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Diseases and Conditions
SARS
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Guide for Healthcare ProfessionalsMiscellaneous
Important Points- A high index of suspicion is crucial for the early diagnosis of SARS.
- SARS presents clinically as a prodromal illness with sudden onset of fever. Lower respiratory phase begins within 3-7 days after onset of prodrome.
- Some cases of SARS may present atypically. If these are not recognised early and appropriate precautions are not taken, clusters of SARS infection may develop.
- Transmission occurs through close contact with a symptomatic person. Close contact means having cared for, lived with or had face to face contact with, or direct contact with respiratory secretions and/or body fluids of a person with SARS.
- The cases that are the most ill are often the most infectious.
- Transmission from an asymptomatic person is unlikely though there may be transmission during the prodromal period (i.e., when early symptoms are present).
- Immuno-suppressed patients or patients with chronic disease may have high viral loads, yet present with less florid symptoms. These patients have multiple opportunities to spread infection amongst their families, and healthcare workers. Extra vigilance is warranted.
- All current evidence indicates that infection control measures, including the use of N95 respirator (mask) or equivalent and eye protection, are effective in preventing transmission to care givers.
- Be extremely cautious every time you consider nebulising a patient.
Basic Facts- SARS
Severe acute respiratory syndrome (SARS) is a respiratory illness that has recently emerged in various regions of Asia, North America, and Europe. The following websites provide up to date information on SARS
- Symptoms of SARS
(Percentages below refer to prevalence of each symptom among local SARS cases)
In general, SARS begins with a fever greater than 38.0°C (100%) following an incubation period ranging from 2 to 10 days. Other symptoms include dry cough (75%) myalgia (45%), malaise (45%) anorexia (45%) shortness of breath (40%) nausea/vomiting (35%) Sore throat, diarrhoea, headache, rigors and rhinorrhoea also occur 15-25% of the time. In the elderly, malaise and lethargy may be a more prominent feature. They also may not exhibit such a febrile response. Chronic disease may mask an underlying SARS infection and medical staff need to have a high index of suspicion in any patient with breathing difficulties, especially if there has been a positive contact history.
(Source: SARS in Singapore: Clinical Features of Index Patient and Initial Contacts.) - Clinical Information
Initial clinical features of SARS are nonspecific. Dry cough is common, although other symptoms of upper respiratory tract infection are not unusual. Physical signs on chest examination are minimal, and chest X-rays may be normal on week 1 of illness. Laboratory tests often show lymphopenia, mild thrombocytopenia, and elevated liver enzymes. Therefore, in early stages, it may be hard to differentiate SARS from other viral infections, and diagnostic delays may contribute to the spread of the epidemic. Early diagnosis relies on known history of potential exposure to SARS. Clinicians must maintain a high index of suspicion and be familiar with the rapidly changing epidemiology of this infection. The key to success in containing SARS is early identification and early isolation of infected persons. - How SARS spreads
SARS appears to spread predominantly through close person-to-person contact. Most cases of SARS have involved people who cared for or lived with someone with SARS, or had direct contact with infectious material such as respiratory secretions of other bodily fluids from a person who has SARS. Evidence does not currently support airborne spread. - How did SARS spread to Singapore?
Most of Singapore's cases of probable SARS can be traced back to a single index case of a previously healthy Chinese woman who had stayed on the 9th floor of a hotel during a vacation to Hong Kong. When she was first seen in early March, the clinical features and highly infectious nature of SARS were not known. For the first 6 days, she was hospitalised in a general ward without the enhanced methods of infection control now recognised to be necessary for SARS. A physician, 9 nurses, a patient in an adjacent bed and 30 family members and friends became infected and resulted in the spread of SARS in Singapore.
(Source: MMWR: SARS Syndrome - United States, 2003.) - Possible cause of SARS
Scientists working collaboratively in laboratories around the world have detected a new pathogenic coronavirus in patients with SARS. The genomic sequence of the virus in Singapore, Vietnam, Hong Kong and Canada is slightly different from that found in isolates from Guangzhou and North China. This may be a mutation in response to immunological challenges. It is not known at this stage whether these differences in genomic sequence translate into any biological or clinical differences.
