Upcoming Respiratory Virus Season

1
Upcoming Respiratory Virus Season
Thomas Haupt, M.S. Respiratory Disease
Epidemiologist Wisconsin Division of Public
Health Carol Kirk Laboratory Network
Coordinator Wisconsin State Laboratory of
Hygiene
October 10, 2007
2
Preview

• The Other Respiratory Viruses (in brief)
• Respiratory Syncytial Virus (RSV)
• Parainfluenza Viruses
• Rhinoviruses
• Adenoviruses
• Influenza
• Seasonal Influenza
• Avian Influenza and Pandemic Influenza
• Surveillance
• Pandemic Preparedness

3
Respiratory Syncytial Virus (RSV)

• The most common cause of bronchiolitis and
  pneumonia among infants and children lt1 yr of age
• 0.5 to 2 of children (mostly lt 6 mo. of age)
  require hospitalization during 1st RSV infection
• Most children have serologic evidence of RSV
  infection by 2 years of age
• Causes repeated infections throughout life,
  usually with moderate-to-severe cold-like
  symptoms
• Causes annual epidemics, peak activity in winter

4
Number of Respiratory Specimens Tested and
Positive for RSV - Wisconsin - 2001-2007
Culture Tests
Antigen Detection Tests
5
Parainfluenza Viruses (HPIV), Types 1-4

• Cause approximately one third of gt5 million lower
  respiratory infections in U.S. annually
• 2nd to RSV as cause of lower respiratory tract
  disease in young children.
• Like RSV, HPIVs cause repeated infections
  throughout life, usually an upper respiratory
  infection
• 90 to 100 of children gt age 5 years have
  antibodies to HPIV- 3 75 have antibodies to
  HPIV-1 and -2.

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Parainfluenza Viruses (HPIV), Types 1-4

• HPIV-1 leading cause of croup in children (gt50
  of croup cases) causes biennial outbreaks in the
  fall, usually odd-numbered years in the U.S.
• HPIV-2 also causes croup, less frequently
  detected causes annual or biennial fall
  outbreaks.
• HPIV-3 more often associated with bronchiolitis
  and pneumonia virus detected throughout the
  year, peaks in spring and early summer.
• HPIV-4 infrequently detected, possibly because
  it is less likely to cause severe disease and/or
  more difficult to detect

7
Number of Respiratory Specimens Tested and
Positive for HPIV- Wisconsin - 2001-2007
8
Number of Respiratory Specimens Tested and
Positive for HPIV, Wisconsin, 2001-2007
HPIV 1 2
HPIV 3, 4 Unknown Type
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Rhinoviruses (100 Serotypes)

• The Common Cold Virus
• Symptoms rhinorrhea, sneezing, nasal
  obstruction, pharyngitis, cough fever is
  uncommon
• Estimated to cause 50 of acute respiratory
  illnesses
• Detected year-round, with peak activity in spring
  and fall

10
Number of Respiratory Specimens Tested and
Positive for Rhinoviruses - Wisconsin - 1995-2007
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Respiratory Adenoviruses (49 Serotypes)

• Commonly cause respiratory illness but may also
  cause other illnesses, e.g., gastroenteritis,
  conjunctivitis, cystitis, rashes
• Respiratory illness ranges from common cold to
  pneumonia, croup, and bronchitis.
• Can cause acute respiratory disease (ARD)
  outbreaks during crowding and stress, first
  recognized among military recruits during World
  War II.
• Infections occur throughout the year, but
  outbreaks of adenovirus respiratory disease more
  common in late winter, spring, and early summer

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Number of Respiratory Specimens Tested and
Positive for Adenoviruses - Wisconsin - 1995-2007
13
Focus on Influenza
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Influenza The Disease

• A respiratory disease caused by influenza virus
• Abrupt onset of fever, cough, sore throat,
  chills, body aches
• Not typically associated with vomiting or
  diarrhea
• Transmitted by airborne route (coughing,
  sneezing)
• Typical incubation period 14 days
• Infectious period
• Adults - the day before to 5 days after onset
• Children - several days before to gt 10 days after
  onset
• Severely immunocompromised can shed virus for
  weeks or months.

