Influenza : Etiologic Agent

1
?? ? ??? ??
?? ???? ? Rhinovirus major cause of the common
cold ? Coronavirus 10-20 of common cold ?
Respiratory syncytial virus ? Parainfluenza
virus ? Adenovirus
2
?? ? ??? ??

• ?? ???? ???? ?? ???? ??? ?? ?? ??? ???? ?? ???.
• ??? 24 72 ??
• ???? ???, ??, ??? ??? ??? ????? ??? ?? ?? ???
  ?? ? ???, ?? ????? ??? ?? ?? ????, ???? ?? ??
  ???? ??? ??? ?? ???? ?? ??? ?? ?????? ?? ?? ???
  ???? ?? ? ?? ???.
• ?? ?? 3 5? ???, ??? ????(?? ?? ??)
• ?? ??
• ? 60 ???? sinusitis ??? 2/3 ???? ??? ?? ???
  ?(NEJM 33025, 1994).
• ??? ???? 0.5, ??? 2
• ? Postviral bronchial hyperreactivity ?? ? 6
  8? ??? ?? ?? ???? ??? ??? ?? ???? cough asthma?
  ???? ??.
• ? ???? ??, ??, ???, ???, ?? ??, ???? ???? ?? ??
  ??, ??
• ? ???, ????, ???
• ? ???? ??, ??, ?? ???, ??
• ? ?? ??, ???, ???

