• Immune monitoring after pediatric liver transplantation - the prospective ChilSFree cohort study.

      Goldschmidt, Imeke; Karch, André; Mikolajczyk, Rafael; Mutschler, Frauke; Junge, Norman; Pfister, Eva Doreen; Möhring, Tamara; d'Antiga, Lorenzo; McKiernan, Patrick; Kelly, Deirdre; Debray, Dominique; McLin, Valérie; Pawlowska, Joanna; Hierro, Loreto; Daemen, Kerstin; Keil, Jana; Falk, Christine; Baumann, Ulrich; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-05-16)
      Although trough levels of immunosuppressive drugs are largely used to monitor immunosuppressive therapy after solid organ transplantation, there is still no established tool that allows for a validated assessment of functional degree of immunosuppression or the identification of clinically relevant over- or under-immunosuppression, depending on graft homeostasis. Reliable non-invasive markers to predict biopsy proven acute rejection (BPAR) do not exist. Literature data suggest that longitudinal measurements of immune markers might be predictive of BPAR, but data in children are scarce. We therefore propose an observational prospective cohort study focusing on immune monitoring in children after liver transplantation. We aim to describe immune function in a cohort of children before and during the first year after liver transplantation and plan to investigate how the immune function profile is associated with clinical and laboratory findings. In an international multicenter prospective approach, children with end-stage liver disease who undergo liver transplantation are enrolled to the study and receive extensive immune monitoring before and at 1, 2, 3, 4 weeks and 3, 6, 12 months after transplantation, and whenever a clinically indicated liver biopsy is scheduled. Blood samples are analyzed for immune cell numbers and circulating levels of cytokines, chemokines and factors of angiogenesis reflecting immune cell activation. Statistical analysis will focus on the identification of trajectorial patterns of immune reactivity predictive for systemic non-inflammatory states, infectious complications or BPAR using joint modelling approaches. The ChilSFree study will help to understand the immune response after pLTx in different states of infection or rejection. It may provide insight into response mechanisms eventually facilitating immune tolerance towards the graft. Our analysis may yield an applicable immune panel for non-invasive early detection of acute cellular rejection, with the prospect of individually tailoring immunosuppressive therapy. The international collaborative set-up of this study allows for an appropriate sample size which is otherwise difficult to achieve in the field of pediatric liver transplantation.
    • Changes in risk perceptions during the 2014 Ebola virus disease epidemic: results of two consecutive surveys among the general population in Lower Saxony, Germany.

      Obenauer, Julie; Rübsamen, Nicole; Garsevanidze, Ekaterine; Karch, André; Mikolajczyk, Rafael T; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-05-15)
      The Ebola virus disease (EVD) outbreak 2014 received extensive news media coverage, which faded out before the outbreak ended. News media coverage impacts risk perception; it is, however, unclear if the components of risk perception (affective and cognitive responses) change differently over time. In an online panel, we asked participants (n = 1376) about EVD risk perceptions at the epidemic's peak (November 2014) and after news media coverage faded out (August 2015). We investigated worry (affective response), perceived likelihood of infection, perceived personal impact, and coping efficacy (dimensions of cognitive response), and knowledge about transmission. Differences between the surveys with respect to manifestations of affective and cognitive dimensions were tested using the Wilcoxon signed-rank test. The association between individual change in knowledge and worries about EVD in the first survey was investigated using linear regression. In November 2014, the survey was filled in by 974 participants. Ten months later, 662 of them were still members of the online panel and were invited to the follow-up survey. Among the 620 respondents, affective response decreased between the surveys. Knowledge about EVD also decreased; however, participants worried about EVD in 2014 had increased knowledge in 2015. Perceived likelihood of infection decreased over time, while perceived personal impact and coping efficacy did not. Risk communication appealing to cognitive reactions by informing clearly on the risk of infection in unaffected countries may decrease inappropriate behaviors.
    • Optimized Management of Endovascular Treatment for Acute Ischemic Stroke.

