29. marca 2003r. w szpitalu                  w Bangkoku w wieku 43 lat zmarł włoski epidemiolog Carlo Urbani. 

Dr Urbani stał na czele Lekarzy Bez Granic - Medecins Sans Frontieres, kiedy ta wielce zasłużona organizacja otrzymała w 1999r. pokojową nagrodę Nobla. 

Ofiarny i mądry lekarz  zginął w walce z nieznaną zarazą o globalnym zasięgu, na którą pierwszy zwrócił uwagę, obserwując przypadki nietypowego zapalenia płuc wśród pacjentów i załogi Francuskiego Szpitala w Hanoi, w Wietnamie. 

Pozostała po nim wdowa Giuliana i troje dzieci: Tommaso (17 lat), Luca (8 lat) i Maddalena (2 lata). 

To describe the epidemiology of SARS and to monitor the magnitude and the spread of this disease, in order to provide advice on prevention and control. 

Case definitions (revised 1 May 2003)

Introduction
The surveillance case definitions based on available clinical and epidemiological data are now being supplemented by a number of laboratory tests and will continue to be reviewed as tests currently used in research settings become more widely available as diagnostic tests. Preliminary clinical description of Severe Acute Respiratory Syndrome summarizes what is currently known about the clinical features of SARS. Countries may need to adapt case definitions depending on their own disease situation. Retrospective surveillance is not expected. 

Clinicians are advised that patients should not have their case definition category downgraded while awaiting results of laboratory testing or on the bases of negative results. See Use of laboratory methods for SARS diagnosis.

Suspect case
1.   A person presenting after 1 November 2002¹ with history of:
-  high fever (>38 °C)
AND
-   cough or breathing difficulty
AND one or more of the following exposures during the 10 days prior to onset of symptoms:
-  close contact² with a person who is a suspect or probable case of SARS;
-  history of travel, to an area with recent local transmission of SARS
-  residing in an area with recent local transmission of SARS

2.  A person with an unexplained acute respiratory illness resulting in death after 1 November 2002,¹ but on whom no autopsy has been performed
AND one or more of the following exposures during to 10 days prior to onset of symptoms:
-  close contact,² with a person who is a suspect or probable case of SARS;
-   history of travel to an area with recent local transmission of SARS
-  residing in an area with recent local transmission of SARS

Probable case
1.  A suspect case with radiographic evidence of infiltrates consistent with pneumonia or respiratory distress syndrome (RDS) on chest X-ray (CXR).
2.   A suspect case of SARS that is positive for SARS coronavirus by one or more assays. See Use of laboratory methods for SARS diagnosis.
3.   A suspect case with autopsy findings consistent with the pathology of RDS without an identifiable cause. 

Exclusion criteria
A case should be excluded if an alternative diagnosis can fully explain their illness. 

Reclassification of cases
As SARS is currently a diagnosis of exclusion, the status of a reported case may change over time. A patient should always be managed as clinically appropriate, regardless of their case status.
-   A case initially classified as suspect or probable, for whom an alternative diagnosis can fully explain the illness, should be discarded after carefully considering the possibility of co-infection.
-   A suspect case who, after investigation, fulfils the probable case definition should be reclassified as "probable".
-   A suspect case with a normal CXR should be treated, as deemed appropriate, and monitored for 7 days. Those cases in whom recovery is inadequate should be re-evaluated by CXR.
-   Those suspect cases in whom recovery is adequate but whose illness cannot be fully explained by an alternative diagnosis should remain as "suspect".
-   A suspect case who dies, on whom no autopsy is conducted, should remain classified as "suspect". However, if this case is identified as being part of a chain transmission of SARS, the case should be reclassified as "probable".
-   If an autopsy is conducted and no pathological evidence of RDS is found, the case should be "discarded". 

¹   The surveillance period begins on 1 November 2002 to capture cases of atypical pneumonia in China now recognized as SARS. International transmission of SARS was first reported in March 2003 for cases with onset in February 2003. 

