# Presentation: 453791

## Influenza, RSV, and SARS:  What Every Laboratory Should KnowAudioconference sponsored byNational Laboratory Training NetworkDecember 16, 2003

- Pete Shult, Ph.D. 		    	Carol Kirk
- Chief Virologist and 			Virology Program Coordinator &
- Director, 				Laboratory Network Coordinator
- Communicable Disease Division
- & Emergency Laboratory Response
- Telephone 608-262-5419		Telephone 608-262-1021 	    E-mail shult@mail.slh.wisc.edu	E-mail  _[cjk@mail.slh.wisc.edu](mailto:cjk@mail.slh.wisc.edu)_
- 		Wisconsin State Laboratory of Hygiene
- Communicable Disease Division
- 465 Henry Mall
- Madison, WI

## Objectives

- At the end of the session, the participant will be able to:
- Describe the epidemiology and clinical presentations of influenza, respiratory syncytial virus, and the SARS-coronavirus.
- Discuss the importance of disease prevalence on test predictive values and test result interpretation.
- Summarize the current CDC recommendations for specimen testing and laboratory safety.

## Overview

- Clinical presentations of influenza, respiratory syncytial virus (RSV) and SARS.
- Epidemiology of influenza, RSV and SARS.
- Laboratory diagnostic methods for influenza, RSV and SARS-coronavirus.
- Predictive values, test performance characteristics, disease prevalence, and result interpretation.
- CDC recommendations for specimen collection, testing and laboratory safety for SARS
- Closing comments.

## Human Respiratory Viruses

_*Orthomyxoviridae*_
-          **INFLUENZA  TYPE  A** *(2 subtypes, new strains each year)*
-          **INFLUENZA  TYPE  B** *(new strains each year)*
_*Paramyxoviridae*_
-          **RESPIRATORY  SYNCYTIAL  VIRUS** *(2 subgroups)*
-          PARAINFLUENZA  VIRUS  *(4 serotypes)*
-          **HUMAN METAPNEUMOVIRUS**
_*Picornaviridae*_
-          RHINOVIRUSES *(at least 113 serotypes)*
-          ENTEROVIRUSES *(68 serotypes)*
_*Adenoviridae*_
-          ADENOVIRUSES *(49 serotypes)*
_*Coronaviridae*_
-          **CORONAVIRUSES** *(2 subgroups, unknown # of strains)*

## Resource:  http://www.nap.edu/books/030908864X/html/

## Epidemiology, Clinical Presentations, and Public Health Importance

## Influenza:  Resources (I)

- CDC home page for influenza
- http://www.cdc.gov/ncidod/diseases/flu/overview.htm
- ACIP recommendations
- _[http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5208a1.htm](http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5208a1.htm)_
- National Immunization Program
- http://www.cdc.gov/nip/Flu/default.htm

## Influenza:  Resources (II)

- National Influenza Summary – Weekly Update
- _[http://www.cdc.gov/ncidod/diseases/flu/weekly.htm](http://www.cdc.gov/ncidod/diseases/flu/weekly.htm)_

## Influenza

- Family:	Orthomyxoviridae
- segmented (8), ssRNA genome
- lipid envelop
- Genera:	Influenzavirus Types A, B and C
- Subtypes:	Human - **H****1****N****1****, H****2****N****2****, H****3****N****2**, H5N1, 			H9N2 ,H1N2, H7N7
-                            Animals – H1 to H15, N1 to N9
- Strains:	A/Moscow/10/99 (H3N2) - like
- (2003)	A/New Caledonia/20/99 (H1N1) - like
- 			B/Hong Kong/330/2001- like

## Influenza:  Clinical Syndrome

- Incubation period 1 to 3 days
- Abrupt onset of high fever and chills
- Associated symptoms
- headache, malaise, myalgia, cough, sore throat, nasal congestion
- Duration of intense symptoms 3 to 5 days
- Prolonged recovery
- Note: CDC definition of ***influenza-like illness***
- Temp > 100°F orally and either cough or sore throat

## Influenza:  Potential Complications 

- Pneumonia: 	primary viral
-  		secondary bacterial
- Exacerbations**	**of asthma, chronic bronchitis
- Myocarditis and pericarditis
- Meningitis/encephalitis
- Reye’s syndrome
- Guillain-barre syndrome
- Myositis, myoglobinuria

