Title Promoter Affiliations Abstract "Point of care gathering and real-time utilization of smartphone generated movement traces of patients for infectious disease containment in the community." "Emmanuel Andre" "Laboratory of Clinical Microbiology" "In this PhD thesis, we applied different methods in clinical and epidemiological studies to understand the factors that contributed to respiratory pathogen transmission. These insights could, in turn, improve pathogen surveillance and interruption of transmission. In one chapter, we compared SARS-CoV-2 shedding in different respiratory samples and analytical tests – nasopharyngeal (NP) quantitative polymerase chain reaction (qPCR), NP rapid antigen tests (RAT) and exhaled breath (EB) qPCR – and between different SARS-CoV-2 viral variants (Alpha and Omicron BA.1). We showed that EB shedding, as determined by qPCR, had a distinct shedding pattern characterised by high sensitivity in early infection and low sensitivity in late infection, compatible with a contagiousness test. Shedding was similar across virus variants. In another chapter, we looked at the merits and limitations of qPCR on ambient air sampling as a non-invasive, scalable surveillance tool for infectious diseases in general and respiratory diseases in particular, as a tool to provide insight into (airborne) transmission patterns, and to evaluate transmission reduction efforts. We detected high rates of respiratory pathogen positivity, by multiplex qPCR, in community settings. We saw clear trends in the detection rates throughout the sampling period and across age groups. Also, the influence of indoor air quality on pathogen detection rates was very clear. A second study demonstrated high virus detection rates, by PCR, of mpox (previously monkeypox) in a sexual health clinic. In a third chapter, we used contact tracing data gathered as part of a testing and tracing programfor Leuven students during COVID-19 to determine risk factors for pathogen transmissionand evaluate the effectiveness of different contact tracing strategies. In a first large cohortstudy, we provided the first empirical evidence for the efficiency of backward contact tracing to interrupt SARS-CoV-2 transmission. In a second study focused on SARS-CoV-2 transmission risk instudent residences, we showed that the built environment (a high number of individuals sharing sanitary facilities) and behavioral factors (the recent occurrence of a social gathering) could significantly increase the risk transmission. In a third study, we used individual-leveldata on the use of the Belgian digital contact tracing app, the sharing of an infectionby a newly diagnosed case, and the receipt of an exposure notification by their manuallytraced contacts to empirically evaluate the comprehensiveness of digital proximity tracing(DPT). We showed that the overall comprehensiveness of DPT was very low, that the infection risk in digitally traced contacts was lower than that of conventionally traced non-app users, and that DPT was not instantaneous. These results highlighted major limitations of a digital proximity tracingsystem based on the dominant Google-Apple Exposure Notificaiton (GAEN) framework. Collectively, these chapters demonstrate how we were able to generate some interestinginsights into respiratory pathogen transmission, surveillance and mitigation." "Complex patterns of host-pathogen interaction: the role of behaviour in mediating the spread of infectious disease through structured host populations." "Herwig Leirs" "Evolutionary ecology group (EVECO)" "Contrary to the large, well-mixed theoretical populations on which the spread of infectious disease has traditionally been modelled, most wildlife and human populations are socially or spatially structured into distinct groups. This is significant, as infection transmission within a structured population will also depend on group dynamics including group connectivity via individual movements. But while theoretical studies have modelled the effects of population structure and connectivity on infection dynamics, the behavioural mechanisms driving connectivity have remained largely unstudied. This project will redress this fundamental issue, using the quintessential infectious disease, plague (Yersinia pestis), and one of its major hosts, great gerbils (Rhombomys opimus), to explore how social and spatial structures within populations affect infection dynamics. Specifically, this project aims to: 1) examine how the movements of great gerbils, their predators and other secondary hosts contribute to connectivity within structured great gerbil populations, and whether there are systematic differences in these measures in different landscapes; 2) implement a large field experiment to test whether derived hypotheses of connectivity account for the spread of fleas (and potentially, therefore, of plague) through structured populations; and 3) seek complex but coherent spatial patterns in