the current season: a review of the 2003-04 influenza season

1. The Current Season: A Review of the 2003-04 Influenza Season Nancy J. Cox, Ph.D. Chief, Influenza Branch National Center for Infectious Diseases Centers for Disease Control and Prevention

3. Influenza Virus Types & Subtypes in Humans (Trivalent Vaccine) Type A Seasonal epidemics caused by H3N2, H1N1, and H1N2 subtypes Pandemics (caused by new subtypes) Type B No subtypes Seasonal epidemics only

5. Antigenic Change Antigenic ‘drift” occurs in HA and NA Continual development of new strains secondary to genetic mutations/seasonal epidemics A viruses >> B viruses Antigenic “shift” occurs in HA and NA Associated with pandemics Appearance of novel influenza A viruses bearing new HA or HA & NA

8. Influenza Disease National morbidity and mortality data Comparison with other influenza seasons Mortality in children The circulating viruses

9. What Was Different About the 2003-04 Influenza Season? Sustained increases in influenza activity were reported unusually early Reports of influenza-related pediatric deaths were prominently reported by national media Vaccine manufacturers had sold almost all vaccine by mid-December, a time when demand continued There was a less than optimal match between the predominant circulating viruses (A/Fujian/411/02-like) and the corresponding vaccine component, A/Panama/2007/99

10. Virologic Surveillance Virologic data are the foundation of influenza surveillance Specific for influenza Detect changes in circulating strains Detect novel influenza viruses Used for vaccine strain selection Monitor vaccine match

11. WHO/NREVSS Collaborating LaboratoriesNational Summary, 2003-04

12. Percentage of Specimens Testing Positive for Influenza National Summary, 2003-04

13. Percentage of Visits for Influenza-like IllnessReported by Sentinel ProvidersNational Summary, 2003-04

16. Pneumonia and Influenza Mortality for 122 U.S. CitiesWeek Ending 01/24/04

17. Summary of 2003-04 Influenza Activity in the U.S. as of Week 3 Influenza activity has declined in all regions For week 51 of 2003, widespread influenza activity was reported by more states than during any week during the past 10 years Influenza-related deaths rose above the “epidemic threshold” for the first time during week 51 and has stayed above the baseline for 5 consecutive weeks Reports suggest that highest ILI attack rates were among children and young adults

18. Influenza-Associated Deaths Among Children < 18 Years of Age 121 influenza-associated deaths (lab confirmed) reported to CDC Median age, 3.8 years (2 weeks to 17 years) 72 (60%) < 5 years of age 33 (27%) 6-23 months of age 26 (21%) had underlying medical conditions Available vaccination histories indicate 57 unvax and 2 vax according to recs

19. Is 2003-04 Different in Impact Among Children? Influenza-associated deaths not reportable conditions in the U.S. and annual average number of influenza deaths unknown. During 1990-1999, and estimated annual average of 92 respiratory and circulatory deaths occurred among children < 5 years; estimate based on mathematical modeling, not on counting lab confirmed fatalities. Studies to determine if hospitalization increased in children are ongoing.

20. The Viruses: 2003-04 Influenza Season 573 influenza viruses from U.S. characterized antigenically by CDC’s WHO Collaborating Center 565 were H3N2 viruses (2 H1s and 6 Bs) 106 (18.8%) were well inhibited by antiserum to the A/Panama vaccine strain 459 (81.2%) were similar to the A/Fujian/411/2002 drift variant and not well inhibited by antiserum to A/Panama

21. Why Wasn’t an A/Fujian-like Virus Included in the 2003-04 Influenza Vaccine? The A/Fujian/411/02 (H3N2) antigenic variant was identified at CDC on January 31, 2003. European and U.S. regulatory authorities have required that influenza viruses used to produce vaccine be isolated and passaged only in eggs or cells such as primary chick kidney cells for safety reasons. An A/Fujian-like (H3N2) egg-derived vaccine candidate was first available in April and its use required further characterization and preparation of reagents, steps that would have delayed vaccine availability. Time constraints and uncertainty about antigenic differences among circulating strains led to a decision retain A/Panama/2007/99 (H3N2) in the 2003-04 vaccine.

