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Takeshita K, Takeuchi N, Takahashi Y, Fukasawa C, Hishiki H, Hoshino T, Ishiwada N, Shimojo N. Pneumococcal serotype-specific IgG and opsonophagocytic activity in young Japanese patients with asplenia. Hum Vaccin Immunother 2021; 17:3687-3691. [PMID: 34213395 DOI: 10.1080/21645515.2021.1943989] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
Patients with asplenia are at high risks of severe infections caused by encapsulated bacteria, particularly Streptococcus pneumoniae. Thirteen-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) are recommended for invasive pneumococcal disease prevention; however, little is known about the immunity to pneumococci in young patients with asplenia. We measured pneumococcal serotype-specific IgG (Pn-IgG) levels and pneumococcal opsonophagocytic activity (Pn-OPA) against some PCV13-contained serotypes (1, 3, 5, 6A, 7 F, 19A) in 23 young patients with asplenia using surplus serum samples. In this study, 5 and 13 patients had received PCV13 during routine immunizations and PPSV23, respectively; however, >5 years had passed since the last dose in most cases. The geometric mean concentrations (GMCs) of Pn-IgG in all study patients were not under the cutoff level against six serotypes, but they were lower than the those of age-matched healthy controls, as we have previously published. The patients who had received only PPSV23 had significantly lower GMCs against four serotypes (serotypes 1, 6A, 7 F, and 19A) than that of the patients who had received at least one PCV13 vaccination. The patients who had received only PPSV23 also had significantly lower geometric mean titers (GMTs) of Pn-OPA against all three serotypes we measured (serotypes 3, 5, and 19A) than that of the patients who had received at least one PCV13 vaccination. Our findings are useful data that can indicate insufficient immunity in young patients with asplenia against some PCV13 pneumococci serotypes and suggest the need for appropriate vaccinations in the post-PCV13 era.
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Affiliation(s)
- Kenichi Takeshita
- Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba-shi, Japan.,Department of Infectious Diseases, Medical Mycology Research Center, Chiba University, Chiba-shi, Japan
| | - Noriko Takeuchi
- Department of Infectious Diseases, Medical Mycology Research Center, Chiba University, Chiba-shi, Japan
| | - Yoshiko Takahashi
- Department of Pediatrics, Seikeikai Chiba Medical Center, Chiba-shi, Japan
| | - Chie Fukasawa
- Division of Infectious Diseases, Chiba Children's Hospital, Chiba-shi, Japan
| | - Haruka Hishiki
- Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba-shi, Japan
| | - Tadashi Hoshino
- Division of Infectious Diseases, Chiba Children's Hospital, Chiba-shi, Japan
| | - Naruhiko Ishiwada
- Department of Infectious Diseases, Medical Mycology Research Center, Chiba University, Chiba-shi, Japan
| | - Naoki Shimojo
- Center for Preventive Medical Sciences, Chiba University, Chiba-shi, Japan
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Casciani F, Trudeau MT, Vollmer CM. Perioperative Immunization for Splenectomy and the Surgeon's Responsibility: A Review. JAMA Surg 2020; 155:1068-1077. [PMID: 32936229 DOI: 10.1001/jamasurg.2020.1463] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Importance Patients who have had splenectomy have a lifelong risk of overwhelming postsplenectomy infection (OPSI), a condition associated with high mortality rates. Surgeons must be aware of the rationale of vaccination in the case of splenectomy, to provide appropriate immunization in the perioperative time. Observations English-language articles published from January 1, 1990, to December 31, 2019, were retrieved from MEDLINE/PubMed, Cochrane Library, and ClinicalTrials.gov databases. Randomized clinical trials as well as systematic reviews and observational studies were considered. Asplenia yields an impairment of both innate and adaptive immunity, thus increasing the risk of severe encapsulated bacterial infections. Current epidemiology of OPSI ranges from 0.1% to 8.5% but is hard to ascertain because of ongoing shifts in patients' baseline conditions and vaccine penetration. Despite the lack of randomized clinical trials, immunization appears to be effective in reducing OPSI incidence. Unfortunately, vaccination coverage is still suboptimal, with a great variability in vaccination rates being reported across institutions and time frames. Notably, current guidelines do not advocate any particular health care qualification responsible for vaccine prescription or administration. Given the dearth of high-level basic science or clinical evidence, the optimal vaccination timing and the need for booster doses are not yet well established. Although almost all guidelines indicate to not administer vaccines within 14 days before and after surgery, most data suggest that immunization might be effective even in the immediate perioperative time, thus placing the surgeon in a primary position for vaccine delivery. Furthermore, revaccination schedules are the target of ongoing debates, since a vaccine-driven hyporesponsiveness has been postulated. Conclusions and Relevance In patients who have undergone splenectomy, OPSI might be effectively prevented by proper immunization. Surgeons have the primary responsibility for achieving adequate, initial immunization in the setting of both planned and urgent splenectomy.
