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Institute of Medicine (US) Forum on Microbial Threats; Knobler S, Mahmoud A, Lemon S, et al., editors. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington (DC): National Academies Press (US); 2004.

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Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary.

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SARS: LESSONS FROM TORONTO

, M.D., FRCPC.

Toronto Medical Laboratories, Mt. Sinai Hospital, Toronto

Toronto’s experience with severe acute respiratory syndrome (SARS) illustrated how quickly the disease can spread in hospitals and highlighted the dangerous phenomenon of SARS superspreaders (see Figure 1-1). Unrecognized cases in Toronto caused significant morbidity and mortality (see Tables 1-4 and 1-5). The absence of rapid tests to distinguish this new disease from pneumonia, influenza, or other common diseases bodes ill for future outbreaks. In the meantime, however, it is clear that a number of simple precautionary measures can significantly reduce hospital-based transmission of the SARS coronavirus, SCoV, during an outbreak.

FIGURE 1-1. SARS Toronto: Phases I and II.

FIGURE 1-1

SARS Toronto: Phases I and II. The two SARS outbreaks that occurred in Toronto and the age distribution of cases. The majority of cases, which occurred between the ages of 18 and 64, were among health care workers, patients, and visitors to patients in (more...)

TABLE 1-4. Case Distribution by Age Group.

TABLE 1-4

Case Distribution by Age Group.

TABLE 1-5. Case Fatality by Age Group.

TABLE 1-5

Case Fatality by Age Group.

During the first phase of the outbreak in Toronto, SARS chiefly affected health care workers (HCW), patients, and their visitors at four hospitals (see Table 1-6). The second phase of the outbreak occurred primarily in the workers and visitors of a single hospital ward. The following text chronicles the two phases of the SARS outbreak in Ontario and describes the preventive measures taken by hospitals and individual HCWs once the outbreak became apparent.

TABLE 1-6. SARS Toronto: Phases I and II.

TABLE 1-6

SARS Toronto: Phases I and II.

Phase I of the Toronto SARS Outbreak

The index case and her husband had vacationed in Hong Kong and had stayed at a hotel in Kowloon from February 18 to 21, 2003. The index case began to experience symptoms after her return on February 23 and died at home on March 5. During her illness, family members, including her son (case A), provided care at home. Case A became ill on February 27 and presented to the index hospital on March 7 (Varia et al., 2003).

Nosocomial transmission in the hospital began when case A presented to the emergency department on March 7 with severe respiratory symptoms. He was placed in a general observation area of the emergency department and received nebulized salbutamol. During this time, SARS was transmitted to two other patients in the emergency department (cases B and C). Case B, who had presented with rapid atrial fibrillation, was in the bed adjacent to case A, about 1.5 meters away and separated by a curtain, and was discharged home after 9 hours in the emergency department. Case C, who had presented with shortness of breath secondary to a pleural effusion, was three beds (about 5 meters) away from case A and was transferred to a hospital ward and later discharged home on March 10. The three patients were cared for by the same nurse.

Case A was transferred briefly to a medical unit, then to the intensive care unit (ICU) 18 hours after his presentation to the emergency department. Three hours later, he was placed in airborne isolation because tuberculosis was included in his differential diagnosis. Contact and droplet precautions were implemented on March 10 by ICU staff caring for case A, and the patient remained in isolation until his death, on March 13. Case A’s family visited him in the ICU on March 8, 9, and 10. During this time, some family members were febrile, and two were experiencing respiratory symptoms. Chest radiographs were taken of the family members on March 9 and again on March 11. Four members had abnormal radiographs and were instructed to wear masks at all times, wash their hands upon entering and leaving the ICU, and limit their visits to the ICU.

On March 12, the WHO alerted the global community to a severe respiratory syndrome that was spreading among HCWs in Hanoi, Vietnam, and Hong Kong. The alert was forwarded to infectious disease and emergency department physicians in Toronto. The following day, case A died and it became clear that several other family members had worsening illness. The clinicians involved and the local public health unit suspected the family’s illnesses might be linked to cases of atypical pneumonia reported in Hong Kong. Four family members were admitted to three different hospitals on March 13, and another family member was admitted to hospital on March 14. All were managed using airborne, droplet, and contact precautions. No further transmission from these cases occurred after admission to hospital.

