Infectious Diseases: February 15, 2004

John Bartlett, MD


February 17, 2004

In This Article


Peiris JS, Yuen KY, Osterhaus AD, Stohr K. The severe acute respiratory syndrome. N Engl J Med. 2003;349:2381-2382. The authors provide a summary in the "Current Concepts" section on SARS, which is described as the first pandemic of the 21st century.

Cause: SARS-CoV is a novel coronavirus that has been shown by reverse transcriptase polymerase chain reaction (RT-PCR) to appear in respiratory secretions, stool, urine, and lung tissue. The hypothesis is that this virus originated from animals and the markets that trade in live game animals and was the potential source of interspecies transmission.

Epidemiology: The average number of secondary cases was 2-4, but some patients were "super spreaders." The incubation period was 2-10 days, with a median of 4-7 days and a possible maximum in recent studies of up to 20 days. Asymptomatic and mild cases are documented but uncommon; they do not appear to be important in transmission, and viral isolation has not been successful in these patients. Transmission is primarily in healthcare settings, usually at least 5 days after the onset of illness and primarily from those who are most seriously ill. There is no clear transmission before onset of symptoms. It is difficult to isolate the virus after the third week of disease. The major mechanism of transmission is from respiratory droplets or fomites to mucous membranes in the eyes, nose, or mouth; aerosol-generating procedures such as intubation, bronchoscopy, or aerosol treatments amplify transmission. Fecal-oral transmission is not established, but may be important since watery diarrhea is a common feature and stool contains large quantities of virus. The outbreak involving more than 300 cases in the Amoy Gardens apartment complex in Hong Kong may have been due to virus-containing droplets in contaminated sewage that entered bathrooms through dried-up U-traps. Global dissemination was facilitated by the 65-year-old physician from Guangdong Province who stayed 1 day at "Hotel M" on March 21, 2003 and transmitted the virus to other hotel guests, who then returned to Vietnam, Singapore, and Toronto. Molecular epidemiology shows the outbreaks in Hong Kong, Vietnam, Singapore, Toronto, and Taiwan were clonally related; those from Guangdong Province are genetically more diverse.

Table 4 lists the chronology of events, starting with the first case of atypical pneumonia diagnosed in Guangdong Province, that comprised the SARS outbreak.

Clinical illness: Initial features are fever, myalgia, malaise, chills or rigor, and cough. Features that distinguish this from other common respiratory infections are the lack of upper respiratory infection (URI) symptoms and the frequent presence of watery diarrhea. The initial chest x-ray is abnormal in 60% to 100% of patients, depending on the time interval from onset of fever to hospitalization. About 1/3 improve and 2/3 have progressive disease with persistent fever, dyspnea, oxygen desaturation, and worsening chest x-ray with multiple consolidations and sometimes a pneumomediastinum that is described as a characteristic x-ray sign of SARS. About 20% to 30% require care in the ICU, primarily for mechanical ventilation. An analysis of case series from China, Hong Kong, Canada, and Singapore with an aggregate total of 752 patients is summarized in Table 5 .

Diagnosis: The "gold standard" is seroconversion with indirect fluorescent antibody immunofluorescent assay (IFA) or ELISA with the convalescent specimen obtained at least 21 and preferably 28 days after the onset of symptoms. Immunoglobulin M (IgM) antibody does not permit an earlier diagnosis. The preferred test for viral detection is reverse-transcriptase polymerase chain reaction (RT-PCR), but this lacks sensitivity during the first 5 days. Respiratory secretions are most useful but are difficult to obtain due to the lack of a productive cough, thus requiring nasopharyngeal aspirates or throat swabs. The preferred current test for early detection is real-time RT-PCR, as described by Poon and colleagues.[6] With a low probability of SARS, any positive test must be interpreted with caution, and the recommendation for RT-PCR is confirmation with another clinical sample with a RT-PCR test that targets a different part of the viral genome.

