Seasonal Influenza: Vaccines & Prevention

1. Seasonal Influenza:Vaccines & Prevention Kristin Nichol, MD, MPH, MBA Professor of Medicine University of Minnesota Chief of Medicine and Director Primary Care Service Line Minneapolis VA Medical Center Minneapolis, MN

2. Overview • Trivalent inactivated (TIV) and live attenuated influenza virus (LAIV) vaccines • Efficacy & effectiveness in children, adults, elderly • Cost effectiveness of vaccination • Vaccination rates • Remaining issues

3. Epidemic Influenza Continuesto Have a Huge Annual Impact + Avg respiratory & circulatory = 294,000 1979-80 thru 2000-01. * Avg all cause, 1976-77 thru 1998-99. **Avg all cause 1990-91 thru 1998-99. MMWR. 2005;54 (RR-8). Thompson et al. JAMA. 2003;289:79. Thompson et al. JAMA. 2004;292:1333. Adams PF et al. Vital Health Stat. 1999;10(200).

4. Options for Preventingand Controlling Influenza • Hand hygiene • Respiratory hygiene/cough etiquette • Contact avoidance • Antivirals • Immunization CDC. Preventing the Flu. www.cdc.gov/flu/protect/stopgerms.htm

5. Influenza Vaccines: A Trivalent Defense TypeAH1N1 TypeAH3N2 InfluenzaProtection Type B CDC. MMWR Morb Mortal Wkly Rep. 2005;54(RR-8).

6. Trivalent Inactivated (TIV) and Live Attenuated Influenza Virus (LAIV) Vaccines MMWR. 2005;54 (RR-8).

7. Outcome / case definition & RRR vs ARR • Typical kinds of outcomes assessed in VE studies • Cause specific (specific outcomes) • Infection • Lab confirmed illness (LC ILI) • LC Influenza + otitis media • “All cause” (sensitive outcomes) • Clinical illness (ILI) without lab confirmation • Complications • Otitis media • Pneumonia hospitalization • Death • Cause specific outcomes provide highest RRR because there is less “noise” • But this does not mean that the lower RRR seen with all cause outcomes means that the vaccine is less effective (ie the ARR would be the same or greater if it could be measured)

8. Influenza Vaccine Efficacy in Children 1. Jefferson TJ, et al. Lancet. 2005;365:773-80. 2. Negri E, et al. Vaccine. 2005;23: 2851-61.

9. Influenza Vaccine Efficacy in Healthy Adults Demicheli V, et al. Cochrane Library 2004; issue 3.

10. Effectiveness of Influenza Vaccination in High Risk Persons < 65 Years of Age Hak E, et al. Arch Intern Med 2005; 165: 274.

11. Influenza VE in Community Dwelling Elderly (Results of 2 Meta Analyses) Vu T, et al. Vaccine. 2002;20:1831. Jefferson T, et al. Lancet. 2005;366:1165-74.

12. Influenza VE in LTCF Elderly(results of 2 meta analyses) Gross PA, et al. Ann Intern Med. 1995;123: 518 – 27. Jefferson TJ, et al. Lancet. 2005;366:1165-74.

13. Influenza Vaccination Has Downstream Benefits • Vaccination of school children • Lower illness rates in the community • Tecumseh, MI study [1] • Texas study [2] • Lower death rates in the elderly • Japanese experience [3] • Vaccination of children in households [4] • Lower illness rates in school-aged siblings • Fewer work loss days among parents • Vaccination of healthcare workers • Lower death rates in residents of LTCFs [5] • Monto AS et al. J Infect Dis. 1970;122:16. • Piedra PA et al. Vaccine. 2005;23:1540. • Reichert T, et al. NEJM. 2001;344:889. • Hurwitz ES. JAMA. 2000;284:1677. • Carman WF, et al. Lancet. 2000;355:93.

14. Sensitivity of Symptoms Adapted from Monto AS, et al. Arch Intern Med 2000; 160: 3243-7.

15. Sensitivity of Laboratory Diagnostic Tests Based on data from 533 US subjects included in neuraminidase trials. Zambon M et al. Arch Intern Med 2001; 161: 2116-22.

16. Impact of More Sensitive Outcomes on ARRMore sensitive outcomes will have a higher ARR – ie they are more inclusive Nichol KL. Virus Res 2004; 103: 3 – 8.

17. CEA Studies of Influenza Vaccination of Children 1. Nichol KL. Vaccine. 2003;21. 2. Meltzer MI. Vaccine. 2005;23:1004.

18. CEA Studies of Influenza Vaccinationof Working Adults Around the Globe 1. Nichol KL. Vaccine. 2003;21:1769. 2. Rothberg MB. Am J Med. 2005;118:68. 3. Turner D et al. HTA. 2003;7(35). 4. Martin DJ. Occup Health SA. 1997;3:23.

19. CEA Studies of Influenza Vaccinationof the Elderly Around the Globe Nichol KL. Vaccine. 2003;21:1769.

20. Expansion of Goals for Influenza Vaccination – Everyone Can Benefit

21. ACIP Recommendations 2005-06 • High Priority • High risk for serious complications • Age 65+ • Chronic medical conditions • Conditions that compromise respiratory function or ability to handle secretions • Residents of LTCFs • Pregnant women • Children/adolescents on chronic ASA Rx • Children 6 to 23 months of age • Likely to be high risk (ages 50–64) • Persons who can transmit to high risk groups • Special emphasis on HCWs • Others CDC. MMWR. 2005;54 (RR-8).

22. 2010 Goal Influenza and Pneumococcal Vaccination Rates Are Still Too Low MMWR 2001;50(25):532-537. NHIS (‘01, ’03, Jan – Jun ‘04).

23. Disparities by Age: Influenza & Pneumococcal Vaccination of High Risk Persons, 2003 MMWR. 2004;53:1007.

24. Disparities by Race: Influenza & Pneumococcal Vaccination of Elderly Persons, 2004 NHIS early release estimates, Jan – Jun 2004.

25. Influenza Vaccination Coverage2004-05 CDC; MMWR. 2005; 54:304-7.

26. Summary • Influenza is a bad disease (for everyone) and current vaccines provide many benefits (for everyone) • Current vaccines are underused • Current vaccines are imperfect • Roles for • More effective vaccine delivery • To expanded target groups (?) • More timely availability and adequate quantities of vaccine • Better vaccines