Niel Hens | Universiteit Hasselt (original) (raw)

Papers by Niel Hens

Mediators of Inflammation, 2015

In healthy individuals, one exercise bout induces a substantial increase in the number of circula... more In healthy individuals, one exercise bout induces a substantial increase in the number of circulating leukocytes, while their function is transiently suppressed. The effect of one exercise bout in multiple sclerosis (MS) is less studied. Since recent evidence suggests a role of dendritic cells (DC) in the pathogenesis of MS, we investigated the effect of one combined endurance/resistance exercise bout on the number and function of DC in MS patients and healthy controls. Our results show a rapid increase in the number of DC in response to physical exercise in both MS patients and controls. Further investigation revealed that in particular DC expressing the migratory molecules CCR5 and CD62L were increased upon acute physical activity. This may be mediated by Flt3L-and MMP-9-dependent mobilization of DC, as demonstrated by increased circulating levels of Flt3L and MMP-9 following one exercise bout. Circulating DC display reduced TLR responsiveness after acute exercise, as evidenced by a less pronounced upregulation of activation markers, HLA-DR and CD86, on plasmacytoid DC and conventional DC, respectively. Our results indicate mobilization of DC, which may be less prone to drive inflammatory processes, following exercise. This may present a negative feedback mechanism for exercise-induced tissue damage and inflammation.

BMC Infectious Diseases

Background An increasing number of infectious disease models consider demographic change in the h... more Background An increasing number of infectious disease models consider demographic change in the host population, but the demographic methods and assumptions vary considerably. We carry out a systematic review of the methods and assumptions used to incorporate dynamic populations in infectious disease models. Methods We systematically searched PubMed and Web of Science for articles on infectious disease transmission in dynamic host populations. We screened the articles and extracted data in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results We identified 46 articles containing 53 infectious disease models with dynamic populations. Population dynamics were modelled explicitly in 71% of the disease transmission models using cohort-component-based models (CCBMs) or individual-based models (IBMs), while 29% used population prospects as an external input. Fertility and mortality were in most cases age- or age-sex-spec...

Eurosurveillance, 2022

Background COVID-19 mortality, excess mortality, deaths per million population (DPM), infection f... more Background COVID-19 mortality, excess mortality, deaths per million population (DPM), infection fatality ratio (IFR) and case fatality ratio (CFR) are reported and compared for many countries globally. These measures may appear objective, however, they should be interpreted with caution. Aim We examined reported COVID-19-related mortality in Belgium from 9 March 2020 to 28 June 2020, placing it against the background of excess mortality and compared the DPM and IFR between countries and within subgroups. Methods The relation between COVID-19-related mortality and excess mortality was evaluated by comparing COVID-19 mortality and the difference between observed and weekly average predictions of all-cause mortality. DPM were evaluated using demographic data of the Belgian population. The number of infections was estimated by a stochastic compartmental model. The IFR was estimated using a delay distribution between infection and death. Results In the study period, 9,621 COVID-19-relate...

Machine Learning and Knowledge Discovery in Databases. Applied Data Science and Demo Track, 2021

Epidemics of infectious diseases are an important threat to public health and global economies. Y... more Epidemics of infectious diseases are an important threat to public health and global economies. Yet, the development of prevention strategies remains a challenging process, as epidemics are non-linear and complex processes. For this reason, we investigate a deep reinforcement learning approach to automatically learn prevention strategies in the context of pandemic influenza. Firstly, we construct a new epidemiological meta-population model, with 379 patches (one for each administrative district in Great Britain), that adequately captures the infection process of pandemic influenza. Our model balances complexity and computational efficiency such that the use of reinforcement learning techniques becomes attainable. Secondly, we set up a ground truth such that we can evaluate the performance of the "Proximal Policy Optimization" algorithm to learn in a single district of this epidemiological model. Finally, we consider a large-scale problem, by conducting an experiment where we aim to learn a joint policy to control the districts in a community of 11 tightly coupled districts, for which no ground truth can be established. This experiment shows that deep reinforcement learning can be used to learn mitigation policies in complex epidemiological models with a large state space. Moreover, through this experiment, we demonstrate that there can be an advantage to consider collaboration between districts when designing prevention strategies.

