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INFLUENZA Epidemiology, Prevention and Control

SPEAKER:- Shubhanshu GuptaTEACHER I/C:- Dr.Dheeraj MahajanDATE:- 09/09/2014

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Contents1. History

2. About the disease and types

3. Epidemiological trends

4. Prevention and Control.

5. Pandemic Influenza(h1n1) 2009

6. Special-avian Influenza(outbreaks).

7. Newer vaccines and strains.

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History of influenza

• 412 BC - first mentioned by Hippocrates

• 1580 - first pandemic described

• 1580-1900 - 28 pandemics

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Discovery of Influenza Virus

• First isolated from a pig in 1931 (swine flu)

• Isolated from human in 1933

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WHAT IS INFLUENZA?(ALSO KNOWN AS THE FLU)

• The flu is a contagious respiratory illness

• It is caused by influenza viruses

• It can cause mild to severe illness and at times can lead to death

• It can be prevented by getting the flu vaccination each year

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Influenza: A Viral infection• Acute respiratory infection caused by Influenza virus

– Three types A, B and C.

• Currently viruses circulating in human population – Influenza A (H3N2), A (H1N1) and B Strains.

• All known pandemics (global outbreaks) were caused by Influenza A.

• Animal influenza viruses may affect humans in special circumstances – Bird Flu: A (H5N1).

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Naming influenza viruses

A/Hong Kong/156/97 (H5N1)

StrainID

Hemagglutinin NeuraminidaseType

Origin Yearisolated

16 9

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Influenza types

Type A Potentially severe illness

Epidemics and pandemics

Rapidly changing

Type B Usually less severe illness

Epidemics

More uniform

Type C Usually mild or asymptomatic illness

Minimal public health impact

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Classification of Influenza virus

• Classified on the basis of hemagglutinin (HA) and neuraminidase (NA).

• 16 subtypes of HA and 9 subtypes of NA are known to exist in animals (HA 1-16, 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

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Epidemiology

• Worldwide distribution

• Outbreaks usually occur suddenly.

• Flu spreads through communities resulting in an epidemic. Cases tend to peak after about 3 weeks and begin to subside after another 3-4 weeks

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Causative Agent of Influenza

• Caused by a virus belonging to the MYXOVIRUS group which comprises of Orthomyxovirus and Paramyxovirus

• Influenza virus is an Orthomyxovirus

Influenza A Virus Structure• Hemagglutinin (HA)

– Receptor binding (sialic acid)– Membrane fusion– Neutralizing antibody target

• Neuraminidase (NA)– Remove sialic acid residues– Virion release

• Ion channel (M2)– H+-dependent uncoating– Influenza A only

• Influenza A subtypes based on HA (16) and NA (9)

– H1N1, H3N2– A/Hong Kong/8/68

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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

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• Antigenic Drift– minor change, same subtype– caused by point mutations in gene– may result in epidemic

• Example of antigenic drift– in 2002-2003, A/Panama/2007/99 (H3N2) virus

was dominant– A/Fujian/411/2002 (H3N2) appeared in late 2003

and caused widespread illness in 2003-2004

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Priority Groups/CDC Recommendations

• People 65 years of age and older• People 2-64 years with chronic health

conditions• Children 6-23 months• Pregnant women• Healthcare personnel who provide direct

patient care• Household contact and out-of-home

caregivers of children less than 6 months of age

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Epidemiology cont.

• Peak season is November through March

• Each year about 10 to 20% of indians develop influenza

• Overcrowding enhances transmission.

