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Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary (2004)

Chapter: 1. SARS: Emergence, Detection, and Response

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Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
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1
SARS: Emergence, Detection, and Response

OVERVIEW

The story of the emergence, spread, and control of severe acute respiratory syndrome (SARS) is the latest, most vivid episode of a microbial threat in our highly connected world. The SARS epidemic of 2002–2003 not only demonstrated the ease with which a local outbreak can rapidly transform into a worldwide epidemic, but also how news of such a threat can travel faster than a microbe. Notably, the experience demonstrated how effectively the global public health community can collaborate to contain a novel microbial threat.

SARS emerged in November 2002 in the southern Chinese province of Guangdong and has been linked with the handling and preparing of exotic mammals for human consumption. The virus ultimately spread to 30 countries and administrative regions within 6 months. Key points in the chronology of the epidemic are included in the Summary and Assessment.

This chapter begins with a description of the World Health Organization’s (WHO) coordination of a massive and multinational public health response to SARS. While the authors emphasize that the actions of individual nations ultimately contained the epidemic, they describe the many ways that WHO supported governments through its Global Outbreak Alert and Response Network (GOARN) and its country offices. These efforts served to highlight the important brokering role that can be played by the WHO in catalyzing and galvanizing the capacity of its member states in response to global public health challenges. This is followed by a discussion of the contributions made by the U.S. Centers for Disease Control and Prevention (CDC) in responding to and helping contain the SARS outbreak in the U.S. and overseas. In both of these papers, the authors describe not just the actions taken by the WHO and the CDC during the recent

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

epidemic but also the lessons that were learned and the preparations being made to handle any future challenges that may arise from SARS or other emerging diseases.

The chapter continues with a broad overview of what is known and hypothesized about the emergence of SCoV, the natural history of the epidemic, the evolution of the virus, and the clinical profile of SARS. The authors suggest studies to answer some of the many remaining questions about this new disease.

Given the likelihood of an animal reservoir for the virus in China that could reinfect the human population, continued vigilance for SARS is warranted. This chapter explores the value of modern quarantine in curtailing the spread of infectious disease in general and SARS in particular. Risks for the reintroduction of SARS include the possibility of initial low-level transmission that eludes surveillance and a laboratory-acquired infection, as occurred in Singapore in September 2003 and in Taiwan in December 2003.

During the epidemic, hospitals in Hong Kong, Singapore, Vietnam, and Canada struggled to contain SARS within their walls. For example, in the first phase of the Toronto epidemic, which began on February 23, unrecognized SARS patients infected scores of other patients, family members, and hospital workers. Even after increased infection control measures were undertaken, this scenario was replayed in several area hospitals, as well as others around the globe. A sobering analysis of mistakes made in the communication and practice of hospital and community hygiene during the epidemic concludes the chapter.

THE WHO RESPONSE TO SARS AND PREPARATIONS FOR THE FUTURE

J.S. Mackenzie, P. Drury, A. Ellis,1T. Grein, K.C. Leitmeyer, S. Mardel, A. Merianos, B. Olowokure, C. Roth, R. Slattery, G. Thomson, D. Werker, and M. Ryan

Global Alert and Response, Department of Communicable Disease Surveillance and Response

Severe acute respiratory syndrome (SARS) is the first severe and readily transmissible new disease to emerge in the 21st century. Initially recognized as a global threat in mid-March 2003, SARS was successfully contained in less than 4 months, largely because of an unprecedented level of international collaboration and cooperation. The international response to SARS was coordinated by the World Health Organization (WHO) with the assistance of the Global Outbreak

1  

Strategy for Development and Monitoring Zoonoses, Foodborne Diseases and Kinetoplastidae, Department of Communicable Diseases Control, Prevention and Eradication, World Health Organization, Geneva, Switzerland.

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

Alert and Response Network (GOARN) and its constituent partners made up of 115 national health services, academic institutions, technical institutions, and individuals. The SARS outbreak has also shown how, in a closely interconnected and interdependent world, a new and poorly understood infectious disease can have an adverse affect not only on public health, but also on economic growth, trade, tourism, business and industrial performance, and political and social stability.

The chronology of the outbreak has been published on the WHO website (WHO, 2003a). The first recorded case occurred in mid-November in the city of Foshan, Guangdong Province, China. The Chinese Ministry of Health officially reported to WHO in mid-February that there had been 300 cases and 5 deaths in an outbreak of “acute respiratory syndrome” in which symptoms were clinically consistent with atypical pneumonia, and that the outbreak was coming under control. To complicate the issue, however, there were also cases of avian influenza, influenza A (H5N1), with three deaths among members of a Hong Kong family who had traveled to Fujian Province. WHO activated its global influenza laboratory network and called for heightened global surveillance on February 19, 2003; GOARN partners were alerted on February 20.

The SARS virus was carried out of southern China on February 21, when a 64-year-old medical doctor who had treated patients in Guangzhou and was himself suffering from respiratory symptoms checked into a room on the ninth floor of the Metropole Hotel in Hong Kong. Through mechanisms that are not yet fully understood, he transmitted the SARS virus to at least 16 other guests, all linked to the ninth floor. Those guests carried the disease to Toronto, Singapore, and Hanoi, or they entered hospitals in Hong Kong. The medical doctor fell severely ill the following day, was hospitalized immediately, and died on March 4. A global outbreak was thus seeded from a single person on a single day on a single floor of a Hong Kong hotel.

A businessman, infected in the Metropole Hotel, traveled to Hanoi, fell ill, and was hospitalized on February 26. He was attended by a WHO official, Dr. Carlo Urbani, following concerns raised by hospital staff. Alarmed at the unusual disease and concerned that it could be an avian influenza, Dr. Urbani contacted the WHO Western Pacific Regional Office (WPRO) on February 28.

On March 10, the Ministry of Health in China asked WHO to provide technical and laboratory support to clarify the cause of the Guangdong outbreak of atypical pneumonia. On March 12, WHO alerted the world to the appearance of a severe respiratory illness of undetermined cause that was rapidly spreading among hospital staff in Vietnam and Hong Kong. Three days later, on March 15, it became clear that the new disease was carried along major airline routes to reach new areas, and WHO issued a further global alert, giving the new disease its name: severe acute respiratory syndrome, or SARS.

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

The WHO Response

As the outbreak of SARS moved into the spotlight of intense global concern, an unprecedented multifaceted, multilateral, and multidisciplinary response was coordinated jointly by WHO Headquarters, Switzerland, and by WHO WPRO, the Philippines. The management of the global SARS response involved intense daily coordination in the areas of etiology and laboratory diagnosis, surveillance and epidemiology, clinical issues, animal sources, and field operations.

WHO Regional Offices, working through a worldwide network of Country Offices and intercountry networks, were the main channels for support to affected countries. While the six WHO Regional Offices were fully engaged in the global coordination of the SARS response, the Western Pacific Regional Office—covering the area where the vast majority of cases were occurring—bore the brunt of the response, deploying a total of 116 additional experts as short-term consultants during the outbreak. At WHO Headquarters, 75 people worked on the SARS outbreak response, with additional surge capacity provided by partners in the GOARN.

The GOARN is a global technical partnership, coordinated by WHO, to provide rapid multidisciplinary support for outbreak response to affected populations (WHO, 2000; 2001). The GOARN provided critical operational capacity for the initial response to SARS. Responding to requests for assistance from several countries, WHO and its GOARN partners mobilized field teams to support outbreak response in China, Hong Kong, Singapore, Taiwan, and Vietnam. Throughout the outbreak, WHO continued to work with GOARN partners to ensure ongoing support to health authorities, and GOARN teams continued in the field until the chains of transmission were conclusively broken.

Through GOARN, WHO coordinated development of a number of networks that proved pivotal in developing tools and standards for containment of the epidemic. The networks met regularly by teleconference, usually on a daily basis, to share information and data in real time. They were also assisted by dedicated, secure websites on which network participants were able to share preliminary information. The networks brought frontline workers and international experts together, and demonstrated the international collaboration and cooperation that was characteristic of the response to the SARS outbreak. A virtual network of clinicians was set up to exchange experiences, thoughts, and findings about SARS in an attempt to better understand and treat the disease effectively. The clinical network linked infection control issues closely with every aspect of case management, from clinical diagnosis and investigation to therapy. The discussions also allowed the rapid evaluation of the infection control risks of a number of interventions and helped to indicate potential alternative approaches.

A virtual network of epidemiologists brought together public health institutions, ministries of health, and WHO Country Offices to analyze the spread of SARS and to define appropriate public health measures. Activities of the epidemiology network have included the preparation of a consensus document on the

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

epidemiology of SARS (WHO, 2003b). The laboratory network was established to assist with identifying the etiologic agent of SARS and to develop specific and robust laboratory diagnostic tests for the agent responsible. The network comprised members of the international influenza laboratory network in those countries in which cases of SARS had been reported. Thus a total of 11 expert laboratories in nine countries were included in the network. The success of the laboratory network was quickly demonstrated by the discovery and characterization of the etiological agent, the SARS coronavirus (SCoV), and the rapid development of the first generation of diagnostic tests.

WHO Country Offices: A Critical In-Country Presence

WHO Country Offices work as direct partners with Member States on all issues related to health, including those related to health and poverty, health and macroeconomic reforms, and the Millennium Development Goals. SARS dramatically illustrated the effects of a new disease on the broader health and development agenda.

Traditionally, the Ministry of Health is the primary working partner at the national level; however, in many countries WHO is encouraging a more inclusive definition of the nature of the health sector, leading to greater collaboration with other government institutions, United Nations agencies, nongovernmental organizations (NGOs), and the international donor community—this was particularly important in the SARS outbreak response.

During the SARS outbreak, WHO was widely recognized as a key organization to assist health authorities with national policy formulation and multisectoral coordination of preparedness activities and the SARS outbreak response. WHO provided objective and neutral policy and technical advice to strengthen the capacity of national health administrations to better manage preparedness activities and the SARS outbreak response and to build local capacity. WHO Country Offices—particularly in China and Vietnam—provided extensive technical input on policy development, guidelines and strategies, dissemination of information on key issues, and technical advice for preparedness and response activities. The WHO Country Offices in Beijing and Hanoi, supported considerably by experts from partners in GOARN and WPRO, worked with national authorities to address rapidly developing needs: strengthening disease surveillance and reporting systems; improving the classification and reporting of cases; and advising on field epidemiology, contact tracing, infection control in health care settings, rumor management, and risk communications.

Ultimately, controlling the course of SARS in China and elsewhere was the result of concerted multisectoral preparedness and outbreak response activities by national authorities. WHO’s activities and advice played an important role in catalyzing and coordinating this reponse. These activities are increasingly the routine work of a WHO Country Office anywhere in the world; however, the

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

scale of the SARS outbreak and the attendant political and media interest ensured that the scale of operations was enormous.

In addition to providing direct support through WHO to affected areas, many GOARN partners were also involved in other SARS activities, including providing bilateral assistance to affected areas and supporting other countries in the Western Pacific and Southeast Asia regions. The International Federation of Red Cross and Red Crescent Societies helped to ensure that marginalized sections of society were reached by social mobilization activities. International NGOs and United Nations organizations were also involved in addressing humanitarian aspects of the response and preparedness activities. National surveillance and response institutions provided experts for field teams and, participating in the virtual networks, were also working at their own national levels to enhance preparedness and reporting on SARS cases to WHO. Regional disease surveillance networks provided information on measures and activities to be undertaken to prevent and control outbreaks of SARS.

The initial call for global surveillance was followed by a more detailed description of the surveillance system, which had as its objectives describing the epidemiology of SARS and monitoring the magnitude and spread of the disease in order to provide advice on prevention and control. This description, including revised case definitions and reporting requirements to WHO, was distributed with tools for its implementation through the WHO network to national public health authorities. It was also published on April 4, 2003, in the Weekly Epidemiological Record (Anonymous, 2003). With some minor changes, this global surveillance system remained in place until July 11, 2003, a week after the last chain of human transmission was broken.