Prognosis: The major bad prognostic factors are age and coexisting disease such as diabetes and heart disease. For patients over 65 years of age, the mortality rate exceeds 50%.

Treatment: There is no specific treatment with documented benefit. In vitro tests suggest potential value of interferon beta, glycyrrhizin, and, to a lesser extent, interferon alfa. Pathogenesis is poorly understood. This seems to differ from other respiratory viral infections in that viral load in respiratory secretions increases to about the 10th day of illness and then decreases.[7] Some patients deteriorate during the second week of illness when the viral load is decreasing, and there is anecdotal evidence that steroids are helpful, suggesting that it is an immunopathologic disorder.

Prevention: The major factors emphasized are triage, early case detection, isolation, public education, contact tracing, quarantine of contacts and surveillance at borders with health-declaration forms, and monitoring of fever. Infection-control precautions emphasize the need for respiratory droplets and contact precautions plus airborne transmission precautions with aerosol-generating procedures. Strict hand hygiene and care in degowning are also essential due to the stability of the virus in the environment and the potential for fomite and protective equipment as sources of transmission. The authors also emphasize communication to facilitate public health measures without "economic and social paralysis."

Comment: The preferred diagnostic test for early detection was reported by Poon and colleagues.[6] This consists of a real-time quantitative RT-PCR assay using a modified RNA extraction method. Tests of 50 nasopharyngeal aspirates collected during the first 3 days of illness showed positive results in 40 (80%) compared with 11 (22%) using a first-generation assay.

Shortridge KF. Severe acute respiratory syndrome and influenza: virus incursions from Southern China. Am J Respir Crit Care Med. 2003;168:1416-1420. The author reviews the common roots of the SARS coronavirus and some of the pandemic or potentially pandemic strains of influenza in southern China. This location has a reputation as a potential epicenter for pandemic influenza viruses based to some extent on prior experience, including the 1968 epidemic of H3N2 (Hong Kong strain) pandemic influenza.[8] The animal origin of that strain led to emphasis on the human-animal interface as a critical component of an inevitable influenza pandemic.[9] This scenario played out again in 1997 with the emergence of a potential pandemic strain caused by H5N1 influenza virus of avian origin that was transmitted from chickens to humans in Hong Kong.[10] The authors conclude that strain was "only 1 or 2 mutational events away" from a pandemic. This strain did not escape from Hong Kong presumably because of sound human and disease surveillance systems that have been in place for a long time. This led to recognition and intervention with slaughter of poultry in live markets and farms plus ring vaccination on farms.[11]

The similarities between influenza and SARS led to a World Health Organization (WHO) intervention with the Global Influenza Surveillance Network in February 2003. The result was an extraordinary and unprecedented level of international cooperation to prevent the further spread of SARS, with 30 countries implementing control measures. The result was the announcement in early July 2003 that the SARS outbreak had been contained, but this experience also called attention to the need for global vigilance for possible re-emergence of this virus. The author notes that the earliest SARS cases in Guangdong Province occurred in restaurant workers who handled wild animals that were regarded as exotic foods. This led to the identification of SCoV-like viruses with 99.8% genetic homology with SCoV in masked palm civets and raccoon dogs. The authors speculates that SARS outbreaks may have occurred in the countryside many times previously but were limited from spread due to the relative isolation of villages.[12,13] The difference in this epidemic was that the exotic mammals were brought to densely populated centers. The reason for live animal marketers is the marked preference for fresh meat. Thus, the live retail market represents a potential common denominator for both H5N1 influenza virus and SCoV. The author concludes that the key to prevention of these potential pandemics is "surveillance, surveillance, surveillance" and employment of prevention strategies based in part on a Han Dynasty from 206 BC-220AD that concludes: "a skillful doctor cures illness when there is no sign of disease, and thus the disease never comes."

Comment: This report predated the recent decision for slaughtering civet cats in China in a fashion possibly analogous to the response to the potential outbreak of H5N1 influenza in 1997.