(Source: Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection.)
A similar coronavirus has been isolated in civet cats and raccoon dogs in Guangdong. Positive antibodies to the virus have also been found in asymptomatic animal traders. WHO is currently looking into the significance of these findings.
Epidemiology
In Singapore the median age of probable SARS cases was 36 years (range 4 to 90) and 66% were female. The ethnic breakdown was Chinese (65%), Malay (12%), Indian (11%) and Others (12%).
Healthcare workers represented 42% of probable SARS cases. Just over half of these were nurses.
Of the eight people that acquired probable SARS outside Singapore, only one resulted in additional cases.
(Source: MMWR: SARS - Singapore 2003.)
Case Definition
The case definition for SARS includes both clinical features and travel/contact history.
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Fever (>38°C)
AND
Cough or breathing difficulty | AND | Positive travel history*
OR
Close contact history in preceding 10 days | Fever (>38°C)
AND
Cough or breathing difficulty
AND
X-ray changes of pneumonia OR
Respiratory distress syndrome OR
Autopsy findings of RDS without an identifiable cause | AND | Positive travel history*
OR
Close contact history in preceding 10 days
OR
Positive PCR or serological test for coronavirus (by WHO/US CDC criteria) | |
* Positive travel history: Travel in the previous 10 days to SARS-affected areas as listed by WHO.- Observation for SARS
In the post SARS period we must remain vigilant for SARS, and maintain our ability to detect and respond to the re-emergence of SARS, should it occur. The previous case definition relied heavily on contact or travel history, however since July 4th when Taiwan was removed from WHO list of countries, these are no longer applicable. Patients who do not fit the previous case definition, but are considered at risk, may therefore be admitted as "Observation for SARS". Patients likely to be observed under this category are:
- Inpatients (>16 years) with atypical pneumonia.
- Inpatients with fever >72 hours and relevant travel history.
- Sudden, unexpected or unexplained deaths with acute respiratory symptoms.
- Fever clusters among healthcare staff and inpatients of hospitals/residents of nursing homes.
This is to ensure that appropriate infection control and public health measures are implemented until SARS has been ruled out.
- Deaths
In cases where SARS cannot be excluded as a cause of death (e.g. pneumonia without an identifiable cause, postmortem findings of respiratory distress syndrome), the body of the deceased should be handled as that of a SARS case.
Patients who die from SARS are to be cremated immediately after preparation of the body. No embalming of the body is allowed. The body should be double-bagged, placed in a windowless coffin and hermetically sealed. No wakes are allowed for SARS deaths. However, burial is allowed for religious reasons.
Investigations and Diagnosis
Data from Singapore's first 85 SARS patients revealed the following:
- Lymphocyte count decreased
- White Blood Cell (WBC) count normal or decreased
- At peak of illness leukopaenia, thrombocytopaenia
- Creatinine phosphoKinase (CK) raised (up to 30,000IU/L)
- Transaminase raised (2-6 times normal limit)
- Lactate Dehdrogenase (LDH) raised
- C-Reactive Protein (CRP) raised
- Hypoxia for 60% of patients occurring at the end of the first week.
(Source: SARS in Singapore: Clinical Features of Index Patient and Initial Contacts.)
- Laboratory tests for SARS coronavirus (CoV)
Background
Three diagnostic laboratory tests are available for the SARS-CoV.
- Molecular tests: RT-PCR (Reverse transcriptase - Polymerase chain reaction).
- Antibody tests: ELISA (Enzyme Linked ImmunoSorbant Assay) and IFA (Immunofluorescence Assay).
- Cell culture.
SARS follows a different pattern from many other viral diseases. Normally large amounts of the causative virus are excreted in the first few days after symptoms occur. However, the SARS virus is only produced in small amounts initially and does not peak until around 10 days. Early tests are therefore often negative because the tests are not sensitive enough to pick up the small amounts of virus or genetic material. In SARS patients, a detectable immune response does not begin until day 5 or 6 and reliable antibody tests can only detect the virus by around day 10.
