosis of pneumonia. His X-ray nurse in Zarqa hospital with an esti- Case 3 and contacts showed right lung consolidation and mated onset of symptoms on 29 March Case 3 was a 40-year-old female ICU he was later treated for pericarditis. He 2012. This was a probable case, who nurse at the Zarqa hospital with on- was then transferred to the CCU a day recovered. The patient had no travel set of symptoms on 2 April 2012 and after admission and later transferred to history and no reported contact with was a laboratory-confirmed case who Prince Hamzah hospital in Amman for animals in the 10 days before the onset later died. From the limited information

S14

Book 19 Supplement.indb 14 5/16/2013 2:27:23 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

Number of Cases Lab confirmed and deceased Probable and recovered

First Wave Second Wave 3 2 3 8 1 12 2 1 5 4 7 9 6 10 11 13 20 21 22 23 24 25 26 27 28 29 30 31 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1 2 3 4 March April May Date of Onset of Symptoms

Figure 1 Epidemic curve of confirmed and probable cases of novel coronavirus infection, Zarqa, Jordan, 20 March to 4 May 2012

available, there was no travel history March to May 2012 acute respiratory infection at admis- or contact with animals in the 10 days The onset of symptoms was between sion and later died. His date of onset before the onset of her illness. She was 11–19 April 2012 for 8 cases and was of symptoms was at the end of March admitted to the ICU of Zarqa hospital 26 April for the last reported probable 2012. No laboratory results for nCoV on 9 April with right-sided pneumo- case. Seven of these probable cases were were performed for this case. Interviews nia. She was transferred to the ICU of HCW (2 CCU nurses, 1 internist, 1 with nurses from the CCU revealed Islamic private hospital in Amman on nurse in the internal ward and 2 nurses 2 other non-Jordanian patients with 14 April, was intubated the following working in the emergency ward) and 2 signs of respiratory infection. Review day and died on 19 April with a dissemi- cases were relatives of HCW (mother was only possible for 1 of them and this nated coagulopathy. A total of 4 close of case 2 and brother of case 3). Based did not show any documented acute contacts of case 3 were identified (all on the available information all of them respiratory disease. household contacts), one of whom was were likely to have had significant con- All admitted cases identified in this a brother of case 3 (hereafter referred to tact with at least 1 of the 2 confirmed cluster were transferred from Zarqa as case 9) and developed pneumonia in cases, apart from the mother of the hospital to 2 other hospitals in Amman the 10 days post-exposure. probable case 2, for whom a contact to a (Islamic hospital and Prince Hamzah confirmed case was not documented in hospital). The 2 referral hospitals were Case 4 and contacts the 10 days before onset of symptoms. asked to analyse their discharge statis- Case 4 was a 65-year-old medical doc- To prevent stigmatization of patients tics (using International Classification tor, head of the internal ward, a probable the HCW reported that they did not of Diseases, version 10 codes) for the case who recovered. The onset of symp- use any personal protective equipment month of March to May 2012 and toms was on 2 April 2012 with fever apart from gloves when caring for the 2011. The information retrieved from and fatigue. There was no travel history patients. one of the referral hospitals (Islamic or contact with animals in the 10 days hospital) suggested an increase in the before the onset of his illness His chest Investigation for additional number of visits to that hospital of pa- X-ray showed bilateral pneumonia. He cases tients with pneumonia, with 74 cases refused admission to the hospital and The initial outbreak investigation report in April 2011 compared with 205 cases took self-care at home. No respiratory stated that there was no unusual pattern recorded in April 2012. No further in- disease was reported in any of his house- of community-acquired respiratory dis- formation was available explaining this hold contacts. ease noted in the community or other apparent rise in cases of severe acute hospitals. It was not possible to validate respiratory infection. this information during the investigation. Review of the ICU admission log Exposure of the patients Epidemiological book in Zarqa hospital revealed 6 other Some information on exposure from investigation of the cases for whom admission could have the initial phase of the outbreak was secondary phase been due to respiratory symptoms and available for the 3 HCW and not for whose files were reviewed. While 5 cases the deceased patient. All of the HCW The secondary phase consisted of 9 were discarded due to irrelevant symp- had no history of travel or contact probable cases who all developed pneu- toms, only 1 case, a 22-year-old patient with animals. The only known fact was monia? and recovered (Figure 2). with Down syndrome, had signs of an that case 3, with onset of symptoms

S15

Book 19 Supplement.indb 15 5/16/2013 2:27:24 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale Secondery phase Initial phase 4 3 2 May 1 30 29 28 27 26 25 24 23 Hamza Hospital CCU worker Care Health 22 contact with case 2 21 HCW 20 19 18 17 16 15 April 14 13 Death Zarqa Hospital CCU 12 11 10 9 8 contact with case 6 Date of Onset of Symptoms 7 6 5 contact with case 1, 2, 3 4 ss contact with case 3 3 Possible period contact Admittion to ward 2 1 31 30 29 contact with case 1 28 27 26 25 24 March Islamic Hospital CCU Hospital Islamic Mildly ill (home sick) ill (home Mildly 23 22 21 20 brother of case 3 Nurse Emergency Ward Nurse CCU Nurse Internal ward CCU Nurse CCU staff CCU student Nurse Emergency Ward Nurse ICU Internist Internist mother ofmother 2 case Nurse Timeline ofTimeline 13 cases of infection, = critical novel coronavirus to May 2012 (CCU March Jordan, unit) Zarqa, care Case 4 Case 8 Case 7 Case 6 Case 5 Case 9 Case 2 Case 1 Case 10 Case 3 Case 13 Case 12 Case 11 Figure 2 Figure

S16

Book 19 Supplement.indb 16 5/16/2013 2:27:24 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

bronchoalveolar lavage from 9 patients on 2 April 2012, had her sister visiting For the index case of this outbreak, were tested at US-NAMRU-3 by RT- from Saudi Arabia 1 month before the we had 2 main hypotheses. Case 1, PCR for coronaviruses (229E, HKU1, onset of symptoms. No information who was a student and admitted with NF69, OC), parainfluenza viruses 1–3, was available regarding residence and pneumonia and pericarditis, was the adenovirus, human metapneumovirus or health status of the visiting sister. first nCoV patient and case 2, who was a and for severe acute respiratory syn- The 2 probable cases in the initial phase HCW became infected from him. How- drome (SARS) virus by nested PCR, of this outbreak had contact with the ever, there remained the question how using published sequences. Except for laboratory-confirmed cases in the CCU the HCW was exposed, as the index case 1, where the RNA extracts from na- of Zarqa hospital, while the 2 other case’s admission was after the 2 HCW sopharyngeal swabs were weakly posi- probable cases in the second phase of had already developed symptoms. It tive for CV 229E by RT-PCR, all other this outbreak—case 13 and case 8— is possible that there might have been cases were negative for all viruses tested. were the household contacts of cases 2 contact between the index case and any Following the discovery of nCoV, an- and 3 respectively. It was also possible of these HCW in the outpatient clinic other set of these stored samples (5 that the 7 HCWs who were the prob- before the index patient’s admission or that each case had different exposure serum samples and 2 nasopharyngeal able cases in the second phase of this histories that could not be identified or swabs and 2 bronchoalveolar lavages) outbreak had some contacts with the 2 established. were sent to US NAMRU-3 for retest- laboratory-confirmed cases of the first ing in October 2012. No additional phase; however, the investigation could Another hypothesis was that case 2 was the initial case and that he infected samples from the outbreak were avail- not establish this link. his colleagues as well as case 1, who he able for nCoV testing in during the Age and sex was caring for. The HCW was present at autumn in 2013. The US NAMRU-3 The median age of patients was 33 years work while he was already symptomatic also tested another 234 nasopharyngeal (range 25–65 years). Males accounted with cough and fever. He also would samples that were collected from the for 77% of the 13 cases. have been in contact with cases 3 and severe acute respiratory infection sen- 4 at his workplace. This would suggest tinel surveillance sites from April and Clinical picture that case 1 was admitted due to signs October 2012 and all samples tested The earliest date of onset of symptoms and symptoms of a different disease and negative for nCoV. was 21 March 2012 and most cases had acquired the infection while in the (70%) were described as having cough CCU at Zarqa hospital. If this is the case, the question then is: from where did Discussion followed by high fever. The duration of admission for admitted patients (2 case 2 contract the infection and why were only HCW infected (beside the In this report of the Jordan 2012 patients refused admission) ranged from 3–17 days with a mean of 9 days. 1 patient and relatives)? The hospital nCoV outbreak we present evidence The white blood cell count in a major- set-up, as well as the stated contact of of limited person-to-person transmis- ity of cases was disproportionately low the HCW while caring for symptomatic sion of nCoV following contact but it considering the extent of infection and cases (i.e. without using precautions seems that transmission did not occur body temperature of the patients. The to prevent transmission) means that frequently. The secondary cases that chest X-rays showed evidence of single- human–human transmission was very were detected had a putative incuba- lobular, bi-lateral or multi-lobular pneu- likely to have occurred. Further pos- tion period within 10 days of reported monias. No sequelae were reported in sibilities are that there was a common contact with cases. The secondary cases the recovered patients. No case had source of infection outside the hospital, were mostly HCW, who most likely renal failure. Case 1 had a pericarditis but again we would expect more cases acquired the infection in health-care set- with huge fluid accumulation. outside the hospital, or that there was tings. However, nCov was not detected yet another patient who would have among the close contact of the index Laboratory investigations: infected the HCW as well as case 1. case or among the 4 close contacts of patient samples For the secondary phase, person- the 2 other cases reported in the initial During the outbreak of acute respira- to-person transmission in health-care phase. These findings suggest that -al tory illnesses in April 2012, the US settings seemed very likely, and close though person-to-person infection is NAMRU-3, Cairo, was requested to contact with respiratory secretions possible, there is no evidence at present support the laboratory investigation seems to be the most likely route of of sustained person-to-person transmis- of cases reported from this out- transmission, despite the limited infor- sion of nCoV in relation to this cluster. break. Nasopharyngeal swabs and 1 mation available. Based on the available

S17

Book 19 Supplement.indb 17 5/16/2013 2:27:24 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

information, the outbreak seems to have social perceptions made access and Further work is required to determine been limited to the direct contacts of data collection from the relatives and how widely nCoV is circulating in the patients (brother and mother). It is other contacts extremely difficult. Other area. To establish the final links and to unclear if there might have been more factors were the death of 2 possible in- investigate the risk factors for transmis- cases with less severe presentations that dex cases, the unavailability of stored sion, a seroepidemiological study needs were not admitted to the hospital and respiratory specimens for the majority to be conducted in various population eventually might have been excluded of patients to be tested for nCoV, the groups—HCW, among families and from the list of probable cases, as the absence of serological tests for confir- the community—to understand the definition for the probable case did not mation of previous infection with nCoV extent of this outbreak. Until that time, include those who presented with mild and the case definition of the outbreak it is important to strengthen both the illness and were not admitted. The lim- which excluded patients without radio- epidemiological and virological surveil- ited transmissibility is consistent with logical evidence of pneumonia. lance for severe acute respiratory infec- the data available to date, with 2 other tions in Zarqa hospitals and to detect reports of small, self-limited clusters of any changes over time. severe disease in the Eastern Mediter- Conclusion and ranean Region in a household setting recommendations [7] and in the United Kingdom in a Acknowledgements household setting [8]. Furthermore, This outbreak of nCoV, with evidence intensive follow-up of the close contacts of likely transmission in a health-care The Jordan Ministry of Health expresses of 2 other cases imported to European setting, together with our observation it is appreciation and thanks to the World countries has failed to demonstrate on- of limited secondary transmission, Health Organization Regional Office for ward transmission [8,9]. highlights the importance of ongoing the Eastern Mediterranean, the World Our investigation had some impor- vigilance and rapid investigation of Health Organization Jordan country of- tant limitations. The main limitation cases or clusters of severe respiratory fice, the United States Naval Medical Re- was recall bias, as the epidemiological illness, including HCW, with pneumo- search Unit-3 in Cairo and the Centers for investigation was conducted 7 months nia from any area that match the cur- Disease Control and Prevention, Atlanta, after the outbreak. The complexity of rent case definition from WHO [6]. Georgia for their assistance and support.

References

1. Severe respiratory disease of unknown origin—Jordan—out- int/csr/don/2012_11_30/en/index.html, accessed 7 May break in ICU. Communicable Disease Threats Report, week 18, 2013). 29 April–May 2012 (http://www.ecdc.europa.eu/en/publi- 6. World Health Organization. Interim surveillance recom- cations/Publications/CDTR%20online%20version%204%20 mendations for human infection with novel coronavirus as May%202012.pdf, accessed 9 May 2013). of 18 March 2013 (http://www.who.int/csr/disease/corona- 2. Zaki AM et al. Isolation of a novel coronavirus from a man with virus_infections/InterimRevisedSurveillanceRecommenda- pneumonia in Saudi Arabia. New England Journal of Medicine, tions_nCoVinfection_18Mar13.pdf, accessed 9 May 2013) 2012, 367:1814–1820. 7. Albarrak AM et al. Recovery from severe novel coronavirus 3. Severe respiratory illness associated with a novel coronavirus- infection. Saudi Medical Journal, 2012, 33:1265–1269. -Saudi Arabia and Qatar, 2012. Morbidity and Mortality Weekly 8. Health Protection Agency (HPA) UK NCoV Investigation team. Report, 2012, 61(40):820–820. Evidence of person-to-person transmission within a family 4. Bermingham A et al. Severe respiratory illness caused by a cluster of novel coronavirus infections, United Kingdom, Feb- novel coronavirus, in a patient transferred to the United King- ruary 2013. Eurosurveillance, 2013, 18(11):pii 20427. dom from the Middle East, September 2012. Eurosurveillance, 9. Buchholz U et al. Contact investigation of a case of human 2012, 17(40): pii: 20290. novel coronavirus infection treated in a German hospital, 5. Novel coronavirus infection—update. 30 November 2012. October–November 2012. Eurosurveillance, 2013, 18(8):pii World Health Organization [online] http://www.who. 20406.

S18

Book 19 Supplement.indb 18 5/16/2013 2:27:24 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

Review The early response to a novel coronavirus in the Middle East A. Mounts,1 S. De La Rocque,2 J. Fitzner,1 E. Garcia,3 H.L. Thomas,4 D. Brown,5 H. Schuster,6 K. Vandemaele,1 H. Esmat,7 S. Eremin 8 and A. Mafi 9

املواجهة الباكرة لفريوس تاجي جديد يف الرشق األوسط أنطوين ماونتس، ستيفان دي الروكي، جوليا فيتزنر، إيريكا غارسيا، لويس توماس، ديفيد براون، هلموت شوسرت، كات فاندماييل، هالة عصمت، سريغي إيرمي، عيل رضا معايف 2012 Coronavirus اخلالصـة: َّأدى كشف فريوس تاجي جديد لدى مرىض من شبه اجلزيرة العربية يف أواخر عام إىل إثارة مكامن قلق ِّجدية الحتامل حدوث فاشية دولية. وقد دعا وزراء الصحة يف البلدان الثالثة املتأثرة بعثات من منظمة الصحة العاملية للمسامهة يف إجراء مراجعة للمعطيات وللقدرات الالزمة لكشف املزيد من احلاالت واالستجابة هلا. وقد تم بالفعل إصدار توصيات حول االستقصاءات لإلجابة عن األسئلة احلاسمة حول االنتقال من إنسان إلنسان وحول املدى اجلغرايف للفريوس. كام صدرت توصيات أخرى لتحسي قدرات ُّالرتصد من خالل اكتساب القدرات يف إجراء ّحتري الفريوسات وتعزيز ُّترصد املتالزمات. وتتواصل ِّالبينات املتوافرة التي تشري إىل وجود مستودع حيواين غري معروف للفريوس مع انتقال ُفرادي حيواين املصدر باعتباره النمط الوبائي األويل لالنتقال. أما االنتقال من إنسان إلنسان، فهو عىل الرغم من إمكان حدوثه - ال يبدو أنه ُم نْس َت َد ٌام يف املجتمع.

ABSTRACT The detection of a novel coronavirus in patients from the Arabian Peninsula in late 2012 raised serious concerns of a possible international outbreak. Ministries of health of the three affected countries invited missions from the World Health Organization to participate in a review of data and capacity to detect and respond to further cases. Recommendations were made for investigations to answer critical questions about human-to- human transmission and the geographic extent of the virus. Additional recommendations were made to improve surveillance capacity by acquiring the capacity to test for the virus and enhance syndromic surveillance. Available evidence continues to suggest an unknown animal reservoir for the virus with sporadic zoonotic transmission as the primary epidemiological pattern of transmission. Human-to-human transmission, while it can occur, does not appear to be sustained in the community.

Riposte rapide au nouveau coronavirus au Moyen-Orient

RÉSUMÉ La détection d'un nouveau coronavirus chez des patients de la Péninsule arabique à la fin de l'année 2012 a soulevé de graves inquiétudes concernant une possible flambée internationale. Les ministères de la Santé des trois pays affectés ont invité des missions de l'Organisation mondiale de la Santé à participer à une revue des données et à un examen des capacités pour dépister les cas à venir et y riposter. Des recommandations ont été formulées pour les recherches visant à répondre aux questions critiques sur la transmission interhumaine et la propagation géographique du virus. Des recommandations supplémentaires ont été effectuées afin d'améliorer les capacités de surveillance en développant la capacité de détection du virus et en renforçant la surveillance syndromique. Les données dont nous disposons semblent toujours indiquer un réservoir animal viral inconnu avec un mode de transmission zoonotique sporadique comme principal modèle épidémiologique de transmission. La transmission interhumaine, si elle est possible, ne semble pas soutenue au sein de la communauté.

1Global Influenza Programme;2 IHR Monitoring, Procedure and Information; 3 Alert and Response Operations; 8Infection Prevention and Control in Health Care, World Health Organization, Geneva, Switzerland (Correspondence to A. Mounts: [email protected]). 4Field Epidemiology Training Programme; 5Virus Reference Department, Public Health England, London, United Kingdom. 6Public Health England, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom. 7Public Health Laboratory Unit, World Health Organization Regional Office for the Eastern Mediterranean, Cairo, Egypt. 9Pandemic and Epidemic Disease, Division of Communicable Disease Control, World Health Organization Regional Office for the Eastern Mediterranean, Cairo, Egypt.

S19

Book 19 Supplement.indb 19 5/16/2013 2:27:24 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

Background transmission in the human population Initial missions to explain the pattern of occurrence. The detection of a novel coronavirus in Furthermore, early comparisons with The initial assessment by the World two patients from the Arabian Penin- other known coronaviruses suggested Health Organization (WHO) was sula in late 2012 captured the attention a similarity to viruses previously de- aimed primarily at reviewing the data of the global public health community scribed in bats, although this may only already collected during investigations for a number of reasons. The virus was reflect the paucity of coronavirus se- by the respective ministries of health of the same family that was responsi- quences available in public databases in Saudi Arabia, Qatar and Jordan to ble for a large multinational outbreak for comparison [3]. Finally, it has been evaluate the possibility that this event of severe acute respiratory syndrome demonstrated that the virus could be constituted a Public Health Emergency (SARS) in 2003 and while the novel easily grown in a number of widely used of International Concern (PHEIC) as virus was not closely related genetically, cell lines [4], and therefore would have defined in the IHR (2005). In addition, the clinical syndrome associated with likely been detected earlier through the WHO missions sought to support the early confirmed cases was severe routine diagnostic testing if circulating the ministries by assisting in a review [1,2]. In addition, the first two reported widely in human populations over a of their capacity to detect and respond cases had a history of having been in long period of time. However, the use to potential further emergence of the the area around Mecca and Medina in of cell culture as a standard diagnostic novel pathogen. The information re- the weeks before their illnesses and the tool has decreased markedly in the past viewed included: second case occurred close in time to decade in favour of polymerase chain • The histories given by the cases of the Hajj. The subsequent retrospective reaction (PCR), which is much less likely to detect novel pathogens. exposures to animals, potential en- confirmation of an outbreak among vironmental sources, and other sick The appearance of a novel patho- health care workers (HCW) in Jordan humans in the days before infection, gen can have serious public health and with two confirmed and a number of including a history of travel outside of probable cases raised concerns that the economic impacts but the immediate the area where illness first occurred. virus could be transmissible between concern is to assess its potential interna- humans. The appearance of the virus tional implications as described in the • Data from investigations of close contacts of the known cases, including in three widely separated areas over at International Health Regulations, 2005 members of the household, close so- least a six-month period further demon- [5]. As such, the primary questions to cial contacts and HCWs exposed in strated the virus’ persistence and wide be addressed early in the course of an the hospital. distribution. These concerns prompted event include: i) does the pathogen the ministries of health of all three coun- transmit from human to human, if not, • Historical trends in data from hos- tries (Saudi Arabia, Qatar and Jordan) ii) what is its geographic distribution pital and intensive care unit admis- to invite teams of international experts and iii) what are the risk factors for ac- sions for severe respiratory infections, to review their data and capacity to de- quiring infection. For a pathogen to mortality from pneumonia and the tect and respond to a serious outbreak have truly pandemic potential it would occurrence of severe respiratory dis- of a novel pathogen. need to be easily transmissible from hu- ease reported to sentinel surveillance man to human. However, even if non- systems. transmissible among humans, a zoono- • Hospital infection control policies Primary questions sis that is widespread in an animal popu- and procedures. lation could cause widespread disease • Respiratory disease surveillance At the outset, the working hypothesis among humans, particular if contact system procedures, policies and ca- regarding the emergence of the novel between human and animal is frequent pacity, including the capacity to in- coronavirus was that it had a zoonotic or transmission is easy. Answering corporate testing for novel viruses in origin with animal host(s) and sporadic these critical questions requires thor- the laboratory. spill-over into humans. However, the ough field investigation to determine evidence for this was entirely circum- the exposure(s) that result in infection, stantial. If this was not a zoonosis, the investigate whether human-to-human Answering the sporadic appearance of severe human transmission has occurred, search for critical questions cases with long periods of time between unrecognized cases and detect signals them and the wide area over which the that may represent previously unrecog- Several recommendations were made virus was apparently distributed would nized circulation of the novel pathogen by the missions to specifically address have required unrecognized ongoing in the community (Table 1). the critical questions (Table 1).

S20

Book 19 Supplement.indb 20 5/16/2013 2:27:25 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

Table 1 Critical initial questions to address in the initial stages of investigation of a novel pathogen Question Investigation Does human-to-human transmission occur? • Survey of exposed health care workers with serological and virological testing • Contact tracing of exposed family and social contacts supported by serological testing What exposures result in infection? • Interview of cases or proxies; case–control study of exposures What is the source of the novel pathogen? • Virological and serological testing of animals, food stuffs; environmental sampling • Seroepidemiological surveys of specific human risk groups • Testing of stored animal clinical specimens Is the pathogen new? When did it first appear? • Review of recent surveillance data, admission records and vital statistics data for the relevant clinical syndrome • Retrospective testing of stored clinical specimens from studies, surveillance or health care facility archives

Human-to-human cases have acquired infection through Because of the challenges in disen- transmission human-to-human transmission. Pri- tangling potential sources of infection in The first clue to both the source of mary among these is the fact that a clear household investigations, HCWs car- infection and the presence of human- history of exposure to potential sources ing for patients with the novel infection to-human transmission will often occur of virus may not be remembered, cases may provide the best first evidence of in the initial interview with the patient are often incapacitated or dead, and human-to-human transmission. Care- and family. Patients or their proxies in household clusters, the majority of ful exposure histories using standard should be carefully questioned using the members of a household will likely questionnaires to document duration memory prompts such as calendars, share common environmental expo- and intensity of exposure and the use menus, travel records, etc. about recent sures. Investigation of the first reported of personal protective equipment are travel, exposure to sick individuals, expo- case was complicated by the fact that he important. If carried out prospectively, sure to animals, activities, hobbies, and had died many months prior to discov- PCR testing can be used to test symp- consumption of unprocessed foods and ery of the virus that caused his illness. tomatic workers exposed to the patient. beverages. Questions should initially be The second case, however, offered a However, the more likely scenario will open-ended and broad in scope but may unique opportunity to tease out poten- involve retrospective investigations of become more specific as hypotheses are tial sources of infection and help clarify workers exposed before recognition generated about possible sources of in- the incubation period. His history il- of the novel agent and subsequent im- fection. Ultimately, exposures of interest lustrates the utility of household inves- plementation of enhanced infection identified during the interview process tigations. The patient had travelled with control. In this situation, serological can be tested for significance through select members of his household to assays are used to confirm infection. As carefully designed case–control studies Mecca and Medina, the same location acute and convalescent sera may not comparing rates of exposure in the cases where the first case may have acquired be possible and diagnosis may rely on to rates in similar randomly selected indi- infection, two to four weeks prior to single sera, the use of control groups viduals from the community. Members illness onset. He then returned home chosen from a similar group of unex- of the household and others with close to Doha but also made a visit with posed workers will enable investiga- physical contact should be asked about other members of his household to a tors to control for rates of background symptoms occurring around the same family farm outside the city. Different seropositivity and exposures occurring time as the known case. If symptoms are members of his household had three external to the health care environment. reported, virological testing can be used different types of exposure: exposure to diagnose infection, if the time frame to the same environment in Mecca/ Is the agent a novel pathogen? is appropriate; if the window of oppor- Medina, exposure to the household While a newly recognized agent is tunity for virological testing has passed, environment in Doha but not Mecca presumed to be a novel pathogen, serological testing will be required. and not the farm, and exposure to the nonspecific clinical presentation and There are several challenges to de- farm but not Mecca /Medina or Doha the absence of pre-existing labora- termining whether cases or clusters of (farm workers). tory tests require a careful search for

S21

Book 19 Supplement.indb 21 5/16/2013 2:27:25 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

evidence of previous circulation to caused by a wide variety of pathogens. specimens from animal health laborato- confirm that it is indeed novel. In the The absence of a post-introduction ries or from importation screening can case of nCoV, the most commonly rec- surge in cases does provide reassurance provide evidence of both the species of ognized clinical presentation is severe that the virus was not transmitting with animal and the geographic origin of the respiratory disease. However, even in the same degree of frequency as seen in virus if external to the country where the prospective studies, the etiology of most SARS. Retrospective testing of stored cases have occurred, once an appropri- community acquired pneumonias are SARI specimens indicated that the virus ate test is developed. not proven and patients are very often had not been widely circulating prior to treated empirically [6,7]. Consequently, the recognition of the first cases [Jordan single, sporadic infections with novel Ministry of Health unpublished data] Secondary respiratory pathogens may be undetect- investigations able if not investigated as thoroughly Source of the virus as the first diagnosed case of nCoV. Several recent zoonotic outbreaks have Even before the public health impor- However, the appearance of a novel indicated how complicated transmis- tance of a novel pathogen is completely transmissible agent may cause a de- sion from a zoonotic source to humans understood, there are a number of criti- monstrable increase in background can be. In SARS, the endemic source of cal secondary questions that need to rates of respiratory disease. A review of the virus was ultimately discovered to be be addressed in order to be adequately temporal trends in hospital admissions, horseshoe bats. However, palm civets prepared to respond in case of accel- deaths in the community and cases were initially implicated as the source of erating transmission (Table 2). These reported to surveillance systems, such transmission to humans and human− are questions that will inform control as the sentinel system for Severe Acute bat exposure likely did not play a direct measures and include the incubation Respiratory Infection (SARI), can pro- role in the outbreak [9,10]. Likewise, period, mode of transmission, degree of vide clues as to the timing of the first the Nipah virus has displayed circuitous transmissibility, the spectrum of disease appearance of novel respiratory patho- transmission routes from bat to human. severity, and natural history of infection. gens. In addition, stored specimens In Malaysia, swine acted at the interme- The data related to these characteristics previously collected from similar cases diary vector and amplifier of infection of the novel pathogen will determine either as part of specific studies or ongo- [11]. In Bangladesh, raw palm sap con- the need for and duration of isolation ing surveillance programmes can be taminated with bat guano has served as and quarantine, inform case definitions tested retrospectively for the presence a vector [12]. In the nCoV event, both for case finding and other containment of the virus. Such strategies have been of the first two reported cases had a strategies, such as social distancing, if used to push back the time of first ap- history of having visited farms with a va- they are needed. pearance of human immunodeficiency riety of animals in the two weeks prior to virus (HIV) in Africa. [8]. Retrospec- illness. However, no direct exposure to tive testing of specimens collected in an animals was reported and no illness was Recommendations for earlier outbreak of respiratory disease reported in the animals on the farms. In system enhancements in Jordan demonstrated that the nCoV addition, many thousands of animals had been present longer than initially are imported into the region every year There are also several areas in which thought. However, review of pneumo- both for consumption and for ritual sac- enhancements are likely to be needed nia admission records, admissions to rifice, and an animal reservoir need not to existing systems in order to monitor intensive care for respiratory disease, exist in the country where the cases were for future cases and enable appropriate vital statistics data and data from the reported in order to result in exposure. management (Table 3). SARI surveillance system all indicated Finding the animal source of a zo- that background rates of respiratory onotic virus can be even more com- Surveillance disease in the three affected countries plicated when associated with wildlife The primary goal of surveillance en- had been stable in recent years and had and a clear route of transmission can be hancements in the context of a novel not increased notably since the first difficult to find as demonstrated by the pathogen should be to monitor for the appearance of the virus. This would in- example of Nipah virus in Bangladesh occurrence of human-to-human or ac- dicate that either the agent has not been noted above. However, capture and celerating transmission. Two situations previously circulating in the community testing of animals from the environment that can be useful indicators are clusters or that the number of cases has been low of cases is often the first step in identify- of cases with a compatible clinical pres- enough or mild enough that they are ing the reservoir of a novel agent. In entation and the occurrence of disease lost in the “background noise” of disease addition, retesting of stored diagnostic in HCWs. Tight clusters of severe

S22

Book 19 Supplement.indb 22 5/16/2013 2:27:25 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

