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The WHO Response to SARS, and
Preparations for the Future
Global Alert and Response
Institute of Medicine
Forum on Microbial Threats
Learning from SARS: Preparing for the Next Disease Outbreak
Washington
30 September 2003
E P I D E M I C
A L E R T
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R E S P O N S E
1
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.
E P I D E M I C
A L E R T
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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)
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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
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Global Alert:
Severe Acute Respiratory Syndrome (SARS)

12 March: First global alert - describing atypical

14 March - Four persons Ontario and three persons in Singapore, with

15 March - Medical doctor with atypical pneumonia fitting description of
pneumonia in Viet Nam and Hong Kong
severe atypical pneumonia fitting description of 12 March alert reported
to WHO
12 March reported by Ministry of Health, Singapore on return flight from
New York
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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.
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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.
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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.
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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.
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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.
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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)
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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)

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?Faecal-oral (Amoy Gardens)

?Faecal inhalation (Amoy Gardens)

?Aerosolisation rarely (airline transmission)
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Controlling the outbreak
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Effective “traditional” public health measures implemented before
aetiological agent known.
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Surveillance.
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Active case finding, case isolation and case management
– Fever screening, fever clinics etc to reduce detection time.

Stringent infection control and use of PPE.
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Contact tracing, contact education and voluntary home quarantine.

Applied research – international collaboration.
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Risk communication.
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The course of the epidemic
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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
E P I D E M I C
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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.
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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.
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The Challenge
Outbreak Alert and Response

Timely detection and verification of outbreak events

Rapid and effective response to:
No single institution
– contain international spread
has all the capacity!
– reduce human suffering
– minimize impact on travel and trade

Sustained epidemic preparedness at all levels
WHO brings partners together to focus global resources on
the problem
E P I D E M I C
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EPIDEMIC ALERT & RESPONSE
I N T E R NAT I O NAL H EALT H R E G U LAT I O N S
Contain
known risks
Respond to
the unexpected
Improve
preparedness
G LO BAL PARTN E R S H I P
E P I D E M I C
A L E R T
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R E S P O N S E
Alert and Response Operations at WHO
Intelligence
 WHO Operational Support Team
• HQ - Geneva
• 6 Regional Offices
• 141 WHO country offices
Verification
 WHO outbreak event management
system
• a human process
• supported by IT tools
Response
Follow-up
E P I D E M I C
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Global Health Security - WHO
Alert and Response Operations
Logistic
support
Alert
Coordination of
Response
International Health Regulations
Global Outbreak Alert and Response Network
National Preparedness
WHO BTW Working Group
Operations
Centre
Information
Management
Disease Specific Programmes
PublicMedia
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
E P I D E M I C
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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
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A “Network of Networks”
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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…
E P I D E M I C
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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.

E P I D E M I C
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Alert and Response Operations
Formal
Epidemic
Intelligence
WHO laboratory networks,
regional/sub-regional networks,
WROs & MoH, UNOs
Official Sources
e.g. WRO, MoH
Informal
Global Public Health Intelligence
Network
(Media), NGOs
Verification/Confirmation
Unofficial Sources
e.g. NGOs, WHO CCs
Risk Assessment
World Health Organization
Response
Co-ordination
HQ Departments
Regional Offices
WROs
Epi/Lab
Investigation
Global Outbreak Alert
and Response Network
Prevention incl.
Env. Control Measures
E P I D E M I C
A L E R T
110 partner institutions
and networks
Case
Management
A N D
R E S P O N S E
Public
Information
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.
E P I D E M I C
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12 March: WHO issues a Global alert
E P I D E M I C
A L E R T
A N D
R E S P O N S E
15 March: WHO issues emergency travel
advice
E P I D E M I C
A L E R T
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R E S P O N S E
WHO SARS web site
http://www.who.int/csr/sars


Latest information
Cumulative cases
Current cases

WHO travel recommendations
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Press releases

Daily updates

WHO guidelines
Blood safety
Case definitions
Case management
Infection control
Laboratory diagnosis
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WHO collaborative networks
Clinical
Epidemiology
Global Outbreak Alert & Response Network
Laboratory
http://www.who.int/csr/sars
E P I D E M I C
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R E S P O N S E
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

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Face to face meetings of various WGs in Geneva & in Kuala Lumpur
Applied research focus changing in light of new knowledge eg animal
studies
E P I D E M I C
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R E S P O N S E
WHO Alert & Response
Responding to SARS
Communication
GLOBAL ALERT & RESPONSE
Recommendations
I N T E R N A Travel-related
TIONAL HE
ALTH REGULATIONS
Contain
known risks
Respond to
the unexpected
Global
Influenza
Programme
Epidemic
Intelligence
Improve
preparedness
Capacity
strengthening
GOAR
Network
WR Vietnam
WR China
WR Thailand
Regional
AMRO,
G L O BOffices:
A L P AWPRO,
RTNE
R S H EURO
IP
E P I D E M I C
A L E R T
A N D
R E S P O N S E
WHO Alert & Response
Responding to SARS
 Global partnership fully used (e.g. WHO Influenza GLN; GOARN)
 WHO Global network fully mobilised (e.g. Regular global teleconference
with Field teams, Country Offices, Regional Offices, HQ)
WHO Geneva
WHO Beijing
E P I D E M I C
A L E R T
A N D
WHO Hanoi
R E S P O N S E
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)

E P I D E M I C
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Rationale for continued vigilance
for SARS

Increasing evidence of an animal reservoir in southern China that may reseed 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.
E P I D E M I C
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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
E P I D E M I C
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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.
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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.
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Staged approach to surveillance

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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
E P I D E M I C
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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.
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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
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No alternative diagnosis can fully explain the illness.
E P I D E M I C
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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.
E P I D E M I C
A L E R T
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R E S P O N S E
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.
E P I D E M I C
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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.
E P I D E M I C
A L E R T
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R E S P O N S E
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 reemergence 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.
E P I D E M I C
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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 an external reference laboratory.
E P I D E M I C
A L E R T
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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
E P I D E M I C
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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.

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Infectious disease outbreaks reveal weaknesses in public health infrastructure.
Emerging infections can be contained with high level government commitment and
international collaboration if necessary.
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E P I D E M I C
A L E R T
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R E S P O N S E