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Preface

Summary

1. Timeline

2. Virology

3. Transmission

4. Epidemiology

5. Prevention

6. Case Definition

7. Diagnostic Tests

8. Clinical Presentation and Diagnosis

9. SARS Treatment

10. Pediatric SARS



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1. Timeline

November 16, 2002

The initial cases of SARS appear in the Guangdong Province, South China.

February 14, 2003

A small notice in the Weekly Epidemiological Record reports 305 cases and 5 deaths from an unknown acute respiratory syndrome which occurred between 16 November and 9 February 2003 in the Guangdong Province, China. (WHO WER 7/2003) The illness is spread to household members and healthcare workers. The Chinese Ministry of Health informs the WHO that the outbreak in Guangdong is clinically consistent with atypical pneumonia. Further investigations rule out anthrax, pulmonary plague, leptospirosis, and hemorrhagic fever.

Two weeks later, at the end of February, the Chinese Ministry of Health reports that the infective agent causing the outbreak of the atypical pneumonia was probably Chlamydia pneumoniae. (WHO WER 9/2003)

February 21

A 65-year-old medical doctor from Guangdong checks into the 9th floor of the Metropole hotel in Hong Kong. He had treated patients with atypical pneumonia prior to departure and is symptomatic upon arrival in Hong Kong. He infects at least 12 other guests and visitors to the 9th floor of the hotel (WHO. SARS: Status of the Outbreak).

February 28

Dr Carlo Urbani, a WHO official based in Vietnam, is alarmed by these cases of atypical pneumonia in the French Hospital, where he has been asked to assist. He is concerned it might be avian influenza, and notifies the WHO Regional Office for the Western Pacific.

March 7

New reports of outbreaks of a severe form of pneumonia come in from Hong Kong, and Vietnam. The outbreak in Vietnam traces back to a middle-aged man who was admitted to hospital in Hanoi with a high fever, dry cough, myalgia and mild sore throat. Following his admission, approximately 20 hospital staff become sick with similar symptoms. In some cases, this is followed by bilateral pneumonia and progression to acute respiratory distress.

March 10

Eighteen healthcare workers on a medical ward in the Prince of Wales Hospital in Hong Kong report that they are ill. Within hours, more than 50 of the hospital's healthcare workers are identified as having had a febrile illness over the previous few days. On March 11, 23 of them are admitted to the hospital for observation as a precautionary measure. Eight develop early X-ray signs of pneumonia (Lee et al.) The outbreaks, both in Hanoi and Hong Kong, appear to be confined to the hospital environment. Hospital staff seem to be at highest risk.

The new syndrome is now designated "severe acute respiratory syndrome", or SARS.

March 12

The WHO issues a global alert about cases of severe atypical pneumonia following mounting reports of cases among staff in the Hanoi and Hong Kong hospitals.

March 14

The Ministry of Health in Singapore reports 3 cases of atypical pneumonia, including a former flight attendant who had stayed at the Hong Kong hotel. Contact tracing will subsequently link her illness to more than 100 SARS cases in Singapore (MMWR 52: 405-11).

March 15

The WHO issues a heightened global health alert about the mysterious pneumonia after cases are also identified in Singapore and Canada. The alert includes a rare emergency travel advisory to international travelers, healthcare professionals and health authorities, advising all individuals traveling to affected areas to be watchful for the development of symptoms for a period of 10 days after returning (http://www.who.int/csr/sarsarchive/2003_03_ 15/en/).

March 17

The WHO calls upon 11 leading laboratories in 9 countries to join a network for multicenter research into the etiology of SARS and to simultaneously develop a diagnostic test. The network takes advantage of modern communication technologies (e-mail; secure website) so that the outcomes of investigations on clinical samples from SARS cases can be shared in real time (http://www.who.int/csr/sars/project/en/). On the secure WHO website, network members share electron microscope pictures of viruses, sequences of genetic material for virus identification and characterization, virus isolates, various samples from patients, and postmortem tissues. Samples from one patient can be analyzed in parallel by several laboratories and the results shared in real time. The goal: detection of the causative agent for SARS and the development of a diagnostic test.

March 19

One week after the global alert, the WHO publishes an update on the situation, saying that the failure of all previous efforts to detect the presence of bacteria and viruses known to cause respiratory disease strongly suggests that the causative agent might be a novel pathogen.

March 21

The Center for Disease Control (CDC) publish a preliminary clinical description of SARS (http://www.cdc.gov/mmwr/preview/mmwrhtm l/mm5212a5.htm).

