Influenza and Influenza Vaccines

K. Vahdat25/11/1391

InfluenzaInfluenza

• Highly infectious viral illness

• Epidemics reported since 16th century

Influenza Virus Strains

• Type A – moderate to severe

illness– all age groups– humans and other

animals

• Type B– changes less rapidly than

type A – milder epidemics– humans only– primarily affects children

NN

H

• Subtypes of type A determined by hemagglutinin (H) and neuraminidase (N)

• Subtypes of type A determined by hemagglutinin (H) and neuraminidase (N)

Influenza Type A SubtypesInfluenza Type A Subtypes

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.

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

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

Influenza Vaccines

• Inactivated subunit (TIV)– Intramuscular– Trivalent– Annual

• Live attenuated vaccine (LAIV)– Intranasal– Trivalent– Annual

• influenza vaccines for 2012–13 contain:• A/California/7/2009 (H1N1)-like, A/Victoria/361/2011

(H3N2)-like, B/Wisconsin/1/2010-like (Yamagata lineage) antigens.

• Children aged 6 months through 8 years require 2 doses of influenza vaccine (administered a minimum of 4 weeks apart) during their first season of vaccination to optimize immune response.

Inactivated Influenza Vaccines

Vaccine Package Dose Age ThimerosalFluzone(sanofi pasteur)

Multidose vial* Age-dependent >6 mos Yes

Single dose syringe*

0.25 mL 6-35 mos No

Single dose syringe*

0.5 mL >36 mos No

Single dose vial*

0.5 mL >36 mos No

FluvirinFluvirin(Novartis)(Novartis)

Multidose vialMultidose vial 0.5 mL0.5 mL >4 yrs>4 yrs YesYes

FluarixFluarix

(GSK)(GSK)

FlulavalFlulaval(GSK)(GSK)

Single dose Single dose syringesyringe

Multidose vialMultidose vial

0.5 mL0.5 mL

0.5 mL0.5 mL

>18 yrs>18 yrs

>18 yrs>18 yrs

TraceTrace

YesYes

*inactivated vaccines approved for children younger than 4 years *inactivated vaccines approved for children younger than 4 years

Why a Yearly Influenza Vaccination

• Influenza vaccine expires June 30 (10 Tir) each year.

• Antibodies wane during the year.

• Surface antigens drift and shift.

Inactivated Influenza Vaccine Efficacy

• 70% - 90% effective among healthy persons <65 years of age

• 30 - 40% effective among frail elderly persons

• 50% - 60% effective in preventing hospitalization

• 80% effective in preventing death

Inactivated Influenza Vaccine Adverse Reactions

• Local reactions 15% - 20%

• Fever, malaise uncommon

• Allergic reactions rare

• Neurological very rare reactions

Inactivated Influenza Vaccine Adverse Reactions

• Inactivated influenza vaccine contains only noninfectious fragments of influenza virus

• Inactivated influenza vaccine cannot cause influenza disease

AgeGroup

6-35 mos

3-8 yrs

9 yrs and older

AgeGroup

6-35 mos

3-8 yrs

9 yrs and older

Dose0.25 mL

0.50 mL

0.50 mL

Dose0.25 mL

0.50 mL

0.50 mL

No.Doses1 or 2

(4 week interval)

1 or 2(4 week interval)

1

No.Doses1 or 2

(4 week interval)

1 or 2(4 week interval)

1

LAIV Efficacy

• Against lab-confirmed influenza following experimental challenge– LAIV 85% effective– TIV 71% effective– No significant difference

Live Attenuated Influenza Vaccine Adverse Reactions

• Children– No significant increase in URI symptoms, fever, or

other systemic symptoms– Increased risk of asthma or reactive airways disease

in children 12-59 months of age• Adults

– Increased rate of cough, runny nose, nasal congestion, sore throat, and chills reported among vaccine recipients

– No increase in the occurrence of fever • No serious adverse reactions identified

LAIV Indications• Healthy* persons 5 – 49 years of age

– Close contacts of persons at high risk for complications of influenza (except severely immunosuppressed)

– Persons who wish to reduce their own risk of influenza

– Healthcare workers

*Persons who do not have medical conditions that increase their risk for complications of influenza*Persons who do not have medical conditions that increase their risk for complications of influenza

LAIV Schedule

AgeGroup6 mos – 8 years

9 yrs and older

Dose0.2 mL

0.2 mL

No.Doses1 or 2 (4 week

interval)

1

Transmission of LAIV Virus

LAIV replicates in the NP mucosaMean shedding of virus 7.6 days – longer in

childrenOne instance of transmission of vaccine virus

documented in a day care settingTransmitted virus retained attenuated, cold

adapted, temperature sensitive characteristicsTransmitted attenuated vaccine virus unlikely to

cause typical influenza symptoms

Use of LAIV Among Healthcare Personnel

No instances of transmission of LAIV have been reported in the U.S.