Global SARS surveillance was primarily based on the reporting mechanism established through the Daily Country Summary of Cases of SARS. This form requested national public health authorities to report to WHO Geneva (with a copy to the WHO country and regional office) the number of new cases and deaths since the previous report, the cumulative number of probable cases and their geographic distribution, and the areas where local chains of transmission had occurred. Case numbers and information on areas with local transmission were updated daily on the WHO website in accordance with the information received by the national public health authorities. Local transmission was defined as one or more reported probable case(s) of SARS having most likely acquired the infection locally, regardless of the setting in which this may have occurred. An area was removed from the list 20 days after the last reported locally acquired probable case died or was appropriately isolated.

By July 11, 2003, 29 countries had reported a total of 8,437 probable cases, including 813 deaths (crude case fatality ratio 8.6 percent) from November 1, 2002. Ninety-two percent (n = 7,754) of the reports were received from China (including Hong Kong, Macao, and Taiwan). In the final compilation of reports received from public health authorities, there were 18 areas in 6 countries that

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

experienced local transmission of SARS, with the first reported chain transmission starting on November 16, 2002, in Guangdong Province, China (WHO, 2003c).

The Origin of the Etiological Agent

As the SARS outbreak spread, and before the etiological agent was identified, questions were being raised as to where this new infection had originated. Early discussions between members of the first WHO Mission in China and colleagues from the Chinese Centers for Disease Control (CDC and Guangdong CDC implicated food preparers possibly connected with preparation of animals for food as being a particular risk group. As a result, on April 10 WHO formed an internal working group to address the potential that SARS could be a zoonotic disease. With the collaboration of the Food and Agriculture Organization (FAO) and the Office of International des Epizooties (OIE), an international working group on the animal reservoir of SARS was established. Animal susceptibility studies were carried out in various laboratories around the world. Subsequently, findings from Guan et al. (2003) from the University of Hong Kong indicated that masked palm civets and raccoon dogs sampled in a Shenzen market carried a virus very similar to SCoV.

In mid-July, WHO received permission to organize a mission to China to review animal studies conducted by Chinese scientists and recommend further research on the role of animals in the transmission of SCoV. The mission was carried out as a joint endeavor among the government of China, FAO, and WHO from August 10 to 22, 2003. A comprehensive report of the mission and recommendations were provided to the government of China for review. Important collaborations were established between members of the mission and Chinese scientists. Collaborative projects are ongoing and focus on developing a screening test for animals, animal susceptibility studies, and further testing of animals from markets. As part of enhanced SARS surveillance in China, wild animal handlers are considered a high-risk group. Protocols have been developed to prompt an appropriate epidemiological investigation should this group begin presenting at hospitals with symptoms of SARS.

Preparations for the Future

Reemergence

Will SARS return? This is difficult to answer without recourse to a crystal ball. If SARS is to return, it has to reemerge from one of three sources: (1) from undetected transmission cycles in areas with little or no health care facilities; (2) from an animal source; or (3) from a laboratory accident. With respect to the first possible source, it is difficult to believe that there have been continued, undetected transmission cycles. However, as SCoV is believed to have spread into the

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

human population from a wild animal source, this has to remain a possibility, but whether it will occur this year or sometime in the future remains unknown. Preliminary results would indicate that SCoV, or a related virus, occurs in a number of wildlife species. However, the ability of the virus to cross the species barrier to cause disease in humans, and then to become adapted to transmit between humans, may be a relatively rare event. Of greater immediate concern is the threat posed by stocks of SCoV and clinical specimens potentially containing SCoV, which are kept in many laboratories globally, as well as the paucity of safer biosafety level 3 (BSL3) facilities in many parts of south and eastern Asia.

Surveillance and Laboratory Safety

WHO has been very active in preparing for the possible return of SARS. Of particular importance has been the preparation of an epidemiological and surveillance document, Alert, Verification and Public Health Management of SARS in the Post-Outbreak Period, which was posted on the WHO website on August 14 (WHO, 2003d); a workshop concerned with laboratory preparedness and planning to ensure rapid, sensitive, and specific early diagnosis of SCoV infections, and aspects of biosafety in the laboratory (WHO, 2003e); clinical trial preparedness; a meeting to determine SARS research priorities; training courses on SARS diagnosis and epidemiology; a meeting to discuss the development of SCoV vaccines (WHO, 2003f); and a series of capacity-building developments and assistance to countries within the Western Pacific Region as well as a continuing dialogue with and assistance to China.

Health authorities in nodal areas, where cases had occurred previously, and in areas of potential re-emergence (WHO, 2003d) have maintained heightened SARS surveillance established during the outbreak period, and continue doing so for the foreseeable future. WHO will also continue to identify and verify rumors about SARS through its usual, well-established mechanisms.

Laboratory preparedness has been a major concern as the northern hemisphere has approached the winter season with the prospects of increased influenza activity and other respiratory diseases, potentially leading to a significant increase in requests for diagnostic tests for SCoV. This could lead to an unsustainable surge in the work of clinical diagnostic laboratories, and the strong possibility of false-positive test results. Thus a number of recommendations were made at a SARS laboratory workshop held in Geneva in October 2003, all of which have been introduced or are in the process of being introduced (WHO, 2003e). The major outcomes have been the establishment of an International SARS Reference and Verification Laboratory Network to provide a diagnostic service to those countries and areas that do not have the necessary diagnostic facilities and to verify any laboratory-diagnosed case of SCoV infection reported in the interepidemic period; the development of a panel of positive control sera; and the formulation of strong recommendations about laboratory safety. Indeed, biosafety

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

has become a major issue since the occurrence of the laboratory-acquired cases in Singapore and Taiwan (WHO, 2003f), and a major biosafety document is nearing completion with respect to the containment level and conditions under which work is undertaken with live SCoV. This document will support and extend the earlier document posted on the WHO website (WHO, 2003g). Finally, the workshop attendees considered the algorithms under which laboratory diagnosis should be undertaken, and these have been incorporated into the algorithms developed in the epidemiological document Alert, Verification and Public Health Management of SARS in the Post-Outbreak Period.

Diagnostics and Therapeutic Countermeasures

Insufficient evidence is available to evaluate the effectiveness of specific treatment measures, including antivirals, steroids, traditional Chinese medicine, and the appropriate type of mechanical ventilation. Therefore, generic protocols urgently need to be developed for SARS and other future disease outbreaks. The WHO SARS Clinical team hosted a workshop to plan future clinical trials for SARS with the following objectives: (1) to review treatment experiences in different countries during the last outbreak; (2) to share existing plans for future clinical trials and identify candidate therapies; (3) to agree on basic trial design, including a hierarchy of outcome parameters and agreed standards of care; and (4) to assist in preparedness for clinical trials at relatively short notice.

A SARS Research Advisory Committee was established to determine the major gaps in our knowledge of the origin, ecology, epidemiology, clinical diagnosis and treatment, and social and economic impacts of SARS, and to discuss research needs required to fill these gaps for effective public health management of SARS, including preparedness and response to future outbreaks. The committee was asked to prioritize the research issues with the aim that the prioritized list of issues could be widely circulated to international and national funding bodies as a consensus blueprint of international research objectives aimed at achieving a better understanding of the virus, its origins, and pathogenesis, so that public health management could be improved if SCoV returns. A report on the meeting is available on the WHO website (WHO, 2003h), and the full recommendations will be placed on the website in early 2004.

Training courses on laboratory diagnosis of SCoV were held in the fall in collaboration with WHO Regional Offices in Europe and Africa, and a further “train-the-trainer” course is being planned in association with the WHO Regional Office for the Americas (AMRO/PAHO) in 2004.

WHO has also held a meeting to discuss possible SCoV vaccines, and a number of recommendations were made to facilitate and accelerate SARS vaccine development and evaluation (WHO, 2003i).

In the Western Pacific Region, a number of activities have been started that are aimed at improving preparedness for the possible reemergence of SCoV, in-

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

cluding updating existing guidelines for surveillance and response activities in the interoutbreak period, updating an assessment protocol for national preparedness, and developing a WPRO SARS risk assessment and preparedness framework (WHO Western Pacific Regional Office, 2003). Other priorities have been to strengthen infection control and establish a regional laboratory network. The objectives of the latter are to ensure proper laboratory diagnosis by providing coordination, technical support, and communication among country and regional reference laboratories.

Concluding Comments

WHO’s vision for global health security is a world on alert and ready to respond rapidly—both locally and globally—to epidemic-prone and emerging disease threats, whether they are natural or intentional in origin, minimizing their impact on the health and economy of the world’s populations.

Defense against the threat posed by epidemics such as SARS requires a collaborative, multifaceted response. National and international public health systems represent a major pillar of action for rapid and effective containment.

Through unprecedented collaboration the world community has demonstrated that it is possible to contain a serious infectious threat to the world population. Pivotal to addressing future threats is the need for a global coordinating mechanism that allows the worldwide community to be alerted and to respond to health events of international concern as rapidly, appropriately, and effectively as possible. The World Health Assembly recognized the role played by WHO, its staff, and GOARN partners during the 56th Assembly in passing a resolution, WHA56.29, in which it strongly supported the GOARN partnership and WHO’s global role in surveillance and response to infectious disease threats.

Harnessing the undoubted global capacities for detection, characterization, and containment of epidemic threats will require sustained strategic investment in initiatives like GOARN. However, at the end of the day these threats can only truly be faced with the courage and personal sacrifice as made by the thousands of individuals who came together to put a genie back in the bottle.

THE CENTERS FOR DISEASE CONTROL AND PREVENTION’S ROLE IN INTERNATIONAL COORDINATION AND COLLABORATION IN RESPONSE TO THE SARS OUTBREAK

James W. LeDuc and Anne Pflieger

National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia

The global outbreak of an acute respiratory illness that became known as severe acute respiratory syndrome (SARS) was the first major international out-

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

break of the 21st century and clearly had a dramatic, worldwide effect far exceeding the morbidity and mortality that directly resulted from infection with the novel coronavirus that causes SARS. In addition to the infection and hospitalization of several thousand individuals and the nearly 900 deaths that occurred in the countries with SARS cases, the entire global economy was affected by SARS, leading to serious losses of revenue, collapse of regional tourist and travel industries, and significant decreases in the gross national product among the nations affected (Lee and McKibbin, 2003). Despite several introductions of the virus from returning infected travelers, the United States was spared from the worst of SARS, given that there was no significant secondary spread, no large hospital-based outbreaks as seen in several countries, and no fatalities.

The fact that the United States had relatively few cases belies the enormous effort put forth by public health officials in responding to the outbreak. The Centers for Disease Control and Prevention (CDC) worked closely with state and local governments, the health care delivery industry, and other federal agencies to actively alert the traveling public about the risks of SARS, to prepare the health care delivery system to recognize and treat suspected SARS patients, and to assure the public that appropriate interventions to protect them from infection were being taken. These efforts were undertaken in close collaboration with international partners in the World Health Organization (WHO) and in the countries most affected by SARS. The collaborative international response can be considered in five parts: coordination of response, collaborations in science, communications at home and abroad, capacity building and response preparedness, and challenges and lessons learned.

Coordination of Response

More than 800 CDC staff members were organized into 13 domestic teams, with core members serving throughout most of the 7-month response period. Domestic teams each focused on one critical aspect of the response, including clinical care and infection control, epidemiology of the outbreak, diagnostics and laboratory studies, quarantine issues, information management, occupational health issues (included staff from the National Institute for Occupational Safety and Health), communications, environmental issues, and community outreach programs focused on the challenges of providing accurate information to special groups such as immigrants and the Asian community. In addition, two teams were organized to review and offer constructive criticism of the response as it unfolded and to plan for possible pandemic transmission of SARS, and two other teams engaged in international efforts to respond to the outbreak and conduct subsequent scientific studies. Each group worked closely with experts from throughout the CDC Centers and often included members from other federal agencies (e.g., Department of Defense, Department of State, and National Institutes of Health, Food and Drug Administration [FDA], and others from the Department

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

of Health and Human Services [DHHS]) or affected countries (specifically Canada). Many of the groups held frequent telephone conference calls with their constituents and academic experts to brainstorm and discuss next steps. For example, weekly telephone conference calls with virologists from several academic centers were held to coordinate laboratory studies, share results, and design collaborative studies, which often were undertaken by these same scientists at their own facilities.

