CASE DEFINITION OF SARS:

SEVERE ACUTE RESPIRATORY SYNDROME

APRIL 30, 2003

The previous CDC SARS case definition (published April 20, 2003) has been updated as follows:

Laboratory criteria for evidence of infection with the SARS-associated coronavirus (SARS-CoV) have been added.

Clinical criteria have been revised to reflect the possible spectrum of respiratory illness associated with SARS-CoV. Epidemiologic criteria have been retained. Taiwan has been added to the areas with current documented or suspected community transmission of SARS; Hanoi, Vietnam is now an area with recently documented or suspected community transmission of SARS.

A. CLINICAL CRITERIA:

1. Asymptomatic or mild respiratory illness

2. Moderate respiratory illness: [a] Temperature of >100.4º F (>38º C)*, and; [b] One or more clinical findings of respiratory illness (e.g., cough, shortness of breath, difficulty breathing, or hypoxia).

3. Severe respiratory illness: [a] Temperature of >100.4º F (>38º C)*, and; [b] One (1) or more clinical findings of respiratory illness (e.g., cough, shortness of breath, difficulty breathing, or hypoxia), and; [c] Radiographic evidence of pneumonia, or respiratory distress syndrome, or autopsy findings consistent with pneumonia or respiratory distress syndrome without an identifiable cause.

B. EPIDEMIOLOGIC CRITERIA:

1. Travel (including transit in an airport) within 10 days of onset of symptoms to an area with current or recently documented or suspected community transmission of SARS, or

2. Close contact§ within 10 days of onset of symptoms with a person known or suspected to have SARS infection

C. LABORATORY CRITERIA:

1. Confirmed Positive: Involves:

[a] Detection of antibody to SARS-CoV in specimens obtained during acute illness or >21 days after illness onset, or

[b] Detection of SARS-CoV RNA by RT-PCR confirmed by a second PCR assay, by using a second aliquot of the specimen and a different set of PCR primers, or

[c] Isolation of SARS-CoV

2. Negative - Absence of antibody to SARS-CoV in convalescent serum obtained >21 days after symptom onset

3. Undetermined: laboratory testing either not performed or incomplete.

Case Classification**

1. Probable case: meets the clinical criteria for severe respiratory illness of unknown etiology with onset since February 1, 2003, and epidemiologic criteria; laboratory criteria confirmed, negative, or undetermined

2. Suspect case: meets the clinical criteria for moderate respiratory illness of unknown etiology with onset since February 1, 2003, and epidemiologic criteria; laboratory criteria confirmed, negative, or undetermined.

Use of laboratory methods for SARS diagnosis. Recommendations on interpretation of laboratory results

A. POSITIVE SARS DIAGNOSTIC TEST FINDINGS:

1. Confirmed positive PCR for SARS virus: [a] At least 2 different clinical specimens (eg nasopharyngeal and stool); [b] OR: the same clinical specimen collected on 2 or more days during the course of the illness (eg 2 or more nasopharyngeal aspirates); [c] OR: 2 different assays or repeat PCR using the original clinical sample on each occasion of testing

2. Seroconversion by ELISA or IFA: [a] Negative antibody test on acute serum followed by positive antibody test on convalescent serum; [b] 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.

B. CONFIRMATION OF POSITIVE PCR:

1. The PCR procedure should include appropriate negative and positive controls in each run, which should yield the expected results: [a] 1 negative control for the extraction procedure and 1 water control for the PCR run; [b] 1 positive control for extraction and PCR run: [c] the patient sample spiked with a weak positive control to detect PCR inhibitory substances (inhibition control)

2. If a positive PCR result has been obtained, it should be confirmed by: [a] repeating the PCR using the original sample; [b] OR: having the same sample tested in a second laboratory.
Amplifying a second genome region could further increase test specificity.

C. RECOMMENDATIONS FOR LABORATORIES TESTING FOR SARS: Reference laboratories should be identified at national level

1. PCR testing
Laboratories testing for SARS by PCR should already have experience with PCR testing. They should adopt quality control procedures and identify a partner laboratory in their country or among the WHO collaborating research laboratories listed in Multi-centre Collaborative Network: Laboratories testing for SARS to cross-check their positive findings.
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. A PCR-kit for SARS is commercially available, including internal controls. PCR primers and procedures have been published and can be adapted by laboratories. Positive control RNA is available from the Bernhard-Nocht Institute in Hamburg, Germany.
The sensitivity of PCR tests for SARS depends on the specimen and the time of testing during the course of the illness. This may result in real cases of SARS testing negative by PCR (false negative results). Sensitivity can be increased if multiple specimens/ multiple body sites are tested.
The specificity of PCR tests for SARS is excellent if technical procedures used follow quality control guidelines. False positive results may arise as a result of technical problems (e.g. laboratory contamination), so every positive PCR test should be verified.

2. Antibody testing - ELISA and IFA tests are being developed by research laboratories. Because SARS is a new disease in humans, SARS-CoV antibodies are not found in populations that have not been exposed to the virus. An antibody rise between acute and convalescent phase sera tested in parallel is very specific