Influenza and Influenza Vaccines

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Influenza and Influenza Vaccines

• Clinicians Outreach and Communication Activity

• 2007-2008 Season

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Influenza

• Highly infectious viral illness
• Epidemics reported since 16th century
• Virus first isolated in 1933

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Influenza Virus Strains

• Type A
• moderate to severe illness
• all age groups
• humans and other animals
• Type B
• changes less rapidly than type A
• milder epidemics
• humans only
• primarily affects children

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Influenza Type A Subtypes

• Subtypes of type A determined by hemagglutinin
  (H) and neuraminidase (N)

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Surface Antigens and Immunity

• Immunity reduces likelihood of infection and
  severity of disease
• Antibodies are specific to different types of
  surface antigens
• Changes in H and N allow virus to evade
  previously developed immune responses
• Antigenic changes drift and shift

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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 2003-2004, A/Fujian/411/2002-like (H3N2) virus
  was dominant
• A/California/7/2004 (H3N2) began to circulate and
  became the dominant virus in 2005

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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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Burden of Influenza

• 10 to 20 of the population is infected with
  influenza virus each year
• Average of more than 200,000 excess
  hospitalizations each year
• Persons 65 and older and 2 years and younger at
  highest risk
• Average of 36,000 deaths each year
• Persons 65 and older at highest risk of death

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Influenza Associated Pulmonary and Circulatory
Deaths, 1998

• Age Group (yrs) Rate (per 100,000)
• 0 49 0.4 0.6
• 50 64 7.5
• gt65 98.3

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Hospitalization Rates for Influenza By Age and
Risk Group
Rate (high-risk) 808 471 231 92 62 318 507
Rate (not high-risk) 274 72 39 23 16 22 182
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 - 2004
Hospitalizations per 100,000 population
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Influenza Epidemiology

• Reservoir Human, animals (type A only)
• Transmission Respiratory Probably
  airborne
• Temporal pattern Peak December - March in
  temperate area May occur earlier or
  later
• Communicability Maximum 1-2 days before to
  4-5 days after onset

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Influenza Seasonal Trends
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Influenza Regional Epidemiology
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Influenza Vaccines

• Inactivated subunit (TIV)
• Intramuscular
• Trivalent
• Annual
• Live attenuated vaccine (LAIV)
• Intranasal
• Trivalent
• Annual

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Influenza Vaccine Supply

• Manufacturer Doses Projected
• GSK 30-35 million
• MedImmune 7 million
• Novartis 40 million
• sanofi pasteur 50 million
• CSL No estimate
• provided
• Total Up to 127-132 m

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Inactivated Influenza Vaccines Available in
2007-2008
Vaccine Package Dose Age Thimerosal
Fluzone (sanofi pasteur) Multidose vial Age-dependent gt6 mos Yes
Single dose syringe 0.25 mL 6-35 mos No
Single dose syringe 0.5 mL gt36 mos No
Single dose vial 0.5 mL gt36 mos No
Fluvirin (Novartis) Multidose vial 0.5 mL gt4 yrs Yes
Fluarix (GSK) Flulaval (GSK) Single dose syringe Multidose vial 0.5 mL 0.5 mL gt18 yrs gt18 yrs Trace Yes
inactivated vaccines approved for children
younger than 4 years
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Afluria Influenza Vaccine

• Trivalent inactivated vaccine produced in hens
  eggs
• Approved for persons 18 years and older
• Available in
• Preservative-free prefilled syringe
• Multidose vial
• Similar adverse reaction profile as other
  inactivated influenza vaccines

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Why a Yearly Influenza Vaccination

• Influenza vaccine expires June 30 each year
• Antibodies wane during the year
• Surface antigens drift and shift

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2007-2008 Influenza Vaccine

• A/Wisconsin/67/2005-like (H3N2)
• A/Solomon Islands/3/2006-like (H1N1)
• B/Malaysia/2506/2004-like (Victoria)

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Inactivated Influenza Vaccine Efficacy

• 70 - 90 effective among healthy persons lt65
  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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Inactivated Influenza Vaccine Adverse Reactions

• Local reactions 15 - 20
• Fever, malaise uncommon
• Allergic reactions rare
• Neurological very rare reactions

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Inactivated Influenza Vaccine Adverse Reactions

• Inactivated influenza vaccine contains only
  noninfectious fragments of influenza virus
• Inactivated influenza vaccine cannot cause
  influenza disease

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• TIV Schedule

Dose 0.25 mL 0.50 mL 0.50 mL
No. Doses 1 or 2 (4 week interval) 1 or 2 (4
week interval) 1
Age Group 6-35 mos 3-8 yrs 9 yrs and older
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LAIV Efficacy

• Against lab-confirmed influenza following
  experimental challenge
• LAIV 85 effective
• TIV 71 effective
• No significant difference
• NEJM 2007 LAIV more effective in preventing
  culture-confirmed influenza in children younger
  than five years

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Live Attenuated Influenza Vaccine Adverse
Reactions

