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Influenza secrets do you know
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Influenza Drama
Premier john
Secrets Behind Him
Let us Start Enjoy
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The premier john of the
drama
Pandemics
Spanish flue A (H1N1) 1918
Asian flue A (H2N2) 1957
Hong Kong flue A (H3N3) 1968
Russian flue A (H1N1) 1977
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What we will speak about
Introduction
Family orthomyxoviridae
Influenza virus
Anatomy
Naming
Zoonosis
Transmission to human How?
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Influenza Pathogenethis 4
7 DAYS POST-INFECTION
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Influenza life cycle
Steps
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Diagnosis
The act of
professional
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Classification
Influenza is one of orthomyxoviridae
ss(-) RNA virus
minus sense single strand RNA virus
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Haemeagglutinine
Neuramidinase
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HA protein - attachment,
fusion HA
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S S
S S
S S
cell enzymes
acid pH
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anatomy orthomyxoviridae 10
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
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ORTHOMYXOVIRUSES 11
M1 protein
helical nucleocapsid (RNA plus
NP protein)
HA - hemagglutinin
polymerase complex
lipid bilayer membrane
NA - neuraminidase
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Influenza Virus 12
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pictures
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From inside himself
infuenza
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Human influenza
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ORTHOMYXOVIRUSES 16
pleomorphic
influenza types A,B,C
febrile, respiratory illness with systemic symptoms
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Family
orthomyxoviridae
Influenza A B and C
Only A and B can cause Human disease
Influenza A
infect awide variety of mammals
And tends undergo antigenic changes
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Virus character
Enveloped (80-120 nM )
Segmented negative stranded RNA
8 segment A and B
7 segments c
Total genome size average 13.6
Average 0.89 – 2.34 kb each segment
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type A, B, C : NP, M1
protein
sub-types: HA or NA protein
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M1 protein
helical nucleocapsid (RNA plus
NP protein)
HA - hemagglutinin
polymerase complex
lipid bilayer membrane
NA - neuraminidase
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Influenza Asubtypes
15 hemagglutinine
9 Neuraminidase subtypes
Subtypes of type A
Important for human
H1N1
H2N2
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Antigentic shift drift
Antigenic shift
Completely new HA subtype
Only with influenza A
Assocaited with pandemics
Antigenic drift
Relatively minor subtype changes
Influenza A and B
EPIDEMIC and regional out break
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Influenza virus
3types
Type A
Associated with widespread epidemic
Pandemic
TYPE B infrequently associated with regional wide spread epidemic
Type C
associated with sporadic cases minor localized disease
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How to name influenza
virus
Type ABC\ city\strain#\year isolated\glycoprotein
HA (1-15)
NA ( 1-9)
eg. A\HONG KONG\03\1968\H3N3
World wide pandemics= pandemic
1918-1919 influenza pandemic caused
2o million deathes
1947 asian influenza
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Influenza changes rapidely
Antigenic drift
substitution in HA and NA
This can increase the escape from the immune system
Antigenic shift assortment of gene segment in cells
Infected by different strain avian gene substituted with human strain gene
Swine can replicate both strain
This can open up for infection of new host
Both make it difficult to obtain good vaccine
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Humanvirus
Reassortant
virus
Non-human
virus
Transmission of Avian
Influenza A Viruses to Humans
15 HAs
9 NAs
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where26
where do “new” HA
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27Timeline of Emergence of
Influenza Viruses in Humans
1918 1957 1968 1977 1997
1998/9
2003
H1
H1
B
H2
H7H5H5
H9
SpanishInfluenza
AsianInfluenza
RussianInfluenza
AvianInfluenza
Hong KongInfluenza
H3
Pa
nd
em
icva
ccin
es
Re
gu
lar
va
ccin
es1918
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Influenza Virus Types &
Subtypes in Humans
(Trivalent Vaccine) Type A
Seasonal epidemics caused by H3N2, H1N1, and
H1N2 subtypes
Pandemics (caused by new subtypes)
Type B
No subtypes
Seasonal epidemics only
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29Timeline of Emergence of
Influenza Viruses in Humans
1918 1957 1968 1977 1997
1998/9
2003
H1
H1
B
H2
H7H5H5
H9
SpanishInfluenza
AsianInfluenza
RussianInfluenza
AvianInfluenza
Hong KongInfluenza
H3
Pa
nd
em
icva
ccin
es
Re
gu
lar
va
ccin
es
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Variation 30
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cycle 31
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History of antigenic shift 32
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Shift 33
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Antigenc shift =34
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Reasortment35
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variation 36
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Transmission 37
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Influenza pandemics
Antigenic shift has occurred at least 3 times in the past, each time resulting in highly lethal pandemics.
All three pandemics in the 20th century spread world wide within 1 year of detection
1918 Spanish flu (H1N1) which caused the death of 20-40 million people
1957 Asian flu (H2N2)
1968 Hong Kong flu (H3N2). This subtype still circulates today.
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Lessons from the past
Hospital in
pandemic
39
.
