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1976 Swine Flu Vaccine
Debacle and U.S.
Vaccine Strategy for
Avian Flu: History
Repeating Itself?
Jacqueline Doamekpor
Advisor: Jonathon Erlen, Ph.D.
Presentation Outline
I.
II.
III.
IV.
V.
VI.
Research Objectives and Methodology
General Information about Influenza
Viruses, Vaccines, and Disease
Terminology
Profile of Swine Flu Vaccine Program of
1976
Mistakes of Swine Flu Program/Lessons
learned
Profile of Avian Influenza Outbreak/U.S.
Vaccine Strategy for Avian Influenza
Potential Obstacles in my Project
Research Project Objectives
1. Thoroughly research background information on
President Ford’s swine flu vaccine program and current
Avian flu outbreak/U.S. vaccine strategy for avian flu
2. Identify reasons why the swine flu vaccination program
failed
3. Compare and contrast the vaccine strategies for 1976
swine flu and avian flu to see whether the poor decisionmaking elements which led to the failure of 1976 vaccine
program are also present in the U.S. government’s (CDC
and HHS) mobilization of current vaccination strategies
against avian flu
Research Methodology
 Objective 1 and 2: Obtain thorough
background info by using journal articles
(etc. JAMA, WHO, CDC), books,
newspapers, videos, primary sources
 Objective 3: Research/Develop criteria
for evaluating effectiveness of vaccine
programs

Evaluate swine flu vaccine program and
US vaccine program
Why Should I Care?
1. Understanding the failure of the swine flu vaccine
program and applying the lessons learned from the
situation to management of the avian flu threat are critical
if the U.S. wants to have an effective avian flu
vaccination strategy
2. A form of the H5N1 virus which is transmissible from
human to human could be devastating to the U.S. if there
is no effective vaccine strategy in place (CDC)
3. If the U.S. government wants to protect its citizens
against avian flu without wasting millions of dollars, it
must avoid committing the errors associated with the
swine flu vaccine strategy
General Info about Influenza
Viruses: Types

There are three types of influenza viruses: A, B, and C:

Type A = main focus of research

Widely considered the most dangerous type because of its ability to infect a
wide variety of mammals and birds
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Birds are only infected with type A
Causes the most cases of the flu in humans and is the type most likely to
become epidemic
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Type B
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Infects humans and birds
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Produces a milder disease than type A, but can also cause epidemics

Type C
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Infects only humans
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Produces either a very mild illness indistinguishable from a common cold or
no symptoms at all

Does not cause epidemics
Influenza A Viruses:
Subtypes/Strains
 Subtypes of influenza type A
viruses (e.g. swine flu and
avian flu) are named
according to two specific
surface proteins:
hemagglutinin (HA) and
neuraminidase (NA)


Hemagglutinin allows the
virus to “stick” to a cell
and initiate infection
Neuraminidase helps
newly constructed viruses
exit host cell
 Subtypes could also named
by geographical region
Avian Flu Virus
(www.rkm.com.au/.../ VIRUS-FLU-structure-L-500.jpg)
Influenza A Viruses:
Subtypes/Strains (cont.)
 Currently, 16 known variants of HA
protein and 9 known variants of NA
protein
 Swine flu virus = H1N1 New Jersey
strain

Variant 1 HA and variant 1 NA
 Avian flu virus = H5N1

Variant 5 HA and variant 1 NA
Disease Terminology
 Endemic = “native to,” infection that can be
maintained in a certain population without
external input
 Epidemic = occurrence of disease within a
specific geographical area or population that is
in excess of what is normally expected
(example with chicken pox)
 Pandemic = an epidemic which spreads
worldwide, or over a large region (e.g. bubonic
plague, Spanish flu)
How Vaccines Prevent
Disease
 Vaccines contain weakened or killed viruses or bacteria specific
to the disease that is to be prevented

Sometimes live pathogens for stronger immune response
 Vaccines help your body recognize and fight these germs and
protect you each time you come in contact with someone who is
sick with any of these diseases
 First: Vaccine usually given by a shot
 Next: Over the next few weeks, the body makes antibodies
and memory cells against the weakened or dead pathogens in
the vaccine
 Then: The antibodies can fight the real pathogens if the person
is exposed to the germs and they invade the body

