Prevalence of vaccine-derived hepatitis B surface antibodies in children and adolescents in Germany: results from a population-based survey, 2014-2017.

INTRODUCTION: Childhood vaccination against hepatitis B has been recommended in Germany since 1995. WHO defines a primary vaccination series as successful if the initial hepatitis B surface antibody (anti-HBs) level is ≥ 10 IU/L directly after vaccination. Anti-HBs levels vary depending on the number of doses, type of vaccine, and time interval between the last two doses. In 2021, Germany began to recommend three instead of four doses of polyvalent hepatitis-B-containing vaccines. Our aim was to estimate the proportion of vaccinated children in Germany with anti-HBs levels < 10 IU/L, 10-99 IU/L, and ≥ 100 IU/L by number and type of vaccine, and assess if number of doses and compliance with recommended time interval between the last two doses are associated with an anti-HBs level ≥ 10 IU/L when considering type of vaccine and time since last dose. METHODS: We used data from a national cross-sectional study (2014-2017) of children (3-17 years). We excluded participants with unknown vaccination dates, unreadable or incomplete vaccination cards, and hepatitis B virus (HBV)-positive participants. We defined a recommended schedule as a vaccination series with at least six months between the two last doses and having three doses or more. We calculated weighted anti-HBs sero-prevalence for three anti-HBs levels: < 10 IU/L, 10-99 IU/L and ≥ 100 IU/L. We fitted two logistic regression models to examine the relationship between number of doses and recommended schedule on anti-HBs levels (≥ 10 IU/L and ≥ 100 IU/L) considering time since last dose and type of vaccine (Infanrix, Hexavac, Monovalent). RESULTS: We included 2,489 participants. The weighted proportion of vaccinated children per anti-HBs level was < 10 IU/L: 36.3% [95%CI 34.0-38.7%], 10-99 IU/L: 35.7% [33.2-38.2%] and ≥ 100 IU/L: 28.0% [25.9-30.2%]. We did not find an association between a recommended schedule of three versus four doses and anti-HBs ≥ 10 IU/L or ≥ 100 IU/L. CONCLUSIONS: Anti-HBs levels in later childhood were about equal, whether children received three or four doses. This implies that the change in the recommendations does not affect the anti-HBs level among children in Germany. Future studies are needed on the association of anti-HBs levels and adequate sustained protection against HBV.

The application of new molecular methods in the investigation of a waterborne outbreak of norovirus in Denmark, 2012.

In December 2012, an outbreak of acute gastrointestinal illness occurred in a geographical distinct area in Denmark covering 368 households. A combined microbiological, epidemiological and environmental investigation was initiated to understand the outbreak magnitude, pathogen(s) and vehicle in order to control the outbreak. Norovirus GII.4 New Orleans 2009 variant was detected in 15 of 17 individual stool samples from 14 households. Norovirus genomic material from water samples was detected and quantified and sequencing of longer parts of the viral capsid region (>1000 nt) were applied to patient and water samples. All five purposely selected water samples tested positive for norovirus GII in levels up to 1.8×10(4) genomic units per 200 ml. Identical norovirus sequences were found in all 5 sequenced stool samples and 1 sequenced water sample, a second sequenced water sample showed 1 nt (<0.1%) difference. In a cohort study, including 256 participants, cases were defined as residents of the area experiencing diarrhoea or vomiting onset on 12-14 December 2012. We found an attack rate of 51%. Being a case was associated with drinking tap-water on 12-13 December (relative risk = 6.0, 95%CI: 1.6-22) and a dose-response relation for the mean glasses of tap-water consumed was observed. Environmental investigations suggested contamination from a sewage pipe to the drinking water due to fall in pressure during water supply system renovations. The combined microbiological, epidemiological and environmental investigations strongly indicates the outbreak was caused by norovirus contamination of the water supply system.

Serological evidence of asymptomatic infections during Escherichia coli O104:H4 outbreak in Germany in 2011.

INTRODUCTION: The largest known outbreak caused by a rare hybrid strain of Shiga toxin-producing E.coli (STEC) and enteroaggregative E. coli (EAEC) (E.coli O104:H4) of serotype O104:H4 occurred in Germany in 2011. Fenugreek sprouts acted as a transmission vehicle and were widely consumed in the outbreak area at the time of the epidemic. In total 3,842 people developed a clinical illness caused by this strain; however the rates of asymptomatic infections remain unclear. We aimed to develop a serological assay for detection of E.coli O104 LPS specific antibodies and to establish the post-outbreak levels of seropositivity among people with documented exposure to contaminated sprouts. RESULTS AND DISCUSSION: Developed serological assays (ELISA with 84% sensitivity, 63% specificity and Western Blot with 100% sensitivity, 82.5% specificity) identified 33% (16/49) level of asymptomatic infection. Relatively small sample size and a significant time- lapse between the onset of symptoms and serum samples collection (appr. 8 weeks) might explain the assay variability. No association was found between clinical or demographic characteristics and assay positivity. Larger studies are needed to understand the complexity of human immune response and factors influencing development of clinical symptoms. Development of intra-outbreak research plans will substantially aid the conduct of more thorough scientific investigation during an outbreak period.