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1.  SARS: Systematic Review of Treatment Effects 
PLoS Medicine  2006;3(9):e343.
Background
The SARS outbreak of 2002–2003 presented clinicians with a new, life-threatening disease for which they had no experience in treating and no research on the effectiveness of treatment options. The World Health Organization (WHO) expert panel on SARS treatment requested a systematic review and comprehensive summary of treatments used for SARS-infected patients in order to guide future treatment and identify priorities for research.
Methods and Findings
In response to the WHO request we conducted a systematic review of the published literature on ribavirin, corticosteroids, lopinavir and ritonavir (LPV/r), type I interferon (IFN), intravenous immunoglobulin (IVIG), and SARS convalescent plasma from both in vitro studies and in SARS patients. We also searched for clinical trial evidence of treatment for acute respiratory distress syndrome. Sources of data were the literature databases MEDLINE, EMBASE, BIOSIS, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to February 2005. Data from publications were extracted and evidence within studies was classified using predefined criteria. In total, 54 SARS treatment studies, 15 in vitro studies, and three acute respiratory distress syndrome studies met our inclusion criteria. Within in vitro studies, ribavirin, lopinavir, and type I IFN showed inhibition of SARS-CoV in tissue culture. In SARS-infected patient reports on ribavirin, 26 studies were classified as inconclusive, and four showed possible harm. Seven studies of convalescent plasma or IVIG, three of IFN type I, and two of LPV/r were inconclusive. In 29 studies of steroid use, 25 were inconclusive and four were classified as causing possible harm.
Conclusions
Despite an extensive literature reporting on SARS treatments, it was not possible to determine whether treatments benefited patients during the SARS outbreak. Some may have been harmful. Clinical trials should be designed to validate a standard protocol for dosage and timing, and to accrue data in real time during future outbreaks to monitor specific adverse effects and help inform treatment.
A systematic review and comprehensive summary of reported treatments of SARS-infected patients, requested by the WHO expert panel on SARS, could not determine whether any treatments benefited patients.
Editors' Summary
Background.
Severe acute respiratory syndrome (SARS) is caused by a virus; the main symptoms are pneumonia and fever. The virus is usually passed on when people sneeze or cough. SARS became a much-talked about disease in 2003, when over 8,000 cases and 774 deaths occurred worldwide. The situation was alarming, because the first-ever cases had only just appeared in 2002, in China, so the best way to treat this new disease was unknown. Not many drugs are effective against viruses, and all doctors can usually do with a viral disease is to treat specific symptoms (e.g., fever and inflammation) and rely on the body's own immune system to fight off the virus itself. However, in recent years a number of antiviral drugs have been developed (for example, several are in use against HIV/AIDS), so there was hope that some of them might be active against SARS. Steroids were also often used in SARS treatment to try to reduce the inflammation of the lungs. In order to find out which, if any, of the potential treatments for SARS were effective, a number of research studies were carried out, both during and since the recent outbreak.
Why Was This Study Done?
Health care decisions should be based on all the information that is available. It is important to try to bring together all the reliable evidence that exists on each possible treatment for a disease. The process of doing so is called a systematic review. In October 2003 the World Health Organization (WHO) established an International SARS Treatment Study Group, consisting of experts experienced in treating patients with SARS. The group recommended a systematic review of potential treatments for SARS. In particular, it was considered important to summarise the available evidence on the use of certain antiviral drugs (ribavirin, lopinavir, and ritonavir), steroids, and proteins called immunoglobulins, which are found naturally in human blood. The WHO group wanted to know how these treatments affected the virus outside the body (“in vitro”) and whether it helped the condition of patients and reduced the death rate, particularly in those patients who developed the dangerous complication called acute respiratory distress syndrome (ARDS). This study is a systematic review conducted in response to the WHO request.
What Did the Researchers Do and Find?
They did no new work with patients or in the laboratory. Instead they conducted a comprehensive search of the scientific and medical literature for published studies that fitted their carefully predefined selection criteria. They found 54 SARS treatment studies, 15 in vitro studies, and three ARDS studies that met these criteria. Some of the in vitro studies with the antiviral drugs found that a particular drug reduced the reproduction rate of the viruses, but most of the studies of these drugs in patients were inconclusive. Of 29 studies on steroid use, 25 were inconclusive and four found that the treatment caused possible harm.
What Do These Findings Mean?
From the published studies, it is not possible to say whether any of the treatments used against SARS were effective. No cases of SARS have been reported since 2004 but it is always possible that the same or a similar virus might cause outbreaks in the future. It is disappointing that none of the research on SARS is likely to be useful in helping to decide on the best treatments to use in such an outbreak. The authors discuss the weaknesses of the studies they found and urge that more effective methods of research be applied, in a timely fashion, in any similar outbreaks in the future. While the systematic review suggests that we do not know which if any of the potential treatments against SARS are effective, its recommendations mean that researchers should at least be better prepared to learn from potential future outbreaks.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030343.
Wikipedia entry on SARS (Wikipedia is a free online encyclopedia that anyone can edit)
MedlinePlus pages on SARS
Wikipedia entry on systematic reviews, which includes links to other Web sites where more detailed information may be found
doi:10.1371/journal.pmed.0030343
PMCID: PMC1564166  PMID: 16968120
2.  Anatomy of the Epidemiological Literature on the 2003 SARS Outbreaks in Hong Kong and Toronto: A Time-Stratified Review 
PLoS Medicine  2010;7(5):e1000272.
Weijia Xing and colleagues reviewed the published epidemiological literature on SARS and show that less than a quarter of papers were published during the epidemic itself, suggesting that the research published lagged substantially behind the need for it.
Background
Outbreaks of emerging infectious diseases, especially those of a global nature, require rapid epidemiological analysis and information dissemination. The final products of those activities usually comprise internal memoranda and briefs within public health authorities and original research published in peer-reviewed journals. Using the 2003 severe acute respiratory syndrome (SARS) epidemic as an example, we conducted a comprehensive time-stratified review of the published literature to describe the different types of epidemiological outputs.
Methods and Findings
We identified and analyzed all published articles on the epidemiology of the SARS outbreak in Hong Kong or Toronto. The analysis was stratified by study design, research domain, data collection, and analytical technique. We compared the SARS-case and matched-control non-SARS articles published according to the timeline of submission, acceptance, and publication. The impact factors of the publishing journals were examined according to the time of publication of SARS articles, and the numbers of citations received by SARS-case and matched-control articles submitted during and after the epidemic were compared. Descriptive, analytical, theoretical, and experimental epidemiology concerned, respectively, 54%, 30%, 11%, and 6% of the studies. Only 22% of the studies were submitted, 8% accepted, and 7% published during the epidemic. The submission-to-acceptance and acceptance-to-publication intervals of the SARS articles submitted during the epidemic period were significantly shorter than the corresponding intervals of matched-control non-SARS articles published in the same journal issues (p<0.001 and p<0.01, respectively). The differences of median submission-to-acceptance intervals and median acceptance-to-publication intervals between SARS articles and their corresponding control articles were 106.5 d (95% confidence interval [CI] 55.0–140.1) and 63.5 d (95% CI 18.0–94.1), respectively. The median numbers of citations of the SARS articles submitted during the epidemic and over the 2 y thereafter were 17 (interquartile range [IQR] 8.0–52.0) and 8 (IQR 3.2–21.8), respectively, significantly higher than the median numbers of control article citations (15, IQR 8.5–16.5, p<0.05, and 7, IQR 3.0–12.0, p<0.01, respectively).