• Children
• No significant increase in URI symptoms, fever,
  or other systemic symptoms
• Increased risk of asthma or reactive airways
  disease in children 12-59 months of age
• Adults
• 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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LAIV Indications

• Healthy persons 5 49 years of age
• Close contacts of persons at high risk for
  complications of influenza (except severely
  immunosuppressed)
• Persons who wish to reduce their own risk of
  influenza
• Healthcare workers

Persons who do not have medical conditions that
increase their risk for complications of influenza
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LAIV Schedule

• No.
• Doses
• 1 or 2 (4 week interval)
• 1

• Dose
• 0.2 mL
• 0.2 mL

• Age
• Group
• 6 mos 8 years
• 9 yrs and older

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Transmission of LAIV Virus

• LAIV replicates in the NP mucosa
• Mean shedding of virus 7.6 days longer in
  children
• One instance of transmission of vaccine virus
  documented in a day care setting
• Transmitted virus retained attenuated, cold
  adapted, temperature sensitive characteristics
• Transmitted attenuated vaccine virus unlikely to
  cause typical influenza symptoms

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Use of LAIV Among Healthcare Personnel

• No instances of transmission of LAIV have been
  reported in the U.S.
• ACIP recommends that LAIV can be given to
  eligible HCWs except those that care for severely
  immuno-suppressed persons (hospitalized and in
  isolation)
• No special precautions are required for HCWs who
  receive LAIV

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LAIV Storage

• Must be stored at 35 - 46 degrees Fahrenheit
• Similar to TIV
• If inadvertently frozen, return to refrigerator

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Influenza Season 2007-2008

• Recommended Groups for Vaccination
• Children 6-59 months of age
• Healthy adults 50 years old and older
• Persons 5 49 years old at high risk for
  complications
• Pregnant women
• Residents of nursing homes
• Household contacts of persons at high risk for
  complications
• Health care workers

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Influenza High Risk for Complications

• Birth through 59 months of age
• Adults 50 years old and older
• Chronic lung disease, asthma
• Chronic heart disease
• Metabolic diseases, e.g. diabetes
• Chronic renal disease
• High risk of aspiration
• Immunosuppression
• Pregnancy
• Chronic aspirin therapy 18 years old and younger

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HIV Infection and Inactivated Influenza Vaccine

• Persons with HIV at higher risk for complications
  of influenza
• TIV induces protective antibody titers in many
  HIV-infected persons
• Transient increase in HIV replication reported
• TIV will benefit many HIV-infected persons

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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 for all women
  who will be pregnant during the influenza season,
  regardless of gestational age

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Influenza Vaccine Recommendations, 2007-2008

• Immunization providers should administer
  influenza vaccine to any person who wishes to
  reduce the likelihood of becoming ill with
  influenza or transmitting influenza to others

Healthy persons 5-49 years of age, including
healthcare personnel may receive either TIV or
LAIV
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New Influenza Vaccine Recommendation 2007-2008

• Children 6 months through 8 years being
  vaccinated for the first time should receive TWO
  doses
• Some children do not return for the second dose
• Beginning in influenza season 2007-2008 ACIP and
  AAP will recommend these children receive TWO
  doses the second vaccination year

MMWR 200756 (RR-6)
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The Priming Effect

• 1st dose primes the immune system
• 2nd dose generates specific antibody response
• Ideal if first dose given in the fall
• Less ideal if first dose given in Spring,
  especially if a new B strain the following Autumn

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Second Vaccination Season

• Doses this Season
• 2
• 1

• Doses in 1st season
• 1
• 2

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Mix and Match

• If two doses are indicated
• None are contraindicated
• Can mix and match TIV/LAIV
• Use interval of vaccine given first

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The Magic of Ninth Birthday

• On or after ninth birthday
• Priming effect caused by natural infection
  thought to be significant
• Only one dose per season required
• Regardless of previous doses

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Inactivated Influenza VaccineContraindications
and Precautions

• Contraindications
• Severe allergic reaction to a vaccine component
  (e.g., egg) or following a prior dose of vaccine
• Precaution
• Moderate or severe acute illness
• History of Guillain-Barre within 6 weeks of prior
  dose

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Live Attenuated Influenza VaccineContraindication
s and Precautions

• Contraindications
• Children lt2 years of age
• Persons gt50 years of age
• Pregnancy
• Persons with underlying medical conditions
  including children and adolescents receiving
  chronic aspirin therapy
• Immunosuppression
• Precautions
• History of Guillain-Barré Syndrome within 6 weeks
  of a previous dose of influenza vaccine

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Influenza Antivirals

• Use neuraminidase inhibitors
• Oseltamavir chemoprophylaxis and treatment
• Zanamavir treatment only
• Avoid adamantanes due to resistance

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Healthy Habits

• When Healthy
• Avoid close contact with those who are sick
• Wash your hands often
• Avoid touching your eyes, nose and mouth to
  decrease the spread of germs
• When Ill
• Cover your mouth and nose with a tissue (or upper
  sleeve) when you sneeze or cough
• Stay home from work or school when you are sick