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Affiliation(s)
- Fabio Casciani
- Perelman School of Medicine, Department of Surgery, University of Pennsylvania, Philadelphia
| | - Maxwell T Trudeau
- Perelman School of Medicine, Department of Surgery, University of Pennsylvania, Philadelphia
| | - Charles M Vollmer
- Perelman School of Medicine, Department of Surgery, University of Pennsylvania, Philadelphia
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Laws HJ, Baumann U, Bogdan C, Burchard G, Christopeit M, Hecht J, Heininger U, Hilgendorf I, Kern W, Kling K, Kobbe G, Külper W, Lehrnbecher T, Meisel R, Simon A, Ullmann A, de Wit M, Zepp F. Impfen bei Immundefizienz. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020; 63:588-644. [PMID: 32350583 PMCID: PMC7223132 DOI: 10.1007/s00103-020-03123-w] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Hans-Jürgen Laws
- Klinik für Kinder-Onkologie, -Hämatologie und Klinische Immunologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - Ulrich Baumann
- Klinik für Pädiatrische Pneumologie, Allergologie und Neonatologie, Medizinische Hochschule Hannover, Hannover, Deutschland
| | - Christian Bogdan
- Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander Universität FAU Erlangen-Nürnberg, Erlangen, Deutschland
- Ständige Impfkommission (STIKO), Robert Koch-Institut, Berlin, Deutschland
| | - Gerd Burchard
- Ständige Impfkommission (STIKO), Robert Koch-Institut, Berlin, Deutschland
- Bernhard-Nocht-Institut für Tropenmedizin, Hamburg, Deutschland
| | - Maximilian Christopeit
- Interdisziplinäre Klinik für Stammzelltransplantation, Universitätsklinikum Eppendorf, Hamburg, Deutschland
| | - Jane Hecht
- Abteilung für Infektionsepidemiologie, Fachgebiet Nosokomiale Infektionen, Surveillance von Antibiotikaresistenz und -verbrauch, Robert Koch-Institut, Berlin, Deutschland
| | - Ulrich Heininger
- Ständige Impfkommission (STIKO), Robert Koch-Institut, Berlin, Deutschland
- Universitäts-Kinderspital beider Basel, Basel, Schweiz
| | - Inken Hilgendorf
- Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Jena, Deutschland
| | - Winfried Kern
- Klinik für Innere Medizin II, Abteilung Infektiologie, Universitätsklinikum Freiburg, Freiburg, Deutschland
| | - Kerstin Kling
- Abteilung für Infektionsepidemiologie, Fachgebiet Impfprävention, Robert Koch-Institut, Berlin, Deutschland.