CDC staff were deployed either directly to affected countries, as was the case with Taiwan, or as part of the WHO-coordinated Global Outbreak Alert and Response Network deployments. A total of 84 staff members were dispatched on 92 deployments to 11 countries affected by the SARS outbreak (CDC, unpublished) (see Tables 1-1 and 1-2). The largest group of personnel, 30 individuals, was sent to Taiwan, where a total of 696 person-days of assistance were provided. In all, staff were deployed for a total of 1,959 days, or 7.8 work-years, as determined on the basis of the standard U.S. federal work schedule. Deployed staff contributed diverse skills and expertise to these deployments (Table 1-2). Medical officers and epidemiologists were dispatched most often, with these personnel going to Taiwan (17), China (12), Vietnam (8), Singapore (2), the Philippines (3), Hong Kong (4), Canada (4), Switzerland and Thailand (2 shared), and Cambodia and Laos (1 shared). Other critical staff included pathologists and laboratory scientists, infection control officers, industrial hygienists, information management specialists, public health administrators, and communications experts. As the outbreak continued and staff rotations were required, it soon became apparent that CDC staff alone would be insufficient to meet a sustained demand for deployment of skilled personnel. As a result, the search to identify appropriate and available personnel was expanded to include public health professionals at state and local health departments, hospitals, other public health agencies, and academic centers.

TABLE 1-1 CDC’s 2003 International SARS Response by Center, Institute, Office (CIO)

CIO

Number (%) of Staff Deployed

Number (%) of Days Deployed

EPO

7 (8.3)

197 (10)

NCCDPHP

3 (3.6)

68 (3.5)

NCEH

1 (1.2)

29 (1.5)

NCHSTP

4 (4.8)

115 (5.9)

NCID

59 (70.2)

1,345 (68.7)

NIOSH

6 (7.1)

83 (4.2)

NIP

4 (4.8)

122 (6.2)

Total number

84

1,959

NOTE: EPO = Epidemiology Program Office; NCCDPHP = National Center for Chronic Disease Prevention and Health Promotion; NCEH = National Center for Environmental Health; NCID = National Center for Infectious Diseases; NIOSH = National Institute for Occupational Safety and Health; NIP = National Immunization Program.

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

TABLE 1-2 CDC International SARS Response: Staff Deployed by Country and Area of Technical Expertise

Country

Number (%) of Staff Deployed

No. (%) of Days Deployed

Med/Epi

Path/Lab

Inf Cont

Ind Hyg

Data/IT

PHA

Consult

Media

Taiwan

30 (32.6)

696 (35.5)

17

1

5

4

 

3

 

 

China

17 (18.5)

498 (25.4)

12

5

 

 

 

 

 

 

Vietnam

10 (10.9)

226 (11.5)

8

1

1

 

 

 

 

 

Singapore

5 (5.4)

137 (7)

2

2

 

 

1

 

 

 

Philippines

4 (4.3)

98 (5)

3

 

1

 

 

 

 

 

Hong Kong

6 (6.5)

88 (4.5)

4

 

1

 

1

 

 

 

Thailand

4 (4.3)

60 (3.1)

2

 

 

 

 

2

 

 

Canada/Ottawa

5 (5.4)

57 (2.9)

3

 

 

 

 

 

 

2

Canada/Toronto

4 (4.3)

46 (2.5)

1

 

 

3

 

 

 

 

Switzerland

4 (4.3)

33 (1.7)

 

 

 

 

 

 

2

 

Cambodia

1 (1.1)

15 (0.8)

 

 

 

 

 

 

 

 

Laos

2 (2.2)

5 (0.3)

1

 

 

 

 

1

 

 

Total:

By deployment

92

 

53

9

8

7

2

6

2

2

and by staff

84

1,959

52

8

7

7

2

4

2

2

NOTES: Areas of technical expertise: Consult = scientific consultant; Data/IT = data manager/analyst or information technology specialist; Ind Hyg = industrial hygienist or environmental engineer; Inf Cont = nurse or infection control specialist; Med/Epi = physician or epidemiologist; Media = communications or media relations specialist; Path/Lab = pathologist or laboratorian; PHA = public health advisor. The difference in the total number of personnel deployed (84) versus the total number of deployments (92) reflects the redeployment of 8 staff members, whose areas of expertise are shown by the differences in the totals for 4 public health specialties.

Fortunately, the outbreak peaked before serious personnel shortages were encountered; however, it is clear that CDC must both enhance retention of the uniquely skilled staff needed to assist with such outbreak responses and identify external partners who can be recruited when needed to help meet such challenges. The outbreak also highlighted the benefit of having well-established laboratory Infections Program, which was established in 2001 in partnership with the Thailand Ministry of Health, repeatedly proved its value as skilled staff were deployed rapidly to assist affected countries within the region and to work with Thai health officials responding to the importation of SARS cases. The CDC staff assisted Thai officials with caring for Dr. Carlo Urbani, the WHO physician who acquired SARS and died early in the course of the outbreak.

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

Collaborations in Science

Early in the course of the outbreak, WHO facilitated the exchange of laboratory information being generated in response to the SARS outbreak by establishing daily conference calls with representatives of the 11 leading laboratories participating in the response (WHO, 2003j). They also created a secure website where laboratory findings could be posted and shared with others, and they assisted with the acquisition and distribution of clinical material for laboratory testing (Stohr, 2003). These critical steps led to the rapid and virtually simultaneous recognition by several international laboratories of a new coronavirus (SCoV) as the likely cause of the outbreak (Ksiazek et al., 2003; Peiris et al., 2003a), and soon thereafter, the determination of the complete genomic sequence of the virus (Rota et al., 2003). The rapidity with which these results were obtained was truly historic and clearly emphasized the benefits of global data sharing and scientific collaboration. Despite widespread application of molecular techniques to determine the cause of the outbreak, it was the traditional virologic procedure of inoculation of acutely acquired patient specimens into cell cultures and laboratory animals that ultimately proved successful in isolating SCoV.

Communications at Home and Abroad

One of the most daunting challenges faced by public health officials in responding to the SARS outbreak was meeting the need for timely, accurate, and consistent information regarding the evolving outbreak and response activities. WHO did an exceptional job in providing information through nearly daily press briefings and updates on its website, by hosting global conference calls with international partners to discuss specific issues, and by effectively using a secure website to post sensitive information, such as results of ongoing laboratory investigations. Video conferences were arranged between the Director General of WHO, the Secretary of DHHS, and the Director of CDC to provide an opportunity for direct dialogue between agency leaders and their key staff. All of these activities served to calm a nervous world by rapidly providing accurate information on the evolution of the outbreak and interventions under way and on the evolving discovery of the cause of the outbreak and development of treatment and prevention strategies.

The communications burden faced by CDC was enormous and as intense as any previous public health emergency experienced by the agency. More than 10,000 news media calls were handled, 12 SARS news releases were issued, and 21 live telebriefings and news conferences were broadcast. Thirty specialized conference calls were made to the health care provider community, and nearly 35,000 public inquires were answered by telephone. A special clinical hotline was established for physicians inquiring about SARS, and more than 2,000 such calls were answered. Over 1.9 million global participants are estimated to have seen one or more of the three SARS satellite broadcasts directed to health care workers, and more than 17 million hits were recorded on the CDC SARS websites, with 3.8 million hits occurring during the week of April 20–26 alone (Personal

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

TABLE 1-3 CDC Shipments of Diagnostic Materials During the 2003 SARS Outbreak, by Recipient

Recipient

RNA

Virus

Antigen

Total, All Materials

Academic centers

32

13

1

46

Commercial companies

26

15

1

42

Government agencies

21

18

4

43

Total, all recipients

79

46

6

131

communications, Dan Rutz and Bill Pollard, CDC, September 26, 2003). Providing accurate, real-time information to meet these demands was one of the most challenging aspects of the entire outbreak response effort.

Capacity Building and Response Preparedness

With recognition that SCoV was responsible for the outbreak, laboratory efforts quickly turned to establishment of diagnostic tests to identify infected patients. Several laboratories rapidly developed prototype assays to measure SCoV—specific nucleic acid sequences, viral antigen in tissues, and the serologic response to infection. CDC distributed assays to measure both SCoV genomic material by polymerase chain reaction and specific immunoglobulin response by enzyme immunoassay; recipients of these assays included state health departments, members of the Laboratory Response Network established to respond to bioterrorism threats, and several countries following their requests for assistance. CDC also reisolated SCoV under formal Good Laboratory Practices conditions, using FDA-approved certified cells provided by Aventis Pasteur and clinical material obtained from an acutely ill American traveler who had returned recently from Hong Kong. This isolate was made available to vaccine manufacturers free of charge and has now been used in the development of candidate new vaccines by several companies (WHO, 2003i). In all, CDC provided purified RNA, virus, or antigen to more than 130 academic centers, commercial firms, and government agencies (Personal communication, Betty Robertson, CDC, September 26, 2003) (see Table 1-3).

Challenges and Lessons Learned

The SARS outbreak of 2003 gave the world a clear example of future challenges in addressing emerging infectious diseases. As demonstrated by SARS, an outbreak of infection even in seemingly remote areas of the world can pose a threat to the health and economies of countries worldwide. All nations need to have access to accurate and timely information and must be prepared to respond appropriately. The benefit of having well-established partnerships with countries was demonstrated repeatedly, especially as it became apparent that there is a serious shortage of available United States–based skilled personnel. Similarly,

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

because specialized skill sets, such as infection control expertise, were in critically short supply, future preparedness planning should include establishing contingency plans whereby partners from outside the government can assist with outbreak response efforts as needed. The benefit of global collaboration in addressing scientific challenges was well documented; nevertheless, serious challenges were encountered in the acquisition and transport of clinical material critical to establishing the cause of the outbreak, clearly indicating the need to further facilitate technology transfer and enhance preparedness. Once the cause of the outbreak was determined, an enormous demand for validated diagnostics, training, and technical assistance emerged. Meeting this demand proved to be a major undertaking as well. Last, the long-standing political obstacle in regard to WHO’s interactions with Taiwan was highlighted as the SARS outbreak exploded across the island. Initially, only CDC experts responded to Taiwan’s call for assistance; however, a decision by the director general of WHO soon led to formal WHO participation in the outbreak response. Once again, we learned that infectious diseases respect neither geographic nor political boundaries.

ROLE OF CHINA IN THE QUEST TO DEFINE AND CONTROL SARS

Robert F. Breiman,1Meirion R. Evans,2Wolfgang Preiser,3James Maguire,4Alan Schnur,5Ailan Li,5Henk Bekedam,5and John S. MacKenzie6

*Reprinted with permission from the Centers for Disease Control and Prevention

© Copyright Centers for Disease Control and Prevention, 2003

China holds the key to solving many questions crucial to global control of severe acute respiratory syndrome (SARS). The disease appears to have originated in Guangdong Province, and the causative agent, SARS coronavirus, is likely to have originated from an animal host, perhaps sold in public markets. Epidemiologic findings, integral to defining an animal-human linkage, may be confirmed by laboratory studies; once animal host(s) are confirmed, interventions may be needed to prevent further animal-to-human transmission. Community seroprevalence studies may help determine the basis for the decline in disease incidence in Guangdong Province after February 2002. China will also be

1  

International Centre for Diarrheal Disease Research, Bangladesh–Centre for Health and Population Research, Dhaka, Bangladesh.

2  

National Public Health Service for Wales, Cardiff, United Kingdom.

3  

Institute for Medical Virology, Frankfurt, Germany.

4  

Centers for Disease Control and Prevention, Atlanta, Georgia.

5  

World Health Organization, Beijing, China.

6  

University of Queensland, Brisbane, Australia.

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

able to contribute key data about how the causative agent is transmitted and how it is evolving, as well as identifying pivotal factors influencing disease outcome.

SARS is a newly emerged disease, caused by a previously unknown coronavirus. The first known cases occurred in Guangdong Province in southern China in November and December 2002. During late February 2003, a physician who was incubating SARS traveled from Guangzhou, the provincial capital, to Hong Kong, Special Administrative Region of China, and stayed at a hotel. There, the virus was transmitted from him to local residents and to travelers, who became ill and transmitted disease to others when they returned to Vietnam, Singapore, Canada, and Taiwan, Province of China (Tsang et al., 2003). SARS has now occurred in >8,450 people with >800 deaths worldwide.

The tally of SARS climbed rapidly in China through May 2003, then decelerated markedly during June. The disease has now been reported in 24 of China’s 31 provinces. By June 26, 2003, a total of 5,327 SARS cases and 348 deaths had been reported from mainland China, including 2,521 cases in Beijing and 1,512 in Guangdong Province.