Case B became febrile on March 10, 3 days after exposure to case A in the emergency department and discharge home. Respiratory symptoms evolved over the next 5 days. He was brought to the index hospital on March 16 by two Emergency Medical Services paramedics, who did not immediately use contact and droplet precautions. After 9 hours in the emergency department, where airborne, contact and droplet precautions were used, case B was transferred to an isolation room in the ICU. His wife became ill on March 16. She was in the emergency department with case B on March 16 (no precautions used) and visited him in the ICU on March 21 (precautions used); he died later that day. The infection also spread to three other members of case B’s family. SARS developed in a number of people who were in contact with case B and his wife on March 16, including the 2 paramedics who brought him to the hospital, a firefighter, 5 emergency department staff, 1 other hospital staff, 2 patients in the emergency department, 1 housekeeper who worked in the emergency department while case B was there, and 7 visitors who were also in the emergency department at the same time as case B (symptom onset March 19 to 26). The 16 hospital staff, visitors, and patients transmitted the infection to 8 household members and 8 other family contacts. In the ICU, intubation for mechanical ventilation of case B was performed by a physician wearing a surgical mask, gown and gloves. He subsequently acquired SARS and transmitted the infection to a member of his family. Three ICU nurses who were present at the intubation and who used droplet and contact precautions had onset of early symptoms between March 18 and 20. One transmitted the infection to a household member.

Case C became ill on March 13 with symptoms of a myocardial infarction and was brought to the index hospital by paramedics. It was unknown that he had been in contact with case A on March 7, and thus it was not recognized that he had SARS. As a result, he was not isolated, and other precautions were not used. He was admitted to the coronary care unit (CCU) for 3 days and then transferred to another hospital for renal dialysis. He remained in the other hospital until his death, on March 29. Subsequent transmission of SARS occurred within that hospital (Dwosh et al., 2003). Case C’s wife became ill on March 26. At the index hospital, case C transmitted SARS to 1 patient in the emergency department, 3 emergency department staff, 1 housekeeper who worked in the emergency department while case C was there, 1 physician, 2 hospital technologists, 2 CCU, patients, and 7 CCU staff. One of the paramedics who transported case C to the index hospital also became ill. Further transmission then occurred from ill staff at the index hospital to 6 of their family members, 1 patient, 1 medical clinic staff, and 1 other nurse in the emergency department.

On March 23, 2003, officials recognized that the number of available negative pressure rooms in Toronto was being exhausted. In a 4-hour period on the afternoon of March 23, staff at West Park Hospital, a chronic care facility in the city, recommissioned 25 beds in an unused building formerly used to house patients with tuberculosis. Despite the efforts of West Park physicians and nurses, and assistance from staff at the Scarborough Grace and Mount Sinai Hospitals, qualified staff could be found to care for only 14 patients.

Faced with increasing transmission, the Ontario government designated SARS as a reportable, communicable, and virulent disease under the Health Protection and Promotion Act on March 25, 2003. This move gave public health officials the authority to track infected people, and issue orders preventing them from engaging in activities that might transmit the new disease. Provincial public health activated its emergency operations center.

By the evening of March 26, 2003, the West Park unit and all available negative pressure rooms in Toronto hospitals were full; however, 10 ill Scarborough Hospital staff needing admissions were waiting in the emergency department, and others who were ill were waiting at home to be seen. Overnight, with the declaration of a provincial emergency, the Ontario government required all hospitals to create units to care for SARS patients.

By March 25, 2003, Health Canada was reporting 19 cases of SARS in Canada—18 in Ontario and the single case in Vancouver. But 48 patients with a presumptive diagnosis of SARS had in fact been admitted to hospital by the end of that day. Many more individuals were starting to feel symptoms, and would subsequently be identified as SARS patients. Epidemic curves later showed that this period was the peak of the outbreak. On March 19, nine Canadians developed “probable” SARS, the highest single-day total. Taking “suspect” and “probable” cases together, the peak was March 26, and the 3 days, March 25 to 27 are the highest 3-day period in the outbreak.

The Ontario government declared SARS a provincial emergency on March 26, 2003. Under the Emergency Management Act, the government has the power to direct and control local governments and facilities to ensure that necessary services are provided.

All hospitals in the Greater Toronto Area (GTA) and Simcoe County were ordered to activate their “Code Orange” emergency plans by the government. “Code Orange” meant that the involved hospitals suspended nonessential services. They were also required to limit visitors, create isolation units for potential SARS patients, and implement protective clothing for exposed staff (i.e., gowns, masks, and goggles). Four days later, provincial officials extended access restrictions to all Ontario hospitals.

