Severe Acute Respiratory Syndrome (SARS)

Definition::
Severe acute respiratory syndrome  is a respiratory disease in humans which is caused by the SARS coronavirus (SARS-CoV). There was one near pandemic, between the months of November 2002 and July 2003, with 8,422 known infected cases and 916 confirmed human deaths (a case-fatality rate of 10.9%) worldwide being listed in the World Health Organization’s (WHO) 21 April 2004 concluding report. Within a matter of weeks in early 2003, SARS spread from Hong Kong to rapidly infect individuals in some 37 countries around the world.

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As of today, the spread of SARS has been fully contained, with the last infected human case seen in June 2003 (disregarding a laboratory induced infection case in 2004). However, SARS is not claimed to have been eradicated (unlike smallpox), as it may still be present in its natural host reservoirs (animal populations) and may potentially return into the human population in the future.

Mortality by age group as of 8 May 2003 is below 1% for people aged 24 or younger, 6% for those 25 to 44, 15% in those 45 to 64 and more than 50% for those over 65. For comparison, the case fatality rate for influenza is usually around 0.6% (primarily among the elderly) but can rise as high as 33% in locally severe epidemics of new strains. The mortality rate of the primary viral pneumonia form is about 70%.

Symptoms:
The main symptoms of SARS are:

•High fever (above 38°C)
•Dry cough
•Breathing difficulties
*Other breathing symptoms
•Headache
•Muscular aches and stiffness
•Loss of appetite
•Malaise or tiredness
•Confusion
•Rash

The most common symptoms are:
*Chills and shaking
*Cough — usually starts 2-3 days after other symptoms
*Fever
*Headache
*Muscle aches

Less common symptoms include:
*Cough that produces phlegm (sputum)
*Diarrhea
*Dizziness
*Nausea and vomiting
*Runny nose
*Sore throat

These symptoms are typical of many severe respiratory infections. There have only ever been a few cases of SARS reported in the UK, so if you’ve similar symptoms, it’s far more likely to be a more typical form of pneumonia. Even if you’ve recently returned from south-east Asia, there’s little risk that you have SARS as the virus has been contained.

Causes:
Coronaviruses are positive-strand, enveloped RNA viruses that are important pathogens of mammals and birds. This group of viruses cause enteric or respiratory tract infections in a variety of animals including humans, livestock and pets.

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Initial electron microscopic examination in Hong Kong and Germany found viral particles with structures suggesting paramyxovirus in respiratory secretions of SARS patients. Subsequently, in Canada, electron microscopic examination found viral particles with structures suggestive of metapneumovirus (a subtype of paramyxovirus) in respiratory secretions. Chinese researchers also reported that a Chlamydophila-like disease may be behind SARS. The Pasteur Institute in Paris identified coronavirus in samples taken from six patients, so did the laboratory of Malik Peiris at the University of Hong Kong, which in fact was the first to announce (on 21 March 2003) the discovery of a new coronavirus as the possible cause of SARS after successfully cultivating it from tissue samples and was also amongst the first to develop a test for the presence of the virus. The CDC noted viral particles in affected tissue (finding a virus in tissue rather than secretions suggests that it is actually pathogenic rather than an incidental finding). Upon electron microscopy, these tissue viral inclusions resembled coronaviruses, and comparison of viral genetic material obtained by PCR with existing genetic libraries suggested that the virus was a previously unrecognized coronavirus. Sequencing of the virus genome — which computers at the British Columbia Cancer Agency in Vancouver completed at 4 a.m. Saturday, 12 April 2003 — was the first step toward developing a diagnostic test for the virus, and possibly a vaccine. A test was developed for antibodies to the virus, and it was found that patients did indeed develop such antibodies over the course of the disease, which is highly suggestive of a causative role.

On 16 April 2003, the WHO issued a press release stating that a coronavirus identified by a number of laboratories was the official cause of SARS. Scientists at Erasmus University in Rotterdam, the Netherlands demonstrated that the SARS coronavirus fulfilled Koch’s postulates thereby confirming it as the causative agent. In the experiments, macaques infected with the virus developed the same symptoms as human SARS victims.