Seasonality Incubation period• Time from exposure to onset of symptoms• 1 to 4 days (IQ range = 2-3 days)• Peak shedding first 3 days of illness

Seasonality• In temperate zones, increases in winter months

– Driven by mutations and viral preference for cold, dry weather conditions

• In tropical zones, circulates year-round – Fall-winter and rainy season increase has been observed– More international data is needed

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Northern hemisphere

Southern hemisphere

Tropics

Influenza activity peak: November-March2,3

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Influenza activity peak: April-September4,5

Year-round activity3,4

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Influenza spread occurs inseasonal patterns

E.g. India

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Karnataka

Andhra Pradesh

Maharashtra

Orissa

Gujarat

Rajasthan

Madhya Pradesh

Uttar Pradesh

Jharkhand

Jammu Kashmir

Punjab

Chattisgarh

Uttaranchal

Himachal Pradesh

Haryana

Bihar

New Delhi

Tamil NaduKerala

West Bengal

Sikkim

Arunachal Pradesh

Assam Nagaland

Manipur

Tripura

Mizoram

Meghalaya

• Location: Chennai (22nd Feb-22nd March 2008) Total Sample Collected : 55 Samples Total No. of Sample +ve : 23 Samples % + ve : 41.82 % +ve Influenza A :13 Samples (56.5%) Influenza B : 10 Samples (43.3%)

MONTHLY INFLUENZA ACTIVITY REPORTED BY-INDIAN SENTINEL DOCTOR’S NETWORK FEB-MAR 2008

No Report

• Location: Delhi ( Jan- Mar 2008 ) Total Sample Collected :86 samples Total No. of Sample +ve :12 Samples % +ve :14%+ve Influenza A/H1N1 : 6 Samples Influenza B : 4 Samples Not determined but +ve : 2 Samples

Source: Sentinel Doctor’s Network,March 2008

> 10 % positvity

> 40% positivity

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March- April August - October

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India 2011

Influenza virus circulation peaks in June-August

J J A S

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Global surveillance network:

106 Member countries136 NIC6 WHO CCS4 ERLS11 H5 Ref Labs

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Influenza Activity And Peaks

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WHO National Influenza Center(as of April 2011)

• Pune (NIV),• Kasauli (CRI)• Mumbai(Haffkine

Institute)

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Influenza: Transmission• Incubation period: 1-4 days, average 2 days.

• Transmission may start 1 or 2 days before onset of symptoms and last for a

week.

• Immunocompromised patients may transmit the virus for up to a month

after onset of symptoms .

• Virus particles spread through coughing and sneezing .

• One infectious particle can generate up to 1,000 virus particles.

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Influenza transmission is by 3 ways :

1. Direct transmission into the mucous membrane of a person .

2. Airborne route – that is via droplets .(0.5-5 µm diameter)

3. Contaminated surfaces, handles etc…

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Common Symptoms

• Respiratory disease• Abrupt onset of symptoms• Fever (up to 104° F)• Chills (sometimes shaking)• Muscle aches and pains• Sweating• Dry Cough• Nasal congestion• Sore throat• Headache• Malaise• Fatigue

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Influenza Pathogenesis

• Respiratory transmission of virus

• Replication in respiratory epithelium with subsequent destruction of cells

• Viremia usually not demonstrable

• Viral shedding in respiratory secretions for 5-10 days

Laboratory Testing for Influenza

• Rapid diagnostic tests Can provide results

<30 minutes ~ 70+% sensitive,

90+% specific

• SerologyMust used paired

serum samples>2 week delay for

results

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.Viral culture Gold standard Results take 7 days Influenza isolates for yearly vaccine

development

.RT-PCR Most sensitive Becoming more widely available

.Immunofluorescence Requires intact cells and laboratory

skill/experience

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CDC swab kit availableMethod: horizontal, away from nasal

septum

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Influenza Complications

• Pneumonia– primary influenza– secondary bacterial

• Reye syndrome

• Myocarditis• Guillian barre syndrome

• Death ~0.5-1 per 1000 cases

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PREVENTION and CONTROL OF INFLUENZA

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Importance of the Early Treatment

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Infection control at Individual level• Respiratory Hygiene / Cough Etiquette

– Cover the nose/mouth with a handkerchief/ tissue paper when coughing or sneezing

– Use tissues to contain respiratory secretions and dispose of them in the nearest waste receptacle after use

• Hand hygiene – Hand washing with non-antimicrobial soap and water,

alcohol-based hand rub, or antiseptic hand wash after having contact with respiratory secretions and contaminated objects /materials

• Use of mask– Three layered surgical mask– For cases and immediate family and social contacts.