| | - Guido Kobbe
- Klinik für Hämatologie, Onkologie und Klinische Immunologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - Wiebe Külper
- Abteilung für Infektionsepidemiologie, Fachgebiet Impfprävention, Robert Koch-Institut, Berlin, Deutschland
| | - Thomas Lehrnbecher
- Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Frankfurt, Frankfurt am Main, Deutschland
| | - Roland Meisel
- Klinik für Kinder-Onkologie, -Hämatologie und Klinische Immunologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - Arne Simon
- Klinik für Pädiatrische Onkologie und Hämatologie, Universitätsklinikum des Saarlandes, Homburg/Saar, Deutschland
| | - Andrew Ullmann
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Maike de Wit
- Klinik für Innere Medizin - Hämatologie, Onkologie und Palliativmedizin, Vivantes Klinikum Neukölln, Berlin, Deutschland
- Klinik für Innere Medizin - Onkologie, Vivantes Auguste-Viktoria-Klinikum, Berlin, Deutschland
| | - Fred Zepp
- Ständige Impfkommission (STIKO), Robert Koch-Institut, Berlin, Deutschland
- Zentrum für Kinder- und Jugendmedizin, Universitätsmedizin Mainz, Mainz, Deutschland
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Szenborn L, Osipova IV, Czajka H, Kharit SM, Jackowska T, François N, Habib MA, Borys D. Immunogenicity, safety and reactogenicity of the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in 2-17-year-old children with asplenia or splenic dysfunction: A phase 3 study. Vaccine 2017; 35:5331-5338. [PMID: 28866290 DOI: 10.1016/j.vaccine.2017.08.039] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2017] [Revised: 07/26/2017] [Accepted: 08/20/2017] [Indexed: 11/30/2022]
Abstract
BACKGROUND Immunization with pneumococcal vaccines is an important prophylactic strategy for children with asplenia or splenic dysfunction, who are at high risk of bacterial infections (including S. pneumoniae). This study aimed to assess immunogenicity and safety of pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, GSK) in this at-risk population. METHODS This phase III, multi-centre, open-label, controlled study, in which at-risk children with asplenia or splenic dysfunction were enrolled (age strata: 2-4, 5-10 and 11-17years), was conducted in Poland and the Russian Federation. For the 2-4years at-risk group, healthy age-matched children were enrolled as control. Unprimed children (not previously vaccinated with any pneumococcal vaccine) received 2 PHiD-CV doses (≥2months apart) and pneumococcal vaccine-primed children received 1 dose. Immune responses were assessed pre-vaccination and one month post-each dose. Solicited and unsolicited adverse events (AEs) were recorded for 4 and 31days post-vaccination, respectively, and serious AEs (SAEs) throughout the study. RESULTS Of 52 vaccinated children (18 at-risk primed, 28 at-risk unprimed and 6 control unprimed), 45 (18, 23 and 4, respectively) were included in the according-to-protocol cohort for immunogenicity. Post-vaccination (post-dose 1 in primed and post-dose 2 in unprimed children), for each vaccine pneumococcal serotype and vaccine-related serotype 6A all at-risk children had antibody concentrations ≥0.2µg/mL, and for vaccine-related serotype 19A at least 94.4%. Increases in antibody geometric mean concentrations were observed. For most serotypes, all at-risk children had post-vaccination opsonophagocytic activity (OPA) titers ≥8 and increases in OPA geometric mean titers were observed. No safety concerns were raised. One non-fatal SAE (respiratory tract infection, considered not vaccine-related) was reported by one at-risk unprimed child. CONCLUSION PHiD-CV was immunogenic and well tolerated in 2-17-year-old children with asplenia or splenic dysfunction. Clinical Trial Registry: www.clinicaltrials.gov, NCT01746108.
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Affiliation(s)
- L Szenborn
- Department of Pediatrics and Infectious Diseases, Medical University Wroclaw, Chalubinskiego 2-2A, 50-368 Wroclaw, Poland.
| | - I V Osipova
- Departmental Clinical Hospital at Barnaul Railway Station, Molodiozhnaya st. 20, 656038 Barnaul, Russian Federation.
| | - H Czajka
- Infectious Diseases Outpatient Clinic, The St. Luis Provincial Specialist Children's Hospital, 2a Strzelecka St., 31-503 Kraków, Poland.
| | - S M Kharit
- Scientific and Research Institute of Children's Infections, Prof. Popova st. 9, 197022, Saint-Petersburg, Russian Federation.
| | - T Jackowska
- Department of Pediatrics, The Center of Postgraduate Medical Education, Marymoncka 99/103, 01-813 Warsaw, Poland.
| | - N François
- GSK, 20, Avenue Fleming, B-1300 Wavre, Belgium.
| | - M A Habib
- GSK, 20, Avenue Fleming, B-1300 Wavre, Belgium.
| | - D Borys
- GSK, 20, Avenue Fleming, B-1300 Wavre, Belgium.
