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Background: The Borna disease virus (BoDV-1) is an emerging zoonotic virus causing severe and mostly fatal encephalitis in humans. Methods and Results: A local cluster of fatal BoDV-1 encephalitis cases was detected in the same village three years apart affecting two children. While the first case was diagnosed late in the course of disease, a very early diagnosis and treatment attempt facilitated by heightened awareness was achieved in the second case. Therapy started as early as day 12 of disease. Antiviral therapy encompassed favipiravir and ribavirin, and, after bioinformatic modelling, also remdesivir. As the disease is immunopathogenetically mediated, an intensified anti-inflammatory therapy was administered. Following initial impressive clinical improvement, the course was also fatal, although clearly prolonged. Viral RNA was detected by qPCR in tear fluid and saliva, constituting a possible transmission risk for health care professionals. Highest viral loads were found post mortem in the olfactory nerve and the limbic system, possibly reflecting the portal of entry for BoDV-1. Whole exome sequencing in both patients yielded no hint for underlying immunodeficiency. Full virus genomes belonging to the same cluster were obtained in both cases by next-generation sequencing. Sequences were not identical, indicating viral diversity in natural reservoirs. Specific transmission events or a common source of infection were not found by structured interviews. Patients lived 750m apart from each other and on the fringe of the settlement, a recently shown relevant risk factor. Conclusion: Our report highlights the urgent necessity of effective treatment strategies, heightened awareness and early diagnosis. Gaps of knowledge regarding risk factors, transmission events, and tailored prevention methods become apparent. Whether this case cluster reflects endemicity or a geographical hot spot needs further investigation. [ABSTRACT FROM AUTHOR]

Background: HPV vaccination has been recommended and reimbursed for girls in Germany since 2007. In June 2018 the German Standing Committee on Vaccination (STIKO) recommended the gender-neutral vaccination of adolescents aged 9 to 14 years with catch-up through age 17. Objectives of this study were to describe the uptake of vaccination in boys before and during the COVID-19 pandemic. Methods: The study used data from a proprietary electronic medical record database and a database with information on nationally dispensed vaccine doses. The monthly number of first doses of HPV vaccinations in boys and girls aged 9–17 years in the period from 01/2018 to 12/2021 was determined. In addition, for boys the cumulative vaccination rates were calculated for initiated and completed vaccination series. Results: Four months after the introduction of mandatory reimbursement for boys, the monthly numbers of first doses were comparable to that of girls. Compared to the same month in 2019, the number of first doses declined by up to 49% (girls) in 2020 and 71% (boys) in 2021. At the end of 2021, the vaccination rate for 15-year-old boys (2006 birth cohort) reached 44.4% for initiated and 26.4% for completed series. Conclusion: After an initial dynamic increase in HPV vaccinations in boys, the impact of COVID-19 was particularly strong in the second year of the pandemic. At the end of 2021 vaccination rates were still low. Efforts are needed to catch-up on adolescents that missed doses during the pandemic and to increase uptake. [ABSTRACT FROM AUTHOR]

Purpose: Resistance of Staphylococcus aureus to vancomycin includes a general increase of minimal inhibitory concentrations (MIC) within the susceptible range over time (Vancomycin MIC Creep) and the presence of a subset of the bacterial population that expresses resistance (heterogeneous glycopeptide-intermediate S. aureus; hGISA). Increased MICs have been associated with adverse clinical outcomes. However, the vancomycin MIC creep is not a uniform trend suggesting the importance of regional surveys. Methods: We performed a retrospective analysis at a German pediatric tertiary care hospital. Isolates from 2002 to 2017 were selected which were newly identified methicillin-resistant S. aureus (MRSA) or samples from invasive methicillin-susceptible S. aureus (MSSA) or MRSA infections. Vancomycin and oxacillin MICs as well as GISA/hGISA were measured using MIC test strips and resistance was evaluated over time. Results: A total of 540 samples were tested, 200 from the early (2002–2009) and 340 from the later period (2010–2017). All samples were vancomycin susceptible, but the MIC was higher for the earlier samples as compared to the later ones (1.11 vs 0.99; p < 0.001). 14% of the samples were hGISA, GISA strains were not detected. Again, vancomycin resistance decreased over time with 28 vs. 6% hGISA (p < 0.001). There was no significant difference between MRSA and MSSA samples with respect to vancomycin MIC and hGISA prevalence. Conclusion: This study shows a decreasing trend for both MIC values and presence of hGISA strains highlighting the importance of monitoring local susceptibilities. Vancomycin remains a first-line treatment option for suspected severe infection with Gram-positive cocci and proven infection with MRSA. [ABSTRACT FROM AUTHOR]

