Alert, verification and public health management of SARS in the post-outbreak period


14 August 2003


1.Rationale for continued vigilance for SARS

First recognized as a global threat in mid-March 2003, Severe Acute Respiratory Syndrome (SARS) was successfully contained in less than four months. On 5 July 2003, WHO reported that the last human chain of transmission of SARS had been broken.

While much has been learned about this syndrome since March 2003, including its causation by a new coronavirus (SARS-CoV), our knowledge about the epidemiology and ecology of SARS coronavirus infection and of this disease remains limited. Resurgence of SARS remains a distinct possibility and does not allow for complacency.

In the post-outbreak period, all countries must remain vigilant for the recurrence of SARS and maintain their capacity to detect and respond to the re-emergence of SARS should it occur. The WHO case definitions during the outbreak period relied heavily on epidemiological criteria to increase the specificity of syndromic clinical criteria for atypical pneumonia or respiratory distress syndrome (RDS). However, epidemiological links to cases of SARS and areas reporting recent local transmission are no longer of use in helping to define incident cases. Furthermore, the non-specific clinical features of SARS, the lack of a current rapid diagnostic test that can reliably detect SARS-CoV in the first few days of illness, and the seasonal occurrence of other respiratory diseases, including influenza, may confound any surveillance for SARS or demand a level of quality and intensity which few health care system worldwide can sustain. Even with the most sophisticated surveillance systems, the first case of SARS in the post-outbreak period may escape early detection.

This document describes a SARS alert mechanism for the post-outbreak period. It provides guidance for managing a SARS "alert" through to laboratory confirmation or exclusion of persons under investigation as SARS cases. The document does not address complex surveillance issues or case categorization for SARS.

It also provides guidance to clinicans on the clinical presentation, laboratory and radiological findings to assist in diagnosis of SARS and in decisions to implement transmission-based infection control.

For additional information on the previous SARS outbreak, please also refer to SARS: breaking the chains of transmission

2. Risk assessment

Ideally, each Member State should determine the intensity of its surveillance for SARS in the post-outbreak period on the basis of a risk assessment. WHO has defined three major areas that take into account the experience during the recent outbreak of SARS and the potential for resurgence:

Potential zone of re-emergence of SARS-CoV

Nodal areas

Low risk areas

Thus, WHO recommends a staged approach to surveillance:

Potential zone of re-emergence of SARS

Nodal areas

Low risk areas

3. The SARS Alert

The SARS Alert is an operational definition to ensure that appropriate infection control and public health measures are implemented until SARS has been ruled out as a cause of the atypical pneumonia or RDS.

3.1 Objectives of the SARS Alert

Definition of a SARS Alert

Two or more health care workers in the same health care unit fulfilling the clinical case definition of SARS (see section 3.3) and with onset of illness in the same 10-day period.

OR

Hospital acquired illness in three or more persons (health care workers and/or other hospital staff and/or patients and/or visitors) in the same health care unit fulfilling the clinical case definition of SARS (see section 3.3) and with onset of illness in the same 10-day period.

A jurisdiction may chose, based on its experience, to increase the minimum number of "alert" cases defining a cluster. The definition of the health care unit in which the cluster occurs will depend on the local situation. Unit size may range from an entire health care facility if small, to a single department or ward of a large tertiary hospital.

3.2 Case description of SARS

See Annex 1 Clinical description of SARS. The case description provides details of the clinical evolution of SARS and radiological and laboratory findings to assist clinicians with its diagnosis. It provides information on the spectrum of the disease, including atypical presentations.

3.3 Case Definitions

Clinical case definition of SARS
The following clinical case definition has been developed for public health purposes.

A person with a history of:

Fever (≥ 38°C)

AND One or more symptoms of lower respiratory tract illness (cough, difficulty breathing, shortness of breath)

AND

Radiographic evidence of lung infiltrates consistent with pneumonia or RDS OR autopsy findings consistent with the pathology of pneumonia or RDS without an identifiable cause.

