Research Niel Hens

Abstract

Chronic Hepatitis B Virus infections affect 3.6% of the worldwide population and result in liver-related death in over 700000 people annually. Current standard of care, consisting of nucleos(t)ide analogues (NA), efficiently suppress viral replication, prevent liver disease, but do not cure the infection, defined as Hepatitis B surface antigen (HBsAg) loss. Lifelong NA treatment is therefore often required. However, in some patients with long term viral suppression, treatment withdrawal may lead to persistent off-treatment viral control and an upto 40% chance of HBsAg loss after 5 years. Obviously, identifying upfront which patients will benefit from a treatment cessation is of utmost importance. We are currently coordinating the COIN-B study, a multicentric national study in which 90 patients stop their antiviral treatment, and 50 continue. The design of this study allows for the evaluation of baseline host factors, such as ethnicity, on off-treatment outcomes, but not the effects of viral flares or retreatment. To this end, we will combine the data of the COIN-B study with several international prospective NA withdrawal studies with intensive monitoring schedules and retreatment criteria. We will apply and refine advanced statistical modelling to evaluate rare events, such as off-treatment HBsAg loss. This will enable a full picture of the different viral and host factors associated with viral control or functional cure (HBsAg loss) after NA withdrawal. This will further establish the optimal monitoring interval, retreatment indications and role of flares. Apart from statistical modelling, we will apply bio-informatics approaches to investigate gene signatures in blood of COIN-B patients. The goal of this substudy is to find a genetic biomarker able to select patients upfront for a NA treatment cessation. In addition, this will learn how the blood transcriptome is modulated during off-treatment responses and yield insight in the pathogenesis of flares and viral control. The combination of both approaches will ultimately lead to the optimal predictive model of clinical parameters and gene signatures that will guide future treatment decisions in the vast number of NA-treated patients.

Researcher(s)

• Promoter: Vanwolleghem Thomas
• Co-promoter: Hens Niel
• Fellow: Ballet Fleur

Research team(s)

• Laboratory Experimental Medicine and Pediatrics (LEMP)

Project type(s)

• Research Project

Abstract

Around 10% of newborns in Europe will be admitted to a neonatal intensive care unit (NICU). Critically ill babies are a highly vulnerable population for the acquisition of resistant bacteria. Sepsis is among the most common events in NICU and is known to be associated with high mortality and poor long-term outcomes. Despite rising awareness of high rates of resistant bacterial colonisation reported in NICU, there is very little robust specific data on globally applicable infection prevention and control (IPC) measures. NeoIPC focuses on new approaches to the prevention and management of resistant bacterial colonization and infection on NICU. The project builds on and further extends the collaboration between 13 partners with a proven track record in relevant areas, including neonatal infection, IPC, implementation science, microbiology and surveillance. NeoIPC aims to develop and implement an innovative approach towards the evaluation of IPC interventions combining a robust cost-efficient randomised trial combined with the evaluation of a suitable implementation science strategy and novel targeted clinical and genotypic surveillance. A further goal is to generate widely relevant pan-European network strategies to improve IPC in routine neonatal care. This will be achieved through six interrelated work packages to deliver a cluster randomised trialimplementation hybrid investigating the impact of skin antisepsis on infant hospital-acquired clinical sepsis and resistant bacterial colonisation, coupled with a comprehensive implementation strategy incorporating optimal targeted surveillance in a clinical network with tailored dissemination and exploitation to facilitate sustainable embedding of outputs. NeoIPC will generate globally transferrable outputs to reduce hospital transmission of resistant pathogens, foster and facilitate collaborative research and IPC implementation efforts with a broad and long-lasting impact for critically ill newborns and infants.

Researcher(s)

• Promoter: Malhotra Surbhi
• Co-promoter: Goossens Herman
• Co-promoter: Hens Niel

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

VAXINFECTIO-PD is an established Industrial Research Fund (IOF) consortium, well equipped to build an ecosystem offering research, valorisation, innovation and development to answer existing and new challenges in the field of infectious diseases and vaccinology. These domains fall within one of the valorisation domains of the Antwerp University, and the newly established business unit Antwerp Valorisation & Development (AVD) of the UAntwerp. The VAXINFECTIO-PD consortium built up a unique and extensive track record through research, services, spin-off creation and innovative pathways, in generating product concepts/prototypes and research platforms that form the basis of medical innovation. The various core research units have had an important international image in the recent years with publications in leading journals, coordination of several European projects, as well as active presence and involvement in international scientific and policy forums. For the 6-year period the IOF-consortium will further focus on 5 interlinked valorisation avenues, all creating or guaranteeing growth on the parameters P3, P4, P5 and P6: translational vaccination platform for improved and new preventive and therapeutic vaccines, prognostic and diagnostic platforms, core facilities (for cellular vaccines, human challenge studies and biobanks), infectious disease and immune modelling and prediction, and improved vaccine delivery and medical devices through product development.