Pang X, Zhu Z, Xu F, et al. Evaluation of control measures implemented in the severe acute respiratory syndrome outbreak in Beijing, 2003. JAMA. 2003;290:3251-253. The authors report the efforts to control SARS during the 2003 outbreak in which there were 2521 probable cases from March 5 to May 29, 2003.

Infrastructure: An emergency command center was established at a downtown hotel, 3565 public health workers were mobilized to assist in outbreak management, and the following supplies were distributed: surgical masks - 11 million, gowns - 758,000, latex gloves - 2,954,000, thermometers - 1,130,000, peracetic acid disinfectant - 302 tons, new ambulances - 76, mechanical ventilators - 759.

Medical facilities: There were 4 hospital closures. Designated SARS hospitals included 16 for "probable cases" and 30 for "possible cases." A new 1000-bed facility was established for exclusive use by SARS patients and was constructed in 7 days. This facility treated 40% of SARS cases; of note, there were no healthcare workers who contracted SARS in the new hospital, but 407 cases (16%) were acquired in other facilities. The total designated SARS beds were 6700, and the peak census was 3400. There were 127 fever clinics that had 65,321 visits. Of the patients seen, only 0.1% were thought to have SARS, but these accounted for 84% of all cases.

Quarantine: All close contacts of hospitalized patients with SARS were notified within 1 hour and were quarantined for 14 days, about 60% at home and the rest at various sites such as hotels, universities, etc. Quarantined persons measured temperatures twice daily and were not allowed to leave the site of quarantine except to attend funerals. Quarantine was monitored by community committees who reported breaches through a SARS hotline. A subset analysis of 5 districts with good data showed 2195 close contacts of 582 cases (average of 3.8 contacts per case). Of these, 2120 (97%) were located and quarantined, and 6.3% were subsequently identified as probable cases -- with the highest rates in spouses (15%), other household members (9%), and nonhousehold relatives (12%). School and work contacts had a rate of only 0.4%.

Facility closures: All public entertainment sites and schools were closed from April 24 to early July.

Fever monitoring: Fever checks were implemented at the Beijing airport, train stations, and all 41 roads connecting Beijing to other areas. All persons were screened with infrared thermometers and then axillary thermometers in those with a positive screening test. The total screened was 13,838,000; the number with fever was 5097 (0.03%), and 12 of these were eventually thought to have probable SARS (1 per 1 million screened).

Information dissemination: There were multiple media efforts including press conferences, billboards, bus advertisements, a 2-hour television educational program, a 24-hour hotline, 6672 community seminars, and distribution of 8,280,000 educational pamphlets.

Conclusions: The authors conclude that the SARS outbreak was brought to rapid resolution by multiple interventions that emphasized triage and information dissemination.

WHO Western Pacific Regional Office Press Release. China and WHO Confirmed SARS Case in Guangdong Province 5 January 2004. ProMED. 2004;5 January 2004:0105.0046. The authors report that the patient, a 32-year-old television producer from Guangzhou, Guangdong Province, has confirmed SARS on the basis of viral neutralization antibody test confirmed by 3 laboratories. The patient became sick on December 16th, was hospitalized on December 20th, and has subsequently recovered. Health officials identified 81 contacts including 25 considered close contacts, 39 considered casual contacts, and 17 healthcare workers. The close contacts and casual contacts were quarantined and have subsequently been released. Healthcare workers will be quarantined until 14 days after the last patient contact. All contacts have remained well. This represents the first case of SARS that is not laboratory-associated since the prior outbreak was declared over by WHO on July 5, 2003. Subsequently, there have been at least 2 other patients with possible SARS.[14] The decision has been made to sacrifice the civet cats that are the suspected source of many cases, but not clearly linked to the most recent case. Authorities in Guangdong Province threatened merchants that sell civet cats with fines up to $12,000 if merchants try to hide the cats.


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