2. Influenza

• caused by H1N1 subtype
• disproportionate mortality among infants and young adults
• 3 pandemic waves

• influenza virus
• ssRNA virus, segmented
• three genera exist

• 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

• 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

• 7 gene segments
• 9 viral proteins, HEF unique
• humans and swine
• antigenic drift only,
• mild disease without seasonality

• 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

• 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 RNA segments allow high frequency of reassortment during mixed infection
• uses antigenic variation to avoid immune system

• accumulation of mutations within the antibody binding sites of HA and NA
• slow, subtle process involving small changes

• replacement of HA or NA with a novel subtype from waterfowl reservoir
• usually will result in pandemic
• fast, drastic process involving large changes

• animal co-infected with strains from different animals allows reassortment of RNA segments
• direct transmission is also possible

virus type / geographic origin / strain number / year of isolation (virus subtype)

only infectious disease in developed countries that causes alteration of death rate (increases in winter)

• 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

• respiratory route by droplet infection - all sizes
• infected humans have high virus concentration in secretions
• air travel important in international spread

• marked seasonal variation in temperate climates
• occurs year round in tropical climates

• 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

• 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

• 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

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

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

• clinical - not definitive
• tissue culture of throat washings
• reverse transcriptase PCR
• serology
• rapid influenza diagnostic tests - look for antigen using ELISA or immunochomotography

• mostly only palliative - rest, hydration, medicines without aspirin
• antivirals for high risk patients

• 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

• WHO uses information from network of countries to decide on that seasons vaccine formulation
• new vaccine every year with 3 viruses

• 15 subtypes of influenza virus infect birds
• high pathogenic H5N1 occasionally infects humans - must acquire from bird

• epidemic killed chickens, some human cases
• china is considered epicenter

• 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

• 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

• new influenza virus of swine origin
• has similarities to avian, human and swine viruses - chimeric virus, picked up from different sources

• 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

• 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

H1N1 - easily spread, rarely fatal

H5N1 - spreads slowly, often fatal

• RT-PCR
• resistant to M1 inhibitors, neuraminidase inhibitors
• prevention same as seasonal influenza

• same type
• novel viruses with little immunity in population
• both began in spring
• highest morbidity and mortality in young population

• enhances expression of antimicrobial peptides by monocytes and neutrophils
• suppressive effect on macrophages and therefore inflammatory response
• mostly suppressive effects on adaptive immunity

• 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