Researcher(s)

• Promoter: Van Damme Pierre
• Co-promoter: Beutels Philippe
• Co-promoter: Cools Nathalie
• Co-promoter: Hens Niel
• Co-promoter: Lion Eva
• Co-promoter: Malhotra Surbhi
• Co-promoter: Verwulgen Stijn
• Co-promoter: Vorsters Alex
• Fellow: Bamberger Martina

Research team(s)

• Centre for the Evaluation of Vaccination (CEV)

Project type(s)

• Research Project

Abstract

This PhD project includes the statistical modelling of the results from the EBL2007 clinical trial, which is part of EBOVAC3 (IMI Horizon 2020 project) and aims to investigate the immunogenicity (WP4) of the prophylactic Ebola vaccine in Phase III (developed by Janssen Vaccines & Prevention B.V. in partnership with Bavarian Nordic A/S) in health care providers in the Democratic Republic of Congo (DRC).

Researcher(s)

• Promoter: Hens Niel
• Fellow: Garcia-Fogeda Irene

Research team(s)

• Centre for Health Economics Research and Modelling of Infectious Diseases (CHERMID)

Project type(s)

• Research Project

Abstract

The aim of this research project is the development of new advanced, state-of-the-art methodology for epidemiologists, mathematical modellers and biostatisticians interested in modelling vector-borne infectious disease transmission. More specifically, we focus on the estimation of age- and time-dependent epidemiological malaria parameters, correcting for other attribute data, governing the spread and transmission of malaria. In addition, interest is in the identification of key individuals responsible for sustained malaria transmission in low transmission settings. Based on social network analysis techniques, we aim at gaining insights relevant for the development of malaria elimination strategies. In conclusion, the main objectives in this proposal are (1) the development of novel methodology to integrate mathematical and statistical models to estimate time- and age-varying malaria epidemiological parameters in the presence of unobserved heterogeneity; (2) the development of approaches to deal with doubly interval censored observations in combination with outcome-dependent sampling and heterogeneity; and (3) the study of heterogeneity in household conditions and individual attribute data using social network data. Although special attention is directed to malaria, the methodology developed in this project is more widely applicable in the context of vector-borne infections in both human and animal populations.

Researcher(s)

• Promoter: Abrams Steven
• Co-promoter: Hens Niel
• Fellow: Grosso Alessandro

Research team(s)

• Global Health Institute (GHI)

Project type(s)

• Research Project

Abstract

New interventions are required to prevent the emergence of antimicrobial resistance in contemporary sexually transmitted infection (STI) epidemics in men who have sex with men (MSM). Here, we perform a double-blinded single centre, crossover, randomized controlled trial of antibacterial vs. placebo mouthwash to study reduction in incidence of gonorrhoea/chlamydia/syphilis in MSM taking preexposure prophylaxis.

Researcher(s)