Frontiers in Medicine, 2020

Coronavirus disease 2019 (COVID-19) is a rapidly evolving, highly transmissible, and potentially ... more Coronavirus disease 2019 (COVID-19) is a rapidly evolving, highly transmissible, and potentially lethal pandemic caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of June 11 2020, more than 7,000,000 COVID-19 cases have been reported worldwide, and more than 400,000 patients have died, affecting at least 188 countries. While literature on the disease is rapidly accumulating, an integrated, multinational perspective on clinical manifestations, Abu-Raya et al. Coronavirus Disease-19: An Interim Evidence Synthesis immunological effects, diagnosis, prevention, and treatment of COVID-19 can be of global benefit. We aimed to synthesize the most relevant literature and experiences in different parts of the world through our global consortium of experts to provide a consensus-based document at this early stage of the pandemic.

Several important aspects related to SARS-CoV-2 transmission are not well known due to a lack of ... more Several important aspects related to SARS-CoV-2 transmission are not well known due to a lack of appropriate data. However, mathematical and computational tools can be used to extract part of this information from the available data, like some hidden age-related characteristics. In this paper, we present a method to investigate age-specific differences in transmission parameters related to susceptibility to and infectiousness upon contracting SARS-CoV-2 infection. More specifically, we use panel-based social contact data from diary-based surveys conducted in Belgium combined with the next generation principle to infer the relative incidence and we compare this to real-life incidence data. Comparing these two allows for the estimation of age-specific transmission parameters. Our analysis implies the susceptibility in children to be around half of the susceptibility in adults, and even lower for very young children (preschooler). However, the probability of adults and the elderly to c...

Statistics in Medicine, 2021

Censoring due to a limit of detection or limit of quantification happens quite often in many medi... more Censoring due to a limit of detection or limit of quantification happens quite often in many medical studies. Conventional approaches to deal with censoring when analyzing these data include, for example, the substitution method and the complete case (CC) analysis. More recently, maximum likelihood estimation (MLE) has been increasingly used. While the CC analysis and the substitution method usually lead to biased estimates, the MLE approach appears to perform well in many situations. This article proposes an MLE approach to estimate the association between two measurements in the presence of censoring in one or both quantities. The central idea is to use a copula function to join the marginal distributions of the two measurements. In various simulation studies, we show that our approach outperforms existing conventional methods (CC and substitution analyses). In addition, rank‐based measures of global association such as Kendall's tau or Spearman's rho can be studied, hence...

BMC Infectious Diseases, 2021

Background In response to the ongoing COVID-19 pandemic, several countries adopted measures of so... more Background In response to the ongoing COVID-19 pandemic, several countries adopted measures of social distancing to a different degree. For many countries, after successfully curbing the initial wave, lockdown measures were gradually lifted. In Belgium, such relief started on May 4th with phase 1, followed by several subsequent phases over the next few weeks. Methods We analysed the expected impact of relaxing stringent lockdown measures taken according to the phased Belgian exit strategy. We developed a stochastic, data-informed, meta-population model that accounts for mixing and mobility of the age-structured population of Belgium. The model is calibrated to daily hospitalization data and is able to reproduce the outbreak at the national level. We consider different scenarios for relieving the lockdown, quantified in terms of relative reductions in pre-pandemic social mixing and mobility. We validate our assumptions by making comparisons with social contact data collected during a...

