SARS

Severe acute respiratory syndrome (SARS) is a respiratory disease in humans which is caused by the SARS coronavirus (SARS-CoV).[1] There has been one near pandemic to date, between November 2002 and July 2003, with 8,096 known infected cases and 774 deaths (a case-fatality rate of 9.6%) worldwide being listed in the World Health Organization's (WHO) 21 April 2004 concluding report.[2] Within a matter of weeks in early 2003, SARS spread from the Guangdong province of China to rapidly infect individuals in some 37 countries around the world[3]

Mortality by age group as of 8 May 2003 is below 1 percent for people aged 24 or younger, 6 percent for those 25 to 44, 15 percent in those 45 to 64 and more than 50 percent for those over 65.[4] For comparison, the case fatality rate for influenza is usually around 0.6 percent (primarily among the elderly) but can rise as high as 33 percent in locally severe epidemics of new strains. The mortality rate of the primary viral pneumonia form is about 70 percent.

The epidemic of SARS appears to have started in Guangdong Province, China in November 2002. The first case of SARS was reportedly originated in Shunde, Foshan, Guangdong in Nov 2002, and the patient, a farmer, was treated in the First People's Hospital of Foshan (Mckay Dennis). The patient died soon after, and no definite diagnosis was made on his cause of death. ("Patient #0" -- first reported symptoms -- has been attributed to Charles Bybelezar of Montreal, Quebec, Canada) and, despite taking some action to control it, Chinese government officials did not inform the World Health Organization of the outbreak until February 2003, restricting media coverage in order to preserve public confidence. This lack of openness caused delays in efforts to control the epidemic, resulting in criticism of the People’s Republic of China (PRC) from the international community. The PRC has since officially apologized for early slowness in dealing with the SARS epidemic.[6]

The first clue of the outbreak appears to be 27 November 2002 when Canada's Global Public Health Intelligence Network (GPHIN), an electronic warning system which is part of the World Health Organization's (WHO) Global Outbreak and Alert Response Network (GOARN), picked up reports of a "flu outbreak" in China through internet media monitoring and analysis and sent them to the WHO. Importantly, while GPHIN's capability had recently been upgraded to enable Arabic, Chinese, English, French, Russian and Spanish translation, the system was limited to English or French in presenting this information. Thus, while the first reports of an unusual outbreak were in Chinese, an English report was not generated until 21 January 2003.[7][7][8] Subsequently, the WHO requested information from Chinese authorities on 5 and 11 December. Despite the successes of the network in previous outbreak of diseases, it was proven rather defective after receiving intelligence on the media reports from China several months after the outbreak of SARS. Along with the second alert, WHO released the name, definition, as well as an activation of a coordinated global outbreak response network that brought sensitive attention and containment procedures (Heyman, 2003). However, by then although the new definitions do give nations a guideline to contain SARS, over five hundred deaths and an additional two thousand cases had already occurred worldwide.[8]

In early April, there appeared to be a change in official policy when SARS began to receive a much greater prominence in the official media. Some have directly attributed this to the death of American James Earl Salisbury.[9] However, it was also in early April that accusations emerged regarding the undercounting of cases in Beijing military hospitals. After intense pressure, PRC officials allowed international officials to investigate the situation there. This revealed problems plaguing the aging mainland Chinese healthcare system, including increasing decentralization, red tape, and inadequate communication.

In late April, revelations occurred as the PRC government admitted to under-reporting the numerous cases of SARS due to the problems inherent in the healthcare system. Dr. Jiang Yanyong exposed the coverup that was occurring in China, at great personal risk. He reported that there were more SARS patients in his hospital alone than were being reported in all of China. A number of PRC officials were fired from their posts, including the health minister and mayor of Beijing, and systems were set up to improve reporting and control in the SARS crisis. Since then, the PRC has taken a much more active and transparent role in combating the SARS epidemic. However, the death toll occurred in the epidemic was disastrous. PRC government's initial denial was considered to be irresponsible and put the whole world at great risk.

The epidemic reached the public spotlight in February 2003, when an American businessman traveling from China became afflicted with pneumonia-like symptoms while on a flight to Singapore. The plane stopped at Hanoi, Vietnam, where the victim died in The French Hospital of Hanoi. Several of the medical staff who treated him soon developed the same disease despite basic hospital procedures. Italian doctor Carlo Urbani identified the threat and communicated it to WHO and the Vietnamese government; he later succumbed to the disease. The severity of the symptoms and the infection of hospital staff alarmed global health authorities fearful of another emergent pneumonia epidemic. On 12 March 2003, the WHO issued a global alert, followed by a health alert by the United States Centers for Disease Control and Prevention (CDC). Local transmission of SARS took place in Toronto, Ottawa, San Francisco, Ulan Bator, Manila, Singapore, Taiwan, Hanoi and Hong Kong, whereas within the mainland China it spread to Guangdong, Jilin, Hebei, Hubei, Shaanxi, Jiangsu, Shanxi, Tianjin and Inner Mongolia.

In Hong Kong the first cohort of affected people were discharged from the hospital on 29 March 2003. The disease spread in Hong Kong from a mainland doctor who arrived in February and stayed at the 9th floor of the Metropole Hotel in Kowloon Peninsula, infecting 16 of the hotel visitors. Those visitors traveled to Canada, Singapore, Taiwan and Vietnam, spreading SARS to those locations.[10] Another, larger, cluster of cases in Hong Kong centred on the Amoy Gardens housing estate. Its spread is suspected to have been facilitated by defects in the sewage system of the estate. Concerned citizens in Hong Kong worried that information was not reaching people quickly enough and created a website called sosick.org, eventually forced the Hong Kong government to provide information related to SARS in a timely manner.
Initial symptoms are flu like and may include: fever, myalgia, lethargy, gastrointestinal symptoms, cough, sore throat and other non-specific symptoms. The only symptom that is common to all patients appears to be a fever above 38 °C (100.4 °F). Shortness of breath may occur later. Symptoms usually appear 2–10 days following exposure, but up to 13 days has been reported. In most cases symptoms appear within 2–3 days. About 10–20% of cases require mechanical ventilation.

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 high. 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.[5] There is currently no rapid screening test for SARS and research is ongoing.

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.

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. Many clinicians now suspect that ribavirin is detrimental.[citation needed]

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. There may be some benefit from using steroids and other immune modulating agents in the treatment of the more acute SARS patients. 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.[11]

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.[12]

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 affect 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.