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Recent developments in seasonal influenza epidemiology and prevention


Recent developments in seasonal influenza epidemiology and prevention. Anthony Fiore, MD, MPH ... Seasonal influenza vaccine effectiveness ... – PowerPoint PPT presentation

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Title: Recent developments in seasonal influenza epidemiology and prevention

Recent developments in seasonal influenza
epidemiology and prevention Anthony Fiore, MD,
MPH Influenza Division National Center for
Immunization and Respiratory Diseases
CDC Clinician Outreach and Communication
Activity (COCA) Teleconference May 27, 2008
  • Continuing Education Credits DISCLAIMER In
    compliance with continuing education
    requirements, all presenters must disclose any
    financial or other relationships with the
    manufacturers of commercial products, suppliers
    of commercial services, or commercial supporters
    as well as any use of unlabeled product(s) or
    product(s) under investigational use. CDC, our
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    investigational use.

  • Brief review of clinical presentation and
    epidemiology of influenza
  • Review of the 2007-8 US influenza season
  • Seasonal influenza vaccine effectiveness
  • New and updated recommendations from the Advisory
    Committee on Immunization Practices (ACIP)
  • Recent influenza vaccine coverage data, United

Human Influenza
  • Highly transmissible respiratory illness caused
    by influenza viruses
  • Yearly winter epidemics (seasonal or
    interpandemic influenza)
  • Sporadic, unpredictable pandemics

  • Annual Interpandemic Influenza Impact
  • 2.5-20 of population ill
  • Highest rates in children
  • Attack rates over 30 in children reported
  • Average of gt36,000 deaths (wide range)
  • gt90 in those gt64 years
  • Average of gt200,000 hospitalizations (wide range)
  • About 50 in those gt64 years
  • Risk of hospitalization for children lt2 years
    similar to elderly
  • Substantial economic impact
  • Burden of annual epidemics estimated at 87.1
    billion annually

  • Influenza Virus Type A
  • Subtyped based on surface glycoproteins
  • 16 hemagglutinin (HA) and 9 neuraminidase (NA)
  • Current human subtypes H1N1 H3N2
  • Capable of epidemics and pandemics
  • Infects multiple other species and can jump
    between them
  • Birds, pigs, horses, dogs…
  • Birds are the reservoir for new subtypes H1-16

  • Influenza A Antigenic Drift and Shift
  • Antigenic drift
  • Point mutations in viral genes
  • Continual process
  • Diminished immune response among previously
    infected or immunized persons to drifted
  • Results in yearly epidemics
  • Requires that vaccine updated yearly
  • Antigenic shift
  • Replacement of HA or HA NA (i.e., new subtype)
    from an animal influenza A
  • Sporadic, unpredictable event
  • No immunity within the population
  • Can result in a pandemic
  • However Many reports of transmission of animal
    influenza viruses to humans that do not result in
  • H5N1, H7N2, H7N9, swine influenza viruses

Influenza A(H5N1)
  • Numerous outbreaks among among wild birds in
    Asia, Africa, Europe, Middle East
  • Highly lethal to domestic poultry (numerous
    ongoing outbreaks in multiple countries)
  • 382 human cases, including 241 deaths since 2003
  • Close contact with infected domestic birds
    established in nearly all cases
  • No efficient human-to-human transmission
  • H5N1 is the influenza virus with pandemic
    potential of greatest concern, but other
    influenza A viruses in animals also of concern

As of May 20, 2008
  • Influenza Virus Types B and C
  • Influenza B
  • Humans only reservoir
  • Less mortality in most years c/w type A
  • Associated with epidemics, not pandemics
  • One influenza B strain in the annual seasonal
    influenza vaccine
  • Influenza C
  • Causes mild disease, sporadic cases
  • Not included in vaccine

