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Severe Acute Respiratory Syndrome (SARS)

Severe Acute Respiratory Syndrome (SARS) . Lydia Ho & Rui Yang BISC 209 Professor Mary Allen. November 16, 02 Initial cases of SARS appeared in South China. February 14, 03 305 cases & 5 deaths from an unknown acute respiratory syndrome. March 03:

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Severe Acute Respiratory Syndrome (SARS)

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  1. Severe Acute Respiratory Syndrome (SARS) Lydia Ho & Rui Yang BISC 209 Professor Mary Allen

  2. November 16, 02 Initial cases of SARS appeared in South China • February 14, 03 • 305 cases & 5 deaths from an unknown acute respiratory syndrome

  3. March 03: New reports of outbreaks came in from Hong Kong, Singapore & Vietnam New syndrome was designated as “severe acute respiratory syndrome,” or SARS

  4. March 12, 03: WHO issued global alert about SARS March 17, 03: WHO called for global collaborative research on SARS

  5. March 24, 03: Scientists in CDC and HK announced isolation of new coronavirus from SARS patients DNA sequencing shows this virus is distinct from all known human pathogens

  6. April 20-25, 03: • Outbreaks in Hanoi, Hong Kong, China, Singapore & Toronto showed signs of peaking April 25, 03: Nearly 3000 SARS cases have been identified in China City closed down schools & imposes strict quarantinemeasures

  7. By the end of June, 03: Most countries were removed from the list of areas with recent local transmission of SARS: • Singapore, Hong Kong, Beijing , Toronto , Taiwan But the investigation continues…

  8. The Pathogen behind it all… SARS-CoV Virus

  9. Discovery of the new virus • Kochs postulates • Discovery of novel coronavirus in patient • Isolation of cell culture • Reproducible symptom in cell culture • Identical isolates produced Novel coronavirus is the cause of SARS

  10. Coronaviridae • A family of large, enveloped, positive-sense single stranded RNA virus • Irregular shape • Characteristic ‘club-shaped’ surface projections (~20nm)

  11. SARS-CoV Genome • 71% of the genome codes for polyproteins • Remainder: codes for structural proteins • S (spike): receptor binding, cell fusion, major antigen • E (envelop): envelop-associated protein • M (membrane): transmembrane-budding • N (nucleocapsid): genome-associated phosphoprotein

  12. SARS-CoV Genome

  13. SARS-CoV Life Cycle • S-protein binds to receptor  initiation of induced endocytosis • Translation of viral RNA polymerase • Transcription of (+) RNA into genomic and subgenomic mRNA in the cytoplasm • N protein synthesized from free ribosome • S and M protein synthesized in RER • Budding from RER as virion, excretion from cell via Golgi

  14. SARS Case Definition

  15. Clinical Symptoms High fever

  16. Clinical History • 10 days before onset of symptoms • Close contact with probable/suspected SARS patients • Live in / travel to area with transmission of SARS

  17. Transmission of SARS

  18. Transmission of SARS-CoV • Highly probable: origination is a cross-species jump from civet cat to human • Human-to-human transmission • Direct contact • Spread in droplets shed from respiratory secretions • Possible fecal transmission

  19. Infectiousness of SARS • Debatable • Most patients are moderately infectious • Cases of “superspreaders” reported • Factors affecting infectiousness are • Viral load of the secretion from index patient • Aerosol-generation procedures • Distance of the index patient

  20. Methods of Diagnosis

  21. Virus Detection • Virus isolation: inoculate suitable cell culture with patient specimens

  22. Antibody Detection When infected by SARS-CoV  antibodies (e.g. IgM and IgG) are produced / change in level • Enzyme-linked immunosorbent assay (ELISA)

  23. Antibody Detection • Immunofluorescence assay (IFA): • Sample: patient serum • Method: • Fix SARS-CoV-infected cells on microscope’s slide (patient antibodies already bound to viral antigens) • Immunofluorescent-labeled 2º antibodies bind to human IgG/IgM • Significance: positive result after 10 days of onset of illness

  24. Clinical Findings • Clinical history & observation • Chest radiography: important role • 70-80% patients have abnormal chest radiographs SARS patient Normal

  25. Method of Cure

  26. Immunomodulatory therapy • Corticosteroid • Very powerful: affect entire body • Anti-inflammatory & immunosuppressive effects • Significance: early improvement of fever, better radiographic infiltrates • Controversy: • ? Effectiveness • Adverse side effects

  27. Antiviral Agents • Ribavirin: nucleoside analog • Most frequently administered • Have antiviral activity against many DNA & RNA viruses • Criticism: • ? Effectiveness • Adverse side effects

  28. Antiviral Agents • Protease inhibitor: • Lopinavir-ritonavir co-formulation: protease inhibitor used to treat HIV infection • With ribavirin: block processing of the viral replicase polyprotein  prevent RNA replication

  29. Method of Prevention & Control

  30. Principle of Disease Confinement • Principle: to break the chain of transmission from infected to healthy person • 3-step protocol of disease confinement • Case detection • Prompt isolation • Contract tracing • Daily health check • Voluntary home isolation

  31. Epidemic Containment • Creation of emergency operating center • Institutional support • Efficient quarantine measures • Legislation • International collaboration—WHO • Travel alerts and restrictions • Coordination for research • Agreement of countries on containment protocol

  32. SARS and Beyond… The early management of SARS epidermic may serve as a model for the containment of future epidermics and pandemics

  33. References Cann, A. (January 20, 2004). Severe acute respiratory syndrome (SARS). Retrieved from: http://www-micro.msb.le.ac.uk/3035/coronaviruses.html Dept. of Communicable Disease Surveillance and Response, WHO. (2003). Consensus document on the epidemiology of severe acute respiratory syndrome (SARS). Kamps, Hoffmann. (October, 2003). SARS Reference. Retrieved from: www.SARSreference.com Shanghai Center for Bioinfomatics Technology. (2004). Life cycle of the SARS virus. Retrieved from: http://www.scbit.org/english/sars/Life%20cycle%20of%20SARS%20virus.htm Siddell, S, Wege H., ter Meulen V. The biology of coronaviruses. J. Gen Virol. 1983; 64 (Pt4): 761-776 Thiel, et al. (June 19, 2003). Mechanisms and enzymes involved in SARS coronavirus genome expression, Journal of general virology. Retrieved from: http://www.socgenmicrobiol.org.uk/JGVDirect/19424/19424ft.htm Tsang KW, Ho PL, Ooi GC, Yee WK, et al. A Cluster of Cases of Severe Acute Respiratory Syndrome in Hong Kong. N Engl J Med 2003, 348:1977-85. http://SARSReference.com/lit.php?id=12671062 World Health Organization. (2004). Case Definition. Retrieved from: www.who.int/csr/sars/casedefinition/en/ World Health Organization. (2004). Diagnostic Tests. Retrieved from www.who.int/csr/sars/diagnostictests/en/

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