Our research
The first priority of epidemiologists at HZI is investigating infectious agents that are under-researched and of particular public relevance. These include infections that can primarily be transferred from human to human (e.g. influenza) or from animal to human (e.g. Lyme disease), pathogens that are antibiotic resistant (e.g. MRSA), vaccine preventable infections (e.g. human papilloma virus, HPV) and others that are frequently acquired in hospitals (e.g. sepsis). Methodological priorities for research are short and long-term prospective cohort studies and cross-sectional surveys among the general public, secondary-data analyses and mathematical modelling.
A particular area of focus for epidemiology at HZI is the German National Cohort study (GNC) which the Helmholtz Association is carrying out together with other research facilities in Germany. The National Cohort includes a total of 200,000 individuals aged 20 to 69 years, who are recruited through a network of 18 study centers, organized in eight geographic clusters throughout Germany, representing the population of almost all federal states and covering metropolitan, urban and rural regions.
The National Cohort is designed to address research questions concerning a wide range of possible causes of major chronic diseases, to investigate factors which increase the risk of acquiring infections and to study the long term consequences of infections. The overarching objective of the National Cohort is to provide a sound knowledge base for improved and more targeted measures for the primary and secondary prevention of major diseases, tailored for the German population. The HZI has an epidemiological study centre in Hannover where 10,000 of the 200,000 test persons are examined.
The group also coordinates the PhD programme “Epidemiology”.
What exactly does an epidemiologist do?
Epidemiologists are concerned with, among other things, the distribution and determinants of health related states or events, including diseases and the application of this study to the control of diseases and other health problems. Epidemiologists employ a range of study designs, from the observational to experimental, to investigate factors that contribute to health or disease. Epidemiology is the cornerstone of public health; it supports policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive medicine.
Our research
The first priority of epidemiologists at HZI is investigating infectious agents that are under-researched and of particular public relevance. These include infections that can primarily be transferred from human to human (e.g. influenza) or from animal to human (e.g. Lyme disease), pathogens that are antibiotic resistant (e.g. MRSA), vaccine preventable infections (e.g. human papilloma virus, HPV) and others that are frequently acquired in hospitals (e.g. sepsis). Methodological priorities for research are short and long-term prospective cohort studies and cross-sectional surveys among the general public, secondary-data analyses and mathematical modelling.
A particular area of focus for epidemiology at HZI is the German National Cohort study (GNC) which the Helmholtz Association is carrying out together with other research facilities in Germany. The National Cohort includes a total of 200,000 individuals aged 20 to 69 years, who are recruited through a network of 18 study centers, organized in eight geographic clusters throughout Germany, representing the population of almost all federal states and covering metropolitan, urban and rural regions.
The National Cohort is designed to address research questions concerning a wide range of possible causes of major chronic diseases, to investigate factors which increase the risk of acquiring infections and to study the long term consequences of infections. The overarching objective of the National Cohort is to provide a sound knowledge base for improved and more targeted measures for the primary and secondary prevention of major diseases, tailored for the German population. The HZI has an epidemiological study centre in Hannover where 10,000 of the 200,000 test persons are examined.
The group also coordinates the PhD programme “Epidemiology”.
What exactly does an epidemiologist do?
Epidemiologists are concerned with, among other things, the distribution and determinants of health related states or events, including diseases and the application of this study to the control of diseases and other health problems. Epidemiologists employ a range of study designs, from the observational to experimental, to investigate factors that contribute to health or disease. Epidemiology is the cornerstone of public health; it supports policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive medicine.
In the Epidemiology Department, we use infectious disease epidemiological methods such as modeling, evidence synthesis, and epidemiological studies to capture the dynamics and disease burden of infectious diseases. We then develop and evaluate measures and (digital) tools to reduce this disease burden.
Berit Lange is a physician and epidemiologist. After studying medicine in Freiburg, Madrid, Chile and Peru, she worked for several years in Infectiology and Internal Medicine at the University Hospital Freiburg. In 2013, she graduated with a Master of Science in epidemiology from the London School of Hygiene and Tropical Medicine (LSHTM) and returned to the University Hospital of Freiburg after a postdoctoral period at the Infectious Disease Epidemiology at LSHTM. Between 2016 and 2019, she was responsible for the core module and the epidemiology course of a newly established Master's programme (Global Urban Health) at the University of Freiburg. From 2017 to 2019, she also led a research group on infectious disease epidemiology and global health there, in addition to her clinical work in Infectious Diseases.
In May 2019, Berit Lange took over the Clinical Epidemiology team in the Department of Epidemiology at the HZI. Her work focuses on better understanding the spread and burden of disease caused by respiratory infections and evaluating measures to reduce the burden of disease. To do this, she uses multicentre clinical and population-based cohort studies, surveillance data, evidence synthesis and infection modelling.
In March 2023, she additionally took over as acting head of the Epidemiology Department.
Berit Lange is elected Deputy President of the German Society of Epidemiology for 2023 and 2026 and President for 2024 and 2025. She has been spokesperson for the Modeling Network for Serious Infectious Diseases since November 2022 and has been responsible for epidemiology on the TBNet Steering Committee since 2017.
Department Management
Administration
Team Clinical Epidemiology
Team Clima, Cohorts and PIA
Team Digital Infectious Disease Surveillance (SORMAS)
Team Adaptive Infectious Disease Diagnostics
Team Strategy, Administration & Coordination
GNC Study Centre Hannover
PhD Program „Epidemiology“
Team Clinical Epidemiology
Teamleader: Dr Berit Lange
Deputy: Dr Carolina Klett-Tammen
Other team members, see team page
In the Clinical Epidemiology research team, we conduct clinical and population-based epidemiological studies (e.g. https://hzi-c19-antikoerperstudie.de/en/), do evidence synthesis and meta-analyses (www.serohub.net) and investigate the dynamics of respiratory infectious diseases within large modelling networks (e.g. www.respinow.de). For this purpose, we use and evaluate digital tools and build platforms for data exchange and In the German Centre for Infection Research (https://www.dzif.de/en), we are co-coordinator of the unit of "Translational Infrastructure Bioresources, Biodata and Digital Health" (https://www.dzif.de/en/infrastructure/bioresources-biodata-and-digital-health). We are part of the Modelling Network for Serious Infectious Diseases (MONID, website to come) with two modelling consortia.
