2. 2
‘FLU’
• True influenza
– influenza virus A or influenza virus B (or
influenza virus C infections - much milder)
• Febrile respiratory disease with
systemic symptoms caused by a variety
of other organisms often called ‘flu’
3. 3
South Carolina 1996-1997 DHEC bulletin
http://www.state.sc.us/dhec/LAB/labbu017.htm
no virus
influenza A
influenza B
CULTURE
RESULTS
malathia influenzae per le stelle
4. 4
1918-19 Spanish flu 500,000 US
20,000,000 world
1957-58 Asian flu 70,000 US
1968-69 Hong Kong
flu
34,000 US
THE IMPACT OF INFLUENZA
PANDEMICS
Deaths:
5. 5
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)
6. 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
8. 8
ORTHOMYXOVIRUSES
M1 protein
helical nucleocapsid (RNA plus
NP protein)
HA - hemagglutinin
polymerase complex
lipid bilayer membrane
NA - neuraminidase
type A, B, C : NP, M1 protein
sub-types: HA or NA protein
19. 19
INTERFERON
THE VIRUSES ARE COMING!
http://www.paulreverehouse.org/midnight.html
PAUL REVERE
http://www.mfa.org/collections/one_hour/6.htm
20. 20
TYPES OF INTERFERON
• TYPE I
•Interferon-alpha (leukocyte interferon, about 20
related proteins)
- leukocytes, etc
•Interferon-beta (fibroblast interferon)
- fibroblasts, epithelial cells, etc
•TYPE II
•Interferon-gamma (immune interferon)
- certain activated T-cells, NK cells
21. 21
INDUCTION OF INTERFERON
•interferon-alpha and interferon-beta
- viral infection (especially RNA viruses), double
stranded RNA, certain bacterial components
- strong anti-viral properties
•interferon-gamma
- antigens, mitogenic stimulation lymphocytes
24. 24
interferon-alpha, interferon-beta
interferon receptor
induction of
2’5’oligo A synthase
induction of a
protein kinase
2’5’oligo A
induction of
ribonuclease L
activated
ribonuclease L
ATP
ds RNA ds RNA
activated
protein kinase
activated
2’5’oligo A synthase
ATP
2’5’oligo A
mRNA degraded
phosphorylated initiation
factor (eIF-2)
inhibition of protein synthesis
26. 26
OTHER EFFECTS OF
INTERFERONS
• ALL TYPES
– INCREASE MHC I EXPRESSION
• CYTOTOXIC T-CELLS
– ACTIVATE NK CELLS
• CAN KILL VIRALLY INFECTED CELLS
27. 27
OTHER EFFECTS OF
INTERFERONS
• INTERFERON-GAMMA
– INCREASES MHC II EXPRESSION ON APC
• HELPER T-CELLS
– INCREASES ANTIVIRAL POTENTIAL OF
MACROPHAGES
• INTRINSIC
• EXTRINSIC
28. 28
THERAPEUTIC USES OF
INTERFERONS
• ANTI-VIRAL
– e.g. interferon-alpha is currently approved for certain
cases of acute and chronic HCV and chronic HBV
• MACROPHAGE ACTIVATION
– interferon-gamma has been tried for e.g. lepromatous
leprosy, leishmaniasis, toxoplasmosis
• ANTI-TUMOR
– have been used in e.g. melanoma, Kaposi’s sarcoma,
CML
• MULTIPLE SCLEROSIS
– interferon-beta
29. 29
Viral response to host immune
system
Viruses may :
block interferon binding
inhibit function of interferon-induced proteins
inhibit NK function
interfere with MHC I or MHC II expression
block complement activation
inhibit apoptosis
etc!