The Lancet Infectious Diseases, 2021

Background Despite the universal use of the two-dose trivalent measles-mumps-rubella (MMR) vaccin... more Background Despite the universal use of the two-dose trivalent measles-mumps-rubella (MMR) vaccine in the past two decades, outbreaks of these diseases still occur in countries with high vaccine uptake, giving rise to concerns about primary and secondary failure of MMR vaccine components. We aimed to provide seroconversion and waning rate estimates for the measles, mumps, and rubella components of MMR vaccines. Methods In this systematic review and meta-analysis we searched PubMed (including MEDLINE), Web of Science, and Embase for randomised controlled trials, cohort studies, or longitudinal studies reporting the immunogenicity and persistence of MMR vaccines, published in English from database inception to Dec 31, 2019. Studies were included if they investigated vaccine-induced immunity in healthy individuals who received a trivalent MMR vaccine, including different dosages and timepoints of vaccine administration. Studies featuring coadministration of MMR with other vaccines, maternal immunity to the MMR vaccine, or non-trivalent formulations of the vaccine were excluded. Pooled seroconversion and waning rates were estimated by random-effects meta-analyses. This study is registered with PROSPERO, CRD42019116705. Findings We identified 3615 unique studies, 62 (1•7%) of which were eligible for analysis. Estimated overall seroconversion rates were 96•0% (95% CI 94•5-97•4; I²=91•1%) for measles, 93•3% (91•1-95•2; I²=94•9%) for mumps when excluding the Rubini strain, 91•1% (87•4-94•1; I²=96•6%) for mumps when including the Rubini strain, and 98•3% (97•3-99•2; I²=93•0%) for rubella. Estimated overall annual waning rates were 0•009 (95% CI 0•005-0•016; I²=85•2%) for measles, 0•024 (0•016-0•039; I²=94•7%) for mumps, and 0•012 (0•010-0•014; I²=93•3%) for rubella. Interpretation Our meta-analysis provides estimates of primary and secondary vaccine failure, which are essential to improve the accuracy of mathematical and statistical modelling to understand and predict the occurrence of future measles, mumps, and rubella outbreaks in countries with high vaccine uptake. Funding European Research Council.

Contemporary Clinical Trials, 2020

Starting from historic reflections, the current SARS-CoV-2 induced COVID-19 pandemic is examined ... more Starting from historic reflections, the current SARS-CoV-2 induced COVID-19 pandemic is examined from various perspectives, in terms of what it implies for the implementation of non-pharmaceutical interventions, the modeling and monitoring of the epidemic, the development of early-warning systems, the study of mortality, prevalence estimation, diagnostic and serological testing, vaccine development, and ultimately clinical trials. Emphasis is placed on how the pandemic had led to unprecedented speed in methodological and clinical development, the pitfalls thereof, but also the opportunities that it engenders for national and international collaboration, and how it has simplified and sped up procedures. We also study the impact of the pandemic on clinical trials in other indications. We note that it has placed biostatistics, epidemiology, virology, infectiology, and vaccinology, and related fields in the spotlight in an unprecedented way, implying great opportunities, but also the need to communicate effectively, often amidst controversy.

Current outbreaks of SARS-CoV-2 are threatening the health care systems of several countries arou... more Current outbreaks of SARS-CoV-2 are threatening the health care systems of several countries around the world. The control of SARS-CoV-2 epidemics currently relies on non-pharmaceutical interventions, such as social distancing, teleworking, mouth masks and contact tracing. However, as pre-symptomatic transmission remains an important driver of the epidemic, contact tracing efforts struggle to fully control SARS-CoV-2 epidemics. Therefore, in this work, we investigate to what extent the use of universal testing, i.e., an approach in which we screen the entire population, can be utilized to mitigate this epidemic. To this end, we rely on PCR test pooling of individuals that belong to the same households, to allow for a universal testing procedure that is feasible with the current testing capacity. We evaluate two isolation strategies: on the one handpool isolation, where we isolate all individuals that belong to a positive PCR test pool, and on the other handindividual isolation, wher...