By building and sustaining infrastructures such as rapid epidemic panels, modelling platforms and rapid evidence synthesis, we conduct epidemiological studies to better understand the dynamics, transmission and burden of respiratory infections in particular. We also evaluate pharmaceutical and non-pharmaceutical interventions and diagnostics. Study sites are both national and international in Europe, Africa and Asia.
Our work is divided into the following areas with corresponding projects:
Modelling platforms to improve the effective response to epidemics and improved understanding of infection
Respinow
RESPINOW
Consortium coordinator, BMBF:
In this modelling consortium, which we lead, the medium- and long-term effects of non-pharmaceutical interventions (NPIs) used during the COVID-19 pandemic on respiratory infections such as respiratory syncytial virus, influenza and pneumococcal disease are being researched. Our aim here is to develop an integrated model to simulate the transmission of different respiratory infections and the collateral effects of NPIs on their medium- and long-term disease burden. We are working with 10 partners from Germany and Poland to use evidence synthesis and population-based surveys to better understand the dynamics of respiratory infections during and after the pandemic, create integrated modelling and a platform for short-term predictions.
OPTIM-Agent
OPTIM-AGENT
Partner, BMBF:
This modelling consortium, led by the University of Halle, will develop a standardised framework for decision-making during a pandemic based on a specific agent-based mathematical model tailored to the German population. Particular attention will be paid to conceptualising the model incorporating expertise from different disciplines and a realistic design that takes into account heterogeneities in population structure, intra- and inter-individual contacts, mobility, individual sociological and psychological characteristics, and links epidemiological results to a framework for public health decision-making. This includes health economic analyses of direct outcomes and the impact of non-pharmaceutical interventions (NPIs) on society as a whole. The Clinical Epidemiology Unit of the HZI is particularly responsible for evidence synthesis and meta-analysis on collateral effects of non-pharmaceutical interventions to parameterise the emerging model.
SUNRISE
SUNRISE
Partner, EU:
This is an EU project to evaluate existing critical infrastructures within the EU and their interdependencies in the context of pandemics. Our task is the modelling of different pandemic scenarios and the compilation of literature on the likely effect of these scenarios on critical infrastructures.
LOKI
LOKI
Under the leadership of SIMM, HZI, this modelling consortium is establishing a local early warning system for epidemiologically relevant outbreaks of infection. The Jülich Research Centre (FZJ), the German Aerospace Centre (DLR) and the Helmholtz Centre for Environmental Research (UFZ) are involved. Clinical Epidemiology at the HZI is leading the first work package, which is concerned with providing current and retrospective data for the parameterisation of the model.
OPTI-ITS
OPTI-ITS
Partner, MWK:
This project uses agent-based modelling to investigate structural optimisation of intensive care units. The project is led by the TU Braunschweig, and the WWU Münster, the University of Halle and the University Medical Centre Göttingen are also involved.
Establishment of rapid epidemic panels and clinical cohorts for a better understanding of the infection dynamics of respiratory infections
MuSPAD
MUSPAD
Lead, Helmholtz Association:
MuSPAD is a population-based epidemic panel led by us with >33,000 participants across Germany. It was set up during the pandemic to track seroprevalence against SARS-CoV-2 throughout the pandemic. In the meantime, we have converted this study into an epidemic panel, so that rapid surveys for different infectious diseases, including sample collection at study centres, are possible.
PCR4All
PCR4ALL
Partner, EU:
To be better prepared for future pandemics originating from a yet unknown pandemic-causing agent X, more advanced measures need to be developed that can be immediately deployed as soon as a potential PX is detected, while balancing economic activity with public safety. The PCR-4-ALL team aims to achieve this in a holistic manner by bringing together expertise in (1) epidemiology, disease modelling and e-health platforms, (2) disease econometrics and (3) high-throughput screening, diagnostic technologies and clinical testing of infectious diseases. Clinical Epidemiology is responsible for conducting investigations in the MuSPAD cohort and infection modelling - in the Epidemiology Department this is done jointly with the PIA, Cohorts and Climate team.
NUM-IMMUNEBRIDGE
NUM-IMMUNEBRIDGE
Within the ad hoc NUM-IMMUNEBRIDGE project, we merged data from eight studies on protection against infection and severe course of SARS-CoV-2 and made them available to the Modelling Network for Severe Infectious Diseases (MONID). Here, the Serohub was used as a tool for data pooling.
DZIF Transplant cohort
DZIF TRANSPLANT COHORT
With the help of the DZIF Transplant Cohort, medical data and biological samples from transplanted patients throughout Germany can be collected and managed. These data and samples form the basis of scientific studies. In the process, correlations between the numerous factors that can have an influence on susceptibility to infection and the function of the organs are investigated.
TBNet
TBNET
TBNet is a network of more than 300 researchers and over 50 clinical tuberculosis centres in Europe, in which multicentre studies are carried out jointly. In TBNet we are responsible for the epidemiological part, help with the design of studies, with the evaluation and with the consolidation of studies that have already taken place.
Digital Health Tools, evidence synthesis and meta-analysis platforms
DZIF TI BBD
DZIF TI BBD
Co-coordinator, DZIF:
The infrastructure "Bioresources, Biodata and Digital Health" will in future enable overarching standardisation of biomedical data and interoperability of database systems as well as improved access to relevant biospecimens, (medical) analysis data or digital tools and methods at DZIF. The infrastructure provides information on biospecimens and pathogen collections, databases, analysis tools or apps, as well as templates, samples or work instructions, which are needed more than ever for translational infection research. Since 2021, the previous infrastructures "Biobanking", "Bioinformatics and Machine Learning", "Epidemiology" and the "Pathogen Repository" have been pooling their expertise in this new infrastructure. All DZIF researchers can use and benefit from the services, training and workshops.
DIGG-TB
DIGG-TB
Collaborative Coordinator, BMBF:
In this collaborative project, which we lead, we are working with the National Reference Laboratories in Kyrgyzstan and Armenia, the University of Freiburg, Synlab Gauteng. The aim is to establish an evidence base for the use of digital tools for TB control in the South Caucasus and Central Asia and to build potential capacity for context-sensitive and patient-centred controlled implementation of such tools in this region. Therefore, we would like to evaluate these digital tools for patients and from the user perspective in a collaborative project with the national TB control programme and create solutions for gaps that are already emerging and would be found in the process.
Serohub
SEROHUB
(Coordinator, BMBF and DZIF):
The serohub is a virtual research environment that enables individual participant data meta-analyses of various studies on SARS-CoV-2, but also on influenza, RSV and tuberculosis to be carried out on different questions. It was set up jointly by the HZI, UKK and RKI via the DZIF and the NUM project COVIM and collects individual participant data from population-based seroprevalence studies in Germany. The data can be made available anonymously to other academic researchers.