Since February 2003, teams of technical consultants for the World Health Organization have been working in China to provide assistance to the Ministry of Health and provincial governments on public health responses to the SARS outbreak. A team that began working in China in March reviewed considerable clinical, epidemiologic, and laboratory data with scientists and officials from a variety of settings in Guangdong Province and Beijing. The team worked closely with colleagues from the National and Guangdong Provincial Centers for Disease Control, and together were able to establish that cases occurring in Guangdong beginning in November were clinically and epidemiologically similar to subsequent cases of SARS documented elsewhere.

The team observed detailed, comprehensive data collection forms, which are completed for activities and behaviors and clinical manifestations of patients with SARS. The team was informed that serum and respiratory secretion specimens collected from many patients from Guangdong were being held under appropriate storage conditions, awaiting further laboratory testing.

While a dedicated, collaborative international effort has resulted in substantial understanding of this disease with remarkable speed, critical information is still lacking. We detail a variety of knowledge gaps that should be addressed through a set of activities to optimize prevention and control of SARS.

Emergence of SARS-Associated Coronavirus in Humans

Available evidence suggests that SARS emerged in Guangdong Province, in southern China. How and when did it emerge? Did the causative agent evolve in an animal species and jump to humans (or perhaps first to other animal species), or did the virus evolve within humans? The genetic sequence of the virus has been obtained in several laboratories, and phylogenetic analyses have shown that

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

it is unlike other coronaviruses of animal and human origin. Indeed, the virus has been tentatively placed in a new fourth genetic group (Marra et al., 2003; Rota et al., 2003).

Why is it so important to answer the question of how SARS emerged? Most recently recognized novel emergent viruses have been zoonotic, usually with a reservoir in wildlife (Ludwig et al., 2003; Williams et al., 2002). Thus, SARS coronavirus, if zoonotic, may provide the basis for modeling and predicting the appearance of other potential zoonotic human pathogens. More importantly, the information may be crucial for control of SARS. If this disease is to be curtailed or eliminated by strict public health measures, blocking further animal-to-human transmission is indicated. Only about half of the cases in Guangdong are attributed to contact with a SARS patient. Transmission from an unknown, but persisting animal reservoir might explain this finding; however, a nonspecific case definition (i.e., many “cases” might not actually be SARS) and limitations in contact-tracing capacity are other potential explanations.

Finding a potential animal source is, however, a daunting task. The province is famous for its “wet markets,” where a bewildering variety of live fauna are offered for sale (sometimes illegally) for their medicinal properties or culinary potential. The opportunity for contact, not only with farmed animals but also with a variety of otherwise rare or uncommon wild animals, is enormous. More than one third of early cases, with dates of onset before February 1, 2003, were in food handlers (persons who handle, kill, and sell food animals, or those who prepare and serve food) (Guangdong Province Center for Disease Control and Prevention, unpub. data,).

Hypothesis-generating epidemiologic studies are indicated to focus on early cases of SARS and cases in persons without known contact with infected persons. These studies should also collect information from appropriately selected controls (i.e., matched by categories such as community and age), regarding exposures to animals of any kind in any setting (including food preparation, dietary habits, pets, and a variety of other activities and behaviors in the community).

Plausible hypotheses generated by epidemiologic studies should be briskly followed by intensive, focused, laboratory studies where relevant, including surveys of specific animal populations to identify SARS-associated coronaviruses (by culture and polymerase chain reaction [PCR]) or to measure specific antibodies. Some virologic surveys have already been conducted among prevalent animal populations, including those known to harbor other coronaviruses or other viruses transmissible to humans or wild animals, handled and sold in the markets; a variety of animals, most notably masked palm civets, have been reported to harbor SARS-associated coronavirus. However, whether these animals are transmitting virus or are recipients of virus transmission is not yet clear. Solutions will lie with identifying epidemiologic links, which should guide targeted animal studies. Molecular epidemiologic and genetic studies can then be helpful in evaluating viruses isolated from animals and from humans.

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

Natural History of the Epidemic

Since the earliest known cases were in Guangdong Province, China has had more time than any other location to observe disease incidence over time. Evidence from Guangdong Provincial Centers for Disease Control suggests that the disease incidence peaked in mid-February, and declined weekly through May. What were the reasons for the decline? Introduction of stringent infection-control measures in hospital settings undoubtedly resulted in reduced incidence in healthcare settings but would not likely have accounted for reductions in community transmission. Efforts have been made to reduce the interval between onset of illness and hospitalization (minimizing the potential for community transmission). This effort likely had substantial impact in reducing disease incidence, as shown elsewhere (Riley et al., 2003).

The initial hypothesis was that the virus attenuated after multiple generations of transmission; this hypothesis now seems unlikely. We note several other considerations. Were there a limited number of susceptible people within the population to begin with? Such a concept is possible if there had been earlier spread of a less virulent coronavirus, providing some immunity to a proportion of the population. If so, whether this occurrence was unique to Guangdong will be important to determine.

Alternatively, did the population develop widespread immunity to the causative agent itself? This scenario would require a good deal of asymptomatic or mildly symptomatic disease. At this stage, no reason exists to exclude the possibility of a much wider spectrum of disease than is currently appreciated, since the spectrum of illness has not been fully evaluated.

Another possibility is that a second agent might be required, in addition to coronavirus, to produce severe illness; if this is the case, the epidemiology (like seasonality) of the second agent (perhaps a less recently emerged pathogen for which there is already fairly widespread immunity), rather than coronavirus, may actually be responsible for the decline of the incidence of SARS in Guangdong.

Extensive seroprevalence studies will be helpful for sorting through these possibilities. Analyzing stored serum samples, collected before the onset of this outbreak, could be of immense value in evaluating the possibility of preexisting immunity. Some researchers have found human metapneumoviruses (Poutanen et al., 2003) and species of Chlamydia in patients with SARS, but the importance of these findings is unclear. Systematic evaluation of specimens available from all cases, severe cases, and healthy controls in China regarding the presence of antibodies to coronavirus, as well as hypothesized co-infecting agents, should be done. Important clues may come from seroprevalence and other epidemiologic studies in children. As in other affected countries, children were disproportionately less affected by SARS than adults. Carefully working through the bases for reduced incidence and severity may uncover cross-protecting infectious or immunizing agents or crucial host factors for protection.

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

Superspreading Events

When documenting the source of person-to-person transmission of SARS has been possible, a substantial proportion of cases have emanated from single persons, so-called superspreaders (Tsang et al., 2003). While contact tracing is undoubtedly incomplete, most infected patients have transmitted illness to few other people. Understanding the differentiating characteristics of persons who transmit, especially patients who are able to transmit to several other people, often after minimal contact, may provide important clues for public health strategies focused on preventing transmission. In addition, better defining environmental settings or circumstances that facilitate high transmission rates would be helpful. China is not unique in documenting superspreaders. The country could participate in multinational studies to define the characteristics of superspreaders and their role in the epidemiology of SARS. Of particular interest is the virus load of superspreaders, compared with those of other infected persons.

Little is known about the importance of fecal-oral transmission or about the length of time that infectious virus shedding occurs in the gastrointestinal tract. Virus shedding in feces has major implications for control strategies and for the possibility of continued carriage and shedding by clinically recovered patients. China has the opportunity to explore the role of fecal spread in the transmission of SARS.

Evolution of the Virus

The causative agent is a coronavirus, and the entire genome of several strains has been fully sequenced by many laboratories globally (Marra et al., 2003; Rota et al., 2003; Ruan et al., 2003). Tests have been developed to detect coronavirus genetic sequences by PCR. In addition, tests to detect SARS-associated coronavirus antibodies have been developed, but the sensitivity and specificity of these tests are low, especially early in the illness when public health and clinical needs are greatest. A good test for SARS would be important not only for diagnosis and management but also for investigating the origin of the disease and for defining its epidemiology.

If the causative agent can be isolated from stored specimens from the earliest group of patients (from November 2002 to January 2003), how their genetic sequences compare with those from viruses isolated later from various parts of China and elsewhere, and from animals from Guangdong and Guanxi Provinces, would be useful to know. Mutations may be important for a number of reasons. They may affect transmissibility and virulence; they may provide (or frustrate) therapeutic targets for new drugs; and they may pose challenges for development of diagnostic tests and vaccines. Specimens from Chinese patients provide the longest observation window with which mutational tendencies can be evaluated.

An analysis of 14 full-length sequences suggests that two genetic lineages might have arisen from Guangdong. One lineage is represented by the chain of

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

transmission associated with the physician from Guangzhou who traveled to Hong Kong, Special Administrative Region, in February. The other lineage is associated with isolates from Hong Kong, Guangzhou, and Beijing (Ruan et al., 2003). If two genetic lineages arose in Guangdong, were there two separate transmission events from an animal host to humans, or did the lineage diverge within humans? Specimens from early cases in Guangdong may be helpful in addressing this question.

Outcomes of Infection

Epidemiologic, immunologic, and microbiologic factors associated with severe outcome are not fully defined. Clearly, though, a principal determinant for poor outcome is advancing age. As with other respiratory diseases, age-related coexisting conditions reduce the capacity to compensate to conditions associated with severe disease. Understanding other specific factors that result in poor outcome will have value for optimizing therapeutic approaches.

Clinicians disagree about the value of early treatment with ribavirin and highdose corticosteroids,7 and some are reticent to ventilate patients because of high risk for transmission to health-care workers associated with intubation. More data are needed to help define the most effective treatment strategy, particularly for areas with limited resources.

Extraordinary clinical expertise exists among health professionals in Guangdong Province. They have substantial experience with a variety of antivirals, antibiotics, alternative (herbal) medicines, and corticosteroids, and with using assisted ventilation in the treatment of patients with SARS (Zhong and Zeng, 2003). While randomized clinical trials have not been conducted, careful compilations of existing case series data would be helpful in evaluating the potential effectiveness of various management regimens.

The store of clinical data, accumulated from treating hundreds of SARS cases, needs to be put to good use. One priority is to investigate clinical, epidemiologic, and laboratory predictors of poor outcome. Such experience will supplement other recently published data from Hong Kong, Special Administrative Region (Donnelly et al., 2003; Lee et al., 2003; Peiris et al., 2003b; Tsang et al., 2003), and Singapore (Hsu et al., 2003).

Several questions remain unanswered. Do patients exposed to high viral doses (for which a short incubation period may be a surrogate) or to a co-infecting pathogen have poorer outcomes? What is the impact of multiple exposures to SARS-associated coronavirus, like that which occurred among health-care workers early in the epidemic? Do patients infected early in the transmission cycle perform more poorly than those infected during subsequent cycles of transmission?

7  

[IOM editor’s note: For more on the controversy over ribavirin use, see Zhaori, G., 2003, Antiviral treatment of SARS: Can we draw any conclusions? Canadian Medical Association Journal 169(11): 1165-6.]

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

Learning from the SARS Epidemic

Seldom have intersections between politics, economic development, and public health been more graphically demonstrated. While awaiting the development of effective prophylactic and therapeutic options, many countries have had to muster substantial political will for quick and transparent steps to declare the presence of a lethal pathogen within their borders; conduct surveillance and report the results; use contact tracing, quarantine, and border control measures when needed; and apply stringent infection control measures in health-care settings. Providing the general public with timely and candid information about the magnitude of the problem, the known risks, and how persons can protect themselves has also been necessary. These actions were necessary even when they appeared contrary to economic interests in the short run. Delaying implementation can result in major public health consequences, in addition to damage to the economy and national image.

The work outlined here involves descriptive and epidemiologic inquiry, fundamental to establishing an understanding of this new pathogen and disease. While refined and esoteric research will likely also be conducted, support must first be established for systematically addressing these basic questions and rapidly disseminating results through publication in international journals, presentations at international meetings, and public communications. In China, in contrast with many other settings globally, scientific inquiry and dissemination of results to the international community are subject to institutional interference. The SARS pandemic has shown that virulent pathogens are beholden to no political philosophy or edict. Only careful and rapid application of knowledge and reason through a variety of public health measures has been effective in minimizing the spread and severity of the SARS epidemic. More information and data generated from studies of the epidemic in China are needed immediately to save lives and to prevent fear and disease, both in China itself and elsewhere in the world.