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Shao PL, Wu MH, Wang JK, Hsu HW, Huang LM, Chiu SN. Pneumococcal vaccination and efficacy in patients with heterotaxy syndrome. Pediatr Res 2017; 82:101-107. [PMID: 28419083 DOI: 10.1038/pr.2017.39] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2016] [Accepted: 01/23/2017] [Indexed: 12/18/2022]
Abstract
BackgroundPneumococcal vaccines, including pneumococcal polysaccharide vaccine (PPV) and pneumococcal conjugated vaccine (PCV), are crucial in preventing invasive pneumococcal diseases. We analyzed the pneumococcal vaccination rate, efficacy, and durability in patients with heterotaxy.MethodsAll patients with heterotaxy and CCHD who were followed up at our institution between 2010 and 2015 were included. Pneumococcal vaccine status and geometric mean concentration (GMC) of serotypes 6B, 14, 19F, and 23F were analyzed. Splenic function was considered abnormal when the percentage of IgM memory B cell was less than 1%.ResultsThe GMCs of the four serotypes did not differ significantly between patients with heterotaxy and those with CCHD; the GMCs were also not affected by abnormal splenic function. Most patients had GMCs >0.35 μg/ml (protection level) 4-5 years after either PPV or PCV injection; however, it may decay gradually in some serotypes. In addition, 21.4% of 42 patients with heterotaxy did not receive pneumococcal vaccine, and none completely adhered to the vaccine guidelines.ConclusionsVaccine efficacy was acceptable, even in patients with abnormal splenic function. In some patients, the durability of PPV and PCV decreased with time, highlighting the importance of booster doses. Vaccination rate in patients with heterotaxy is unsatisfactory.
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Affiliation(s)
- Pei-Lan Shao
- Department of Laboratory Medicine and Department of Pediatrics, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Mei-Hwan Wu
- Department of Pediatrics, National Taiwan University Hospital and Medical College, Taipei, Taiwan
| | - Jou-Kou Wang
- Department of Pediatrics, National Taiwan University Hospital and Medical College, Taipei, Taiwan
| | - Hui-Wen Hsu
- Department of Pediatrics, National Taiwan University Hospital and Medical College, Taipei, Taiwan
| | - Li-Min Huang
- Department of Pediatrics, National Taiwan University Hospital and Medical College, Taipei, Taiwan
| | - Shuenn-Nan Chiu
- Department of Pediatrics, National Taiwan University Hospital and Medical College, Taipei, Taiwan
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Fletcher MA, Balmer P, Bonnet E, Dartois N. PCVs in individuals at increased risk of pneumococcal disease: a literature review. Expert Rev Vaccines 2015; 14:975-1030. [DOI: 10.1586/14760584.2015.1037743] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Nived P, Jørgensen CS, Settergren B. Vaccination status and immune response to 13-valent pneumococcal conjugate vaccine in asplenic individuals. Vaccine 2015; 33:1688-94. [PMID: 25707692 DOI: 10.1016/j.vaccine.2015.02.026] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2014] [Revised: 02/01/2015] [Accepted: 02/11/2015] [Indexed: 11/19/2022]
Abstract
Overwhelming post-splenectomy infection (OPSI) is immediately life-threatening and vaccination against encapsulated bacteria, in particular pneumococci, decreases its incidence. First, we investigated the adherence to vaccination guidelines in a retrospective study of the hospital records of splenectomised patients. Second, patients were asked to complete a questionnaire and invited to participate in a study where 12-valent pneumococcal serotype-specific IgG concentrations were determined before and 4 to 6 weeks after vaccination with PCV13. Of 79 individuals who underwent splenectomy between 2000 and 2012: 81.0% received pneumococcal vaccine, 51.9% received vaccine against Haemophilus influenzae type B and 22.8% received meningococcal vaccine. 31 individuals were deceased. 33 individuals completed questionnaires and accepted participation in the second part of the study. The participants consisted of two groups: (1) prior PPV23 (n=24) and (2) prior PPV23+PCV13 (n=9). In group 1, pre-PCV13 GMC's≥0.35μg/mL were observed for serotypes 1, 4, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F, and GMC's<0.35μg/mL for serotypes 3 and 5, significant increases pre- to post-PCV13 were found for serotypes 1, 3, 4, 5, 7F, 18C, 19A, 23F (p≤0.001) and 19F (p=0.01) and all 12 serotypes-specific GMC were above 0.35μg/mL after vaccination. Group 2 did not receive vaccine in this study, but blood tests showed all 12 serotype-specific GMC>0.35μg/mL. Adherence to guidelines regarding primary pneumococcal vaccination was adequate but only a minority received the recommended meningococcal vaccination. High levels of pneumococcal serotype-specific antibodies were observed in the previous PPV23 vaccinated group, and more pronounced in the previous PCV13 group, and our data suggests that PCV13 is immunogenic for serotypes 1, 3, 4, 5, 7F, 18C, 19A, 19F and 23F, if used as a booster dose in asplenic patients with previous PPV23 vaccination.
