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GIDSAS
PART IV: The Disease
Chotani, 2003
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SARS: What do we know so far?
Viral infection – a new mutation of
coronavirus
Affects all age groups, highest number
of deaths have been among people
with pre-existing chronic conditions
Suspected to have originated in
Guandong, China
Causes atypical pneumonia in infected
patients.
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Methods Of Transmission
Most frequent method of
transmission of coronavirus from
person to person is droplet
transmission
If the sick person coughs or sneezes,
the virus can be carried in saliva
droplets to people nearby, infecting
them
Environmental transmission from
sewer/water, cockroach, and fomites
implicated
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Wayne Stayskal, Tampa Tribune, 4/26/03
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Airborne Transmission
Coronavirus family also has the
property of surviving in dry air/surfaces
for up to 3 hours.
In these conditions, the virus
crystallizes, and can float in the air like
dust.
It is suspected that the SARS
virus can be transmitted in
this manner.
Schematic
view of a
crystallized
virus particle
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Clinical manifestations and pathogenesis
of coronavirus infections
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(AFP/File/Torsten Blackwood)
Health authorities in Hong Kong are
investigating whether cockroaches could spread
the deadly SARS virus
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Incubation Period
After the virus enters the body, it
requires 3-10 days incubation period
before the disease appears.
According to current data, infected
people do not pass on the virus to
others during the incubation period.
They become infectious only when
the first symptoms appear: cough,
sneezing – which spread droplets
containing virus particles.
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Symptoms
Cough, nasal congestion, sneezing
High fever (39°C or higher)
Severe muscle and joint pain
Difficulty in breathing – similar to
asthma
Continuous localized pain in the
chest, which increases when taking
a breath
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Case Definition - WHO
Suspect case
1. A person presenting after 1 November
2002(1) with history of:
high fever (>38 °C)
AND
cough or breathing difficulty
AND
one or more of the following exposures during
the 10 days prior to onset of symptoms:
• close contact(2) with a person who is a suspect or
probable case of SARS;
• history of travel, to an area with recent local
transmission of SARS
• residing in an area with recent local transmission of
SARS
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Case Definition - WHO
Suspect case (continued)
2. A person with an unexplained acute
respiratory illness resulting in death after
1 November 2002,(1) but on whom no
autopsy has been performed
AND one or more of the following
exposures during to 10 days prior to onset
of symptoms:
close contact,(2) with a person who is a
suspect or probable case of SARS;
history of travel to an area with recent local
transmission of SARS
residing in an area with recent local
transmission of SARS
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Case Definition - WHO
Probable case
1. A suspect case with radiographic
evidence of infiltrates consistent with
pneumonia or respiratory distress
syndrome (RDS) on chest X-ray (CXR).
2. A suspect case of SARS that is positive
for SARS coronavirus by one or more
assays.
3. A suspect case with autopsy findings
consistent with the pathology of RDS
without an identifiable cause.
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Case Definition - WHO
Exclusion criteria
A case should be excluded if an
alternative diagnosis can fully explain
their illness.
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Case Definition - CDC
Suspected Case:
Respiratory illness of unknown
etiology with onset since February 1,
2003, and the following criteria:
Measured temperature greater than
100.4° F (greater than 38° C) AND
One or more clinical findings of
respiratory illness (e.g. cough,
shortness of breath, difficulty
breathing, hypoxia, or radiographic
findings of either pneumonia or acute
respiratory distress syndrome) AND
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Case Definition - CDC
Travel† within 10 days of onset of
symptoms to an area with documented
or suspected community transmission
of SARS (see list below; excludes areas
with secondary cases limited to
healthcare workers or direct household
contacts)
OR
Close contact* within 10 days of onset
of symptoms with either a person with a
respiratory illness who traveled to a
SARS area or a person known to be a
suspect SARS case.
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Atypical Pneumonia
Atypical pneumonia: the tissue
surrounding the alveoli swells,
collapsing the alveoli, reducing the
blood supply to the area, and
obstructing the oxygen transfer. Chest
X-ray shows a fuzzy shadow without
clear boundaries.
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Pneumonia
Typical
Pneumonia
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Atypical
Pneumonia
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Frontal CXR in a
46 y/o male. An
obvious area of
air space
shadowing
(arrows) on the
left side.
Ref: Lee et al. A major
outbreak of Severe Acute
Respiratory Syndrome in
Hong Kong. NEJM April 7,
2003
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Follow-up CXR
showed
progression of
the disease, with
multiple, bilateral
areas of
involvement.
