Efficacy of Pneumococcal Conjugate Vaccines (PCV) against Otitis Media Terhi Kilpi National Public Health Institute Department of Vaccines 3rd Regional Pneumococcal Symposium 13 Feb 2008
Incidence of AOM episodes during the first 2 years of life* Per person-year Northern Finland 1 1991 0.93 Southern Finland 2 2001 1.24 Boston 3 1989 1.15 Northern California 4 2003 1.50 England and Wales 5 2004 0.24 ** Czech Republic and Slovakia 6 2005 0.13 Netherlands 7 2006 0.28 Turkey 8 2006 0.56 *** Israel 9 2005 0.88 * in children who have not received PCV ** <1 yrs 5.2.2008 2 *** children aged 0.5 to 5 yrs with at least one AOM during 6 months
1 Alho et al Inf J Pediatr Otorhinolaryngol 1991; 21: 7-14 2 Eskola et al. N Engl J Med 2001; 344: 403-9 3 Teele et al. J Infect Dis 1989; 160: 83-94 4 Fireman et al. Pediatr Infect Dis J 2003; 22: 10-6 5 Melegaro et al. Vaccine 2004; 22: 4203-22 6 Prymula et al. Lancet 2006; 367: 740-8 7 Plasschaert et al. Pediatrics 2006; 117: 1879-86 8 Ozgur et al. Pediatr Infect Dis J 2006; 25: 401-4 9 Barkai et al. Emerg Infect Dis 2005; 11: 829-37 5.2.2008 3
Bacterial causes of AOM 50 45 40 35 30 25 20 15 10 5 0 Finland USA* Czech Republic and Slovakia Costa Rica Turkey Pnc H infl M cat StrA * US study: % of MEF isolates, not AOM events 5.2.2008 4
Finland: Kilpi et al Pediatr Infect Dis J 2001; 20: 7-14 USA: Block et al. Pediatr Infect Dis J 2003; 23: 829-33 Czech Republic and Slovakia: Prymula et al. Lancet 2006; 367: 740-8 Cosa Rica: Arguedas et al. Pediatr Infect Dis J 2003; 22: 1063-8 Turkey: Bulut et al. Eur J Pediatr 2007; 166: 223-8 5.2.2008 5
PCVs evaluated for efficacy against otitis media PCV7-CRM Carrier protein CRM197, a nontoxic mutant of diphtheria toxin PCV7-OMP Eskola et al. N Engl J Med 2001;344: 403-9 Black et al. Pediatr Infect Dis J 2000; 19: 187-95 Kilpi et al. Clin Infect Dis 2003;37: 1155-64 Carrier outer membrane protein complex of Neisseria meningitidis group B PCV11-PD Carries protein D, cell-surface lipoprotein of Haemophilus influenzae Prymula et al. Lancet 2006; 367: 740-8 5.2.2008 6
Otitis media outcomes AOM due to vaccine serotypes vaccine-related serotypes non-vaccine serotypes Any pneumococcal AOM Any AOM Tympanostomy tube placements 5.2.2008 7
Age at PCV administration and efficacy against OM Start during the first year of life Before the first AOM Start after the firs year of life After the first AOM Effect questionable 5.2.2008 8
Efficacy studies with pneumococcal OM outcomes FinOM study Finland in 1995-99 PCV7-CRM (N=831), PCV7-OMP (N=835) and HBV (N=831) vaccine at 2, 4, 6, 12 months POET study Czech Republic and Slovakia in 2000-2002 PCV11-PD (N=2455) and HAV (N=2452) at 3, 4, 5, and 12-15 months 5.2.2008 9
Efficacy of PCV against AOM due to vaccine serotypes Vaccine efficacy 95% CI FinOM study PCV7-CRM PCV7-OMP POET study PCV11-PD 57 56 58 44 67 44 66 41 69 5.2.2008 10
Efficacy of PCV against AOM due to vaccine-related serotypes Vaccine efficacy 95% CI FinOM study PCV7-CRM PCV7-OMP POET study PCV11-PD 51-5 66 27 67-47 25 22 85 5.2.2008 11
Efficacy of PCV against AOM due to non-vaccine serotypes Vaccine efficacy 95% CI FinOM study PCV7-CRM PCV7-OMP POET study PCV11-PD -33-27 9-80 1-70 6-64 49 5.2.2008 12
Efficacy of PCV against any pneumococcal AOM Vaccine efficacy 95% CI FinOM study PCV7-CRM PCV7-OMP POET study PCV11-PD 34 25 52 21 45 11 37 37 63 5.2.2008 13
Efficacy studies with clinical OM outcomes FinOM study POET study NCKP study Black et al. Pediatr Infect Dis J 2000; 19: 187-95 Northern California in 1995-99 PCV7-CRM (N=18927) and Men C (N=18941) vaccine at 2, 4, 6, 12-15 months 5.2.2008 14
Efficacy of PCV against any AOM Vaccine efficacy FinOM study PCV7-CRM 6 PCV7-OMP -1 POET study PCV11-PD 34 NCKP study PCV7-CRM 7 95% CI -4 16-12 10 21 44 4 10 5.2.2008 15
Efficacy of PCV against AOM due to H influenzae Vaccine efficacy 95% CI FinOM study PCV7-CRM PCV7-OMP POET study PCV11-PD -11-9 36-34 8-32 10 4 57 5.2.2008 16
Frequency of tube placements % with tubes by age NCKP control group* 3.9 3.5 yrs FinOM control group** 18 2 yrs POET control group*** 0.41 2 yrs *Fireman et al. Pediatr Infect Dis J 2003; 22: 10-6 **Palmu et al. Pediatr Infect Dis J 2004; 23: 732-8 ***Prymula et al. Lancet 2006; 367: 740-8 5.2.2008 17
Efficacy of PCV against tube placements Vaccine efficacy FinOM study PCV7-CRM, up to 2 yrs 4 PCV7-CRM, 2 4-5 yrs 44 POET study PCV11-PD, up to 2 yrs 60 NCKP study PCV7-CRM, up to 3.5 yrs 23 95% CI -19 23 19 62 27 88 11 34 5.2.2008 18
Effectiveness of PCV on otitis media visits Grijalva et al. Pediatrics 2006; 22: 10-6 Authors conclusion: OM visits reduced by 20 % after introduction of PCV in children >2 yrs of age Introduction of PCV7 5.2.2008 19
Conclusions Pneumococcal conjugate vaccines have potential to reduce the disease burden caused by AOM Considerable variability in the incidence of AOM makes estimation of ultimate vaccine effect extremely challenging 5.2.2008 20