Severe Acute Respiratory Syndrome (SARS)

Presented by Parth Dave & Kuan-Mei Lin

December 2, 2005

Outbreaks

• In November 2002, highly contagious and severe atypical pneumonia were observed in the Guangdong Province of southern China

• The virus was spread to Hong Kong in February 2003 by a doctor who died 10 days after admission into local hospital a mysterious death

• Similar outbreaks occurred at different local communities subsequently

• The virus was identified by Hong Kong, the U.S. and Germany in March 2003

www.medizin.de/news/ kw04/images/sars-cdc.gif

Outbreaks

• The considered “hot zones” were Vietnam, Hong Kong, Singapore and Toronto and China

Younger victims • In Hong Kong, a group of younger people killed by Sars causes concern• More countries report cases, including India and South Africa. • In China, the situation is described as "very grave" by officials• Worldwide, 8,450 cases have been reported, caused 810 deaths in 33 countries

Investigation

Similar to: Influenza virus found in birds from outbreak in Hong Kong in 1997 Chlaymydia like organisms from atypical pneumonia patients in Guangdong outbreak Paramyxovirus – similar particles

ALL RULED OUT

WHO announced new Coronavirus never before seen in humans termed SARS (Severe Acute Respiratory Syndrome) or SARS – HCoVs

•Techniques used – cell culture isolates, electron microscopy, PCR, microarray,•Immunofluorescent antibody test from inoculated cynomolgus macaques monkeys

Coronavirus classification

• Order Nidovirales

• Family Coronaviridae

• Genus Coronavirus

• Non-segmented (+) ssRNA virus

• There are 4 major groups within coronavirus:

group 1- HCoV-229E (6 species)

group 2- HCoV-OC43 (7 species)

group 3- Avian CoV (1 specie)

SARS- CoV (1 specie)- responsible for SARS epidemiology in 2003

http://www-micro.msb.le.ac.uk/3035/Coronaviruses.html#SARS

Coronavirus

• Viral protein structure: Pleomorophic and enveloped particles

Characteristic long projected surface protein (spike) about 20 nm long

•The first coronavirus was isolated from chickens in 1937

• Viral genome structure: The non-segmented RNA genome has 5’ cap and 3’ poly A tail

Genome size ranging from 27 to 32 kb contains 6 ORFs Monocistronic mRNA The virions is about 100 to 140 nm in diameter

www.cell-research.com/ 20033/sars.jpg

Genome organization

Characteristic gene order of Typical coronaviruses and SARS:

5’-- Replicase (Rep)-- Spike (S)-- Envelope (E)-- Membrane (M)-- Nucleocapsid (N) –3’

Rota. P. et. al

Replication

Viral entry Binds by using spike proteins. Enters either by membrane fusion or reseptor mediated endocytosis (clathrin pits)

Viral replication (+) ssRNA used to create (-) ssRNA in cytoplasmHas its own RNA poly(-) strand forms replication complex attached to membraneComplex produces new genomic RNAs and subgenomic mRNAs. mRNAs code for N, M & SRibonucleoprotiens form from N + genomic RNARibonucleoprotiens attach to S & M proteins at membraneThis complex comes detached into lumen (immature virion)Mature as they progress through periphery of Golgi apparatus and becoming denser and more icosohedral.Buds off

SARS natural host

Masked palm civets (Paguma larvata)• 6 species were found by PCR to harbor the SARS virus initially• SARS-like CoV with > 99 % nucleotide homology with human SARS-CoV was identified • 10,000 civets killed, as well as other animals suspected of harboring SARS

Evidences suggested palm civets are not SARS reservoir

• No widespread infection in wild or farmed civets• Civets have no immunity agaisnt SARS-CoV

www.kostich.com/ Indian_Civet.jpg

www.genomenewsnetwork.org/.../ Paguma_larvata.jpg

SARS natural hosts

SARS may have originated in wild horseshoe bats in ChinaIndications:• 92% similar to the human SARS virus from three species of bats found at the Zoology at the Chinese Academy of Sciences, Beijing• Infected bats shows little or no symptoms

Direct human infection is not likely to occur• The differences in genes is in the genes which able the binding of virus particle and host cell• Possibly the virus can jump to intermediate animal such as the civet and adapt in such a way that it is able to infect humans