Theodor Escherich (1857–1911) was one of the key players in early paediatric infectious diseases (PID). In fact, he can be regarded as the first paediatric infectious diseases physician and the founder of this subspecialty. During his long years in service for children, he spent 6 years at the Dr von Hauner children's hospital (1884–1890), laying the foundations for PID clinical care and research in Munich. Walter Marget, founder of this journal and co-founder of the German Society for Infectious Diseases (DGI) graduated from medical school in 1946 and practised in Munich since 1967. His tireless efforts went into establishing close links between clinical paediatrics and microbiological diagnostics culminating in the foundation of the Department of Antimicrobial Therapy and Infection Epidemiology at the Dr von Hauner children's hospital. Walter Marget was a key figure for PID in Germany having trained and supported many clinician scientists who followed in his footsteps. This article gives a brief overview of the history of PID in Munich while commemorating Walter Marget and his achievements in this field and for INFECTION. [ABSTRACT FROM AUTHOR]

Background: During COVID-19-related public health non-pharmaceutical prevention measures, such as social distancing, lockdown periods and use of face masks, a decrease in viral respiratory and gastroenterological infections was observed worldwide. Following discontinuation of preventative measures, a potential increase of respective infections outside of their usual seasons was a matter of concern. Method: We aimed to illustrate annual distribution of confirmed viral infections between 2017 and 2021 based on 32,506 clinical samples in a German pediatric tertiary care center and to explore the impact of the COVID-19 pandemic on the epidemiology of these infections in children. Results: While a decrease in overall viral infections was observed during the first and second lockdown period, an extraordinary increase in the number of viral respiratory infections, predominantly caused by human Rhino-/Enterovirus and respiratory syncytial virus (RSV), was observed after relaxation of preventive measures. Notably, Rhino-/Enterovirus infections increased 4-fold (2020 vs. 2019) and 16-fold (2021 vs. 2019). The occurrence of RSV was observed beginning from June to August 2021 and reached an all-time record with a 25- to 50-fold increase in numbers in September and October 2021 in relation to previous pre-pandemic years (2017–2019). In contrast, for non-respiratory viruses (i.e. Rota-/Norovirus), the effect on respective seasonal patterns was only minimal compared to previous years. Conclusion: The observed increase in respiratory infections in children is worrying and is already causing hospitals to become overburdened. Enhanced vigilance will be key to face clinical challenges due to these epidemiological changes in viral disease patterns in the months to come. [ABSTRACT FROM AUTHOR]