Network for University Medicine
Within the Network for University Medicine, we are responsible as work package leaders in NUM-COVIM 1.0 and 2.0 for population immunity, in NUM-IMMUNEBRIDGE for data pooling and analysis, and contribute evidence synthesis and expertise as partners in NUM-CoverChild and NUM-Prepared.
Selected Publications
Heinsohn, T., Lange, B., Vanella, P., Rodiah, I., Glöckner, S., Joachim, A., Becker, D., Brändle, T., Dhein, S., Ehehalt, S., Fries, M., Galante-Gottschalk, A., Jehnichen, S., Kolkmann, S., Kossow, A., Hellmich, M., Dötsch, J., & Krause, G. (2022b). Infection and transmission risks of COVID-19 in schools and their contribution to population infections in Germany: A retrospective observational study using nationwide and regional health and education agency notification data. PLoS Med, 19(12), e1003913. https://doi.org/10.1371/journal.pmed.1003913
Rodiah, I., Vanella, P., Kuhlmann, A., Jaeger, V. K., Harries, M., Krause, G., Karch, A., Bock, W., & Lange, B. (2023). Age-specific contribution of contacts to transmission of SARS-CoV-2 in Germany. Eur J Epidemiol. https://doi.org/10.1007/s10654-022-00938-6
Fricke, L. M., Glockner, S., Dreier, M., & Lange, B. (2021). Impact of non-pharmaceutical interventions targeted at COVID-19 pandemic on influenza burden - a systematic review. J Infect, 82(1), 1-35. https://doi.org/10.1016/j.jinf.2020.11.039
Gornyk, D., Harries, M., Glöckner, S., Strengert, M., T., K., Bojara, G., Castell, S., Frank, K., Gubbe, K., Heise, J.-K., Hernandez, P., Kappert, O., Kern, W., Illig, T., Klopp, N., Maaß, H., Ortmann, J., Barbora Kessel, B., Roller, G., . . . Krause, G. (2021). SARS-CoV-2 seroprevalence in Germany - A population based sequential study in seven regions. Deutsches Ärzteblatt Int, 118: 824.https://doi.org/10.3238/arztebl.m2021.0364
Rishi K. Gupta, Claire J. Calderwood, Alexei Yavlinsky, Maria Krutikov, Matteo Quartagno, Maximilian C. Aichelburg (…),Berit Lange (…) Ibrahim Abubakar; Discovery and validation of a personalised risk predictor for incident tuberculosis in settings aiming towards pre-elimination (PERISKOPE-TB), Nature Medicine, 2020 , doi.org10.1038/s41591-020-1076-0
Climate, Cohorts and PIA
Team leader: Dr. Stefanie Castell
Deputy team leader: N.N.
Further team members, see team page
The research of the "Climate, Cohorts and PIA" team is concerned with the (digital) implementation of population-based long-term cohorts. Scientific projects are anchored in particular in the German National Cohort (NAKO). The team is dedicated to the epidemiological investigation of determinants including multi-omics and (long-term) consequences of infections or susceptibility to infections. In addition, infectious diseases are evaluated in the context of planetary health. The team is also involved in the field of citizen science and is interested in participatory approaches in epidemiological research.
One focal point of the team is applied digital epidemiology. Here we focus on the further development and establishment of our free and open source (FOSS) eResearch system PIA ("Prospective Monitoring and Management App") as a digital management tool for long-term epidemiological studies. As a generic system, PIA offers the possibility to conduct cohort studies or surveys including biosample management digitally. PIA has been developed at the HZI since 2017 under the leadership of Dr. Stefanie Castell as Product Owner and was used for the first time in 2019 as part of an additional project of the NAKO for population-based research of transient infections. Since then, further projects from the field of infection research have been continuously integrated.
The team also includes the Hanover Study Center.
Climate, Cohorts and PIA
Integrated DZIF Infection Cohort within German National Cohort (ZIFCO)
The ZIFCO study is an L3 project (additional project) integrated into the German National Cohort (NAKO) with the aim of investigating risk factors for susceptibility to transient infectious diseases. In the future, the consequences of these infections will also be researched. The long-term infrastructure of the NAKO provides an ideal basis for this. ZIFCO complements this with a specially developed digital application for translational infection research. ZIFCO not only relies on regular digital self-reports from participants, but also supplements these in the case of acute respiratory infections with self-collected nasal swabs. These are analyzed for various viruses using multiplex PCR at Hannover Medical School. As an L3 project of the NAKO, ZIFCO thus offers the opportunity to expand the extensive standard program of the largest German cohort study to include epidemiological research on acute respiratory, gastrointestinal and urogenital infections. This enhances the examination of participants at the study center (approximately every 5 years) through the digital support of the participants by PIA in everyday life.
Funded by the Helmholtz Centre for Infection Research (HZI), the Helmholtz Association and the German Center for Infection Research (DZIF)
Partners: German National Cohort (NAKO), Institute of Virology at Hannover Medical School, Hannover Unified Biobank, Helmholtz Institute for RNA-based Infection Research (HIRI)
Paving the way towards individualized vaccination (i.Vacc) - Exploring multi-omics Big Data in the general population based on a digital mHealth cohort (i.Vacc)
The i.Vacc project uses data and biosamples from the intensified infection cohort (ZIFCO), in particular living immune cells (PBMC) and plasma. These are used to create multi-omics profiles that include levels of genetics, proteomics and immune profiling. The focus is on the prediction of susceptibility to infection and immunological response to infection or vaccination. Due to the SARS-CoV-2 pandemic, the project also includes parameters of the immune response to a SARS-CoV-2 infection or vaccination as an outcome. The overall project objective is to generate hypotheses for more stratified, i.e. individualized, vaccination recommendations as a conceptual basis. The methodological focus is on statistical analyses in the area of big data. In i.Vacc, highly complex molecular datasets are combined with longitudinal cohort data collected repetitively via PIA in ZIFCO and epidemiological-clinical baseline data from the German National Cohort (NAKO).
