1976 Swine Flu Vaccine Debacle and U.S. Vaccine Strategy for Avian Flu: History Repeating Itself?

1. 1976 Swine Flu Vaccine Debacle and U.S. Vaccine Strategy for Avian Flu: History Repeating Itself? Jacqueline Doamekpor Advisor: Jonathon Erlen, Ph.D.

2. Presentation Outline • 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

3. Research Project Objectives • Thoroughly research background information on President Ford’s swine flu vaccine program and current Avian flu outbreak/U.S. vaccine strategy for avian flu • Identify reasons why the swine flu vaccination program failed • Compare and contrast the vaccine strategies for 1976 swine flu and avian flu to see whether the poor decision-making 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

4. 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

5. Why Should I Care? • 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 • 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) • 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

6. 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 • 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 • Type B • Infects humans and birds • Produces a milder disease than type A, but can also cause epidemics • Type C • Infects only humans • Produces either a very mild illness indistinguishable from a common cold or no symptoms at all • Does not cause epidemics

7. 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)

8. 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

9. 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)

10. 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

11. Antivirals • Four antiviral medications have been approved by the U.S. Food and Drug Administration (FDA) for treatment of influenza: • 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 • Benefits of antivirals • 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 • 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

12. Potential for an Influenza Pandemic • 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 • 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.

13. Past Influenza Pandemics • There were three influenza pandemics in the 20th century, and all of them spread worldwide within 1 year of being detected: • Spanish flu (1918-19), most severe • Killed 20-100 million worldwide • ~675,000 died in US • H1N1 • Asian flu (1957-58) • Killed 1-4 million people worldwide including 70,000 in US • H2N2 • Hong Kong flu (1967-68) • Killed 750,000 to 2 million people worldwide including 34,000 in US • H3N2

14. 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 • 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

15. Spanish flu Sanatorium in U.S. during 1918 Pandemic

16. 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: • 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

17. 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 • 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

18. CDC Report and Its Significance • On Feb. 12, 1976, the CDC delivered a chilling report: • 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-to-human transmission • Could easily lead to pandemic • Spanish flu pandemic of 1918 was also caused by influenza A H1N1 virus endemic to pigs • 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

19. Ford’s National Influenza Immunization Program (NIIP) • 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 • 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

20. 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) • This meant that yields ~50% of what was planned • In addition, one company used the wrong virus and had to start over

21. 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

22. 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

23. Some Mistakes from NIIP • Failure to deal with uncertainties in a tentative manner • 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 • Vaccine given too early • 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 • Prevailing perception that the program was motivated by politics rather than science • Contributing Factors • Sensationalism in media (e.g. 1918 photographs during news broadcasts)

24. Mistakes of NIIP (cont.) • Still researching!

25. 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 • 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 • Current H5N1 strain is a fast-mutating, highly pathogenic avian influenza virus (HPAI) found in multiple bird species

26. Avian Flu Timeline • MAY 1997, HONG KONG: H5N1 Bird flu virus is isolated for first time from human patient • Entire chicken population slaughtered in Hong Kong • 2003, ASIA: Bird flu virus continues to spread in humans and birds • JAN 2004: WHO confirms H5N1 infection in 11 people • 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

27. Avian Influenza in Birds • 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

28. 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: • 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 90-100% within 48 hours

29. Avian Influenza in Humans • H5N1 virus does not usually infect people, but infections 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

30. Global Impact of Avian Flu • 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: • 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

31. HHS map of Avian Flu Outbreaks in Birds and Humans as of 6/6/06

32. WHO Pandemic Phase Chart

33. WHO Statistics on Avian Flu Victims • Age of victims • 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% • 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 • Cases have occurred all year round • Incidence of human cases peaked during the winter and spring in the northern hemisphere

34. Symptoms of Avian Flu (WHO) • Incubation period = ~7 days • Symptoms range from typical flu-like symptoms to life-threatening symptoms • Minor Symptoms: • 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: • Pneumonia (often fatal) • Multi-organ failure

35. 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 • 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

36. 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 drug-resistant strains

37. 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 • 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

38. U.S. Vaccine Strategy • Need to research!

39. 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

40. 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

41. 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!