1. Influenza and Influenza Vaccine Epidemiology and Prevention of Vaccine- Preventable Diseases National Immunization Program Centers for Disease Control and Prevention Revised March 2002

2. Influenza Highly infectious viral illness Epidemics reported since at least 1510 At least 4 pandemics in 19th century Estimated 21 million deaths worldwide in pandemic of 1918-1919 Virus first isolated in 1933

3. Influenza Virus Single-stranded RNA virus Family Orthomyxoviridae 3 types: A, B, C Subtypes of type A determined by hemagglutinin and neuraminidase

4. Influenza Virus Strains Type A- moderate to severe illness - all age groups - humans and other animals Type B- milder epidemics - humans only - primarily affects children Type C- rarely reported in humans - no epidemics

5. Influenza Virus A/Moscow/21/99 (H3N2) Neuraminidase Hemagglutinin Type of nuclear material Virus type Geographic origin Strain number Year of isolation Virus subtype

6. Structure of hemagglutinin (H) and neuraminidase (N) periodically change ShiftMajor change, new subtype Exchange of gene segment May result in pandemic DriftMinor change, same subtype Point mutations in gene May result in epidemic Influenza Antigenic Changes

7. Examples of Influenza Antigenic Changes Antigenic shift: –H2N2 circulated in 1957-1967 –H3N2 appeared in 1968 and completely replaced H2N2 Antigenic drift –In 1997, A/Wuhan/359/95 (H3N2) virus was dominant –A/Sydney/5/97 (H3N2) appeared in late 1997 and became the dominant virus in 1998

8. Influenza Type A Antigenic Shifts Year 1889 1918 1957 1968 1977 Subtype H3N2 H1N1 H2N2 H3N2 H1N1 Severity of Pandemic Moderate Severe Moderate Mild

9. Impact of Pandemic Influenza 200 million people could be affected Up to 40 million require outpatient visits Up to 700,000 hospitalized 89,000 - 200,000 deaths

10. Influenza Pathogenesis Respiratory transmission of virus Replication in respiratory epithelium with subsequent destruction of cells Viremia usually not demonstrable Viral shedding in respiratory secretions for 5-10 days

11. Influenza Clinical Features Incubation period 2 days (range 1-5 days) Severity of illness depends on prior experience with related variants Abrupt onset of fever, myalgia, sore throat, nonproductive cough, headache

12. Influenza Complications Pneumonia –primary influenza –secondary bacterial Reye syndrome Myocarditis Death ~0.5-1 per 1000 cases

13. Impact of Influenza Highest rates of hospitalization among young children and person >65 years Average of 114,000 influenza-related excess hospitalizations per year since 1969 57% of all hospitalizations among persons <65 years of age Greater number of hospitalizations during type A (H3N2) epidemics

14. Impact of Influenza 20,000 excess deaths in each of 11 epidemics between 1972 and 1995 >40,000 excess deaths in 6 epidemics >90% of deaths among persons >65 years of age

15. Influenza Diagnosis Clinical and epidemiological characteristics Isolation of influenza virus from clinical specimen (e.g., nasopharynx, throat, sputum) Significant risk in influenza IgG by serologic assay Direct antigen testing for type A virus

16. Influenza Epidemiology Reservoir Human, animals (type A only) Transmission Respiratory Probably airborne Temporal pattern Peak December - March in temperate area May occur earlier or later Communicability Maximum 1-2 days before to 4-5 days after onset

17. Month of Peak Influenza Activity – United States, 1976-2001

18. Influenza Vaccine CompositionSplit (subvirion) virus Trivalent (H3N2, H1N1, B) EfficacyVaries by similarity to circulating strain, age, underlying illness Duration of Immunity<1 year Schedule1 dose annually* *2 doses for first vaccination of children <9 years

19. Influenza Vaccine Efficacy 70% to 90% effective among persons <65 years of age 30%-40% effective among frail elderly persons 50%-60% effective in preventing hospitalization 80% effective in preventing death

20. Influenza and Complications Among Nursing Home Residents VaccinatedUnvaccinated RR=1.9 RR=2.0RR=2.5RR=4.2 Genesee County, MI, 1982-1983

21. Timing of Influenza Vaccine Programs Influenza activity peaks between late December and early March Optimal time for vaccination programs October through November First available vaccine should be targeted to persons at highest risk of complication of influenza

22. Actively target vaccine available in September and October to persons at increase risk of influenza complications, children <9 years, and health care workers Vaccination of all other groups should begin in November Continue vaccinating through December and later, as long as vaccine is available Timing of Influenza Vaccine Programs