Conclusions
A majority of the epidemiological articles on SARS were submitted after the epidemic had ended, although the corresponding studies had relevance to public health authorities during the epidemic. To minimize the lag between research and the exigency of public health practice in the future, researchers should consider adopting common, predefined protocols and ready-to-use instruments to improve timeliness, and thus, relevance, in addition to standardizing comparability across studies. To facilitate information dissemination, journal managers should reengineer their fast-track channels, which should be adapted to the purpose of an emerging outbreak, taking into account the requirement of high standards of quality for scientific journals and competition with other online resources.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every now and then, a new infectious disease appears in a human population or an old disease becomes much more common or more geographically widespread. Recently, several such “emerging infectious diseases” have become major public health problems. For example, HIV/AIDS, hepatitis C, and severe acute respiratory syndrome (SARS) have all emerged in the past three decades and spread rapidly round the world. When an outbreak (epidemic) of an emerging infectious disease occurs, epidemiologists (scientists who study the causes, distribution, and control of diseases in populations) swing into action, collecting and analyzing data on the new threat to human health. Epidemiological studies are rapidly launched to identify the causative agent of the new disease, to investigate how the disease spreads, to define diagnostic criteria for the disease, to evaluate potential treatments, and to devise ways to control the disease's spread. Public health officials then use the results of these studies to bring the epidemic under control.
Why Was This Study Done?
Clearly, epidemics of emerging infectious diseases can only be controlled rapidly and effectively if the results of epidemiological studies are made widely available in a timely manner. Public health bulletins (for example, the Morbidity and Mortality Weekly Report from the US Centers from Disease Control and Prevention) are an important way of disseminating information as is the publication of original research in peer-reviewed academic journals. But how timely is this second dissemination route? Submission, peer-review, revision, re-review, acceptance, and publication of a piece of academic research can be a long process, the speed of which is affected by the responses of both authors and journals. In this study, the researchers analyze how the results of academic epidemiological research are submitted and published in journals during and after an emerging infectious disease epidemic using the 2003 SARS epidemic as an example. The first case of SARS was identified in Asia in February 2003 and rapidly spread around the world. 8,098 people became ill with SARS and 774 died before the epidemic was halted in July 2003.
What Did the Researchers Do and Find?
The researchers identified more than 300 journal articles covering epidemiological research into the SARS outbreak in Hong Kong, China, and Toronto, Canada (two cities strongly affected by the epidemic) that were published online or in print between January 1, 2003 and July 31, 2007. The researchers' analysis of these articles shows that more than half them were descriptive epidemiological studies, investigations that focused on describing the distribution of SARS; a third were analytical epidemiological studies that tried to discover the cause of SARS. Overall, 22% of the journal articles were submitted for publication during the epidemic. Only 8% of the articles were accepted for publication and only 7% were actually published during the epidemic. The median (average) submission-to-acceptance and acceptance-to-publication intervals for SARS articles submitted during the epidemic were 55 and 77.5 days, respectively, much shorter intervals than those for non-SARS articles published in the same journal issues. After the epidemic was over, the submission-to-acceptance and acceptance-to-publication intervals for SARS articles was similar to that of non-SARS articles.
What Do These Findings Mean?
These findings show that, although the academic response to the SARS epidemic was rapid, most articles on the epidemiology of SARS were published after the epidemic was over even though SARS was a major threat to public health. Possible reasons for this publication delay include the time taken by authors to prepare and undertake their studies, to write and submit their papers, and, possibly, their tendency to first submit their results to high profile journals. The time then taken by journals to review the studies, make decisions about publication, and complete the publication process might also have delayed matters. To minimize future delays in the publication of epidemiological research on emerging infectious diseases, epidemiologists could adopt common, predefined protocols and ready-to-use instruments, which would improve timeliness and ensure comparability across studies, suggest the researchers. Journals, in turn, could improve their fast-track procedures and could consider setting up online sections that could be activated when an emerging infectious disease outbreak occurred. Finally, journals could consider altering their review system to speed up the publication process provided the quality of the final published articles was not compromised.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000272.
The US National Institute of Allergy and Infectious Diseases provides information on emerging infectious diseases
The US Centers for Control and Prevention of Diseases also provides information about emerging infectious diseases, including links to other resources, and information on SARS
Wikipedia has a page on epidemiology (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The World Health Organization has information on SARS (in several languages)
doi:10.1371/journal.pmed.1000272
PMCID: PMC2864302  PMID: 20454570
3.  Vaccine Efficacy in Senescent Mice Challenged with Recombinant SARS-CoV Bearing Epidemic and Zoonotic Spike Variants  
PLoS Medicine  2006;3(12):e525.
Background
In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV) was identified as the etiological agent of severe acute respiratory syndrome, a disease characterized by severe pneumonia that sometimes results in death. SARS-CoV is a zoonotic virus that crossed the species barrier, most likely originating from bats or from other species including civets, raccoon dogs, domestic cats, swine, and rodents. A SARS-CoV vaccine should confer long-term protection, especially in vulnerable senescent populations, against both the 2003 epidemic strains and zoonotic strains that may yet emerge from animal reservoirs. We report the comprehensive investigation of SARS vaccine efficacy in young and senescent mice following homologous and heterologous challenge.
Methods and Findings
Using Venezuelan equine encephalitis virus replicon particles (VRP) expressing the 2003 epidemic Urbani SARS-CoV strain spike (S) glycoprotein (VRP-S) or the nucleocapsid (N) protein from the same strain (VRP-N), we demonstrate that VRP-S, but not VRP-N vaccines provide complete short- and long-term protection against homologous strain challenge in young and senescent mice. To test VRP vaccine efficacy against a heterologous SARS-CoV, we used phylogenetic analyses, synthetic biology, and reverse genetics to construct a chimeric virus (icGDO3-S) encoding a synthetic S glycoprotein gene of the most genetically divergent human strain, GDO3, which clusters among the zoonotic SARS-CoV. icGD03-S replicated efficiently in human airway epithelial cells and in the lungs of young and senescent mice, and was highly resistant to neutralization with antisera directed against the Urbani strain. Although VRP-S vaccines provided complete short-term protection against heterologous icGD03-S challenge in young mice, only limited protection was seen in vaccinated senescent animals. VRP-N vaccines not only failed to protect from homologous or heterologous challenge, but resulted in enhanced immunopathology with eosinophilic infiltrates within the lungs of SARS-CoV–challenged mice. VRP-N–induced pathology presented at day 4, peaked around day 7, and persisted through day 14, and was likely mediated by cellular immune responses.
