PART IV: The Disease

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PART IV The Disease
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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 (39C 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
• A person presenting after 1 November 2002(1) with
  history of
• high fever (gt38 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
• A suspect case with radiographic evidence of
  infiltrates consistent with pneumonia or
  respiratory distress syndrome (RDS) on chest
  X-ray (CXR).
• A suspect case of SARS that is positive for SARS
  coronavirus by one or more assays.
• 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)ORClose
  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
Atypical Pneumonia
Typical 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
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
• 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
• 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
• 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
  tests 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 cant
  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 regionOR
• 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