Samar Musmar,MD,FAAFPVice Dean for Clinical AffairsAn-Najah National University

Faculty of Medicine Head, Medicine and Society Dep.

Flu Vaccination in Children 2008

Objectives

• Biology of Influenza• Influenza complications• Influenza epidemiology• Influenza Control• Influenza vaccine• Effectiveness of vaccine• SE of TIV flu vaccine• LAIV• Recommendations for flu

Vaccine in Children• Antiviral medications

Influenza Virus• Highly transmissible respiratory

illness caused by influenza viruses

• 3 types A,B,C

• Yearly winter epidemics (seasonal or interpandemic influenza)

• Sporadic, unpredictable pandemics

Human Influenza (Flu)

Influenza virus type A

•Subtyped based on surface glycoproteins

•16 hemagglutinin (HA) and 9 neuraminidase (NA)

•Current human subtypes: H1N1 & H3N2

•Capable of epidemics and pandemics•Antigenic shift--pandemics and drift—yearly epidemic

•Infects multiple other species and can jump between them

•Birds, pigs, horses, dogs…

•Birds are the reservoir for new subtypes: H1-16

Influenza Virus Types B and C

•Influenza B•Humans only reservoir•Less mortality in most years c/w type A

•Associated with epidemics, not pandemics

•One influenza B strain in the annual seasonal influenza vaccine

•Influenza C•Causes mild disease, sporadic cases•Not included in vaccine

Why to use vaccine?• Complication in Children

1.Serious illnesses----hospitalization (Influenza pneumonia mainly)

2.Influenza-associated deaths – uncommon

• data indicate -- although deaths are more common among children with risk factors for influenza complications, the majority of pediatric deaths occur among children of all age groups with no known high-risk conditions

Annual Interpandemic Influenza Impact*

•2.5-20% of population ill•Highest rates in children•Attack rates over 30% in children reported

•Average of >36,000 deaths (wide range)•>90% in those >64 years

•Average of >200,000 hospitalizations (wide range)•About 50% in those >64 years•Risk of hospitalization for children <2 years similar

to elderly

•Substantial economic impact•Burden of annual epidemics estimated at $87.1

billion annually

Influenza Laboratory-Confirmed Cumulative Hospitalization, Children 0 -

4 Years, 2007- 08 and Previous 4 Seasons

0

2

4

6

8

10

12

14

40-41 42-43 44-45 46-47 48-49 50-51 52 -1 2-3 4-5 6-7 8-9 10-11 12-13 14-15 16-17 18-19 20-21

2007-2008 Influenza Season 2 Week Reporting Period

Pop

ulat

ion-

Bas

ed R

ate

per

10,0

00 C

hild

ren

2003-2004 2004-2005 2005-2006 2006-2007 2007-2008

Average Influenza-Associated Illness Rates by Age Group*

0%

5%

10%

15%

20%

25%

30%

35%

40%

<5 5 to 14 15 to 24 25 to 60 >60Age group

Illin

ess

rate

s

Michigan

Houston

Sources: Monto J Infect Dis Glezen N Engl J Med

Types of Flu vaccine

• Trivalent inactivated influenza vaccine (TIV)

1.Annual

2.Any person aged >6 months

• Live, attenuated influenza vaccine (LAIV)

1.Annual

2.Healthy, nonpregnant persons aged 2--49 years

Determinants of Antibody Response to Influenza Vaccines

• Age• Elderly, infants and chronically ill generally lower antibody

response

• Prior exposure to virus strains similar to those in vaccine (infection or previous vaccination)

• Immune competence of person being vaccinated

• Amount of antigen in vaccine

• Virus – strains can vary as to how robust immune responses will be

Age/Risk groupOutcomeEffectiveness*

6m-16 years, healthyInfluenza50-90%

18-64 years, healthyInfluenza 50-90%

>65 years, communityInfluenza30-70%

Elderly, nursing homeInfluenza 30-40%

Elderly, nursing homeHospitalization30-60%

Inactivated Vaccine Effectiveness by Age and Risk Group

*Overall range from studies conducted when good antigenic match between vaccine and circulating strains with lab-confirmed influenza. Effectiveness may be lower when vaccine and circulating strains antigenically different.