²   Close contact: having cared for, lived with, or had direct contact with respiratory secretions or body fluids of a suspect or probable case of SARS. 

Reporting procedures
- All probable SARS categories should be managed in the same way for the purposes of infection control and outbreak containment See Management of Severe Acute Respiratory Syndrome (SARS).

-At this time, WHO is maintaining surveillance for clinically apparent cases only ie probable and suspect cases of SARS. (Testing of clinically well contacts of probable or suspect SARS cases and community based serological surveys are being conducted as part of epidemiological studies which may ultimately change our understanding of SARS transmission. However, persons who test SARS CoV positive in these studies will not be notified as SARS cases to WHO at this time). 

- Where laboratory tests are not available or not done, probable SARS cases as currently defined above should continue to be reported in the agreed format. 

- Suspect cases with positive laboratory results will be reclassified as probable cases for notification purposes only if the testing laboratories use appropriate quality control procedures.

- No distinction will be made between probable cases with or without a positive laboratory result and suspect cases with a positive result for the purposes of global surveillance. WHO will negotiate sentinel surveillance of SARS with selected partners to collect detailed epidemiological, laboratory and clinical data. 

- Cases that meet the surveillance case definition for SARS should not be discarded on the basis of negative laboratory tests at this time. 

Rationale for retaining the current surveillance case definitions for SARS

The reason for retaining the clinical and epidemiological basis for the case definitions is that at present there is no validated, widely and consistently available test for infection with the SARS coronavirus. Antibody tests may not become positive for three or more weeks after the onset of symptoms. We do not yet know if all patients will mount an antibody response. Molecular assays must be performed using appropriate reagents and controls under strictly controlled conditions, and may not be positive in the early stages of illness using currently available reagents. We are not yet able to define the optimal specimen to be tested at any given stage of the illness. This information is accruing as more tests are being performed on patients with known exposures and/or accompanied by good clinical and epidemiological information. We hope that in the near future an accessible and validated diagnostic assay(s) will become available which can be employed with confidence at a defined, early stage of the illness.
 

An "Affected Area" is defined as a region at the first administrative level where the country is reporting local transmission of SARS, within the last 20 days.

*Area with limited local transmission and no evidence of international spread from area since 15 March 2003 and no transmission other than close person-to-person contact reported.

Notes: 

Local transmission has occurred when one or more reported probable cases of SARS have most likely acquired their infection locally regardless of the setting in which this may have occurred. If no new locally acquired cases are identified 20 days after the last reported locally acquired probable case died or was appropriately isolated, the area will be removed from this list. 

Pattern A
Imported probable SARS case(s) have produced only one generation of local probable cases, all of whom are direct personal contacts of the imported case(s). 

Pattern B
More than one generation of local probable SARS cases, but only among persons that have been previously identified and followed-up as known contacts of probable SARS cases. 

Pattern C
Local probable cases occurring among persons who have not been previously identified as known contacts of probable SARS cases. 

Pattern Uncertain
Insufficient information available to specify areas or extent of local transmission. 

*WHO is currently recommending, as a measure of precaution, that people planning to travel to these areas consider postponing all but essential travel.

Please refer to Case Definitions for Surveillance of Severe Acute Respiratory Syndrome (SARS)

Management of Suspect and Probable SARS Cases

• Hospitalize under isolation or cohort with other suspect or probable SARS cases (see Hospital Infection Control Guidance )
• Take samples (sputum, blood, sera, urine,) to exclude standard causes of pneumonia (including atypical causes); consider possibility of coinfection with SARS and take appropriate chest radiographs.
• Take samples to aid clinical diagnosis SARS including:

