Update on hepatitis B vaccination in Italy 10 years after its implementation

doi:10.1016/S0264-410X(00)00458-8

Vaccine

Volume 19, Issues 17–19, 21 March 2001, Pages 2380-2383

https://doi.org/10.1016/S0264-410X(00)00458-8 Get rights and content

Abstract

Since the beginning of the Italian program of immunization against hepatitis B, vaccine has been given to more than 9 million children, with an outstanding record of safety and efficacy. The coverage rate is globally around 94%, with differences between Northern and Southern regions, the latter having the lower acceptance rate. According to the National Surveillance System (SEIEVA), the incidence of acute hepatitis B per10⁵ inhabitants declined from 5.4 in 1990 to 2.9 in 1998. The reduction was even greater among 15–24-year-old individuals, where the incidence rate per 10⁵ decreased from 17.3 to 4.2 in the same period. In parallel with the decline of hepatitis B, Δ hepatitis has also dropped significantly. We expect that by the year 2003 (12 years after the beginning of the program) this vaccination strategy will have led to the protection of all Italians aged 0–24 years, who are those at the higher risk for acquiring hepatitis B virus (HBV) and for developing the chronic carrier state.

Section snippets

The Italian program of vaccination against hepatitis B: rationale and perspectives

At the mid of the eighties, hepatitis B was a major cause of morbidity and mortality in Italy, with an estimated 1.5 million carriers of hepatitis B surface antigen (HBsAg) and an associated mortality rate of around 9000 deaths per year from such HBV related-disease as cirrhosis and liver cancer. According to the data collected in those years by the national surveillance system specific for acute viral hepatitis (SEIEVA), the annual incidence for acute hepatitis B was around 12 per 10⁵

Safety and compliance of the hepatitis B vaccination campaign

Since the beginning of the mandatory program of vaccination against hepatitis B for both infants and 12-year-old adolescents, vaccine has been given to more than 9 million children. The coverage rate among adolescents is currently 94% on the average, with geographical differences. According to a national survey carried out on 113 230 teenagers, the percentage of coverage was 98% in Northern Italy, 97% in the Center and around 70% in the South [6]. The lower acceptance rate in the South was

The impact of vaccination on the burden of the disease

Hepatitis B vaccination is highly immunogenic and able to confer long-term protection [8], [9]. A study recently carried out in Milan on a cohort of 525 teenagers who were vaccinated in 1992 showed that 95% of them still have anti-HBs antibody at levels considered protective (>10 mIU/ml), 7 years after immunization. Four vaccinees (0.8%) seroconverted to anti-HBc antibody but none became HBsAg carrier or had detectable HBV-DNA [10]. This finding confirms the data reported in several published

Conclusions

In Italy, hepatitis B has progressively decreased in the last 20 years as a result of general improvements in the standard of living and hygiene and the introduction of such public health measures as refinement in blood screening, use of universal precautions in medical settings, vaccination of people at high risk for infection and, more recently, the implementation of universal vaccination of both infants and 12-year-old adolescents [17]. Since the beginning of this immunisation program,

