FLU FACTS FOR PANDEMIC PLANNERS

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FLU FACTS FOR PANDEMIC PLANNERS

• John D. Malone, MD, MPH
• Infectious Diseases
• Center for Biological Monitoring and Modeling
• Pacific Northwest National Laboratory
• Richland, Washington
• John.Malone_at_pnl.gov 509-376-9635 619-838-7784

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INFLUENZA VIRUS STRUCTURE

• H - hemagglutinin (HA) receptor binding surface
  glycoprotein (400 spikes) results in viral
  entry by fusion with respiratory cells (sialic
  acid)
• N neuraminidase (NA) glycoprotein (100 spikes)
  mediates newly formed flu virus release from
  respiratory cells (breaks sialic acid bonds)
• RNA single strand high error replication
  rate Reassortment (mixing) 8 viral genes when
  cell infected with 2 different viral strains
• Genus Influenza 3 types A, B, C A occurs
  vertebrates (birds/swine) B, C primarily
  human Ref Transmission of Epidemic
  Influenza, Plenum Press,1992

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INFLUENZA
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PANDEMIC INFLUENZA THREAT

• Major Pandemics 1918 Spanish Influenza -
  H1N1 (W epi curve) 1957 Asian Influenza -
  H2N2 1968 Hong Kong H3N2 (A/Hong
  Kong/1/68)
• Flu virus adaption bird ? human ? human through
  reassortment (1957/1968 pandemic) antigenic
  drift minor change (point mutations) H/N
  antigenic shift major genetic reassortment H
  gene
• Only 1 amino acid (serine) change in PB1 gene in
  respect to avian strains shared among all 3
  pandemics Nature 2005437889
• 1997 Avian H5N1 SE Asia
  poultry/migratory birds/pigs (human/animal) gt200
  human cases, gt 50 mortality J Infect Dis
  2006194S77-81//PNAS 2006103 (Nov 7)16936

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H5N1 EPIDEMIOLOGY 27 DEC 2006

• 261 Human cases in 10 countries Dead - 157
  (60)
• Top Four Countries cases and mortality rate
  () Viet Nam - 93 (45) Indonesia - 74
  (77) China - 21 (67) Egypt -
  18 (56)
• Majority close contact poultry/1case human/human
• Constantly changing 2 clades (genetic distinct
  groups) 3 distinct sub clades
• Air flights Seattle major hub United (Fly
  the Friendly Sky's) starting direct to China
  SARS traced to Metropole Hotel Hong Kong
  Chinese doctor infected others (elevator?)
• Airplane transmission example Iowa Mumps
  outbreak 2 cases transmitted in flight 11
  possible infected 575 exposed 33 commercial
  flights 8 airlines MMWR 200655559

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PEDIATRIC POPULATION

• Young children (daycare/initial elementary
  age) High influenza attack rate - 40 Secrete
  virus prolonged period - (5-7 days) Asymptomatic
  period before clinical illness
• The pediatric population experiences preventable
  hospitalizations and serves as a reservoir for
  influenza and its transmission to other children
  as well as adultsoseltamivir therapy accelerated
  resolution of clinical illnessresistance was not
  a frequent event, but has been documented in
  Japanese children treated with this
  medication Whitley RJ, Monto AS. J Infect Dis
  2006 (Nov 1) Suppl 2S133-8

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INFLUENZA PEDIATRIC POPULATION

• Clinical presentation varies by age group Older
  children/adults fever, cough, headache,
  myalgia, sore throat, runny nose Younger
  children (lt5 yo) fever, cough, runny nose
  (similar to all common pathogens rsv,
  paraflu, common cold) Infants fever alone
• Attack rates pre-school and school age - 15-42
• Otitis media/bacterial pneumonia flu associated
• High risk hospitalization ? lt 5 yo, ? ? lt
  1yo ACIP 2004 universal flu shot Kids 6-59
  m Pregnancy any trimester (cover lt 6 m)
  MMWR 200655(RR10)1

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SCHOOL AGE CHILDREN FLU TRANSMISSION

• Tecumsah, MI 1968 study Elementary/High school
  vaccinated against Hong Kong (AH3N2) pandemic.
  Significantly lower rate resp Ilness age lt 40 to
  comparable community J Infect Dis 197012216
• Texas community ? flu vaccination rate 15 ?
  30, significantly lowered risk respiratory
  illness in children and adults gt35 yo Vaccine
  2005231540
• Stochastic flu simulation model (Longini,
  Atlanta, Oct 2005) Vaccination 20 children 5-18
  yo ? all age mortality 40 Vaccination
  50 children ? all age mortality 75
• (www.medicine.emory.edu/id/ecirve/faculty_spea
  ker_slides/longiniflu)

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INFLUENZA PEDIATRIC POPULATION

• Children play a significant role in the
  introduction and spread of influenza virus into
  households and in the community. Cases among
  school-age children usually peak in the early
  stage of an epidemic and are followed by cases in
  infants and adults. The presence of school age
  children in the household is the most important
  determinant related to the occurrence of
  influenza infection. There is also evidence that
  seroconversion to influenza virus in children
  continues to occur between epidemic, suggesting
  persistence of viral activity throughout the
  year. Munoz. Paediatr Respir Rev
  2003499-104

