Influenza Important Flashcards
What are the more common ILI
- *Influenza A and B are most common
- Some others include influenza C, parainfluenza virus, respiratory syncytial virus, mycoplasma pneumoniae
How is influenza spread
- Inhalation of droplets
- Direct and indirect contact with contaminated respiratory secretions
What is the incubation period for influenza
- 1.5-2 days (range between1-4 days)
How long is influenza spread for
- Adults can spread virus for 1 day before symptoms and 5 days after onset
- Children/immunocompromised can be infectious longer
What is the biology of virus
- They are a negative strand RNA viruses that are covered with a protective envelope
- Each RNA segment is encapsulated by nucleoproteins-> this forms a ribonucleotide nucleoprotein complex (RNP)
- The lipid envelope is covered in a haemagglutinin (HA), neuraminidase (NA) and matrix 2 (M2) ion channels (the antigenic portion)
What are the steps in invasion and replication of influenza
- Step 1
- HA molecule starts infection through binding to receptors on host cells within the respiratory tract
- Endocytosis brings the virus into the cell
- Step 2
- Viral RNA (vRNA) along with other things are released into the cytoplasm
- Transported into the nucleus
- Step 3/4
- Complementary (+) sense vRNA is transcribed and may be exported into the cytoplasm to get translated or stay in the nucleus
- Step 5
- New viral proteins (HA, NA…) are secreted through the golgi apparatus onto the cell surface or may be transported back to the nucleus to form new viral genome particles
- Step 6
- Viral RNA and important proteins leave nucleus and bulge out of the host cell membrane which is coated in viral surface proteins (HA, NA)
- Step 7
- The mature virus buds off from the cell
- After release of the new viruses the cell dies
What is the most important step in invasion and replication of influenza in regards to drugs
- Step 7
- Drugs inhibit this step so the virus cant infect other cells
What does the H and N in influenza mean
- H= hemagglutinin
- N= neuraminidase
What are signs and symptoms of influenza
- Sudden onset
- High fever (chills first) for 7-10 days
- Cough (2 weeks)
- Sore throat
- Myalgias and fatigue (can be weeks)
- Can include headache, loss of appetite, fatigue, coryza, NVD (in kids)
What kind of infection is influenza
- Acute respiratory tract infection
What are the respiratory complications of influenza
- Pneumonia (most common): viral or secondary bacterial
- Can make chronic lung disease worse
- Croup/ bronchiolitis (kids)
- Otitis media
What are non respiratory complications of influenza
a) Exacerbation of comorbid conditions
- Febrile seizures
- Reye syndrome
- Encephalitis
- Guillain barre syndrome
- Myositis (inflammation of muscle)
- Myocarditis (inflammation of heart muscle)
Patients with what conditions have a higher risk of complications with influenza
- Heart disease
- Lung disease
- Diabetes
- Renal disease
- Rheumatologic disease
- Dementia
- Stroke
- Pregnant (3rd trimester is worst), extremes of age, immunosuppressed
What is the best way to prevent influenza
- Vaccine
What does the WHO recommend be included in the vaccine
- 3 strains be included in the trivalent vaccine being 1 influenza A (H1N1), one influenza A (H3N2) and one influenza B
What strains are included in the trivalent/ quadrivalent vaccines (based on the WHO)
a) Trivalent
- Influenza A: H1N1
- Influenza A: H3N2
- One influenza B
b) Quadrivalent
- Same 3 as above
- One more influenza B (from lineage that is not included in trivalent)
How many lineages of influenza B is there
2
What does IIV3 mean
- Inactivated influenza vaccine trivalent
What does IIV4
- Inactivated influenza vaccine quadrivalent
What does LAIV3 mean
- Live attenuated influenza vaccine trivalent
- Not available in canada
What does LAIV4 mean
- Live attenuated influenza vaccine quadrivalent
Available but not publicly funded
What does IIV3-SD/ IIV4-SD refer to
- Standard dose, unadjuvanted IM administered
what does IIV3-Adj refer to
- Adjuvanted; IM administered
What is the benefit of an attenuated vaccine
- Live vaccine can give you disease while attenuated is a weaker version
Can you get influenza from an inactivated vaccine
- No you cant
What does IIV3-HD refer to
- High dose, unadjuvanted; IM administered
What does IIV4-HD refer to
- High dose, unadjuvanted; IM administered
What does IIV4-cc refer to