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Affiliation(s)
- Per Nived
- Department of Infectious Diseases, Central Hospital, Kristianstad, Sweden.
| | | | - Bo Settergren
- Department of Infectious Diseases, Central Hospital, Kristianstad, Sweden
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Jahromi AS, Rahmanian K, Davami MH, Zabetian H, Yousefi A, Madani A. Natural immunity against Haemophilus influenza type B in splenectomised Beta-thalassaemia children. Pak J Biol Sci 2014; 17:1190-1194. [PMID: 26027165 DOI: 10.3923/pjbs.2014.1190.1194] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
Patients with beta-thalassaemia major and asplenia have an increased risk of encapsulated bacterial infections. The aim of this study was to determine the Haemophilus influenza type b (Hib) antibody concentrations in beta-thalassaemia patients with or without spleens. The Hib antibody concentrations were investigated in 850 patients with thalassaemia major, of whom 437 had undergone splenectomy. Hib antibody levels equal or greater than 1.0 μg mL(-1) were classified as long-term protection, those between 0.15 and less than 1.0 μg mL(-1) as short-term protection and those less than 0.15 μg mL(-1) as no protection. The mean Hib antibody level was lower in asplenic subjects than in non splenectomised subjects (0.39 ± 0.5 vs. 1.08 ± 0.55 μg mL(-1), p < 0.001). The protective antibody level prevalence in asplenic patients was significantly lower than that in patients with spleens (32.3% vs. 85.7%, p < 0.001). Protection against Hib decreased as the time interval after splenectomy increased from 57.2% at a less than 60 months interval to 10.8% at a greater than 120 months interval (p = 0.001). Nearly 30% of the 437 splenectomised subjects had long-term protection against Hib, whereas 64.4% of the 413 non splenectomised subjects had long-term protection (p < 0.001). Asplenic subjects had lower Hib antibody levels than non splenectomised subjects. Additionally, the antibody levels decreased as the time interval increased after splenectomy. A Hib vaccine recommendation for splenectomised thalassaemia major seems essential.
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Mitchell R, Trück J, Pollard AJ. Use of the 13-valent pneumococcal conjugate vaccine in children and adolescents aged 6 - 17 years. Expert Opin Biol Ther 2013; 13:1451-65. [PMID: 23889554 DOI: 10.1517/14712598.2013.824419] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
INTRODUCTION The introduction of pneumococcal conjugate vaccines into infant immunization schedules has successfully reduced the incidence of pneumococcal disease caused by vaccine serotypes. Disease incidence is low in healthy 6 - 17-year-old children and young people; however, there are a number of clinical conditions that put individuals in this age group at increased risk. Expansion of the license of a 13-valent pneumococcal conjugate vaccine , PCV-13, to include the 6 - 17 age group has recently been approved by European and American regulatory bodies. AREAS COVERED Studies assessing the safety, immunogenicity, and efficacy of pneumococcal conjugate vaccines in both healthy and high-risk 6 - 17-year-old children and adolescents are covered and the potential impact of PCV-13 in these populations is discussed. The use of the 23-valent pneumococcal polysaccharide vaccine, PPV-23, in high-risk children and adolescents is also considered. EXPERT OPINION Expanding the use of PCV-13 to include high-risk children and adolescents aged 6 - 17 has the potential to prevent additional cases of disease; however, vaccination of this population may no longer be necessary when herd immunity to PCV-13 serotypes becomes fully established. Despite the broader serotype coverage of PPV-23, the benefits of this vaccine in high-risk populations are uncertain.