## Influenza – Seasonality/Epidemicity Wisconsin, 1995-2003

## Influenza:  Public Health Importance

- Pandemic potential
- Significant annual (inter-pandemic) morbidity and mortality
- Prophylactic and therapeutic measures available
- Advent of rapid diagnostic methods

## Influenza: Epidemic (Inter-Pandemic) Influenza

- Disease caused by a new _strain _of influenza virus that has evolved gradually by point mutations within the hemagglutinin or neuraminidase or both such that preexisting antibody cannot completely neutralize the new strain.
- The mechanism: **ANTIGENIC DRIFT**

## Influenza: Annual (Inter - pandemic) Morbidity and Mortality

- Greater than 35,000 deaths in US each year
-  90% of mortality among elderly
-  Increased mortality in other risk groups
- From 15,000 to >200,000 flu-associated  hospitalizations per epidemic
- Nursing home attack rate of 60%
- Attack rates of 5-20% in general population
- A significant childhood pathogen

## Pandemic Influenza

- Disease caused by a **reassortment of **_**Influenza A **_**subtypes** that results in the emergence of a new virus containing a novel hemagglutinin and/or neuraminidase that is _immunologically distinct _from previously circulating strains.
- The mechanism:  **ANTIGENIC SHIFT**
- Resource:  _[http://www.cdc.gov/od/nvpo/pandemics](http://www.cdc.gov/od/nvpo/pandemics/)__[/](http://www.cdc.gov/od/nvpo/pandemics/)_

##  Influenza: Noteworthy events 

- 1997:  “Avian flu” (H5N1)
- 1997: “A/Sydney” (H3N2)
- 1999:  Influenza A (H9N2)
- 2003:  H5N1 strikes again
- 2003:  Avian influenza A (H7N7)
- 2003:  “A/Fujian” (H3N2)
- 2001-03:  H1N2

## hRSV:  Resources

- National Respiratory and Enteric Virus Surveillance System (NREVSS) home page _[http://www.cdc.gov/ncidod/dvrd/revb/nrevss/index.htm](http://www.cdc.gov/ncidod/dvrd/revb/nrevss/index.htm)_
- National RSV Data

## hRSV:  Clinical Syndrome (I)

- Incubation period of 2-8 days
- Acute respiratory illness
- Fever
- Cough
- Copious nasal discharge
- Malaise
- Respiratory distress and decreased feeding
- Leading cause of severe lower respiratory tract illness (bronchiolitis/pneumonia) in infants
- Infants with underlying cardiopulmonary disease are at particularly high risk

## hRSV:  Clinical Syndrome(II)

- Otitis media is a major complication
**Highly contagious**-a leading cause of nosocomial infections in infants and the elderly
- Symptomatic re-infections occur throughout life:
- Upper respiratory tract illness (URI)/bronchitis in adults
- Severe lower respiratory illness in the elderly
- May be important precursor to asthma in later life

## hRSV:  Epidemicity/Seasonality

- NREVSS National RSV Data

## hRSVNREVSS Regional RSV Data Examples

## hRSV:  Public Health Importance

- Virtually all children are infected with RSV during the first 3 years
- The major viral cause of serious life-threatening lower respiratory tract illness (LRI) in infants worldwide
- Significant morbidity and mortality in U.S.
- 1-2% hospitalization rate of infants
- many others with LRI not hospitalized
-  up to 5,000 deaths/yr in US

## Metapneumovirus:  “The new kid on the block”

*References*
- www.cdc.gov
- ↓
- Homepage
- ↓
- Click on search
- ↓
- Enter: metapneumovirus

## Metapneumovirus:  Clinical Syndrome Similarities To and Differences From RSV

- Presumed similar incubation period
- Similar clinical spectrum and risk groups
- Wide range of illness severity
- Lower incidence of clinically significant disease than hRSV
- 1.5-7%  RTI; year-to year variability; similar to PIV
- Asymptomatic and mild illness much more common, especially in older children and adults
- Reinfections???
- Age extremes and immunocompromised may experience severe LRI with hospitalization
- Similar relationship to asthma: initiation & exacerbation

## Metapneumovirus:  Epidemiological Characteristics

- 2 genetic lineages with 2 subgroups each
- World-wide distribution
- Similar age/infection profile
- Seroprevalence:    70-80% - < 5 yrs
-                                  100% in adults
- Similar seasonality; however, summer infections may occur
- Serologic studies indicate hMPV circulation at least 50 years ago

