Avian Influenza Should We be Scared!!

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Avian InfluenzaShould We be Scared!!

• Hail M. Al-Abdely, MD
• Consultant, Infectious Diseases
• King Faisal Specialist Hospital and Research
  Center

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November 30, 2004W.H.O. Official Says Deadly
Pandemic Is Likely if the Asian Bird Flu Spreads
Among People By KEITH BRADSHER and LAWRENCE K.
ALTMAN HONG KONG, Nov 29 - A pandemic of human
influenza could kill up to 100 million people
around the world in a worst case, a World Health
Organization official said Monday, significantly
raising the agency's earlier estimates of the
potential number of deaths in such a catastrophe.
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The 1918 Spanish flu pandemic
                                                                        
National Museum of Health and Medicine, Armed
Forces Institute of Pathology
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INFLUENZA History

• Epidemics and pandemics
• Most well known pandemic 1918-1919
• 40-50 million deaths worldwide
• Subsequent pandemics
• 1957 Asian flu
• 1968 Hong Kong flu
• 1977 Russian flu
• 1.5 million deaths
• Economic impact estimated at 32 billion dollars

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Images from the 1918 Influenza Epidemic
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Infectious Disease Mortality, United States--20th
Century
Armstrong, et al. JAMA 199928161-66.
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Americas deaths from influenza and major wars
Thousands
Civil WWI 1918-19 WWII
Korean Vietnam War
Influenza War War

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Spread of H2N2 Influenza in 1957Asian Flu
Worldwide Spread in 6 Months
Feb-Mar 1957Apr-May 1957Jun-Jul-Aug 1957
69,800 deaths (U.S.)
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The world has changed

• Global population in 19th century
• was lt1 billion vs. 6 billion today
• Intercontinental travel is in hours rather than
  months and in millions rather than hundreds
• Human crowding has increased
• Population health has improved
• Animal husbandry has changed
• Interdependence has increased

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Whats needed for a pandemic strain?

• Novel virus (little to no immunity)
• Capable of causing disease in humans
• Highly pathogenic / virulent
• Capable of sustained person to person transmission

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World Health Organization Phases of an Influenza
Pandemic
Phase Definition
1 Inter-pandemic Period No new flu subtypes in humans Possibly present in animals Risk to humans is low.
2 Inter-pandemic Period No new flu subtypes in humans A circulating animal flu subtype poses a substantial risk of human disease.
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World Health Organization Phases of an Influenza
Pandemic
Phase Definition
3 Pandemic Alert Period Human infections with a new subtype, No human-to-human spread, or rare instances of spread to a close contact.
4 Pandemic Alert Period Small clusters, limited human-to-human transmission Spread is highly localized Virus is not well adapted to humans.
5 Pandemic Alert Period Larger clusters but human-to-human spread still localized Virus becoming better adapted to humans
6 Pandemic Period Increased and sustained transmission in general population.
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The Organism
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Influenza Virus

• Family Orthomyxoviridae
• Three main types
• Type A
• Multiple species
• Type B
• Humans
• Type C
• Humans and swine

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Influenza A

• Multiple species
• Humans
• Avian Influenza
• Most virulent group
• Classification by surface antigensinto subtypes
• Hemagglutinin (H or HA)
• Neuraminidase (N or NA)

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Surface Antigens and Subtypes

• 15 HA and 9 NA for influenza A
• All in aquatic birds
• Hemagglutinin (HA)
• Function Sites for attachment to infect host
  cells
• Neuraminidase (NA)
• Function Remove neuraminic acid from mucin and
  release from cell

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Influenza A
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Influenza B

• Mostly humans
• Common
• Less severe than A
• Epidemics occur less often than A

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Influenza C

• Humans and swine
• Different pattern of surface proteins
• Rare
• Mild to no symptoms
• By age 15, most have antibodies