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Affiliation(s)
- Ruth Mitchell
- University of Oxford, Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Churchill Hospital, Department of Paediatrics, Oxford Vaccine Group , Old Road, Headington, Oxford, OX3 7LE , UK +44 0 1865 857420 ; +44 0 1865 857420 ;
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Rosado MM, Gesualdo F, Marcellini V, Di Sabatino A, Corazza GR, Smacchia MP, Nobili B, Baronci C, Russo L, Rossi F, Vito RD, Nicolosi L, Inserra A, Locatelli F, Tozzi AE, Carsetti R. Preserved antibody levels and loss of memory B cells against pneumococcus and tetanus after splenectomy: tailoring better vaccination strategies. Eur J Immunol 2013; 43:2659-70. [PMID: 23813052 DOI: 10.1002/eji.201343577] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2013] [Revised: 06/17/2013] [Accepted: 06/25/2013] [Indexed: 01/07/2023]
Abstract
Splenectomized patients are exposed to an increased risk of septicemia caused by encapsulated bacteria. Defense against infection is ensured by preformed serum antibodies produced by long-lived plasma cells and by memory B cells that secrete immunoglobulin in response to specific antigenic stimuli. Studying a group of asplenic individuals (57 adults and 21 children) without additional immunologic defects, we found that spleen removal does not alter serum anti-pneumococcal polysaccharide (PnPS) IgG concentration, but reduces the number of PnPS-specific memory B cells, of both IgM and IgG isotypes. The number of specific memory B cells was low in splenectomized adults and children that had received the PnPS vaccine either before or after splenectomy. Seven children were given the 13-valent pneumococcal conjugated vaccine after splenectomy. In this group, the number of PnPS-specific IgG memory B cells was similar to that of eusplenic children, suggesting that pneumococcal conjugated vaccine administered after splenectomy is able to restore the pool of anti-PnPS IgG memory B cells. Our data further elucidate the crucial role of the spleen in the immunological response to infections caused by encapsulated bacteria and suggest that glycoconjugated vaccines may be the most suitable choice to generate IgG-mediated protection in these patients.
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Affiliation(s)
- M Manuela Rosado
- Immunology Area, Bambino Gesù Children's Hospital IRCCS, Rome, Italy
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Di Sabatino A, Brunetti L, Carnevale Maffè G, Giuffrida P, Corazza GR. Is it worth investigating splenic function in patients with celiac disease? World J Gastroenterol 2013; 19:2313-2318. [PMID: 23613624 PMCID: PMC3631982 DOI: 10.3748/wjg.v19.i15.2313] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2012] [Revised: 12/13/2012] [Accepted: 01/19/2013] [Indexed: 02/06/2023] Open
Abstract
Celiac disease, an immune-mediated enteropathy induced in genetically susceptible individuals by the ingestion of gluten, is the most frequent disorder associated with splenic hypofunction or atrophy. Defective splenic function affects more than one-third of adult patients with celiac disease, and it may predispose to a higher risk of infections by encapsulated bacteria and thromboembolic and autoimmune complications, particularly when celiac patients have concomitant pre-malignant and malignant complications (refractory celiac disease, ulcerative jejunoileitis and enteropathy-associated T-cell lymphoma). However, the clinical management of patients with celiac disease does not take into account the evaluation of splenic function, and in patients with high degree of hyposplenism or splenic atrophy the prophylactic immunization with specific vaccines against the polysaccharide antigens of encapsulated bacteria is not currently recommended. We critically re-evaluate clinical and diagnostic aspects of spleen dysfunction in celiac disease, and highlight new perspectives in the prophylactic management of infections in this condition.