## SARS-Coronavirus:  Resources

- CDC’s Home Page on Severe Acute Respiratory Syndrome (SARS)
- _[http://](http://www.cdc.gov/ncidod/sars/)__[www.cdc.gov/ncidod/sars](http://www.cdc.gov/ncidod/sars/)__[/](http://www.cdc.gov/ncidod/sars/)_
- CDC’s Draft Plan for Preparedness and Response to Severe Acute Respiratory Syndrome (SARS)
- _[http://www.cdc.gov/ncidod/sars/sarsprepplan.htm](http://www.cdc.gov/ncidod/sars/sarsprepplan.htm)_
- CDC’s archived webcasts (September 23 &30, 2003 - Parts 1 & 2) “Preparing for the Return of SARS: Are we ready?” _[http://www.phppo.cdc.gov/PHTN/webcast/sars-return/](http://www.phppo.cdc.gov/PHTN/webcast/sars-return/)_
- WHO
- _[http://www.who.int/csr/sars/en/index.html](http://www.who.int/csr/sars/en/index.html)_
- http://* *www.who.int/csr/sarsarchive/2003_04_11/en/print.html

## SARS – What is it?

- _S_evere _A_cute _R_espiratory _S_yndrome
- Often severe influenza-like illness
- Fever, chills, headache, malaise, myalgia, respiratory symptoms
- Development of dry cough, 2-7 days
- Diarrhea (10-20%)
- Most develop pneumonia
- Mechanical ventilation required (10-20%)
- Mortality rate ~15%; >50% in elderly
- Etiology: Novel, previously unrecognized coronavirus
**SARS-CoV**

## SARS – Key Epidemiologic Features

- Incubation period: 2 - 7 days; as long as 10d
- Transmission: Close person - to - person contact
- Droplet spread, fomite
- Mechanism of community spread?
- Infectivity: Maximum with symptoms (fever, cough)
- Asymptomatic virus shedding?
- Duration and scope of immunity?
- Good antibody response; often delayed
- Re - infection possible?

- _[www.who.int/csr/sars/en/index.html](http://www.who.int/csr/sars/en/index.html)_

## The SARS Outbreak: 2002-03

- First cases: 11/16/02, Quangdong Province, China
**First cases reported: 02/11/03, China**
**                                              ****Singapore**
**                                                     ****↑**
- Initial spread:  **China **→ **Hong Kong** → **Vietnam**
-                                                      ↓
-                                                **Toronto**
- Initial “hot zones” with rapid increase in cases
-  1 ̊ Tx in healthcare settings
-  2 ̊ community chains of Tx
- Final totals - World: 8422 cases; 916 deaths; 30 countries
-                       U.S.:   33 cases; 0 deaths

## -  SARS - “ A particular threat to international health”

- Pathogenicity; high mortality
- Human - to - human spread; no vector
- Initial sxs non-specific, common
- Targets healthcare workers
- Relatively long incubation period
- High proportion of patients requiring intensive care
- Possible zoonotic source
- No vaccine or treatment

## Laboratory Diagnostic Methods

## Influenza:  Laboratory Diagnosis

- Culture
- 1-5 days
- “Gold standard”
- Direct Specimen Immunofluorescence
- Dependent on reader expertise
- Limited to laboratories with IF capability
- Variable sensitivity & specificity
- Molecular
- Not yet widely available/used
- Serology
- Retrospective
- Rapid EIA and “EIA-Like” Tests
- Note:  The nasal mist vaccine may replicate in cell cultures and produce a positive result in rapid tests up to 3 weeks post-immunization.

## Influenza:  Rapid EIA and “EIA-Like” Tests

| 
Test | CLIA Status | Antigen
Detected |
| --- | --- | --- |
| Directigen Flu A | Moderate | A |
| Directigen Flu A & B | Moderate | A & B |
| Flu OIA | Moderate | A / B |
| Flu OIA A/B | Moderate | A & B |
| NOW Flu A | Waived | A |
| NOW Flu A/B | Waived | A & B |
| QuickVue Influenza | Waived | A / B |
| Xpect Flu A/B | Pending 
(interim moderate) | A & B |
| ZstatFlu | Waived | A / B |