On May 14, 2003, WHO removed Toronto from the list of areas with recent local transmission. This was widely understood to mean that the outbreak had come to an end. Consistent with the notion that the disease was contained, the government of Ontario lifted the emergency on May 17. Directives continued to reinforce the need for enhanced infection control practices in health care settings. Code Orange status for hospitals was revoked.

It appeared that the total number of cases had reached a plateau—140 probable and 178 suspect infections. Twenty-four Canadians had died, all in Ontario.

Phase II of the Toronto SARS Outbreak

During early and mid-May, as recommended by provincial SARS-control directives, all hospitals discontinued SARS expanded precautions (i.e., routine contact precautions with use of an N95 or equivalent respirator) for non-SARS patients without respiratory symptoms in all hospital areas other than the emergency department and the ICUs. In addition, staff no longer were required to wear masks or respirators routinely throughout the hospital or to maintain distance from one another while eating.

On May 20, five patients in a rehabilitation hospital in Toronto were reported with febrile illness. One of these five patients was determined to have been hospitalized in the orthopedic ward of North York General (NYG) Hospital during April 22 to 28, and a second was found on May 22 to have SARS-associated SCoV by nucleic acid amplification test. On investigation, a second patient was determined to have been hospitalized in the orthopedic ward of NYG hospital during April 22 to 28. After the identification of these cases, an investigation of pneumonia cases at NYG hospital identified eight cases of previously unrecognized SARS among patients.

The first patient linked to the second phase of the Ontario outbreak was a man aged 96 years who was admitted to NYG hospital on March 22 with a fractured pelvis. On April 2, he was transferred to the orthopedic ward, where he had fever and an infiltrate on chest radiograph. Although he appeared initially to respond to antimicrobial therapy, on April 19, he again had respiratory symptoms, fever, and diarrhea. He had no apparent contact with a patient or an HCW with SARS, and aspiration pneumonia and Clostridium difficile—associated diarrhea appeared to be probable explanations for his symptoms. In the subsequent outbreak investigation, other patients in close proximity to this patient and several visitors and HCWs linked to these patients were determined to have SARS. At least one visitor became ill before the onset of illness of a hospitalized family member, and another visitor was determined to have SARS although his hospitalized wife did not.

On May 23, NYG hospital was closed to all new admissions other than patients with newly identified SARS. Soon after, new provincial directives were issued, requiring an increased level of infection-control precautions in hospitals located in several greater Toronto regions. HCWs at NYG hospital were placed under a 10-day work quarantine and instructed to avoid public places outside work, avoid close contact with friends and family, and wear a mask whenever public contact was unavoidable. As of June 9, of 79 new cases of SARS that resulted from exposure at NYH hospital, 78 appear to have resulted from exposures that occurred before May 23.

Transmission

The SCoV has been isolated in sputum, nasal secretions, serum, feces, and bronchial washings (Drosten et al., 2003; Peiris et al., 2003b). Evidence suggests that SCoV is transmitted via contact and/or droplets (Peiris et al., 2003a; Poutanen et al., 2003) and that the use of any mask (surgical or N95) significantly decreases the risk of infection (Seto et al., 2003). However, there are cases that defy explanation based on these modes of transmission suggesting that alternative modes of transmission may also occur (Varia et al., 2003). SCoV remains viable in feces for days and the outbreak at the Amoy Gardens apartments highlights the possibility of an oral-fecal or fecal-droplet mode of transmission (WHO, 2003m,n).

A number of cases occurred in HCWs wearing protective equipment following exposure to high risk aerosol- and droplet-generating procedures such as airway manipulation, administration of aerosolized medications, noninvasive positive pressure ventilation, and bronchoscopy or intubation (Lee et al., 2003; Ofner et al., 2003). When intubation is necessary, measures should be taken to reduce unnecessary exposure to health care workers, including reducing the number of health care workers present and adequately sedating or paralyzing the patient to reduce cough. Updated interim infection control precautions for patients who have SARS are under development and will be available from CDC at http://www.cdc.gov/ncidod/sars/index.htm.

Currently, epidemiological evidence suggests that transmission does not occur prior to the onset of symptoms or after symptom resolution. Despite this, shedding of SCoV in stool has been documented by reverse-transcription polymerase chain reaction (RT-PCR) for up to 64 days following the resolution of symptoms (Ren et al., 2003). A small group of patients appear to be highly infectious and have been referred to as superspreaders (CDC, 2003a). Such superspreaders appear to have played an important role early in the epidemic but the reason for their enhanced infectivity remains unclear. Possible explanations for their enhanced infectivity include the lack of early implementation of infection control precautions, higher load of SCoV, or larger amounts of respiratory secretions.

