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Severe Acute Respiratory Syndrome (SARS):
Global Alert, Global Response
Jun Min Jung
Partnership for global alert and response to infectious
diseases: network of networks
WHO Regional
& Country Offices
WHO Collaborating
Centres/Laboratories
Countries/National
Disease Control
Centres
Epidemiology and
Surveillance Networks
Military
Laboratory
Networks
UN
Sister Agencies
GPHIN
NGOs
Media
Electronic
Discussion sites
FORMAL
INFORMAL
Surveillance network partners in Asia
APEC
FluNet
SEAMIC
Mekong
Basin
Disease
Surveillance
(MBDS)
EIDIOR
SEANET
ASEAN
Pacific Public Health
Surveillance Network
(PPHSN)
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: report to WHO office Beijing of outbreak of atypical pneumonia
(WHO)
•
14 February
– Guangdong Province, China: Official confirmation of an outbreak of atypical pneumonia with 305
cases and 5 deaths (China)
•
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)
Intensified surveillance for pulmonary infections,
WHO 2003
•
26 February
– Hanoi, Viet Nam: Official report of 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
•
5 March
– Hanoi, Viet Nam: Official report of 7 medical staff from French Hospital reported with atypical
pneumonia
•
Early March
– Hong Kong, SAR China Official report of 77 medical staff from Hospital reported with atypical
pneumonia`, WHO teams arrive Hong Kong and Hanoi, and with governments advise on
investigation and containment activities
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, 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
Global Alert, 15 March 2003
1) Atypical pneumonia with rapid progression to respiratory failure
2) Health workers appeared to be at greatest risk
3) Unidentified cause, presumed to be an infectious agent
4) Antibiotics and antivirals did not appear effective
5) Spreading internationally within Asia and to Europe and
North America
Global Alert:
Severe Acute Respiratory Syndrome (SARS)
•
15 March: Second global alert
• 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
Global Alert:
Severe Acute Respiratory Syndrome (SARS)
•
1 April:
Evidence accumulating from exported cases that three criteria were potentially increasing
international spread:
– magnitude of outbreak and number of new cases each day
– pattern of local transmission
– exportation of probable cases
•
2 April to present:
Guidance provided to general public to postpone non-essential travel to areas with local
transmission that met above criteria
SARS: cumulative number of probable cases worldwide as of 12
June 2003 – Total: 8 445 cases, 790 deaths
Canada (238)
Europe:
10 countries (38)
Russian Fed. (1)
Mongolia (9)
China (5328)
USA (70)
Kuwait (1)
Korea Rep. (3)
Macao (1)
Hong Kong (1755) Taiwan (688)
India (3)
Viet Nam (63)
Malaysia (5)
Colombia (1)
Singapore (206)
Brazil (3)
Indonesia (2)
Philippines (14)
Thailand (9)
South Africa (1)
Outbreaks before 15 March global alert
Outbreaks after 15 March global alert
Australia (5)
New Zealand (1)
Probable cases of SARS by date of onset,
Hanoi: n = 62
1 February – 12 June 2003
10
9
Number of cases
8
7
6
5
4
3
2
1
0
1 Feb.
11 Feb.
21 Feb.
3 March
13 March 23 March
2 April
12 April
22 April
2 May
12 June
Probable cases of SARS by date of onset,
Singapore: n = 206
14
1 February – 12 June 2003
12
Number of cases
10
8
6
4
Source: Ministry of
Health, Singapore, WHO
2
0
1 Feb.
13 Feb. 25 Feb. 9 Mar.
21 Mar. 2 Apr.
14 Apr. 26 Apr. 8 May
20 May 29 May
12 Jun.
Probable cases of SARS by date of onset,
Canada: n = 227*
1 February – 12 June 2003
10
9
8
Number of cases
7
6
* As of 12 June 2003, 11
additional probable cases
of SARS have been reported
from Canada for whom no dates
of onset are available.
Source: Health Canada
5
4
3
2
1
0
1 Feb.
13 Feb.
25 Feb.
9 Mar.
21 -Mar.
2 Apr.
14 Apr.
26 Apr.
8 May
20 May
1 Jun.
12 Jun.
Probable cases of SARS by date of onset,
Taiwan: n = 688
1 February – 12 June 2003
30
Number of cases
25
20
15
10
5
0
1 Feb.
13 Feb.
25 Feb.
9 Mar.
21 Mar.
2 Apr.
14 Apr.
26 Apr.
8 May
20 May
1 Jun.
12 Jun.
Probable cases of SARS by date of onset,
Beijing: n = 2,522
350
300
number of cases
250
200
150
100
50
0
30-Mar-03
13-Apr-03
27-Apr-03
11-May-03
date of report
25-May-03
8-Jun-03
SARS: chain of transmission among guests
at Hotel Metropole, Hong Kong, 21 February
Hospital 2
Hong Kong
4 HCW +
2
156 close
contacts
of HCW
and
patients
Index case
from
Guangdong
Hospital 3
Hong Kong
3 HCW
Hospital 1
Hong Kong
99 HCW
4 other
Hong Kong
hospitals
28 HCW
Ireland
K
Hotel M
Hong Kong
J
B
Hospital 4
Hong Kong
C
D
I
E
USA
Viet Nam
37 HCW +
?
