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- Angelin, Martin, et al.
(författare)
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Qdenga® - A promising dengue fever vaccine; can it be recommended to non-immune travelers?
- 2023
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Ingår i: Travel Medicine and Infectious Disease. - : Elsevier. - 1477-8939 .- 1873-0442. ; 54
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Tidskriftsartikel (refereegranskat)abstract
- Qdenga® has been approved by the European Medicines Agency (EMA) for individuals > 4 years of age and for use according to national recommendations. The vaccine shows high efficacy against virologically confirmed dengue and severe dengue in clinical studies on 4–16-year old's living in endemic areas. For individuals 16–60 years old only serological data exists and there is no data for individuals > 60 years. Its use as a travel vaccine is still unclear. We present the studies behind the approval and the recommendations for travelers as issued by the Swedish Society for Infectious Diseases Physicians.
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| 3. |
- Ljunghill Hedberg, Anna, 1972-
(författare)
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Impact of the inflammatory response on specific immunity in neurosurgical patients
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Vaccination with a T-cell-dependent pneumococcal conjugate vaccine (PCV) followed by a T-cell-independent pneumococcal polysaccharide vaccine (PPSV) is recommended after basilar skull fracture to reduce the risk of meningitis. The optimal time frame for vaccination has not yet been established and varies widely in practice. Because the risk of meningitis is at its peak shortly after the trauma incident, early vaccination might be more desirable. After trauma and central nervous system (CNS) injury, T-cell defects leading to trauma and CNS injury-induced immune deficiency syndromes may affect the vaccine response. In light of the above information, the overall aim of this thesis was to investigate the impact of neurotrauma and neurosurgery on the response to T-cell-dependent and T-cell-independent vaccines.In Paper I, we compared the antibody response to a T-cell-dependent conjugate vaccine in patients vaccinated within 10 days after neurotrauma or neurosurgery with those vaccinated after >3 weeks. To avoid interference with pneumococcal vaccination, a conjugate vaccine against Haemophilus influenzae type b (Hib) was chosen for the study. The majority of the patients responded to the vaccination, although the number of responders was significantly lower in patients vaccinated early.In Paper II, we investigated the antibody response to the T-cell-independent vaccine PPSV in patients vaccinated within 10 days after neurotrauma or neurosurgery and in patients vaccinated after >3 weeks. Patients vaccinated early responded similarly to those vaccinated after the acute period, indicating that PPSV can be administered early after neurotrauma or neurosurgery.In Paper III, we compared the response to Hib vaccine with the response to PPSV. We also examined whether individual clinical or immunological parameters might predict the response to T-cell-dependent vaccine and thereby help identify non-responders before vaccination. No correlation between Hib vaccine and PPSV responses was found, indicating that B-cell function is not similarly depressed as T-cell function. It was not possible to predict the T-cell-dependent vaccine response by standardized grading of the trauma or by parameters reflecting the innate immune response.In Paper IV, we found a significant reduction in the ex vivo CD4+ T-lymphocyte response to PCV in patients after neurotrauma or neurosurgery as compared with healthy controls.Our results suggest that PPSV might be a viable alternative to T-cell-dependent PCV in early vaccination after neurotrauma.
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| 5. |
- Ljunghill Hedberg, Anna, et al.
(författare)
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Lower response to early T-cell-dependent vaccination after neurotrauma or neurosurgery in adults
- 2015
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Ingår i: Journal of Infection. - : Elsevier BV. - 0163-4453 .- 1532-2742. ; 70:6, s. 577-584
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent international guidelines recommend vaccination with a 13-valent pneumococcal conjugate vaccine to reduce the risk of meningitis after neurotrauma with cerebrospinal fluid leak. The antibody response and optimal time point for vaccination have not been established and because the risk of meningitis is at the highest shortly after trauma, early vaccination is preferable. This study aimed to investigate the antibody response and to ensure that central nervous system injury-induced immunodepression did not affect the response to a T-cell-dependent conjugate vaccine when administered shortly after the injury. Methods: So as not to interfere with routine pneumococcal vaccination, a conjugate vaccine against Haemophilus influenza type b (Hib) was chosen for the study. Thirty-three patients with basilar skull fracture and 23 patients undergoing transsphenoidal pituitary gland surgery were vaccinated within 10 days after trauma/surgery and 29 control patients at least three weeks after trauma/surgery. Sera were collected pre- and post-vaccination for analysis of anti-Hib concentration. Results: Four patients with post-vaccination target antibody concentration before vaccination were excluded from analysis. In the neurotrauma and neurosurgery groups 10/32 (31%) and 5/20 (25%) patients, respectively, were non-responders compared with 3/29 (10%) in the control group. Log(10) anti-Hib concentrations in the neurotrauma, neurosurgery and control groups were 1.52 +/- 0.15, 1.38 +/- 0.15 and 1.81 +/- 0.12 mu g/ml, respectively. Conclusions: The majority of the patients responded to vaccination. However, the number of responders was significantly decreased and antibody concentration significantly lower in patients vaccinated early after the trauma/surgery. Investigation of the pneumococcal conjugate vaccine response in neurotrauma patients is therefore urgent. (C) 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
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| 6. |
- 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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| 7. |
- Ljunghill Hedberg, Anna, et al.