Table 2 Important secondary investigations to describe key characteristics of novel pathogens Key questions Investigations/Studies Transmissibility Outbreak investigations including: • Period of infectivity and duration of • Investigations of contacts in health-care settings, households, other institutions. viral shedding Define attack rates based on exposures within the institutions, time intervals from • Serial interval last exposure to onset of illness. Define types of exposures based on surveys. Use • Ro (basic reproductive rate) serology in addition to PCR/culture to identify mild and asymptomatic cases. • Secondary attack rate • Community transmission studies. Rates of increase in outpatient visits and admissions • Mode of transmission and types of to hospital. Phone surveys to monitor rates of change in illness in the community exposure • Enhanced syndromic surveillance • In the event of widespread community transmission, serological surveys before and after transmission (may need to identify archived pre-transmission sera) • Serial testing of confirmed cases to determine duration of viral shedding • Animal studies of transmission and shedding Clinical presentation and course Detailed chart review with data extraction: • Signs, symptoms, laboratory and X-ray findings at initial presentation of confirmed cases • Risk factors for severe vs mild infection • Course of illness including changes in key laboratory parameters, development of complications and interventions needed • Duration of illness • Follow-up of patients for long term sequelae • Development of case definition. Clinical management best practices Detailed chart review documenting treatment modalities and outcomes Morbidity, mortality and case-fatality rate • SARI surveillance data • Hospital/ICU trend data on pneumonia (perhaps also renal or multi-organ failure) • Pneumonia and influenza mortality rates • All-cause mortality rates • Proportion of probable and confirmed cases that die • Proportion of admitted cases that die • Serological survey of exposed population to determine attack rate • Community death surveys Source of virus Animal studies to identify reservoir: • Animal capture surveys • Surveys of markets, farms, etc. • Testing of archived materials from animal diagnostic laboratories, food and importation screening Laboratory diagnosis, sensitivity and • Validation of PCR sensitivity/specificity specificity • Best specimen for testing • Define different PCR targets to be • Best timing of collection used according to type of specimen • Production of control material and timing from onset of illness. • Serological testing of symptomatic cases with comparison to PCR/culture from • Development of sensitive and specific multiple sites (e.g. nasopharyngeal, oropharyngeal, sputum, lower airway, stool) serological test • Community serosurveys and/or seroprevalence in stored sera Virological characteristics • Laboratory characterization • Duration of survival in environment • Comparison of genomic sequences and viability • Viral culture in range of cells from different species • Receptor distribution • Genetic characterization: degree of variation between viruses, relatedness to other viruses • Sensitivity to disinfectants • Antiviral sensitivity ICU = intensive care unit; SARI = Severe Acute Respiratory Infection; PCR = polymerase chain reaction

S23

Book 19 Supplement.indb 23 5/16/2013 2:27:25 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

Table 3 Recommendations for enhancing detection capacity and preparedness for response to novel pathogens Domain Enhancement Surveillance • Implement monitoring for clusters, health care workers and/or cases fitting case definition • Introduce laboratory testing for novel agent • Review quality of routine surveillance monitoring systems

Infection control • Ensure implementation of standard precautions and appropriate specific measures aimed at novel pathogen (e.g. droplet precautions in the case of a respiratory pathogen) • Review patient triage and flow processes in health care facilities to ensure appropriate handling of potential cases • Voluntary quarantine of exposed contacts and isolation of cases, depending on available epidemiological data

respiratory disease occurring in small in the community and can be adapted and reagents in a multiplex PCR plat- groups of individuals such as a family or for monitoring nCoV by the incorpora- form requires a great deal of testing classroom are an unusual event outside tion of specific testing into the operating and validation. The primers for novel of chronic care facilities and gener- procedures. In the case of nCoV, limited agents will initially have to be tested in ally represent an event of public health evidence from early cases indicated that a separate PCR to determine optimal importance [13]. Pneumonia related the virus might be more easily detected cycling conditions before being incor- to seasonal influenza, pneumococci, in lower respiratory tract specimens ne- porated in the multiplex PCR. Finally, haemophilus influenza infections and cessitating a slight adjustment of speci- the interpretation of PCR results can be other commonly recognized pathogens men collection practice in the existing problematic as their sensitivity and rela- typically does not occur in multiple system [15]. The addition of testing for tionship to actual infection is generally members of the same family, classroom nCoV as a routine diagnostic tool for unknown early in the course of an event or work place in a short period of time. community acquired pneumonias used with a novel pathogen. Without actual As such, clusters always deserve inves- at the discretion of the treating clinician culture and the support of serology to tigation. Indeed, the occurrence of a in areas where the virus is thought to document seroconversion, it may prove family cluster was the first indication of be present can also provide additional difficult to clearly know that infection the appearance of influenza A(H7N90) monitoring. has in fact occurred with a positive PCR. in China in April 2013. HCWs likely Enhancing laboratory capacity in Infection control acquire pneumonias at a similar rate as the age of molecular techniques such as Health care facilities played an impor- other adults of similar age and health PCR is often a matter of incorporation of tant role in the transmission of SARS status. However, due to the fact that new primers into existing testing panels. in the 2003 outbreak and the imple- they may have a higher risk of exposure However two important considerations mentation of rigorous infection control to human sources of infection and are are required in the context of a novel practices was critical to breaking chains not from the same home environment pathogen. The first is biosecurity in the of transmission. The successful preven- as the cases for whom they care, they extraction of RNA. With a novel agent, tion of amplification of nCoV infections may provide a useful marker of human- especially one known to cause severe associated with health care facilities will to-human transmission for novel patho- and fatal disease, at least a BSL2 facility depend on the full implementation of all gens. including use of a microbiological safety core components for infection preven- The presence of a pre-existing cabinet (class 1, 2, or 3) is required tion and control (IPC) programmes surveillance system for SARI greatly for the handling of potentially infec- 16]. Most nosocomial transmissions facilitates the establishment of a system tious materials. While this is beyond occur in the absence of basic IPC pre- to monitor for widespread community the capacity of most routine virological cautions and before a specific infection transmission and real-time detection of a diagnostic laboratories, the facility may is suspected or confirmed, hence the sudden surge in cases. These systems are be available in laboratories handling routine application of standard IPC usually established for influenza moni- tuberculosis specimens. In addition, precautions and additional measures toring and use molecular techniques to the widespread use of multiplex PCR to prevent spread of acute respiratory test for influenza viruses as part of the platforms may complicate the introduc- infections (ARI) when caring for symp- system [14]. They provide baseline data tion of new primers for novel agents. tomatic patients is essential to reduce on the occurrence of respiratory disease The interplay between different primers the spread of any ARI in health-care

S24

Book 19 Supplement.indb 24 5/16/2013 2:27:25 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

settings. These as well as the additional have not markedly changed the initial rapid investigation and response with precautions to be applied when caring assessment. However, further vigilance the support of international partners, as for patients with probable or confirmed is needed along with expanded testing needed. The International Health Regu- infection with nCoV are discussed in to determine the full geographic extent lations ratified by WHO Member States detail in the accompanying article in this of the virus. The source of the virus re- in 2005 established a mechanism for the issue of EMHJ by Seto et al. on infection mains a mystery that urgently needs to confidential sharing of information be- prevention and control measures [17]. be solved. tween WHO and other Member States The appearance of a novel patho- early in an event before its significance is even fully evaluated. This greatly reduces Conclusions gen carries many inherent risks over and above those to global public health disincentives to information sharing and facilitates global cooperation. The SARS Early investigations into the appearance that create a reluctance by national au- of a novel coronavirus in the Middle thorities to announce its appearance. experience of 2003 taught many lessons East indicated that sustained commu- The economic impact can be substantial about how to respond to global crises. nity transmission was not occurring. Re- as demonstrated in Mexico when the The elements that made the response view of the available data suggested that novel influenza A(H1N1) virus first ap- successful included the open sharing of while nosocomial human-to-human peared [18]. As such, the risk to global information internationally, the rapid transmission might have occurred in public health from a novel pathogen deployment of teams to support and sup- Jordan in April 2012, transmission did with unknown potential for international plement manpower in affected countries, not appear to occur frequently or easily. spread must be balanced with the risk and the global coordination of research Enhancements to surveillance includ- to local economies from an exagger- activities and the sharing of results being acquiring the appropriate prim- ated and unnecessary response from a fore their publication so that they could ers for diagnosing infection with the concerned public. The most effective inform response efforts. Answering novel agent have enabled the affected way to mitigate the negative impact of the critical questions around this novel countries to detect further cases which an emerging novel pathogen is through pathogen will require similar efforts

References

1. Corman V et al. Detection of a novel human coronavirus by 10. Li W et al. Bats are natural reservoirs of SARS-like coronavi- real-time reverse-transcription polymerase chain reaction. ruses. Science, 2005, 310(5748):676–679. Eurosurveillance, 2012, 17(39):pii 20285. 11. Parashar UD et al. Case-control study of risk factors for human 2. Zaki A et al. Isolation of a novel coronavirus from a man with infection with a new zoonotic paramyxovirus, Nipah virus, pneumonia in Saudi Arabia. New England Journal of Medicine, during a 1998–1999 outbreak of severe encephalitis in Malay- 2012, 367(19):1814–1820. sia. Journal of Infectious Diseases, 2000, 181:1755–1759. 3. Public Health England. Health Protection Agency. Genetic se- 12. Luby SP et al. Foodborne transmission of Nipah virus, Bang- quence information for scientists about the novel coronavirus ladesh. Emerging Infectious Diseases, 2006, 12(12):1888–1894. 2012 (http://www.hpa.org.uk/Topics/InfectiousDiseases/ 13. Puro VGE. Clustered cases of pneumonia among healthcare InfectionsAZ/NovelCoronavirus2012/, accessed 6 May 2013). workers over a 1-year period in three Italian hospitals: applying 4. Müller MA et al. Human coronavirus EMC does not require the the WHO SARS alert. Infection, 2006, 34(4):219–221. SARS-coronavirus receptor and maintains broad replicative 14. Interim epidemiological surveillance standards for influenza. capability in mammalian cell lines. mBio, 2012, 3(6):1–5. Geneva, World Health Organization, 2012. 5. International Health Regulations, 2005, 2nd ed. Geneva, World 15. Bermingham A et al. Severe respiratory illness caused by a Health Organization, 2005:43. novel coronavirus, in a patient transferred to the United King- 6. Mandell LA et al. Infectious Diseases Society of America/ dom from the Middle East, September 2012. Eurosurveillance, American Thoracic Society Consensus Guidelines on the 2012, 17(40):pii 20290. Management of Community-Acquired Pneumonia in Adults. 16. Core components of infection prevention and control pro- Clinical Infectious Diseases, 2007, 44(Suppl. 2):S27–S72. grammes in health care. Aide-memoire. Geneva, World Health 7. Bartlett JG et al. Practice guidelines for the management of Organization, 2011 (Aide-memoire) (http://www.who.int/csr/ community-acquired pneumonia in adults. Clinical Infectious resources/publications/AM_CoreCom_IPC.pdf, accessed 6 Diseases, 2000, 31:347–382. May 2013). 8. Zhu T et al. An African HIV-1 sequence from 1959 and implica- 17. Seto WH et al. Infection prevention and control measures for tions for the origin of the epidemic. Nature, 1998, 391:594–597. acute respiratory infections in healthcare settings: an update. 9. Guan Y et al. Isolation and characterization of viruses related to Eastern Mediterranean Health Journal, 2013, 19(Suppl.):S39–S47 the SARS coronavirus from animals in southern China. Science, 18. Flu and the Mexican economy; a painful tune. The Economist, 2003, 302(5643): 276–278. 1 May 2009.

S25

Book 19 Supplement.indb 25 5/16/2013 2:27:25 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

Review Novel coronavirus: the challenge of communicating about a virus which one knows little about G. Härtl1

حتدي التواصل اإلعالمي حول فريوس تندر املعلومات عنه غريغوري هارتل 2013/2012 اخلالصـة: بعد حدوث املتالزمة التنفسية احلادة الوخيمة )سارس( يف َعام نْي ، َّأعدت منظمة الصحة العاملية دالئل إرشادية للتواصل اإلعالمي حول الفاشيات، ومع اندالع الفريوس التاجي Coronavirus اجلديد يف أيلول/سبتمرب ،2012 انطلقت استجابة منظمة الصحة العاملية للتواصل اإلعالمي مع اجلمهور وتم ختطيطها عىل ضوء الدالئل اإلرشادية، واملبادئ اخلمسة وهي الثقة والشفافية واإلعالن الباكر واالستامع والتخطيط. وتصف هذه الدراسة استجابة منظمة الصحة العاملية يف التواصل اإلعالمي حول الفريوس التاجي اجلديد واجلهود التي بذلتها املنظمة لتقديم معلومات باكرة ودقيقة عرب خمتلف الوسائل اإلعالمية ُب نْغ َةي إبقاء عموم الناس عىل ّاطالع عىل األوضاع، إىل جانب التزام املنظمة باالستمرار يف التواصل اإلعالمي عىل ٍنحو ال ينقطع.

ABSTRACT Following the severe acute respiratory syndrome (SARS) event in 2002/2003, the World Health Organization (WHO) developed outbreak communications guidelines. With the emergence in September 2012 of a novel coronavirus, WHO’s public communications response was initiated and planned in light of these guidelines and 5 principles of trust, transparency, announcing early, listening and planning. This review describes WHO’s communication response to the novel coronavirus event and its efforts to provide early, accurate information via various media to keep the public appraised of the situation, and its commitment to continued communication on an ongoing basis.

Nouveau coronavirus : difficultés de communication sur un virus encore mal connu

RÉSUMÉ Suite à l'épisode du syndrome respiratoire aigu sévère en 2002/2003, l'Organisation mondiale de la Santé a élaboré des lignes directrices sur la communication lors des flambées de maladies. Après l'émergence d'un nouveau coronavirus en septembre 2012, l'Organisation mondiale de la Santé a lancé des actions de communication publique à la lumière de ces recommandations et des cinq principes de confiance, de transparence, d'annonce précoce, d'écoute et de planification. Le présent article décrit les actions de communication menées par l'Organisation mondiale de la Santé face à l'émergence du nouveau coronavirus, les efforts pour fournir rapidement des informations exactes par l'intermédiaire de divers médias afin de tenir le public au courant de la situation. Il présente également l'engagement de l'OMS pour une communication continue et régulière.

1Coordinator, Department of Communications, World Health Organization, Geneva, Switzerland ([email protected]).

S26

Book 19 Supplement.indb 26 5/16/2013 2:27:26 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضاىف 1

Introduction source of information and its audiences by the authorities in the United King- would follow its public health advice. dom, where the patient then was, of a The experience of communicating and 49 year-old Qatari national with acute the lessons learned during the severe respiratory syndrome and renal failure acute respiratory syndrome (SARS) who had a travel history to Saudi Arabia event led the World Health Organi- WHO’s and Qatar. The clinical sample collected zation (WHO) to develop the WHO communication from the 49 year-old Qatari patient was Outbreak Communications Guidelines response compared with that of a virus sequenced [1]. These Guidelines stipulated that all previously by the Erasmus University acute public health event communica- WHO was notified on 22 September Medical Centre, Netherlands from lung 2012 of a Qatari national, in the United tions should be planned, organized and tissue of a fatal case earlier in 2012 in a Kingdom in the intensive care unit of a executed in keeping with the 5 princi- 60-year-old Saudi national. WHO was London hospital, who had been found ples: trust, transparency, announcing able to confirm that the 2 virus samples to be infected with a novel coronavi- early, listening and planning. were 99.5% identical, but no further rus genetically almost identical to that information was available [3]. Since the SARS event 10 years found in a Saudi Arabian patient in June ago, WHO has communicated during Social media, Twitter in particu- 2012. Very little further information was lar, have become the main means for acute public health events according to available at this time. these tenets. WHO has also conducted WHO to get news out quickly. WHO’s Within WHO, a communications considerable training—both of its own first experience with social media came team was immediately established as a and of Ministry of Health staff around during the influenza pandemic in key component of the larger response the world—in the art of communicat- 2009–2010, when WHO tweeted out team. The operational team consisted the daily increases in case numbers and ing quickly and effectively, according both of public communications and also monitored what was being said to these 5 principles. The benefits of information management profession- about WHO in the social media sphere, early, transparent and effective outbreak als: a communications coordinator, a but at that time the organization’s en- communications have been seen in nu- full-time communications staff member gagement did not go beyond that: it merous instances, as have the pitfalls seconded to the response team, 2 social had no policy, and little experience, of of not communicating using these 5 media professionals monitoring the how to deal with social media and how principles. event in various media channels and to respond when WHO was mentioned Of the 5 principles, trust is the key. putting out information via those same or, worse, criticised in this medium. It is the hardest to build and the easiest channels as needed, an information However, this was to change when the to lose. Trust is earned over long pe- management manager, a report writer recommendations of the International riods by being open and honest with and an intern (the Director of Commu- Health Regulations Review Committee one’s audiences, while trust is easily lost nications was a member of the Senior on the performance of WHO during when those same audiences believe that Policy Group on Novel Coronavirus the influenza pandemic noted that one the communicator is hiding or being and took decisions in policy areas when of the areas where WHO needed sub- economical with the truth. The first needed but was not involved in the day- stantial strengthening was social media/ goal, therefore, of any and all commu- to-day operational team). communications. nications during an acute public health The first communications actions As a result, WHO established a event must be to build and retain trust, were to monitor what was being said dedicated social media function at the for only when audiences trust the com- in public about the event, issue a Dis- start of 2012, and what had been 500 municator, will they listen to and take ease Outbreak News (DON), and then followers of WHO’s Twitter feed in the protective public health actions tweet the same information as had been April 2009 had grown into more than which the public health spokesperson is released in the DON via social media 600 000 by the start of 2013. Many of recommending. channels. A dedicated website on the the most active followers of WHO are The public communications efforts novel coronavirus soon followed, where journalists and public health experts of the WHO during the novel corona- all information known about the virus and practitioners. A priority, therefore, virus event were initiated and planned and the cases, and relevant guidance was to re-transmit the news contained in this light: it was the Organization’s in- was posted in a single place [2]. in the DON via WHO’s Twitter feed: tention to communicate openly about According to the first DON posting Some of the most prominent of the what it did and did not know concern- on the novel coronavirus, on 23 Sep- bloggers and tweeters who engaged ing this virus so that it became a trusted tember 2012, WHO had been notified with WHO and re-tweeted WHO on

S27

Book 19 Supplement.indb 27 5/16/2013 2:27:26 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

the novel coronavirus issue from the remained on high alert, and investiga- With no new cases, and no develop- outset included Mike Coston, Maryn tions continued, but the fact that there ments to report on from the laboratory McKenna, Helen Branswell, Tom had not been any new cases by this date and field investigations, the 10 October “Treyfish” Watkins, Crawford Killian led WHO to state that the novel coro- 2012 DON seems, however, to have and Henry Niman. navirus could not be transmitted easily acted as a summary to an event which General media interest was also high from person-to-person [6]. By this date, apparently was increasingly being re- and, predictably, journalists grabbed with no new cases, and apparently no garded as waning, or closed, or having no onto the fact that the novel coronavirus growing story, media interest began to more media interest, because between is from the same family as SARS. A typi- wane. 15 October and 20 November, not one cal lead paragraph was the one from the Behind the scenes, WHO contin- article appeared in the English-language BBC’s online article of 24 September ued to work to try gain more infor- mainstream media on the subject. 2012: “A new respiratory illness similar mation on the virus: much about its In light of these events, the WHO to the Sars virus that spread globally in origins, its transmissibility, its virulence, operational team was wrapped up. 2003 and killed hundreds of people has its geographic spread and how it spread, This was all to change rapidly, how- been identified in a man who is being remained unknown. In fact, on 10 Oc- ever, with the announcement to WHO treated in Britain” [4]. The headlines tober 2012, in the next DON which on 23 November of a new family cluster and leads were disturbing from a public WHO published [7], it was stated in Saudi Arabia and an additional case health point of view because a) very little that the governments of Saudi Ara- in Qatar. WHO responded publicly by was known about this virus; and b) what bia, Qatar and the United Kingdom, issuing a DON [9], sending an email information was being relayed by media supported by WHO, were continuing notification to journalists and alerting was misinformation: what public health to try to gain a better understanding its over 600 000 Twitter subscribers to officials did know did not indicate that of the disease and the likely source of the DON and its contents—as can be the transmissibility was at all like that of infection. Despite WHO and other seen in the jump in Twitter activity on the SARS virus, or that nearly as many organizations having deployed teams 23 November (Figure 1). to Saudi Arabia and Qatar, and even people had been infected. Internally, WHO reconvened its after careful follow-up of close contacts WHO, with its public partners, had rapid response team, and the Com- of the 2 confirmed cases, and with a to move quickly to correct these mis- heightened state of global surveillance munications Team was once again a key perceptions before incorrect and inap- in place, there was no evidence of part of this team. propriate, and potentially-damaging, human-to-human transmission of the The Saudi Arabian/Qatari cases public health and other measures were virus, or even of more cases. were followed rapidly by the notifica- taken in the belief that the world was While public interest in general in tion to WHO of cases in Jordan: WHO facing a new SARS. the virus had died down (as judged by issued a DON on 30 November 2012 On 25 September 2012, the Head of the number of stories written on the alerting the world to the fact that Jordan Media for WHO briefed Geneva-based topic), some of the more specialized had, through retrospective investiga- journalists, emphasizing on numerous health journalists who were pursuing tion, found 2 cases of novel coronavirus occasions during the press conference the story now turned from simply fol- infection that had occurred in April that the only similarity between the lowing the story to asking the ques- [10]. coronavirus and SARS were that they tions which WHO and its partners Throughout that week, however, were from the same family. Similarities, so far had not been able to answer. traditional media interest remained e.g, epidemiological, ended there. In Richard Knox of National Public Ra- small. Conversation on social media, addition, to reinforce this message that dio, on 5 October, speculated in an on the other hand, picked up pace, with novel coronavirus was not like SARS, article entitled Arabian Coronavirus: public health commentators and health a second DON was issued on 25 Sep- Plot Thickens but Virus Lies Low [8] that, journalists carrying on a discussion tember with this message (and others, given the fact that 1 of the 2 cases was around WHO’s announcements. Espe- including an interim case definition) from Riyadh, Saudi Arabia, whilst the cially after the cases in Jordan were an- [5], and WHO’s social media team other was from Qatar, the virus had to nounced, journalists started to ask how distributed this information via social be widespread and that public health widespread the virus was, and wondered media channels. investigators weren’t picking up what both how likely it was that the disease A third DON was issued on 28 had to be more cases. Knox went on to could spread to other countries and September. Because of the severity of do what no one else had so far done: even other continents, and how good the first 2 cases, WHO and its partners give a name to the virus. the world’s surveillance systems were.

S28

Book 19 Supplement.indb 28 5/16/2013 2:27:26 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضاىف 1

Reach: Exposure: Activity: Contributors: reminded that SARS was also a coro- 2,005,172 people 20,362,896 impressions 2,560 tweets 1,615 users navirus of zoonotic origin that, with the help of a super spreader, became the 1,200,000 source of a large global epidemic” [12]. 1,000,000 800,000 Conclusion 600,000

400,000 The fact that interest is still there, that the public continues to associate novel 200,000 coronavirus with SARS, and that people 0.0 want answers, should serve as a remind- 12:00 am 4:00 am 8:00 am 12:00 pm 4:00 pm 8:00 pm er to WHO and its partners: the more answers public health experts can pro- Figure 1 Twitter activity for 23 November 2012 (top hashtag was #coronavirus) vide now, the greater the public’s trust in these institutions will be if and when the virus should become easily transmis- Traditional media interest between operational team, which was then stood sible between humans and cause more 20 November 2012 and 15 December down as no new cases were found. widespread morbidity and mortality. 2012 was not as extensive as it had been WHO again stood down its operational WHO, for its part, will continue to give in September and October. Was this team. Media chatter, i.e. interest in novel communications primacy as a public because the pattern of infection was no coronavirus continues, however: in health tool and advocate amongst its different from the cases seen originally January and February 2013, numer- partners for gaps in information to be in Saudi Arabia and Qatar? Or was it be- ous scientific and specialist journalists filled and the results of epidemiological, cause there was no sustained human-to- continued to write about the virus and laboratory and other work on the virus human transmission, no large events? what is known about it. For example, to be communicated publicly and in a Were the infections, and the cases, too Yanzhong Huang wrote in the blog of timely manner. The more WHO and distant and too sporadic to care about? the Council of Foreign Relations on 4 its partners can communicate on an With no sign of human-to-human February 2013 that, “SARS has had a ongoing basis, even when this (or any) transmission, maybe the cases would be lasting impact on our collective psyche. event is not in an acute phase, the bet- isolated and people outside the region In September 2012, a novel coronavirus ter WHO and its partners will be able would not be affected, contrary to what was identified in 2 patients from the to build and maintain trust and thus the situation had been during the SARS Middle East, raising the spectre of a new be more effectively listened to when event? SARS-like outbreak” [11]. Medscape giving public health advice in the heat The event seems to have followed cites the 9 cases and 5 deaths through of an acute public health event. Good the same pattern in November and 2012, and warns that, “this might turn outbreak communications practices December as it had in September and out to be a very limited and unimpor- in and outside of acute public health October: a flurry of cases and activity, tant outbreak in the global scheme of events make communications a more with the setting up of an internal WHO infectious diseases. However, we are effective public health tool.

References

1. WHO Outbreak communications guidelines. Geneva, World 4. Roberts M. New 'Sars-like' coronavirus identified by UK officials. Health Organization, 2005 (http://www.who.int/infectious- BBC news website, 2012 (http://www.bbc.co.uk/news/ disease-news/IDdocs/whocds200528/whocds200528en. health-19698335, accessed 8 May 2013). pdf, accessed 8 May 2013) . 5. Novel coronavirus infection – update. Geneva, World Health 2. Coronavirus infections. Geneva, World Health Organization, Organization, Global Alert and Response (GAR), 2012 (http:// Global Alert and Response (GAR), 2013 (http://www.who.int/ www.who.int/csr/don/2012_09_25/en/index.html, ac- csr/disease/coronavirus_infections/en/index.html, accessed cessed 8 May 2013). 8 May 2013). 3. Novel coronavirus infection in the United Kingdom. Geneva, 6. Novel coronavirus infection – update. Geneva, World Health World Health Organization, Global Alert and Response (GAR), Organization, Global Alert and Response (GAR), 2012 (http:// 2012 (http://www.who.int/csr/don/2012_09_23/en/index. www.who.int/csr/don/2012_09_28/en/index.html, ac- html, accessed 8 May 2013). cessed 8 May 2013).

S29

Book 19 Supplement.indb 29 5/16/2013 2:27:26 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

7. Novel coronavirus infection – update. Geneva, World Health 10. Novel coronavirus infection – update. Geneva, World Health Organization, Global Alert and Response (GAR), 2012 (http:// Organization, Global Alert and Response (GAR), 2012 (http:// www.who.int/csr/don/2012_10_10/en/index.html, accessed www.who.int/csr/don/2012_11_30/en/index.html, accessed 8 May 2013). 8 May 2013). 8. Knox R. Arabian coronavirus: plot thickens but virus lies low. 11. Hang Y. Ten years after SARS: five myths to unravel. New York, Washingto, NPR (website), 2012 (http://www.npr.org/blogs/ Council on Foreign Relations, Asia Unbound (blog), 2013 health/2012/10/05/162394086/arabian-coronavirus-plot- (http://blogs.cfr.org/asia/2013/02/04/ten-years-after-sars- thickens-but-virus-lies-low, accessed 8 May 2013). five-myths-to-unravel/, accessed 8 May 2013). 9. Novel coronavirus infection – update. Geneva, World Health 12. Bartlett JG. 2012’s top 10 stories in infectious disease that will Organization, Global Alert and Response (GAR), 2012 (http:// change practice. Novel coronavirus: another SARS? Medscape www.who.int/csr/don/2012_11_23/en/index.html, accessed Today News, 24 January 2013 (http://www.medscape.com/ 8 May 2013). viewarticle/777952_6, accessed 11 May 2013).

S30

Book 19 Supplement.indb 30 5/16/2013 2:27:26 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

Review Novel coronavirus infection in the Eastern Mediterranean Region: time to act M.R. Malik,1 A.R. Mafi ,1 J. Mahjour,2 M. Opoka,1 M. Elhakim 1 and M.O. Muntasir 1

العدوى بالفريوس التاجي اجلديد يف إقليم رشق املتوسط: آن أوان العمل مامونار مالك، عيل رضا مايف، جواد حمجور، مارتن أوبوكا، حممد احلكيم، حممد منترص اخلالصـة:أصبح إقليم رشق املتوسط ملنظمة الصحة العاملية بؤرة االهتامم للصحة يف العامل بعد اكتشاف العدوى بالفريوس التاجي Coronavirus اجلديد، يف بعض بلدان اإلقليم. فقد شهد اإلقليم بالفعل ًعددامن األمراض احليوانية املصدر املستجدة التي يمكن أن تسبب األوبئة. ويف ظل وجود هذا الفريوس اجلديد، متس احلاجة اآلن إىل ُّتيقظ ورصد قويييف جمال الصحة العمومية ملتابعة تطور هذا الفريوس يف اإلقليم. بل إن هذه األوضاع متثل ِّحتد ًيا ًواختبارا للسلطات الصحية ومرونتها وقدرهتا عىل االستجابة يف الوقت املناسب. ِّوتقدم هذه املراجعة ًتلخيصا ِّللبينات ذات الصلة بام َظ َهريف اإلقليم من أمراض وبائية جديدة يغلب أن تكون حيوانية املصدر، والتحديات النامجة عن اكتشاف العدوى بالفريوس التاجي اجلديد، وتستعرض التوصيات ّاملوجهة للبلدان من أجل الكشف الباكر والوقاية واملكافحة للتهديدات عىل الصحة العمومية الناشئة عن العدوى هبذا الفريوس التاجي اجلديد.

ABSTRACT The Eastern Mediterranean Region of World Health Organization has been an emerging focus for global health after the discovery of a novel coronavirus infection in some countries in the Region. The Region has already witnessed a number of emerging zoonoses with epidemic potential. In view of this new virus, there is now an urgent need for strong public health vigilance and monitoring of the evolution of the virus in the Region. The situation will challenge and test the national health authorities’ resilience and ability to respond in a timely manner. This review summarizes the evidence related to the emergence in the Region of new epidemic diseases of predominantly zoonotic origin and the challenges posed by the discovery of the novel coronavirus infection, and outlines recommendations for the countries for early detection, prevention and control of public health threats from this novel coronavirus infection.

Infection par le nouveau coronavirus dans la Région de la Méditerranée orientale : l'heure est à l'action

RÉSUMÉ La Région de la Méditerranée orientale de l'Organisation mondiale de la Santé est progressivement devenue un centre d'attention en matière de santé mondiale après la découverte d'une infection par un nouveau coronavirus dans certains pays de la Région. La Région a déjà connu un certain nombre de zoonoses émergentes à potentiel épidémique. Face à ce nouveau virus, une grande vigilance en matière de santé publique et une surveillance de l'évolution du virus dans la Région sont maintenant nécessaires de manière urgente. Cette situation risque de mettre à l'épreuve les capacités de résilience et de riposte rapide des autorités sanitaires nationales. Le présent article synthétise les données concernant l'émergence dans la Région de nouvelles maladies épidémiques, principalement d'origine zoonotique, et les difficultés découlant de la découverte de cette infection par un nouveau coronavirus. Il esquisse en outre des recommendations à l'intention des pays pour le dépistage précoce et la prévention de l'infection par le nouveau coronavirus et l'endiguement de la menace qu'elle représente pour la santé publique.

