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THE INFLUENZA VIRUS

NN

H

Dr M P Sharma

Professor

IMPORTANCE OF INFLUENZAIMPORTANCE OF INFLUENZAIMPORTANCE OF INFLUENZAIMPORTANCE OF INFLUENZA

� One of the most important International Emerging and Reemerging infectious diseases

� Unpredictable behavior � Causes high morbidity and mortality in

communities (epidemic) and worldwide (pandemic)

� Epidemics are associated with excess mortality

� May occur pandemics every 10-15 yrs� In between pandemic , epidemics trends to

occur at interval of 2-3 yrs in case of Influenza A & 4-7 yrs in Influenza B

BURDEN OF INFLUENZA

� 10% to 20% of the population is infected with influenza virus each year

� Average of more than 200,000 excess

hospitalizations each year

� Persons 65 and older and 2 years and

younger at highest risk

� Average of 36,000 deaths each year

� Persons 65 and older at highest risk of death

The The

InfluenzaVirusInfluenzaVirus

INFLUENZA VIRUS

•Commonly known as the flu

•infectious disease of birds and

mammals

•RNA viruses

• Commonly confused with a

cold

• flu is a much more severe

disease and caused by a

different virus

CLASSIFICATION OF INFLUENZA VIRUS

� Classified on the basis of hemagglutinin (HA)

and neuraminidase (NA)

� 15 subtypes of HA and 9 subtypes of NA are

known to exist in animals (HA 1-15, NA 1-9)

� 3 subtypes of HA (1-3) and 2 subtypes of NA (1-

2) are human influenza viruses. HA 5, 7, 9 and

NA 7 can also infect humans

� At present 3 types of influenza viruses are

circulating in world: A (H1N1), A (H2N1) & B

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INFLUENZA CLASSIFICATION

� Family orthomyxoviridae� Three types: A, B, C

� Types distinguished by antigenic differences in matrix and nucleoprotein antigens

� A is more pathogenic than B. C is not a big problem� Type A undergoes infects humans, swine, horses, seals,

mink, whales, birds � Primary reservoir is birds

� In birds, infection is mostly asymptomatic, virus can replicate in lungs and intestinal mucosa; shed in feces

� Respiratory infection in humans

� Interspecies transmission

� Influenza B and C are human viruses; do not infect birds

CHARACTERISTICS OF INFLUENZA VIRUS

� Types A, B, C

� Diameter 80 - 120 nm

� Pleomorphic, spherical, filamentous particles

� Single-stranded RNA

� Segmented genome, 8 segments in A and B

� Hemagglutinin and Neuraminidase on surface of virion

� H Ag initiate infection following attachment of virus to susceptible cells

� N Ag responsible for release of virus from infected cell

� Influenza A and B responsible for epidemics of

disease

� No cross immunity between them

CHARACTERISTICS OF INFLUENZA EPIDEMIC

� Suddenness with which cases arises & speed & ease they spread

� Short incubation period

� Large no. of subclinical cases

� High proportion of susceptible population

� Short duration of immunity

� Absence of cross immunity

� Peak of epidemic is reached in 3-4 weeks, before tending to

decline

� Time scale is compressed for smaller geographical areas

Seasonal Influenza

� A public health problem each year

� Usually some immunity built up from previous exposures to the same subtype

� Infants and elderly most at risk

Influenza Pandemics

� Appear in the human population rarely and unpredictably

� Human population lacks any immunity

� All age groups, including healthy young adults

Seasonal Epidemics vs. Pandemics

The new virus must be The new virus must be efficiently efficiently

transmitted from one human to anothertransmitted from one human to another

PREREQUISITES FOR PANDEMIC INFLUENZA

A new influenza virus emerges to which the general population has little/no

immunity

The new virus must be able to replicate in humans and cause disease

WHO Pandemic PhasesWHO Pandemic Phases

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� Influenza A virus; the most virulent human pathogens among the three influenza types.

�Frequent antigenic variation

� Influenza A virus; capable of infecting human as well as animals (ducks, chickens, pigs, whales, horses and seals). Wild aquatic birds are the natural hosts for a large variety of influenza A.

� Influenza A virus is the main cause of worldwide pandemics.

� Influenza A viruses subtypes e.g., (H1N1), (H5N1),….

Influenza A virusINFLUENZA B VIRUS

� Influenza B virus; it almost exclusively infects humans.