Horseshoe bats are considered SARS natural reservoir host

galleries.news24.com/. ../images/11.jpg

zmmu.msu.ru/bats/rusbats/ pictures/rhboch.jpg

Transmission

SARS-CoV is predominantly spread in droplets shed from respiratory secretions of patients direct or indirect contacts

Less likely by oral-fecal transmission fecal or airborne transmission

• Viral load is peaked at around 10 days and 13 -14 days in stool

It is believed that only the symptomatic patients can spread the SARS virus in a moderate rather than explosive way

• Toronto case-woman went home to Toronto from Hong Kong, she died 9 days later after symptoms

• 5 of 6 family members showed SARS symptoms

Superspreaders: Infectivity of a large population by major viral shedding by patients due to high concentration of virus

• Singapore epidemic

idsc.tokyo-eiken.go.jp/ SARS/fig1.gif

Symptoms

www.health24.com/ images/center/sars_flu.jpg

• Clinical course: short incubation period (6 days) time period from exposure to onset of symptoms ranging from 2 to 16 days intensive care usually required about 10 days after onset of symptoms

•There are generally 3 phases: week 1: cold like symptoms,fever, myalgia, chill and a sore throat week 2, recurrence of fever. Onset of diarrhea, and oxygen desaturation only 20% of patients reach this phase, requires ventilatory support

The fatality rate is about 10% upon infection

Sudden onset of high fever (>38°C) & dry cough Chills and shivering & muscle aches

Breathing difficulties 3-7 days from onset of symptoms

Antiviral drugs/Vaccines

•Currently, no specific antiviral drugs available for SARS-CoV•Vaccines are under development:

In China, a second-phase human trials of a SARS vaccine- using inactivated SARS-CoV

might have safty concerns

The first U.S. SARS vaccine trial at NIH by using recombinant plasmid for S protein expression

Development of transgenic tomato and tobacco expressing SARS-CoV S protein

An experimental attenuated Vesicular Stomatitis Virus (VSV)-based vaccine

Control measures

image.guardian.co.uk/.../ 2003/12/29/sars.jpg

• Close contacts of a probable or suspect case of SARS are at high risk of becoming a case, and should be isolated in the community during their potential incubation period

• Travelers from areas with recent local transmission of SARS should be given advice about whom to contact, and what to do if they develop a fever within their potential incubation period • Health departments should assign staff to undertake contact tracing and daily review of contacts in the community. Ideally, this should be in conjunction with a 24-hour SARS hotline

• The recovered patients will be quarantined at home for at least 14 days after discharged from hospital

Wearing N95 mask was one of the main public preventive measures against SARS

Questions and Comments

References

• Association of Southeast Asia nations. Copyright 2003 ASEAN Secretariat. http://www.aseansec.org/sars_symptoms.htm• Cann, Alan. Microbiology @ Leicester - Coronavirus & SARS. June 10, 2005. http://www-micro.msb.le.ac.uk/3035/Coronaviruses.html• Russell Kightley Media: Scientific Illustration Virus Pictures: Coronavirus life cycle /SARS virus replication http://www.rkm.com.au/VIRUS/CORONAVIRUS/coronavirus-replication.html• Black, Richard. BBC News - Bats a 'likely source' of Sars. Sept 29, 2005 http://news.bbc.co.uk/1/hi/sci/tech/4291386.stm• Jiang, S., He, Y., and Liu, S. 2005. SARS vaccine development. Vol. 11 (7).http://www.cdc.gov/ncidod/EID/vol11no07/05-0219.htm • Pogrebnyak, N., Golovkin, M., Andrianov, V., Spitsin, S., Smirnov, Y., Egolf, R., and Koprowski, H. 2005. Severe acute respiratory Syndrom (SARS) S protein production in plants: Development of recombinant vaccine. PNAS. 102:9062-9067•Kamps, Bernd. Hoffman Christian. 2005. SARS Reference.http://sarsreference.com/sarsref.htm•Chan, Henry. Tsui, Stephen. Sung, Joseph. Coronavirus in severe acute respiratory syndrome. Trend in Molecular Medicine. Vol 9 No. 8 August 2003