Conclusions
This study identifies gaps and challenges in vaccine design for controlling future SARS-CoV zoonosis, especially in vulnerable elderly populations. The availability of a SARS-CoV virus bearing heterologous S glycoproteins provides a robust challenge inoculum for evaluating vaccine efficacy against zoonotic strains, the most likely source of future outbreaks.
Experiments in mice suggest challenges in vaccine design for controlling future SARS-CoV zoonosis, especially in vulnerable elderly populations.
Editors' Summary
Background.
Severe acute respiratory syndrome (SARS) is a flu-like illness and was first recognized in China in 2002, after which the disease rapidly spread around the world. SARS was associated with high death rates, much higher than those for flu. Around 10% of people recognized as being infected with SARS died, and the death rate approached 50% among elderly people. The virus causing SARS was identified as a member of the coronavirus family; it is generally thought that this virus “jumped” to humans from bats, which harbor related viruses. Although SARS was declared eradicated by the World Health Organization in May 2005, there is still the possibility that similar viruses will again cross the species barrier and infect humans, with potentially serious consequences. As a result, many groups are working to develop vaccines that will protect against SARS infection.
Why Was This Study Done?
A SARS vaccine should be effective in people of all ages, including the elderly who are more likely to get seriously ill or die if they become infected. In addition, potential vaccines should protect against different variants of the virus, because there are different types of the virus that could potentially cross the species barrier from animals to humans. Of the different proteins that make up the SARS coronavirus, the spike glycoprotein is thought to elicit an immune response in humans that can protect against future infection. The researchers therefore examined vaccine candidates based on this particular protein (termed SARS-CoV S), as well as a second one called SARS-CoV N, in mice. Specifically, they tested whether the vaccines would protect against SARS infection in both young and older mice, and whether they would protect against infection by different strains of the SARS virus.
What Did the Researchers Do and Find?
The researchers created vaccines based on SARS-CoV S and SARS-CoV N by taking the genes coding for those proteins and inserting them into another type of virus particle that acted as a delivery vehicle. They injected mice with these vaccines and then tested whether the mice generated an immune response against the specific SARS proteins, which they did. The next step was to work out whether mice injected with the vaccines would be protected against later infection with SARS-CoV. The researchers found that mice injected with vaccine based on SARS-CoV S were protected against later infection with a standard SARS-CoV strain, both in the short term (eight weeks after vaccination) and the long term (54 weeks after vaccination). However, the vaccine based on SARS-CoV N did not seem to result in protection, and, worryingly, caused pathological changes in the lungs of mice following virus challenge. To find out if their candidate vaccines would protect against different strains of SARS, the researchers made a synthetic test virus that contained a mixture of genetic material from different natural variants of the virus. This test virus was used to “challenge” mice that had been immunized with the two different vaccines. The researchers found that the vaccine based on SARS-CoV S protected against infection by the test virus when mice were vaccinated young, but it failed to efficiently protect when administered to older mice.
What Do These Findings Mean?
The findings confirm others suggesting that vaccines based on the SARS-CoV S protein are more effective than those based on SARS-CoV N. They also suggest that the former can provide long-term protection in animals vaccinated young against closely related viruses. However, protection against more distantly related viruses remains a challenge, especially when vaccinating older animals. The differences seen between young and older mice suggest that older mice might provide a useful model for animal testing of candidate vaccines for diseases like SARS, flu, and West Nile virus that pose a particular threat to elderly people. Overall, these results provide useful lessons toward future SARS vaccine development in animals. The synthetic virus strain generated here, and others like it, are likely to be useful tools for such future studies.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030525.
• The World Health Organization provides guidance, archives, and other information resources on SARS
• Information from the US Centers for Disease Control on SARS
• Wikipedia (an internet encyclopedia anyone can edit) has an entry on SARS
• Collected resources from MedLinePlus about SARS
doi:10.1371/journal.pmed.0030525
PMCID: PMC1716185  PMID: 17194199
4.  Lessons from SARS: A retrospective study of outpatient care during an infectious disease outbreak 
BMC Pediatrics  2010;10:51.
Background
During severe acute respiratory syndrome (SARS) outbreak in Toronto, outpatient clinics at SickKids Hospital were closed to prevent further disease transmission. In response, a decision was made by the neonatal neuro-developmental follow up (NNFU) clinic staff to select patients with scheduled appointments to have a mail/telephone assessment using Ages and Stages Questionnaire (ASQ) or to postpone/skip their visit. The objective of this study was to compare the developmental assessment and its outcome in two groups of NNFU clinic patients, SARS versus non-SARS, over three standard clinic appointments.
Methods
We compared the diagnostic accuracy (identification of developmental delay), and patient management (referral for therapy or communication of a new diagnosis) of the strategies used during SARS, April/May 2003, to the standard assessment methods used for patients seen in April/May 2005 (non-SARS). In all cases data were obtained for 3 patient visits: before, during and after these 2 months and were compared using descriptive statistics.
Results
There were 95 patients in the SARS group and 99 non-SARS patients. The gestational age, sex, entry diagnosis and age at the clinic visit was not different between the groups. The NNFU clinic staff mailed ASQ to 27 families during SARS, 17 (63%) were returned, and 8 of the 17 were then contacted by telephone. Criteria used to identify infants at risk selected for either mailed ASQ or phone interviews were not clearly defined in the patients' charts. There was a significant under identification of developmental delay during SARS (18% versus 45%). Of those who responded to the mailed questionnaire, referrals for therapy rates were similar to non-SARS group. The lost to follow up rate was 24% for the SARS group compared with 7% for non-SARS. There was no difference in the overall rate of developmental delay in the two groups as identified at the 'after' visit.
Conclusions
Poor advanced planning led to a haphazard assessment of patients during this infectious disease outbreak. Future pandemic plans should consider planning for outpatient care as well as in hospital management of patients.
doi:10.1186/1471-2431-10-51
PMCID: PMC2914048  PMID: 20646293
5.  What Internet Services Would Patients Like From Hospitals During an Epidemic? Lessons From the SARS Outbreak in Toronto 
Background
International health organizations and officials are bracing for a pandemic. Although the 2003 severe acute respiratory syndrome (SARS) outbreak in Toronto did not reach such a level, it created a unique opportunity to identify the optimal use of the Internet to promote communication with the public and to preserve health services during an epidemic.
Objective
The aim of the study was to explore patients’ attitudes regarding the health services that might be provided through the Internet to supplement those traditionally available in the event of a future mass emergency situation.
Methods
We conducted “mask-to-mask” surveys of patients at three major teaching hospitals in Toronto during the second outbreak of SARS. Patients were surveyed at the hospital entrances and selected clinics. Descriptive statistics and logistic regression models were used for the analysis.
