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  • Global, regional, and national burden of neurological disorders during 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.

    GBD 2015 Neurological Disorders Collaborator Group.; Karch, André; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-11-01)
    BACKGROUND: Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level. METHODS: We estimated global and country-specific prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for various neurological disorders that in the GBD classification have been previously spread across multiple disease groupings. The more inclusive grouping of neurological disorders included stroke, meningitis, encephalitis, tetanus, Alzheimer's disease and other dementias, Parkinson's disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, medication overuse headache, brain and nervous system cancers, and a residual category of other neurological disorders. We also analysed results based on the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility, to identify patterns associated with development and how countries fare against expected outcomes relative to their level of development. FINDINGS: Neurological disorders ranked as the leading cause group of DALYs in 2015 (250·7 [95% uncertainty interval (UI) 229·1 to 274·7] million, comprising 10·2% of global DALYs) and the second-leading cause group of deaths (9·4 [9·1 to 9·7] million], comprising 16·8% of global deaths). The most prevalent neurological disorders were tension-type headache (1505·9 [UI 1337·3 to 1681·6 million cases]), migraine (958·8 [872·1 to 1055·6] million), medication overuse headache (58·5 [50·8 to 67·4 million]), and Alzheimer's disease and other dementias (46·0 [40·2 to 52·7 million]). Between 1990 and 2015, the number of deaths from neurological disorders increased by 36·7%, and the number of DALYs by 7·4%. These increases occurred despite decreases in age-standardised rates of death and DALYs of 26·1% and 29·7%, respectively; stroke and communicable neurological disorders were responsible for most of these decreases. Communicable neurological disorders were the largest cause of DALYs in countries with low SDI. Stroke rates were highest at middle levels of SDI and lowest at the highest SDI. Most of the changes in DALY rates of neurological disorders with development were driven by changes in YLLs. INTERPRETATION: Neurological disorders are an important cause of disability and death worldwide. Globally, the burden of neurological disorders has increased substantially over the past 25 years because of expanding population numbers and ageing, despite substantial decreases in mortality rates from stroke and communicable neurological disorders. The number of patients who will need care by clinicians with expertise in neurological conditions will continue to grow in coming decades. Policy makers and health-care providers should be aware of these trends to provide adequate services.
  • Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.

    GBD 2016 Disease and Injury Incidence and Prevalence Collaborators.; Karch, André; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-09-16)
  • Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970-2016: a systematic analysis for the Global Burden of Disease Study 2016.

    GBD 2016 Mortality Collaborators.; Karch, André; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-09-16)
  • Poor knowledge of vaccination recommendations and negative attitudes towards vaccinations are independently associated with poor vaccination uptake among adults - Findings of a population-based panel study in Lower Saxony, Germany.

    Akmatov, Manas K; Rübsamen, Nicole; Deyneko, Igor V; Karch, André; Mikolajczyk, Rafael T; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018)
    The aims of this study were to (a) assess knowledge of official vaccination recommendations and attitudes towards vaccinations among adults and (b) examine their association with vaccination uptake among adults.
  • Influence of demographic changes on the impact of vaccination against varicella and herpes zoster in Germany - a mathematical modelling study.

    Horn, Johannes; Damm, Oliver; Greiner, Wolfgang; Hengel, Hartmut; Kretzschmar, Mirjam E; Siedler, Anette; Ultsch, Bernhard; Weidemann, Felix; Wichmann, Ole; Karch, André; Mikolajczyk, Rafael T; elmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018)
    Epidemiological studies suggest that reduced exposure to varicella might lead to an increased risk for herpes zoster (HZ). Reduction of exposure to varicella is a consequence of varicella vaccination but also of demographic changes. We analyzed how the combination of vaccination programs and demographic dynamics will affect the epidemiology of varicella and HZ in Germany over the next 50 years.
  • Cerebrospinal fluid neurofilament light levels in neurodegenerative dementia: Evaluation of diagnostic accuracy in the differential diagnosis of prion diseases.

