Moving towards universal varicella vaccination:the German experience

P. WutzlerJena, Germany

Friedrich Schiller University, Jena, GermanyInstitute of Virology and Antiviral Therapy

Current situation in Germany

Incidence of VZV infections per year: about 760,000 cases of varicella 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)

Unvaccinated 1215 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

Health economics project to calculate the clinical and cost-effectiveness of a

universal vaccination programme

Serological survey of the general population

Epidemiological study to evaluate the burden of disease for children, adolescents and adults (retrospective)

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.

VZV antibody prevalence in the German population

Months Years

0

10

20

30

40

50

60

70

80

90

100

Ser

op

osi

tive

(%

)

1-3

4-6

7-9

10-12

2-3

4-5

6-7

8-9

10-11

12-13

14-15

16-17

18-19

20-29

30-39

40-49

50-59

60-69

>=

70

Age groups

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

Random sample selected from German telephone directory, stratified according to appropriate medical field,

letters written to physicians

PaediatricianGeneral

practitionerInternist

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

Basic epidemiological data

0 .0 0 0

0 .0 5 0

0 .1 0 0

0 .1 5 0

0 .2 0 0

0 .2 5 0

0 .3 0 0

2 6 1 0 1 4 1 8 2 2 2 6 3 0 3 4 3 8 4 2 4 6 5 0 5 4

A g e a t v a r ic e l la d ia g n o s is ( y e a r s )

R e la t iv e f r e q u e n c y o fin f e c t io n

16.3%

5.7% 0.8%

0.0%

5.0%

10.0%

15.0%

20.0%

Inci

den

ce r

ate

Severe course Complications Hospitalizations

Complications and severe courses

Basic epidemiological data

Projection of the frequency of varicella complications for Germany in 1999

Basis for projection: Prescription index, IMS 2000

0

5,000

10,000

15,000

20,000

25,000

30,000

35,000

40,000

Children Adolescents and adults

Bacterial superinfections Acute neurological disordersPneumonia & bronchitis Otitis mediaOthers

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?

0

100.000

200.000

300.000

400.000

500.000

600.000

700.000

800.000

900.000

1.000.000

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30

Time in years

Var

icel

la c

ases

Children younger than 5 yrs

Children 610 years Adolescents 1115 yearsAdolescents 1620 years Adults older than 20 years

Varicella incidence over a timeframe of 30 years in anunvaccinated population

Vaccination strategies

Adolescent strategy: Vaccination of susceptible persons at the age of 1115 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 1112 years

Potential clinical effects of varicella vaccination

Annual rates

No vaccination Adolescent Children Combined strategy strategy strategy

__________________________________________________________________________

Varicella cases 739,000 702,000 128,000 122,000

Total complications(any severity) 39,720 37,650 6,850 6,510

Major complications requiringhospitalization 5,740 5,300 1,000 940

Deaths 22 20 4 4

Potential clinical effects of varicella vaccination

Vaccination strategy

No immuni- Risk- General vaccination zation groups Basic Pessimistic Optimistic

Varicella cases 739,000 721,400 166,500 182,000 147,100

Total complications(any severity) 39,700 38,700 8,900 9,800 7,900

Major complications requiringhospitalization 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 yearsPessimistic case scenario : vaccination increases 5% to 85% within 9 yearsOptimistic case scenario : vaccination increases 22% to 85% within 7 years

Economic effects of varicella vaccination

Incremental costs (Mio Euro)

Vaccination strategiesAdolescents Children Combined

_____________________________________________________________ Soc. SF Soc. 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_________________________________________________________________ Benefitcost

ratio 8.44 1.13 4.12 1.75 4.10 1.70 _________________________________________________________________

Soc. Societal perspective, SF Sickness funds’ (payers’) perspective

12

14

16

18

20

22

24

26

28

75% 80% 85% 90% 95% 100%

Maximum vaccination coverage

Yea

rs

Children vaccination strategy Combined vaccination strategy

Time to eliminate varicella

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

Involved in the study were:

German Association for the Control of Virus Diseases (DVV) Varicella Vaccination Working Group

Institute of Medical Statistics and EpidemiologyTechnical University, Munich, Germany

Institute of Virology and Antiviral TherapyFriedrich-Schiller University, Jena, Germany

Outcomes International, Basle, Switzerland

GSK - Advisory Board on Varicella Vaccination GlaxoSmithKline, Munich, GermanyGlaxoSmithKline, Rixensart, Belgium

Robert Koch Institute, Berlin, Germany

July 2004

Varicella vaccination was included into the vaccination

schedule as standard vaccination

Universal varicella vaccination for all children preferably between the completed 11th14th month of age

Catch-up vaccination for all older children and adolescents without history of varicella (9 17 years)

Varicella vaccination - German recommendations(STIKO-Permanent Vaccination Commission, July, 2004)

9 – 175 – 615 2311 14432

Alter in voll. JahrenAlter 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

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

Current situation Universal vaccination*Every hour: 82 varicella cases! 2 varicella cases!

Every day: 322 severe courses of 9 severe courses ofvaricella! varicella !

Every week: 744 complications! 21 complications!

Every month: 460 hospitalizations! 14 hospitalizations!

Every year: 21 deaths! 1 death!

*Annual average during the 2nd decade after implementation of universal vaccination

Universal varicella vaccination is very effective!