Results
In total, 1019 of 1130 patients responded to the survey (90% overall response rate). With respect to Internet use, 70% (711/1019) used the Internet by themselves and 57% (578/1019) with the help of a friend or family member. Of the Internet users, 68% (485/711) had already searched the World Wide Web for health information, and 75% (533/711) were interested in communicating with health professionals using the Internet as part of their ongoing care. Internet users expressed interest in using the Web for the following reasons: to learn about their health condition through patient education materials (84%), to obtain information about the status of their clinic appointments (83%), to send feedback to the hospital about how to improve its services (77%), to access screening tools to help determine if they were potentially affected by the infectious agent responsible for the outbreak (77%), to renew prescriptions (75%), to consult with their health professional about nonurgent matters (75%), and to access laboratory test results (75%). Regression results showed that younger age, higher education, and English as a first language were predictors of patients’ interest in using Internet services in the event of an epidemic.
Conclusion
Most patients are willing and able to use the Internet as a means to maintain communication with the hospital during an outbreak of an infectious disease such as SARS. Hospitals should explore new ways to interact with the public, to provide relevant health information, and to ensure continuity of care when they are forced to restrict their services.
doi:10.2196/jmir.7.4.e46
PMCID: PMC1550678  PMID: 16236698
Severe acute respiratory syndrome; communicable diseases, emerging; information services; Internet; public health; questionnaires
6.  Identification and containment of an outbreak of SARS in a community hospital 
Background
Severe acute respiratory syndrome (SARS) is continuing to spread around the world. All hospitals must be prepared to care for patients with SARS. Thus, it is important to understand the transmission of this disease in hospitals and to evaluate methods for its containment in health care institutions. We describe how we cared for the first 2 patients with SARS admitted to our 419-bed community hospital in Richmond Hill, Ont., and the response to a SARS outbreak within our institution.
Methods
We collected clinical and epidemiological data about patients and health care workers at our institution who during a 13-day period had a potential unprotected exposure to 2 patients whose signs and symptoms were subsequently identified as meeting the case definition for probable SARS. The index case at our hospital was a patient who was transferred to our intensive care unit (ICU) from a referral hospital on Mar. 16, 2003, where he had been in close proximity to the son of the individual with the first reported case of SARS in Toronto. After 13 days in the ICU, a diagnosis of probable SARS was reached for our index case. Immediately upon diagnosis of our index case, respiratory isolation and barrier precautions were instituted throughout our hospital and maintained for a period of 10 days, which is the estimated maximum incubation period reported for this disease. Aggressive surveillance measures among hospital staff, patients and visitors were also maintained during this time.
Results
During the surveillance period, 15 individuals (10 hospital staff, 3 patients and 2 visitors) were identified as meeting the case definition for probable or suspected SARS, in addition to our index case. All but 1 individual had had direct contact with a symptomatic patient with SARS during the period of unprotected exposure. No additional cases were identified after infection control precautions had been implemented for 8 days. No cases of secondary transmission were identified in the 21 days following the implementation of these precautions at our institution.
Interpretation
SARS can easily be spread by direct personal contact in the hospital setting. We found that the implementation of aggressive infection control measures is effective in preventing further transmission of this disease.
PMCID: PMC155957  PMID: 12771070
7.  Homelessness and the Response to Emerging Infectious Disease Outbreaks: Lessons from SARS 
Journal of Urban Health   2008;85(3):402-410.
During the 2003 severe acute respiratory syndrome (SARS) outbreak in Toronto, the potential introduction of SARS into the homeless population was a serious concern. Although no homeless individual in Toronto contracted SARS, the outbreak highlighted the need to develop an outbreak preparedness plan that accounts for unique issues related to homeless people. We conducted key informant interviews with homeless service providers and public health officials (n = 17) and identified challenges specific to the homeless population in the areas of communication, infection control, isolation and quarantine, and resource allocation. Planning for future outbreaks should take into account the need to (1) develop systems that enable rapid two-way communication between public health officials and homeless service providers, (2) ensure that homeless service providers have access to infection control supplies and staff training, (3) prepare for possible homeless shelter closures due to staff shortages or high attack rates among clients, and (4) plan for where and how clinically ill homeless individuals will be isolated and treated. The Toronto SARS experience provided insights that are relevant to response planning for future outbreaks in cities with substantial numbers of homeless individuals.
doi:10.1007/s11524-008-9270-2
PMCID: PMC2329752  PMID: 18347991
Contact tracing; Disease outbreaks; Homeless persons; Human; Influenza; Patient isolation; Quarantine; Severe acute respiratory syndrome.
8.  Clinical review: SARS – lessons in disaster management 
Critical Care  2005;9(4):384-389.
Disaster management plans have traditionally been required to manage major traumatic events that create a large number of victims. Infectious diseases, whether they be natural (e.g. SARS [severe acute respiratory syndrome] and influenza) or the result of bioterrorism, have the potential to create a large influx of critically ill into our already strained hospital systems. With proper planning, hospitals, health care workers and our health care systems can be better prepared to deal with such an eventuality. This review explores the Toronto critical care experience of coping in the SARS outbreak disaster. Our health care system and, in particular, our critical care system were unprepared for this event, and as a result the impact that SARS had was worse than it could have been. Nonetheless, we were able to organize a response rapidly during the outbreak. By describing our successes and failures, we hope to help others to learn and avoid the problems we encountered as they develop their own disaster management plans in anticipation of similar future situations.
doi:10.1186/cc3041
PMCID: PMC1269424  PMID: 16137388
9.  Interpretation of diagnostic laboratory tests for severe acute respiratory syndrome: the Toronto experience 
Background
An outbreak of severe acute respiratory syndrome (SARS) began in Canada in February 2003. The initial diagnosis of SARS was based on clinical and epidemiological criteria. During the outbreak, molecular and serologic tests for the SARS-associated coronavirus (SARS-CoV) became available. However, without a “gold standard,” it was impossible to determine the usefulness of these tests. We describe how these tests were used during the first phase of the SARS outbreak in Toronto and offer some recommendations that may be useful if SARS returns.
Methods
We examined the results of all diagnostic laboratory tests used in 117 patients admitted to hospitals in Toronto who met the Health Canada criteria for suspect or probable SARS. Focusing on tests for SARS-CoV, we attempted to determine the optimal specimen types and timing of specimen collection.
Results
Diagnostic test results for SARS-CoV were available for 110 of the 117 patients. SARS-CoV was detected by means of reverse-transcriptase polymerase chain reaction (RT-PCR) in at least one specimen in 59 (54.1%) of 109 patients. Serologic test results of convalescent samples were positive in 50 (96.2%) of 52 patients for whom paired serum samples were collected during the acute and convalescent phases of the illness. Of the 110 patients, 78 (70.9%) had specimens that tested positive by means of RT-PCR, serologic testing or both methods. The proportion of RT-PCR test results that were positive was similar between patients who met the criteria for suspect SARS (50.8%, 95% confidence interval [CI] 38.4%–63.2%) and those who met the criteria for probable SARS (58.0%, 95% CI 44.2%–70.7%). SARS-CoV was detected in nasopharyngeal swabs in 33 (32.4%) of 102 patients, in stool specimens in 19 (63.3%) of 30 patients, and in specimens from the lower respiratory tract in 10 (58.8%) of 17 patients.
