Search bioRxiv⌕ Search

Biology subjects

ten Bosch, Q.

Publications and source records attributed to ten Bosch, Q..

8 recordsLinked to original sources

Quantifying circulation and antibody cross-reactivity for co-circulating flaviviruses: the case of Usutu and West Nile virus in blackbirds

Serological testing is important for assessing past exposure and immunity, but interpretation can be complicated by antibody cross-reactivity between closely related viruses. We assess this challenge for Usutu virus (USUV) and West Nile virus (WNV), flaviviruses that recently emerged in Europe. We analysed samples from wild blackbirds collected in the Netherlands between 2016-2022. Samples (N=1742) were screened using an NS1-based protein micro-array, with positives confirmed by Focus Reduction Neutralization Tests (FRNT). We jointly estimated seroprevalence and antibody responses by fitting a Bayesian latent-variable model to FRNT values. Estimates of homologous and cross-reactive antibody responses were used to improve interpretation of observed titres for serosurveillance. Estimated seroprevalence varied across time and regions between 4.9% (95%CrI 3.5-6.7) to 18.5% (95%CrI 14.9-22.7) for USUV and between 2.4% (95%CrI 1.3-3.8) to 6.4% (95%CrI 3.9-9.6) for WNV. These were 1.5 (USUV) to 2.4 times (WNV) higher than estimates based on the current threshold-based algorithm. USUV induced a higher antibody response and was more likely to induce a cross-reactive response than WNV. Our classification algorithm informed by these estimates showed high sensitivity (WNV: 0.88, USUV: 0.97) and specificity (both: >0.99). Our results illustrate how quantitative frameworks can improve serological interpretation in settings with co-circulating pathogens.

ecology↗

Implications of future change scenarios for mosquito-borne disease transmission in the Netherlands

BackgroundMosquito-borne virus transmission is shaped by its ecological context, including land use, climate, and population dynamics. Future changes in these factors may therefore affect the risk and intensity of Usutu virus (USUV) and West Nile virus (WNV) outbreaks in the Netherlands. Methodology & findingsWe compared a reference scenario to four future Shared Socio-economic Pathway scenarios developed for the Netherlands, which differed in land use, host distribution, mosquito distribution, and temperature. Temperature (between +1.0{degrees}C and +1.7{degrees}C) and mosquito abundance (between +5% and +10%) were predicted to increase during the transmission season across the scenarios. Scenario effects on hosts differed between species. We found that outbreak size and growth rate were expected to increase in all future scenarios for both USUV and WNV. These effects were most pronounced early in the season and in scenarios characterised by a high temperature increase and little concern about environmental change. Changes in outbreak risk differed between locations due to spatial variation in changes in host and vector abundance ConclusionsAcross a range of possible future scenarios, USUV and WNV outbreaks are expected to become larger, grow faster, and last longer. This is mostly driven by increased temperatures, highlighting the importance of climate mitigation measures to reduce disease outbreak risk and impact.

ecology↗

Silent reservoirs are shaping disease emergence: the case of Usutu virus in the Netherlands

Disentangling contributions of different hosts to disease transmission is highly complex, but critical for improving predictions, surveillance, and response. This is particularly challenging in wildlife, with pathogens often infecting multiple species and data collection being difficult. Using the emergence of Usutu virus (USUV) in the Netherlands as a case study, we demonstrate the use of an Approximate Bayesian Computation framework on diverse data sources to uncover drivers of spatio-temporal wildlife disease emergence. We calibrated single- and multi-host mechanistic transmission models to five types of wildlife surveillance and research data, describing molecular and serological evidence of USUV in birds. Although Eurasian blackbirds, the primary target species for surveillance, were most severely affected, our models indicated that USUV could not persist in blackbirds alone. Our framework provided statistical support for additional, unobserved bird species to have contributed to transmission. This population of bird species is characterised by limited infection mortality, a longer lifespan, and likely further dispersal than blackbirds. Immunity in this population appears to have protected blackbirds from further USUV-related population decline. Our results underscore the importance of considering multiple host populations to understand outbreak dynamics. Neglecting the multi-host context of transmission can impact the reliability of predictions and projected impact of interventions.

ecology↗

Multivariate resilience indicators to anticipate vector-borne disease outbreaks: a West Nile virus case-study