Influenza Clinical Diagnosis
  • Clinical symptoms are non-specific
  • Symptoms overlap with many pathogens
  • Laboratory data needed to verify diagnosis
  • Rapid tests most often used but some have poor
    sensitivity in adults
  • Culture, PCR available but typically not timely
  • Even at peak influenza season, about 25-35 of
    specimens from persons with symptoms of acute
    respiratory infection test positive for influenza

Influenza Surveillance in the United States,
2007-08 Influenza Season
National Influenza Surveillance System
State and Territorial Epidemiologists
Population-based Hospitalization
Pediatric Mortality
Vital Statistics Registrars
Sentinel Providers
Novel influenza A
Health Departments
Public Health Officials
Seasonal Influenza
  • Geographic Spread
  • Virus Monitoring
  • Mortality
  • Outpatient Illness
  • Hospitalizations
  • Antiviral Resistance

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Seasonal Influenza
  • Geographic Spread
  • Virus Monitoring
  • Mortality
  • Outpatient Illness
  • Hospitalizations
  • Antiviral Resistance

U.S. WHO/NREVSS Collaborating Laboratories Nationa
l Summary, 2007-08
Updated Week 18 (April 27 May 3, 2008)
Strain Characterization, 2007-8 Season
  • CDC has characterized 881 viruses
  • A (H1) n381
  • 69 - A/Solomon Islands/3/2006-like viruses
    (similar to vaccine virus)
  • A (H3) n280
  • 21 - A/Wisconsin/67/2005-like viruses (similar
    to vaccine virus)
  • B n220
  • 3 in B/Victoria lineage that are
    B/Ohio/01/2005-like viruses similar to vaccine

Seasonal Influenza
  • Geographic Spread
  • Virus Monitoring
  • Mortality
  • Outpatient Illness
  • Hospitalizations
  • Antiviral Resistance

Pneumonia and Influenza Mortality for 122 U.S.
Cities Week Ending 05/10/2008
Epidemic Threshold
Seasonal Baseline
50 10 20 30 40 50
10 20 30 40 50 10 20
30 40 50 10 20 30
40 50 10
Influenza-Associated Pediatric Mortality
  • 71 influenza-associated deaths reported (as of
    May 14, 2008)
  • Median age 4.5 years
  • Vaccine status (n62)
  • 5 of 55 children eligible for vaccination were
    fully vaccinated
  • Bacterial co-infections (n53)
  • 23 (43) children had Staphylococcus aureus
  • 12 methicillin resistant S. aureus (MRSA)
  • 9 methicillin sensitive S. aureus (MSSA)
  • 2 no sensitivities done

Seasonal Influenza
  • Geographic Spread
  • Virus Monitoring
  • Mortality
  • Outpatient Illness
  • Hospitalizations
  • Antiviral Resistance

Percentage of Visits for ILI ARI Reported by
Sentinel Providers and BioSense Outpatient
Facilities Week 18 (April 27- May 3, 2008)
Seasonal Influenza
  • Geographic Spread
  • Virus Monitoring
  • Mortality
  • Outpatient Illness
  • Hospitalizations
  • Antiviral Resistance

NVSN Influenza Laboratory-Confirmed Cumulative
Hospitalization, Children 0 - 4 Years, 2007- 08
and Previous 4 Seasons
Seasonal Influenza
  • Geographic Spread
  • Virus Monitoring
  • Mortality
  • Outpatient Illness
  • Hospitalizations
  • Antiviral Resistance

Antiviral Resistance (as of May 10, 2008)
  • Neuraminidase Inhibitor Resistance (1,591 samples
  • 106 (11) of 969 influenza A (H1N1) viruses
    resistant to oseltamivir
  • All of the resistant viruses have H274Y mutation
  • 2006-7 season 4 (0.7) of 588 influenza A (H1N1)
    viruses isolated in U.S. were resistant
  • 0 of 332 influenza A (H3N2) viruses resistant to
  • 0 of 290 influenza B viruses resistant to
  • All tested viruses remain sensitive to zanamivir
  • Given type/subtype prevalence in the United
    States, low rate of overall resistance (2)
  • Adamantane Resistance
  • 136 (99) of 137 influenza A (H3N2) viruses
    tested were resistant
  • 79 (14) of 565 influenza A (H1N1) viruses tested
    were resistant

