Kerstin Kling

Safety, immunogenicity, and preliminary clinical efficacy of a vaccine against extraintestinal pathogenic Escherichia coli in women with a history of recurrent urinary tract infection: a randomised, single-blind, placebo-controlled phase 1b trial

BACKGROUND Escherichia coli infections are increasing worldwide in community and hospital settings. The E coli O-antigen is a promising vaccine target. We aimed to assess the safety and immunogenicity of a bioconjugate vaccine containing the O-antigens of four E coli serotypes (ExPEC4V). METHODS In this multicentre phase 1b, first-in-human, single-blind, placebo-controlled trial, we randomly assigned (1:1) healthy adult women with a history of recurrent urinary tract infection (UTI) to receive a single injection of either intramuscular ExPEC4V or placebo. The primary outcome was the incidence of adverse events among vaccine and placebo recipients throughout the study. Secondary outcomes included immunogenicity and antibody functionality, and the incidence of UTIs caused by E coli vaccine serotypes in each group. This study is registered with ClinicalTrials.gov, number NCT02289794. FINDINGS Between Jan 20, 2014, and Aug 27, 2014, 93 women received target-dose ExPEC4V and 95 received placebo. The vaccine was well tolerated: no vaccine-related serious adverse events occurred. Overall, 56 (60%) target-dose vaccines and 47 (49%) placebo recipients experienced at least one adverse event that was possibly, probably, or certainly related to injection. Vaccination induced significant IgG responses for all serotypes: at day 30 compared with baseline, O1A titres were 4·6 times higher, O2 titres were 9·4 times higher, O6A titres were 4·9 times higher, and O25B titres were 5·9 times higher (overall p<0·0001). Immune responses persisted at 270 days but were lower than those at 30 days. Opsonophagocytic killing activity showed antibody functionality. No reduction in the incidence of UTIs with 103 or more colony-forming units per mL of vaccine-serotype E coli was noted in the vaccine compared with the placebo group (0·149 mean episodes vs 0·146 mean episodes; p=0·522). In post-hoc exploratory analyses of UTIs with higher bacterial counts (≥105 colony-forming units per mL), the number of vaccine serotype UTIs did not differ significantly between groups (0·046 mean episodes in the vaccine group vs 0·110 mean episodes in the placebo group; p=0·074). However, significantly fewer UTIs caused by E coli of any serotype were noted in the vaccine group compared with the placebo group (0·207 mean episodes vs 0·463 mean episodes; p=0·002). INTERPRETATION This tetravalent E coli bioconjugate vaccine candidate was well tolerated and elicited functional antibody responses against all vaccine serotypes. Phase 2 studies have been initiated to confirm these findings. FUNDING GlycoVaxyn, Janssen Vaccines.

Fieber bei Reiserückkehrern

Kenntnisse des regionalen Vorkommens bzw. der geographischen Verteilung infrage kommender Infektionskrankheiten sind fur die Abklarung besonders wichtig. Dabei gilt auch hier: «Haufiges ist haufig, Seltenes ist selten».

Fièvre au retour d’un voyage

La connaissance de l’epidemiologie regionale et de la distribution geographique des maladies infectieuses possibles est particulierement essentielle pour l’evaluation.

Serum 25-hydroxyvitamin D levels and intramuscular vitamin D3 supplementation among Eritrean migrants recently arrived in Switzerland

In a cross-sectional screening programme, we assessed serum vitamin D levels in adult Eritrean refugees recently arrived in Switzerland. Median vitamin D level among 107 participants (95 males and 12 females) was 27 nmol/l (interquartile range 23-42 nmol/l), 86% had insufficient vitamin D levels (≤50 nmol/l) and 36% severe deficiency (<25 nmol/l). In 29 participants who received single-dose intramuscular vitamin D substitution (300 000 IU), median vitamin D levels increased from 25 to 35 nmol/l after 3 months (p = 0.005); only 11 (38%) reached sufficient vitamin D levels. Eritrean migrants should be routinely screened for vitamin D deficiency. Single-dose intramuscular supplementation appeared to be insufficient to achieve optimal levels in the majority of participants.

To vaccinate or let it be--current recommendations and the reality about yellow fever vaccination.

Recommendations to travellers regarding yellow fever vaccination (YFV) are based on personal risk, previous vaccinations, health status of the traveller and border regulations. Recently, WHO extended the recommendation regarding protection after YFV from 10 years to lifelong. We present the results of a survey among Swiss tropical and travel medicine experts, in which they were asked to decide upon