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Long-term antibody persistence and immune memory to hepatitis B virus in adult celiac patients vaccinated as adolescents
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Citation Excerpt :
Safe and effective vaccines have been available since the early 1980 and in 1991 WHO recommended that all countries should introduce hepatitis B vaccination into their national immunization programs, by 1997 [3]. In Italy, vaccination against hepatitis B became mandatory for all infants and 12-year-old adolescents starting from 1991 [4,5]. Evidence shows that immunological memory persists more than 10 years after immunization of infants and adolescents with a primary course of vaccination and that booster doses of vaccine may be not necessary to sustain long term protection [6–8].
Aim of this study was to investigate the anti-HBs antibody persistence and immune memory to hepatitis B virus in adult celiacs vaccinated as adolescents and the effect of a booster administration in non-protected individuals. Eleven years after primary vaccination, the proportion of vaccinees with titres ≥10 mIU/ml and antibody geometric mean concentrations (GMCs) were lower among celiac patients than among controls (68.6% vs 91.7%, p < 0.01; GMCs 29.38 mIU/ml vs 250.6 mIU/ml, p < 0.001). Participants with anti-HBs below 10 mIU/ml received a booster dose and were retested 2 weeks later to assess the anamnestic response. Post-booster anti-HBs levels were still <10 mIU/ml in 71.4% celiacs and 25% controls (p < 0.01).
Our findings indicate that the prevalence of seroprotective levels of anti-HBs detected eleven years after primary immunization as well as the frequency of response to a booster dose of vaccine are lower in celiac patients compared to healthy controls.
Should hepatitis B vaccination be introduced into childhood immunisation programmes in northern Europe?
2007, Lancet Infectious Diseases
Citation Excerpt :
Previous experience has shown that an immediate effect on HBV prevalence will most often be observed in the vaccinated age-cohorts, and is soon followed by effects on the general population. When routine childhood hepatitis B vaccination was introduced in Italy in 1991, there was an immediate effect on the two vaccinated age-cohorts (infants and 12-year-olds), whereas over the 10-year follow-up period the most pronounced decrease occurred in 15–24-year-olds, the age-group with the previously highest incidence of HBV.11,48 To date, hepatitis B immunisation policies have largely been based on the endemicity status of individual countries.
Infection with hepatitis B causes between 500 000 and 1·2 million deaths per year worldwide, and is the leading cause of liver cancer. Over 12 years ago, WHO recommended that universal childhood hepatitis B vaccination be implemented globally. Despite this, Denmark, Finland, Iceland, Ireland, the Netherlands, Norway, Sweden, and the UK have yet to implement such a policy and instead currently adopt an “at-risk” strategy. Although all eight countries are classed as having low endemicity, factors such as increased travel and integration of immigrant communities are increasing the number of at-risk individuals in these countries. Considering the difficulty in identifying all at-risk individuals, and the lack of effectiveness of at-risk vaccination on reducing the overall incidence of hepatitis B, we recommend that these countries reassess their hepatitis B prevention strategies. Universal vaccination against hepatitis B is the only way to eliminate the major public-health impact of this disease.
Long-term immunogenicity of hepatitis B vaccination and policy for booster: An Italian multicentre study
2005, Lancet
Citation Excerpt :
However, even in these instances, loss of antibody does not necessarily imply loss of protection, since the long incubation period of hepatitis B virus could allow time for the immunological memory to protect them against acute disease or the development of chronic carriage. During the past 20 years, the frequency of hepatitis B infection has declined greatly in Italy, as a result of social, behavioural, and demographic changes; the general improvement in standard of living and hygiene; and the introduction of public-health measures including refinement in blood screening, use of universal precautions in medical settings, and implementation of universal vaccination policies.25,26 Because of the high quality of the vaccination delivery services and public awareness of the disease, Italy's hepatitis B vaccination programme has been successful with a good coverage rate, although there is a somewhat lower acceptance in the south than in the northern regions.
Universal anti-hepatitis-B vaccination of infants and adolescents was implemented in Italy in 1991. We undertook a multicentre study in previously vaccinated individuals to assess the duration of immunity and need for booster, over 10 years after vaccination.
In 1212 children and 446 Italian Air Force recruits vaccinated as infants and adolescents, respectively, we measured the concentrations of antibodies to hepatitis-B surface antigen (anti-HBs) and the presence of antibodies to hepatitis-B core antigen (anti-HBc) at enrolment; postimmunisation values were not available. Individuals positive for anti-HBc were tested for hepatitis B surface antigen (HBsAg) and hepatitis B viral DNA. Individuals with anti-HBs concentrations at 10 IU/L or more were regarded as protected; those with antibody less than 10 IU/L were given a booster dose and retested 2 weeks later. Individuals showing postbooster anti-HBs concentrations of less than 10 IU/L were offered two additional vaccine doses and retested 1 month after the third dose.