SARS became a public health emergency for China, where investment in health services has been given low priority for many years. Maintaining control in a country so large and diverse will be a major challenge for the months, and perhaps years, to come. Each of China’s mainland provinces (including municipalities with equivalent status, autonomous regions, and special administrative regions) is like a country within a country. Many are larger than most countries in Europe. Some, such as Shanghai, are wealthy and highly developed, while others such as Guangxi (bordering Guangdong and Vietnam) are poor and typical of developing countries. Given the potential for reemergence of SARS in the future, if sustained control measures are not in place in China, the possibility of controlling the global threat posed by the disease until new technology (i.e., an effective vaccine) is available may be slight. Key strategies include effective disease surveillance and reporting with early detection and isolation; hospital infection con-

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

trol during triage and treatment of cases; and transparent, open public communication about risk and disease magnitude.

China has recently begun to vigorously address the need for better surveillance, accurate reporting, and forthright public communication. Substantial epidemiologic, clinical, virologic, and immunologic expertise and interest are available within China to address the fundamental questions. International expertise is also available to provide guidance, feedback, and assistance when requested. Identifying the modest resources needed to implement the work should not be a barrier. Support from the government will be needed to carry out valid, transparent studies, and for permission to report the findings, regardless of the conclusions. SARS provides a jarring reminder of the preparedness that is needed to respond to emerging and existing disease threats; it highlights the need to reinvest in health in China, and strengthen public health programs, including surveillance systems and response capacity.

While disease incidence has abated in China and in other locations globally, the disease may still represent an important threat in the future. Many of the solutions to solve the multifaceted puzzle of SARS and to prevent future epidemics must come from China. Without solutions from that country, the degree of difficulty for sustained control of the problem globally is raised still higher.

SARS: LESSONS FROM TORONTO

Donald E. Low, M.D., FRCPC

Toronto Medical Laboratories, Mt. Sinai Hospital, Toronto

Toronto’s experience with severe acute respiratory syndrome (SARS) illustrated how quickly the disease can spread in hospitals and highlighted the dangerous phenomenon of SARS superspreaders (see Figure 1-1). Unrecognized cases in Toronto caused significant morbidity and mortality (see Tables 1-4 and 1-5). The absence of rapid tests to distinguish this new disease from pneumonia, influenza, or other common diseases bodes ill for future outbreaks. In the meantime, however, it is clear that a number of simple precautionary measures can significantly reduce hospital-based transmission of the SARS coronavirus, SCoV, during an outbreak.

During the first phase of the outbreak in Toronto, SARS chiefly affected health care workers (HCW), patients, and their visitors at four hospitals (see Table 1-6). The second phase of the outbreak occurred primarily in the workers and visitors of a single hospital ward. The following text chronicles the two phases of the SARS outbreak in Ontario and describes the preventive measures taken by hospitals and individual HCWs once the outbreak became apparent.

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

FIGURE 1-1 SARS Toronto: Phases I and II. The two SARS outbreaks that occurred in Toronto and the age distribution of cases. The majority of cases, which occurred between the ages of 18 and 64, were among health care workers, patients, and visitors to patients in hospitals.

TABLE 1-4 Case Distribution by Age Group

 

Phase I

Phase II

Age Group

No.

%

No.

%

<18

18

7

2

2

18-35

71

28

20

17

36-64

132

51

70

59

>64

36

14

26

22

Total

257

100

118

100

TABLE 1-5 Case Fatality by Age Group

 

Phase I

Phase II

Age Group

No.

%

No.

%

<18

0

0

0

0

18-35

0

0

0

0

36-64

10

38

6

31

>64

16

62

11

69

Phase I of the Toronto SARS Outbreak

The index case and her husband had vacationed in Hong Kong and had stayed at a hotel in Kowloon from February 18 to 21, 2003. The index case began to experience symptoms after her return on February 23 and died at home

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

TABLE 1-6 SARS Toronto: Phases I and II

 

Phase

 

I

II

Exposure

No. (%)

No. (%)

2002

91 (33%)

52 (42%)

Hospital -worker patient/visitor

49 (18%)

64 (51%)

Other health care (clinic, EMS)

8 (2.9%)

2 (1.6%)

Household contact

76 (28%)

9 (7.2%)

“Community”

16 (5.9%)

Travel

12 (4.4%)

Under investigation

21 (7.7%)

on March 5. During her illness, family members, including her son (case A), provided care at home. Case A became ill on February 27 and presented to the index hospital on March 7 (Varia et al., 2003).

Nosocomial transmission in the hospital began when case A presented to the emergency department on March 7 with severe respiratory symptoms. He was placed in a general observation area of the emergency department and received nebulized salbutamol. During this time, SARS was transmitted to two other patients in the emergency department (cases B and C). Case B, who had presented with rapid atrial fibrillation, was in the bed adjacent to case A, about 1.5 meters away and separated by a curtain, and was discharged home after 9 hours in the emergency department. Case C, who had presented with shortness of breath secondary to a pleural effusion, was three beds (about 5 meters) away from case A and was transferred to a hospital ward and later discharged home on March 10. The three patients were cared for by the same nurse.

Case A was transferred briefly to a medical unit, then to the intensive care unit (ICU) 18 hours after his presentation to the emergency department. Three hours later, he was placed in airborne isolation because tuberculosis was included in his differential diagnosis. Contact and droplet precautions were implemented on March 10 by ICU staff caring for case A, and the patient remained in isolation until his death, on March 13. Case A’s family visited him in the ICU on March 8, 9, and 10. During this time, some family members were febrile, and two were experiencing respiratory symptoms. Chest radiographs were taken of the family members on March 9 and again on March 11. Four members had abnormal radiographs and were instructed to wear masks at all times, wash their hands upon entering and leaving the ICU, and limit their visits to the ICU.

On March 12, the WHO alerted the global community to a severe respiratory syndrome that was spreading among HCWs in Hanoi, Vietnam, and Hong Kong. The alert was forwarded to infectious disease and emergency department physicians in Toronto. The following day, case A died and it became clear that several

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

other family members had worsening illness. The clinicians involved and the local public health unit suspected the family’s illnesses might be linked to cases of atypical pneumonia reported in Hong Kong. Four family members were admitted to three different hospitals on March 13, and another family member was admitted to hospital on March 14. All were managed using airborne, droplet, and contact precautions. No further transmission from these cases occurred after admission to hospital.

Case B became febrile on March 10, 3 days after exposure to case A in the emergency department and discharge home. Respiratory symptoms evolved over the next 5 days. He was brought to the index hospital on March 16 by two Emergency Medical Services paramedics, who did not immediately use contact and droplet precautions. After 9 hours in the emergency department, where airborne, contact and droplet precautions were used, case B was transferred to an isolation room in the ICU. His wife became ill on March 16. She was in the emergency department with case B on March 16 (no precautions used) and visited him in the ICU on March 21 (precautions used); he died later that day. The infection also spread to three other members of case B’s family. SARS developed in a number of people who were in contact with case B and his wife on March 16, including the 2 paramedics who brought him to the hospital, a firefighter, 5 emergency department staff, 1 other hospital staff, 2 patients in the emergency department, 1 housekeeper who worked in the emergency department while case B was there, and 7 visitors who were also in the emergency department at the same time as case B (symptom onset March 19 to 26). The 16 hospital staff, visitors, and patients transmitted the infection to 8 household members and 8 other family contacts. In the ICU, intubation for mechanical ventilation of case B was performed by a physician wearing a surgical mask, gown and gloves. He subsequently acquired SARS and transmitted the infection to a member of his family. Three ICU nurses who were present at the intubation and who used droplet and contact precautions had onset of early symptoms between March 18 and 20. One transmitted the infection to a household member.

Case C became ill on March 13 with symptoms of a myocardial infarction and was brought to the index hospital by paramedics. It was unknown that he had been in contact with case A on March 7, and thus it was not recognized that he had SARS. As a result, he was not isolated, and other precautions were not used. He was admitted to the coronary care unit (CCU) for 3 days and then transferred to another hospital for renal dialysis. He remained in the other hospital until his death, on March 29. Subsequent transmission of SARS occurred within that hospital (Dwosh et al., 2003). Case C’s wife became ill on March 26. At the index hospital, case C transmitted SARS to 1 patient in the emergency department, 3 emergency department staff, 1 housekeeper who worked in the emergency department while case C was there, 1 physician, 2 hospital technologists, 2 CCU, patients, and 7 CCU staff. One of the paramedics who transported case C to the index hospital also became ill. Further transmission then occurred from ill staff at the index hospital to 6 of their family members, 1 patient, 1 medical clinic staff, and 1 other nurse in the emergency department.

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

On March 23, 2003, officials recognized that the number of available negative pressure rooms in Toronto was being exhausted. In a 4-hour period on the afternoon of March 23, staff at West Park Hospital, a chronic care facility in the city, recommissioned 25 beds in an unused building formerly used to house patients with tuberculosis. Despite the efforts of West Park physicians and nurses, and assistance from staff at the Scarborough Grace and Mount Sinai Hospitals, qualified staff could be found to care for only 14 patients.

Faced with increasing transmission, the Ontario government designated SARS as a reportable, communicable, and virulent disease under the Health Protection and Promotion Act on March 25, 2003. This move gave public health officials the authority to track infected people, and issue orders preventing them from engaging in activities that might transmit the new disease. Provincial public health activated its emergency operations center.

By the evening of March 26, 2003, the West Park unit and all available negative pressure rooms in Toronto hospitals were full; however, 10 ill Scarborough Hospital staff needing admissions were waiting in the emergency department, and others who were ill were waiting at home to be seen. Overnight, with the declaration of a provincial emergency, the Ontario government required all hospitals to create units to care for SARS patients.

By March 25, 2003, Health Canada was reporting 19 cases of SARS in Canada—18 in Ontario and the single case in Vancouver. But 48 patients with a presumptive diagnosis of SARS had in fact been admitted to hospital by the end of that day. Many more individuals were starting to feel symptoms, and would subsequently be identified as SARS patients. Epidemic curves later showed that this period was the peak of the outbreak. On March 19, nine Canadians developed “probable” SARS, the highest single-day total. Taking “suspect” and “probable” cases together, the peak was March 26, and the 3 days, March 25 to 27 are the highest 3-day period in the outbreak.

The Ontario government declared SARS a provincial emergency on March 26, 2003. Under the Emergency Management Act, the government has the power to direct and control local governments and facilities to ensure that necessary services are provided.

All hospitals in the Greater Toronto Area (GTA) and Simcoe County were ordered to activate their “Code Orange” emergency plans by the government. “Code Orange” meant that the involved hospitals suspended nonessential services. They were also required to limit visitors, create isolation units for potential SARS patients, and implement protective clothing for exposed staff (i.e., gowns, masks, and goggles). Four days later, provincial officials extended access restrictions to all Ontario hospitals.

On May 14, 2003, WHO removed Toronto from the list of areas with recent local transmission. This was widely understood to mean that the outbreak had come to an end. Consistent with the notion that the disease was contained, the government of Ontario lifted the emergency on May 17. Directives continued to

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

reinforce the need for enhanced infection control practices in health care settings. Code Orange status for hospitals was revoked.

It appeared that the total number of cases had reached a plateau—140 probable and 178 suspect infections. Twenty-four Canadians had died, all in Ontario.

Phase II of the Toronto SARS Outbreak

During early and mid-May, as recommended by provincial SARS-control directives, all hospitals discontinued SARS expanded precautions (i.e., routine contact precautions with use of an N95 or equivalent respirator) for non-SARS patients without respiratory symptoms in all hospital areas other than the emergency department and the ICUs. In addition, staff no longer were required to wear masks or respirators routinely throughout the hospital or to maintain distance from one another while eating.

On May 20, five patients in a rehabilitation hospital in Toronto were reported with febrile illness. One of these five patients was determined to have been hospitalized in the orthopedic ward of North York General (NYG) Hospital during April 22 to 28, and a second was found on May 22 to have SARS-associated SCoV by nucleic acid amplification test. On investigation, a second patient was determined to have been hospitalized in the orthopedic ward of NYG hospital during April 22 to 28. After the identification of these cases, an investigation of pneumonia cases at NYG hospital identified eight cases of previously unrecognized SARS among patients.

