—from Epidemiological Bulletin, Vol. 24 No. 1, March 2003—

Global Alert: Severe Acute Respiratory Syndrome (SARS)

Since March 12, 2003, the world has been alerted to a global outbreak of a severe acute respiratory syndrome (SARS), a previously unrecognized, infectious disease that has reached 21 countries and affecting directly as many as 3000 people in less than a month. In response to this epidemic, the World Health Organization (WHO) has issued case definitions, case management guidelines, infection control recommendations and travel advisories to detect and prevent further dissemination (See SARS case definition for surveillance, Hospital Infection Control Guidance for SARS, and Management of SARS). In addition, WHO has coordinated a global response by forming networks of investigative teams to control this disease.

Retrospective epidemiologic investigations have shown that the first known cases of SARS originated from the Guangdong Province of China in an outbreak of atypical pneumonia that started in November 2002. It was not until February 2003 that SARS was first described in Hanoi, Vietnam when previously healthy hospital staff fell sick and were found to have had direct contact with a 48 year-old patient, who had traveled to Hong Kong before becoming unwell.

At the same time, in a local hospital in Hong Kong, an increase in the number of cases of respiratory illness in health care workers was reported to the Department of Health. As in Hanoi, these cases were also epidemiologically linked to an index case. It was later discovered that this Hong Kong index patient had visited a friend in the Hotel Metropol in late February while an ill visitor from the Guangdong Province was staying there.

At first these outbreaks seemed to be isolated. However, tracing their origins led investigators to a common factor. Both index cases had stayed in the Hotel Metropol during the same time period. Upon further investigation, a cluster of 13 persons was identified, most of whom had stayed on the same floor of the hotel. Many had traveled internationally and several became index patients in subsequent clusters in Canada, Hong Kong, Singapore, United States and Vietnam.

Since then, SARS has emerged in various places proving to be a contagious and in some cases, a fatal disease in a highly mobile and interconnected world. As of 13 May 2003, there are 7,548 probable cases including 573 deaths in 29 countries (1). Many initial reports of cases were tightly linked to clusters that, so far, have characterized the epidemiology of this disease. The majority of these cases has been among health care workers and close, person-to-person contacts. It has been determined that transmission occurs mainly by respiratory droplets, direct contact with secretions, or that the virus may be, in some cases, airborne. There have been preliminary studies showing the presence of the virus in feces and other body fluids, which may suggest other mechanisms for SARS transmission.

The hardest hit areas have been China, Hong Kong, Singapore and Canada, despite established hospital infection and patient isolation guidelines. In these areas, outbreaks have gone beyond hospitals giving rise to considerable concern and emphasizing that SARS’ epidemiology is not yet fully understood. Outbreaks occurring in a hotel and a residential building, Amoy Gardens, in Hong Kong indicate that transmission may involve an environmental component as a cofactor in spreading the disease. In addition, some cases have shown to be “super-spreaders”, that is, they infected an unexpected large amount of people. It is not known whether these “super-spreaders” are secreting large amounts of infectious material or whether some other factor is working to amplify transmission.

The remaining countries have reported limited transmission to family members and health care workers, perhaps due to heightened surveillance with strict patient isolation and infection control practices. However, should SARS spread beyond clusters before a sensitive and specific diagnostic test becomes available, accurate clinical descriptions will be very important in modifying the current WHO case definition. Unfortunately, because this syndrome is not distinct from common wintertime illnesses, early detection might be difficult.

As of May 7 2003, WHO estimates an overall case fatality ratio of 14 to 15% depending on the age group of the cases and the existence of underlying illnesses. Based on available data to date, the case fatality ratio is estimated to be less than 1% in persons 24 years old or younger, 6% in persons 25 to 44, 15% in persons 45 to 64 and greater than 50% in persons aged 65 years and older.

As part of the global response to the SARS outbreak, WHO has established a laboratory research network consisting of 11 laboratories in 9 countries: Canada, France, Germany, Japan, Hong Kong, the Netherlands, Singapore, United Kingdom and United States of America.

