1. Varicella epidemiology and varicella vaccination strategies in Italy Rome, March 18, 2005 Luigi D. Notarangelo Department of Pediatrics University of Brescia – Italy notarang@med.unibs.it

2. Dicembre 2002 Tot. Pazienti: 117 Italy Population:57,321,070 inhabitants Northern Italy:25,782,796 Central Italy:10,980,912 Southern Italy:20,557,362 Newborns:544,063 Northern Italy:236,498 Central Italy: 99,501 Southern Italy: 208,064 ISTAT, December 2003

3. Thousands inhabitants Italy: Demographic data

4. Monthly incidence of diseases under active surveillance SPES, years 2000  2003 Mumps Pertussis Measles Rubella Number of cases per 100,000 inhabitants

5. NotificationSPES PopulationAll ages Entire country Up to 14 years Population sample (4%) Period Regularly, since 1934 Regularly, since 2000 Case definition clinic only Data flow From doctor to ASL From ASL to Region From Region to Ministery, ISS, ISTAT Data reported by SIMI From pediatrician to ISS

6. Notification (SIMI) vs sentinel-pediatricians surveillance (SPES) varicella in Italy – year 2000 SPES: 20,513 cases reported 4.4% of individuals <14 years (470 primary-care pediatricians, 370,000 citizens) SIMI: 90,540 cases notified 4,820/100,000 1,252/100,000 Ciofi degli Atti, Ann Ig 2002; ;14 (S6):11. SPES

7. Age group Under-reporting rate 0-4 years 3.9 5-9 years 3.0 10-14 years 6.5 Total 3.8 Under-reporting rate of varicella infection by age-group Children 014 years; Italy 2000 Ciofi degli Atti, Ann Ig 2002;14(S6):11.

8. Incidence of varicella in Italy among infants and children SPES (sentinel pediatricians) – years 2002 and 2003 Incidence (per 100,000) year 2002 year 2003

9. VZV seroprevalence by age-group and geographic area in Italy, 1996  1997 Reproduced from Gabutti, et al.Epidemiol Infect.2001;126:433-40, with permission from Cambridge University Press (http://.journals.cambridge.org) 17.9%

10. Anti-VZV antibodies GMT by age-group in the Italian population, 1996-1997 mUI/ml Age-groups (years) 0 250 500 750 1000 1-6 months 7-11 months 12-45-910-1415-1920-39> 40 Gabutti, et al. Epidemiol Infect. 2001;126:433-440

11. 1992  931998  2000 0 100 200 300 400 500 seropos. dim increase serorev (1) seroconv. seroneg. 22.8% 11.1% booster first infection Changes of seroprevalence between 12 and 18 years 561 children born in 1981, first studied in 1992, and then again in 2000 Romanò, Ann Ig 2002;14(S6):7

12. The burden of varicella in Italia Fornaro, et al. Pediatr Infect Dis J 1999;18:414-19 Giaquinto, et al. Ann Igiene 2002;14(S6):21-7 - complications reported in 3.5 – 4.8% of infected children - hospitalization required in 0.18 – 0.34% of infected children skin infections pneumonia neurological complications

13. 1.432 1.538 1.628 1.690 1.000 1.100 1.200 1.300 1.400 1.500 1.600 1.700 1.800 1.900 2.000 1999200020012002 Year Nr. hospitalizations Incidence of varicella-related hospitalizations (per 100,000) by age group – year 2000 39.27 20.32 7.85 2.68 1.80 0.500.37 0.17 0 10 20 30 40 50 < 11-45-1415-2425-4445-6465-74> 75 Incidence ( per 100,000 ) Varicella-related hospitalizations in Italy – 1999-2002 Ministry of Health Age (years) The burden of varicella in Italia

14. 0 5 10 15 20 25 <112345-910-1415-1920-2425-4950-5960-69> 70 Deaths due to varicella, by age-group. Italy, 1981-2000  ISTAT Age (years) 96 deaths in 20 years (4.8 deaths/year)

15. Deaths due to/with herpes zoster, by age-group. Italy, 1981-2000  ISTAT 0 50 100 150 200 250 300 350 400 450 500 25-4950-5960-69> 69 N. cases Age (years) 550 deaths in 20 years (27.5 deaths/year) due to zoster or with zoster?

16. The economic burden of varicella in Italy For the family OTC medications Loss of work Private lessons Home-care Other costs (telephone, transportation) For the NHS Consultations Medications Hospitalization Lab testing For the society Work-loss

17. The economic burden of varicella in Italy For each pediatric patient Fornaro et al. Coudeville et al. <1 year1  6 ys7  17y - prescriptions10.90 €10.90 €10.90 € - OTC medications 3.98 € 3.98 € 3.98 € - hospitalizations 9.06 €43.20 € 4.70 € 4.70 € - consultations 19.02 €37.80 €37.80 €35.60 € - complications 0.78 € - additional examinations 0.71 € 0.71 € 0.71 € - work losses 81.24 €84.50 €84.50 €84.50 € - school losses 11.25 € Total 129.24 € 181.09 € 142.59 € 140.39 € Fornaro, et al. Pediatr Infect Dis J 1999;18:414-19 Coudeville, et al., Pharmacoeconomics 2004; 22: 839-55. 7.89 €

18. Zotti Coudeville - prescriptions 18.30 € - OTC medications 3.98 € - hospitalizations 47.20 € 33.00 € - consultations 15.00 € 30.00 € - additional examinations 1.55 € - work losses710.00 €681.40 € Total792.80 €768.23 € Zotti, et al. Ann Igiene 2002;14:29-33. Coudeville, et al. Pharmacoeconomics 2004;22:839-55. The economic burden of varicella in Italy For each adult patient 20.60 €

19. w=0,003 0 100000 200000 300000 400000 500000 600000 -10 -5 05 10 15 2025 30 35 40 45 anni dalla vaccinazione numero di nuovi casi reduction rate: 26% years from vaccination number of new cases Vaccination at 12 years, 80% coverage w=0,003 0 100000 200000 300000 400000 500000 600000 -10 -5 05 101520 25 30354045 anni dalla vaccinazione numero di nuovi casi Vaccination at 1 year, 80% coverage and at 12 years, 50% coverage reduction rate: 94% years from vaccination w=0,003 0 100000 200000 300000 400000 500000 600000 -10 -5 0 5 1015 20 25 30 3540 45 anni dalla vaccinazione numero di nuovi casi Vaccination at 1 year, 80% coverage reduction rate: 82% years from vaccination number of new cases w=0,003 0 100000 200000 300000 400000 500000 600000 -10 -5 05 101520 253035 4045 anni dalla vaccinazione numero di nuovi casi Vaccination at 1 year, 20% coverage reduction rate: 18% years from vaccination number of new cases 0-4 years 5-18 years 19-24 years >24 years Modelling of varicella vaccination in Italy (Salmaso) Salmaso, et al. Epidemiol Prev 2003;27:154–60. Reproduced with permission.

20. < 50% 50-75% >75% 19982003 MMR vaccine coverage in Italy ICONA, years 1998 and 2003

21. Universal varicella vaccination in Sicily - identified as a priority by the Regional Health Authority (22.07.2002) - approved with a law by Regione Sicilia, 23.03.2004 - aims: - immunize at least 80% of infants at 15 months - immunize at least 50% of susceptible individuals at 12 years - monitor vaccination coverage - monitor adverse events (including identification of strain) - monitor epidemiology of varicella in Sicily - officially started in March 2003

22. - universal varicella vaccination (1  2 years) recommended for those Regions able to reach >80% coverage - varicella vaccination recommended for susceptible adolescents State-Regions Conference March 2005