As the tests for SARS-CoV are still new, caution must be taken in using these tests to diagnose or exclude SARS. A negative SARS test does not exclude the illness and should not cause healthcare staff to relax their vigilance on infection control practices.
(Source: WHO: Use of laboratory methods for SARS diagnosis.) - Interpretation of diagnostic tests for SARS-CoV
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| RT-PCR Molecular tests | Presence of genetic material (RNA) of the SARS-CoV is in the sample.
(This does not mean that there is live virus present, or that it is present in a quantity large enough to infect another person.)
A confirmation of a SARS-COV infection occurs when:
- At least 2 different clinical specimens (e.g. nasopharyngeal and stool), OR
- The same clinical specimen collected on 2 or more days during the course of the illness (e.g. 2 or more nasopharyngeal aspirates), OR
- 2 different assays or repeat PCR using the original clinical sample on each occasion of testing
| Does not exclude SARS. The result could be negative for the following reasons:
- The patient is not infected with the SARS-CoV;
- The test results are incorrect (i.e. false negative), because of the low sensitivity. This is a situation where there was genetic material present but it was not detected by the test.
- Genetic material was not present at the time of the collection of the sample.
| | Antibody tests (ELISA & IFA) | Paired sera results are required to indicate a recent infection with SARS-CoV:
- Seroconversion from negative to positive result, OR
- A four-fold rise in antibody titre from acute to convalescent phase
| No detection of antibody after 21 days from onset of illness may indicate that no infection with SARS-CoV took place. | | Cell culture | Indicates the presence of a live SARS-CoV in the sample tested. | Does not exclude SARS. This could be because:
- the patient is not infected with the SARS-CoV;
- the test results are incorrect (i.e. false negative), because of the low sensitivity. This is a situation where genetic material present but was not detected by the test;
- genetic material was not present at the time of the collection of the sample.
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- Radiology
Key Points:- Patients without respiratory symptoms may still have opacities on chest X-ray.
- Opacities tend to be peripheral in mid or lower zones.
- A multifocal pattern is common and keeping in mind the technological limitations of portable chest X-ray machines, some air space shadowing may improve in one area and actually worsen in another.
Chest X-rays may be normal during the febrile prodromal period. Radiological changes initially appear as interstitial infiltrates or small unilateral patchy shadowing. This patchy shadowing may be present in the absence of chest symptoms or clinical signs and may progress over days to become multi-focal and bilateral. In the initial cohort of cases, all contacts with fever eventually developed radiological changes, although the extent of chest X-ray changes and respiratory failure varied widely and subsequent observations suggest a less severe illness in many. The more severe cases progress to Respiratory Distress Syndrome with diffuse bilateral opacities.
Management- Management
Management includes standard treatment for community acquired pneumonia. Until a reliable test is widely available, physicians should consider the use of empiric antibiotic therapy for atypical organisms in cases of probable SARS in which bacterial pneumonia cannot be excluded. Ribavarin has been used in some cases but without clear evidence for its efficacy. Steroids and more latterly, pulsed steroids have also been tried with mixed success. Staged ribavarin during early viral replication, followed by steroids later during the period when most immunological damage is occurring, is currently under investigation. Other treatments being studied include serological therapies and HIV developed protease inhibitors. All are experimental treatments based on a theoretical chance of benefit. Evidence from randomised controlled trials is needed before any particular therapy can be advocated for routine use in SARS patients.
Between 10 and 20% of patients show a drop in oxygen saturation below 95% and require supplemental oxygen. Half of these will progress to a need for mechanical ventilation. This clinical deterioration generally occurs in week 2 or 3 of the illness often after a period of apparent improvement and accompanied by a recurrent fever(85%) and watery diarrhoea (73%). An early study of clinical progression and viral loads published in the Lancet Online (Peiris, Chu et al) did not find an uncontrolled increase in viral replication to explain this deterioration. It is thought this deterioration may be related to immuno-pathological damage.
