【病毒外文文献】2015 CDC_s Early Response to a Novel Viral Disease, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), September 2

Special Report Public Health Reports July August 2015 Volume 130 307 CDC s Early Response to a Novel Viral Disease Middle East Respiratory Syndrome Coronavirus MERS CoV September 2012 May 2014 Holly Ann Williams PhD MN RN a Richard L Dunville MPH b Susan I Gerber MD c Dean D Erdman DrPH c Nicki Pesik MD d David Kuhar MD e Karen A Mason MPA c Lia Haynes PhD c Lisa Rotz MD FIDSA d Jeanette St Pierre MPH MA c Sarah Poser BS c Sudhir Bunga MD a Mark A Pallansch PhD c David L Swerdlow MD f On behalf of the MERS CoV Working Group a Centers for Disease Control and Prevention Division of Global Health Protection Atlanta GA b Centers for Disease Control and Prevention Division of Adolescent and School Health Atlanta GA c Centers for Disease Control and Prevention Division of Viral Diseases Atlanta GA d Centers for Disease Control and Prevention Division of Global Migration and Quarantine Atlanta GA e Centers for Disease Control and Prevention Division of Health Care Quality and Promotion Atlanta GA f Centers for Disease Control and Prevention Office of Science and Integrated Programs National Center for Immunization and Respiratory Diseases Atlanta GA Address correspondence to Holly Ann Williams PhD MN RN Centers for Disease Control and Prevention Emergency Response and Recovery Branch MS F 57 4770 Buford Hwy NE Atlanta GA 30341 tel 770 488 0693 fax 770 488 3266 e mail ABSTRACT The first ever case of Middle East Respiratory Syndrome Coronavirus MERS CoV was reported in September 2012 This report describes the approaches taken by CDC in collaboration with the World Health Organization WHO and other partners to respond to this novel virus and outlines the agency responses prior to the first case appearing in the United States in May 2014 During this time CDC s response integrated multiple disciplines and was divided into three distinct phases before during and after the initial activation of its Emergency Operations Center CDC s response to MERS CoV required a large effort deploying at least 353 staff members who worked in the areas of surveillance laboratory capacity infection control guidance and travelers health This response built on CDC s experience with previous outbreaks of other pathogens and provided useful lessons for future emerging threats 308 Special Report Public Health Reports July August 2015 Volume 130 Within the past eight decades an average of five or six emerging infectious diseases have appeared annually worldwide 1 In an era of rapid global travel a novel pathogen can quickly disseminate and cause wide spread illness and death which can stress health care systems and devastate economies Almost any emerg ing illness regardless of its origin has the potential to become a public health emergency On September 20 2012 one such illness was reported in the online Program for Monitoring Emerging Diseases ProMED The report noted that a novel human coronavirus had been isolated from a patient in Saudi Arabia Three days later Public Health England sent a notification through the Early Warning and Response System for Communicable Diseases 2 about the presence of a novel coronavirus in a patient from Qatar in the United Kingdom with severe respiratory illness Under the International Health Regulations IHRs 3 the British agency alerted the World Health Organization WHO to the issue With these notices countries began to quickly initiate surveillance to detect additional cases of this new disease describe its features and monitor the evolution of the illness Working with WHO and using lessons learned from previous global outbreaks 1 4 5 the U S Centers for Dis ease Control and Prevention CDC quickly launched a response to this novel virus later referred to as the Middle East Respiratory Syndrome Coronavirus MERS CoV The emphasis of the response was on preven tion case identification and mitigation as there were and still are no vaccines available and no antivirals recommended for MERS CoV This article describes how CDC used a multidisciplinary approach to prepare for possible cases of MERS CoV in the United States and to assist both domestic and international partners It details the array of public health activities under taken in the various stages of the response describes the domestic and global collaboration that has been needed to strengthen the response highlights success ful strategies and identifies additional lessons learned This article is not offered as a critique of CDC s performance during the MERS CoV response rather it is intended to provide a glimpse of the many kinds of activities that comprised the early response explain how the activities were coordinated internally at CDC and comment on what worked well Insights from this response are already being used to help strengthen planning for threats from future emerging diseases Although cases of MERS CoV are continuing to occur in the world as of May 2015 this article focuses on the period of time after the initial recognition of the disease and before the first case of MERS CoV was reported in the United States on May 2 2014 BACKGROUND When MERS CoV began to emerge public health authorities recognized that lessons learned from previ ous global outbreaks e g the Severe Acute Respiratory Syndrome SARS pandemic in 2002 2003 and the 2009 pandemic of influenza A H1N1 virus in 2009 could prove highly useful An Institute of Medicine report 4 had critically examined the response to SARS and noted the importance of early detection through global disease surveillance effective communication promotion of research and development strategies for containment and multinational collaboration in implementing response strategies 5 10 The multi pronged strategies mentioned in these reports included adequate and timely production of vaccines and antivirals equitable access to antivirals and vaccines community mitigation strategies case management strategies including case ascertainment and strong diagnostics health resource management health care system readiness including educating health care work ers about the threat health education for the public rumor control improved integration of health care and public health consideration of a one health approach that focuses on the interaction among animal and human health within an environmental context and effective and timely communication with the public including specific information for patients and significant others health care workers news media policy makers and within the response teams The literature emphasized that global communication and technical collaboration