| 1. |
- Ahlstrand, Erik, 1974-
(författare)
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Coagulase-negative staphylococci in hematological malignancy
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bacterial infections are common in hematological malignancy. Coagulase-negative staphylococci (CoNS) are among the most prevalent causes of bacteremia in patients with hematological malignancies.In this thesis, different aspects of CoNS in hematological malignancy have been studied in four papers:In paper 1, CoNS blood culture isolates from patients with hematological malignancies treated at the University Hospital of Örebro from 1980 to 2009 were revaluated for the presence of reduced sensitivity to glycopeptides. A high incidence of heterogeneous-intermediate glycopeptide resistance was observed and there was a trend towards increasing incidence of this phenotype over time.In paper 2, the colonization pattern of CoNS among patients undergoing intensive chemotherapy for hematological malignancy was investigated. A successive homogenization and an accumulation of CoNS phenotypes mutually present in a majority of included patients were demonstrated.In paper 3, a PCR method to determine the clinical significance of positive blood cultures of the CoNS species Staphylococcus epidermidis was evaluated. The test failed to discriminate bloodstream infection from blood culture contamination.Finally, in paper 4, the long-term molecular epidemiology of S. epidermidis blood culture isolates from patients with hematological malignancies was studied with multilocus sequence typing. A predominance of sequence type 2 was demonstrated during the entire 30 year study period.In conclusion, the results are consistent with that CoNS have established as important pathogens by its capacity to colonize the human skin, its ability to reside and spread in the hospital environment and its rapid adaptation to stressors such as antimicrobials.
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| 2. |
- Berglund, David, et al.
(författare)
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Expression of Intratumoral Forkhead Box Protein 3 in Posttransplant Lymphoproliferative Disorders : Clinical Features and Survival Outcomes
- 2015
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Ingår i: Transplantation. - : Lippincott Williams & Wilkins. - 0041-1337 .- 1534-6080. ; 99:5, s. 1036-1042
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Tidskriftsartikel (refereegranskat)abstract
- Background. The infiltration of regulatory T cells (Tregs) in lymphomas is associated with better prognosis for some types of lymphomas, but knowledge of their role in posttransplant lymphoproliferative disorders (PTLDs) is limited. We therefore investigated the association between the expression of the Treg marker forkhead box protein 3 (FoxP3) in biopsies of PTLDs and survival, PTLD subtype, and clinical characteristics.Methods. Seventy-four cases of PTLD after solid organ transplantation with sufficient material for further analysis were included from a population-based study of PTLDs in Sweden. The PTLD biopsies were reevaluated and stained with the 236A/E7 antibody to detect FoxP3 in lymphoma tissue. Detailed clinical data were collected retrospectively from medical records.Results. Based on a cutoff level of 29 FoxP3+ cells per mm2, most (80%) of the PTLDs were FoxP3-. Forty-seven of 74 PTLDs displayed no FoxP3+ cells at all. The frequency of FoxP3+ cells did not influence median overall survival. The FoxP3- PTLDs were more frequently of T-cell phenotype (P=0.04), located at the graft (P=0.03), occurred earlier after transplantation (P=0.04), were more likely to develop in lung recipients (P=0.04), and in patients that had received anti T-cell globulin as induction therapy (P=0.02). The FoxP3+ PTLDs were associated with hepatitis C seropositivity (P=0.03). In multivariate analysis, B-cell PTLD and hepatitis C infection were independent predictors of FoxP3 positivity.Conclusion. Our findings suggest that intratumoral FoxP3+ Tregs do not influence survival in patients with PTLD. FoxP3+ Tregs are rare in PTLD, possibly because of heavy immunosuppression.
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| 3. |
- Berglund, Åke, et al.
(författare)
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The response to vaccination against influenza A(H1N1) 2009, seasonal influenza and Streptococcus pneumoniae in adult outpatients with ongoing treatment for cancer with and without rituximab
- 2014
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Ingår i: Acta Oncologica. - : Taylor & Francis Group. - 0284-186X .- 1651-226X. ; 53:9, s. 1212-1220
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Tidskriftsartikel (refereegranskat)abstract
- It is debated whether cancer patients treated with chemotherapy can mount an adequate response to vaccination.Material and methods: Ninety-six adult outpatients with cancer, who were undergoing chemotherapy and/or monoclonal antibody, tyrosine kinase inhibitor, irradiation or corticosteroid treatments, were studied. Two doses of the pandemic infl uenza A(H1N1)/09 AS03-adjuvanted split virion vaccine, one dose of the seasonal infl uenza vaccine and one dose of the 23-valent pneumococcal polysaccharide vaccine were given. Serum haemagglutination inhibition (HI) assays were used to determine antibody titres against the infl uenza strains. For the pneumococcal vaccine 14 different serotypespecifi c anti-capsular antibodies were measured by bead assay xMAP ® .Results: Patients treated with rituximab did not respond to vaccination. For patients without rituximab treatment 4% had putatively protective antibodies before vaccination (HI 40) to the pandemic-like strain A/California7/2009HINI. After the fi rst and second dose of vaccine, seroprotection rates (SPR) were 62% and 87%, and seroconversion rates (SCR) 62% and 84%, respectively. Before seasonal fl u vaccination SPR against infl uenza A/Brisbane/59/2007H1N1 and A/Uruguay/10/2007H3N2 were 19% and 17%, respectively. After vaccination, SPR were 70% and 59% and SCR 42% and 50%, respectively. For the pneumococcal vaccine protective antibodies were found to 40% of the 14 strains before and to 68% after vaccination. The mean response to pneumococcal vaccination was to 44% of the 14 serotypes. A response to at least 50% of the 14 serotypes was found in 49% of the patients. No serious adverse events were reported.Conclusion: A substantial number of adult cancer patients with ongoing chemotherapy treatment could mount an adequate serological response to infl uenza and pneumococcal vaccination without severe adverse events. Thus, vaccination should be recommended. Adjuvanted vaccines may improve the vaccine response among this patient group. Patients recently treated with rituximab do not respond to vaccination.
