Severe Acute Respiratory Syndrome (SARS): Global Alert, Global Response

Jun Min Jung

Electronic Discussion sitesMedia

NGOs

MilitaryLaboratoryNetworks

WHO Collaborating Centres/Laboratories Epidemiology and

Surveillance Networks

WHO Regional & Country Offices

Countries/National Disease Control

Centres

UNSister Agencies

FORMALFORMAL

GPHIN

Partnership for global alert and response to infectious Partnership for global alert and response to infectious diseases: network of networksdiseases: network of networks

INFORMALINFORMAL

Surveillance network partners in Asia

Mekong Basin Disease Surveillance (MBDS)

Pacific Public Health Surveillance Network (PPHSN)

ASEAN

APEC

SEAMIC

SEANET

EIDIOR

FluNet

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

• 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: Global Alert: Severe Acute Respiratory Syndrome (SARS)Severe Acute Respiratory Syndrome (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

China (5328)

Singapore (206)

Hong Kong (1755)

Viet Nam (63)

Europe:10 countries (38)

Thailand (9)

Brazil (3)

Malaysia (5)

South Africa (1)

Canada (238)

USA (70)

Outbreaks before 15 March global alert

Colombia (1)

Kuwait (1)

South Africa (1)

Korea Rep. (3)

Macao (1)

Philippines (14)

Indonesia (2)

Mongolia (9)

India (3)

Australia (5)New Zealand (1)

Taiwan (688)

Outbreaks after 15 March global alert

Mongolia (9)

Russian Fed. (1)

Probable cases of SARS by date of onset,Hanoi: n = 62

1 February – 12 June 20031 February – 12 June 2003

0

1

2

3

4

5

6

7

8

9

10

1 Feb. 11 Feb. 21 Feb. 3 March 13 March 23 March 2 April 12 April 22 April 2 May 12 June

Num

ber o

f cas

es

Probable cases of SARS by date of onset,Singapore: n = 206

1 February – 12 June 20031 February – 12 June 2003

Source: Ministry of Health, Singapore, WHO

0

2

4

6

8

10

12

14

1 Feb. 13 Feb. 25 Feb. 9 Mar. 21 Mar. 2 Apr. 14 Apr. 26 Apr. 8 May 20 May 29 May

Num

ber o

f cas

es

12 Jun.

Probable cases of SARS by date of onset,Canada: n = 227*

1 February – 12 June 20031 February – 12 June 2003

Num

ber o

f cas

es

0

1

2

3

4

5

6

7

8

9

10

1 Feb. 13 Feb. 25 Feb. 9 Mar. 21 -Mar. 2 Apr. 14 Apr. 26 Apr. 8 May 20 May 1 Jun. 12 Jun.

* 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

Probable cases of SARS by date of onset,Taiwan: n = 688

1 February – 12 June 20031 February – 12 June 2003

Num

ber o

f cas

es

0

5

10

15

20

25

30

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

0

50

100

150

200

250

300

350

30-Mar-03 13-Apr-03 27-Apr-03 11-May-03 25-May-03 8-Jun-03

date of report

nu

mb

er o

f ca

ses

156 closecontacts

of HCW and

patients

Index case from

Guangdong

Index case from

Guangdong

Hospital 2Hong Kong

4 HCW +2

Hospital 2Hong Kong

4 HCW +2

Hospital 3Hong Kong

3 HCW

Hospital 3Hong Kong

3 HCW

Hospital 1Hong Kong

99 HCW

Hospital 1Hong Kong

99 HCW

Canada12 HCW +

4

Canada12 HCW +

4

Hotel MHong Kong

IrelandIreland

USAUSA

New YorkNew York

Singapore34 HCW +

37

Singapore34 HCW +

37

Viet Nam37 HCW +

?

Viet Nam37 HCW +

?

BangkokHCW

BangkokHCW

4 otherHong Konghospitals28 HCW

4 otherHong Konghospitals28 HCW

Hospital 4Hong KongHospital 4

Hong Kong

B

I

K

F G

ED

CJ

H

A

SARS: chain of transmission among guests SARS: chain of transmission among guests at Hotel Metropole, Hong Kong, 21 Februaryat Hotel Metropole, Hong Kong, 21 February

GermanyHCW +

2

GermanyHCW +

2

As of 26 March,

249 cases have been traced to

the A case

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

Num

ber o

f cas

es

01 Feb. 13 Feb. 25 Feb. 9 Mar. 21 Mar. 2 Apr. 14 Apr. 26 Apr. 8 May 20 May 1 Jun. 9 Jun.

0

20

40

60

80

100

120

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 virus 의 복제

ssRNA – 자신의 RNA 를 mRNA 의 주형으로 사용하는 경우

ssRNA – 자신의 RNA 를 DNA 의 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 syndrome (SARS)

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:

– 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

< 1% < 24 years old6% 25–44 years old

15% 45–64 years old> 50% > 65 years old

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, Conjugation1. Transformation

Transformation, Transduction, Conjugation1. Transformation

Transformation, Transduction, Conjugation2. Transduction

Transformation, Transduction, Conjugation3. Conjugation

Transformation, Transduction, Conjugation3. Conjugation