BackgroundThe rising COVID-19 pandemic caused many governments to impose policies restricting soc... more BackgroundThe rising COVID-19 pandemic caused many governments to impose policies restricting social interactions. These policies have slowed down the spread of the SARS-CoV-2 virus to the extent that restrictions can be gradually lifted. Models can be useful to assess the consequences of deconfinement strategies with respect to business, school and leisure activities.MethodsWe adapted the individual-based model “STRIDE” to simulate interactions between the 11 million inhabitants of Belgium at the levels of households, workplaces, schools and communities. We calibrated our model to observed hospital incidence and seroprevalence data. STRIDE can explore contact tracing options and account for repetitive leisure contacts in extended household settings (so called “household bubbles”) with varying levels of connectivity.FindingsHousehold bubbles have the potential to reduce the number of COVID-19 hospital admissions by up to 90%. The effectiveness of contact tracing depends on its timin...

ObjectiveScrutiny of COVID-19 mortality in Belgium over the period 8 March – 9 May 2020 (Weeks 11... more ObjectiveScrutiny of COVID-19 mortality in Belgium over the period 8 March – 9 May 2020 (Weeks 11-19), using number of deaths per million, infection fatality rates, and the relation between COVID-19 mortality and excess death rates.DataPublicly available COVID-19 mortality (2020); overall mortality (2009 – 2020) data in Belgium and demographic data on the Belgian population; data on the nursing home population; results of repeated sero-prevalence surveys in March-April 2020.Statistical methodsReweighing, missing-data handling, rate estimation, visualization.ResultsBelgium has virtually no discrepancy between COVID-19 reported mortality (confirmed and possible cases) and excess mortality. There is a sharp excess death peak over the study period; the total number of excess deaths makes April 2020 the deadliest month of April since WWII, with excess deaths far larger than in early 2017 or 2018, even though influenza-induced January 1951 and February 1960 number of excess deaths were si...

Journal of Neuroinflammation, 2019

Background: Although effective in reducing relapse rate and delaying progression, current therapi... more Background: Although effective in reducing relapse rate and delaying progression, current therapies for multiple sclerosis (MS) do not completely halt disease progression. T cell autoimmunity to myelin antigens is considered one of the main mechanisms driving MS. It is characterized by autoreactivity to disease-initiating myelin antigen epitope(s), followed by a cascade of epitope spreading, which are both strongly patient-dependent. Targeting a variety of MSassociated antigens by myelin antigen-presenting tolerogenic dendritic cells (tolDC) is a promising treatment strategy to re-establish tolerance in MS. Electroporation with mRNA encoding myelin proteins is an innovative technique to load tolDC with the full spectrum of naturally processed myelin-derived epitopes. Methods: In this study, we generated murine tolDC presenting myelin oligodendrocyte glycoprotein (MOG) using mRNA electroporation and we assessed the efficacy of MOG mRNA-electroporated tolDC to dampen pathogenic T cell responses in experimental autoimmune encephalomyelitis (EAE). For this, MOG 35-55immunized C57BL/6 mice were injected intravenously at days 13, 17, and 21 post-disease induction with 1α, 25-dihydroxyvitamin D 3-treated tolDC electroporated with MOG-encoding mRNA. Mice were scored daily for signs of paralysis. At day 25, myelin reactivity was evaluated following restimulation of splenocytes with myelin-derived epitopes. Ex vivo magnetic resonance imaging (MRI) was performed to assess spinal cord inflammatory lesion load.