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| 4. |
- Boutry, Céline, et al.
(författare)
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The Adjuvanted Recombinant Zoster Vaccine Confers Long-Term Protection Against Herpes Zoster : Interim Results of an Extension Study of the Pivotal Phase 3 Clinical Trials ZOE-50 and ZOE-70
- 2022
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press. - 1058-4838 .- 1537-6591. ; 74:8, s. 1459-1467
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Tidskriftsartikel (refereegranskat)abstract
- Efficacy against herpes zoster and immune responses to the adjuvanted recombinant zoster vaccine plateaued at high levels between 5.1 and 7.1 years (mean) post-vaccination, suggesting that its clinical benefit in older adults is sustained for at least 7 years post-vaccination. Background This ongoing follow-up study evaluated the persistence of efficacy and immune responses for 6 additional years in adults vaccinated with the glycoprotein E (gE)-based adjuvanted recombinant zoster vaccine (RZV) at age >= 50 years in 2 pivotal efficacy trials (ZOE-50 and ZOE-70). The present interim analysis was performed after >= 2 additional years of follow-up (between 5.1 and 7.1 years [mean] post-vaccination) and includes partial data for year (Y) 8 post-vaccination. Methods Annual assessments were performed for efficacy against herpes zoster (HZ) from Y6 post-vaccination and for anti-gE antibody concentrations and gE-specific CD4[2+] T-cell (expressing >= 2 of 4 assessed activation markers) frequencies from Y5 post-vaccination. Results Of 7413 participants enrolled for the long-term efficacy assessment, 7277 (mean age at vaccination, 67.2 years), 813, and 108 were included in the cohorts evaluating efficacy, humoral immune responses, and cell-mediated immune responses, respectively. Efficacy of RZV against HZ through this interim analysis was 84.0% (95% confidence interval [CI], 75.9-89.8) from the start of this follow-up study and 90.9% (95% CI, 88.2-93.2) from vaccination in ZOE-50/70. Annual vaccine efficacy estimates were >84% for each year since vaccination and remained stable through this interim analysis. Anti-gE antibody geometric mean concentrations and median frequencies of gE-specific CD4[2+] T cells reached a plateau at approximately 6-fold above pre-vaccination levels. Conclusions Efficacy against HZ and immune responses to RZV remained high, suggesting that the clinical benefit of RZV in older adults is sustained for at least 7 years post-vaccination.
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| 5. |
- Cherif, Honar, et al.
(författare)
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Adjuvanted influenza a (H1N1) 2009 vaccine in patients with hematological diseases : good safety and immunogenicity even in chemotherapy-treated patients
- 2013
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 90:5, s. 413-419
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with hematological malignancies are more susceptible to viral infections including influenza. In 2009, the World Health Organization classified the novel influenza A (H1N1) virus as pandemic. The potential impact of this pandemic for patients with hematological disorders was unknown. Institutional guidelines recommended two doses of AS03-adjuvanted influenza A (H1N1) 2009 pandemic vaccine for these patients. Objectives We aimed to determine the safety, immunogenicity, and clinical efficacy of this vaccine in patients with hematological diseases. Furthermore, we compared the immunological responses to that obtained by the non-adjuvanted trivalent seasonal influenza vaccine (TIV). Methods All included patients received adjuvanted pandemic vaccine and the majority received TIV. Serum for antibody analyses was collected at five time points. Results Thirty-one patients with different hematological diseases were included. After the second vaccine dose, a total of 25 (81%) reached both protective levels of antibodies and seroconversion response. Antibody titers1:40 persisted for 50% of responding patients at 1yr. Seroconversion was observed in 69% of 14 patients who had undergone hematopoietic stem cell transplantation and in all (9/9) patients with myeloma (five with ongoing treatment including high-dose corticosteroids). After vaccination with TIV, seroconversions against the three included strains were detected in 28%, 40%, and 20%. Response to the adjuvanted pandemic vaccine was superior (P<0.009). Conclusions A substantial proportion of patients with hematological malignancies including patients undergoing chemotherapy mounted a good response to the adjuvanted pandemic vaccine. This vaccine had superior immunogenicity as compared to the non-adjuvanted TIV.
