1 influenza virus. 2 ‘flu’ true influenza –influenza virus a or influenza virus b (or...
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INFLUENZA VIRUS
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‘FLU’
• True influenza– influenza virus A or influenza virus B (or
influenza virus C infections - much milder)
• Febrile (showing signs of fever) respiratory disease with systemic symptoms caused by a variety of other organisms often called ‘flu’
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South Carolina 1996-1997 medical bulletin
http://www.state.sc.us/dhec/LAB/labbu017.htm
no virus
influenza A
influenza B
CULTURE RESULTS
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1918-19 Spanish flu 500,000 US20,000,000 world
1957-58 Asian flu 70,000 US
1968-69 Hong Kongflu
34,000 US
THE IMPACT OF INFLUENZAPANDEMICS
Deaths:
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THE IMPACT OF INFLUENZA
• 1972-1994 (19 influenza seasons)
– >20,000 US deaths in 11 seasons
– >40,000 US deaths in 6 of these
– many more hospitalizations (~110,000 per year)
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THE IMPACT OF INFLUENZA
• recently some increase in morbidity and mortality - possible factors?– more elderly people– CF patients live longer– more high risk neonates– more immunosuppressed patients
What virus causes influenza?
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ORTHOMYXOVIRUSES
• Pleomorphic – can alter shape in response to environment
• influenza types A,B,C• febrile, respiratory
illness with systemic symptoms
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ORTHOMYXOVIRUSES
M1 protein
helical nucleocapsid (RNA plus NP protein)
HA - hemagglutinin
polymerase complex
lipid bilayer membrane
NA - neuraminidase
HA allows for viral entry into host cell NA allows for viral exit from host cell
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TRANSMISSION
• AEROSOL– 100,000 TO
1,000,000 VIRIONS PER DROPLET
• 18-72 HR INCUBATION
• SHEDDING
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NORMAL TRACHEAL MUCOSA
3 DAYS POST-INFECTION 7 DAYS POST-INFECTION
Lycke and Norrby Textbook of Medical Virology 1983
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• DECREASED CLEARANCE
• RISK BACTERIAL INFECTION
• VIREMIA (when virus enters blood stream) - rare
Lycke and Norrby Textbook of Medical Virology 1983
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RECOVERY
• INTERFERON - SIDE EFFECTS INCLUDE:– FEVER, MYALGIA (muscle pain), FATIGUE,
uneasiness/discomfort
• CELL-MEDIATED IMMUNE RESPONSE
• TISSUE REPAIR– CAN TAKE SOME TIME
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An immunological diversion
INTERFERON
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INTERFERON
timecourse of virus production will vary from virus to virus
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INTERFERON
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INTERFERON
antiviral stateantiviral state
antiviral state
antiviral state
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INTERFERON
antiviral stateantiviral state
antiviral state
antiviral state
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INTERFERON
antiviral stateantiviral state
antiviral state
antiviral state
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INTERFERON
• induce various proteins in target cells
• many consequences, not all fully understood
• only made when needed
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EFFECTS OF INTERFERONS
– INCREASE amount of cytotoxic T-cells resent/active
– ACTIVATE NK cells– ACTIVATE helper T cells
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THERAPEUTIC USES OF INTERFERONS
• ANTI-VIRAL • MACROPHAGE ACTIVATION
– interferon-gamma has been tried for e.g. lepromatous leprosy, leishmaniasis, toxoplasmosis
• ANTI-TUMOR• MULTIPLE SCLEROSIS
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Viral response to host immune system
Viruses may :
block interferon binding
inhibit NK function
interfere with cytotoxic T cell response
inhibit apoptosis
etc!
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SIDE EFFECTS OF INTERFERONS
• FEVER
• DISCOMFORT/UNEASINESS
• FATIGUE
• MUSCLE PAINS
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BACK TO INFLUENZA
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PROTECTION AGAINST RE-INFECTION
• IgG and IgA– IgG less efficient but lasts longer
• antibodies to both HA and NA important– antibody to HA more important (can
neutralize)
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SYMPTOMS
• FEVER
• HEADACHE
• MYALGIA
• COUGH
• RHINITIS (inflammation of mucous membrane
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CLINICAL FINDINGS
• SEVERITY– VERY YOUNG– ELDERLY– IMMUNO-
COMPROMISED– HEART OR LUNG
DISEASE
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PULMONARY COMPLICATIONS
• CROUP (YOUNG CHILDREN)• PRIMARY INFLUENZA VIRUS
PNEUMONIA• SECONDARY BACTERIAL
INFECTION– Streptococcus pneumoniae– Staphlyococcus aureus– Hemophilus influenzae
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MORTALITY
• MAJOR CAUSES OF INFLUENZA VIRUS- ASSOCIATED DEATH– BACTERIAL PNEUMONIA– CARDIAC FAILURE
• 90% OF DEATHS IN THOSE OVER 65 YEARS OF AGE
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ANTIGENIC DRIFT
• HA and NA accumulate mutations– RNA virus
• immune response no longer protects fully
• sporadic outbreaks, limited epidemics
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ANTIGENIC SHIFT
• “new” HA or NA proteins
• pre-existing antibodies do not protect
• may get pandemics
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INFLUENZA A PANDEMICS
Ryan et al., in Sherris Medical Microbiology
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where do “new” HA and NA come from?
• 13 types HA• 9 types NA
– all circulate in birds
• pigs– avian and human
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where do “new” HA and NA come from?
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VACCINE
• ‘BEST GUESS’ OF MAIN ANTIGENIC TYPES– CURRENTLY
• type A - H1N1• type A - H3N2• type B• each year choose which variant of each
subtype is the best to use for optimal protection
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CDC
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