The New Flu? Avian Flu, SARS and Other Emerging Respiratory Illnesses

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ABSTRACT For decades, public health officials
have been concerned about the reoccurrence of
pandemic influenza. The worst documented
pandemic occurred in 1918-1919, killing an
estimated 20-40 million people worldwide.
Although influenza has not wreaked such havoc
since then, there have been close calls -- most
recently with the avian influenza strain
currently circulating in SE Asian poultry flocks.
In the meantime, new threats have emerged. SARS
has been the most widespread of these, and has
carried a high human and economic toll where it
has struck. Will one of these new diseases take
the place of the dreaded influenza?
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The New Flu? Pandemic Influenza, Avian Flu, and
SARS

• Amy D. Sullivan, Ph.D, MPH
• Epidemiologist
• Multnomah County Health Department

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Then
Now
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Topics for This Evening

• Review the Pandemic Flu of 1918-1919
• Was it really that bad? (Hint Yes)
• How could it have happened?
• Subsequent threats
• Avian flu
• SARS
• Discuss Is another event like pandemic flu
  inevitable?

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What Was So Striking

• Characteristic symptoms outcomes
• High global death tolls
• Large numbers of deaths among healthy adults
• So completely ignored for so long

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Characteristic Symptoms and Outcomes

• dusky heliotrope cyanosis of the face, lips,
  and ears and purulent bronchitis with
  bronchopneumonia (Oxford, 2001)
• Case fatality proportion 25-50

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The Death Toll

• Global estimates
• 1920s 21.5 million dead
• India alone 18 million
• 1998 conference 50-100 million
• Varied greatly by country region
• Europe N. America 3-20 deaths/1,000
• Africa 20-445 deaths/1,000 people
• Asia/Pacific 3-220 deaths/1,000 people

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Oct-Nov 1918 (second wave)
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Deaths Among Healthy Adults

• Influenza deaths usually among youngest oldest
• Rates during 1918
• Infants over 40 2-10-fold higher
• 10-20 yrs old 20-100-fold higher
• 20-30 yrs old 20-180-fold higher

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Multnomah County Deaths (3 month period Total
deaths 20,200)
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Was Pandemic Flu Really That Bad?

• Yes
• In thinking about the potential of Avian flu (or
  other emerging respiratory illnesses) to wreak
  havoc, useful to understand

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How Could Such a Catastrophic Event Occur?

• Biologic factors
• Segmented genome of the influenza virus
• Unique to influenza viruses?
• Epidemiologic Factors
• Route of transmission
• Population movements/migrations
• Seeding the population

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The Influenza A Virus

• Typically spherical
• 50-120 nm diameter
• Single-stranded RNA virus
• Genome in 8 segments
• Encode key surface glycoproteins
• Haemagglutinin (HA)
• Neuraminidase (NA)

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The Segmented Genome At Work
Role of HA in cell infection
Genome segments can exist inside host cell naked
free
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Flu Haemaglutinin

• 15 subtypes identified allow for
• Variability in human infection
• H1, H2, H3 pandemic potential
• H5 poor human-human spread
• H7 birds not humans
• Different possible host species
• H1 birds, pigs, people
• H5 birds people

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Shift vs. Drift

• Influenza viruses change regularly
• Usually antigenic drift
• Normal mutations
• Changes in surface glycoprotiens but can
  cross-react with existing immunity
• Sometimes antigenic shift
• Segments can rearrange when co-infecting same
  cell
• Reassortments by very different strains can
  profoundly change ability to recognize

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Spanish Flu Antigenic Shift

• H1N1 subtype of Influenza A
• H1 from an antigenic shift
• Avian origin? Avian via swine?
• Poor population-level immunity key in devastation
  
• Virulence factors not ruled out

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Influenza Virulence

• Infects respiratory tract epithelial cells
• Ciliated serous not basal
• Upper respiratory infection less severe then
  infection in lungs
• Mutation(s) affecting speed or invasiveness of
  infection?
• Affect mortality
• And transmission?