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| 6. |
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| 7. |
- Chlibek, Roman, et al.
(författare)
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Long-term immunogenicity and safety of an investigational herpes zoster subunit vaccine in older adults
- 2016
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 34:6, s. 863-868
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Tidskriftsartikel (refereegranskat)abstract
- Background: An investigational subunit vaccine containing the varicella-zoster virus (VZV) glycoprotein E (gE) and the AS01(B) adjuvant system is being evaluated for the prevention of herpes zoster (HZ) in older adults. A phase II trial evaluating different formulations of this vaccine (containing 25 mu g, 50 mu g, or 100 mu g gE) was conducted in adults >= 60 years of age and showed that all formulations elicited robust cellular and humoral immune responses for up to 3 years after vaccination. In this follow-up study in subjects who received two doses of the 50 mu g gE/AS01(B) formulation (HZ/su), we assessed the persistence of the immune responses for up to 6 years after vaccination. Methods: This phase II, open-label, multicenter, single-group trial conducted in the Czech Republic, Germany, Sweden, and the Netherlands followed 129 subjects who had received two doses (2 months apart) of HZ/su during the initial trial. Vaccine-induced immune responses (frequencies of gE-specific CD4(+) T cells expressing >= 2 activation markers and serum anti-gE antibody concentrations) were evaluated at 48, 60, and 72 months after the first HZ/su dose. Results: Six years after vaccination with HZ/su, gE-specific cell-mediated immune responses and anti-gE antibody concentrations had decreased by 20-25% from month 36, but remained higher than the prevaccination values. At month 72, the gE-specific cell-mediated immune response was 3.8 times higher than the prevaccination value (477.3 vs. 119.4 activated gE-specific CD4(+) T cells per 10(6) cells), and the anti-gE antibody concentration was 7.3 times higher than the prevaccination value (8159.0 vs. 1121.3 mIU/mL). No vaccine-related serious adverse events were reported between months 36 and 72. Conclusions: gE-specific cellular and humoral immune responses persisted for 6 years after two-dose vaccination with HZ/su in healthy older adults. No safety concerns were identified.
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| 8. |
- Chlibek, Roman, et al.
(författare)
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Safety and immunogenicity of three different formulations of an adjuvanted varicella-zoster virus subunit candidate vaccine in older adults : A phase II, randomized, controlled study
- 2014
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 32:15, s. 1745-1753
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study investigated the safety and immunogenicity of different formulations and schedules of a candidate subunit herpes zoster vaccine containing varicella-zoster virus glycoprotein E (gE) with or without the adjuvant system ASO1(B). Methods: In this phase II, single-blind, randomized, controlled study, adults aged >= 60 years (N = 714) received one dose of 100 mu g gE/AS01(B), two doses, two months apart, of 25, 50, or 100 mu g gE/AS01(B), or two doses of unadjuvanted 100 mu g gE/saline. Frequencies of CD4(+) T cells expressing >= 2 activation markers following induction with gE were measured by intracellular cytokine staining and serum anti-gE antibody concentrations by ELISA. Results: Frequencies of gE-specific CD4(+) T cells were >3-fold higher after two doses of all gE/AS01(B) formulations than after one dose of 100 mu g gE/AS01(B) or two doses of 100 mu g gE/saline. Frequencies were comparable after two doses of 25, 50, or 100 mu g gE/AS01g. Serum anti-gE antibody concentrations were comparable after two doses of 50 or 100 mu g gE/AS01(B) and higher than in the other groups. Immune responses persisted for at least 36 months. Reactogenicities of all gE/AS01(B) formulations were similar but greater than with gE/saline. Conclusions: The three formulations of gE/AS01(B) were immunogenic and well tolerated in adults aged >= 60 years. Two vaccinations with gE/AS01(B) induced higher immune responses than one and the dose of gE impacted humoral but not cellular immune responses (NCT00434577).
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| 9. |
- Cordonnier, Catherine, et al.
(författare)
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Immune response to the 23-valent polysaccharide pneumococcal vaccine after the 7-valent conjugate vaccine in allogeneic stem cell transplant recipients : Results from the EBMT IDWP01 trial
- 2010
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 28:15, s. 2730-2734
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Tidskriftsartikel (refereegranskat)abstract
- The current recommendations for active immunization after stem cell transplant (SCT) include 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7) from 3 months after transplant, followed by a 23-valent polysaccharide pneumococcal vaccine (PPV23). However, until now, the immune response to PPV23 after PCV7 has not been assessed after SCT. In the EBMT IDWP01 trial, 101 patients received 1 dose of PPV23 at 12 or 18 months, both after 3 doses of PCV7. The efficacy of PPV23 was assessed 1 month later and at 24 months after transplant by the pneumococcal serotype 1 and 5 antibody levels. Serotype 1 and 5 are not included in PCV7. Although the geometric mean concentrations were significantly higher 1 month after PPV23, for both antigens, the response rates (>= 0.15 mu g/mL), in the range of 68-94%, were not different between groups independent of the assessment date. One PPV23 dose after 3 PCV7 doses, already known to increase the response to PCV7, also extends the serotype coverage given 12 or 18 months after transplant. (C) 2010 Elsevier Ltd. All rights reserved.