## Influenza: Rapid EIA and “EIA-Like” Test - Specimens & Storage

| Test | Specimen Type | Specimen 
Storage |
| --- | --- | --- |
| Directigen Flu A | NP wash/asp, NP Sw,Throat Sw | 2-8C/72 hr. |
| Directigen Flu A+B | NP wash/asp, NP Sw, Nasal wash, Th Sw, BAL | 2-8C/72 hr. |
| Flu OIA | Nasal asp, NP Sw, Th Sw, Sputum | 2-8C/24 hr. |
| Flu OIA A/B | Nasal aspirate, nasopharyngeal swab, throat swab, or sputum  | 2-8C/24 hr. |
| NOW Flu A | Nasal wash, NP Sw | 2-8C/24 hr. (elute swabs) |
| NOW Flu A/B | Nasal wash, NP Sw | 2-8C/24 hr. (elute swabs) |
| QuickVue Influenza | Nasal Sw, wash, asp | 2-30C/8 hr. |
| Xpect Flu A/B | Nasal wash, swab, Th Sw | 2-8C/72 hr (in transport medium) or -20C/6 mo. |
| ZstatFlu | Th Sw | 0-40C/24 hr. |

## Influenza:  Rapid EIA and “EIA-Like” Test Performance Characteristics*

| Test | Sensitivity | Specificity |
| --- | --- | --- |
| Directigen Flu A | 91% (A) | 95% (A) |
| Directigen Flu A+B | 86% (A)
81% (B)  | 91% (A)
99.5% (B)  |
| FLU OIA | 62-88% (A/B)  | 52-80% (A/B)  |
| FLU OIA A/B | 62-88% (A/B)  | 52-80% (A/B)  |
| NOW Flu A | 78-82 (A)  | 92-94 (A)  |
| NOW Flu A/B | 78-82% (A)
58-71% (B)  | 92-94% (A)
97% (B)  |
| QuickVue Influenza | 73-81% (A/B) | 96-99% (A/B) |
| Xpect Flu A/B | 89-100% (A)
83-100% (B)  | 100% (A)
100% (B)  |
| ZstatFlu | 58-65% (A/B)  | 98-100% (A/B)  |

- *  Per Manufacturer, without discrepant analysis

## hRSV:  Laboratory Diagnosis

- Culture
- 1-10 days
- Direct Specimen Immunofluorescence
- Dependent on reader expertise
- Limited to laboratories with IF capability
- More sensitive than culture
- Molecular
- Not yet widely available/used
- Serology
- Retrospective
- Rapid EIA and “EIA-Like” Tests

## hRSV:  Rapid EIA and “EIA-Like” Tests

| 
Test | CLIA Status |
| --- | --- |
| Directigen RSV | Moderate |
| Directigen EZ RSV | Moderate |
| RSV OIA | Moderate |
| NOW RSV | Waived |
| Xpect RSV | Pending
(interim moderate) |

## hRSV:  Rapid EIA and “EIA-Like” Tests -  Specimens & Storage

| Test | Specimen Type | Specimen 
Storage |
| --- | --- | --- |
| Directigen RSV | NP wash/asp, NP Sw, Throat Sw | 2-8C/48 hr. |
| Directigen EZ RSV | NP wash/asp, NP Sw, Throat Sw | 2-8C/72 hr. |
| RSV OIA | Nasal wash, NP Sw | Room temp/2 hr
2-8C/24 hr.
Frozen |
| NOW RSV | Nasal wash | Room temp/4 hr
2-8C/24 hr.  |
| Xpect RSV | NP wash, asp., swab | 2-8C/48 hr
-20C/1 week  |

## hRSV:  Rapid EIA and “EIA-Like” Test Performance Characteristics*

| Test | Sensitivity | Specificity |
| --- | --- | --- |
| Directigen RSV | 93-97% | 90-97% |
| Directigen EZ RSV | 67% (NPS)
87% (NPW) | 92% (NPS)
86% (NPW) |
| RSV OIA | 67% (NPS) 87% (NW) | 96% (NPS) 83% (NW) |
| NOW RSV | 89% | 98-100% |
| Xpect RSV | 96% | 94% |

- *  Per Manufacturer, without discrepant analysis

## SARS-Coronavirus:  Laboratory Diagnosis

- All methods developmental
- Culture
- Not recommended
- Test for other respiratory viruses
- Strong evidence
- Direct Specimen Immunofluorescence
- Not available
- Molecular
- Real-time PCR
- Available at CDC & state public health laboratories
- Available as “home-brews”??, non-FDA approved kits??
- Serology
- “Gold standard”
- ELISA for total antibody (IgG, IgM, and IgA)
- Retrospective

## SARS-CoV Laboratory Testing:

- Real-time RT-PCR
- Good sensitivity (1-10 copies).
- Highly specific for SARS-CoV, but <50% sensitive during 1st week of infection.
- Low viral titers early in infection
- Pathogenesis of disease may not allow a definitive diagnosis early in illness.
- Changes in type, quality, and quantity of specimens and in specimen processing procedures may improve the detection of SARS-CoV infection in patients.
- Potential for false negatives and false positives.
- PPV low when prevalence is low.
- Positive result considered presumptive until confirmed.
- Negative result does not rule out SARS & should not affect patient management.
- Must be used and interpreted carefully.

