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      Immunogenicity of the Currently Recommended Pneumococcal Vaccination Schedule in Patients With Inflammatory Bowel Disease

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          Abstract

          Background

          Patients with inflammatory bowel disease (IBD) are at increased risk of invasive pneumococcal infections. Therefore, vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) 2 months later is recommended. However, the level of immunogenicity induced by this vaccination schedule in IBD patients with and without immunosuppressive medication remains unclear.

          Methods

          We prospectively assessed the immunogenicity of PCV13 followed by PPSV23 in IBD patients by measuring serotype-specific pneumococcal immunoglobulin G antibody concentrations at baseline and 4–8 weeks postvaccination. Response to vaccination was defined as a postvaccination antibody concentration ≥1.3 μg/mL for 70% of the measured serotypes. We analyzed the immunogenic effect of 4 different medication regimens: (1) conventional immunomodulators (ie, oral prednisolone >10 mg/day, thiopurines, methotrexate); (2) anti–tumor necrosis factor agents; (3) combination therapy; and (4) no treatment with immunosuppressive agents (control group).

          Results

          One hundred forty-one IBD patients were included, of whom 37 were controls. Adequate response to vaccination was 59% (61/104) in patients using immunosuppressive agents (groups 1–3) vs 81% (30/37) in controls (odds ratio, 0.33 [95% confidence interval, .13–.82]). A combination of different immunosuppressive drugs most severely impaired the immune response to pneumococcal vaccination (response, 52% [15/29]).

          Conclusions

          Although the sequential vaccination schedule of PCV13 followed by PPSV23 is safe, immunogenic, and thus beneficial in the majority of IBD patients, those receiving immunosuppressive agents, and especially those receiving combination therapy, have an impaired immune response compared to controls. Therefore, preferably, vaccinations should be administered before the initiation of immunosuppressive therapy.

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          Most cited references33

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          Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typable Haemophilus influenzae: a randomised double-blind efficacy study.

          Acute otitis media is one of the most commonly-diagnosed childhood infections. This study assessed the efficacy of a novel vaccine that contained polysaccharides from 11 different Streptococcus pneumoniae serotypes each conjugated to Haemophilus influenzae-derived protein D in prevention of acute otitis media. 4968 infants were randomly assigned to receive either pneumococcal protein D conjugate or hepatitis A vaccine at the ages of 3, 4, 5, and 12-15 months and were followed-up until the end of the second year of life. Middle-ear fluid was obtained for bacteriological culture and serotyping in children who presented with abnormal tympanic membrane or presence of middle-ear effusion, plus two predefined clinical symptoms. The primary endpoint was protective efficacy against the first episode of acute otitis media caused by vaccine pneumococcal serotypes. Analysis was per protocol. From 2 weeks after the third dose to 24-27 months of age, 333 clinical episodes of acute otitis media were recorded in the protein D conjugate group (n=2455) and 499 in the control group (n=2452), giving a significant (33.6% [95% CI 20.8-44.3]) reduction in the overall incidence of acute otitis media. Vaccine efficacy was shown for episodes of acute otitis media caused by pneumococcal vaccine serotypes (52.6% [35.0-65.5] for the first episode and 57.6% [41.4-69.3] for any episode). Efficacy was also shown against episodes of acute otitis media caused by non-typable H influenzae (35.3% [1.8-57.4]). The vaccine reduced frequency of infection from vaccine-related cross-reactive pneumococcal serotypes by 65.5%, but did not significantly change the number of episodes caused by other non-vaccine serotypes. These results confirm that using the H influenzae-derived protein D as a carrier protein for pneumococcal polysaccharides not only allowed protection against pneumococcal otitis, but also against acute otitis media due to non-typable H influenzae. Whether this approach would also allow improved protection against lower respiratory tract infections warrants further investigation.
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            Effect of methotrexate, anti-tumor necrosis factor α, and rituximab on the immune response to influenza and pneumococcal vaccines in patients with rheumatoid arthritis: a systematic review and meta-analysis.

