1 INFLUENZA VIRUS

2 ‘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’

3 South Carolina medical bulletin no virus influenza A influenza B CULTURE RESULTS

4 THE IMPACT OF INFLUENZA PANDEMICS Deaths:

5 THE IMPACT OF INFLUENZA (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)

6 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? 7

8 ORTHOMYXOVIRUSES Pleomorphic – can alter shape in response to environment influenza types A,B,C febrile, respiratory illness with systemic symptoms

9 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

10 TRANSMISSION AEROSOL –100,000 TO 1,000,000 VIRIONS PER DROPLET HR INCUBATION SHEDDING

11 NORMAL TRACHEAL MUCOSA 3 DAYS POST-INFECTION 7 DAYS POST-INFECTION Lycke and Norrby Textbook of Medical Virology 1983

12 DECREASED CLEARANCE RISK BACTERIAL INFECTION VIREMIA (when virus enters blood stream) - rare Lycke and Norrby Textbook of Medical Virology 1983

13 RECOVERY INTERFERON - SIDE EFFECTS INCLUDE: –FEVER, MYALGIA (muscle pain), FATIGUE, uneasiness/discomfort CELL-MEDIATED IMMUNE RESPONSE TISSUE REPAIR –CAN TAKE SOME TIME

14 An immunological diversion INTERFERON

15 INTERFERON timecourse of virus production will vary from virus to virus

16 INTERFERON

17 INTERFERON antiviral state

18 INTERFERON antiviral state

19 INTERFERON antiviral state

20 INTERFERON induce various proteins in target cells many consequences, not all fully understood only made when needed

21 EFFECTS OF INTERFERONS –INCREASE amount of cytotoxic T-cells resent/active –ACTIVATE NK cells –ACTIVATE helper T cells

22 THERAPEUTIC USES OF INTERFERONS ANTI-VIRAL MACROPHAGE ACTIVATION –interferon-gamma has been tried for e.g. lepromatous leprosy, leishmaniasis, toxoplasmosis ANTI-TUMOR MULTIPLE SCLEROSIS

23 Viral response to host immune system Viruses may : block interferon binding inhibit NK function interfere with cytotoxic T cell response inhibit apoptosis etc!

24 SIDE EFFECTS OF INTERFERONS FEVER DISCOMFORT/UNEASINESS FATIGUE MUSCLE PAINS

25 BACK TO INFLUENZA

26 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)

27 SYMPTOMS FEVER HEADACHE MYALGIA COUGH RHINITIS (inflammation of mucous membrane

28 CLINICAL FINDINGS SEVERITY –VERY YOUNG –ELDERLY –IMMUNO- COMPROMISED –HEART OR LUNG DISEASE

29 PULMONARY COMPLICATIONS CROUP (YOUNG CHILDREN) PRIMARY INFLUENZA VIRUS PNEUMONIA SECONDARY BACTERIAL INFECTION –Streptococcus pneumoniae –Staphlyococcus aureus –Hemophilus influenzae

30 MORTALITY MAJOR CAUSES OF INFLUENZA VIRUS- ASSOCIATED DEATH –BACTERIAL PNEUMONIA –CARDIAC FAILURE 90% OF DEATHS IN THOSE OVER 65 YEARS OF AGE

31 ANTIGENIC DRIFTDRIFT HA and NA accumulate mutations –RNA virus immune response no longer protects fully sporadic outbreaks, limited epidemics

32 ANTIGENIC SHIFTSHIFT “new” HA or NA proteins pre-existing antibodies do not protect may get pandemics

33 INFLUENZA A PANDEMICS Ryan et al., in Sherris Medical Microbiology

34 where do “new” HA and NA come from? 13 types HA 9 types NA –all circulate in birds pigs –avian and human

35 where do “new” HA and NA come from?

36 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

37 CDC

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