32. 32
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)
36. 36
NON-PULMONARY
COMPLICATIONS
• myositis (rare, > in children, > with type B)
• cardiac complications
• recent studies report encephalopathy
– studies of patients <21 yrs in Michigan - 8 cases seen
last season
• liver and CNS
– Reye syndrome
• peripheral nervous system
– Guillian-Barré syndrome
40. 40
MORTALITY
• MAJOR CAUSES OF INFLUENZA
VIRUS- ASSOCIATED DEATH
– BACTERIAL PNEUMONIA
– CARDIAC FAILURE
• 90% OF DEATHS IN THOSE OVER 65
YEARS OF AGE
53. 53
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
54. 54
VACCINE
• inactivated
• egg grown
• sub-unit vaccine for children
• reassortant live vaccine approved 2003
– for healthy persons (those not at risk for
complications from influenza infection)
ages 5-49 years
56. 56
RECOMMENDATIONS
Persons at High Risk for Influenza-Related Complications
· 65 years
· residents of nursing homes and other chronic-care facilities
· adults/children who have chronic pulmonary or cardiovascular
disorders, including asthma
· adults/children who have required regular medical follow-up or
hospitalization during the last year because of chronic metabolic
diseases (including diabetes mellitus), renal dysfunction,
hemoglobinopathies, or immunosuppression (including
immunosuppression caused by medications)
57. 57
RECOMMENDATIONS
Persons at High Risk for Influenza-Related Complications
· children and teenagers (6 mths to 18 yrs) receiving long-term
aspirin therapy - might be at risk for developing Reye syndrome
after influenza
· women who will be in the 2nd or 3rd trimester of pregnancy
during the influenza season.
58. 58
RECOMMENDATIONS
Persons aged 50-64 years
increased prevalence of high-risk conditions
from public health point of view, easier to target by age
than by high-risk condition (which may not have been
discovered)
59. 59
RECOMMENDATIONS
Persons Who Can Transmit Influenza to Those at High
Risk
Persons who are clinically or subclinically infected can
transmit influenza virus to persons at high risk for
complications from influenza.
60. 60
RECOMMENDATIONS
· physicians, nurses, and other personnel in both hospital and
outpatient-care settings
· employees of nursing homes and chronic-care facilities who
have contact with patients or residents
· employees of assisted living and other residences for persons in
high-risk groups
· persons who provide home care to persons in high-risk groups
· household members (including children) of persons in high-risk
groups.
61. 61
RECOMMENDATIONS
Children from 0-23 mths are at increased risk for
hospitalization from influenza, vaccination is encouraged
for their household contacts and out-of-home caretakers,
particularly for contacts of children aged 0–5 months
because influenza vaccines have not been approved for
use among children aged <6 months.
63. 63
PREVENTION - DRUGS
• RIMANTADINE (M2)
• type A only
• AMANTADINE (M2)
• type A only
• ZANAMIVIR (NA)
• types A and B, not yet approved for prevention
• OSELTAMIVIR (NA)
• types A and B
64. 64
TREATMENT - DRUGS
• RIMANTADINE (M2)
• type A only, needs to be given early
• AMANTADINE (M2)
• type A only, needs to be given early
• ZANAMIVIR (NA)
• types A and B, needs to be given early
• OSELTAMIVIR (NA)
• types A and B, needs to be given early
66. 66
OTHER TREATMENT
• REST, LIQUIDS, ANTI-FEBRILE
AGENTS (NO ASPIRIN FOR AGES
6MTHS-18YRS)
• BE AWARE OF COMPLICATIONS
AND TREAT APPROPRIATELY
67. 67
TYPE A
++++
yes
yes
yes
shift, drift
yes
sensitive
sensitive
2
severity of illness
animal reservoir
human pandemics
human epidemics
antigenic changes
segmented genome
amantadine, rimantidine
zanamivir
surface glycoproteins
TYPE B
++
no
no
yes
drift
yes
no effect
sensitive
2
TYPE C
+
no
no
no (sporadic)
drift
yes
no effect
(1)
Rapid tests - signifcance in ascertaining whether the infection is influenza and which type it is since now have therapeutic agents (some of which are type specific)
- signifcance in differential diagnosis - eg if need to determine if Flu v. SARS
- advent of rapid easy tests may increase diagnosis - may realise that flu involved in more illnesses than realised (eg enhanced surveillance of patients &lt;21 at low risk for complications who were admitted to hospital for a variety of symptoms revealed that more severe morbitity and mortality assoc with influenza that was realised -2003).
