Influenza: Virus and Disease

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Influenza Virus and Disease
Kenneth H. Fife, MD, PhD Indiana University
School of Medicine
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Clinically Relevant Influenza Viruses

• Type A Potentially severe illness
• Epidemics and pandemics
• Rapidly changing
• Type B Usually less severe illness
• Epidemics
• Genetically more stable

Centers for Disease Control and Prevention.
Influenza Prevention and Control. Influenza.
Available at http//www.cdc.gov/ncidod/diseases
/flu/fluinfo.htm.
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Influenza Surface Proteins
Neuraminidase
Hemagglutinin
RNA
M2 protein (only on type A)
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ROLE OF H AND N PROTEINS

• H Hemagglutinin and N Neuraminidase
• Hemagglutinin allows the virus to bind to host
  cells
• Neuraminidase helps the virus to release itself
  from the highjacked cells in which it has
  reproduced

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Hemagglutinin Subtypes of Influenza A Virus

• Subtype Human Swine Horse Bird
• H1
• H2
• H3
• H4
• H5
• H6
• H7
• H8
• H9
• H10
• H11
• H12
• H13
• H14
• H15

Adapted from Levine AJ. Viruses. 1992165, with
permission.
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Neuraminidase Subtypes of Influenza A Virus

• Subtype Human Swine Horse Bird
• N1
• N2
• N3
• N4
• N5
• N6
• N7
• N8
• N9

Adapted from Levine AJ. Viruses. 1992165, with
permission.
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Influenza A Virus Constantly Changes

• Antigenic drift
• Small changes in H or N proteins that occur from
  year to year
• Population is partially immune, but may be
  re-infected over time (periodic epidemics)
• Antigenic shift
• Acquisition of new H or N protein, possibly from
  an animal virus
• Population is not immune, everyone is susceptible
  (pandemics)

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Influenza Pandemics in the 20th Century

• Years Flu Virus Mortality
• 1918-19 Spanish Type A (H1N1) 20 million
  worldwide 550,000 US
• 1957-58 Asian Type A (H2N2) 70,000 US
• 1968-69 Hong Kong Type A (H3N2) 34,000 US

Glezen WP. Epidemiol Rev. 19961865.Centers
for Disease Control and Prevention. Influenza
Prevention and Control. Influenza. Available
athttp//www.cdc.gov/ncidod/diseases/flu/fluinfo
.htm.
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1918 Spanish Flu Pandemic

• Type A virus (H1N1)
• 20-50 million deaths worldwide
• 550,000 deaths in the United States
• 21,000 Flu-Orphans in NYC

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1918 Pandemic

• It killed more people in 25 weeks than AIDS has
  killed in 25 years
• It killed more people in a year than the plagues
  of the Middle Ages killed in a century
• Seven times as many people died of influenza
  than in the First World War

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1957 Pandemic

• 1957-1958 Asian Flu
• Type A virus (H2N2)
• First identified in China February 1957
• Spread to U.S. by June 1957
• 70,000 deaths in the United States

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1968 Pandemic

• 1968-1969 Hong Kong Flu
• Type A virus (H3N2)
• First detected in Hong Kong early 1968
• Spread to U.S. later that year
• Approx 34,000 deaths in the United States
• Our seasonal flu kills 36,000
• Virus still circulating today

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1977 Pandemic

• H1N1 reintroduced in 1977 Russian Flu
• Affected mostly young adults not exposed to
  influenza before 1957
• Still circulating

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Natural History of Influenza Viruses
H3N2
H3N8
H2N2
H2N?
H1N1
H1N1
1880
1890
1900
1910
1920
1930
1940
1950
1960
1970
1980
1990
2000
Topley and Wilsons Microbiology and Microbial
Infections. 9th ed, Vol 1, Virology. Mahy and
Collier, eds, 1998, Arnold, page 387, with
permission.
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Influenza Type A (H5N1)

• First appeared in humans in Hong Kong, 1997
• Primarily associated with avian species
• Fatal epidemic among Hong Kong poultry in 1997
• Continuing avian epidemics through 2006
• To date, 225 human cases with 128 deaths
• No sustained human-to-human transmission

