Avian Influenza

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Avian Influenza

• Elvin Adams, MD, MPH, FACPM
• Medical Director/Health Authority
• Tarrant County Public Health
• March 21, 2005

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Flu virus basics

• Birds are the primary host for flu viruses.
• There are a wide variety of avian flu viruses.
• Identified by H (hemagglutinin H1-H15) and N
  (neuraminidase N1-N9) proteins.
• Most avian flu viruses dont cause symptoms in
  humans.
• High and Low Pathogenic Strains of each type of
  flu virus.

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Species Affected
Genetic Reservoirs
H3, H7
H1, H2, H3
Intermixing
H5N1
Commercial, LBMs Others
H10
H1-12 H14-15
H1-2, 4-7, H9-13, 15-16
Other Aquatic Birds?
H1, H3, H4, H7, H13
H1, H3
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Human Influenza Pandemics
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Annual Endemic Flu (H3N2) in the United States
each Year Causes

• 36,000 deaths and
• 114,000 hospitalizations

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Virus Evolution

• Genetic Drift. Slow continuous changes.
• Genetic Shift. Appearance of new H and N
  surface proteins.
• Genetic Reassortment Mixing of genetic
  material from two different viruses. Often in
  one coinfected host.

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Pandemic Flu is Different

• Appears suddenly.
• No one has immunity.
• Spreads globally in a short time.
• Secondary waves may occur.
• May be mild or severe.

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Pandemic Flu is more Deadly

• First, the global population is larger and
  increasingly urbanized, allowing viruses to be
  transmitted within populations more easily.
  
  
• Second, levels of international travel are much
  greater than in the past, allowing viruses to
  spread globally more quickly than in the past.
  
  
• Third, populations in many countries consist of
  increasing numbers of elderly persons and those
  with chronic medical conditions, thus increasing
  the potential for more complicated illnesses and
  deaths to occur.

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WHO Pandemic PhasesInterpandemic Period
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WHO Pandemic PhasesPandemic Alert Period
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WHO Pandemic PhasesPandemic Period
Post Pandemic Period
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Clinical Features of Avian Influenza

• Persistent fever, lymphopenia
• Severe pneumonia or ARDS
• unusual presentations possible
• GI symptoms abdominal pain, diarrhea
• Exposure to sick poultry
• Exposure to affected areas or persons
• Clustering may indicate a public health emergency

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Influenza A H5N1 Replication Sites in Humans

• Mongkol Uiprasertkul et.al.
• Mahidol University, Bangkok, Thailand and
• University of Hong Kong, China.
• Emerging Infectious Diseases Vol 11, No. 7,
• July 2005

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Subject

• 6 year old boy
• Viral pneumonia
• ARDS and Death 17 days after onset
• H5N1 diagnosed on day 7
• Oseltamivir started on day 15
• Methylprednisone started on day 15
• CSF-GM from day 5-10

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Tissue Analysis

• Standard autopsy
• Routine histological analysis
• H5N1 Viral detection by antigen, culture and
  RT-PCR
• Immuno-histochemical analysis.
• Cytokine expression TNF-a, IFN-g, IL-6
• Analysis was done organ by organ

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Lung Damage

• Interstitial pneumonia
• Proliferative phase of diffuse alveolar damage
• Bronchiolitis
• Reactive hyperplasia of pneumocytes without
  virus-associated cytopathic changes

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Where Was H5N1 Found?

• Lung and strand RNA
• Small bowel and strand RNA
• Large bowel and strand RNA
• Spleen only strand RNA
• ( strand RNA serves as mRNA for virus so little
  or no replication occurs in the spleen)

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Where was H5N1 NOT Found?

• Adrenal glands
• Brain
• Bone Marrow
• Kidneys
• Liver
• Pancreas
• Plasma

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H5N1 in the Lung

• Virus antigen was found in the nuclei of
  alveoli-lining cells (type II pneumocytes)
  (confirmed by staining for intracytoplasmic
  surfactant and for viral antigen)
• No virus in the trachea (columnar cells)
• No virus in bronchioles (columnar cells)

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H1, H3 vs. H5

• No GI involvement
• Less diarrhea
• Stool isolation neg
• Infects upper airway
• Nasal swab positive
• Sputum variable

• GI replication
• More diarrhea
• Stool isolation pos
• Infects lower airway
• Nasal swab negative
• Sputum virus positive

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Lymphopenia Predicts Mortality
Chotpitayasunondh et al. EID 200511201
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Avian FluHuman Cases (Deaths)

• 2003 3 (3)
• 2004 46 (32)
• 2005 95 (41)
• 2006 40 (27)
• TOTAL 184 (103) 3/21/06

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How Deadly is H5N1?(What is the Denominator?)

• Anna Thorson, Karolinska Institute reported Jan
  9, 2006 a study in Vietnam.
• Surveyed 45,478 random people
• 18 had recent flu-like illness and 25 of this
  group had contact with sick or dead poultry.
• Probably there were 650-750 cases of bird flu
  that was mild and undiagnosed. (2.5)
• Vietnam reports 61 cases 19 deaths. (31)

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Containing Pandemic Influenza

• In developing countries a rural outbreak may not
  be detected for a long time.
• Lab capability for rapid diagnosis is needed.
• Anti viral stockpiles are needed.
• Contacts need prophylactic antiviral agents
• Quarantine may be effective
• Speed in detecting cases and responding is
  critical to containing a pandemic.

