Denver Post, 41106

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Denver Post, 4/11/06
Any community that fails to prepare with the
expectation that the federal government will
come to their rescue,will be sadly
disappointed. Michael Leavitt, US Secretary of
Health
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AVIAN INFLUENZA
What everyone needs to know
Sandhill Cranes from Arizona to the Northern US
Canada
Vincent A. Fulginiti, MD Professor
Emeritus University of Arizona
(UAHSC)
University of Colorado (UCHSC)
Former Department Head, UAHSC
Former Dean, Tulane School of Medicine
Former Chancellor, UCHSC
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WHAT DO WE NEED TO KNOW?

• Nature of influenza virus
• Nature of the disease(s) caused
• Epidemic ? Pandemic?
• History of epidemics and pandemics
• Current status of avian influenza in both birds,
  sub-human mammals, and humans
• Likeliness of a pandemic
• What can we do..before, during, after a pandemic?
  (Focus on preparedness)
• What are the scientific, legal, ethical and human
  concerns

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INFLUENZA VIRUSES

• THREE GROUPS (TYPES) A B C A infects
  humans, birds, mammals
• B C - infects only humans (B some
  mammals)
• Surface antigens - Hemaglutinin 16
  Neuraminidase 9
• 144 combinations possible but only a few actually
  have occurred that are significant
• Internal RNA 8 genes in
  packets,segmented,code for multiple viral
  proteins

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THE VIRUS
H AND N SURFACE ANTIGENS
RNA CORE
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VIRAL FUNCTIONS

• Hemagglutinin allows for attachment
• Neuraminidase enhances spread of virus
• Virulence factors NS1 protein-reduces
  interferon, flux of immunologic cytokines
• Other proteins efficient replication, binding
  of critical cell proteins reducing normal cell
  function
• Cleavage of H initiates infection
• H5N1 has enhanced virulence factors that may
  account for the lethality of infection in
  combination with the attachment of the virus in
  deep lung cells.

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(No Transcript)
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HOW FLU VIRUS CHANGES
H5N1
TRANSMISSIBLE HUMAN FLU
H3N2 (CURRENT HUMAN STRAIN
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GENETIC DIVERSITY
The 8 component segmented genome permits easy
reassortment and, because of constant
reassortment in influenza virus Surface antigens
change with time small change DRIFT
yearly epidemics large change SHIFT
pandemic
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THE DISEASESymptoms

• Fever chills
• Headache
• Fatigue-often extreme-climb stairslike a
  mountain
• Dry cough
• Rhinitis
• Myalgias
• Sore throat

• Various GI symptoms Nausea Vomiting Diarrhea
  Discomfort to pain

Duration of symptoms varies often biphasic
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Complications

• Pneumonia and other respiratory -up to 5-much
  higher in virulent pandemic strains
• Rarely
• Liver and neurologic (Reyes) associated with
  concomitant aspirin use
• Muscle inflammation
• Heart inflammation
• Brain inflammation
• Rates increase for newborns, young children, all
  with underlying blood, lung, heart, cancer,
  kidney and other chronic diseases.

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INFLUENZA-EPIDEMIC AND PANDEMIC

• Epidemic every year a limited number of
  susceptible persons become infected Involve
  5-20 of persons in U.S. 200,000
  hospitalized 20,000-35,000 die
• Spread by close contact, usually in family
  settings and community groups
• Pandemic entire world affected with massive
  numbers of persons with disease and with large
  number of deaths

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PANDEMICS

• 1889-90 ?Asia/Russia ?H2N2, high mortality
• 1900 possible H3N8
• 1918-19 SPANISH FLU- H1N1
• Deaths 500,000 U.S. ?50 million world
• 1957-8 ASIAN FLU H2N2
• Deaths 70,000 U.S.
• 1968-69 HONG KONG FLU H3N2 (progeny of this
  virus have drifted from year to year since
  then, causing epidemics) Deaths 34,000 U.S.
• Some threats since then Swine Flu, Russian Flu,
  Asian flu, but not followed by pandemic
• ALL PANDEMICS INVOLVED VIRUS COMBINING HUMAN AND
  AVIAN STRAINS

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Belshe, et al, NEJM, Dec 2005
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PANDEMIC PHASES

• Phase New type Animals Risk to Humans Spread
  Clusters Pan (Human) (New)
• 1 No /- Low
  0 0 0
• 2 No
  0 0 0
• 3 Yes
  Rare 0 Alert Avian
  Flu is at phase 2-3 with rare spread
• 4 Yes
  Limited Small 0
• 5 Yes
  Localized Large 0
• 6 Yes
  Unlimited Large Yes Sustained
  transmission in population

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DIAGNOSIS,PREVENTION AND TREATMENT

• Vaccine Prophylaxis
• Will be covered by next speaker
• Diagnosis, surveillance and other public health
  measures will be covered by other speakers in
  this conference

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ANTIVIRAL THERAPY

• TWO CLASSES OF DRUGS Inhibitor of viral
  proteins (amantadines) Inhibitor of
  neuraminidase osteltamivir (Tamiflu),
  zanamivir inhaled(Relenza)
• PREVENTIVE USE Evidence for efficacy in
  preventing disease Dosage same as for
  treatment
• USE IN TREATMENT
• Must be started early ineffective later
• Tamiflu prevented disease in 11 in
  Turkey given within 48 hrs several
  persons died treated later than that.
• Drug resistance reported for amantadines in
  2006 epidemic in US
• Some isolates H5N1
  avian resistant to Tamiflu

