Avian Influenza Shoreland, Inc.

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Avian Influenza Shoreland, Inc.

• April 2006

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Taipei Wet Market
China--Backyard Farms
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Pandemic Influenza

• Next pandemic inevitable in the near term
• Wide agreement by WHO, CDC, others
• Current H5N1 bird flu or another strain
• Worldwide spread within 2-3 months possible
• Initial quarantine may close borders for weeks to
  months
• Highly contagious
• Humans have no immunity to new strains
• Vaccine availability will lag by months
• Insufficient anti-viral drugs currently available
• Significant mortality
• 1 of worlds population (30 million) died in
  1918 pandemic
• 1-2 million died in 1957 1968 pandemics
• Similar mortality possible if no effective
  intervention

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H5N1 Confirmed Cases in Humans, Wild Birds,
Poultry (April 4, 2006)
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H5N1 Confirmed Cases in Humans 192 cases / 109
deathsWHO counts only lab-confirmed cases
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The 2 Mechanisms Whereby Pandemic Influenza
Originates
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WHO Pandemic Phases

• Inter-Pandemic Period
• Phase 1 Animal virus present no human
  transmission
• Phase 2 Animal virus with features posing risk
  of human transmission
• Pandemic Alert Period
• Phase 3 Human infection through animal contact
  but no human-to-human spread (rarely, spread to a
  close contact)
• Phase 4 Small clusters of limited human-to-human
  transmission highly localized
• Phase 5 Larger clusters of human-to-human
  transmission but still localized
• Pandemic Period
• Phase 6 Worldwide human-to-human infection
  increased and sustained transmission in general
  population

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Terminology Pathogenic Avian Serotypes(defined
according to disease caused in birds)

• Influenza A has many subtypes, classified
  according to 16 H and 9 N proteins
• Poultry cases
• H5 (generally highly pathogenic)
• H7 (high or low pathogenic varies by strain)
• H9 (always low pathogenic)
• Human cases
• H5 (generally severe)
• H7 (mild disease even if highly pathogenic in
  birds)
• H9 (mild disease only 3 cases documented)

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Avian Influenza A (H5N1)

• Occurs primarily in poultry, waterfowl, or other
  birds
• Mammals are susceptible to infection--ingested
  chicken
• Become ill and die
• Thus far dont serve as natural carriers
• 2004 pigs (China) tigers domestic cats
  (Thailand)
• 2006 domestic cat, stone marten (Germany)
• Emerged in Asia sometime before 1997 in poultry
• 1997 - Mutated into highly pathogenic form
• Infected 18 humans (6 deaths) in Hong Kong
• 2003 - Re-emerged in poultry
• Mutated slightly to Z strain
• Current wave of bird to human cases since Dec.
  03

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Reasons for Concern for Pandemic H5N1

• H5N1 can infect many avian and animal species
• Facilitates geographic spread
• Recombination event is not necessary for a
  pandemic
• 1918 strain pure avian virus that underwent 10
  spontaneous mutations, became infective for
  humans, and was exceptionally virulent
• Several similar mutations present in currently
  circulating H5N1 virus
• NS1 gene possible virulence factor
• one variant of a specific NS1 gene
  present in all AI isolates
• (plus 1918 strain), but no human
  influenza A

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H5N1 Outbreaks in Birds

• Countries with H5N1 Outbreaks in 2005-06
• Asia Africa Europe
• Cambodia Cameroon Albania Serbia
  Montenegro
• China Egypt Austria Slovakia
• Hong Kong Niger Bosnia Herzegovina
  Slovenia
• Indonesia Nigeria Bulgaria Sweden
• India Burkina Faso Croatia Switzerland
• Kazakhstan Denmark Ukraine
• Malaysia France United Kingdom
• Mongolia Mid-East Germany
• Pakistan (H5) Azerbaijan Greece
• Russia Iran Hungary
• Thailand Iraq Italy
• Viet Nam Israel Poland
• Georgia Jordan Romania
• Burma (Myanmar) Turkey
• Cases were reported in birds in the following
  provinces or autonomous regions during 2005
  and/or 2006 Anhui, Guizhou, Hubei, Hunan, Inner
  Mongolia, Jiangxi, Liaoning, Ningxia, Qinghai,
  Shanxi, Sichuan, Xinjiang, Xizang (Tibet), and
  Yunnan.