March 24

Scientists at the CDC and in Hong Kong announce that a new coronavirus has been isolated from patients with SARS. (http://www.cdc.gov/od/oc/media/pressrel/r 030324.htm)

Within days, sequences of the coronavirus polymerase gene are compared with those of previously characterized strains and scientists are able to demonstrate that this virus is distinct from all known human pathogens. In addition, serum from patients with SARS is evaluated to detect antibodies to the new coronavirus, and seroconversion is documented in several patients with acute- and convalescent-phase specimens.

March 26

The first global "grand round" on the clinical features and treatment of SARS is held by the WHO. The electronic meeting unites 80 clinicians from 13 countries; a summary of their discussions and conclusions is being made available on the SARS page of the WHO website, http://www.who.int/csr/sars/cliniciansco nference/en/.

March 28

The CDC reports on the investigation into a cluster of 12 persons with suspected/probable SARS in Hong Kong which could be traced back to the medical doctor from southern China who arrived on 21 February 2003 and stayed in the Metropole hotel (http://www.cdc.gov/mmwr/preview/mmwrhtm l/mm5212a1.htm).

March 30

In Hong Kong, a steep rise in the number of SARS cases is detected in Amoy Garden, a large housing estate consisting of ten 35-storey blocks, which are home to around 15,000 persons. The Hong Kong Department of Health issues an isolation order to prevent the further spread of SARS. The isolation order requires residents of Block E of Amoy Gardens to remain in their flats until midnight on 9 April (WHO Update 15). Residents of the building are subsequently moved to rural isolation camps for 10 days.

March 31

The New England Journal of Medicine publishes two articles about clusters of SARS patients in Hong Kong and in Toronto on its website (Tsang, Poutanen).

April 2

The WHO recommends that persons traveling to Hong Kong and the Guangdong Province of China consider postponing all but essential travel (http://www.who.int/csr/sarsarchive/2003_04_ 02/en/).

April 2

The WHO's Weekly Epidemiological Record publishes a new case definition, recommends measures to prevent the international spread of SARS, and proposes the implementation of a global surveillance system (see http://www.who.int/wer/pdf/2003/wer7814.pdf, which includes a template of case reporting form).

The WHO recommends that airport and port health authorities in affected areas undertake screening of passengers presenting for international travel. In addition, the WHO issues guidance on the management of possible cases on international flights, disinfection of aircraft carrying suspect cases and surveillance of persons who have been in contact with suspect cases while undertaking international travel. Although this guidance is primarily directed at air travel, the same procedures are recommended for international travel by road, rail or sea from affected areas.

April 8-10

Three research groups publish results which suggest that a novel coronavirus might be the etiologic agent of SARS (Peiris, Drosten, Ksiazek).

Using serological tests and a reverse-transcriptase polymerase chain reaction (RT-PCR) specific for the new virus, one group of researchers found that 45 out of 50 patients with SARS, but none of the controls, had evidence of infection with the virus (Peiris). Electron-microscopic examination of cultures reveals ultrastructural features characteristic of coronaviruses. With specific diagnostic RT-PCR primers, several identical nucleotide sequences are identified in 12 patients from several locations; a finding which is consistent with a point source outbreak (Ksiazek). High concentrations of viral RNA of up to 100 million molecules per milliliter are found in sputum (Drosten).

April 12

Canadian researchers announce the first successful sequencing of the coronavirus genome believed to be responsible for the global epidemic of SARS. Scientists from the CDC confirm these reports. The new sequence has 29,727 nucleotides which fits well with the typical RNA boundaries of known coronaviruses. The results come just 12 days after a team of 10 scientists, supported by numerous technicians, began working around the clock to grow cells from a throat culture, taken from one of the SARS patients, in Vero cells (African green monkey kidney cells) in order to reproduce the ribonucleic acid (RNA) of the disease-causing coronavirus (see press release http://www.cdc.gov/od/oc/media/pressrel/r 030414.htm).

April 16

The WHO announces that a new pathogen, a member of the coronavirus family never before seen in humans, is the cause of SARS.

To prove the causal relationship between the virus and SARS, scientists had to meet Koch's postulates which stipulate that a pathogen must meet four conditions: it must be found in all cases of the disease, it must be isolated from the host and grown in pure culture, it must reproduce the original disease when introduced into a susceptible host, and it must be found in the experimental host that was so infected (http://www.who.int/csr/sarsarchive/2003_04_ 16/en/).

To confirm whether the new virus was indeed the cause of the illness, scientists at Erasmus University in Rotterdam, the Netherlands, infected monkeys with the pathogen. They found out that the virus caused similar symptoms - cough, fever, breathing difficulty - in the monkeys to that seen in humans with SARS, therefore providing strong scientific evidence that the pathogen is indeed the causative agent.