The first patient linked to the second phase of the Ontario outbreak was a man aged 96 years who was admitted to NYG hospital on March 22 with a fractured pelvis. On April 2, he was transferred to the orthopedic ward, where he had fever and an infiltrate on chest radiograph. Although he appeared initially to respond to antimicrobial therapy, on April 19, he again had respiratory symptoms, fever, and diarrhea. He had no apparent contact with a patient or an HCW with SARS, and aspiration pneumonia and Clostridium difficile—associated diarrhea appeared to be probable explanations for his symptoms. In the subsequent outbreak investigation, other patients in close proximity to this patient and several visitors and HCWs linked to these patients were determined to have SARS. At least one visitor became ill before the onset of illness of a hospitalized family member, and another visitor was determined to have SARS although his hospitalized wife did not.

On May 23, NYG hospital was closed to all new admissions other than patients with newly identified SARS. Soon after, new provincial directives were issued, requiring an increased level of infection-control precautions in hospitals located in several greater Toronto regions. HCWs at NYG hospital were placed under a 10-day work quarantine and instructed to avoid public places outside work, avoid close contact with friends and family, and wear a mask whenever public contact was unavoidable. As of June 9, of 79 new cases of SARS that

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
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resulted from exposure at NYH hospital, 78 appear to have resulted from exposures that occurred before May 23.

Transmission

The SCoV has been isolated in sputum, nasal secretions, serum, feces, and bronchial washings (Drosten et al., 2003; Peiris et al., 2003b). Evidence suggests that SCoV is transmitted via contact and/or droplets (Peiris et al., 2003a; Poutanen et al., 2003) and that the use of any mask (surgical or N95) significantly decreases the risk of infection (Seto et al., 2003). However, there are cases that defy explanation based on these modes of transmission suggesting that alternative modes of transmission may also occur (Varia et al., 2003). SCoV remains viable in feces for days and the outbreak at the Amoy Gardens apartments highlights the possibility of an oral-fecal or fecal-droplet mode of transmission (WHO, 2003m,n).

A number of cases occurred in HCWs wearing protective equipment following exposure to high risk aerosol- and droplet-generating procedures such as airway manipulation, administration of aerosolized medications, noninvasive positive pressure ventilation, and bronchoscopy or intubation (Lee et al., 2003; Ofner et al., 2003). When intubation is necessary, measures should be taken to reduce unnecessary exposure to health care workers, including reducing the number of health care workers present and adequately sedating or paralyzing the patient to reduce cough. Updated interim infection control precautions for patients who have SARS are under development and will be available from CDC at http://www.cdc.gov/ncidod/sars/index.htm.

Currently, epidemiological evidence suggests that transmission does not occur prior to the onset of symptoms or after symptom resolution. Despite this, shedding of SCoV in stool has been documented by reverse-transcription polymerase chain reaction (RT-PCR) for up to 64 days following the resolution of symptoms (Ren et al., 2003). A small group of patients appear to be highly infectious and have been referred to as superspreaders (CDC, 2003a). Such superspreaders appear to have played an important role early in the epidemic but the reason for their enhanced infectivity remains unclear. Possible explanations for their enhanced infectivity include the lack of early implementation of infection control precautions, higher load of SCoV, or larger amounts of respiratory secretions.

Clinical Disease

Case Definition

The Centers for Diseases Control and Prevention in Atlanta (CDC) has classified SARS into suspect and probable with further classification based on laboratory findings (CDC, 2003b). The World Health Organization has a similar case

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

classification (WHO, 2003d). Although these classifications have proven epidemiologically useful, they have a low sensitivity for diagnosis in patients early in disease (sensitivity, 26 percent; specificity, 96 percent) (Rainer et al., 2003), underscoring the importance of a rapid, accurate diagnostic test.

Presentation

The typical incubation period of SARS ranges from 2 to 10 days but may rarely be as long as 16 days (Booth et al., 2003; Lee et al., 2003). The prodrome includes influenza-like symptoms such as fever, myalgias, headache, and diarrhea (Booth et al., 2003; Lee et al., 2003). Fever can vary from low to high grade, and can occasionally be absent on presentation, particularly in older patients. The respiratory phase, consisting of an early and late stage, starts 2-7 days after the prodrome and can be associated with watery diarrhea (Booth et al., 2003; Lee et al., 2003; Peiris et al., 2003b). The early stage includes a dry nonproductive cough and mild dyspnea. Patients may only have prodromal or early respiratory symptoms at the time of presentation making the diagnosis of SARS difficult. Chest radiographic and laboratory findings may help in making an early diagnosis. Early chest radiographs often show subtle peripheral pulmonary infiltrates, that can be more readily detected as consolidation or ground-glass appearance using high-resolution computed tomographic (CT) lung scans (Wong et al., 2003a, b). Atypical presentations of the disease have been described also complicating the diagnosis (Fisher et al., 2003; Wu and Sung, 2003). Interestingly, the disease has been rare in children and if present appears to be milder (Hon et al., 2003; Li et al., 2003).

Natural History

SARS is characterized by a spectrum of disease. Asymptomatic cases have been described but only in small number (Gold et al., 2003). Another infrequent subset of cases includes those who have a febrile illness without a respiratory component. More frequent is a mild variant of the disease that includes mild respiratory symptoms with fever. Within this category is a cough variant with persistent intractable cough. The classic moderate-severe variant is characterized by a more serious later respiratory phase with dyspnea on exertion or at rest, and hypoxia. This later respiratory phase often occurs 8 to 12 days after the onset of symptoms (Booth et al., 2003; Lee et al., 2003; Peiris et al., 2003b). In 10-20 percent of hospitalized patients, persistent or progressive hypoxia results in intubation and mechanical ventilation (Booth et al., 2003; Fowler et al., 2003; Lew et al., 2003). Among patients developing respiratory failure, intubation was required at a median of 8 days following symptom onset. Subtle but progressive declines in oxygen saturation are often indicative of impeding respiratory failure and should trigger more intensive monitoring and preparation for intubation under

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

controlled circumstances. In total, the respiratory phase lasts approximately 1 week. The recovery phase begins approximately 14 to 18 days from the onset of symptoms with resolution of the lymphopenia and thrombocytosis.

Clinical Outcome

The case fatality rate during recent outbreaks was 9.6 percent ranging from 0 to 40 percent (WHO, 2003o). Advanced age is the most important risk factor for death with patients older than 60 years having a case fatality rate of 45 percent (Booth et al., 2003; Peiris et al., 2003b). Other risk factors for death include diabetes mellitus and hepatitis B virus infection (Booth et al., 2003; Fowler et al., 2003; Lee et al., 2003; Lew et al., 2003; Peiris et al., 2003b). Little data exist regarding the long-term morbidity of SARS although preliminary studies suggest that the psychological impact of the disease is considerable (Maunder et al., 2003; Styra et al., 2003).

Conclusion

The experience with SARS in Toronto indicates that this disease is entirely driven by exposure to infected individuals. Transmission occurred primarily within health care settings or in circumstances where close contacts occurred. The infectious agent was spread by respiratory droplets in the great majority of cases, and some patients were more infectious than others. Ultimately, the strict adherence to precautions—and practice implementing them—was critical to the containment of SARS in Toronto and the restoration of safe conditions for hospital staff and patients.

ISOLATION AND QUARANTINE: CONTAINMENT STRATEGIES FOR SARS 2003

Martin Cetron, M.D., Susan Maloney, M.D., M.H.Sc., Ram Koppaka, M.D., and Patricia Simone, M.D.

National Center for Infectious Diseases, Centers for Disease Control and Prevention

Quarantine is an ancient tool used to prevent the spread of disease. The Bible describes the sequestering of persons with leprosy, and the practice was used widely in 14th-century Europe to control the spread of bubonic and pneumonic plague. To prevent disease transmission, ships were required to stay in harbor for 40 days before disembarkation (thus the term quarantine, which derives from the Latin quadragina or the Italian quaranta, meaning 40).

Quarantine has been used for centuries, but because it was often implemented in a way that equated disease with crime, the practice has negative connotations.

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
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Persons under quarantine were often detained without regard to their essential needs. Those who were exposed but not yet ill were not always separated from the ill, allowing disease to spread within the detained group. Populations targeted for quarantine, such as foreigners, were stigmatized. In some cases, the power of quarantine was abused; for example, at the end of the 19th century, the steerage passengers on arriving ships were frequently quarantined while the first-and second-class passengers were allowed to disembark without being examined for illness.

Despite its history, quarantine—when properly applied and practiced according to modern public health principles—can be a highly effective tool in preventing the spread of contagious disease. It may play an especially important role when vaccination or prophylactic treatment is not possible, as was the case with severe acute respiratory syndrome (SARS). Even when direct medical countermeasures are available (e.g., smallpox and pneumonic plague), reducing mobility in the at-risk population may enable the most rapid and efficient delivery of postexposure vaccination and chemoprophylaxis.

Isolation and Quarantine

Before discussing the role of quarantine as a component of community response and containment for SARS, it is necessary to distinguish, from a public health perspective, between the related practices of isolation and quarantine. Both are usually imposed by health officials on a voluntary basis; however, federal, state, and local officials have the authority to impose mandatory quarantine and isolation when necessary to protect the public’s health.

Isolation refers to the separation and restricted movement of ill persons who have a contagious disease in order to prevent its transmission to others. It typically occurs in a hospital setting, but can be done at home or in a special facility. Usually individuals are isolated, but the practice may be applied in larger groups.

Quarantine refers to the restriction of movement or separation of well persons who have been exposed to a contagious disease, before it is known whether they will become ill. Quarantine usually takes place in the home and may be applied at the individual level or to a group or community of exposed persons.

Contact surveillance, in the context of quarantine, is the process of monitoring persons who have been exposed to a contagious disease for signs and symptoms of that disease. Surveillance may be done passively, for example, by informing contacts to seek medical attention if signs or symptoms occur. Contact surveillance can also be performed actively, for example, by having health workers telephone contacts daily to inquire about signs and symptoms or even having health workers directly assess contacts for fever or other symptoms. All quarantined persons should be monitored for development of signs and symptoms of disease to ensure appropriate isolation, management, and/or treatment. For persons without a known contact but believed to be at increased risk for disease or

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
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exposure, enhanced surveillance and education can be used for risk assessment monitoring. During the SARS epidemic, this approach was used effectively with airline passengers arriving in the United States from areas of high transmission during the SARS epidemic.

Principles of Modern Quarantine

Quarantine as it is now practiced is a public health tool and a collective action for the common good. Today’s quarantines are more likely to involve a few people exposed to contagion in a small area, such as on an airplane or at a public gathering, and only rarely are applied to entire cities or communities. The main goal of modern quarantine is to reduce transmission by increasing the “social distance” between persons; that is, reducing the number of people with whom each person comes into contact (see Figure 1-2).

If quarantine is to be used, the basic needs of those infected and exposed must be met. The following key principles of modern quarantine ensure that it strikes the appropriate balance between individual liberties and the public good:

  • Quarantine is used when persons are exposed to a disease that is highly dangerous and contagious.

  • Exposed well persons are separated from those who are ill.

  • Care and essential services are provided to all people under quarantine.

  • The “due process” rights of those restricted to quarantine are protected.

FIGURE 1-2 Effectiveness of vaccination and quarantine to contain a smallpox outbreak after the release of bioengineered, aerosolized smallpox in an airplane carrying 500 people.

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
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  • Quarantine lasts no longer than is necessary to ensure that quarantined persons do not become ill. Its maximum duration would be one incubation period from the last known exposure, but it could be shortened if an effective vaccination or prophylactic treatment is available and can be delivered in a timely fashion.

  • Quarantine is used in conjunction with other interventions, including—

    • Disease surveillance and monitoring for symptoms in persons quarantined.

    • Rapid diagnosis and timely referral to care for those who become ill.

    • The provision of preventive interventions, including vaccination or prophylactic antibiotics.