- Standard dose, unadjuvanted, IM administered, cell culture based (usually cultured birds or ducks)
What does RIV4 refer to
- Recombinant protein; IM administered
What were the strains for influenza in quadrivalent vaccines for 2022-2023
- Influenza A (H1N1)
- Influenza A (H3N2)
- Influenza B (Victoria lineage)
- Influenza B (Yamagata lineage)
Explain the IIV4-SD vaccines
- Afluria Tetra (>5 years) Flulaval tetra (>6 months) Influvac tetra (>6 mounths
- It is unadjuvanted; has 15 ug HA per strain
- 0.5mL dose through IM
Explain the IIV4-HD vaccine
- High dose
- Fluzone High dose (>65 years)
- 50ug HA for a 0.7mL dose
Explain the IIV4-cc vaccine
- Flucelvax (>6 month)
- Unadjuvanted
- 15ug HA per strain
- 0.5 ml dose through IM
Explain the RIV4 vaccine
- Supemtek (>18 years)
45ug; 0.5 mL dose through IM
Explain the LAIV4 vaccine
- Flumist quadrivalent (2-59 years)
- Given as 0.1 mL per nostril
- Live attenuated
Explain the characteristics of the IIV-Adj influenza vaccine
- Trivalent
- Adjuvant MF59
- Fluad pediatric (6-23 months): 7.5 ug HA per strain as a 0.25mL dose through IM
- Fluad for adults (65<): 15 ug HA per strain as a 0.5mL dose through IM
What does an adjuvant agent do within a vaccine
- It increase the immune response to the vaccine
What are the two ways of producing vaccines
a) Split virus vaccine
- Virus has been disrupted by a detergent
b) Subunit virus vaccine
HA and NA are further purified by removal of other viral components
Explain the characteristics of the FluMist quadrivalent influenza vaccine
- Live attenuated, quadrivalent (2-59 years), intranasal spary; 0.1ml per nostril)
- Common side effects: nasal congestion and runny nose
- don’t want to give it to immune compromised as it is live so the individual needs its immune system to keep the virus at bay
- Not recommended for HCW
What does effectiveness of the influenza vaccine depend on
- Age
- Immunocompetence
- Match of vaccine to the circulating virus
How is the vaccine beneficial to elderly and kids (also people with COPD)
- Elderly: decreases incidence of pneumonia, hospital admissions and death
- Kids: decrease mortality in older adults as less risk of the child bringing home the virus
- COPD: reduces exacerbations
Once the influenza vaccine is administered what occurs (when protection occurs)
- As soon as it is administered it results in production of IgG antibodies to the viral HA and NA
- Protection occurs in about 2 weeks and lasts about 6 months (in elderly only 4 months)
If the vaccine does not protect all patients from disease what is the benefit to it
- Decrease severity of illness
- Decrease risk of death
- Decrease rate of hospitalization and pneumonia
What are the people at high risk of complications or hospitalization who it is recommended to get the vaccine
- Pregnant women
- Cardiac or pulmonary disorders
- Diabetes mellitus (other metabolic diseases too)
- Cancer, immune compromising conditions
- Renal disease
- Anemia/ hemoglobinopathy
- Neurologic/ neurodevelopment conditions
- Morbid obesity (BMI >40)
- Kids on long term ASA treatment
- Age >65
- Children 5-59 months
- Indigenous
- Residents of nursing homes/ chronic care facilities
- People capable of giving flu to those at high risk
- Providing essential community services
- In direct contact during culling operations with poultry infected with avian influenza
What are the dosing recommendations for influenza
- First time children (<9) get 2 doses (min interval of 4 weeks)
- Everyone else gets a single dose
- NACI recommends full doses to everyone (even kids)
What are adverse effects of the influenza vaccine
- Soreness at injection site (up to 48 hours)
- Fever, malaise, myalgia (starts in 6-12 hours and lasts up to 2 days): an immune response and occurs in about 12% of people
- Oculo-respiratory syndrome (ORS): benefits outweigh the risk and not a CI to future vaccinations
What are contraindications to the influenza vaccine
- Anaphylaxis to previous influenza vaccine
- Anaphylactic allergy to a component of the virus (except egg allergy)
- Developed Guillain- Barre syndrom within 6 weeks of previous vaccine
- Has a serious acute illness (wait till symptoms relieve)
If an person has a minor or moderate acute illness should they get the vaccine
- Yes do not delay
What are strategies to increase use of influenza vaccine
- Standing order policies (hospitals, LTC)
- Opt out rather then opt in
- At discharge from hospital/ ER
- Promotions
- Increase accessibility