The unprecedented speed with which the causative agent of SARS was identified - just over a month since the WHO first became aware of the new illness - was made possible by an unprecedented collaboration of 13 laboratories in 10 countries.

April 20

The Chinese government discloses that the number of SARS cases is many times higher than previously reported. Beijing now has 339 confirmed cases of SARS and an additional 402 suspected cases. Ten days earlier, Health Minister Zhang Wenkang had admitted to only 22 confirmed SARS cases in Beijing.

The city closes down schools and imposes strict quarantine measures. Most worrying is the evidence that the virus is spreading in the Chinese interior, where medical resources might be inadequate.

April 20

After the identification of a cluster of illness among employees of a crowded wholesale market in Singapore, the market is closed for 15 days and the vendors placed in home quarantine.

April 23

The WHO extends its SARS-related travel advice to Beijing and the Shanxi Province in China and to Toronto, Canada, recommending that persons planning to travel to these destinations consider postponing all but essential travel. http://www.who.int/csr/sarsarchive/2003_04_ 23/en/

April 25

Outbreaks in Hanoi, Hong Kong, Singapore, and Toronto show signs of peaking.

April 27

Nearly 3,000 SARS cases have been identified in China. China closes theaters, Internet cafes, discos and other recreational activities and suspends the approval of marriages in an effort to prevent gatherings where SARS can be spread.

7,000 construction workers work around-the-clock to finish a new 1,000-bed hospital for SARS patients in Beijing.

April 29

The first report on SARS in children, published by the Lancet (Hon), suggests that young children develop a milder form of the disease with a less-aggressive clinical course than that seen in teenagers and adults.

May 1

The complete SARS virus genome sequence is published by two groups in Science (Marra, Rota).

May 2

The Xiaotangshan Hospital opens its doors for 156 SARS patients from 15 hospitals in urban areas in Beijing. The Xiaotangshan Hospital was built by 7,000 builders in just eight days.

Taiwan, which has a rapidly evolving outbreak, reports a cumulative total of 100 probable cases, with 11 new cases in 24 hours. Eight SARS deaths have occurred in Taiwan.

May 4

Scientists in the WHO network of collaborating laboratories report that the SARS virus can survive after drying on plastic surfaces for up to 48 hours; that it can survive in feces for at least 2 days, and in urine for at least 24 hours; and that the virus could survive for 4 days in feces taken from patients suffering from diarrhea (WHO Update 47).

May 7

The WHO revises its initial estimates of the case fatality ratio of SARS. It now estimates that the case fatality ratio of SARS ranges from 0% to 50% depending on the age group affected, with an overall estimate of case fatality of 14% to 15%. Based on new data, the case fatality ratio is estimated to be less than 1% in persons aged 24 years or younger, 6% in persons aged 25 to 44 years, 15% in persons aged 45 to 64 years, and greater than 50% in persons aged 65 years and older (Donnelly, WHO Update 49).

May 8

The WHO extends its SARS-related travel advice to the following areas of China: Tianjin, Inner Mongolia, and Taipei in Taiwan province ("postpone all but essential travel"; WHO Update 50).

May 9

Publication of the first prospective study on SARS (Peiris et al., http://image.thelancet.com/extras/03art443 2web.pdf).

May 20

In Taiwan, more than 150 doctors and nurses quit various hospitals in one week, because of their fear of contracting SARS. Nine major hospitals have been fully or partly shut down.

May 22

Health authorities in Canada inform the WHO of a cluster of five cases of respiratory illness associated with a single hospital in Toronto. This is the second outbreak of SARS in Toronto.

May 23

The World Health Organization removes its recommendation that people should postpone all but essential travel to Hong Kong Special Administrative Region and the Guangdong province, China (http://www.who.int/csr/don/2003_05_23/en/).

May 23

Research teams in Hong Kong and Shenzhen announce that they have detected several coronaviruses closely related to the SARS coronavirus in animal species taken from a market in southern China. Masked palm civets, racoon-dogs, and Chinese ferret badgers are wild animals that are traditionally considered delicacies and are sold for human consumption in markets throughout southern China (http://www.who.int/csr/don/2003_05_23b/en/).

May 23

Two studies assess the epidemic potential of SARS, and the effectiveness of control measures. Their main message is that the SARS virus is sufficiently transmissible to be able to cause a very large epidemic if unchecked, but not so contagious as to be uncontrollable with good, basic public health measures (Lipsitch, Riley).