Interpretation
These findings suggest that the rapid diagnostic tests in use at the time of the initial outbreak lack sufficient sensitivity to be used clinically to rule out SARS. As tests for SARS-CoV continue to be optimized, evaluation of the clinical presentation and elucidation of a contact history must remain the cornerstone of SARS diagnosis. In patients with SARS, specimens taken from the lower respiratory tract and stool samples test positive by means of RT-PCR more often than do samples taken from other areas.
PMCID: PMC305313  PMID: 14707219
10.  Population mortality during the outbreak of Severe Acute Respiratory Syndrome in Toronto 
BMC Public Health  2007;7:93.
Background
Extraordinary infection control measures limited access to medical care in the Greater Toronto Area during the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak. The objective of this study was to determine if the period of these infection control measures was associated with changes in overall population mortality due to causes other than SARS.
Methods
Observational study of death registry data, using Poisson regression and interrupted time-series analysis to examine all-cause mortality rates (excluding deaths due to SARS) before, during, and after the SARS outbreak. The population of Ontario was grouped into the Greater Toronto Area (N = 2.9 million) and the rest of Ontario (N = 9.3 million) based upon the level of restrictions on delivery of clinical services during the SARS outbreak.
Results
There was no significant change in mortality in the Greater Toronto Area before, during, and after the period of the SARS outbreak in 2003 compared to the corresponding time periods in 2002 and 2001. The rate ratio for all-cause mortality during the SARS outbreak was 0.99 [95% Confidence Interval (CI) 0.93–1.06] compared to 2002 and 0.96 [95% CI 0.90–1.03] compared to 2001. An interrupted time series analysis found no significant change in mortality rates in the Greater Toronto Area associated with the period of the SARS outbreak.
Conclusion
Limitations on access to medical services during the 2003 SARS outbreak in Toronto had no observable impact on short-term population mortality. Effects on morbidity and long-term mortality were not assessed. Efforts to contain future infectious disease outbreaks due to influenza or other agents must consider effects on access to essential health care services.
doi:10.1186/1471-2458-7-93
PMCID: PMC1894965  PMID: 17535440
11.  Investigation of a nosocomial outbreak of severe acute respiratory syndrome (SARS) in Toronto, Canada 
Background
Severe acute respiratory syndrome (SARS) was introduced into Canada by a visitor to Hong Kong who returned to Toronto on Feb. 23, 2003. Transmission to a family member who was later admitted to a community hospital in Toronto led to a large nosocomial outbreak. In this report we summarize the preliminary results of the epidemiological investigation into the transmission of SARS between 128 cases associated with this hospital outbreak.
Methods
We collected epidemiologic data on 128 probable and suspect cases of SARS associated with the hospital outbreak, including those who became infected in hospital and the next generation of illness arising among their contacts. Incubation periods were calculated based on cases with a single known exposure. Transmission chains from the index family to hospital contacts and within the hospital were mapped. Attack rates were calculated for nurses in 3 hospital wards where transmission occurred.
Results
The cases ranged in age from 21 months to 86 years; 60.2% were female. Seventeen deaths were reported (case-fatality rate 13.3%). Of the identified cases, 36.7% were hospital staff. Other cases were household or social contacts of SARS cases (29.6%), hospital patients (14.1%), visitors (14.1%) or other health care workers (5.5%). Of the 128 cases, 120 (93.8%) had documented contact with a SARS case or with a ward where there was a known SARS case. The remaining 8 cases without documented exposure are believed to have had exposure to an unidentified case and remain under investigation. The attack rates among nurses who worked in the emergency department, intensive care unit and coronary care unit ranged from 10.3% to 60.0%. Based on 42 of the 128 cases with a single known contact with a SARS case, the mean incubation period was 5 days (range 2 to 10 days).
Interpretation
Evidence to date suggests that SARS is a severe respiratory illness spread mainly by respiratory droplets. There has been no evidence of further transmission within the hospital after the elapse of 2 full incubation periods (20 days).
PMCID: PMC180651  PMID: 12925421
12.  Risk Factors for SARS Transmission from Patients Requiring Intubation: A Multicentre Investigation in Toronto, Canada 
PLoS ONE  2010;5(5):e10717.
Background
In the 2003 Toronto SARS outbreak, SARS-CoV was transmitted in hospitals despite adherence to infection control procedures. Considerable controversy resulted regarding which procedures and behaviours were associated with the greatest risk of SARS-CoV transmission.
Methods
A retrospective cohort study was conducted to identify risk factors for transmission of SARS-CoV during intubation from laboratory confirmed SARS patients to HCWs involved in their care. All SARS patients requiring intubation during the Toronto outbreak were identified. All HCWs who provided care to intubated SARS patients during treatment or transportation and who entered a patient room or had direct patient contact from 24 hours before to 4 hours after intubation were eligible for this study. Data was collected on patients by chart review and on HCWs by interviewer-administered questionnaire. Generalized estimating equation (GEE) logistic regression models and classification and regression trees (CART) were used to identify risk factors for SARS transmission.
Results
45 laboratory-confirmed intubated SARS patients were identified. Of the 697 HCWs involved in their care, 624 (90%) participated in the study. SARS-CoV was transmitted to 26 HCWs from 7 patients; 21 HCWs were infected by 3 patients. In multivariate GEE logistic regression models, presence in the room during fiberoptic intubation (OR = 2.79, p = .004) or ECG (OR = 3.52, p = .002), unprotected eye contact with secretions (OR = 7.34, p = .001), patient APACHE II score ≥20 (OR = 17.05, p = .009) and patient Pa02/Fi02 ratio ≤59 (OR = 8.65, p = .001) were associated with increased risk of transmission of SARS-CoV. In CART analyses, the four covariates which explained the greatest amount of variation in SARS-CoV transmission were covariates representing individual patients.
Conclusion
Close contact with the airway of severely ill patients and failure of infection control practices to prevent exposure to respiratory secretions were associated with transmission of SARS-CoV. Rates of transmission of SARS-CoV varied widely among patients.
doi:10.1371/journal.pone.0010717
PMCID: PMC2873403  PMID: 20502660
13.  Effect of widespread restrictions on the use of hospital services during an outbreak of severe acute respiratory syndrome 
Background
Restrictions on the nonurgent use of hospital services were imposed in March 2003 to control an outbreak of severe acute respiratory syndrome (SARS) in Toronto, Ont. We describe the impact of these restrictions on health care utilization and suggest lessons for future epidemics.
Methods
We performed a retrospective population-based study of the Greater Toronto Area (hereafter referred to as Toronto) and unaffected comparison regions (Ottawa and London, Ont.) before, during and after the SARS outbreak (April 2001–March 2004). We determined the adjusted rates of hospital admissions, emergency department and outpatient visits, diagnostic testing and drug prescribing.