New and Updated Recommendations from the

Advisory Committee on Immunization Practices (ACIP)

New from the ACIP: Influenza Vaccination Recommendations

for Children

All children aged 6 months through 18 years should receive annual influenza vaccination, beginning in 2008 if feasible, and beginning no later than during the 2009-2010 influenza season

Timeline of ACIP Recommendation Changes for use of Influenza Vaccine

Before 2000: Persons aged 65 or olderPersons with chronic medical conditions that make them more likely to have complications of

influenza Pregnant women in the second or third trimesterContacts (household and out of home caregivers) of the above groupsHealthcare workers

2000: Adults 50 and older

2004: Children aged 6--23 months Contacts (household and out of home caregivers) of children aged 0--23 months

Women who will be pregnant during influenza season

2006: Children aged 6--59 monthsContacts (household and out of home caregivers) of children aged 0-59 months

2008: All children aged 6 months—18 years

Rationale for Expanding Vaccination Recommendations to Include all School-

age Children and Adolescents*Rationale

• Evidence that influenza has substantial adverse impacts among school age children and their contacts (e.g., increased school absenteeism, antibiotic use, medical care visits, and parental work loss)

• Evidence that influenza vaccine is effective and safe for school-age children

• The expectation that a simple age-based influenza vaccine recommendation will improve current low vaccine coverage levels among the approximately 50% of school-age children who already had a risk- or contact-based indication for annual influenza vaccination

Also noted

• The potential for the indirect effect of reducing influenza among persons who have close contact with children, and reducing overall transmission within communities, if sufficient vaccination coverage among children can be achieved

*Approved at February 27, 2008 ACIP meeting.

Begins in 2008-09 influenza season

Other options “Antiviral drugs”• Adjunct to vaccination• Effective when administered as treatment and when used for

chemoprophylaxis after an exposure to influenza virus• Amantadine and rimantadine

– effective against influenza A only

– approved for treatment and prophylaxis

– High Levels of Adamantane Resistance Among Influenza A (H3N2) MMWR 05-06

• Zanamivir (aged >7 year) and oseltamivir (aged >1 years)

– neuraminidase inhibitors

– effective against influenza A and B

– Oseltamivir(Tamiflu) approved for prophylaxis

Antiviral Resistance 2008 USA• Neuraminidase Inhibitor Resistance :

– (11%) A (H1N1) viruses resistant to oseltamivir

• Was (0.7%) in 2005-2006

– 0 (H3N2) viruses resistant to oseltamivir

– 0 B viruses resistant to oseltamivir

– All tested viruses remain sensitive to zanamivir

– Given type/subtype prevalence in the United States, low rate of overall resistance (~2%)

• Adamantane Resistance

– 14% influenza A (H1N1) viruses tested were resistant

– (99%) influenza A (H3N2) viruses tested were resistant

Other optionsNonpharmacologic interventions

• Advising frequent hand washing and improved respiratory hygiene

• Reasonable and inexpensive

• Have been demonstrated to reduce respiratory diseases but

• Have not been studied adequately to determine if they reduce transmission of influenza virus

Universal flu vaccine

• intended to provide protection against all ‘A’ strains of the virus that causes human influenza, including pandemic strains

• Will not need to be renewed annually

• targets M2e(matrix protien 2 ectodomain) a relatively invariant viral determinant

• Successful clinical trials, animal ,phase I human

Other Key Updates in the 2008 ACIP Influenza Vaccine Recommendations

• Either TIV or LAIV should be used when vaccinating healthy persons aged 2--49 years

• 2 doses separated by >4 weeks for children aged 6 months—8 years receiving vaccination for the first time

• Children 2—4 years old should be screened for reactive airways disease before receiving LAIV (MMWR Nov 23 2007)

• “Healthy” means no underlying chronic illness that confers increased risk for influenza complications

• All new 2008–2009 trivalent vaccine virus strains• A/Brisbane/59/2007 (H1N1)-like• A/Brisbane/10/2007 (H3N2)-like• B/Florida/4/2006-like

– Neuraminidase inhibitors (oseltamivir or zanamivir) remain drugs of choice in prevention or treatment• High levels of resistance among adamantane class drugs

Thank You for your Attention