May 31

Singapore is removed from the list of areas with recent local transmission of SARS because 20 days (i.e., twice the maximum incubation period) have elapsed since the most recent case of locally acquired SARS was isolated or a SARS patient has died, suggesting that the chain of transmission had terminated.

May 31

Toronto is back on the WHO list of areas with local transmission after Canada reported new clusters of 26 suspected and eight probable cases of the disease linked to four Toronto hospitals.

June 6

82 cases are now being reported in the second outbreak of SARS in Ontario, Canada.

June 13

The World Health Organization removes its recommendation that people should postpone all but essential travel to Hebei, Inner Mongolia, Shanxi and Tianjin regions in China.

In addition, the WHO removes Guangdong, Hebei, Hubei, Inner Mongolia, Jilin, Jiangsu, Shaanxi, Shanxi and Tianjin from the list of areas with recent local transmission.

June 17

The WHO removes Taiwan from its list of areas to which travelers are advised to avoid all but essential travel. The move follows vast improvements in case detection, infection control, and the tracing and follow-up of contacts that led to a steep drop in the daily number of new cases.

June 21

A study by Rainer et al. suggests that the current WHO guidelines for diagnosing suspected SARS may not be sufficiently sensitive in assessing patients before admission to hospital. Daily follow-up, evaluation of non-respiratory, systemic symptoms, and chest radiography would be better screening tools (see Chapter 5: Prevention).

June 23

The WHO removes Hong Kong from its list of areas with recent local transmission of SARS (http://www.who.int/csr/don/2003_06_23/en/).

June 24

The WHO removes Beijing from its list of areas with recent local transmission and removes its travel recommendation (http://www.who.int/csr/don/2003_06_24/en/).

July 2

The WHO removes Toronto from its list of areas with recent local transmission (http://www.who.int/csr/don/2003_07_02/en/).

July 5

The WHO removes Taiwan from its list of areas with recent local transmission (http://www.who.int/csr/don/2003_07_05/en/).

September 8

Singapore: A 27-year-old researcher is diagnosed with SARS.

September 24

The Singapore Ministry of Health releases the report of an investigation of the recent SARS case. The investigation concludes that the patient most likely acquired the infection in a laboratory as the result of accidental contamination. The patient was conducting research on the West Nile virus in a laboratory that was also conducting research using active SARS coronavirus. The full report of the review panel is available at http://www.moh.gov.sg/sars/pdf/Repor t_SARS_Biosafety.pdf.


References

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  2. CDC. Severe Acute Respiratory Syndrome - Singapore, 2003. MMWR 2003; 52: 405-11. http://www.cdc.gov/mmwr/preview/mmwrhtm l/mm5218a1.htm
  3. Chan-Yeung M, Yu WC. Outbreak of severe acute respiratory syndrome in Hong Kong Special Administrative Region: case report. BMJ 2003; 326: 850-2. http://bmj.com/cgi/content/full/326/7394/850
  4. Donnelly CA, Ghani AC, Leung GM, et al. Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong. Lancet 2003; 361:1761-6. Published online May 7, 2003. http://image.thelancet.com/extras/03art445 3web.pdf
  5. Drazen JM. Case Clusters of the Severe Acute Respiratory Syndrome. N Engl J Med 2003; 348:e6-7. Published online Mar 31, 2003. http://content.nejm.org/cgi/reprint/NEJ Me030062v2.pdf
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  25. WHO, WER 15/2003. WHO Multicentre Collaborative Networks for Severe Acute Respiratory Syndrome (SARS) diagnosis. Weekly Epidemiological Record 2003; 78: 121-122. http://www.who.int/wer/pdf/2003/wer7815.pdf
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  27. WHO Update 47: Studies of SARS virus survival, situation in China. May 5. http://www.who.int/csr/sarsarchive/2003_05_ 05/en/
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  30. WHO Update 84. Can SARS be eradicated or eliminated? http://www.who.int/entity/csr/don/2003_06_19/ en
  31. WHO Update 87. World Health Organization changes last remaining travel recommendation for Beijing, China. http://www.who.int/entity/csr/don/2003_06_24/ en
  32. WHO Update 92. Chronology of travel recommendations, areas with local transmission. http://www.who.int/entity/csr/don/2003_07_01/ en
  33. WHO Update 93. Toronto removed from list of areas with recent local transmission. http://www.who.int/entity/csr/don/2003_07_02/ en
  34. WHO Update 95. Update 95 - SARS: Chronology of a serial killer. http://www.who.int/csr/don/2003_07_04/en/
  35. WHO Update 96. Taiwan, China: SARS transmission interrupted in last outbreak area. http://www.who.int/csr/don/2003_07_05/en/


 

 
 
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