• Promoter: Malhotra Surbhi
• Co-promoter: Hens Niel

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the central nervous system (CNS) for which no cure is currently available. It is the leading cause of non-traumatic disabling neurological disease in young adults with more than 500,000 people affected in Europe. Since MS strikes during the primary productive time of one's personal and professional life, it leads to a major physical and socio-economic burden to the patient, family and society. Therefore, new therapeutic interventions with improved efficacy over existing drugs and good tolerability are warranted. As chronic inflammatory processes drive the neurodegeneration, we hypothesize that improved clinical outcome depends on restoring the balance between inflammation and the remaining capacity of neuronal self-renewal. In this perspective, cell therapy that specifically targets the damaging immune reactions that cause MS and induce disease-specific tolerance without affecting protective immunity against pathogens and cancer is a promising approach. Recently, we set-up a collaborative network of European centers working in cell therapy (COST Action BM1305). From this, centers from four different EU countries with two additional partners now aim to take the next step and join efforts to bring antigen-specific therapy for MS to the clinic. Our objectives are to evaluate safety, clinical practicality and demonstrate first proof-of-principle of therapeutic efficacy of antigen-specific tolerance-inducing dendritic cells (tolDC) in MS patients in two single-center clinical trials while comparing different modes of tolDC administration. Coordinated patient monitoring and centralized MRI monitoring, including radiological correlates of neurodegeneration, and immunomonitoring will enable us to directly compare results between trials and enable consented biobanking, data safeguarding and accessibility to support future efforts in the field of MS therapy. Antigen-specific cell therapy has the potential to provide this chronic inflammatory disease with a personalized and effective treatment option and therefore fits within current program. An effective therapy that lowers morbidity by uniting efficacy with reduced occurrence of side effects and less frequent hospitalizations will enhance quality of life of patients as well as dramatically reduce economic burden. This would represent a breakthrough for healthcare in MS.

Researcher(s)

• Promoter: Cools Nathalie
• Co-promoter: Hens Niel

Research team(s)

• Laboratory for Experimental Hematology (LEH)

Project type(s)

• Research Project

Abstract

Respiratory syncytial virus (RSV) is not well known outside medical circles, yet most people have probably suffered from it in childhood, as it is the most common cause of severe respiratory illness in infants and children worldwide. The elderly and people with weakened immune systems are also vulnerable to RSV infection. While most people's symptoms are mild, it can result in pneumonia and 3.4 million cases annually require hospitalisation. There is no specific treatment or vaccine for RSV. The goal of the RESCEU project is to gather information on the scale of RSV infection in Europe and its economic impacts. It will then use this information to design best practice guidelines to improve the way RSV cases are monitored in Europe, and to shape future vaccination programmes. The team will also gather and analyse patient samples to identify biological markers associated with severe RSV infection. This information could aid in diagnosis and facilitate the development of new treatments and vaccines.

Researcher(s)

• Promoter: Beutels Philippe
• Co-promoter: Bilcke Joke
• Co-promoter: Hens Niel

Research team(s)

• Centre for Health Economics Research and Modelling of Infectious Diseases (CHERMID)

Project website

Project type(s)

• Research Project

Abstract

TransMID focuses on the development of novel methods to estimate key epidemiological parameters from both serological and social contact data, with the aim to significantly expand the range of public health questions that can be adequately addressed using such data. Using new statistical and mathematical theory and newly collected as well as readily available serological and social contact data (mainly from Europe), fundamental mathematical and epidemiological challenges as outlined in the following work packages will be addressed: (a) frequency and density dependent mass action relating potential effective contacts to transmission dynamics in (sub)populations of different sizes with an empirical assessment using readily available contact data, (b) behavioural and temporal variations in contact patterns and their impact on the dynamics of infectious diseases, (c) close contact household networks and the assumption of homogeneous mixing within households, (d) estimating parameters from multivariate and serial cross-sectional serological data taking temporal effects and heterogeneity in acquisition into account in combination with the use of social contact data, and (e) finally the design of sero- and social contact surveys with specific focus on serial cross-sectional surveys. TransMID is transdisciplinary in nature with applications on diseases of major public health interest, such as pertussis, cytomegalovirus and measles. Translational methodology is placed at the heart of TransMID resulting in the development of a unifying methodology for other diseases and settings. The development of a toolbox and accompanying software allow easy and effective application of these fundamentally improved techniques on many infectious diseases and in different geographic contexts, which should maximize TransMID's impact on public health in Europe and beyond.

Researcher(s)

• Promoter: Hens Niel

Research team(s)

• Centre for Health Economics Research and Modelling of Infectious Diseases (CHERMID)

Project type(s)

• Research Project

Abstract

The aim of the project is to develop a suite of advanced, state-of-the-art methodology for epidemiologists and biostatisticians interested in modeling infectious diseases spread from person to person. The key mechanism underlying infectious disease spread is the contacts susceptible people make with infectious people. The individuals in the population can be represented by nodes and the contacts between them as lines connecting the nodes. The collection of nodes and connecting lines is called a contact network. This project aims to collect data on contact networks at home, at school and at work and to develop new statistical methodology that allows for the estimation of key epidemiological parameters such as the basic reproduction number and the generation interval distribution while dealing with complexities as missing data. There are five main objectives: (1) Design and conduct a pilot contact network survey; (2) Develop statistical methodology to estimate the network from egocentric or second generation network data; (3) Augment existing methodology to estimate parameters from observed outbreaks using network theory; (4) Develop methodology to estimate parameters from partially observed outbreaks; (5) Develop an easy-to-use statistical toolbox for epidemiologists interested in the surveillance of epidemics.