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Avian Influenza

• Pathogenicity based on genetic features and/or
  severity of disease in poultry
• Low pathogenic AI (LPAI)
• H1 to H15 subtypes
• Highly pathogenic AI (HPAI)
• Some H5 or H7 subtypes
• LPAI H5 or H7 subtypes can mutate into HPAI

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Epidemiology
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Economic Impact

• Direct losses
• Depopulation and disposal
• High morbidity and mortality
• Quarantine and surveillance

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Economic Impact

• 1997 Hong Kong outbreak (H5N1)
• 13 million for depopulation and indemnities
• 1.4 million birds
• 2001 Hong Kong
• outbreak (H5N1)
• 1.2 million birds
• 3.8 million

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Economic Impact

• 2003 European outbreak (H7N7)
• Over 33 million birds destroyed
• ¼ of Netherlands poultry stock
• Cost?
• 2003-2004 SE Asia (H5N1)
• 8 countries
• gt100 million birds destroyed
• Cost?
• 2004-2005 SE Asia and Eurasia
• Spread to Eurasia by migratory birds

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Geographic Distribution

• Worldwide distribution
• Reservoir
• Free flying aquatic birds Ducks, geese,
  shorebirds
• Recent outbreaks
• The Netherlands, Australia, Mexico, U.S., SE
  Asia, Eurasia
• Similarity to avian diseases makes actual
  distribution difficult to define
• Altered avian ecosystems have created new niche
  for AI viruses

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Morbidity/Mortality in Animals

• Approaches 100in commercialpoultry flocks
• Deaths within 2 to 12 days after first signs of
  illness
• Survivors inpoor condition

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Transmission
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Animal Transmission

• Initial source of infection
• Other poultry, migratory waterfowl, pet birds
• Spread by aerosol, shared drinking water, fomites
• Virus in respiratory secretions and feces
• Virus present in eggs but eggs unlikely to
  survive and hatch

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Diagnosis

• Suspect with
• Sudden death
• Drop in egg production
• Facial edema, cyanotic combs and wattles
• Petechial hemorrhages
• Virology and serology necessary for definitive
  diagnoses

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Diagnosis

• Laboratory Tests
• HP AI is usually diagnosed by virus isolation
• Presence of virus confirmed by
• AGID
• ELISA
• RT-PCR
• Serology may be helpful

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Human Transmission
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Human Transmission

• Previously considered non-pathogenic for humans
• 1997, Hong Kong
• 18 humans infected, 6 died
• H5N1 virus linked to outbreak in live bird
  market and area farms
• 2003, the Netherlands
• 83 confirmed cases in humans, 1 death
• H7N7 strain

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Human Transmission

• 2004-2005, SE Asia
• 130 cases, 67 deaths
• Indonesia, Viet Nam, Thailand, Cambodia
• H5N1 strain
• Within the vicinity of poultry outbreaks
• ?Evidence for human-to-human transmission
• Role of swine
• Proposed mixing vessel

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Cases of Avian influenza in people
Year Strain Country Number of confirmed human cases Number of confirmed human deaths
1997 A/H5N1 Hong Kong 18 6
1999 A/H9N2 Hong Kong 2 0
2003 A/H5N1 Hong Kong 2 1
2003 A/H7N3 Canada 2 0
2003 A/H7N7 Netherlands 84 1
2003 A/H9N2 Hong Kong 1 0
2003-2005 A/H5N1 Viet Nam, Cambodia, Indonesia and Thailand 130 67
Data up to 17 November 2005
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INFLUENZA Versatility

• Amazing ability to change
• Antigenic Drift (A and B)
• Comparatively minor antigenic change
• Point mutations accumulated during virus
  replication
• Why we need a new vaccine each year
• Causes epidemics a higher than normal level in
  the population, usually much higher than endemic,
  and usually short-term
• Antigenic Shift (A only)
• Major antigenic change
• Hybrid virus emerges when cell infected with two
  different influenza viruses
• Human, avian, swine, equine
• Novel strain, little immunity, epidemic spreading
  between continents
• Caused pandemics in 1918, 1957, 1968, and ?

