Transcript SARS: Epidemiology in Action

SARS: An Emerging Infectious
Disease
June 11, 2003
Edward L. Goodman, MD
Emerging Infectious Diseases:
Institute of Medicine Definition
New, reemerging or drug-resistant
infections whose incidence in humans
has increased within the past two
decades….
Major Factors Contributing to
EID
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Human demographics and behavior
Technology and industry
Economic development and land use
International travel and commerce
Microbial adaptation and change
Breakdown of public health measures
Emerging Infectious Diseases USA
1996 - 2003
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Ebola in non human primates, Texas
Racoon rabies, Ohio
Cyclospora gastroenteritis, multiple states
Non imported Malaria, Georgia and Florida
E coli 0157:H7 in apple juice, multiple states
West Nile Virus 1999, NY and now nationwide
Anthrax 2001; Fla., NYC, DC, NJ
Monkeypox: Prairie Dogs to Humans 2003; Wisc
Goals of today’s presentation
• Show the power of epidemiology
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Case definition/revisions
Descriptive epidemiology
Geographic Variation
Clinical findings
Infection Control Recommendations
• Even before knowing an etiology
• Show the extent of modern microbiology
– Virology
– Gene detection technology
– Serology
Epidemiology
• The science of studying diseases in populations
• Examples
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Cholesterol and CAD
Smoking and lung cancer
Tampons and TSS before Staph identified
Defined risk groups for AIDS before HIV identified
• Draws conclusions on transmission and control
even when etiology not known
Epidemiologic Investigation of
an Apparent Outbreak
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Preliminary Case Definition
Compare Features of Cases to Non-cases
Refine Case Definition
Case-control studies
Refine Case Definition multiple times
Investigate Etiology in refined definition group
Define Clinical Features
– comparing proven to unproven cases
Case Report
Radiology of typical case
Lee NEJM 4/7/04
Initial signs of a worldwide outbreak
• February 11, 2003
– Respiratory illness in Guangdong province, China
– 305 cases, 5 deaths since November 16, 2002
• February 26—March 12, 2003
– Disease spreads to large number of health care workers in
Hong Kong and Vietnam
• March 12, 2003
– Global alert for Severe Acute Respiratory Syndrome (SARS)
– CDC offers assistance to the WHO
Preliminary Case Definition
March 19, 2003
Epidemics Within Epidemics
• HIV
– Predominantly MSM/IVDU in US and Europe
– Predominantly heterosexual in Africa
• Lyme Borreliosis
– Predominantly joint disease in US
– Disproportionately CNS disease in Europe
Epidemics within Epidemics
• SARS
– Asia and Canada
• Healthcare Workers and families
– USA
• Mostly imported from Asia
• Little transmission
The Hong Kong connection:
Hotel M
February
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March
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Onset of symptoms
Stayed at Hotel M
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The Hong Kong connection:
Hotel M
February
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March
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B
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Onset of symptoms
Stayed at Hotel M
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The Hong Kong connection:
Hotel M
February
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March
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Onset of symptoms
Stayed at Hotel M
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Spread from Hotel M
Reported as of March 28, 2003
Canada
Guangdong
Province,
China
F,G
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18 HCW
11 close contacts
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Hotel M
Hong
Kong
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Hong Kong SAR
95 HCW
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H,J
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B
Ireland
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0 HCW
I, L,M
C,D,E
I,L,M
>100 close contacts
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C,D,E
Vietnam
Singapore
37 HCW
34 HCW
21 close contacts
37 close contacts
United
States
1 HCW
SARS in Canada
Poutenan et al. NEJM May 15, 2003
Timeline linked Candadian cases
SARS in Greater Toronto Area
JAMA June 4, 2003
Epidemic Curve USA May 30
363 cases
CDC Update June 4, 2003
• WHO reports 8402 cases from 29 countries
– November 1, 2002 – June 4, 2003
– 772 deaths (9.2% CFR)
• US and PR Cases 373, no deaths
– 67 probable, 306 suspect
– 65/67 attributed to international travel
– One each HCW and household contact
Finding the Pathogen
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Pathology
Virology
Gene detection
Classification
Diagnostics
What are Coronaviruses?