Protective anti-HBs concentrations were retained in 779 (64%, 95% CI 61·6–67) children and 398 (89%, 86·4–92·1) recruits. We recorded antibody amounts of less than 10 IU/L in 433 children (36%, 33–38·4) and 48 (11%, 7·9–13·6) recruits. One child and four recruits were positive for anti-HBc, but negative for HBsAg and hepatitis B viral DNA. Antibody concentrations were higher in recruits than in children (geometric mean titre 234·8 IU/L vs 32·1 IU/L, p=0·0001). 332 (97%) of 342 children and 46 (96%) of 48 recruits who received a booster showed an anamnestic response, whereas ten (3%) children and two (4%) recruits remained negative for anti-HBs or had antibody concentrations of less than 10 IU/L. Prebooster and postbooster antibody titres were strongly correlated with each other in both groups. All individuals given two additional vaccine doses (eight children and two recruits) showed anti-HBs amounts of more than 10 IU/L at 1 month after vaccination.
Strong immunological memory persists more than 10 years after immunisation of infants and adolescents with a primary course of vaccination. Booster doses of vaccine do not seem necessary to ensure long-term protection.
Pregnant women as a sentinel population to target and implement hepatitis B virus (HBV) vaccine coverage: A three-year survey in Palermo, Sicily
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Hepatitis B virus (HBV) vaccine coverage was assessed using serologic patterns of infection (HBsAg, anti HBc) and vaccine-induced immunity (isolated anti HBs) among 3318 pregnant women attending the Obstetrical Unit of the University Hospital in Palermo who were screened over 3 years (2001–2003). Three thousand and eight of them (90.6%) were born in Sicily, whereas 310 (9.4%) were immigrants from non-EU countries. The overall prevalence of HBsAg was 1.1%, and it was significantly higher among immigrant than indigenous women (4.2% versus 0.8%; OR 5.26; p < 0.0001). Serologic evidence of past HBV infection (anti HBc) also was significantly higher in immigrants than in Sicilian women (24.5% versus 5.2%, respectively). Women aged 17–21 in our study were in cohorts that had been targeted since 1991 for mandatory HBV vaccination at age 12. In this targeted age group, 74.2% of the Sicilian women had isolated anti HBs, compared to only 15.0% among immigrants.
The results suggest the need to improve HBV immunization of Sicilian adolescents and especially to implement active surveillance and to launch an HBV immunization programme that targets immigrants to Sicily.
Long-term persistence of anti-HBs after vaccination against HBV: An 18 year experience in health care workers
2004, Vaccine
Citation Excerpt :
In the early 1980s, hepatitis B virus (HBV) was a major cause of morbidity and mortality in Italy, with an estimated 1.5 million HBsAg carriers and an associated mortality rate of around 9000 deaths a year from HBV-related diseases, such as cirrhosis and liver cancer [1].
The aim of the present study was to evaluate the long-term persistence of seroprotection after hepatitis B virus (HBV) vaccination. A total of 422 health care workers (HCWs) were evaluated 4.8–18.8 years after primary immunization (mean follow-up 11.8 years); 241 of them had received plasma-derived vaccines and 181 had been given yeast-derived vaccines; 107 subjects received a booster dose of yeast-derived vaccine 6 years after primary immunization with either plasma-derived or yeast-derived vaccines. Seroprotection was assumed when the anti-HBs titers were >10 mIU/ml. The overall response after primary immunization was 98.8%. Among subjects who reached a 10 year follow-up, those treated with plasma-derived vaccine had a seroprotection rate of 87.8 compared to 81.6% of those vaccinated with yeast-derived vaccines (P<0.001). Anti-HBs geometric mean titers (GMTs) after primary immunization were similar in the two groups, but were significantly lower at 10 years follow-up in the group that had received a yeast-derived vaccine (104 mIU/ml versus 244 mIU/ml in those who used a plasma-derived vaccine, P<0.05). Anti-HBs GMTs in the 107 subjects given the booster dose were 242 mIU/ml pre-booster titer, and rose to 35,171 mIU/ml after the booster dose. A mean 10.1 years after the booster dose, GMTs were 952 mIU/ml. Overall, the anti-HBs seroprotection rate was 95.4% (102 subjects). Based on GMT results, no booster dose is necessary in healthy adults for at least 10 years after primary immunization.

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Update on hepatitis B vaccination in Italy 10 years after its implementation

Abstract

Section snippets

The Italian program of vaccination against hepatitis B: rationale and perspectives

Safety and compliance of the hepatitis B vaccination campaign

The impact of vaccination on the burden of the disease

Conclusions

Progress on the control of hepatitis B infection through immunisation

Gut

Integration of hepatitis B vaccination into national immunisation programmes

Br. Med. J.

Mass vaccination against hepatitis B in infants in Italy

Lancet

Vaccination against hepatitis B: the Italian strategy

Vaccine

Vaccination campaign against hepatitis B for 12-year-old subject in Italy

Vaccine

Central-nervous-system demyelination after immunisation with recombinant hepatitis B vaccine

Lancet

Vaccines to prevent viral hepatitis

New Engl. J. Med.

Over a decade of experience with a yeast recombinant hepatitis B vaccine

Vaccine