Photo of the caution taken by officials duringthe influenza epidemic of 1918
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isolation 40
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41
TRACHEAL MUCOSA NORMAL
7 DAYS POST-INFECTION3 DAYS POST-INFECTION
Lycke and Norrby Textbook of
NORMAL TRACHEAL MUCOSA
DAYS POST-INFECTION3 DAYS
POST-INFECTION
pathogenesis
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changes
DECREASED CLEARANCE
RISK BACTERIAL INFECTION
VIREMIA RARE
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Diagnosis
Avian influenza
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Avian influenza
The highly pathogenic
form of avian
influenza A was first
recognized in Italy in
1878
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Highly pathogenic
This strain
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It is extremely contagious and rapidly fatal in birds with a mortality approaching 100%.
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All outbreaks of the highly pathogenic form of avian
influenza have been caused by subtypes H5 and H7.
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The virus multiplies in the intestines of these birds and is
shed in saliva, nasal secretions and feces.
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A single gram of contaminated feces contains enough virus to infect 1 million birds
The virus can survive in contaminated manure for up to 3 months and in contaminated water up to 30 days.
Birds that survive infection excrete virus for at least 10 days, orally and in feces, thus facilitating further spread.
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H5N1 has jumped the species barrier on 2 separate occasions in the recent past causing severe disease in humans.
The first documented human infection by H5N1 occurred in Hong Kong, China in 1997.
18 people were hospitalized, 6 died.
The entire domestic bird population of Hong Kong, 1.5 million birds, was culled in 3 days.
Human infection stopped after all chickens were culled.
Limited human-to-human transmission of H5N1 was documented.
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How do people die?
Unlike influenza viruses we are more familiar with in which respiratory symptoms dominate, H5N1 replicates in a wide range of cell types
This results in severe disseminated disease affecting multiple organs and causing high mortality.
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Presentation
Patients with documented H5N1 typically present to the hospital 2-6 days after the onset of fever and cough.
Other early symptoms include sore throat, runny nose and myalgia's. SOB develops in 1 to 5 days.
At admission all patients have clinically apparent pneumonia with either patchy or interstitial infiltrates.
Leukocyte count is normal or decreased, and transaminases may be mildly to moderately elevated.
Patients go on to develop disseminated disease affecting multiple organs
Secondary bacterial infection has not been a factor
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There are 2 classes of drugs available that are
effective against the influenza virus:
The M2 inhibitors: amantidine and ramantidine
The neuraminidase inhibitors: oseltamivir and
zaminivir
In preliminary studies H1M5 has been shown to be
resistant to the M2 inhibitors
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Another interesting bit of information
H5N1 infection has been confirmed in a
single household of domestic cats in
Thailand. 14 of 15 cats in the household
died.
One dead cat was known to have
contact with a dead chicken.
Up to now, domestic cats were not been
considered susceptible to infection with
influenza viruses although some older
studies from the 1970s reported
experimental infection of domestic cats
under laboratory conditions.
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Diagnosis
The role of profetional
How it is down
At what level
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avian
History of high
mortality
Clinical signs
nervous signs
Diarhae
Sudden death
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diagnosis
PM
The respiratory
digestive system
Multiorgans
affected
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Laboratory diagnosis
Sample
Live bird
Tracheal swap
Cloacal swap
Faeces
Dead bird
Organs
faeces
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identification
Procedures
Inoculation of 9-11day old emryonatedchicken eggs followed by
Haemagglutination immunodiffusion test
Confirm presence of influenza virus
Subtype determination with nonspecific antisera
Strain virulence evaluation of intravinouspathogencity index (IVPI) in 4-8 week old chicken
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Serology
Tests available
ELISA Detect antibodies to AI virus
Doesn’t distinguish subtypes
AGID
Agar gel diffusion
Both within 1 week of infection
HI haemagglutination I inhibition test
Serotype specific test
Available for each H subtype
HI titers are positive a few days later than ELISA
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Enzyme linked
immunabsorbant assay (ELISA)
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Sample to be tested
virus
capturing antibody
Detecting antibody
Enzyme -> colour
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Haemagglutination (HA) 63
virus
No virus
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Haemagglutination 64
Dilution
2 4 8 16 32 64 128 256 512
prozone titre
1024No
virus
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immunoflourscent
Able to detect
antibodies to
specific
neuraminidase
subtype
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RT -PCR
Reverse transcriptase polymerase chain reaction
Able to detect virus at very low level
The presence of subtype H5or H& can be confirmed BY using H5 or H7 specific primer
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Human
FEVER
HEADACHE
MYALGIA
COUGH
RHINITIS
OCULAR SYMPTOMS
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Clinical finding
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 pneumonia
Staphylococcus aurous
Hemophilius 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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DIAGNOSIS
ISOLATION
NOSE, THROAT SWAB
TISSUE CULTURE OR EGGS
SEROLOGY
RAPID TESTS
provisional - clinical picture + outbreak
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48hours of incubtion
IPA on MDCK cells infected by A/H1N1
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Prevention by 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
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Prevention of Influenza
Avoid close contact with people who are sick
Stay home when you are sick
Cover Your Cough
Frequent hand washing
Avoid touching eyes, nose or mouth
Antiviral drugs
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surveillance 75
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Drugs preventive
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
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Treatment drug
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
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Avian influenza vaccine
Convential vaccine
Inactivated oil emulsion vaccine used world wide
Recominant vaccine
Vector I LT vaccine or pox
Heteroglogous vaccine
In avian influenza contain the same agglutinine
Adifferent Neuramindase
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