Influenza and Influenza Vaccine

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• Influenza and Influenza Vaccine

Epidemiology and Prevention of Vaccine-Preventable
Diseases National Center for Immunization and
Respiratory Diseases Centers for Disease Control
and Prevention
Revised May 2009
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Note to presenters Images of vaccine-preventable
diseases are available from the Immunization
Action Coalition website at http//www.vaccineinfo
rmation.org/photos/index.asp
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Influenza

• Highly infectious viral illness
• First pandemic in 1580
• At least 4 pandemics in 19th century
• Estimated 21 million deaths worldwide in pandemic
  of 1918-1919
• Virus first isolated in 1933

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Influenza Virus

• Single-stranded RNA virus
• Orthomyxoviridae family
• 3 types A, B, C
• Subtypes of type A determined by hemagglutinin
  and neuraminidase

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Influenza Virus Strains

• Type A - moderate to severe illness - all age
  groups - humans and other animals
• Type B - milder disease - primarily affects
  children - humans only
• Type C - rarely reported in humans - no
  epidemics

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• Influenza Virus

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Influenza Antigenic Changes

• Hemagglutinin and neuraminidase antigens change
  with time
• Changes occur as a result of point mutations in
  the virus gene, or due to exchange of a gene
  segment with another subtype of influenza virus
• Impact of antigenic changes depend on extent of
  change (more change usually means larger impact)

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Influenza Antigenic Changes

• Antigenic Shift
• major change, new subtype
• caused by exchange of gene segments
• may result in pandemic
• Example of antigenic shift
• H2N2 virus circulated in 1957-1967
• H3N2 virus appeared in 1968 and completely
  replaced H2N2 virus

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Influenza Antigenic Changes

• Antigenic Drift
• minor change, same subtype
• caused by point mutations in gene
• may result in epidemic
• Example of antigenic drift
• in 2002-2003, A/Panama/2007/99 (H3N2) virus was
  dominant
• A/Fujian/411/2002 (H3N2) appeared in late 2003
  and caused widespread illness in 2003-2004

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• Influenza Type A Antigenic Shifts

Severity of Pandemic Moderate Severe
Severe Moderate Mild
Year 1889 1918 1957 1968 1977
Subtype H3N2 H1N1 H2N2 H3N2 H1N1
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Impact of Pandemic Influenza

• 200 million people could be affected
• Up to 40 million require outpatient visits
• Up to 700,000 hospitalized
• 89,000 - 200,000 deaths

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Influenza Pathogenesis

• Respiratory transmission of virus
• Replication in respiratory epithelium with
  subsequent destruction of cells
• Viremia rarely documented
• Viral shedding in respiratory secretions for 5-10
  days

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Influenza Clinical Features

• Incubation period 2 days (range 1-4 days)
• Abrupt onset of fever, myalgia, sore throat,
  nonproductive cough, headache
• Severity of illness depends on prior experience
  with related variants

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Influenza Complications

• Pneumonia
• secondary bacterial
• primary influenza viral
• Reye syndrome
• Myocarditis
• Death 0.5-1 per 1,000 cases

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Impact of Influenza-United States, 1990-1999

• Approximately 36,000 influenza-associated deaths
  during each influenza season
• Persons 65 years of age and older account for
  more than 90 of deaths
• Higher mortality during seasons when influenza
  type A (H3N2) viruses predominate

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Impact of Influenza-United States, 1990-1999

• Highest rates of complications and
  hospitalization among young children and person
  65 years and older
• Average of more than 200,000 influenza-related
  excess hospitalizations
• 57 of hospitalizations among persons younger
  than 65 years of age
• Greater number of hospitalizations during type A
  (H3N2) epidemics

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Impact of Influenza

• Rates of hospitalization among children 2 years
  and younger are similar to those of persons 65
  and older with high-risk medical conditions
• Children 24 through 59 months of age are at
  increased risk for influenza-related clinic and
  emergency department visits

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Hospitalization Rates for Influenza By Age and
Risk Group
Rate (not high-risk) 496-1038 186 86 41 23-25
13-23 125-228
Rate (high-risk) 1900 800 320 92 56-110 392-6
35 399-518
Age Group 0-11 mos 1-2 yrs 3-4 yrs 5-14
yrs 15-44 yrs 45-64 yrs gt65 yrs
Data from several studies 1972 - 1995
Hospitalizations per 100,000 population
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Influenza Among School-Aged Children