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| 10. |
- Cordonnier, Catherine, et al.
(författare)
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Randomized study of early versus late immunization with pneumococcal conjugate vaccine after allogeneic stem cell transplantation
- 2009
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 48:10, s. 1392-1401
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Invasive pneumococcal disease is a life-threatening complication after allogeneic stem cell transplantation, and at least 20% of cases occur within 1 year after transplantation. The 23-valent pneumococcal polysaccharide vaccine (PPV23) has limited efficacy, especially during the first year after transplantation. The immune response to the conjugated vaccines is expected to be better than that to the polysaccharide vaccine, but the optimal timing of vaccination is not defined. Our objective was to show that a 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar) was not inferior when first given 3 months after transplantation, compared with when first given 9 months after transplantation. METHODS: We performed a multicenter, randomized, noninferiority study involving 158 patients from 13 European Group for Blood and Marrow Transplantation centers who were randomly allocated at approximately 100 days after myeloablative stem cell transplantation to receive a series of vaccinations (3 doses of PCV7 given 1 month apart) that was started immediately (i.e., 3 months after transplantation) or 6 months later (i.e., 9 months after transplantation). The primary evaluation criterion was the rate of response (antibody level, > or = 0.15 microg/mL for each of the 7 serotypes) at 1 month after the third dose of PCV7. The noninferiority margin was 20%. All patients were followed up for 24 months after transplantation or until death, whichever occurred first. RESULTS: We found that the response rate was not lower after early vaccination (79% [45 of 57 patients]) than after late vaccination (82% [47 of 57 patients]) (difference, -3.5%; 90% confidence interval, -15.6 to 8.6; not significant). CONCLUSIONS: We conclude that PCV7 vaccination at 3 months after stem cell transplantation is not inferior to PCV7 vaccination at 9 months after transplantation. Because invasive pneumococcal disease can occur early, we recommend starting the PCV7 vaccination series at 3 months after transplantation to ensure earlier protection against Streptococcus pneumoniae. However, the early vaccination may result in only short-lasting response and may not prime for a 23-valent pneumococcal polysaccharide vaccine boost as efficiently as the late vaccination.
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| 11. |
- Fjaertoft, Gustav, et al.
(författare)
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Cell surface expression of FcgammaRI (CD64) on neutrophils and monocytes in patients with influenza A, with and without complications
- 2005
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 37:11-12, s. 882-889
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Tidskriftsartikel (refereegranskat)abstract
- The expression of the Fcgamma-receptor I (FcgammaRI), CD64 on normal neutrophils is up-regulated during bacterial infections. CD64 is a promising diagnostic tool in the diagnosis of acute infections. The aim was to study surface expressions of CD64 on neutrophils and monocytes in patients with influenza A with and without complications and evaluate these as diagnostic tools in comparison with serum levels of HNL (human neutrophil lipocalin). CD64 expression on neutrophils and monocytes was evaluated by flow cytometry. HNL was assayed by a specific radioimmunoassay. 22 patients with influenza A with or without complications were included and the results compared with those of 29 patients with acute bacterial infections and 29 healthy subjects. Neutrophil expression of CD64 was increased in influenza A with raised proportion expressing CD64 in complicated compared to uncomplicated influenza. The expression was significantly higher in bacterial infections compared to both influenza groups. Serum levels of HNL were raised in all infection groups, but significantly more so in the group with bacterial infection. ROC-curve analysis showed that neutrophil expression of CD64 and the serum levels of HNL had similar diagnostic power in the discrimination between acute bacterial infections and influenza A. Monocyte expression of CD64 was raised in all infections with no differences between subgroups. We conclude that neutrophil expression of CD64 and serum levels of HNL are both promising assays in the distinction between infections caused by bacteria or influenza A, whereas CD64 could identify patients with complications of their influenza A infection.
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| 12. |
- Fjaertoft, Gustav, et al.
(författare)
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Neutrophil CD64 (FcgammaRI) expression is a specific marker of bacterial infection : A study on the kinetics and the impact of major surgery
- 2007
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 39:6-7, s. 525-535
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophil CD64 expression is a diagnostic marker for the early detection of bacterial infections. The aim was to investigate the kinetics of neutrophil CD64 expression during bacterial infection and the possible impact of surgical trauma. Blood samples were collected daily during 3 d after admission for analysis by flow cytometry of the surface expressions on neutrophils and monocytes of CD64, CD16, CD32, CD11b/CD18 and CD35, and analysis of serum CRP and blood WBC. Serum concentrations of IFNgamma, G-CSF, IL-6 and IL-8 were also analysed in adults. Eight children and 19 adult patients with bacterial infections, 12 patients admitted for hip-arthroplasty because of coxarthrosis and 30 healthy adults were studied. Neutrophil CD64 was increased all 3 d after start of treatment (p<0.0001) in children and adults with bacterial infections. The postoperative increase after surgery was less than the increase seen during bacterial infections (p<0.0001). CRP, G-CSF, IL-6 and IL-8 were raised both in bacterial infections and after surgery. Our results indicate that the expression of CD64 on neutrophils is a specific sign of bacterial infections. Neutrophil expression of CD64, therefore, seems to be a promising tool for the early detection of bacterial infections even during surgery.
