1. Influenza 101
Nebraska Public Health Laboratory

2. Influenza: The Virus Family: Orthomyxoviridae
Genera: 3 Influenza virus Types
Type A influenza viruses infect humans, birds & other mammals.
Type B influenza viruses primarily infects humans.
Type C influenza viruses primarily infects humans.

3. Influenza Virus Genera
Type A
moderate to severe illness-respiratory disease-fever, aches, cough, secondary pneumonia
all age groups
humans and other animals
can be typed by hemagglutinin and neuraminidase protein (i.e. H3N2)
Type B
milder epidemics
mainly affects humans
primarily affects children
Type C
sporadic infections
primarily affects children and young adults
Type A occurs in both human and animals. It causes moderate to severe illness in all age groups. Type B only occurs in humans and primarily affects children. It generally causes milder epidemics. Type C is rarely reported as a cause of human illness. Most cases of Type C disease are subclinical or manifest as afebrile common colds. Type C rarely (if ever) produces the influenza syndrome. It does not cause epidemics.

4. Influenza structure Influenza A Subtypes: -Based on: Hemagglutinin (H)
H1 to H16
Neuraminidase (H)
N1 to N9
144 different combinations

5. Influenza: Nomenclature
Location of Original Isolation
Year of Initial Isolation
A/Fujian/411/2002 (H3N2)-like
Strains: A/Wisconsin/67/2005 (H3N2)-like
(2006-7) A/New Caledonia/20/99 (H1N1)-like
B/Malaysia/2506/2004
Subtype
(Influenza A Viruses Only)
Type
Original Lab ID #

6. Influenza: Nomenclature (adapted from CDC)
Seasonal Influenza (“common” influenza)
A respiratory illness that can be transmitted person to person. Most people have some immunity, & a vaccine is available.
Avian Influenza (“bird flu”)
Influenza viruses that occur naturally among wild birds. There is no human immunity & no vaccine.
The H5N1 variant is deadly to domestic fowl & can be transmitted from birds to humans.
Pandemic Influenza
A virulent human influenza that causes a global outbreak, or pandemic, of serious illness. There is little natural immunity, so the disease can spread easily from person to person.
Currently, there is no pandemic influenza.

7. ~10%-20% Infected (29-59 million) ~50% Symptomatic (15-30 million)
Influenza: Annual Impact
~10%-20% Infected (29-59 million)
U.S. population ~290 million
Hospitalized>200,000 1
Each year ~10-20% of the US population becomes infected with influenza virus
Most, but not all of those infected will be symptomatic.
Of those that are symptomatic, most will treat at home but some will seek healthcare.
Of those that seek healthcare, some will require hospitalization and a subset of both the outpatients and the hospitalized patients will be tested for influenza.
Some of the people with influenza virus infection will die.
Seek Care
~50% Symptomatic (15-30 million)
Death
~36,000
Treat at Home

8. Prerequisites for the Start of a Pandemic
First, a new virus must emerge to which the general population will have no or little immunity
Second, the new virus must be able to replicate in humans and cause disease, spread regionally
Third, the new virus must be efficiently transmitted from one human to another.
Spread of disease world-wide = Pandemic

9. Pandemic Flu Outbreaks occurred in:
1918 Spanish Flu (H1N1)
1957 Asian Flu (H2N2)
1968 Hong Kong Flu (H3N2)

10. 1918 Spanish Flu Pandemic

11. 1918 Flu Epidemic Emergency Hospital, Camp Funston, Kansas Photo Courtesy of National Museum of Health and Medicine,Armed Forces Institute of Pathology
Haskell county

12. 1918 Spanish Flu Pandemic 20% of World and 28% Americans infected
Shortage of health professionals and supplies due to WWI
675,000 people died in U.S. out of 105 million
million died worldwide out of almost 2 billion

13. 1918

14. Bird Flu – The Next Pandemic Concern – WHY?
Influenza is a disease of birds
Rapidly mutates and changes
Birds are mobile
Birds that survive infection shed virus in feces for weeks

15. Bird (avian) Influenza
December 2003-June 2007
41 countries reported H5N1 bird flu in poultry
Bird to humans-high mortality rate.
Limited human to human transmission-only close contacts.
Controlled by the depopulation of large flocks of poultry

16. Bird (avian) Influenza cases

17. Cause for concern?
Wild ducks are now found that can shed virus without signs of infection.
Experimental evidence that the virus is more lethal than when the epidemic first started in Asia.
Has spread to mammalian species-large cats-previously thought to be immune.
Large die-offs of migratory birds in China-unprecedented.

