The document discusses the 1918 flu pandemic, which originated from a virus that underwent an antigenic shift allowing it to spread easily between humans. It killed 20-50 million people worldwide and 675,000 in the US. The pandemic occurred in three waves, with a severe second wave in the fall of 1918. Even today, influenza remains a threat as the virus can undergo antigenic drift and shifts, sometimes resulting in new pandemic strains against which humans have little immunity. Monitoring efforts focus on tracking current flu strains and outbreaks.

1. The 1918 Flu
Pandemic
Lindsey Randle
MLT 2080 - Microbiology

2. An Introduction
- The Flu pandemic of 1890: a precursor
- The Public Health Service began requiring health reports from communities in
1918.
- Influenza wasn’t a reportable disease.
- In March of 1918 “18 cases of influenza of a severe type” from Haskell County
Kansas were reported.

3. In Coming
- Reports of a severe flu came in from Europe.
- most young male soldiers recovered quickly but some developed
secondary pneumonia of “a most virulent and deadly type”.
- “Within two months, influenza had spread from the military to the civilian
population in Europe. From there, the disease spread outward”

4. The Beginning
– August the virus broke out in three port cities.
- Freetown, Sierra Leone
- Brest, France
- Boston, Massachusetts
- Large numbers of Boston dock workers at the Commonwealth Pier reported
sick.
- By September the disease had spread to California, Florida, North Dakota, and
Texas.

6. Three Waves
The First Wave
- A mild flu in the spring and summer of 1918
The Second Wave
- A severe flu in the fall of 1918
The Third Wave
- The spring of 1919
- 20 - 50 million people died around the world
- 675,000 dead in the United States out of a population of 105 million
- Took 3 times as many lives as WW1

8. Minnesota Stats.
– The first case was reported in early October 1918.
– In less than a week later “more than a thousand cases of ‘The Spanish Flu’ were
reported in Minneapolis alone”.
– On October 11th the Minneapolis Department of Health ordered the shut down
of many public places such as schools, churches, and theaters.
– In NE Minnesota wild fires forced mass evacuations and devastation to homes
and the deaths of hundreds. This caused the further spread of the flu across the
state.

9. Influenza A and B
- Belongs to the family Orthomyxoviridae.
- Zoonotic infection is typically carried by birds and mammals.
- The “viruses are enveloped, and types A and B have eight segments of ssRNA”.
- 2 major surface antigens hemagglutinin (H) and neuraminidase (N)

10. Hemagglutinin
– H antigen binds to receptors and fuses to host cell membranes
– There are 15 known H antigens
– H1, H2, and H3 are known to infect humans

11. Neuraminidase
- N antigen “cleaves budding viruses from infected cells”.
- There are 9 N antigens
- Human infections are caused by N1 and N2.

13. Influenza’s Persistence
– Today a mild flu outbreak may kill 30,000 Americans.
– “In six different years from 1972 to 1995 influenza deaths in the United States
exceeded 40,000”.
– There are two ways the antigens can change.
– 1) antigenic drifts: a minor change in antigenic structure caused by RNA
replication errors.
– 2) antigenic shift: a drastic change in surface antigens.
– There are two modes by which antigenic shifts occur.

14. Antigenic Shift
– Mechanism 1: Genetic Reassortment
– This “occurs when pieces of both influenza viruses become mixed into a viron,
resulting in a new strain of influenza”.
– Mechanism 2: Adaptive Mutation
– A virus adjusts and becomes transmissible
– Results in a novel virus “against which there is little to no pre-existing
immunity”
– This increases new risks for pandemics

15. Influenza C
– Enveloped
– Contains only 7 ssRNA segments.
– Is missing the gene for neuraminidase.
– More stable than influenza A.
– Can cause mild upper respiratory illness in humans.

16. Symptoms
– The virus is spread by aerosols and it attacks ciliated epithelial cells lining the
respiratory tract.
– Causes necrosis and sloughing of the cells
– Incubates 1-4 days
– Symptoms include “rapid onset of malaise, fever, myalgia, and nonproductive
cough”
– Fever as high as 41* C or 105.8* F
– Can cause fatal viral pneumonia including secondary bacterial pneumonia

17. The Spanish Flu
– Young adults were particularly targeted
– “Death rates for 15-34 year olds were 20 times higher than the previous year”
– “most deaths were caused by secondary bacterial pneumonia”
– Sickness lasted 5 days before patients were killed from a viral pneumonia
accompanied by a “massive acute pulmonary hemorrhage or pulmonary
edema”

18. The Spanish Flu
– Transmissibility “is mediated by the hemagglutinin membrane glycoprotein”
– Alterations allowed for transmission between birds and humans and then from
human to human
– This shift was H1N1.