among countries is essential for response networks such as the Global Outbreak Alert and Response Network 11 to function efficiently Lastly adequate resources both financial and technical are needed to ensure a robust response To bolster global public health efforts to address potential public health emergencies the IHRs revised in 2005 and enacted in 2007 now say that all member states have obligations for surveillance response and collaboration when facing a global disease threat 12 However developing countries face large challenges in meeting the requirements of the IHRs due to insufficient capacity for planning and preparedness inadequate health infrastructure and a paucity of technical expertise 13 In these circumstances the need for collaborative support and resources from other countries becomes critical 6 13 Consideration of these lessons learned and a strong history of outbreak response laid the framework for CDC s preparations for MERS CoV and preceded recognition of the first case in the United States CDC Preparedness Activities for MERS CoV 309 Public Health Reports July August 2015 Volume 130 CDC EARLY RESPONSE TO A NOVEL DISEASE A new disease emerges In June 2012 Erasmus Medical Center in the Nether lands sequenced a previously unknown human corona virus from a patient from the Kingdom of Saudi Arabia KSA This first case of MERS CoV was reported in September 2012 Later and retrospectively CDC and the global community learned of a hospital associated outbreak of respiratory illnesses that had occurred in Jordan in April 2012 at that time no cause of the ill nesses was identified and testing for other respiratory pathogens was negative In September 2012 however available specimens from two individuals tested posi tive for MERS CoV Following the report in ProMED in September 2012 CDC acting with its domestic and global partners including WHO initiated response activities WHO published an interim case definition on September 25 2012 CDC published the first Morbidity and Mortality Weekly Report on MERS CoV on October 12 2012 14 On September 27 2012 methods for the first diagnostic molecular assays for MERS CoV were published and assay reagents were made available by the Institute of Virology University of Bonn Medical Center 15 In November 2012 the complete genome sequence was published by a multinational group of scientists 16 WHO convened two meetings of the IHR Emergency Health Committee on July 9 and July 17 2013 to assess the situation 17 The committee determined that the situation was serious and of great concern but the conditions for a public health emergency of interna tional concern 18 had not been met During the second of the July meetings and in subsequent meetings on September 25 2013 December 4 2013 and May 13 2014 members of the committee stressed the need for investigations including international case control serological environmental and animal human inter face studies to better understand the epidemiology and risk factors 19 The first U S case of MERS CoV was reported on May 2 2014 By that time a total of 261 WHO confirmed cases with 93 deaths worldwide had been reported At that time an additional 190 cases includ ing 41 deaths were pending WHO s confirmation Reported illness onset for confirmed cases occurred from April 2012 to April 2014 Figure 1 Most of the confirmed cases resided in KSA 183 cases 70 1 and a Cases to be confirmed are reported by the Ministry of Health and are pending World Health Organization confirmation Data shown are as of May 1 2014 Figure 1 Middle East Respiratory Syndrome Coronavirus MERS CoV reported cases by outcome and month of onset April 2012 April 2014 451 total cases a Fatal cases n5134 Nonfatal cases n5317 310 Special Report Public Health Reports July August 2015 Volume 130 were male 178 cases 68 2 with a median age of 50 years range 2 94 years All of the confirmed cases to that point either resided in or had recently traveled to the Arabian Peninsula or had been in contact with an ill traveler from that area Importations of the disease had been reported in the United Kingdom France Tunisia Italy and Malaysia Among the fatalities as of May 2 2014 information was not available for five cases Among the remaining 88 fatal cases 70 84 3 were male with a median age of 59 years Notably 73 83 0 of these fatal cases had a comorbidity e g chronic renal or cardiac disease Reminiscent of SARS health care workers represented 59 23 cases Twenty four distinct spatiotemporal clusters had been reported CDC Unpublished surveillance data 2014 Early response phases and framework CDC began its response to the emergence of MERS CoV in September 2012 substantially before the first U S case was identified CDC s early response can be divided into three phases best illustrated in relationship to the activation of CDC s Emergency Operations Center EOC pre EOC activation during EOC activation and post EOC activation Each phase was characterized by its own organizational structure access to staff support and scaling of operations up or down Throughout the three phases CDC collaborated widely with domestic and global partners and mounted an agency response that involved experts from across CDC s various centers As of May 1 2014 at least 353 CDC staff members had been involved in some aspect of this response Established in 2003 the EOC serves as CDC s com mand center for public health threats in the United States and globally Staffed 24 hours per day it coor dinates response activities provides resources to state and local public health departments and supports the Secretary s Operations Center of the U S Department of Health and Human Services Phase 1 pre EOC activation September 2012 June 2 2013 After the electronic ProMED report CDC staff members gathered additional data through profes sional contacts media reports and international health authorities CDC s National Center for Immunization and Respiratory Diseases NCIRD Division of Viral Diseases was the primary point of contact for all MERS CoV related activities and worked in collabora tion with CDC s Center for Global Health CGH primarily the Global Disease Detection Operations Center of the Division of Global Health Protection and the National Center for Emerging and Zoonotic Infectious Diseases particularly the Division of Global Migration and Quarantine and the Division of Health care Quality Promotion Subject matter experts from many areas were recruited virology global migration and travelers health epidemiology laboratory science law event based surveillance occupational health medical care countermeasures health care systems response health care worker safety statistics and math ematical