1Pandemic and Epidemic Disease, Department of Communicable Disease Prevention and Control. World Health Organization. Regional Office for Eastern Mediterranean (Correspondence to M.R. Malik: [email protected]). 2Department of Communicable Disease Prevention and Control. World Health Organization. Regional Office for Eastern Mediterranean.

S31

Book 19 Supplement.indb 31 5/16/2013 2:27:27 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

Introduction countries are in a state of protracted services in crisis-affected countries, have humanitarian emergencies or recover- also contributed considerably to the The Eastern Mediterranean Region ing from conflict. Providing emergency surge of emerging infectious diseases in of the World Health Organization medical assistance to these countries the Region [5]. (WHO) comprises 22 Member States has become a normative function of In this paper, we summarize the and the occupied Palestinian territory the WHO’s Regional Office for Eastern evidence related to emergence of new and is home to over 583 million people Mediterranean in recent years [3]. Over epidemic diseases in our Region that [1]. The Region extends from Pakistan the past decade, the Region has faced are predominantly zoonotic in origin in the east to Morocco in the west and repeated outbreaks from emerging in- and the challenges posed by the discov- as far south as Somalia and as far north as fectious diseases as a result of various ery of a novel coronavirus infection in the Islamic Republic of Iran (Figure 1). factors [4]. International travel either for the Region, and outline some specific Although the countries of the Re- tourism, business or religious reasons, recommendations for the countries for gion share many common elements of globalization and the varying capacity early detection and prevention of public history and culture, the Region abounds of surveillance systems in the countries health threats from this novel coronavi- with sociopolitical contrast and contra- in the Region to detect and diagnose rus infection. dictions. There is wide variation in the early an unknown pathogen are signifi- gross national income (GNI) per capita cant risk factors for rapid international among the countries [2]. Such variation spread of any emerging infections once Emerging infectious and income disparities have a major in- such infections or diseases emerge in disease in EMR fluence on overall health spending and the Region. Certain disease amplifiers, a significant impact on current health such as population movement, frag- The Region presents daunting health achievements in the Region. mented health systems, weak response challenges in the field of emerging The geopolitical situation of the Re- and laboratory diagnostic capacity, zoonoses. Evidence shows that over

!( gion is extremely challenging since many and disruption of routine public health !( 60% of the emerging infectious diseases

!( !( !(

!( !( !( !(

Ireland Belarus United Kingdom Netherlands Poland Lebanon (! Germany Belgium !( Beirut Czech Republic B'abda Zahle Luxembourg (! !( !( !( Guernsey Sidon Slovakia !( Damascus Syria Nabatiyet ! Ukraine et Tahta ( !( Austria Russia !( Hungary Moldova Kazakhstan Liechtenstein Al Qunaytirah !( France Switzerland Slovenia Romania Croatia !( As Suwayda Italy Dar'a !( Irbid !( !( !( Bosnia & San Herzegovina Serbia & Monaco Marino Al Mafraq Montenegro !(

Az Zarqa' !( Bulgaria As-Salt !( Andorra !( Amman (! Georgia !( Vatican City Macedonia Kyrgyzstan Uzbekistan Albania Spain Palestine Armenia Azerbaijan !( Turkmenistan An Nabk !( !( Saudi Greece !( Al Karak El'Arish !( Jordan Portugal !( !( TurkeyArabia !( !( !( Tabriz !( Tajikistan China At Tafilah !( !( Orumiyeh !( !( Rasht !( Egypt !( Mazar-E Feyzabad L'Ariana Al- Dahuk !( !( Tunis!( !( !( !( Zanjan Sheberghan Sharif Konduz Taloqan (! Hasakah !( Sari !( !( !( !( !( !( Mashhad !( Arbil Aybak !( !( !( Gibraltar Sousse Idlib Ar Raqqah Tehran Meymaneh !( Baghlan !( Malta !( !( !( !( Al Ladhiqiyah Kirkuk (! Semnan !( Dayr az !( !( !( Qal Mahmud- Hamah !( As- !( Sanandaj !( !( Zawr eh-ye E Eraqi Cyprus Tartus Sulaymaniyah Hamadan !( !( !( Asadabad Oujda !( Syria !( Bamian!( Charikar !( !( (! Chaghcharan Kabu!( l Gafsa !( Kermanshah Herat !( Jalabad !( Samarra !( Mayda!( (! Mehtar!( Rabat Fes !( !( Arak Peshawar !( Gabes !( Shahr Lam (! !( !( Lebanon Ba qubah !( !( Islamabad Casablanca Meknes !( !( Zahle !( Ilam !( Beirut(! !( Khorramabad Baraki Gardez !( !( B'abda !( !( !( !( (! S!(idon (! Damascus !( Baghdad Afghanistan Ghazni Barak Nabatiyet et Tahta Ar- (! Tarin Tripoli !( Al Qunaytirah Zareh Tunisia Az Zawiyah Darnah Ramadi Al- Shahr- Esfahan Kowt !( !( (! !( Iraq Al Khums Dar'a !( !( !( !( As Suwayda !( Hillah Al-Kut !( !( Sharan Al !( !( Farah !( Mafraq E Kord !( Gharyan Misratah Benghazi Irbid !( Karbala' !( Iran Qalat !( !( Morocco !( !( !( Az Zarqa' Al 'Amarah Yazd Lashkar !( As-Salt An Najaf !( !( Ad Diwaniyah !( Marrakech !( Marsa (! !( Gah Kandahar Lahore !( Kafr el Dumyat !( !( !( Matruh !( Amman An Nabk As- Ahvaz !( Sheikh !( Port El'Arish !( !( !( Zaranj El Mansura Said !( Samawah !( !( !( Ar'ar !( !( Ajdabiya Damanhur !(Tanta Al Karak !( !( !( !( !( Zagizig !( An- Yasuj Agadir Shibin el Kom !( !( !( At Tafilah !( !( !( Benha Ismailia Ma'an Nasiriyah Kerman Quetta !( Sakakah !( !( Pakistan (! !( Al- Cairo Shiraz Zahedan El Faiyum Jahrah Kuwait !( !( !( Jordan !( (!!( !( Beni !(Hawalli Bushehr Al-Ahmadi !( Suef Tabuk El Tur !( !( El Minya !( Algeria !( !( Kuwait Ha'il Bandar- !( Asyut Al Ghurdaqah !( E Abbas Sabha !( !( !( !( !( Sohag !( !( Buraydah Jidd Al Manamah Qena !( Ad Damman !( !(!( Ra's Al- Egypt !( Hafs(!!(!( Khaymah Libya SitrahAr Rifa !( El- Ajman !( Umm Al Qaywayn !( Doha !(!( Kharga ! !( Dubai Qata(r Sharjah !( Karachi Riyadh Abu Fujairad !( El Madina (! !( Dhabi Aswan !( (! !( !( Muscat Saudi United Arab United !( (! !( Emirates Arab Arabia Emirates India

!( Jedah Oman !( !( Makkah !(

!( Mauritania Dongola !( !(

Abha Mali !( !( Najran Niger !( Jaizan Sa'Dah !( !( !( !( Khartoum Eritrea Hajjah Sudan !( San'a Iran (! !( Yemen Senegal Chad (! Marib Al Mukalla Al Hudaydah !( !( 'Ataq Sudan !( Dhamar !( Ibb Al Bayda !( !( (! El Fasher Ta'izz The Gambia !( !( !( !( Jidd National capital A!( l Manamah Lahij Hafs Al-Muharraq (! !( !( (! Ar Rifa Sitrah Burkina Faso !( !(

Guinea-Bissau Djibo!( uti Bahrain !( Obock !( Tadjoura (! Boosaaso !( Dikhil !( Djibouti !( Provincial capital !( !( Umm Al Ali Ceerigaabo Qaywayn Guinea Sabieh !( !( Benin Ajman !( Malakal Hargeysa Burao !( !( Doha Sharjah !( !( Dubai Nigeria (! !( Major Rivers Ethiopia Somalia Sierra Togo Laascaanood Qatar !( South !( !( Leone Garoowe Wau Cote Ghana !( d'Ivory Central Sudan African Republic Gaalkacyo Abu Disputed borders (! !( Liberia Dhuusa Dhabi Mareeb (! Juba !( (! Beledweyne Cameroon !( Xuddur EMR Countries !(

Garbahaarey !( !( Baydhabo Jawhar !( Mogadishu Non EMR Countries Marka (! United Arab Emirates !( Equatorial Bu'aale Guinea Uganda !( Sao Saudi Arabia Congo, DRC Kenya Tome & Congo Oman Principe Kismaayo 0 200 400 800 1,200 1,600 Gabon !( KM Maldives

Rwanda Tanzania

Burundi

Disclaimer: The presentation of material on the maps contained herein does not imply the expression of any Production Date February 19th, 2012 opinion whatsoever on the part of the World Health Organization concerning the legal status Source WHO / EMRO of any country, territory, city or areas or its authorities of its frontiers or boundaries Produced by GIS & Health Informatics Support Dotted lines on maps represent approximate border lines for which there may not yet be full agreement !( Evidence-based Health Situation & Trend Assessment © WHO 2012. All r ights r eser ve d

Figure 1 Map of the countries in the Eastern Mediterranean Region of the World Health Organization

S32

Book 19 Supplement.indb 32 5/16/2013 2:27:36 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

that have been identified since 1940 old and new infectious diseases seen majority of cases reported in the Region are zoonotic [6] and thus the Region by the world in the past decade, severe are male (12 out of 14) and the cases continues to witness both sporadic and acute respiratory syndrome (SARS) reported so far show preponderance epidemic occurrence of emerging zoon- was the only emerging zoonoses that among older age groups (Table 2). oses (Table 1). did not strike the Region in 2003. Most cases have been sporadic. The Region has recently seen out- However, by March 2013, limited breaks of yellow fever in Sudan [7], human-to-human transmission had Chikungunya in Yemen [8], West Novel coronavirus been noted within a household setting Nile fever in Tunisia [9] and Q fever infections in EMR in Saudi Arabia and in a healthcare set- in Afghanistan [10,11 ] and Iraq [12]. ting in Jordan [44]. The region is home to a number of As if to remind the Region that emerg- arbo and filoviruses. While outbreaks ing zoonoses can occur anywhere Risk assessment and mitigation from Crimean–Congo haemorrhagic anytime and that no country is immune fever (CCHF) occur periodically in to the threats of these diseases, human The appearance of a new disease in the Afghanistan [13], Islamic Republic of infection with a novel coronavirus Region that had not been seen before Iran [14] and Pakistan [15–18], noso- (nCoV) arose in the Region in 2012 and about which little was known of comial outbreaks of the disease have and rapidly focused global attention on its origin or mode of transmission [44] been reported in recent years as a sea- this new virus [40]. First detected in a may constitute a serious worldwide sonal surge in Iraq [16], United Arab Saudi Arabian national in September threat with profound implications for Emirates [18] and Sudan [19–21]. Viral 2012 who had died of acute respiratory global health security. The Region, haemorrhagic fevers are perpetual risks illness in June, it was soon confirmed in especially the countries where these in the Region. Ebola haemorrhagic fever a patient from Qatar in London in Oc- novel coronavirus infections occurred, in South Sudan in 2004 was the only tober 2012 with similar illness [41]. In is a favourite destination for millions viral haemorrhagic fever caused by a November, two laboratory-confirmed of tourists and religious pilgrims com- filovirus seen the Region [22,23]. The cases were reported retrospectively ing from outside the Region and hence sudden expansion of Rift Valley fever, by diagnosis of stored respiratory and represents a substantial risk and major endemic in sub-Saharan Africa, along serum specimens of two deceased pa- conduit for the global spread of diseases the animal trade routes to Yemen [24], tients in Jordan with an occurrence date as has been seen with the outbreak of Saudi Arabia [25,26] and Sudan [27], is in March–April 2012 from a cluster meningococcal meningitis W135 in a characteristic example of geographic of healthcare workers whose initial di- 2000 and 2001 [45] and cholera in expansion of emerging zoonoses in the agnosis was inconclusive [42]. On 26 1984–1986 [46]. Region. March 2013, Germany notified WHO Religious mass gatherings like the The highly pathogenic avian influ- of an imported case of novel corona- Hajj pilgrimage in Saudi Arabia is the enza spread rapidly through the Region virus infection from the United Arab largest annual religious mass gathering in 2006 with large epizootics reported Emirates [43]. By the end of March worldwide with over 3 million people in a number of countries while human 2013, of the 17 laboratory-confirmed performing the Hajj every year [44]. infections occurred in Djibouti [28], cases of nCoV infections, including 10 Also over six million Umrah pilgrims Iraq [29], Pakistan [30] and Egypt [31]. deaths, that were reported to WHO visit Saudi Arabia every year. The coun- Avian influenza is now presumed en- globally [43], 14 cases (82%), including tries reporting the nCoV infections are trenched in Egypt with a low level of 9 deaths (90%), were reported from also home to large numbers of migrant transmission throughout the year [32]. four countries in the Region (Jordan, populations from Asia and Africa. A In 2009, the influenza A (H1N1)pdm Saudi Arabia, Qatar and the United more cautious approach is therefore 09 of swine origin affected all countries Arab Emirates) (Figure 2). needed to understand fully the global in the Region [33]. Other emerging zo- It is unclear where the initial infec- threat posed by this novel virus for inter- onotic diseases have occurred in the Re- tion occurred. In the cluster of health- national spread. gion and, while rare, can still cause high care workers in Jordan, the date of onset Of the total cases reported in the Re- morbidity. These include monkey pox of symptoms of a confirmed case was in gion, five were sporadic with no second- [34], sandfly fever [35] and plague [36]. March 2012, while at least three other ary transmission, while the remainder As illustrated by the Alkhurma virus, this cases reported in 2013 had a history of occurred in two clusters, two cases in Region is also home to newly emerging travel to another country (including one cluster in an intensive care unit in pathogens of zoonotic origin [37–39]. Pakistan and Egypt) where cases have Jordan [42] and others in a family clus- In the midst of the occurrence of these not been reported previously [44]. The ter in Saudi Arabia [44]. Investigations

S33

Book 19 Supplement.indb 33 5/16/2013 2:27:36 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

Table 1 Selected outbreaks from emerging zoonoses in the Eastern Mediterranean Region of World Health Organization, 2000-March 2013 Disease Country Period Host/reservoir Human health References impact Casesa Deaths 10 Sep– Yemen 653 80 24 19 Oct 2000 Cattle, sheep, goats; 26 Aug 2000– Rift Valley fever Saudi Arabia Aedes mosquitoes 886 123 25,26 22 Sep 2001 (vector) 18 Oct 2007– Sudan 747 230 27 15 Jan 2008 Pakistanb 2000–2012 585 113 15-18 Wild and domestic Iran (IR)b 2000–2011 animals (cattle, 3235 122 14 CCHF Afghanistanb 2007–2012 goats and sheep); 104 15 13 Hyalomma ticks Sudanc 2007-2011 19-21 Sep–Dec 2005 605 163 59 Sudan Primates (mainly Yellow fever 02 Sep–24 Dec 2012 monkeys); Aedes 849 171 7 South Sudan May-Jun 2003 mosquitoes (vector) 178 27 60 Ebola haemorrhagic South Sudan 24 May–26 Jun 2004 Monkeys 17 7 22, 23 fever

Unknown but 20 Sep 2005– rodents, sun squirrels, Monkey pox Sudan, Unity State 49 0 34 31 Jan 2006 even monkeys are implicated

Al-Khurma Camels and sheep; haemorrhagic Saudi Arabia 2001–2009 37–39 Mammalian ticks feverd Phlebotomine Sandfly fever Lebanon 01 Jul–18 Sep 2007 800 – 35 sandflies Iraq Jan–Mar 2006 3 2 29 Poultry, birds, wild Djibouti 23 Apr 2006 1 – 28 Avian influenza fowl (H5N1)e Pakistan 29 Oct–21 Nov 2007 4 2 30 Egypt Jan 2006–Mar 2013 172 62 32 Plague Libya 09–18 Jun 2009 Rodents; fleas 5 1 36 25 May 2009– Pandemic influenza All countries Birds; pigs 1019 33 6 Aug 2010 Domestic animals Q feverf Afghanistan 29 May–02 Jun 2011 (sheep, cattle, goats); 147 f birds Monkeys; Aedes Chikungunya Yemen Oct 2010–Mar 2011 1657 0 8 mosquitoes (vector) West Nile virus Tunisia 14 Aug–14 Nov 2012 Birds; mosquitoes 63 10 9 fever (vector) Novel coronavirus Saudi Arabia, Qatar, 21 Mar 2012–30 Apr Unknown but bats are 14 9 43 infection Jordan, UAE 2013 suspected aSuspected cases including those laboratory-confirmed. bCases reported during the outbreak are included. cNosocomial transmission. dSporadic cases have continued to be reported since 2001. eLaboratory-confirmed cases. fWorld Health Organization. Eastern Mediterranean Regional Office. Weekly Epidemiological Monitor, 2011, 5(28 & 29). CCHF = Crimean–Congo haemorrhagic fever; UAE = United Arab Emirates.

S34

Book 19 Supplement.indb 34 5/16/2013 2:27:37 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

First case reported from Jordan Died Survived acute respiratory infections (SARI). In (diagnosed retrospectively), 21 March countries where routine surveillance for

First case reported from SARI may be too resource-intensive, an Saudi Arabia, 6 June alternative “best buy” can be a sentinel-

First case reported from based surveillance system for SARI in a Qatar, 3 September geographically representative area com-

First case reported from bined with appropriate strategies for 6 United Arab Emirates, 8 March routine collection and rapid laboratory 5 4 testing of samples to confirm or rule out 3 any circulating nCoV and immediate 2 notification of WHO of any new or

Number of cases 1 Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar untypeable respiratory pathogen. Any unusual cluster of acute respiratory 2012 2013 disease needs to be reported to WHO Date of onset (month) promptly as well. The countries of the Region where cases have occurred or Figure 2 Epidemic curve of confirmed cases of novel coronavirus infection in the have been linked to in the past need Eastern Mediterranean Region, March 2012–March 2013 to establish case-based surveillance for SARI and conduct universal screening of SARI patients for nCoV using around previous clusters and cases have been missed. It is not clear if or when the the latest WHO case definition [48] not demonstrated onward transmission low levels of sporadic transmission cur- to determine if the virus is still circulat- or increases in rates of severe disease in rently seen with this virus will change. ing and the extent of its distribution. the area [47]. The fact that this is a new In the current situation, there is a need From the global perspective, the key virus and an animal origin is presumed to constantly assess and monitor the would be to detect early any event that [41,47] and that the mortality rate was evolving threats from this new disease. signals sustained secondary or tertiary high amongst the confirmed cases, it The only way this can be achieved is transmission in the community. appears that people of all ages may have through early detection of any unusual little protective immunity. As such, the patterns in the disease manifestations Laboratory tests global pandemic threat associated with that can spread on a global scale and The prompt recognition of nCoV infec- this virus should not be understated. by adequate and timely sharing of such tions will largely depend on the labora- The ability of this virus to spread be- disease patterns. tory capacity of the countries to detect yond first or second generation should and identify such novel pathogens in a be closely monitored and tracked. The Surveillance timely manner. Epidemiological surveil- mild presentation and the uncertainty From the public health perspective, lance for SARI will be meaningful only around exposure raise concern that oth- all countries of the Region need to when the laboratory can test the pa- er mild infections and links might have enhance their surveillance for severe tient’s respiratory specimens routinely

Table 2 Characteristics of 14 confirmed cases of nCoV including 9 deaths in the Eastern Mediterranean Region, March 2012– March 2013 Age group (years)a Sex Acute renal failureb Comorbiditiesc Outcome Male Female Died Recovered Still hospitalized 25–34 2 1 1 35–44 2 1 1 3 45–54 3 2 2 2 1 55–64 1 1 1 2 65+ 4 2 1 3 1 Total 12 2 6 3 9 4 1

aNo cases have been found in people under 25 years of age. bInformation for the remaining cases are not available. cComorbidities include pre-existing chronic health conditions such as diabetes, chronic kidney disease, heart disease, lung disease, multiple myeloma, etc.

S35

Book 19 Supplement.indb 35 5/16/2013 2:27:37 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

and detect any emerging new pathogen. Clinical care Risk communication Specific laboratory testing procedures No recognized effective treatment is The initial days surrounding any out- for nCoV have been published [49]. yet available for nCoV infection [50]. break of a novel disease is challenging Capacities need to be increased rapidly Possible interventions that need to as knowledge about its epidemiology is in all countries for routine confirmation be investigated include convalescent minimal, accurate predictions are diffi- of cases of novel coronavirus infection. plasma from recovered cases. The cult and have to rely on historical events premise of this approach is based on that parallel the diseases as closely as Investigation of cases and close contacts some evidence from the treatment possible [56]. As these days are usually of cases with severe acute respiratory marked by confusion, uncertainty and A standardized approach for full-scale virus infection caused by SARS-CoV a sense of urgency, good and effective epidemiological investigation needs to [52], highly pathogenic avian influenza communication is with the media as well be instituted as soon as any case is con- A (H5N1) [53] and most recently by as the general public in order to increase firmed. The close contacts (households the 2009 pandemic influenza virus public trust and confidence on the or healthcare provider) need to be [54]. This will require that affected measures taken by the national health identified and followed up for at least 10 countries, WHO and the WHO Col- authorities to protect the health of their days, which is the putative incubation laborating Centres work together to population. Risk communication needs period for nCoV infection. If respira- establish an international novel coro- to an integral part of control efforts be- tory illness occurs within the 10 days navirus convalescent plasma centre cause with good communication, sup- after last exposure in a close contact, the that can strengthen the Region’s port can be galvanized, the public can be contact should be investigated urgently public health preparedness against reassured and information that may save for nCoV infection. Such investigation this infection. The countries may also lives can be provided. As much as good is important to help understand the benefit from the interim rapid advice communication can mobilize public spectrum of illness and risk of infection document published by WHO [53] support and increase credibility, there in those exposed. for care of patients, which may need to have been numerous communication failures that have delayed outbreak con- Infection prevention and be adapted to the local settings. control during healthcare trol and as a result prolonged economic Transparency in sharing and social turmoil [56]. The current global knowledge on information the risk of transmission of nCoV in The emergence of any new infectious Seroepidemiological studies healthcare settings is limited and based disease, particularly one with the capac- Many questions about this novel on a small number of cases reported ity to transmit from person-to-person, coronavirus remain unanswered. One so far globally. However as there is creates several challenges. Transpar- assumption that the virus was circu- now evidence of limited human-to- ency of the countries where nCoV lating in one or more animal groups, human transmission, in at least two cases have occurred or are likely to yet remained unrecognized for some healthcare settings possibly involving occur in the future will be central to our time, and is transmitted sporadically to different modes of transmission [50], understanding of how this virus tran- humans as a zoonotic infection [44,50] strict infection control measures need scends into a pandemic threat. Greater needs to be studied in-depth. Although to be rapidly applied to prevent on- understanding of the epidemiology of all cases to date have had some connec- ward transmission that may be associ- and disease manifestations caused by tion with the Arabian Peninsula, more ated with health care. The successful the virus can only help to determine information is needed about the full geo- prevention of amplification of nCoV the evolving risk to global health as- graphical extent of the virus. Serological infections associated with health care sociated with this novel virus. As such studies for the virus are urgently needed will depend on the full implementation information is critical to global health to accurately assess sub-clinical infec- of the core components for Infection security, countries need to use to the tion rates (both mild and asymptomatic Prevention and Control programmes full all the mechanisms enshrined in the infections) in countries where cases [51] including standard precautions. framework of the International Health have occurred, and large multicountry Additional precautions while caring for Regulations (IHR) (2005) [55] for serosurveys need to be conducted to patients with probable or confirmed their benefit. The IHR (2005) also -un better understand the epidemiology infection with nCoV should depend derscores the importance of minimiz- and geographic extent of the infection. on risk assessment especially when ing adverse publicity effects or unfair Controlled studies of cases and con- aerosol-generating procedures are be- and unwarranted treatment of affected tacts can also give a clue to the source ing performed. countries. of infection [44]. Several laboratories

S36

Book 19 Supplement.indb 36 5/16/2013 2:27:37 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

are currently working to develop and and unpredictable events. Another les- international health bodies who are also validate serological assays for nCoV. son that has been learned is that any responsible for global health. While the Two approaches for serological testing disease outbreak anywhere today could global efforts should continue to fill the have recently been published [57,58]. be a problem for the world tomorrow. current gaps in knowledge associated Further validated assays and protocols These novel diseases will continue to with this virus, much greater regional for serosurvey need to be developed and confront and challenge national health cooperation is needed to protect the applied in all countries in a standard way. authorities’ resilience and responsive- health of the people living in the Region. ness. Likewise, the ability of regional From the regional perspective, the pre- and global communities to cooperate sent situation should not be treated as Conclusion and to control these diseases that cross na- just a sequel to the long list of epidemic future perspective tional boundaries will be a real test for zoonotic diseases that the Region has global health security. witnessed in the past decade or so. It The Region has borne the brunt of What is important now is not to should trigger a clear need for the detec- several emerging infectious diseases lower our guard and to continue to as- tion, prevention and control of this and of zoonotic origin and is now a focus sess the risk of global threats associated other emerging zoonoses in the Region for global health after the discovery of with emergence of this novel virus. This that may cross borders. In the mean nCoV. A lesson of this experience is will involve close regional collabora- time, one can only hope that this new that emerging infectious diseases that tion between the countries where virus does not unfold into one that is are of zoonotic origin are unexpected cases have occurred, WHO and other easily transmissible between humans.

References

1. World Health Organization. Eastern Mediterranean Regional 12. Leung-Shea C, Danaher PJ. Q Fever in Members of the United Office. About us. Available from http://www.emro.who.int/ States Armed Forces Returning from Iraq. Clinical Infectious entity/about-us/. Diseases, 2006, 43(8):e77–e82. 2. World Bank. World Development Indicators. Available from 13. Mofleh J, Ahmad AZ. Crimean–Congo haemorrhagic fever http://data.worldbank.org/ outbreak investigation in the Western Region of Afghani- 3. Shaping the future of health in the WHO Eastern Mediterranean stan in 2008. Eastern Mediterranean Health Journal, 2012, Region: reinforcing the role of WHO. Cairo, World Health Or- 18(5):522–526. ganization Regional Office for the Eastern Mediterranean, 2012 14. Chinikar S et al. Crimean–Congo Hemorrhagic Fever (http://applications.emro.who.int/dsaf/EMROPUB_2012_ (CCHF). In: Lorenzo-Morales J, ed. Zoonosis. InTech, 2012 EN_742.pdf, accessed 9 May 2013). (http://www.intechopen.com/books/zoonosis/crimean- 4. Report on the Meeting on establishing an outbreak alert and congo-hemorhagic-fever-, accessed 10 May 2013) (DOI: response network in the Eastern Mediterranean Region Casa- 10.5772/38851). blanca, Morocco 21–23 October 2012. Cairo, World Health 15. Sheikh AS et al. Bi-annual surge of Crimean–Congo haemor- Organization Regional Office for the Eastern Mediterranean, rhagic fever (CCHF): a five-year experience.International Jour- 2013 (http://applications.emro.who.int/docs/IC_Meet_ nal of Infectious Diseases, 2005, 9:37–42. Rep_2013_EN_14863.pdf, accessed 9 May 2013). 16. Athar MN et al. Crimean–Congo hemorrhagic fever outbreak 5. Growing threat of viral haemorrhagic fevers in the Eastern Medi- in Rawalpindi, Pakistan, February 2002: contact tracing and terranean Region: a call for action. World Health Organization risk assessment. American Journal of Tropical Medicine and Regional Office for the Eastern Mediterranean (Technical Hygiene, 2005, 72:471–473. paper EM/RC54/5) (http://applications.emro.who.int/docs/ 17. Rai MA et al. Crimean–Congo hemorrhagic fever in Pakistan. EM_RC54_5_en.pdf, accessed 9 May 2013). Journal of medical virology, 2008, 80:1004–1006. 6. Jones KE, Patel N, Levy M, et al. Global trends in emerging 18. Mofleh JA, Ashgar RJ, Kakar RS. Nosocomial outbreak of infectious diseases. Nature 2008, 451:990–994. Crimean–Congo hemorrhagic fever in Holy Family Hospital, 7. Markoff, L. Yellow fever outbreak in Sudan. New England Jour- Rawalpindi, Pakistan, 2010. Journal of Public Health and Epide- nal of Medicine, 2013, 368(8):689–691. miology, 2013, 5(4):173–177. 8. Zayed A et al. Detection of Chikungunya virus in Aedes aegypti 19. Aradaib I et al. Multiple Crimean–Congo hemorrhagic fever during 2011 outbreak in Al Hodayda, Yemen. Acta Tropica, virus strains are associated with disease outbreaks in Sudan, 2012, 123(1):62–66. 2008–2009. PLoS Neglected Tropical Diseases, 2011, 5(5):e1159. 9. Report of new health events occurring inside the Episouth area. 20. Elata A et al. A nosocomial transmission of Crimean–Congo Tunisia. EpiSouth Weekly Epi Bulletin, No. 243 (7 November–14 No- hemorrhagic fever to an attending physician in north Kordu- vember 2012) (http://www.episouthnetwork.org/sites/default/ fan, Sudan. Virology Journal, 2011, 8(1):303. files/bulletin_file/eweb_243_15_11_12.pdf, accessed 9 May 2013). 21. Aradaib I et al. Nosocomial outbreak of Crimean–Congo 10. Aronson NE. Infections Associated with War: the American hemorrhagic fever, Sudan. Emerging Infectious Diseases, 2010, Forces Experience in Iraq and Afghanistan. Clinical Microbiol- 16:837–839. ogy Newsletter, 2008, 30(18):135–140. 22. Onyango CO et al. Laboratory diagnosis of Ebola hemorrhagic 11. Hartzell JD et al. Atypical Q fever in US soldiers. Emerging Infec- fever during an outbreak in Yambio, Sudan, 2004. Journal of tious Diseases, 2007, 13(8):1247–1249. Infectious Diseases, 2007, 196(Suppl. 2):S193–S198.

