Importance of Influenza Vaccination in Children

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Importance of Influenza Vaccination in Children
Henry (Hank) Bernstein, DOChief, General
Academic Pediatrics Professor of
Pediatrics Dartmouth Medical School
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Objectives

• Review influenza incidence, clinical presentation
  and burden
• Focus on the impact of influenza in children
• Review 2007-08 recommendations
• Highlight universal expansion timeline

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Seasonal Occurence of Influenza, RSV and
Parainfluenza U.S. 1996-99
Influenza data collected only from October-May
each year through WHO Collaborating Laboratories
Surveillance System. RSV and parainfluenza data
collected through National Respiratory Enteric
Viruses Surveillance System. Thus, the relative
contribution of influenza may not be to scale
compared with RSV and parainfluenza.
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Influenza Disease Burdenin the U.S. in an
Average Year
Deaths 25,000 to 72,000
Hospitalizations 117,000 to 816,000
Physician visits 25 million
Infections and illnesses 50 to 60 million
All-cause hospitalization and mortality
associated with influenza virus
infection. Thompson WW, et al. JAMA.
2003289179 Thompson WW, et al. JAMA.
20042921333 Couch RB. Ann Intern Med.
2000133992 Patriarca PA. JAMA.
199928275ACIP. MMWR. 200453(RR06)1.
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The Spread of Influenza

• Highly contagious--efficient spread
• Primarily spread person-to-person by coughing and
  sneezing of infected persons
• Other routes possible
• Direct and indirect contact
• Small droplet (i.e., airborne)
• Can spread rapidly
• Classrooms
• Households
• Offices
• Medical settings (e.g., hospital wards and
  nursing homes)

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Influenza Pathogenesis

• Incubation 1-4 days, average 2 days
• Sudden onset of symptoms
• Symptoms persist for 7 days
• Infectious period / viral shedding
• Adults typically shed virus from 1 day before
  through 5 days after onset of symptoms
• Children shed higher titers of virus for a longer
  duration than adults
• Asymptomatic carriage is possible, but such
  persons are still infectious

ACIP. MMWR. 2004,53(RR06)1 Kavet J. Am J Public
Health. 1977671063 Frank AL, et al. J Infect
Dis. 1981144433.
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Clinical Manifestations by Age
Monto AS, et al. Arch Intern Med. 20001603243
Cox NJ, et al. Lancet. 19993541277.
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Influenza Manifestationsand Complications
Loughlin J, et al. Pharmocoeconomics.
200321273 Treanor JJ. Influenza virus. In
Mandell GL, Bennett JE, Dolin R, eds. Mandell,
Douglas, and Bennetts Principles and Practice of
Infectious Diseases. 5th ed. Philadelphia, PA
Churchill Livingstone 20001823 ACIP. MMWR.
200453(RR06)1.
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Possible Complications of Influenza Infection in
Children

• Death (3.8/100,000 children infected)1
• Acute otitis media1
• Bronchiolitis/laryngotracheobronchitis1
• Febrile seizures1,2
• Myocarditis/pericarditis2
• Encephalopathy2
• Reye syndrome2
• Myositis2
• Transverse myelitis2

1AAP. Pediatrics 20021101246-1252 2CDC. MMWR
2003 RR-81-36.
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Influenza Hospitalizations
per 100,000
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Methicillin-resistant S. aureus
Community-Acquired Pneumonia

• On the rise with 10 cases of severe MRSA CAP in
  Dec/Jan 2006-07, including 6 deaths
• Concomitant with influenza infection
• Difficult to differentiate from other causes
• Occurs in previously healthy children and adults
• High fatality rate and rapid clinical progression
  
• Consider with severe pneumonia, cavitary
  infiltrates, and history of MRSA infection

MMWR 2007 56325-329.
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Bhat N, Wright J, Broder K, et al.
Influenza-Associated Deaths among children in
the United States, 2003- 2004. NEJM. 2005 353
2559-2567.
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Influenza-Attributable Events
Outpatient Visits Antibiotic Courses
Per 100 Children
Age (years)
Neuzil KM. NEJM. 2000342(4)225-31.
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Children Play an Important Role in the
Transmission of Influenza
Family members and other close contacts
Other children
Day care, preschool and schoolchildren
Community including high-risk populations
Adapted from Elveback LR, et al. Am J Epidemiol
1976103152.
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Glezen WP, Couch RB. NEJM 1978298(11)587-92.
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Interrupting Transmission to Children

• Youngest children are at highest risk of
  influenza-related morbidity and mortality
• Protect children younger than 6 months by
  preventing transmission
• Infants lt6 months cannot be vaccinated
• Household contacts, out-of-home caregivers,
  health care workers should be vaccinated annually

CDC. MMWR. 200554(RR-8)1-40.
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Influenza Vaccination Primary Means of Prevention

• Best way to prevent influenza infection and
  prevent spreading influenza to others is
  vaccination
• Influenza antiviral medications an important
  adjunct, but not a substitute for vaccination
• Particularly useful in influenza institutional
  outbreak control
• Limited by antiviral resistance

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Infection Control Practices to Prevent Spread of
Influenza

• Standard precautions, especially hand hygiene
• Droplet precautions
• Add contact precautions for infants
• Respiratory hygiene/cough etiquette
• Screen, restrict sick visitors

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Influenza Surface Proteins
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Influenza Antigenic Changes