Mortality
WHO has revised its initial estimates of case fatality. Overall estimate is 14% ( Singapore 13.6%) with higher case fatality occurring in the elderly and those with comorbid disease. To put this in perspective, the case fatality of community acquired pneumonia in Singapore in 2001 was 16.4% across all ages.
Infection Control
A VCD on Preventive Measures for Healthcare Workers (5.95MB) has been circulated to all medical practitioners along with the Manual for SARS Infection Control in Hospitals (123KB).
The keys to containing SARS are:
- Early identification
- Exposure management
- Infection control
- Self-protection
The recommendations are based on the assumptions listed in Important Points listed earlier.
In addition to routine practices, infection control measures for suspect and probable SARS patients should include:
- Airborne Precautions - including an isolation room with negative pressure relative to the surrounding area and use of an N95 respirator (mask) or equivalent for persons entering the room.
- Droplet and Contact Precautions - including use of gown, gloves and eye protection for contact with patients or their environment.
More stringent infection control recommendations may be required in specific situations.
Please refer to the VCD on Preventive Measures for Healthcare Workers (5.95MB) for details on the measures needed to protect yourself and your staff.
- Post discharge procedures
The following procedure has been adopted for patients discharged from TTSH, SGH & NUH. This is to minimise the risk of an infectious patient with atypical presentation of SARS being discharged into the community and re-igniting a fresh outbreak cycle. It was just such a case that caused new clusters in Singapore and overseas.
Such measures are needed due to uncertainty over:
- How long some patients continue to shed virus.
- Longer incubation period of SARS in some individuals.
- Atypical presenting features in patients with chronic disease or who are immuno-compromised such as those on cancer chemotherapy or with chronic renal failure.
- Discharge from "hot" wards in TTSH, SGH, NUH
"Hot" wards are those which have cared for probable SARS patients or had clear exposure to SARS patients or had clusters of suspect staff or patients:
- All patients from these wards with fever or chest symptoms will be isolated for at least 20 days usually in single rooms with strict infection control by hospital staff.
- Before any patients are discharged there should be no cases in the ward with fever or chest symptoms suggestive of SARS for at least 20 days from the date of onset of the last probable SARS case or cluster of suspect cases.
- Serology and stool PCR for coronavirus will be done for all patients and should be negative.
- Patients from these wards that fulfil these conditions can be discharged and placed on home quarantine for a further 10 days.
- At the end of the 10 days, these patients will be recalled for medical review and chest X-ray.
- Discharge of inpatients from other wards
- For all other wards, patients be discharged if they have been afebrile for 72 hours.
- Patients who have chronic co-morbid conditions will be discharged to home quarantine for 10 days.
- At the end of the 10 days, these patients will be recalled for medical review and chest X-ray.
They will be transported by MOH ambulance to SOC for medical review and chest X-ray. If cleared, they are able to use their normal transport to return home.
Travel Guidance
You may be approached by your patients for advice on travel. You can refer them to the general travel information outlined in the Advice on Sars for Singaporeans and Residents Travelling Overseas (21KB). In addition, you should remind your clients of the following:
- If they are unwell or have one or more symptoms of SARS, they should see a doctor and not travel. The trip should be postponed until they have recovered.
- If they are contacts of SARS patients, they should not travel until 10 days after the last contact, assuming that they remain well.
- If they have worked in or visited hospitals handling SARS cases, they should not travel until a 10-day period with no exposure has passed.
- Check with their travel agents before leaving if there are extra precautions/restrictions for Singaporeans, particularly on group tours or cruises, in the countries they are visiting.
