1. Hepatitis B vaccination Safety issues Impact of safety issues and international point of view France Nicole Guérin

2. Impact of safety issues On recommendations and immunization schedule On surveillance of hepatitis B –Compulsory report On surveillance of AEFI On immunization coverage –Children and adolescents –At risk population On producers –Sales –Judiciary affairs Conclusion

3. Hepatitis B Policy in France Until 1994: targetted policy –Beneficial for at risk immunized persons –Ineffective on carriers and viral propagation From 1994 à 1998, in addition to targetted policy –vaccination of infants and 11-13 years old children during 10 to 12 years –boosters at 11-13 years for children immunized during infancy

4. Policy since 1998 Vaccination of infants with a 3 doses schedule Vaccination of 11-13 years old children with a 3 doses schedule Clear definition of at risk groups (3 doses schedule) Suppression of boosters except for special indications Source: (BEH 4 Août 1998)

5. Definition of at risk groups for hepatitis B Personnel of health care and prevention centers Personnel possibly in contact with blood (direct or not) Other expositions: –Newborns from infected mothers, IV drug users, children living in collectivity –patients susceptible of receiving massives ou iteratives transfusions –Persons in contact with an infected persosn (including sexual contacts) –Travellers to, and residents in, countries of medium or high endemy, Source: (BEH 4 Août 1998)

6. Policy of booster doses for hepatitis B vaccination No more recommandation of booster dose after the 3 injections of the initial schedule Except for health workers and other professionnel submitted to the article L 3111 of the « Code de la Santé Publique » –if age at first 3 doses < 25 years: no booster –si age at first 3 doses > 25 ans and serology showing –anti HBs > 10mUI/ml: no booster. –anti HBs < 10 mUI/ml: booster dose followed by another serology : if antibody anti HBs  10 mUI/ml no more booster if antibody anti HBs < 10 mUI/ml, discuss need for additional doses (no more than a total of 6) Source: BEH 4 Août 1998

7. Impact on recommendations: Rapport « Dartigues » published in 2002 Advice of the Academy of Medecine Immunization schedule 2003 –Immunization of infants –Catch up of children up to 11 years –at risk population: definition (+ piercing..) –2003 schedule includes recommendations for use of Hexavalent vaccines, in order to increase Hep B coverage in infants

8. Surveillance of hepatitis B Compulsory report by decree 1999 Implementation since february 2003 Case definition : –Tout tableau clinique ou biologique évocateur d'une hépatite virale aiguë peut être imputé au VHB si des IgM anti-HBc sont détectées dans le sérum du patient. –Tout tableau clinique ou biologique évocateur d'une hépatite virale chronique peut être imputé au VHB si l'AgHBs est mis en évidence dans le sérum du patient.

9. Surveillance of adverse events Studies Benefit risk But the conclusion of Afssaps is for exemple: « 2 epidemiological studies have been recently published in the NEJM. These studies still do not allow to formally eliminate anassociation between the vaccine and the occurrence of a poussée de SEP (06-02-01) »

10. Coverage at 24 months: (through health certificates) DRESS 2/08/02, provisional figures

11. Impact on immunization coverage Survey on 6779 children 0 to 24 months (2001) –At 4 months: 24,2% –A 6 months: 33,2% –A 12 months: 39,1% –A 24 months: 41,4%

12. Coverage between 6 months and 24 months (through a survey 2001on 6779 children) Gaudelus and al. Submitted to Arch fr Pédiatr 2003

13. Reasons for delays and no Hep B vaccinations Delays –Infections 40% –Too many shots 9% –Polemic6% –Forgotten 3% –Others 27% No vaccination –Fear of MS 2% –Too many shots 19% –Wait until 2 years 23% –Not proposed 16% –Others 27% Gaudelus and al. Submitted to Arch fr Pédiatr 2003

16. Immunization coverage Hepatitis B April 2002 GSK-Sofres survey Percentage of persons having received at least one dose of vaccine

17. Children immunization coverage Hepatitis B GSK Sofres survey April 2002 Percentage of persons having received at least one dose of vaccine

18. Hepatitis B immunization coverage in a reference center for drug users (BEH 07/2003) Caracteristics of new patients, without history of Hep B (clinical or serological), knowing their immunization status 199920002001 Men/Total49/6458/7798/120 >=3 doses29 (45%)12 (16%)26 (22%) 1-2 doses10 (16%)13 (17%)21 (18%) 0 dose25 (39%)52 (68%)73 (61%)

19. Impact on producers Sales Judiciary affairs –138 suits currently treated (GSK) –….

21. Controls measures against Hep B National plan for 2002-2005 –Assess different strategies of Hep B vaccination At risk groups Recall compulsory immunization for health workers Information for private health workers Information for occupational hasard Organisation of a large consultation on conditions of implementation of the recommended strategy

22. Conclusions Technical recommendations are here But no political commitment Resulting in poor coverage Hundreds of suits being treated …. The only hope is the use of hexavalent vaccines for infants, recommended, but not yet on the market