Funded by the Ministry of Science and Culture of Lower Saxony and the German Volkswagen Foundation
Partners: Hannover Unified Biobank (Hannover Medical School), Department of Vaccinology and Applied Microbiology (HZI), Institute for Information Engineering at the Ostfalia University of Applied Sciences, Department of Bioinformatics of Infection Research (HZI), Department of Cellular Proteome Research (HZI), Translational Alliance Lower Saxony TRAIN Omics / BIOMEDAS (BIOMEdical DAta Science) at the MHH
Pre4D
To ensure that PIA can be used successfully in epidemiological research on transient infections in the long term and be established in other market areas in the future, the adherence of study participants is crucial and requires special demands on the user-friendliness of PIA. In the Pre4D project from the field of technology transfer, solutions for improving the user-friendliness of PIA are being identified and implemented. This also includes optimizing maintainability and partial refactoring in order to reduce bugs and problems that impair usability. Gamification approaches are also included by developing a feedback module tailored to PIA. Attention is paid to the greatest possible generic functionality to enable broad future use.
Funding: Pre-4-D Fund of the Helmholtz Center for Infection Research
Partners: --
Needs and requirements for PIA (“Prospective Monitoring and Management App”) - Potential client and user perspective (NeRe4PIA)
This project aims to systematically gain knowledge about what needs and requirements are necessary from the perspective of potential users for a desired broader application of PIA in order to compare the vision with the needs and interests of both future stakeholders and the open source software community as an existing FOSS.
Funding: Supported by the Initiative and Networking Fund as part of the "Helmholtz Enterprise" funding program
Partners: --
RESIST Cohort
The RESIST Cluster of Excellence focuses on infections and people who are particularly susceptible to them. For population-based research in this area, a specific cohort of predominantly older people has been established. The cohort participants are interviewed and examined on site at the Hannover Study Center of Dr. S. Castell's team on behalf of the Hannover Medical School. The results are documented by the study team in PIA. The aim of this cohort is to gain a better understanding of individual susceptibility to infections and human defense mechanisms.
Funding: Resist Cluster of Excellence, co-funded by the German Research Foundation
Partners: Implementation on behalf of the Hannover Medical School
App-based Infection Assessment in RESIST (iAR)
The primary aim is the prospective investigation of risk factors for common infectious diseases such as acute respiratory infections. We also integrate questions related to the gut microbiome as well as investigate symptoms of vector-borne diseases caused by tick bites.
In both ZIFCO and iAR, questions regarding user acceptance and usability of the digital HZI application PIA as well as compliance with the mobile/web-based application and the study concept are being analyzed.
Funding: Resist Cluster of Excellence, co-funded by the German Research Foundation
Partners: Institute of Virology at Hannover Medical School, Hannover Unified Biobank
Impact and viability of a novel mass PCR testing method as a pandemic-fighting strategy (PCR-4-All)
In order to be prepared for future major outbreaks, measures must be developed that can be implemented immediately in the event of a pandemic. The PCR-4-ALL project brings together expertise from the fields of (1) epidemiology, disease modeling and e-health platforms, (2) disease econometrics and (3) high-throughput screening, diagnostic technologies and clinical testing of infectious diseases. Within the project, the "Climate, Cohorts and PIA" team is responsible for the further development of digital requirements, integrating cohorts into the project and evaluating practical feasibility. In the Department of Epidemiology, this is done together with the "Clinical Epidemiology" team.
Funding: European Union
Partners: Katholieke Universiteit Leuven, Belgium, Università Degli Studi Di Verona, Italy, Fundació Privada Institut de Recerca de la Sida Caixa, Spain
Pilot Digitale Citizen Science Kohorte (PIA4All)
Sensors for measuring aerosols and reactive gases and analyzing their impact on health (SMARAGD)
The aim of this citizen science project is to link pollutant measurements with health data together with citizen scientists. To this end, the participants install special pollutant sensors in their environment and report their health status using the HZI application PIA ("Prospective Monitoring and Management App", www.info-pia.de). The Research Center Jülich is responsible for the scientific supervision of the pollutant measurement. The sensors record particulate matter, nitrogen oxides, ozone and carbon monoxide. The health data focuses on respiratory infections. The project is a feasibility study. As a citizen science project, SMARAGD also aims to integrate interested citizens into the project planning and to actively shape the process. Therefore workshops are organized with citizens in which framework conditions and content are discussed, developed and modified to enable joint learning and knowledge transfer in both directions.
Funding: Helmholtz Association
Partners: Research Center Jülich, Helmholtz Center Munich - German Research Center for Environmental Health (HMGU)
Digital epidemiology in the German National Cohort (NAKO): "Participant Involvement"
As part of the 3rd funding phase of the German National Cohort (NAKO), further digitalization of the study is planned. The HZI is responsible for the "Participant Involvement" sub-project. Here, participants should be involved more closely via digital structures so that information can flow efficiently from NAKO institutions to participants and vice versa. In order to adequately consider the user perspective in the development, we plan to implement the design thinking approach in the sense of citizen science with interested NAKO participants and other stakeholders in the first project phase.
Funding: Federal government, federal states and Helmholtz Association
Partners: German National Cohort (NAKO)
New health risks due to biodiversity-based urban ecosystem disservices (Kontravital)
Urban green infrastructure can be associated with effects that can be perceived as harmful, unpleasant or undesirable, the so-called counterproductive ecosystem services (CES). For sustainable planning of urban green infrastructure, it is important to consider these in addition to the benefits. The aim of the project is to close existing gaps in knowledge about CES. It examines aspects of physical and mental health such as allergies, zoonoses and stress. It is planned to integrate the findings into a communal planning tool. The HZI is involved in the project in the area of zoonoses and digital study infrastructure.
Funding: Federal Ministry of Education and Research (BMBF)
Partners: Magdeburg-Stendal University of Applied Sciences
Climate changes and their impact on vector-borne Lyme disease (Hi-Cam)
As part of the Helmholtz Climate Initiative, this project aims to estimate the occurrence of Lyme disease in Germany as a function of climatic variables using statistical-mathematical modeling. In a second part, we deal with the serostatus in relation to Lyme disease and associated factors. Therefore biosamples and data from the German National Cohort (NAKO) and the Rhineland Study are used.
