The WHO Response to SARS, and Preparations for the Future Global Alert and Response

1. The WHO Response to SARS, and Preparations for the FutureGlobal Alert and Response Institute of Medicine Forum on Microbial Threats Learning from SARS: Preparing for the Next Disease Outbreak Washington 30 September 2003

2. SARS: a puzzling and new disease • SARS is the first severe and readily transmissible new disease to emerge in the 21st century. • Much about the disease remains poorly understood. • SARS has shown a clear capacity for spread. • High morbidity and a global case fatality rate of 9.5%. • There was unprecedented international cooperation in efforts to identify, contain and control SARS. This presentation will briefly describe the chronology of the outbreak, and then discuss the WHO response and mechanisms involved in the response, and finally address some of the issues of current concern.

3. Reports of respiratory infection, WHO global surveillance networks, 2002–2003 • 27 November • Guangdong Province, China: Non-official report of outbreak of respiratory illness with government recommending isolation of anyone with symptoms (GPHIN) • 11 February • Guangdong Province, China: WHO received a report from the Chinese MOH of an outbreak of acute respiratory syndrome with 305 cases and 5 deaths (WHO) • 19 February • Hong Kong, SAR China:Official report of 33-year male and 9 year old son in Hong Kong with Avian influenza (H5N1), source linked to Fujian Province, China (Hong Kong- FluNet)

4. Intensified surveillance for pulmonary infections, WHO 2003 • 21 February - Hong Kong: A medical doctor from Guangdong checks into the 9th floor of a hotel in Hong Kong; he had treated patients with atypical pneumonia prior to departure • 28 February - Hanoi, Viet Nam:Report to WHO-WPRO from Dr Carlo Urbani of a 48-year-old business man with high fever (> 38 ºC), atypical pneumonia and respiratory failure with history of previous travel to China and Hong Kong • 4 – 10 March - Hong Kong/ Hanoi: Reports of medical staff from Kwong Wah Hospital (Hong Kong) and French Hospital (Hanoi) with atypical pneumonia • 10 March - WHO teams arrive Hong Kong and Hanoi, and with governments begin investigation and containment activities

5. Global Alert:Severe Acute Respiratory Syndrome (SARS) • 12 March:First global alert- describing atypical pneumonia in Viet Nam and Hong Kong • 14 March - Four persons Ontario and three persons in Singapore, with severe atypical pneumonia fitting description of 12 March alert reported to WHO • 15 March - Medical doctor with atypical pneumonia fitting description of 12 March reported by Ministry of Health, Singapore on return flight from New York

6. Global Alert: Severe Acute Respiratory Syndrome (SARS) • 15 March: Second global alert/first travel advisory • Case definition provided • Name (SARS) announced • Advice given to international travellers to raise awareness • 26 March: Evidence accumulating that persons with SARS continued to travel from areas with local transmission, and that adjacent passengers were at small, but non-quantified risk • 27 March: Guidance provided to airlines and areas with local transmission to screen passengers leaving in order to decrease risk of international travel by persons with SARS • 28 March: Confirmation by the first WHO mission to China that the cases of atypical pneumonia in Guangdong Province were consistent with the case definition of SARS, and data from Guangdong suggestive of an animal/food association.

7. First WHO Mission to China Several important findings: • Confirmed that the atypical pneumonia in Guangdong was due to SARS; • Changed the WHO case definition by back-dating the earliest recognisable cases to mid-November; • From data provided by Guangdong CDC, suggested there was an association between food preparation/food source and SARS, perhaps as a zoonosis.

8. First WHO mission to China • The Mission clearly warned the Chinese MOH: ‘If SARS is not brought under control in China, there will be no chance of controlling the global threat of SARS’. • Many problems: • Lack of good surveillance systems in place; • The ability of the MOH to obtain information from Provinces was not clear; • Strong belief by the Chinese CDC that the epidemic was caused by a chlamydia; • Unaware that many hospitals were not under MOH control.

9. Spreading internationally within Aasia and to Europe and North America 26 March - Evidence accumulating that persons with SARS continued to travel from areas with local transmission, and that adjacent passengers in aircraft were at small but non-quantified risk. 27 March - Guidance provided to airlines and areas with local transmission to screen passengers leaving in order to decrease risk of international travel by persons with SARS. • Only 1 major new outbreak occurred after 15 March despite initial exported cases to a total of 30 countries. • Symptomatic persons with SARS no longer travelling internationally. • Prior to 23 March, 27 persons on 4 of 32 international flights believed to be carrying symptomatic persons with SARS, appear to have been infected (1 flight alone on 15 March has accounted for 22 of these 27 cases); no known SARS cases have travelled by air after this date.