Purpose: Recommendations regarding the optimal number of blood cultures in children are not available. The aim of this article is to describe the correlation between blood culture (BC) rates and laboratory-confirmed bloodstream infection (LCBSI) rates, on different paediatric wards of a tertiary-care centre in Germany. Methods: We conducted a retrospective cohort study in a paediatric university hospital, from 1st January to 31st December 2018. All blood cultures collected from neonatal (NICU) and paediatric intensive-care units (PICU), haematology/oncology, and general paediatric wards were included. There were no exclusion criteria. BC taken/1000 patients-days (BC rates/BCR) and LCBSI/1000 patient-days at risk (LCBSI rates) were calculated for each unit. Results: A total of 6040 patients were admitted to the hospital with 3114 of them into wards studied. Of the 3072 BCs collected, 200 (6.5%) were positive. Collection of BCs was performed in 51/77 (66.2%) of admitted patients on NICU, in 151/399 (37.8%) of PICU patients, in 163/755 (21.6%) of haematology/oncology patients, and in 281/1883 (14.9%) of children on general paediatric wards. Gram-positive bacteria were the most commonly detected organisms in blood cultures from all wards with exception of NICU. The BCR in NICU, PICU, haematology/oncology wards, and general wards were 61.6, 196.2, 358.4, and 52.3, respectively. Excluding commensal pathogens and possible contaminations, the LCBSI rates in the same units were 2.4, 5.6, 4.4, and 1.0, respectively. Conclusion: We found different BCR values according the ward studied, being higher in patients with high risk of bloodstream infection such as haematology/oncology patients. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacteria (NTM) are an emerging cause of infections, including chronic lymphadenitis in children. To identify risk factors for NTM lymphadenitis, particularly complicated disease, we collected epidemiologic, clinical, and microbiological data on 138 cases of NTM lymphadenitis in children across 13 centers in Germany and Austria. We assessed lifestyle factors but did not identify specific risk behaviors. We noted that more cases of NTM lymphadenitis occurred during cold months than during warm months. Moreover, we noted female sex and age <5.5 years as potential risk factors. Complete extirpation of the affected lymph node appeared to be the best therapeutic measure. We integrated the study data to develop a simple risk score to predict unfavorable clinical outcomes for NTM lymphadenitis. [ABSTRACT FROM AUTHOR]

Antibiotic consumption (AC) is a key component of antimicrobial stewardship programs to recognize local patterns of antibiotic use. Our aim was to measure AC in neonatal units, including neonatal (NICU)/paediatric (PICU) intensive care units in different countries. We conducted a multicenter, retrospective, cohort study in three NICUs, one neonatal ward, and three PICUs with a total of 84 beds. Global and individual AC in days of therapy (DOT) and DOT per 1000 patient-days were assessed. During the study period, 2567 patients were admitted, corresponding to 4961 patient-days in neonatal units and 9243 patient-days in PICUs. Multidrug-resistant Gram-negative bacteria and methicillin-resistant Staphylococcus aureus were more frequent in Brazil than in Germany. Average AC was 386.5 and 1335.5 DOT/1000PD in German and Brazilian neonatal units, respectively. Aminopenicillins plus 3rd generation cephalosporins were the most commonly prescribed antibiotics in German neonatal units, while aminopenicillins plus aminoglycosides were the class most commonly used in Brazilian NICU. Average AC was 888.1 and 1440.7 DOT/1000PD in German and Brazilian PICUs, respectively. Antipseudomonal penicillins were most commonly used in the German PICU, and glycopeptides were the most frequently prescribed in Brazilian PICUs. Carbapenems represented 2.3–14% of total DOTs in German neonatal units and 4% in the Brazilian NICU and 13.0% in the German PICU and 6–12.2% in Brazilian PICUs. We concluded that different patterns of most commonly prescribed antibiotics were observed in neonatal units and PICUs in these two countries, probably related to different local patterns of antibiotic resistance, with a higher antibiotic consumption in Brazilian study units. [ABSTRACT FROM AUTHOR]

Purpose: Due to early antenatal screening and treatment, HIV mother-to-child transmission (MTCT) rarely occurs in Germany. The study aimed to investigate the impact on prevalence of HIV infection in the antenatal population and the incidence of late-presenting HIV-infected mothers attributable to increased numbers of refugees. Methods: Retrospective analysis and comparison were performed for all deliveries in HIV-infected pregnant women presenting to medical care in Munich (southern Germany) and Hamburg (northern Germany) covering two time periods, A (2010–2012) and B (2013–2015). Results: In Munich, deliveries in HIV-infected pregnant women increased 1.6-fold from period A (n = 50) to B (n = 79) with late-presenting cases rising significantly from 2% (1/50) in period A to 13% (10/79) in B. In contrast, late-presenting cases in Hamburg decreased from 14% (14/100) in period A to 7% (7/107) in B, while the total number of HIV-infected women giving birth remained stable. From 2010 to 2015, one late-presenting pregnant woman transmitted HIV in Munich by presumed in utero mode of infection (case reviewed here), while no MTCT occurred in Hamburg. Conclusions: HIV infections diagnosed late in pregnancy and leading to delayed ART initiation are rising in Munich compared to Hamburg. Antenatal care of HIV-infected pregnant women in Munich appears to have been more affected by the recent refugee influx than Hamburg. Our study highlights the importance of screening all pregnant women for HIV early in pregnancy and providing timely health care access for pregnant refugees and asylum seekers to effectively prevent MTCT in Germany. [ABSTRACT FROM AUTHOR]