The antibodies will help destroy the germs and the person will
not become ill
 Finally: Antibodies and memory cells stay on guard in the body
for years after vaccination
Antivirals

Four antiviral medications have been approved by the U.S. Food and Drug Administration (FDA)
for treatment of influenza:
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Benefits of antivirals

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Antivirals can reduce influenza symptoms and may shorten duration of illness by 1 or 2 days
Makes people less contagious
Antivirals should be taken within 2 days after symptoms emerge to be effective
Setbacks
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Amantadine
Rimantadine
Zanamavir
Oseltamivir (commercially known as Tamiflu)
All must be prescribed by doctor and taken for 3-5 consecutive days
Four antiviral medications are effective only against influenza viruses
Influenza strains can become resistant to these drugs, and drugs may not always be effective
They will not help symptoms associated with the common cold or many other influenza-like illnesses caused
by viruses that circulate in the winter
Antiviral use during flu epidemic

Public health practice is to combine the use of influenza vaccine and antiviral medications

E.g. If outbreak at nursing home, residents and staff are vaccinated and also given antiviral
medications to prevent influenza until the vaccine takes effect (about 2 weeks)

This practice continues as long as influenza is occurring in that setting
Potential for an Influenza
Pandemic

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Flu viruses species-specific = each strain only infects a certain species
All influenza viruses have the potential to change, or mutate

Influenza virus strain which normally infects specific non-human species
could mutate into form which spreads easily amongst humans
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Flu viruses lack a “proofreading” mechanism, so small errors that occur when
the virus replicates are not corrected
As a result, their genetic composition constantly changes in small ways.
Updated influenza vaccine needed each year
Little or no immune protection against them in the human population.
If an avian virus were able to infect people and gain the ability to spread
easily from person to person, an “influenza pandemic” could begin
 An influenza pandemic is a global outbreak of influenza and occurs
when a new influenza virus emerges, spreads, and causes disease
worldwide
 Past influenza pandemics have led to high levels of illness, death, social
disruption and economic loss.
Past Influenza Pandemics

There were three influenza pandemics in the 20th
century, and all of them spread worldwide within 1 year
of being detected:
1.
Spanish flu (1918-19), most severe
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2.
Asian flu (1957-58)
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3.
Killed 20-100 million worldwide
~675,000 died in US
H1N1
Killed 1-4 million people worldwide including 70,000 in
US
H2N2
Hong Kong flu (1967-68)
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Killed 750,000 to 2 million people worldwide including
34,000 in US
H3N2
Spotlight on Spanish Flu
Pandemic (1918-19)
 So devastating that it is commonly used as a basis of
comparison for all modern pandemics
 According to HHS, approximately 20-40% of the
worldwide population became infected with the Spanish
influenza virus
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20-100 million people died
500,000-675,000 died in US
 Global mortality rate = 2.5-5% of human population
 25 million killed in its first 25 weeks, while AIDS killed 25
million in its first 25 years
 Caused by an H1N1 influenza A RNA virus which was
endemic to pigs

Through mutation gained ability to infect people
Spanish flu Sanatorium in U.S.
during 1918 Pandemic
Spotlight on Spanish Flu
Pandemic (1918-19) cont.
 True origin unknown

Did not originate in Spain/Name from less censored Spanish
media during WWI
 Spanish flu strain was unusual because most victims were
previously young and healthy victims

Common influenzas kill mostly newborns and the old and infirm
 Upon infection, the Spanish flu virus killed victims within a short
time period:
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victims who felt well in the morning would become sick by noon
and dead by nightfall, pneumonia
 By April 1919, pandemic had mysteriously ceased

