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Severe Acute Respiratory Syndrome (SARS) David S. Stephens MD

Severe Acute Respiratory Syndrome (SARS) David S. Stephens MD. Age of Aquarius. “ One can think of the middle of the 20 th century as one of the most important social revolutions in history- the elimination of the infectious disease as a significant factor in social life”

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Severe Acute Respiratory Syndrome (SARS) David S. Stephens MD

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  1. Severe Acute Respiratory Syndrome (SARS)David S. Stephens MD

  2. Age of Aquarius • “One can think of the middle of the 20th century as one of the most important social revolutions in history- the elimination of the infectious disease as a significant factor in social life” Sir Frank MacFarland Burnet 1962, 1960 Nobel Laureate for Medicine “Infectious Diseases will be eliminated as a major threat to human health” US Surgeon General 1967

  3. Microbial Evolution • Ignored historical and ecological data that emergence and reemergence of infections have been common place in nature throughout evolution • Plague - Hepatitis C - Diphtheria • Anthrax - Dengue - Helicobacter • HIV - EBOLA - Hantavirus • Lyme - Legionnaire’s Disease - West Nile

  4. Factors in Emergence and Reemergence of Infections • Microbial Mutation and Horizontal Recombination • Rapid generation time and high copy number • 3.8 billion years of microbial evolution and diversity • The vast majority of microorganisms remain uncultured and unknown • Urbanization and Land Use • Globalization and Population Growth • Environmental and Social Changes

  5. Severe Acute Respiratory Syndrome (SARS) • Emergence • Clinical Features • Pathogenesis • Transmission and Infection Control • Treatment • The Future

  6. Severe Acute Respiratory Syndrome (SARS) • Atypical pneumonia/ARDS caused by a newly identified coronavirus • First recognized in Hanoi, Vietnam on February 26th, 2003 by Dr Carlo Urbani. • As of June 6th, WHO had received reports of 8404 cases of probable SARS from China, Hong Kong Special Administrative Region of China, Canada, Vietnam, Singapore, Thailand, United States and 22 other countries. • Thus far 779 people have died and 5937 have recovered (11.6 % mortality).

  7. PATIENT A • Physician from Guangdong province China • Onset of symptoms on February 15, 2003 • Visit to relatives in Hong Kong 21 February • Stayed in Hotel M in Room 911 • Admitted to Hong Kong Hospital 22 February and died the next day • 12 patients in Hotel M, 2 family members and 4 Health Care Workers infected

  8. Patient B • 47 YO Asian-American textile businessman stayed on 9th floor at Hotel M on 21 February • On February 23rd traveled to Hanoi and became ill on February 26th was admitted to a hospital in Hanoi with high fever, dry cough, myalgias and mild sore throat. Over the next 4 days he developed increasing respiratory difficulties, thrombocytopenia and then ARDS. • He was transferred to a hospital in Hong Kong but died on March 12th, 2003

  9. On March 5th, 2003, seven healthcare workers who had cared for the patient B in Hanoi also became ill…

  10. Canada 18 HCW F,G F,G 11 close contacts Ireland 0 HCW K K A Hong Kong SAR 95 HCW H,J I, L,M H,J B C,D,E I,L,M >100 close contacts C,D,E B United States 1 HCW Vietnam 37 HCW Singapore 34 HCW 21 close contacts 37 close contacts Spread from Hotel M MMWR 2003; 52(12):241 Guangdong Province, China A A Hotel MHong Kong

  11. SARS Cases Worldwide Reported to WHO as of June 6, 2003 Europe: 8 countries (38) Canada (219) U.S. (68) China (5329) Hong Kong (1750) Vietnam (63) SA (2) Taiwan (676) Singapore (206) Thailand (8) Australia&NZ (6) Total: 8404 cases; 779 deaths (~10%case fatality)

  12. Donnelly, Lancet.com May 7, 2003

  13. Masked shop owner in Amoy Gardens complex photo by Christian Keenan

  14. Timeline of SARS Cases in Canada NEJM 2003;348;1995

  15. SARS cases by date of hospitalization, Singapore*—Feb 25–Mar 22, 2003 * Data provided by WHO

  16. 68 Reported Cases of Probable SARS, United States through June 5, 2003 2 3 9 1 MA 2 2 1* 1 2 1 1* CT 3 3 21* 1 3* 2 NJ 1* 2 2 1 1* 1 1 1 1 4 HI 2

  17. SARS - Clinical Features • Asymptomatic or mild respiratory illness • Moderate respiratory illness • Temperature of >100.4º F (>38º C)*, and • One or more clinical findings of respiratory illness (e.g., cough, shortness of breath, difficulty breathing, or hypoxia). • Severe respiratory illness • Fever and respiratory symptoms as above and • radiographic evidence of pneumonia, or • respiratory distress syndrome, or • autopsy findings consistent with pneumonia or respiratory distress syndrome without an identifiable cause

  18. SARS – Clinical presentation • Incubation period 2-7(10) days • Patients abruptly develop high fever (>38° C), chills and rigors and other and flu-like symptoms including headache, myalgias followed in 3-7 days by symptoms of respiratory illness including cough, shortness of  breath and hypoxia. • Radiographic findings can be initially normal or those of patchy pneumonia which may progress to bilateral infiltrates and ARDS.

