BURDEN OF INFLUENZA The InfluenzaVirus
Transcript of BURDEN OF INFLUENZA The InfluenzaVirus
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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