Funding: Helmholtz Center for Infection Research (HZI), Helmholtz Association
Partners: Rhineland Study of the German Center for Neurodegenerative Diseases e.V. (DZNE), NAKO Health Study, Helmholtz Centre for Environmental Research (UFZ), Climate Service Center Germany (GERICS)
Effectiveness of antibiotic training for general practitioners (WASA)
Treating common infections such as upper/lower respiratory tract and urinary tract infections can be a challenge for GPs. According to an analysis of health insurance data, almost 30% of all antibiotic prescriptions are unnecessary (see DAK). At the same time, the WHO declared antibiotic resistance to be one of the ten most threatening global health problems (see WHO). Treatment with antibiotics is one of the main factors in the development of this resistance. As 85% of antibiotics are prescribed in the outpatient sector (GERMAP), the project "Effectiveness of training in rational antibiotic management for general practitioners" was developed. In collaboration with the Southeast Lower Saxony Hygiene Network, GPs in the region were offered a guideline-based training module on upper and lower respiratory tract and urinary tract infections. The module was evaluated by the Department of Epidemiology at the HZI with regard to participation and effectiveness. To this end, the participating GPs were surveyed and antibiotic prescription data from the AOK Lower Saxony was analyzed.
Funding: Federal Ministry of Health (BMG)
Partners: Southeast Lower Saxony Hygiene Network, Braunschweig Health Department, Braunschweig Municipal Hospital, Lower Saxony State Health Office, AOK Lower Saxony, Lower Saxony Medical Association
Evaluation and Expansion Evaluation of existing cohorts to address One Health Topics in Germany (PanCo)
One Health (OH) considers the health of humans, animals and ecosystems as interdependent. OH surveillance (OHS) involves systematic and comprehensive longitudinal data collection that is manageable, including, if possible and relevant, biosamples from humans, animals and the environment. OHS is based on longitudinal data collection, i.e. cohort research. Therefore, in PanCo we aim to develop a OH framework suited for OHS including a stakeholder analysis, semi-structured interviews and group discussions. We also map ongoing OH epidemiological studies and assess existing population-based cohorts in German speaking areas, such as NAKO and SHIP, for their relevance to OH issues, despite their primary focus or main data collection not being intended for OH research. By identifying OH-relevant information and there availability in these and other existing studies, the project seeks to inform the development of OH-specific modules for integration into existing cohorts or the establishment of a new OHS study.
Hence, the project will provide recommendations for OH-module development and longitudinal OHS.
Partner institutions: Friedrich-Löffler-Institut, Helmholtz Institute for One Health, Universitätmedizin Greifswald
Selected Publications
Soja, S. M., Wegener, R., Kille, N., & Castell, S. (2023). Merging citizen science with epidemiology: design of a prospective feasibility study of health events and air pollution in Cologne, Germany. Pilot and Feasibility studies, 9(1), 28. https://doi.org/10.1186/s40814-023-01250-0.
Ortmann, J., Heise, J. K., Janzen, I., Jenniches, F., Kemmling, Y., Frömke, C., & Castell, S. (2023). Suitability and user acceptance of the eResearch system "Prospective Monitoring and Management App (PIA)"-The example of an epidemiological study on infectious diseases. PloS One, 18(1), e0279969. https://doi.org/10.1371/journal.pone.0279969.
Heise, J-K., Dey, R., Emmerich, M., Kemmling Y., Sistig S., Krause G., et al. (2022). Putting digital epidemiology into practice: PIA- prospective monitoring and management application. Inform Med Unlocked. 30, 100931. https://doi.org/10.1016/j.imu.2022.100931.
Coors, A., Hassenstein, M. J., Krause, G., Kerrinnes, T., Harries, M., Breteler, M. M. B., & Castell, S. (2022). Regional seropositivity for Borrelia burgdorferi and associated risk factors: findings from the Rhineland Study, Germany. Parasites & Vectors, 15(1), 241. https://doi.org/10.1186/s13071-022-05354-z.
Gornyk, D., Scharlach, M., Buhr-Riehm, B., Klett-Tammen, C. J., Eberhard, S., Stahmeyer, J. T., Großhennig, A., Smith, A., Meinicke, S., Bautsch, W., Krause, G., & Castell, S. (2021). Effectiveness of Trainings of General Practitioners on Antibiotic Stewardship: Methods of a Pragmatic Quasi-Experimental Study in a Controlled Before-After Design in South-East-Lower Saxony, Germany (WASA). Frontiers in Pharmacology, 12, 533248. https://doi.org/10.3389/fphar.2021.533248.
Team “Digital Infectious Disease Surveillance (SORMAS)”
Team Leader: Dr. Anja M. Hauri
Deputy: N.N.
Other team members, see team page
Surveillance Outbreak Response Management and Analysis System (SORMAS)
The Surveillance Outbreak Response Management and Analysis System (SORMAS) is an open-source software that started in 2015 as a research project at the Epidemiology Department of the Helmholtz Centre for Infection Research (HZI) in cooperation with Nigerian partners specifically for the control of epidemics. The system, that allows not only the routine disease surveillance but also the detection and control of outbreaks, has evolved into a fully functional tool. SORMAS has already been implemented in 11 countries in five WHO regions.
The large success of the SORMAS implementation and expansion has led to the possibility to establish a spin-off with the aim to ensure the sustainability of SORMAS. The SORMAS Foundation was established in 2022 and is now responsible for the curation of the software, support of its deployment in countries, community building and trainings. The Digital Infectious Disease Surveillance research group at HZI retains the responsibility of research into its implementation, its further development and the type of data it collects.
Currently, the team is developing a module for environmental surveillance in SORMAS and has ongoing projects to expand the implementation of SORMAS in Nepal, Cote d’Ivoire and DR Congo.
To support the use of SORMAS exported data in research as well as support the interpretation of epidemiological parameters for public health stakeholders, we developed the SORMAS Statistics (SORMAS-Stats) application for real-time estimation of epidemiological parameters (Silenou et al., 2022). We will leverage the R Shiny application (SORMAS-Stats) to develop models including those that incorporate data from the environment and animals for forecasting case incidence and outbreaks in real-time. We will also develop statistical packages and apps to permit field users to perform analyses using the developed models.
SORMAS@DEMIS
The SORMAS@DEMIS project, led by the Helmholtz Centre for Infection Research (HZI) and with the active participation of the Robert Koch Institute (RKI), aimed to develop, implement and evaluate a pilot system that significantly reduces the workload in the Public Health Service (ÖGD). For this purpose, interfaces to existing systems were developed. These included SurvNet – the reporting software developed by the RKI, the German Electronic Reporting and Information System for Infection Protection (DEMIS), and the Climedo symptom diary. The existing software solutions were adapted to the needs of the ÖGD, and the individual components were harmonized with each other. A major focus of the project was also on ensuring data protection, data security, and quality assurance. Within this project, among other things, we developed SORMAS-to-SORMAS, the first solution for public health offices to exchange reporting data without media discontinuity not only between laboratories, hospitals and the RKI, but also between counties using SORMAS. The project ended in December 2023.