In less than two months, progress has been made in finding the causative agent. Collaborating laboratories have concluded that the etiology of SARS is a novel coronavirus, now a new member of the family Coronaviridae comprising of 15 species that infect vertebrates. Although several laboratories have completed the genome sequence of the virus, the origin of the virus is still unclear. To understand its origins, epidemiologic studies of the first cases of SARS that are believed to have occurred in Guangdong, China, have to be conducted. The role of other pathogens in the causality or as cofactors of SARS, such as Human metapneumovirus (hMPV) and Chlamydia spp found in respiratory specimens, has yet to be determined.

Collaborative efforts are still being focused on developing valid and consistent detection and rapid diagnostic tests. Progress in these developments continues to be critical for detecting disease in early stages, understanding the pathways of transmission and developing preventive measures.

Three diagnostic tests have been described but all have limitations in bringing the SARS outbreak under control. The ELISA test detects antibodies but only 21 days or more after onset of illness. Therefore, it cannot be used to detect cases at an early stage before they have a chance to spread the infection to others. The second test, immunofluorescence assay (IFA) detects antibodies 10 days or more after infection, but it is time consuming. The polymerase chain reaction (PCR) molecular test for detection of SARS virus genetic material has been shown to be useful in the early stages of infection but produces many false-negatives - many persons who actually carry the virus may not be detected – creating a dangerous sense of false security for a virus that is known to spread easily in close person-to-person contact. PCR results can be used to complement clinical diagnosis. However, tests have not been validated for confirmation of cases or exclusion of the disease. The WHO case definition (see box 1) remains unchanged at present.

Most patients identified have been previously healthy adults aged 25-70 years. Most cases (90%) have been mild and 10% have been severe. A few suspected cases of SARS have been reported among children (15 years or less).

As of 7 May 2003, WHO estimates the maximum incubation period to be 10 days. The illness generally begins with a prodrome of fever (>38°C), which is often high, sometimes associated with chills and rigors and sometimes accompanied by other symptoms including headache, malaise, and myalgias. At the onset of illness, some cases have mild respiratory symptoms. Typically, rash and neurologic or gastrointestinal findings are absent, although a few patients have reported diarrhea during the febrile prodrome. After 3-7 days, a lower respiratory phase begins with the onset of a dry, non-productive cough or dyspnea that may be accompanied by or progress to hypoxemia.

Chest radiographs may be normal during the febrile prodrome and throughout the course of illness. However, in a substantial proportion of patients, the respiratory phase is characterized by early focal infiltrates progressing to more generalized, patchy, interstitial infiltrates. Some chest radiographs from patients in the late stages of SARS have also shown areas of consolidation.

Early in the course of disease, the absolute lymphocyte count is often decreased. Overall white cell counts have generally been normal or decreased. At the peak of the respiratory illness, up to half of patients have leukopenia and thrombocytopenia or low-normal platelet counts (50,000-150,000/ml). Early in the respiratory phase, elevated creatine phosphokinase levels (up to 3000 IU/l) and hepatic transaminases (2 to 6 times above normal) have been noted. Renal function has remained normal in the majority of patients.

Treatment regimens have included a variety of antibiotics to presumptively treat known bacterial agents of atypical pneumonia. In several locations, therapy has also included antiviral agents such as oseltamivir or ribavirin. Steroids have also been given orally or intravenously to patients in combination with ribavirin and other antimicrobials. At present, there is still no recommended etiological treatment for SARS. Ancillary support, especially assisted respiratory ventilation for severe respiratory distress syndrome, continues to be helpful.

The Pan American Health Organization has been disseminating information on the global SARS outbreak and its clinical, laboratory and epidemiological features to the countries of the Region since its initial developments. PAHO is also supporting countries in the strengthening of preparedness in public health and medical care services for the prevention and control of SARS. In addition, a special reporting mechanism has been established to monitor the situation and trends of SARS in the Americas. The majority of the countries have developed functional technical and operational guidelines through their early warning and response systems to detect, investigate, prevent and control the dissemination of emerging and reemerging infectious diseases.