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Personal Protective Equipment(PPE)

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N-95 Filtering Masks• Protect from inhalation

of airborne particles.

• Fit tightly to face.

• Approved by NIOSH.

• Particles<100µm.

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• Protect from spit and mucous discharges in procedures only.

• Do not have adequate filtering.

• Do not pass the fit test.• Approved by FDA.

Droplet precautions: Surgical Masks

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Isolation Precautions

Cough etiquette

• Respiratory etiquette– Cover nose / mouth when

coughing or sneezing

• Hand washing!

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Prevention of Swine Flu

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Control Measures

• Immunoprophylaxis with vaccine• Chemoprophylaxis and

chemotherapy

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Influenza Vaccines• Inactivated subunit (TIV)

– intramuscular– trivalent– split virus and subunit types– duration of immunity 1 year or less

• Live attenuated vaccine (LAIV)– intranasal– trivalent– duration of immunity at least 1 year

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Vaccination Schedules

* 2 doses at least 1 month apart for children receiving vaccine for the first time

Age group Dosage (im/sc) No. of doses

6-35 months 0.25 ml 1 or 2*

3-8 years 0.5 ml 1 or 2*

> 9 years 0.5 ml 1

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•Live viruses with limited replication in the upper respiratory tract

•Prevents (>90%) disease symptoms

•Limited use: Only approved for people 5 to 49 years old in good

health condition

•Children between 5 and 8 years old: two doses with an interval of 60

days (if not previously vaccinated with Flumist®)

.Expensive ($70?) Cold adapted influenza viruses:

ca A/Ann Arbor/6/60 (H2N2)

ca B/Ann Arbor/1/66

Flumist®: Efficacy and limitations

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Fluzone Intradermal

• Licensed by FDA in May 2011• Approved only for persons 18 through 64 years

of age• Dose is 0.1 mL administered in the deltoid area

by a specially designed microneedle and injector system

• Formulated to contain more HA (27 mcg) than a 0.1 mL dose of regular Fluzone formulation (9 mcg)

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Fluzone TIV Formulations

Formulation (age) HA per dose• Adult (>36 mos) - 45 mcg/0.5 mL• Pediatric (6-35 mos) - 22.5 mcg/0.25 mL• High dose (>65 yrs) - 180 mcg/0.5 mL• Intradermal (18-64 yrs) - 27 mcg/0.1 mL

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Nasal Spray Vaccine

• Live, attenuated vaccine administered by nasal spray.

• Option for those healthy people ages 2 to 49 years old.

• Option for health care workers who take care of sick persons or care for babies under 6 months of age and who are healthy between 2 and 49 years of age.

• Not to be used in pregnancy.

• Not to be used by those who care for or live with someone with a compromised immune system or children less than 2 years of age.

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Comparison of Influenza Vaccines

Vaccine type Composition Immunogenicity Reactogenecity

Whole-virus (no longer used)

Whole virus +++ +++

Split-virion Surface proteins, nucleocapsid and matrix proteins

++ ++

Subunit Surface proteins ++ +

Virosomal Surface proteins plus virosomes

++ +

Adjuvanted Surface proteins plus adjuvant

+++ ++

Intradermal (subunit)

Surface proteins +++ ++

+Low; ++ Medium; +++ High.

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Who Should Not be Vaccinated?

• Those with severe allergy to chicken eggs• Those who have had a severe reaction to a flu

vaccine in the past• Those who have developed Guillain Barre

Syndrome within 6 weeks of getting a flu vaccine previously

• Children less than 6 months of age• Those who have a moderate or severe illness

with fever (May return for the vaccine when symptoms lessen)

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. Medical conditions like Asthma, heart disease Blood disorders like sickle cell anaemia Liver disorders , kidney disorders Endocrine disorders like diabetes mellitus. Metabolic disorders ( inherited metabolic disorders

or mitochondrial isorders) Immunocompromised states – HIV/AIDS;

prolonged steroid therapy; malignancies. Morbidly obese (BMI > 40) Long term aspirin therapy.

