200809 Seasonal Influenza Update

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2008-09 Seasonal Influenza Update

• Carolyn B. Bridges, MD
• Influenza Division
• National Center for Immunization and Respiratory
  Diseases
• Centers for Disease Control and Prevention

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• Continuing Education Credits DISCLAIMERIn
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  investigational use.

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• Thanks to my many colleagues who contributed data
  and slides to my presentation, especially
• Lyn Finelli
• Tony Fiore
• Lene Blanton
• Scott Epperson
• Lynnette Brammer
• Gary Euler
• Laura Williams
• Alicia Fry
• Larissa Gubareva
• This presentation represents the views of the
  presenter and may not represent the views of CDC.

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Human Influenza

• Contagious respiratory illness caused by
  influenza virus
• Characterized fever (often high), cough, body
  aches, headache, malaise, rhinnitis
• Yearly winter epidemics
• Peak activity usually in January and February
• Sporadic, unpredictable pandemics

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Burden of Influenza

• Seasonal in U.S.
• Average 6-7 adults and up to 30 children ill
• 36,000 deaths, 200,000 hospitalizations
• 20,000 hospitalizations in
• Pandemic
• 30 illness rates across age groups

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Average influenza-associated illness rates by age
group
Low estimate based on Tecumseh community
studies. High estimate based on Houston family
studies. Adapted from Sullivan KM.
PharmacoEconomics 19969 Suppl.326-33.
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Influenza-Associated Hospitalizations By Age
Group (Thompson, JAMA, 2004)
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Influenza-Associated Deaths By Age Group,
1990-2001 (Thompson, JAMA 2003)
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Influenza Surveillance Activities for 2008-09
Season
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Goals of Influenza Surveillance

• Describe the onset and duration of the season
• Identify and characterize viruses/strains
• Vaccine strain selection
• Antiviral resistance
• Track geographic spread
• Monitor severity
• Provide information to partners

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Types of Influenza Surveillance in US

• Virologic
• Morbidity
• Mortality
• Influenza activity
• Novel influenza A virus infection

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2008-2009 Influenza Season Week 42, ending
October 18, 2008 (All data are preliminary and
may change as more reports are received.) Synopsi
s During week 42 (October 12-18, 2008), a low
level of influenza activity was reported in the
United States.   - Ten (1.0) specimens tested by
US World Health Organization (WHO) and National
Respiratory and Enteric Virus Surveillance System
(NREVSS) collaborating laboratories and reported
to CDC/Influenza Division were positive for
influenza. - The proportion of deaths attributed
to pneumonia and influenza (PI) was below the
epidemic threshold. - The proportion of
outpatient visits for influenza-like illness
(ILI) was below national and region-specific
baseline levels. - Eleven states, the District of
Columbia, and Puerto Rico reported sporadic
influenza activity 38 states reported no
influenza activity and one state did not report.
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Virologic Surveillance

• 140 participating laboratories from two networks
  (WHO, NREVSS)
• Weekly reports
• 80 WHO collaborating labs
• 65 NREVSS labs
• specimens tested
• positive for influenza type, subtype, age
• Analyzed weekly and included in weekly report of
  influenza activity October through May
• National and regional level analysis

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WHO/NREVSS Collaborating LaboratoriesNational
Summary, 2007-08
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Virus Type/Subtype by Region2007-08
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Types of Influenza Surveillance

• Virologic
• Morbidity
• Mortality
• Influenza activity
• Novel influenza A virus infection

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Influenza-like Illness Surveillance in the U.S.

• 2,400 physicians/clinics enrolled for the
  2007-08 season
• Weekly reports
• Total of patient visits
• visits for influenza-like illness (ILI) by age
  group
• ILI fever ? 100 F (38 C) and cough or sore
  throat, in absence of a known cause
• Data weighted by state population for analysis

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Percentage of Visits for Influenza-like
IllnessReported by Sentinel Providers, National
Summary 2007-08 and Previous 3 Seasons
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Hospitalization Surveillance
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Hospitalization Surveillance

• Two Networks
• Emerging Infections Program (EIP) 10 sites
• Persons hospitalized with laboratory-confirmed
  influenza infection
• New Vaccine Surveillance Network (NVSN) 3 sites
• children laboratory-confirmed influenza infection