Ref: Lee et al. A major
outbreak of Severe Acute
Respiratory Syndrome in
Hong Kong. NEJM April 7,
2003
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Subsequent CXR
shows
improvement of
bilateral lung
opacities after
therapy
Ref: Lee et al. A major
outbreak of Severe Acute
Respiratory Syndrome in
Hong Kong. NEJM April 7,
2003
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A High-Resolution CT Scan Showing the Characteristic
Ground-Glass Abnormality in a Subpleural Location, the
Anterior Segment of the Right Upper Lobe.
There is no cavitation. A convenient ional CT scan did not show
pleural effusion or lymphadenopathy
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Ref: Lee et al. A major outbreak of Severe Acute Respiratory
Syndrome in Hong Kong. NEJM April 7, 2003
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SARS Interpretation of
laboratory results - WHO
Positive SARS diagnostic test findings
1. Confirmed positive PCR for SARS virus:
at least 2 different clinical specimens
(eg nasopharyngeal and stool) OR
the same clinical specimen collected on
2 or more days during the course of the
illness (eg 2 or more nasopharyngeal
aspirates) OR
2 different assays or repeat PCR using
the original clinical sample on each
occasion of testing
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SARS Interpretation of
laboratory results - WHO
Positive SARS diagnostic test findings
2. Seroconversion by ELISA or IFA:
negative antibody test on acute serum
followed by positive antibody test on
convalescent serum OR
four-fold or greater rise in antibody titre
between acute and convalescent phase sera
tested in parallel
3. Virus isolation:
Isolation of SARS-CoV in cell culture from any
specimen with PCR confirmation using a
validated method.
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Laboratory
Status of laboratory tests currently
under development
Antibody tests:
• ELISA (Enzyme Linked ImmunoSorbant
Assay) detects antibodies in the serum of
SARS patients reliably as from day 21 after
the onset of clinical symptoms and signs.
• Immunofluorescence Assays detect
antibodies in serum of SARS patients after
about day 10 of illness onset. This is a
reliable test requiring the use of fixed SARS
virus, an immunofluorescence microscope
and an experienced microscopist. Positive
antibody tests indicate that the patient was
infected with the SARS virus.
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Laboratory
Status of laboratory tests
currently under development
Molecular tests (PCR)
• PCR can detect genetic material of the SARS
virus in various specimens (blood, stool,
respiratory secretions or body tissue)
• Primers, which are the key pieces for a PCR
test, have been made publicly available by
WHO network laboratories on the WHO web sit.
• The primers have since been used by
numerous countries around the world.
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Laboratory
Status of laboratory tests currently
under development
Molecular tests (PCR)
• A ready-to-use PCR test kit containing primers and
positive and negative control has been developed.
• Testing of the kit by network members is expected to
quickly yield the data needed to assess the test’s
performance, in comparison with primers developed by
other WHO network laboratories.
• Existing PCR tests are very specific but lack sensitivity.
That means that negative tests can’t rule out the
presence of the SARS virus in patients. Various WHO
network laboratories are working on their PCR protocols
and primers to improve their reliability.
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Laboratory
Status of laboratory tests currently
under development
Laboratories performing SARS specific PCR tests
should adopt strict criteria for confirmation of
positive results, especially in low prevalence
areas, where the positive predictive value might be
lower:
The PCR procedure should include appropriate
negative and positive controls in each run, which
should yield the expected results:
1 negative control for the extraction procedure and
1 water control for the PCR run
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Laboratory
Status of laboratory tests currently
under development
Laboratories performing SARS specific PCR tests
should adopt strict criteria for confirmation of
positive results, especially in low prevalence
areas, where the positive predictive value might be
lower:
1 positive control for PCR and extraction and a parallel
sample to each patient test reaction spiked with a weak
positive control to detect substances inhibitory to PCR
(inhibition control)
If a positive PCR result has been obtained, it should be
confirmed by:
• repeating the PCR starting from the original sample
AND
• amplifying a second genome region
OR
• having the same sample tested in a second laboratory.
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Laboratory
Status of laboratory tests
currently under development
3 Cell culture
• Virus in specimens (such as respiratory
secretions, blood or stool) from SARS
patients can also be detected by infecting
cell cultures and growing the virus.
• Once isolated, the virus must be identified
as the SARS virus with further tests. Cell
culture is a very demanding test, but the
only means to show the existence of a live
virus.
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Treatment
Hospitalized patients have been
administered antibiotics, alone or in
combination therapy without any
clinical improvement
IV Ribavirin (antiviral) + high-dose
corticosteroids have been
responsible for some clinical
improvement of critically ill patients
in Hong Kong
Intensive & good supportive care
with and without antivirals has also
improved prognosis
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