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ANIMAL HOSTS TRANSMISSION for avian
influenza

• H5N1 in migratory birds - domestic fowl- pigs
  a few humans thus far
• Cats (domestic and wild), marten, other mammals
  infected
• More than 200,000,000 birds
• destroyed
• Ducks can be infected, excrete virus, and not get
  sick

(Marten)
(?)
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This painting of a folk scene by Mian
Situ illustrates the close affinity between
families and fowl In certain cultures. One of
the mysteries in The current outbreak is why
transmission is more frequent in rural and
para-urban areas. Also, why are families like
this one more prone to infection than commercial
workers with fowl and others who contact fowl in
non-family settings?.
The Grandson by Mian Situ (Trailside Galleries)
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MODES OF TRANMISSION

• BIRDS TO HUMANS Direct Contact (slaughter,
  defeathering, preparation for food, feces
  exposure, ?swimming in contaminated water, ? use
  of fecal fertilizers)
• Fomite spread -(shoes, clothing
  etc)
• Religious and cult practices (drinking blood,
  kissing beaks)
• Unknown why commercial workers
  are not affected why is disease
• more common in rural areas, and
  why are outbreaks concentrated
• among healthy children and
  young adults? Bird smuggling exotic birds
  imported into European countries may have played
  a role in transmission?
• HUMAN TO HUMAN Inhalation of droplets
• Hand to nose more common than most think
  

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• 109
• (56)

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Avian Influenza now infects birds in China
Hong Kong Indonesia Cambodia Japan Laos
Myanmar Mongolia Thailand Vietnam Malaysia
Cameroon Niger Nigeria (?others) Albania
Austria Azerbaijan Bosnia Herzegovina Bulgaria
Croatia France Denmark Georgia Germany Greece
Hungary Italy Poland Romania Serbia Russia
Montenegro Slovak Slovenia Sweden Switzerland
Turkey Ukraine Egypt Iraq Iran Israel Jordan
Afghanistan India Kazakhstan Pakistan
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SOME EXPERTS PREDICT PANDEMIC AS INEVITABLE AND
DISASTROUS 7.5 TO 150,000,000 DEATHS
There are some skeptics
Tucson Region Weil combats bird flu 'paranoia'
By Carla McClain ARIZONA DAILY STAR
01.22.2006 Our anxiety over bird flu the fear
it might set off a worldwide pandemic is making
us sicker than the virus itself, says Tucson's
celebrity physician, Dr. Andrew Weil. Trying to
calm what he sees as rampant "paranoia" about
bird flu, Weil is using national media to stress
that the virus remains a threat almost
exclusively to birds
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HOW LIKELY A PANDEMIC?

• Current hemagglutinin of H5N1 does not attach
  well to nasal mucosal cells, but does attach to
  deep lung cells
• Implication is that unless there is a major
  change in H, there is less likelihood that it
  will transmit human to human, as that mode of
  transmission is dependent on nasal infection.
• However, all is speculative. Change in virus can
  occur with change in capacity for human target
  cells
• IN SHORT, WE SIMPLY DO NOT KNOW IF AND WHEN A
  PANDEMIC WILL OCCUR MOST EXPERTS BELIEVE IT IS
  INEVITABLE GIVEN PAST HISTORY

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PERSONAL ACTIONS
This brochure was prepared by the American
Council of Science and Health it offers common
sense advice for personal protection It has
been distributed with your syllabus today
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Presidents Plan
(If no pandemic occurs these initiatives are
vital for public health in US)

• 2.8 B cell culture
• 1.5 B buy flu vaccine
• 1 B stockpile antivirals
• 251 M detect contain global outbreaks
• 800 M new Rx vaccine research
• 644 M promote preparedness federal, state, local
  levels for response to outbreak

• Decrease litigation by providing liability for
  vaccine and drug manufacturers
• Will promote international cooperation for
  biosurveillance
• Encourage cooperation between all elements of the
  U.S. to prepare for and react to the potential
  epidemic

How much will Congress actually appropriate? Is
it enough?
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THE REMAINDER OF THE CONFERENCE WILL CONSIDER THE
FOLLOWING ISSUES
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SPECIFIC SCIENTIFIC ISSUES

• 297,000,000 US population
• Will there be enough -
• Personal protective equipment ?.. Vaccine
  (will it be the right one?)?... Antivirals
  (? Resistance of emerged virus)?
  Medical care?
• Essential community personnel?

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ETHICAL, LEGAL HUMANISSUES

• How to deal with hoarding during preparatory
  phase
• IF PANDEMIC OCCURS
• Whos in charge?
• What measures will work to contain? Legal basis
  for same?
• Who will manage isolation and quarantine? Who
  will enforce?
• Can the government force quarantine and
  isolation? Which government?
• Can health workers be forced to work?
• Can the FDA respond to need for rapid approval
  even if all evidence is not in?
• Will we have a vaccine? If yes, enough?
• Who gets it if doses are limited?
• Will antivirals work? (resistance to amantadines
  of H5N1)
• Will there be enough?
• Are businesses prepared?
• Are health care institutions prepared?
• What is the role of volunteers in the community?

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TO KEEP UP TO DATE GO TO www.cdc.gov
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OR WWW.WHO.ORG
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OR WWW.PANDEMICFLU.GOV
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SOME ADDITIONAL USEFUL SITES

• http//www.azdhs.gov/pandemicflu/pandemic_flu_plan
  .htm
• www.usaid.org
• www.nature.com/nature/focus/avianflu
• www.aasta.net/avianflu.htm