modeling policy analysis and health and risk communication The agency focused on a variety of activities simul taneously To maintain situational awareness and to ensure communication across all aspects of the response the agency held twice weekly senior lead ership and daily briefings with staff members from NCIRD s Division of Viral Diseases Other activities included creating essential documents e g internal daily and monthly reports fashioning key points of communication and posting Web based travel notice updates e g electronic messaging on airport moni tors CDC also collaborated with WHO to develop and maintain a line listing of all reported cases Legal agreements were written and signed to share biological samples a critically important activity to validate assays and characterize the virus genome By the end of Febru ary 2013 CDC had signed a cooperative research and development agreement with Public Health England and received serum samples and a viral isolate from a MERS CoV patient in the United Kingdom CDC also had collaborated in global field investigations related to MERS CoV in Jordan and KSA Phase 2 EOC activation June 3 August 13 2013 To meet increasing demands for information and strengthen preparedness as the potential threat of MERS CoV grew and the number of cases rose CDC leaders activated the agency s EOC on June 3 2013 at a level III In a level III activation response activities are conducted Monday Friday during regular working hours with the expectation that only the Incident Man ager and other members of the command staff and or experts will work extended hours and on weekends Level III activation implies that with minimal aug mentation the designated lead national center can address the primary needs of the response with the EOC staff supporting Incident Management System IMS services 20 The decision to activate the EOC was based on the increased work demands on the response team i e number of briefings and level of reporting required and the need to augment staffing As for all such responses CDC used an IMS structure 21 Once the EOC was activated key management activi ties were completed quickly with the help of the EOC staff An Incident Action Plan IAP was developed that detailed planning assumptions as well as agency CDC Preparedness Activities for MERS CoV 311 Public Health Reports July August 2015 Volume 130 strategic and operational objectives including param eters for deactivation Staff members developed a daily routine that was meant to assist team coordination and communication across all areas of the response Tasks and reporting became organized and systematized under the IAP and the daily staff rhythm An organiza tional chart of the response was developed and updated as needed An abbreviated version of the organizational chart illustrating the leadership sections and teams is shown in Figure 2 During this phase CDC staff members implemented a response framework based on the principles of IMS Table 1 The framework was divided into three main components Incident Command Scientific Response Section and Emergency Operations Incident Com mand oversaw all response activities and was staffed by senior level scientists The same person held the position of Incident Manager throughout the early response allowing for continuity of operations The position of Deputy Incident Manager rotated among several senior scientists The Command structure also had an Operations Coordinator a liaison position that directly interfaced with CGH on global issues a Chief Science Officer an Associate Director for Sci ence and policy and communications teams CDC experts on safety security ethics and law assisted the response team The Scientific Response Section provides a good example of the teamwork required in this response This section was divided into topic specific teams led by disease control experts who had become familiar with MERS CoV when it first emerged Teams included Epi demiology and Surveillance Laboratory International Response Global Migration and Quarantine Medical Countermeasures Health care Systems Response Health care and Worker Safety Modeling and State Coordination Some of these areas were extensively staffed and contained subgroups The teams comprised mostly staff members who already knew each other and had worked together in other job assignments which reduced the time needed for training and team building When needed CDC staff members from other national centers were recruited for temporary duty Overall activating the EOC strengthened the early response to MERS CoV in that it allowed staff members to focus more directly on response activi ties while relying for support on the 22 Division of the Emergency Operations staff members who are permanently assigned to all response activities During this phase staff members interacted fre quently with global and domestic partners Table 2 Activities focused on building laboratory capacity domestically and globally to detect MERS CoV testing specimens as they arrived from states or global partners developing protocols for epidemiologic investigations working with WHO to revise testing and surveillance recommendations redesigning and updating the MERS CoV Web pages preparing clinicians customs and border protection agents as well as laboratorians for the potential importation of cases into the United States strengthening potential border health measures assessing air routes and traveler volumes into and out of the Arabian Peninsula to evaluate areas at potentially higher risk for MERS CoV translocation and educating the general public and international travelers about disease risks Border health measures did not include screening travelers at quarantine stations CDC signed material transfer agreements with global partners i e Hong Kong University for the HKU5 N plasmid Eras mus University for virus and Koch Institute for serum which made it easier to share specimens By August 13 2013 94 laboratory confirmed cases and 47 deaths had been reported globally However the United States remained free of cases and the course of the epidemic indicated that spread of the virus did not appear to have pandemic potential By early August 2013 the scope and scale of the response was reduced In addition the planning objectives for the response had been met multiple Web based resources were available for the general public international travelers and public health health care practitioners that covered both prevention and management of imported cases The triggers in the IAP for reducing the level of response had been met and CDC began to reduce its scope and scale CDC command staff and agency leadership deactivated the EOC for th