The global epidemic potential of SARS, should the present pathogenicity and transmissibility of the SARS virus be maintained, will require that countries strengthen their preparedness and promptly respond to the occurrence of any suspected cases of the disease.

For additional and updated information on SARS, please visit the following URLs:
http://www.who.int/csr/sars
http://www.paho.org/english/ad/dpc/cd/sars_info.htm
http://www.cdc.gov/ncidod/sars/
http://www.hc-sc.gc.ca/english/protection/warnings/sars/index.html

Note:
(1) List of countries that have reported cases: Australia, Brazil, Bulgaria, Canada, China (mainland, Hong Kong, Macao and Taiwan), Colombia, Finland, France, Germany, India, Indonesia, Italy, Kuwait, Malaysia, Mongolia, New Zealand, Philippines, Republic of Ireland, Republic of Korea, Romania, Singapore, South Africa, Spain, Sweden, Switzerland, Thailand, United Kingdom, United States, and Vietnam.

Related Articles and Reports:
– Drosten C, et al.. Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome. N Engl J Med 2003 [Internet Site]. Available at: http://content.nejm.org/early_release/sars.dtl. Accessed on 8 May 2003.
– Ksiazek, T., et. al.. A Novel Coronavirus Associated with Severe Acute Respiratory Syndrome. N Engl J Med 2003 [Internet Site]. Available at: http://content.nejm.org/early_release/sars.dtl. Accessed on 8 May 2003.
– Falsey AR, Walsh EE. Novel coronavirus and severe acute respiratory syndrome. Lancet 2003;361(9366);1312-1313.
– World Health Organization. WHO Multicentre Collaborative Networks for Severe Acute Respiratory Syndrome (SARS) diagnosis. Wkly Epidemiol Rec 2003;78(15):121-122.
– Ho W. Guideline on management of severe acute respiratory syndrome (SARS). Lancet 2003;361(9366):1313-15.
– World Health Organization. WHO recommended measures for persons undertaking international travel from areas affected by Severe Acute Respiratory Syndrome (SARS). Wkly Epidemiol Rec;78(14):97-100.
– Update: outbreak of severe acute respiratory syndrome – worldwide, 2003. Morb Mortal Wkly Rep 2003;52(13):269-272.
– Gerberding, JL. Faster…but Fast Enough? N Engl J Med 2003 [Internet Site]. Available at: http://content.nejm.org/early_release/sars.dtl. Accessed on 8 May 2003.
– Peiris J, Tai S, Poon L, Guan Y, et. al.. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet
2003;361(9366):1319-1325.
– Poutenen, SM, et. al., Identification of Severe Acute Respiratory Syndrome in Canada. N Engl J Med 2003 [Internet Site]. Available at: http://content.nejm.org/early_release/sars.dtl. Accessed on 8 May 2003.
– Tsang, KW, et. al., A cluster of cases of Severe Acute Respiratory Syndrome in Hong Kong. N Engl J Med 2003 [Internet Site]. Available at: http://content.nejm.org/early_release/sars.dtl. Accessed on 8 May 2003.
– Drazen, JM, Case Clusters of the Severe Acute Respiratory Syndrome. N Engl J Med 2003 [Internet Site]. Available at: http://content.nejm.org/early_release/sars.dtl. Accessed on 8 May 2003.
– Outbreak News – Severe acute respiratory syndrome (SARS). Wkly Epidemiol Rec;78(12);81-8.
– Acute respiratory syndrome China, Hong Kong Special Administrative Region of China, and Vietnam. Wkly Epidemiol Rec;78:73-74.
– Outbreak news – Influenza A(H5N1), Hong Kong Special Administrative Region of China – update. Wkly Epidemiol Rec;78(10):65-66.
– Outbreak News – Acute respiratory syndrome, China – update. Wkly Epidemiol Rec;78(9):57-58.

Source: PAHO’s Area of Disease Prevention and Control, Communicable Diseases Unit.

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Epidemiological Bulletin, Vol. 24 No. 1, March 2003