Oseltamivir Resistance in Influenza A(H1N1)
Determinants of Antibody Response to Influenza
  • Age
  • Elderly, infants and chronically ill generally
    lower antibody response
  • Prior exposure to virus strains similar to those
    in vaccine (infection or previous vaccination)
  • Immune competence of person being vaccinated
  • Amount of antigen in vaccine
  • Virus strains can vary as to how robust immune
    responses will be

Seasonal Influenza Vaccine Effectiveness
Measuring Seasonal Influenza Vaccine Effectiveness
  • Effectiveness varies by
  • Age group
  • Risk group
  • Timing and intensity of season
  • Degree of antigenic match between vaccine strains
    and circulating strains
  • Variety of outcomes/methods in literature make
    comparisons difficult
  • Influenza-like illness (e.g., fever and cough
    or sore throat) non-specific but relatively
    easy to ascertain
  • Laboratory-confirmed influenza -- most specific
    but requires clinical specimens and lab

Vaccine Effectiveness when Vaccine Strains and
Circulating Strains are not Well-matched
  • Studies conducted in drift years (predominant
    circulating virus is significantly drifted from
    vaccine strain) show lower vaccine effectiveness
    in preventing laboratory-confirmed influenza
  • 95 confidence interval for VE estimate against
    drifted strains might include 0 (i.e., no
  • Some studies in these years still show
    significant protection for more severe outcomes
    (hospitalization or need to seek medical care)
  • Presumed due to partial protection

Suggested reading Herrera Vaccine 2007
Ritzwoller N Engl J Med 2006
Inactivated Vaccine Effectiveness by Age and Risk
Overall range from studies conducted when good
antigenic match between vaccine and circulating
strains with lab-confirmed influenza.
Effectiveness may be lower when vaccine and
circulating strains antigenically different.
Interim Within-Season Estimate of the
Effectiveness of Trivalent Inactivated Influenza
Vaccine Marshfield, Wisconsin, 2007-08
Influenza Season
  • MMWR 200857393-8.
  • DK Shay (CDC), E Belongia (Marshfield Clinic), et

  • Estimate vaccine effectiveness (VE) for
    preventing medically attended acute respiratory
    illness (MAARI) which is lab-confirmed as
  • Provide interim and final estimates of vaccine
    effectiveness (VE) for the 2007-08 influenza

Interim Within-Season Estimate of VE Marshfield,
Wisconsin, 2007-08 Influenza Season
  • Estimate VE for preventing medically attended
    acute respiratory illness (MAARI) which is
    lab-confirmed as influenza
  • Patients living in a 14 postal-code area
    surrounding the Marshfield Clinic eligible for
    the study
  • Enrollment began on 21 Jan 2008, and interim data
    through 8 Feb reported
  • Enrolled subjects
  • Cases MAARI with influenza infection diagnosed
    by RT-PCR
  • Controls MAARI negative by RT-PCR

Vaccine Effectiveness Conclusions
  • Despite a suboptimal match (based on antigenic
    characterization) between 2 of 3 vaccine strains
    and viruses isolated from study participants,
    interim VE was 44
  • VE for influenza A(H3N2) medically attended
    infections was 58, vs. no VE for influenza B
  • Must interpret antigenic characterization data
    with clinical effectiveness data
  • Feasible to produce within-season estimates of
    VE in the United States
  • Final end-of-season estimate will be available
    this summer

MMWR 200857393-8
Summary 2007-08 Influenza Season, United States
  • Moderately severe season with Feb-March peak
  • Mixed viral types with influenza A(H3N2)
  • Oseltamivir resistance emerged
  • Increased global surveillance underway to monitor
  • Studies to evaluate clinical importance of
  • Vaccine effectiveness likely moderate despite
    antigenic differences between the circulating
    influenza H3N2 and B strains and those in the

