2. Influenza

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2. Influenza
2011-08-11 02:56:00
PH162A midterm3

public health microbiology midterm 3 lecture 2
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  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