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      Discrepancies between Vaccine Documentation and Serologic Status for Diphtheria, Tetanus, and Hepatitis B in Internationally Adopted Children

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          Abstract

          Internationally Adopted Children (IAC) often show suboptimal immunisation coverage, but available data are discordant. Data at the first evaluation of 2073 IAC (median age: 6 years) referred to the Meyer Children’s University Hospital (Florence, Italy) in 2009–2019 were analysed in order to evaluate their immunisation status against diphtheria, tetanus, and hepatitis B. Negative antibody titres were observed in 11.5% of the IAC for diphtheria, 18.6% for tetanus, and 39.0% for hepatitis B. At multivariate analysis, originating from Africa was an independent risk factor for seronegativity for the three diseases ( p < 0.001), while age below four years was an independent factor associated with protective immunity, only considering hepatitis B ( p < 0.001). Vaccine documentation was an additional factor independently associated with protective immunity. However, a discrepancy between documentation (indicating previous vaccinations) and serology (showing negative antibody titres) was evidenced in 3.8% of the children for diphtheria, 12.6% for tetanus, and 29.6% for hepatitis B. This finding suggests that although vaccine documentation may reflect the presence of protective antibody titres, it should not be accepted as absolute evidence of protective immunity, underlining the importance of a complete assessment of immunisation status in IAC, particularly in those originating from Africa and aged over four years.

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          Long-term immunogenicity of hepatitis B vaccination and policy for booster: an Italian multicentre study.

          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 enrollment; 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.
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            Hepatitis B surface antigen-specific T and B cell memory in individuals who had lost protective antibodies after hepatitis B vaccination.

            Long-term protection after hepatitis B vaccination is dependent on the persistence of a strong immunologic memory. In search of reliable markers for a hepatitis B surface antigen (HBsAg)-specific immunological memory we studied the cellular and humoral immune responses of 15 healthy individuals who were successfully vaccinated but had lost anti-HBs titers. To determine the reactivity of vaccine-induced HBsAg-specific T cells of both effector and memory phenotype CD4+/CD45RA+ and CD4+/CD45R0+ T cells, respectively, were isolated, stimulated with HBsAg and tested for IFN-gamma and IL-5-secretion by enzyme-linked immunospot assays (Elispot). To detect even small numbers of specific T cells, we enriched the appropriate subpopulation from the entire PBMC population. B cell memory was analysed by cocultivation of isolated B cells with CD4+ T cells and identification of anti-HBs-secreting cells by Elispot. All individuals were revaccinated and humoral and cellular responses were determined. The results showed significant numbers of HBsAg-specific memory T and B cells present in all vaccinees despite the absence of specific antibodies. Our data suggest that individuals who had lost their anti-HBs seropositivity still show immunologic T cell memory and that these T cells are able to trigger anti-HBs production of B cells activated by revaccination.
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              The law on compulsory vaccination in Italy: an update 2 years after the introduction

              Italy introduced a national law extending the number of compulsory vaccines from four to 10 in July 2017. The implementation placed a further burden on immunisation centres as they were required to cover the increased demand of vaccination by the parents of unvaccinated children. Vaccine coverage (VC) estimated 6 months and 1 year later, at 24 and 30 months (same birth cohort), had increased for all vaccines. At 24 months of age, measles VC increased from 87.3% in 2016 to 91.8% in 2017 and 94.1% at 30 months of age as at June 2018. In six of 21 regions and autonomous provinces, VC for measles was >95%. Despite the implementation of this law, vaccine hesitancy is still a problem in Italy and the political and social debate on mandatory vaccination is ongoing. Regardless of the policy to be adopted in the future, strategies to maintain high vaccination rates and the related herd immunity should be considered, including adequate communication to the population and the implementation of electronic immunisation registries.
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                Author and article information

                Journal
                Vaccines (Basel)
                Vaccines (Basel)
                vaccines
                Vaccines
                MDPI
                2076-393X
                30 August 2020
                September 2020
                : 8
                : 3
                : 489
                Affiliations
                [1 ]Department of Health Sciences, University of Florence, 50134 Florence, Italy; angela.bechini@ 123456unifi.it (A.B.); sara.boccalini@ 123456unifi.it (S.B.); beatrice.zanella@ 123456unifi.it (B.Z.)
                [2 ]Meyer Children’s University Hospital, Department of Health Sciences, University of Florence, 50139 Florence, Italy; ilaria.rancan@ 123456stud.unifi.it (I.R.); luisa.galli@ 123456unifi.it (L.G.)
                Author notes
                Author information
                https://orcid.org/0000-0002-6013-8779
                https://orcid.org/0000-0002-9695-7549
                https://orcid.org/0000-0002-7912-3366
                Article
                vaccines-08-00489
                10.3390/vaccines8030489
                7563378
                32872676
                1155e188-5277-4a24-ab56-ea88c97a6066
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 17 July 2020
                : 27 August 2020
                Categories
                Article

                seroprevalence,immunological status,vaccine,internationally adopted children,hepatitis b,tetanus,diphtheria

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