http://edoc.rki.de/176904/49 Tue, 14 Apr 2026 08:45:39 GMT 2026-04-14T08:45:39Z http://edoc.rki.de/176904/10753 Classifying Emergency Department Data to Improve Syndromic Surveillance: From Mixed Data Types to ICD Codes and Syndromes Wagner, Birte Syndromic surveillance systems are used to monitor public health and enable a timely outbreak detection. Emergency department (ED) data can serve as an important data source for syndromic surveillance, but a high amount of missing diagnosis codes can make analyses relying on this information impossible. This study aims at enhancing an ED dataset from a piloted syndromic surveillance system in Germany to enable the monitoring of an influenza-like illness (ILI) syndrome. Routinely collected data from one ED containing mixed-type variables are analysed and two different approaches are implemented to deal with the missing data. Within the first approach, the missing diagnosis codes are imputed by predicting them from the remaining variables, using a multi-class naive Bayes classifier and a deep learning imputation package. In the second approach, a logistic regression model and a binary naive Bayes classifier are used to predict the ILI syndrome from all variables except the diagnosis code. The resulting ILI cases are evaluated on time series level with regard to seasonal patterns. The diagnosis codes were predicted from mixed-type input variables with sufficient precision (34.37% F1-measure in the best model). By taking into account the hierarchical structure of the ICD-10 codes, the performance was improved. Predicting the ILI syndrome independent of the diagnosis code from the remaining variables worked well (39.63% F1-measure in the best model) and the predictions showed medical similarity with the ILI syndrome. The models differed in their sensitivity of including cases, which can be adjusted by changing the threshold of the classifiers. The resulting ILI cases from all models were positively correlated with the reference cases on a time series basis (r = 0.865 for best model) and were comparable with an external data source, a surveillance of severe acute respiratory infections (SARI) (r = 0.867 for best model). The present study showed that the ED dataset can be enhanced to enable the syndromic surveillance of an ILI syndrome based on the diagnosis codes, even if this variable is missing. Additionally, a flexible case definition for an ILI syndrome was developed that is independent of the diagnosis code and the underlying generic method can be applied to other syndromes as well. Thu, 16 Feb 2023 00:00:00 GMT http://edoc.rki.de/176904/10753 2023-02-16T00:00:00Z http://edoc.rki.de/176904/9838 Using routine emergency department data for syndromic surveillance of acute alcohol intoxication Schlump, Carmen Background: The prevalence and intensity of alcohol use varies among subgroups in the population and changes over time. Routine emergency department data provide a potential for monitoring mental health use cases to gather information on frequencies and distri-butions of specified health events in real time. For this purpose, the development of syndrome definitions for the continuous recording and detection of acute changes in alcohol-related visits and acute alcohol intoxications was explored. Methods: Routinely collected data from 18 emergency departments in Germany were analysed. Syndrome definitions were developed by combining chief complaints and diagnoses to portray alcohol-related health events presenting to the emergency department. Identified cases were described by characteristics of their distributions and compared to another data source of inpatient health care. Further, cases were presented over time and by separate time period before and during the COVID-19 pandemic. Results: From a total of 2,123,492 emergency department attandances, 18,270 cases (0.86%) were identified as alcohol-related visits and 14,141 (0.67%) as acute alcohol intoxica-tions for the observation period between 1 January 2018 to 2 May 2021. Among all acute alcohol intoxications, 71.8% were male and most cases presented in the age category of 45-54 years (20.0%). The syndrome definition continuously recorded cases and displayed acute changes due to the COVID-19 pandemic as well as trends in patient characteristics of identified acute alcohol intoxications. Conclusion: The potential and proof of principle for syndromic surveillance of alcohol-related visits, especially acute alcohol intoxications, using emergency department data was demon-strated. The syndrome definition to identify acute alcohol intoxications can be applied for various surveillance purposes. This systematic data collection provides a first foun-dation for timley information on patterns and changes of alcohol consumption to sup-port prevention and intervention efforts in reducing alcohol-related