Update on the role of dtpa-ipv vaccine as a booster in the pre-school age

Transcription

1 Update on the role of dtpa-ipv vaccine as a booster in the pre-school age Gabutti G 1, Conversano M 2, Ferrera G 3, Matera R 4, Parlato A 5, Zivelonghi G 6, Azzari C 7 1 Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi, Ferrara, Italy 2 Dipartimento di Prevenzione ASL TA/1, Taranto, Italy 3 Dipartimento di Prevenzione ASP, Ragusa, Italy 4 Servizio di Igiene Pubblica ASL BAT/1, Andria, Italy 5 U.O. di Epidemiologia ASL ex Napoli 2, Napoli, Italy 6 Dipartimento di Prevenzione Usl 20, Verona, Italy 7 Laboratorio di Immunologia, Ospedale Meyer, Firenze, Italy

2 Introduction Enhancing population adhesion to vaccine boosters is linked to a number of factors, including tolerability. Increasing available evidences confirm that combined diphtheriatetanus-acellular pertussis-polio vaccines with reduced antigen content (dtpa-ipv) provide a higher level of safety and lower reactogenicity versus DTPa-IPV vaccine with comparable immunogenicity in the middle-long term follow up. Different European Countries (Germany, Denmark, etc.) already implemented such a booster strategy being dtpa-ipv vaccine licensed for the use in children aged > 4 years. Nevertheless, the E-CDC Guidance on DTP vaccination issued in November 2009 recommends the use of DTPa-IPV vaccine for the booster dose in preschool children due to higher diphtheria antitoxin level without higher rates of side effect.

3 Methods and Results (I) Methods. A review of the literature on the dtpa-ipv vaccine was carried out with particular focus on the performance of the anti-diphtheria titer (anti-d) over time. dtpa-ipv vaccine in pre-school age children is supposed to induce a lower response (E-CDC Guidance, 2009) and decline earlier (Ciofi degli Atti, 2002). Results. In different clinical studies results published between the dtpa(-ipv) vaccine in children and adolescents has proved to be immunogenic (Figure 1) with less reactogenicity and decreased frequency of adverse events compared to DTPa vaccine (Figure 2).

4 Figure 1. Immunogenicity response elicited by dtpa or dtpa-ipv in pre-school children Seroprotection rate (%) Country Age (years) Vaccine Anti-D Anti-T Anti-polio type 1 Anti-polio type 2 Anti-polio type 3 Thailand (1) 4-6 dtap DTPw Germany (2) dtap DTPa dt Taiwan (3) 6-8 dtap Germany (4) dtap-ipv dtap+ipv (1) Kosumon et al Vaccine 2003; (2) Zepp et al ESPID 2003; (3) Huang et al. J Adolesc Health 2005; (4) Sanger et al, Eur J Ped. 2007

5 Figure 2. Summary of reactogenicity data from dtpa or dtpa-ipv vaccines in preschool children and adolescents Local Symptoms (%) General Symptoms (%) Country Age (years) Vaccine Pain Redness Swelling Fever Irritability Drowsiness All Grade 3 All Grade 3 All Grade 3 All Grade 3 All Grade 3 All Grade 3 dtap Germany (1) 4-6 DTPa Australia (2) 4-6 dt dtap * NS NS NS NS NS DTPa * NS NS NS NS NS 1 Zepp et al. ESPID 200 3; 2 Marshall et al. Pediatrics 2006 * within 24 hours after vaccination Italy (3) DT dt Chile (4) RR 95% CI n=371 % n=381 % Fever > 37,5 31 8,4 29 7,7 1,09 0,67-1,77 Fever > Irritability 41 11, ,9 0,86 0,58-1,27 Itchiness, any 42 11, ,03 0,69-1,54 Itchiness, extensive 3 0,8 2 0,5 1,54 0,26-9,17 * Redness, any , ,7 1,99 1,51-2,62 Redness, > 5 cm 22 5,9 6 1,6 3,77 1,54-9,18 Swelling, any , ,2 1,39 1,12-1,72 * Swelling, > 5 cm 20 5,4 10 2,6 2,05 0,97-4,33 Swelling, extensive 4 1,1 3 0,8 1,37 0,31-6,08 Pain ,06 0,93-1,21 Pain, severe 64 17, ,3 1,53 1,07-2,19 * p<0.05 * * * * (3) Ciofi degli Atti M et al, Vaccine 2002 (4) Vergara R et al, Eur J Pediatr 2005

6 Results (II) and Conclusions The results of recent randomized controlled trials with anti-d follow up in children, adolescents and adults up to 10 years from the previous dtpa(-ipv) booster (Figure 3,4,5,6) confirmed the assumption. Conclusions. The new Immunization Calendar recommended by 3 Italian Scientific Societies introduces the use of dtpa-ipv vaccine as a booster in pre-school age providing > 80% vaccine coverage in adolescents is reached ( The use of dtpa-ipv vaccine as a booster in pre-school age is increasingly documented and an update on its role is warranted.

7 Figure 3. Percentage of subjects with anti-d antibodies > 0.1 (ELISA) until 5 years after the 4 8 year booster dose and one month after the dtpa-ipv booster dose at 9 13 years of age diamonds = dtpa-ipv group, squares = dtpa + IPV group. Error bars = 95% CIs. Knuf M et al, Hum Vacc 2010

8 Figure 4. Anti-D antibody GMCs up to 60 months after vaccination in adults McIntyre P.B. et al, Vaccine 2009

9 Figure 5. Anti-diphteria antibody geometric mean antibody concentrations (GMCs) up to 10 years after initial vaccination and 1 month after the booster dose vertical lines, 95% confidence intervals dtpa DT+pa Mertsola J et al, Clin infect Dis 2010

10 Figure 6. Geometric mean concentrations (GMC) of diphtheria and tetanus antibodies before and after booster vaccinations with dtpa over a 10-year period, in older adults Error bars: 95% confidence intervals Mertsola J et al WSIPD 2009