PART IV: The Disease

1. PART IV: The Disease

2. 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.

3. 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

4. Wayne Stayskal, Tampa Tribune, 4/26/03

5. 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

6. Clinical manifestations and pathogenesis of coronavirus infections

7. (AFP/File/Torsten Blackwood) Health authorities in Hong Kong are investigating whether cockroaches could spread the deadly SARS virus

8. 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.

9. 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

10. Case Definition - WHO Suspect case • 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

11. 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

12. 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.

13. Case Definition - WHO Exclusion criteria • A case should be excluded if an alternative diagnosis can fully explain their illness.

14. 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

15. 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.

16. 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.

17. Pneumonia Atypical Pneumonia Typical Pneumonia

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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.

24. 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.

25. 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.

26. 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.

27. 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

28. 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.

29. 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.

30. 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