2. Influenza

  1. 1918 pandemic
    • caused by H1N1 subtype
    • disproportionate mortality among infants and young adults
    • 3 pandemic waves
  2. influenza etiology
    • influenza virus
    • ssRNA virus, segmented
    • three genera exist
  3. influenza A
    • 8 gene segments
    • 10 viral proteins, M2 unique
    • humans, swine, equine, avian, marine mammals
    • antigenic shift and drift
    • may cause large pandemics with significant mortality in young persons
  4. influenza B
    • 8 gene segments
    • 11 viral proteins, NB unique
    • humans only
    • antigenic drift only
    • severe disease generally confined to older adults or persons at high risk, pandemics not seen
  5. influenza C
    • 7 gene segments
    • 9 viral proteins, HEF unique
    • humans and swine
    • antigenic drift only,
    • mild disease without seasonality
  6. hemagglutinin (HA)
    • glycoprotein spike antigen in envelope
    • binds sialic acid residues on host cell surface
    • facilitates attachment and penetration
    • neutralizing antibodies against HA are protective
    • 15 subtypes in waterfowl reservoir
  7. neuraminidase (NA)
    • glycoprotein spike antigen in envelope
    • cleaves N-acetyl-neuramic acid from mucopolysaccharides
    • facilitates release of virus from cell surface
    • 9 subtypes in waterfowl reservoir
  8. Influenza A genetics
    • 8 RNA segments allow high frequency of reassortment during mixed infection
    • uses antigenic variation to avoid immune system
  9. antigenic drift
    • accumulation of mutations within the antibody binding sites of HA and NA
    • slow, subtle process involving small changes
  10. antigenic shift
    • replacement of HA or NA with a novel subtype from waterfowl reservoir
    • usually will result in pandemic
    • fast, drastic process involving large changes
  11. mixing vessel hypothesis
    • animal co-infected with strains from different animals allows reassortment of RNA segments
    • direct transmission is also possible
  12. influenza nomenclature
    virus type / geographic origin / strain number / year of isolation (virus subtype)
  13. Influenza A occurrence
    only infectious disease in developed countries that causes alteration of death rate (increases in winter)
  14. Influenza A reservoir
    • wild waterfowl main reservoir
    • occasionally transmitted to other host animals
    • some of the viruses may become established in the new hosts
    • humans then serve as the main reservoir for these viruses that are adapted to humans
  15. Influenza A transmission
    • respiratory route by droplet infection - all sizes
    • infected humans have high virus concentration in secretions
    • air travel important in international spread
  16. Influenza A temporal variation
    • marked seasonal variation in temperate climates
    • occurs year round in tropical climates
  17. reasons for Influenza A temporal variation
    • no definitive reasons
    • greater indoor crowding has been suggested
    • damage to nasal mucosa could facilitate infection
    • low relative humidity enhances infectivity
    • seasonal variation of serum vitamin D levels
  18. Influenza A communicability
    • adults are contagious 5-7 days after start of symptoms, children longer
    • super spreaders account for much of transmission
    • 20/80 rule = 20% of infectious persons account for 80% of transmission
  19. Influenza A pathogenesis
    • HA binds sialic acid on cellular surface of respiratory epithelial cells
    • viral envelope fuses with endosome
    • RNA transported to nucleus for transportation
    • mRNA translated into viral proteins
    • HA and NA embedded in cellular membrane
    • NA facilitates viral budding from cellular membrane
    • induces strong inflammatory response - causes signs and symptoms
  20. Influenza A immune response
    infection induces both humoral and cellular immune response

    humoral - B cells differentiate into plasma cells and produce virus specific antibodies, which prevent binding and release

    cellular response - cytotoxic T lymphocytes target infected cells for killing

    memory cells provide extended protection against identical strain, but antigenic variation quickly alters virus
  21. Influenza A clinical
    upper respiratory tract signs and symptoms - conjuctivitis, nasal decongestion, sore throat, otitis media

    lower respiratory tract signs and symptoms - cough

    • systemic signs and symptoms - fever, muscle pain
    • major complication is pneumonia
  22. Influenza A diagnosis
    • clinical - not definitive
    • tissue culture of throat washings
    • reverse transcriptase PCR
    • serology
    • rapid influenza diagnostic tests - look for antigen using ELISA or immunochomotography
  23. Influenza A treatment
    • mostly only palliative - rest, hydration, medicines without aspirin
    • antivirals for high risk patients
  24. Influenza A prevention
    • covering of coughs
    • avoidance of close contact
    • voluntary home isolation
    • social distancing
    • school dismissal
    • masks for healthcare workers
    • hand hygiene
    • antiviral treatment of index case, prophylaxis of contacts
    • vitamin D optimization
    • vaccines
  25. Influenza A vaccines
    • WHO uses information from network of countries to decide on that seasons vaccine formulation
    • new vaccine every year with 3 viruses
  26. Avian Influenza background
    • 15 subtypes of influenza virus infect birds
    • high pathogenic H5N1 occasionally infects humans - must acquire from bird
  27. Avian Influenza epidemiology
    • epidemic killed chickens, some human cases
    • china is considered epicenter
  28. features of H5N1 Avian Influenza
    • reservoir is wild aquatic birds
    • humans acquire infection from close contact with birds
    • disease is not easily transmissible between humans
    • global spread likely due to bird migration and trade of birds
  29. H5N1 Influenza disease
    • mostly infects the lower respiratory tract
    • potent inducer of inflammation
    • typical signs of influenza with a higher frequency of diarrhea
    • diagnosis and treatment similar to human influenza
    • prevention through bird control
  30. 2009 H1N1 influenza etiology
    • new influenza virus of swine origin
    • has similarities to avian, human and swine viruses - chimeric virus, picked up from different sources
  31. 2009 H1N1 pandemic
    • most illness acute and self-limited
    • highest incidence in children and young adults - people over 60 had exposure to similar virus earlier in life
    • most serious illness in children and adults
  32. H1N1 epidemiology
    • primary reservoir remains unknown
    • transmission appears similar to seasonal influenza
    • pandemic began in spring in northern hemisphere and continued through summer - unusual
    • communicability appears similar to seasonal influenza
  33. H1N1 vs. H5N1
    H1N1 - easily spread, rarely fatal

    H5N1 - spreads slowly, often fatal
  34. H1N1 diagnosis, treatment and prevention
    • RT-PCR
    • resistant to M1 inhibitors, neuraminidase inhibitors
    • prevention same as seasonal influenza
  35. 1918 H1N1 and 2009 H1N1 similarities
    • same type
    • novel viruses with little immunity in population
    • both began in spring
    • highest morbidity and mortality in young population
  36. vitamin D and the immune system
    • enhances expression of antimicrobial peptides by monocytes and neutrophils
    • suppressive effect on macrophages and therefore inflammatory response
    • mostly suppressive effects on adaptive immunity
  37. vitamin D debate
    • institute of medicine concluded most people have sufficient levels but used low cutoff
    • dismissed studies suggesting benefits beyond bone health, but took serious studies which suggested negative effects of high doses
Author
cornpops
ID
95894
Card Set
2. Influenza
Description
public health microbiology midterm 3 lecture 2
Updated