� Influenza B virus; less common than influenza A.

� Influenza B viruses are not divided into subtypes, but can be further broken down into different strains.

� Influenza B virus; mutates at a rate 2–3 times lower than type A. This reduced rate of antigenic change, combined with its limited host range ensures that pandemics of influenza B do not occur.

INFLUENZA C VIRUS

� Influenza C virus; infects humans.

� Influenza C virus; less common than the other

types and usually only causes mild disease in

children.

�Appear to be antigenically stable

Infuenza Transmission Rates (CDC,2009)

Body fluids and hand to hand contact 70%Air borne 29%

Animal 1%

Following are proven to destroy Influenza Virus (CDC,2009)

Bleach70% ethanol

AldehydesOxidizing agents

Quaternary amonium compoundsInactivated by heat (133 F) for 60 minutesPH less than 2 (very acidic)

Silver Sol (Liquid and Gel)

INFLUENZA EPIDEMIOLOGY

� Reservoir Human, animals (type A only)

� Incubation period 18-72 hoursTransmission Respiratory Probably airborne

� Attack rate 10-50 %

� Temporal pattern December - March in Norther Hemisphere

Winter or rainy session in southern Hemisphere

Summer in India

� Communicability Maximum 1-2 days before to 4-5 days after onset

� Overcrowding Enhance transmission

� Source of Infectionusually case or subclinical case

In epidemic- mild & asymptomatic infection also

� Age & Sex: all ages & both sex,

High risk group, < 18 months, chronic disease

� Human Mobility

� Immunity

INFLUENZA A RESERVOIR

Wild aquatic birds are the main reservoir of influenza A viruses. Virus transmission has been reported from weild waterfowl to poultry, sea mammals,

pigs, horses, and humans. Viruses are also transmitted between pigs and humans, and from poultry to humans. Equine influenza viruses have

recently been transmitted to dogs. (From Fields Vriology (2007) 5th edition, Knipe, DM & Howley, PM, eds, Wolters Kluwer/Lippincott Williams &

Wilkins, Philadelphia, Fig 48.1)

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HEMAGGLUTININ AND NEURAMINIDASE

There are 16 H and 9 N subtypes known, but only H 1, 2

and 3, and N 1 and 2 are commonly found in humans.

Hemagglutinin (HA) is a lectin that mediates binding of

the virus to target cells and entry of the viral genome into

the target cell.

Neuraminidase (NA) is involved in the release of progeny

virus from infected cells, by cleaving sugars that bind the

mature viral particles.

These proteins are targets for antiviral drugs.

NOMENCLATURE OF HUMAN INFLUENZA

VIRUS

Type Subtype Prototype

A H1N1 A/PR/8/34

A/NJ/8/76

H2N2 A/JP/305/57

H3N2 A/HK/1/68

B None B/Lee/40

C None C/Taylor/47

Influenza A hemagglutinin and neuraminidase subtypes

Fields Virology, 4th ed, Knipe & Howley, eds, Lippincott Williams & Wilkins, 2001, Table 47-1 Pathogenesis of influenza A virus. The symptoms of influenza are caused by viral pathologic and immunopathologic effects, but the infection may

promote secondary bacterial infection. CNS, Central nervous system. (From Medical Microbiology, 5th ed., Murray, Rosenthal & Pfaller, Mosby

Inc., 2005, Figure 60-3.)

Influenza pathogenesis

• Children at risk for severe disease

– Otitis Media frequent in children (12%)

– Reye syndrome

◦ Most common in children

◦ CNS and hepatic symptoms

◦ Salicylates a co-factor

• Complications

– Predominantly in high risk patients

◦ Elderly

◦ Immunocompromised

◦ Cardiopulmonary disease

– Primary viral pneumonia

– Secondary bacterial pneumonia

– Myositis and cardiac involvement

– Neurologic syndromes

◦ Guillain-Barre syndrome

◦ Encephalopathy, encephalitis

◦ Reye syndrome

MODE OF TRANSMISSION IN HUMAN

� The virus is spread from person- to-person through respiratory secretions either as droplets (close contact) or as airborne infection by droplet nuclei suspended in the air.

� Incubation period 1-3 days

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CLINICAL MANIFESTATIONS

� Influenza is an acute respiratory illness characterized by fever, cough, headache, nasal congestion, Chills, myalgia, coryza, sore throat Fatigue, and Body aches.