White blood cell count, platelet count, creatine phosphokinase, liver function tests, urea and electrolytes, C reactive protein and paired sera. (Pair sera will be invaluable in the understanding of SARS even if the patient is later not considered a SARS case)
• At the time of admission the use of antibiotics for the treatment of community-acquired pneumonia with atypical cover is recommended
• Pay particular attention to therapies/interventions which may cause aerolization such as the use of nebulisers with a bronchodilator, chest physiotherapy, bronchoscopy, gastroscopy, any procedure/intervention which may disrupt the respiratory tract. Take the appropriate precautions (isolation facility, gloves, goggles, mask, gown, etc. ) if you feel that patients require the intervention/therapy.
• In SARS, numerous antibiotic therapies have been tried with no clear effect. Ribavirin with or without use of steroids has been used in an increasing number of patients. But, in the absence of clinical indicators, its effectiveness has not been proven. It has been proposed that a coordinated multicentred approach to establishing the effectiveness of ribavirin therapy and other proposed interventions be examined.

• Give information on clinical picture, transmission, etc. of SARS to the contact
• Place under active surveillance for 10 days and recommend voluntary home isolation
• Ensure contact is visited or telephoned daily by a member of the public health care team
• Record temperature daily
• If the contact develops disease symptoms, the contact should be investigated locally at an appropriate health care facility
• The most consistent first symptom that is likely to appear is fever

• Give information on clinical picture, transmission etc of SARS to the contact
• Place under passive surveillance for 10 days
• If the contact develops any symptoms, the contact should self report via the telephone to the public health authority
• Contact is free to continue with usual activities
• The most consistent first symptom which is likely to appear is fever

Revised 24 April 2003

Outpatient/triage setting

• Those presenting to health care facilities who require assessment for SARS should be rapidly diverted by triage nurses to a separate area to minimize transmission to others
• Those patients should be given a face mask to wear, preferably one that provides filtration of their expired air.
• Staff involved in the triage process should wear a face mask (see below) and eye protection and wash hands before and after contact with any patient, after activities likely to cause contamination and after removing gloves
• Wherever possible, patients under investigation for SARS should be separated from the probable cases.
• Soiled gloves, stethoscopes and other equipment have the potential to spread infection.
• Disinfectants such as fresh bleach solutions, should be widely available at appropriate concentrations.

Care for probable SARS cases (see Case Definitions for Surveillance of Severe Acute Respiratory Syndrome (SARS)

• Probable SARS cases should be isolated and accommodated as follows in descending order of preference:
1. negative pressure rooms with the door closed
2. single rooms with their own bathroom facilities
3. cohort placement in an area with an independent air supply, exhaust system and bathroom facilities
• Turning off air conditioning and opening windows for good ventilation is recommended if an independent air supply is unfeasible. Please ensure that if windows are opened they are away from public places
• WHO advises strict adherence to the barrier nursing of patients with SARS, using precautions for airborne, droplet and contact transmission
• All staff, including ancilliary staff should be trained in the infection control measures required for the care of such a patient
• A member of staff must be identified who will have the responsibility of observing the practice of others and provide feedback on infection control
• Disposable equipment should be used wherever possible in the treatment and care of patients with SARS and disposed of appropriately. If devices are to be reused, they should be sterilized in accordance with manufacturers’ instructions. Surfaces should be cleaned with broad spectrum disinfectants of proven antiviral activity
• Movement of patients outside of the isolation unit should be avoided. If moved the patients should wear a face mask
• Visitors, if allowed by the health care facility should be kept to a minimum. They should be issued with personal protective equipment (PPE) and supervised
• All non-essential staff (including students) should not be allowed on the unit/ward
• Handwashing is crucial: therefore access to clean water is essential

Hands should be washed before and after contact with any patient, after activities likely to cause contamination and after removing gloves
• Alcohol-based skin disinfectants could be used if there is no obvious organic material contamination
• Particular attention should be paid to interventions such as the use of nebulisers, chest physiotherapy, bronchoscopy or gastroscopy; any other intervention which may disrupt the respiratory tract or place the healthcare worker in close proximity to the patient and potentially infected secretions.
• PPE should be worn by all staff and visitors accessing the isolation unit
• The PPE worn in this situation should include:

