influenza

• Type A influenza virus


  Moderate to severe illness in all age groups, infects humans and other animals

  
• Type B influenza virus


  Moderate disease, infects humans only
• Type C influenza virus


  Rarely reported in humans, no epidemics
• Type D influenza virus


  Primarily affects cattle, not known to cause illness in humans
• Influenza A and B viruses


  • RNA viruses
  • Genome: 8 RNA segments
  • Two important proteins: Haemagglutinin (HA) and Neuraminidase (NA)
  • Subtypes depend on HA and NA
  • Type A has different subtypes of HA and NA
  • Type B had variant but NOT subtypes
• Haemagglutinin (HA)

  Binds with sialic acid
• Neuraminidase (NA)

  Cuts sialic acid to release virus particles
• The 1918 pandemic flu virus was an H1N1 virus
• Emergence of variant strains in type A influenza virus

  1. Antigenetic drift= gradual small change --> epidemic potential

  includes mutations

  2.Antigenetic shift= large change --> pandemic potentional

  includes reassortment

  
• Influenza virus transmission

  • Direct transmission human-to-human: droplets made when people cough, sneeze, or talk
  • Less often by touching a surface or object that has flu virus on it and then touching their own mouth, nose, or possibly their eyes
• Flu virus detection

  Can be detected in most infected persons beginning one day before symptoms develop and up to five to seven days after becoming sick
• Flu contagiousness

  People with flu are most contagious the first three to four days after their illness begins
• • The burden of influenza disease in the United States can vary widely and is determined by a number of factors like season, vaccine working, and how many people got vax
  • The impact of flu places a substantial burden on the health of people in the United States each year.
  • Also large economic effect!
• 1918 Flu pandemic

  • infected 500 million people (1/3rd of the world's population) and caused 50 million deaths worldwide
  • The US lost more soldiers to disease than combat in WWI
  • Killed more Americans than died in WWI, WWII, and Vietnam combined
  • Lowered life expectancy by 12 years
  • killed more people in 2 months than black dead did in one yr
• The 1918 flu pandemic had 3 waves, with the second wave being the deadliest. Caused severe and high mortality in previously healthy people
• The 1918 flu pandemic was nicknamed the "Spanish flu" due to wartime censorship in other countries, while Spain as a neutral country was free to report on the epidemic's effects
• The 1918 flu pandemic first emerged in the US at Fort Riley, Kansas
• Reasons why the 1918 flu was difficult to control

  • No vaccines
  • No antibiotics to treat secondary bacterial infections
  • Cramped living arrangements of animals and people during World War I
  • Lack of healthcare providers with many doctors off fighting in the war
  • Exceptional ability of the virus to infect
• The 1918 flu: control through non-pharmaceutical interventions


  1. Isolation

  2. Quarantine

  3. Good personal hygiene

  4. Use of disinfectants

  5. Use of facemasks

  6. Limitations of public gatherings
• Six-ply gauze masks were mandatory in several cities and states. Also controversial at the time!
• Why the 1918 Influenza virus was so deadly


  • A new pandemic strain - came from birds, with no prior immunity in the majority of the human population
  • No antibiotics to treat secondary bacterial infections
  • The virus was very virulent
  • The lack of effective treatment, due in part to the unknown cause at the time
  • The cramped living arrangements of animals and people, especially the military, during World War I
  • The lack of healthcare providers; a significant percentage of doctors were off fighting in the war
  • The exceptional ability of the virus to infect and replicate in the lungs
  • Cytokine storm
• Molecular biology technologies


  Advances that allow studying the 1918 flu virus
• Avian influenza (bird flu)

  • H5 and H7 avian influenza viruses - low pathogenic (or low path) strains can mutate to highly pathogenic (high-path) strains
  • High-path strains cause a lethal disease in domestic birds and some wild birds
  • High-path avian influenza viruses cause severe disease in humans
  • Requires direct close contact with infected birds
  • No human-to-human transmission

  
• H5N1: Globally, from January 2003 to January 2023, there have been 868 cases of human infection and 457 deaths (case fatality rate: 53%)
• H7N9: since early 2013, a total of 1,568 human infections and 616 deaths (case fatality rate: 39%)
• H9N1: since December 2015, a total of 82 cases and 2 deaths (case fatality rate: 2.4%)
• Pigs have both avian and human influenza virus receptors
• Highly pathogenic avian influenza H5N1 has been detected in wild birds and mammals in the US
• Why annual influenza vaccines?

  • because of antigenic drift and its small mutations in the influenza virus that require a new vaccine to be developed each year
• Influenza vaccine formulation

  1. WHO recommends strains (4 candidates each yer)

  2. Candidate vaccine viruses are grown in chicken eggs or mammalian cells

  3. Recombinant vaccines generated in insect cells
• Cell-based flu vaccine

  Candidate vaccine viruses are grown in mammalian cells

  
• Recombinant flu vaccine

  HA proteins of the candidate vaccine viruses are produced through recombinant DNA technology in insect cells
• Cold-adapted strains

  For live, intranasal vaccination
• Universal vaccine

  One vaccine to protect humans from infections with any current and future influenza A viruses
• Antiviral drugs to treat influenza infections target which viral proteins?

  Neuraminidase and virus polymerase complex

  Ex. Neuraminidase and virus polymerase complex inhibitors (medicine)
• Diversity in Influenza A virus

  • Influenza A viruses naturally exist in water birds (natural reservoir)
  • Influenza A viruses of humans, mammals etc represent combinations of 1 of 18 HA subtypes and 1 of 11 NA subtypes
  • Subtypes H1-H16 and N1-N9 exist in wild birds
  • Subtypes H17, H18, N10, N11 exists in bats
• Pig is a mixing vessel for Influenza A viruses because?


  Pigs can be infected by both avian and human influenza virus.
• Antigenic shift in flu pandemic strains

  • 3 Pandemic in 20th century
  • 1918: H1N1 Virus; birds to humans
  • 1957: H2N2 virus; avian and human virus joined (reassortment)
  • 1968: H3N2; H3 avian and N2 human reassortment
  • 1st pandemic in 21st century
  • 2009: quadruple reassortment virus

  
• Influenza Clinical Signs

  1. Uncomplicated influenza
  2. fever, chills, headache, malaise, cough
  3. in children- nausea diarrhea
  4. typically resolves after 3-7 days for the majority
  5. cough may persist for old and w/ lung disease
  6. 2. Complicated Influenza
  7. In children- otitis media and resp. complications such as croup, bronchitis, tracheitis
  8. pneumonia, death
• Influenza causative agent misdiagnosis

  • 1892; two german microbiologists isolated bacterium from flu patients
  • Called it Bacillus influenza, today its called Haemophilus influenzae
  • cause pneumonia, but not flu
  • 1918: h. influenza repeatedly isolate so thought to be cause
  • vaccines against it were helpful BUT did not prevent/reduce 1918 flu
  • in early 1930s, flu virus isolated from pigs