Impact of Universal Vaccination Against Hepatitis B: The Italian Model

Abstract

In the 70s and 80s, Italy was one of the countries with the highest prevalence of hepatitis B in Europe; the overall endemic of hepatitis B virus (HBV) was classified as intermediate, yet it resulted from a dual pattern of high endemic in south Italy and of low endemic in most of north Italy parts. The mean countrywide rate of carriers of the HB surface antigen (HBsAg) was 2.5 %; however figures were as high as 10 % in areas of south Italy. HBsAg rate in pregnant women was 2.4 % in average; however in some areas as many as 5 % of the women were carriers [1]. Screening of pregnant women during the last three months of pregnancy was recommended from the early 80s; only one third of women were initially screened, but the percentage increased at the end of the decade. The incidence of hepatitis B in the mid of the 80s was over 40 cases per 100.000 young italian (15-24 years old), around 10 cases/100.000 among subjects who aged over 24 years and 5 cases per 100.000 in children aged up to 14 years. Starting from the mid-1980s, the incidence of hepatitis B progressively declined, as a return of the alert to the infection with the human immunodeficiency virus (HIV), the changing of social behavior, the introduction of public health measures such as refinement in blood screening, the use of universal precautions in medical settings and the implementation of vaccination [1][2][3][4][5][6]. The first step in achieving active HBV prophylaxis in the country was the recommendation in 1983 to selective immunizes groups at risk for HBV infection. In 1991 hepatitis B vaccination became universal with a program based on a two cohort’s strategy: vaccination became mandatory for all newborns and for all 12 years old adolescents. It was programmed for 12 years until 2003 when the two cohorts joined. In parallel, screening of pregnant women in the third trimester of pregnancy was also made mandatory and vaccination continued to be offered free of charge to risk groups [7]. In 2003 when the two cohorts of the vaccination program bonded together all the population from zero to 24 years was immunized by vaccination. At this time the Italian Health Authority decided to stop vaccination in the 12 years cohort and to continue in newborns. Since then and up to now, 179 countries have enforced hepatitis B birth vaccination [3][8][9][10]. New questions have been raised in the meanwhile: how long anti-HBs remain detectable, how long vaccine-induced immunity is expected to last, is the finding of anti-HBs an obligatory expression of immunity to HBV. Answering these questions a multicenter study was carried out in 2003, involving more than 1200 children who were vaccinated at birth and were enrolled into the study 11 years later. They were tested for HBV markers (HBsAg, anti-HBs and anti-HBc) and none turned out positive to HBsAg. Only one subject was positive to anti-HBc: he was negative to HBV-DNA and had an anti-HBs titer higher than 1000 mIU/ml. Overall 64 % of the vaccines had anti-HBs titers higher and 27 % lower than 10 mIU/ml respectively and 9 % were negative. Second part of the study was controling of 590 recruits who received a primary course of vaccination in 1991 when they were 12 years old. The majority (87 %) had high antibody titers; 4 had anti-HBc without sign of active infection, 8.5 % had titers lower than 10 mIU/ml and 4 % were negative [11]. The data from Italy corresponded to the worldwide experience; in 15-50 % of children responded to a primary course of vaccination the titer of anti-HBs diminished or the antibody became undetectable after five to 15 years [12].