    Zerr, Inga; Schmitz, Matthias; Karch, André; Villar-Piqué, Anna; Kanata, Eirini; Golanska, Ewa; Díaz-Lucena, Daniela; Karsanidou, Aikaterini; Hermann, Peter; Knipper, Tobias; Goebel, Stefan; Varges, Daniela; Sklaviadis, Theodoros; Sikorska, Beata; Liberski, Pawel P; Santana, Isabel; Ferrer, Isidro; Zetterberg, Henrik; Blennow, Kaj; Calero, Olga; Calero, Miguel; Ladogana, Anna; Sánchez-Valle, Raquel; Baldeiras, Inês; Llorens, Franc; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-02-03)
    Neurofilament light (NFL) levels in the cerebrospinal fluid are increased in several neurodegenerative dementias. However, their diagnostic accuracy in the differential diagnostic context is unknown.
  • Utilization of host polyamines in alternatively activated macrophages promotes chronic infection byBrucella abortus.

    Kerrinnes, Tobias; Winter, Maria G; Young, Briana M; Diaz-Ochoa, Vladimir E; Winter, Sebastian E; Tsolis, Renée M; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-12-04)
    Treatment of intracellular bacterial pathogens with antibiotic therapy often requires a long course of multiple antibiotics. A barrier to developing strategies that enhance antibiotic efficacy against these pathogens is our poor understanding of the intracellular nutritional environment that maintains bacterial persistence. The intracellular pathogenBrucella abortussurvives and replicates preferentially in alternatively activated macrophages (AAM), however knowledge of the metabolic adaptations promoting exploitation of this niche is limited. Here we show that one mechanism promoting enhanced survival in AAM is a shift in macrophage arginine utilization from production of nitric oxide (NO) to biosynthesis of polyamines, induced by IL-4/IL-13 treatment.B. abortusis unable to synthesize polyamines, however production of polyamines by infected AAM promoted both intracellular survival of bacteria and chronic infection in mice, as inhibition of macrophage polyamine synthesis or inactivation of theB. abortusputrescine transporterpotIHGFreduced both intracellular survival in AAM and persistence in mice. These results demonstrate that increased intracellular availability of polyamines induced by arginase-1 expression in IL-4/IL-13-induced AAM promotes chronic persistence ofB. abortuswithin this niche and suggest that targeting of this pathway may aid in eradicating chronic infection.
  • Partial verification bias and incorporation bias affected accuracy estimates of diagnostic studies for biomarkers that were part of an existing composite gold standard.

    Karch, Annika; Koch, Armin; Zapf, Antonia; Zerr, Inga; Karch, André; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2016-10)
    To investigate how choice of gold standard biases estimates of sensitivity and specificity in studies reassessing the diagnostic accuracy of biomarkers that are already part of a lifetime composite gold standard (CGS).
  • ["I cannot kiss my wife"- An Analysis of Daily Experiences of MRSA-carriers].

    Raupach-Rosin, H; Klett-Tammen, C J; Schmalz, O; Karch, A; Castell, S; Mikolajczyk, R; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2016-12)
    Objectives: There are no data available on the quality of care after discharge from hospital and only limited data are available on the psychosocial effects of being an MRSA carrier within the German health system.Methods:Patients who tested positive for MRSA in the previous year were invited to take part in focus groups.Results:2 focus groups with a total of 9 MRSA-carriers were conducted. The level of knowledge about MRSA differed between participants. In some cases, lack of information led to uncertainty and inappropriate measures to counteract MRSA. Some participants restricted their social contacts, especially to children, in order to prevent transmission. Patients experienced stigmatization in the health care system more often in inpatient care than in the outpatient sector. Only in a few cases both eradication therapy and swabs for control purposes were carried out.Conclusions:Information about the appropriate treatment and management of MRSA should be made available to patients more easily; in particular, patients need to be informed that MRSA is no threat to healthy individuals. Despite the desire of MRSA-carriers to become MRSA negative, treatment and control of MRSA seem to have low priority in the ambulant health care sector in Germany.
  • Public Health Research Resulting from One of the World's Largest Outbreaks Caused by Entero-Hemorrhagic Escherichia coli in Germany 2011: A Review.