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| 13. |
- Hallböök, Helene, et al.
(författare)
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Ciprofloxacin prophylaxis delays initiation of broad-spectrum antibiotic therapy and reduces the overall use of antimicrobial agents during induction therapy for acute leukaemia : A single-centre study
- 2016
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Ingår i: INFECTIOUS DISEASES. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 48:6, s. 443-448
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Tidskriftsartikel (refereegranskat)abstract
- Background Due to an outbreak of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, the routine use of fluoroquinolone prophylaxis was questioned. As a result, this study was conducted with the aim to evaluate the impact of ciprofloxacin-prophylaxis on the use of broad-spectrum antibioctics and anti-mycotics. Methods A cohort of 139 consecutive patients with acute leukaemia treated with remission-inducing induction chemotherapy between 2004-2012 at the Department of Haematology in Uppsala University Hospital was analysed. Results Fifty-three patients (38%) received broad-spectrum antibiotics at the initiation of chemotherapy and were not eligible for prophylaxis. Of the remaining patients, the initiation of broad-spectrum antibiotics was delayed by 3 days in those receiving ciprofloxacin prophylaxis (n = 47) compared with those receiving no prophylaxis (n = 39). The median duration of systemic antibiotic treatment was 6 days shorter in patients receiving ciprofloxacin prophylaxis (12 vs 18 days; p = 0.0005) and the cumulative (total) median days on systemic antibiotic treatment was shortened by 8 days (15 vs 23 days, p = 0.0008). Piperacillin/tazobactam (p = 0.02), carbapenems (p = 0.05) and empiric broad-spectrum antifungals (p < 0.01) were used significantly less often when ciprofloxacin prophylaxis was given. Conclusions Ciprofloxacin prophylaxis delayed empiric therapy by 3 days and reduced overall antibiotic use in this study. These benefits must be evaluated vs the risks of development of resistant bacterial strains, making fluoroquinolone prophylaxis an open question for debate.
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| 14. |
- Havelka, Aleksandra, et al.
(författare)
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Calprotectin, a new biomarker for diagnosis of acute respiratory infections
- 2020
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Respiratory tract infections require early diagnosis and adequate treatment. With the antibiotic overuse and increment in antibiotic resistance there is an increased need to accurately distinguish between bacterial and viral infections. We investigated the diagnostic performance of calprotectin in respiratory tract infections and compared it with the performance of heparin binding protein (HBP) and procalcitonin (PCT). Biomarkers were analyzed in patients with viral respiratory infections and patients with bacterial pneumonia, mycoplasma pneumonia and streptococcal tonsillitis (n=135). Results were compared with values obtained from 144 healthy controls. All biomarkers were elevated in bacterial and viral infections compared to healthy controls. Calprotectin was significantly increased in patients with bacterial infections; bacterial pneumonia, mycoplasma pneumonia and streptococcal tonsillitis compared with viral infections. PCT was significantly elevated in patients with bacterial pneumonia compared to viral infections but not in streptococcal tonsillitis or mycoplasma caused infections. HBP was not able to distinguish between bacterial and viral causes of infections. The overall clinical performance of calprotectin in the distinction between bacterial and viral respiratory infections, including mycoplasma was greater than performance of PCT and HBP. Rapid determination of calprotectin may improve the management of respiratory tract infections and allow more precise diagnosis and selective use of antibiotics.
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| 15. |
- Hertzell, Katarina Brodin, et al.
(författare)
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Tick-borne encephalitis (TBE) vaccine to medically immunosuppressed patients with rheumatoid arthritis : A prospective, open-label, multi-centre study
- 2016
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 34:5, s. 650-655
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Tick-borne Encephalitis (TBE) is endemic in south-eastern Sweden as well as in the Baltic regions, Central Europe and Russia. Ageing and immunosuppressed individuals are more prone to severe disease and neurological complications. We assessed the immunogenicity of TBE-vaccine in rheumatoid arthritis (RA) patients treated with tumor necrosis factor-inhibitors (TNFi) and/or methotrexate (MTX).METHODS: TBE vaccine, FSME-Immune(®) or Encepur(®), was administered to non-immune RA patients as well as age and gender matched healthy controls. Individuals <60 years of age were given three doses at month 0, 1, 12. Individuals ≥60 years old were given an additional priming dose at month 3, i.e. a total of four doses. Tick-borne encephalitis neutralizing antibodies were assessed by a rapid fluorescent focus inhibition test.RESULTS: The study population consisted of 66 patients and 56 age and gender matched healthy controls. Median age was 58.5 years. The patients were either treated with TNFi (n=16), TNFi+MTX (n=36) or MTX (n=14). After the last TBE-vaccine dose, given one year after the first, 39% of the patients compared to 79% of the healthy controls had seroprotective levels (p=<0.05).CONCLUSIONS: Standard TBE-vaccine schedule does not confer enough immunogenicity in this group of immunosuppressed patients, who should be carefully informed about a higher risk for vaccination failure and risk of infection when exposed in high-endemic areas.