AND
No alternative diagnosis can fully explain the illness.

Laboratory case definition of SARS

A person with symptoms and signs that are clinically suggestive of SARS AND with positive laboratory findings for SARS-CoV based on one or more of the following diagnostic criteria:

a) PCR positive for SARS-CoV
PCR positive using a validated method from:

b) Seroconversion by ELISA or IFA

c) Virus isolation

Testing should only be undertaken in a national or regional reference laboratory as per WHO recommendations (Use of laboratory methods for SARS diagnosis). WHO will assist resource poor countries to confirm their first cases of SARS through laboratory collaboration.

3.4 Public health management of a SARS Alert

When a SARS Alert is raised:
1. Patient(s) should be immediately isolated and transmission-based precautions instituted, if not already in place (see clinical management guidelines)

2. The diagnosis should be expedited (see Annex 2 Guidance regarding the diagnosis of SARS in the post-outbreak period – A concern for all health care workers). WHO will assist in the investigation of SARS alerts as appropriate, including the facilitation of access to laboratory services (see Annex 3 WHO Focal Points for SARS).

3. Contacts of persons under investigation for SARS should be traced and quarantined until SARS has been ruled out as the cause of the illness.

International reporting of SARS

A new outbreak of SARS is defined as the occurrence of one or more clinically compatible, laboratory-confirmed cases of SARS in any country based on definitive laboratory investigations. The reappearance of SARS in the human population would be considered a global public health emergency.

For the purposes of the international reporting of SARS in the post-outbreak period, Member States are requested to inform WHO of laboratory-confirmed cases only.

Laboratory confirmed cases of SARS could be detected through a SARS alert verification process but also as sporadic case(s) of acute respiratory illness on which SARS-CoV testing was undertaken (i.e. fulfil the case definition described in section 3.3). Reporting to WHO should include both of these scenarios but should exclude asymptomatic persons with a positive laboratory test or symptomatic persons without laboratory confirmation. No nil reporting is required.

WHO requests that Members States immediately inform the focal points at Regional Offices or Headquarters of every person meeting the laboratory-confirmed case definition of SARS (see Annex 3 WHO Focal Points for SARS). This will allow WHO to assess the need for a global alert and re-institute global surveillance for SARS on the basis of that notification as appropriate.

The development of new case definitions applicable to the new situation, surveillance standards and a step-down strategy may be required once laboratory-confirmed cases have been reported.

In the event of an international traveller being investigated for SARS, all Member States involved in international contact tracing around the case(s) should communicate directly with each other during the investigation. WHO should be informed only when the incident is laboratory confirmed.

WHO will continue to identify and verify rumours of events of international public health concern, including rumours about SARS, through its usual well-established mechanisms.

Indicators of the quality of the SARS alert mechanism

WHO recommends that national public health authorities monitor the quality of the SARS alert mechanism, e.g. by establishing indicators based on:

This list is not meant to be exhaustive but rather a suggested approach to monitoring the alert mechanism.

4. Enhanced surveillance and special studies for SARS-CoV infections in animal and human populations

Jurisdictions in nodal areas and areas of potential re-emergence have maintained heightened SARS surveillance established during the outbreak period, and continue doing so for the foreseeable future. WHO will encourage these jurisdictions to make available to the global community the details of these surveillance activities and will offer its assistance in summarizing and updating available information on its web site.

Depending on risk assessment and available resources, nodal areas and areas of potential re-emergence may include one or more of the following activities:

This list is not meant to be exhaustive but rather a suggested approach to enhanced surveillance.

Annex 1 Clinical case description of SARS

Aetiology

Severe acute respiratory syndrome (SARS) is a disease caused by SARS coronavirus (SARS-CoV).

Epidemiology

Nosocomial transmission of SARS CoV has been a striking feature of the SARS outbreak. The majority of the cases are adults. Children are rarely affected.

The mean incubation period is 5 days with the range of 2-10 days although there are isolated reports of longer incubation periods. There have been no reports of transmission occurring before the onset of symptoms.