• School-aged children
• typically have the highest attack rates during
  community outbreaks of influenza
• serve as a major source of transmission of
  influenza within communities

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Influenza Diagnosis

• Clinical and epidemiological characteristics
• Isolation of influenza virus from clinical
  specimen (e.g., nasopharynx, throat, sputum)
• Significant rise in influenza IgG by serologic
  assay
• Direct antigen testing for type A virus

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Influenza Epidemiology

• Reservoir Human, animals (type A
• only)
• Transmission Respiratory Probably airborne
• Temporal pattern Peak December March in
  temperate climate May occur earlier or later
• Communicability 1 day before to 5 days after
  onset (adults)

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Pneumonia and Influenza Mortalityfor 122 U.S.
CitiesWeek Ending 05/17/2008
Epidemic Threshold
Seasonal Baseline
2008
2005
2006
2007
2004
50 10 20 30 40 50
10 20 30 40 50 10 20
30 40 50 10 20 30
40 50 10
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Month of Peak Influenza Activity United States,
1976-2008
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19
13
13
3
3
MMWR 20065522
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Influenza Vaccines

• Inactivated subunit (TIV)
• intramuscular
• trivalent
• split virus and subunit types
• duration of immunity 1 year or less
• Live attenuated vaccine (LAIV)
• intranasal
• trivalent
• duration of immunity at least 1 year

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Composition of the 2009-20010 Influenza Vaccine

• A/Brisbane/59/2007 (H1N1)
• A/Brisbane/10/2007 (H3N2)
• B/Brisbane/60/2008

manufacturers may use strains that are
antigenically identical to the selected strains.
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Inactivated Influenza Vaccines Available in
2008-2009
vaccines approved for children younger than 4
years all multi-dose vials contain thimerosal as
a preservative
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Inactivated Influenza Vaccines Available in
2008-2009
all multi-dose vials contain thimerosal as a
preservative
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Transmission of LAIV Virus

• LAIV replicates in the nasopharyngeal mucosa
• Mean shedding of virus 7.6 days longer in
  children
• One instance of transmission of vaccine virus
  documented in a child care setting
• Transmitted virus retained attenuated,
  cold-adapted, temperature-sensitive
  characteristics
• No transmission of LAIV reported in the U.S.

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Inactivated Influenza Vaccine Efficacy

• 70-90 effective among healthy persons younger
  than 65 years of age
• 30-40 effective among frail elderly persons
• 50-60 effective in preventing hospitalization
• 80 effective in preventing death

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• Influenza and Complications Among Nursing Home
  Residents

RR1.9
RR2.0
RR2.5
RR4.2
Inactivated influenza vaccine. Genesee County,
MI, 1982-1983
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LAIV Efficacy in Healthy Children

• 87 effective against culture-confirmed influenza
  in children 5-7 years old
• 27 reduction in febrile otitis media (OM)
• 28 reduction in OM with accompanying antibiotic
  use
• Decreased fever and OM in vaccine recipients who
  developed influenza

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LAIV Efficacy in Healthy Adults

• 20 fewer severe febrile illness episodes
• 24 fewer febrile upper respiratory illness
  episodes
• 27 fewer lost work days due to febrile upper
  respiratory illness
• 18-37 fewer days of healthcare provider visits
  due to febrile illness
• 41-45 fewer days of antibiotic use

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Timing of Influenza Vaccine Programs

• Influenza activity can occur as early as October
• In more than 80 of seasons since 1976, peak
  influenza activity has not occurred until January
  or later
• In more than 60 of seasons the peak was in
  February or later

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Timing of Influenza Vaccine Programs

• Providers should begin offering vaccine soon
  after it becomes available, if possible by
  October
• To avoid missed opportunities for vaccination,
  providers should offer vaccine during routine
  healthcare visits or during hospitalizations
  whenever vaccine is available

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Timing of Influenza Vaccine Programs

• Persons planning organized vaccination campaigns
  should consider scheduling these events after at
  least mid-October
• Scheduling campaigns after mid-October will
  minimize the need for cancellations because
  vaccine is unavailable
• Continue to offer influenza vaccine in December
• Providers should continue to vaccinate throughout
  influenza season