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Transmission

• Spread by domestic ducks, poultry, wild migratory
  birds
• Transmitted bird to human through
• Direct contact with sick / infected birds
• Surfaces contaminated with droppings, respiratory
  secretions, ocular secretions
• Possibly eating under-cooked eggs poultry,
  duck blood
• Human-to-human transmission non-existent or rare
  with existing H5N1 strain
• Incubation period unknown -- 2-8 days
• Pandemic virus (after human adaptation) likely
  1-4 days

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Transmission (contd)

• Mainly large droplet spread
• 3 feet
• Emphasis on social distancing
• Environmental contact (H5N1 viruses can survive
  for up to 6 days)
• Airborne transmission possible?
• Isolate first cases with airborne precautions
• Infectious period
• 1 day before onset of symptoms to 5 days after in
  adults and 3 weeks in young children
• Big contrast to SARS
• Seasonally unclear winter may be still be higher

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H5N1 Clinical -- Symptoms

• Initially cannot differentiate from other cases
  of severe influenza
• Presents with fever and influenza-like symptoms,
  cough, sore throat, rhinitis, muscle aches,
  headache
• Conjunctivitis
• Rapid onset of viral pneumonia, ARDS
• H5N1 mouse studies indicate diffuse
  extrapulmonary involvement, macrophage
  activation, cytokine storm effect
• Severest mortality in young adults
• Other symptoms, e.g., severe diarrhea,
  encephalitis, etc. (see notes)

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Use of Antivirals

• Stand-by treatment
• For use (after medical consultation) after
  becoming ill in an outbreak situation
• Dosing as per treatment regimen on Treatment of
  Avian Influenza slide
• Prophylaxis
• In an outbreak situation, antivirals to be taken
  as instructed before becoming ill

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Types of Antivirals

• Oseltamivir (Tamiflu) -- recommended
• Active against H5N1 in vitro and likely effective
  in vivo (mice)
• Shelf life at least 5 years
• Supplies limited not currently in retail stores
• Until this year 2 million doses per year
• U.S. current stockpile of antiviral drugs 5.5
  million treatment courses
• an additional 12.4 million treatment courses of
  Tamiflu and 1.75 million treatment courses of
  Relenza due by Sept 2006
• ? production issues
• Zanamivir (Relenza) -- may also be effective
• Taken via inhalation - less convenient to use
• Amantadine, rimantadine H5N1 is resistant to
  these drugs

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Treatment of Avian Influenza

• Need to start antiviral treatment in first 48
  hours
• Reduce mortality / complications
• Non-severe cases
• 75 mg oseltamivir (Tamiflu) po bid for 5 days
• 2 Vietnamese cases with oseltamivir-resistant
  mutation developing during therapy with death.
• Higher dosing may be necessary
• Resistant virus not necessarily infectious
• OR
• 10 mg zanamivir (Relenza) inhaled bid for 5 days
• Almost none currently available
• Severe cases
• 150 mg oseltamivir po bid for 7-10 days
• Consider adding inhaled zanamivir (Relenza)
• Consider po/IV ribavirin

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Prophylaxis of Avian Influenza

• Oseltamivir 75 mg po once daily during period of
  exposure and for 7-10 days after last exposure
• If staying in an area of on-going epidemic with
  no vaccine available, this could mean taking
  prophylaxis for 2 months or longer.
• Prophylaxis of general public not in current HHS
  plan

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Prevention for the Traveler Pre-travel

• Check for any travel restrictions
• Prohibit travel with a fever to/from H5N1 areas
• Educate provide handout on avian influenza
• Provide travel health kit
• Supply antivirals (e.g., oseltamivir) if
  traveling to H5N1-affected area (Freedman DO,
  Leder K. J Trav Med 2005 12 36-44)
• Vaccinate with conventional influenza vaccine
• Does not protect against H5N1 but may decrease
  chance of confusing human influenza with H5N1
• Identify in-country health care resources

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Education Preventive Measures During Travel