      Schregel, Katharina; Behme, Daniel; Tsogkas, Ioannis; Knauth, Michael; Maier, Ilko; Karch, André; Mikolajczyk, Rafael; Bähr, Mathias; Schäper, Jörn; Hinz, José; Liman, Jan; Psychogios, Marios-Nikos; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (2018-01-18)
      This manuscript describes a streamlined protocol for the management of patients with acute ischemic stroke, which aims at the minimization of time from hospital admission to reperfusion. Rapid restoration of cerebral blood flow is essential for the outcomes of patients with acute ischemic stroke. Endovascular treatment (EVT) has become the standard of care to accomplish this in patients with acute stroke due to large vessel occlusion (LVO). To achieve reperfusion of ischemic brain regions as fast as possible, all in-hospital time delays have to be carefully avoided. Therefore, management of patients with acute ischemic stroke was optimized with an interdisciplinary standard operating procedure (SOP). Stroke neurologists, diagnostic as well as interventional neuroradiologists, and anesthesiologists streamlined all necessary processes from patient admission and diagnosis to EVT of eligible patients. Target times for every step were established. Actually achieved times were prospectively recorded along with clinical data and imaging scores for all endovascularly treated stroke patients. These data were regularly analyzed and discussed in interdisciplinary team meetings. Potential issues were evaluated and all staff involved was trained to adhere to the SOP. This streamlined patient management approach and enhanced interdisciplinary collaboration reduced time from patient admission to reperfusion significantly and was accompanied by a beneficial effect on clinical outcomes.
    • Antibiotic use on paediatric inpatients in a teaching hospital in the Gambia, a retrospective study.

      Chaw, Pa Saidou; Schlinkmann, Kristin Maria; Raupach-Rosin, Heike; Karch, André; Pletz, Mathias W; Huebner, Johannes; Nyan, Ousman; Mikolajczyk, Rafael; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-01-01)
      Antibiotics are useful but increasing resistance is a major problem. Our objectives were to assess antibiotic use and microbiology testing in hospitalized children in the Gambia. We conducted a retrospective analysis of paediatric inpatient data at The Edward Francis Small Teaching Hospital in Banjul, The Gambia. We extracted relevant data from the admission folders of all patients (aged > 28 days to 15 years) admitted in 2015 (January-December), who received at least one antibiotic for 24 h. We also reviewed the microbiology laboratory record book to obtain separate data for the bacterial isolates and resistance test results of all the paediatric inpatients during the study period. Over half of the admitted patients received at least one antibiotic during admission (496/917) with a total consumption of 670.7 Days of Antibiotic Therapy/1000 Patient-Days. The clinical diagnoses included an infectious disease for 398/496, 80.2% of the patients on antibiotics, pneumonia being the most common (184/496, 37.1%). There were 51 clinically relevant bacterial isolates, More than half of the admitted patients received antibiotics. The reported antibiotic resistance was highest to the most commonly used antibiotics such as ampicillin. Efforts to maximize definitive antibiotic indication such as microbiological testing prior to start of antibiotics should be encouraged where possible for a more rational antibiotic use.
    • Survival of children after liver transplantation for hepatocellular carcinoma.

      Baumann, Ulrich; Adam, René; Duvoux, Christophe; Mikolajczyk, Rafael; Karam, Vincent; D'Antiga, Lorenzo; Chardot, Christophe; Coker, Ahmet; Colledan, Michele; Ericzon, Bo-Goran; Line, Pål Dag; Hadzic, Nedim; Isoniemi, Helena; Klempnauer, Jürgen L; Reding, Raymond; McKiernan, Patrick J; McLin, Valérie; Paul, Andreas; Salizzoni, Mauro; Furtado, Emanuel San Bento; Schneeberger, Stefan; Karch, André; the European Liver and Intestine Transplant Association; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-01-01)
      Hepatocellular carcinoma (HCC) in childhood differs from adult HCC because it is often associated with inherited liver disease. It is, however, unclear whether liver transplantation (LT) for HCC in childhood with or without associated inherited disease has a comparable outcome to adult HCC. On the basis of data from the European Liver Transplant Registry (ELTR), we aimed to investigate if there are differences in patient and graft survival after LT for HCC between children and adults and between patients with underlying inherited versus noninherited liver disease, respectively. We included all 175 children who underwent LT for HCC and were enrolled in ELTR between 1985 and 2012. Of these, 38 had an associated inherited liver disease. Adult HCC patients with (n = 79) and without (n = 316, matched by age, sex, and LT date) inherited liver disease served as an adult comparison population. We used multivariable piecewise Cox regression models with shared frailty terms (for LT center) to compare patient and graft survival between the different HCC groups. Survival analyses demonstrated a superior longterm survival of children with inherited liver disease when compared with children with HCC without inherited liver disease (hazard ratio [HR], 0.29; 95% CI, 0.10-0.90; P = 0.03) and adults with HCC with inherited liver disease (HR, 0.27; 95% CI, 0.06-1.25; P = 0.09). There was no survival difference between adults with and without inherited disease (HR, 1.05; 95% CI, 0.66-1.66; P = 0.84). In conclusion, the potential survival advantage of children with an HCC based on inherited disease should be acknowledged when considering transplantation and prioritization for these patients. Further prospective studies accounting for tumor size and extension at LT are necessary to fully interpret our findings. Liver Transplantation 24 246-255 2018 AASLD.
    • 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.
    • 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.
    • 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.
    • Factors associated with attrition in a longitudinal online study: results from the HaBIDS panel.

