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.

Case-control study of behavioural and societal risk factors for sporadic SARS-CoV-2 infections, Germany, 2020-2021 (CoViRiS study).

During the COVID-19 pandemic in Germany, a variety of societal activities were restricted to minimize direct personal interactions and, consequently, reduce SARS-CoV-2 transmission. The aim of the CoViRiS study was to investigate whether certain behaviours and societal factors were associated with the risk of sporadic symptomatic SARS-CoV-2 infections. Adult COVID-19 cases and frequency-matched population controls were interviewed by telephone regarding activities that involved contact with other people during the 10 days before illness onset (cases) or before the interview (controls). Associations between activities and symptomatic SARS-CoV-2 infection were analysed using logistic regression models adjusted for potential confounding variables. Data of 859 cases and 1 971 controls were available for analysis. The risk of symptomatic SARS-CoV-2 infection was lower for individuals who worked from home (adjusted odds ratio (aOR) 0.5; 95% confidence interval (CI) 0.3-0.6). Working in a health care setting was associated with a higher risk (aOR: 1.5; 95% CI: 1.1-2.1) as were private indoor contacts, personal contacts that involved shaking hands or hugging, and overnight travelling within Germany. Our results are in line with some of the public health recommendations aimed at reducing interpersonal contacts during the COVID-19 pandemic.

The Multicomponent Medicinal Product Hepar Compositum Reduces Hepatic Inflammation and Fibrosis in a Streptozotocin- and High-Fat Diet-Induced Model of Metabolic Dysfunction-Associated Steatotic Liver Disease/Metabolic Dysfunction-Associated Steatohepatitis.

Metabolic dysfunction-associated steatotic liver disease (MASLD)-formerly known as non-alcoholic fatty liver disease (NAFLD)-is the most common chronic liver disease worldwide. Since there is currently no approved pharmacotherapy for MASLD, there is an urgent unmet need for efficacious therapeutics for this disease. Hepar compositum (HC-24) is a multicomponent medicinal product that consists of 24 natural ingredients. It has been shown to have anti-inflammatory properties in an obesity-associated MASLD mouse model, but its potential to reduce MASLD-associated fibrosis had not been explored before this study. Here, we investigated the hepatic anti-inflammatory and anti-fibrotic potential of HC-24 in a streptozotocin (STZ)- and high-fat diet (HFD)-induced model of MASLD. Mice received a single injection of low-dose STZ at 2 days of age, followed by HFD feeding from 4 to 9 weeks of age. Mice were treated every second day with HC-24 or daily with the positive control telmisartan from 6 to 9 weeks of age. A non-diseased control group was included as a healthy reference. An explorative small-scale pilot study demonstrated that HC-24 improved liver histology, resulting in a lower NAFLD activity score and reduced liver fibrosis. A subsequent full study confirmed these effects and showed that HC-24 reduced hepatic inflammation, specifically reducing T helper cell and neutrophil influx, and decreased hepatic fibrosis (with qualitatively reduced collagen type I and type III immunopositivity) in the absence of an effect on body and liver weight, blood glucose or liver steatosis. These results show that HC-24 has hepatoprotective, anti-inflammatory, and anti-fibrotic properties in an STZ- and HFD-induced model of MASLD/MASH, suggesting that this multicomponent medicine has therapeutic potential for MASLD patients.

Caregiver acceptance of malaria vaccination for children under 5 years of age and associated factors: cross-sectional household survey, Guinea and Sierra Leone, 2022.