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NVSN Influenza Laboratory-Confirmed Cumulative
Hospitalization Rates for Children 0 - 4 Years,
2007- 08 and Previous 4 Seasons
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EIP Influenza Laboratory-Confirmed Cumulative
Hospitalization Rates for Children Aged 0-4 and
5-17 yrs, 2007-2008 and Previous 4 Seasons
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Types of Influenza Surveillance

• Virologic
• Morbidity
• Mortality
• Influenza activity
• Novel influenza A virus infection

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122 Cities Mortality Reporting System

• Purpose
• Monitor PI related mortality in a timely manner
• Weekly reports from vital statistics offices in
  122 US cities
• Total of death certificates filed
• with pneumonia or influenza listed anywhere
• 1/4 of US deaths
• Timely
• Reporting lag 1-2 weeks

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Pneumonia and Influenza Mortalityfor 122 U.S.
CitiesWeek Ending 08/02/2008
Epidemic Threshold
Seasonal Baseline
2005
2006
2007
2004
2008
50 10 20 30 40 50
10 20 30 40 50 10 20
30 40 50 10 20 30 40
50 10 20 30
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Influenza-Associated Pediatric Mortality

• Initiated during the 2003-04 season
• 153 deaths in 40 States
• In June 2004, CSTE recommended influenza-associate
  d pediatric mortality become a nationally
  notifiable condition.
• Reporting began in October 2004
• Data reported weekly in MMWR and influenza update
• All influenza pediatric deaths asked to be
  reported to state/local health departments

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Influenza-Associated Pediatric Mortality Case
Definition

• Death resulting from a clinically compatible
  illness that was confirmed to be influenza by an
  appropriate laboratory or rapid diagnostic test
• Age
• Case report form also requests information on
  bacterial co-infections

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Number of Influenza-Associated Pediatric Deaths
by Week of Death2005-06 season to October 2008
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Influenza Associated Pediatric Mortality 2007-08
Season

• As of August 2, 2008, received 85 reports of
  influenza-associated pediatric deaths
• Median age 5 years (range 29 days 17 years)
• Of 67 tested for bacterial co-infection, 43
  positive, 28 (42) had S. aureus infection
• 15 MRSA
• Increasing proportion of cases with Staph. aureus
  co-infections concerning
• 2 in 2004-05
• 6 in 2005-06
• 30 in 2006-07

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Types of Influenza Surveillance

• Virologic
• Morbidity
• Mortality
• Influenza activity
• Novel influenza A virus infection

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Influenza Activity Report(State Epidemiologists
Report)

• Assessment of overall influenza activity at state
  level
• None, sporadic, local, regional, widespread
• Overall impression of virus circulation,
  outbreaks illness
• Only system reporting state-level data

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(No Transcript)
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Types of Influenza Surveillance

• Virologic
• Morbidity
• Mortality
• Influenza activity
• Novel influenza A virus infection

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Novel Influenza A Virus Infections

• Novel influenza A virus infections are human
  infections with influenza A virus subtypes that
  are different from the currently circulating
  human subtypes (A/H1 and A/H3)
• Human infections with novel influenza A viruses
  transmissible person to person may signal the
  beginning of an influenza pandemic
• Require rapid evaluation to assess risk of spread
  among humans

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New Reporting Requirements for Novel Influenza A
Virus Infections

• June 2007, CSTE added novel influenza A
  infections to the National Notifiable Diseases
  Surveillance System (NNDSS)
• Reporting of new subtypes of influenza in people
  also required under International Health
  Regulations (IHR) 2005

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H5N1 Avian Influenza

• Currently spreading through Asia, Africa, Europe,
  Middle East
• Highly lethal to domestic poultry and other
  animal species
• 387 humans cases, including 245 deaths since
  2003
• No efficient human to human transmission
• Virus of greatest concern for pandemic potential,
  but other viruses in animals also of concern

As of Oct. 20, 2008
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Recent Improvements in Influenza Diagnostic
Capabilities

• Substantial pandemic planning resources devoted
  to improving PCR-testing capacity for novel
  influenza A at public health laboratories
• APHL provided public health labs with RT-PCR
  procedures and training for differential
  detection and characterization of human A/H1,
  A/H3 and Asian avian H5N1 (2004-2005)
• Approximately 140 labs with RT-PCR capacity
• More labs can do subtyping than ever before
• Labs advised to quickly forward any
  unsubtypables to CDC to confirm