      Rübsamen, Nicole; Akmatov, Manas K; Castell, Stefanie; Karch, André; Mikolajczyk, Rafael T; Hemholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-08-31)
      Knowing about predictors of attrition in a panel is important to initiate early measures against loss of participants. We investigated attrition in both early and late phase of an online panel with special focus on preferences regarding mode of participation.
    • Evaluation of vaccination herd immunity effects for anogenital warts in a low coverage setting with human papillomavirus vaccine-an interrupted time series analysis from 2005 to 2010 using health insurance data.

      Thöne, Kathrin; Horn, Johannes; Mikolajczyk, Rafael T; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-08-14)
      Shortly after the human papillomavirus (HPV) vaccine recommendation and hence the reimbursement of vaccination costs for the respective age groups in Germany in 2007, changes in the incidence of anogenital warts (AGWs) were observed, but it was not clear at what level the incidence would stabilize and to what extent herd immunity would be present. Given the relatively low HPV vaccination coverage in Germany, we aimed to assess potential vaccination herd immunity effects in the German setting.
    • Sociodemographic determinants of spatial disparities in early childhood caries: An ecological analysis in Braunschweig, Germany.

      Meyer, Frederic; Karch, André; Schlinkmann, Kristin Maria; Dreesman, Johannes; Horn, Johannes; Rübsamen, Nicole; Sudradjat, Henny; Schubert, Rainer; Mikolajczyk, Rafael; Helmholtz Centre for infection research, Inhoffenstr.7, 38124 Braunschweig, Germany. (2017-05-26)
      To identify spatial disparities in dental caries experience (measured by dmft (decayed missing filled teeth) index) of children in the city of Braunschweig and to evaluate whether these disparities can be explained by sociodemographic characteristics.
    • Transcranial doppler sonography is not a valid diagnostic tool for detection of basilar artery stenosis or in-stent restenosis: a retrospective diagnostic study.

      Koh, Woori; Kallenberg, Kai; Karch, André; Frank, Tobias; Knauth, Michael; Bähr, Mathias; Liman, Jan; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-05-11)
      There are contradictory reports concerning the validity of transcranial sonography (TCD and TCCS) for examinations of the basilar artery. Here we investigated sensitivity and specificity of transcranial sonography for the detection of basilar artery stenosis and in-stent-restenosis compared to cerebral angiography.
    • Incidence and comparison of retrospective and prospective data on respiratory and gastrointestinal infections in German households.

      Schlinkmann, Kristin Maria; Bakuli, Abhishek; Mikolajczyk, Rafael T; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-05-11)
      Acute respiratory infections (ARI) and acute gastrointestinal infections (AGI) are the most common childhood infections, and corresponding data can either be collected prospectively or retrospectively. The aim of this study was to estimate the incidence of respiratory and gastrointestinal episodes in German households with children attending day care and to compare results of prospective and retrospective data collection.
    • Structure of the Escherichia coli ProQ RNA-binding protein.