Quarantine encompasses a range of strategies that can be used to detain, isolate, or conditionally release individuals or populations infected or exposed to contagious diseases, and should be tailored to particular circumstances. Quarantine activities can range from only passive or active symptom monitoring or short-term voluntary home curfew, all the way to cancellation of public gatherings, closing public transportation, or, under extreme circumstances, to a cordon sanitaire: a barrier erected around a geographic area, with strict enforcement prohibiting movement in or out. In a “snow day” or “sheltering in place” scenario, schools may be closed, work sites may be closed or access to them restricted, large public gatherings may be cancelled, and public transportation may be halted or restricted. People who become ill under these conditions would need specific instructions for seeking evaluation and care; they would only expose others in their households—or perhaps no one at all, if precautions are taken as soon as symptoms develop. The fact that most people understand the concept of sheltering at home during inclement weather, regarding home in these circumstances as the safest and most sensible place to be, increases the likelihood that similar conditions of quarantine will be accepted. “Snow day” measures can be implemented instantaneously, and most essential services can be met without inordinate additional resources, especially if the quarantine lasts only a few days.

Another important feature of quarantine is that it need not be absolute to be effective. Even a partial or “leaky” quarantine, such as occurs with voluntary compliance, can reduce the transmission of disease. Voluntary measures, which rely on the public’s cooperation, reduce or remove the need for legal enforcement and leverage the public’s instinct to remain safely sheltered. In contrast, compulsory confinement may precipitate the instinct to “escape.” If an effective vaccine is available, partial quarantine can be an effective supplement to vaccination, further reducing transmission of disease. For example, Figure 1-3 shows a model illustrating various outcomes of a hypothetical scenario of 500 people, all of whom are vaccinated against smallpox, exposed to an intentional aerosol release of that contagion on an airplane. In the model,

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

FIGURE 1-3 Impact of varying Ro and percent quarantined on total smallpox cases. Even with 100 percent vaccination against smallpox, quarantine effectively reduces the spread of disease in the community. This effect remains significant even at lower reproductive rates, and differs little between 90 and 100 percent quarantine.

all 500 people are offered postexposure smallpox vaccine; the model assumes that the vaccine is 95 percent effective. Even under these unlikely and theoretical circumstances, the addition of even partial (50 percent to 90 percent) quarantine to vaccination can have a profound effect on reducing the number of eventual cases in the community. This trend remains significant even at low rates of transmission (“reproductive rates”).

In order to implement modern quarantine effectively, there must be a clear understanding of the roles of public health staff at federal, state, and local levels, and each group should know their legal authorities. Effective implementation also requires identifying appropriate partners, including transportation authorities and law enforcement officials, and engaging them in coordinated planning. Finally, quarantine can be most successful if the public has advance knowledge of the disease threat and understands the role of quarantine in containing an epidemic. People who are actually quarantined need to believe that their sacrifice is justified and that they will be supported during the period of quarantine.

Quarantine and the Response to SARS

Containment strategies employed during the recent SARS epidemic included case and contact management, infection control in hospitals and other facilities, community-wide temperature screening, mask use, isolation and quarantine, and

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

FIGURE 1-4 Reported cases of SARS, United States, May 19, 2003.

the monitoring of travelers and response at national borders. Various combinations of these strategies were applied in different places, depending on factors such as the magnitude and scope of the local outbreak, the availability of resources to support containment, and the level of public cooperation and trust. In the United States, where only eight laboratory-confirmed cases of SARS and no community transmission occurred (see Figure 1-4), the principal strategies of containment were education of high-risk populations (e.g., international travelers and health-care workers); early detection of suspected and probable cases; and rapid implementation of isolation and other infection control tools. Additional measures such as quarantine were used in other countries where SARS presented a greater threat.

Case and Contact Management

In the United States, most people with suspected or probable SARS were isolated at home; hospital isolation was reserved for those who required such care or had no suitable home environment. (e.g., homeless, out-of-town visitors). Isolation was continued while symptoms persisted and for 10 days thereafter. In some other countries, most persons with suspected or probable SARS were isolated in the hospital. For contact management, the U.S. Centers for Disease Control and Prevention (CDC) recommended quarantine only for health-care workers who had a high-risk exposure to a SARS patient. In several states, however, local

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

health officials “furloughed” health-care workers who were exposed to high-risk probable cases. In general, CDC recommended only passive surveillance. Persons who were exposed to suspected or probable SARS, as well as travelers returning from areas with SARS transmission, were asked to monitor their health for 10 days and seek medical attention immediately if fever or respiratory symptoms developed. Active surveillance was reserved for probably and lab-confirmed cases and their high risk close contacts; this was usually conducted by members of the local or state health departments.

In some countries other than the United States (e.g., China, Taiwan [ROC],8 Singapore, and Canada), home quarantine was used for most close contacts of people with suspected or probable SARS. Designated quarantine facilities were used in some situations for homeless persons, travelers, and people who did not wish to be quarantined at home. In some situations, as a result of staffing shortages and relatively high exposure rates in hospitals, exposed health-care workers and ambulance personnel were placed on “work quarantine,” which entailed working during their regular shifts, using comprehensive infection control precautions and personal protective equipment, and staying either at home or in a building near the hospital when off duty. Most persons in home quarantine were asked to monitor their temperature regularly, once or twice a day; health workers called them twice a day to get a report on temperature and symptoms. Other health-care workers had their temperature checked twice a day or more at work. In Singapore, video cameras linked to telephones were occasionally used to monitor patients.

Authorities used a variety of methods to enforce quarantine during the SARS epidemic. In select places, quarantine orders were given to all persons placed in quarantine, while in the majority, only those who demonstrated noncompliance were given orders. Under some orders, noncompliant individuals were isolated in guarded rooms; others were confined at home wearing security ankle bracelets; yet others received fines or even jail sentences. However, these instances of compulsory enforced quarantine orders were clearly the exception rather than the norm during the SARS epidemic.

Community Containment

In the United States, community containment strategies consisted mainly of coordinating the SARS response activities through emergency operations centers and providing information and education to the public, health workers, and others. This strategy included publishing guidelines and fact sheets on websites, holding press conferences, making presentations to a variety of audiences, and meeting with groups and communities who were experiencing stigmatization.

8  

ROC stands for Republic of China.

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
×

On some occasions, such as occurred in mainland China, Hong Kong (SAR), Taiwan (ROC), and Singapore, large-scale quarantine was imposed on travelers arriving from other SARS areas, work and school contacts of suspected cases, and, in a few instances, entire apartment complexes where high attack rates of SARS were occurring.

In addition to imposing large-scale quarantine in some cases, many areas with high transmission (e.g., Hong Kong, Singapore, Taiwan, Toronto, and mainland China) used strategies such as mandated fever screening before entry to schools, work, and other public buildings; requiring masks in certain settings; and implementing populationwide temperature monitoring and disinfection campaigns. Community mobilization programs were also developed to educate the public about SARS and what to do to prevent and control it; for example, a populationwide body temperature monitoring campaign and a SARS hotline to promote early detection of fever as a warning sign for SARS. Taiwan and mainland China also undertook a series of community disinfection campaigns in which streets, buildings, and vehicles were sprayed with bleach and bleach was distributed free throughout the community.

Several important lessons can be gained from the experience of countries where large-scale quarantine measures were imposed in response to SARS. First, when the public was given clear messages about the need for quarantine, it was well accepted—far better, in fact, than many public health officials would have anticipated. Indeed, voluntary quarantine was effective in the overwhelming majority of cases. Yet, despite the widespread acceptance of and cooperation with quarantine, it represented a great sacrifice for many people through consequences such as loss of income, concerns for the health of their families, feelings of isolation, and stigma. Finally, large-scale quarantine was found to be complicated and resource intensive to implement, creating enormous logistic, economic, ethical, and psychological challenges for public health authorities. Recent data evaluating the efficacy of quarantine in Taiwan and Beijing, China, during the SARS epidemic suggest that efficiency could be improved by focusing quarantine activities on persons with known or suspected contact with SARS cases. In order to prepare for future epidemics, enhanced systems and personnel will need to be established to deliver essential services to persons in quarantine, to monitor their health and refer them to necessary medical care, and to offer mental health and other support services.

Border and Travel Response

Several strategies for border and travel response were used in the United States, including issuing travel advisories and alerts, distributing health alert notices at ports of entry, and meeting planes and responding to reports of ill passengers. Additional strategies used in other countries (e.g., Canada, China, and Singapore) included predeparture screening of temperature, SARS symptoms,

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
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TABLE 1-7 Travel Alerts and Advisories for SARS, March–July 2003

Region

Advisory Started

Advisory Stopped

Alert Started

Alert Stopped

Mainland China

3/13/03

6/17/03

6/17/03

7/3/03

Beijing, China

6/17/03

6/25/03

6/25/03

7/11/03

Taiwan

6/25/03

6/25/03

6/25/03

7/15/03

Hong Kong

5/1/03

6/25/03

6/25/03

7/1/03

Hanoi, Vietnam

3/13/03

4/29/03

4/29/03

5/15/03

Toronto

Never had an advisory

Never had an advisory

4/23/03 restarted: 5/23/03

5/20/03 restopped: 7/8/03

Singapore

3/13/03

5/4/03

5/4/03

6/4/03

and recent exposures to SARS patients; postarrival disembarkation screening with questions about travel and exposure to SARS, maintaining “stop lists” of people with suspected SARS and their contacts at airports to prevent such individuals from traveling, isolation of ill travelers with suspected or probable SARS, and quarantine of healthy travelers returning from other areas with high SARS transmission.

In the United States, CDC issued a series of travel alerts and advisories related to SARS (see Table 1-7). A travel alert describes a health situation in a particular area and gives recommendations about appropriate precautions, while a travel advisory goes a step further and recommends postponement of nonessential travel to an affected area. During the SARS epidemic, CDC staff met nearly 12,000 flights and distributed more than 2.7 million health alert notices to passengers arriving directly and indirectly from affected areas. The notices instructed travelers to monitor their health for fever and respiratory symptoms for 10 days and immediately seek medical attention (with advance notice to the health-care facility) if the symptoms occurred. Health alert notices (HANs) were also distributed at 13 U.S.–Canada land crossings, as well as in the predeparture area at the Toronto airport. If an ill passenger was reported on a flight arriving in the United States, it was met by members of the CDC quarantine staff. They evaluated the affected passenger for possible SARS, provided referral to a health-care provider, collected locating information from other passengers, and coordinated with federal, state, and local public health authorities.

Preparedness Planning

Preparations for a resurgence of SARS (or indeed an outbreak of any contagious disease) should be made at all levels of government. Plans must encompass general logistics and planning for case and contact management, including quarantine. A framework for the community containment of SARS (see Figure 1-5) lists several criteria for establishing movement restrictions and a range of options for containment that could be applied in response. In deciding whether and how

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
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FIGURE 1-5 Range of available responses to SARS at the national, state, and community levels.

to restrict movement during an epidemic, community officials would consider factors such as:

  • the number of suspected, probable, and confirmed cases;

  • whether cases have well-defined exposure risks;

  • how many potential new exposures each case has been in contact with;

  • what type of transmission is predominant (e.g., airborne, droplet, fomite);

  • how many generations of transmission have occurred; and

  • the morbidity and case-fatality rate of the epidemic.

Decision makers would also need to consider the baseline amount of movement in the community, the impact of curtailing movement on critical infrastructure, the resources available to support containment, and the public’s reaction to the epidemic.

Planning for Community Containment

In some circumstances, containment of SARS or other microbial threats at the community level could be accomplished without restricting movement, with the focus instead on educating the public through such means as press releases

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
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and travel alerts and advisories (as was done in the United States in 2003). In other situations, targeted restrictions, including quarantine of close contacts and restriction of some group gatherings, would be appropriate. A more restrictive option would include general voluntary movement restrictions, including measures such as fever screening at entrances of public places, “snow-day” or “shelter-in-place” quarantines, closing public places, canceling public gatherings, and restricting mass transit. Rarely, in the most extreme circumstances, compulsory movement restrictions, including the closing of airports and borders, would be warranted.

Advance planning is necessary to enable officials to assess risk, make decisions, and implement necessary measures as effectively as possible in the event of a disease outbreak. Jurisdictions should establish an emergency operations center structure and a legal preparedness plan, and forge connections among essential partners such as law enforcement officials, first responders, health-care facilities, educators, the media, and the legal community. Provisions must be made to monitor and assess factors such as those above to determine response level for both implementing and scaling back interventions and movement restrictions. Educational message strategies should be developed to disseminate information to government decision makers, health-care providers and first responders, and the public; it will be especially important to address the possibility that some people may experience stigmatization as a result of containment. A draft of the CDC SARS Preparedness Plan entitled, “Public Health Guidance for Community-Level Preparedness and Response to Severe Acute Respiratory Syndrome (SARS) is posted at http://www.cdc.gov/ncidod/sars/updatedguidance.htm. Appendices D and E specifically address Community Containment and Border Strategies, respectively. A SARS preparedness checklist (available at http://www.astho.org) also provides guidance for public health officials in developing such plans.