� Cough is frequently severe and protracted.

� Though similar symptoms occur with a cold, they are much more severe with the flu!

� Duration of illness is usually 2-7 days.

CLINICAL DIAGNOSIS

� The clinical picture of influenza is

nonspecific.

� Influenza-like illness can be caused by many microbial agents other than influenzavirus, such as adenovirus,

parainfluenza viruses, coronavirus, Mycoplasma pneumoniae, Chlamydia

pneumoniae, beta-hemolytic streptococcus.

LABORATORY DIAGNOSIS

� Since the clinical

picture of influenza is

nonspecific, its specific diagnosis must be

confirmed by

laboratory tests.

� This is usually made by

virus isolation,

Culture,

hemadsorbtion, viral antigen detection

INFLUENZA: HIGH RISK FOR COMPLICATIONS

� Birth through 59 months of age� Adults 50 years old and older

� Chronic lung disease, asthma� Chronic heart disease

� Metabolic diseases, e.g. diabetes� Chronic renal disease

� High risk of aspiration

� Immunosuppression� Pregnancy

� Chronic aspirin therapy: 18 years old and younger

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

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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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SURFACE ANTIGENS AND IMMUNITY

� Immunity reduces likelihood of infection and severity of disease

� Antibodies are specific to different types

of surface antigens

� Changes in H and N allow virus to evade

previously developed immune responses

� Antigenic changes: drift and shift

ANTIGENIC VARIATIONANTIGENIC VARIATION

INFLUENZA VIRUSES TEND TO UNDERGO INFLUENZA VIRUSES TEND TO UNDERGO

CHANGES FROM TIME TO TIME. THERE ARE CHANGES FROM TIME TO TIME. THERE ARE

TWO TYPES OF CHANGES: (1) ANTIGENIC TWO TYPES OF CHANGES: (1) ANTIGENIC

SHIFT, (2) ANTIGENIC DRIFT. THESE SHIFT, (2) ANTIGENIC DRIFT. THESE

CHANGES IN THE ANTIGENIC CHANGES IN THE ANTIGENIC

CHARACTERISTICS OF INFLUENZA VIRUSES CHARACTERISTICS OF INFLUENZA VIRUSES

DETERMINE THE EXTENT AND SEVERITY OF DETERMINE THE EXTENT AND SEVERITY OF

INFLUENZA EPIDEMICSINFLUENZA EPIDEMICS

ANTIGENIC SHIFTANTIGENIC SHIFTANTIGENIC SHIFTANTIGENIC SHIFT

� This term denotes COMPLETE or MAJOR changes in hemagglutinin and neuraminidase resulting from reassortment of gene segments involving two different influenza viruses.

� Genetic recombination of human with animal or avian virus

� When this occurs, worldwide epidemics may be the consequence since the entire population is susceptible to the virus.

ANTIGENIC SHIFT

� Viruses may reassort in a non-human species, shielded from human immunity.� Reassortment may involve interspecies

transmission.

� Reassorted viruses may enter the human population through interspecies transmission.

� Reassorted viruses express “new” HA, for which population has no immunity.

� Shift accounts for major pandemics.

Viral Re-assortment

Reassortment in pigs

Reassortment in

humans

Pandemic Influenza

Virus

ANTIGENIC DRIFTANTIGENIC DRIFTANTIGENIC DRIFTANTIGENIC DRIFT

� This term denotes MINOR changes in

hemagglutinin and neuraminidase of influenza

virus.

� Mutation in the RNA segments coding for either

the HA or NA

� Involves “Point Mutation”in gene owing to

selection pressure by immunity in host

population

� This involves no change in serotype; there is

merely an alteration in amino acid sequence of

HA or NA leading to change in antigenicity.

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INFLUENZA ANTIGENIC CHANGES

� Antigenic Drift

� Minor change, same subtype

� Caused by point mutations in gene

� May result in epidemic

� Example of antigenic drift

� In 2003-2004, A/Fujian/411/2002-like (H3N2) virus was dominant

� A/California/7/2004 (H3N2) began to circulate and became the dominant virus in 2005

INFLUENZA ANTIGENIC CHANGES

� Antigenic Shift� Major change, new subtype� Caused by exchange of gene segments� May result in pandemic