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| 16. |
- Jackson, Lisa A., et al.
(författare)
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Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine in adults 70 years of age and older previously vaccinated with 23-valent pneumococcal polysaccharide vaccine
- 2013
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 31:35, s. 3585-3593
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Tidskriftsartikel (refereegranskat)abstract
- Background: The currently recommended single dose of the 23-valent pneumococcal free polysaccharide vaccine (PPSV23) for adults 65 years of age and older does not provide extended protection into older age. This reflects a significant unmet medical need for alternative strategies to protect older adults against pneumococcal infection, which may be met by the 13-valent polysaccharide conjugate vaccine (PCV13). Methods: We performed a randomized, modified double-blind trial in 936 adults aged 70 years and older who had previously received PPSV23 at least 5 years before study entry and were now vaccinated with PCV13 or PPSV23. At 1 year after enrollment, all subjects received a follow-on dose of PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured before and at 1 month after each vaccination. Results: Following the enrollment vaccination, OPA titers were significantly greater in the PCV13 group compared to the PPSV23 group for 10 of the 12 serotypes common to both vaccines and to serotype 6A which is unique to PCV13. Responses were noninferior for the other 2 common serotypes. Responses to PCV13 given at 1 year were generally lower in the group that received PPSV23 at enrollment. Conclusion: In adults aged 70 years and older previously vaccinated with PPSV23, PCV13 was significantly more immunogenic than PPSV23 for most of the common serotypes and for serotype 6A. The OPA responses after a follow-on dose of PCV13 one year later indicate that a prior dose of PPSV23, but not PCV13, diminishes the response to the subsequent administration of PCV13.
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| 17. |
- Kinch, Amelie, et al.
(författare)
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A population-based study of 135 lymphomas after solid organ transplantation : The role of Epstein-Barr virus, hepatitis C and diffuse large B-cell lymphoma subtype in clinical presentation and survival.
- 2014
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 53:5, s. 669-679
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Tidskriftsartikel (refereegranskat)abstract
- Background. Epstein-Barr virus (EBV) plays a major role in the development of post-transplant lymphoproliferative disorder (PTLD), but there is an increasing awareness of EBV-negative PTLD. The clinical presentation of EBV-negative PTLD has not been as well characterised as EBV-positive cases. Further, there is limited knowledge on the clinical importance of diffuse large B-cell lymphoma (DLBCL) cell of origin subtype post-transplant. Materials and methods. We studied the role of EBV, hepatitis C (HCV) and DLBCL subtype in clinical presentation and survival in 135 post-transplant lymphomas diagnosed 1980-2006 in a population-based cohort of 10 010 Swedish solid organ transplant recipients. The lymphomas were re-evaluated according to WHO 2008, examined for EBV, and clinical data were collected from medical records. Results. Lymphoma incidence rate was 159/100 000 person-years and is also reported by lymphoma subtype. EBV-negative lymphomas constituted 48% and were associated with HCV infection (p = 0.02), bone marrow involvement (p < 0.001), and T-cell phenotype (p = 0.002). Among DLBCL, 78% were of non-germinal centre subtype, which was associated with EBV-positivity (69%, p = 0.001), early occurrence (p = 0.03), heart/liver/lung/pancreas recipients (p = 0.02), anti-T-cell globulin (p = 0.001), and tacrolimus treatment (p = 0.02). DLBCL subtypes had similar overall survival. Five-year overall survival was 42% in all treated patients. Independent poor prognostic factors were older age, B symptoms, ECOG 2-4, kidney/pancreas/heart recipients, T-cell lymphoma, and HCV-infection. Conclusions. With long follow-up, a large part of PTLD is EBV-negative, due to a high proportion of T-cell lymphomas and low of polymorphic PTLD. EBV-negative PTLD have a different clinical presentation. HCV may play an aetiological role in late-onset PTLD and was revealed as a new prognostic factor for inferior survival that needs to be confirmed in larger studies. The heavier immunosuppression in non-kidney transplantations seems to play a role in the development of non-germinal centre DLBCL. DLBCL cell of origin subtype lacks prognostic importance in the transplant setting.
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| 18. |
- Kinch, Amelie, 1973-, et al.