• Avoid contact with birds, animal markets / farms,
  bird droppings or secretions, and potentially
  contaminated surfaces
• Frequent thorough hand washing
• Carry and use alcohol hand sanitizer / wipes
• Need for paper towels in washrooms
• After shaking hands
• Ingestion of eggs and poultry that are well
  cooked
• Good respiratory hygiene
• When possible, change of airplane seats to avoid
  travelers with respiratory symptoms masks when
  appropriate
• Seek early medical consultation for any fever or
  influenza-like symptoms during or after travel to
  H5N1 areas

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Travel Kit for H5N1 Areas

• First aid and medical supplies
• Oral thermometer and probe covers
• Household disinfectant
• Disposable gloves and plastic storage bags
• Alcohol-based wipes / hand sanitizer
• Masks (2- or 3-ply surgical, N95, others)
• Consider antivirals (e.g., oseltamivir)

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Masks

• Surgical masks 2- or 3-ply
• Benefit controversial but may be cultural mandate
• N-95 masks
• Fit testing required some limitations but may be
  good stand-by protection and useful on airplanes
• N-95 or N-100 with exhalation valve
• Alternative to N-95
• Exhalation valve increases comfort, temperature,
  and wetness of mask
• May be difficult to ensure compliance unless high
  risk exists

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Employees/Visitors After Return from H5N1 Areas

• Employees/visitors with fever or respiratory
  illness lt 10 days from H5N1-affected area should
  inform appropriate contact point by telephone and
  have their illness assessed by the corporate or
  other health care provider before going into the
  workplace

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Pandemic Planning Assumptions

• Two or more waves in same year or in successive
  flu seasons
• Second wave may occur 3-9 months later may be
  more serious than first (seen in 1918)
• Each wave lasts about 6 weeks in a given community

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30 Attack Rate 10 of Workforce
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Community-based Containment Measures

• Slow spread locally allow for preparation
• Slow spread to other communities
• Local containment plan
• Care, food, services to the isolated or
  quarantined
• Legal preparedness
• Flu/fever clinics hotlines
• Community communication cooperation
• Voluntary quarantine can work

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Pandemic Public Health Measures

• Respiratory etiquette
• Cover mouth/nose with sneeze/cough
• Use tissues
• Dispose of tissues
• Immediate hand hygiene
• Avoid large gatherings
• Surgical masks in public controversial
• Social distancing (3 feet) more effective
• Symptomatic individuals to wear masks
• Snow days Closure of public places
• Cordon sanitaire

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Avian Vaccines - Poultry

• Avian vaccines used in poultry
• Used extensively in several locales, including
  China
• Feb 2004 to Jan 2005 China inoculated 2.68
  billion birds
• Not currently thought to be an effective control
  measure

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Avian Vaccines - Human

• Human monovalent H5N1-only vaccines undergoing
  trials in U.S. and elsewhere
• Sanofi 2 doses were needed at 90 µg given 1
  month apart--only 50 of subjects protected
  (seasonal flu vaccine contains 15 µg)
• GSK Human trials have begun in Europe with low
  antigen content vaccines with adjuvants
• 8 million H5N1 doses on hand by 2/06 (4 million
  people)
• NIH long-term project (MedImmune) to develop seed
  virus strains against all known H types,
  including H5N1
• Egg technology Long time-line (3-6 months) for
  additional doses once decision made, current
  capacity 5 million doses / month
• Cell culture techniques new investment, several
  years off
• Priority plans HCWs at top
• 50 of the population that are healthy and 2-64
  years at bottom
• Current flu vaccines do NOT include avian strains
  and offer no partial or cross-protection

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Eliminate pandemic virus strain at source?

• Recent mathematical models of massive antiviral
  administration in a localized epidemic situation
• Ring eradication feasible if
• Low to moderate transmissibility (R0 lt 1.8)
• Chemoprophylaxis of 90 of population within 1-3
  weeks
• 1-3 million courses of oseltamivir needed
• Movement restrictions high compliance

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Recombined pandemic H5N1 strain vs. SARS

• Much more explosively contagious than SARS
• Airborne spread
• Easy in-flight spread compared to SARS
• More difficult to contain with simple quarantine
  measures than SARS
• Will still more rapidly lead to definitive
  international travel prohibition
• May not be seasonal

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