BACKGROUND: Malaria is a leading cause of death and reduced life span in Guinea and Sierra Leone, where plans for rolling out the malaria vaccine for children are being made. There is little evidence about caregiver acceptance rates to guide roll-out policies. To inform future vaccine implementation planning, this analysis aimed to assess potential malaria vaccine acceptance by caregivers and identify factors associated with acceptance in Guinea and Sierra Leone. METHODS: A cross-sectional household survey using lot quality assurance sampling was conducted in three regions per country between May 2022 and August 2022. The first survey respondent in each household provided sociodemographic information. A household member responsible for childcare shared their likelihood of accepting a malaria vaccine for their children under 5 years and details about children's health. The prevalence of caregiver vaccine acceptance was calculated and associated factors were explored using multivariable logistic regression modelling calculating adjusted odds ratios (aOR) with 95% confidence intervals (CI). RESULTS: Caregivers in 76% of 702 sampled households in Guinea and 81% of 575 households in Sierra Leone were accepting of a potential vaccine for their children. In both countries, acceptance was lower in remote areas than in urban areas (Guinea: aOR 0.22 [95%CI 0.09-0.50], Sierra Leone: 0.17 [0.06-0.47]). In Guinea, acceptance was lower among caregivers living in the richest households compared to the poorest households (0.10 [0.04-0.24]), among those whose children were tested for malaria when febrile (0.54 [0.34-0.85]) and in households adopting more preventative measures against malaria (0.39 [0.25-0.62]). Better knowledge of the cause of malaria infection was associated with increased acceptance (3.46 [1.01-11.87]). In Sierra Leone, vaccine acceptance was higher among caregivers living in households where the first respondent had higher levels of education as compared to lower levels (2.32 [1.05-5.11]). CONCLUSION: In both countries, malaria vaccine acceptance seems promising for future vaccine roll-out programmes. Policy makers might consider regional differences, sociodemographic factors, and levels of knowledge about malaria for optimization of implementation strategies. Raising awareness about the benefits of comprehensive malaria control efforts, including vaccination and other preventive measures, requires attention in upcoming campaigns.

Statutory health insurance-covered pre-exposure prophylaxis in Germany: changing trends in nationwide tenofovir disoproxil/emtricitabine prescriptions during the COVID-19 pandemic.

Background: In 2019, Germany introduced a law to reimburse high-incidence populations for pre-exposure prophylaxis (PrEP), prescribed as tenofovir-disoproxil/emtricitabine (TDF/FTC), via statutory health insurance (SHI). We studied changes in TDF/FTC-prescriptions after the implementation of this law and during the COVID-19 pandemic. Methods: We performed an interrupted time series analysis with monthly prescriptions per defined time period as the outcome. We considered the introduction of SHI-covered PrEP (09/2019) as an interruption, and four COVID-19 waves and two national lockdowns (2020-2021) as explanatory variables. We extrapolated prescriptions had the lockdowns not occurred, and compared this to the actual prescriptions. We performed sub-analyses based on stratification by five federal states with the highest proportion of PrEP users. We assessed the models' goodness-of-fit based on the adjusted R-squared using RStudio. Results: The best fitting model included SHI-covered PrEP and the first COVID-19 lockdown (04/2020). The decrease in prescriptions during the first lockdown was significant nationally, and in the five federal states for single-month prescriptions. The first lockdown resulted in reductions of 57.7% (95% prediction interval (PI): 23.0%-92.4%) for single-month prescriptions, while 17.4% (95% PI: 0.28%-34.5%) nationally, and 13.9% (95% PI: -3.67%-31.5%) for 3-month prescriptions. Conclusion: Introduction of SHI-covered PrEP resulted in a doubling of TDF/FTC-prescriptions nationwide in the first month alone. A drop in prescriptions was most apparent after the first lockdown, and particularly affected PrEP initiations, possibly due to reduced healthcare access and behavioural changes. Ongoing monitoring of TDF/FTC-prescriptions is needed to safeguard access to preventative care such as PrEP and particularly PrEP initiation during public health crises like COVID-19.

Epidemiology of common infectious diseases before and during the COVID-19 pandemic in Bavaria, Germany, 2016 to 2021: an analysis of routine surveillance data.