## SARS-CoV Laboratory Testing:

- Serology
- Specific; no cross reactions with other coronavirus infections.
- Serology can be positive 8-10 days after onset.
- Serology cannot be considered negative until >28 days post onset
- Must be used and interpreted carefully.

##  Test Performance Characteristics

## Appropriate use of the rapid tests requires the integration of knowledge of epidemiology with knowledge of  test performance characteristics.

## Test Performance Characteristics:  Definitions

- Sensitivity
- The probability of a positive test result given the presence of disease
- How good is the test at detecting infection in those who have the disease?
- Specificity
- The probability of a negative test result given the absence of disease.
- How good is the test at calling uninfected people negative?

## Sensitivity and Specificity

**DISEASE**

**TEST**

- Sensitivity = TP/TP+FN
- Specificity = TN/TN+FP

## Predictive Value

- The probability of the presence or absence of disease given the results of a test
- PVP is the probability of disease in a patient with a positive test result.
- PVN is the probability of not having disease when the test result is negative.

## Predictive Value

**DISEASE**

**TEST**

- Predictive Value Positive (PVP) = TP/TP+FP
- Predictive Value Negative (PVN) =TN/TN+FN

## Predictive Value

- How predictive is this test result for this particular patient?
- Determined by the sensitivity and specificity of the test, ***and*** the prevalence rate of disease in the population being tested.

## Prevalence Rate

-    Number of cases of illness existing at a given time divided by the population at risk

## Hypothetical Influenza Test PerformancePrevalence = 20.0%

**Disease**

**Test**

- Sensitivity = 380/400 = 95.0%
- Specificity = 1536/1600 = 96.0%
- Predictive Value Positive (PVP) = 380/444 = 85.6%
- Predictive Value Negative (PVN) = 1536/1556 = 98.7%

## Hypothetical Influenza Test PerformancePrevalence = 1.0%

**Disease**

**Test**

- Sensitivity = 19/20 = 95.0%
- Specificity = 1900/1980 = 96.0%
- Predictive Value Positive (PVP) = 19/99 = 19.2%
- Predictive Value Negative (PVN) = 1900/1901 = 99.9%

## Predictive Value PositiveDependence on Sensitivity, Specificity and Prevalence

## Recommendations for Use of Rapid Tests for Influenza or RSV

- Use prevalence indicators to decide:
- When to test
- Whether to qualify result
- Whether to confirm results
- Potential prevalence indicators:
- Laboratory Detections
- CDC
- Statewide data
- Your laboratory data
- “Sister” laboratory’s data
- Culture confirm your first influenza positives, others as needed
- Educate clinicians on predictive values & limitations of tests

## CDC Recommendations for Specimen Collection, Testing and Laboratory Safety for SARS

## SARS-CoV Laboratory Testing:   Specimen Submission

- Consult with your state health department for evaluation of case
- If possible, include informed consent form for serology testing
- Testing will be performed if consent not obtained
- FDA regulation for use of non-licensed test
**Allows use of patient specimen for future studies**
- _[http://www](http://www/)__._
- cdc.gov/ncidod/sars/specimen_collection_sars2.htm

## SARS-CoV Laboratory Testing:  Specimens to collect during the course of illness

| SPECIMEN | <1 week post symptom onset | 1-3 weeks post symptom onset | >3 weeks post symptom onset |
| --- | --- | --- | --- |
| Serum | ++ |  ++ |  ++ |
|  
Blood (EDTA/purple top) |  
++
 | 
 +
 | 
—
 |
| Respiratory (sputum, BAL, nasal aspirate/wash, NP swab, throat swab) | 
++
 | 
 ++
 | 
+ |
| Stool |  + |  ++ |  ++ |

- ++ Preferred specimen
- - Not recommended

## SARS-CoV Laboratory Testing: Specimens for PCR

- Lower respiratory tract specimens
- Sputum, broncheoalveolar lavage, tracheal aspirate, pleural tap
- Upper respiratory tract specimens
- Nasopharyngeal aspirate/wash
- Nasopharyngeal/oropharyngeal swab
- Place in dry sterile container
- Dacron or rayon with plastic shaft
- NOT calcium alginate or wooden shafted swab
- Blood
- 5-10ml in EDTA tube (Purple top)
- Stool
- 10 - 50cc in stool cup or urine container, no preservatives
- Store all specimens at 4oC prior to shipping