Results
During the early and late SARS restriction periods, the rate of overall and medical admissions decreased by 10%–12% in Toronto; there was no change in the comparison regions. The rate of elective surgery in Toronto fell by 22% and 15% during the early and late restriction periods respectively and by 8% in the comparison regions. The admission rates for urgent surgery remained unchanged in all regions; those for some acute serious medical conditions decreased by 15%–21%. The rates of elective cardiac procedures declined by up to 66% in Toronto and by 71% in the comparison regions; the rates of urgent and semi-urgent procedures declined little or increased. High-acuity visits to emergency departments fell by 37% in Toronto, and inter-hospital patient transfers fell by 44% in the circum-Toronto area. Drug prescribing and primary care visits were unchanged in all regions.
Interpretation
The restrictions achieved modest reductions in overall hospital admissions and substantial reductions in the use of elective services. Brief reductions occurred in admissions for some acute serious conditions, high-acuity visits to emergency departments and inter-hospital patient transfers suggesting that access to care for some potentially seriously ill patients was affected.
doi:10.1503/cmaj.061174
PMCID: PMC1891122  PMID: 17576979
14.  A Severe Acute Respiratory Syndrome extranet: supporting local communication and information dissemination 
Background
The objective of this study was to explore the use and perceptions of a local Severe Acute Respiratory Syndrome (SARS) Extranet and its potential to support future information and communication applications. The SARS Extranet was a single, managed electronic and limited access system to manage local, provincial and other SARS control information.
Methods
During July, 2003, a web-based and paper-based survey was conducted with 53 SARS Steering Committee members in Hamilton. It assessed the use and perceptions of the Extranet that had been built to support the committee during the SARS outbreak. Before distribution, the survey was user-tested based on a think-aloud protocol, and revisions were made. Quantitative and qualitative questions were asked related to frequency of use of the Extranet, perceived overall usefulness of the resource, rationale for use, potential barriers, strengths and limitations, and potential future uses of the Extranet.
Results
The response rate was 69.4% (n = 34). Of all respondents, 30 (88.2%) reported that they had visited the site, and rated it highly overall (mean = 4.0; 1 = low to 5 = high). However, the site was rated 3.4 compared with other communications strategies used during the outbreak. Almost half of all respondents (44.1%) visited the site at least once every few days. The two most common reasons the 30 respondents visited the Extranet were to access SARS Steering Committee minutes (63.3%) and to access Hamilton medical advisories (53.3%). The most commonly cited potential future uses for the Extranet were the sending of private emails to public health experts (63.3%), and surveillance (63.3%). No one encountered personal barriers in his or her use of the site, but several mentioned that time and duplication of email information were challenges.
Conclusion
Despite higher rankings of various communication strategies during the SARS outbreak, such as email, meetings, teleconferences, and other web sites, users generally perceived a local Extranet as a useful support for the dissemination of local information during public health emergencies.
doi:10.1186/1472-6947-5-17
PMCID: PMC1166558  PMID: 15967040
15.  Clinical course and management of SARS in health care workers in Toronto: a case series 
Background
Severe acute respiratory syndrome (SARS) has only recently been described. We provide individual patient data on the clinical course, treatment and complications experienced by 14 front-line health care workers and hospital support staff in Toronto who were diagnosed with SARS, and we provide follow-up information for up to 3 weeks after their discharge from hospital.
Methods
As part of the initial response to the SARS outbreak in Toronto, our health care centre was asked to establish a SARS unit for health care workers who were infected. Patients were admitted to this unit and were closely monitored and treated until they were well enough to be discharged. We prospectively compiled information on their clinical course, management and complications and followed them for 3 weeks after discharge.
Results
The 11 women and 3 men described here (mean age 42 [standard deviation {SD} 9] years) were all involved in providing medical or ancillary hospital services to patients who were later found to have SARS. Onset of symptoms in 4 of our patients who could clearly identify only a single contact with a patient with SARS occurred on average 4 (SD 3) days after exposure. For the remaining 10 patients with multiple patient contacts, symptom onset followed exposure by a mean of 3.5 (SD 3) days after their exposure. All patients were treated with ribavirin, and all patients received levofloxacin. Many experienced major complications. Dyspnea was present in 12 patients during their stay in hospital, and all developed abnormalities on chest radiograph; 3 patients developed severe hypoxemia (PaO2 < 50 mm Hg). All patients experienced a drop in hemoglobin. Nine patients had hemolytic anemia. Three patients experienced numbness and tingling in their hands and feet, and 2 developed frank tetany. All 3 had magnesium levels that were less than 0.1 mmol/L. All patients recovered and were discharged home. At a follow-up examination 3 weeks after discharge (5 weeks after onset of illness), all patients were no longer weak but continued to become fatigued easily and had dyspnea on minimal exertion. For 5 patients, chest radiographs still showed residual disease.
Interpretation
SARS is a very serious illness even in healthy, relatively young people. The clinical course in our patients, all of whom met the case definition for SARS (which requires pulmonary involvement), resulted in dyspnea and, in some individuals, severe hypoxemia. Severe hemolytic anemia may be a feature of SARS or may be a complication of therapy, possibly with ribavirin.
PMCID: PMC161610  PMID: 12821618
16.  The impact of SARS on a tertiary care pediatric emergency department 
Background
The Greater Toronto Area (GTA) was considered a “hot zone” for severe acute respiratory syndrome (SARS) in 2003. In accordance with mandated city-wide infection control measures, the Hospital for Sick Children (HSC) drastically reduced all services while maintaining a fully operational emergency department. Because of the GTA health service suspensions and the overlap of SARS-like symptoms with many common childhood illnesses, this introduced the potential for a change in the volumes of patients visiting the emergency department of the only regional tertiary care children's hospital.
Methods
We compared HSC emergency department patient volumes, admission rates and length of stay in the emergency department in the baseline years of 2000–2002 (non-SARS years) with those in 2003 (SARS year). The data from the prior years were modeled as a time series. Using an interrupted time series analysis, we compared the 2003 data for the periods before, during and after the SARS periods with the modeled data for significant differences in the 3 aforementioned outcomes of interest.
Results
Compared with the 2000–2002 data, we found no differences in visits, admission rates or length of stay in the pre-SARS period in 2003. There were significant decreases in visits and length of stay (p < 0.001) and increases in admission rates (p < 0.001) during the periods in 2003 when there were new and active cases of SARS in the GTA. All 3 outcomes returned to expected estimates coincident with the absence of SARS cases from September to December 2003.