Background and aimTo prevent the spread of infectious diseases, successful interventions require early detection. The timing of implementation of preventive measures is crucial, but as outbreaks are hard to anticipate, control efforts often start too late. This applies to mosquito-borne diseases, for which the multifaceted nature of transmission complicates surveillance. Resilience indicators have been studied as a generic, model-free early warning method. However, the large data requirements limit their use in practice. In the present study, we compare the performance of multivariate indicators of resilience, combining the information contained in multiple data sources, to the performance of univariate ones focusing on one single time series. Additionally, by comparing various monitoring scenarios, we aim to find which data sources are the most informative as early warnings. Methods and resultsWest Nile virus was used as a case study due to its complex transmission cycle with different hosts and vectors interacting. A synthetic dataset was generated using a compartmental model under different monitoring scenarios, including data-poor scenarios. Multivariate indicators of resilience relied on different data reduction techniques such as principal component analysis (PCA) and Max Autocorrelation Factor analysis (MAF). Multivariate indicators outperformed univariate ones, especially in data-poor scenarios such as reduced resolution or observation probabilities. This finding held across the different monitoring scenarios investigated. In the explored system, species that were more involved in the transmission cycle or preferred by the mosquitoes were not more informative for early warnings. ImplicationsOverall, these results indicate that combining multiple data sources into multivariate indicators can help overcome the challenges of data requirements for resilience indicators. The final decision should be based on whether the additional effort is worth the gain in prediction performance. Future studies should confirm these findings in real-world data and estimate the sensitivity, specificity, and lead time of multivariate resilience indicators. Author summaryVector-borne diseases (VBD) represent a significant proportion of infectious diseases and are expanding their range every year because of among other things climate change and increasing urbanization. Successful interventions against the spread of VBD requires anticipation. Resilience indicators are a generic, model-free approach to anticipate critical transitions including disease outbreaks, however the large data requirements limit their use in practice. Since the transmission of VBD involves several species interacting with one another, which can be monitored as different data sources. The information contained by these different data sources can be combined to calculate multivariate indicators of resilience, allowing a reduction of the data requirements compared to univariate indicators relying solely on one data source. We found that such multivariate indicators outperformed univariate indicators in data-poor contexts. Multivariate indicators could be used to anticipate not only VBD outbreaks but also other transitions in complex systems such as ecosystems collapse or episodes of chronic diseases. Adapting the surveillance programs to collect the relevant data for multivariate indicators of resilience entails new challenges related to costs, logistic ramifications and coordination of different institutions involved in surveillance.

systems biology↗

Biological tick control: modeling the potential impact of entomopathogenic fungi on the transmission of East Coast fever in cattle

Biological control of ticks using entomopathogenic fungi (EPF) is a highly desired alternative to chemical acaricides for the control of tick-borne pathogens. For Metarhizium anisopliae isolate ICIPE 7, one of these EPFs, efficacy against multiple tick species has been demonstrated in laboratory and field settings. However, we currently have little quantitative understanding of how EPFs can impact transmission. We developed a deterministic model of tick-host-pathogen interactions to explore how the effects of EPF on Rhipicephalus appendiculatus ticks may impact the transmission dynamics of East Coast fever (ECF) in cattle populations. We parameterized the multi-faceted effects of EPFs on tick dynamics using experimental data on Tickoff(R) biopesticide (a novel formulation of M. anisopliae ICIPE 7) and related EPFs. The epidemiological impact of EPF was evaluated across a range of product profiles and implementation strategies. Model results indicate that, for the explored product profiles, EPF derives most of its epidemiological impact through the delayed mortality effect. This EPF-induced mortality could not only reduce the onward Theileria parva transmission to cattle (both treated and untreated) but could also cause a reduction in the tick-to-host ratio and thus cattle exposure to ticks. The effects of EPF on reproduction fitness and engorgement of ticks elicit negligible impact. High levels of population coverage and treatment frequency are needed to reduce the tick population size and reach meaningful epidemiological impact in cattle populations. Additionally, increasing the persistence time of fungal conidia on cattle skin - through technological improvements to the EPF formulation - can substantially reduce acute infections when combined with appreciable population coverage levels, treatment frequency, and efficient spraying techniques. Our model analysis provides insights into the potential impact of EPF when deployed at a population level, and lends support to further research and development of this biological tick control tool.

