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Influenza Flashcards

1
Q

Characteristics (4)

A
  1. ssRNA, enveloped
  2. Helical nucleocapsid
  3. 8 sement genome
  4. Viral family:
    Orthomyxoviridae
    Influenza A, B, C
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2
Q

Influenza Surface Antigens (2) spikes

A

H (Hemagglutinin):
Binds sialic acid/promotes viral ENTRY into host cell

N (Neuraminidase):
Promotes progeny VIRION RELEASE

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3
Q

Antigenic Drift

A

Minor changes based on random POINT mutations of H or N genes

One virus has certain H that binds to antibody, can block interaction of virus with that sialic acid receptor

Change in AA sequence via point mutation, change of tip of H protein, virus now free to interact with receptor

Frequency: human > equine/swine > avian

(Avian is causing more recent pandemics)

Causes local epidemics

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4
Q

Antigenic Shift

A

Reassortment of viral genome segments (H1, H2, H3, N)
Major change in H and sometimes N

“Recycling” of older viruses

“New” viruses to which the population has no immunity

Causes influenza A pandemics (all parts of the world, more deadly)

Often when you hear about a flu coming from an animal population to human hosts
Adaption of animal viruses (jumping the species barrier)

Ex. swine flu. Deaths in children because elder adults likely already been exposed to similar types of flu in their lives

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5
Q

What are Pandemics characterized by?

A
  1. Higher attack rate
  2. Different age distribution
  3. Occur outside window of seasonality
  4. Multiple waves
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6
Q

Transmission

A

Via large droplets
Via small particle aerosols person to person

Requires close contact; can only travel ~6 feet

Possible to transmit via small droplets, (from fomites) but less common

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7
Q

Clinical Symptoms

A

Fever 104-106, chills, headaches, myalgias (involve extremities and long back muscles), malaise (discomfort), anorexia

In children: calf muscle myalgia

Persist for 3 days (fever as well)

Respiratory symptoms can last much longer:
Dry cough
Pharyngeal pain
Nasal congestion
Discharge
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8
Q

Pulmonary Complications of Influenza

A
  1. Primary influenza viral pneumonia (produce cough, infiltrates)
  2. Pneumonia secondary to bacterial infection
    Streptococcus pneumoniae
    Staphylococcus aureus
    Streptococcus pyogenes
    Haemophilus influenzae
  3. Croup (children)
    Harsh barking cough, hypoxia
    More severe than parainfluenza
  4. COPD exacerbation in adults
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9
Q

Non-pulmonary complications of influenza

A
  1. Myositis in children; may interfere with walking
  2. Cardiac: Toxic shock syndrome, likely secondary to change in colonization and replication of staph
  3. Guillain-Barre: only with influenza A; rare
  4. Transverse myelitis (inflammation of both sides of spinal cord)
  5. Encephalitis (inflammation of the brain)
  6. Reye syndrome (with use of Aspirin in children)
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10
Q

RT-PCR

A

For acute phase: virus detection in throat swabs, nasopharyngeal swabs, sputum

1-24 hours

High sensitivity and specificity

Highly recommended

Can differentiate between A and B

Multiplex PCR: looks for other respiratory illnesses too

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11
Q

Rapid Antigen Detection (EIA) (RIDTs)

A

For acute phase: virus detection in throat swabs, nasopharyngeal swabs, sputum

Immunologic or enzymatic techniques

10-20 minutes
Used in ERs and PCPs

Sensitivity around 62%, so lots of false negatives
High specificity

Some can test between A and B

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12
Q

Shell viral culture

A

48-72 hours

Moderately high sensitivity and specificity

Can confirm screening tests/be helpful in public health surveillance

Not useful in clinical management

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13
Q

Serologic tests (hemagglutinin, ELISA, complement-fixation, neutralization)

A

Variable time frame

Available only in reference labs

Not useful for timely clinical management

Recommended only for retrospective diagnosis, survelliance, or research

Acute vs. convalescent antibody titers (looking for standard 4 fold increase)

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14
Q

Rimantadine

A

Blocks viral uncoating by blocking the M2 proton channel (H+ flow acidified endosome)

Administered orally, treats influenza A

CNS effects, GI intolerance

Best if administered within 48 hours

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15
Q

Amantidine

A

Blocks viral uncoating by blocking the M2 proton channel (H+ flow acidified endosome)

Administered orally, treats influenza A

Best if administered within 48 hours

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16
Q

Oseltamivir (Tamiflu)

A

Pro-drug, activated in the gut and liver

Inhibits functioning of influenza virus neuraminidase, preventing viral particle from being released affecting neighboring cells (virus shedding)

Administered PO, treats A and B

Well tolerated, some nausea and vomiting

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17
Q

Zanamivir (Relenza)

A

Inhibits functioning of influenza virus neuraminidase, preventing viral particle from being released affecting neighboring cells (virus shedding)

Inhaled, treats A and B

Bronchospasm in asthmatics, nausea, diarrhea

18
Q

Peramivir (Rapivab

A

Inhibits functioning of influenza virus neuraminidase, preventing viral particle from being released affecting neighboring cells

IV, treats A and B

Can cause diarrhea

19
Q

Influenza Prophylaxis

A

Not a subsititution for vaccines

Given when person has been in close contact with someone who has been probably expected/confirmed with influenza if high risk for complication

If <48 hours since last contact
If contact within 24 hours of infectious period

Aka someone who has cared for person, or been face to face

Zanamivir/Oseltamivir

20
Q

Who is at high risk for complications?