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Current Influenza Situation

• In Wisconsin, NO confirmed cases of influenza
  this season.
• 1 positive rapid test reported during October,
  but no specimen available for confirmatory
  testing

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Current Influenza Situation

• In U.S., during May 20-September 15, 2007, 398 of
  21,029 specimens (2) were positive for
  influenza.
• 68 (17) were influenza B viruses
• 330 (83) were influenza A viruses
• 67 (20) influenza A (H1) viruses
• 85 (26) influenza A (H3) viruses
• 178 (54) influenza A viruses not subtyped.
• Two human cases of swine influenza detected in
  Ohio
• Both handled ill pigs both recovered

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Expectations for the 2007-2008 Season

• Expected Strains
• Vaccine
• A/Wisconsin/67/2005 (H3N2)
• A/Solomon Islands/3/2006 (H1N1) - NEW
• B/Malaysia/2506/2004
• Globally, influenza A(H1), A(H3) and B
  circulated, but A(H1) and A(H3) viruses were more
  numerous
• Many of the influenza A(H3) viruses from other
  parts of the world showed reduced reactivity with
  A/Wisconsin sera

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Expectations for the 2007-2008 Season

• Vaccine
• Increased number of doses available
• Expanded recommendations for use
• Expanded age range for use of LAIV
• Antivirals
• Oseltamivir and Zanamivir available for
  prevention and treatment
• Specific guidelines available through CDC
• Amantadine and Rimantadine NOT recommended due to
  increased resistance

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Seasonal Influenza Wisconsin Influenza-Like
Illness Rates 2001-2002 through 2005-2006
20
Seasonal Influenza Wisconsin Influenza-Like
Illness Rates 2006-2007
21
Number of Respiratory Specimens Tested and
Positive for Influenza by Culture - Wisconsin -
2001-2007
22
Number of Respiratory Specimens Tested and
Positive for Influenza by Antigen Detection -
Wisconsin - 2001-2007
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Influenza The Virus

• Family Orthomyxoviridae
• Genera 3 Influenzavirus Types
• - A B C
• - Type B influenza viruses only infect humans.
• - Type A influenza viruses infect humans birds
  other mammals.
• Influenza A Subtypes
• Human - H1N1, H3N2, H1N2, H2N2
• Birds - H1 to H16, N1 to N9
• Bird ?Human - H5N1, H9N2 ,H7N7, H7N2, H7N3

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Influenza Antigenic Change

• Antigenic Drift
• Process of gradual and continuous change in
  hemagglutinin (HA )and neuraminidase (NA)
  glycoproteins
• Accumulation of point mutations in the genes
  during viral replication
• Occurs with both influenza A B, leading to new
  viral strains
• Allows for repeated infections over lifetime
• Responsible for annual epidemics

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Influenza Antigenic Change

• Antigenic Shift
• Process(es) whereby existing surface HA and/or NA
  proteins are replaced by HA and NA proteins that
  are significantly different (novel)
• An abrupt change, infrequent unpredictable
• Occurs only with influenza A
• Results in a a new subtype (novel virus)
• Can result in pandemic influenza

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Laboratory Diagnosis of Influenza
27
Rapid Influenza TestsCLIA Status and Agents
Detected
Antigen Detected A B Detects
differentiates A / B Detects, does not
differentiate
28
Rapid Influenza TestsCLIA Status and Agents
Detected (continued)
29
Influenza Rapid Tests Specimens and Storage
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Influenza Rapid Tests Specimens and Storage (2)
RTRoom Temperature TMin Transport Medium
31
Rapid Tests Performance Characteristics(Per
Manufacturer, Without Discrepant Analysis
1 Equivalent to BioStar OIA FLU 2 Compared to
NOW Flu A Flu B tests
32
Rapid Tests Performance Characteristics (2)(Per
Manufacturer, Without Discrepant Analysis
33
Quick Tips Influenza Test Performance

• Children shed more virus than elderly, which can
  impact sensitivity of a test.
• Traditionally, throat specimens yield less virus
  than nasopharyngeal.
• Rapid tests may not detect novel strains of
  influenza in patients.
• A negative test result does not rule out
  influenza and should not affect patient
  management or infection control decisions.

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Quick Tips Biosafety for Influenza Testing

• Perform risk assessment
• Consider use of biosafety cabinet (BSC) or
  physical barriers (e.g., bench shields) for
  testing
• Consider use of additional personal protective
  equipment (PPE) during testing
• Sequester/isolate testing area
• Evaluate completeness of patient information to
  assess risk of specimen testing
• Collect patient travel history communicate risk
  factors to testing staff

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Quick Tips Optimizing Rapid Influenza Tests

• Consider confirmatory testing of
• Positive specimens when prevalence is low, due to
  low predictive value positive (PVP)
• Negative specimens when prevalence is high, due
  to lower predictive value negative (PVN)
• Use prevalence indicators to decide
• When to test, when to qualify/confirm results
• Potential prevalence indicators
• CDC reports, States data or reports, your data,
  related institutions data

