SARS (Severe Acute Respiratory Syndrome) “viral pneumonia” Sejal Patel December 6 th, 2004

Where SARS was first found!  In a health care worker  In Guangdong Province, China.  In November,  SARS-CoV Urbani strain named after Dr. Carlo Urbani (WHO) notified WHO of unusual respiratory disease in patient (index patient) in Hanoi.

SARS Taxonomy Scientific Classification Group IV: Positive Sense Single Stranded RNA (“Nested” viruses) Order: Nidovirales (“Nested” viruses) Family: Coronaviridae Genus: Coronavirus Species: SARS coronavirus (SARS –CoV, Urbani strain) Hosts: Vertebrates ©McGraw-Hill, Inc.2005 Courtesy of Dr. Alan Cann.

Coronaviridae(s) 2 genus 1. Coronavirus (SARS-CoV) * Previously Unknown 2. Torovirus(Equine torovirus) Pathogenesis proven by Koch’s Postulate on Monkeys Coronavirus * healthy masked palm civets (paguma larvata) * China, Hong Kong, Singapore, Hanoi, and Toronto. * single stranded RNA (+ssRNA); encodes five major proteins maybe even more. * responsible for the death of more than 800 patients in over 27 countries. Courtesy of Dr. Alan Cann.

Coronavirus Pathogenesis “The envelope carries three glycoproteins: S - Spike protein: receptor binding, cell fusion, major antigen E - Envelope protein: small, envelope-associated protein M - Membrane protein: transmembrane - budding & envelope formation In a few types, there is a third glycoprotein: HE - Haemagglutinin-esterase The genome is associated with a basic phosphoprotein, N.” Courtesy of Dr. Alan Cann.

Coronavirus Pathogenesis cont…, Courtesy of Dr. Alan Cann. enters via endocytosis & membrane fusion + sense genome is translated to produce viral polymerase Viral polymerase produces full length – sense strand (poorly understood step) - sense strand used as a template to produce mRNA (monocistronic), “nested set” of transcripts assembled in the golgi apparatus and transport using secretory nature and released. REPLICATION OCCURS IN CYTOPLASM

Symptoms and Diagnostic Tests Initial Symptoms: fever of о F or higher, headaces, body aches, and malaise. Week Later: dry cough, difficulty breathing and severe diarrhea are seen in patients. Recovery: starts after 5 to 6 days  Early Diagnosis:  patient is given antibiotics, antiviral, and steroids used for atypical pneumonia.  Patient is are quarantined in specially ventilated rooms.  Laboratory tests:  RT-PCR (reverse transcription-polymerase chain reaction) assay  Detection of SARS-CoV RNA  EIA (enzyme immunoassay)  Detection of serum antibody to SARS-CoV RNA  Enzyme-linked immunosorbent assays (ELISA)  Detects antibodies against the virus produced in response to infection

Treatment and Prevention  No standard treatment yet  Patients receive combination therapy  effective antiviral and steroid (Lopinavir/ritonavir plus ribavirin)  Prevention  Isolation  Sterilization of area occupied by SARS patients  Caution and extra precautionary measure taken by medical workers and doctors.  Vaccines  According to the SAVI researchers 3 vaccines are possible to be used in the future: Whole killed vaccine, adenovirus vector, and recombination spike protein.( a bit more later in the presentation.)

Epidemiology of SARS Animal and environmental reservoirs Farms: raising and slaughtering of infected animals like unlucky palm civets Might SARS-CoV recombine with other strains of the coronavirus? NO not likely! Onset of illness Incubation period: 4 to 6 days Infectious period is very dangerous if not treated right away leads to death of infected person/animal Transmission Close contact – droplet, fomites, direct contact Airborne Fecal-oral

Latest on Morbidity and Mortality Reports “Scientists test blood in Beijing. China's government announced that a vaccine for Severe Acute Respiratory Syndrome (SARS) had emerged from the first phase clinical test as both safe and effective.” 2(Right) “An infrared thermograph system at Tokyo airport. French airport authorities are planning to experiment with heat-detecting cameras to identify passengers with a fever as part of efforts to combat the spread of infectious diseases, like SARS and bird flu.(AFP/JIJI Press)” 2(Left)

Latest on Morbidity and Mortality Reports “SARS Molecular Detection External Quality assurance: Commercial Test kit used to perform tests on inactivated severe acute respiratory syndrome associated Coronavrius significantly improved the outcome. 3 Reference material has been created for the fist time in this study which can be obtained from WHO (World Health Organization). 3 Figure:" Probity analysis of the fractions of laboratories achieving a positive result (y-axis) in relation to the virus RNA concentration in a given positive sample (x-axis). Data points represent individual samples in proficiency test panel. The thick line is the regression line calculated on the basis of a probity model (dose-response curve); the thin lines are 95% confidence intervals. Data fit into the model with p < ” 3

At the Present time “Currently, there is no known SARS transmission anywhere in the world. The most recent human cases of SARS-CoV infection were reported in China in April 2004 in an outbreak resulting from laboratory-acquired infections (see link for more details). CDC and its partners, including the World Health Organization, continue to monitor the SARS situation globally.” CDC QUESTIONS!!!!!!

References 1. “Consensus document on the epidemiology of severe acute respiratory syndrome (SARS).” World Health Organization 2003., December 5, “China says first SARS vaccine ‘safe and effective’” agence France presse December 5, Dorsten. C., Doerr. H., Lim. W., Stohr. K., Niedrig. M., “SARS Molecular Detection External Quality Assurance.” Emerging Infectious Diseases Vol. 10, No. 12, December “Current SARS Situation” Centers for Disease Control and Prevention December 5, Prescott. L., Harley.J., Klein. D, “Microbiology” McGraw Hill Inc Dr. Alan Cann, “Coronaviruses” Microbiology & Immunology “Public Health Guidance for Community-Level Preparedness and Response to Severe Acute Respiratory Syndrome (SARS) Version 2” Centers for Disease Control and Prevention, January 8, “Map of Guangdong.” Muztagh Travel, December 4,