No vaccine created
 Overarching fear of similar pandemic recurring during swine flu
and avian flu outbreaks
How the Swine Influenza
Panic of 1976 Began
 Feb. 4, 1976, Army recruit died at Fort Dix, N.J.
(recruit training camp) during an epidemic of
respiratory infections following the holidays
 Throat washings were taken from 19 ill soldiers
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Majority tested positive for that winter's dominant
strain of the influenza virus: A/Victoria
But four samples had inconclusive test results, and
New Jersey public health officials sent them to the
CDC to be identified
CDC Report and Its
Significance
 On Feb. 12, 1976, the CDC delivered a chilling report:
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The four samples from Fort Dix (which included one from the
dead soldier) contained influenza A H1N1 virus which was
endemic to pigs a.k.a swine flu
 Further studies of Fort Dix's soldiers showed that about 500 had
been infected with swine flu
 Officials also noted that the recruits were infected via human-tohuman transmission
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Could easily lead to pandemic
 Spanish flu pandemic of 1918 was also caused by influenza A
H1N1 virus endemic to pigs
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Spanish flu virus (H1N1) and swine flu (H1N1) in four samples
are not identical but antigenically related to each other
 Fear of 1918 pandemic recurring
 Within days of identifying the swine flu strain, federal health
officials met at the CDC to discuss what to do
Ford’s National Influenza
Immunization Program (NIIP)
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On March 24, 1976, the Ford
Administration officially launched the
National Influenza Immunization
Program (NIIP), which was one of
the most aggressive and universal
vaccination programs in recent U.S.
history

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Objective: “to inoculate every
man, woman and child in the
United States against swine flu”
$135 million appropriation from
Congress
Early production of swine flu vaccine
was possible because there was
sufficient time between the period
when the initial isolates were
discovered and the beginning of the
upcoming flu season
On October 1, 1976, the first
vaccines were given
Obstacles Facing NIIP
 Pharmaceutical companies undertook crash
programs to make enough of the vaccine by the
start of flu season in October
 But the Fort Dix bug grew poorly in chicken
eggs (the growth medium for the influenza virus
used in vaccine)
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This meant that yields ~50% of what was planned
In addition, one company used the wrong virus and
had to start over
Obstacles Facing NIIP (cont.)
 Within the first two weeks of the program’s initiation,
three elderly people who had been vaccinated by the
same clinic in Pittsburgh died
 On October 12, Pittsburgh health officials closed down
the immunization program in Allegheny County pending
an investigation of the recent deaths
 By the end of October, a total of 41 recently vaccinated
people had died across US
 54 cases of Guillain-Barré syndrome (GBS) were
reported in 10 states among people who had received the
swine flu vaccine

GBS is a serious neurological disease which is
characterized by paralysis, loss of muscle control, and
muscle weakness
Suspension of NIIP
 December 1976, the GBS cases led to a
suspension of NIIP

Never restarted
 In its entirety, Ford’s program only lasted for
two and a half months
 After NIIP ended, the federal government was
bombarded by lawsuits from people requesting
compensation because they contracted
Guillain-Barré syndrome (GBS) after being
vaccinated
 One final blow: a pandemic of swine flu never
materialized
Some Mistakes from NIIP
1.
Failure to deal with uncertainties in a tentative manner
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2.
Vaccine given too early
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3.
A few experts suggested the vaccine be made and stockpiled but used only if
there was more evidence of an epidemic
Considered but rejected early on
Argument against stockpiling was that the influenza vaccine had few, if any,
serious side effects, and that it would be far easier (and more defensible) to get it
into people's bodies before people started dying
Effective communication from scientifically qualified persons lacking
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Idea that a swine flu epidemic was unlikely never received a full airing or a fair
hearing, even though numerous experts held this view
Notion that an epidemic was likely enough to warrant nation-wide vaccination
grew from dominant opinion to unquestioned gospel
Prevailing perception that the program was motivated by politics rather than
science
Contributing Factors

Sensationalism in media (e.g. 1918 photographs during news broadcasts)
Mistakes of NIIP (cont.)
 Still researching!
What is Avian Influenza?
The H5N1 strain of the influenza virus, gold globules
Courtesy of BBC News