ACIP recommends that LAIV can be given to eligible HCWs except those that care for severely immuno-suppressed persons (hospitalized and in isolation)

No special precautions are required for HCWs who receive LAIV

LAIV Storage

Must be stored at 35 - 46 degrees FahrenheitSimilar to TIVIf inadvertently frozen, return to refrigerator

• TIV preparations, with the exception of Fluzone Intradermal (Sanofi Pasteur), should be administered intramuscularly.

• Fluzone Intradermal is indicated for persons aged 18 through 64 years

• The intranasally administered live-attenuated influenza vaccine (LAIV), FluMist (MedImmune), is indicated for healthy, nonpregnant persons aged 2 through 49 years

• No preference is indicated for LAIV versus TIV in this age group

• Persons with a history of egg allergy should receive TIV rather than LAIV.

Influenza Season

• Recommended Groups for Vaccination• Children 6-59 months of age• Healthy adults 50 years old and older• Persons 5 – 49 years old at high risk for

complications• Pregnant women• Residents of nursing homes• Household contacts of persons at high risk for

complications• Health care workers

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

HIV Infection and Inactivated Influenza Vaccine

• Persons with HIV at higher risk for complications of influenza

• TIV induces protective antibody titers in many HIV-infected persons

• Transient increase in HIV replication reported• TIV will benefit many HIV-infected persons

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

Influenza Vaccine Recommendations

• Immunization providers should administer influenza vaccine to any person who wishes to reduce the likelihood of becoming ill with influenza or transmitting influenza to others

*Healthy persons 5-49 years of age, including healthcare personnel may receive either TIV or LAIV*Healthy persons 5-49 years of age, including healthcare personnel may receive either TIV or LAIV

New Influenza Vaccine Recommendation

• Children 6 months through 8 years being vaccinated for the first time should receive TWO doses

• Some children do not return for the second dose

• Beginning in influenza season 2007-2008 ACIP and AAP will recommend these children receive TWO doses the second vaccination year

MMWR 2007;56 (RR-6)MMWR 2007;56 (RR-6)

The Priming Effect

• 1st dose primes the immune system• 2nd dose generates specific antibody

response• Ideal if first dose given in the fall• Less ideal if first dose given in Spring,

especially if a new B strain the following Autumn

The Magic of Ninth Birthday

• On or after ninth birthday Priming effect caused by natural infection thought to be significant.

• Only one dose per season required Regardless of previous doses.

Inactivated Influenza VaccineContraindications 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

Egg allergy• Persons with a history of egg allergy who have experienced

only hives after exposure to egg should receive influenza vaccine, with the following additional safety measures:

• a) TIV rather than LAIV should be used.• b) Vaccine should be administered by a

health-care provider who is familiar with the potential manifestations of egg allergy.

• c) Vaccine recipients should be observed for at least 30 minutes for signs of a reaction after administration of each vaccine dose.

• Dividing and administering the vaccine by a two-step approach and skin testing with vaccine, are not necessary.

• Persons who report having had reactions to egg involving such symptoms as angioedem persons should be referred to a physician with expertise in the management of allergic conditions.

Live Attenuated Influenza VaccineContraindications 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

Quadrivalent Influenza Vaccines

• All currently available influenza vaccines are trivalent.

• There are two antigenically distinct lineages of influenza B viruses referred to as Victoria and Yamagata lineages . Immunization against B virus strains of one lineage provides limited cross-protection against strains in the other lineage.

• LAIV, FluMist (MedImmune). This vaccine would be available on 2013–14 .

• Inactivated quadrivalent influenza vaccines currently are in development.

Health Care Workers & Vaccine Maximum efforts over many years to reach the

goal that >90% of HCW be immunized for influenza have failed.

2006-2007 national HCW influenza vaccine coverage rate 44%.

Significant effort by Occupational Health and Infection Control groups in recent years to maximize influenza vaccination.

In 2009,(98.4%) employees vaccinated.

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