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• Inactivated Influenza Vaccine Schedule

Dose 0.25 mL 0.50 mL 0.50 mL
Age Group 6-35 mos 3-8 yrs gt9 yrs
No. Doses 1 or 2 1 or 2 1
Only one dose is needed if the child received 2
doses of influenza vaccine during the previous
influenza season
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Influenza Vaccination of Children

• Children 6 months through 8 years of age who did
  not receive the recommended second dose of
  influenza vaccine in the initial year that they
  received influenza vaccine should receive 2 doses
  during the next influenza season
• Children 6 months through 8 years of age who are
  being vaccinated two or more seasons after
  receiving an influenza vaccine for the first time
  should receive a single annual dose, regardless
  of the number of doses administered previously

applies only to the influenza season that
follows the first season that a child younger
than 9 years receives influenza vaccine
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Influenza Vaccination of Children 6 Months
Through 8 Years Of Age

• Previous vaccination
• One dose last year
• One dose in each of the last 2 years
• One dose 3 years ago
• One dose in each of the last 3 years

• Vaccine THIS year
• Two doses
• One dose
• One dose
• One dose

children 9 years and older should receive only
one dose of influenza vaccine per year regardless
of the number of doses in previous years
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Inactivated Influenza Vaccine Recommendations

• All persons 50 years of age or older
• Healthy children 6 months through 18 years of age
• Residents of long-term care facilities
• Pregnant women
• Persons 6 months through 18 years receiving
  chronic aspirin therapy
• Persons 6 months of age and older with chronic
  illness

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Influenza Vaccination of Children

• Children 6-59 months at increased risk of
  hospitalization and physician visits
• Inactivated influenza vaccination of healthy
  children 6-59 months is recommended
• Vaccination of household contacts and other
  caregivers of children younger than 59 months is
  encouraged

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Inactivated Influenza Vaccine Recommendations

• Persons with the following chronic illnesses
  should be considered for inactivated influenza
  vaccine
• pulmonary (e.g., asthma, COPD)
• cardiovascular (e.g., CHF)
• metabolic (e.g., diabetes)
• renal dysfunction
• hemoglobinopathy
• immunosuppression, including HIV infection
• any condition that can compromise respiratory
  function or the handling of respiratory
  secretions

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Pregnancy and Inactivated Influenza Vaccine

• Risk of hospitalization 4 times higher than
  nonpregnant women
• Risk of complications comparable to nonpregnant
  women with high-risk medical conditions
• Vaccination (with TIV) recommended if pregnant
  during influenza season
• Vaccination can occur during any trimester

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HIV Infection and Inactivated Influenza Vaccine

• Persons with HIV at increased risk of
  complications of influenza
• TIV induces protective antibody titers in many
  HIV infected persons
• TIV will benefit many HIV-infected persons
• Do not administer LAIV to persons with HIV
  infection

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Influenza Vaccine Recommendations

• Healthcare providers, including home care
• Employees of long-term care facilities
• Household contacts of high-risk persons

LAIV should not be administered to healthcare
workers who have contact with severely
immunosuppressed persons who require
hospitalization and care in a protective
environment
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Influenza Vaccine Recommendations

• Providers of essential community services
• Persons traveling outside the U.S.
• Persons in institutional settings (e.g., students
  who reside in a dormitory persons in a
  correctional facility)
• Anyone who wishes to reduce the likelihood of
  becoming ill from influenza

these groups may receive TIV, and some may be
eligible for LAIV
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In the 2004 National Health Interview Survey,
only 40 of healthcare personnel reported
receiving influenza vaccine in the previous 12
months.
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Influenza Vaccination of HCPs

• Educate HCWs about the benefits of vaccination
  for themselves, their families, and their
  patients
• Educate staff about vaccine adverse reactions
• Provide free vaccine at the work site to all
  employees, including night and weekend staff

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Live Attenuated Influenza VaccineSchedule

• Age Group
• 2 - 8 years, no previous influenza vaccine
• 2 - 8 years, previous influenza vaccine
• 9 - 49 years

• Number of Doses
• 2
• (separated by 4 weeks)
• 1
• 1

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Live Attenuated Influenza VaccineIndications