To plan for case and contact management, jurisdictions should secure necessary protocols for clinical evaluation and monitoring, contact tracing and monitoring, and reporting of disease. Standards, tools, and supplies must be established for home and nonhospital isolation facilities. A telecommunications plan should be developed to provide for case and contact monitoring and fever triage, as well as to provide information to decision makers, health-care workers, and the public. Provisions must be made to ensure that all isolated and quarantined individuals receive food, medicine, and mental health and other supporting services, including transportation to medical facilities. Jurisdictions should also identify and develop assessment procedures for appropriate nonhospital residential facilities. These sites could be used for quarantining contacts or persons for whom “home isolation” is indicated, but who do not have an appropriate “home” environment.

To prepare for the implementation of community containment measures, jurisdictions must establish legal authorities and procedures to implement all levels

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
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FIGURE 1-6 Range of available responses to SARS at borders.

of movement restrictions. Essential personnel for the implementation of quarantine and other movement restrictions will include law enforcement officials, first responders and other deployable government services workers, and key personnel from the transportation, business, and education sectors. Training programs and deployment drills should be developed for these partners, as well as for public health personnel.

Preparing to Respond and Secure National Borders

Similar criteria to those used to determine community-level containment policy must be considered when determining appropriate responses to SARS at national borders (see Figure 1-6). In addition to considering circumstances in their area, officials contemplating movement across national borders must also monitor events in adjacent areas and, given the frequency of global travel, throughout the world. A limited border response could resemble that mounted by the United States in 2003 (i.e., issuing travel advisories and alerts; meeting flights from SARS areas to triage arriving ill passengers; and monitoring contacts for symptoms of illness). More intensive arrival screening could include questionnaires on symptoms and exposure to SARS, temperature screening, or even requiring health certification or registration with the local health department. In some circumstances, predeparture screening also would be appropriate. A further step would be to quarantine arriving passengers from affected areas, and under the most extreme circumstances, restriction of inbound and outbound travel may be necessary.

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
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Conclusion

Modern quarantine represents a wide range of scalable interventions to separate or restrict movement (e.g. detain, isolate, or conditionally release) of individuals or populations infected by or exposed to highly dangerous contagions. These strategies can be an important part of the public health toolbox for suppressing transmission and stopping epidemics such as SARS. However, the ethical implementation of modern quarantine can be resource and labor intensive. Quarantine is most effective when it is tailored to specific circumstances and used in conjunction with other containment measures; people affected by quarantine must be ensured appropriate support services. The effectiveness of quarantine is further improved by comprehensive preparedness planning. Effective communication and public trust are quintessential components; consequently, the public must receive clear messages about the role and importance of quarantine as a means of containing certain infectious disease in advance of, as well as during, the epidemic.

If a future epidemic affects the United States as SARS did other countries in 2003, it may be necessary to recommend quarantine, among other containment measures, in this country. Thus, it is essential that planning for the effective implementation of quarantine and other containment measures be undertaken at every level of government, and well in advance of the need. Strategic and operative plans should be exercised at all levels to expose and rectify gaps and pitfalls in nonurgent settings to ensure our readiness in an emergency.

Acknowledgments

The authors thank Alison Mack, Katherine Oberholtzer, Alexandra Levitt, and Ava Navin for technical assistance in the preparation and review of the manuscript.

IMPACTS OF SARS ON HEALTH CARE SYSTEMS AND STRATEGIES FOR COMBATING FUTURE OUTBREAKS OF EMERGING INFECTIOUS DISEASES

Abu Saleh M. Abdullah,9Brian Tomlinson,10G. Neil Thomas,9and Clive S. Cockram10

Severe acute respiratory syndrome (SARS), resulting from a novel coronavirus, originated in November 2002 in, Guangdong Province, China. By February 2003 it had spread to Hong Kong and subsequently to 32 countries or regions on most continents, infecting about 8,098 patients and resulting in 774 deaths

9  

Department of Community Medicine, The University of Hong Kong.

10  

Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong.

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
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(WHO, 2003k). The overall case fatality ratio is approximately 15 percent (WHO, 2003b). The nonspecific disease presentation, coupled with a long incubation period and the initial absence of a reliable diagnostic test, limited the understanding of the magnitude of the outbreak. The outbreak has identified a number of deficiencies in hospital and community infection control systems in Hong Kong. The lessons learned should be applied on a worldwide basis to help prevent the spread of other new infections that may emerge (Abdullah et al., 2003). In this chapter we outline our experience with medical and public health issues that have arisen in dealing with the outbreak of SARS in Hong Kong and suggest appropriate strategies for combating future infections.

The SARS Epidemic in Hong Kong

The first case of SARS to be identified in Hong Kong was a physician, who had been treating patients in Guangzhou. He traveled to Hong Kong on February 21, 2003. He rapidly became ill and was hospitalized, and he died soon after. This doctor apparently was able to warn his medical attendants of the highly infectious nature of his illness based on his own experience. Precautions were taken to prevent the spread of infection, so there were few cases of transmission within the hospital from this case (Tsang et al., 2003).

In contrast, the index case at the Prince of Wales Hospital who was the source of the first large hospital-based outbreak was not known to be highly infectious (Lee et al., 2003; Tomlinson and Cockram, 2003). This patient was admitted before the discovery of the SARS coronavirus and any international recognition of the disease. The clinical picture was that of “typical” community-acquired pneumonia with no suspicious circumstances. This patient was thus treated using standard protocols established for previous cases in Hong Kong—in an eight-bed cubicle of an open general medical ward. Heightened infection control precautions were not instituted.

During the epidemic, cases who were admitted to hospitals who did not show symptoms suggestive of SARS may not have been treated with strict isolation precautions, and this resulted in larger hospital outbreaks in areas such as Hong Kong and Toronto (Simmerman et al., 2003). In Hong Kong, this first received attention when 11 health care workers from the same ward of a hospital went on sick leave simultaneously in early March 2003. At that point different hypotheses were tested and different control measures were instituted to combat the disease. However, the prolonged epidemic affected a total of 1,755 individuals over a period of 3 months in Hong Kong. The last case was confirmed on June 11, 2003.

Learning from the Experience

A few important lessons were learned over the course of the SARS outbreak. Cardiopulmonary resuscitation and endotracheal intubation were identified as

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
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procedures causing very high risk to medical personnel. During some resuscitation procedures and difficult intubations, cases were reported of health care workers becoming infected despite the use of what was believed to be appropriate protective equipment. The use of nebulizers received particular attention in relation to the index patient at the Prince of Wales Hospital in Hong Kong (Lee et al., 2003). Other procedures such as nasopharyngeal aspiration, bronchoscopy, airway suction, and noninvasive ventilation procedures such as Bi-level Positive Airway Procedure (BiPAP) were also suspected to increase the dissemination of infection. It soon became apparent that respiratory secretions were not the only source of transmission of infection. Feces and urine were recognized to be major hazards. Cleaning the patient and the bedding after fecal incontinence, often performed by health care workers less trained in infection control procedures, proved to be a high-risk duty.

Another problem found with the hospital management of SARS patients was that even after implementation of usual infection precautions for staff with gloves, gowns, and face masks, new infections in health care workers continued to occur (Lee and Sung, 2003). These may have been partly related to lapses in following standard procedures and partly because of initial lack of awareness of the mode of spread of the virus. Although it was concluded at an early stage that the infection was spread by droplets, it was not immediately recognized that the virus was so tenacious that it could survive outside the body on surfaces for long periods of time. The estimates of the time that the virus could survive on various surfaces grew longer and longer—from hours to days over the period of the outbreak—as understanding of the virus increased.

Another contributing factor to the spread of infection within hospitals in Hong Kong was probably the relative inexperience of most hospital staff with respiratory pathogens with such a degree of infectivity. In recent years the only common infective respiratory conditions encountered in Hong Kong hospitals have been tuberculosis and influenza, and these generally have been contained quite easily within hospitals without specialized isolation facilities. Lack of experience in dealing with such a novel agent as the SARS coronavirus must have contributed to the high rate of infection within hospitals. This must be addressed by appropriate training, with repeated reinforcement and checking of infection control techniques so that hospital staff are ready for the next emerging infection.

It is also likely that over the years a degree of complacency has developed, and that procedures that should be considered routine, such as washing hands between examining different patients, are no longer strictly implemented. Furthermore, the use of face masks in Hong Kong hospitals was previously a rarity except in operating rooms and designated high-risk areas.

Guidelines need to be developed that are based on the best available evidence. In hospital settings in Hong Kong, such guidelines were established at a relatively early stage of the outbreak (Ho, 2003), but in the general community, it was more difficult to provide clear guidelines apart from applying the principles

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
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of common hygiene. The use of face masks outside of the hospital environment was adopted by a large percentage of the population, but guidelines for the use of this and other preventive measures were often vague and inconsistent.

In the community setting, contact tracing and quarantining of people who had been in close contact with cases who developed SARS was rapidly introduced and was of vital importance in curtailing the spread of the disease and bringing the epidemic to an end (Riley et al., 2003). Again much experience was gained during the course of the outbreak, particularly regarding communication between different sectors of the health services, and mechanisms have been introduced to improve such communications. The initial case of the Guangzhou doctor was reported to the Hong Kong Department of Health, but contact tracing was not initially conducted at the Metropole Hotel where he stayed because there were no other reports of atypical pneumonia related to that hotel and little was understood about the nature of the condition. In retrospect such contact tracing clearly should have been attempted, although it is unlikely that it could have prevented the spread of disease to other countries. The other people who were infected at the hotel would have left Hong Kong soon afterward, at a time when they were still asymptomatic.

International travel provides a means to disseminate an infection like SARS throughout the world. Fortunately few cases seem to have actually acquired the infection during air travel. Although measures were instituted to stop people with fever from traveling by air, those who were incubating the disease and were still asymptomatic would not be identified, so perhaps stricter measures are needed to effectively reduce the risk of spread of such diseases to other countries. The ease and frequency of international travel demand effective channels be established for rapid international communication of information about infectious diseases. Rapid alerting to potential threats will help ensure that appropriate measures can be instituted and official public information can be disseminated to mitigate public alarm.

Conclusion

Based on our current understanding about its pathogenicity and transmissibility, SARS needs to be regarded as a serious disease. Health care workers and service providers should use SARS as an example to prepare themselves with potential measures to combat any future outbreak of infectious disease. The SARS outbreak provides a timely reminder of the importance of the reorganization of health care systems with an international focus to ensure adequate surveillance mechanisms, rapid response to epidemics, effective prevention and control strategies, and maintenance of optimal infrastructure nationally and internationally (Lee and Abdullah, 2003). In advance of future disease outbreaks, countries where no SARS cases have been reported should be prepared with clear national and provincial contingency plans and mechanisms for integrating such plans into an international response (Lee and Abdullah, 2003).

Suggested Citation:"1. SARS: Emergence, Detection, and Response." Institute of Medicine. 2004. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/10915.
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The emergence of severe acute respiratory syndrome (SARS) in late 2002 and 2003 challenged the global public health community to confront a novel epidemic that spread rapidly from its origins in southern China until it had reached more than 25 other countries within a matter of months. In addition to the number of patients infected with the SARS virus, the disease had profound economic and political repercussions in many of the affected regions. Recent reports of isolated new SARS cases and a fear that the disease could reemerge and spread have put public health officials on high alert for any indications of possible new outbreaks. This report examines the response to SARS by public health systems in individual countries, the biology of the SARS coronavirus and related coronaviruses in animals, the economic and political fallout of the SARS epidemic, quarantine law and other public health measures that apply to combating infectious diseases, and the role of international organizations and scientific cooperation in halting the spread of SARS. The report provides an illuminating survey of findings from the epidemic, along with an assessment of what might be needed in order to contain any future outbreaks of SARS or other emerging infections.

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