3
?? ? ??? ??? ??(1)
1. ??? ??? ????. ? ?????? ????? ??? ??? ?? ????
???, ??? ??????? ??? ???? ?? ??? ?? ??? ???? ???
??? ????. ???? ?? ???? ??? ???? ebastine,
cetrizine, clarityne ?? ??? ??? ??? ???? ?? ???
?? ???. ? ?????? ??? placebo ?? ?? ???? ???
??? ???? ???? ?? ?? ?? ??, ??? ? 1?? ??????,
ipratropium ? ??, ?? ???? ???(?? ???, ?? ???)?
??? ???. ? Interferon alpha 2b nasal spray ??
?? ?? ??? ??? ??? ?? ??? ??? ??? ??? ?? ??? ?? ??
?? ?? ????? ??? ?? ?. ? Vitamin C ??? ??? ??
??? ?? 23 ?????? ??? ??? ?? 1g ????? ?? ??? ?? ?
??, ?? ?? ???? ????? ??? ???, oxalate ???? ???
???? ??. ? ?????? nebulized ribavirin ?
respiratory syncytial virus ? ??? ? ???, ????? ??
???? RSV ? ?? ?? ?? ??? ???? ?? ? ??. ?
Amantadine, rimantadine Influenza A virus ???
???? 48?? ???? ?? 2. ??? ?? ??? ????. ???? ??
???? ?????? ??? 2 3?? ?? ???? ??? ??? ????? ???
?? ??? ?? ?? 4?? ???? ??.
4
?? ? ??? ??? ??(2)
3. ???? ????. ? ?? ?? ???? ? ???? ?? ?? ???? ???
??? ????? ??. ? ??????, ??? ???, ?? ??? ???
?????, ??, ???, ??, ??? ??, ??? ? ? ???? ???? ???
? ?? ??? ?? ???? ???? ?? ? ??? ?? ?? ? ??? ??. ?
??? ??? ??? ???? ??? ??? ??? ??? ?? ??? ????
????? ?? ???? ??? ??? ?? ???? ????? ??? ???? ????
??? ??? ?? ??? ???? ??? ???? ??? ??? ??. ? ?? ???
?? ?? ?????? ??????? ?? 4?? ??? ????? ??? ???
???? ???? ?? ??. ? ??? ?????? ?? ?? ?? ??? ???
???? ?? ??. ? Steven Johnson ??? ? ??? ?? ???? ??
?????? ??? ??? ????? ?? ??? ???? ??? ?? ???? ??
???? ??? ????? ?? ???? ?? ???? ??.
5
?? ? ??? ??? ??(3)
4. ?? ??? ????. ? ?? ???? ??, ???? ??? ?????? ??
codein, tramadol ?? narcotics ?? ??, ???? ??? ?
??. ? ?? ???? ??? ?? ?? ??? ???? ??? ? ??. ?
sulindac, indomethacin, naproxen ? ?? ?? ????
???? ??? ???? ?? ?? ??? ?? ??? ????? ????
????. 5. ?? ??? ??? ?? ?? ????. ?? ???? ??? ? ???
??? ?? ?? ???? ???? ??? ???? ??? ??? ?? 6. ????,
??, ?? ?????? ???? ???? ??. ? ???? ?? ????? 39?
?? ??, ????, ?? ? ?? ??? ??? ?? ??? ???? ???
10-14? ?? ??? ??? ???? ???? 10-14? ??? ???? ????
10? ??? ??, ????? ???? ???? ?? ?? ????. ? ??
????? ??, ??? ?? ?? ?? ????, ??? ???? 1?? ?? ????
?? ?? ??? ????? tetracycline?, macrolide? ????
??? ? ??. ? ??? ?? ?? ??? ???? peroxydase ???
verdobilin? ???? ???? ? ??? ??? ???? ???.
6
?? ? ??? ??? ??(4)
????? ??? ???? ???? ???? ??? ???? ??? ???? ??? ??
??? ??? ?????? ???? ???? ??? ??? ??. ?? ?? ????
85 ??? ??????? ???? ???? ??. ???? ??? ??
Streptococcus pyogenes? ?? ???? ? ???? ????? ??
??? ?? ???? ?? ??? ?? ????. ?? ??? ?? ???? ???
???? ???? ?? ??? ??? ??? ?? ??? ????. ??? ??? ??
? ??? ?? ?????? ?? ???? ????. ???? ?-lactam ??
macrolides ? ??? 10?? ?????, ??? 2/3??
cephalosporin ?? azithromycin ? 5? ???
????. ????? ???? 1-2?? ??? ? ????? ???? ?, ??,
??, ??, ???, ???, ???? ? ????? ?? ??. ?? ???? ???
?? ???? ?? ???? ?? ??? ???. ?? ???, ???? ??, ??
???? ?? ? ??. ?? ??? ??? 3? ?? ??? ??? ? ????
???? ???, ??, ???? ??? ?? ??? ?? ?? ??? ???? ????
??? ?? ?? ???? ???? ???? ???? ????. Influenza
???? ??? ??? ????? ?? ????? ??? 15,000/mm3 ???
??? ????? ??? ??? ??. ?? 48?? ???? amantadine ?
????. ??? ????? acetaminophen,chlorpheniramine,
pseudoephedrine, ??? ??? ??, ?????, 1/2?? ???,
erythromycin ?? ????. ?? ???? S. pneumoniae(30),
H. influenzae(20), Moraxella catarrhalis ?? ???
?? ???? ? ????. ??? ? ??? decongestants ? ??? ?
??? topical intranasal steroid ? ???? ??? ????
??? ??. ???????? ?? noninfectious sinusitis,
allergic mediated infection? ??? ??.
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?? ? ?????? ??
?? 1. ?? ??? ??, ??, ?? ??? ?? ?? Acetaminophen
600mg Chlopheniramine 2-4mg Pseudoephedrine
30mg 1 po, pc, tid ??2. ??, ??, ??? ??? ??, ?
??? ?? ??? ?? ??, ?? ???? ??? ??. Acetaminophen
600mg ? 4??(?? 1,000mg 4?) Codein 20mg ?
6?? Terbutaline ??? 5mg, Lorazepam 0.5mg
??? Cough syrup 15-20cc ???? ??? ?? ?? ??
?? ??3. ?? ??, ???? ??? ?????? ??? ????? ?? ??,
?? ??? ??? ? ??.(??, ???) Diphehexamide
methiodide, chlorcinnazine, phenylpropanolamine
??? (Thymico?) 1? ?? 2? Mefenamic acid 250mg,
dextromethorphan 15mg, ??? 1? ?? 3? ?? Tramadol
50mg, pseudoephedrine 60mg, chlorpheniramine 4mg
??? ??4. ??, ?? ??? ? ??? 5???? ??? ???? ?? ???
?? ?? ??? 1? ?? ??, ??? ??? ?? ?? ??? ??, ?????
?? ??, ??? ?? ??. Acetaminophen 600mg
2-3? Terbutaline ??? 5mg 2? ?? ??,
??? Benproferine 20mg 4ghl Doxycycline 100mg
1?(??? 2?)
8

