Qdenga® - A promising dengue fever vaccine; can it be recommended to non-immune travelers?

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.

Relationship between T-cell-dependent and T-cell-independent vaccines after neurotrauma; is the B-cell response preserved?

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. METHODS: 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.

Intracranial pressure dynamics and cerebral vasomotor reactivity in community-acquired bacterial meningitis during neurointensive care.

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.