19. Influenza: Antigenic Change- A Hallmark
Antigenic Drift
Gradual & continuous change in influenza virus hemagglutinin (HA) & neuraminidase (NA) during replication
Occurs with influenza A & B
Leads to new strains, allowing repeated infections
Causes annual epidemics of seasonal influenza

20. Influenza: Antigenic Change- A Hallmark
Antigenic Shift
An abrupt change, infrequent & unpredictable
Process whereby existing surface HA and/or NA proteins are replaced by HA and NA proteins that are significantly different
Occurs only with influenza A
Results in a a new subtype (novel virus)
Can result in pandemic influenza

21. Transmission to Humans
Antigenic Shift

22. H3N2
H5N1
Situation for concern ??!!!

23. Avian Flu Human Infections 1918-2007
H1N1
1957
H2N2
1968
H3N2
1997
1999
H9N2
2003
H5N1
2004
H7N7

24. Vaccines vs. Antivirals
Vaccines: Best prevention option, however…
limited supply of Avian influenza vaccine (bird strain)
lag time to produce 6-9 months (human strain)
manufacturing capacity stretched in pandemic
efficacy dependent on correct match with strain
Antivirals: Best at STOPPING spread….
effective for treatment and prophylaxis
valuable adjunct to vaccines
limited supply
not all antivirals against avian flu strains

25. How do Influenza vaccines work?
World Health Organization (WHO) / Centers for Disease Control and Prevention (CDC)
pick what influenza viruses subtypes
done 9-10 months prior to current season
2 type A (H3N2, H1N),1 type B
flu shot (inactivated virus) and nasal spray flu vaccine (live attenuated vaccine)

26. Antivirals Four main antivirals
Amantadine and rimantadine
prevent virus replication (M2 ion channel inhibitors)
affective only against Influenza A
H5N1 is resistant
Oseltamivir (Tamiflu) and Zanamivir (Ralenza)
prevent virus from entering the cell (Neuraminidase inhibitors)
affective against Influenza A and B
48 hours after symptoms or for prophylaxis

28. Who’s Watching Around the World?
The World Health Organization (WHO)
6 Regional Offices (PAHO)
112 National influenza centers (NICs) in 82 countries
4 WHO collaborating centers -WHOCCs (Australia, Japan, UK, and the USA)
World-wide surveillance laboratories
WHO makes recommendations on influenza vaccine
The World Health Organization maitains a worldwide-year-round flu-surveillance system. Through the Centers for Diseases Control and Prevention, our country, along with other countries around the world, participates in this surveillance system. Based on information gathered, the World Health Organization makes recommendations regarding the influenza vaccine that can be most effective to prevent flu epidemics and flu pandemics.

29. Pandemic Influenza: W.H.O. Phases
Interpandemic Period
Phase 1
No new influenza virus subtypes in humans
Phase 2
No new influenza virus subtypes in humans, but an animal influenza virus poses substantial risk
Pandemic Alert Period
Phase 3
Human infection(s) with new subtype, but no or rare human-to-human spread
Phase 4
Small cluster(s) of limited human-to-human transmission, highly localized
Phase 5
Larger cluster(s) but human-to-human spread still localized
Pandemic Period
Phase 6
Pandemic phase: increased and sustained transmission in general population.
Postpandemic period
Return to Interpandemic Period

30. Who’s Watching the Nation?
HHS Pandemic Influenza Response and Preparedness Plan,
Centers for Disease Control
HHS ordered 2 million doses of H5N1 vaccine from Aventis Pasteur Inc.
US is working with WHO and SE Asian countries to enhance surveillance and Containment

31. Who’s Watching in Nebraska?
Influenza Sentinel Provider Surveillance System
11 health care providers (report to CDC)
Local Health Departments have flu surveillance plans
Lab test result reporting
About 65 labs reporting report total and (+) test results
School absenteeism survey
Local Health Departments enter data and do monitoring
Hospital admissions survey (with influenza like illness)
19 district / local health departments
89 acute care hospitals
Here in Nebraska we keep track of the number of cases of influenza, the population being affected, its severity, its geographic distribution, etc. At least four surveillance systems were active during the present flu season: One uses reports from health care providers and local health departments; other uses test results reported by laboratories; other keep track of school absenteeism, and the last-one keeps track of the number of patients admitted to acute care hospitals with a diagnosis of influenza-like-illness.