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Tarrant County Role in Pandemic Control Measures

• Limit travel
• Limit public gatherings
• Close schools
• Close businesses
• Close large shopping centers

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Response Stage 1 No Vaccine Available

• Interventions will be limited to measures to
  decrease the spread of infection (such as
  quarantine, closing schools, canceling public
  events, infection control in hospitals and
  long-term care facilities).
• Distribution of drugs for prophylaxis and
  treatment.

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Treatment Options

• A vaccine would be effective but would take 6-8
  months to produce.
• Amantadine and rimantadine are helpful in
  preventing the flu.
• Oseltamivir (Tamiflu) is effective in treating
  this flu if started within 48 hours.
• Avoiding exposure strategies.

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Prophylaxis

• All persons who live or work in institutions
  caring for people at high risk of serious
  complications of influenza infection should be
  given antiviral medications in the event of an
  institutional outbreak.
• Amantadine or rimantadine are used for
  chemoprophylaxis.

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Treatment

• Oseltamivir or zanamivir for treatment.
• Any person experiencing a potentially
  life-threatening influenza-related illness should
  be treated with antiviral medications.
• Any person at high risk for serious complications
  of influenza and who is within the first 2 days
  of illness onset should be treated with antiviral
  medications.

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Response Stage 2 Limited Vaccine Supply

• Priority groups for vaccination will need to be
  identified.
• Plans for rapid, efficient, and equitable
  distribution of vaccine will need to be
  formulated.
• Vaccine effectiveness and safety need to be
  monitored.

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Priority Groups

• Persons 65 and older
• Children under the age of 2
• Nursing home residents
• Dialysis centers
• Assisted living centers
• First responders
• Hospital staff
• Private health care providers
• Home health agencies

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Response Stage 3 Adequate Vaccine Supply

• Shift from targeted vaccination of priority
  groups to widespread vaccination.
• Public sector vaccination clinics and private
  sector providers.
• Identify potential barriers to vaccination of
  racial and ethnic minority populations

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PREVENTION of FLU Good Health Habits that
Prevent the Flu

• Avoid close contact with people who are sick.
• Stay home when you are sick.
• Cover your mouth and nose when coughing.
• Clean your hands.
• Avoid touching your eyes, nose or mouth.

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How Will this Unfold?

• A pandemic strain develops somewhere.
• Rural epidemic spreads to cities.
• Containment strategies are instituted.
• Vaccine development begins.
• U.S. ports of entry are monitored.
• Spread to U.S. cities delayed by several weeks or
  months.
• Prevention and treatment resources are funneled
  to U.S. outbreak areas.

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Medical care during an influenza pandemic

• Surge capacity of the hospital system is limited.
  
• Primary treatment at home.
• Challenges
• Magnitude and duration
• Staff shortages
• Limited ability to call in external resources

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Avian Flu Time Line

• 1996 China
• 1997 Hong Kong
• 2003 Dec South Korea (Free)
• 2004 Jan Vietnam
• 2004 Jan Cambodia
• 2004 Jan Japan (Free)
• 2004 Jan Laos

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Avian Flu Time Line

• 2004 Feb Indonesia
• 2004 Aug Malaysia (Free)
• 2005 Jan Thailand
• 2005 July Russia, Siberia
• 2005 Aug Kazakhstan
• 2005 Aug Tibet
• 2005 Aug Mongolia

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Avian Flu Time Line

• 2005 Oct Romania
• 2005 Oct Croatia
• 2005 Oct Turkey
• 2005 Dec Ukraine
• 2006 Jan Iraq
• 2006 Jan Iran
• 2006 Jan 29 Cyprus

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Avian Flu Time Line

• 2006 Feb 8 Nigeria (Africa)
• 2006 Feb 10 Azerbaijan
• 2006 Feb 11 Greece
• 2006 Feb 11 Bulgaria
• 2006 Feb 12 Italy
• 2006 Feb 12 Slovenia
• 2006 Feb 14 Slovakia

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Avian Flu Time Line

• 2006 Feb 12 Austria
• 2006 Feb 14 Germany
• 2006 Feb 18 France
• 2006 Feb 20 Kenya (Africa)
• 2006 Feb 24 Egypt (Africa)
• 2006 Feb 24 Hungary
• 2006 Feb 28 Ethiopian (Africa)

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Avian Flu Time Line

• 2006 Feb 28 Niger, Africa
• 2006 Feb 28 Pakistan
• 2006 Feb 28 Sweden
• 2006 March Denmark
• 2006 March Portugal
• 2006 March Cameroon
• 2006 March Israel

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Sentinel Swans
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Sentinel Swans
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Sentinel Swans
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PREVENTION of FLU Good Health Habits that
Prevent the Flu

• Avoid close contact with people who are sick.
• Stay home when you are sick.
• Cover your mouth and nose with tissue when
  coughing or sneezing.
• Clean your hands with soap and water or a
  sanitizer.
• Avoid touching your eyes, nose or mouth.

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THE END