Mobile Digital Preparedness and Response without Borders (DigiPREW)
The DigiPREW project is developing solutions for biological threat detection and response management in four work packages. As a digital eHealth tool, SORMAS is the technical backbone of DigiPREW. The overall goal of the project is to develop a mobile digital threat response tool and a mobile digital laboratory information and management system (LIMS) for the European Mobile Laboratory (EMLab) network. This further includes support to user training and field piloting in DR Congo. Partners in this collaborative project are the Bernhard Nocht Institute for Tropical Medicine (BNITM), the Bordeaux School of Public Health, Univ. Bordeaux (ISPED), and the Alliance for International Medical Action (ALIMA). The consortium is coordinated by the team “digital infectious disease epidemiology”.
SORMAS goes One Health: Water-based Outbreak Prediction in Peri-Urban Africa (SORMAS-WOPPA)
The partnership of this project is led by the Institute for International Animal Health/One Health of the Friedrich-Löffler-Institute (FLI), in collaboration with the Department of Epidemiology of the HZI, the Institute of Diagnostic Virology (FLI), the Institute of Epidemiology (FLI), the Institute of Pharmacy of the University of Greifswald, the Kwame Nkrumah University of Science and Technology (KNUST) and the Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR).
The objectives of this project are: a) to develop a concept for the incorporation of environmental (water) signals into SORMAS for the prevention of public and veterinary health outbreaks, and b) to establish baseline data and new knowledge on the depth of microbial diversity and pathogens with epidemic potential in peri-urban Africa, and for consistent monitoring of water reservoirs.
Current infectious disease surveillance systems typically employ strategies to monitor communicable diseases at a time when these diseases are already present in a given population. While environmental water samples are already used to monitor biodiversity of terrestrial and aquatic pathogens, the data are rarely linked to veterinary and public health surveillance systems. Water samples provide an easy-to-use matrix for laboratory analysis, accumulating microbes circulating at the human-pet-wildlife interface, often before disease outbreaks are reported, and combine early detection with reliable and standardised laboratory-based testing. An automated monitoring and subsequent management of water sources in peri-urban Africa would tackle diseases before they manifest in humans or animals. Since the software has already been integrated into the national public health surveillance system in Ghana, we team up with our long-term collaborator – the KCCR at KNUST.
COVID-19-Outbreak Response combining E-health, Serolomics, Modelling, Artificial Intelligence and Implementation Research (CORESMA)
CORESMA is a Horizon Europe project that started on the Corona pandemic in April 2020 and will end in December 2023. The consortium is coordinated by Dr. Berit Lange – head of the Department of Epidemiology. CORESMA combines an accelerated ad hoc outbreak response to address urgency and a sustainable strategy that goes beyond the current public health threat of COVID-19. Our approach is innovative, combining unique mHealth technology, multiplex serolomics, state-of-the-art modeling, artificial intelligence, and implementation research. For more information, visit www.coresma.eu.
The "Digital Surveillance of Infectious Diseases (SORMAS)" team is responsible for WP1 – improving public health preparedness and availability of meaningful real-time data through digital health surveillance with SORMAS. Within this WP, SORMAS is being piloted in Nepal and Côte d'Ivoire.
Selected Publications
Silenou, B. C., Nyirenda, J. L. Z., Zaghloul, A., Lange, B., Doerrbecker, J., Schenkel, K., & Krause, G. (2021). Availability and Suitability of Digital Health Tools in Africa for Pandemic Control: Scoping Review and Cluster Analysis. JMIR Public Health Surveill, 7(12), e30106. https://doi.org/10.2196/30106
Silenou, B. C., Tom-Aba, D., Adeoye, O., Arinze, C. C., Oyiri, F., Suleman, A. K., Yinka-Ogunleye, A., Dorrbecker, J., Ihekweazu, C., & Krause, G. (2020). Use of Surveillance Outbreak Response Management and Analysis System for Human Monkeypox Outbreak, Nigeria, 2017-2019. Emerg Infect Dis, 26(2), 345-349. https://doi.org/10.3201/eid2602.191139
Silenou, B. C., Verset, C., Kaburi, B. B., Leuci, O., Ghozzi, S., Duboudin, C., & Krause, G. (2022). A Novel Tool for Real-time Estimation of Epidemiological Parameters of Communicable Diseases Using Contact-Tracing Data: Development and Deployment. JMIR Public Health Surveill, 8(5), e34438.https://doi.org/10.2196/34438
Gupta R.K., Calderwood C.J., Yavlinsky A., .., Hauri A.M., ...,Lange B., …., Abubakar I. Discovery and validation of a personalized risk predictor for incident tuberculosis in low transmission settings. Nat Med. 2020 Dec;26(12):1941-1949. doi: 10.1038/s41591-020-1076-0.
Tom-Aba, D., Silenou, B. C., Doerrbecker, J., Fourie, C., Leitner, C., Wahnschaffe, M., Strysewske, M., Arinze, C. C., & Krause, G. (2020). The Surveillance Outbreak Response Management and Analysis System (SORMAS): Digital Health Global Goods Maturity Assessment. JMIR Public Health Surveill, 6(2), e15860. https://doi.org/10.2196/15860
Team "Adaptive Infectious Disease Diagnostics"
Team leader: Dr Monika Strengert
Deputy team leader: Dr Vanessa Melhorn
Other team members, see team page
Our work focuses on the development of non-invasive and easy-to-use biosampling technologies and innovative systems for molecular and immunological pathogen diagnostic. By combining those two research areas, novel biomaterials and multi-parametric biological data sets become available to epidemiological studies which analyze the frequency of infectious diseases and their risk factors, the immune status of a population or an individual and the influence of (non)pharmaceutical interventions on disease burden and transmission.
Bead-based multiplex assays to characterize immune responses
Serological methods are essential tools across multiple research disciplines to investigate previous pathogen exposures within populations as part of epidemiological studies, to understand the role of antibody responses in disease progression or to develop novel therapeutics or vaccines. In contrast to conventional single-analyte technologies such as ELISAs, our work primarily focuses on the development of resource- and time-saving multiplex immunoassays based on Luminex technology with a particular focus on differentiating vaccine- from infection-elicited antibody responses. By utilizing fluorescently labelled magnetic beads which allow a separation into spectrally distinct populations up to 500 different analytical endpoints can be measured in parallel, while at the same time only using ~5µL of sample making multiplex immunoassay ideal for studies where sample volume is limited.