Researcher(s)

• Promoter: Hens Niel
• Fellow: Torneri Andrea

Research team(s)

• Centre for Health Economics Research and Modelling of Infectious Diseases (CHERMID)

Project type(s)

• Research Project

Abstract

It is our goal to conceptualise mathematical models that describe the basic immunology with regard to varicella-zoster virus (VZV) and immunological perturbations caused by VZV at the individual level. Furthermore, at the population based level we will formulate mathematical models describing the transmission of VZV between individuals. Simulations of both withinhuman and between-human dynamics will be based on biological and epidemiological parameters. These parameters will be estimated from our previous studies, and other international studies, as well as this project's experimental study, which is designed to provide major insights in the immunology of latency and reactivation. More specifically, we will longitudinally assess the immune response of about 120 VZV immune persons whose immune systems were recently perturbed for different reasons such as re-exposure to VZV and reactivation of VZV as shingles (Herpes Zoster). In an innovating way we will also perform similar analyses in 30 healthy individuals thereby creating a control group and defining a benchmark for longitudinal variation in immunity. The biological parameters will be implemented in our newly developed mathematical models after thorough statistical analysis. For the first time in this field, we will apply certain advanced statistical techniques (nonlinear mixed and growth mixture models).

Researcher(s)

• Promoter: Beutels Philippe
• Co-promoter: Hens Niel
• Co-promoter: Van Damme Pierre
• Co-promoter: Van Tendeloo Vigor
• Fellow: Ogunjimi Benson

Research team(s)

Project type(s)

• Research Project

Abstract

The general aim is (1) to quantify exogenous boosting by means of an observational longitudinal study, (2) implement this result in newly adapted epidemiological models, (3) assess the population effects of vaccination against VZV and (4) apply this to inform a cost-utility analysis examining vaccination against VZV.

Researcher(s)

• Promoter: Beutels Philippe
• Co-promoter: Hens Niel
• Co-promoter: Smits Evelien
• Co-promoter: Van Damme Pierre

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand FAGG. UA provides FAGG research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Beutels Philippe
• Co-promoter: Hens Niel

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand FAGG. UA provides FAGG research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Beutels Philippe
• Co-promoter: Hens Niel

Research team(s)

Project type(s)

• Research Project

Abstract

In infectious disease epidemiology, one is strongly interested in predicting the evolution of a newly emerging pathogen or in monitoring the effects of targeted or universal intervention programs on infectious disease spread in a human population. For many of these research questions such as at the initial phase of a pandemic, 'chance' ("stochasticity") and heterogeneity in risks are key determinants on whether or not the infection will spread or mitigation strategies would be effective and cost-effective. Therefore, stochastic individual-based infectious disease models provide a valuable alternative to the hitherto widely applied deterministic compartmental models. Because of the computational complexity associated with the use of individual-based models in large populations, efficient programming techniques need to be developed and implemented to allow uncertainty analysis and meaningful calibration procedures. The central research questions of this project are fourfold: (1) Which is the most computationally efficient way to simulate an emerging infectious disease epidemic by means of a stochastic individual-based model? (2) Which is the most efficient way to conduct uncertainty analysis and calibration procedures in a stochastic individual-based model applied to pandemic influenza? (3) Which are the main factors that would influence the spread of pandemic influenza in Flanders? (4) Given key characteristics of pandemic influenza (scenarios defined in relation to the basic reproduction number, serial interval and morbidity and mortality in various groups of the population), which prevention and control measures are most effective and most cost-effective to mitigate their spread in Flanders? Initially, the model will be applied to Flanders but generic efficient programming is crucial to enable efficient application to other regions in the world and other emerging pathogens.

Researcher(s)

• Promoter: Beutels Philippe
• Co-promoter: Broeckhove Jan
• Co-promoter: Hens Niel

Research team(s)

Project website

Project type(s)

• Research Project