� Example of antigenic shift� H2N2 virus circulated in 1957-1967� H3N2 virus appeared in 1968 and completely

replaced H2N2 virus

PREVENTION & TREATMENT OF THE FLU

•Practice good hygiene and personal health habits

•Cover your mouth when whilesneezing and wash your hands regularly as the virus spreads through aerosols

•Since the flu is a virus, antibiotics won’t work unless there is a secondary bacterial infection

•Get the flu vaccine each year due to high mutation rate of the virus

PREVENTION & TREATMENT OF THE FLU

� Good ventilation of public buildings

� Avoidance of crowded places during epidemics

� To stay home at first sign of influenza are all sensible

precautions

� Vaccine is not recommended to control spread in general

population

� To be effective the vaccine must be administrated at least 2

weeks before onset of epidemic or preferably 2-3 months before influenza expected

� Vaccine not control epidemics, they are recommended only in certain select population group

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CONTROL MEASURES

�Immunoprophylaxis with vaccine

�Chemoprophylaxis and chemotherapy

TYPES OF VACCINE

� Killed Vaccine

� Live attenuated� Temperature sensitive

� Nose drops in respiratory tract

� Stimulate local & systemic immunity

� Frequent antigenic mutations present in diffculties in

production

� New Vaccines� Split Virus vaccine

� Neuraminidase specific vaccine

� Recombinant vaccine

KILLED INFLUENZA VACCINE

� Purified killed vaccine

� One dose contain 15mcg of Ha

� SC/IM administration

� Dose

� 0.5 ml for >3 years

� 0.25 ml for 6-36 months

� 2 doses at interval of 3-4 weeks

� Protection value 70-90 % for 6-12 months

� Revaccination on an annual basis is recommended

� Adverse reaction- fever, local inflammation , Rarely GBS

NEWER VACCINE

� Split virus vaccine (sub-virion vaccine)

� Highly purified

� Require several injection

� Neuraminidase specific vaccine

� Contain only N Ag

� Recombinant vaccine

INFLUENZA VACCINE, WHO SHOULD RECEIVE IT

� Persons 65 yrs or older

� Persons with heart, pulmonary, renal and metabolic diseases.

� Persons in nursing homes and other long-term care facilities

� Persons 6 mos-18 yrs old receiving aspirin therapy

INFLUENZA VACCINE RECIPIENTS--

CONTINUED� Women in 2nd or 3rd

trimester of pregnancy during flu season.

� Household members of persons in high-risk groups

� Health care workers and others providing essential community services.

� others, including travellers and the general population may wish to be vaccinated

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AVIAN INFLUENZA

�Avian influenza is an infectious disease of birds caused

by type A strains of the influenza virus.

�These viruses occur naturally among wild aquatic birds

worldwide and can infect domestic poultry and other bird

and animal species. The disease, which was first

identified in Italy more than 100 years ago.

AVIAN INFLUENZA

� Fifteen subtypes of influenza virus are known to infect

birds, thus providing an extensive reservoir of influenza

viruses potentially circulating in bird populations.

� H5N1; the strain of avian flu known as has been behind

outbreaks of deadly avian flu.

AVIAN INFLUENZA

� Avian influenza transmitted by birds usually through

feces or saliva.

� Avian influenza is not usually passed on to humans,

although it has been contracted by people who have

handled infected birds or touched surfaces contaminated

by the birds.

AVIAN INFLUENZA

�Migratory water birds, especially wild ducks. They may

do not show clinical disease. The virus colonizes the

intestinal tract and is spread in the feces . They act as a

reservoir for the infection of other species .

�Pigs can be infected by bird influenza (as well as by the

form of influenza that affects humans) and can pass on

the flu to humans.

AVIAN INFLUENZA

� Low pathogenicity (LPAI) - usually only causing mild

respiratory disease in domestic poultry .

� High pathogenicity (HPAI) - the more virulent type

formerly known as fowl plague which often results in up

to a 100% flock mortality.

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Source: WHO

SWINE FLU

� Swine influenza (swine flu) is a respiratory disease of pigs caused by type A influenza virus that regularly cause outbreaks of influenza in pigs.

� Like human influenza viruses, there are different subtypes and strains of swine influenza viruses. The main swine influenza viruses circulating in U.S. pigs in recent years are: H1N1 influenza virus, H3N2 virus, H1N2 virus.

SWINE FLU

� Influenza in swine was first recognized as an epizootic

disease in 1918.

� Swine influenza virus was first isolated from humans in

1974. Serologic evidence of infections with a swine

influenza virus in humans has also been obtained.