Vaccine InformationAdverse Events

Intramuscular Injection (TIV)• Local Reactions:

pain 20-50% redness 10-13%swelling 6-8%

• Muscle aches: 18-30%• Headache: 14-30%• Malaise: 14-22%• Fever: 2-3%• Allergic reactions:

<1 in 1 million• Guillain Barre Syndrome:

1 in 1 million.

Intradermal (ID)• Local Reactions:

redness 76%hardness 58%swelling 57%pain 51% itching 47%

• Systemic side effects: similar to TIV

Nasal Spray (LAIV)• Local Reactions:

cough 14% runny nose 45%sore throat 28%chills 9%

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Antivirals drugs

• M2 ion channel inhibitors:

– Amantadine– Rimantidine

• Neuraminidase inhibitors:

– Tamiflu™ (oseltamivir)-in the form of pills/tablets– Relenza® (zanamivir)-in the form of inhaled

powder

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What is Pandemic Influenza?• Pandemic influenza is a respiratory (or breathing)

illness that is new to humans and can make them very sick.

• It happens about 3 times per century and spreads around the world, killing many people and making many people sick.

• Pandemic influenza also causes many serious problems in municipalities, such as problems with food, water, and electricity.

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The new virus must be efficiently transmitted 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

Human 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

– Result of Antigenic Drift

Influenza Pandemics– Appear in the human

population rarely and unpredictably

– Human population lacks immunity to a new influenza A virus subtype

– All age groups, including healthy young adults, may be at increased risk for serious complications

– Result of Antigenic Shift59

Seasonal Epidemics vs. Pandemics

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What is H1N1?• A new virus that emerged in 2009 in Mexico City

and quickly spread across the globe.

• H1N1 declared a pandemic in June 2009.Initially referred to as “swine” influenza because the virus was found to contain genetic material from swine influenza A strains, as well as avian and human strains.

-A human virus, and people get it from people – not from pigs. During 2011 India reported 603 cases,275 deaths, case fatality rate=12.44%.

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Case definitions for pandemic Influenza

• Suspected case: with onset in 7 days of close contact OR within 7 days of travel to community OR residing in community with a confirm case of pandemic influenza A.

• Probable case: suspected case + positive for influenza A by immunofluorescence assay.

• Confirmed case: laboratory confirmed pandemic influenza A case by: RT-PCR,VIRUS CULTURE and FOUR FOLD RISE IN ANTIBODY TITRE.

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STARTMarch 2009

April 2009

May 2009

Pandemic H1N1 rapidly spread worldwide: May 2009

29 May *, 15,510 cases including 99 deaths reported by 53 countries

1-1011-50

51–500

500-5,000

Cumulative cases

>5,000

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Pandemic influenza in the 20th Century

1920 1940 1960 1980 2000

H1N1 H2N2 H3N2

1918 “Spanish Flu” 1957 “Asian Flu” 1968 “Hong Kong Flu”

20-40 million deaths 1 million deaths 1 million deaths

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Pandemic Phases

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WHO Pandemic Phases and Currently Circulating Novel

Viruses• H1N1

– April 25, 2009: Declaration of a Public Health Emergency of International Concern

– April 28, 2009: WHO declares Phase 4– April 29, 2009: WHO declares Phase 5– June 11, 2009: WHO declares Phase 6

• H5N1– First human cases reported 1997– Increase in reports of human cases began in 2003– WHO Phase 3

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Pandemic Precautions

• If a pandemic occurs:– Avoid crowded conditions and close contact with

other people – Consider wearing respirators or other protective

equipment– Follow good hygiene measures– Practice social distancing– Quarantine ill individuals– Vaccination

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What is Avian Influenza (Bird Flu)?• It is a disease that spreads from bird to bird, causing

some birds to become very sick or die.