S37

Book 19 Supplement.indb 37 5/16/2013 2:27:38 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

23. World Health Organization. Global Alert and Response (GAR). 42. World Health Organization. Global Alert and Response (GAR). Ebola haemorrhagic fever in South Sudan – update 8. 6 July 2004 Novel coronavirus infection – update. 30 November 2012 [webpage] (http://www.who.int/csr/don/2004_07_06/en/ [webpage] (www.who.int/csr/don/2012_11_30/en/index. index.html, accessed 9 May 2013). html, accessed 9 May 2013). 24. World Health Organization. Global Alert and Response (GAR). 43. World Health Organization. Global Alert and Response (GAR). Rift Valley fever in Yemen –update 4. 26 October 2000 [web- Novel coronavirus infection – update. 26 March 2013 [webpage] (http://www.who.int/csr/don/2000_10_26/en/index. page] (http://www.who.int/csr/don/2013_03_26/en/index. html, accessed 9 May 2013). htm, accessed 9 May 2013). 25. Rift Valley fever, Saudi Arabia. August–October 2000. Weekly 44. McCloskey B et al. Applying lessons from SARS to a newly iden- Epidemiological Record, 2000, 75:370–371. tified coronavirus.The Lancet Infectious Diseases, 13(5):384–385. 26. Madani TA et al. Rift Valley fever epidemic in Saudi Arabia: 45. Ahmed QA, et al. Health risks at the Hajj. Lancet. 2006 Mar epidemiological, clinical, and laboratory characteristics. Clini- 25;367(9515):1008-15 cal Infectious Diseases, 2003, 37(8):1084–1092. 46. Memish ZA, Venkatesh S, Ahmed QA. Travel epidemiology: 27. Hassan OA et al. The 2007 Rift Valley fever outbreak in Sudan. the Saudi perspective. International Journal of Antimicrobial PLoS Neglected Tropical Diseases, 2011, 5(9):e1229. Agents, 2003, 21:96–101. 28. World Health Organization. Global Alert and Response (GAR). 47. The Health Protection Agency (HPA) UK Novel Coronavirus Avian influenza – situation in Djibouti, 12 May 2006 [webpage] Investigation team. Evidence of person-to-person transmission (http://www.who.int/csr/don/2006_05_12/en/index.html, within a family cluster of novel coronavirus infections, United accessed 9 May 2013). Kingdom, February 2013. Eurosurveillance, 2013, 18(11):pii 29. World Health Organization. Global Alert and Response (GAR). 20427 (http://www.eurosurveillance.org/ViewArticle. Avian influenza – situation in Iraq – update 5. 19 September 2006 aspx?ArticleId=20427, accessed 9 May 2013). [webpage] (http://www.who.int/csr/don/2006_09_19/en/ 48. World Health Organization. Interim surveillance recom- index.html, , accessed 9 May 2013). mendations for human infection with novel coronavirus as 30. World Health Organization. Global Alert and Response (GAR). of 18 March 2013 (http://www.who.int/csr/disease/corona- Avian influenza –situation in Pakistan – update 2. 3 April 2008 virus_infections/InterimRevisedSurveillanceRecommenda- [webpage] (http://www.who.int/csr/don/2008_04_03/en/ tions_nCoVinfection_18Mar13.pdf, accessed 9 May 2013) index.html, accessed 9 May 2013). 49. WHO Laboratory testing for novel coronavirus (Available from 31. World Health Organization. Influenza at the human–animal http://www.who.int/csr/disease/coronavirus_infections/en/ interface. Summary and assessment as of 26 April 2013. http:// index.html, accessed 10 May 2013). www.who.int/influenza/human_animal_interface/Influen- 50. Pebody R, Zambon M, Watson J. Novel coronavirus: how za_Summary_IRA_HA_interface_26Apr13.pdf, accessed 9 May much of a threat? BMJ, 2013, 346:f1301. 2013). 51. Core components of infection prevention and control programmes 32. New cases of avian influenza A(H5N1) in Egypt. Weekly Epide- in health care. Geneva, World Health Organization, 2011 (Aide- miological Monitor, 2012, 6(15 and 16) (http://applications. memoire). (http://www.who.int/csr/resources/publications/ emro.who.int/dsaf/epi/2013/Epi_Monitor_2013_6_15-16.pdf, AM_CoreCom_IPC.pdf, accessed 9 May 2013). accessed 9 May 2013). 52. Cheng Y et al. Use of convalescent plasma therapy in SARS pa- 33. World Health Organization. Eastern Mediterranean Regional tients in Hong Kong. European Journal of Clinical Microbiology Office. Report on Pandemic H1N1 and progress on the re- and Infectious Disease, 2005, 24(1):44–46. sponse. ( http://applications.emro.who.int/docs/RC_techni- 53. Zhou B et al. Treatment with convalescent plasma for influenza cal_papers_2011_inf_doc_7_14208.pdf, accessed 10 May 2013) A (H5N1) infection. New England Journal of Medicine, 2007, 34. Formenty P et al. Human monkeypox outbreak caused by 357(14):1450–1451. novel virus belonging to Congo Basin clade, Sudan, 2005. 54. Hung IF et al. Convalescent plasma treatment reduced mor- Emerging Infectious Diseases, 2010, 16:1539–1545. tality in patients with severe pandemic influenza A (H1N1) 35. Sandfly fever in Lebanon (July 2007–September 2007).Week - 2009 virus infection. Clinical Infectious Diseases, 2011, ly Epidemiological Monitor, 2008, 1(5) (http://applications. 52(4):447–456. emro.who.int/dsaf/epi/2008/Epi_Monitor_2008_1_5.pdf, 55. International Health Regulations, 2005. Geneva, World Health accessed 9 May 2013). Organization, 2005. 36. Cabanel N et al. Plague outbreak in Libya, 2009, unrelated to 56. Tabbaa D. Emerging zoonoses: responsible communication plague in Algeria. Emerging Infectious Diseases, 2013, 19:230– with the media – lessons learned and future perspective. In- 236. ternational Journal of Antimicrobial Agents, 2010, 36S:S80-S83. 37. Madani TA. Alkhumra virus infection, a new viral hemorrhagic 57. Corman VM et al. Assays for laboratory confirmation of novel fever in Saudi Arabia. Journal of Infection, 2005, 51:91–97. human coronavirus (hCoV-EMC) infections. Eurosurveillace, 38. Madani TAet al. Alkhumra (Alkhurma) virus outbreak in Najran, 2012, 17(49):pii 20334 (http://www.eurosurveillance.org/ Saudi Arabia: epidemiological, clinical, and laboratory charac- ViewArticle.aspx?ArticleId=20334, accessed 9 May 2013). teristics. Journal of Infection, 2011, 62(1):67–76. 58. Reusken C et al. Specific serology for emerging human corona- 39. Memish Z et al Alkhumra haemorrhagic fever: case report and viruses by protein microarray. Eurosurveillance, 2013;18(14):pii infection control details. British Journal of Biomedical Science, 20441. (http://www.eurosurveillance.org/ViewArticle. 2005, 62:37–39. aspx?ArticleId=20441, accessed 9 May 2013 40. Zaki AM et al. Isolation of a novel coronavirus from a man with 59. Gould LH et al. An outbreak of yellow fever with concurrent pneumonia in Saudi Arabia. New England Journal of Medicine, chikungunya virus transmission in South Kordofan, Sudan, 2012, 367:1814–1820. 2005. Transactions of the Royal Society of Tropical Medicine and 41. Malik M et al. Emergence of novel human coronavirus: public Hygiene, 2008, 102(12):1247–1254. health implications in the Eastern Mediterranean Region. East- 60. Onyango CO et al. Yellow fever outbreak, southern Sudan, ern Mediterranean Health Journal, 2012, 18:1084–1085. 2003. Emerging Infectious Diseases, 2004, 10(9):1668–1670.

S38

Book 19 Supplement.indb 38 5/16/2013 2:27:38 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

Review Infection prevention and control measures for acute respiratory infections in healthcare settings: an update W.H. Seto,1 J.M. Conly,2 C.L. Pessoa-Silva,3 M. Malik 4 and S. Eremin 3

تدابري الوقاية من العداوى التنفسية احلادة ومكافحتها يف مواقع الرعاية الصحية: حتديث للمعلومات وينغ هونغ سيتو، جون كونيل، كارمن بيسوا سيلفا، مأمون الرمحن مالك، سريغي إيرمي 4 إن اخلالصـة:الفريوسات مسؤولة عن معظم حاالت العدوى التنفسية احلادة عىل الصعيد العاملي، ِّوتؤدي لوفيات تتجاوز ماليي كل عام. وأكثر هذه الفريوسات ًشيوعا ًمرتبةوفق تواترها هي: اإلنفلونزا، والفريوس املخلوي التنفيس، ونظرية اإلنفلونزا، والفريوس الغدي. وتشري ِّالبينات ًحاليا إىلأنالنمط الرئييس النتقال العدوى التنفسية احلادة هي من خالل القطريات الكبرية احلجم، إال أن االنتقال من خالل املالمسة )بام يف ذلك تلوث اليدين وما يتلوه من عدوى ذاتية(، والضبائب التنفسية احلاملة للعدوى بمختلف أحجامها ويف املجاالت القصرية )ويطلق عليها مصطلح االنتقال االنتهازي املنقول باهلواء(، يمكن أن حيدث لبعض العوامل ِّبة املسبلألمراض، وقد حيدث االنتقال االنتهازي املنقول باهلواء ًأيضا يف اإلجراءات التي تؤدي إىل إنتاج ضبائب مرتفعة االختطار، مما يتطلب احتياطات من العدوى املنقولة باهلواء يف تلك املواقع. وقد استعرض الباحثون التدابري العامة ملكافحة العدوى َّالةيف الفعمجيع حاالت العدوى الفريوسية التنفسية، وناقشوا بعض الفريوسات الشائعة بام يف ذلك الفريوس التاجي ِّاملسبب للمتالزمة التنفسية احلادة الوخيمة )سارس(، والفريوس التاجي Coronavirus، الذي ُاكتشف ًحديثا.

ABSTRACT Viruses account for the majority of the acute respiratory tract infections (ARIs) globally with a mortality exceeding 4 million deaths per year. The most commonly encountered viruses, in order of frequency, include influenza, respiratory syncytial virus, parainfluenza and adenovirus. Current evidence suggests that the major mode of transmission of ARIs is through large droplets, but transmission through contact (including hand contamination with subsequent self- inoculation) and infectious respiratory aerosols of various sizes and at short range (coined as “opportunistic” airborne transmission) may also occur for some pathogens. Opportunistic airborne transmission may occur when conducting high- risk aerosol generating procedures and airborne precautions will be required in this setting. General infection control measures effective for all respiratory viral infections are reviewed and followed by discussion on some of the common viruses, including severe acute respiratory syndrome (SARS) coronavirus and the recently discovered novel coronavirus.

Prévention des infections et mesures de lutte contre les infections respiratoires aiguës en milieu de soins : le point sur la situation

RÉSUMÉ Les virus sont responsables de la majorité des infections des voies respiratoires aiguës dans le monde avec une mortalité supérieure à quatre millions de décès par an. Les virus les plus fréquents sont, par ordre décroissant, celui de la grippe, le virus respiratoire syncytial, le virus paragrippal et l'adénovirus. Les données actuellement disponibles laissent penser que les grosses gouttelettes constituent le principal mode de transmission des infections des voies respiratoires aiguës, mais que la transmission par le contact (notamment la contamination par les mains suivie par une auto-inoculation) et par des aérosols respiratoires infectieux de différentes tailles et de courte portée (appelées transmissions par voie aérienne « opportunistes ») peut aussi se produire pour certains agents pathogènes. Une transmission par voie aérienne opportuniste peut survenir lors de l'utilisation de procédures générant des aérosols impliquant un risque élevé. Dans ce cas, des précautions contre une transmission aérienne sont requises. Des mesures de lutte anti-infectieuses générales efficaces contre toutes les infections respiratoires virales font l'objet d'un examen puis de discussions concernant certains virus courants, notamment le coronavirus du syndrome respiratoire aigu sévère et le nouveau coronavirus découvert récemment.

1Department of Community Medicine, School of Public Health, University of Hong Kong, Hong Kong, People's Republic of China. 2Departments of Medicine, Microbiology, Immunology and Infectious Diseases, Calvin, Phoebe and Joan Synder Institute for Chronic Diseases, Faculty of Medicine, University of Calgary, Calgary, Canada. 3Department of Pandemic and Epidemic Diseases, World Health Organization, Geneva, Switzerland (Correspondence to S. Eremin: [email protected]). 4Department of Communicable Disease Prevention and Control, World Health Organization Regional Office for the Eastern Mediterranean, Cairo, Egypt.

S39

Book 19 Supplement.indb 39 5/16/2013 2:27:38 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

Introduction Health Organization guideline released Some respiratory viruses, notably on this subject [8] which covers infec- RSV, parainfluenza, and adenovirus, Acute respiratory infections (ARIs) tion control recommendations on key may be emitted in large quantities in cause widespread diseases globally and issues which are summarized later in respiratory secretions. With extensive are responsible for over 4 million deaths this article. contamination of the patient’s environ- each year [1]. The incidence of ARIs is ment, contact transmission can occur. especially high among infants, children, Contact transmission refers to transfer and the elderly and is more pronounced of viruses and other microbes resulting in low- and middle-income countries General infection from direct physical contact between [1,2]. ARIs may affect either or both control measures for infectious secretions from an infected the upper or lower respiratory tract and ARIs in healthcare or colonized person or via hands, envi- infections involving the lower respiratory settings ronmental surfaces or inanimate objects tract may be especially severe. Although which are contaminated by infectious bacteria are significant pathogens, the To develop effective strategies for secretions [9]. The isolation measure most common etiologies of ARIs are viral infection control, it is critical to first for these settings is designated “con- and they are frequent causes of hospital understand the mode of transmission tact precautions”, which will also be admissions and nosocomial outbreaks. of these viruses. As these pathogens discussed below. In these settings with Determining the magnitude of the extent infect the respiratory tract and the virus viruses associated with large droplet of disease due to ARIs has been difficult can be disseminated into the air by and contact transmission (including because of the lack of laboratory diagnos- coughing, it had been assumed in the metapneumovirus [12] because of its tic capabilities, but in recent years many past that the airborne route of trans- similarity to RSV) a patient generally hospital laboratories have established mission was important. Research over will not cough out droplet nuclei of < 5 rapid viral diagnostic capabilities. In the years has provided evidence that µ and therefore infectious material will Hong Kong, for example, the capacity for this is not the case. Though knowledge not be disseminated for long distances both rapid diagnosis and viral culture has of transmission modes continues to through the air. Thus “airborne precau- existed for the public sector since 1995, evolve, current evidence indicates that tions” are generally not necessary. At covering 90% of hospital beds in the ter- the major mode of transmission of present, none of these acute respiratory ritory. Laboratory data from Hong Kong most ARIs is through large droplets, viral pathogens is classified as airborne identified influenza A and influenza B as but transmission through contact [13]. However it should be noted that accounting for about 50% of the patients (including hand contamination with those respiratory viruses typically as- diagnosed with viral respiratory infec- subsequent self-inoculation) and infec- sociated with large droplet and con- tions, followed by respiratory syncytial tious respiratory aerosols of various tact transmission may spread by the virus (RSV) at about 20%, and parainflu- sizes and at short range may also occur airborne route under special circum- enza and adenovirus at about 15% each. for some pathogens [9]. In an infected stances. Thus modes of transmission are Rhinovirus accounts for about 3%, but individual, a cough would generally not mutually exclusive and there may be this is probably an underestimate since produce large droplets, in the order of settings or circumstances where transi- specimens are less frequently submitted 10 μm in diameter or larger, and these tions between modes of transmission for these cases, which generally have mild large droplets would generally fall to may occur. This mode of transmission symptoms [3]. ground within 1 metre of the patient is described as “opportunistic airborne The practice of infection control [10]. This distance of 1 metre for viral transmission” by Roy and Milton [14], for patients with ARIs has its own par- droplets was first identified for RSV who also stressed that such infections ticular challenges. The present review in a study by Hall and Douglas [11]. would not require “airborne infection focuses mainly on infection prevention Large droplets of this size, because of isolation”. Rather, one should be alert to and control measures that are consid- their weight and size, generally cannot settings and circumstances where this ered effective in healthcare settings, and remain suspended in the air [9]. Conse- “opportunistic airborne transmission” discusses the relevance of these meas- quently, infection control precautions may occur, such as with aerosol generat- ures during health care for probable or will only be necessary when the health- ing procedures. confirmed case of novel coronavirus care worker comes within 1 metre of Airborne or aerosol transmission infections. Of special pertinence are the patient. This is the rationale behind refers to dissemination of microorgan- 4 related systematic reviews recently the recommendations under “droplet isms by aerosolization, and occurs when commissioned by the World Health precautions”, which will be discussed microorganisms are contained in drop- Organization [4–7] and a World below. let nuclei of a size < 5–10 μm, that result

S40

Book 19 Supplement.indb 40 5/16/2013 2:27:38 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

from evaporation of large droplets or in infection control measures shown in Once admitted into the healthcare dust particles that remain suspended in the upper box of Figure 1 should be facility, the essential general infection the air [9]. Airborne transmission may implemented. They are basically general control measures include rigorous hand occur over long distances (> 1 metre) infection control measures but include hygiene, standard precautions and respir- and the microorganisms usually settle in accommodating patients at least 1 me- atory hygiene. Hand hygiene is extremely the lower respiratory tract [14]. tre away from other patients. important and every hospital should Both epidemiological and clinical implement the WHO hand hygiene clues should be obtained from patients. guideline that has been introduced world- The emergence of severe, novel viral wide [15]. It has been demonstrated that Administrative respiratory infections of public health alcohol hand rubs are effective against controls and measures concern such as a new pandemic influ- all the respiratory viruses. Standard for early recognition enza strain should prompt an appropri- precautions are the measures initially and isolation ate travel and occupational history. A introduced for all patients to reduce the contact history with any known case risk of blood-borne pathogens. It also Infection control measures can only be or cluster of ARIs of public health covers respiratory viral infections and as effectively implemented in healthcare concern should be elucidated. Clinical part of standard precautions, healthcare facilities when administrative controls clues, such as the patient having severe workers must utilize surgical masks and are in place; this includes including es- respiratory illness after exposure to a eye protection when there is significant tablishing sustainable infrastructure and cluster of ARI of unknown etiology but risk of contamination from patients with activities to maintain infection control with a high mortality rate, may also be profuse acute respiratory symptoms. For practices, clear policies on early recogni- important. If these clues suggest that the person with a cough, “respiratory hy- tion of ARIs of potential concern, and the patient has an ARI of public health giene” is a measure to contain respiratory access to prompt laboratory testing for concern, he/she should be isolated in a secretions by providing them with tissues identification of the etiologic agents. single, well-ventilated room if possible. for covering the mouth and nose while The healthcare facilities should also However if it is a new virus, and the coughing or providing surgical masks for have adequate patient-to-staff ratios, mode of transmission is still unclear, the patients [13]. provide adequate staff training, and es- an airborne precaution room is recom- The 2 main isolation precautions tablish appropriate staff vaccination and mended. The details surrounding the for acute viral respiratory infections are prophylaxis programmes [8]. case may also be reported to the public droplet and contact precautions. It is Given the ongoing spread of viral health authorities depending on local important to stress that standard pre- respiratory infections globally, the policies. Relevant specimens should cautions and strict hand hygiene are World Health Organization (WHO) be submitted to the laboratory and integral parts of all of these precautions. released a guideline in 2007 entitled once a specific etiologic diagnosis is The key element of droplet precautions Infection prevention and control of epi- made (Figure 1), the specific infection is wearing a surgical mask whenever demic- and pandemic-prone acute respira- control measures, as recommended in healthcare workers come within 1 metre tory infections in health care [8]. It will be the guidelines or in Table 1, should be of the patient; for contact precautions, it referred to as the “ARI guideline” in followed. is wearing a gown and gloves on enter- subsequent discussion. This guideline ing the patient’s room and removing recommends that in all hospitals, ad- General measures within them on leaving [8]. Recent systematic ministrative measures should be taken healthcare settings reviews [5,6] have shown the effective- to set up a system for patients with ARI Surveillance is extremely useful so that ness of these measures. so that they are managed in a coordinat- hospitals are alerted to outbreaks cir- “Quarantine” is an infection control ed manner with timely reporting to the culating in the community and will be measure recommended for some infec- public health authorities. The decision an aid to early diagnosis and isolation tious diseases, but it should be noted tree algorithm is shown in Figure 1 [8]. of patients. A system to alert infection that there is no such recommendation When a patient is first seen in the control personnel, e.g when there are in any guidelines for the present list of hospital or other healthcare site, usu- ≥ 3 patients with influenza-like illnesses acute viral respiratory infections [8]. ally in an outpatient setting, a system from a single ward, is also extremely use- Quarantine involves the segregation of should be established for clinical triage ful. Immediate assessment of the possi- healthy contacts and it was the policy where patients are screened for specific bility of an outbreak should be initiated, for severe acute respiratory syndrome signs and symptoms of ARI. The mo- so that early isolation or discharge of (SARS) in many countries. Such a dras- ment these symptoms are detected, the patients can be undertaken [8]. tic measure for SARS was carried out

S41

Book 19 Supplement.indb 41 5/16/2013 2:27:38 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

Patient Infection control measures

-- HCWs should perform adequate hand hygiene, use medical mask and, if splashes onto eyes are anticipated, eye protection (goggles/face shield) (Table 2.1) -- Pediatric patients with clinical symptoms and signs indicating specific diagnosis (e.g. croup for Patient enters triage with parainfluenza, acute bronchiolitis for respiratory symptoms of acute febrile syncytial virus), especially during seasonal outbreaks, respiratory illness may require isolation precautions (Table 2.1) as soon as possible -- Encourage respiratory hygiene (i.e. use of medical mask or tissues when coughing or sneezing followed by hand hygiene) by the patient in the waiting room -- If possible, accommodate patients at least 1 m away from other patients

-- HCWs should use PPE (medical mask, eye protection, gown and gloves) and perform adequate hand hygiene (Table 2.1) plus clinical and -- Use separate adequately ventilated or Airborne epidemiological clues for Precautionb room (Table 2.1) ARI of potential concerna -- If no separate room available, cohort patients with same laboratory-confirmed etiological diagnosis -- If etiology cannot be laboratory confirmed and no separate room, adopt special measuresc

Patient diagnosed with ARI Other diagnosis of potential concerna Report to public health authorities

IPC precautions (Table 2.1) Reassess IPC to remain in place for the precautions duration of symptomatic (Table 2.1) illness (see Section 2.2.4)

Figure 1 Decision-tree for infection prevention and control (IPC) measures for patients known or suspected to have an acute respiratory infection (ARI) [8] (PPE = personal protective equipment)

for the sake of caution, but the present and where there is insufficient isola- permission, which is especially impor- evidence does not support the need for tion capacity to place them in separate tant for paediatric patients, and also the quarantine because subclinical infec- rooms before a specific viral diagnosis is common play area found in most pae- tion is shown to be almost nonexist- available. A possible solution, suggested diatric wards. When an etiologic diag- ent [16] and even mildly symptomatic in the ARI guideline is to place all of nosis is established, infected patients are cases have not been reported [17]. these patients on droplet precautions taken from this area and placed under Cohorting is the process of isolat- in the same room but ensuring that the appropriate precautions as shown ing patients with the same diagnosis all beds are at least 1 metre apart and in Table 1. Such modified cohorting of in the same isolation room and since having healthcare workers wear medical respiratory illnesses has been reported significant surges of these viral respira- masks whenever they are within 1 metre to be successful in reducing nosocomial tory infections do occur, especially in of the patient [8]. There is no sharing of respiratory viral infections in paediatric the winter months, it often is needed. specific patient care equipment, such units [18,19]. For adult wards, such Many hospitals have the problem of as stethoscopes, and patient medical measures may also be adapted with care, admitting large numbers of patients records are not placed by the bedside but when toilets are shared, it is impor- with infectious respiratory syndromes, but at the nursing station. Patients are tant to ensure proper disinfection and especially among paediatric patients, advised not to leave their beds without adequate hand hygiene after use [8].

S42

Book 19 Supplement.indb 42 5/16/2013 2:27:39 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

b b b b -- Yes Yes Yes Yes Yes Yes Yes Yes Yes Contact Airborne Standard Standard Novel ARI Not routinely Not routinely -- Yes Yes Yes Yes Yes Yes Yes Yes SARS Contact Droplet Standard

Not routinely Not routinely Not routinely

-- Yes Yes Yes Yes Yes Yes Yes Yes Contact Droplet Standard Standard virus with no sustained Not routinely Not routinely Not routinely New influenza avian influenza) transmission (e.g. transmission human-to-human -- -- No No No Yes Yes Yes Yes Droplet Pathogen Standard Standard with sustained Yes, if available Yes, Influenza virus Risk assessment Risk assessment Risk assessment transmission (e.g. transmission human-to-human seasonal influenza, seasonal pandemic influenza) c -- No No No Yes Yes Yes Yes Yes Contact Droplet Standard Standard Yes, if available Yes, Risk assessment RSV, adenovirus) RSV, Other ARI viruses (e.g. parainfluenza (e.g. parainfluenza Risk assessment /Yes Risk assessment

-- -- TB No No Yes Yes Yes Yes Yes Yes Risk Risk Risk Airborne Standard Standard assessment assessment assessment ------No No No No Yes Yes Yes , including plague a Bacterial Standard Standard ARI Risk assessment Risk assessment Risk assessment Risk assessment

-- -- No No No Yes Yes Yes Yes Droplet Standard Standard No pathogen Yes, if available Yes, Risk assessment Risk assessment Risk assessment factor for ARI of identified, no risk potential concern) factor for TB or ARI (e.g. ILI without risk of potential concern for room for room entry within 1 m of patient for aerosol- generating procedures Infection prevention precautions and control for patients for health-care care providing (HCW) and caregivers workers with infection acute respiratory (TB) (ARI) and tuberculosis Bacterial ARI refers to common bacterial respiratory infections caused by organisms such as Streptococcus pneumoniae, Haemophilus influenzae, Chlamydophila spp. and Mycoplasma pneumoniae. and Mycoplasma Chlamydophila spp. infections pneumoniae, Haemophilus influenzae, bacterial respiratory to common such as Streptococcus Bacterial ARI refers by organisms caused Precaution Hand hygiene Gloves Gown protection Eye Medical mask for HCWs and caregivers Particulate respirator for HCWs and caregivers Medical mask for patient when outside isolation areas Adequately ventilated room separate Airborne precaution room Summary of isolation precautions for routine patient excluding care, aerosol-generating procedures When a novel ARI is newly identified, is usually unknown. Implement the mode of transmission level of IPC precautions,the highest available until the situation is clarified. and mode of transmission a Adenovirus ARI may require use of medical mask. use of medical Adenovirus ARI may require Table 1 Table I b c syncytialrespiratory RSV = illness; syndrome. respiratory acute ILI = influenza-like virus; SARS severe

S43

Book 19 Supplement.indb 43 5/16/2013 2:27:39 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

Aerosol generating on 10 key issues in the recently revised recommended for aerosol generating procedures ARI guideline, illustrated in Table 2 [8]. procedures such as intubation [27]. As mentioned previously, ARIs are gener- Synthesizing the evidence and formu- A study published in 2012 demon- ally not transmitted by air but aerosols lating the recommendations was done strated the effectiveness of the WHO of < 5 μ may be generated in certain pro- using the GRADE (Grading of Recom- pandemic infection control guideline. cedures labelled as “aerosol generating mendations Assessment, Development When the WHO guideline was adopt- procedures” and transmitted at short dis- and Evaluation) framework according ed, there was no significant difference tance. The risk of “opportunistic” airborne to the WHO Handbook for Guideline in the infection rate of clinical staff who transmission will then be a real possibility, Development [22]. were exposed to pH1N1 2009-infected and airborne precautions will be required patients compared to non-clinical staff in these settings. Measures for specific viral who do not see patients at all [28]. infections There is intense debate on the list of Avian influenza aerosol generating procedures that are The measures for specific viral infections that are commonly encountered There is now general consensus that associated with increased risk of infec- the mode of transmission for avian in- tion transmission. Recently the Canadian are summarized in Table 1, adapted from the 2007 guideline [8]. Key is- fluenza is via droplet, and studies have Agency for Drugs and Technologies in shown that human-to-human spread Health completed a systematic review [4] sues for the various viral infections are discussed below. is possible but is a rare event [29] and which demonstrated that tracheal intu- sustained, efficient, human-to-human bation was most consistently associated Influenza transmission has not been reported to across multiple studies with an increased Controversy surrounds the mode of date. The WHO recommends droplet risk of SARS transmission to health-care transmission of influenza, especially and contact precautions in their ARI workers, or was a risk factor for trans- with an outbreak report suggesting guideline [8] and the first community mission of SARS. Four cohort studies that it could be airborne [23]. How- outbreak of avian influenza reported in revealed a pooled odds ratio [OR] of 6.6 ever, recent reviews suggest that the Hong Kong in 1997 [30] was success- [95% confidence interval (CI): 2.3–18.9], basic mode of transmission is still fully controlled in hospital clusters using and 4 case–control studies revealed a considered to be via droplets [24–26]. such precautions. pooled OR of 6.6 (95% CI: 4.1–10.6), Currently, influenza as listed in the which were remarkably consistent. No Severe acute respiratory syndrome Centers for Disease Control and Pre- (SARS) and coronavirus infections other procedures emerged with such a vention guidelines requires droplet When SARS was first reported, the clear association. There were 2 studies re- precautions [13], and, similarly, the emotional response was intense and ported for non-invasive ventilation which World Health Organization (WHO) demonstrated a pooled OR of 3.1, but widespread. This is understandable, be- recommends that standard precau- cause it was a new disease and more than they were low quality studies in which tions and droplet precautions suffice the association in one was not statistically 1700 healthcare workers were infected. for caring for patients infected with Subsequently, studies conducted in significant [20] and the other was also not influenza [8]. significant after multivariate analysis [21]. Hong Kong and elsewhere clearly dem- Annual vaccination with trivalent in- On the basis of the review, the WHO has onstrated that infection control meas- activated (the most common) vaccine made a strong recommendation in the ures are effective. A case–control study is the primary means of prevention and recently revised ARI guideline that identi- on staff providing direct patient care to fies intubation for special attention as a control of seasonal influenza, and is one 11 proven SARS patients was reported procedure associated with risk of trans- of the recommendations in Table 2. A comparing the infection control precau- mission of respiratory viruses [8] (see systematic review has been conducted tions of the 241 non-infected staff with recommendations 6 and 7 in Table 2). which supports the recommendation the 13 infected staff [31]. Four specific for vaccinating healthcare workers but measures were expressly studied: (1) the quality of evidence is actually low the washing of hands and the wear- [7]. ing of (2) masks, (3) gowns, and (4) Recommendations for The WHO guideline recommends gloves. The results showed that if proper infection control in the both standard and droplet precautions, droplet and contact precautions were WHO ARI guideline which includes the use of a medical undertaken by the staff, they would be mask rather than a facial particulate protected [31]. Based on the systematic reviews, the respirator for the healthcare worker. Although standard infection control WHO has updated recommendations Use of the particulate respirators is only measures will prevent transmission of

S44

Book 19 Supplement.indb 44 5/16/2013 2:27:39 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

Table 2 Ten WHO recommendations for infection prevention and control (IPC) and of acute respiratory infections (ARIs) Recommendations Overall ranking 1. Use clinical triage for early identification of patients with ARIs to prevent the transmission of ARI Strong pathogens to HCWs and other patients. 2. Respiratory hygiene (i.e. covering the mouth and nose during coughing or sneezing with a medical Strong mask, tissue, or a sleeve or flexed elbow followed by hand hygiene) should be used in persons with ARIs to reduce the dispersal of respiratory secretions containing potentially infectious particles. 3. Maintain spatial separation (distance of at least 1 m) between each ARI patient and others, including Strong HCWs (without the use of PPE), to reduce the transmission of ARI. 4. Consider the use of patient cohorting (i.e. the placement of patients infected or colonized with the Conditional same laboratory-identified pathogens in the same designated unit, zone or ward). If cohorting is not possible apply special measures (i.e. the placement of patients with the same suspected diagnosis – similar epidemiological and clinical information – in the same designated unit, zone or ward) within a health-care setting to reduce transmission of ARI pathogens to HCWs and other patients. 5. Use appropriate PPE as determined by risk assessment (according to the procedure and suspected Strong pathogen). Appropriate PPE when providing care to patients presenting with ARI syndromes may include a combination of the following: medical mask (surgical or procedure mask), gloves, long- sleeved gowns and eye protection (goggles or face shields). 6. Use PPE, including gloves, long-sleeved gowns, eye protection (goggles or face shields) and facial Conditional mask (surgical or procedure mask, or particulate respirators) during aerosol-generating procedures that have been consistently associated with an increased risk of transmission of ARI pathogens.1 The available evidence suggests that performing or being exposed to endotracheal intubation either by itself or combined with other procedures (e.g. cardiopulmonary resuscitation or bronchoscopy) is consistently associated with increased risk of transmission. 7. Use adequately ventilated single rooms when performing aerosol-generating procedures that have Conditional been consistently associated with increased risk of ARI transmission. 8. Vaccinate HCWs caring for patients at high risk of severe or complicated influenza disease, to reduce Strong illness and mortality among these patients. 9. Considerations for Ultraviolet Germicidal Irradiation – no recommendations possible. – 10. Implement additional IPC precautions at the time of admission and continue for the duration of Conditional symptomatic illness, and modify according to the pathogen and patient information. Always use Standard Precautions. There is no evidence to support the routine application of laboratory tests to determine the duration of IPC precautions.