Viruses of swine may be a potential source of epidemic

disease for humans.

SWINE FLU

Symptoms and Signs/ In pigs

� Fever, lethargy, sneezing, coughing, difficulty

breathing and decreased appetite.

�Although mortality is usually low (around 1–4%), the

virus can produce weight loss and poor growth, causing

economic loss to farmers.

� In some cases, the infection can cause abortion.

SWINE FLU

Symptoms and Signs/In Human

�Systemic: fever

�Nasopharynx: Runny nose; sore throat

�Respiratory: Coughing

�Gastric: Nausea; Vomiting

�Intestinal: Diarrhea

�Psychological: Lethargy; Lack of appetite

Source: WHO

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THE H1N1 H1N1/H5N1

WHY DO WE NOT HAVE INFLUENZA B PANDEMICS?

� so far no shifts have been

recorded

� no animal reservoir

known

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PREGNANCY AND INACTIVATED INFLUENZA

VACCINE

�Risk of hospitalization 4 times higher than nonpregnant women

�Risk of complications comparable to nonpregnant women with high risk medical conditions

�Vaccination (with TIV) recommended for all women who will be pregnant during the influenza season, regardless of gestational age

INACTIVATED INFLUENZA VACCINE

CONTRAINDICATIONS AND PRECAUTIONS

� Contraindications

� Severe allergic reaction to a vaccine component (e.g., egg) or following a prior dose of vaccine

� Precaution

� Moderate or severe acute illness

� History of Guillain-Barre within 6 weeks of prior dose

LIVE ATTENUATED INFLUENZA VACCINE

CONTRAINDICATIONS AND PRECAUTIONS

� Contraindications� Children <2 years of age� Persons >50 years of age� Pregnancy� Persons with underlying medical conditions including

children and adolescents receiving chronic aspirin therapy

� Immunosuppression

� Precautions� History of Guillain-Barré Syndrome within 6 weeks of

a previous dose of influenza vaccine

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ANTIVIRAL DRUGS

� Amantadine, rimantadine. Effective for prevention and treatment of flu A only.

� Zanamivir, oseltamivir are approved for

treatment of uncomplicated flu A & B; oseltamivir also approved for prophylaxis.

� Prophylaxis must be continued throughout the epidemic; treatment must begin within 24

hrs of onset of illness.

HEALTHY HABITS

� When Healthy:�Avoid close contact with those who are

sick

�Wash your hands often

�Avoid touching your eyes, nose and mouth to decrease the spread of germs

� When Ill:�Cover your mouth and nose with a tissue

(or upper sleeve) when you sneeze or cough

�Stay home from work or school when you are sick

COUGH ETIQUETTE

�Respiratory

etiquette� Cover nose / mouth

when coughing or sneezing

�Hand washing!

VOLUNTARY ISOLATION

� Separation and restricted movement of illpersons with contagious disease (often in a hospital setting and Primarily individual level)� Isolate severe and mild cases

� Location of isolation (home, hospital) depends on several factors (severity of illness, the number of affected persons, the domestic setting)

� Do not wait for lab confirmation

� Plan for large number of severe cases

� Provide medical and social care

VOLUNTARY QUARANTINE

� Separation and restricted movement of well

persons presumed exposed

� Identification of contacts

� Often at home, but may be designated residential facility or hospital

� Applied at the individual or community level

� Regular health monitoring is essential part of quarantine

� Self-health monitoring and reporting

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HAND WASHING

Method

� Wet hands with clean (not hot) water

� Apply soap

� Rub hands together for at least 20 seconds

� Rinse with clean water

� Dry with disposable towel or air dry

� Use towel to turn off faucet

ALCOHOL-BASED HAND RUBS

�Effective if hands not visibly soiled

�More costly than soap & water

Method

�Apply appropriate (3ml) amount to palms

�Rub hands together, covering all surfaces until dry

PATIENTS CARED FOR AT HOME

� Potential for transmission

� Must educate family caregivers

� Fever / symptom monitoring

� Infection control measures

� Hand washing

� Use of available material as mask …

Isolation Precautions

Source: Rosie Sokas, MD MOH UIL at Chicago

Droplet precautions: Surgical Droplet precautions: Surgical

MasksMasks

N-95 FILTERING MASKS

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Personal Protective Equipment

(PPE)

Thank YouThank You