  19. Symptoms Commonly Reported By Patients with SARS1-5 Symptom Range (%) Fever 100 Cough 57-100 Dyspnea 20-100 Chills/Rigor 73-90 Myalgias 20-83 Headache 20-70 Diarrhea 10-67 • 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

  20. SARS – Diagnostic evaluation • Chest x-ray • O2 saturation • Blood cultures • Sputum Gram stain and culture • Testing for bacterial and viral respiratory pathogens: • Influenza A and B and RSV • Legionella, C. pneumoniae, mycoplasma, etc • Save clinical specimens for possible additional testing • Respiratory, Blood, Serum • Acute and convalescent sera (>21 days from symptom onset)

  21. SARS – Laboratory findings • Hypoxemia • Leucopenia with lymphopenia • Thrombocytopenia • Transaminase elevation (ALT/AST 1-3 times upper limit of normal) • CPK elevation • LDH elevation

  22. Common Clinical Findings in Patients with SARS1-5 Finding Range (%) Examination Rales 38-90 Hypoxia 60-83 Laboratory Leukopenia 17-34 Lymphopenia 54-89 Low platelet 17-45 Increased ALT 23-78 Increased LDH 70-94 Increased CPK 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

  23. 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

  24. NEJM Lee et al. 348 (20): 1986

  25. Evolution of Radiographic Findings NEJM Lee et al. 348 (20): 1986

  26. NEJM, Ksiazek et al. 2003;348: 1953

  27. Coronaviruses Single Strand RNA, nonsegmented, enveloped, ~31,000 bps Order: Nidovirales Family: Coronaviridae • Torovirus and Coronavirus :Grp I, Grp II, Grp III • 229E and OC43 in humans cause ~1/3 of common colds , reinfections common • May remain viable for several hours after drying on surfaces

  28. Relative Size of Coronaviruses Compared to Other Microbes NY Times 4/27/03

  29. Structure of Coronavirus Virion - The spikeglycoproteins create corona, bind and fuse with host cell membranes Holmes, NEJM 2003;348: 1948

  30. Coronavirus Biology and Disease: General Themes • Recurrent / repeated infections • Prolonged or persistent virus shedding • Direct viral and immune mediated disease • “loose” species barrier: cross infections (natural or experimental) M Denison Vanderbilt

  31. Coronavirus Molecular Biology: General Themes • High mutation rate: 104 per template per replication (3 changes per genome) • RNA-RNA homologous recombination • Result: rapid adaptation, recovery from deleterious mutations, mechanisms to acquire and regain virulence. M Denison, Vanderbilt

  32. Coronaviruses, Hosts and Diseases Antigenic Group Virus HostRespiratoryEntericOther IHCoV-229E human X TGEV pig X PRCoV pig X FIPV cat X X X FECoV cat X CCoV dog X IIHCoV-OC43 human X ?? MHV mouse X X X RCoV rat X X HEV pig X X BCoV cattle X X III IBV chicken X X TCoV turkey X CDC

  33. release attachment entry translation mRNA synthesis maturation assembly replication nucleus M Denison, Vanderbilt

  34. CDC A Genome Organization E 1a 29,727 nt 1b S M N 5,000 10,000 15,000 20,000 25,000 30,000 1 B 20,001 25,000 30,000 X1 E X3 M N S X2 X4 X5 8.3 kb RNA 2 4.5 kb RNA 3 3.4 kb RNA 4 2.5 kb RNA 5 1.7 kb RNA 6 - Replicases (1a/1b) & structural genes (S,E,M,N) - Multiple small genes (X1-X5)-these vary in number, location, and sequence in different coronaviruses

  35. SARS-CoV is similar in general genome organization to other coronaviruses SARS-CoV is genetically distinct from other known coronaviruses • Structural proteins are < 40% identical • Replicase proteins are < 70% identical • SARS-CoV nsps are not homologous to known proteins Specific RT-PCR assays will allow the rapid and sensitive detection of the virus, aiding in control CDC Enterovirus Reference Laboratory

  36. - Distinct from other known coronaviruses • Neither a mutant nor recombinant • Previously unknown, probably from a nonhumanhost, has acquired the ability to infect humans.

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