(författare)
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Donor or Recipient Origin of Posttransplant Lymphoproliferative Disorders Following Solid Organ Transplantation
- 2014
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Ingår i: American Journal of Transplantation. - : Wiley-Blackwell. - 1600-6135 .- 1600-6143. ; 14:12, s. 2838-2845
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies of donor or recipient origin of posttransplant lymphoproliferative disorders (PTLDs) following solid organ transplantation (SOT) have either been small or with selected patient groups. We studied tumor origin in a population-based cohort of 93 patients with PTLD following SOT. Tumor origin of PTLD tissue was analyzed by fluorescence in situ hybridization of the sex chromosomes in cases of sex mismatch between donor and recipient (n=41), or HLA genotyping in cases of identical sex but different HLA type (n=52). Tumor origin of PTLD could be determined in 67 of the 93 cases. All 67 PTLDs were of recipient origin. They were found in recipients of kidney (n=38), liver (n=12), heart (n=10) and lung (n=7). The most common recipient-derived lymphomas were monomorphic B-cell PTLDs (n=45), monomorphic T cell PTLDs (n=9), indolent lymphomas (n=6), and polymorphic PTLD (n=4). Half of the recipient-derived PTLDs were Epstein–Barr virus-positive. Twelve of the recipient-derived PTLDs were located in the grafts: in four cases exclusively and in eight cases in combination with disseminated disease outside the graft. Tumor origin was indeterminable in 26 cases, probably due to low DNA quality. We conclude that the vast majority of PTLDs after SOT was of recipient origin.
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| 19. |
- Kinch, Amelie, et al.
(författare)
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Post-transplant lymphoproliferative disease and other Epstein-Barr virus diseases in allogeneic haematopoietic stem cell transplantation after introduction of monitoring of viral load by polymerase chain reaction
- 2007
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 39:3, s. 235-244
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Tidskriftsartikel (refereegranskat)abstract
- The clinical value of monitoring of Epstein-Barr virus (EBV) viraemia by quantitative polymerase chain reaction during 1 y was evaluated. 39 recipients of allogeneic hematopoietic stem cell transplantation (SCT) were followed. More than 100 EBV genome equivalents (gEq)/ml in blood or plasma were found in 16/39 patients (41%) at 34 d (range 1-139) post-transplant. Seven of these 16 patients developed EBV disease; 3 post-transplant lymphoproliferative disease (PTLD), 1 myelitis, 1 encephalitis and 2 reactivations with fever. EBV diseases were only found in the high-risk group among recipients of mismatched related or unrelated donor grafts or in patients who underwent reduced-intensity conditioning. In this group, 3/20 (15%) developed PTLD. Conditioning with antithymocyte globulin was significantly associated with EBV disease (p<0.01). EBV load in plasma was more strongly associated with EBV disease than viral load in blood. A cut-off level of 1000 gEq/ml plasma distinguished EBV disease from asymptomatic viraemia, but not PTLD from other EBV diseases. Weekly monitoring of EBV load in plasma in high-risk patients in the first 3 months following SCT seems to be of value for prediction of EBV disease. Therapy for PTLD including rituximab was evaluated during 2 y and showed response in 4/6 cases.
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| 20. |
- Kinch, Amelie, 1973-
(författare)
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Posttransplant Lymphoproliferative Disorders : Studies of Epstein-Barr Virus, Regulatory T Cells and Tumor Origin
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Epstein-Barr virus (EBV) infects almost all humans and establishes lifelong latency in B cells. Posttransplant lymphoproliferative disorder (PTLD) is a rare but serious complication after transplantation triggered by immunosuppression and often related to EBV infection. The aim of this thesis was to study the role of EBV in relation to clinical and histological features of PTLD, regulatory T cells (Tregs), and donor or recipient origin of PTLD.EBV surveillance after allogeneic hematopoietic stem cell transplantation (allo-HSCT) showed that EBV reactivations were common, but that symptomatic EBV disease (including PTLD) only occurred in the high-risk group (unrelated or mismatched related grafts, reduced-intensity conditioning). A threshold of 1000 copies/ml plasma distinguished EBV disease from asymptomatic reactivations.In a population-based cohort of 135 PTLDs/lymphomas after solid organ transplantation (SOT) almost half were EBV–. EBV+ PTLDs were associated with B cell phenotype, non-germinal center subtype of diffuse large B cell lymphoma (DLBCL), early-onset, graft involvement, antithymocyte globulin treatment, and younger age. EBV– PTLDs were associated with T cell phenotype, bone marrow involvement, and hepatitis C. Most PTLDs displayed few or no intratumoral Tregs with the marker FoxP3, possibly due to heavy immunosuppression. Half of both FoxP3+ and FoxP3– PTLDs were EBV+. FoxP3+ PTLDs were associated with B cell phenotype and hepatitis C. All PTLDs for which tumor origin could be determined were recipient-derived and half of them were EBV+. Eight of twelve recipient-derived graft PTLDs were disseminated outside the graft. T cell PTLD and hepatitis C were independently associated with inferior overall survival, whereas subtype of DLBCL, FoxP3-expression, and EBV-status did not influence survival.In conclusion, monitoring of EBV DNAemia in high-risk patients after allo-HSCT and pre-emptive therapy is valuable for prevention of PTLD. Use of antithymocyte globulin increases the risk for EBV+ PTLDs after allo-HSCT and SOT. With long follow-up time, a large proportion of PLTDs after SOT are EBV– with a different clinical presentation. Tregs are rare in PTLD and do not affect survival. The vast majority of PTLDs after SOT is of recipient origin. Graft PTLDs are more likely recipient-derived if disseminated. EBV-status is not associated with intratumoral Tregs or PTLD of recipient origin.