• ?? 1. ???, ???, ????, ??, ??????, ??????, ??? ???
  ??,??? ?? ?? ??? ? ?? ????
• Acetaminophen
• Chlorpheniramine
• Ibuprofen
• Pseudoephedrine
• ?? 2. ???? ??? ?? ????
• 25? ?? ?? ?? ?? 10?
• 33? ?? ??? ?? 3?
• 2? ?? ??? ?? 5?
• 45? ?? ?? ??, ??, ??? ??? ??? ??

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???? ???? ??
???(generic name)(????) ?? ???
Acetaminophen(B) Aspirin(C) Ibuprofen(B)
Naproxen(B) Mefenamic acid(C) ???
tramadol(C) ????? Codein ??/??(C)
Dextromethorphan(C) benproperine ??????
Chlorpheniramine(B) Clemastine(C) ?????
pseudoephedrine(C) ??????, ????? ? ???
diphehexamide methiodide 1mg, chlorcinnazine
5mg, phenylpropanolamine 30mg(C)
triprolidine 2.5mg, pseudoephedrine 60mg(C)
1? ?? 300-600mg,1000mg 300-600mg 200-400mg 200-5
00mg 250mg 25mg, 50mg 10-20mg/15-60mg 10-20mg,30
mg 20-40mg 2-4mg 1-2mg 30-60mg, ???
120mg 1? 1?
???? 1? ?? ? 4-6??, ?? 3-4? ? 4-6?? ? 4-6?? ??
3? ? 4-6?? ? 4-6??/2-3? ? 4-6?? ? 4-6??,?
6-8?? ?? 3? ?? 2-3? ? 4-6??, ?12?? 3? ?? ?
4-6?? ?? 3?
1? ?? 4gm 4gm 1.2gm 1.5gm 1.25gm 200mg 120mg/
360mg 120mg 120mg 240mg 3? 4?
?? 3?? 3??? D
10
???(generic name) Cough syrup 20ml ?(C)
dextromethorphan 15mg, methylephedrine 26mg,
chlorpheniramine 3mg, ammonium chloride
200mg ?????? Terbutaline 5mg ??(B)
1? ?? 10-20ml 1?
???? 1? ?? ? 4-6?? ?? 3-4? 1-2?
1? ?? 80ml 15mg
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Influenza

• Etiologic agent influenza virus
• Orthomyxoviridae family
• Hemagglutinin site by which virus binds to cell
  receptors
• Neuraminidase degrades the receptor
• release of virus from
  infected cells
• Influenza type A, B, C subtype H1,H2,H3 / N1,N2
• Nomenclature
• influenza A / Sydney / 5 / 97 (H3N2)

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Hemagglutinin
Neuraminidase
Lipid bilayer
Matrix protein
Polymerase
Neucleoprotein
RNA
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Epidemiology(1)

• The most extensive and severe outbreaks
• ? influenza A viruses
• Peak incidence children age 5 14 (50)
• ? Antigenic variation
• frequent in influenza A virus
• two external glycoproteins of the virus, HA
  and NA
• HA is more important
• ? more frequent antigenic variation than NA
• ? Antibody to HA neutralizes infection
• Antigenic drift minor change within same
  subtype
• A/Aichi/68(H3N2) -gt A/Sydney/5/97(H3N2)
  
• Antigenic shift major change in subtype(
  H1-gtH2)
• coinfection with two different virus
• -gt reassembly of gene fragment -gt
  pandemic

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Epidemiology(2)

• ? Pandemic influenza by antigenic shift
• influenza A every 10 40 year
• influenza B every 4 7 year
• ? Epidemic influenza by antigenic drift
• influenza A every 2-3 year
• 1997. 10 1998. 4 in Korea
• Majority Subtypes of H3N2
• A/Sydney/5/97(H3N2)
• A/Johannesburg/33/94(H3N2)
• Minority H1N1

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Parainfluenza A and subtypes
Severity
Subtype H2N2 H3N8 H1N1 H2N2 H3N2 H1N1
Year 1989 1900 1918 1957 1968 1977
Interval ? 11 18 39 11 9
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Clinical Features

