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INFLUENZA VIRUS

INFLUENZA VIRUS

CDC WEBSITE

http://www.cdc.gov/ncidod/diseases/flu/fluinfo.htm

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THE IMPACT OF INFLUENZA

PANDEMICS

Deaths:

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THE IMPACT OF INFLUENZA

• In the United States, on average:

• 36,000 deaths per year

• 114,000 hospitalizations per year

CDC: MMWR 53:8-11, 2004

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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

•Virus

hemagglutinin

sticks new virus

particle to sialic

acid on cell

surface

•Hemaggulutinin(HA)

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Replication

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•hemagglutinin

binds to sialic

acid on other

virus particles:

virus clumps

•OR virus sticks

to mucous in

respiratory tract

Neuraminidase(NA)

•Neuraminidase

of virus removes

sialic acid from

cell surface

thereby releasing

virus

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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 RARE

Lycke and Norrby Textbook of Medical Virology 1983

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RECOVERY

• INTERFERON - SIDE EFFECTS INCLUDE:

– FEVER, MYALGIA, FATIGUE, MALAISE

• CELL-MEDIATED IMMUNE RESPONSE

• TISSUE REPAIR

– CAN TAKE SOME TIME

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SIDE EFFECTS OF

INTERFERONS

• FEVER

• MALAISE

• FATIGUE

• MUSCLE PAINS

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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

• OCULAR SYMPTOMS

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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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NON-PULMONARY

COMPLICATIONS• myositis (rare, > in children, > with type B)

• cardiac complications

• recent studies report encephalopathy– 2002/2003 season studies of patients younger than

21 yrs in Michigan - 8 cases (2 deaths)

• liver and CNS– Reye’s syndrome

• peripheral nervous system– Guillian-Barré syndrome

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Reye’s syndrome

• liver - fatty deposits

• brain - edema

• vomiting, lethargy, coma

• risk factors

– youth

– certain viral infections (influenza, chicken

pox)

– aspirin

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Guillian-Barré syndrome

• 1976/77 swine flu vaccine

– 35,000,000 doses

• 354 cases of GBS

• 28 GBS-associated deaths

• recent vaccines much lower risk

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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

• PCR

• RAPID TESTS

• provisional - clinical picture + outbreak

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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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Years One year

HA or NA

HAOrNA

Antigenic drift Antigenic shift

Decr

easi

ng s

ero

logic

rela

tedness

NP

Antigenic shift and drift

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Where do “new” HA and NA come from

- can ‘new’ bird flu directly infect humans?

Bird flu H5N1?

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H5N1 – in birds

• Avian H5N1 has spread to humans

• So far human cases in Asia and Africa– 256 cases (12-1-03 through 10-16-06)

– 151 (59%) fatal

• Have been a few instances where may have spread human-to-human

• So far no sustained spread in humans

• Surveillance continues

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why do we not have influenza

B pandemics?

• so far no shifts

have been

recorded

• no animal

reservoir

known

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VACCINE

• ‘BEST GUESS’ OF MAIN ANTIGENIC

TYPES

– CURRENTLY

• type A - H1N1

• type A - H3N2

• type B

• each year choose which strain of each subtype

is the best to use for optimal protection

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VACCINE

• inactivated

• egg grown

• some formulations licensed 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 - DRUGS

• RIMANTADINE (M2)• type A only

• AMANTADINE (M2)• type A only

• 2005-6 season• H3N2 virus - 92% isolates resistant to rimantadine and

amantadine in US, so these drugs not recommended until % resistance in major circulating type drops

• ZANAMIVIR (NA)• types A and B

• OSELTAMIVIR (NA)• types A and B

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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

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OTHER TREATMENT

• REST, LIQUIDS, ANTI-FEBRILE

AGENTS (NO ASPIRIN FOR AGES

6MTHS-18YRS)

• BE AWARE OF COMPLICATIONS

AND TREAT APPROPRIATELY

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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,oseltamivir

surface glycoproteins

TYPE B

++

no

no

yes

drift

yes

no effect

sensitive

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TYPE C

+

no

no

no (sporadic)

drift

yes

no effect

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