the distribution of infected groups using point pattern analyses." "Complex patterns of host-pathogen interaction: the role of behaviour in mediating the spread of infectious disease through structured host populations." "Nelika Hughes" "Evolutionary ecology group (EVECO)" "In this project, I propose to examine fundamental questions of how the social and spatial structure of host populations affects the spread and persistence of an infectious disease and the behavioural mechanisms that drive this structure. To do so, I will use the quintessential infectious disease, plague (Yersinia pestis), and the major host of plague within Central Asia, the great gerbil (Rhombomys opimus)." "Bsalomics - Identifying the genomic basis of amphibian immunity to Bsal, the emerging infectious disease devastating salamander populations across Europe." "An Martel" "Department of Pathobiology, Pharmacology and Zoological Medicine" "Amphibians worldwide are threatened by emerging infectious diseases. This includes the recently discovered invasive fungal pathogen Batrachochytrium salamandrivorans (Bsal), which causes chytridiomycosis and is decimating salamander populations in Europe. Continued spread of Bsal is inevitable, and research on host responses and natural immunity is crucial to predict and mitigate the negative consequences to salamanders and cascading impacts to the ecosystems they inhabit. Our understanding of salamander immunity is limited by a lack of functional genomic resources and expertise, which is exacerbated by salamanders’ exceptionally large and complicated genomes. This project will leverage a newly sequenced reference genome and a unique system of two hybridizing Triturus newts with different disease outcomes, to decode the genetic basis of immunity to Bsal. Combining controlled Bsal infections, experimental crosses between resistant and susceptible newts and state-of-the-art genomic techniques and analyses, we will identify the genes associated with Bsal disease resistance in both captive and natural populations. This work will bring major insights into the Bsal-salamander system and amphibian immunity more broadly. The project is expected to have profound long-term implications on captive breeding efforts, and help wildlife managers make informed decisions on population management and disease spread mitigation." "Breaking the silence after the storm: the amphibian response to an emerging infectious disease" "An Martel" "Department of Pathobiology, Pharmacology and Zoological Medicine" "Counteracting the loss of biodiversity presents one of the defining challenges of our time. Amphibian declines have become iconic of global extinctions, and two lethal pathogenic chytrid fungi - Batrachochytrium dendrobatidis (Bd) and B. salamandrivorans (Bsal) - are implicated among the main factors driving their demise. The former caused extensive extirpations in frogs, but the latter emerged recently and is currently causing unprecedented die-offs in European fire salamanders (Salamandra salamandra) after invasion from east Asia, with the potential to decimate worldwide salamander diversity. In the known outbreak sites, a tiny proportion of individuals persists. Understanding the mechanisms of adaptation that allow extant populations to persist after pathogen invasion is key to design conservation measures. Here, we propose an integrative gene-to-ecosystem study to examine the factors underpinning salamander persistence, linking host genetic, phenotypic and ecological differentiation through analyses of RNA sequence and expression data, skin defenses and spatial population structure. Furthermore, we will develop and apply a new genotyping assay for Bsal to map its diversity and frame results in the genetic context of the pathogen, and present a direct resource for efficient global monitoring of the disease. These objectives each address outstanding questions on Bsal host-pathogen evolution, but together provide a comprehensive account of salamander adaptability." "Elucidate the role of death receptor 3 (DR3) in thymic immune activation in infectious disease" "Peter Vandenabeele" "Department of Biomedical molecular biology" "Death receptors (DR) have a major impact on numerous inflammatory processes in the body. DR3 signals through the cytokine TL1A and have been shown to play a crucial role in mucosal inflammation. Recently, we have identified some unexpected immune subsets exiting the thymus extracted from neonatal mice. By stimulating lobes in thymic organ culture with the cytokines TL1A and IL-18, we consistently observe major subsets of myeloid-like cells exiting the thymic lobes along with a profound loss of developing T cells. The possible development and exit of other immune cells than T cells in the thymus in any notable amounts is a novel finding. We hypothesize that the ability to shift the primary output of the neonatal thymus from T cells to myeloid-like cells through pro-inflammatory