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Novel influenza A reportingin the US

• Increase in the number of unsubtypable isolates
  submitted to the CDC laboratory that are
  classified as non-circulating subtypes
• Swine influenza virus infection being identified
  more frequently than before

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Swine Influenza Virus (SIV)

• Swine influenza virus (SIV) first identified in
  1930
• Human influenza identified 3 years later
• Endemic in pig herds throughout world
• Causes respiratory symptoms (cough, runny nose,
  lethargy, decreased feeding)
• Secondary bacterial infections common
• Herds often vaccinated in U.S.

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Interspecies Transmission of SIV

• Interspecies transmission well documented
• Recent review of 37 human civilian cases from
  1976 though 2006 (Myers KP, et al. CID 2007)
• CFR 6/35 (17)
• H9N2 avian influenza found among pigs in
  Southern China and confirmed in 2 humans in HK
• 5 possible cases, S. China(Peiris Lancet 1999,
  Peiris J Virology 2001, Cong J Virology 2007 )

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Swine Influenza in North America
1930
Slide courtesy of Dr. Amy Vincent, USDA
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Recent Swine Influenza Infections in the United
States

• 9 human cases of swine influenza identified since
  December 2005
• Previously 1 case every 1-2 years
• All triple reassortant viruses
• Varying exposures and levels
• of investigation

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Non-occupational Exposures to Pigs

• Occupationally exposed persons with increased
  levels antibody to SIV
• Non-work venues provide potential for exposure by
  persons
• Without pre-existing immunity
• Immune compromised
• E.g. fairs, petting zoos

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USDA Swine Influenza Surveillance Pilot Project

• Interagency Agreement between CDC and US
  Department of Agriculture (USDA) signed in
  September 2008
• Objectives
• Identify antigenic variation among SIV
  circulating in US
• Increase testing and reporting of outbreaks in
  swine associated with
• Novel subtypes in pigs
• Unusually severe disease in pigs
• Suspected or confirmed human illness
• Improve understanding of risk of interspecies
  transmission

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Influenza Vaccine and Antiviral Medication
Recommendations for United States
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Influenza Vaccines

• Live and inactivated vaccines available for
  seasonal influenza
• Live, intranasal spray vaccine for healthy
  persons 2-49 years
• No asthma or recurrent wheezing in 2-4 year olds
• Inactivated, injectable vaccine for persons 6
  months and older
• Primary influenza prevention tool
• More than 140 million doses anticipated for US
  market this year

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U.S. Influenza Vaccine Recommendations

• Recommended annually for persons
• Increased risk influenza-related complications
• 65 years
• 6 months-64 years with high risk conditions
• Close contact with high risk
• Household members
• Health care workers
• 50-64 year old persons
• 24-32 have high risk conditions
• Anyone else who wish to decrease risk of
  influenza
• 2008 6 months through 18 years

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Medical Conditions for Which Influenza
Vaccination Recommended

• Residents of long-term care facilities
• Chronic heart or lung disease
• Metabolic disease, including diabetes
• Renal disease
• Hemoglobinopathies
• Weakened immune system due to illness or
  medication, including HIV/AIDS
• Conditions that interfere with lung
  function/control of secretions, e.g. neurologic
  or neuromuscular disorders
• 6m 18 years on chronic aspirin therapy
• Pregnant during influenza season

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Self-Reported Influenza Vaccination Coverage
Levels Among Selected Priority U.S. Adult
Populations, 1989-2007, National Health
Interview Survey
Source CDC, NHIS. http//www.cdc.gov/flu/professi
onals/vaccination/pdf/vaccinetrend.pdf Preliminar
y data from 2006-07 influenza season
Vaccine shortage 2004-05 season
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Percentage of children fully vaccinated (i.e., 1
or 2 doses as appropriate) against influenza
among children 6-23 months of age, IIS Sentinel
Site Project, 2004-05 through 2007-08 influenza
seasons
Preliminary Data
Percent ()
IIS Sentinel Site
Note OR sentinel site expanded from Washington
County in 2004-5 through 2006-7 seasons to
include Multnomah county in 2007-8 season.
Michigan added one county to its sentinel site
region in 2007-8 season.
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Percentage of children fully vaccinated (i.e., 1
or 2 doses as appropriate) against influenza
among children 24-59 months of age, IIS Sentinel
Site Project, 2006-07 2007-08 influenza seasons
Preliminary Data
Percent ()
IIS Sentinel Site
Note OR sentinel site expanded from Washington
County in 2004-5 through 2006-7 seasons to
include Multnomah county in 2007-8 season.
Michigan added one county to its sentinel site
region in 2007-8 season.
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Influenza Antiviral Medications