• Abrupt onset of systemic symptoms
• Headache, fever, chills, myalgia, malaise, cough,
  sore throat
• Fever 38-44? , gradual defeverescence over a 3-5
  days
• Respiratory complaints more prominent as systemic
  symptoms subside
• Frank dyspnea, hyperpnea, cyanosis, consolidation
• ? suggest pulmonary complications
• Uncomplicated influenza resolves over a 2-5 day
  period
• In elderly patients weakness for several weeks

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Complications (1)

• ? pneumonia (most common)
• ? primary influenza viral pneumonia
• less common but most severe
• diffuse interstitial infiltrates, ARDS
• High risk with chronic pulmonary and cardiac
  disease, pregnancy
• ? secondary bacterial pneumonia
• reappearance of symptoms after improvement
• S.pneumoniae, S. aureus, H. influenzae
• High risk with chronic pulmonary and cardiac
  disease, elderly
• ? mixed viral and bacterial pneumonia
• Most common of the pneumonic complications
• Acute illness progress -gt bacterial pneumonia

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Complications(2)

• ? Other pulmonary complications
• worsening of COPD, asthma
• Croup in children
• ? Extrapulmonary complications
• Reyes syndrome
• myositis, rhabdomyolysis, myoglobinuria
• myocarditis, pericarditis
• CNS disease encephalitis, transverse
  myelitis,
• Guillain-Barré syndrome
• Gradual deterioration of underlying
  cardiovascular, pulmonary or renal
• function

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Treatment

• In uncomplicaed cases acetaminophen
• Salicylates should be avoided in children below
  age18
• Amantadine and rimantadine
• 200mg/d for 3-7 days
• active only against influenza A viruses
• reduces the duration of symptoms of influenza
  by approximately 50
• Ribavirin aerosol effecive both influenza A
  and B
• Antibacterial drugs should be reserved until
  bacterial complications
• develop.

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Prophylaxis (1)

• ? Influenza vaccine
• ? Killed vaccine
• type A(H3N2, H1N1) type B
• whole-virus vaccine
• split vaccine less side effect, lower
  efficacy
• Expected protection
• Child, young adult 60-90
• Middle age 40-70
• Old age( gt 60 ) 58
• ? Live attenuated influenza virus vaccine(LAIV)
• via nasal route, 93 effect of prevention

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Prophylaxis (2)

• ? Side effects of vaccine
• ? Local response erythema, pain, itching within
  12-24 hours
• ? Systemic response(1) fever, myalgia,
  arthralgia, headache
• split vaccine -gt lower systemic response
• ? Allergic response(urticaria, angioedema,
  asthma, anaphylaxis)
• rare, hypersensitivity to egg protein ?
  split vaccination
• ? Neurologic complication
• optic neuritis, cranial nerve palsy,
• Guillain-Barré syndrome(1/1000,000)
• Minimal risk of influenza vaccine
• considering influenza associated mortality
  300-1,500/1000,000

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Prophylaxis (3)

• ? Indication
• High risk group (older than 6 month) ? vaccine
  should be administered
• early in the autumn before influenza outbreaks
  occur.
• lt High risk group gt
• ? gt 65 years old
• ? chronic cardiovascular or pulmonary
  disorder(including asthma)
• ? residents of nursing homes and other
  chronic-care facilities
• ? diabetes mellitus, renal disese,
  hemoglobinopathies, immunosuppression
• ? expecting midtrimester or term pregnancy during
  epidemic period
• ? risk of Reye syndrome due to long-term aspirin
  treatment

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?? ??

• 1. ??? ?? ??? ??? ??
• ? ?????? ?? ??????? ? ??
• ? ?? 65? ??? ??
• ? ???(nursing home), ?? ?? ???? ???? ?? ???? ????
  ??
• ? ?? ????? ????? ?? ??(?? ??)
• ? ?? ????(??? ??), ???, ??? ??, ???? ?? ??? ????
  ?? ?? ??
• ??? ??? ?? ??
• ? ?? ???? ??? ?? ??? ??? ??? Reye ???? ?? ???? ??
  ??? ?
• 10?(6??- 18?)
• ? ????? ???? ?? ?? ?? ??? ? ???
• ? ???? ???? ?????? ???? ? ?? ???
• ? ?? ? ?? ?? ??, ???, ?? ?? ???
• ? ??? ?? ?? ???????? ???? ????? ???? ?? ???? ??
• ? ?? ???? ??? ??? ?? ???? ??
• ? ??? ??? ??(??? ??)