10. Continued chronology of the epidemic • March-April - cluster in a housing estate in Hong Kong (Amoy Gardens). • 28 April - Viet Nam became the first country to stop local transmission of SARS. • Last cases of SARS reported to WHO in mid-June 2003. • 5 July 2003 - WHO announced that the last human chain of SARS transmission had been broken. • New WHO guidance for SARS vigilance in the post-outbreak period released globally on 14 August 2003.

11. A global epidemic • Cases reported by 30 countries in 6 continents based on WHO’s surveillance case definition. • Cumulative total 8098 cases and 774 deaths; 21% HCWs. • Almost exceeded the surge capacity of acute care facilities and public health services. • Social, political and economic impact, including psychosocial impact. • Estimated economic cost of $US30 billion (Stanley Morgan); $US100 billion (Nature); $US48 billion in China alone (Chinese Center for Economic Research)

12. Routes of transmission and infectious dose • Contact and droplet spread through close person to person contact • Within 1 metre • Sustained exposure or short, intense exposure • Breaches in infection control • Aerosol generating procedures • Fomites (intense environmental contamination in hospitals, Hotel M, Amoy Gardens) • ?Faecal-oral (Amoy Gardens) • ?Faecal inhalation (Amoy Gardens) • ?Aerosolisation rarely (airline transmission)

13. Controlling the outbreak • Effective “traditional” public health measures implemented before aetiological agent known. • Surveillance. • Active case finding, case isolation and case management • Fever screening, fever clinics etc to reduce detection time. • Stringent infection control and use of PPE. • Contact tracing, contact education and voluntary home quarantine. • Applied research – international collaboration. • Risk communication.

14. The course of the epidemic

15. Origins of SARS • Limited data on the role of animals as reservoirs and in transmission. • Available data • SARS-CoV genetically distinct from other coronaviruses • Early SARS cases associated with wildlife markets, care and slaughter of wildlife for human consumption • Wildlife handlers seroconverted, possibly asymptomatically or after a mild illness • Wildlife show evidence of the SARS-CoV-like virus

16. The WHO Response • The WHO response to the SARS outbreak was largely undertaken and coordinated by the Department of Communicable Diseases, Surveillance and Response (CSR) through its Global Alert and Response (GAR) Division, by the WHO Western Pacific Regional Office, and by the WHO Country Offices. • WHO did not have the surge capacity in either Geneva or Manila, but personnel were brought in to help from UK, Canada, USA, Australia, Germany, France and other country heath services to cope with the surge requirements. • The ability to mount the response was in due in large part to the Global Outbreak Alert and Response Network (GOARN) – a partnership between WHO and over 115 partners.

17. Outbreak alert and response • Prior to SARS, WHO’s Global Alert and Response group had only had to deal with single-country outbreaks – SARS was the first international outbreak. • Even responding to a number of single-country outbreaks was proving difficult for WHO, both in terms of personnel and resources, and for both verification and control activities. • Thus, the Global Outbreak Alert and Response Network was established.

18. No single institution has all the capacity! The Challenge Outbreak Alert and Response • Timely detection and verification of outbreak events • Rapid and effective response to: • reduce human suffering • contain international spread • minimize impact on travel and trade • Sustained epidemic preparedness at all levels WHO brings partners together to focus global resources on the problem

19. E P I D E M I C A L E R T & R E S P O N S E I N T E R N A T I O N A L H E A L T H R E G U L A T I O N S Contain known risks Respond to the unexpected Improve preparedness G L O B A L P A R T N E R S H I P

20. Alert and Response Operations at WHO Intelligence • WHO Operational Support Team • HQ - Geneva • 6 Regional Offices • 141 WHO country offices • WHO outbreak event management system • a human process • supported by IT tools Verification Response Follow-up

21. National Preparedness WHO BTW Working Group Information Management Public Media Global Health Security - WHO Alert and Response Operations Alert Logistic support Coordination of Response International Health Regulations Global Outbreak Alert and Response Network Operations Centre Disease Specific Programmes Viral Haemorrhagic Fevers Epidemic Bacterial Diseases Epidemic Diarrhoeal Diseases Zoonoses Influenza Programme on Chemical Safety Others Response: Technical Assistance to Regional Offices, Country Offices and Member States

22. Global Outbreak Alert and Response Network A “Network of Networks” • A technical partnership of 115 institutions and other networks who mobilize and pool resources for outbreak alert and response • Contain outbreaks by rapid identification, verification and communication of threats • Deliver appropriate technical assistance to affected state(s) • Contribute to long-term outbreak preparedness

23. A “Network of Networks” • Public Health Laboratory Service, UK • Centers for Disease Control, Atlanta • Health Canada • GEIS, USA • Pacific Public Health Surveillance Network (PPHSN) • CEE-Baltics Network • EU Surveillance Network • MSF Family (MSF-INT, MSF-F, MSF-B, MSF-H, MSF-CH, MSF-E) • WHO Collaborating Centre Network ( > 250 laboratories) • Amazon and Southern Cone Networks • Mekong Basin Disease Surveillance Networks • Epicentre, Paris • Institute Pasteur Network • Many others…

24. Global Outbreak And Response Network • The GOARN network is a partnership between WHO and technical institutions, networks and individuals aimed at fighting outbreaks. • Formally recognised by the World Health Assembly in 2001 (WHA 2001). • For SARS, GOARN provided a framework for “field collaboration” on a global scale. • Supporting collaboration among clinicians, epidemiologists, laboratory scientists amongst others.

