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

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

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

ORTHOMYXOVIRUSES 11

M1 protein

helical nucleocapsid (RNA plus

NP protein)

HA - hemagglutinin

polymerase complex

lipid bilayer membrane

NA - neuraminidase

Influenza Virus 12

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

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

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

where26

where do “new” HA

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

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

Variation 30

cycle 31

History of antigenic shift 32

Shift 33

Antigenc shift =34

Reasortment35

variation 36

Transmission 37

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

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.

Photo of the caution taken by officials duringthe influenza epidemic of 1918

isolation 40

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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

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%.

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

Haemagglutination (HA) 63

virus

No virus

Haemagglutination 64

Dilution

2 4 8 16 32 64 128 256 512

prozone titre

1024No

virus

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

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

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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