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which influenza strains affect humans only? which ones affect both humans and animals?
- human only: influenza B
- both: influenza A
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what are two major surface antigenic glycoproteins?
- hemagglutin (HA) 80%: attaches virus to respiratory epithelial cells, virus enters cytoplasm and replicates
- neuraminidase (NA) 20%: releases newly produced virus particles from host to infect other cells (causes contagious-ness)
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M2 protein is found in which influenza strain?
influenza A only
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how is influenza A named?
according to particular antigenic determinants of HA and NA
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how many HA subtypes and NA subtypes are there?
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how is influenza B categorized?
not categorized into subtypes but separated further based on antigenic similarities
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what is the primary reservoir for influenza A?
what kind of disease does influenza A cause?
- wild birds
- causes mild or asymptomatic disease
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Define antigenic drift. does it have cross protection? which influenza undergoes antigenic drift?
- due to mutations in the genes encoding glycoproteins HA and NA resulting in new strains
- occurs during viral replication
- pre-existing antibodies will cross-protect if slight antigen drift. however, if major antigenic drift, strain will cause an infection. could lead to epidemic
- both A and B undergo drift but B less rapidly.
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what is cross protection?
protected against reinfection by that same virus strain or other strains with similar antigen composition
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define antigenic shift. when does it occur? what is the biggest cause of antigenic shift? is there cross protection? what could antigenic shift lead to?
- results in a NEW subtype of the virus.
- sudden change in antigenicity
- recombination of the influenza genome
- occurs when a cell becomes simultaneously infected by 2 different strains of type A influenza
- mixing of strains that can infect birds, pigs and humans is thought to be responsible for most antigenic shifts.
- no cross protection
- pandemic
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is pandemic predictable?
nope
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what three criteria defines pandemic?
- development of a new influenza subtype
- ability of the virus to infect and cause serious disease
- sustabinable transmissibility from human to human
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Does avian influenza H5N1 have risk in US? how does it transmit? how do you treat?
- no
- from chicken to human
- oseltamivir 75mg BID or 150mg BID longer duration
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how does swine influenza (novel H1N1) transmit?
human to human
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how do avian, human and swine influenza trasmit to human?
- they bind to molecules found in the human airway
- sialic acid linked to galactose (SAa2,3Gal, SAa2,6Gal)
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where does human virus bind to during tramission? where is the binding site located? does it transmit easily?
- SAa2,6Gal
- found mainly in epithelial cells in paranasal sinuses, pharynx, trachea, bronchi
- viral replication can be easily spread by coughing and sneezing swine influenza viruses that generally bind to SAa2,6Gal receptors
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where does avian virus bind to during transmission? where is this located? how is the transmissability?
- SAa2,3Gal
- located more often in alveolar cells (lungs)
- this is more restrictive location so harder for human-human transmission.
- but once you get avian flu, it will be very serious.
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seasonal transmissibility
how long can droplet travel?
how long is viral shedding?
how long is the incubation period?
how long does it take to resolve?
how long do cough and malaise persist up to?
- droplet spread <6 feet
- viral shed 5-10 days or longer
- incubation period 1-4 days
- resolves 3-7 days
- cough and malaise persist up to 2 weeks
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how do you diagnose seasonal influenza?
- NP swab (just look for antigen for A and B)
- rapid test - 15 min results test for A and B (but low sensitivity of 20-70%)
- RT-PCR (has better sensitivity so we wait for this even when the rapid test results negative)
- serology is not recommended (takes too long)
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what are avian influenza symptoms?
- diarrhea, vomit, abdominal pain
- rapid deterioration (higher mortality than seaonal)
- chest pain, bleed from nose/gum
- fever, cough, soar throat, myalgia
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what are seasonal influenza symptoms?
- exacerbation of underlying medical conditions (i.e. asthma, COPD, cardiac disease)
- fever, chills, headache, myalgia, lethargy, rhinorrhea, sore throat
- pediatric: OM, NV
- viral and bacterial pneumonia (mortality!!)
- sinusitis
- OM
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what are the months for immunization?
october to april
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what does seasonal immunization vaccine contain?
what does 2010-2011 vaccine contain?
- 2 influenza A strains and 1 influenza B strain
- A (H1N1), A (H3N2) and B (victoria)
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which route is TIV administered?
IM
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which age group can receive TIV?
>6mo
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which age group can receive LAIV?
- 2-49 yo
- healthy nonpregnant
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does LAIV cause flu?
- NOPE
- however potential to cause mild signs or symptoms related to vaccine virus infection (i.e. rhinorrhea, nasal congestion, fever, sore throat)
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what is the dose for LAIV?
0.2ml divided equally btwn each nostril
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LAIV contains thimerosal. T or F
nope
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does immunized patients shed virus after receiving LAIV?