25. Alert and Response Operations Global Outbreak Alert and Response Network World Health Organization HQ Departments Regional Offices WROs 110 partner institutions and networks Formal WHO laboratory networks, regional/sub-regional networks, WROs & MoH, UNOs Informal Global Public Health Intelligence Network (Media), NGOs Epidemic Intelligence Verification/Confirmation Official Sources e.g. WRO, MoH Unofficial Sources e.g. NGOs, WHO CCs Risk Assessment Response Co-ordination Epi/Lab Investigation Public Information Case Management Prevention incl. Env. Control Measures

26. The role of WHO in the SARS outbreak • SARS Global alert 12 and 15 March, 2003. • Travel recommendations - to government, industry& the public. • Global surveillance - case definitions, risk assessment. • Creation of SARS virtual networks. • Guidance documents or statements: • surveillance case definitions, global case count, epidemic curves, CFR • clinical case description, clinical alert, diagnosis and clinical management of patients and contacts, hospital infection control, discharge policy • laboratory sampling and testing of SARS-CoV, laboratory case definitions, virus stability and resistance, virus detection and survival in food and water, • food safety, blood safety, biosafety guidelines for handling SARS specimens.

27. 12 March: WHO issues a Global alert

28. 15 March: WHO issues emergency travel advice

29. WHO SARS web site http://www.who.int/csr/sars http://www.who.int/csr/sars

30. Respond to the unexpected - the operational response to SARS • Global reporting system, rumour management and verification • information sources (media, NGOs, other UN agencies, and partners in the Global Outbreak Alert and Response Network (GOARN) • On the ground support to affected areas (STC recruited through GOARN; 60+ teams placed in the field) • Focusing global resources in applied research through SARS working groups/networks • Daily teleconference networks, including epidemiology network, clinical network, and laboratory network: crucial in understanding the epidemic and finding the aetiological agent • Face to face meetings of various WGs in Geneva & in Kuala Lumpur • Applied research focus changing in light of new knowledge eg animal studies

31. WHO Alert & Response I N T E R N A T I O N A L H E A L T H R E G U L A T I O N S Contain known risks Respond to the unexpected Improve preparedness WR Vietnam WR China WR Thailand G L O B A L P A R T N E R S H I P Regional Offices: WPRO, AMRO, EURO Responding to SARS Communication G L O B A L A L E R T & R E S P O N S E Travel-related Recommendations Global Influenza Programme Epidemic Intelligence Capacity strengthening GOAR Network

32. WHO Alert & ResponseResponding to SARS • Global partnership fully used(e.g. WHO Influenza GLN; GOARN) • WHOGlobal network fully mobilised(e.g. Regular global teleconference with Field teams, Country Offices, Regional Offices, HQ) WHO Geneva WHO Beijing WHO Hanoi

33. Can SARS be eradicated? • Key question at the WHO Global Meeting on SARS, Kuala Lumpur, Malaysia, 17-18 June 2003. • Synthesis of breakout groups • Epidemiology • Laboratory • Animal studies • Environmental health • Modelling SARS • Conclusion – too early to say. “Hope for the best, prepare for the worst” (Margaret Chan, Hong Kong SAR)

34. Rationale for continued vigilancefor SARS • Increasing evidence of an animal reservoir in southern China that may re-seed the human population. • Concern of transmission below the level of detection by “routine surveillance”. • The possible re-introduction through a laboratory-acquired infection. • Possible seasonal recurrence seen with other human coronaviruses. Reappearance during the influenza season? • WHO guidance for SARS vigilance in the post-outbreak period, released globally on 14 August 2003, and is available on the WHO SARS website.

35. Objectives of WHO SARS Alert guidelines 1 • To provide early warning of the potential recurrence of SARS to: • rapidly implement appropriate infection control measures • expedite diagnosis • activate the public health response • To raise a global alert if indicated

36. Underlying assumptions • The first cases or clusters of SARS may be missed (and hence the importance of “false alarms” in testing the system). • Epidemiological linkage no longer useful in defining incident SARS cases. • SARS alert still relies on syndromic surveillance • non-specific clinical features of SARS • lack of a rapid diagnostic test that can reliably detect SARS-CoV in the first few days of illness • seasonal occurrence of other respiratory diseases, including influenza and other human coronaviruses.