BackgroundUnprecedented non-pharmaceutical interventions to control the COVID-19 pandemic also had an effect on other infectious diseases.AimWe aimed to determine their impact on transmission and diagnosis of notifiable diseases other than COVID-19 in Bavaria, Germany, in 2020 and 2021.MethodsWe compared weekly cases of 15 notifiable infectious diseases recorded in Bavaria between 1 January 2016 and 31 December 2021 in time series analyses, median age and time-to-diagnosis using Wilcoxon rank sum test and hospitalisation rates using univariable logistic regression during three time periods: pre-pandemic (weeks 1 2016-9 2020), pandemic years 1 (weeks 10-52 2020) and 2 (2021).ResultsWeekly case numbers decreased in pandemic year 1 for all diseases assessed except influenza, Lyme disease and tick-borne encephalitis; markedly for norovirus gastroenteritis (IRR = 0.15; 95% CI: 0.12-0.20) and pertussis (IRR = 0.22; 95% CI: 0.18-0.26). In pandemic year 2, influenza (IRR = 0.04; 95% CI: 0.02-0.09) and pertussis (IRR = 0.11; 95% CI: 0.09-0.14) decreased markedly, but also chickenpox, dengue fever, Haemophilus influenzae invasive infection, hepatitis C, legionellosis, noro- and rotavirus gastroenteritis and salmonellosis. For enterohaemorrhagic Escherichia coli infections, median age decreased in pandemic years 1 and 2 (4 years, interquartile range (IQR): 1-32 and 3 years, IQR: 1-18 vs 11 years, IQR: 2-42); hospitalisation proportions increased in pandemic year 1 (OR = 1.60; 95% CI: 1.08-2.34).ConclusionReductions for various infectious diseases and changes in case characteristics in 2020 and 2021 indicate reduced transmission of notifiable diseases other than COVID-19 due to interventions and under-detection.

International harm reduction indicators are still not reached: results from a repeated cross-sectional study on drug paraphernalia distribution in Germany, 2021.

BACKGROUND: To prevent the transmission of blood-borne infections and reach the elimination of viral hepatitis by 2030, the World Health Organization (WHO) has set the goal to distribute 300 sterile needles and syringes each year per person who injects drugs (PWID). We aimed to assess drug paraphernalia distribution in Germany in 2021, including the WHO indicator, and to analyse changes to the distribution measured in 2018. METHODS: We conducted a repeated cross-sectional study of low-threshold drug services in Germany. We assessed type and quantity of distributed drug paraphernalia and the number of supplied PWID in 2021 using an online and paper-based questionnaire. We conducted a descriptive statistical analysis of data from 2021, assessed fulfillment of the WHO indicator and changes in services that participated 2021 and in the previous study 2018. RESULTS: Five hundred and eighty-nine of 1760 distributed questionnaires were returned in 2021. 204 drug services from 15 out of 16 federal states confirmed drug paraphernalia distribution, covering 20% of Germany's rural and 51% of urban counties. 108 services had also participated in 2018. The most frequently distributed paraphernalia for injecting drug use in 2021 were syringes (97% of services), needles (96%) and vitamin C (90%). Pre-cut aluminium foil (79% of services) and pipes (28%) for inhaling, and sniff tubes (43%) for nasal use were distributed less frequently. We found a median reduction in distributed syringes by 18% and by 12% for needles compared to 2018. Of 15 states, two reached the 2030 WHO-target for needles and one for syringes. CONCLUSIONS: The current national estimates and changes from 2018 to 2021 for drug paraphernalia distribution seem far from meeting the WHO target. Reasons could include a change in drug consumption behaviour towards less injecting use and more inhaling, and effects of the COVID-19 pandemic (supply difficulties, social distancing, lockdown, reduced opening hours of services). We observed pronounced regional differences in drug paraphernalia distribution. To close existing gaps, Germany should expand its drug paraphernalia distribution programmes and other harm reduction services, such as drug consumption rooms. Further investigation of determinants for adequate distribution is essential to reduce blood-borne infections in this key population.

Travel-related giardiasis: incidence and time trends for various destination countries.

