Impact of the Present Influenza Vaccination Strategy in the US

1. Impact of the Present Influenza Vaccination Strategy in the US Kathleen M. Neuzil, MD, MPH October 24, 2005

2. Questions • What is the goal of the influenza vaccination program? • How do we measure its impact? • How do we measure the impact of other vaccine-preventable diseases? • What are alternative ways to measure impact?

3. What are the goals of the vaccination program? • Eradicate the disease? • Prevent illness? • Prevent hospitalizations? • Prevent death? • Save money?

4. What are we trying to reduce? • All-cause mortality? • P&I mortality? • Influenza-specific mortality? • All hospitalizations? • P&I hospitalizations? • Influenza-specific hospitalizations?

5. How do we measure influenza morbidity and mortality? • Large, population-based estimates based on statistical modeling methods • Non-specific outcomes

6. Influenza: A Seasonal Respiratory Disease Associated with Increased Mortality, 1887-1921

8. Estimated Annual Influenza-related Mortality Rate per 100,000 Person-years, US 1990-1999 Deaths AGE (years) Thompson et al. JAMA 2003; 289:179.

9. Hospitalization Rates by Age and Risk Group Number High-Risk Low-Risk 200 150 100 50 0 <1 1 - <5 5 - <15 15 - 44 45 - 64 >65 Age (years) Glezen et al. Am Rev Respir Dis 1987;155(6):1119-1126; Neuzil et al. NEJM 2000;342:225-231; Neuzil et al. J Pediatr 2000;137:856-864.

10. What is wrong with statistical modeling methods when applied to impact of influenza vaccine? • No individual data on underlying risk factors, vaccine use (are the people at high risk for morbidity and mortality getting vaccine?) • Non-specific outcome measures • Vaccine coverage rates too low

11. What impact would we expect to see in an ecologic study? • 2-10% of all winter mortality in elderly due to influenza (Simonsen. Arch Intern Med 2005) • RCT in >60-year-olds suggests that influenza vaccine prevents 58% influenza illness (Govaert JAMA 1994) • An estimated 1-5% of all winter mortality in elderly could be prevented by vaccination, with variation by season • Would require a large ecologic study to show an effect of this size on a non-specific mortality outcome

12. Questions • What is the goal of the influenza vaccination program? • How do we measure impact in this country? • How do we measure the impact of other vaccine-preventable diseases? • What are alternative ways to measure impact?

13. Other vaccine-preventable disease have specific outcome measures

14. MMWR. January 2, 2004.

15. HIB, invasive disease Hepatitis A Hepatitis B Measles Meningococcal disease Mumps Pertussis Poliomyelitis, paralytic Rubella Rubella, congenital syndrome Streptococcus pneumoniae, invasive disease (drug-resistant, < 5 years) Tetanus Varicella Varicella deaths Added in 2004: Influenza deaths and encephalopathy < 18 years Notifiable Diseases Potentially Preventable by Vaccination, U.S. MMWR 2005; 52 (54); 1-85.

16. Common Notifiable Diseases, U.S., 2003 MMWR 2005; 52 (54); 1-85.

17. Influenza Morbidity and Mortality in Children, U.S. 2003-04 • As of June 18, 2004, 152 deaths in persons <18 years, all laboratory-confirmed • 73% had no known high-risk medical conditions • Between 1990-99, modeling estimated that an average of 92 deaths from influenza occurred in children <5 years • As of June 18, 50 cases of encephalopathy • 21% died and 38% neurologic sequalae Thompson et al. JAMA 2003; 289; 179. MMWR April 9, 2004 Presentation at ACIP. June 23, 2004

18. Questions • What is the goal of the influenza vaccination program? • How do we measure impact in this country? • How do we measure the impact of other vaccine-preventable diseases? • What are alternative ways to measure impact?

19. What about laboratory-based surveillance? • Emerging Infections Program: hospitalizations for persons aged <18 years in 11 metropolitan areas (passive) • New Vaccine Surveillance Network: hospitalization rates among children <5 years in 3 sentinel counties (active) • State of Colorado (passive)

20. Limitations of laboratory-based surveillance • Influenza testing is not likely to be performed on all seriously persons with full spectrum of influenza illness (acute respiratory illness, febrile illness in children, exacerbations of underlying disease) • Sensitivity of tests (when in course of illness is tested performed? What test is performed? What is the specimen?) • Rapid influenza tests can have low positive predictive value both early and late in the influenza season

21. Disease Estimates Based on Active and Passive Surveillance Methods: NVSN and EIP, 2003-04 Grijalva et al. EID 2005 (in press)

22. Rate per 100,000 of laboratory-confirmed influenza-associated hospitalizations, Colorado, 2004-05 MMWR 2005; 54: 535-537.

23. 38-yo influenza and asthma exacerbation 56 yo s/p BMT - primary influenza pneumonia 73 yo woman with primary influenza pneumonia 81 yo man influenza and S. aureus pneumonia

24. Alternative Strategy: Universal Vaccination – Canadian Province of Ontario • 2000: Program of free influenza vaccine, recommended for everyone 6 months and older • Rationale: Reduce seasonal and economic impact of the disease and improve pandemic preparedness Johansen H et al. Influenza vaccination. Health Reports 2004; 15: 33-43.

25. Summary • Substantial morbidity and mortality due to influenza each year; precise effect of current vaccination strategy on this morbidity is difficult to measure. • More precise surveillance methods are needed to discern if influenza control could best be improved by increasing coverage rates among currently targeted groups, by increasing the proportion of the healthy population vaccinated, and/or by developing more immunogenic vaccines.

26. Critical information gaps