22. Considerations for Recommendations Are there new antigenic variants? Are new variants spreading? Are current vaccines able to induce antibodies to the new variants? Are any new variants useful for vaccine production?

23. Influenza Vaccine Vaccine uptake Vaccine production and distribution Vaccine effectiveness What we know from past studies What we know about this year

24. Influenza Vaccination Coverage Estimated per Influenza Season1988 – 2001, U.S. This chart shows the upward trend in self-reported influenza vaccination in the past year from 1989 through 2000 by age group in the U.S. The highest coverage is among persons aged 65 years or more (red lines), followed by persons aged 50-64 (blue lines) and those aged 18-49 years (green lines). Data from both the NHIS (1989-2000) and BRFSS (1993-1999) are shown. Based on preliminary data from the 2000 NHIS, for persons interviewed Jan. – June 2000, influenza vaccine coverage was 68.1% among persons aged 65 or more, and 22.9% among adults aged 18-64 years. From the 1998 NHIS, vaccine coverage for high risk persons, not shown on this graph, was 43% for persons aged 50-64 (vs. 29% among healthy), and 23% for those 18-49 (vs. 14% healthy). Influenza vaccination coverage among persons aged 65 years or may has increased at a slower rate in recent years and may be approaching a plateau. Between 1997 and 2000, coverage increased 1 percentage point per year, while coverage nearly doubled from 30% in 1989 to 58% in 1995. Because of the 12 month recall period, coverage estimates by survey year primarily reflects vaccinations received for the prior season. This chart shows the upward trend in self-reported influenza vaccination in the past year from 1989 through 2000 by age group in the U.S. The highest coverage is among persons aged 65 years or more (red lines), followed by persons aged 50-64 (blue lines) and those aged 18-49 years (green lines). Data from both the NHIS (1989-2000) and BRFSS (1993-1999) are shown. Based on preliminary data from the 2000 NHIS, for persons interviewed Jan. – June 2000, influenza vaccine coverage was 68.1% among persons aged 65 or more, and 22.9% among adults aged 18-64 years. From the 1998 NHIS, vaccine coverage for high risk persons, not shown on this graph, was 43% for persons aged 50-64 (vs. 29% among healthy), and 23% for those 18-49 (vs. 14% healthy). Influenza vaccination coverage among persons aged 65 years or may has increased at a slower rate in recent years and may be approaching a plateau. Between 1997 and 2000, coverage increased 1 percentage point per year, while coverage nearly doubled from 30% in 1989 to 58% in 1995. Because of the 12 month recall period, coverage estimates by survey year primarily reflects vaccinations received for the prior season.

25. Influenza Vaccine Production and Distribution, 1999-2003

26. Influenza Vaccine Effectiveness

27. Estimates of Vaccine Effectiveness for the 2003-04 Influenza Season Study conducted by NIP/CDC among HCW at a hospital in Denver Endpoint was effectiveness against influenza like illness (not vs. lab-confirmed influenza more specific endpoint or vs.more serious outcomes, such as hospitalization or death) This study was unable to demonstrate vaccine effectiveness vs. influenza-like illness Other studies ongoing in the U.S. One study in France has reported approx. 60% effectiveness against lab-confirmed influenza

28. Improvements Underway or Being Discussed Enhancing global influenza surveillance (early warning system)- Asia, Central and South America Establishing confirmatory tests for hemagglutination inhibition test (virus neutralization) Using reverse genetics for making vaccine reference viruses if egg derived virus unavailable Conducting annual vaccine effectiveness studies Requiring reporting of laboratory confirmed deaths in children

29. Acknowledgements Members of the Influenza Branch The WHO National Influenza Centers The WHO Collaborating Centers in London, Tokyo and Melbourne The WHO Regional Offices WHO Headquarters in Geneva