It is an infectious disease that is endemic in birds–rarely afflicts humans
but this has occurred recently
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highly contagious among birds, and can be fatal to them
Caused by an Influenza A H5N1 virus
Prior H5N1 strains have existed, but they were significantly different
from the current H5N1 strain on a genetic level
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Current H5N1 strain is a fast-mutating, highly pathogenic avian
influenza virus (HPAI) found in multiple bird species
Avian Flu Timeline
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MAY 1997, HONG KONG: H5N1 Bird flu virus is isolated for first time
from human patient
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2003, ASIA: Bird flu virus continues to spread in humans and birds
JAN 2004: WHO confirms H5N1 infection in 11 people
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Entire chicken population slaughtered in Hong Kong
The virus has wreaked havoc among poultry in Thailand, Vietnam,
Japan and South Korea, and has also appeared in a duck farm in China
NOV. 2004: WHO warns that H5N1 bird flu virus might spark a
pandemic, and is concerned that "much of the world is unprepared for a
pandemic" and needs to enhance preparedness to reduce its potential
impact
 NOV 2005: The WHO's official count of human cases of H5N1 reaches
122, with 62 deaths, in Vietnam, Thailand, Indonesia, and Cambodia
 PRESENT: WHO has confirmed a total of 229 human cases of H5N1
flu; 131 have been fatal
Avian Influenza in Birds
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Avian influenza viruses occur naturally
among birds
Wild birds worldwide carry the viruses in
their intestines, but usually do not get sick
from them
Avian influenza is very contagious among
birds and can make some domesticated
birds (chickens, ducks, and turkeys) very
sick and kill them
Infected birds shed influenza virus in their
saliva, nasal secretions, and feces
Susceptible birds become infected when
they have contact with contaminated
secretions, excretions or surfaces
Domesticated birds may become infected
with avian influenza virus through direct
contact with infected waterfowl or other
infected poultry, or through contact with
surfaces or materials that have been
contaminated with the virus
Avian Influenza in Birds (cont.)
 15 different subtypes of influenza virus
circulating in bird populations
 Infection with avian influenza viruses in
domestic poultry causes two main forms of
disease:
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Low pathogenic form = may go undetected and
usually causes only mild symptoms (e.g. ruffled
feathers and a drop in egg production)
Highly pathogenic form = spreads more rapidly
through flocks of poultry
 May cause disease that affects multiple internal
organs and has a mortality rate that can reach 90100% within 48 hours
Avian Influenza in Humans
 H5N1 virus does not usually infect people, but infections
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with these viruses have occurred in humans
All of human cases during current outbreak have resulted
from people having direct or contact with H5N1-infected
poultry (slaughtering or de-feathering infected birds) or
H5N1-contaminated surfaces
In all human cases of current outbreak, avian influenza
has been spread from birds to humans
There have no incidences of human-to-human
transmission
Experts say avian flu is not a food-borne virus, so eating
poultry is safe
Global Impact of Avian Flu
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Countries affected by human cases: Azerbaijan,
Cambodia, China, Djibouti, Egypt, Indonesia, Iraq,
Thailand, Turkey, and Vietnam
As of July 4, 2006: 229 cases total, 131 of these
fatal
Tens of millions of birds have died of H5N1
influenza
Collectively, hundreds of millions of birds have
been slaughtered and disposed of to limit the
spread of H5N1 in the following countries:
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Korea, Vietnam, Japan, Thailand, Cambodia,
Laos, Indonesia, China, Malaysia, Russia,
Kazakhstan, Mongolia, Turkey, Romania,
Croatia, Ukraine, Cyprus, Iraq, Nigeria, Egypt,
India, France, Niger, Bosnia, Azerbaijan, Albania,
Cameroon, Myanmar, Afghanistan, Israel,
Pakistan, Jordan, Burkina Faso, Germany,
Sudan, Ivory Coast, Djibouti. Austria, Bulgaria,
Czech Republic, Denmark, Greece, Hungary,
Iran, Italy, Kuwait, Poland, Serbia and
Montenegro, Slovakia, Slovenia, Spain, Sweden,
Switzerland, United Kingdom
Millions of birds have also been vaccinated
HHS map of Avian Flu Outbreaks
in Birds and Humans as of 6/6/06
WHO Pandemic Phase Chart
WHO Statistics on Avian Flu
Victims
 Age of victims
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Half of the cases occurred in people under the age of 20 years
90% of cases occurred in people under the age of 40 years.
 Overall Mortality Rate = 56%
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Highest mortality rates in persons aged 10-39 years
Case-fatality profile by age group differs from that seen in
seasonal influenza, where mortality is highest in the elderly.
The overall case-fatality rate was highest in 2004 (73%),
followed by 63% to date in 2006, and 43% in 2005.
 Seasonal Effects
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Cases have occurred all year round
Incidence of human cases peaked during the winter and spring
in the northern hemisphere
Symptoms of Avian Flu (WHO)
 Incubation period = ~7 days
 Symptoms range from typical flu-like symptoms to life-
threatening symptoms
 Minor Symptoms:
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Fever higher than 100.4°C
Cough
Lower respiratory tract infections
Bleeding from nose and gums
Diarrhea, vomiting
Abdominal and chest pain
 Possibly Fatal Symptoms:
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Pneumonia (often fatal)
Multi-organ failure
How would an Avian Flu
pandemic materialize?
 Current H5N1 strain is responsible for bird-to-bird and bird-to-
human transmission of avian flu