When a novel ARI is identified and the mode of transmission is unknown, it may be prudent to implement the highest level of IPC precautions whenever possible, including the use of fit tested particulate respirators, until the mode of transmission is clarified. Patient information (e.g. age, immune status and medication) should be considered in situations where there is concern that a patient may be infectious for a prolonged period. HCW = health-care workers; PPE = personal protective equipment.

the SARS coronavirus (SARS-CoV), study but it was a simulation, and pre- There are now reports supporting this the correct practices must be inculcated sents a level of evidence not comparable contention, and that the use of medical in a properly organized programme for to actual epidemiological comparative masks when working within 1 metre of the entire hospital. The importance of studies involving real patients with con- the patient is effective in preventing the leadership, intensive surveillance, and comitant controls. The authors correctly transmission of SARS [36,37]. intense education of healthcare work- point out in their conclusions that their ers with adequate logistics cannot be study only “supports the probability of overemphasized [32,33]. an airborne spread of SARS in the out- There was controversy in the lit- break in Amoy Gardens.” In an editorial Infection prevention erature regarding the transmission of regarding the article by Yu et al., Roy and and control SARS-CoV as to whether it was air- Milton stated that “Hydraulic aerosol recommendations borne, but this issue was addressed by experiments combined with aerosol and Seto and Tang [34]. The outbreak in the epidemiologic modelling clearly impli- The emergence of a novel strain of Amoy Garden in Hong Kong published cated airborne transmission within the coronavirus in September 2012 raised by Yu et al. used computerized fluid apartment complex” [14]. However, this a global health alert as this novel virus dynamic modelling and suggested that “should not be considered to represent belonged to the same family Coronaviri- SARS-CoV could be transmitted by the evidence that airborne infections neces- dae as the SARS-CoV was [38]. There is airborne route [35]. It was an elegant sarily cause explosive outbreaks” [14]. now clear evidence [39] of limited, not

S45

Book 19 Supplement.indb 45 5/16/2013 2:27:39 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

sustained, human-to-human transmis- controls. Droplets and contact pre- available information, the isolation sion, possibly involving different routes cautions and eye protection should precautions need to be applied con- of transmission such as droplet and be added to standard precautions for sistently during the duration of symp- contact transmission, but the informa- health-care workers or visitors in close tomatic illness and continued for not tion on transmission and other fea- contact when caring for patients with less than 24 hours after the resolution tures of the novel coronavirus (nCoV) probable or confirmed nCoV infec- of symptoms. Until the epidemiology is based on a small number of cases tion in healthcare settings. Additional of the nCoV is better understood, and reported globally so far. Further stud- precautions should also be applied also considering other factors, test- ies are required to understand better when performing aerosol-generating ing for viral shedding could assist in the transmission dynamics associated procedures that are thought to be as- decision-making, when available. On with this nCoV infection. sociated with an increased risk of infec- the other hand, a positive result for Based on currently available in- tion transmission. The experience with viral shedding does not necessarily formation, however, it does not seem SARS-CoV has clearly shown that it imply effective infection transmission, rational to change the current recom- is crucial that health-care workers are and the epidemiological studies are mendations on infection, prevention provided with the appropriate pro- the cornerstone for better informed and control (IPC) measures which tection for caring for nCoV-infected decision making. Patient information have proven to be effective for SARS patients and followed up if exposure (e.g. age, immune status and medi- and other coronaviruses. The success- has occurred. The detailed IPC recom- cation) should also be considered in ful prevention of further amplifica- mendations are available in the ARI situations where there is concern that tion of nCoV infections associated guideline and on the WHO Coronavi- a patient may be shedding the virus for with health care will depend on the rus web page [8,40]. a prolonged period. In such situations maturity of IPC programmes and the The current scientific knowledge a more cautious approach, such as a implementation of administrative on the duration of infectivity of nCoV longer duration of IPC precautions, and engineering and environmental infection is limited. Based on currently may be necessary

References

1. The world health report 2004: changing history. Geneva, World 10. Rabenau HF et al. Efficacy of various disinfectants against SARS Health Organization, 2004 (http://www.who.int/whr/2004/ coronavirus. Journal of Hospital Infection, 2005, 61:107–111. en/, accessed 7 May 2013). 11. Hall CB, Douglas RG Jr. Modes of transmission of respiratory 2. Nair H et al. Global burden of respiratory infections due to syncytial virus. Journal of Pediatrics, 1981, 99:100–103. seasonal influenza in young children: a systematic review and 12. Crowe JEJ Jr. Human metapneumovirus as a major cause of meta-analysis. Lancet, 2011, 378:1917–1930. human respiratory tract disease. Pediatric Infectious Disease 3. Seto W, Ho J. Healthcare-associated respiratory viral infec- Journal, 2004, 23(Suppl.):S215–S221. tions. In: Jarvis W, ed. Bennett and Brachman’s hospital infec- 13. Siegel JD et al., and the Healthcare Infection Control Practices tions, 6th ed. (In press). Advisory Committee. 2007 Guideline for isolation precautions: 4. Tran K et al. Aerosol generating procedures and risk of trans- preventing transmission of infectious agents in healthcare set- mission of acute respiratory infections to healthcare workers: tings. Atlanta, Georgia, Centers for Disease Control, 2007 a systematic review. PLoS ONE, 2012, 7:e35797. (http://www.cdc.gov/hicpac/2007ip/2007isolationprecauti ons.html, accessed 7 May 2013). 5. Jefferson T et al. Physical interventions to interrupt or reduce the spread of respiratory viruses: systematic review. BMJ, 14. Roy CJ, Milton DK. Airborne transmission of communicable in- 2008, 336:77. fection–the elusive pathway. New England Journal of Medicine, 2004, 350:1710–1712. 6. Lee K et al. Physical interventions to interrupt or reduce the spread of respiratory viruses - resource use implications: 15. WHO guidelines on hand hygiene in health care. Geneva, World a systematic review. CADTH Technology Overviews, 2012, Health Organization, 2009 (http://www.who.int/gpsc/5may/ 2(3):e2302. tools/9789241597906/en/index.html, accessed 7 May 2013). 7. Dolan GP et al. Vaccination of health care workers to protect 16. Leung GM et al. SARS-CoV antibody prevalence in all Hong patients at increased risk for acute respiratory disease. Emerg- Kong patient contacts. Emerging Infectious Diseases, 2004, ing Infectious Diseases, 2012, 18:1225–1234. 10:1653–1656. 8. Infection prevention and control of epidemic-and pandem- 17. Leung GM et al. The epidemiology of severe acute respiratory ic-prone acute respiratory diseases in health care. Geneva, syndrome in the 2003 Hong Kong epidemic: an analysis of all World Health Organization, Global Alert and Response, 1755 patients. Annals of Internal Medicine, 2004, 141:662–673. 2007 (WHO/CDS/EPR/2007.6) (http://www.who.int/csr/ 18. Karanfil LV et al. Reducing the rate of nosocomially transmit- resources/publications/swineflu/WHO_CD_EPR_2007_6/ ted respiratory syncytial virus. American Journal of Infection en/index.html, accessed 7 May 2013). Control, 1999, 27:91–96. 9. Hall CB. The spread of influenza and other respiratory viruses: 19. Mlinarić-Galinović G, Varda-Brkić D. Nosocomial respiratory complexities and conjectures. Clinical infectious disease, 2007, syncytial virus infections in children’s wards. Diagnostic Micro- 45(3):353–359. biology and Infectious Disease, 2000, 37:237–246.

S46

Book 19 Supplement.indb 46 5/16/2013 2:27:39 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

20. Fowler RA et al. Transmission of severe acute respiratory syn- 31. Seto WH et al.; Advisors of Expert SARS group of Hospital Au- drome during intubation and mechanical ventilation. Ameri- thority. Effectiveness of precautions against droplets and con- can Journal of Respiratory and Critical Care Medicine, 2004, tact in prevention of nosocomial transmission of severe acute 169:1198–1202. respiratory syndrome (SARS). Lancet, 2003, 361:1519–1520. 21. Raboud J et al. Risk factors for SARS transmission from patients 32. Seto WH, Ching PTY, Ho PL. Infection control for SARS: requiring intubation: a multicentre investigation in Toronto, evidence for efficacy of good practice and description of a Canada. PLoS ONE, 2010, 5:e10717. successful model. In: Perris M, ed. Severe acute respiratory syndrome. Oxford, England, Blackwell Publishing, 2005:176–183. 22. WHO Handbook for Guideline Development. Geneva, World Health Organization, 2010 (http://www.who.int/hiv/topics/ 33. Ho PL, Tang XP, Seto WH; HO. SARS: hospital infection control mtct/grc_handbook_mar2010_1.pdf, accessed 7 May 2013. and admission strategies. Respirology (Carlton, Vic.), 2003, 8(Suppl.):S41–S45. 23. Moser MR et al. An outbreak of influenza aboard a commercial airliner. American Journal of Epidemiology, 1979, 110:1–6. 34. Tong TR, Tsang D. SARS infection control. Lancet, 2003, 362:76–77, author reply 76–77. 24. Salgado CD et al. Influenza in the acute hospital setting. Lancet Infectious Diseases, 2002, 2:145–155. 35. Yu ITS et al. Evidence of airborne transmission of the severe acute respiratory syndrome virus. New England Journal of Medi- 25. Bridges CB, Kuehnert MJ, Hall CB. Transmission of influenza: cine, 2004, 350:1731–173. implications for control in health care settings. Clinical infectious diseases, 37(8):1094–1101. 36. Peck AJA et al.; SARS Pennsylvania Case Investigation Team. Lack of SARS transmission and U.S. SARS case-patient. Emerg- 26. Stott DJ, Kerr G, Carman WF. Nosocomial transmission of ing Infectious Diseases, 2004, 10:217–224. influenza. Occupational Medicine (Oxford, England), 2002, 37. Park BJ et al. Lack of SARS transmission among healthcare 52:249–253. workers, United States. Emerging Infectious Diseases, 2004, 27. Human infection with pandemic (H1N1) 2009 virus: updated 10:244–248. interim WHO guidance on global surveillance. Geneva, World 38. Malik M et al. Emergence of novel human coronavirus: public Health Organization, 2009 (http://www.who.int/csr/disease/ health implications in the Eastern Mediterranean Region. East- swineflu/WHO_case_definition_swine_flu_2009_04_29.pdf, ern Mediterranean Health Journal, 2012, 18:1084–1085. accessed 7 May 2013). 39. The Health Protection Agency (HPA), UK Novel Coronavirus 28. Seto WH et al. Clinical and nonclinical health care workers Investigation Team. Evidence of person-to-person trans- faced a similar risk of acquiring 2009 pandemic H1N1 infection. mission within a family cluster of novel coronavirus infec- Clinical infectious diseases, 2011, 53(3):280–283. tions, United Kingdom, February 2013. Eurosurveillance, 2013, 29. Buxton Bridges C et al. Risk of influenza A (H5N1) infection 18(11):pii 2042 (http://www.eurosurveillance.org/images/ among health care workers exposed to patients with influ- dynamic/EE/V18N11/art20427.pdf, accessed 7 May 2013). enza A (H5N1), Hong Kong. Journal of Infectious Diseases, 2000, 40. Coronavirus infections. Geneva, World Health Organization, 181:344–348. Global Alert and Response, 2013 (http://www.who.int/csr/ 30. Yuen KY, Wong SS. Human infection by avian influenza A disease/coronavirus_infections/en/index.html, accessed 7 H5N1. Hong Kong Medical Journal, 2005, 11(3):189–199. May 2013).

S47

Book 19 Supplement.indb 47 5/16/2013 2:27:39 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

Review Emerging respiratory and novel coronavirus 2012 infections and mass gatherings J.A. Al-Tawfiq,1 C.A.H. Smallwood,2 K.G. Arbuthnott,2 M.S.K. Malik,3 M. Barbeschi 2 and Z.A. Memish 4

العداوى التنفسية الناشئة والفريوس التاجي اجلديد 2012والتجمعات احلاشدة جعفر التوفيق، كاثرين سمول وود، كاثرين أربثنوت، مامونار مالك، ماريزيو باربييش، زياد ميمش اخلالصـة:تشهد التجمعات احلاشدة ًأعداداغفرية من احلضور من شتى أرجاء العامل مما يثري القلق من احتامل حدوث خماطر حادة عىل الصحة العامة ال تصادف ًعادة يف السكان الذين يستضيفون ُّالتجمع احلاشد. ومن تلك املخاطر األمراض السارية، ومن بينها األمراض املستجدة واألمراض املنبعثة يف السكان املستضيفي ويف السكان الزائرين. ويستعرض الباحثون يف هذه املقالة جمموع ما ُن ِ شرحول العداوى التنفسية يف التجمعات احلاشدة، ثم 2012 يصفون أثر الفريوس التاجي ّاملستجد ، وهو فريوس جديد يسبب ًمرضا ًتنفسيا، عىل االستعدادات ُّع للتجماحلاشد. وعىل الرغم من أن هذا 2012 الفريوس اجلديد قد ظهر قبل موسم احلج ، فإن ّاحلجاج قد استكملوا أداء شعائرهم دون أن يصابوا بالعدوى بذلك الفريوس، ومن الواضح أن الطبيعة العاملية للتجمعات احلاشدة وما قد حتمله من خماطر عىل الصحة الدولية جتعل من املحتم أن تتواءم البحوث املجراة حول مثل هذا احلدث ِ والدالئل اإلرشادية الالزمة ملعاجلته مع خمتلف السياقات، وأن تكون حصيلة جهود تعاونية من ق َبل خمتلف اخلرباء يف العامل.

ABSTRACT Mass gatherings are attended by an increasingly global audience and thus raise the concern of possible acute public health risks not normally encountered by the host population. The potential acute risks to individual and population health include communicable diseases. The communicable disease risks include emerging and re-emerging diseases in host and visiting populations. In this review, we provide an overview of the literature on respiratory infections at mass gatherings, then describe the impact of novel coronavirus 2012 (nCoV), an emerging respiratory disease virus, on the preparations for mass gathering. Although, nCoV emerged prior to the 2012 Hajj pilgrimage season, Muslims completed their religious duty without acquiring infections by nCoV. Clearly, the global nature of mass gatherings and their potential risks to international health make it imperative that research on such events and guidelines produced for their management are relevant to diverse contexts and are a collaborative effort between global experts.

Infections respiratoires émergentes, nouveau coronavirus 2012 et rassemblements de masse

RÉSUMÉ Les rassemblements de masse réunissent un public de plus en plus mondial et soulèvent par conséquent des inquiétudes concernant des risques aigus potentiels pour la santé publique que la population hôte ne connaît pas habituellement. Les maladies transmissibles font partie des risques aigus potentiels pour la santé au niveau de l'individu et de la population. Les risques liés aux maladies transmissibles comprennent les affections émergentes ou réémergentes dans les populations hôtes et de passage. Dans la présente revue, nous proposons un aperçu de la littérature sur les infections respiratoires lors de rassemblements de masse, puis nous décrivons l'impact du nouveau coronavirus 2012, un virus respiratoire émergent, sur les préparatifs des rassemblements de masse. Toutefois, le nouveau coronavirus a sévi avant la saison du pèlerinage du Hadj de 2012 et les musulmans ont accompli leurs obligations religieuses sans contracter d'infection par ce virus. En clair, la nature mondiale des rassemblements de masse et les risques potentiels pour la santé internationale rendent impératif que la recherche sur de tels événements et les recommandations pour leur prise en charge soient adaptées aux divers contextes et soient le résultat d'une concertation d'experts mondiaux.

1Saudi Aramco Medical Services Organization, Dhahran, Saudi Arabia. 2Alert and Response Operations, Global Capacities, Alert and Response, World Health Organization, Geneva, Switzerland. 3Pandemic and Epidemic Disease, Regional Office for the Eastern Mediterranean, World Health Organization, Cairo, Egypt. 4Ministry of Health, Riyadh, Saudi Arabia; College of Medicine, Al Faisal University, Riyadh, Saudi Arabia (Correspondence to Z.A. Memish: [email protected]).

S48

Book 19 Supplement.indb 48 5/16/2013 2:27:40 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

Risks of infectious among host countries is the spread of gathering location. Laboratory capacity disease at mass respiratory disease. The risk of respira- may also be strengthened to accommo- gatherings tory pathogen spread may, among other date surge capacity and for diagnosis of factors, depend on crowd density and non-endemic diseases. With the advent of more widely avail- length of stay, in addition to hygiene A number of large mass gatherings able air travel, mass gatherings are facilities and the capacity for diagnostics took place in 2012, including the Olym- and appropriate isolation. The type of attended by an increasingly global audi- pic Games in London, annual events respiratory disease risk will be influ- ence [1]. This, combined with poten- such as the Hajj pilgrimage in Mecca enced by the endemic disease patterns tially increased crowd numbers, raises and many spontaneous political rallies in the host and visiting nations, and by the concern of possible acute public in countries of the Eastern Mediterra- seasonality or climate [6]. The ability to health risks. Some risks are common nean Region. The discovery of the novel detect and diagnose specific respiratory to most mass gatherings, but others are coronavirus (nCoV), with evidence of pathogens at mass gatherings depends specific to a given gathering or crowd. human cases appearing approximately on the participants seeking health care, The potential acute risks to individual 1 month before Hajj 2012, necessitated ready access to health-care treatment and population health range from non- an iterative approach to risk assessment facilities, and the availability of rapid lab- communicable disease concerns, such and management before, during and oratory diagnostics to the health-care as crush injuries [2], to infectious agents after the event. clinicians. The probability of a specific [3]. Minimizing the risk of communica- pathogen causing an epidemic among ble diseases at mass gathering is there- the participants at mass gathering de- Objectives of the review fore an important part of global health pends on the population immunity to security. A mass gathering is defined the pathogen, the incubation period of a This review, based on information up by the World Health Organization particular infectious agent before symp- to March 2013, presents some of the (WHO) as an occasion that “attracts toms of disease emerge and the length issues surrounding emerging respiratory a sufficient number of people to strain of time the mass gathering participants infections at mass gatherings, with a par- the planning and response resources are in close contact with each other. If an ticular focus on nCoV and the Hajj. An of a community, state or nation” [4]. outbreak were to occur at a mass gather- overview of the literature on respiratory It follows that mass gathering can be ing, there are potential implications for infections at mass gatherings is present- planned or spontaneous, and can be international public health and for the ed, followed by a narrative describing the diverse in purpose, from music festivals revised International Health Regulations impact of nCoV, an emerging respira- and protests to large-scale religious [7]. Under Annex 2, the revised Regula- tory disease, on the preparations before, events. At mass gatherings, communi- tions outline criteria for the assessment during and after Hajj 2012. cable disease risks include emerging and and notification of potential public re-emerging diseases in host and visiting health events of international concern. populations. The possible impact of These criteria may be influenced by the such outbreaks during mass gathering occurrence of a mass gathering. Viral respiratory is serious, potentially resulting in the To better prepare for the increased infections at Hajj and dissemination of the disease to different communicable disease threats, public other mass gatherings countries upon the return of attendees health preparations for all mass gath- to their countries of origin [5]. erings should include a specific focus The Hajj takes place during the 12th Concerns about communicable dis- on enhanced disease surveillance and month of the Islamic calendar, and ease spread at a given mass gathering are risk assessment. This extends from the according to Islam, every able Mus- focused on the problems of crowding, local level of the mass gathering, to the lim must undertake the pilgrimage to lack of sanitation and temporary food national and international levels. For Mecca once in their lifetime. Just as stalls, travel and movement of popula- example, additional diseases, which are for any international mass gathering, tion groups. Communicable disease non-endemic in the host country but the potential for large epidemics dur- threats may arise from pathogens with endemic in the visitors’ countries, may ing Hajj has been, and will continue, different modes of transmission, such be included on “priority condition” lists to present a considerable challenge to as faeco–oral, vector-borne, zoonotic, for reporting. Furthermore, surveillance attending pilgrims and the local com- sexually transmitted and bloodborne sites may be implemented at additional munities. The risks, comprehensively pathogens and these risks have been geographical locations, for example described in other publications, arise reviewed elsewhere [3]. One concern at ports of entry or around the mass from the attendance of close to 4 million

S49

Book 19 Supplement.indb 49 5/16/2013 2:27:40 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

pilgrims from more than 180 countries 2.0 [8]. The number of foreign pilgrims

attending Hajj is increasing every year 1.8 (Figure 1). This change in population attendance may affect the disease risks present at Hajj. 1.6 It has been argued that the potential for respiratory tract infections during 1.4 mass gatherings is related to the large number of people coming from different 1.2 parts of the world. Intense crowding of people in limited spaces facilitates the No. ofNo. visitors (million) foreign 1.0 transmission of disease, especially that of airborne infections [8]. The congested conditions of the Hajj and the crowded 0.8 nature of the accommodation contrib- 1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 ute to the transmission of communica- Year ble diseases at the pilgrimage [9]. Figure 1 Annual counts of foreign visitors to the Hajj, 1996 to 2011 (Source: Influenza outbreaks during mass Ministry of Health, Saudi Arabia) gathering have been described previously [10–13]. A modelling study by Shi et al. has suggested that mass gathering influenza A(H1N1)pdm09 by real-time [10,11] and influenza was 0.2%–37.4% could be associated with a 10% increase polymerase chain reaction (PCR) assay [10,11,19,21–23]. The difference in the in the attack rate of influenza if they oc- [15]. The incidence was 3.7 times the detection rates in these studies were re- cur within 10 days before an influenza overall European value, and may have lated to the study design and the included pandemic [14]. Studies on the occur- been higher since attendees may not have population. For example, using a PCR as- rence of influenza during mass gatherings sought medical treatment [15]. Dur- say, influenza was detected in 10%–12% were also undertaken during the 2002 ing the inauguration of the Asian Youth of symptomatic pilgrims [11,22] versus Winter Olympics in Salt Lake City in the Games in Singapore in 2009, 66 suspect- 1% among a sample of Egyptian return- United States and during World Youth ed cases of influenza H1N1 virus were ing pilgrims without the mention of any Day 2008 in Sydney, Australia [12,13]. screened; 6 were confirmed for influenza specific symptoms 21[ ]. In another study Among the total 188 patients tested at A(H1N1)pdm09 and were admitted of 305 pilgrims arriving at Shiraz airport, the World Youth Day 2008, influenza A to hospital for isolation and treatment Islamic Republic of Iran, pandemic 2009 and B were diagnosed in 19% [13]. Dur- [16]. In Serbia, a few influenza A(H1N1) influenza A(H1N1) virus was detected ing World Youth Day 2008, a number cases were identified among participants in 1.6% pilgrims and other influenza A of influenza strains were identified and attending 2 mass gatherings and it was viruses were detected in 2.6% [26]. A these included oseltamivir-resistant and not possible to assess their impact on recent study reviewed respiratory tract -sensitive influenza A(H1N1) viruses, in- local populations [17]. Transmission of infections during the annual Hajj with fluenza A(H3N2) viruses and influenza influenza A(H1N1) was inevitable, but comments on the potential risks [27]. B lineages (B/Florida/4/2006-like virus preparations were put in place to mitigate and B/Malaysia/2506/2004-like virus) the situation, including detection, isola- [13]. The presence of multiple viruses tion options and treatment of cases [17]. among those attending mass gathering Further studies on respiratory viruses Emergence of novel may increase the opportunity for the at mass gatherings have been related to coronavirus infections emergence of novel reassortment viruses the Hajj [10,11]. A range of respiratory vi- prior to Hajj 2012 [13]. ruses have been described among pilgrims In a third study describing the occur- attending the annual Muslim pilgrimages The first recorded infections with rence of influenza during a rock festival in Saudi Arabia [18–25]. In these studies, the 2012 nCoV occurred only a few in Hungary, among the total attendants the prevalence of parainfluenza virus was months before the Hajj season in 2012 of 390 000 young people, 14 individu- 1%–7.4% [19,23], adenovirus was 5.4% and were only reported publicly a few als were examined at St Margareta hos- [23], influenza A(H1N1) was 2.5%– weeks ahead of the pilgrimage [28]. pital and 8 (57.1%) tested positive for 21.8% [18], influenza B was 0.8%–2.6% The first reported infection with nCoV

S50

Book 19 Supplement.indb 50 5/16/2013 2:27:40 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

was identified in the Saudi Arabian [33]. As attention turned to the possible account for this new disease. A unique port city of Jeddah, in a Saudi Arabian implications of nCoV infections for the component of Saudi Arabia’s approach male who died in June 2012 [29,30]. Hajj, the available information about to managing public health risks to pil- A second case was reported in a Qatari the virus was extremely limited. Geneti- grims is the preparation and revision on male with a history of travel to Saudi cally, it closely resembled other coro- an annual basis of the recommendations Arabia in late September 2012 [31,32]. naviruses associated with bats, but the and health requirements for the period The emergence of this virus in humans reservoir, the mechanism of acquisition of the pilgrimage. Once developed by came at a time when Muslims from and its spread were not known. Based the Ministry of Health of Saudi Arabia, around the world were preparing to on the initial information provided by these requirements are shared through converge on Saudi Arabia for the Hajj the first reported cases of nCoV, no national and international platforms, pilgrimage given that the first reported human-to-human transmission had oc- including WHO’s Weekly Epidemiologi- case occurred in Jeddah, where Hajj curred [32] and, as such, there were no cal Record. Since 2009, the Weekly Epi- pilgrims assemble, risks to Hajj had to travel restrictions to areas with reported demiological Record has communicated be considered by Saudi authorities, by cases. different types of information to the WHO, and by the national authorities international community. This ranges of countries of the participating pilgrims from general advice to target popula- [29]. Figure 2 illustrates the timing of Risks of novel tions, to requirements at points/ports initial infections with nCoV and Hajj coronavirus to public of entry, to vaccination obligations for 2012. The first 2 reported cases of nCoV health at Hajj 2012 all pilgrims. For instance, during pan- sparked significant media interest in demic influenza A(H1N1) 2009, Saudi the implications of a new virus that Preparations leading to Hajj Arabia recommended that immuno- was of the same family as the severe 2012 compromised, extremely overweight or acute respiratory syndrome (SARS) As described above, evidence exists for pregnant individuals defer travel plans coronavirus. Studies of the 2003 SARS sustained communicable disease trans- to another year [34]. In 2000 and 2001, outbreak found that the SARS virus was mission at mass gathering such as Hajj. coinciding with Hajj, an international not easily transmitted between humans The discovery of nCoV infections in the outbreak of disease was caused by a and required close contact or facilitated location of the Hajj meant that the late rare strain of Neisseria meningitidis, se- transmission by aerosol production stages of planning for Hajj 2012 had to rogroup W135. This prompted Saudi

30 November Jordan reports 2 13–24 June 3 September retrospec- Saudi case Qatari case Hajj 2012 tive cases presents with onset of takes place from a symptoms symptoms in from 10–30 hospital and dies Qatar October cluster

Mid July 20 and 23 23 11 Erasmus September November February Medical Pro Med/WHO Saudi 2013 Centre tests report infections. Arabia onwards samples and First reports Further obtains virus annoucement family cases of culture of the virus cluster of nCoV nCoV detected cases. Qatar reports additional case.