Vaccine, 2019

Clinical trials covering the immunogenicity of a vaccine aim to study the longitudinal dynamics o... more Clinical trials covering the immunogenicity of a vaccine aim to study the longitudinal dynamics of certain immune cells after vaccination. The corresponding immunogenicity datasets are mainly analyzed by the use of statistical (mixed effects) models. This paper proposes the use of mathematical ordinary differential equation (ODE) models, combined with a mixed effects approach. ODE models are capable of translating underlying immunological post vaccination processes into mathematical formulas thereby enabling a

Frontiers in Neuroscience, 2018

Statistical methods in medical research, Jan 3, 2018

Bivariate binary response data appear in many applications. Interest goes most often to a paramet... more Bivariate binary response data appear in many applications. Interest goes most often to a parameterization of the joint probabilities in terms of the marginal success probabilities in combination with a measure for association, most often being the odds ratio. Using, for example, the bivariate Dale model, these parameters can be modelled as function of covariates. But the odds ratio and other measures for association are not always measuring the (joint) characteristic of interest. Agreement, concordance, and synchrony are in general facets of the joint distribution distinct from association, and the odds ratio as in the bivariate Dale model can be replaced by such an alternative measure. Here, we focus on the so-called conditional synchrony measure. But, as indicated by several authors, such a switch of parameter might lead to a parameterization that does not always lead to a permissible joint bivariate distribution. In this contribution, we propose a new parameterization in which t...

Scientific Reports, 2017

Re-exposure to chickenpox may boost varicella-zoster virus (VZV) immunity in the elderly. This se... more Re-exposure to chickenpox may boost varicella-zoster virus (VZV) immunity in the elderly. This secondary immune response is hypothesized to confer protection against herpes zoster. We longitudinally sampled 36 adults over the course of one year after re-exposure to chickenpox. The resulting 183 samples and those of 14 controls were assessed for VZV-specific T-cell immunity and antibody titres. The percentages of VZV-specific CD4+ IL-2-producing T-cells were increased in re-exposed grandparents compared to control participants up to 9 months after re-exposure. Using a longitudinal mixture modelling approach, we found that 25% and 17% of re-exposed grandparents showed a boosting of VZV-specific CD4+ IL-2-producing T-cells and VZV-specific antibodies, respectively. The antibody boosting occurred exclusively in cytomegalovirus (CMV) IgG-positive participants. CMV IgG-positive participants also had higher VZV IE62-specific CD4+ IFN-γ-producing T-cell percentages and VZV-specific antibody...

Pediatric Infectious Disease Journal, 2017

Background: Pertussis is a vaccine-preventable respiratory disease that may cause death mainly in... more Background: Pertussis is a vaccine-preventable respiratory disease that may cause death mainly in infants. The schedules for primary pertussis vaccination are set in each country by the local health authorities. Several different schedules meet World Health Organization recommendations, 2–4–6 months, 6–10–14 weeks, 2–3–4 months and 3–4–5 months being the most commonly used worldwide. In this work, we analyze the benefits of changing the vaccination schedule to control the disease. Methods: We used an age-structured deterministic mathematical model for pertussis transmission to compute the incidences for the 4 above-mentioned schedules. Different vaccination coverages and vaccine effectiveness levels were considered. Immunization data from Argentina and Belgium were used. Results: The highest reduction in incidence was obtained by adopting the 6–10–14 weeks schedule, reaching about a 36% reduction of 0–1-year incidence with respect to the 2–4–6 months schedule. We show the dependence...

BMC infectious diseases, May 18, 2017

Varicella is generally considered a mild disease. Disease burden is not well known and country-le... more Varicella is generally considered a mild disease. Disease burden is not well known and country-level estimation is challenging. As varicella disease is not notifiable, notification criteria and rates vary between countries. In general, existing surveillance systems do not capture cases that do not seek medical care, and most are affected by underreporting and underascertainment. We aimed to estimate the overall varicella disease burden in Europe to provide critical information to support decision-making regarding varicella vaccination. We conducted a systematic literature review to identify all available epidemiological data on varicella IgG antibody seroprevalence, primary care and hospitalisation incidence, and mortality. We then developed methods to estimate age-specific varicella incidence and annual number of cases by different levels of severity (cases in the community, health care seekers in primary care and hospitals, and deaths) for all countries belonging to the European M...