The Sofia fluorescent immunoassay showed excellent sensitivity and specificity compared to conventional fluorescent immunoassay for Influenza A (Influenza B was not detected during the study period) and RSV in patients with suspected ILI (influenza-like illness). Thus the fast and easy-to-handle Sofia FIA leads to rapid and reliable diagnosis, which can be used by clinicians to avoid unnecessary antibiotic treatment and rapidly identify patients who need to be isolated upon hospital admission. [ABSTRACT FROM AUTHOR]

Purpose: Bacteremia with Staphylococcus aureus (SAB) is a serious clinical condition and is associated with a high mortality, ranging from 20 to 40 %. Different trials from tertiary referral hospitals demonstrate that infectious disease consultation and adherence to standard of care indicators reduce the high mortality. Data from <250-bed general hospitals are lacking in this context. Methods: Patient cases at a community 200-bed general hospital with documented SAB were retrospectively analyzed from January 2010 to March 2013 regarding defined standard of care indicators. In April 2013, an antibiotic stewardship bundle approach was implemented targeting SAB. Follow-up was available until December 2013. Adherence to the different components of the bundle was analyzed. Results: There were 64 cases of SAB reported. After exclusion of five cases, 39 cases were included in the pre-intervention period and 20 patients in the post-intervention period. Mean average bundle adherence increased from a baseline score of 0.8-3.7 ( p < 0.001) in the post-intervention period, whereas in-hospital mortality decreased significantly (44 vs. 10 %, p < 0.001) despite or even because the absolute number of detected cases of SAB increased substantially after the intervention was initiated. Conclusion: Although we were unable to identify whether the bundle, one of its components, or procedural improvements are responsible for the success of the intervention, our study indicates that the applied approach is feasible and is accompanied by a significant reduction of in-hospital mortality in the secondary care setting. The intervention may serve as a model for other hospitals with similar structures and baseline situations. [ABSTRACT FROM AUTHOR]

Introduction: To establish strategic priorities for the German national public health institute (RKI) and guide the institute's mid-term strategic decisions, we prioritized infectious pathogens in accordance with their importance for national surveillance and epidemiological research. Methods: We used the Delphi process with internal (RKI) and external experts and a metric-consensus approach to score pathogens according to ten three-tiered criteria. Additional experts were invited to weight each criterion, leading to the calculation of a median weight by which each score was multiplied. We ranked the pathogens according to the total weighted score and divided them into four priority groups. Results: 127 pathogens were scored. Eighty-six experts participated in the weighting; "Case fatality rate" was rated as the most important criterion. Twenty-six pathogens were ranked in the highest priority group; among those were pathogens with internationally recognised importance (e.g., Human Immunodeficiency Virus, Mycobacterium tuberculosis, Influenza virus, Hepatitis C virus, Neisseria meningitides), pathogens frequently causing large outbreaks (e.g., Campylobacter spp.), and nosocomial pathogens associated with antimicrobial resistance. Other pathogens in the highest priority group included Helicobacter pylori, Respiratory Syncytial Virus, Varicella zoster virus and Hantavirus. Discussion: While several pathogens from the highest priority group already have a high profile in national and international health policy documents, high scores for other pathogens (e.g., Helicobacter pylori, Respiratory syncytial virus or Hantavirus) indicate a possible under-recognised importance within the current German public health framework. A process to strengthen respective surveillance systems and research has been started. The prioritization methodology has worked well; its modular structure makes it potentially useful for other settings. [ABSTRACT FROM AUTHOR]