Interpretation
During the SARS outbreak in the GTA, the HSC emergency department experienced significantly reduced volumes of patients with low-acuity complaints. This gives insight into utilization rates of a pediatric emergency department during a time when there was additional perceived risk in using emergency department services and provides a foundation for emergency department preparedness policies for SARS-like public health emergencies.
doi:10.1503/cmaj.1031257
PMCID: PMC527337  PMID: 15557588
17.  Modelling strategies for controlling SARS outbreaks. 
Severe acute respiratory syndrome (SARS), a new, highly contagious, viral disease, emerged in China late in 2002 and quickly spread to 32 countries and regions causing in excess of 774 deaths and 8098 infections worldwide. In the absence of a rapid diagnostic test, therapy or vaccine, isolation of individuals diagnosed with SARS and quarantine of individuals feared exposed to SARS virus were used to control the spread of infection. We examine mathematically the impact of isolation and quarantine on the control of SARS during the outbreaks in Toronto, Hong Kong, Singapore and Beijing using a deterministic model that closely mimics the data for cumulative infected cases and SARS-related deaths in the first three regions but not in Beijing until mid-April, when China started to report data more accurately. The results reveal that achieving a reduction in the contact rate between susceptible and diseased individuals by isolating the latter is a critically important strategy that can control SARS outbreaks with or without quarantine. An optimal isolation programme entails timely implementation under stringent hygienic precautions defined by a critical threshold value. Values below this threshold lead to control, but those above are associated with the incidence of new community outbreaks or nosocomial infections, a known cause for the spread of SARS in each region. Allocation of resources to implement optimal isolation is more effective than to implement sub-optimal isolation and quarantine together. A community-wide eradication of SARS is feasible if optimal isolation is combined with a highly effective screening programme at the points of entry.
doi:10.1098/rspb.2004.2800
PMCID: PMC1691853  PMID: 15539347
18.  Lessons learned from international responses to severe acute respiratory syndrome (SARS) 
In early February 2003, a previously unknown disease causing severe pneumonia was recognised. This disease which is now known as severe acute respiratory syndrome (SARS) is believed to have had its origins in the Guangdong Province of China, and was the cause of a multi-country epidemic resulting in significant morbidity and mortality. The World Health Organization (WHO) has been coordinating the international response to provide the epidemiological, laboratory, clinical and logistic requirements needed to contain this disease.
A rapid spread of SARS around the world occurred at its onset, facilitated greatly by air travel. Between November 2002 and July 2003, a total of 8,094 cases and 774 cases were reported from 26 countries worldwide.
WHO responded quickly to this multi-country outbreak and on 12 March released a “global alert” about SARS. This was followed by the first WHO travel advisory on 15 March. The Global Outbreak Alert and Response Network was activated, and international experts were brought together to implement enhanced global surveillance systems for SARS.
The international community has learned a lot of lessons from the SARS outbreak. Particularly, rapid and transparent information sharing between countries is critical to prevent international spread of the disease. However, information exchange was less than optimal in the early phase of the outbreak.
doi:10.1007/BF02897698
PMCID: PMC2723407  PMID: 21432127
SARS; WHO; global outbreak alert; response network; international health regulations
19.  Prevalence of Psychiatric Disorders Among Toronto Hospital Workers One to Two Years After the SARS Outbreak 
Objective
This study aimed to determine the incidence of psychiatric disorders among health care workers in Toronto in the one- to two-year period after the 2003 outbreak of severe acute respiratory syndrome (SARS) and to test predicted risk factors.
Methods
New-onset episodes of psychiatric disorders were assessed among 139 health care workers by using the Structured Clinical Interview for DSM-IV and the Clinician-Administered PTSD Scale. Past history of psychiatric illness, years of health care experience, and the perception of adequate training and support were tested as predictors of the incidence of new-onset episodes psychiatric disorders after the SARS outbreak.
Results
The lifetime prevalence of any depressive, anxiety, or substance use diagnosis was 30%. Only one health care worker who identified the SARS experience as a traumatic event was diagnosed as having PTSD. New episodes of psychiatric disorders occurred among seven health care workers (5%). New episodes of psychiatric disorders were directly associated with a history of having a psychiatric disorder before the SARS outbreak (p=.02) and inversely associated with years of health care experience (p=.03) and the perceived adequacy of training and support (p=.03).
Conclusions
Incidence of new episodes of psychiatric disorders after the SARS outbreak were similar to or lower than community incidence rates, which may indicate the resilience of health care workers who continued to work in hospitals one to two years after the SARS outbreak. In preparation for future events, such as pandemic influenza, training and support may bolster the resilience of health care workers who are at higher risk by virtue of their psychiatric history and fewer years of health care experience.
doi:10.1176/appi.ps.59.1.91
PMCID: PMC2923654  PMID: 18182545 CAMSID: cams1445
20.  The immediate psychological and occupational impact of the 2003 SARS outbreak in a teaching hospital 
Background
The outbreak of severe acute respiratory syndrome (SARS) in Toronto, which began on Mar. 7, 2003, resulted in extraordinary public health and infection control measures. We aimed to describe the psychological and occupational impact of this event within a large hospital in the first 4 weeks of the outbreak and the subsequent administrative and mental health response.
Methods
Two principal authors met with core team members and mental health care providers at Mount Sinai Hospital, Toronto, to compile retrospectively descriptions of the experiences of staff and patients based on informal observation. All authors reviewed and analyzed the descriptions in an iterative process between Apr. 3 and Apr. 13, 2003.
Results
In a 4-week period, 19 individuals developed SARS, including 11 health care workers. The hospital's response included establishing a leadership command team and a SARS isolation unit, implementing mental health support interventions for patients and staff, overcoming problems with logistics and communication, and overcoming resistance to directives. Patients with SARS reported fear, loneliness, boredom and anger, and they worried about the effects of quarantine and contagion on family members and friends. They experienced anxiety about fever and the effects of insomnia. Staff were adversely affected by fear of contagion and of infecting family, friends and colleagues. Caring for health care workers as patients and colleagues was emotionally difficult. Uncertainty and stigmatization were prominent themes for both staff and patients.
Interpretation
The hospital's response required clear communication, sensitivity to individual responses to stress, collaboration between disciplines, authoritative leadership and provision of relevant support. The emotional and behavioural reactions of patients and staff are understood to be a normal, adaptive response to stress in the face of an overwhelming event.
PMCID: PMC154178  PMID: 12743065
21.  The Impact of Severe Acute Respiratory Syndrome on Medical House Staff 
OBJECTIVE
To explore the impact of severe acute respiratory syndrome (SARS) on a medical training program and to develop principles for professional training programs to consider in dealing with future, similar crises.
DESIGN
Qualitative interviews analyzed using grounded theory methodology.
SETTING
University-affiliated hospitals in Toronto, Canada during the SARS outbreak in 2003.
PARTICIPANTS
Medical house staff who were allocated to a general internal medicine clinical teaching unit, infectious diseases consultation service, or intensive care unit.
RESULTS
Seventeen medical residents participated in this study. Participants described their experiences during the outbreak and highlighted several themes including concerns about their personal safety and about the negative impact of the outbreak on patient care, house staff education, and their emotional well-being.
CONCLUSION
The ability of residents to cope with the stress of the SARS outbreak was enhanced by the communication of relevant information and by the leadership of their supervisors and infection control officers. It is hoped that training programs for health care professionals will be able to implement these tenets of crisis management as they develop strategies for dealing with future health threats.
doi:10.1111/j.1525-1497.2005.0099.x
PMCID: PMC1490116  PMID: 15963157
medical house staff; severe acute respiratory distress syndrome; training program; outbreak
22.  How infectious disease outbreaks affect community-based primary care physicians 
Canadian Family Physician  2014;60(10):917-925.