23. Influenza Vaccine 2001-2002 A/Moscow/10/99 (H3N2) A/New Caledonia/20/99 (H1N1) B/Sichuan/379/99

24. Influenza Vaccine Schedule Age Group 6- 35 mos 3-8 yrs 9-12 yrs >12 yrs Dose 0.25 ml 0.50 ml No. Doses 1 or 2 1

25. Influenza Vaccine Recommendations All persons 50 years of age or older Persons >6 months of age with chronic illness Residents of long-term care facilities Pregnant women Persons 6 months to 18 years receiving chronic aspirin therapy

26. Influenza Vaccine Recommendations Routine annual influenza vaccination for persons 50 years and older –Up to a third of persons 50-64 years have high risk conditions –Only 35% received influenza vaccine in 1999 –May increase coverage in HCWs –Reduced sick days

27. Influenza Vaccine Recommendations Persons with the following chronic illnesses should be considered for influenza vaccine: –pulmonary (e.g., asthma, COPD) –cardiovascular (e.g., CHF) –metabolic (e.g., diabetes) –renal dysfunction –hemoglobinopathies –immunosuppression, including HIV infection

28. Pregnancy and Influenza Vaccine Risk of hospitalization 4 times higher than nonpregnant women Risk of complications comparable to nonpregnant women with high risk medical conditions Vaccination recommended if >14 weeks gestation during influenza season

29. HIV Infection and Influenza Vaccine Persons with HIV at higher risk of complications of influenza Vaccine induces protective antibody titers in many HIV infected persons Transient increase in HIV replication reported Vaccine will benefit many HIV-infected persons

30. Influenza Vaccination of Children Children <24 months at increased risk of hospitalization Vaccination of healthy children 6-23 months is encouraged Vaccination of household contacts and out-of-home caretakers is encouraged

31. Influenza Vaccine Recommendations Health care providers, including home care Employees of long-term care facilities Household members of high-risk persons (including children 0-23 months)

32. In the 2000 National Health Interview Survey, only 38% of health care workers reported receiving influenza vaccine in the previous 12 months.

33. Influenza Vaccination of HCWs Educate HCWs about the benefits of vaccination for themselves, their families, and their patients Educate staff about vaccine adverse reactions Provide free vaccine at the work site to all employees, including night and weekend staff

34. Influenza Vaccine Recommendations Providers of essential community services Foreign travelers Students Anyone who wishes to reduce the likelihood of becoming ill from influenza

35. Influenza Vaccine Adverse Reactions Local reactions15%-20% Fever, malaiseuncommon Allergic reactionsrare Neurologicalvery rare reactions

36. Influenza Vaccine Contraindications and Precautions Severe allergy to vaccine component (e.g., egg, thimerosal) or following prior dose of vaccine Moderate to severe acute illness

37. Influenza Vaccine Strategies to Improve Coverage Ensure systematic and automatic offering of vaccine to high-risk groups Educate health care providers and patients Address concerns about adverse events Emphasize physician recommendation

38. Influenza Vaccine Missed Opportunities Up to 75% of persons at high risk for influenza or who die from pneumonia and influenza may have received care in a physician's office in the previous year. In one study all non-nursing home persons who died from pneumonia or influenza had at least one medical visit in the previous year.

39. Influenza Antiviral Agents Amantadine and rimantadine –effective against influenza A only –approved for treatment and prophylaxis Zanamivir and oseltamivir –neuraminidase inhibitors –effective against influenza A and B –oseltamivir approved for prophylaxis

40. Live-attenuated, Cold-adapted Intranasal Influenza Vaccine Vaccine efficacy 93% among children for influenza A (H3N2) and influenza B Vaccinated children had 21% fewer febrile illnesses Vaccinated children had 30% fewer episides of febrile otitis media Belshe et al, NEJM 1998;338:1405-12

41. Safe and effective in children May increase influenza vaccine coverage among high-risk children Cost-effectiveness and impact of wider use among children unknown Live-attenuated, Cold-adapted Intranasal Influenza Vaccine

42. Influenza Surveillance Monitor prevalence of circulating strains and detect new strains Rapidly detect outbreaks Assist disease control through rapid preventive action Estimate influenza-related morbidity, mortality and economic loss

43. National Immunization Program Hotline800.232.2522 Emailnipinfo@cdc.gov Websitewww.cdc.gov/nip