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?