An article published in The Lancet identifies a coronavirus as the probable causative agent.

In late May 2003, studies from samples of wild animals sold as food in the local market in Guangdong, China found that the SARS coronavirus could be isolated from palm civets (Paguma sp.), but the animals did not always show clinical signs. The preliminary conclusion was that the SARS virus crossed the xenographic barrier from palm civet to humans, and more than 10,000 masked palm civets were destroyed in Guangdong Province. Virus was also later found in raccoon dogs (Nyctereuteus sp.), ferret badgers (Melogale spp.) and domestic cats. In 2005, two studies identified a number of SARS-like coronaviruses in Chinese bats. Phylogenetic analysis of these viruses indicated a high probability that SARS coronavirus originated in bats and spread to humans either directly, or through animals held in Chinese markets. The bats did not show any visible signs of disease, but are the likely natural reservoirs of SARS-like coronaviruses. In late 2006, scientists from the Chinese Centre for Disease Control and Prevention of Hong Kong University and the Guangzhou Centre for Disease Control and Prevention established a genetic link between the SARS coronavirus appearing in civet cats and humans, bearing out claims that the disease had jumped across species

Viral replication:
Coronavirus (CoV) genome replication takes place in the cytoplasm in a membrane-protected microenvironment and starts with the translation of the genome to produce the viral replicase. CoV transcription involves a discontinuous RNA synthesis (template switch) during the extension of a negative copy of the subgenomic mRNAs. The requirement for base pairing during transcription has been formally demonstrated in arteriviruses and CoVs. The CoV N protein is required for coronavirus RNA synthesis and has RNA chaperon activity that may be involved in template switch. Both viral and cellular proteins are required for replication and transcription. CoVs initiate translation by cap-dependent and cap-independent mechanisms. Cell macromolecular synthesis may be controlled after CoV infection by locating some virus proteins in the host cell nucleus. Infection by different coronaviruses cause in the host alteration in the transcription and translation patterns, in the cell cycle, the cytoskeleton, apoptosis and coagulation pathways, inflammation and immune and stress responses. The balance between genes up- and down-regulated could explain the pathogenesis caused by these viruses. Coronavirus expression systems based on single genome constructed by targeted recombination, or by using infectious cDNAs, have been developed. The possibility of expressing different genes under the control of transcription regulating sequences (TRSs) with programmable strength and engineering tissue and species tropism indicates that CoV vectors are flexible. CoV based vectors have emerged with high potential vaccine development and possibly for gene therapy

Possible Complications:
*Respiratory failure
*Liver failure
*Heart failure
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Diagnosis:
SARS may be suspected in a patient who has:

1.Any of the symptoms, including a fever of 38 °C (100.4 °F) or higher, and
2.Either a history of:
…..1.Contact (sexual or casual) with someone with a diagnosis of SARS within the last 10 days OR
…..2.Travel to any of the regions identified by the WHO as areas with recent local transmission of SARS (affected regions as of 10 May 2003[13] were parts of China, Hong Kong, Singapore and the province of Ontario, Canada).

A probable case of SARS has the above findings plus positive chest X-ray findings of atypical pneumonia or respiratory distress syndrome.

With the advent of diagnostic tests for the coronavirus probably responsible for SARS, the WHO has added the category of “laboratory confirmed SARS” for patients who would otherwise fit the above “probable” category who do not (yet) have the chest x-ray changes but do have positive laboratory diagnosis of SARS based on one of the approved tests (ELISA, immunofluorescence or PCR).

The chest X-ray (CXR) appearance of SARS is variable. There is no pathognomonic appearance of SARS but is commonly felt to be abnormal with patchy infiltrates in any part of the lungs. The initial CXR may be clear.

White blood cell and platelet counts are often low. Early reports indicated a tendency to relative neutrophilia and a relative lymphopenia — relative because the total number of white blood cells tends to be low. Other laboratory tests suggest raised lactate dehydrogenase and slightly raised creatine kinase and C-Reactive protein levels.

With the identification and sequencing of the RNA of the coronavirus responsible for SARS on 12 April 2003, several diagnostic test kits have been produced and are now being tested for their suitability for use.