Directly after the emergence of SARS-CoV-2 in early 2020, MULTICOV-AB™ was developed. By combining the trimeric SARS-CoV-2 Spike protein, its S1, S2 and the Receptor-Binding domain, as well as the Nucleocapsid (N) protein a thorough characterization of antibody-driven immune responses after vaccination and infection is possible. The inclusion of the S1 and N antigens from the seasonal “common-cold” coronaviruses NL63, HKU1, OC43 and 229E further enables the assessment of cross-reactive antibody patterns within a single measurement. While MULTICOV-ABTM was originally designed for use with human serum or plasma samples, it was later expanded to measure saliva [3], enabling insights into immune protection at the primary site of infection. For the functional analysis of SARS-CoV-2 antibodies responses, RBDCoV-ACE2, a competitive cell- and virus-free ACE2 binding inhibition assay is now also available . To keep up with the rapid genomic evolution of SARS-CoV-2 into various sub-lineages, the antigen panels of both assays have been continuously expanded with emerging variants of concern receptor-binding domains which made their use in a variety of studies possible. For instance, in household transmission studies (Example Study 1; Example study 2) or in SARS-CoV-2 seroprevalence studies in Germany, Nepal and Colombia. With the approval of multiple SARS-CoV-2 vaccines, both complementary methods are now more dominantly used to analyze antibody responses after different immunizations schemes in the general population and among at risk individuals for severe COVID-19.
Using insights and expertise gained from the SARS-CoV-2 pandemic, we are currently working on developing additional multiplex immunoassays for other pathogens, such as respiratory syncytial virus or influenza virus. Those novel assays are then utilized to generate biological data for RESPINOW. RESPINOW, a modeling consortium led by Berit Lange, investigates the medium- and long-term effects of non-pharmaceutical interventions used during the COVID-19 pandemic on the transmission of other respiratory infections.
Next to developing tools to study antibody responses towards those respiratory pathogens, multiplex immunoassays to measure humoral immunity towards viral hepatitis A-D, measles, mumps, varicella and rubella viruses are currently established. For vaccine-preventable infections such as measles and hepatitis A and B, the capability of our assays to differentiate vaccination from infection antibodies will result in the generation of valid and reproducible indicators in population-based serosurveys to assess the efficiency of vaccination campaigns independent of vaccination registers or documentation and determine infection prevalence without targeted molecular surveillance. Last, we aim to develop further bead-based assays for a functional evaluation of B-cell responses beyond mere antigen-antibody binding analysis for instance to define neutralization strength and Fc-mediated antibody effects.
Partners: NMI Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen, Klinik für Rheumatologie und Immunologie der Medizinischen Hochschule Hannover, Hannover Unified Biobank, Niedersächsisches Landesgesundheitsamt, Luxembourg Institute of Health, Technologieplattform Rekombinante Proteinexpression des HZI
Funding: Helmholtz-Gemeinschaft, Deutsches Zentrum für Infektionsforschung, Niedersächsisches Ministerium für Wissenschaft und Kultur, Europäische Union
New approaches in biosample collection, conservation and stabilization
Epidemiological field studies depend on high-quality biomaterials for significant and reliable results. As molecular and immunological detection capabilities has much faster evolved than the actual biosampling technologies, we are developing novel concepts and devices for (self-)sampling at home and as part of cohort studies. For instance, a sampling method to enrich and collect pathogens from the lower respiratory tract non-invasively and with minimal resources compared to the current standard procedure of bronchoscopy is developed (PADFEX - A device for direct pathogen detection in filtered expirates). Next to increasing available biosamples types for down-stream analysis, the development of preservation and stabilization methods that maintain the quality of biomaterials, which need to be collected outside of strictly controlled and highly standardized study conditions is also of importance (study). Those new developments are carried out in an interdisciplinary approach in cooperation with experts from life, engineering and material sciences.
Selected Publications and Patents
Becker, M., M. Strengert, D. Junker, P. D. Kaiser, T. Kerrinnes, B. Traenkle, H. Dinter, J. Haring, S. Ghozzi, A. Zeck, F. Weise, A. Peter, S. Horber, S. Fink, F. Ruoff, A. Dulovic, T. Bakchoul, A. Baillot, S. Lohse, M. Cornberg, T. Illig, J. Gottlieb, S. Smola, A. Karch, K. Berger, H. G. Rammensee, K. Schenke-Layland, A. Nelde, M. Marklin, J. S. Heitmann, J. S. Walz, M. Templin, T. O. Joos, U. Rothbauer, G. Krause, and N. Schneiderhan-Marra. "Exploring Beyond Clinical Routine Sars-CoV-2 Serology Using Multicov-Ab to Evaluate Endemic Coronavirus Cross-Reactivity." Nat Commun 12, no. 1 (Feb 19 2021): 1152. https://dx.doi.org/10.1038/s41467-021-20973-3.
Strengert, M., M. Becker, G. M. Ramos, A. Dulovic, J. Gruber, J. Juengling, K. Lürken, A. Beigel, E. Wrenger, G. Lonnemann, A. Cossmann, M. V. Stankov, A. Dopfer-Jablonka, P. D. Kaiser, B. Traenkle, U. Rothbauer, G. Krause, N. Schneiderhan-Marra, and G. M. N. Behrens. "Cellular and Humoral Immunogenicity of a Sars-Cov-2 mRNA Vaccine in Patients on Haemodialysis." EBioMedicine 70 (Aug 2021): 103524. https://dx.doi.org/10.1016/j.ebiom.2021.103524.