- Collaborate with HCP
What is the role of the pharmacist in regards to influenza vaccine
a) Patient education
- Vaccine doesn’t cause the flu
- Benefits
- Symptom treatment
b) Get immunized
c) Host clinics
d) Identify patients who are at higher risk and get into contact
When are neuraminidase inhibitors (NA inhibitors) used
- In prevention and treatment of influenza
What are NA inhibitors effective against
- Influenza A and B
What is the MOA of NA inhibitors
Bind the influenza virus neuraminidase (NA) active site -> stops sialidase activity and release from cell
What are the NA inhibitors on the market
- Oseltamivir (Tamiflu)
- Zanamivir (Relenza)
What will NA inhibitors do for the patient
- Decrease severity of symptoms
- Cause resolution of symptoms up to 1.5 days quicker
- May reduce hospitalization in high risk patients
- Oseltamivir may reduce mortality
What are the NA inhibitors on the market
- Oseltamivir (Tamiflu)
- Zanamivir (Relenza)
What will NA inhibitors do for the patient
- Decrease severity of symptoms
- Cause resolution of symptoms up to 1.5 days quicker
- May reduce hospitalization in high risk patients
- Oseltamivir may reduce mortality
Explain characteristics of Zanamivir (Relenza)
- A disk haler
- Treatment and prophylaxis in patients >7 yo
- 10-20% systemically absorbed (goes to lungs so less systemic side effects)
- Better in vitro activity against influenza B in comparison to oseltamivir
What is the treatment plan of Zanamivir (Relenza)
- Inhale 10mg (2 inhalations) BID for 5 days
- Must have started within 48 hours of symptoms
- Can be used longer for those with severe immunodeficiency who remain symptomatic
What is treatment with Zanamivir (Relenza) usually indicated for
- Those with severe ilness
- Those most likely to develop complications or die early
What is the prophylaxis treatment plan of Zanamivir (Relenza)
- Inhale 10mg od for 10 days
- Caution with patients with lung disease
- Need to counsel on inhaler use
What are the side effects of Zanamivir (Relenza)
- Many were reported but no difference btw placebo/ drug (headache, cough, sore muscles)
- Some reports of nightmares, delirium, abnormal behaviour (in kids): high fever or complications from influenza could have caused this
- Not much concern of side effects
When is Oseltamivir (Tamiflu) used
- Treatment and prophylaxis in patients >1 yo
- Must begin within 48 hours of symptoms
What formulations is Oseltamivir (Tamiflu) available in
- A 30,45, 75mg capsule
- 6 mg/ml suspension
What is treatment plan of Oseltamivir (Tamiflu) (adults)
- Adults (>13yo): 75 mg BID for 5 days
- It is age/ weight dosing in pediatrics
- Must adjust dose based on renal function: reduce dose with ClCR < 60 mL/min)
What is the prophylaxis treatment plan of Oseltamivir (Tamiflu) (adults)
a) Adults: 75mg daily for 10 days unless a child or >65 yo then used for 14 days
What is the treatment plan and prophylaxis plan using Oseltamivir (Tamiflu) in kids
- <15kg: 30mg
- 15-23kg: 45mg
- 23-40kg: 60mg
- > 40kg: 75 mg
a) BID for treatment
b) OD for prophylaxis
What are the adverse effects with Oseltamivir (Tamiflu)
- Nausea/ vomiting (take with food to minimize)
- Headache
When does antiviral resistance occur
- Most common in patients who are immunocompromised and with prolonged therapy
- Rare with zanamivir
- Uncommon with oseltamivir but seen
When deciding who should be treated with an antiviral what should you consider
- Severity of symptoms
- Risk factors/ comorbid medical conditions
- Interval between start of illness and start of antiviral treatment (wont consider is outside of 48 hours and goal is within 12 hours)
When should prophylaxis with antiviral drugs be used
- Seasonal prophylaxis is not practical
- Post exposure prophylaxis (PEP): is effective if stated within the first 48 hours of exposure to influenza, early treatment is preferred
What is the use of prophylaxis using antiviral agents in influenza (in institutions/ closed facilities)
a) Control of influenza A/ B outbreaks within high risk residents of institutions or closed
- Give to all residents who arent ill
- Give to unvaccinated staff
- Use until outbreak is over (min of 8 days after start of last case)
- Those ill with flu receive antiviral treatment
- Combine with vaccination
What is the treatment options for influenza symptoms
- Analgesics/ antipyretics
- Cough suppressants
- Sore throat
- Hydration
- Bed rest
- Stay home (to avoid spread)