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Human Cases of H5N1 Avian Flu 2003-2006
As of 06/16/06 Source World Health Organization
(laboratory confirmed cases)
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Distribution of H5N1 Infection 2006
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Epizootiology - Birds

• Natural Hosts
• Domestic fowl, ducks, geese, turkeys, guinea
  fowl, quail, and pheasants
• Source of Infection
• Domestic flocks felt to be primary source
• Migratory waterfowl may spread over wide areas
• Spread
• Rapid in flocks by direct contact
• Viral shed in feces and nasal and ocular
  discharges

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Implications of H5N1 Infection

• Potential for pandemic infection by little-known
  pathogen
• Morbidity and mortality in both young and old
• No previous human exposure no vaccine
• Signals need for
• Pandemic readiness plan
• Rapid detection and diagnosis of new viral
  strains
• Veterinary surveillance
• Continuing research for new antiviral agents

Lee, Mak, Saw. Public Health and Epidemiology
Bulletin. 199981-7.
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Pandemic Response

• Many communities throughout the U.S. will be
  affected at the same time, others will be at risk
• Each community will have to deal with the
  pandemic mostly on their own
• Society as a whole will have to work together to
  minimize the impact of the pandemic

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Influenza Illness (Typical Case)

• Incubation period (time between exposure and
  symptoms) short 1-3 days
• Infected person may shed virus for 12-24 hours
  before onset of symptoms
• Viral shedding peaks on day 2 or 3 then declines
• Virus may be present as long as there are
  symptoms (usually 5-10 days)

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Influenza Spread

• Nearly all spread is person-to-person
• Spread is by small droplets (as from a cough or
  sneeze) inhaled by a susceptible person
• Inanimate object (doorknobs, towels) and physical
  contact (handshaking) may contribute to spread,
  but their role is minor

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Signs and Symptoms

• Abrupt onset of symptoms
• Fever, usually over 100F
• Cough with little or no sputum
• Chills and/or sweats
• Headache
• Muscle aches
• Sore throat
• Potentially severe, persistent malaise
• Chest soreness, light sensitivity, and eye pain

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Differences Between H5N1 and Current Strains

• Typical influenza involves only the upper
  respiratory tract
• Persons with underlying medical problems (lung
  disease, heart disease, cancer) or the elderly
  are at increased risk of secondary bacterial
  pneumonia
• Influenza viral pneumonia is rare
• H5N1 has the ability to infect the upper and
  lower respiratory tract (including the lung)
• Anyone who is susceptible to H5N1 can get
  pneumonia caused by the influenza virus
• The resulting influenza virus pneumonia is severe
  and may be fatal

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Economic Costs of Influenza Outbreak

• Total annual costs of influenza are estimated at
  14.6 billion in the US
• 10 Direct costs of increased medical care
• 90 Indirect costs (lost productivity, employee
  absenteeism)

American Lung Association. Fact Sheet
Influenza, at http//www.lungusa.org/diseases/infl
uenza_factsheet.html. Accessed 3/25/99.
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Inactivated Influenza Virus Vaccine

• History First developed in 1940s
• Content Updated yearly to protect
  against anticipated strains, consists of type A
  (2) and type B (1)
• Process Grown in embryonated chicken eggs and
  formalin inactivated

MMWR. 1999484-5.
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Influenza Virus Vaccine

• Most effective in young, healthy people
• Often prevents infection, usually prevents
  serious disease
• Less effective in the elderly
• Many develop infection, but vaccine reduces the
  frequency of serious disease and death
• Response directly related to overall state of
  health

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Selective Neuraminidase Inhibitors Currently
Available

• Zanamivir Oseltamivir
• (Relenza) (Tamiflu)
• Indication Treatment Treatment, Prophylaxis
• Spectrum Type A, type B Type A, type B
• Administration Inhaled Oral 2 puffs bid 1
  tablet bid for 5 days for 5 days