A
  1. Chronic pulmonary/CVD (except hypertension)
  2. Renal dysfunction
  3. Native american/alaska natives
  4. Children <19 on aspirin therapy
  5. Pregnant women or within 2 weeks of delivery
  6. Immunodeficiency (diabetes, cancer, transplant)
  7. Hemoglobinopathies (Sickle cell disease)
  8. Neurologic conditions that compromise handling of respiratory secretions
  9. Morbid obesity
  10. Nursing homes
  11. Kids under 5
21
Q

Early antiviral treatment

A
  1. Can shorten duration of fever/illness symptoms
  2. May reduce risk of complications
  3. Reduces death in hospitalized
  4. Shorten hospital stay in children
  5. Clinical benefit when administered EARLY

Recommended as early as possible for:
Hospitalized
Severe, complicated illness
High risk for complications

22
Q

Recombinant technology

A

Insect cells

Currently the only egg-free vaccine production in market
Important for allergies

Flublok: recombinant H proteins purified from tissue culture cells

> = 18years

23
Q

Vaccination for special population

A

Adults >=65: high dose
Kids 6mo - 8 years: 2 doses if first vaccination
High risk for complications (HIV): high dose

24
Q

Respiratory Syncytial Virus (RSV)

A

Most common cause of respiratory death in young children and those 65+

Looks like the flu

25
Relative measure of effect
(1-odds ratio) X 100 Odds of vaccination among ppl with influenza/ Odds of vaccination among ppl w/o influenza = odds ratio Observational data Adjusted for cofounders
26
Type A
Antigenic drift and shift, major pathogen Mortality rate is only 0.1% Machieavellan: don't kill host so it can spread
27
Type B
Antigenic drift only, milder infections Not associated with pandemics
28
Type C
Relatively stable, pediatric
29
Influenza A/*/California/07/2009 (H1N1)
Type based on antigenicity of nucleoprotein (NP) and matrix protein (M1) Host of origin (* not designated if from humans) Geographic origin Strain Year isolated Antigenic subtype of H and N proteins
30
Influenza Health Burden (deaths, percentage, costs, HC)
3-49k deaths/year 90% of deaths are due to pneumonia/influenza in people >65yrs Costs $4.6b annually 25% of HC workers develop influenza each year
31
Main Virulence Factors
1. Hemagglutitin (H) 18 subtypes Sialic acid receptor 2. Neuroaminidase (N) 11 subtypes Sialidase (enzyme) target for neuraminidase inhibitors 3. M2 ion channel Sensing acidification in endosome Target for amantidine/rimantidine Sits in envelope since it's an enveloped virus 4. M1 (matrix) protein Structural 5. NP (nucleoprotein) 6. NS1 (non-structural protein 1) Reprograms host cell to replicate ssRNA
32
Shedding
Viral shedding can happen from one day prior to symptoms to 8-10 days after symptom onset (peak day 3-4) Prolonged in children
33
Virus is stable and favors...
``` Low humidity Cool temperatures (fall and winter) ``` Unusual for enveloped virus
34
Pathogenesis of Influenza A
1. Aerosol inoculation 2. Replication in resp. tract 3. Downstream immune effect IgA Antibody response CD4 CD8 T cell response IFN induction 4. Desquamation of mucus-secreting and ciliated cells Secondary bacterial infection > pneumonia Primary viral pneumonia (high risk: elder, cardiopulm) CNS, muscle involvement (myositis, enceph. children, GB) (cilia gone, mucus gone, losing defenses) 5. Influenza syndrome: Fever, chills, malaise, headache, myalgia, loss of appetitie
35
Reyes Syndrome
Explains why we shouldn't treat influenza with aspirin Rare and serious Associated with use of salicylates (aspirin) Rapid progressive non-inflammatory encephalopathy Fatty infiltration of viscera (liver)
36
Innate Antiviral Immune Response
Cytokine storm Pro-inflammatory responses against viruses PRRs identify viral RNA as non-self by binding to PAMP motifs RNA viruses: TLRs (TLR3, TLR7, retinoic acid inducible gene 1 (RIG-1) Examples of pamps: LPS, lipoprotiens
37
Mediators of cytokine storm
``` IL-6 TNF-a IFN-a/B IFN-g IL-1a/B ```
38
Lab findings and diagnosis (acute phase, serology, leukocyte count)
Acute phase: Virus detection in throat swabs, nasopharyngeal swabs, sputum RT-PCR: identifies sub
39
Live vaccines
2-49 years Flumist: administered intranasally Grown in eggs, cold-adapted (25 C), temperature sensitive (limited growth at 37 C), attenuated for virulence Doesn't grow well in our body Antibodies (mainly IgA) against H and N antigens are protective
40
Inactivated vaccines
>=3/4 years Viruses that have been grown in eggs and inactivated with formaldehyde and detergents Fluzone, Fluvirin, Fluarix Antibodies (mainly IgA) against H and N antigens are protective

Pathogens (3 decks)

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