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Recurrent bacterial meningitis by three different pathogens in an isolated asplenic child. J Infect Chemother 2011; 18:576-80. [PMID: 22147274 DOI: 10.1007/s10156-011-0341-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2011] [Accepted: 10/25/2011] [Indexed: 10/15/2022]
Abstract
Isolated congenital asplenia (ICA) is a rare condition at risk for overwhelming infection. When complicated by invasive infection, the mortality remains high, at greater than 60%. We describe a girl with ICA who developed recurrent meningitis by three different pathogens. The first, meningitis by Escherichia coli, occurred 4 days after premature birth. The other two pathogens were serotype 6B Streptococcus pneumoniae and Haemophilus influenzae type b (Hib), at 18 and 25 months of age, respectively. The patient was successfully treated with prompt antimicrobial therapy in all episodes. Serum anti-polyribosylribitol phosphate (PRP) and anti-6B-type pneumococcal antibodies were below the levels for protective activity after natural infections. Although anti-PRP antibody was significantly increased after Hib vaccination, two (6B and 19F) of seven serotype-specific pneumococcal antibodies were not elevated to protective levels after the second 7-valent pneumococcal conjugate vaccine (PCV7). We, therefore, added a third PCV7. To our knowledge, this is the first neonatal ICA patient with invasive infection and the first case of bacterial meningitis occurring three times. Our findings indicate that monitoring of immune responses after natural infections and vaccinations, and reevaluations of vaccine schedule, are important for ICA patients to prevent subsequent invasive infections.
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Abstract
The spleen is crucial in regulating immune homoeostasis through its ability to link innate and adaptive immunity and in protecting against infections. The impairment of splenic function is defined as hyposplenism, an acquired disorder caused by several haematological and immunological diseases. The term asplenia refers to the absence of the spleen, a condition that is rarely congenital and mostly post-surgical. Although hyposplenism and asplenia might predispose individuals to thromboembolic events, in this Review we focus on infectious complications, which are the most widely recognised consequences of these states. Because of the high mortality, the fulminant course, and the refractoriness to common treatment of overwhelming infections caused by encapsulated bacteria, prevention through vaccination and antibiotic prophylaxis is the basis of the management of patients who have had splenectomy or have hyposplenism. In this Review, we critically assess clinical and diagnostic aspects of splenic dysfunction and highlight new perspectives in the prevention of overwhelming post-splenectomy infections.
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Affiliation(s)
- Antonio Di Sabatino
- First Department of Medicine, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S Matteo, University of Pavia, Italy
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Meerveld-Eggink A, de Weerdt O, van Velzen-Blad H, Biesma DH, Rijkers GT. Response to conjugate pneumococcal and Haemophilus influenzae type b vaccines in asplenic patients. Vaccine 2010; 29:675-80. [PMID: 21115060 DOI: 10.1016/j.vaccine.2010.11.034] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2009] [Revised: 11/12/2010] [Accepted: 11/14/2010] [Indexed: 11/28/2022]
Abstract
We determined the immunogenicity of conjugated Haemophilus influenzae type b and pneumococcal vaccines by quantitative analysis of the antibody response in asplenic patients. To that end, we vaccinated 92 patients with a conjugated Hib vaccine and 54 received two doses of conjugated pneumococcal vaccine (PCV7), followed at six months by a plain polysaccharide pneumococcal vaccine (PPV23). Antibody concentrations were measured before and three weeks after vaccination. After one dose of pneumococcal conjugate vaccine, 46% of the patients reached the antibody threshold of ≥ 1.0 μg/mL for all 7 tested vaccine serotypes. This percentage rose to 54% after the second dose of PCV7 and did not increase further after PPV23. Over 90% of patients had antibody concentrations ≥ 1.0 μg/mL for at least 5 out of the 7 conjugated pneumococcal serotypes after 2 doses of PCV7. For serotypes, included in the PPV23 vaccine only, 25% (PPS3)-100% (PPS19A) of the patients reached antibody concentrations ≥ 1.0 μg/mL after one dose of PPV23. For Hib, 97% of the patients reached the threshold concentration of ≥ 1.0 μg/mL after one dose of vaccine. It can be concluded that the majority of asplenic patients had a sufficient response to conjugated vaccines against Streptococcus pneumoniae and Hib, reflected by a ≥ 1.0 μg/mL antibody response. Inclusion of conjugated pneumococcal polysaccharide vaccines might be of additional value in the vaccination schedule for asplenic patients because of their high immunogenicity.
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Affiliation(s)
- A Meerveld-Eggink
- Department of Internal Medicine, St. Antonius Hospital Nieuwegein, The Netherlands.