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?? ??

• 2. ? ?? ??
• ? HIV ???
• ? ??? (?? ?? ??, ??? 4-9? ??)
• ? ?? ???
• 3. ????? ??? ????? ?? ??
• ? ???? ??? ?? ??? ??? ??????? ????? ???? ??
• ? amantadine, rimantadine
• ? ?? ??? ?????? ???? ?? ????? ???? ????
• Desensitization ?? ??
• ? ?? ?? ??? ?? ??

25
?? ??? ??

• ????? ??? ?? 12??? 3? ?? ??
• ????? ? ??? 9??? ??,
• ???? ??? ?? ???? 10-11? ?? ??
• ??????? A?? ?? ??? ?? ?? 11??? ??
• ??????? ???? ? ???? ????? ?? ?? ???? ?? ?? ??.
• ?? ????? ??? ??????? ?????? ??? ??? ??.

????? ???? ??
?? 6-35?? 3-8? 9-12? 12? ??
???? ?? ?? ?? ?? ?? ?? ?? ?? ?????
?? 0.25ml 0.5ml 0.5ml 0.5ml
???? 1-2?(4???) 1-2?(4???) 1? 1?
?? ?? ?? ?? ??
9? ???? ?? ???? ????4? ?? ??? ?? 2? ??, ? ? H,
N ??? ??? ??? ? ??? 1? ??
26
??????

• ?????? ??? ??? ??? ????.
• ????? A? ??? ?? amantadine, rimantadine
• ????? ?????? ??? ? 70-90 ????? ???, ???? ?? ????
  ????? ?? ??? ??.
• ?? 48?? ??? ???? ??? ??? ??? ???? ? ??.
• ??? ?? ??? ??? ????? ????? ??? ??, ??? ?????? ?
  2?? ??????? ????.
• ??, ??? ? ??? ??? ?? ????? ? ??? ?????? ????.
• ?? ??? ?? ??? ???? ?? ???? ??(? HIV ???)???
  ????.
• 1999?, neuraminidase ???? zanamivir, oseltamivir
  ? FDA?? ?? ???? ????? A? B? ??? ???? ?????? ???
  amantadine, rimantadine ?? ??? ??? ???.

27
1. ????? ????? ??? ??? ???? ?? ??? ???? ?) ?? ??
?) hemagglutinin ?) neuraminidase ?) ?? 2.
????? ?? ????? ?? ???? ??? ?????? ?) M1 ?)
neucleoprotein ?) M2 ?)
hemagglutinin 3. ??? ???(antigenic shift)? ??? ??
?? ??? ?) H, N ?? ?? ??? ??? ??. ?)
???(pandemic)? ? ? ??. ?) ??? ??? ??? ??? ?? ???
??. ?) 10-40??? ??? ? ??. 4. ?????? ???? ?? ??
5-14? ????? ????? ?) 10 ?) 15
?) 50 ?) 90 5. ?? ? ??? ??????
???? ?????? ?? ?? ??? ????? ?) H1N1 ?) H2N3
?) H3N2 ?) H2N2
28
6. ?????? ???? ?? ?? ???? ?) 1-5? ?) 5-14?
?) 15-60? ?) 65? ?? 7. ????? ?????
?????? ?? ?? ??? ??? ?) ??? ??? ?) ? ???? ??? ?)
?? ?? ?) DNA ?? 8. ?????? ???? ??? ?? ? ?? ?? ??
???? ?) ???? ??? ?? ?) ?????
?? ?) ??? C? ?? ?? ?) ?????
?? 9. ??? ????? ?? ??? ?? ???? ?) 65? ??? ?) ???
??? ?? ?? ?) ??? ?? ??? ?) ?? ?-?? ?) ?? ?? 10.
????? ?? ???? ?) ?? ?? ?) ?? ?? ?) ???? ?) ???
?? ?) ?? ??