36
Influenza Testing at the Wisconsin State
Laboratory of Hygiene

• Real-time PCR is now the primary (1st line)
  test for influenza at WSLH
• Specimens negative for influenza PCR are tested
  by Respiratory Virus Panel PCR
• Selected specimens positive for influenza by PCR
  are cultured for further characterization state
  repository
• Selected specimens negative for respiratory
  viruses by PCR can be cultured under special
  circumstances
• Influenza A positives subtyped by PCR for H1
  H3, H5 if necessary

37
Influenza Testing at the Wisconsin State
Laboratory of Hygiene

• Advantages of PCR
• Does not require viable virus
• Provides more rapid result
• Sensitivity equal to or greater than culture
• More conducive to high volume testing

38
Avian Influenza and Pandemic Influenza
39
Influenza Nomenclature (adapted from CDC)

• Seasonal Influenza (common influenza)
• A respiratory illness that can be transmitted
  person to person. Most people have some immunity,
  a vaccine is available.
• Pandemic Influenza
• A virulent human influenza that causes a global
  outbreak, or pandemic, of serious illness. There
  is little natural immunity, so the disease can
  spread easily from person to person.
• Currently, there is no pandemic influenza.
• Avian Influenza (bird flu)
• Influenza viruses that occur naturally among wild
  birds. There is no human immunity and no vaccine.
• The H5N1 variant is deadly to domestic fowl and
  can be transmitted from birds to humans.

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Avian Influenza

• Not all outbreaks of avian influenza are caused
  by influenza A (H5N1).
• Avian influenza is not uncommon
• Many types of influenza virus occur naturally
  among wild birds.
• Some avian influenza viruses make wild and
  domestic birds very sick.

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Human H5N1 Cases Reported to W.H.O. 2003 through
October 2, 2007
42
Map of Human and Avian Cases of Influenza A/H5N1
October 12, 2007
43
Avian (H5N1) Influenza Current Status

• Continued expansion of geographic and host range
  via wild birds
• Continuing large outbreaks in domestic fowl
• All genes of avian origin in human isolates
• Viral resistance to adamantanes sensitive to
  oseltamivir
• Continued evolution of pathogenicity and
  antigenicity
• No evidence of sustained human-to-human
  transmission!

44
Three Requirements for a Human Influenza
PandemicStatus of Avian Influenza (H5N1)

• Emergence of a novel subtype of influenza
• An immunologically naïve population
• Replication in humans ? disease
• Efficient human-to-human transmission

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Pandemic Influenza W.H.O. Phases
46
Seasonal vs. Pandemic Influenza
47
Influenza Seasonal Impact
WISCONSIN Population 5.4 million
Outpatient Care 120,000-240,000
5-20 Infected 270,000-1.1 million
Deaths 600-1000
Hospitalized 3,500-7,000
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Influenza Pandemic Impact
WISCONSIN Population 5.4 million
Outpatient Care 1.4 million
35 Infected 1.9 million
Deaths 8500
Hospitalized 27,500
49
Pandemic Influenza The Basics

• An influenza pandemic is inevitable, not
  imminent.
• Can occur at any time with little warning.
• Caused by an influenza Type A virus never/rarely
  identified among humans (a novel virus)
• Spreads quickly from person-to-person
• Occurs in multiple or widespread geographic areas
  worldwide locally explosive epidemics
• Associated with unusually high rates of morbidity
  and mortality possible unique age predilection
  for severe disease
• Extremely rapid global spread
• May last 2 or more years with multiple waves of
  disease
• Vaccine and antivirals likely unavailable or
  limited

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What Can We Expect in the Next Pandemic?

• Everyone affected
• Shortages of materials
• Entire national infrastructure rapidly affected
• Extraordinary strain on human and material
  resources and infrastructure
• Absenteeism (30-40)
• Employee illness and family members
• Death
• Fear
• Possible closures (hopefully short term)
• Financial Issues

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Influenza-Like Illness Rates During Seasonal
Influenza 1997/1998 2000/2001
1999
2000
2001
1998
1997
52
Influenza-Like Illness Rates Expected During a
Pandemic
1999
1997
2000
2001
1998
53
Influenza Pandemics and Novel Influenza
Viruses in U.S. History

• Past Pandemics
• 1918 Spanish Flu
• 1957 Asian Flu
• 1968 Hong Kong Flu

• Novel viruses
• 1977 - Swine Flu (New Jersey)
• 1988 - Swine flu case in Wisconsin
• 2003-05 - H5N1 avian Influenza, SE Asia
• 2005, 2006, 2007 Sporadic human cases of swine
  influenza in Wisconsin, Iowa, Ohio