• Taxonomy
– Order Nidovirales
• Family Coronaviridiae
– Genus Coronavirus
• Structure: large, enveloped, positivestranded RNA
• Genome: 30,000 nucleotides, the largest of
any RNA virus
Structure
More than you want to know!
• Group 1 and 2 are mammalian
• Group 3 are avian
• Major veterinarian pathogens
– Infectious bronchitis virus
– Feline infectious peritonitis virus
– Transmissible gastroenteritis virus
Enough already!
• Human coronavirus infections
– Group 1 and 2
– 30% of common cold viruses
• SARS human coronavirus (SARS-CoV)
– Urbani strain, named after Italian physician
who succumbed to this virus
– Distinct from other CoV
Relatedness to other
Coronaviruses
Clinical Aspects of
Severe Acute Respiratory Syndrome
(SARS)
• Incubation period 2-10 days
• Onset of fever, chills/rigors, headache, myalgias,
malaise
• Respiratory symptoms often begin 3-7 days after
symptom onset
Symptoms Commonly Reported
By Patients with SARS1-5
Symptom
Fever
Cough
Dyspnea
Chills/Rigor
Myalgias
Headache
Diarrhea
Range (%)
100
57-100
20-100
73-90
20-83
20-70
10-67
1. Unpublished data, CDC. 2. Poutanen SM, et al. NEJM 3/31/03. 3. Tsang KW, et
al. NEJM. 3/31/03 4. Peiris JSM, et al. Lancet 4/8/03 5. Lee N. et al NEJM 4/7/03
Symptoms Reported by Patients With
Diagnostic SARS-CoV Laboratory
Testing, United States, 2003
Symptom
Coronavirus Positive
(n=6) %
Coronavirus Negative
(n=28) %
Fever
100
96
Cough
100
93
Dyspnea
100
61*
Myalgias
83
75
Chills/Rigor
83
68
Headache
67
68
Diarrhea
67
25*
Coryza
17
43
Sore Throat
17
43
*p=.07
Common Clinical Findings in
Patients with SARS1-5
Finding
Range (%)
Examination
Rales/Rhonci
Hypoxia
38-90
60-83
Laboratory
Leukopenia
Lymphopenia
Low platelet
Increased ALT
Increased LDH
Increased CPK
17-34
54-89
17-45
23-78
70-94
26-56
1. Unpublished data, CDC. 2. Booth CM, et al. JAMA 5/6/03. 3. Tsang KW, et al.
NEJM. 3/31/03 4. Peiris JSM, et al. Lancet 4/8/03 5. Lee N. et al NEJM 4/7/03
Clinical Findings in Patients With
Diagnostic SARS-CoV Laboratory
Testing, United States, 2003
Symptom
Coronavirus
Positive
(n=6) %
Coronavirus
Negative
(n=28) %
83
23*
Hypoxia
83
29*
Infiltrates
100
30*
Laboratory
Leukopenia
17
5
Lymphopenia
83
53
Low platelets
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5
Increased ALT
60
17
Examination
Rales/rhonci
*p<.05
Radiographic Features of SARS
• Infiltrates present on chest radiographs in
> 80% of cases
• Infiltrates
– initially focal in 50-75%
– interstitial
– Most progress to involve multiple lobes,
bilateral involvement
Lee N. et al NEJM 4/7/03
Lee N. et al NEJM 4/7/03
Clinical Outcome of Patients
with SARS, 2003
U.S.1
Canada2
Hong Kong3
Hong Kong4
Hong Kong5
Singapore1
n
6
144
10
50
138
178
Progression to
Resp. Failure
(%)
17
14
20
38
14
12
1. Unpublished data, CDC. 2. Booth CM SM, et al. JAMA 5/6/03. 3. Tsang KW, et
al. NEJM. 3/31/03 4. Peiris JSM, et al. Lancet 4/8/03 5. Lee N. et al NEJM 4/7/03
Clinical Outcome of Probable
SARS Cases*, 2003
n
U.S.