  A face mask providing appropriate respiratory protection (see below)
  Single pair of gloves
  Eye protection
  Disposable gown
  Apron
  Footwear that can be decontaminated
• All sharps should be dealt with promptly and safely
• Linen from the patients should be prepared on site for the laundry staff. Appropriate PPE should be worn in this preparation and the linen should be put into biohazard bags
• The room should be cleaned by staff wearing PPE using a broad spectrum disinfectant of proven antiviral activity
• Specific advice concerning air conditioning units will be available soon
• Respiratory protection. This should where feasible be provided at *P100/FFP3, or P99/FFP2 filter level (99.97% and 99% efficiency respectively). *N95 filters (95% filter efficiency) also provide high levels of protection and could be worn where no acceptable higher protection alternatives are available for example staff working in triage areas, prior to isolation. Ideally, the masks used should be fit tested using an appropriate "fit test kit" in accordance with the manufacturing instructions. Disposable masks should not be reused.

The below table provides the first compilation of data on resistance of the SARS Coronavirus against environmental factors and disinfectants. This information has been provided by Members of the WHO multi-center collaborative network on SARS diagnosis . More detailed information on methods utilized and material used is being compiled and will be available shortly. The major conclusions from these studies are: 

Virus survival in stool and urine

• Virus is stable in faeces(and urine) at room temperature for at least 1-2 days.
• Virus is more stable (up to 4 days) in stool from diarrhea patients (which has higher pH than normal stool).
Disinfectants and fixatives (for use in laboratories)
• Virus loses infectivity after exposure to different commonly used disinfectants and fixatives.
Virus survival in cell-culture supernatant
• Only minimal reduction in virus concentration after 21 days at 4°C and -80°C.
• Reduction in virus concentration by one log only at stable room temperature for 2 days. This would indicate that the virus is more stable than the known human coronaviruses under these conditions.
• Heat at 56°C kills the SARS coronavirus at around 10000 units per 15 min (quick reduction).

 

Lab*	Substrate	Initial viral count log10PFU	Condition	Survival time	Method of testing viability
GVU	virus spiked in baby stool	1.00E+03	pH 6-7	3 hr	Virus isolation in cell culture
	virus spiked in normal stool	7.50E+03	pH 8	6hr	Virus isolation in cell culture
	virus in diarrheal stool	7.50E+03	pH 9	4days	Virus isolation in cell culture
QMH	stool	1.00E+03	Room Temperature	at least 2 days	Virus isolation in cell culture
	urine	1.00E+03	Room Temperature	at least 24 hr	Virus isolation in cell culture
	Virus culture medium+ 1% bovine serum	1.00E+03	on plastic surface in room temperature	at least 2 days	Virus isolation in cell culture
	Virus culture medium+ 1% bovine serum	1.00E+04	30-37°C	at least 1hr	Virus isolation in cell culture
	Virus culture medium+ 1% fetal calf serum	1.00E+04	56°C	degration of titre over time (10 000 infectious virus units in 15 min)	Virus isolation in cell culture
	virus in Acetone, 10% Formaldehyde and Paraformaldehyde, 10% Clorox, 75%ethanol, 2% phenol	1.00E+06	Room Temperature	less than 5 min	Virus isolation in cell culture
NIID	Virus culture+ 2% bovine serum	1.00E+06	minus 80°C	at least 4 days	Virus isolation and RT-PCR
	Virus culture+ 2% fetal calf serum	1.00E+06	4°C	at least 4 days	Virus isolation and RT-PCR
	Virus culture+ 2% fetal calf serum	1.00E+06	37°C	less than 4 days	Virus isolation and RT-PCR
	Virus culture+ 2% fetal calf serum	1.00E+05	56°C	less than 30min
UniM	Virus culture	1.00E+06	4°C	at least 21 days	Virus isolation
	Virus culture	1.00E+06	minus 80°C	at least 21 days	Virus isolation