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Influenza Surveillance
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Objectives of Seasonal Influenza Surveillance

• Determine when influenza viruses are circulating
• Determine where influenza viruses are circulating
• Determine how much influenza activity is
  occurring (intensity and impact)
• Identify the types and strains of circulating
  influenza viruses
• Detect unusual events
• Infection by unusual viruses
• Unusual syndromes caused by influenza viruses
• Unusually large/severe outbreaks of influenza
• Increased mortality
• Optimize use of vaccines and antivirals

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Objectives of Pandemic Influenza Surveillance

• Provide earliest detection of novel viruses
• Monitor spread of pandemic virus
• Monitor changes in virus and antiviral resistance

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Expectations for Pandemic Influenza Surveillance

• Will be adjusted as pandemic progresses
• Enhanced at introduction, initial spread and 1st
  waves
• Will likely depend on current surveillance
  systems
• Will return to interpandemic surveillance when
  pandemic strain becomes routine strain

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U.S. Influenza Surveillance - Weekly Updates
athttp//www.cdc.gov/flu/weekly.htm
State and Territorial Epidemiologists
Pediatric Hospitalization
Pediatric Mortality
Health Departments
Vital Statistics Registrars
Sentinel Providers
CDC
Laboratories
Other
Public Health Officials
Public
Physicians
Media
59
Influenza Surveillance in Wisconsin
Sentinel Providers
Institutional/Outbreak Reports
Pediatric Mortality
WDPH
Laboratories
Other
Public Health Officials
Public
Clinicians
Media
60
Laboratory-Based Influenza Surveillance in
Wisconsin
Virology Laboratories
Sentinel Submitters
Rapid Test Sites
WSLH
Public Health Epidemiologists
Laboratories
Clinicians
WSLH Wisconsin State Laboratory of Hygiene
61
Influenza Rapid Test ReportingWSLH Requesting
Year-Round Reporting
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Surveillance for Avian Influenza
63
Surveillance for Avian Influenza (1)

• Wisconsin Division of Public Health instituted
  Enhanced Surveillance for Avian Influenza in
  2003-2004 to identify potential human cases.
• Remains in effect today.
• Criteria Patient with illness within 10 days of
  return from affected country.
• Contact DPH immediately to receive approval for
  testing.

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Surveillance for Avian Influenza (2)

• If approved for testing by DPH
• LHD is immediately notified to follow-up.
• Patients are asked to self-isolate 24-48 hours
  pending results.
• Submit NP and throat swabs (in virus transport
  medium) to the WSLH.
• Arrange transport so specimens are received at
  WSLH within 24 hours of collection.
• Call WSLH if you need assistance with transport
  special pick-up may be authorized.

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Surveillance for Avian Influenza (3)

• WSLH performs RT-PCR for influenza A B
• Influenza A positives subtyped as H1 or H3, H5 if
  needed, by PCR
• If specimen is positive for influenza A, but
  negative for H1 and H3
• Results are considered presumptive until
  confirmation by CDC
• DPH notified immediately
• Specimen immediately forwarded to CDC

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Pandemic Influenza Preparedness
67
Pandemic Influenza Planninghttp//www.pandemicflu
.gov/

• National Strategy
• Stopping, slowing or limiting the spread of a
  pandemic to the U.S.
• Limiting the domestic spread of a pandemic, and
  mitigating disease, suffering and death
• Sustaining infrastructure and mitigating impact
  to the economy and the functioning of society

68
National Pandemic Planning Resources

• Plans
• Community Mitigation Plan
• Checklists
• State and Local Planning
• Business Planning / Health Insurer / Travel
  Industry
• Individuals Families
• Schools (Child Care and Preschool, School
  District (K-12), Colleges and Universities)
• Home Health Care Services
• Medical Offices and Clinics / Hospital
  Preparedness
• Emergency Medical Service Medical Transport
• Faith-Based and Community Organizations
• Long-Term Care and Other Residential Facilities

69
Elements of Community Strategy for Pandemic
Influenza Mitigation (Partial Listing)

• Rationale for Proposed Nonpharmaceutical
  Interventions (NPI)
• Pre-pandemic Planning Pandemic Severity Index
• Use of NPI by Severity Category
• Triggers for Initiating Use of NPI
• Duration of Implementation of NPI
• Critical Issues for the Use of NPI
• Assessment of the Public on Feasibility of
  Implementation and Adherence
• Planning to Minimize Consequences of Community
  Mitigation Strategy
• Testing and Exercising Community Mitigation
  Interventions

70
Wisconsins Plan

• Wisconsins Pandemic Influenza Response Document
• Created in 2001, Revised in 2003
• http//dhfs.wisconsin.gov/preparedness/pdf_files/W
  IPandemicInfluenzaPlan.pdf
• State of Wisconsin Response to Animal Influenza
• Created in 2005
• http//dhfs.wisconsin.gov/preparedness/pdf_files/w
  ipandemicfluplanforanimals.pdf

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Objectives of the Wisconsin Response to Pandemic
Influenza

• Structured response by designating who is in
  charge of what.
• Surveillance for index cases of the novel
  influenza virus.
• Maintenance of essential services including
  health care.
• Develop and implement an effective communication
  system.
• Identify, deliver, and administer vaccine and
  antivirals.

