Clin Med - Influenza Flashcards
Background history
- Spanish flu pandemic of 1918
- 3% of worlds population died - more than entire loss of WWI
- more deaths than all 4 yrs of Bubonic plague
- US population set back 10 yrs
influenza definition
- infection disease caused by the RNA viruses of the Orthomyxoviridae (affects mammals and birds)
- 3 genera: A; B; C
general epidemiology of the flu
- 3-5 million cases yearly
- 250k-500k deaths worldwide
- 5-20% of US pop. gets flu: 200k hospitalized, 35k die
epidemiology specific to OK
- 2017: 2150 hospitalizations, 68 deaths
- 2018: 253 deaths
infectivity/spread of influenza is primarily through?
- aerosol transmission
- lesser transmission through inanimate vectors and contact (hand shaking etc)
when is a person w/ the flu most infective?
-2nd and 3rd days after infection
how long does infectivity of the flu last?
about 10 days
virus inactivation
- can survive indefinitely if frozen
- inactivated at 132 degrees F for a min. of 60 min
- or by pH <2
influenza A facts
- genus has 1 species
- wild aquatic birds are natural host
- most virulent of all 3
- causes most severe dz
- seasonal
- present every year in epidemic and often pandemic outbreaks
how are the flu types are classified
- by their serotypes
- based on Ab reaction to the virus (antigenicity of HA and NA)
influenza virus structure
- all 3 types are similar
- viral envelope w/ 2 glycoproteins wrapped around a central core
- central core contains viral RNA genome and proteins
haemagglutinin (HA)
- one of the 2 surface glycoproteins on viral structure
- allows the virus to go inside of the host cell and begin to replicate
neuraminidase (NA)
- one of the 2 surface glycoproteins
- allows virus to break out of the cell
confirmed human** serotypes of influenza A causing pandemics
- H1N1 (Spanish and 2009 flu)
- H2N2 (Asian flu)
- H3N2 (Hong Kong flu - genetic drift from H2N2)
- H5N1 (current threat - bird flu)
non-human subtypes of influenza A
- H16N1 (black headed gulls)
- H17N1 (fruit bats)
- H7N7 (highly mutanigenic)
antigenic drift
- slow change over longer period of time d/t small mistakes in replication
- usually influenza B
- this is why we can keep some sort of immunity to flu B usually
antigenic shift
- large mutations over a very short period of time
- usually flu A
- this is why we have pandemics and why it’s hard to develop vaccines
What is the common link for all types of influenza A?
birds
influenza B facts
- only 1 species
- exclusively infects humans
- mutates much slower (2-3 times slower) than flu A
- less genetically diverse
- only 1 serotype but many strains
- usually some immunity acquired at an early age
influenza C
- 1 species
- very mild, rarely pandemic
- only specialty labs do testing
How are viruses IDd
by their HA and NA
influenza trends in 2017 and 2018
- predominately A for first 10 weeks then evenly split b/w A and B
- of the A viruses:
2017: 88% H3N2
2018: 90% H3N2 - B had little mutation
H1N1 typically affects what area?
- upper airways
- to a lesser extent the lungs
H5N1 typically effects what area?
- lungs
- less upper airway involvement
- more fatal b/c associated w/ pneumonia but not as easily transmitted
What is responsible for determining where in the respiratory tract a strain of flu will bind?
HA proteins
Which strains are easily transmitted b/w people?
those that have HA proteins that bind to receptors in the upper respiratory tract
what pathophysiology may help explain why healthy people die of the flu?
- cytokine storm/cascade (>150 inflammatory mediators)
- there is an over reaction of the immune system
- essentially produces ARDS, airways become constricted
- body initiates inhibitory feedback so then there’s no response at all
Influenza H5N1 frequently cause what type of secondary problem and why?
- viral pneumonia characterized by diffuse alveolar damage and interstitial fibrosis
- the virus replicates in the alveoli causing them to rupture
clinical presentation of the flu
- ***Abrupt onset of fever
- chills, rigors, shivering
- cough
- congestion/coryza/rhinorrhea
- body aches, myalgia, arthralgias
- fatigue
- sore throat
- HA
- flushing
- GI sxs (more predominant in children)
What distinguishes the flu from a cold?
- abrupt and sudden onset
- extreme fatigue
- lack of GI sxs except in children
influenza vaccine
- efficacy varies but always recommended for high risk groups
- usually trivalent, some quadrivalent
- inactivated - can’t get flu from it
- live attenuated vaccine is available (intranasal) - can get flu but very rare
What strain is hard to produce a vaccine for?
H5N1 - lysed eggs
antiviral adamantine class
- amantadine and rimantadine
- M2 protein inhibitor
- blocks M2 ion channels to prevent virus from infecting cells
adamantine antiviral effectiveness over the different flu types
- some effect against flu A, though resistance is rising quickly
- no effect against flu B - B does not posses M2
Neuraminidase inhibitors
- Oseltamivir (Tamiflu), Zanamivir (Relenza), Peramivir (Rapivab)
- they prevent viruses from being released from infected cells and subsequently infecting further cells
What is the official CDC recommendation for antiviral treatment of influenza?
-antiviral tx as early as possible for pts w/ confirmed or suspected flu who have severe, complicated or progressive illness; require hospitalization; or who are at high risk for serious flu-related complications
What is “high risk” for getting serious complications from the flu?
- asthma
- blood disorders
- chronic lung dz
- endocrine disorders
- extreme obesity
- heart dz
- kidney/liver disorders
- metabolic disorders
- neuro conditions
- people younger than than 19 on long term aspirin
- immunocompromised
other people at high risk from the flu
- adults 65 or older
- children younger than 5 but especially younger than 2
- pregnant women or women up to 2 weeks after end of pregnancy
- american indians and Alaska natives
Tamiflu
- use caution in evidence
- cochrane review says not significant clinical evidence and possible side effects
- review this in slides if needed
NNT cure of influenza using Tamiflu
- there is no NNT for cure
- NNT for prophylaxis: 13
- NNH for vomiting: 14
- NNH for pysch disturbances in children: 19
Peramivir (Rapivab)
- single IV dose, bio-active for 5 days
- cost to hospital = $950 / dose
- trial data not released for public review (trial was terminated)
- official FDA release showed lessening of sxs by 21 hrs
- not FDA approved for serious flu in patients requiring hospitalization
What is the new tx being researched for flu?
- laninamivir octanoate
- NA inhibitor - still in trials
- appears to have fewer side effects, lowers viral load and better inhibition of transmission
True flu treatments
- anti-pyretics
- pain meds
- fluids
- rest
- stop smoking
- treat/avoid pregnancy ladies
- hand hygiene
- seclusion
- hospitalization
- AVOID abx
What strongly determines the virulence of a flu strain?
HA proteins
What do complications from flu generally occur from?
-d/t inhibition of stress hormones couples w/ massive viral replication and inappropriate immune response (cytokine storm)
Best offense is a good defense strategy
- annual flu vaccine
- hand washing
- covered coughs/sneezes