Natural history of the disease

Week 1 of illness

Patients initially develop influenza-like prodromal symptoms. Presenting symptoms include fever, malaise, myalgia, headache, and rigors. No individual symptom or cluster of symptoms has proven specific. Although history of fever is the most frequently reported symptom, it may be absent on initial measurement.

Week 2 of illness

Cough (initially dry), dyspnoea and diarrhoea may be present in the first week but more commonly reported in the second week of illness. Severe cases develop rapidly progressing respiratory distress and oxygen desaturation with about 20% requiring intensive care. Up to 70% of the patients develop diarrhoea which has been described as large volume and watery without blood or mucus. Transmission occurs mainly during the second week of illness.

Clinical outcomes

Based on an analysis of data from Canada, China, Hong Kong SAR, Singapore, Viet Nam and the United States the case fatality ratio (CFR) of SARS is estimated to range from 0% to more than 50% depending on the age group affected, with an overall CFR estimate of approximately 11% (see Update 49 - SARS case fatality ratio, incubation period). Higher mortality has also been associated with male sex and presence of co-morbidity in various studies.

Elderly and paediatric cases and SARS in pregnancy

Atypical presentations such as afebrile illness or concurrent bacterial sepsis/pneumonia have been highlighted as a particular problem in the elderly. Underlying chronic conditions and their more frequent use of health facilities have both contributed to initially unrecognized nosocomial transmission events.

SARS occurred less frequently and was observed to be a milder illness in the paediatric population.

Known cases of SARS in pregnancy have suggested an increase in fetal loss in early pregnancy and maternal mortality in later pregnancy.

Radiological findings

Early chest radiograph or CT changes are observed in most of the patients as early as days 3-4 of illness in spite of the absence of respiratory signs. These typically show patchy consolidation starting with a unilateral peripheral lesion which progress to multiple lesions or ground glass appearance. Some lesions follow a shifting pattern. Features during the later stages have sometimes included spontaneous pneumothorax, pneumomediastinum, sub-pleural fibrosis and/or cystic changes.

Haematological and biochemical findings

There are no haematological or biochemical parameters specific for SARS; however, studies have consistently highlighted the following:

Haematological findings

Lymphopenia is common on presentation and progresses during the course of the illness. Sometimes thrombocytopenia and prolonged APTT are observed.

Biochemical findings

LDH is frequently high and some reports have suggested association with poor prognosis. ALT, AST and CPK elevation are less frequently reported. Abnormal serum electrolytes have also been reported on presentation or during hospitalization including hyponatraemia, hypokalaemia, hypomagnesaemia and hypocalcaemia.

Annex 2 Guidance regarding the diagnosis of SARS in the post-outbreak period – A concern for all health care workers (HCW's)

Making a diagnosis of SARS sufficiently early in the disease to implement effective infection control and public health measures will prove a challenge that requires all HCWs to always incorporate risk-based infection control measures in care provision. This will only occur within a culture that treats infection prevention and control as everyone’s responsibility. All HCWs should be encouraged to consider the possibility of SARS in a patient under their care. If there are features suggestive of SARS then any concerns should be raised promptly and trigger risk-based infection control measures. There must be monitoring and feedback on this process.

The non-specific nature of the presentation of SARS could lead to concern being raised in a vast number of patients who will ultimately prove to have another diagnosis. In practice, concern about the possibility of SARS may often be expressed at the stage where atypical pneumonia is suspected.

This process should not rely wholly on clinicians but should be responsive to the concerns raised by other HCWs.

Concern of SARS raised by clinicians

For clinicians the process of diagnosis from initial concern to confirmation or exclusion of a SARS diagnosis (see case description) is usually an incremental one following sequential information gathering from various sources that include:

Concern about SARS raised by other health professionals

Concerns regarding SARS may be raised by any HCW. All HCW's need to ensure they are fully aware of what constitutes a clinical concern about SARS and how, in the course of their duties they could be involved in the presentation, investigation or treatment of an unrecognized SARS case.