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CATEGORY 4/5 PANDEMIC

• Very Severe 1918-1920 (H1N1) like Clinical
  attack rate 20-40, Case fatality ratio gt 2,
  Excess death rate gt 500 cases/100,000
• Community Mitigation Procedures All schools
  and day cares close for 12 weeks Children/teen
  congregation limited Social distancing
  adult/teen/children Home isolation ill no
  hospital surge capacity Home quarantine
  (voluntary) household contact
• Goal Cut the death rate Minimize attack rate
  ?Impact economy/security/mental health Flatten
  and broaden epidemiologic curve

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NEURAMINIDASE INHIBITORS Oseltamivir Tamiflu TM
(Roche)

• Age limit gt1 years
• Treatment use Initiate lt 2 days symptoms Dose -
  75mg oral 2X/day Efficacy- ? severity symptoms
  1 day ? elderly hospitalization
  (initiate 24 hr)
• Children ? symptoms 1.5 days ? asthma
• Prophylaxis 75mg qd - initiated in 2 days of
  index case symptoms high prophylactic
  efficacy in 4 household studies - oseltamivir
  (81) zanamivir (75). Oseltamivir ?
  infectiousness 80 ? pathogenicity (cause
  disease) 79/56 Am J Epidemiology
  2006 Nov 6 (doi10.1093/aje/kwj362)

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NEURAMINIDASE INHIBITORS Oseltamivir Tamiflu TM
(Roche)

• Avian flu strains (H5N1,H7N3, H7N7,
  H9N2) Suspect cases, early treatment (prior
  lab tests) dose?
• Prophylaxis (AHFS Drug Information
  2006) HCW respiratory secretions (droplet)
  Household contacts confirmed cases
  Poultry/contaminated surface direct
  contact Post panflu immunization (2
  wks) Long term (4 weeks) during waves
• Cost 46.50 Navy Pharmacy (10 tabs BID 5 days)/
  shelf life 5 years. Federal stockpile cost listed
  15 Euros 18.81
• US National stockpile FY06 purchases to 20M
  courses Oregon (Pop 3.5M) allotment FY06 - 241K
  (374K with optional 25 state purchase) FY07
  total Fed allotment ?531K (http//pandemicflu.g
  ov/plan/states/antivirals.html)

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NEURAMINIDASE INHIBITORS Zanamivir RelenzaTM
(GlaxoSmithKline)

• Age limit gt7 years
• Treatment use Initiate lt 2 days symptoms Dose
  - 5mg inhalation 2X/day for 5 days
• Special use Oseltamivir resistance
• Pregnancy preferred
• Concerns Bronchospasm in COPD/Asthma Young
  children use of inhaler
• Side effects 1-3 (very low rate) diarrhea,
  nausea, vomiting, bronchitis, sinusitis, no CNS
  issues like amantidine/rimantidine

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NEURAMINIDASE INHIBITORS ACIP/NVAC
PRIORITIZATION

• Treatment hospitalized patients health care
  workers (HCW) with direct patient contact and
  EMS pandemic health responders public safety
  and key government decision makers high risk
  individuals (immunocompromised, elderly,lt1yo)
• Post exposure prophylaxis certain institutions
  (nursing homes), EMS workers HCWs-ERS, ICU,
  Dialysis units,
• Outpatient treatment
• Prophylaxis high risk patients, other HCWs
  patient contact
• ACIPAdvisory Committee on Immunization Practice
  NVAPNational Vaccine Advisory Committee
  Ref AHFS Drug
  Information 2006

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INTERVENTIONS

• Targeted Layer Containment (TLC) Response
  geared to severity
• Non-Pharmaceutical Interventions (NPI) Public
  education - cough etiquette, wash hands,
  Masks/Respirators (N95)-large droplet/airborne S
  ocial distancing-avoid close contact outside
  home Congregations discouraged Isolat
  ion of ill/ Quarantine of exposed
• NPI effectiveness evidence thin and
  controversial IOM- Panflu modeling/containment
  report 25-26 Oct 2006, Washington DC DTRA-
  Workshop on panflu1918 lesson learned 6-7 April
  2006 (www.dtra.mil/documents/be/pandemicworkshop
  report.pdf)
• Protective sequestration early community
  isolation Navy Base Goat Island Yerba Buena,
  CA San Francisco Bay 1918 Markel et al Emerg
  Infect Dis 2006121961

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CONTINUITY OF OPERATIONS

• Pandemic vaccine prioritization (18 months for
  appropriate supplies)
• Neuraminidase (Oseltamivir) prophylaxis/treat
• Family demands ill members or children at home
• Threat actual/perceived occupational
  exposure 6500 HCW survey NYC most willing
  to report snowstorm (80) least willing SARS
  (48) most able to report mass casualty
  (81) least able smallpox (67) Qureshi
  et al. J Urban Health 20582378