      Gonzalez, Grecia M; Hardwick, Steven W; Maslen, Sarah L; Skehel, J Mark; Holmqvist, Erik; Vogel, Jörg; Bateman, Alex; Luisi, Ben F; Broadhurst, R William; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-05)
      The protein ProQ has recently been identified as a global small noncoding RNA-binding protein in Salmonella, and a similar role is anticipated for its numerous homologs in divergent bacterial species. We report the solution structure of Escherichia coli ProQ, revealing an N-terminal FinO-like domain, a C-terminal domain that unexpectedly has a Tudor domain fold commonly found in eukaryotes, and an elongated bridging intradomain linker that is flexible but nonetheless incompressible. Structure-based sequence analysis suggests that the Tudor domain was acquired through horizontal gene transfer and gene fusion to the ancestral FinO-like domain. Through a combination of biochemical and biophysical approaches, we have mapped putative RNA-binding surfaces on all three domains of ProQ and modeled the protein's conformation in the apo and RNA-bound forms. Taken together, these data suggest how the FinO, Tudor, and linker domains of ProQ cooperate to recognize complex RNA structures and serve to promote RNA-mediated regulation.
    • Deciding on the mode of birth after a previous caesarean section - An online survey investigating women's preferences in Western Switzerland.

      Bonzon, Magali; Gross, Mechthild M; Karch, André; Grylka-Baeschlin, Susanne; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-04-21)
      promoting vaginal births after caesarean section (VBAC) for eligible women and increasing rates of successful VBACs are the best strategies to reduce the number of repeat caesarean sections (CS). Knowledge of factors that are associated with women's decision-making around mode of birth after CS is important when developing strategies to promote VBAC. This study assessed which factors are associated with women's preferences for VBAC versus elective repeat caesarean section (ERCS) in a new pregnancy after one previous caesarean in Switzerland.
    • Deficits in knowledge, attitude, and practice towards blood culture sampling: results of a nationwide mixed-methods study among inpatient care physicians in Germany.

      Raupach-Rosin, Heike; Duddeck, Arne; Gehrlich, Maike; Helmke, Charlotte; Huebner, Johannes; Pletz, Mathias W; Mikolajczyk, Rafael; Karch, André; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-02-15)
      Blood culture (BC) sampling rates in Germany are considerably lower than recommended. Aim of our study was to assess knowledge, attitudes, and practice of physicians in Germany regarding BC diagnostics.
    • Association between Embolic Stroke Patterns, ESUS Etiology, and New Diagnosis of Atrial Fibrillation: A Secondary Data Analysis of the Find-AF Trial.

      Maier, Ilko L; Schregel, Katharina; Karch, André; Weber-Krueger, Mark; Mikolajczyk, Rafael T; Stahrenberg, Raoul; Gröschel, Klaus; Bähr, Mathias; Knauth, Michael; Psychogios, Marios-Nikos; Wachter, Rolf; Liman, Jan; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017)
      Background. Atrial fibrillation (AF) is an important cause of embolic stroke of undetermined source (ESUS). Imaging-patterns like multiple infarcts, simultaneous involvement of different circulations, infarcts of different ages, and isolated cortical infarcts are likely to indicate cardioembolic stroke. The aim of our study was to evaluate the association between embolic stroke patterns, ESUS, and the new diagnosis of AF. Methods. Stroke etiology and imaging characteristics from patients included in the Find-AF study were obtained. Embolic stroke patterns in CT- or MR-imaging were correlated with the diagnosis of ESUS as well as the short- (on baseline ECG and during 7-day Holter) and long-term (12-month follow-up) diagnosis of AF. Results. From 281 patients included in the Find-AF study, 127 (45.2%) patients with ischemic lesions detected in CT or MRI were included. 26 (20.5%) of these patients had ESUS. At least one embolic stroke pattern was detected in 67 (52.7%) patients. Embolic stroke patterns were not associated with ESUS (OR 1.57, 0.65-3.79, p = 0.317), the short-term (OR 0.64, 0.26-1.58, p = 0.327) or long-term diagnosis of AF (OR 0.72, 0.31-1.68, p = 0.448). Conclusions. This secondary data analysis of the Find-AF study could not provide evidence for an association between embolic stroke patterns, ESUS, and the new diagnosis of AF.
    • Comparison of response patterns in different survey designs: a longitudinal panel with mixed-mode and online-only design.

      Rübsamen, Nicole; Akmatov, Manas K; Castell, Stefanie; Karch, André; Mikolajczyk, Rafael; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017)
      Increasing availability of the Internet allows using only online data collection for more epidemiological studies. We compare response patterns in a population-based health survey using two survey designs: mixed-mode (choice between paper-and-pencil and online questionnaires) and online-only design (without choice).
    • 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.