1. National Immunization Conference March 9, 2006 Walter A. Orenstein, M.D. Professor of Medicine and Pediatrics Director, Emory Vaccine Policy and Development Associate Director, Emory Vaccine Center Universal Influenza Vaccination in the United States

2. “The nation’s top advisers on vaccine policy have taken a wise if timid step in recommending that all children from 2 to 5 years old be vaccinated against influenza every year, along with their parents, siblings and caregivers….. Any mother or father can endorse the wisdom of vaccinating young children – not just to protect the youngsters, but also to prevent them from infecting the rest of the household….. Our only qualm is to wonder whether even more children should be vaccinated to protect us all from the flu bugs…. But in the long run, it would make sense to ramp up production capacity and vaccinate virtually everyone as a prelude to preparing for mass vaccinations should an influenza pandemic strike.” From: Editorial – New York Times, February 25, 2006

3. Influenza is a Serious Disease Each year in the US, influenza causes an average of 36,000 deaths and > 200,000 hospitalizations From Thompson WW et al, JAMA 2003; 289:179-186 and Thompson WW et al, JAMA 2004; 292:1333-1340

4. From Simonsen L, et al. Arch Intern Med 2005:165:265-272 Figure 3. Seasonal excess pneumonia and influenza (P&I) in persons 65 years or older from 1968 through 2001. The green line shows influenza vaccination coverage. Adjusting for age and controlling for dominant influenza virus subtypes modified the excess P&I and all-cause mortalities rates; here, red squares indicate mortality rates for individual seasons dominated by influenza A (H3N2) viruses. Seasons dominated by influenza A (H1N1) and/or B viruses are shown as triangles.

5. Why Consider Universal Vaccination?  Direct protection of vaccinees against influenza and its complications  Indirect protection of the community through herd immunity  Simplify complex indications facilitating program implementation  Build manufacturing capacity which could also be useful in a pandemic

6. Proportions of the Population Covered by Current Influenza Vaccine Recommendations* Adults > 65 years100% Adults 50-64 years100% Adults 18-49 years51% † Children 2-17 years40% † Children 6-23 months100% Children <6 months0% Source: Gary Euler, CDC, email 10/28/05 *Does not include ACIP recommendation for vaccination of 24-59 month old children and their contacts

7. The ACIP’s New Recommendation  Vaccination of all children 24-59 months of age (5.3 million new children)  Vaccination of their household contacts (11.6 million new persons)  Based primarily on morbidity especially outpatient visits, antibiotic courses etc.  Prior focus on mortality and hospitalization reduction

8. Differences in the Rates of Influenza Associated Outpatient Visits During Influenza Periods versus Peri-seasonal and Summer Baseline Rates (per 100 person months) Healthy Children Peri-seasonal and Baseline Rate Summer Baseline Rate 6 - 23 months 1.8 (1.1 - 2.4) 8.9 (8.3 - 9.5) 2 - 4 years 1.6 (1.2 - 2.0) 5.8 (5.5 - 6.2) 5 - 17 years 1.2 (1.0 - 1.4) 3.6 (3.4 - 3.7) From: O’Brien MA et al. Pediatrics 2004;113:585-93

9. Critical Questions to be Addressed Before Recommending All Persons 5- 49 Years of Age Be Vaccinated Annually Against Influenza - I  Health burden of influenza in healthy children and adults  Economic burden of influenza in healthy children and adults  Direct benefits of influenza vaccine  Herd immunity impact of vaccination of healthy children and adults

10. Critical Questions to be Addressed Before Recommending All Persons 5- 49 Years of Age Be Vaccinated Annually Against Influenza - II  Cost-effectiveness  Logistics and feasibility  Vaccine supply  Vaccine safety  Acceptance  Potential phase-in strategies

11. Influenza in School-aged Children: Effect on Children and Family Events per 100 children Illness episodes 28 Total schooldays missed 63 Days work missed by parents 20 Household members ill within 3 days 22 Arch Ped Adol Med 2002; 156: 986. From: Edwards, K. Universal Vaccination Workshop October 2005. Slides posted http://www.medicine.emory.edu/id/ecirve/areweready.cfmhttp://www.medicine.emory.edu/id/ecirve/areweready.cfm