harm. Mon, 20 Jun 2022 00:00:00 GMT http://edoc.rki.de/176904/9838 2022-06-20T00:00:00Z http://edoc.rki.de/176904/9067 Syndromic surveillance using emergency department data for the monitoring of unspecific acute gastrointestinal infections Schranz, Madlen Background: Timely detection is a prerequisite for the successful prevention and management of gastrointestinal infections. Complimentary to already existing surveillance systems, syndromic surveillance can be used for that purpose. This study analyses data from a piloted syndromic surveillance system in Germany, aiming at the definition of syndromes and the exploration of the system’s ability to monitor seasonal patterns and short-time aberrations of gastrointestinal infections. Methods: Routinely collected data from emergency departments were analysed. Within this paper, two Syndromic Surveillance Health Indicators (SySHI) were created in order to combine complaint information. Syndromes were defined based on a combination of SySHI and a set of ICD-10 diagnoses. Identified cases were stratified by emergency department, age and isolation status. Time series were used to analyse seasonal patterns and combined with an algorithm to perform aberration detection. Results: Between 2012 and 2019 data on 935,032 visits of ten emergency departments were analysed. Of those, 2.7% were identified as cases according to the Syndromic Surveillance Health Indicator. The syndrome definition “unspecific GI without bleeding” identified 3,329 and the syndrome definition “bloody diarrhoea” 589 cases. Time series analysis showed seasonal patterns with peaks in the winter months for the first syndrome. Exemplary for one hospital a total of six signals was created by the algorithm. Conclusion: Emergency department data can be used to define appropriate syndromes for the detection of seasonal patterns and aberrations in case numbers. Syndromes incorporating information on chief complaint and diagnosis were able to identify seasonal fluctuations of gastrointestinal infections. Tue, 07 Dec 2021 00:00:00 GMT http://edoc.rki.de/176904/9067 2021-12-07T00:00:00Z http://edoc.rki.de/176904/6496 Analyse der post-entry Prozesse des rekonstituierten humanen endogenen Retrovirus HERV-K113 im Vergleich zu weiteren Beta-Retroviren Krüger, Luise Das humane Genom besteht zu etwa 8% aus retroviralen Sequenzen, den Humanen Endogenen Retroviren (HERV). Davon umfasst die HERV-K(HML-2) Familie die jüngst integrierten Elemente und ist die einzige Gruppe, welche humanspezifische Proviren enthält. Mit HERV-K113 wurde ein Provirus entdeckt, welches vollständige offene Leserahmen für alle viralen Proteine enthält, jedoch aufgrund post-insertionaler Mutationen keine infektiösen Viruspartikel mehr bilden kann. Trotz zahlreicher Nachforschungen konnte bisher kein replikationskompetentes Provirus im Menschen nachgewiesen werden. Das Verschwinden der exogenen Vorläufer kann unter anderem auf zelluläre Restriktionsprozesse, die offenbar während des post-entry/ pre-Integrationsprozesses stattfinden, zurückgeführt werden. In der vorliegenden Arbeit wurden zur genaueren Charakterisierung der post-entry Inhibition von HERV-K(HML-2) und auch für die eng verwandten Beta-Retroviren MMTV und JSRV geeignete Methoden etabliert und Infektionsversuche mit Detektion von Zwischenprodukten der Reversen Transkription durchgeführt. Dafür wurden zunächst zwei verschiedene, auf rekonstituierten HERV-K113 Sequenzen basierte Reportervirussysteme zur Produktion von „virus-like particles“ (VLPs) in verschiedenen Kombinationen eingesetzt und hinsichtlich ihrer viralen RNA Kopien, dem p27 Gehalt und der RT-Aktivität charakterisiert und verglichen. Aufgrund der gewonnenen Daten wurden oriHERV-GFP und HERV-KCON, zusammen mit dem Verpackungsplasmid oricoGPP, für die VLP Produktion ausgewählt. Weiterhin wurden sogenannte Slippery Site Mutanten generiert, welche durch Mutation der Slippery Sequenz(en) eine bzw. beide ribosomale Leserahmenverschiebungen nicht mehr für die Synthese der Vorläuferproteine benötigen. In diesen VLP-Mutanten sollte sich das Verhältnis der Vorläuferproteine zueinander verschieben lassen, sodass VLPs mit einem optimierten Partikel-zu-RT-Aktivität Verhältnis entstehen. Nach Charakterisierung konnte gezeigt werden, dass die Gag-Pro-Pol Doppelmutante zur stärksten RT-Aktivität in den enthaltenen VLPs führte, während die Menge an VLPs bezüglich p27 zu gering war. Für die Infektionsversuche wurden diese Mutanten aus diesem Grund nicht verwendet. Zusätzlich zu den HERV-K(HML-2) Reporterviren erfolgte die Produktion und Charakterisierung von MMTV- und JSRV-Partikeln, welche ebenfalls in die Infektion eingesetzt wurden. Dazu wurde für MMTV ein bereits publiziertes Vektor-basiertes Reportervirussystem etabliert. Die Etablierung der neuen qPCR Systeme zur Untersuchung der RT-Produkte für MMTV und JSRV war