• Healthy, nonpregnant persons 2 through 49 years
  of age, including
• healthy children
• healthcare personnel
• persons in close contact with high-risk groups
• persons who want to reduce their risk of influenza

Persons who do not have medical conditions that
increase their risk for complications of influenza
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Simultaneous Administration of LAIV and Other
Vaccines

• Inactivated vaccines can be administered either
  simultaneously or at any time before or after
  LAIV
• Other live vaccines can be administered on the
  same day as LAIV
• Live vaccines not administered on the same day
  should be administered at least 4 weeks apart

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Inactivated Influenza Vaccine Adverse Reactions

• Local reactions 15-20
• Fever, malaise not common
• Allergic reactions rare
• Neurological very rare reactions

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Live Attenuated Influenza VaccineAdverse
Reactions

• Children
• no significant increase in URI symptoms, fever,
  or other systemic symptoms
• significantly increased risk of asthma or
  reactive airways disease in children 12-59 months
  of age
• Adults
• significantly increased rate of cough, runny
  nose, nasal congestion, sore throat, and chills
  reported among vaccine recipients
• no increase in the occurrence of fever
• No serious adverse reactions identified

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Inactivated Influenza VaccineContraindications
and Precautions

• Severe allergic reaction to a vaccine component
  (e.g., egg) or following a prior dose of vaccine
• Moderate or severe acute illness
• History of Guillian Barre syndrome within 6
  weeks following a previous dose of TIV
  (precaution)

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Live Attenuated Influenza VaccineContraindication
s and Precautions

• Children younger than 2 years of age
• Persons 50 years of age or older
• Persons with chronic medical conditions
• Children and adolescents receiving long-term
  aspirin therapy

These persons should receive inactivated
influenza vaccine
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Live Attenuated Influenza VaccineContraindication
s and Precautions

• Immunosuppression from any cause
• Pregnant women
• Severe (anaphylactic) allergy to egg or other
  vaccine components
• History of Guillian-Barré syndrome
• Children younger than 5 years with recurrent
  wheezing
• Moderate or severe acute illness

These persons should receive inactivated
influenza vaccine
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Live Attenuated Influenza Vaccination of Children
2-4 Years of Age

• Clinicians and immunization programs should avoid
  use of LAIV in children with asthma or a recent
  wheezing episode
• Consult the medical record, when available, to
  identify children 2 through 4 years of age with
  asthma or recurrent wheezing that might indicate
  asthma

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Live Attenuated Influenza Vaccination of Children
2-4 Years of Age

• Parents or caregivers of children 2-4 years
  should be asked
• In the past 12 months, has a healthcare
  provider ever told you that your child had
  wheezing or asthma?
• Children whose parents or caregivers answer "yes"
  to this question, or whose medical record notes
  asthma or a wheezing episode within the past 12
  months, should not receive LAIV
• Inactivated influenza vaccine should be
  administered to children with asthma or possible
  reactive airways diseases

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Influenza VaccineStorage and Handling

• Both types of influenza vaccine must be stored at
  refrigerator temperature (35-46F, 2-8C)
• Neither vaccine should be frozen
• If LAIV is inadvertently frozen the vaccine
  should be placed at refrigerator temperature and
  used as soon as possible

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Influenza VaccineStrategies to Improve Coverage

• Ensure systematic and automatic offering of TIV
  to high-risk groups
• Educate healthcare providers and patients
• Address concerns about adverse events
• Emphasize physician recommendation

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Influenza Antiviral Agents

• Amantadine and rimantadine
• Not recommended because of documented resistance
  in U.S. influenza isolates
• Zanamivir and oseltamivir
• neuraminidase inhibitors
• effective against influenza A and B
• should be used if an influenza antiviral drug is
  indicated for chemoprophylaxis or treatment

see influenza ACIP statement or CDC influenza
website for details
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Influenza Surveillance

• Monitor prevalence of circulating strains and
  detect new strains
• Estimate influenza-related morbidity, mortality
  and economic loss
• Rapidly detect outbreaks
• Assist disease control through rapid preventive
  action

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CDC Vaccines and ImmunizationContact Information

• Telephone 800.CDC.INFO
• Email nipinfo_at_cdc.gov
• Website www.cdc.gov/vaccines