Summary: Objectives: To evaluate the relationship between mortality of bloodstream infection due to Staphylococcus aureus and infectious diseases specialist consultation and other factors potentially associated with outcomes. Methods: A 6-year cohort study was conducted at a 1600-bed university hospital. Consecutive adult patients with S. aureus bacteremia were assessed using a standardised data collection and review form. A new infectious diseases service increased its consultations for S. aureus bacteremia from 33% of cases in 2002 to >80% in 2007. Infectious disease consultation and other factors potentially associated with in-hospital mortality were analysed by multivariate logistic regression. Results: A total of 521 patients were studied. All-cause in-hospital mortality was 22%, 90-day mortality was 32%. Factors significantly associated with in-hospital mortality in multivariate analysis were ICU admission (OR 5.8, CI 3.5–9.7), MRSA (OR 2.6, CI 1.4–4.9), age ≥60 years (OR 2.4, CI 1.4–4.2), a diagnosis of endocarditis (OR 2.8, CI 1.4–5.7), a non-fatal underlying disease/comorbidity according to the McCabe classification (OR 0.2, CI 0.1–0.4), and infectious disease specialist consultation (OR 0.6, CI 0.4–1.0). Conclusions: These data suggest that outcome of S. aureus bacteremia may be improved by an expert consultation service. [Copyright &y& Elsevier]

By means of a nationwide, prospective, multicenter, observational cohort registry collecting data on 7375 patients with laboratory-confirmed SARS-CoV-2 admitted to children's hospitals in Germany, March 2020-November 2022, our study assessed the clinical features of children and adolescents hospitalized due to SARS-CoV-2, evaluated which of these patients might be at highest risk for severe COVID-19, and identified underlying risk factors. Outcomes tracked included: symptomatic infection, case fatality, sequelae at discharge and severe disease. Among reported cases, median age was one year, with 42% being infants. Half were admitted for reasons other than SARS-CoV-2. In 27%, preexisting comorbidities were present, most frequently obesity, neurological/neuromuscular disorders, premature birth, and respiratory, cardiovascular or gastrointestinal diseases. 3.0% of cases were admitted to ICU, but ICU admission rates varied as different SARS-CoV-2 variants gained prevalence. Main risk factors linked to ICU admission due to COVID-19 were: patient age (> 12 and 1-4 years old), obesity, neurological/neuromuscular diseases, Trisomy 21 or other genetic syndromes, and coinfections at time of hospitalization. With Omicron, the group at highest risk shifted to 1-4-year-olds. For both health care providers and the general public, understanding risk factors for severe disease is critical to informing decisions about risk-reduction measures, including vaccination and masking guidelines., (© 2023. The Author(s).)

Are children and adolescents relevant disease vectors when it comes to the transmission of SARS-CoV-2? Moreover, do they play a role as relevant disease vectors in a school or kindergarten setting? These questions could not be sufficiently answered at the beginning of the pandemic. Consequently, schools and childcare facilities were closed to stop the spread of SARS-CoV‑2. Over the past few months, researchers have gained a more detailed understanding of the overall pandemic situation. The SARS-CoV‑2 infection rate in children below 10 years of age in 2020 has been substantially lower than in adults. In addition, it showed that children had a milder course of disease.Although a majority of the analyses performed in schools and childcare facilities revealed that the virus is transmitted in these facilities, these transmissions did not, however, have a considerable influence on the overall rate of new infections. Despite these findings, German politicians continue to advocate for the closure of childcare facilities, including schools, to fight the pandemic, whereas many specialist societies such as the German Society for Pediatric Infectious Diseases (DGPI) have emphasized that such closures should be the measure of last resort in combating the pandemic. The same message is also conveyed by a German evidence-based S3 guideline established by an interdisciplinary expert group that had already put forward clear recommendations for high incidences in the general population at the beginning of February 2021, indicating that school closures were only required in exceptional cases.In this article, we would like to outline the situation based on the currently available data, try to predict the future, and discuss the circumstances necessary to realize normal classroom teaching without accepting the risk of an uncontrolled spread of SARS-CoV‑2., (© 2021. The Author(s).)