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Genesis of New Human Influenza Viruses
15 HAs 9 NAs
Non-human virus
Human virus
Reassortant virus
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Clinical Signs in Humans

• 1997 Hong Kong (H5N1)
• Fever, respiratory, vomiting, diarrhea, pain
• Fatal cases severe bilateral pneumonia, liver
  dysfunction, renal failure, septic shock

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Clinical Signs in Humans

• 2003 Netherlands (H7N7)
• Conjunctivitis
• Mild influenza or respiratory symptoms
• Fatal case acute respiratory distress syndrome
• 2004-2005 S.E. Asia, EurAsia

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AVIAN INFLUENZA PREVENTION AND TREATMENT
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Public Health Significance

• Risk is low
• Strains vary in ability to infect humans
• High occupational exposure may increase risk
• 2003 83 cases
• Human infections from non-compliance with
  personal biosafety measures
• ?Evidence of human-to-human transmission
• 2004-2005 130 cases

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Prevention

• Import restrictions
• Surveillance
• Appropriate biosecurity
• Control human traffic
• Introduction of new birds into flock
• Education of the poultry industry
• Prompt response to outbreaks

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Influenza control

• Education to encourage prompt self-diagnosis
• Public health information (risks, risk avoidance,
  advice on universal hygiene behavior)
• Hand hygiene
• Face masks for symptomatic persons
• School closures (?)
• Deferring travel to involved areas

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Avian Influenza Vaccine

• Traditional killed vaccines are effective
• Vaccines will protect only against other avian
  influenza viruses withthe same hemagglutinin (H)
  type.

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INFLUENZA PREVENTION (contd)

• INACTIVATED INFLUENZA VACCINE
• WHO convenes meeting to determine vaccine
  composition (Feb Northern Hemisphere Sept
  Southern)

SourceWHO
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Vaccine Development
Jan
Feb
Mar
Apr
May
Jun
Jul
Aug
Sep
Oct
Nov
Dec
WHO/CDC)
WHO/CDC/FDA
CDC/FDA
FDA
FDA
FDA
manufacturers
clinic
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Pandemic Vaccine

• Annual vaccine is trivalent (3 strains), pandemic
  vaccine will be monovalent.
• Production using current technologies would
  likely take 4-5 months ? may not be available
  before 1st pandemic wave
• There will be vaccine shortages initially
• 2 doses may be necessary to ensure immunity

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Treatment Prevention Antiviral Drugs

• Antiviral agents
• Effective in preventing human influenza
• Can prevent severe complications
• May not be effective against pandemic virus
• Supplies will be limited
• Establish priority groups for use of available
  drug
• Treatment over prevention

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Pandemic Preparedness

• Strengthening virus surveillanceto detect novel
  strains and monitor impact
• Research to enhance vaccine production / supply /
  delivery systems
• Enhancing Antiviral Supply and setting priorities
  for its use
• Strengthening annual vaccination programs
• Assuring an adequate alert system

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THE NEXT PANDEMIC?

• Potential impact of next pandemic (CDC)
• 2-7.4 million deaths globally
• In high income countries
• 134-233 million outpatient visits
• 1.5-5.2 million hospitalizations
• 25 increase demand for ICU beds, ventilators,
  etc.

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The Next Pandemic Where When?

• It is not possible to predict precisely where or
• when the next pandemic will emerge, but
• I think what were concerned about is looking
• at whats going on in Asia right now with avian
• flu, and a very big worry is that this is a time
• bomb ticking.
• Dr. Julie L. Gerberding, Director, Centers for
  Disease Control and Prevention
• We may be at almost the last stage before the
• pandemic virus may emerge.
• Dr. Jai P. Narain, World Health Organization,
  9/9/05