Figure 2 Timeline of novel coronavirus (nCoV) infections

S51

Book 19 Supplement.indb 51 5/16/2013 2:27:41 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

Arabian health authorities to introduce to seek medical attention if, on return or samples are not available for testing; a mandatory vaccination requirement from Hajj, they developed acute respira- and close contact with a laboratory- of quadrivalent ACWY meningitis vac- tory symptoms. confirmed case [40]. cine for Hajj 2002 [35]. The lack of information or evidence Public health measures Requirements and recommenda- adopted during the Hajj on the severity and transmissibility of tions for Hajj seasons are also revised pilgrimage this novel virus in mass gathering situa- on an ad hoc basis as and when acute tions raised concerns for the Hajj. As for Public health efforts to maintain a high public health events are judged by Saudi other viruses in the coronavirus family, level of excellence during the Hajj are Arabian authorities to present a risk to the infection was thought to spread by coordinated by 24 supervisory commit- Hajj attendees. In July 2012, preliminary aerosol droplets [41]. The pattern of tees [39]. To enhance the effectiveness recommendations and requirements transmission of nCoV in overcrowded of activities, an electronic surveillance for Hajj were issued and published in and congested settings, such as those system is used by public health teams the Weekly Epidemiological Record [36]. of Hajj, posed a big “unknown” to the and teams at points of entry. This en- Viral respiratory infections were ad- international community as well as to hanced surveillance targets influenza, dressed within specific recommenda- the Saudi national health authorities. influenza-like illness, meningococcal tions for seasonal influenza vaccination The risk of international nCoV for national and international pilgrims. disease, food poisoning, viral haemorrhagic fevers, yellow fever, cholera, polio spread as a result of imported cases from In addition, the 2012 recommendations returnee pilgrims was also unknown. made specific reference to the impor- and plague [39]. In line with Saudi Ara- bia’s policy of providing free access to Examples of this had been previous tance of routine vaccinations, especially documented, as seen in the 2000 and for measles and rubella due to the recent health care during the Hajj, there were 2001 outbreaks of meningococcal men- resurgence of these diseases around the 25 hospitals offering 4964 beds includ- ingitis W135 [9,42]. This prompted the globe [36]. Initial information for Hajj ing 547 critical care beds [28]. Health Saudi Arabian national health authori- 2012 did not include specific recom- care was also provided through 141 ties to consult with international health mendations to infections due to nCoV medical centres in the Hajj area [28]. partners, including WHO, to rapidly as in July 2012 the disease had yet to The Saudi Arabian Ministry of develop and put into practice an appro- emerge as a public health risk. Health case definition for nCoV was published in Eurosurveillance [28]. A priate strategy for detection of suspect In October 2012, Saudi Arabia up- nCoV cases among pilgrims. dated information on health hazards suspected case was defined as a per- The annual Hajj took place from and recommendations for Hajj 2012 in son requiring hospitalization with 10–31 October 2012 and approximate- an article published in Eurosurveillance community-acquired acute respiratory ly 4 million pilgrims took part. Pilgrims [28]. These revisions provided further syndrome with symptoms of: fever (≥ requirements for Hajj pilgrims coming 38 °C) and cough; and confirmed came from 187 countries and visited from Uganda, the Democratic Republic lower airways involvement (clinical and the main religious sites of Saudi Arabia of the Congo and Sierra Leone on the radiological evidence of pneumonia) in Mecca and Medina. The Hajj of 2012 basis of ongoing outbreaks of commu- not explained by any other infection or was declared by Saudi Arabia as free nicable disease at that time. The paper other etiology. A confirmed case was from any public health event and not a also recommended specific measures defined as a person with laboratory- single case of nCoV infection was de- to reduce the risk of transmission of confirmed infection with nCoV [28]. tected through the national surveillance viral respiratory infections, including The current WHO definitions for case system. Over 300 sick pilgrims were those associated with nCoV but it did finding include the definition for a tested for nCoV infections and all were not issue any travel restrictions with confirmed case (a person with labora- found to be negative [43]. respect to nCoV infections. Saudi tory confirmation of infection with the Screening of returnee pilgrims was Arabia reminded pilgrims to “practice nCoV) and a probable case [40]. A also carried out in Europe and else- proper hand hygiene, protective be- probable case is defined as a person where. No imported cases of nCoV haviours and cough etiquette to further with an acute respiratory infection with infections were reported to WHO decrease the occurrence of respiratory clinical, radiological or histopathologi- from these countries. In a cohort of 154 diseases”. Other countries also issued cal evidence of pulmonary parenchy- French pilgrims returning from Hajj nCoV guidance to their nationals visit- mal disease (e.g. pneumonia or acute 2012, 83.4% had respiratory symptoms ing Saudi Arabia for the Hajj, such as respiratory distress syndrome); and no and 41% had influenza-like illness [44]. Britain [37] and the United States [38]. possibility of laboratory confirmation All the pilgrims screened tested negative Some countries advised their nationals for nCoV either because the patient for nCoV by real-time PCR assays [44].

S52

Book 19 Supplement.indb 52 5/16/2013 2:27:41 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

Impact of further found to be demographically similar to detecting and testing pilgrims who de- cases on future those attending Hajj, the risks posed to veloped a respiratory infection [40]. An mass gatherings the Hajj may be increased. investigation of potential environmen- Global public health vigilance will tal and animal sources of the nCoV was At the time of writing (March 2013), be important to see how the public carried out by the team from Columbia WHO had been informed of a total of health risk associated with this novel University. 15 confirmed cases of human infection virus unfolds. International collabora- In addition to international col- with nCoV, including 9 deaths [45]. tions will be crucial to protect global laboration with regards to nCoV, the Eight of these cases including 6 deaths health as Hajj and mass gathering in global nature of mass gathering and were reported from Saudi Arabia. The the face of a potentially deadly virus potential risks to international health majority of cases presented with severe that may seriously affect global health and security, make it imperative that illness. Limited, but not sustained, security. the research and guidelines produced human-to-human transmission has also are relevant to diverse contexts and are been reported in cases in the United a collaborative effort between global Kingdom [46] and in Jordan. The cases experts and centres. This is important, in Jordan were detected retrospectively Importance of not only as emergence of new patho- [47]. A Saudi investigation into a fam- international gens is a continued threat with implica- ily cluster of 3 confirmed and 1 prob- collaborations tions for transmission and international able case—conducted after the Hajj in spread at mass gathering, but to foster 2012—remained inconclusive but the As part of this international collabora- a culture of sharing of knowledge and dates of onset of symptoms of this family tion to prevent any global spread of expertise more generally across the field. cluster of cases appeared to be consist- nCoV infection through spread of This should extend to areas as diverse as ent with human-to-human transmission Hajj-related infections, teams of disease communicable and noncommunicable [46]. Given new information on the experts converged on Saudi Arabia diseases and to ensure a legacy of practi- transmission and the reported incidence immediately before the Hajj. These cal knowledge transfer and sharing of of the virus following the Hajj in 2012, included epidemiologists from WHO lessons learned. the epidemiological potential for an and the United States Centers for Dis- There are many centres and indi- outbreak of nCoV infections during this ease Control in Atlanta, virologists from viduals with academic and practical year’s Hajj in 2013 may be more likely. the Center for Infection and Immunity expertise in this mass gathering and a The occurrence of nCoV infections and at Columbia University in New York current commitment exists to bring the possible evolving patterns of trans- and experts in the control of zoonotic such organizations and individuals to- mission should be closely monitored diseases from EcoHealth, a New York gether through formal and informal and assessed by the international com- city-based international organization networks and collaborations. Examples munity and Saudi authorities ahead of for ecology and health. These specialists of these networks include the WHO this year’s Hajj in October 2013. were invited by the Saudi Arabian gov- virtual interactive advisory group on Another factor related to nCoV that ernment. The Saudi Arabian National mass gatherings, the newly formed may impact on the Hajj in 2013 is the Committee for Infectious Diseases Global Mass Gatherings Network and epidemiology of this emerging disease. worked with WHO to rapidly develop the developing network of WHO col- If populations susceptible to nCoV are a case definition and protocol for laborating centres on mass gatherings.

References

1. Al Rabeeah AA et al. Mass gatherings medicine and global 5. Memish ZA, Venkatesh S, Ahmed QA. Travel epidemiology: health security. Lancet, 2012, 380:3–4. the Saudi perspective. International Journal of Antimicrobial 2. Steffen R et al. Non-communicable health risks during mass Agents, 2003, 21:96–101. gatherings. Lancet Infectious Diseases, 2012, 12:142–149. 6. Altizer S et al. Seasonality and the dynamics of infectious dis- 3. Abubakar I et al. Global perspectives for prevention of infec- eases. Ecology Letters, 2006, 9:467–484. tious diseases associated with mass gatherings. Lancet Infec- 7. International health regulations (2005), 2nd ed. Geneva, World tious Diseases, 2012, 12:66–74. Health Organization, 2005. 4. Communicable disease alert and response for mass gatherings. Technical workshop, Geneva, Switzerland, 29–30 April 2008. 8. Al-Tawfiq JA, Memish ZA. Mass gatherings and infectious dis- Geneva, World Health Organization, 2008 (WHO/HSE/ eases: prevention, detection, and control. Infectious Disease EPR/2008.8). Clinics of North America, 2012, 26:725–737.

S53

Book 19 Supplement.indb 53 5/16/2013 2:27:41 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

9. Ahmed QA, Arabi YM, Memish ZA. Health risks at the Hajj. 30. Corman VM et al. Detection of a novel human coronavirus Lancet, 2006, 367:1008–1015. by real-time reverse-transcription polymerase chain reaction. 10. Balkhy HH et al. Influenza a common viral infection among Hajj Eurosurveillance, 2012, 17:pii 20285. pilgrims: time for routine surveillance and vaccination. Journal 31. Novel coronavirus infection—update. 25 September 2012. World of Travel Medicine, 2004, 11:82–86. Health Organization [online] (http://www.who.int/csr/ 11. El Bashir H et al. Influenza among UK pilgrims to hajj, 2003. don/2012_09_25/en/index.html, accessed 7 MAY 2013). Emerging Infectious Diseases, 2004, 10:1882–1883. 32. Bermingham A et al. Severe respiratory illness caused by a 12. Gundlapalli AV et al. Influenza, Winter Olympiad, 2002. novel coronavirus, in a patient transferred to the United King- Emerging Infectious Diseases, 2006, 12:144–146. dom from the Middle East, September 2012. Eurosurveillance, 2012, 17:pii 20290. 13. Blyth CC et al.; World Youth Day 2008 Influenza Study Group. Influenza outbreaks during World Youth Day 2008 mass gath- 33. Skowronski DM et al. Severe acute respiratory syndrome ering. Emerging Infectious Diseases, 2010, 16:809–815. (SARS): a year in review. Annual Review of Medicine, 2005, 14. Shi P et al. The impact of mass gatherings and holiday traveling 56:357–381. on the course of an influenza pandemic: a computational 34. Health conditions for travellers to Saudi Arabia for the pilgrim- model. BMC Public Health, 2010, 10:778. age to Mecca (Hajj). Weekly Epidemiological Record, 2009, 15. Botelho-Nevers E et al. Travel-related influenza A/H1N1 infec- 84:477–480. tion at a rock festival in Hungary: one virus may hide another 35. Al-Tawfiq JA, Clark TA, Memish ZA. Meningococcal disease: one. Journal of Travel Medicine, 2010, 17:197–198. the organism, clinical presentation, and worldwide epidemiol- 16. Van Hal SJ et al. Influenza outbreak during Sydney World Youth ogy. Journal of Travel Medicine, 2010, 17(Suppl.):3–8. Day 2008: the utility of laboratory testing and case definitions 36. Health conditions for travellers to Saudi Arabia for the pilgrim- on mass gathering outbreak containment. PLoS ONE, 2009, age to Mecca (Hajj). Weekly Epidemiological Record, 2012, 4:e6620. 87:277–280. 17. Loncarevic G et al. Public health preparedness for two mass 37. Novel coronavirus—advice for travellers, including Hajj pilgrims. gathering events in the context of pandemic influenza (H1N1) Clinical updates, 15 October 2012. National Travel Health Net- 2009—Serbia, July 2009. Eurosurveillance, 2009, 14:pii 19296. work and Centre [online] (http://www.nathnac.org/pro/ 18. Mandourah Y et al. Clinical and temporal patterns of severe clinical_updates/coronavirus_151012.htm, accessed 7 May pneumonia causing critical illness during Hajj. BMC Infectious 2013). Diseases, 2012, 12:117 38. Severe respiratory illness associated with a novel coronavirus— 19. Alborzi A et al. Viral etiology of acute respiratory infections Saudi Arabia and Qatar, 2012. MMWR Morbidity and Mortality among Iranian Hajj pilgrims, 2006. Journal of Travel Medicine, Weekly Report, 2012, 61(40):820–820. 2009, 16(4):239–242. 39. Memish ZA. The Hajj: communicable and non-communicable 20. Alherabi AZ. Impact of pH1N1 influenza A infections on the health hazards and current guidance for pilgrims. Eurosurveil- otolaryngology, head and neck clinic during Hajj, 2009. Saudi lance, 2010, 15:pi 19671. Medical Journal, 2011, 32:933–938. 40. Revised interim case definition for reporting to WHO—novelcoro - 21. Kandeel A et al. Pandemic (H1N1) 2009 and Hajj pilgrims who navirus. 19 February 2013. World Health Organization [online] received predeparture vaccination, Egypt. Emerging Infectious (http://www.who.int/csr/disease/coronavirus_infections/ Diseases, 2011, 17:1266–1268. case_definition/en/index.html, accessed 7 May 2013). 22. Rashid H et al. Influenza and respiratory syncytial virus infec- 41. Malik M et al. Emergence of novel human coronavirus: public tions in British Hajj pilgrims. Emerging Health Threats, 2008, health implications in the Eastern Mediterranean Region. East- 1:e2. ern Mediterranean Health Journal, 2012, 18:1084–1085. 23. Rashid H et al. Viral respiratory infections at the Hajj: compari- 42. Memish ZA, Venkatesh S, Ahmed QA. Travel epidemiology: son between UK and Saudi pilgrims. Clinical Microbiology and the Saudi perspective. International Journal of Antimicrobial Infection, 2008, 14:569–574. Agents, 2003, 21:96–101. 24. El-Sheikh SM et al. Bacteria and viruses that cause respiratory 43. Novel coronavirus—Eastern Mediterranean (03): Saudi com- tract infections during the pilgrimage (Haj) season in Makkah, ment, 12 February 2013. ProMed, 2013, archive number Saudi Arabia. Tropical Medicine and International Health, 1998, 20130212.1540011. 3:205–209. 44. Gautret P et al. Lack of nasal carriage of novel corona virus 25. Memish ZA et al. Detection of respiratory viruses among pil- (HCoV-EMC) in French Hajj pilgrims returning from the Hajj grims in Saudi Arabia during the time of a declared influenza 2012, despite a high rate of respiratory symptoms. Clinical A(H1N1) pandemic. Journal of Travel Medicine, 2012, 19:15–21. Microbiology and Infection, 2013, Feb 11 (doi: 10.1111/1469- 26. Lim HC et al. The influenza A (H1N1–2009) experience at the 0691.12174 ). inaugural Asian Youth Games Singapore 2009: mass gathering 45. Novel coronavirus infection in the United Kingdom. 23 September during a developing pandemic. British Journal of Sports Medi- 2012, update 12 March 2013. World Health Organization [on- cine, 2010, 44:528–532. line] (http://www.who.int/csr/don/2013_03_12/en/index. 27. Al-Tawfiq JA, Zumla A, Memish ZA. Respiratory tract infections htmlhttp://www.who.int/csr/don/2012_09_23/en/index. during the annual Hajj: potential risks and mitigation strategies. html, accessed 7 May 2013). Current Opinion in Pulmonary Medicine, 2013, 19:192–197. 46. Novel coronavirus infection—update. 16 February 2013. World 28. Al-Tawfiq JA, Memish ZA. The Hajj: updated health hazards Health Organization [online] (http://www.who.int/csr/ and current recommendations for 2012. Eurosurveillance, 2012, don/2013_02_16/en/index.html, accessed 7 May 2013). 17:pii 20295. 47. Novel coronavirus infection—update. 30 November 2012. World 29. Novel coronavirus—Saudi Arabia: human isolate. ProMed, Health Organization [online] http://www.who.int/csr/ 2012, archive number 1302733:20. don/2012_11_30/en/index.html, accessed 7 May 2013).

S54

Book 19 Supplement.indb 54 5/16/2013 2:27:41 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

Short communication Enhanced surveillance and investigation of coronavirus: what is required? R.G. Pebody,1 A. Nicoll,2 U. Buchholz,3 M. Zambon1 and A. Mounts4

تعزيز ُّالرتصد يِّ والتقصللفريوس التاجي: ما هو املطلوب؟ ر. بِ َيبدي، أ. نيكول، أ. ُبشهولز، م. زامبون، أ. ماونتس Coronavirus اخلالصـة: بعد اكتشاف مريضي هلام صلة بإقليم رشق املتوسط، َمصاب نْي باملرض التنفيس الوخيم الناجم عن الفريوس التاجي 2012 اجلديد يف أيلول/سبتمرب ، َّعززت مجيع البلدان أنشطة ُّالرتصد واملختربات الالزمة لكشف املزيد من احلاالت، إىل جانب ا ِّتخاذ تقصيات َّمركزة للمخالطي للحاالت من أجل ُّالتأكد املختربي من احلاالت. وبلغ العدد الكيل للحاالت 30، منها 18 انتهت بالوفاة، مع اكتشاف ثالث جمموعات عنقودية عىل األقل حتى اآلن )جمموعة عنقودية واحدة بي العاملي يف الرعاية الصحية، وجمموعتان عنقوديتان بي أعضاء األرسة( وحتى يومنا هذا، أظهرت الدراسات املجراة عىل انتقال العدوى ًاختطارا ًمنخفضا لالنتقال من اإلنسان لإلنسان يف املستقبل، مع سامت رسيرية التزال وخيمة يفمعظم احلاالت. والتزال هناك أسئلة عديدة، من بينها املصدر احليواين للعدوى، واملدى اجلغرايف للعدوى. وقد تم توسيع نطاق ُّالرتصد ليشمل املجموعات العنقودية للحاالت أو العاملي يف الرعاية الصحية املصابي بمرض تنفيس وخيم غري َّمشخص بغض النظر عن تاريخ السفر. وسوف يكون للدراسات البيئية ُّوالرتصد املستمر ِّوالتقصيات املستمرة للمخالطي للحاالت املرتبطة هبا دور حاسم يف اإلجابة عن بعض تلك األسئلة.

ABSTRACT Following the discovery in September 2012 of 2 patients, both with links to the Eastern Mediterranean Region, with serious respiratory illness due to novel coronavirus, all countries have instigated surveillance and laboratory activities to detect further cases, with intensive case−contact investigations undertaken on laboratory confirmation of cases. A total of 30 cases, of whom 18 have died, and at least 3 clusters have been detected to date (1 cluster among health-care workers and another 2 clusters among family members). To date, transmission studies have shown a low risk of onward human transmission, with clinical presentation remaining severe for the majority. Many questions remain including the zoonotic source and geographical extent of infection. Surveillance has been extended to include clusters of cases or health-care workers with severe, undiagnosed respiratory illness regardless of travel history. Environmental studies, on-going surveillance and linked case− contact investigations will provide a critical role in answering some of these issues.

Surveillance et recherche renforcées pour le coronavirus : quels sont les besoins ?

RÉSUMÉ Suite à la découverte en septembre 2012 de deux patients atteints d'une maladie respiratoire sévère imputable à un nouveau coronavirus, tous deux ayant des liens avec la Région de la Méditerranée orientale, tous les pays ont initié des activités de laboratoire et de surveillance afin de dépister d'autres cas, et notamment des recherches de cas-contacts intensives pour les cas confirmés en laboratoire. Sur 30 cas au total, 18 sont décédés, et au moins trois groupes ont été identifiés à ce jour (un groupe chez des agents de soins de santé et deux autres groupes chez les membres des familles). À ce jour, les études de transmission ont démontré que le risque de future transmission interhumaine était faible, mais que le tableau clinique demeurait sévère pour la majorité des cas. Il reste de nombreuses questions en suspens, notamment la source zoonotique et la propagation géographique de l'infection. La surveillance a été élargie à ces groupes de cas ou aux agents de soins de santé atteints de maladies respiratoires sévères non diagnostiquées indépendamment de leurs voyages passés. Des études environnementales, une surveillance continue et des recherches reliant des cas-contacts seront essentielles pour répondre à certaines de ces questions.

1Public Health England, London, United Kingdom (Correspondence to R.G. Pebody: [email protected]). 2European Centre for Disease Prevention and Control, Stockholm, Sweden. 3Robert Koch Institute, Berlin, Germany. 4Global Influenza Programme,World Health Organization, Geneva, Switzerland.

S55

Book 19 Supplement.indb 55 5/16/2013 2:27:41 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

Introduction World Health Organization (WHO) contacts using approaches developed International Health Regulations [6,7]. during the 2009 influenza pandemic The discovery of a novel coronavirus The detection of the 2 initial cases, [11]. Collection of detailed information (nCoV) in a patient hospitalized with both of whom required intensive care from cases (or their families when cases severe respiratory illness reported in support and who acquired their infec- have died or were seriously unwell) al- September 2012 in Saudi Arabia [1] tion in the Eastern Mediterranean lows a description of the demographic was shortly followed by the laboratory Region, together with the rapid devel- and clinical characteristics of cases and confirmation of nearly identical virus in opment and availability of a sensitive the development of hypotheses about a second individual in a hospital in Lon- and specific polymerase chain reaction risk factors for human infection from an don, United Kingdom [2]. This further, (PCR) diagnostic tool for the detec- as yet unknown reservoir. Describing unlinked case had been transferred for tion of viral genetic material while virus laboratory-confirmed cases by time and medical care from Qatar following on- shedding was still occurring [8], allowed place enables the epidemic curve and set of a severe respiratory illness [3]. The the development of surveillance strat- geographical distribution of this appar- detection of these 2 cases, both infected egies to find further nCoV cases [9]. ent emerging public health problem to with a novel respiratory virus from the Relatively specific clinical case defini- be elaborated. Finally, the identification same genus as severe acute respiratory tions were developed initially to provide and follow-up of close contacts of con- syndrome (SARS)-CoV, led to a global a moderately good predictive value and firmed cases provides the opportunity alert about the emergence of a new virus ensure an efficient use of limited public for detailed case-contact investigations with possible SARS-like properties, with health and laboratory capacity. The hi- that may provide clues to key epidemio- the experience of SARS at the forefront erarchical case definitions developed by logical questions. These investigations of response planning. WHO and national organizations such involve intensive prospective follow-up The appearance of a previously un- as the Centers for Disease Control in of contacts for evidence of respiratory recognized virus, most closely related the United States, Public Health Eng- disease, together with virological and to beta coronaviruses in bats and which land (formerly the Health Protection serological sampling. The availability resulted in severe respiratory illness in Agency) in England, the Robert Koch of newly developed virological and se- humans, raised a series of important Institute in Germany and the Euro- rological assays provides the ability to public health questions. These are sum- pean Centre for Disease Prevention detect secondary infections [14] and marized in the accompanying article by and Control for the European Union to measure the full disease spectrum Nicoll et al. [4]. What was the likely ani- [9–13] focused on the detection of among infected contacts [15]. mal reservoir of this virus? What were individuals with severe undiagnosed These surveillance approaches, the risk factors for animal-to-human respiratory illness with a history of travel together with follow-up of an increas- infection? What was the ability of the from countries where indigenously ingly large number of close contacts, virus to spread from person-to-person? acquired cases had been detected dur- has resulted in 30 laboratory confirmed What was the extent of infection in the ing the putative incubation period of cases of nCoV being reported globally human population? And what was the nCoV. Such “patients under investiga- in the 6 months to 8 May 2013 [16]. spectrum of illness associated with in- tion” were recommended for nCoV Of the 30 confirmed cases, the majority fection in humans? The answers to all testing (Table 1). Detailed laboratory have had severe respiratory disease, with of these questions were unknown based algorithms needed to be established 18 cases having died to date, a high case on the experience of only 2 cases, 1 of with a first-line sensitive assay to detect fatality rate. There is, however, a sugges- which was fatal. the virus, followed by a second-line as- tion of a wider disease spectrum, with a What role can surveillance play say to confirm virus detection, to avoid small number of milder cases, detected in helping to answer these questions? false conclusions about the incidence through intense contact tracing activi- Surveillance was originally described of disease ties [14], although active virological and by Langmuir as “the systematic collec- Early detection and isolation of serological follow-up of case-contacts tion, collation, analysis of data and dis- laboratory-confirmed cases of symp- regardless of symptoms has to date semination of information on a specific tomatic illness allows the rapid imple- failed to uncover a significant hidden disease to inform public health action” mentation of measures to limit potential “iceberg” of mild or asymptomatic cas- [5]. Latterly the epidemic intelligence spread of infection to close contacts. es. The majority (24/30) of cases have role of surveillance, with timely alerting, Case ascertainment also provides an been detected in the Eastern Mediter- analysis and dissemination of informa- opportunity for an in-depth epidemio- ranean Region, with 6 cases diagnosed tion, has gained greater prominence and logical, clinical and virological investiga- in Europe (the United Kingdom and is enshrined in the 2005 revision of the tion of the first cases and their close Germany). Four of these latter 6 cases

S56

Book 19 Supplement.indb 56 5/16/2013 2:27:42 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

Table 1 Definitions of patients and situations requiring public health investigation and testing for novel coronavirus (nCoV) Organization Patient under investigation Other situations under investigation [reference]

World Health A person with an acute respiratory infection, Ill contacts Organization [9] which may include history of fever or Individuals with acute respiratory illness of any degree of measured fever ≥ 38 °C (100.4 °F) and cough; severity who, within 10 days before onset of illness, were AND in close physical contact with a confirmed or probable Suspicion of pulmonary parenchymal disease case of nCoV infection while the case was ill. (e.g. pneumonia or acute respiratory distress Any person who has had close contact with a probable or syndrome), based on clinical or radiological confirmed case while the probable or confirmed case was evidence of consolidation; ill should be carefully monitored for the appearance of AND respiratory symptoms. If symptoms develop with the first Residence in or history of travel to the Arabian 10 days after contact, the individual should be considered a peninsula or neighbouring countries within a “patient under investigation”, regardless of the severity 10 days before onset of illness; of illness, and investigated accordingly. AND Not already explained by any other infection Clusters or etiology, including all clinically indicated Any cluster of severe acute respiratory infection, tests for community-acquired pneumonia particularly clusters of patients requiring intensive care, according to local management guidelines. It without regard to place of residence or a history of travel; is not necessary to wait for all test results for AND other pathogens before testing for nCoV. Not already explained by any other infection or etiology, including all clinically indicated tests for community- acquired pneumonia according to local management guidelines. Health-care workers Health-care workers who care for patients with severe acute respiratory infections, particularly patients requiring intensive care, who develop unexplained pneumonia without regard to place or residence or history of travel.

Centers for A person with an acute respiratory infection, Persons who develop severe acute lower respiratory Disease Control which may include fever ≥ 38 °C (100.4 °F) and illness of known etiology within 10 days after travel from [10] cough; the Arabian peninsula or neighbouring countriesa but do AND not respond to appropriate therapy; Suspicion of pulmonary parenchymal disease OR (e.g. pneumonia or acute respiratory distress Persons who develop severe acute lower respiratory syndrome based on clinical or radiological illness who are close contacts of a symptomatic traveller evidence of consolidation); who developed fever and acute respiratory illness AND within 10 days after travel from the Arabian Peninsula History of travel from the Arabian peninsula or neighbouring countriesa. Close contact is defined as neighbouring countriesa within 10 days; providing care for the ill traveller (e.g. a health-care AND worker or family member), or having similar close physical Not already explained by any other infection contact; or stayed at the same place (e.g. lived with, or etiology, including all clinically indicated visited) as the traveller while the traveller was ill. b tests for community-acquired pneumonia Clusters of severe acute respiratory illness according to local management guidelines. In addition, any clusters of severe acute respiratory illness in health-care workers in the United States should be thoroughly investigated. Occurrence of a severe acute respiratory illness cluster of unknown etiology should prompt immediate notification of local public health for further notification and testing.

Health Protection Any person with severe acute respiratory Health-care worker based in intensive care unit (ICU) Agency [11] infection: caring for patients with severe acute respiratory infection; Symptoms of fever ≥ 38 ºC or history of fever OR and cough; Close contact (i.e. prolonged face-to-face contact) during AND the 10 days before onset of illness with a confirmed case With evidence of pulmonary parenchymal of nCoV infection while the case was ill. disease (e.g. pneumonia or acute respiratory Cluster distress syndrome) based on clinical or Two or more cases of severe acute respiratory infection radiological evidence; requiring ICU admission, regardless of history of travel; AND AND Not already explained by any other infection Not already explained by any other infection or etiology. or etiology; AND History of travel to or residence in an area where infection with nCoV 2012 has recently been reported or where transmission could have occurred in the 10 days before onset of illness.

S57

Book 19 Supplement.indb 57 5/16/2013 2:27:42 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

Table 1 Definitions of patients and situations requiring public health investigation and testing for novel coronavirus (nCoV) (concluded) Organization Patient under investigation Other situations under investigation [reference]

Robert Koch Patient with respiratory symptoms Medical personnel meeting the clinical picture after close Institute [12] independent of its severity; contact with ICU-treated patients meeting the clinical AND “epidemiological exposure A” (close picture and needing intensive care INDEPENDENT of contact); epidemiological exposure. OR Two or more persons treated in ICU meeting the Patient with “clinical picture” and clinical picture, with onset of symptoms within the “epidemiological exposure B”. same 2 -week period and within the same classroom, Clinical picture workplace, household, extended family, hospital, other Patients with acute respiratory syndrome residential facility, barracks or camps INDEPENDENT of (with or without fever ≥ 38 °C) and (with or epidemiological exposure. without cough) for whom based on clinical or radiological signs of an inflammatory infiltrate it is suspected that the lower respiratory tract is affected (e.g. pneumonia or acute respiratory distress syndrome); AND Symptoms not explained by another cause of infection or disease including causes of community-acquired pneumonia (e.g. Streptococcus pneumoniae, Haemophilus influenzae type B, Legionella pneumophila, other bacterial, pneumonia virus, influenza virus type A or B, respiratory syncytial virus). Epidemiological exposure Within the last 10 days before onset of illness: (A) Close contact: With a patient, in particular by medical personnel, or family members; OR Stay in the same place (e.g. living together, visit) as a case, while they were symptomatic. (B) Stay (travel or residence) in the Arabian peninsula or in adjacent countriesc.