Clinical Disease

Case Definition

The Centers for Diseases Control and Prevention in Atlanta (CDC) has classified SARS into suspect and probable with further classification based on laboratory findings (CDC, 2003b). The World Health Organization has a similar case classification (WHO, 2003d). Although these classifications have proven epidemiologically useful, they have a low sensitivity for diagnosis in patients early in disease (sensitivity, 26 percent; specificity, 96 percent) (Rainer et al., 2003), underscoring the importance of a rapid, accurate diagnostic test.

Presentation

The typical incubation period of SARS ranges from 2 to 10 days but may rarely be as long as 16 days (Booth et al., 2003; Lee et al., 2003). The prodrome includes influenza-like symptoms such as fever, myalgias, headache, and diarrhea (Booth et al., 2003; Lee et al., 2003). Fever can vary from low to high grade, and can occasionally be absent on presentation, particularly in older patients. The respiratory phase, consisting of an early and late stage, starts 2–7 days after the prodrome and can be associated with watery diarrhea (Booth et al., 2003; Lee et al., 2003; Peiris et al., 2003b). The early stage includes a dry nonproductive cough and mild dyspnea. Patients may only have prodromal or early respiratory symptoms at the time of presentation making the diagnosis of SARS difficult. Chest radiographic and laboratory findings may help in making an early diagnosis. Early chest radiographs often show subtle peripheral pulmonary infiltrates, that can be more readily detected as consolidation or ground-glass appearance using high-resolution computed tomographic (CT) lung scans (Wong et al., 2003a, b). Atypical presentations of the disease have been described also complicating the diagnosis (Fisher et al., 2003; Wu and Sung, 2003). Interestingly, the disease has been rare in children and if present appears to be milder (Hon et al., 2003; Li et al., 2003).

Natural History

SARS is characterized by a spectrum of disease. Asymptomatic cases have been described but only in small number (Gold et al., 2003). Another infrequent subset of cases includes those who have a febrile illness without a respiratory component. More frequent is a mild variant of the disease that includes mild respiratory symptoms with fever. Within this category is a cough variant with persistent intractable cough. The classic moderate-severe variant is characterized by a more serious later respiratory phase with dyspnea on exertion or at rest, and hypoxia. This later respiratory phase often occurs 8 to 12 days after the onset of symptoms (Booth et al., 2003; Lee et al., 2003; Peiris et al., 2003b). In 10–20 percent of hospitalized patients, persistent or progressive hypoxia results in intubation and mechanical ventilation (Booth et al., 2003; Fowler et al., 2003; Lew et al., 2003). Among patients developing respiratory failure, intubation was required at a median of 8 days following symptom onset. Subtle but progressive declines in oxygen saturation are often indicative of impeding respiratory failure and should trigger more intensive monitoring and preparation for intubation under controlled circumstances. In total, the respiratory phase lasts approximately 1 week. The recovery phase begins approximately 14 to 18 days from the onset of symptoms with resolution of the lymphopenia and thrombocytosis.

Clinical Outcome

The case fatality rate during recent outbreaks was 9.6 percent ranging from 0 to 40 percent (WHO, 2003o). Advanced age is the most important risk factor for death with patients older than 60 years having a case fatality rate of 45 percent (Booth et al., 2003; Peiris et al., 2003b). Other risk factors for death include diabetes mellitus and hepatitis B virus infection (Booth et al., 2003; Fowler et al., 2003; Lee et al., 2003; Lew et al., 2003; Peiris et al., 2003b). Little data exist regarding the long-term morbidity of SARS although preliminary studies suggest that the psychological impact of the disease is considerable (Maunder et al., 2003; Styra et al., 2003).

Conclusion

The experience with SARS in Toronto indicates that this disease is entirely driven by exposure to infected individuals. Transmission occurred primarily within health care settings or in circumstances where close contacts occurred. The infectious agent was spread by respiratory droplets in the great majority of cases, and some patients were more infectious than others. Ultimately, the strict adherence to precautions—and practice implementing them—was critical to the containment of SARS in Toronto and the restoration of safe conditions for hospital staff and patients.

Copyright © 2004, National Academy of Sciences.
Bookshelf ID: NBK92467
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