References- Websites
- Papers
- Imaging Triage of SARS Toronto in the Crucible May 19
- Battling SARS in Hong Kong (Buckley) May 14
- Despite Progress SARS Is Still A Major Threat May 19
- Medscape Promising Targets For SARS Vaccines And Treatments Emerge
- Infection Control Best Defense Against "Super Spreaders"
- Medscape Chest CT Useful In Diagnosing Questionable SARS Cases: Study
- Interim Australian Infection Control Guidelines for SARS
- NEJM 2003; 348:1977 A Cluster of SARS in Hong Kong Tsang et al
- NEJM 2003, May 15 Vol 348:1995-2005 "Identification of SARS in Canada." Poutanen S, Low D et al
- NEJM 2003, April 21 A Major outbreak of SARS in Hong Kong Lee N, Hui D
- NEJM Identification Of A Novel Corona Virus In Patients with SARS Drosten C, et al
- NEJM A Novel Corona Virus Associated With SARS Ksiazek T, et al
- Lancet Lung Pathology Of Fatal SARS; Nicholls J, Poon L:, et al
- Lancet Multicentre Collaboration To Investigate The Cause Of SARS May 17
- Lancet Online Publication May 9, Comparative full length genome sequence of Corona virus May 9
- Lancet, Published Online May 7, Epidemiological determinants of spread of causal agent of SARS in Hong Kong
- Lancet, Online April 29 Research letter Hon KLE, Leung CW et al Clinical Presentations and outcome of SARS in Children
- Lancet, 2003; May 3; Vol 361:1486 SARS: experience at Prince of Wales Hospital Hong Kong. Tomlinson B Cockram C
- Lancet, Online May 2 Correspondence Razum O, Becher H et al SARS, lay epidemiology and fear
- Lancet; Vol 361:1519-20 On Effectiveness of precautions against droplets and contact in prevention of nosocomial transmission of severe acute respiratory syndrome (SARS) Seto W H, Tsang D et al
- Lancet; Vol 361: 1520-21 Haemorrhagic-fever-like changes and normal chest radiograph in a doctor with SARS Wu E, Sung J
- Lancet Correspondence May 3 Vol 361. Aminopeptidase N inhibitors and SARS Kontoyiannis D, Pas
- Lancet, 2003, April 19 Correspondence SARS Infection Control
- Lancet 2003, April 9, Online service. Corona virus as a possible cause of SARS
- Lancet, 2003, April 8 Online Service Guideline on management of SARS, William Ho
- BMJ 2003, 19 April ; Vol 326 Outbreak of SARS in Hong Kong SAR: Case report Moira Chan-Yeung, W C Yu
- CDC Emerg Infect Dis 2003 May 1, Online service SARS in Singapore: Clinic features of Index cases Hsu L Y, LeeC C Green J A et al
- Guidelines on the management of Community Acquired Pneumonia in Adults Bartlett et al
- US CDC References
Medical Publications
SARS Transmission and Hospital Containment (104KB)
Information paper on SARS by Gowri Gopalakrishna et al., published in the March 04 issue of the US medical journal, Emerging Infectious Diseases.
SARS - Associated Coronavirus (NEJM 15 May 2003)
This commentary gives a broad view of the known nature of the corona virus, its past behaviour in animals (and humans) and suggests some possibilities for drug and vaccine development.
Preventing Local Transmission of SARS; Lessons form Singapore (Fisher et al MJA 19 May 2003)
Based on the NUH cluster it cites 5 lessons:
- Contact histories - Rapid identification of a potential index case at points of initial contact. 48 hours of monitoring results in a clearer picture.
- Clinical triggers for isolation - Isolation beds can protect hospital staff and others.
- Preventing a SARS outbreak in Australia - Unidentified SARS cases not in isolation have to date been responsible for most outbreaks.
- Ensuring rapid control of an Australian outbreak - Each health jurisdiction must have a plan for managing SARS at short notice.
- Resources for a potential outbreak - There are substantial costs involved in preventing local disease transmission but these are insignificant compared with the costs of managing a SARS outbreak.
SARS Aetiology - A Research Update from Malik Peiris
Slides and a summary of a talk given by Malik Peiris on May 30 at New York's Aaron Diamond AIDS Research Center. Dr. Peiris is known for identifying a unique coronavirus as the etiological agent of SARS. To go directly to this summary, please see http://nyas.columbia.edu/sars/web/s7/s7_peiris_update.html.
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