BACKGROUND: Giardiasis is a common gastrointestinal illness in travellers. Data on the actual giardiasis risk of travellers to different travel destinations are scarce. We aim to estimate the risk of giardiasis in travellers from Germany by destination country and region. METHODS: We analysed travel-related giardiasis cases, their countries and regions of exposure and the age and sex distribution of cases reported in 2014-19 in Germany. We defined a travel-related giardiasis case as a laboratory-confirmed (i.e. positive microscopy, antigen test or nucleic acid test) symptomatic individual with outbound travel abroad within 3-25 days before symptom onset. Based on the number of reported cases per exposure country and UNWTO travel data for Germany, we calculated the number of travel-related giardiasis cases per 100 000 travellers and compared the incidence in 2014-16 and 2017-19 to identify potential trends. RESULTS: In 2014-19, 21 172 giardiasis cases were reported in Germany, corresponding to an overall incidence of 4.3 per 100 000 population. Of all cases, 6879 (32%) were travel-related with a median age of 34 [interquartile range (IQR): 25-50], 51% were male. Southern Asia was the most frequently reported exposure region and had the highest incidence in travellers (64.1 per 100 000 returning travellers) in 2017-19, followed by Latin America (19.2) and Sub-Saharan Africa (12.9). We observed statistically significant decreasing trends for Southern Asia and Sub-Saharan Africa. Latin America was the only region with a statistically significant increasing trend. CONCLUSIONS: Almost one-third of recent giardiasis cases in Germany were travel-related. Giardiasis incidence in travellers differs greatly depending on the destination region. Decreasing trends in many regions might be due to improvements in food hygiene or travel conditions. Our results may inform medical consultation pre and post patient's travel.

CHROMAgar™ LIN-R as an efficient screening tool to assess the prevalence of linezolid-resistant enterococci in German hospital patients-a multicentre study approach, 2021-2022.

BACKGROUND: In recent years, an increasing number of linezolid-resistant enterococci (LRE) was recognized at the German National Reference Centre (NRC) for Enterococci. National guidelines on infection prevention recommend screening for LRE in epidemiologically linked hospital settings without referring to a reliable and rapid diagnostic method. Since 2020, CHROMAgar™ provide a chromogenic linezolid screening agar, LIN-R, suitable to simultaneously screen for linezolid-resistant staphylococci and enterococci. OBJECTIVES: To assess the applicability of CHROMAgar™ LIN-R in clinical settings for detecting LRE directly from patient material and to infer prevalence rates of LRE amongst German hospital patients. METHODS: During the 3-month trial period, clinical samples were plated on CHROMAgar™ LIN-R. Antimicrobial susceptibility testing was performed using VITEK2 or disc diffusion. At the NRC, linezolid resistance was determined by broth microdilution, multiplex-PCR for cfr/optrA/poxtA and by a restriction-based assay for 23S rDNA mutations. RESULTS: The 12 participating study sites used 13 963 CHROMAgar™ LIN-R plates during the study period. Of 442 presumptive LRE, 192 were confirmed by phenotypic methods. Of these, 161 were received by the NRC and 121 (75%) were verified as LRE. Most of LR-E. faecium 53/81 (65%) exhibited a 23S rRNA gene mutation as the sole resistance-mediating mechanism, whereas optrA constituted the dominant resistance trait in LR-E. faecalis [39/40 (98%)]. Prevalence of LRE across sites was estimated as 1% (ranging 0.18%-3.7% between sites). CONCLUSIONS: CHROMAgar™ LIN-R represents a simple and efficient LRE screening tool in hospital settings. A high proportion of false-positive results demands validation of linezolid resistance by a reference method.

Vaccine effectiveness against severe COVID-19 during the Omicron wave in Germany: results from the COViK study.

PURPOSE: COViK, a prospective hospital-based multicenter case-control study in Germany, aims to assess the effectiveness of COVID-19 vaccines against severe disease. Here, we report vaccine effectiveness (VE) against COVID-19-caused hospitalization and intensive care treatment during the Omicron wave. METHODS: We analyzed data from 276 cases with COVID-19 and 494 control patients recruited in 13 hospitals from 1 December 2021 to 5 September 2022. We calculated crude and confounder-adjusted VE estimates. RESULTS: 21% of cases (57/276) were not vaccinated, compared to 5% of controls (26/494; p < 0.001). Confounder-adjusted VE against COVID-19-caused hospitalization was 55.4% (95% CI: 12-78%), 81.5% (95% CI: 68-90%) and 95.6% (95%CI: 88-99%) after two, three and four vaccine doses, respectively. VE against hospitalization due to COVID-19 remained stable up to one year after three vaccine doses. CONCLUSION: Three vaccine doses remained highly effective in preventing severe disease and this protection was sustained; a fourth dose further increased protection.