    Köckerling, Elena; Karrasch, Laura; Schweitzer, Aparna; Razum, Oliver; Krause, Gerard; Helmhotz Zentrum füt Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017)
    In 2011, Germany experienced one of the largest outbreaks of entero-hemorrhagic Escherichia coli (EHEC) ever reported. Four years thereafter, we systematically searched for scientific publications in PubMed and MEDPILOT relating to this outbreak in order to assess the pattern of respective research activities and to assess the main findings and recommendations in the field of public health. Following PRISMA guidelines, we selected 133 publications, half of which were published within 17 months after outbreak onset. Clinical medicine was covered by 71, microbiology by 60, epidemiology by 46, outbreak reporting by 11, and food safety by 9 papers. Those on the last three topics drew conclusions on methods in surveillance, diagnosis, and outbreak investigation, on resources in public health, as well as on inter-agency collaboration, and public communication. Although the outbreak primarily affected Germany, most publications were conducted by multinational cooperations. Our findings document how soon and in which fields research was conducted with respect to this outbreak.
  • Changing infection patterns - New evidence on the prevalence of nosocomial infections and antibiotic resistance in hospitals in Germany

    Krause, Gerard; Helmholtz Zentrum für Infektionsforschung GmbH, Inhoffenstr.7, 38124 Braunschweig, Germany. (Deutscher Arzte-Verlag GmbH, 2018-02-06)
    Editorial to accompany the articles: „The Prevalence of Nosocomial Infection and Antibiotic Use in German Hospitals“ by Michael Behnke et al. and „Surveillance of Antibiotic Use and Resistance in Intensive Care Units (SARI)—A 15-year Cohort Study“ by Cornelius Remschmidt et al. in this issue of Deutsches Ärzteblatt International
  • Population-level impact, herd immunity, and elimination after human papillomavirus vaccination: a systematic review and meta-analysis of predictions from transmission-dynamic models.

    Brisson, Marc; Bénard, Élodie; Drolet, Mélanie; Bogaards, Johannes A; Baussano, Iacopo; Vänskä, Simopekka; Jit, Mark; Boily, Marie-Claude; Smith, Megan A; Berkhof, Johannes; Canfell, Karen; Chesson, Harrell W; Burger, Emily A; Choi, Yoon H; De Blasio, Birgitte Freiesleben; De Vlas, Sake J; Guzzetta, Giorgio; Hontelez, Jan A C; Horn, Johannes; Jepsen, Martin R; Kim, Jane J; Lazzarato, Fulvio; Matthijsse, Suzette M; Mikolajczyk, Rafael T; Pavelyev, Andrew; Pillsbury, Matthew; Shafer, Leigh Anne; Tully, Stephen P; Turner, Hugo C; Usher, Cara; Walsh, Cathal; Helmholtz Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2016-11)
    Modelling studies have been widely used to inform human papillomavirus (HPV) vaccination policy decisions; however, many models exist and it is not known whether they produce consistent predictions of population-level effectiveness and herd effects. We did a systematic review and meta-analysis of model predictions of the long-term population-level effectiveness of vaccination against HPV 16, 18, 6, and 11 infection in women and men, to examine the variability in predicted herd effects, incremental benefit of vaccinating boys, and potential for HPV-vaccine-type elimination.
  • Effects of pathogen dependency in a multi-pathogen infectious disease system including population level heterogeneity - a simulation study.

    Bakuli, Abhishek; Klawonn, Frank; Karch, André; Mikolajczyk, Rafael T; Helmholtz-Zentrum für Infektionsforschung, GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-12-13)
    Increased computational resources have made individual based models popular for modelling epidemics. They have the advantage of incorporating heterogeneous features, including realistic population structures (like e.g. households). Existing stochastic simulation studies of epidemics, however, have been developed mainly for incorporating single pathogen scenarios although the effect of different pathogens might directly or indirectly (e.g. via contact reductions) effect the spread of each pathogen. The goal of this work was to simulate a stochastic agent based system incorporating the effect of multiple pathogens, accounting for the household based transmission process and the dependency among pathogens.
  • Colonic Butyrate-Producing Communities in Humans: an Overview Using Omics Data.