12. Strategy to reduce influenza-related deaths Deaths per 100,000, 65yrs + Current20% 5-18yrs 50% 5-18yrs 70% 5-18yrs Vaccination Coverage 90% 65yrs + From: Longini I, et al. Universal Vaccination Workshop October 2005. Slides posted http://www.medicine.emory.edu/id/ecirve/areweready.cfmhttp://www.medicine.emory.edu/id/ecirve/areweready.cfm

13. Percent of Children with > 1 Health Care Visit During Flu Vaccination Season (US, 2002) Age Analysis of 2002 MEPS: Visits during Oct-Dec Most children would need > 1 extra visit during flu vac. season From: Szlagyi P. Universal Vaccination Workshop October 2005. Slides posted http://www.medicine.emory.edu/id/ecirve/areweready.cfmhttp://www.medicine.emory.edu/id/ecirve/areweready.cfm

14. ANNUAL IMMUNIZATION OF CHILDREN WITH INACTIVATED VACCINE Immunogenicity in CF Patients  Effect of repeated annual immunization on serum antibody responses assessed in 38 CF patients over 10 yrs  No significant upward or downward trends in GMTs or % with ‘protective titers’ noted over the 10 year period Note: Vaccine antigens differed from year to year Year of Study Percent with 1:40 Post (A/H3N2) Adapted from Gross PA, et al. Vaccine 14:1280, 1996. From: Keitel W. Universal Vaccination Workshop October 2005. Slides posted http://www.medicine.emory.edu/id/ecirve/areweready.cfmhttp://www.medicine.emory.edu/id/ecirve/areweready.cfm

15. Ingredients for a Successful Universal Influenza Vaccination Program - I  Adequate and reliable supply  Funding for infrastructure, communication, and removing cost as a barrier to vaccination  Support from healthcare providers  Effective public awareness campaign Modified from: Beth Rowe-West, Assn of Immunization Managers, Universal Vaccination Workshop October 2005, http://www.medicine.emory.edu/id/ecirve/areweready.cfm http://www.medicine.emory.edu/id/ecirve/areweready.cfm

16. Ingredients for a Successful Universal Influenza Vaccination Program - II  Dispelling myths about influenza vaccination  Addressing thimerosal concerns  Enhanced tracking through immunization registries  Implementation in phases  Effective public/private partnership Modified from: Beth Rowe-West, Assn of Immunization Managers, Universal Vaccination Workshop October 2005, http://www.medicine.emory.edu/id/ecirve/areweready.cfm http://www.medicine.emory.edu/id/ecirve/areweready.cfm

17. Meeting Consensus - I  Attendees favored more universal approaches to vaccination than the current targeted strategy – However, given vaccine supply and the difficulty implementing current influenza vaccination recommendations, rapidly moving to a universal recommendation could have unintended consequences

18. Meeting Consensus - II  A deliberative approach, gradually expanding recommendations, was preferred  Expand vaccination first among children – Higher risk of illness compared with healthy adults – Greater feasibility of implementation – Potential for indirect protection  Initial expansion to children 24-59 months of age logically follows the 2004 expansion to all children 6 to 23 months old.

19. Meeting Consensus - III  Next expansion to include school aged children – Greatest likelihood of indirect protection of adults and the elderly  No commitment to a universal recommendation – Re-evaluate expanding to healthy adults after assessing impact of pediatric vaccination and herd immunity

20. Conclusions - I  More universal approaches to influenza vaccination are needed to decrease the current burden  The ACIP should lay out a vision for influenza prevention including vaccination of the entire population if incremental steps do not substantially reduce what is an unacceptable health burden

21. Conclusions - II  After each new increment, an evaluation should be performed and if data merit, move to next group  Next logical group is school-aged children Website for “Universal Vaccination Against Influenza – Are we Ready?” is www.medicine.emory.edu/id/ecirve/arewerea dy.cfm www.medicine.emory.edu/id/ecirve/arewerea dy.cfm www.medicine.emory.edu/id/ecirve/arewerea dy.cfm