European Centre A person with an acute respiratory infection, A person with an acute respiratory infection, which for Disease which may include history of fever and cough may include history of fever and cough and indications Prevention and and indications of pulmonary parenchymal of pulmonary parenchymal disease (e.g. pneumonia Control [13] disease (e.g. pneumonia or acute respiratory or acute respiratory infection), based on clinical or infection), based on clinical or radiological radiological evidence of consolidation, who requires evidence of consolidation, who requires admission to hospital; admission to hospital; AND any of the following: AND • Is in a cluster that occurs within a 10-day period, Has exposure in the Middle East within 10 without regard to place of residence or history of travel, days before onset of illness, unless another unless another aetiology has been identifiedd. aetiology has been identifiedd. • Occurs in a health-care worker who has been working in an environment where patients with severe acute respiratory infections are being cared for, particularly patients requiring intensive care, without regard to place of residence or history of travel, unless another aetiology has been identifiedd.

aCountries considered in the Arabian peninsula and neighbouring include: Bahrain, Iraq, Islamic Republic of Iran, Israel, Jordan, Kuwait, Lebanon, Oman, Palestinian territories, Qatar, Saudi Arabia, Syrian Arab Republic the United Arab Emirates and Yemen. bExamples of respiratory pathogens causing community-acquired pneumonia include influenza A and B, respiratory syncytial virus, Streptococcus pneumoniae and Legionella pneumophila. cYemen, Qatar, Kuwait, Oman, Saudi Arabia, United Arab Emirates and Iraq, Jordan, Bahrain, Syrian Arab Republic, Lebanon, Islamic Republic of Iran, Palestinian Territories, Israel. dNotes that dual infection has been demonstrated in at least 1 case and so that detection of another pathogen should not exclude testing for nCoV where the first pathogen is unlikely to explain the clinical presentation).

S58

Book 19 Supplement.indb 58 5/16/2013 2:27:42 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

had travelled from the Eastern Mediter- specificity and sensitivity, although protocols and guidelines for these ranean Region during the 10-day puta- many gaps in knowledge remain. Al- case-contact investigations have been tive incubation period. The remaining though onward infection in the human developed [11] and should be deployed 2 cases were both family members of population has been limited to date, for future confirmed cases [11,18]. The one of the imported cases, who were experience with SARS illustrated the emergence of nCoV has also high- infected following contact in the UK, possibility for super-spreading events to lighted the importance of international one in a household setting, the other take place [17], highlighting the impor- collaboration between laboratories and seemingly in a hospital setting [14]. Al- tance of ensuring timely detection of countries where suspect cases have oc- though the majority of cases have been new cases through physician awareness curred. This has allowed the technol- sporadic, follow-up and investigation and early testing and implementation of ogy transfer of real-time PCR diagnostic of close contacts of cases has identified prevention and control measures. The tools. The serological diagnostics for likely evidence of non-sustained per- ongoing detection of new cases linked nCoV remain technically challenging, son-to-person transmission of virologi- (directly or indirectly) to the Eastern and the importance of a global reference cally confirmed infection on at least 3 Mediterranean Region, highlights the laboratory will remain vital. occasions. One cluster (of 2 confirmed importance of continuing surveillance Such surveillance activities need cases and 11 probable cases) of severe for cases of severe respiratory disease to be supported by applied epidemio- respiratory illness among health care with a history of travel from countries logical studies to answer more specific workers in a hospital in Jordan was iden- where sporadic cases have been re- questions and which should be under- tified based on retrospective testing; a ported (Table 1). Global and national taken in a standardized fashion to allow second cluster (of 3 confirmed and 1 nCoV surveillance and investigation global pooling of results [13]. Other probable case) was identified in a family activities have evolved based on the in Saudi Arabia and a third cluster (of emerging epidemiological picture. studies include: environmental and 2 confirmed cases plus the index case) WHO has adapted nCoV surveillance animal studies to identify the source was found among family contacts of guidelines with a focus on detecting the of the infection; serological studies in one of the confirmed cases imported to full geographical extent of cases and to a range of potentially exposed popula- the UK. Investigation of each cluster did detect evidence of person-to-person tions; case–control studies to identify not demonstrate evidence of on-going transmission. Key changes to the case and quantify risk factors for animal-to- person-to-person transmission. In May definition will allow the full geographi- person transmission and retrospective 2013, 13 confirmed cases were reported cal “reach” of the infection in the human testing of sample repositories from from Saudi Arabia to WHO and are population to be better delineated by cases of severe undiagnosed respira- currently under investigation [16]. extending previous surveillance case tory illness in a range of geographical The current picture is thus most definitions to include clusters of severe settings. These studies should provide likely of a severe, zoonotic infection with undiagnosed respiratory disease and answers to the source of nCoV, whether occasional transmission to humans, severe undiagnosed respiratory disease nCoV is occurring in other settings, with limited person-to-person transmis- in health-care workers regardless of his- how long it has been around and what sion. These preliminary and limited data tory of travel (Table 1). Continuing to burden of illness it is responsible for. suggest that the surveillance strategies undertake case-contact transmission Such information is key to informing implemented following the detection studies of new cases and follow-up of the revision and optimization of public of the initial 2 cases are generally ap- contacts of newly confirmed cases is health prevention and control measures propriate, with a focus on severe rather essential to detect evidence of person- to reduce the burden of disease due to than mild disease to maintain optimum to-person transmission. Investigation this novel infection.

References

1. Zaki AM et al. Isolation of a novel coronavirus from a man with 4. Nicoll A. Public health investigations required for protecting pneumonia in Saudi Arabia. New England Journal of Medicine, the population against novel coronaviruses. Eastern Mediter- 2012, 367:1814–1820. ranean Health Journal, 2013, 19(Suppl.):S61–S67. 2. Bermingham A et al. Severe respiratory illness caused by a 5. Langmuir AD. The surveillance of communicable diseases of novel coronavirus, in a patient transferred to the United King- national importance. New England Journal of Medicine, 1963, dom from the Middle East, September 2012. Eurosurveillance, 268:182–192. 2012, 17(40):pii 20290. 6. International health regulations (2005), 2nd ed. Geneva, World 3. Pebody RG et al. The United Kingdom public health response to Health Organization, 2005. an imported laboratory confirmed case of a novel coronavirus 7. Heymann D, Mackenzie J, Peiris M. SARS legacy: outbreak re- in September 2012. Eurosurveillance, 2012, 17(40):pii 202922. porting is expected and respected. Lancet, 2013, 381:779–781.

S59

Book 19 Supplement.indb 59 5/16/2013 2:27:42 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

8. Corman VM et al. Assays for laboratory confirmation of novel 13. Rapid risk assessment. Severe respiratory disease associated with human coronavirus (hCoV-EMC) infections. Eurosurveillance, a novel coronavirus. 19 February 2013. Stockholm, European 2012, 17(39):pii 20285. Centre for Disease Control and Prevention, 2013 (http://www. 9. Interim surveillance recommendations for human infection with ecdc.europa.eu/en/publications/Publications/novel-coro- novel coronavirus (28 November 2012). Geneva, World Health navirus-rapid-risk-assessment-update.pdf, accessed 6 May Organization, 2012 (http://www.who.int/csr/disease/coro- 2013). navirus_infections/InterimRevisedSurveillanceRecommenda- 14. Health Protection Agency (HPA) UK NCoV Investigation team. tions_nCoVinfection_20121128.pdf, accessed 6 May 2013). Evidence of person-to-person transmission within a family 10. Coronavirus. Update, case definitions, and guidance. Centers cluster of novel coronavirus infections, United Kingdom, Feb- for Disease Control and Prevention [online factsheet] (http:// ruary 2013. Eurosurveillance, 2013, 18(11):pii 20427. www.cdc.gov/coronavirus/ncv/case-def.html#case, accessed 15. Buchholz U et al. Contact investigation of a case of human 6 May 2013). novel coronavirus infection treated in a German hospital, Oc- 11. The first few hundred (FF100). Enhanced case and contact tober–November 2012. Eurosurveillance, 2013, 18(8):pii 20406. protocol v4.0. Epidemiological protocols for comprehensive 16. Novel coronavirus infection—update. 8 May 2013. World Health assessment of early novel coronavirus cases and their close Organization [online] (http://www.who.int/csr/disease/ contacts in the United Kingdom. London, Health Protection coronavirus_infections/update_20130508/en/index.html, Agency, 2012 (http://www.hpa.org.uk/webc/HPAwebFile/ accessed 8 May 2013). HPAweb_C/131713630080, accessed 6 May 2013). 17. Peiris JS et al. The severe acute respiratory syndrome. New Eng- 12. Schwere respiratorische Erkrankungen in Verbindung mit einem land Journal of Medicine, 2003, 349:2431–2441. Neuartigen Coronavirus. Falldefinition zur Fallfindung, Meldung und Übermittlung. Aktualisierte Version vom 12.12.201 [Severe 18. Van Kerkhove M et al. The consortium for the standardiza- respiratory disease in conjunction with a novel coronavirus. Case tion of influenza seroepidemiology (CONSISE): a global definition for case finding, reporting and communication. Updat- partnership to standardize influenza seroepidemiology and ed version 12.12.201]. Berlin, Robert Koch Institute, 2012 (http:// develop influenza investigation protocols to inform public www.rki.de/DE/Content/InfAZ/C/Corona/Corona_Falldefi- health policy. Influenza and Other Respiratory Viruses, 2013, nition.pdf?__blob=publicationFile, accessed 6 May 2013). 7(3):231–234.

S60

Book 19 Supplement.indb 60 5/16/2013 2:27:42 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

Short communication Public health investigations required for protecting the population against novel coronaviruses A. Nicoll 1

يِّ يات التقصالصحية العمومية الالزمة حلامية الناس من الفريوس التاجي اجلديد أنغوس نيكول 2012 Coronavirus اخلالصـة: لقد ظهرت ِّتقصيات كثرية ترتكز عىل املختربات منذ ظهور الفريوس التاجي اجلديد يف خريف عام ، إال أنه مل يتم حتىاآلن حتديد معظم املتثابتات املطلوبة إلقامة تدابري املكافحة عىل أسس علمية بحيث حتمي الناس من ذلك الفريوس. ُوق نْل مثل ذلك يف التوزيع العاملي للفريوسات يف مستودعاهتا احليوانية التي مل يتم حتديدها حتى اآلن. وقد أظهرت اخلربة املستفادة من استقصاء ومكافحة فريوس جديد آخر من الفريوسات التاجية، وهو فريوس املتالزمة التنفسية احلادة الوخيمة )السارس( يف عام 2003كيف أن التقصيات الوطنية واملحلية يمكن أن تعمل ًمعاضمن حتالف دويل لتنجح يف تفادي الوباء. وتعرض املقالة قائمة بالدراسات التي ينبغي القيام هبا، َّام والسييف البلدان التي تعاين من رساية الفريوسات.

ABSTRACT There have been many laboratory-based investigations since the emergence of the novel coronaviruses in the autumn of 2012, but most of the parameters required for establishing scientifically the control measures that will protect against them have yet to be determined. Equally, the global distribution of the viruses in their animal reservoir has yet to be established. The experience of investigating and controlling another novel coronavirus, SARS, in 2003 shows how national and local investigations can come together as an international coalition and successfully avert epidemics. A menu of studies that need to be undertaken, especially in the countries experiencing transmission, is presented here.

Etudes de santé publique requises pour la protection de la population contre les nouveaux coronavirus

RÉSUMÉ Depuis l'émergence de nouveaux coronavirus pendant l'automne 2012, de nombreuses études ont été menées en laboratoire, mais la plupart des paramètres requis pour l'établissement scientifique de mesures de lutte qui soient capables de protéger contre ces virus restent à définir. De plus, la répartition mondiale de ces virus dans leur réservoir animal doit encore être établie. En 2003, l'expérience de la recherche sur un autre nouveau coronavirus, le syndrome respiratoire aigu sévère, et de la lutte contre ce virus a démontré comment des recherches nationales et locales permettent de mettre en place un front commun au sein d'une coalition internationale et d'éviter efficacement les épidémies. Les études qui doivent être menées, en particulier dans les pays où la transmission est active, sont répertoriées dans le présent article.

1Influenza and Other Respiratory Viruses Programme, European Centre for Disease Prevention and Control, Stockholm, Sweden (Correspondence to A. Nicoll: [email protected]).

S61

Book 19 Supplement.indb 61 5/16/2013 2:27:42 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

Introduction health research and development preclude the assumption that they will activities. The approach taken is to behave in the same way as SARS-CoV Concerns have been raised globally highlight particular questions that [9]. Indeed the signature characteristic by the appearance in 2012 of a novel need to be answered for the purposes of SARS outbreaks in humans—super coronavirus (nCoV) causing severe of preventing or treating these infec- spreading events—have not been respiratory disease within some coun- tions and diseases—the what and the described so far [3,5,7]. Analytic viro- tries in the Middle East and in patients why of each specific question. This logical studies of nCoV have appeared transferred for medical care in Europe is followed by an explanation of the with impressive speed in peer reviewed [1–3]. The fact that a significant pro- mechanisms by which each question journals and some of the conclusions portion of the confirmed cases have can be answered (the how) leading to reached are concerning [9,11–13]. died and that the cause is a coronavirus a list of the specific studies required to The virus may have the potential to of presumed animal origin has revived achieve this. spread in a range of mammalian cells; memories of the severe acute respira- binds to a receptor that is preserved tory syndrome (SARS) epidemics of across a number of species, including 2003 [3–5]. Patients who survive the humans [11,13]; it can also infect and initial infection often require prolonged Controlling and replicate with cytopathic effect in a artificial respiratory support (me- protecting against wide range of cell-lines across various chanical ventilation or extra corporeal novel coronaviruses human tissue types and from other membrane oxygenation), so even a few species [12]. However virological in- cases impact significantly on higher- The new viruses have been genetically vestigations alone cannot predict how level clinical services. A case travelling sequenced [8,9]. Bats are considered the virus will behave, its pathogenic to Europe on a commercial flight and to be the hosts for animal coronavi- action or how it should be treated or then infecting others indicates how ruses and these novel viruses affecting controlled [14]. easily the infection might spread in- humans are similar to a number of At present (April 2013), there is still ternationally, as seen with the SARS bat coronaviruses isolated in both the a lack of much of the information that coronavirus [6,7]. old and the new world [10]. While would be needed to inform on how The purpose of this short com- they bear some relationship to the to control nCoV infection; prevent munication is to summarize thinking SARS-CoV virus which caused severe initial infections; interrupt any human- on priorities for surveillance, applied acute respiratory syndrome (SARS), to-human transmission; and manage epidemiological studies, and public they are also sufficiently different to and treat human infections (Table 1).

Table 1 Information required from investigations for control or mitigation of a novel respiratory virus affecting humans – the “known unknowns” for influenza and other respiratory viruses (including novel zoonotic coronaviruses) Information required Reservoir of infections: animal, human, environmental Modes of transmission to humans and effective prevention of transmission Survival of the viruses in infectiousness doses in the environment Method of spread: human-to-human Setting when infections are take place and procedures associated with transmission Those at risk of infection: risk factors for transmission Those most likely to transmit Those at highest risk of severe disease Population susceptibility Incubation period When cases are infectious and how this relates to symptoms Reproductive number and serial interval Clinical presentation and clinical spectrum Antiviral susceptibility if any Effectiveness of specific treatment and care strategies Proportionate and effective infection control procedures

S62

Book 19 Supplement.indb 62 5/16/2013 2:27:43 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

Equally, it is unclear what (and where) of over 200 close contacts of the first was determined by the countries in the natural and more recent reservoirs 2 imported cases have not revealed which infection and transmission of infection are. SARS for example a single transmission (serological re- took place—Canada, China, Hong had both a reservoir in bats and an sults are pending for the United King- Kong, Singapore, Taiwan and Viet intermediary host in southern China dom contacts) [16,17,]. Yet a third Nam—working together with WHO. [15]. Similarly, it is unclear whether case who travelled on a commercial Information from detailed field inves- humans are occasionally being in- flight resulted in unsustained human- tigations undertaken around the cases fected outside the Middle East. to-human transmission after arrival in those countries was shared openly, It can be argued that the simplest in the United Kingdom. There were starting with a global video confer- response would be to assume that the 2 secondary transmissions: one in a ence meeting on 16–17 May 2003 parameters for control of the nCoVs family setting, the other a nosocomial [5]. The measures that were agreed on would be the same as those for SARS infection in hospital [1,6]. This same that basis in May 2003 were: general and apply the same measures. How- cluster of 3 cases included the first surveillance of respiratory illnesses; ever, these measures cannot be under- confirmed mild case and another case case finding and investigation; triage taken lightly because some of those with dual infection of the new virus of persons with febrile illness; selec- which were effective in controlling and a seasonal influenza virus [6]. tive quarantine; isolation of cases and SARS were resource-intensive and It would be unwise to base global close contacts of SARS cases; inten- disruptive to societies and, especially, guidance on the experience in a single sive infection control and cleaning health-care economies [3]; therefore country or region, even in an area as in health-care setting and public and the parameters for control of nCoV large as Europe. One of the notable professional education (Table 2) [5]. infection need to be determined features of the SARS coronaviruses in These measures were effective and speedily. This uncertainty and the 2003 was the diversity of experience subsequent reviews indicated that this need for speedy action led the WHO which arose seemingly by chance [7]. early sharing and publishing of the Regional Office for the Eastern Medi- While some countries with imported results did not prejudice any publica- terranean to convene a consultation cases had no transmissions, others tions from the countries [19,20,]. in Cairo in January 2013 attended experienced considerably transmis- by the countries experiencing cases sion, often in association with super- in the Middle East and Europe; the spreading events [5,7]. European Conclusions relevant European laboratories [the Union/European Economic Area Erasmus Medical Centre, Health Pro- countries experienced only 32 prob- It may be concluded that nCoV tection Agency (since April 2013 now able SARS cases in 2003 (0.4% of requires rapid field research studies called Public Health England) and the the global total), with 1 death and no combining epidemiological, clinical, University of Bonn]; and the public further transmissions [18]. So far, the serological and virological data to health authorities from Germany and experience with the nCoV in 2012– complement the published virologi- the United Kingdom (Robert Koch 2013 looks very similar to that with cal studies. These would be a series of Institute and Public Health England, SARS in Europe in 2003 when there studies carried out around the natu- respectively). This ECDC staff mem- were imported confirmed cases but rally-occurring cases as was done at ber also attended and presented an no sustained human-to-human trans- speed in 2003 (Table 3) [5,19–26]. earlier version of this paper. mission [1,7,19]. Hence, the 2012– An advantage now is the availability of Extensive epidemiological investi- 2013 European data alone do not prepared protocols ready for adapta- gations have been undertaken around provide a sufficient basis to conclude tion by the countries that wish to un- the few cases that have come to Eu- that the intense local transmission dertake the work [21–25]. Serological rope. Rapid publications from these that happened in Hanoi, Vietnam, techniques have been developed but are reassuring on transmissibility and Hong Kong, Singapore and Toronto, await both use and validation in the appear to contradict some of the more Canada could not be reproduced with countries experiencing transmission worrying interpretations of the labo- the new coronavirus [5,7]. as well as an indication from the ratory studies [6,16,17]. In Europe It is instructive to consider how International Health Regulations the novel viruses are not behaving the measures that were effective in (Article 6) that these and other sorts in the same way as the SARS viruses controlling SARS were determined of studies should be undertaken and did in countries outside Europe in in 2003. Essentially, the scientific the results communicated in a timely 2003 (Table 1)[18]: to date, testing basis for these measures (Table 2) manner[3,16, 21–27].

S63

Book 19 Supplement.indb 63 5/16/2013 2:27:43 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

Table 2 The parameters that were used for controlling SARS – and how they were determined, 2003 [5,19,20] Parameter Findings Implications for control Modes of transmission Person-to-person via respiratory route; Strict infection control and respiratory hygiene, Direct (and indirect) contact of mucous especially in health-care settings; membranes with respiratory secretions, Regular and high levels of environmental cleaning including fomites; in health-care settings; Aerosol-generating procedures were Avoid aerosol-generating procedures and associated with “super-spreading undertake scrupulous infection control events” procedures when they are essential Method of spread Air travel especially important for Persons with febrile respiratory illnesses should international spread; delay travel; Movement of infected patients between Exit screening for febrile respiratory illness for hospitals for local spread those leaving a country where transmission was taking place regularly; Reduction in movement and transfer of certain patients in complex local health economies Those at risk of infection Health care workers Particular emphasis on infection control in health Patients in hospital care settings including emergency rooms and Adult family members health care waiting rooms Children were only rarely infected No reason to take more than the normal themselves or infected others precautions with children Setting when infections take Mostly health-care settings including Particular emphasis on infection control in health place emergency rooms care settings including emergency rooms and Some transmissions in other closed health care waiting rooms settings such as aircraft Initial triage of febrile patients and those with Some unusual super-spreading events respiratory symptoms seeking care in Hong Kong in one hotel and one Avoid aerosol generating procedures and apartment complex undertake scrupulous infection control procedures when they are essential

Incubation period 2 to 10 days Ten days a reasonable period for quarantine and for judging whether or not a person was likely to have SARS if symptomatic and had been in a country where transmission was taking place regularly

When infectious Low in first few days of symptoms, Early self-isolation was found to be especially maximal in second week effective

Reproductive number Best estimate was R = 1–3 Particular emphasis on infection control in health Most infections did not result in further care settings including emergency rooms and infections but super-spreading events health care waiting rooms took place Clinical presentation Acute, febrile respiratory illness, could In a country where transmission was taking place be difficult to notice in persons with regularly focus efforts on case-finding among other respiratory illness and post- those with acute, febrile respiratory illness: operative cases so-called fever clinics and initial triage of those presenting for care to prevent transmission in waiting areas and emergency rooms

Effective control measures Intensive surveillance for respiratory infections and aggressive case finding where cases were occurring; Early isolation of putative cases Contact tracing around confirmed cases; Triage of persons with acute febrile respiratory illnesses Reduce movement and transfer of patients

Those at highest risk of severe Persons with chronic underlying Particular protection of these groups disease conditions; Pregnant women

S64

Book 19 Supplement.indb 64 5/16/2013 2:27:43 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

Table 3 Specific public health questions needing answered for the novel coronaviruses– the what, why and how What do we need to Why do we need to know How will we find out? Types of studies and notes know? it?

1. Where geographically Determining the level of Case-finding virologic Applied epidemiological and are the human infections threat: is this an infection testing of people laboratory research studies in a occurring worldwide? only occurring in 1 locality fitting the case number of countries testing patients in 1 sub-region or is it more definition for severe with unexplained severe lower widespread? Alternatively cases and others; respiratory tract infection, either using is this an older infection Prospectively, among retrospective contemporaneous that has been around the people fitting archives of suitable stored specimen or some time and simply the Persons Under as prospective planned studies. unrecognised? Investigation (PUI) The ECDC/WHO laboratory survey To inform decisions definitions in any of European Union countries gives a on which patients to clusters and outbreaks mechanism by testing people fitting test among those who of severe respiratory the PUI-with symptoms definition but come to Europe with disease need to distinguish the different groups respiratory infections or therein: who subsequently develop respiratory infections • People with severe disease + within a certain time geographical risk • People with severe disease without geographical risk • Exposed health-care workers Question: Do we need to know the animal reservoir? Question: Have Koch’s postulates been demonstrated? Need to think beyond the Middle East and consider the trade/people movements from the Middle East especially migrant workers from South Asia who work in the Middle East Serological surveys It should be possible to develop to agreed protocols the tools but the importance will be with local adaptations validation and quality assurance from [21,22,24]. the CONSISE and earlier experience. It will be especially important to include validation with ‘sticky’ sera from middle East countries remembering the initial HIV serological experience where tests developed and validated in one region lost specificity in another settinga

What is the reservoir of As for point 1 Environmental and Environmental and animal studies the virus infection? animal surveillance and testing around sporadic unexplained cases 2. The estimated Informing on who to test: Observing and incubation period (from “all people developing investigating clusters exposure to symptoms) severe acute respiratory to agreed protocols and serial interval? infections within a certain with local adaptations number days of coming [21,22]. from countries X, Y, Z” Determining potential for explosive spread. Comparing infections like influenza (short incubation period and serial interval: impossible to control) and SARS and smallpox (long incubation period and serial interval: possible to control)

S65

Book 19 Supplement.indb 65 5/16/2013 2:27:43 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

Table 3 Specific public health questions needing answered for the novel coronaviruses– the what, why and how (concluded) What do we need to Why do we need to know How will we find out? Types of studies and notes know? it?

3. How infectious are these Informing on infection Reviewing the In SARS most cases did not transmit cases and what are the control measures and their outcome of the to secondary cases, but 10%–20% sources of infectious stringency case finding around transmitted to many secondary (and virus? the recognised higher order) cases: super-spreading cases especially in events [7,19,20]. health care staff and household/family contacts 4. When are these cases Informing on the Studies of when and There are some data from this from infectious to others duration of infection at what levels are the Germany (Robert Koch Institute). control measures and viruses detectable Note: a positive feature of SARS was the stringency of control compared to the that the cases were really not infectious measures, as well as symptoms and to before developing symptoms (c.f. possible advice on default cases of influenza) making quarantine and early quarantine of exposed influenza and SARS isolation of cases especially effective persons [5].

5. Are there any super- Informing on infection Reviewing the Watch for these especially in health- spreading events? control measures and outcome of the care settings. What actually happened the stringency of control case finding around in the clusters in Jordan and Saudi measures the recognised Arabia? cases especially in health care staff and household/family contacts 6. What do cases look like? Informing on who to Review of the Note: a problem with SARS was that Who are the high risk test and understanding confirmed cases; infectious cases were not always groups? the scope of illness Serological testing of recognised in a timely manner. Some manifestations; contacts, especially were inapparent for example in Understanding the those with milder those hospitalised for other reasons frequencies and severity symptoms, and (e.g. post major surgery, people with of organ involvement virologic testing of multiple pathology). In a sense this and secondary bacterial contacts exposed in has happened in the cases that were infections to assist in future events [21]. imported into Germany and the United clinical management Kingdom without thinking they might represent serious imported infections.

7. How best to manage and To optimise care and Preparing and Suitable protocols have now been treat the patients to avoid doing harm agreeing protocols, agreed between ISARIC members and from certain medical and those caring for approved by WHO [25]. interventions patients applying these and sharing experience and results in real time

8. How extensive is patient Looking for cases and WHO Member States Note for the cases that came to other movement from the determining which asking the referral countries the long time between the Middle East to Europe? clinicians to inform; centre; arrival and considering testing for novel Considering the risk to Work with people infections. those caring for patients in who look at transport transit trends and patient export importations

aWhen HIV serological tests validated in Europe and North America were applied in Africa in the 1980s without local validation and the consequent publication of analyses suggesting substantial levels of population prevalence in East Africa which were due to cross-reaction with other antibodies (to malaria) [26]. ECDC = European Centre for Disease Prevention and Control. WHO = World Health Organization. CONSISE = consortium for the standardization of influenza seroepidemiology. HIV = human immunodeficiency virus. SARS = severe acute respiratory syndrome. ISARIC = International Severe Acute Respiratory and Emerging Infection Consortium.