19. Reconstruction
– They collected cDNA fragments
– Sample was collected from a frozen lung
– The genetic code didn’t reveal any features associated with virulence.
– They needed to study an intact live replicating virus within a suitable host.
– Lab mice died in 3 days
– They found that unlike the usual seasonal flu it attacks deep in the lungs
resulting in extreme inflammation
– They also found it had two H antigen mutations allowing it to spread between
humans

21. Continued
– Infection also triggered highly sustained innate immune response
– Significant influx of neutrophils and alveolar macrophages to the lungs
– HA receptor binding specificity plays a role in pathogenesis in mice
– “Two amino acids that are responsible for receptor binding specificity and
efficient virus transmission, has also been demonstrated in ferrets.”
– RNA polymerase complex is responsible for viral pneumonia

23. Monitoring the Flu Today
– Hospitalized Surveillance: hospitals report whenever they have lab confirmed
influenza and they submit specimens to MDH-PHL for testing.
– Sentinel Surveillance: healthcare providers monitor influenza-like illnesses and
fill out weekly reports.
– Long-term Facility Surveillance: report suspected or lab confirmed influenza
outbreak.
– School Surveillance: K-12 schools report outbreaks when 5% of enrolled
students or 3 or more students from the same classroom are absent.
– MLS Laboratory Surveillance: labs perform rapid testing for influenza and
Respiratory Syncytial Virus, some preform confirmatory culture testing
– MLS Virology Laboratory Isolate Surveillance: isolates are subtyped to monitor
strains and compared them to current vaccine subtypes.

24. Public Health Emergencies
– CDC provides funding and technical assistance to strengthen local services
ability.
– Respond and support national, state, and local partners to save lives and reduce
suffering by providing scientific and logistic expertise and deploying personnel
to the site of the emergency

25. Legacy
– Two months after the pandemic started reports to the Public Health Service
reduced.
– Communities began lifting quarantine and schools were re-opened and people
celebrated the end of WW1.
– The summer of 1919 hundreds of thousands of Americans were dead and more
were orphaned or widowed.
– The pandemic as led to continual study and observation of influenza to prevent
future pandemics and to develop better vaccines.
– The use of the resurrected 1918 virus is helping scientists understand
transmission from birds to humans and human to human.
– Currently they are watching the Avian flu.

26. Works Cited
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Receptor Binding Properties of the 1918 Influenza Hemagglutinin." Science Magazine. N.p., 19 Mar. 2004. Web. 10 June 2016.
"Influenza Strikes." The Great Pandemic: The United States in 1918-1919. United States Department of Health and Human Services, n.d. Web. 22 May 2016.
"Keeping Track of Flu in Minnesota." Minnesota Department of Health. Minnesota Department of Health, 16 Nov. 2010. Web. 17 June 2016.
Mahon, Connie R., Donald C. Lehman, and George Manusellis. "Clinical Virology." Textbook of Diagnostic Microbiology. 3rd ed. Philadelphia: Saunders, 2000. N. pag.
Print.
"Novel Influenza A Virus Infections 2014 Case Definition." Novel Influenza A Virus Infections. Centers for Disease Control and Prevention, n.d. Web. 01 June 2016.
Singh, Debashis. "Scientists Have Uncovered the Structure of 1918 Flu Virus." US National Library of Medicine National Institutes of Health. BMJ Publishing Group Ltd.,
14 Feb. 2004. Web. 10 June 2016.
Touchette, Nancy. "Shape of the 1918 Flu Protein Provides Clues to Global Pandemic."Genome News Network. N.p., 6 Feb. 2004. Web. 10 June 2016.
Tumpey, Terrence M., and Jessica A. Belser. "Resurrected Pandemic Influenza Viruses." Annual Review of Microbiology. Annual Reviews, 22 Apr. 2009. Web. 10 June
2016.
"What Is CDC's Role in Emergencies?" Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 10 Apr. 2015. Web. 17 June 2016.