The aim of this study was to predict the long-term protection induced after immunisation with inactivated, aluminium-free virosome hepatitis A vaccine. The study population consisted of adult volunteers enrolled in four different clinical trials. Lower 95% confidence interval limits and seroconversion rate were calculated by using a linear mixed model to estimate the persistence of serum antibodies over time. To assess the robustness of the mathematical model, several sensitivity analyses were performed with more conservative protective threshold (20 mIU/ml vs. 10 mIU/ml), higher yearly decline rate, and exclusion of volunteers who had increasing titres over time. Based on 190 volunteers with at least two valid assessments of titres from year 3 onward, the median duration of protection was 55.5 years, with a lower limit of the 95% CI of 48.7 years. Duration below 25.3 years was predicted for only 5% of the subjects. Women tended to have higher titres to start with, but their rate of decline was higher, resulting in similar duration of protection overall. The use of a more conservative threshold, higher yearly decline rate, and exclusion of volunteers with increasing titres over time did not affect these results. According to this model, 95% of the volunteers should have anti-HAV titres above the minimum protective threshold for 20 years or more following immunisation with two doses of this aluminium-free vaccine.
Few studies have examined the duration of protection following vaccination against hepatitis A virus (HAV) with currently licensed HAV vaccines. This study explored the long-term immunogenicity in individuals vaccinated with the virosomal hepatitis A virus, Epaxal. Adult volunteers (N = 130) previously enrolled into four different studies between 1992 and 1994 and who had completed a 0/12-month immunization regimen (primary and booster dose) were asked to participate in this follow-up study. Yearly anti-HAV titers up to 6 years following booster vaccination, and then once 9-11 years after booster were measured using two assays, Enzygnost and AxSYM HAVAB 2.0. Based on the Enzygnost assay, the seroprotection rate 9-11 years after booster was 100%, with a geometric mean concentration (GMC) of anti-HAV antibodies of 526 mIU/ml. Females had markedly higher GMCs than males (741 mIU/ml vs. 332 mIU/ml). Using an anti-HAV cut-off titer of >or=10 mIU/ml, a linear mixed mathematical model predicted a median duration of protection of 52.1 years. A duration of protection >or= 35.7 years was predicted for 95% of subjects. A more stringent cut-off of >or=20 mIU/ml shortened the median predicted duration of protection to 45.0 years. In conclusion, a two-dose Epaxal vaccination regimen confers in healthy adults a real-time protection of at least 9-11 years; this protection is predicted to last at least 30 years in over 95% of individuals. Further studies are necessary to assess the real duration of seroprotection and whether an additional booster is necessary later.
Die spontane Aufrichtung des retroflektierten schwangeren Uterus geschieht in der Regel vor der 12. Schwangerschaftswoche. Spätere spontane Aufrichtungen, vor allem im dritten Schwangerschaftsdrittel, sind höchst ungewöhnlich. Die klinischen und radiologischen Befunde sind vielgestaltig und führen zu differenzialdiagnostischen Schwierigkeiten.
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