1. Samar Musmar,MD,FAAFP Vice Dean for Clinical Affairs An-Najah National University Faculty of Medicine Head, Medicine and Society Dep. Flu Vaccination in Children 2008

2. 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

3. 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)

4. 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

5. 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

6. 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

7. 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

8. Influenza Laboratory-Confirmed Cumulative Hospitalization, Children 0 - 4 Years, 2007- 08 and Previous 4 Seasons

9. Average Influenza-Associated Illness Rates by Age Group* Sources: Monto J Infect Dis Glezen N Engl J Med

10. 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

12. 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

13. Age/Risk groupOutcomeEffectiveness* 6m-16 years, healthyInfluenza50-90% 18-64 years, healthyInfluenza50-90% >65 years, communityInfluenza30-70% Elderly, nursing homeInfluenza30-40% 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.

14. New and Updated Recommendations from the Advisory Committee on Immunization Practices (ACIP)

15. 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

16. Timeline of ACIP Recommendation Changes for use of Influenza Vaccine Before 2000: Persons aged 65 or older Persons with chronic medical conditions that make them more likely to have complications of influenza Pregnant women in the second or third trimester Contacts (household and out of home caregivers) of the above groups Healthcare 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 months Contacts (household and out of home caregivers) of children aged 0-59 months 2008: All children aged 6 months—18 years

17. 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

18. 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

19. 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

20. Other options Nonpharmacologic 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

22. 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

23. 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

24. Thank You for your Attention