    Vital, Marius; Karch, André; Pieper, Dietmar H.; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr.7, 38124 Braunschweig, Germany. (2018-01-18)
    Given the key role of butyrate for host health, understanding the ecology of intestinal butyrate-producing communities is a top priority for gut microbiota research. To this end, we performed a pooled analysis on 2,387 metagenomic/transcriptomic samples from 15 publicly available data sets that originated from three continents and encompassed eight diseases as well as specific interventions. For analyses, a gene catalogue was constructed from gene-targeted assemblies of all genes from butyrate synthesis pathways of all samples and from an updated reference database derived from genome screenings. We demonstrate that butyrate producers establish themselves within the first year of life and display high abundances (>20% of total bacterial community) in adults regardless of origin. Various bacteria form this functional group, exhibiting a biochemical diversity including different pathways and terminal enzymes, where one carbohydrate-fueled pathway was dominant with butyryl coenzyme A (CoA):acetate CoA transferase as the main terminal enzyme. Subjects displayed a high richness of butyrate producers, and 17 taxa, primarily members of the Lachnospiraceae and Ruminococcaceae along with some Bacteroidetes, were detected in >70% of individuals, encompassing ~85% of the total butyrate-producing potential. Most of these key taxa were also found to express genes for butyrate formation, indicating that butyrate producers occupy various niches in the gut ecosystem, concurrently synthesizing that compound. Furthermore, results from longitudinal analyses propose that diversity supports functional stability during ordinary life disturbances and during interventions such as antibiotic treatment. A reduction of the butyrate-producing potential along with community alterations was detected in various diseases, where patients suffering from cardiometabolic disorders were particularly affected. IMPORTANCE Studies focusing on taxonomic compositions of the gut microbiota are plentiful, whereas its functional capabilities are still poorly understood. Specific key functions deserve detailed investigations, as they regulate microbiota-host interactions and promote host health and disease. The production of butyrate is among the top targets since depletion of this microbe-derived metabolite is linked to several emerging noncommunicable diseases and was shown to facilitate establishment of enteric pathogens by disrupting colonization resistance. In this study, we established a workflow to investigate in detail the composition of the polyphyletic butyrate-producing community from omics data extracting its biochemical and taxonomic diversity. By combining information from various publicly available data sets, we identified universal ecological key features of this functional group and shed light on its role in health and disease. Our results will assist the development of precision medicine to combat functional dysbiosis.
  • Hepatitis B vaccination timing: results from demographic health surveys in 47 countries.

    Schweitzer, Aparna; Akmatov, Manas K; Krause, Gerard; BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106 Braunschweig, Germany. (2017-03-01)
    To examine the impact of hepatitis B vaccination schedules and types of vaccines on hepatitis B vaccination timing.
  • Development of a Bead-Based Multiplex Assay for the Analysis of the Serological Response against the Six Pathogens HAV, HBV, HCV, CMV, T. gondii, and H. pylori

    Filomena, Angela; Pessler, Frank; Akmatov, Manas K; Krause, Gérard; Duffy, Darragh; Gärtner, Barbara; Gerhard, Markus; Albert, Matthew; Joos, Thomas; Schneiderhan-Marra, Nicole; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr.7, 38124 Braunschweig, Germany. (2017-10-30)
  • The Risk of Hospitalizations with Injury Diagnoses in a Matched Cohort of Children and Adolescents with and without Attention Deficit/Hyperactivity Disorder in Germany: A Database Study.

    Lindemann, Christina; Langner, Ingo; Banaschewski, Tobias; Garbe, Edeltraut; Mikolajczyk, Rafael T; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr.7, 38124 Braunschweig, Germany. (2017)
    Attention deficit/hyperactivity disorder (ADHD) is a common neuropsychiatric disorder in children and adolescents worldwide, and children with ADHD have elevated risk of injuries. Our aim was to assess the risk of hospitalizations with injury diagnoses and their various subtypes in children and adolescents with newly diagnosed ADHD compared to those without ADHD, as well as to study sex effects on this risk in the setting of the German health care system.
  • Effect of Disease Definition on Perceived Burden of Acute Respiratory Infections in Children: A Prospective Cohort Study Based on Symptom Diaries.

    Zoch, Beate; Günther, Annette; Karch, André; Mikolajczyk, Rafael; Helmholtz-Zentrum für Infektionsfrschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-10)
    Acute respiratory infections (ARIs) are among the most frequent childhood diseases in Western countries. Assessment of ARI episodes for research purposes is usually based on parent-administered retrospective questionnaires or prospective symptom diaries. The aim of our analysis was to compare the effect of ARI definitions on the corresponding disease burden in a prospective cohort study using symptom diaries.

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