They should be encouraged to raise concerns with both the clinicians and infection control team who should provide monitoring and feedback on the process.

Some examples are given:

Atypical pneumonia

Common bacteria, such as Streptococcus pneumoniae and Haemophilus influenzae cause so-called "typical pneumonia". Cases of typical pneumonia present with fever, respiratory symptoms (cough, which is usually early in the illness and often productive, shortness of breath etc.), elevated white cell count and well-defined changes on the chest radiograph. They tend to respond to antibiotic therapy for community acquired pneumonia.

In contrast, "atypical pneumonia" is defined as pneumonia or lower respiratory tract infection with an atypical presentation often with a gradual onset of symptoms such as non-productive, dry cough, a variable white blood cell count and the chest radiograph changes. These include patchy, poorly defined changes, which may be often more severe than the clinical picture would suggest. The causative agents include, Mycoplasma pneumoniae, Chlamydia spp., Legionella pneumophila, Coxiella burnetii.

Diagnosis of atypical pneumonia is in itself challenging but will be assisted by careful clinical assessment (including non-respiratory symptoms), and given the likely absence of auscultatory signs, accurate measurement of respiratory rate and oxygen saturation (where available) becomes even more important. Chest radiography is of great use in achieving diagnosis and should be considered even in the absence of respiratory signs.

Features of SARS that may commonly help with clinical diagnosis

SARS

Example

Caution

Clinical history

Sudden onset of flu-like prodrome, dry cough, non –respiratory symptoms e.g. diarrhoea common

Take a travel history, history of hospitalisation and history of contact with healthcare facility. The absence of such a history should not automatically exclude diagnosis of SARS.

Clinical examination

Does not correlate with chest radiology changes

Lack of respiratory signs particularly in groups such as the elderly

Bedside monitoring

Hypoxia

Temperature may not be elevated on admission, respiratory rate should be documented

Haematology investigations

Low lymphocyte count

 

Biochemistry investigations

Raised LDH

Check profile for electrolytes and liver function

Radiology investigations

CXR changes poorly defined, patchy, progressive changes

May present as a lobar pneumonia, pneumothorax and pneumomediastinum may occur

Microbiology investigations

Investigate for community, and hospital acquired pneumonias including atypical pneumonias

Concurrent infections may occur

Virology investigations

Investigate for other causes of atypical pneumonia

Interpret SARS test results with caution

Treatment

As yet there is not proven treatment for SARS, supportive measures are recommended

Lack of response to treatment with standard antibiotics for community acquired pneumonia including atypical pneumonia may be indicative of SARS

Annex 3 WHO Focal Points for SARS

WHO Geneva
Dr. Angela Merianos,
CSR SARS Coordinator
E-mail: sars@who.int
Please use this email address for all SARS-related correspondence to WHO Geneva.

WHO Regional Office for Africa (AFRO)
Dr Paul Lusamba-Dikassa,
Regional Adviser, Communicable Disease Surveillance and Response
E-mail: lusambap@whoafr.org

Regional Office for the Americas / Pan American Health Organization (AMRO/PAHO)
Dr Marlo Libel,
Regional Adviser in Communicable Diseases, Disease Prevention and Control
E-mail: libelmar@paho.org

Regional Office for the Eastern Mediterranean (EMRO)
Dr Nadia Teleb,
Medical Epidemiologist
E-mail: telebn@emro.who.int

Regional Office for Europe (EURO)
Dr Bernardus Ganter,
Regional Adviser, Communicable Diseases
E-mail: bga@who.dk

Regional Office for South-East Asia (SEARO)
Dr M.V.H. Gunaratne, Regional Adviser on Communicable Disease Surveillance and Response
E-mail: gunaratnem@whosea.org

Regional Office for the Western Pacific (WPRO)
Dr Hitoshi Oshitani, Regional Adviser in Communicable Disease Surveillance and Response
E-mail: outbreak@wpro.who.int

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