Three-dose versus four-dose primary schedules for tick-borne encephalitis (TBE) vaccine FSME-immun for those aged 50 years or older : A single-centre, open-label, randomized controlled trial

Background: TBE vaccination failures among those past middle age have raised concern about immune response declining with age. We investigated immunogenicity of the TBE-vaccine FSME-Immun among those aged 50+ years using the standard three-dose primary series and alternative four-dose schedules. Methods: In this single-centre, open-label, randomized controlled trial, 200 TBE-naive Swedish adults were given primary TBE vaccination with FSME-Immun. Those aged 50+ years (n = 150) were randomized to receive the standard three-dose (days 0-30-360) or one of two four-dose series (0-7-21-360; 0-30- 90-360). For participants < 50 years (n = 50) the standard three-dose schedule was used. Titres of neu-tralizing antibodies were determined on days 0, 60, 120, 360, and 400. The main outcome was the log titre of TBE virus-specific neutralizing antibodies on day 400. Results: The three-dose schedule yielded lower antibody titres among those aged 50+ years than the younger participants on day 400 (geometric mean titre 41 versus 74, p < 0.05). The older group showed higher titres for the four-dose 0-7-21-360 than the standard three-dose schedule both on day 400 (103 versus 41, p < 0.01; primary end point) and at the other testing points (days 60,120, 360). Using the other four-dose schedule (0-30-90-360), no such difference was observed on day 400 (63 versus 41, NS). Conclusion: Immune response to the TBE vaccine declined with age. A four-dose schedule (0-7-21-360) may benefit those aged 50 years or older. This study is registered at ClinicalTrials.gov, NCT01361776. (c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).Peer reviewe

Dengue in Travelers: Kinetics of Viremia and NS1 Antigenemia and Their Associations with Clinical Parameters

Peer reviewe

<b>Clinical characteristics of the 93 travelers with dengue.</b>

a<p>Reference values for males/females in parentheses.</p>b<p>At least once during the 21 days since illness onset. The timing of serum sampling was not standardized.</p>c<p>Selection criterion for entering the study.</p>d<p>Diagnosed according to current practice.</p>e<p>Of these patients, 9/17 (53%) were positive for PCR or NS1 at some point. The patients negative for PCR and NS1 provided samples on illness days 6–21.</p>f<p>Duration of hospitalization: median 4 days, interquartile range 3 to 6 days.</p><p>Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase; DENV, dengue virus; Hb, hemoglobin; Hcr, hematocrit.</p

<b>Background characteristics of the 93 travelers with dengue.</b>

<p>The median age of patients was 37 years (interquartile range: 28 to 45 years).</p>a<p>Data missing for two patients.</p>b<p>Data missing for one patient.</p

Kinetics of diagnostic combinations.

<p>The solid lines and shaded areas provide the predicted probabilities and their 95% confidence intervals for at least one of the two diagnostic tests showing a positive result on a given day of illness. Non-solid lines indicate the predicted probabilities of positive result for each test alone. The circles illustrate time points of samples negative in both tests, the size of the circle being proportional to the number of observations.</p

Kinetics of diagnostic markers.

<p>Relative amounts (A–D) and the probability of a positive result (E–H) of DENV-RNA, NS1 protein, and DENV specific IgM and IgG antibodies in the serum samples of 93 patients with acute dengue fever. Solid lines indicate predicted means (A–D), and probabilities (E–H) from generalized additive mixed models (GAMM), and dashed lines their 95% confidence intervals. In A–D, the circles serve to illustrate individual observations; in E–H, the circles show the positive/negative test results at each given time point, the size of the circle being proportional to the number of observations.</p