S66

Book 19 Supplement.indb 66 5/16/2013 2:27:43 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

References

1. Rapid risk assessment: severe respiratory disease associ- tent/early/2013/03/24/infdis.jit125.full.pdf+html, accessed 11 ated with a novel coronavirus, 19 February 2013. Stockholm, May 2013). European Centre for Disease Prevention and Control, 2013 15. Li W et al. Bats are natural reservoirs of SARS-like coronavi- (http://ecdc.europa.eu/en/publications/Publications/nov- ruses. Science, 2005, 310:676–679. el-coronavirus-rapid-risk-assessment-update.pdf, accessed 11 16. Buchholz U et al. Contact investigation of a case of hu- May 2013). man novel coronavirus infection treated in a German hos- 2. Danielsson N, on behalf of the ECDC Internal Response Team. pital, October–November 2012. Eurosurveillance, 2013, Catchpole M. Novel coronavirus associated with severe res- 18(8):20406 (http://www.eurosurveillance.org/ViewArticle. piratory disease: Case definition and public health measures. aspx?ArticleId=20406, accessed 11 May 2013). Eurosurveillance, 2012, 17(39):pii 20282. 17. Pebody RG et al. The United Kingdom public health response 3. Heymann D, Mackenzie J, Peiris M. SARS legacy: out- to an imported laboratory confirmed case of a novel coro- break reporting is expected and respected Lancet, 2013, navirus in September 2012. Eurosurveillance, 2012, 17(40):pii 381(9869):779–781. 20292. 4. Eurosurveillance editorial team. Note from the editors: A new 18. Summary of probable SARS cases with onset of illness from 1 virus bringing back memories from the past. Eurosurveillance, November 2002 to 31 July 2003 (Based on data as of the 31 De- 2012, 17(39):pii 20284. cember 2003.). Geneva, World Health Organization, Global 5. Consensus document on the epidemiology of severe acute respira- Health and Response, 2003 (http://www.who.int/csr/sars/ tory syndrome. Geneva, World Health Organization, Depart- country/table2004_04_21/en/index.html, accessed 11 May ment of Communicable Disease Surveillance and Response 2013). 2003 (WHO/CDS/CSR/GAR/2003.11) (http://www.who.int/ 19. Anderson RM et al. Epidemiology, transmission dynamics csr/sars/en/WHOconsensus.pdf, accessed 11 May 2013). and control of SARS: the 2002–2003 epidemic. Philosophical 6. Health Protection Agency (HPA) UK, Novel Coronavirus Transactions of the Royal Society of London. Series B, Biological Investigation team. Evidence of person-to-person transmis- Sciences, 2004, 359:1091–1105. sion within a family cluster of novel coronavirus infections, 20. Peiris JS et al. The severe acute respiratory syndrome. New United Kingdom, February 2013. Eurosurveillance, 2013;18(11): England Journal of Medicine, 2003, 349:2431–2441. pii 20427 21. “The First Few Hundred (FF100)” Enhanced Case and Contact 7. Update: Outbreak of Severe Acute Respiratory Syndrome Protocol v4.0. Epidemiological protocols for comprehensive — Worldwide, 2003. Morbidity and Mortality Weekly Report assessment of early novel coronavirus cases and their close (MMWR), 2003, 52(12):241–248. contacts in the United Kingdom. London, Health Protection 8. Genetic sequence information for scientists about the novel Agency, 2012 (http://www.hpa.org.uk/webc/HPAwebFile/ coronavirus 2012. Whole Genome Sequence – Added 18th HPAweb_C/1317136300809, accessed 11 May 2013). February 2013. London, Public Health England, Health Pro- 22. Van Kerkhove M et al. on behalf of the CONSISE steering com- tection Agency 2013 (http://www.hpa.org.uk/Topics/In- mittee. The consortium for the standardization of influenza fectiousDiseases/InfectionsAZ/NovelCoronavirus2012/ seroepidemiology (CONSISE): a global partnership to stand- respPartialgeneticsequenceofnovelcoronavirus/) accessed ardize influenza seroepidemiology and develop influenza in- 11 May 2013. vestigation protocols to inform public health policy. Influenza 9. Cotten M et al. Full-genome deep sequencing and phylo- and Other Respiratory Viruses, 2012, 7(3). genetic analysis of novel human betacoronavirus. Emerging 23. Reusken C et al.Specific serology for emerging human coro- Infectious Diseases, 2013, 19(5) (http://wwwnc.cdc.gov/eid/ naviruses by protein microarray.Eurosurveillance, 2013, 18:pii article/19/5/13-0057_article.htm, accessed 11 May 2013). 20441.) 10. Annan A et al. Human betacoronavirus 2c EMC/2012–related 24. Van Kerkhove M. CONSISE and avian influenza H7N9. CONSISE viruses in bats, Ghana and Europe.[Internet]. Emerging Infec- Working Draft Protocols for influenza. London, CONSISE The tious Diseases, 2013, 19:456–459. Consortium for the Standardization of Influenza Seroepide- 11. Raj VS et al. Dipeptidyl peptidase 4 is a functional receptor for miology, 2013 (http://consise.tghn.org/articles/consise-and- the emerging human coronavirus-EMC. Nature, 2013, 495:251– avian-influenza-h7n9/, accessed 11 May 2013). 254 (http://www.nature.com/nature/journal/v495/n7440/ 25. Longuère K-S. ISARIC and WHO SARI and Natural History Pro- pdf/nature12005.pdf , accessed 11 May 2011). tocols. Oxford, ISARIC (International Severe Acute Respiratory 12. Chan JP et al. Differential cell line susceptibility to the emerg- and Emerging Infection Consortium), 2013 (http://isaric.tghn. ing novel human betacoronavirus 2c EMC/2012: implications org/articles/isaric-and-who-sari-and-natural-history-proto- on disease pathogenesis and clinical manifestation. Journal of cols/, accessed 11 May 2013). Infectious Diseases. (2013) 207(11):1743–1752. 26. Biggar RJ et al. Regional variation in prevalence of anti- 13. Müller M et al. Human coronavirus EMC does not require the body against human T-lymphotropic virus types I and III SARS-coronavirus receptor and maintains broad replicative in Kenya. East Africa International Journal of Cancer, 1985, capability in mammalian cell lines. mBio, 2012, 3(6) (http:// 35(6):763–767 (http://onlinelibrary.wiley.com/doi/10.1002/ mbio.asm.org/content/3/6/e00515-12.long, accessed 11 May ijc.2910350611/abstract, accessed 11 May 2013). 2013). 27. International Health Regulations, 2005, 2nd ed. Geneva, World 14. Mackintosh K. A new virulent human coronavirus: How much Health Organization, 2008 (http://whqlibdoc.who.int/pub- does tissue culture tropism tell us? Journal of Infectious Diseases lications/2008/9789241580410_eng.pdf, accessed 11 May (Advance Access), 2013 (http://jid.oxfordjournals.org/con- 2013).

S67

Book 19 Supplement.indb 67 5/16/2013 2:27:44 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

Meeting report Highlights and conclusions from the technical consultative meeting on novel coronavirus infection, Cairo, Egypt, 14–16 January 2013 C. Joseph,1 M.R. Malik,2 A.W. Mounts,1 A. R. Mafi,2 S. Briand,1 Z.A. Memish 3,4 and the technical working group for the meeting on novel coronavirus

مقتطفات وخالصات من االجتامع التشاوري التقني حول العدوى بالفريوس التاجي اجلديد؛ القاهرة، مرص، 14-16 كانون الثاين/يناير 2013 كارل جوزيف، مامونار مالك، أنطوين واين ماونت، عيل رضا معايف، سيلفي برياند، زياد ميمش، الفريق العامل لالجتامع عىل رواية الفريوس التاجي اخلالصـة: لقد أدى ظهور ذرية جديدة من الفريوس التاجي Coronavirusيف شبه اجلزيرة العربية إىل إثارة القلق الصحي عىل الصعيد العاملي عام 2012 ؛ وذلك يعود ًجزئياإىل أن معظم حاالت العدوى البرشية كانت مميتة، كام يعود ًجزئيا ًأيضا إىل أهنا من مصدر حيواين عىل ما ُي َفرتض. وقد عقدت منظمة الصحة العاملية يف كانون الثاين/يناير ،2012 ً اجتامعا ًعاجاليف ظل املعلومات الضئيلة املتاحة حول السوابق الطبيعية والوبائية للعدوى هبذا الفريوس اجلديد. وقد استعرض االجتامع ِّالبينات الراهنة، َّوحدد الفجوات احلاسمة يف املعارف والالزمة لتحسي الوصول إىل ٍفهم أفضل ملخاطر الصحة العامة التي ترافق هذا الفريوس بحيث يتم حتسي التأهب كام تتم محاية ووقاية الصحة يف العامل.

ABSTRACT The emergence of a novel strain of coronavirus in the Arabian Peninsula raised a global health concern in 2012, partly because the majority of human infections were fatal and partly due to its presumed animal origin. An urgent meeting of scientific and public health experts was convened by WHO in January 2013 in view of the limited knowledge available on the epidemiological and natural history of infection with this novel virus. The meeting reviewed current evidence and identified critical knowledge gaps to improve better understanding of the public health risk associated with the virus so as to improve preparedness and to safeguard and protect global health.

Faits marquants et conclusions de la réunion de consutlation technique sur l'infection par le nouveau coronavirus, Le Caire (Égypte), 14 - 16 janvier 2013

RÉSUMÉ L'émergence d'une nouvelle souche de coronavirus dans la Péninsule arabique a soulevé des inquiétudes sanitaires à l'échelle mondiale en 2012, d'une part parce que la majorité des infections humaines ont été mortelles et d'autre part parce qu'une origine animale était suspectée. L'Organisation mondiale de la Santé a invité des experts en santé publique et scientifiques à une réunion urgente en janvier 2013, étant donné les connaissances limitées disponibles sur l'évolution épidémiologique et naturelle de l'infection par ce nouveau virus. Pendant la réunion, les données disponibles ont été examinées et des lacunes critiques dans les connaissances ont été identifiées en vue d'améliorer la compréhension du risque pour la santé publique associé à ce virus, d'intensifier la préparation et de préserver et de protéger la santé mondiale.

1Global Influenza Programme, Department of Pandemic and Epidemic Disease. World Health Organization, Geneva, Switzerland. 2Pandemic and Epidemic Disease, Department of Communicable Disease Prevention and Control, World Health Organization Regional Office for the Eastern Mediterranean, Cairo, Egypt (Correspondence to M.R. Malik: [email protected]). 3Ministry of Health, Riyadh, Saudi Arabia. 4College of Medicine, Al Faisal University, Riyadh, Saudi Arabia.

S68

Book 19 Supplement.indb 68 5/16/2013 2:27:44 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

Introduction scientists who had been involved with sporadic cases were 6 June—10 Oc- the study of the origin of the virus, and tober. The dates of onset for the cases In 2012, a multi-country outbreak of experts who had participated in the within the family cluster were sequen- severe acute respiratory disease in the global public health response to SARS tial and ranged from 5 October to 3 Arabian Peninsula, caused by a novel and the avian influenza epidemic. The November, consistent with human-to- coronavirus (nCoV), raised a global purpose of this meeting was to review human transmission. No community health alert [1–3]. In light of the severity and discuss the scientific and public transmission was reported. of illness seen amongst the laboratory- health understanding of the emer- The investigation of potential en- confirmed cases reported to the World gence of nCoV to date, identify critical vironmental and animal sources of the Health Organization (WHO) by Janu- knowledge gaps in understanding the nCoV carried out in the Bisha area of ary 2013, where the mortality rate was current risk and identify the next steps Saudi Arabia in September 2012 was not over 55% [4], the discovery of this new to improve knowledge and close up conclusive. Bats and dates were the main virus triggered unprecedented global the research gap for public health ac- focus of investigation. Bats were targeted attention. tion at the national and international because of the genetic relatedness of This novel virus brought back mem- level. The meeting was organized in 5 the nCoV to coronaviruses previously ories of the global epidemic of severe thematic sessions and in each of these found in bats in Mexico and elsewhere acute respiratory syndrome (SARS) in sessions, available scientific informa- [9]. Bat CoVHKU9, bovine respiratory 2003 as this new virus was presumed to tion and up-to-date evidence on nCoV CoV and Kenya Idoline bat viruses were be of animal origin and also belonged to were presented and discussed by the detected among the 755 oral, rectal and the same family of Coronoviridae as that participants. The sessions included serological samples from insectivorous of the SARS virus (SARS–CoV). Clini- (i) epidemiological information; (ii) bats collected in the Bisha area of Saudi Arabia and tested in the United States of cal symptoms caused by nCoV infection virological and animal investigation; America (USA) in October. Sequenc- also matched the clinical picture of acute (iii) development of tests for nCoV; ing by nested polymerase chain reaction primary viral pneumonia seen in many (iv) experience from SARS; and (v) (PCR) showed that Saudi bat virus was patients suffering from SARS [5]. risk communication and preparedness. The final session of the meeting on genetically indistinguishable from the The genetic sequence data indicated “knowledge gaps and priorities for re- nCoV identified by the Erasmus Medi- that this new coronavirus was a beta- search” reviewed the currently available cal Center (EMC) of Rotterdam in the coronavirus similar to bat coronaviruses, scientific evidence and identified the Netherlands. No virus was cultured from but not similar to any other coronavirus critical knowledge gaps that needed to the Bisha bats. No microbiological or previously described in humans, includ- be addressed in order to improve global environmental link was made between ing the coronavirus that caused SARS understanding of the risk associated date farming and date consumption for in 2003 [6–8]. The available evidence with this novel virus. This paper summa- the first confirmed case of nCoV infec- related to this nCoV continued to sug- rizes the currently available information tion and no tests were carried out on gest a zoonotic origin for the virus, and on the virus, knowledge gaps and the camels or goats. Though the inability to experience with the SARS–CoV also priority public health research activities culture the virus or extend the sequence showed that any novel virus that is zo- that were discussed in the meeting in makes interpretation of the results dif- onotic in origin has the potential to effi- order to improve global preparedness ficult, it did suggest that the virus may ciently transmit from person to person, for any potential pandemic caused by have been in the environment at very especially in healthcare settings, and this novel virus. low frequency and concentration. It to cause a global pandemic of severe remained unknown whether the virus human illness. was in livestock or another intermediate An urgent meeting of scientific and Highlights host, nor how it may have been transmit- public health experts involved in the ted to humans. national and global investigations of Environmental and The first case reported from Qatar this nCoV infection was convened by epidemiological investigation had onset of illness on 3 September with WHO at its Eastern Mediterranean Re- By December 2012, 6 laboratory- a travel history to Mecca from 29 July to gional Office in Cairo, Egypt, from 14 to confirmed cases of nCoV, including 18 August. He had no known contact 16 January 2013. The meeting brought 3 deaths, had been reported from with sick people. He owns a farm with together WHO, national experts who Saudi Arabia. Three (3) cases occurred camels and sheep which he visited once had been involved in investigations sporadically and 3 were part of a fam- on his return from Mecca. The patient around the cases that have occurred, ily cluster. The dates of onset for the 3 was transferred to the United Kingdom

S69

Book 19 Supplement.indb 69 5/16/2013 2:27:44 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

(UK) on 12 September where the London tested positive for nCoV. The receptor for nCoV is different from nCoV was identified through culture patient was transferred to Germany on that used by the SARS–CoV, which and PCR. Genetic sequencing indi- 24 October. The estimated number of also causes Severe Acute Respiratory cated that the virus was the same as health-care workers and family con- Syndrome [10]. It has been previously that previously found in the patient in tacts associated with the case was 85. shown that changes in the spike pro- Saudi Arabia. An investigation of health- Respiratory and serum samples were tein (S1) of the coronavirus are an care workers exposed to the patient collected from 20 of these contacts and important means by which the virus identified 4 who became symptomatic the nCoV was not detected in any of the adapts to a new host. The S1 protein after exposure, but laboratory reports respiratory samples. as the presumed binding site in nCoV were negative for all these cases when An investigation of 123 contacts was cloned and tested for binding to tested at the Health Protection Agency (120 hospital and 3 out-of-hospital con- target cells and was found to bind to (HPA) in London. tacts) of the first nCoV case identified in human cells, and in animal models. The UK Health Protection Agency Germany was conducted in November The dipeptidyl peptidase 4 (DPP4) (now known as Public Health Eng- 2012 at the Robert Koch Institute in protein, an enzyme expressed on the land) confirmed on 22 September Berlin, Germany, to evaluate human- surface of some cells, has now been 2012 infection with a novel coronavi- to-human transmission. The case was identified as a receptor to which the rus in a patient in a London hospital a patient with acute respiratory distress S1 virus protein binds in human and who had been transferred from Qa- syndrome of unknown origin and bat cells. tar 11 days previously. Following the symptom onset on 5 October who was Further studies are now going on institution of strict respiratory isola- transferred from Qatar to a specialist in the animal model related to patho- tion, infection control procedures and lung clinic in Germany. Eighty-five con- genic potential of nCoV in human enhanced surveillance as a response tacts provided blood for a serological respiratory tissues to this imported case from Qatar, 64 test and analysis was performed using a contacts (56 health-care workers and 2-stage approach with an initial immu- Sequencing studies 8 family and friends) were identified. nofluorescence assay as a screening test, The complete genome sequence of Ten days after last exposure, none of followed by recombinant immunofluo- the nCoV-EMC/2012 virus has been the 64 had developed severe disease; 13 rescence assays and an nCoV-specific published [8]. By January 2013, only of them had reported mild respiratory serum neutralisation test. None of the 2 viruses were fully sequenced: the symptoms during the 10-day follow- contacts tested positive for antibodies nCoV-EMC from Saudi Arabia and up period. The novel coronavirus was to the nCoV, indicating that no trans- the one from Qatar sequenced by the not detected in 10 of 10 symptomatic mission had occurred to contacts after HPA in London (England1_CoV). contacts tested. The health-care work- 20 days post exposure. The analysis of 3 sequenced genomic ers had a variety of exposures, includ- A cluster of severe acute respiratory fragments showed that the genetic ing some during an aerosol generating infections occurred in April 2012 in a structure of the virus isolate in Germa- procedure. Preliminary results of se- health-care setting in Zarqa, Jordan. In ny was identical to the virus isolated rological testing found no evidence of November 2012, retrospective labora- from the patient in Qatar in the UK. a serological response consistent with tory investigation of a stored specimen Methods for detecting nCoV by 2 infection among close contacts of the of bronchoalveolar lavage and a serum real-time, reverse-transcription PCR confirmed case. sample confirmed nCoV infection in 2 assays (real-time RT-PCR) were The second case from Qatar was patients, both of whom died. Addition- published in September 2012 [6]. a single male and owns a camel and ally, 11 probable cases were identified Two target regions were chosen for goat farm. He had no contact with the through a retrospective epidemiological screening, confirmation and sequenc- animals, had no history of travel, and no investigation. Ten of the 13 persons in known contact with sick people. He was this cluster were health-care workers. ing of the nCoV; the Upstream of treated in 2 hospitals in Qatar from 12 No sustained community transmission the E gene (UpE) for screening and to 24 October. Respiratory samples— was observed. ORF1b for confirmation. nasal swabs and an endotracheal tube A 700-nucleotide segment of the N (ETT) aspirate were collected from the Virological and animal gene of the virus from one of the cases investigations patient on 13 and 17 October and were in Jordan sequenced at the United negative when tested for a standard Pathogenesis of nCoV States Naval Medical Research Unit- panel of respiratory viruses in Qatar. A study conducted at the Univer- 3 (NAMRU-3) had 99% homology The ETT sample sent to the HPA in sity of Bonn found that the cellular to the EMC and London viruses.

S70

Book 19 Supplement.indb 70 5/16/2013 2:27:44 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

Development of laboratory The UK HPA tested 124 sera Experience from SARS tests for nCoV samples from family and health-care The global experience from SARS was a Tests by real-time PCR worker contacts of the imported case stark reminder of how a novel virus can The current WHO interim guidance from Qatar. The sera were screened for cause a global public health emergency, on PCR testing for nCoV states that a reactivity to coronavirus NL63 (CoV from a few sporadic cases to a world- positive PCR test should be followed gp1), OC43 (CoV gp2a), SARS (CoV wide epidemic. The SARS-CoV spread by a confirmatory test with the 1A as- gp2b) and nCoV England/1 2012 to 5 countries within a 24-hour period, say or by sequencing target sites within (CoV gp2c). No reactivity with the before international public health meas- the nucleocapsid protein region of the nCoV England 1 antigen was detected. ures were in place to identify, control genome [11]. Positive control materials When recombinant assays were tested and prevent the spread of infection. developed by the University of Bonn are for cross-reactivity with these strains The importance and challenges in the available for the upE and 1A tests. Two and bat CoV strains from groups 1, 2a, implementation of public health meas- new assays for sequencing, particularly 2b, 2c and 2d, the group 2c bat strains ures such as strict hospital infection where an insertion/deletion polymor- were reactive to the London patient control measures, case identification, phism might exist, as is the case between sera. These results were part of work and comprehensive identification and the EMC virus and the London virus, in progress, and further studies will be quarantine of contacts cannot be over- were also made available in December needed to interpret the data. Cross- emphasized. Sharing of information 2012. The assays are now available reactivity, particularly in older people at the local, national and international commercially worldwide and have been who have been exposed to different level was key to managing public and provided to some of the countries of the coronaviruses over time, can be natu- professional fear and anxiety. The les- WHO Eastern Mediterranean Region ral. Cross reactions might also occur sons learned from the SARS outbreak in where cases have occurred. The Cent- when detecting low titres that might be 2003 emphasized the need to strength- ers for Disease Control and Preven- a result of past infection combined with en international health regulations, have tion (CDC), USA, has developed two a fresh infection of a different CoV. A national plans in place to handle similar nucleocapsid assays for detection of wide range of tests are required to fully future outbreaks, maintain public health nCoV. These assays were distributed to understand these issues. epidemiological and microbiological capacity and keep ahead of the curve. Saudi Arabia and Jordan, and were used Ecological studies by NAMRU-3 to confirm the cases in Risk communication and Jordan. Ecological studies have shown that bats are natural hosts of 2b and 2c beta preparedness Serological tests coronavirus subgroups. Extensive bat The national and international public Two immunofluorescent antibody sampling has been carried out in Africa health organizations have kept the (IFA) detection assays have been de- and Europe, where a high percentage public fully apprised of the emergence veloped; one using conventional IFA of bats among the Nycteris (25%) and and investigation of the nCoV cases methods and the other a rapid method. Pipistrellus (36%) genera were found on their websites through regular bul- Confirmatory tests for positive IFA to be positive with CoV of the 2c clade. letins and updates, question and answer results are carried out through recom- The pipistrellus bats inhabit the Ara- sheets, or through publications such binant subunit assays, plaque reduction bian Peninsula but also migrate to Africa as the rapid reports in Eurosurveillance. neutralization tests, and western blot and other continents. The knowledge The WHO has 3 main communica- to rule out false positive results [6]. that insectivorous bats are natural tion channels: the Event Information Tests for sensitivity and cross-reactivity hosts for betacoronaviruses, and that Site (EIS), a password-protected rapid against other coronaviruses and other coronaviruses have been detected in a reporting system; the disease outbreak respiratory viruses with the nCoV- significant proportion of bats, does not news (DON), which is a public system; EMC found no cross-reactivity using in itself provide definitive evidence that and traditional media through its web- these confirmatory methods. Further they are the source of infection for the site and publications. The important validation studies are needed and the cases of nCoV detected in the Arabian lessons learned were mainly related IFA test is not suitable for broad popula- Peninsula. More studies are needed to to timely and adequate dissemination tion screening of asymptomatic indi- ascertain whether a virus even more of information—the more informa- viduals. Many serological samples are closely related to nCoV-EMC might tion the better—to help the affected in storage from the 9 nCoV cases and be found in other species and whether country, to help other neighbouring their contacts and these could be used other animals might be sources or car- countries, and to help the world be bet- to further validate the IFA tests. riers of the novel human coronavirus. ter prepared.

S71

Book 19 Supplement.indb 71 5/16/2013 2:27:44 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

Gap analysis and priorities for actions to improve the current knowl- in European, American and other na- future research and investigation edge gaps. tional laboratories; of novel coronavirus • encouraging cooperation in the de- A number of key knowledge gaps were velopment of virological studies; identified to better understand the evo- Conclusion and lution and public health risk associated next steps • preparing an inventory of training op- with this nCoV. The most important portunities for laboratory staff testing for nCoV; ones were the source of the virus, the The emergence of new, infectious, exposures that resulted in human infec- global threats in the past 4 decades • preparing an inventory of laboratories tion, and the mode of transmission. (e.g. AIDS, avian influenza A/H5N1 developing nCoV serological tests Those areas where more information is and SARS) has reshaped thinking at and list which laboratories are using needed to characterize the current and both national and international levels which tests; future risk posed to global health by on the nature and level of public health • preparing an inventory of countries this novel virus are: responses needed for these threats. The willing to test cases of severe acute • source of the infection and its animal International Health Regulations (2005) respiratory infection (SARI) for reservoir(s), have emphasized that all countries nCoV; • extent of geographical spread, are at risk from new infections and • liaising with the animal research therefore need to collaborate on in- • route(s) of transmission, group to strengthen collaborative formation sharing and data exchange studies and coordinate future stud- • transmissibility of infection and de- when they occur [12]. In the current ies into the reservoir of infection for gree of infectiousness, age of immediate and ongoing access nCoV; • exposure patterns, to world-wide digital information, • itemizing all collaborating resources there are high expectations globally • incubation periods, and identifying where capacity build- that everything is being done to de- • pathogenesis including age and gen- ing is required; der determinants, tect and control an emerging disease threat. Uncertainties as to how a newly • ensuring that risk assessment guide- • clinical spectrum of severe illness and discovered disease is going to evolve lines, infection control guidelines and evidence of mild infections, means that preparations have to be other documents are regularly re- • what further diagnostic tests should determined at both the national and viewed and communicated to those be developed for detection of virus, the global level. that need to know. • interpretation of test results. During the Cairo meeting, all cur- Four key areas were highlighted rent knowledge about the cases of for guiding future efforts in further- Technical working nCoV infection and about what has group members ing the global understanding and shaped priorities for future actions at knowledge of nCoV. These included the national and the international level The members of the technical work- (i) defining the geographic extent of was evaluated. After consolidating in- virus transmission, (ii) detecting any ing group include: Christian Drosten, formation on current scientific activities Walter Ian Lipkin, Ron Fouchier, escalation in incidence, (iii) improving ongoing at the global level, the delegates the case definition; and (iv) identify- Udo Buchholz, Keiji Fukuda, Jaouad identified activities that would advance ing the source of infection. A number Mahjour, Hala Esmat, Dalia Samhouri, knowledge about this infection in the of recommended actions were also Gregory Hartl, Agnus Nicoll, Richard immediate and long term. These in- proposed and future steps were identi- Pebody, Maria Zambon, Theresa Tam, clude: fied for WHO’s role. Table 1 presents Barbara Raymond, Hamad Eid Al- a summary of these priority research • preparing an inventory of current Romaihi, Said Hamed Al Dhahry and areas and the suggested recommended nCoV virological research activities Sultan Mabdalla.

S72

Book 19 Supplement.indb 72 5/16/2013 2:27:44 PM املجلة الصحية لرشق املتوسط املجلد التاسع عرش العدد اإلضايف 1

Table 1 Priority research area and recommended actions to improve global understanding and knowledge on novel coronavirus infection Priority research area Recommended actions Next steps, with support from WHO Defining the spectrum of • Develop a standardized and sensitive approach • Create a study group and framework disease severity (extent of for seroepidemiological studies to identify for designing appropriate studies using virus transmission) severely and mildly ill persons, including those standardized epidemiological methods. who may have been exposed to the virus but • Identify and prioritize groups for testing. remained well. The studies should focus on: • Develop protocols for standardized • patients with SARI; serological methods. • close contacts of cases who become • Encourage sharing of clinical samples symptomatic; between countries and laboratories. • clusters of SARI occurring in occupational • Initiate serosurveys of contacts and groups, particularly health care workers; probable cases to elucidate the full • Standardize and validate laboratory methods clinical spectrum of the disease, mindful for serological assays (IFA or ELISA) to be used of cross reaction. issues in serological for screening for more specific and conclusive studies. results. • Initiate laboratory training programmes for using standard methods. Detecting any increase or • Establish hospital baselines for pneumonia and • Develop standard surveillance tools decrease in incidence of monitor any unexplained rise in trend. for monitoring changes in rates of infection • Enhance surveillance within groups such as pneumonic illness or detection of illness case contacts, health care workers and clusters in selected population groups. of patients with severe respiratory illness. • Develop a standard protocol for guidance • Prospectively collect and test sputum on types of specimens to collect from specimens from SARI patients and their close selected population groups. contacts. • Ensure countries test single cases of unexplained severe respiratory illness and report positives to WHO.

Improving the case • Collect more data on the clinical spectrum • Contact affected countries to request data definition and natural history of nCoV to inform changes to better define key clinical features of to the case definition (implementing a 2-stage known cases. case definition of initial screening followed by • Obtain clinical information on known closer examination of cases that meet specific cases: pool all information from affected criteria can be considered). countries using a standardized extraction • Utilize protocols from the SARS epidemic to form. develop risk factor studies. • Develop a global case definition for reporting. • Continue to monitor the effectiveness of the case definition and revise when relevant. Identifying the source of • Conduct animal studies to inform sources; • Include animal studies in the framework. infection (protocols from the studies carried out for the SARS epidemic could be utilized for developing risk factor studies into nCoV infection).

ELISA = enzyme-linked immunosorbent assay; IFA = immunofluorescence assay; nCoV = novel coronavirus; SARI = severe acute respiratory infection; SARS = severe acute respiratory syndrome; WHO = World Health Organization.

S73

Book 19 Supplement.indb 73 5/16/2013 2:27:45 PM EMHJ • Vol. 19 Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

References

1. Zaki AM et al. Isolation of a novel coronavirus from a man with 7. Perlman S, Zhao J. Human coronavirus EMC is not the same as pneumonia in Saudi Arabia. New England Journal of Medicine, severe acute respiratory syndrome coronavirus. mBio, 2013, 2012, 367:1814–1820. 4(1). 2. Pebody RG et al. The United Kingdom public health response 8. Van Boheemen S et al. Genomic characterization of a newly to an imported laboratory confirmed case of a novel coro- discovered coronavirus associated with acute respiratory dis- navirus in September 2012. Eurosurveillance, 2012, 17(40):pii tress syndrome in humans. mBio, 2012, 3(6). 20292. 9. Anthony SJ et al. Coronaviruses in bats from Mexico. Journal of 3. Albarrak AM et al. Recovery from severe novel coronavirus General Virology, 2013, 94:1028–1038. infection. Saudi Medical Journal, 2012, 33:1265–1269. 10. Müller M et al. Human coronavirus EMC does not require the SARS-Coronavirus receptor and maintains broad replicative 4. Novel coronavirus infection-update (30 November 2012). capability in mammalian cell lines. mBio, 2012 3(6). Geneva, Switzerland, World Health Organization, Global alert and response (GAR), 2013 (http://www.who.int/csr/ 11. Laboratory testing for novel coronavirus. Interim recommenda- don/2012_11_30/en/index.html, accessed May 10 2013). tions. Geneva, World Health Organization, 2012 (http:// www.who.int/csr/disease/coronavirus_infections/Laborat 5. Malik M et al. Emergence of novel human coronavirus: public oryTestingNovelCoronavirus_21Dec12.pdf, accessed 10 May health implications in the Eastern Mediterranean Region. East- 2013). ern Mediterranean Health Journal, 2012, 18:1084–1085. 12. International health regulations (2005), 2nd ed. Geneva, World 6. Corman VM et al. Detection of a novel human coronavirus Health Organizati0n, 2008 (http://whqlibdoc.who.int/pub- by real-time reverse-transcription polymerase chain reaction. lications/2008/9789241580410_eng.pdf, accessed 10 May Eurosurveillance, 2012, 17(39):pii 20285. 2013).

S74

Book 19 Supplement.indb 74 5/16/2013 2:27:45 PM Members of the WHO Regional Committee for the Eastern Mediterranean املجلة الصحية لرشق املتوسط Afghanistan . Bahrain . Djibouti . Egypt . Islamic Republic of Iran . Iraq . Jordan . Kuwait . Lebanon هى املجلة الرسمية التى تصدر عن املكتب اإلقليمى لرشق املتوسط بمنظمة الصحة العاملية. وهى منرب لتقديم Libya . Morocco . Oman . Pakistan . Palestine . Qatar . Saudi Arabia . Somalia . South Sudan السياسات واملبادرات اجلديدة ىف اخلدمات الصحية والرتويج هلا، ولتبادل اآلراء واملفاهيم واملعطيات الوبائية Sudan . Syrian Arab Republic . Tunisia . United Arab Emirates . Yemen ونتائج األبحاث وغري ذلك من املعلومات، وخاصة ما يتعلق منها بإقليم رشق املتوسط. وهى موجهة إىل كل أعضاء املهن الصحية، والكليات الطبية وسائر املعاهد التعليمية، وكذا املنظامت غري احلكومية املعنية، واملراكز املتعاونة مع منظمة الصحة العاملية واألفراد املهتمني بالصحة ىف اإلقليم وخارجه.

Cover 19 Supplement.indd 2 5/16/2013 1:30:58 PM Contents

Editorial

Novel coronavirus infection: time to stay ahead of the curve...... S3 Perspective

Emergence of novel coronavirus: global context...... S5 Country experiences

Highlights and conclusions from the technical consultative meeting on novel coronavirus infection, Cairo, Egypt, 14–16 January 2013...... S68

املجلد التاسع عرش Volume 19 العدد اإلضايف Supplement 1 / Supplément 1 2013 1

Cover 19 Supplement.indd 1 5/16/2013 1:30:57 PM