32. What can you do? Get vaccinated If you have the flu, don’t go to work
Become educated about influenza.

33. Cover your mouth and wash your hands!

34. Resources CDC home page for influenza http://www.cdc.gov/flu
U.S. web site for pandemic flu & U.S. Pandemic Flu Plan and Preparedness Planning
W.H.O. home page for influenza (including avian
influenza)
ProMED (Program for Monitoring Emerging Diseases, International Society for Infectious Diseases)

35. Safety Resources
Public Health Guidance for Community-Level Preparedness and Response to Severe Acute respiratory Syndrome (SARS),Version 2.3; July
Biosafety in Microbiological and
Biomedical Laboratories (BMBL),5th ed

36. Avian Flu Education
A Short Quiz

37. The current avian flu virus first appeared in:. a. East Asia. b
The current avian flu virus first appeared in: a. East Asia b. South Asia c. Middle East
A) East Asia. The first cases were in the Republic of Korea and Vietnam. Most of the outbreaks have been in East and Southeast Asia, though further outbreaks have been reported recently in Russia, Mongolia, Kazakhstan, Turkey, Croatia, Romania and Ukraine.

38. Avian flu is most commonly spread by: a. Humans b. Pigs c. Birds
C) Birds. Avian flu is passed from bird to bird, though it occasionally transmits to pigs. In very rare cases, the virus, which can be transmitted from wild to domestic birds, has been known to infect people who have come into direct contact with contaminated poultry or their waste.

39. True or False: There is now a bird flu vaccine available for humans.
False. Until the bird flu mutates into a virus that can be transmitted from person to person, no one can be sure if any vaccines being developed will work against the virus. Even if the vaccine works, they take a long time to manufacture so it is unlikely that enough vaccine would exist when a pandemic occurred.

40. True or False: People are safe from the pandemic if they don’t touch or go near any birds.
False. A pandemic will occur if and when the bird flu strain mutates so infected humans can infect other humans. At that time, people who have never gone near birds will be at risk. Right now, birds infected with the bird flu virus can infect humans who come in contact with them.

41. True or False: No matter what type of influenza you have, any of the antivirals available will be able to treat your illness.
False. Tamiflu and Ralenza at this time are known to be affective against Influenza A and B. Amantadine and Rimantadine are only affective against Influenza A, although H5N1 strains are resistant.

42. True or False: The U.S. government will be ready to help victims of any pandemic.
False. Individuals, families, and communities will be on their own. The government has advised individuals of the danger, saying “… thousands of communities could be countering influenza simultaneously with little or no assistance from adjacent communities, the state, or the federal government. Preparedness planning for pandemic influenza response must take the prospect into account.”
Source:

43. True or False: If you are young and healthy, there is little for you to worry about as far as contracting a pandemic illness.
False. In the flu of 1918, the virus affected young people more so than older people. The flu of 1918 also originated from a bird flu virus.

44. True or False: During a pandemic, there may be shortages of food, medicine, and other products.
True. If the pandemic strikes, experts believe there will be shortages of food, medicine, and other products, because individuals who provide us with such items may be sick, disrupting the process. There also will be other social disruptions.

45. Which strain of flu is responsible for more deaths in the United States? a. Hong Kong flu pandemic b. Avian flu c. Typical flu outbreak 20 years ago d. Seasonal flu outbreak expected this year
D) Seasonal flu outbreak expected this year. The CDC estimates that there might be 36,000 fatalities from the flu this year, mostly in the elderly. This is more than the “Hong Kong flu” pandemic caused in the United States in 1968.

46. When as the last major flu pandemic? a. 1900 b. 1918 c. 1950 d. 1968
D) The “Hong Kong flu”, a virus that still circulates today, originated in Hong Kong and eventually spread to the United States, killing 34,000 Americans.