1. Moving towards universal varicella vaccination: the German experience P. Wutzler Jena, Germany Friedrich Schiller University, Jena, Germany Institute of Virology and Antiviral Therapy

2. Current situation in Germany Incidence of VZV infections per year: l about 760,000 cases of varicella l about 350,000 cases of zoster Efficient and safe vaccines are available: - Varilrix ® (Oka, GlaxoSmithKline, on market since 1995) - Varivax ® (Oka, Sanofi Pasteur MSD, on market since 2004)

3. Unvaccinated 12  15 yr-old adolescents without a history of varicella Seronegative staff in medical services as well as new staff at facilities for pre-school children Seronegative patients before or under immunosuppressive therapy or before organ transplantation Seronegative patients with leukaemia Susceptible patients with severe neurodermatitis Susceptible persons with close contact to the above mentioned groups Seronegative women attempting pregnancy German recommendations for varicella vaccination until 2003/2004 (STIKO-Permanent Vaccination Commission) Post-exposure: for use in susceptible persons (with contact to persons at risk) within 3 (5) days

4. Health economics project to calculate the clinical and cost-effectiveness of a universal vaccination programme l Serological survey of the general population l Epidemiological study to evaluate the burden of disease for children, adolescents and adults (retrospective) l Assessment of the potential clinical and economic effects of a universal varicella vaccination programme versus no vaccination development of a decision analysis model (tailored to Germany): EVITA (Economic Varicella Vaccination Tool for Analysis) Wutzler et al. Med Microbiol Immunol 2002;191:89-96. Banz et al. Clin Microbiol Infect 2004;10:425-430.

5. VZV antibody prevalence in the German population

6. Comparison of VZV seroprevalence in different European countries in relation to age (EuroVar, Summary of the 6th meeting, London, April 17-18, 2002)

7. Random sample selected from German telephone directory, stratified according to appropriate medical field, letters written to physicians Paediatrician General practitioner Internist as family doctor Telephone interview: 5 randomly selected varicella cases per practice, diagnosed in 1999 Retrospective study of basic epidemiological data to evaluate the burden of disease for all children, adolescents and adults Letters Data from 1,334 unvaccinated patients from 232 practices Epidemiological data Medical resource utilisation Working days lost by patient or by family

8. Basic epidemiological data

10. Projection of the frequency of varicella complications for Germany in 1999 Basis for projection: Prescription index, IMS 2000

11. In Germany: Every hour:82 varicella cases! Every day:322 severe courses of varicella ! Every week:744 complications! Every month:460 hospitalizations! Every year:21 deaths! Varicella: a harmless childhood disease?

12. 0 100.000 200.000 300.000 400.000 500.000 600.000 700.000 800.000 900.000 1.000.000 123456789101112131415161718192021222324252627282930 Time in years Varicella cases Children younger than 5 yrs Children 6  10 yearsAdolescents 11  15 years Adolescents 16  20 years Adults older than 20 years Varicella incidence over a timeframe of 30 years in an unvaccinated population

13. Vaccination strategies Adolescent strategy: Vaccination of susceptible persons at the age of 11  15 years Children strategy :Universal vaccination of children at the age of 15 months Combined strategy: Vaccination of children at the age of 15 months, and of susceptible persons at the age of 11  12 years

14. Potential clinical effects of varicella vaccination Annual rates No vaccination Adolescent Children Combined strategy strategystrategy __________________________________________________________________________ Varicella cases739,000 702,000 128,000122,000 Total complications (any severity) 39,720 37,650 6,850 6,510 Major complications requiring hospitalization 5,740 5,300 1,000 940 Deaths 22 20 4 4

15. Potential clinical effects of varicella vaccination Vaccination strategy No immuni- Risk- General vaccination zation groups BasicPessimisticOptimistic Varicella cases 739,000 721,400 166,500 182,000147,100 Total complications (any severity) 39,700 38,700 8,900 9,800 7,900 Major complications requiring hospitalization 5,740 5,520 1,290 1,420 1,140 Deaths 22 21 5 5 4 Basic case scenario: vaccination increases 11% to 85% within 8 years Pessimistic case scenario : vaccination increases 5% to 85% within 9 years Optimistic case scenario :vaccination increases 22% to 85% within 7 years

16. Economic effects of varicella vaccination Incremental costs (Mio Euro) Vaccination strategies Adolescents ChildrenCombined _____________________________________________________________ Soc. SFSoc. SF Soc. SF Direct costs +0.25 +0.38 +3.9 +4.3 +4.4 +4.7 Indirect costs- 8.43 - 0.52- 55.2 -16.6- 57.4 -16.8 Total- 8.18 - 0.14- 51.3 -12.3- 53.0 -12.0 _________________________________________________________________ Benefit  cost ratio 8.44 1.13 4.12 1.75 4.10 1.70 _________________________________________________________________ Soc.  Societal perspective, SF  Sickness funds’ (payers’) perspective

17. Time to eliminate varicella

18. Conclusions Varicella causes a high burden of disease Vaccination of children at the age of 15 months and additionally of adolescents at the age of 11 and 12 years: –prevents approximately 80% of varicella cases and their complications per year –eliminates varicella within an acceptable period. Vaccination is effective regarding the reduction of the disease burden of varicella Vaccination is effective regarding the reduction of the economic effects of varicella

19. Involved in the study were: German Association for the Control of Virus Diseases (DVV)  Varicella Vaccination Working Group Institute of Medical Statistics and Epidemiology Technical University, Munich, Germany Institute of Virology and Antiviral Therapy Friedrich-Schiller University, Jena, Germany Outcomes International, Basle, Switzerland GSK - Advisory Board on Varicella Vaccination GlaxoSmithKline, Munich, Germany GlaxoSmithKline, Rixensart, Belgium Robert Koch Institute, Berlin, Germany

20. July 2004 Varicella vaccination was included into the vaccination schedule as standard vaccination  Universal varicella vaccination for all children preferably between the completed 11 th  14 th month of age  Catch-up vaccination for all older children and adolescents without history of varicella (9  17 years)

21. Varicella vaccination - German recommendations (STIKO-Permanent Vaccination Commission, July, 2004) 9 – 175 – 6 15  2311  14 432 Alter in voll. Jahren Alter in vollendeten Monaten 2. 1.3. 4. Sechsfach-Impfung (Tetanus, Diphtherie, Keuchhusten, Hib, Polio, Hep.B) 1.MMR 2.MMR Tetanus/ Diphtherie Tetanus/ Diphtherie/ Keuchh./ Polio Vari- zellen

22. Goals of the new vaccination strategy against varicella  To reduce the rate of morbidity, complications, hospitalizations and mortality  To protect susceptible high-risk patients by herd immunity  To eliminate varicella in the long-term  To save medical and societal costs

23. Current situationUniversal vaccination* Every hour:82 varicella cases! 2 varicella cases! Every day:322 severe courses of 9 severe courses of varicella! varicella ! Every week:744 complications! 21 complications! Every month:460 hospitalizations! 14 hospitalizations! Every year:21 deaths! 1 death! * Annual average during the 2 nd decade after implementation of universal vaccination Universal varicella vaccination is very effective!