Three possible diagnostic tests have emerged, each with drawbacks. The first, an ELISA (enzyme-linked immunosorbent assay) test detects antibodies to SARS reliably but only 21 days after the onset of symptoms. The second, an immunofluorescence assay, can detect antibodies 10 days after the onset of the disease but is a labour and time intensive test, requiring an immunofluorescence microscope and an experienced operator. The last test is a polymerase chain reaction (PCR) test that can detect genetic material of the SARS virus in specimens ranging from blood, sputum, tissue samples and stools. The PCR tests so far have proven to be very specific but not very sensitive. This means that while a positive PCR test result is strongly indicative that the patient is infected with SARS, a negative test result does not mean that the patient does not have SARS.

The WHO has issued guidelines for using these diagnostic tests.  There is currently no rapid screening test for SARS and research is ongoing.

Treatment:
Antibiotics are ineffective as SARS is a viral disease. Treatment of SARS so far has been largely supportive with antipyretics, supplemental oxygen and ventilatory support as needed.

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Suspected cases of SARS must be isolated, preferably in negative pressure rooms, with complete barrier nursing precautions taken for any necessary contact with these patients.

There was initially anecdotal support for steroids and the antiviral drug ribavirin, but no published evidence has supported this therapy.

Researchers are currently testing all known antiviral treatments for other diseases including AIDS, hepatitis, influenza and others on the SARS-causing coronavirus.

There is some evidence that some of the more serious damage in SARS is due to the body’s own immune system overreacting to the virus – a cytokine storm. Research is continuing in this area.

In December 2004 it was reported that Chinese researchers had produced a SARS vaccine, it has been tested on a group of 36 volunteers, 24 of whom developed antibodies against the virus.

A 2006 systematic review of all the studies done on the 2003 SARS epidemic found no evidence that antivirals, steroids or other therapies helped patients. A few suggested they caused harm.

The clinical treatment of SARS has been relatively ineffective with most high risk patients requiring artificial ventilation. Currently, corticosteroids and Ribavirin are the most common drugs used for treatment of SARS (Wu et al., 2004). In vitro studies of Ribavirin have yielded little results at clinical, nontoxic concentrations. Better combinations of drugs that have yielded a more positive clinical outcome (when administered early) have included the use of Kaletra, Ribavirin and corticosteroids. The administration of corticosteroids, marketed as Prednisone, during viral infections has been controversial. Lymphopenia can also be a side effect of corticosteroids even further decreasing the immune response and allowing a spike in the viral load; yet physicians must balance the need for the anti-inflammatory treatment of corticosteroids (Murphy 2008). Clinicians have also noticed positive results during the use of human interferon and Glycyrrhizin. No compounds have yielded inhibitory results of any significance. The HIV protease inhibitors Ritonavir and Saquinavir did not show any inhibitory effect at nontoxic levels. Iminocyclitol 7 has been found to have an inhibitory effect on SARS-CoV in that it disrupts the envelope glycoprotein processing. Iminocyclitol 7 specifically inhibits the production of human fucosidase and in vitro trials yielded promising results in the treatment of SARS, yet one problem exists. A deficiency of fucosidase can lead to a condition known as fucosidosis in which there is a decrease in neurological function.

Prognosis:
The death rate from SARS was 9 to 12% of those diagnosed. In people over age 65, the death rate was higher than 50%. The illness was milder in younger patients.

Many more people became sick enough to need breathing assistance. And even more people had to go to hospital intensive care units.

Public health policies have been effective at controlling outbreaks. Many nations have stopped the epidemic in their own countries. All countries must continue to be careful to keep this disease under control. Viruses in the coronavirus family are known for their ability to change (mutate) in order to spread among humans.
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Prevention:
The WHO set up a network for doctors and researchers dealing with SARS, consisting of a secure web site to study chest x-rays and a teleconference.

A SARS-treating hospital in Taiwan.Attempts were made to control further SARS infection through the use of quarantine. Over 1200 were under quarantine in Hong Kong, while in Singapore and Taiwan, 977 and 1147 were quarantined respectively. Canada also put thousands of people under quarantine.[14] In Singapore, schools were closed for 10 days and in Hong Kong they were closed until 21 April to contain the spread of SARS.