(författare)
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Relationship between T-cell-dependent and T-cell-independent vaccines after neurotrauma : Can the response be predicted?
- 2022
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Ingår i: Human Vaccines & Immunotherapeutics. - : Taylor & Francis Group. - 2164-5515 .- 2164-554X. ; 18:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: After trauma and central nervous system (CNS) injury, trauma-induced immune deficiency syndrome (TIDS) and CNS injury-induced immune deficiency syndrome (CIDS) may negatively affect responses to T-cell-dependent vaccines, such as pneumococcal conjugate vaccine (PCV) recommended after basilar fracture. This study (NCT02806284) aimed to investigate whether there after neurotrauma is a correlation between T-cell-dependent and independent vaccine responses and, thus, if B-cell activity is similarly depressed and whether the T-cell-dependent response is possible to predict.Method: Adult patients with basilar fracture (n = 33) and those undergoing pituitary gland surgery (n = 23) were within 10 days vaccinated with a T-cell-dependent vaccine against Haemophilus influenzae type b (Hib) and a T-cell-independent pneumococcal polysaccharide vaccine (PPSV). Samples reflecting the systemic inflammatory response and pre- and post-vaccination antibody levels after 3–6 weeks against Hib and PPSV were collected and determined by enzyme immunoassays.Results: High and significant correlations were detected in the responses to different pneumococcal serotypes, but none between the Hib and PPSV responses. No differences in trauma scores, C-reactive protein, IL-6, IL-10, pentraxin 3, fractalkine or calprotectin plasma concentrations or in ex vivo TNF-α, IL-6 or IL-10 responses to endotoxin were found between Hib vaccination responders and non-responders.Conclusions: There was no correlation between the pneumococcal responses and that to Hib, indicating that B-cell function is not similarly depressed as T-cell function. Grading of the trauma or parameters reflecting the innate immune response could not predict the T-cell-dependent vaccine response. There is a need of further studies evaluating the vaccine response after neurotrauma.
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| 8. |
- Svedung-Wettervik, Teodor, et al.
(författare)
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Intracranial pressure dynamics and cerebral vasomotor reactivity in community-acquired bacterial meningitis during neurointensive care
- 2022
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Ingår i: Journal of Neurosurgery. - : American Association of Neurological Surgeons. - 0022-3085 .- 1933-0693. ; 136:3, s. 831-839
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Community-acquired bacterial meningitis (CABM) is a severe condition associated with high mortality. In this study the first aim was to evaluate the incidence of intracranial pressure (ICP) insults and disturbances in cerebral vasomotor reactivity and the second aim was to evaluate the management and clinical outcome of CABM patients treated in the neurointensive care unit (NICU).METHODS: CABM patients who were treated in the NICU of Uppsala University Hospital, Sweden, during 2008–2020 were included in the study. Data on demographics, admission variables, treatment, ICP dynamics, vasomotor reactivity, and short-term clinical outcome were evaluated in these patients.RESULTS: Of 97 CABM patients, 81 (84%) received ICP monitoring, of whom 22% had ICP > 20 mm Hg during 5% or more of the monitoring time on day 1, which decreased to 9% on day 3. For those patients with ICP monitoring, 46% required CSF drainage, but last-tier ICP treatment, including thiopental (4%) and decompressive craniectomy (1%), was rare. Cerebral vasomotor reactivity was disturbed, with a mean pressure reactivity index (PRx) above 0.2 in 45% of the patients on day 1, and remained high for the first 3 days. In total, 81 (84%) patients had a favorable outcome (Glasgow Coma Scale motor score [GCS M] 6) at discharge, 9 (9%) patients had an unfavorable outcome (GCS M < 6) at discharge, and 7 (7%) patients died in the NICU. Those with favorable outcome had significantly better cerebral vasomotor reactivity (lower PRx) than the two other outcome groups (p < 0.01).CONCLUSIONS: Intracranial hypertension was frequent following severe CABM and CSF drainage was often sufficient to control ICP. Cerebral vasomotor reactivity was commonly disturbed and associated with poor outcome. Clinical outcome was slightly better than in earlier studies.
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