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Infection Transmission

• 15-60 of infected people develop symptoms
• Incubation period 1-3 days
• Infectious period 3-7 days after symptom onset
• Symptomatic most likely to transmit
• Mode of transmission
• Fomite possible
• Droplet or aerosol

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Droplet vs. Aerosolized Spread

• Droplet transmission
• Respiratory secretions gt5mm
• Fall out of air quickly with 3 feet
• Easier to protect against?
• Aerosolized transmission
• Respiratory secretions lt5mm
• Can stay airborne for hours
• Both can occur for any one disease

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Population Mixing an the Spread of Spanish Flu

• 1918-19 a time of great social upheaval
• 1914 Great Britain declares war on Germany
• 1917 U.S. joins WWI
• 1918 U.S. troops arriving in Europe Armistice
  signed at end of year
• 1919 Armies head home
• Airplanes not a factor, but huge movements of
  people in the world

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Seeding the Population

• First appearance in 1918?
• First described in Fort Riley, Kansas in March
  1918
• near simultaneous appearance of flu in
  March-April 1918 in North America, Europe, and
  Asia (Taubenberger, 2001)
• Pandemic flu strain likely existed before 1918
  (but not for long)

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Etaples, France. 1916

• WWI British Army base
• Crowded conditions animals people
• People from all over the Empire
• Outbreak of Purulent Bronchitis
• Dec 1916 thru spring 1917
• Case fatality 45
• Bacillus influenza (a.k.a. Haemophilis influenza)
  in 18 of 20 cases
• Earliest documented report

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How Could Such a Catastrophic Event Occur?

• Biologic factors
• High infectivity with novel look
  (immunologically)
• Analogous to zoonotic disease but better adapted
• Epidemiologic Factors
• Droplet aerosolized transmission
• Occurred at a time of global migration
• Was able to seed itself around the globe

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Avian Influenza H5N1

• Hong Kong, 1997
• 18 people hospitalized 6 die
• Hundreds likely ill
• Young adults affected
• Infection directly from chickens
• Most avian flu viruses do not directly infect
  humans
• No person-to-person transmission

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Avian Flu in 2003-4

• December 2003 H5N1 avian flu identified in
  Vietnam
• By March 10th, 2004
• 33 cases with 22 deaths in Vietnam and Thailand
• Infected birds in 8 Asian countries
• Cambodia, China, Indonesia, Japan, Laos, South
  Korea, Thailand, and Vietnam
• Investigation of person-person transmission in
  Vietnam case

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Could a Catastrophic Event Occur?

• Biologic factors
• High infectivity with novel look
  (immunologically)
• Epidemiologic Factors
• Droplet aerosolized transmission Rare for
  person-to-person
• Occurred at a time of global migration
• Was able to seed itself around the globe - NO

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Severe Acute Respiratory Syndrome (SARS)

• Pneumonia caused by a coronavirus
• Fatal pneumonia
• Fever (gt100.4 F or 38 C) Dry cough, shortness of
  breath, difficulty breathing
• Tx Supportive therapy only
• Incubation period, 6 days
• Case fatality proportion, 5-15
• Much higher in persons over 60 years

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Discovering SARS

• First recognized in Viet Nam, February 2003
• Businessman traveled from Guangdong
• Hospital outbreak among persons exposed to him
• Occurred in Guangdong Province as early as
  November 2002

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Where Is SARS From

• Dont know for sure
• In Guangdong Province market
• Identified in exotic animals sold for food
• Seropositive asymptomatic individuals among
  sellers
• Circulating before this outbreak?

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How is SARS Spread?

• Droplet?
• Close contact appears important
• Household contacts
• Healthcare workers
• But many unanswered questions
• Aerosol pattern in some cases
• Superspreaders
• Still unsure about
• Fomite transmission
• Asymptomatic transmission

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Amoy Gardens, Hong Kong

• Aerosolized virus from improperly ventilated
  U-traps spread up outside ventilation shaft in an
  apartment building

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SARS Cases Reported to WHO as of June 13, 2003
8,445 cases 790 deaths
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Current SARS Situation

• Chinese outbreak from apparent infection in a
  research lab
• 8 cases (confirmed and suspected)
• All cases epidemiologically linked
• 1,000 contacts under surveillance
• 640 in Beijing 353 in Anhui Provence
• Virology Institute closed

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Could a Catastrophic Event Occur?

• Biologic factors
• High infectivity with novel look
  (immunologically)
• Epidemiologic Factors
• Droplet aerosolized transmission Rare for
  person-to-person
• Occurred at a time of global migration
• Was able to seed itself around the globe - NO

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Discuss

• Is another event like pandemic flu inevitable?