72
Objectives of the Wisconsin Response to Animal
Influenza

• Prepare and implement a coordinated, multi-agency
  approach to an animal influenza event in the
  state.
• Rapidly identify a potential animal influenza
  event.
• Define communication procedures.
• Rapidly collect, ship and test laboratory
  specimens.
• Implement quarantine, de-population and
  disinfection policies.
• Identify persons exposed to animal influenza.

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Pandemic Influenza Planning for the Laboratory
74
Pandemic Influenza Laboratory Assumptions

• Laboratories can expect
• Personnel and supply shortages
• Disruptions of medical community
• Severe disruptions of community infrastructure
• Very high demand for influenza-related diagnostic
  testing
• Continued need for non-influenza testing
• High visibility for laboratory

75
Pandemic Influenza Laboratory Assumptions

• National pandemic response will begin with
  sustained human to human transmission anywhere.
• Laboratory demands may begin when 1st
  lab-confirmed novel virus detected in U.S. or
  increased concern by public.
• Key Laboratory Roles will be
• Communication and Education for clients
• Surveillance - Reporting and Samples
• Testing for patient management and surveillance

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What Should Laboratories Do Now? (1)

• Planning and Exercises
• Participate in pandemic planning and exercises
• Conduct laboratory-specific exercises and
  discussions
• Develop/review Continuity of Operations Plan,
  response plans and checklists
• Adapt Laboratory Checklist for Pandemic Influenza
  to your institution
• Integrate laboratory plans institutional plans,
  community plans, regional and statewide plans,
  other laboratories plans
• Encourage staff to develop individual plans

77
What Should Laboratories Do Now? (2)

• Surveillance Support surveillance activities for
  seasonal influenza and novel influenza subtypes
• Biosafety Perform risk assessment, consider PPE,
  sequestering work, barriers for specimen testing
• Communications Develop communications plan for
  employees, suppliers and customers
• Education Educate clinicians and laboratorians

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Resources

• Wisconsin DPH Influenza http//dhfs.wisconsin.gov/
  communicable/influenza/
• WSLH website
• http//www.slh.wisc.edu/wps/wcm/connect/
• extranet/comdis/influenza.php
• Laboratory graphics
• http//www.slh.wisc.edu/labupdates/index.php

79
Influenza Resources

• CDC home page for influenza
• http//www.cdc.gov/flu
• http//www.cdc.gov/flu/weekly/fluactivity.htm
• U.S. web site for pandemic flu U.S. Pandemic
  Flu Plan and Preparedness Planning
• http//www.pandemicflu.gov/
• W.H.O. home page for influenza (including avian
  influenza)
• http//www.who.int/csr/disease/influenza/en/
• Promed (Program for Monitoring Emerging Diseases,
  International Society for Infectious)
• http//www.promedmail.org

80

Influenza Rapid Test Resources

• U.S. Food Drug Administration (FDA)
• Cautions in Using Rapid Flu Tests
• http//www.fda.gov/cdrh/oivd/tips/rapidflu.html
• Review of Performance Characteristics of Rapid
  Tests
• Uyeki TM. Influenza diagnosis and treatment in
  children a review of studies on clinically
  useful tests and antiviral treatment for
  influenza. Pediatr Infect Dis J 2003 22164-77.
• Verification and Validation of Procedures in the
  Clinical Microbiology Laboratory. Elder BL,
  Hansen SA, Kellogg JA, Marsik FJ, Zabransky RJ..
  Coordinating ed., McCurdy BW. American Society
  for Microbiology, 1997. (Cumitech 31)

81

Influenza Safety Resources

• Public Health Guidance for Community-Level
  Preparedness and Response to Severe Acute
  respiratory Syndrome (SARS),Version 2.3 July 20
  2004
• http//www.cdc.gov/ncidod/sars/guidance
• Biosafety in Microbiological and Biomedical
  Laboratories (BMBL), 5th ed
• http//www.slh.wisc.edu/wps/wcm/connect/
• extranet/comdis/