• Two classes
• Adamantanes rimatadine and amantadine
• Currently not recommended for use due to high
  level of resistance among circulating influenza A
  viruses
• Neuraminidae inhibitors
• Oseltamivir and zanamivir
• Used for both prevention and for treatment

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Neuraminidase Inhibitors

• Oseltamivir (Tamiflu - Roche) and Zanamivir
  (Relenza - GSK)
• Used for the treatment and prevention of seasonal
  influenza A and B virus infections
• Treatment should begin as soon as possible after
  symptom onset
• Ideally within first 2 days of illness

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Neuraminidase Inhibitors

• Reduces duration of influenza symptoms by average
  of 1-1.5 days when administered within 2 days of
  illness onset
• Recent observational study by McGeer, et al
  showed benefit even when treatment started 48
  hours after onset
• Reduces lower respiratory tract complications,
  pneumonia, and hospitalization in some studies
• McGeer study also suggests oseltamivir reduces
  mortality among hospitalized patients with
  lab-confirmed seasonal influenza A
• Effective in preventing seasonal influenza
• 70-90 effectiveness when started within 48 hours
  of exposure in RCT

McGeer et al. Clin Infect Dis 2007
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Oseltamivir

• Available as a capsule or suspension administered
  by mouth
• Approved in the U.S. for treatment or prevention
  of influenza in persons aged 1 year
• Treatment for 5 days
• Prevention regimen typically for 10 days after
  exposure
• Pediatric dosage depends on age and weight
• For treatment of seasonal influenza, administered
  twice a day for 5 days
• Side effects nausea, vomiting in some persons
• Reports of delirium in pediatric patients
  (adolescents, most reports from from Japan)
• Warning added to label in 2007

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Antiviral Resistance PatternsUnited States and
Global, 2007-2008
Global average. NAI resistance varies by country
from 0-100. Resistant A(H1N1) viruses retained
sensitivity to zanamivir, amantadine, and
rimantadine N/A not applicable.
http//www.who.int/csr/disease/influenza/H1N1webup
date20082008_kf.pdf.
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Antiviral Resistance to Oseltamivir in H1N1
StrainsGlobal, 2007-2008
http//www.who.int/csr/disease/influenza/Global_H5
N1Resistance_20080701.jpg See also Sheu TG, et
al. Antimicrob Agents Chemother. 2008 Jul 14.
epub.
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Zanamivir

• Orally inhaled powder administered by mouth via
  special device
• Approved in the U.S. for
• Treatment of seasonal influenza (aged 7 years)
• Prevention of seasonal influenza (aged 5 years)
• Treatment dosage two puffs in the morning and
  two at night for 5 days (5 days)
• Prevention dosage 2 puffs once a day (typically
  for 10 days after exposure)
• Side effects
• Wheezing, and breathing problems
• Precautions
• Persons with chronic respiratory disease
• Pregnant women
• Resistance rare

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ACIP Recommendations 2008 Antiviral Dosage by
Age
60
Conclusions

• Influenza causes substantial morbidity and
  mortality yearly in US
• Influenza activity low as typical for October,
  but expected to increase
• Surveillance updated weekly
• Updates on pediatric deaths and bacterial
  co-infections
• Antiviral resistance
• Any reports of novel influenza A infections
• Vaccine is primary prevention tool
• Oseltamivir and zanamivir are currently
  recommended influenza antiviral medications
• Recommendations for antiviral use will be updated
  based on surveillance data during the season
• Will depend on
• Proportion A/H1N1 viruses that are resistant
• Proportion of all influenza viruses that are
  A/H1N1 versus A/H3N2 or B

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