• Structure of hemagglutinin (H) and neuraminidase
  (N) periodically change
• Antigenic Shift
• Major change, new subtype
• Exchange of gene segment
• May result in pandemic
• Antigenic Drift
• Minor change, same subtype
• Point mutations in gene
• May result in epidemic

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Composition of 2007-08 Influenza Vaccine

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

Variant of A/New Caledonia/20/99
FDA VRBPAC (Vaccine and Related Biological
Products Advisory Committee) Gaithersburg, MD
February 28, 2007
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Influenza Vaccination Risk-Based
Recommendations for Children
Children ?6 months of age at high risk due to
underlying medical conditions
Long-term aspirin therapy
Asthma (lung)
Sickle cell disease
HIV/immuno-suppression
Cardiac disease
Pregnant Teens
Renal disease
Neuromuscular, seizure, or cognitive disorders
Metabolic diseases (diabetes)
CDC. MMWR 200554(RR-8)1-40.
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Burden of Asthma, US Children

• 8.9 million children lt17 years had lifetime
  asthma diagnosis in 2002
• 187 deaths
• 5 million physician/outpatient visits
• 727,000 ED visits
• 196,000 hospitalizations
• 14.7 million missed school days

Statistic for 2002, children lt17 years of
age Statistic for 2002, 5-17 year olds
CDC. Asthma Prevalence, Health Care Use and
Mortality, 2002.
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Milestones in Recommendation Changes

• 2000 All adults 50 and older
• 2004 All children aged 6-23 months All women
  who will be pregnant during influenza season
• 2005 All persons with any condition that can
  compromise respiratory function
• 2006 All children aged 24-59 months and their
  household contacts and out-of-home caregivers

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Pediatric Influenza Vaccination Recommendations,
2007-08

• Those at increased risk for complications (e.g.,
  healthy 6- to 23-month-olds and adults 65
  years)
• Persons aged 50-64 years
• Anyone who can transmit influenza to those at
  high risk, including healthcare workers

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Projection for 2007- 08 Influenza Vaccine Supply

• 130 million doses
• 20 million preservative-free (1 TIV and LAIV)
• sanofi-pasteur, Novartis, GSK, MedImmune
• Estimates contingent on growth characteristics
  of vaccine strains, manufacturing and licensure
  constraints, and market demands
• 150-200 million doses possible next 3-5 years

ACIP February 2007
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TIV Vaccines

• FluZone
• (sanofi pasteur)
• Thimerosal-free
• 0.25 mL/unit dose for 6-35 month olds
• 0.5 mL/unit dose for 3 years old
• Multidose vials have thimerosal

• Fluvirin
• (Novartis)
• 0.5 mL/dose for 4 years
• Multidose vials have thimerosal

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TIV Vaccines (GSK)

• Flulaval
• 0.5 mL/dose for any person 18 years old
• Multidose vials have thimerosal

• FLUARIX
• 0.5 mL/dose for any person 18 years old
• Contains only trace amounts of thimerosal

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Influenza Virus Vaccine Live, Intranasal (FluMist)

• Antigenically representative of influenza viruses
  (3) that may circulate in humans
• Cold-adapted to replicate efficiently at 25C
• Temperature sensitive so they are restricted in
  replication 37C
• Attenuated so as to not produce influenza-like
  symptoms
• Vaccine strain replicates in nasopharynx to
  produce protective immunity

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Efficacy LAIV vs. TIV
TIV
LAIV
Belshe et al. NEJM 2007356(7)685-696
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Offer Influenza Vaccine throughout season

• Seasonal influenza activity can begin early in
  fall
• Influenza activity does not spread uniformly
• Since 1976, 62 of seasons had peak activity in
  February or later
• More than one peak possible

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Peak Influenza Activity By Month () 1976 - 2006
AAP Policy Statement 2006-2007
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Paradigm Shift for Influenza

• Transition from high risk to recommended
• Model prevents morbidity, decreases burden of
  impact (direct effect) and minimizes work/school
  missed (indirect)
• Move to universal protection?

Halloran ME. Science. 2006 311 615-617.
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Universal Vaccine for Children?

• Many older children already recommended annually
  anyway
• Decreases their morbidity and mortality
• May decrease MM in community
• Creates implementation expectations that may be
  difficult to meet
• Needs appropriate lead time to avoid exacerbating
  shortages and distribution delays

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Universal Pediatric Influenza Vaccine

• Success
• Depends on
• Effective vaccine
• delivery
• Increased demand

• Benefits
• DIRECT benefit to
• vaccinated
• children
• INDIRECT benefit
• through herd
• immunity

• Barriers
• Cost
• Supply
• Stepped plan to implement
• necessary

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Parental Concerns about Vaccination

• Health care provider recommendation is a strong
  motivator in patient/parent actions
• Parents not averse to additional vaccinations if
  health care provider recommends them
• Media coverage has a significant impact on
  parents decisions about influenza vaccination

CDC. Epidemiology and Prevention of
Vaccine-Preventable Diseases. 2006 Nichol KL. J
Gen Intern Med 199611(11)673-677 Daley MF.
Pediatrics. 2006117(2)e268-277 Ma KK.
Pediatrics. 2006117(2)e157-163.
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Vaccination Coverage
http//www.cdc.gov/flu/professionals/vaccination/p
df/vaccinetrend.pdf
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Interventions That Increase Immunization Rates
Source Stone EG. Ann Intern Med
2002136(9)641-51.
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Immunization Schedule Ages 0-6 years
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Immunization Schedule Ages 7-18 years