REDUCTION OF INVASIVE DISEASE IN CHILDREN TWO DECADES AFTER THE INTRODUCTION OF HAEMOPHILUS INFLUENZAE TYPE B CONJUGATE VACCINATION IN APULIA REGION, ITALY

Abstract

Background Haemophilus influenzae type b conjugate (Hib) monovalent vaccination, consisting of 2p+1 doses at 3, 5, and 11 months of age, was introduced in the Italy’s infant immunization schedule in 1999 and included in the DTaP-HBV-IPV/Hib hexavalent vaccine since 2001. The estimated vaccination coverage was 83.4% in 2002, >90% by 2005, and >95% by 2011 [1-4]. In the Apulia region of Italy (about 4,000,000 inhabitants), vaccination coverage for 3 doses reached 75% in 2001, >90% by 2002, and >95% by 2007 (Graph. 1).Methods We considered annual age-specific hospitalization rates in infants <1 year and children 1-4 years as a proxy for incidence in the period 1996-2014. The attributable benefit was calculated as the reduction in incidence of Haemophilus influenzae invasive disease among vaccinated children attributable to the routine use of Hib monovalent vaccine during 1999-2000 (“Hib-monovalent period”) and of the hexavalent DTPa-HBV-IPV/Hib vaccine in the period 2001-2014 (“DTPa-HBV-IPV/Hib period”). The prevented fraction was calculated as the proportion of hypothetical total cases that were prevented by the use of monovalent and hexavalent vaccine, respectively (Panel A) [5]Results The hospitalization rate for Haemophilus influenzae invasive disease among infants decreased from 11.5 (95% CI= 1.4-21.6) per 100,000 in the 1996-1998 pre-vaccination period to 6 (95% CI= -1.4-13.3) per 100,000 in the “Hib-monovalent period”, with an estimated AleB of -5.5 per 100,000 and a PedF of 48.2%. It declined further to 1 (95% CI= -2.2-4.1) per 100,000 in the “DTaP-HBV-IPV/Hib period”, with an AleB of -10.5 per 100,000 and a PedF of 91.6% (Graph. 2). The rate of hospitalization among children aged 1-4 year remained stable at 2.4 per 100.000 from the pre- vaccination period through “Hib-monovalent period” (AleB=0; PedF=2%) and declined to 0.1 (95% CI= - 0.4-0.7) per 100,000 in the “DTaP-HBV-IPV/Hib period”, with an AleB of -2.3 per 100,000 and a PedF of 94.3% (Graph. 3)Conclusions * Hib-monovalent period - ** DTPa-HBV-IPV/Hib period In the Apulia region of Italy, the proportion of Haemophilus influenzae invasive disease requiring hospitalization in children aged <5 years presumably prevented by the introduction of Hib universal vaccination amounted to more than nine in ten cases. These findings are consistent with increased vaccine coverage rates as a result of the wide use of the hexavalent combination vaccines