- yes
- so do not give to immunocompromised patients
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which group should you NOT give LAIV to?
- medical risk factors
- immunosuppressed
- close contacts of immunosuppressed persons a protected environment (stem cell transplant, HIV)
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what are underlying medical concerns that restrict patients from receiving LAIV?
- chronic pulmonary (asthma)
- CV (except htn alone)
- renal and hepatic
- hematological (sickle cell disease)
- metabolic disorder (DM)
- neurologic disorder
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age group for Fluzone
- depend on how it is available
- > 6 months
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age group for Fluvirin
> 4 years
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age group for Fluarix
> 3 years
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age group for FluLaval
> 18 years
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age group for Afluria
> 6 months
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age group for Fluzone high dose
> 65yo
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what are contraindications for TIV? if you have the contraindications, what should you do?
- anaphylactic hypersensitivity to eggs or components of influ vaccine
- may use chemoprophylaxis and antiviral therapy
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what is a precaution for TIV?
GBS within 6 wk following a previous dose of influ vaccine
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what are contraindications for LAIV?
allergic reaction to lactose
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what are precaution for LAIV?
- bronchospasm (concern with asthma, COPD)
- neuropsychiatric
- high risk underlying medical condition
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should you give influ vaccine if you have asthma, COPD?
- yes
- but you cannot use LAIV
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what should you do if patient has a prior hx of GBS?
- may want to avoid influ vaccine for those not at high risk for severe influenza complications
- may consider influ antiviral chemoprophylaxis
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when should antiviral be initiated?
must be taken within 48 hours of onset of symptoms or exposure to an index case to be effective
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What are adamantane medications?
what is the MoA? why is this important?
compare the two available agents.
what is the problem with this class?
- amantadine, rimantadine
- inhibit M2 ion channel protein activity, effectively block viral uncoating and reduce infectivity --> thus only active against influenza A
- rimantadine has fewer CNS AE
- widespread resistance
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what are neuraminidase inhibitor medications?
what is the MoA?
which virus are they effective against?
- oseltamivir, zanamivir
- interfere with budding of newly formed influenza virus from infected host cells; prevent further infectivity of host cells; prevent spread of infection in the resp tract
- effective against influ A and B viruses
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is oseltamivir an active drug?
it is a prodrug requiring ester hydrolysis for conversion tot he active form occurring in liver
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how is oseltamivir available?
- 30, 45, 75 mg cap
- 300mg power for oral susp reconstituted to 12mg/mL
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what is the age restriction for oseltamivir?
treatment and prophylaxis for >1yo
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what is the treatment dose for oseltamivir?
- >13yo: 75mg BID x 5 days
- >15kg: 30mg BID
- 15-23kg: 45mg BID
- 23-40kg: 60mg BID
- 40-75kg: 75mg BID
- renal impair (10-30ml/min): 75mg QD
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what is the prophylaxis dose for oseltamivir? when do you start? how about during outbreaks?
- start within 2 days
- >13 yo: 75mg daily x 10 days at least
- 15kg: 30mg daily x 10 days
- 15-23kg: 45mg daily x 10 days
- 23-40kg: 60mg daily x 10 days
- 40-75kg: 75mg daily x 10 days
renal impairment: 75mg every other day or 30mg daily
during outbreaks: 6 weeks for immunocompetent and 12 weeks for immunocompromised
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how should LAIV and antiviral medications be administered if they were to be used together?
LAIV should not be administered within 2 weeks before or 48 hours after oseltamivir
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what are side effects of oseltamivir?
- CNS (more in kids)
- NV
- LFT abnormality
- aggravation of DM
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what is the age recommendation for zanamivir?
- prophylaxis: >5 yo
- treatment: >7 yo
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when is zanamivir NOT recommended?
- treatment/ppx for patients with underlying airway disease (i.e. asthma, COPD)
- ppx in NH patients
- pregnancy category C
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what is the treatment dose for zanamivir?
- 10mg BID x 5 days
- no renal adjustment
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what is the ppx dose for zanamivir? how about during outbreaks?
- 10mg daily x 10 days
- during outbreak: 10mg daily x 28 days
- no renal adjustment
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what are side effects of zanamivir?
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what is antiviral prophylaxis recommendation?
- post exposure: person's risk for influ complications
- type and duration of contact
- start within 48 hours
- NOT a substitue for vaccine
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what is antiviral treatment recommendation?
- for all persons with suspected or confirmed influenza
- - with severe complicated or progressive illness
- - requiring hospitalization
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what is antiviral treatment recommendation for pregnant women?
- antiviral with tylenol for fever
- oseltamivir is better b/c more data
- zanamivir has limited systemic absorption but resp complication issue
- same dosing as non-pregnant
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