Singapore
34 HCW +
37
Bangkok
HCW
As of 26
March,
249 cases
have been
traced to
the A case
F G
A
H
Canada
12 HCW +
4
Germany
HCW +
2
New York
Source: WHO/CDC
Airport screening and health information,
Hong Kong, SARS, 2003
Probable cases of SARS by date of onset,
Hong Kong: n = 1 753, as of 9 June 2003
120
100
Number of cases
80
60
40
20
0
0
1 Feb. 13 Feb.
25 Feb.
9 Mar.
21 Mar.
2 Apr.
14 Apr.
26 Apr.
8 May
20 May
1 Jun.
9 Jun.
SARS and the economy:
impact on global travel, Hong Kong
SARS and the economy:
impact on global travel, Singapore
Virus
Phage Virus – Lytic & Lysogenic cycle
dsDNA, ssDNA virus의 복제
ssRNA – 자신의 RNA를 mRNA의 주형으로 사용하
는 경우
ssRNA – 자신의 RNA를
DNA의 주형으로 사용하는 경우
Structure and Composition
• Enveloped
– Spike proteins resemble solar corona or
crown
• 120-160 nm
• Positive-strand RNA (27-32 kb)
• Cytoplasmic replication
• Budding into ER and Golgi
• Notoriously difficult to propagate in culture
• High frequency of recombination
• Cause colds and severe acute respiratory
Coronavirus Infections
•
Pathogenesis
– Limited knowledge
– Highly species-specific
– Typically mild upper respiratory infections (“colds”) that remain localized
• Exception: SARS
– Immunity is not durable
• Many people become resusceptible after a few years
•
Laboratory Diagnosis
– ELISA - may not discriminate past infections
– HA
– PCR
– Virus isolation is difficult (often impossible) and requires great expertise
Severe Acute Respiratory Syndrome
•
Initial outbreak in SE Asia
– Hong Kong and Singapore first reported
– Disease originated in China
– Originally thought to be from wild game markets
• Palm civet cat (which isn’t a cat) - Paradoxurus hermaphroditus
• Raccoon dog (which isn’t a dog) - Nyctereutes procyonoides
– It is a bat virus
• Chinese horseshoe bats (Rhinolophus sinicus)
• No virus isolation
– Amplification of coronavirus RNA from anal swabs
– Serology
– It is highly-similar, but not identical to SARS-CoV
» Mutations have most likely occurred in transmission from bats
to civets to humans
» Reverse genetics of SARS-CoV and some bat viruses has been
done
– No animal pathogenesis model
SARS CoV
Coronavirus Phylogeny
Chymotrypsin-like protease (3CLpro), RNA-dependent RNA polymerase (Pol), spike
(S), and nucleocapsid (N)
SARS Pathogenesis
• Virus is transmitted by respiratory and fecal routes
• Infection is mediated by human angiotensin-converting enzyme 2 (hACE2)
receptor
– High expression
• Lung alveolar epithelial cells
• Intestinal enterocytes
– Low expression
• Blood vessels (virtually all organs)
• Pneumonia
– Cause of death is lung failure
SARS: what more we know
3 months later
1) Atypical pneumonia with rapid progression to respiratory failure:
– Case fatality rate by age group:
< 1%
6%
15%
> 50%
< 24 years old
25–44 years old
45–64 years old
> 65 years old
– 85% full recovery
– Incubation period: 3–10 days
2) Health workers appeared to be at greatest risk
– Health workers remain primary risk group in second generation
– Others at risk include family members of index cases and health workers, and their contacts
– Majority of transmission has been close personal contact; in Hong Kong environmental factors caused localized
transmission
SARS: what more we know
3 months later
3) Unidentified cause, presumed to be an infectious agents
– Aetiological agent: Coronavirus, hypothesized to be of animal origin
– PCR and various antibody tests developed and being used in epidemiological studies, but PCR
lacks sufficient sensitivity as diagnostic tool
4) Antibiotics and antivirals did not appear effective
– Studies under way to definitively provide information on effectiveness of antivirals alone or in
combination with steroids, and on use of hyperimmune serum in persons with severe disease
– Case detection, isolation, infection control and contact tracing are effective means of
containing outbreaks
– Meeting 30 April at NIH to examine priorities in drugs and vaccine developments
SARS:
what we are learning
•
In the world today an infectious disease in one country is a threat to all: 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
despite heavy pressure to publish academically
•
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
PCR – Polymerase Chain Reaction
PCR – Polymerase Chain Reaction
Transformation, Transduction, Conjugation
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Transformation, Transduction, Conjugation
1. Transformation
Transformation, Transduction, Conjugation
2. Transduction
Transformation, Transduction, Conjugation
3. Conjugation
Transformation, Transduction, Conjugation
3. Conjugation