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ABSTRACT: For decades, public health officials have been concerned aboutthe reoccurrence of pandemic influenza. The worst documented pandemicoccurred in 1918-1919, killing an estimated 20-40 million peopleworldwide. Although influenza has not wreaked such havoc since then,there have been close calls -- most recently with the avian influenzastrain currently circulating in SE Asian poultry flocks. In themeantime, new threats have emerged. SARS has been the most widespread of these, and has carried a high human and economic toll where it hasstruck. Will one of these new diseases take the place of the dreadedinfluenza?
The New Flu? Pandemic Influenza, Avian Flu, and SARS
Amy D. Sullivan, Ph.D, MPH
Epidemiologist
Multnomah County Health Department
Then Now
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?
What Was So Striking…
Characteristic symptoms & outcomes
High global death tolls Large numbers of deaths
among healthy adults So completely ignored for so
long
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%
The Death Toll Global estimates
1920’s: ~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
Oct-Nov 1918(second wave)
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
Multnomah County Deaths
(3 month period; Total deaths ~20,200)
0
1000
2000
3000
4000
5000
6000
Under 5 years5 to 9 years
10 to 14 years15 to 19 years20 to 24 years25 to 34 years35 to 44 years45 to 54 years55 to 59 years60 to 64 years65 to 74 years75 to 84 years
85 years and over
Age Group
Number of Deaths
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…
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
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)
The Segmented Genome At Work
Genome segments can exist inside host cell “naked & free”
Role of HA in cell infection
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
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
“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
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?
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
Droplet vs. Aerosolized Spread
Droplet transmission Respiratory secretions >5m Fall out of air quickly with ~3 feet Easier to protect against?
Aerosolized transmission Respiratory secretions <5m Can stay airborne for hours
Both can occur for any one disease
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
“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)
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
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
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
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
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
Severe Acute Respiratory Syndrome
(SARS) Pneumonia caused by a coronavirus
Fatal pneumonia Fever (>100.4 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
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
Where Is SARS From Don’t know for sure In Guangdong Province market
Identified in exotic animals sold for food
Seropositive asymptomatic individuals among sellers
Circulating before this outbreak?
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
Amoy Gardens,
Hong Kong
Aerosolized virus from improperly ventilated U-traps spread up outside ventilation shaft in an apartment building
SARS Cases Reported to WHO as of June 13, 2003 8,445 cases; 790 deaths
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
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
Discuss
Is another event like pandemic flu inevitable?