# Presentation: 061146

## Influenza and Influenza Vaccines

**Clinician’s Outreach and Communication Activity**

**2007-2008 Season**

## Influenza

**Highly infectious viral illness**** **
**Epidemics reported since 16****th**** century**** **
**Virus first isolated in 1933**

## 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**

## Influenza Type A Subtypes

**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 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 Associated Pulmonary and Circulatory Deaths, 1998

**	**
**Age Group (yrs)** **	****  Rate (per 100,000)**
**      ****0 – 49****	****	****	****	****      0.4 – 0.6**
**    ****50 – 64****	****	****	**** ****	****           7.5**
**          **_**>**_**65****	****	****	****	****         98.3**

## Hospitalization Rates for Influenza By Age  and Risk Group*

**Age Group**
**0-11 mos**
**1-2 yrs**
**3-4 yrs**
**5-14 yrs**
**15-44 yrs**
**45-64 yrs**
_**>**_**65 yrs**

**  ****Rate****
** ****(high-risk)**
**808**
**471**
**231**
**92**
**62**
**318**
**507**

** ****Rate****
** ****(not high-risk)**
**274**
**72**
**39**
**23**
**16**
**22**
**182**

*** Data from several studies 1972 - 2004**
*** Hospitalizations per 100,000 population**

## 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 Seasonal Trends

## Influenza Regional Epidemiology

## Influenza Vaccines

**Inactivated subunit (TIV)**
**Intramuscular**
**Trivalent**
**Annual**
**Live attenuated vaccine (LAIV)**
**Intranasal**
**Trivalent**
**Annual****	**

## Influenza Vaccine Supply

**Manufacturer****	****Doses Projected***
**GSK****	****                  30-35 million**
**MedImmune****	****          7 million**
**Novartis****	****          40 million**
**sanofi pasteur       50 million**
**CSL****	****                  No estimate **
**                                ****provided**
**Total****	****             Up to 127-132 m**

## Inactivated Influenza Vaccines Available in 2007-2008

| Vaccine | Package | Dose | Age | Thimerosal |
| --- | --- | --- | --- | --- |
| Fluzone
(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 |
| Fluvirin
(Novartis) | Multidose vial | 0.5 mL | >4 yrs | Yes |
| Fluarix
(GSK)
Flulaval
(GSK) | Single dose syringe
Multidose vial | 0.5 mL

0.5 mL | >18 yrs

>18 yrs | Trace

Yes |

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

## Slide 17

## 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 each year**
**Antibodies wane during the year**
**Surface antigens drift and shift**

## 2007-2008 Influenza Vaccine

**A/Wisconsin/67/2005-like (H3N2)**
**A/Solomon Islands/3/2006-like (H1N1)**
**B/Malaysia/2506/2004-like (Victoria)**

## 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**

## Local reactions		15% - 20%

Fever, malaise		uncommon

Allergic reactions	rare

Neurological			very rare reactions

**Fever, malaise****	****	****uncommon**
**Allergic reactions****	****rare**
**Neurological****	****	****	****very rare**** reactions**

**Inactivated Influenza Vaccine ****Adverse 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

- _Dose_
- 0.25 mL
- 0.50 mL
- 0.50 mL

- _No._
- _Doses_
- 1 or 2
- (4 week interval)
- 1 or 2
- (4 week interval)
- 1

## LAIV  Efficacy

**LAIV  Efficacy**

**Against lab-confirmed influenza following experimental challenge**
**LAIV 85% effective**
**TIV 71% effective**
**No significant difference**
**NEJM 2007 LAIV more effective in preventing culture-confirmed influenza in children younger than five years**

## 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**

## LAIV Schedule

_**Age**_
_**Group**_
**6 mos – 8 years**
**9 yrs and older**

_**Dose**_
**0.2 mL**
**0.2 mL**

_**No.**_
_**Doses**_
**1 or 2 (4 week interval)**
**1**

## Transmission of LAIV Virus

**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 35 - 46 degrees Fahrenheit**
**Similar to TIV**
**If inadvertently frozen, return to refrigerator****	****	**

## Influenza Season 2007-2008

_**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, 2007-2008

**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 2007-2008

**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)**

## 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 **

## 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-Barr****é 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**

## 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**