Severe Acute Respiratory Syndrome (SARS)

Severe Acute Respiratory Syndrome (SARS)

Lydia Ho & Rui YangBISC 209

Professor Mary Allen

November 16, 02Initial cases of SARS appeared in South China

February 14, 03305 cases & 5 deaths from an unknown acute respiratory syndrome

March 03: New reports of outbreaks came in from Hong Kong, Singapore & Vietnam

New syndrome was designated as “severe acute respiratory syndrome,” or SARS

March 17, 03:

WHO called for global collaborative research on SARS

March 12, 03:

WHO issued global alert about SARS

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

April 25, 03:

Nearly 3000 SARS cases have been identified in China

April 20-25, 03: Outbreaks in Hanoi, Hong Kong, China, Singapore

& Toronto showed signs of peaking

City closed down schools & imposes strict quarantine measures

But the investigation continues…

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

The Pathogen behind it all…

SARS-CoV Virus

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

Coronaviridae

A family of large, enveloped, positive-sense single stranded RNA virus

Irregular shape Characteristic

‘club-shaped’ surface projections (~20nm)

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

SARS-CoV Genome

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

SARS Case Definition

Clinical Symptoms

High fever

Clinical History

10 days before onset of symptoms Close contact with

probable/suspected SARS patients

Live in / travel to area with transmission of SARS

Transmission of SARS

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

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

Methods of Diagnosis

Virus Detection

Virus isolation: inoculate suitable cell culture with patient specimens

Antibody Detection

When infected by SARS-CoV antibodies (e.g. IgM and IgG) are produced / change in level

Enzyme-linked immunosorbent assay (ELISA)

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

Clinical Findings Clinical history & observation

Chest radiography: important role 70-80% patients have abnormal chest

radiographs

Normal SARS patient

Method of Cure

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

Antiviral Agents Ribavirin: nucleoside analog

Most frequently administered

Have antiviral activity against many DNA & RNA viruses

Criticism: ? Effectiveness Adverse side effects

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

Method of Prevention & Control

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

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

SARS and Beyond…

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

ReferencesCann, A. (January 20, 2004). Severe acute respiratory syndrome (SARS). Retrieved

from: http://www-micro.msb.le.ac.uk/3035/coronaviruses.htmlDept. 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.comShanghai 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/