A. Dulovic, B. Kessel, M. Harries, M. Becker, J. Ortmann, J. Griesbaum, J. Jüngling, D. Junker, P. Hernandez, D. Gornyk, S. Glöckner, V. Melhorn, S. Castell, J.K. Heise, Y. Kemmling, T. Tonn, K. Frank, T. Illig, N. Klopp, N. Warikoo, A. Rath, C. Suckel, A.U. Marzian, N. Grupe, P.D. Kaiser, B. Traenkle, U. Rothbauer, T. Kerrinnes, G. Krause, B. Lange, N. Schneiderhan-Marra, M. Strengert. “Comparative magnitude and persistence of humoral SARS-CoV-2 vaccination responses on a population level in Germany.” Front Immunol. 2022;13:828053. Published 2022 Feb 16. doi:10.3389/fimmu.2022.828053
H. Jacobsen, M. Strengert, H. Maaß, M. A. Ynga Durand, B. Kessel, M. Harries, U. Rand, L. Abassi, Y. Kim, T. Lüddecke, P. Hernandez, J. Ortmann, J.-K. Heise, S. Castell, D. Gornyk, S. Glöckner, V. Melhorn, Y. Kemmling, B. Lange, A. Dulovic, J. Häring, D. Junker, N. Schneiderhan-Marra, M. Hoffmann, S. Pöhlmann, G. Krause, L. Cicin-Sain: “Diminished neutralization responses towards SARS-CoV-2 Omicron VoC after mRNA or vector-based COVID-19 vaccinations. ”Scientific Reports 2022. doi.org/10.1038/s41598-022-22552-y
Häring J., Hassenstein MJ., Becker M., Ortmann J., Junker D., Karch A., Berger K., Tchitchagua T., Leschnik O., Harries M., Gornyk D., Hernández P., Lange B., Castell S., Krause G., Dulovic A., Strengert M., Schneiderhan-Marra N.. „Borrelia multiplex: a bead-based multiplex assay for the simultaneous detection of Borrelia specific IgG/IgM class antibodies.“ BMC Infect Dis. 2022. : doi.org/10.1186/s12879-022-07863-9
N. Villalobos, B. Kessel, J. Carolina Torres Páez, J. Strömpl, T. Kerrinnes, F. Pio de la Hoz Restrepo, M. Strengert, G. Krause. “Seroprevalence of Hepatitis E virus in children and adolescents living in urban Bogotá: an explorative cross-sectional study.” Frontiers in Public Health 2023: doi:10.3389/fpubh.2023.981172
Krause G., Castell S., Kerrinnes, T., Strengert M. “PADFEX: assembly for enrichment of microorganisms present in the aerosol including small droplets from respiratory air of a subject and method for enrichment of microorganisms” (EP000004012042A1; WO002022129019A1)
Team Strategy, Administration & Coordination
Teamleader: Dr Vanessa Melhorn
Deputy: Dr Marieke Ahlborn
Other team members, see team page
The Strategy, Administration and Coordination team works on two topics:
On the one hand, the tasks lie in supporting the head of department (secretariat), in internal departmental personnel planning and implementation, budget management of departmental funds and third-party funded projects, project management of existing projects and in the management of existing resources (building and space planning, hardware, etc.).
On the other hand, the team supports the coordination of the strategic orientation of the department's scientific research content and in the acquisition of third-party funding. This includes the development and monitoring of the department's internal research strategy in the context of programme-oriented funding and the standardisation of research organisational processes.
Objectives
During the course of the programme, PhD fellows are being prepared to conduct independent epidemiological and public health relevant research. After successful completion, the fellows can enter career paths in academia, research and science, national health institutions, ministries, health insurances, international organizations or other non-governmental organizations.
The programme supports individual training and career plans according to background studies and interests.
Further objectives of the programme include:
- To gather experience in independent planning, management, implementation, and evaluation of epidemiological research projects
- To acquire comprehensive knowledge on epidemiological and statistical methods
- To scientifically contribute to narrow evidence gaps in epidemiological and health research
- To acquire the ability to present results and methods of epidemiological research at conferences and in peer-reviewed journals
- To support the understanding of Good Epidemiological Practice
Programme and Research
- The duration of each PhD programme cycle is three years.
- The PhD programme is structured into individual epidemiological research activity on the one hand (125 Credit Points) and accompanying mandatory educational programme (55 Credit Points, minimum 300 Teaching Units (TU's)) on the other hand.
- The accompanying educational programme contains lectures and seminars, as well as epidemiological fieldwork in our study centre and epidemiological laboratory.
- All training elements are taught in English. The PhD programme is integrated in and supported by a network of PhD students, PostDocs and supervisors with various scientific backgrounds.
Phd programme
Further information regarding the PhD programme Epidemiology can be found here.
Study centre Hannover
The “National Cohort”, with its Germany-wide 200,000 participants and 18 study centres, is the largest health-study programme in German history. Approximately 10,000 participants from the greater metropolitan area of Hannover are to be examined and interviewed at the study centre Hannover.
Technology Offers
The following technologies were developed by the Epidemiology department and partially have been registered for patent:
- Low Bandwidth Data Base Synchronization (LBDS)
- Multiplex Serology for Population-based Serosurveys
- Pathogen Detection in Filtered Expirates (PADFEX)
- Surveillance Outbreak Response Management & Analysis System (SORMAS)
Selected Publications
Rodiah, I., P. Vanella, A. Kuhlmann, V.K. Jaeger, M. Harries, G. Krause, A. Karch, W. Bock, B. Lange. "Age-Specific Contribution of Contacts to Transmission of Sars-Cov-2 in Germany." European Journal of Epidemiology (2023).
https://doi.org/10.1007/s10654-022-00938-6
Heinsohn, T., B. Lange, P. Vanella, I. Rodiah, S. Glöckner, A. Joachim, D. Becker, et al. "Infection and Transmission Risks of Covid-19 in Schools and Their Contribution to Population Infections in Germany: A Retrospective Observational Study Using Nationwide and Regional Health and Education Agency Notification Data." PLOS Medicine 19, no. 12 (2022)
https://dx.doi.org/10.1371/journal.pmed.1003913
Peters, A., A. Peters, K. Halina Greiser, S. Göttlicher, W. Ahrens, M. Albrecht, F. Bamberg, et al. "Framework and Baseline Examination of the German National Cohort (Nako)." European Journal of Epidemiology (2022).
https://doi.org/10.1007/s10654-022-00890-5
Becker, M., M. Strengert, D. Junker, P. D. Kaiser, T. Kerrinnes, B. Traenkle, H. Dinter, et al. "Exploring Beyond Clinical Routine Sars-Cov-2 Serology Using Multicov-Ab to Evaluate Endemic Coronavirus Cross-Reactivity." Nat Commun 12, no. 1 (2021): 1152.
https://www.ncbi.nlm.nih.gov/pubmed/33608538.
https://doi.org/10.1038/s41467-021-20973-3
Yinka-Ogunleye, A., O. Aruna, M. Dalhat, D. Ogoina, A. McCollum, Y. Disu, I. Mamadu, et al. "Outbreak of Human Monkeypox in Nigeria in 2017–18: A Clinical and Epidemiological Report." The Lancet Infectious Diseases 19, no. 8 (2019): 872-79.
https://doi.org/10.1016/s1473-3099(19)30294-4