ebenfalls notwendig, während diese für HERV-K schon bestanden. Die ddPCR wurde etabliert und für bestimmte RT-Produkte zur Bestätigung der qPCR eingesetzt. Nach der Produktion und Charakterisierung der Reporterviren erfolgte die synchronisierte Infektion von CRFK Zellen. Diese wurden zu bestimmten Zeitpunkten nach der Infektion geerntet. Die extrahierte DNA der infizierten Zellen wurde sodann auf die verschiedenen RT-Produkte mithilfe spezieller Primer-Sonden Kombinationen in der real-time PCR untersucht. Anhand der Nachweisbarkeit der early und late RT-Produkte bei den mit HERV-K- sowie MMTV- und JSRV-infizierten Zellen konnte in dieser Arbeit gezeigt werden, dass die Reverse Transkription in den infizierten Zellen zunächst einmal bis zum Kernimport stattfindet. In Zellen, die mit MMTV bzw. JSRV infiziert waren, konnte jedoch nicht, wie erwartet, der gesamte post-entry Prozess bis hin zur Integration der Proviren demonstriert werden. Dennoch konnten einzelne Kopien der 2-LTR-circles detektiert werden. Die chromosomale Integration konnte bei keiner der infizierten Zellen nachgewiesen werden. Nicht detektierte RT-Produkte könnten eine Inhibierung durch zelluläre Restriktionsfaktoren bedeuten, was bei HERV-K(HML-2) wahrscheinlich ist.; The human genome consists of about 8 % of retroviral sequences, the Human Endogenous Retroviruses (HERV). Of these, the HERV-K (HML-2) family includes the most recently integrated elements and is the only group containing human-specific proviruses. HERV-K113 is a provirus, which contains complete open reading frames for all viral proteins, but can no longer form infectious virus particles due to post-insertional mutations. Despite of numerous investigations, no replication-competent provirus has been detected in humans so far. The vanishing of the exogenous precursors can, among others, be attributed to cellular restriction processes that appear to occur during the post-entry/ pre-integration process. In the present work new methods were established and used for infection experiments, resulting in the detection of early and late products of reverse transcription to further characterize the post-entry inhibition of HERV-K(HML-2). For comparison, the closely related beta-retroviruses MMTV and JSRV were included in these experiments. At first, two different reporter virus systems based on reconstituted HERV-K113 sequences were used in various combinations for the production of virus-like particles (VLPs) and characterized and compared in terms of their viral RNA copies, p27 content and RT-activity. Due to the obtained data, oriHERV-GFP and HERV-KCON in combination with the packaging plasmid oricoGPP were selected for the VLP production. Furthermore, so-called slippery site mutants were generated, which, by mutation of the slippery sequence(s), no longer require one or both ribosomal frameshifts for the synthesis of the precursor proteins. In these VLP mutants, the ratio of precursor proteins should get shifted, resulting in VLPs with an optimized particle-to-RT-activity ratio. After characterization it could be shown that the Gag-Pro-Pol double mutant led to the highest RT-activity in the VLPs, while the amount of VLPs was too low with respect to p27. For this reason, the slippery site mutants were not used for the infection experiments. In addition to the HERV-K(HML-2) reporter viruses, the production and characterization of MMTV and JSRV particles was carried out. For this purpose, an already published vector-based reporter virus system was established for MMTV as well as new qPCR systems for the detection of RT products for MMTV and JSRV. Furthermore, ddPCR was established and used to detect certain RT products, confirming the qPCR. After the production and characterization of the reporter viruses, the synchronized infection of CRFK cells was performed. CRFK cells were harvested at certain time points after infection. The extracted DNA of the infected cells was then analyzed for the different RT products using specific primer-probe combinations in real-time PCR. Based on the detectability of the early and late RT products in the cells infected with HERV-K as well as MMTV and JSRV, it could be shown in this thesis that the reverse transcription takes place at least up to the nuclear import. Using this strategy it was expected to demonstrate the entire post-entry process including the integration of the provirus in cells infected with MMTV or JSRV, however, this was not possible like published before. Nevertheless, single copies of the 2-LTR circles could be detected. Chromosomal integration could not be detected in any of the infected cells. This could be due to the inhibition of the post-entry process by cellular restriction factors, which is likely in the case of HERV-K(HML-2). Tue, 25 Feb 2020 00:00:00 GMT http://edoc.rki.de/176904/6496 2020-02-25T00:00:00Z