QMH: Queen Mary Hospital, The University of Hong Kong, Hong Kong, SAR China
NIID: National Institute of infectious Diseases, Tokyo, Japan
UnivM: University Marburg, Germany

CDC's interim surveillance case definition for severe acute respiratory syndrome (SARS) has been updated to include laboratory criteria for evidence of infection with the SARS-associated coronavirus (SARS-CoV) (Figure, Box). In addition, clinical criteria have been revised to reflect the possible spectrum of respiratory illness associated with SARS-CoV. Epidemiologic criteria have been retained. The majority of U.S. cases of SARS continue to be associated with travel*, with only limited secondary spread to household members or health-care providers (1).

SARS has been associated etiologically with a novel coronavirus, SARS-CoV (2,3). Evidence of SARS-CoV infection has been identified in patients with SARS in several countries, including the United States. Several new laboratory tests can be used to detect SARS-CoV. Serologic testing for coronavirus antibody can be performed by using indirect fluorescent antibody or enzyme-linked immunosorbent assays that are specific for antibody produced after infection. Although some patients have detectable coronavirus antibody during the acute phase (i.e., within 14 days of illness onset), definitive interpretation of negative coronavirus antibody tests is possible only for specimens obtained >21 days after onset of symptoms. A reverse transcriptase polymerase chain reaction (RT-PCR) test specific for viral RNA has been positive within the first 10 days after onset of fever in specimens from some SARS patients, but the duration of detectable viremia or viral shedding is unknown. RT-PCR testing can detect SARS-CoV in clinical specimens, including serum, stool, and nasal secretions. Finally, viral culture and isolation have both been used to detect SARS-CoV. Absence of SARS-CoV antibody in serum obtained <21 days after illness onset, a negative PCR test, or a negative viral culture does not exclude coronavirus infection.

Reported U.S. cases of SARS still will be classified as suspect or probable; however, these cases can be further classified as laboratory-confirmed or -negative if laboratory data are available and complete, or as laboratory-indeterminate if specimens are not available or testing is incomplete. Obtaining convalescent serum samples to make a final determination about infection with SARS-CoV is critical.

No instances of SARS-CoV infection have been detected in persons who are asymptomatic. However, data are insufficient to exclude the possibility of asymptomatic infection with SARS-CoV and the possibility that such persons can transmit the virus. Investigations of close contacts and health-care workers exposed to SARS patients might provide information about the occurrence of asymptomatic infected persons. Similarly, the clinical manifestations of SARS might extend beyond respiratory illness. As more is learned about SARS-CoV infection, clinical and laboratory criteria will provide a framework for classifying the full spectrum of infection (Figure).

This surveillance case definition should be used for reporting and classification purposes only. It should not be used for clinical management or as the only criterion for identifying or testing patients who might have SARS or for instituting infection-control precautions (4,5). This definition will be updated as new data become available or if changes in the epidemiology of SARS occur in the United States.
References

CDC. Update: Severe acute respiratory syndrome --- United States, 2003. MMWR 2003;52:357--60.
Ksiazek TG, Erdman D, Goldsmith C, et al. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. Available at http://content.nejm.org/cgi/reprint/NEJMoa030781v3.pdf.
Drosten C, Gunther S, Preiser W, et al. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med. Available at http://content.nejm.org/cgi/reprint/NEJMoa030747v2.pdf.
CDC. Updated interim domestic guidelines for triage and disposition of patients who may have severe acute respiratory distress syndrome (SARS). Available at http://www.cdc.gov/ncidod/sars/triage_interim_guidance.htm.
CDC. Interim guidance on infection control precautions for patients with suspected severe acute respiratory syndrome (SARS) and close contacts in households. Available at http://www.cdc.gov/ncidod/sars/ic-closecontacts.htm.

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