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| 21. |
- Kulander, Lena, et al.
(författare)
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Soluble adhesion molecules, cytokines and cellular markers in serum in patients with acute infections
- 2001
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Ingår i: Scandinavian Journal of Infectious Diseases. - 0036-5548 .- 1651-1980. ; 33:4, s. 290-300
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the diagnostic capacity of a number of blood components such as soluble adhesion molecules, interleukin-6 (IL-6), myeloperoxidase (MPO) and lysozyme in the distinction of acute bacterial and viral infections. Blood was taken from 115 acutely infected patients at admission before any treatment and in some cases on several consecutive days. 35 of the patients had a definite viral cause for their infection and 66 a bacterial cause. All variables were raised in patients with acute bacterial infections. Soluble vascular cell adhesion molecule-1 (sVCAM-1), sE-selectin, lysozyme and MPO were also raised in acute viral infections, but for sE-selectin and MPO less so than in bacterial infections. Evaluation of the diagnostic power showed that for MPO and IL-6 at cut-offs of 1300 microg/l and 100 ng/l, respectively, the positive predictive value was 97% and 100% and the negative predictive value 78% and 76%, respectively, in the classification of acute bacterial infections. In the distinction between viral or bacterial causes of acute infections in otherwise healthy subjects serum measurements of MPO and IL-6 are valuable tools and should be considered as diagnostic aids in the routine setting. The soluble adhesion molecules did not offer any further information in this respect.
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| 22. |
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| 23. |
- Ljunghill Hedberg, Anna, et al.
(författare)
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Pneumococcal polysaccharide vaccination administered early after neurotrauma or neurosurgery
- 2017
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Ingår i: Vaccine. - : ELSEVIER SCI LTD. - 0264-410X .- 1873-2518. ; 35:6, s. 909-915
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Pneumococcal vaccination is recommended to lower the risk of posttraumatic meningitis, and early vaccination may be of importance. After both trauma and central nervous system injury, immune suppression may occur, which could affect T-cell function and the response to T-cell dependent vaccines. We therefore aimed to investigate the response to early vaccination with a T-cell independent pneumococcal polysaccharide vaccine (PPSV). Methods: Thirty-three patients with basilar skull fracture and 23 patients undergoing transsphenoidal pituitary gland surgery were vaccinated with PPSV within 10 days after neurotrauma or neurosurgery. Twenty-nine neurosurgical patients vaccinated >= 3 weeks after neurotrauma or neurosurgery served as controls. Serotype-specific anti-polysaccharide binding IgG antibody levels to serotypes 4, 6B, 9V, 14, 18C, 19F and 23F were determined by enzyme immunoassay. Results: The vaccination was safe and a highly significant antibody response was found against all serotypes in all groups (p < 0.001 for each of the serotypes). There were no differences between groups or in the group by time interaction in any of the serotypes. After early and late vaccination, protective levels were found in >80% for serotypes 9V, 14, 18C, 19F and 23F and in 70% and 50% for serotypes 6B and 4, respectively. Conclusion: Patients vaccinated with PPSV within 10 days after neurotrauma or neurosurgery respond similarly to those vaccinated after >= 3 weeks, indicating that PPSV can be administered early after neurotrauma or neurosurgery.
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| 24. |
- Maripuu, Linda, et al.
(författare)
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Dynamics of the immune response against extracellular products of group A streptococci during infection
- 2007
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Ingår i: Clinical and Vaccine Immunology. - 1556-6811 .- 1556-679X. ; 14:1, s. 44-51
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Tidskriftsartikel (refereegranskat)abstract
- The immune response against the infecting group A streptococcus (GAS) extracellular products (EP) was determined in acute- and convalescent-phase sera from 75 patients with different clinical manifestations of GAS infection. All EP elicited a high proliferative response in human peripheral blood mononuclear cells. In patients with bacteremia, low neutralization in acute-phase sera was associated with development of streptococcal toxic shock syndrome. Lack of neutralization in acute-phase sera was more common in patients infected with the T1emm1 serotype. The majority of patients did not develop the ability to neutralize the mitogenic activity of their infecting isolate despite a significant increase in enzyme-linked immunosorbent assay titer in early convalescent-phase sera. In patients with the ability to neutralize GAS EP, the immune response remained high over at least 3 years. In contrast, the neutralization capacity conferred by intravenous immunoglobulin and/or plasma treatment disappeared within 3 months.
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| 25. |
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