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      Long-Term Persistence of Seroprotection by Hepatitis B Vaccination in Healthcare Workers of Southern Italy

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          Abstract

          Background

          The impact of hepatitis B virus (HBV) vaccination campaigns on HBV epidemiology needs to be evaluated, in order to assess the long-term immunity offered by vaccines against HBV.

          Objectives

          To evaluate the current status of anti-HBV vaccine coverage among healthcare workers (HCWs) in Southern Italy, and to determine the long-term persistence of antibodies to hepatitis B surface antigens (anti-HBs) in such a cohort of subjects.

          Patients and Methods

          A longitudinal, retrospective seroepidemiological survey was conducted among 451 HCWs, who were working at or visiting, the Occupational Health Department of a city hospital, in Catania, Italy, between January 1976 and December 2010.

          Results

          At the 30-year follow-up (mean follow-up 10.15 ± 5.96 years, range 0.74-30), 261 HCWs had detectable anti-HBs titers indicating a persistence of seroprotection of 89.4% (out of 292 anti-HBs positive results, three months after vaccination). An inadequate vaccination schedule was the strongest predictor of antibody loss during follow-up (OR = 8.37 95% CI: 5.41-12.95, P < 0.001). A Kaplan-Maier survival curve revealed that the persistence of anti-HBs 30 years after vaccination, was 92.2% for high responders, while it was only 27.3% for low responders (P = 0.001).

          Conclusions

          A good level of seroprotection persisted in 57.9% of the subjects after 30 years. Factors related to this immunization status confirmed the importance of vaccinating HCWs early in their careers and ensuring an adequate vaccination schedule. However, with particular reference to the low rate of hepatitis B vaccine coverage among HCWs in Southern Italy, the implementation of a new educational intervention as part of an active vaccination program is needed.

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          Most cited references45

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          Are booster immunisations needed for lifelong hepatitis B immunity? European Consensus Group on Hepatitis B Immunity.

          (2000)
          Long-term protection against clinically significant breakthrough hepatitis B (HB) virus infection and chronic carriage depends on immunological memory, which allows a protective anamnestic antibody response to antigen challenge. Memory seems to last for at least 15 years in immunocompetent individuals. To date there are no data to support the need for booster doses of HB vaccine in immunocompetent individuals who have responded to a primary course. All adequately vaccinated individuals have shown evidence of immunity in the form of persisting anti-HBs and/or in vitro B-cell stimulation or an anamnestic response to a vaccine challenge. Nonetheless several countries and individuals currently have a policy of administering booster doses to certain risk groups. Boosters may be used to provide reassurance of protective immunity against benign breakthrough infection. For immunocompromised patients, regular testing for anti-HBs, and a booster injection when the titre falls below 10 mIU/mL, is advised. Long-term monitoring should continue, to confirm the absence of clinically significant breakthrough episodes of hepatitis B and to find out if a carrier state develops after 15 years. Also, non-responders to a primary course should continue to be studied.
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            The effect of age on immunologic response to recombinant hepatitis B vaccine: a meta-analysis.

            Hepatitis B vaccine is a key tool for the prevention of hepatitis B infection. Age-associated changes in immune function may contribute to decreased vaccine efficacy in older individuals, although research related to this topic has yielded contradictory findings. We performed a meta-analysis of 24 published trials and studies that evaluated the association of age with response to hepatitis B vaccine, using a random-effects model. Pooling of study results suggested a significantly increased risk of nonresponse to hepatitis B vaccine among older individuals (relative risk [RR], 1.76; 95% confidence interval [CI], 1.48-2.10). An elevated risk of nonresponse persisted even after exclusion of poor-quality studies (RR, 1.63; 95% CI, 1.23-2.15) and adjustment for publication bias (RR, 1.52; 95% CI, 1.26-1.83), and it was present even when "older" individuals were defined as being as young as 30 years. These findings have important implications for individuals at risk for hepatitis B infection, including health care workers and travelers.
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              Vaccine induced immunologic memory for hepatitis B surface antigen: implications for policy on booster vaccination.

              This paper reviews published literature on the long-term persistence of immunologic memory for HBsAg after a course of hepatitis B vaccine and the functional significance this has for policy on booster vaccination. Several studies have shown that vaccine induced antibody (anti-HBs) specific for the surface antigen (HBsAg) of hepatitis B virus (HBV) is protective at a serum concentration of 10 milli-International Units per milliliter (mIU ml-1). When acquired passively (e.g. from hepatitis B immune globulin), susceptibility to infection returns as antibody declines. However, vaccine induces active synthesis of anti-HBs accompanied by immunologic memory for HBsAg that affords ongoing protection independent of antibody. Persistent memory over periods of 5 years or more is evident from large, rapid increases in antibody following booster vaccination, even in subjects who have lost antibody. Complementary studies, using an in vitro enzyme linked immunosorbent assay (spot-ELISA), show that the number of memory B lymphocytes able to produce anti-HBs does not diminish as the level of antibody declines. That immunologic memory provides effective immunity is suggested by serologic studies over periods of 5 years or more of vaccinees frequently exposed to HBV. Although many failed to maintain at least 10 mIU ml-1 of antibody, there have been very few clinically significant breakthrough infections. Thus, it appears unnecessary to give healthy vaccinees a booster vaccination when the level of anti-HBs falls below 10 mIU ml-1. Current studies suggest good retention of immunologic memory in healthy vaccinees over periods of 5-12 years. While additional studies will better define the limits of this phenomenon, routine booster vaccination should not be needed to sustain immunologic memory and protection within 5 years and perhaps longer after the primary vaccination series.
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                Author and article information

                Journal
                Hepat Mon
                Hepat Mon
                10.5812/hepatmon
                Kowsar
                Hepatitis Monthly
                Kowsar
                1735-143X
                1735-3408
                September 2012
                04 September 2012
                : 12
                : 9
                : e6025
                Affiliations
                [1 ]G.F. Ingrassia Department, Section of Hygiene and Public Health, University of Catania, Catania, Italy
                [2 ]Rosario Cunsolo, Vittorio Emanuele Hospital of Catania Health Direction, Catania, Italy
                [3 ]Department of Internal Medicine and Systemic Diseases, University of Catania, Catania, Italy
                [4 ]The Great Senescence Research Center, University of Catania, Ospedale Cannizzao, Catania, Italy
                Author notes
                [* ]Corresponding author: Antonio Mistretta, G.F. Ingrassia Department, Section of Hygiene and Public Health, University of Catania, Via Santa Sofia 87, 95123, Catania, Italy. Tel.: +39-953782182, Fax: +39-953782177, E-mail: anmist@ 123456unict.it
                Article
                10.5812/hepatmon.6025
                3475028
                23087756
                9bb63c61-4bae-40ac-ba77-f8455c2be863
                Copyright © 2012, Baqiyatallah Research Center for Gastroenterology and Liver Diseases

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 November 2011
                : 17 May 2012
                : 28 July 2012
                Categories
                Original Article

                Infectious disease & Microbiology
                health personnel,vaccination,vaccines,hepatitis b virus
                Infectious disease & Microbiology
                health personnel, vaccination, vaccines, hepatitis b virus

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