            To assess the current literature on the impact of rheumatoid arthritis (RA) treatments on the humoral response to pneumococcal and influenza vaccines. We systematically searched the literature for studies evaluating the immune response to vaccines in RA patients receiving methotrexate (MTX) and/or biologic agents. The efficacy of vaccination, assessed by the response rate based on increased antibody titers before and 3-6 weeks after vaccination, was extracted by one investigator and verified by another. In total, 12 studies were included. RA patients mainly received MTX, anti-tumor necrosis factor α (anti-TNFα), or rituximab (RTX). Influenza vaccination response was reduced for RTX (43 patients; pooled odds ratio [OR] 0.44 [95% confidence interval (95% CI) 0.17-1.12] for H1N1, OR 0.11 [95% CI 0.04-0.31] for H3N2, and OR 0.29 [95% CI 0.10-0.81] for B) but not for anti-TNFα (308 patients; OR 0.93 [95% CI 0.36-2.37] for H1N1, OR 0.79 [95% CI 0.34-1.83] for H3N2, and OR 0.79 [95% CI 0.37-1.70] for B). For MTX, results differed depending on the method of analysis (222 patients; OR 0.35 [95% CI 0.18-0.66] for at least 2 strains, ORs were close to 1.0 in the single strain analysis). Pneumococcal vaccination response was reduced for 139 patients receiving MTX compared with controls (OR 0.33 [95% CI 0.20-0.54] for serotype 6B and OR 0.58 [95% CI 0.36-0.94] for 23F) but not for anti-TNFα (258 patients; OR 0.96 [95% CI 0.57-1.59] for 6B and OR 1.20 [95% CI 0.57-2.54] for 23F). For RTX, the response was reduced (88 patients; OR 0.25 [95% CI 0.11-0.58] for 6B and OR 0.21 [95% CI 0.04-1.05] for 23F). MTX decreases humoral response to pneumococcal vaccination and may impair response to influenza vaccination. The immune response to both vaccines is reduced with RTX but not with anti-TNFα therapy in RA patients. Copyright © 2014 by the American College of Rheumatology.
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              Pneumococcal vaccines WHO position paper - 2012 - recommendations.

              (2012)
              This article presents the World Health Organization (WHO) recommendations on the use of pneumococcal vaccines excerpted from the Pneumococcal vaccines WHO position paper - 2012 recently published in the Weekly Epidemiological Record. The current document replaces the position paper on the use 7-valent pneumococcal conjugate vaccine published in 2007. Incorporating the most recent developments in the field of pneumococcal vaccines this position paper focuses on the currently available 10-valent and 13-valent conjugate vaccines and their introduction and use in national immunization programmes. It also deals with the 23-valent polysaccharide vaccine, though in less detail than provided in the April 2008 position paper which remains valid. Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of scientific evidence for a few key conclusions. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines worldwide. This paper reflects the recommendations of the WHO's Strategic Advisory Group of Experts (SAGE) on immunization. Recommendations on the use of pneumococcal vaccines were discussed by SAGE at its meetings in November 2006 (conjugate vaccine) and April 2008 (polysaccharide vaccine) and most recently in November 2011. Evidence presented at these meetings can be accessed at http://www.who.int/immunization/sage/previous/en/index.html. Copyright © 2012. Published by Elsevier Ltd.. All rights reserved.
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                Author and article information

                Journal
                Clinical Infectious Diseases
                Oxford University Press (OUP)
                1058-4838
                1537-6591
                March 22 2019
                March 22 2019
                Affiliations
                [1 ]Centre of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Amsterdam University Medical Centres, Nieuwegein
                [2 ]Department of Medical Microbiology and Immunology, St Antonius Hospital, Nieuwegein
                [3 ]Department of Experimental Immunology, Amsterdam University Medical Centres, University of Amsterdam, The Netherlands
                [4 ]Department of Gastroenterology, Amsterdam University Medical Centres, University of Amsterdam, The Netherlands
                [5 ]Institute of Tropical Medicine, University of Tübingen, Germany
                Article
                10.1093/cid/ciz226
                30899961
                a53aebb1-7869-4629-8599-1382db179f5d
                © 2019

                http://creativecommons.org/licenses/by/4.0/

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