New and Updated Recommendations from the Advisory
Committee on Immunization Practices (ACIP)
Universal Vaccination against Influenza
Increasing Interest
  • Better understanding of health and economic
    impact of influenza among older children and
  • Recognition of suboptimal vaccine effectiveness
    among groups at highest risk for influenza
    complications (e.g., elderly, persons with
    chronic illness)
  • Potential for reducing community transmission
    though vaccinating school children and healthy
    adults if high coverage can be achieved
  • Lessened concerns about vaccine supply
  • Belief that current low coverage for most
    recommended groups might be improved by a simple
    universal recommendation
  • Increased concern about an influenza pandemic
    need to learn how to vaccinate an entire
    population against influenza

Rationale for Expanding Vaccination
Recommendations to Include all School-age
Children and Adolescents
  • Rationale
  • Evidence that influenza has substantial adverse
    impacts among school age children and their
    contacts (e.g., increased school absenteeism,
    antibiotic use, medical care visits, and parental
    work loss)
  • Evidence that influenza vaccine is effective and
    safe for school-age children
  • The expectation that a simple age-based influenza
    vaccine recommendation will improve current low
    vaccine coverage levels among the approximately
    50 of school-age children who already had a
    risk- or contact-based indication for annual
    influenza vaccination
  • Also noted
  • The potential for the indirect effect of reducing
    influenza among persons who have close contact
    with children, and reducing overall transmission
    within communities, if sufficient vaccination
    coverage among children can be achieved

Approved at February 27, 2008 ACIP meeting.
Begins in 2008-09 influenza season
New from the ACIP Influenza Vaccination
Recommendations for Children
  • All children aged 6 months through 18 years
    should receive annual influenza vaccination,
    beginning in 2008 if feasible, and beginning no
    later than during the 2009-2010 influenza season

Timeline of ACIP Recommendation Changes for use
of Influenza Vaccine
  • Before 2000
  • Persons aged 65 or older
  • Persons with chronic medical conditions that
    make them more likely to have complications
    of influenza
  • Pregnant women in the second or third trimester
  • Contacts (household and out of home caregivers)
    of the above groups
  • Healthcare workers
  • 2000 Adults 50 and older
  • 2004 Children aged 6--23 months
  • Contacts (household and out of home caregivers)
    of children aged 0--23 months
  • Women who will be pregnant during influenza
  • 2006 Children aged 6--59 months
  • Contacts (household and out of home caregivers)
    of children aged 0-59 months
  • 2008 All children aged 6 months18 years

Recent Influenza Vaccine Coverage Data, United
Coverage levels slow to no increase over 3
years Other recently introduced vaccines
(varicella, hepatitis B, PCV7) have had better
coverage (43-73) 3 years after initial
Source CDC. MMWR 200756963-5
Self-Reported Influenza Vaccination Coverage
Levels Among Selected Priority U.S. Adult
Populations, 1989-2006, National Health
Interview Survey
Vaccine shortage 2004-05 season
Source CDC. http//
Other Key Updates in the 2008 ACIP Influenza
Vaccine Recommendations
  • Either TIV or LAIV should be used when
    vaccinating healthy persons aged 2--49 years
  • 2 doses separated by gt4 weeks for children aged 6
    months8 years receiving vaccination for the
    first time
  • Children 24 years old should be screened for
    reactive airways disease before receiving LAIV
    (MMWR Nov 23 2007)
  • Healthy means no underlying chronic illness
    that confers increased risk for influenza
  • All new 20082009 trivalent vaccine virus strains
  • A/Brisbane/59/2007 (H1N1)-like
  • A/Brisbane/10/2007 (H3N2)-like
  • B/Florida/4/2006-like
  • Neuraminidase inhibitors (oseltamivir or
    zanamivir) remain drugs of choice in prevention
    or treatment
  • High levels of resistance among adamantane class

  • Thank you

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