cytokines may constitute an overlooked, yet fundamental biological function. Using cutting-edge next-generation single-cell RNA sequencing and state-of-the-art functional assays we aim at phenotyping the ectopic cells exiting the thymus and getting a better understanding of their functionalities. In collaboration with the University of Copenhagen, we aim at identifying their role and localization upon commensal colonization using adoptive transfer in germ-free mice. Finally, we will investigate their role in the defense against pathogen infection. Thus, the goal of this project is to elucidate immune mechanisms that could have a substantial impact on this fundamental area of cellular immunology." "Spatio-temporal modeling of infectious diseases" "Christel FAES" "Centre for Statistics" "The specific objectives in this project are: (1) Development of flexible statistical methods for the spatial and spatio-temporal analysis of infectious diseases. This includes (a) the investigation of flexible methods for prevalence estimation and risk factor analysis of infectious diseases, accounting for the different hierarchies in the data and correcting for the possible misclassification of test results using test sensitivity and specificity; (b) the extension of infectious disease models to include the spatial component; (c) the extension of spatio-temporal models for the force of infection to incorporate space-time-varying covariates; (d) study the impact of missing data on the geographical distribution of diseases; (e) investigation of approximate inference based on variational approximation. (2) Describe the temporal and spatial dynamics of infectious diseases using a mathematical model. This includes (a) investigating mathematical models to describe both the spatial and temporal dynamics of the disease; (b) studying the impact of local and global control strategies on the disease dynamics." "FWO travel grant for a short stay abroad for the 9e Annual Summer Institute in Statistics and Modeling in Infectious Diseases (SISMID) during 17-21/07/2017 at Seattle USA" "Niel HENS" "Centre for Statistics" "As a postdoctoral researcher at the Center for Statistics (CENSTAT) of Hasselt University, I am working on modeling infectious diseases. My main research topic is studying co-infections (HIV-HSV2, HIV-HCV and PVB19-VZV), using both deterministic and agent-based modeling. Markov-Chain-Monte-Carlo (MCMC) techniques are important for estimating the parameters in these models. During the 9th Summer Institute in Statistics and Modeling in Infectious Diseases, which will take place in Seattle (WA, US) in July 2017, I want to broaden my knowledge of mathematical epidemiology by attending the modules on MCMC for Infectious Diseases. Attending these modules will provide me with an opportunity to learn more about algorithms for MCMC sampling and how to apply these methods to data from infectious disease outbreaks. Apart from broadening my knowledge, attending the workshop also gives me the opportunity for networking with colleagues from the field of epidemiology." "Disease-modifying characteristics of LXR-dependent signaling pathways in infectious and non-infectious inflammatory lung diseases" "This study aims to unravel the molecular basis by which LXR-dependent pathways contribute to pulmonary inflammation triggered by infectious and non-infectious agents. The disease-modifying potential of LXR-dependent pathways will be investigate using LXR knockout mice and synthetic LXR agonists. Success will aid in the identification of elevant key mediators and novel inflammatory disease-related pathways, essential in triggering lung diseases" "Belgian Clinical Research Alliance on Infectious Diseases (BECRAID)." "Samuel Coenen" "Laboratory of Medical Microbiology (LMM)" "The emergence of new pathogens, such as the coronavirus causing the COVID-19 pandemic, and of antibiotic resistance has further increased mortality and morbidity of infectious diseases (ID). To reduce the impact of ID on individual and population health and to advance clinical research on ID, the European Clinical Research Alliance on Infectious Diseases (ECRAID; www.ecraid.eu) was established, a European research infrastructure. The pandemic demonstrated the importance of innovative research into the best management of COVID-19 patients in primary care, where most patients with ID are treated, ideally preventing hospital admission and worse. This is research where both Belgium and Europe lagged behind, and where Flanders could be a pioneer by supporting (B)ECRAID. BECRAID aims to establish a long-term, financially self-sustainable, research infrastructure for primary care research on ID in Flanders and to represent Flanders in the primary care research of ECRAID. BECRAID receives very strong support from its stakeholders and potential users in Flanders and beyond, and has the ambition to expand to nursing homes, to Belgium and even to other relevant diseases."