Abstract
Objective
To compare how the infectious disease outbreaks H1N1 and severe acute respiratory syndrome (SARS) affected community-based GPs and FPs.
Design
A mailed survey sent after the H1N1 outbreak compared with the results of similar survey completed after the SARS outbreak.
Setting
Greater Toronto area in Ontario.
Participants
A total of 183 randomly selected GPs and FPs who provided office-based care.
Main outcome measures
The perceptions of GPs and FPs on how serious infectious disease outbreaks affected their clinical work and personal lives; their preparedness for a serious infectious disease outbreak; and the types of information they want to receive and the sources they wanted to receive information from during a serious infectious disease outbreak. The responses from this survey were compared with the responses of GPs and FPs in the greater Toronto area who completed a similar survey in 2003 after the SARS outbreak.
Results
After the H1N1 outbreak, GPs and FPs still had substantial concerns about the effects of serious infectious disease outbreaks on the health of their family members. Physicians made changes to various office practices in order to manage and deal with patients with serious infectious diseases. They expressed concerns about the effects of an infectious disease on the provision of health care services. Also, physicians wanted to quickly receive accurate information from the provincial government and their medical associations.
Conclusion
Serious community-based infectious diseases are a personal concern for GPs and FPs, and have considerable effects on their clinical practice. Further work examining the timely flow of relevant information through different health care sectors and government agencies still needs to be undertaken.
PMCID: PMC4196817  PMID: 25316747
23.  The experience of the 2003 SARS outbreak as a traumatic stress among frontline healthcare workers in Toronto: lessons learned. 
The outbreak of severe acute respiratory syndrome (SARS) in the first half of 2003 in Canada was unprecedented in several respects. Understanding the psychological impact of the outbreak on healthcare workers, especially those in hospitals, is important in planning for future outbreaks of emerging infectious diseases. This review draws upon qualitative and quantitative studies of the SARS outbreak in Toronto to outline the factors that contributed to healthcare workers' experiencing the outbreak as a psychological trauma. Overall, it is estimated that a high degree of distress was experienced by 29-35% of hospital workers. Three categories of contributory factors were identified. Relevant contextual factors were being a nurse, having contact with SARS patients and having children. Contributing attitudinal factors and processes were experiencing job stress, perceiving stigmatization, coping by avoiding crowds and colleagues, and feeling scrutinized. Pre-existing trait factors also contributed to vulnerability. Lessons learned from the outbreak include: (i) that effort is required to mitigate the psychological impact of infection control procedures, especially the interpersonal isolation that these procedures promote; (ii) that effective risk communication is a priority early in an outbreak; (iii) that healthcare workers may have a role in influencing patterns of media coverage that increase or decrease morale; (iv) that healthcare workers benefit from resources that facilitate reflection on the effects of extraordinary stressors; and (v) that healthcare workers benefit from practical interventions that demonstrate tangible support from institutions.
doi:10.1098/rstb.2004.1483
PMCID: PMC1693388  PMID: 15306398
24.  Factors associated with nosocomial SARS-CoV transmission among healthcare workers in Hanoi, Vietnam, 2003 
BMC Public Health  2006;6:207.
Background
In March of 2003, an outbreak of Severe Acute Respiratory Syndrome (SARS) occurred in Northern Vietnam. This outbreak began when a traveler arriving from Hong Kong sought medical care at a small hospital (Hospital A) in Hanoi, initiating a serious and substantial transmission event within the hospital, and subsequent limited spread within the community.
Methods
We surveyed Hospital A personnel for exposure to the index patient and for symptoms of disease during the outbreak. Additionally, serum specimens were collected and assayed for antibody to SARS-associated coronavirus (SARS-CoV) antibody and job-specific attack rates were calculated. A nested case-control analysis was performed to assess risk factors for acquiring SARS-CoV infection.
Results
One hundred and fifty-three of 193 (79.3%) clinical and non-clinical staff consented to participate. Excluding job categories with <3 workers, the highest SARS attack rates occurred among nurses who worked in the outpatient and inpatient general wards (57.1, 47.4%, respectively). Nurses assigned to the operating room/intensive care unit, experienced the lowest attack rates (7.1%) among all clinical staff. Serologic evidence of SARS-CoV infection was detected in 4 individuals, including 2 non-clinical workers, who had not previously been identified as SARS cases; none reported having had fever or cough. Entering the index patient's room and having seen (viewed) the patient were the behaviors associated with highest risk for infection by univariate analysis (odds ratios 20.0, 14.0; 95% confidence intervals 4.1–97.1, 3.6–55.3, respectively).
Conclusion
This study highlights job categories and activities associated with increased risk for SARS-CoV infection and demonstrates that a broad diversity of hospital workers may be vulnerable during an outbreak. These findings may help guide recommendations for the protection of vulnerable occupational groups and may have implications for other respiratory infections such as influenza.
doi:10.1186/1471-2458-6-207
PMCID: PMC1562405  PMID: 16907978
25.  Time Course and Cellular Localization of SARS-CoV Nucleoprotein and RNA in Lungs from Fatal Cases of SARS 
PLoS Medicine  2006;3(2):e27.
Background
Cellular localization of severe acute respiratory syndrome coronavirus (SARS-CoV) in the lungs of patients with SARS is important in confirming the etiological association of the virus with disease as well as in understanding the pathogenesis of the disease. To our knowledge, there have been no comprehensive studies investigating viral infection at the cellular level in humans.
Methods and Findings
We collected the largest series of fatal cases of SARS with autopsy material to date by merging the pathological material from two regions involved in the 2003 worldwide SARS outbreak in Hong Kong, China, and Toronto, Canada. We developed a monoclonal antibody against the SARS-CoV nucleoprotein and used it together with in situ hybridization (ISH) to analyze the autopsy lung tissues of 32 patients with SARS from Hong Kong and Toronto. We compared the results of these assays with the pulmonary pathologies and the clinical course of illness for each patient. SARS-CoV nucleoprotein and RNA were detected by immunohistochemistry and ISH, respectively, primarily in alveolar pneumocytes and, less frequently, in macrophages. Such localization was detected in four of the seven patients who died within two weeks of illness onset, and in none of the 25 patients who died later than two weeks after symptom onset.
Conclusions
The pulmonary alveolar epithelium is the chief target of SARS-CoV, with macrophages infected subsequently. Viral replication appears to be limited to the first two weeks after symptom onset, with little evidence of continued widespread replication after this period. If antiviral therapy is considered for future treatment, it should be focused on this two-week period of acute clinical disease.
The SARS coronavirus targets primarily the pulmonary alveolar epithelium. Viral replication seems limited to the first two weeks after symptom onset and restricted to the lungs.
doi:10.1371/journal.pmed.0030027
PMCID: PMC1324951  PMID: 16379499

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