NO reported cases of human-to-human transmission
 In order for pandemic to occur, H5N1 strain must mutate into
strain which is transmitted readily amongst humans

Very good chance that this will happen, but not definite
 Every time bird or human is infected with avian flu, the virus
mutates
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Most mutations will not significantly affect virus’ capability to
infect
However, a small percentage of mutations could alter the avian
flu virus enough so that it can be transmitted amongst humans
"Everything you say in advance of a pandemic is alarmist; anything
you do after it starts is inadequate."
- US HHS Secretary Michael O. Leavitt
How would a pandemic of
avian flu be controlled?
 Same way flu epidemic would be controlled:
combination of antivirals and vaccines
 Current avian flu virus that has caused human
illness and death in Asia is resistant to
amantadine and rimantadine
Experts believe oseltamavir (Tamiflu) and
zanamavir would probably work (additional studies
still need to be done to demonstrate their
effectiveness)
 The mass administration of antiviral drugs to the
general population is not recommended by WHO,
as this could accelerate the development of drugresistant strains

Avian Flu Vaccine Production
 Scientists can only start producing a vaccine
when an avian flu virus strain emerges, which
causes human-to-human transmission of avian
flu
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Such strain has not emerged yet
Currently, there is only the H5N1 strain which
causes bird-to-human transmission
Once an avian flu strain emerges and causes
human-to-human transmission vaccine can be
made to directly combat this strain: at least 6 mts
 Scientists are testing a recently created vaccine
from the circulating H5N1 strain

Only partial protection during pandemic
U.S. Vaccine Strategy
 Need to research!
Obstacles in Research
 Hard time finding primary sources in
researching swine flu
 Defining clear cut criteria to use as
means of comparison between two
vaccine programs
Bibliography
Luke, Catherine. and Subbarao, Kanta. Vaccines for Pandemic Influenza. Emerging
Infectious Diseases (www.cdc.gov/eid). Vol. 12, No. 1. January 2006
Neustadt, Richard and Fineberg, Harvey. The Swine Flu Affair: Decision-Making on a
Slippery Disease. U.S. Dept. of Health, Education, and Welfare, 1978.
Osborn, June. History, Science, and Politics: Influenza in America: 1918-1976. Prodist:
New York, 1977.
Pandemics and Pandemic Threats Since 1900.
http://www.pandemicflu.gov/general/historicaloverview.html
Sencer, David. and Millar, J. Donald. Reflections on the 1976 Swine flu Vaccination
Program. Emerging Infectious Diseases. Vol. 12. No. 1, January 2006.
Vaccine Distribution. U.S. Dept. of Health and Human Services.
http://www.hhs.gov/pandemicflu/plan/sup6.html#S6-II
World Health Organization, Division of Communicable Disease Control.
Avian Influenza. http://www.emro.who.int/pdf/dcdnewsletter7.pdf
World Health Organization. Avian Influenza Fact Sheet.
http://www.who.int/mediacentre/factsheets/avian_influenza/en/#history
World Health Organization. Cumulative Number of Confirmed Human Cases as of June
6, 2006.
http://www.who.int/csr/disease/avian_influenza/country/cases_table_2006_06_6/en/index.html
World Health Organization. Ten Things You Need to Know About Pandemic Influenza.
http://www.who.int/csr/disease/influenza/pandemic10things/en/index.html
Acknowledgments
I would like to thank the Honors College for
giving me this awesome opportunity.
Thanks to all of you for listening and being
a great audience.
Good luck to all the Brackenridge Fellows
with your research projects!