37. Risk assessment • Potential zone of re-emergence of SARS-CoV • Identified as source(s) of the previous outbreak in November 2002 or areas with an increased likelihood of animal to human transmission of SARS-CoV infection. • Nodal areas • Sustained local transmission experienced during the previous outbreak or entry of large numbers of persons from the potential zone of re-emergence of SARS-CoV. • Low risk areas • Never reported cases, reported only imported cases or experienced only limited local transmission during the previous outbreak.

38. Staged approach to surveillance • Potential zone of re-emergence of SARS • SARS Alert • Enhanced surveillance for SARS • Special studies for SARS-CoV infections in animal and human populations • Nodal areas • SARS Alert • Enhanced surveillance for SARS • Low risk areas • SARS Alert

39. Definition of a SARS “Alert” • Two or more health care workers in the same health care unit fulfilling the clinical case definition of SARS and with onset of illness in the same 10-day period. OR • Hospital acquired illness in three or more persons (health care workers and/or other hospital staff and/or patients and/or visitors) in the same health care unit fulfilling the clinical case definition of SARS and with onset of illness in the same 10-day period. • Cluster and unit size should be determined at the local level and reflect local experience.

40. SARS Clinical case definition • Fever (38°C) AND • One or more symptoms of lower respiratory tract illness (cough, difficulty breathing, shortness of breath) AND • Radiographic evidence of lung infiltrates consistent with pneumonia or RDS OR autopsy findings consistent with the pathology of pneumonia or RDS without an identifiable cause AND • No alternative diagnosis can fully explain the illness.

41. SARS Laboratory case definition • PCR positive for SARS-CoV (2 different clinical specimens OR sequential sampling from the same site OR  2 assays or repeat PCR using a new RNA extract from the original clinical sample on each occasion of testing) OR • Seroconversion or 4-fold or greater rise in titre between acute and convalescent phase sera by ELISA or IFA OR • Virus isolation with PCR validation.

42. International reporting of SARS • The reappearance of SARS in the human population would be considered a global public health emergency. • A SARS outbreak defined as the occurrence of 1 clinically compatible, laboratory-confirmed case of SARS in any country based on definitive laboratory investigations. • Inform WHO of laboratory-confirmed cases only. • WHO will continue to identify and verify rumours of events of international public health concern through its existing mechanisms.

43. Problems in the surveillance planning • The post-outbreak plan must be seen as a living document, and indeed it continues to be developed and fine-tuned. • SARS-CoV, like all viruses, undoubtedly causes a range of symptoms, from the inapparent through the mild to severe infections – the plan does not take this range of presentations into account. • Thus, if there is continued community transmission, there might be atypical clinical presentations with laboratory confirmation, especially in a potential zone of re-emergence or a nodal area. • However, at this time, no community transmission has been recognised.

44. Laboratory diagnosis and biosafety: current concerns and future directions • Events over the past two months in Canada, Singapore and Hong Kong have clearly shown major weaknesses in the specificity and sensitivity of laboratory diagnostic procedures. • In addition, the laboratory-acquired case in Singapore has raised some major concerns about the potential for the re-emergence of SARS through a laboratory accident, especially in the belief that community transmission has been interrupted. • These matters will be discussed by a face-to-face meeting of the major laboratory network members and additional partners.

45. Laboratory diagnosis: major issues • WHO priorities for SARS diagnostics • Strenghtening and expanding laboratory networks • Establishing an inventory of test protocols and reagents • Collating and sharing testing algorithms • Establishing an international multi-centre evaluation process of assay protocols and reagents • Establishing an international QA mechanism for SARS tests • Establishing standardised panels of positive samples and reference reagents • WHO will also strongly recommend that in the post-outbreak period, there should be an international verification process for any specimen found to be positive for SARS CoV infection in anexternal reference laboratory.

46. SARS Research Advisory Committee • One of the major suggestions at the SARS Conference in Kuala Lumpur was to establish a SARS public health Research Advisory Committee to identify and prioritise new applied research demands across all disciplines requiring WHO co-ordination and facilitation. This meeting is scheduled for 20-21 October. • It will address many of the areas of continuing concern, such as the possible animal reservoir, super-spreading events, virus persistence, laboratory issues and biosafety, clinical presentations and range of symptoms, etc

47. Lessons from SARS • Infectious diseases do not respect international borders. • Information and travel guidance can contain the international spread of an infectious disease. • Experts in laboratory, epidemiology and patient care can work together for the public health good. • Emerging infectious disease outbreaks often have an unnecessary negative economic impact on tourism, travel and trade. • Infectious disease outbreaks reveal weaknesses in public health infrastructure. • Emerging infections can be contained with high level government commitment and international collaboration if necessary.