Influenza and Influenza Vaccines K. Vahdat 25/11/1391

Influenza Highly infectious viral illness Epidemics reported since 16 th 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

N N H Subtypes of type A determined by hemagglutinin (H) and neuraminidase (N) Influenza 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 , 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 – 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 Epidemiology Reservoir Human, animals (type A only) Transmission Respiratory Probably airborne Temporal pattern Peak December - March in temperate area May occur earlier or later Communicability Maximum 1-2 days before to 4-5 days after onset

Influenza Vaccines Inactivated subunit (TIV) – Intramuscular – Trivalent – Annual Live attenuated vaccine (LAIV) – Intranasal – Trivalent – Annual

Influenza Vaccine Supply ManufacturerDoses Projected* GSK million MedImmune 7 million Novartis 40 million sanofi pasteur 50 million CSL No estimate provided Total Up to m

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 VaccinePackageDoseAgeThimerosal Fluzone (sanofi pasteur) Multidose vial*Age-dependent>6 mosYes Single dose syringe* 0.25 mL6-35 mosNo Single dose syringe* 0.5 mL>36 mosNo Single dose vial* 0.5 mL>36 mosNo Fluvirin(Novartis) Multidose vial 0.5 mL >4 yrs Yes Fluarix(GSK)Flulaval(GSK) Single dose syringe Multidose vial 0.5 mL >18 yrs TraceYes *inactivated vaccines approved for children younger than 4 years

Afluria ® Influenza Vaccine Trivalent inactivated vaccine produced in hen’s eggs Approved for persons 18 years and older Available in – Preservative-free prefilled syringe – Multidose vial Similar adverse reaction profile as other inactivated influenza vaccines

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 % effective among frail elderly persons 50% - 60% effective in preventing hospitalization 80% effective in preventing death

Inactivated Influenza Vaccine Adverse Reactions Local reactions15% - 20% Fever, malaiseuncommon Allergic reactionsrare Neurologicalvery rare reactions

Inactivated Influenza Vaccine Adverse Reactions Inactivated influenza vaccine contains only noninfectious fragments of influenza virus Inactivated influenza vaccine cannot cause influenza disease

TIV Schedule Age Group 6-35 mos 3-8 yrs 9 yrs and older Age Group 6-35 mos 3-8 yrs 9 yrs and older Dose 0.25 mL 0.50 mL Dose 0.25 mL 0.50 mL No. Doses 1 or 2 (4 week interval) 1 or 2 (4 week interval) 1 No. Doses 1 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 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

LAIV Schedule Age Group 6 mos – 8 years 9 yrs and older Dose 0.2 mL No. Doses 1 or 2 (4 week interval) 1

Transmission of LAIV Virus LAIV replicates in the NP mucosa Mean shedding of virus 7.6 days – longer in children One instance of transmission of vaccine virus documented in a day care setting Transmitted virus retained attenuated, cold adapted, temperature sensitive characteristics Transmitted 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 degrees Fahrenheit Similar to TIV If 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

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 ACIP and AAP will recommend these children receive TWO doses the second vaccination year MMWR 2007;56 (RR-6)

The Priming Effect 1 st dose primes the immune system 2 nd 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

Second Vaccination Season Doses in 1 st season 1 2 Doses this Season 2 1

Mix and Match If two doses are indicated None are contraindicated Can mix and match TIV/LAIV Use interval of vaccine given first

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 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

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 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

Influenza Antivirals Use neuraminidase inhibitors Oseltamavir: chemoprophylaxis and treatment Zanamavir: treatment only Avoid adamantanes due to resistance

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.  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