On 27 March 2003, the WHO recommended the screening of airline passengers for the symptoms of SARS.

In Singapore, a single hospital, Tan Tock Seng Hospital, was designated as the sole treatment and isolation centre for all confirmed and probable cases of the disease on 22 March. Subsequently, all hospitals implemented measures whereby all staff members were required to submit to temperature checks twice a day, visitorship was restricted only to pediatric, obstetric and selected other patients, and even then, only one person was allowed to visit at a time. To overcome this inconvenience, videoconferencing was utilised. A dedicated phoneline was designated to report SARS cases, whereupon a private ambulance service was dispatched to transport them to Tan Tock Seng Hospital.

On 24 March, Singapore’s Ministry of Health invoked the Infectious Diseases Act, allowing for a 10-day mandatory home quarantine to be imposed on all who may have come in contact with SARS patients. SARS patients who have been discharged from hospitals were under 21 days of home quarantine, with telephone surveillance requiring them to answer the phone when randomly called up. Discharged probable SARS patients and some recovered cases of suspected SARS patients are similarly required to be home quarantined for 14 days. Security officers from CISCO, a Singaporean auxiliary police force, were utilised to serve quarantine orders to their homes, and installed an electronic picture (ePIC) camera outside the doors of each contact. Sparked in particular by the news surrounding an elderly man who disregarded the quarantine order, flashing it to the public as he strolled to eating outlets and causing a minor exodus of patrons which persisted until the fears over the disease abated, the Singapore government called for an urgent meeting in Parliament on 24 April to amend the Infectious Disease Act and include penalties for violations, revealing at least 11 other violators of quarantine orders. These amendments included:

…*the requirement of suspected persons of infectious diseases to be brought to designated treatment centres, and their prohibition from going to public places;

…*the designation of contaminated areas and the restriction of access to them, and the destruction of suspected sources of infection;

…*the introduction of the power to tag offenders who break home quarantine (persons who failed to be contacted three times by phone consecutively) with electronic wrist tags, and the imposition of fines without court trial;

…*the ability to charge repeated offenders in court which may lead to imprisonment; and

…*the prosecution of anyone caught lying to health officials about their travel to SARS-affected areas or contacts with SARS patients.

Thermal imaging at Taoyuan Airport’s International checkpoint.On 23 April the WHO advised against all but essential travel to Toronto, noting that a small number of persons from Toronto appear to have “exported” SARS to other parts of the world. Toronto public health officials noted that only one of the supposedly exported cases had been diagnosed as SARS and that new SARS cases in Toronto were originating only in hospitals. Nevertheless, the WHO advisory was immediately followed by similar advisories by several governments to their citizens. On 29 April WHO announced that the advisory would be withdrawn on 30 April. Toronto tourism suffered as a result of the WHO advisory, prompting The Rolling Stones and others to organize the massive Molson Canadian Rocks for Toronto concert, commonly known as SARSstock, to revitalize the city’s tourism trade.

Also on 23 April, Singapore instituted thermal imaging scans to screen all passengers departing Singapore from Singapore Changi Airport. It also stepped up screening of travelers at its Woodlands and Tuas checkpoints with Malaysia. Singapore had previously implemented this screening method for incoming passengers from other SARS affected areas but was to include all travelers into and out of Singapore by mid- to late May.

In addition, students and teachers in Singapore were issued with free personal oral digital thermometers. Students took their temperatures daily, usually two or three times a day, but the temperature-taking exercises were suspended with the waning of the outbreak.

Taiwan Taoyuan International Airport also added SARS checkpoints with an infrared screening system similar to Singapore’s Changi Airport.

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:
http://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome
http://health.nytimes.com/health/guides/disease/severe-acute-respiratory-syndrome-sars/overview.html
http://www.bbc.co.uk/health/physical_health/conditions/sars1.shtml

http://www.wpro.who.int/NR/rdonlyres/464C8256-9D58-44B3-B292-DB3518117CA8/0/SchematicdrawingsofSARS.jpg

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