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1918 pandemic
- caused by H1N1 subtype
- disproportionate mortality among infants and young adults
- 3 pandemic waves
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influenza etiology
- influenza virus
- ssRNA virus, segmented
- three genera exist
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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
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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
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influenza C
- 7 gene segments
- 9 viral proteins, HEF unique
- humans and swine
- antigenic drift only,
- mild disease without seasonality
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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
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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
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Influenza A genetics
- 8 RNA segments allow high frequency of reassortment during mixed infection
- uses antigenic variation to avoid immune system
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antigenic drift
- accumulation of mutations within the antibody binding sites of HA and NA
- slow, subtle process involving small changes
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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
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mixing vessel hypothesis
- animal co-infected with strains from different animals allows reassortment of RNA segments
- direct transmission is also possible
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influenza nomenclature
virus type / geographic origin / strain number / year of isolation (virus subtype)
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Influenza A occurrence
only infectious disease in developed countries that causes alteration of death rate (increases in winter)
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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
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Influenza A transmission
- respiratory route by droplet infection - all sizes
- infected humans have high virus concentration in secretions
- air travel important in international spread
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Influenza A temporal variation
- marked seasonal variation in temperate climates
- occurs year round in tropical climates
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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
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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
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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
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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
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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
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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
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Influenza A treatment
- mostly only palliative - rest, hydration, medicines without aspirin
- antivirals for high risk patients
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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
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Influenza A vaccines
- WHO uses information from network of countries to decide on that seasons vaccine formulation
- new vaccine every year with 3 viruses
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Avian Influenza background
- 15 subtypes of influenza virus infect birds
- high pathogenic H5N1 occasionally infects humans - must acquire from bird
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Avian Influenza epidemiology
- epidemic killed chickens, some human cases
- china is considered epicenter
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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
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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
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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
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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
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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
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H1N1 vs. H5N1
H1N1 - easily spread, rarely fatal
H5N1 - spreads slowly, often fatal
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H1N1 diagnosis, treatment and prevention
- RT-PCR
- resistant to M1 inhibitors, neuraminidase inhibitors
- prevention same as seasonal influenza
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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
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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
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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
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