## SARS-CoV Laboratory Testing:  Specimens for Serology

- Acute and convalescent sera
- Acute serum
- Collect ASAP
- approx. 30% positive within 6-10 days post-onset
- Convalescent serum
- Collect >28 days post-onset
- Most patients positive at 2 weeks

## SARS-CoV Laboratory Testing:    Specimen Shipping and Transport 

- Resource: _http://www.cdc.gov/ncidod/sars/packingspecimens-sars.htm_
- Check with your state health department or laboratory for in-state guidance.
- Proper packaging is the responsibility of the shipper.
- In brief:  Package as “Diagnostic Specimens”
- Primary receptacle:  watertight; screw-capped closures wrapped with tape or parafilm; individually wrapped;
- Secondary receptacle:  watertight; include absorbent.
- Outer packaging:  dry ice or coolant outside secondary packaging; allow release of CO2 gas if dry ice used.
- At least 4 inches on smallest side & large enough for documents
- Additional:  Volume limits, container specifications, itemized list of contents, & labelling requirements based on mode of transport (ground, air, USPS)

## Biosafety in the Laboratory:  Resources

- _Biosafety in Microbiological and Biomedical Laboratories (BMBL), _
- _4__th__ edition_
- 	U.S. Department of Health and Human ServicesCenters for Disease Control and PreventionandNational Institutes of HealthFourth Edition, May 1999.US Government Printing OfficeWashington: 1999
- http://www.cdc.gov/od/ohs/biosfty/bmbl4/bmbl4toc.htm

- _Primary Containment for Biohazards:  Selection, Installation and __Use of Biological Safety Cabinets, 2nd Edition_
- U.S. Department of Health and Human Services
- Public Health Service
- Centers for Disease Control and Prevention
*And*
- National Institutes of Health
- September 2000
- http://www.cdc.gov/od/ohs/biosfty/bsc/bsc.htm

## Biosafety in the Laboratory with SARS (I)

- Establish process to identify SARS specimens.
- If recommended safety equipment not available, reduce risk by other means.
- Perform risk assessment
- Consider referral to another laboratory
- Viral culture of suspect SARS specimens must only be performed in BSL-3 facility.

## Biosafety in the Laboratory with SARS (II)

- Blood and urine
- Biosafety Level 2 (BSL-2)
- PPE:  gloves, laboratory coats, face shield or eye protection/surgical mask
- BSC for aerosol potential
- Sealed centrifuge rotors or sample cups, if available.
- Other untreated specimens
- Biosafety Level 2 (BSL-2) facilities using BSL-3 practices
- Use biosafety cabinet (BSC) with PPE:  gloves, solid front gown, full face protection
- If BSC not available/feasible, N-95 respirator, full face protection, other containment devices
- Centrifuge using sealed rotors or sample cups
- Unload in the BSC

## 2003-04 – What can we expect?

- The first SARS case of the season: Singapore, 9/9/03
- Developments to watch for:
- Enhanced  national and international surveillance
- Stages/levels of activity to guide response
- Enhanced public health laboratory testing capability and capacity
- Enhanced public health response strategies
- Isolation, quarantine, travel advisories
- Updated specimen collection, lab testing, results interpretation and biosafety guidelines
- Identification of natural reservoir

## Closing Comments (I)

- CDC and other response partners have developed a plan for SARS preparedness & response.
- The potential for global spread of SARS requires collaboration and communication between healthcare and public health communities.
- Early case detection and diagnosis of SARS cases is critical to prevent transmission and limit the outbreak.
- Because the signs and symptoms are similar, we may not be able to differentiate influenza and SARS clinically if they occur simultaneously.

## Closing Comments (II)

- Results of SARS laboratory tests in the clinical setting are only relevant _IF_ SARS cases have been documented.
- Inappropriate laboratory testing that produces false positive or negative results will have adverse consequences.
- Identification of another respiratory pathogen in SARS-like illnesses can be significant.
- Current specimen collection and test procedures for SARS are _interim guidelines_ that may change as we learn more.
- A new model for biosafety in the laboratory?
- Universal precautions for blood in the 80’s; respiratory precautions in the 2000’s?