• It can spread from birds to humans, but not easily.

• It is not yet capable of spreading from human to human except in very rare cases.

• There is a risk that it could become pandemic influenza, but this has not happened yet with the type of bird flu that has recently killed so many chickens.

– Direct and close contact with sick or dead poultry.• Visiting a live poultry market.

– No evidence of sustained person-to-person spread.

– Limited probable person-to-person spread.

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Human H5N1 Epidemiology

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Pathogenicity • High pathogenicity avian influenza (HPAI)

– Causes severe disease in poultry– Contains subtypes H5 or H7

• Low pathogenicity avian influenza (LPAI)– Causes mild disease in poultry– Contains other H subtypes

• Includes non-HPAI H5 and H7.

• LPAI H5 or H7 subtypes can mutate into HPAI.

Worldwide H5N1 Outbreak in Humans: 2003 - 2007

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Avian Influenza (outbreaks)

• In 2003, the avian influenza virus strain H7N7 occurred in poultry farms in the Netherlands, spreading to Germany and Belgium. Infection, mainly conjunctivitis occurred in 83 humans with 1 death. The outbreak was controlled by destroying over 30 million domestic poultry.In 2003, the avian influenza virus, H9N2 was identified in a child in Hong Kong with influenza who recovered.

• 2011- 62 cases in cambodia,indonesia,china,bangladesh.

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Newer strains and vaccines for Influenza

• Influenza A (H1N1)– Retain current vaccine strain A/California/7/2009 (H1N1)-like virus.

• Influenza A (H3N2)– Replace current vaccine strain A/Victoria/361/2011 (H3N2) - like virus

with an A(H3N2) virus antigenically like the cell-propagated prototype virus A/Victoria/361/2011.

• Influenza B– Replace current vaccine strain with a B/Massachusetts/2/2012-like virus

(B/Yamagata lineage)– Retain current B/Wisconsin/1/2010 - like virus (B/Yamagata lineage)– Replace current vaccine strain with an alternative candidate vaccine virus

from the B/Victoria lineage

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Recent Influenza Vaccine Approvals

• Fluarix QuadrivalentDecember 14, 2012

• First licensed quadrivalent inactivated influenza vaccine to prevent seasonal influenza

• For use in persons ages 3 years and older• Contains four strains of the influenza virus, two influenza A

strains (H1N1 and H3N2) and two influenza B strains (Yamagata and Victoria lineages)

• Flublok– January 16, 2013

• Trivalent vaccine• First licensed influenza vaccine manufactured using an

insect virus (baculovirus) expression system and recombinant DNA technology

• For use in persons ages 18 through 49.

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Influenza Vaccine Presentations 2011-2012

Vaccine Dose form AgeFluzone TIV(sanofi pasteur)

SDS, SDV, MDV

6 months and older

Fluarix TIVFluLaval TIV(GSK)

SDSMDV

3 years and older18 years and older

Fluvirin TIV(Novartis)

SDS, MDV 4 years and older

Afluria TIV(CSL)

SDS 9 years and older

Flumist LAIV(MedImmune)

Nasal spray 2-49 years (healthy, nonpregnant)

SDS=single dose syringe; SDV=single dose vial; MDV=multidose vial SDS=single dose syringe; SDV=single dose vial; MDV=multidose vial

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WHO Recommended strains 2011 -12 season

• It is recommended that vaccines for use in the 2011-2012 influenza season (northern hemisphere) contain the following:

an A/California/7/2009 (H1N1)-like virus;

an A/Perth/16/2009 (H3N2)-like virus;

a B/Brisbane/60/2008-like virus. 2011-12 season WHO recommended strain are similar to 2010-11 season

northern hemisphere strains

2009

-10

2010

-11

2011

- 12

Brisbane

Brisbane

Brisbane

BA/H3N2A/H1N1

California

Perth

Brisbane

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