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Heterotaxy syndrome: defining contemporary disease trends. Pediatr Cardiol 2010; 31:1052-8. [PMID: 20730421 DOI: 10.1007/s00246-010-9764-z] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2010] [Accepted: 07/26/2010] [Indexed: 10/19/2022]
Abstract
The purpose of this study was to define a population of visceral heterotaxy and to investigate the incidence of bacterial sepsis in the current era of universal pediatric pneumococcal immunization. Pediatric echocardiography and radiology databases, along with electronic medical records, were searched for patients followed-up since birth between 1999 and 2009 with either asplenia or polysplenia and cardiac anatomy consistent with heterotaxy syndrome. A total of 29 patients were identified. Seven patients (24%) had a total of 8 sepsis events, and 6 patients (86%) developed sepsis while taking appropriately prescribed antibiotic prophylaxis. Of the patients with sepsis, 5 had polysplenia and 2 had asplenia. Sixty-two percent of sepsis events were nosocomially acquired. No cases of pneumococcal sepsis occurred after the introduction of the conjugated pneumococcal vaccination to the pediatric vaccination schedule. Bacterial sepsis was associated with a 44% mortality rate. An unexpected finding in 3 patients with visceral heterotaxy, asplenia, and an interrupted inferior vena cava (IVC) as the only anomaly on echocardiography was associated intestinal malrotation. Children with visceral heterotaxy remain at significant risk of life-threatening bacterial infection. In addition, the finding of interrupted IVC on echocardiography should prompt screening for intestinal malrotation, even in the absence of additional structural heart disease.
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Langley JM, Dodds L, Fell D, Langley GR. Pneumococcal and influenza immunization in asplenic persons: a retrospective population-based cohort study 1990-2002. BMC Infect Dis 2010; 10:219. [PMID: 20649965 PMCID: PMC2920873 DOI: 10.1186/1471-2334-10-219] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2009] [Accepted: 07/22/2010] [Indexed: 01/19/2023] Open
Abstract
Background Splenectomy is associated with increased risk for bacteremia, due to impaired clearance of bloodborne agents and to altered phagocytosis and humoral immunity. We conducted a retrospective cohort study of patients at risk for splenectomy for a 13-year period to determine immunization coverage, and outcomes of those with and without splenectomy, and with or without receipt of influenza or pneumococcal vaccine. Methods Data were extracted from the provincial Medical Services Insurance database for insured services rendered by a physician for 1990-2002, and from the Vital Statistics Death database. The eligible cohort was selected based on diagnostic codes for hematologic conditions for which splenectomy might be considered, such as immune thrombocytopenia. Each patient was followed longitudinally from the date of first diagnosis until 31Dec2002, or death, or relocation out-of province. In addition, persons with splenectomy and no hematologic condition were identified and followed for 6 months post-surgery. Infectious illness rates per 100 person-years of observation and death rates were calculated with and without splenectomy. Death rates were determined using splenectomy status as a time-dependent covariate. The relationship between splenectomy and death according to immunization status was examined using Cox proportional hazard ratios. Results Of 38,812 persons in the cohort 427 subjects with a hematologic diagnosis had splenectomy and another 452 subjects without a hematologic diagnosis had this surgery. 72% were > 18 years of age. Pneumococcal immunization was recorded in 16.5% of asplenic patients overall, and was not associated with reduced risk of death in these persons (adjusted Hazard Ratio [HR] = 1.07, 95% CI 0.70 - 1.65). Influenza immunization was recorded in 53.1% of asplenic patients overall, and was associated with reduced risk of death (adjusted HR = 0.46, 0.33-0.62). No pneumococcal or influenza immunization was recorded in patients with a hematologic diagnosis without splenectomy. Infectious illness visits were higher among all patients who had a splenectomy than among those without a splenectomy (151 visits/100 person-years of observation in the post-splenectomy period vs. 120 visits/100 person-years; p < 0.0001). Conclusions In asplenic patients, influenza immunization is associated with a 54% reduced risk of death compared to unimmunized asplenic persons; no reduction in risk was demonstrated with (polysaccharide) pneumococcal vaccine. Vaccine coverage in the entire cohort was less than routinely recommended. Improved delivery of infection prevention programs to this population is warranted. Conjugate pneumococcal vaccines should be urgently studied in this immunocompromised population.
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Affiliation(s)
- Joanne M Langley
- Department of Pediatrics, Dalhousie University, IWK Health Centre, 5850 University Avenue, Halifax Nova Scotia B3K6R8, Canada.
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