Canada
Hong Kong
Singapore
65
146
1654
178
Case
Fatality
Proportion
(%)
0
15
12
13
* http://www.who.int/csr/sarscountry/2003_05_07/en/
Clinical Features Associated with
Severe Disease
• Older Age
• Underlying illness
• ? Lactate dehydrogenase levels
• ? Severe lymphopenia
Transmission
• Probable major modes of transmission
– Large droplet aerosolization
– Contact
• Direct
• Fomite
• Airborne transmission cannot be ruled out
– ? Role of aerosol-generating procedures
• ? Fecal-oral
• Transmission efficiency may vary among
individuals
SARS Virus Survival
• Survive on plastic surfaces: up to 48 hours
• Survival in feces: 2 days (solid) – 4 days
(loose)
• Survival in urine: at least 24 hours
• Source: WHO May 5, 2003
Diagnostic Approach to Patients with
Possible SARS
• Consider other etiologies
– Diagnostic workup
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Chest radiograph
Blood and sputum cultures
Pulse oximetry
Testing for other viral pathogens (e.g.
influenza)
• Consider urinary antigen testing for
Legionella spp. and Streptococcus
pneumoniae
Diagnostic Approach to Patients with
Possible SARS
– Diagnostic workup (continued)
• Save clinical specimens for possible
additional testing
– Respiratory
– Blood
– Serum
• Acute and convalescent sera (>21 days
from symptom onset) should be collected
• Contact Local and State Health Departments
for SARS-CoV testing
Treatment of Patients with SARS
• Most effective therapy remains
unknown
– Optimize supportive care
• Treat for other potential causes of
community-acquired pneumonia of
unknown etiology
Treatment of Patients with SARS
• Potential Therapies Requiring
Further Investigation
– Ribavirin
– ?other antiviral agents
– Immunomodulatory agents
• Corticosteroids
• Interferons
• Others?
Infection Control
• Early recognition and isolation is key
– Heightened suspicion
– Triage procedures
• Transmission may occur during the
early symptomatic phase
– Potentially before both fever and
respiratory symptoms develop
Infection Control
• Isolation
– Hand hygiene
– Contact Precautions (gloves, gown)
– Eye protection
– Environmental cleaning
– Airborne Precautions (N-95 respirator,
negative pressure)
Why Such Variation in
Epidemiology and Outcome?
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Viral variation?
Genetic host susceptibility?
Prevalence of smoking?
In adequate Infection Control Measures?
A Word About Quarantine
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Complex legal process
Poorly understood by lay public
Rarely invoked
Hard to enforce
Every medication has 2 effects. . .
1. The one you want
2. The one you don’t wan
Quarantine/Isolation
Limit transmission
Individual liberties
Economic loss
Social isolation
Social Stigma…
Quarantine/Isolation
…unintended consequences?
Limiting transmission
Maintaining transmission
e.g., HIV, leprosy
EXECUTIVE ORDER 13295: REVISED LIST OF
QUARANTINABLE COMMUNICABLE DISEASES
(a) Cholera; Diphtheria; infectious Tuberculosis; Plague; Smallpox;
Yellow Fever; and Viral Hemorrhagic Fevers
(Lassa, Marburg, Ebola, Crimean-Congo, South American,
and others not yet isolated or named).
(b) Severe Acute Respiratory Syndrome (SARS), which is a
disease associated with fever and signs and symptoms of
pneumonia or other respiratory illness, is transmitted from person
to person predominantly by the aerosolized or droplet route, and, if
spread in the population, would have severe public health
consequences.
President George W. Bush
April 4, 2003
What Next
• Rapid Diagnostic Tests (at present only at CDC)
– Antigen detection
– Gene detection: PCR
– Serology (ELISA and IFA)
• Seroepidemiology
– Prevalence of antibody in healthy persons = 0
– Is there asymptomatic seroconversion?
– Does antibody confer immunity?
What Next?
• Expect epidemic curve to peak and die out
– Warmer weather should reduce transmission
– Fewer susceptibles in community
– Likely another epidemic in 2004
• Since genome sequenced
– Expect progress on determining protective
epitopes, thus leading to
– Candidate Vaccine trials
Summary
In Memory