Background: Intravenous artesunate (ivA) is the standard treatment for severe malaria. Data systematically evaluating the use of ivA in pediatric patients outside malaria-endemic regions are limited. The aim of this case series was to summarize efficacy and safety of ivA for imported severe malaria in children in Germany., Methods: Our retrospective case series included pediatric patients with imported severe malaria treated with at least 1 dose of ivA (Artesun, Guilin Pharmaceutical; Shanghai, China) at 4 German tertiary care centers. Severe malaria was defined according to World Health Organization criteria., Results: Between 2010 and 2018, 14 children with a median [interquartile range (IQR)] age of 6 (1;9.5) years were included. All children were of African descent. All but 2 patients had Plasmodium falciparum malaria; 1 child had P. vivax malaria and 1 child had P. falciparum and P. vivax co-infection. Median (IQR) parasitemia at admission in patients with P. falciparum was 9.5% (3;16.5). Patients were treated with 1-10 [median (IQR) 3 (3;4)] doses ivA. All but one patient received a full course of oral antimalarial treatment. Parasite clearance was achieved within 2-4 days, with the exception of 1 patient with prolonged clearance of peripheral parasitemia. Three patients experienced posttreatment hemolysis but none needed blood transfusion. Otherwise ivA was safe and well tolerated., Conclusions: ivA was highly efficacious in this pediatric cohort. We observed episodes of mild to moderate posttreatment hemolysis in approximately one-third of patients. The legal status and usage of potentially lifesaving ivA should be evaluated in Europe.

In September 2018, a child who had returned from Somalia to Germany presented with cutaneous diphtheria by toxigenic Corynebacterium diphtheriae biovar mitis. The child's sibling had superinfected insect bites harbouring also toxigenic C. diphtheriae . Next generation sequencing (NGS) revealed the same strain in both patients suggesting very recent human-to-human transmission. Epidemiological and NGS data suggest that the two cutaneous diphtheria cases constitute the first outbreak by toxigenic C. diphtheriae in Germany since the 1980s.

Background: Current guidelines regarding Lyme neuroborreliosis [LNB] require the presence of intrathecal Borrelia burgdorferi-specific antibody production for the definite diagnosis of LNB. However, about 20% of early stage infections present without an elevated antibody index. Moreover, intrathecal B. burgdorferi specific antibody synthesis may persist long after successful therapy of LNB. Recently published data indicate that CXCL13 seems to be a promising diagnostic tool for early stage LNB. In addition, CXCL13 might be suitable for treatment monitoring., Case Presentation: We report on a 39-year-old male patient from southern Germany, who has been suffering from subfebrile body temperatures and meningeal headache for six weeks. On the second day after hospital admission he developed peripheral palsy of the VII. cranial nerve. Cerebrospinal fluid (CSF) analysis showed granulocytic pleocytosis, elevated total protein and blood-CSF barrier dysfunction. Differential diagnostics for granulocytic pleocytosis were unremarkable. Only a second lumbar puncture, on day 6 after admission, revealed a lymphocytic pleocytosis. Serologic testing pointed to clear intrathecal Borrelia specific IgG antibody production. Interestingly, no anti-OspC antibodies were detectable. DNA of the rare Borrelia garinii OspA-type 7 could be amplified from the first CSF sample. The monitoring of CXCL13 in all CSF samples documented a fast decrease from 5000 pg/ml to 450 pg/ml after appropriate antibiotic treatment., Conclusion: CXCL13 is a novel biomarker with high sensitivity and specificity for acute LNB. Our data show, that CXCL13 might be helpful in unclear cases and support the presumption that it might be a valuable tool for treatment monitoring. Anti-OspC antibody negativity is a rare observation, given the need of OspC for infection of the human hosts. Most likely this is due to a lack of sensitivity of OspC immunoblots that are unable to detect rare OspC variants.