BNT162b2 vaccination reduced infections and transmission in a COVID-19 outbreak in a nursing home in Germany, 2021.

BACKGROUND: A SARS-CoV-2 outbreak was detected in a nursing home in February 2021 after residents and staff had received two doses of BNT162b2 vaccine in January 2021. METHODS: Nursing home staff, long-term residents and day-care receivers were included in a retrospective cohort study. We calculated attack rates (AR), secondary AR (SAR) and their 95% binomial confidence interval (CI), and we compared them using Fisher's exact test or chi-squared test, depending on the sample size. We used Poisson regression with robust error estimates to calculate vaccine effectiveness against SARS-COV-2 infections. We selected variables based on directed acyclic graphs. As a proxy for viral load at diagnosis, we compared the mean Ct values at diagnosis using t tests or Mann-Whitney U tests. RESULTS: The adjusted vaccine effectiveness against infection was 56% (95% CI: 15-77%, p = 0.04). Ct values at diagnosis were higher when intervals after receiving the second vaccination were longer (>21 vs. ≤21 days: 4.48 cycles, p = 0.08). The SAR was 67% lower in households of vaccinated (2/9 [22.2%]) than of unvaccinated infected staff (12/18 [66.7%]; p = 0.046). Vaccination rates were lowest among staff with close physical contact to care-receivers (46%). The highest AR in vaccinated staff had those working on wards (14%). CONCLUSIONS: Vaccination reduced the risk for SARS-CoV-2 infection, viral load and transmission; however, non-pharmaceutical interventions remain essential to reduce transmission of SARS-CoV-2 infections, even for vaccinated individuals. Vaccination coverage of staff ought to increase reduction of infections among themselves, their household members and residents.

Effectiveness of vaccines in preventing hospitalization due to COVID-19: A multicenter hospital-based case-control study, Germany, June 2021 to January 2022.

We included 852 patients in a prospectively recruiting multicenter matched case-control study in Germany to assess vaccine effectiveness (VE) in preventing COVID-19-associated hospitalization during the Delta-variant dominance. The two-dose VE was 89 % (95 % CI 84-93 %) overall, 79 % in patients with more than two comorbidities and 77 % in adults aged 60-75 years. A third dose increased the VE to more than 93 % in all patient-subgroups.

Outbreak of imported diphtheria with Corynebacterium diphtheriae among migrants arriving in Germany, 2022.

From July 2022, cases of imported diphtheria with toxigenic Corynebacterium diphtheriae remarkably increased among migrants arriving in Germany. Up to 30 September 2022, 44 cases have been reported to the national public health institute, all laboratory-confirmed, male, and mainly coming from Syria (n = 21) and Afghanistan (n = 17). Phylogeny and available journey information indicate that most cases (n = 19) were infected along the Balkan route. Active case finding, increased laboratory preparedness and epicentre localisation in countries along this route are important.

Left-censored dementia incidences in estimating cohort effects.

We estimate the dementia incidence hazard in Germany for the birth cohorts 1900 until 1954 from a simple sample of Germany's largest health insurance company. Followed from 2004 to 2012, 36,000 uncensored dementia incidences are observed and further 200,000 right-censored insurants included. From a multiplicative hazard model we find a positive and linear trend in the dementia hazard over the cohorts. The main focus of the study is on 11,000 left-censored persons who have already suffered from the disease in 2004. After including the left-censored observations, the slope of the trend declines markedly due to Simpson's paradox, left-censored persons are imbalanced between the cohorts. When including left-censoring, the dementia hazard increases differently for different ages, we consider omitted covariates to be the reason. For the standard errors from large sample theory, left-censoring requires an adjustment to the conditional information matrix equality.