microbiology↗

Mechanistic models for West Nile Virus transmission:A systematic review of features, aims, and parameterisation

Mathematical models within the Ross-Macdonald framework increasingly play a role in our understanding of vector-borne disease dynamics and as tools for assessing scenarios to respond to emerging threats. These threats are typically characterised by a high degree of heterogeneity, introducing a range of possible complexities in models and challenges to maintain the link with empirical evidence. We systematically identified and analysed a total of 67 published papers presenting compartmental West Nile Virus (WNV) models that use parameter values derived from empirical studies. Using a set of fifteen criteria, we measured the dissimilarity compared to the Ross-Macdonald framework. We also retrieved the purpose and type of models and traced the empirical sources of their parameters. Our review highlights the increasing refinements in WNV models. Models for prediction included the highest number of refinements. We found uneven distributions of refinements and of evidence for parameter values. We identified several challenges in parameterising such increasingly complex models. For parameters common to most models, we also synthesise the empirical evidence for their values and ranges. The study highlights the potential to improve the quality of WNV models and their applicability for policy by establishing closer collaboration between mathematical modelling and empirical work.

ecology↗

Quantifying Rift Valley fever virus transmission efficiency in a lamb-mosquito-lamb model

Rift Valley fever virus (RVFV) is a (re)emerging mosquito-borne pathogen impacting human and animal health. How RVFV spreads through a population depends on population-level interactions between hosts and vectors (e.g., vector-to-host ratio and biting preference) and also on potential differences in individual following virus exposure (e.g., transmission efficiencies from host to vector and vice versa). Here, we estimated the probability for RVFV to transmit to naive animals by experimentally exposing lambs to a bite of an infectious mosquito (the transmission efficiency) and assessed if and how RVFV infection subsequently developed in the exposed animal. Aedes aegypti mosquitoes, previously infected via feeding on a viremic lamb, were used to expose naive lambs to the virus. Lambs were either exposed to 1-3 (low exposure) or 7-9 (high exposure) infectious mosquitoes. All lambs in the high exposure group became viremic and showed characteristic signs of Rift Valley fever within 2-4 days post exposure. In contrast, 3 out of 12 lambs in the low exposure group developed viremia and disease, with similar peaks in viremia as the high exposure group but with some heterogeneity in the onset of viremia. These results suggest that the likelihood for successful infection of a ruminant host is affected by the number of infectious mosquitoes biting, but also highlights that a lamb can be infected by a single mosquito. The per bite mosquito-to-host transmission efficiency was estimated at 28% (95% confidence interval: 15 - 47%). We subsequently combined this transmission efficiency with estimates for mosquito life traits into a Ross-McDonald mathematical model to illustrate scenarios under which major RVFV outbreaks could occur in naive populations (i.e., R0 >1). The model revealed that for efficient RVFV transmission relatively high vector-to-host ratios as well as strong feeding preference for competent hosts are required. Altogether, this study highlights the importance of experiments that mimic natural exposure to RVFV. The experiments facilitate a better understanding of the natural progression of disease and a direct way to obtain epidemiological parameters for mathematical models.

microbiology↗

Statistical and biological uncertainties associated with vaccine efficacy estimates and their implications for dengue vaccine impact projections

Given the limited effectiveness of strategies based solely on vector control to reduce dengue virus (DENV) transmission, it is expected that an effective vaccine could play a pivotal role in reducing the global disease burden of dengue. Of several dengue vaccines under development, Dengvaxia(R) from Sanofi Pasteur recently became the first to become licensed in select countries and to achieve WHO recommendation for use in certain settings, despite the fact that a number of uncertainties about its profile complicate projections of its public health impact. We used a stochastic, agent-based model for DENV transmission to perform simulations of the public health impact of dengue vaccines in light of two key uncertainties: (1) \"statistical uncertainty\" about the numerical value of the vaccines efficacy against disease, and (2) \"biological uncertainty\" about the extent to which its efficacy against disease derives from the amelioration of symptoms, blocking of DENV infection, or some combination thereof. Simulations of a generic dengue vaccine showed that the proportion of disease episodes averted following 20 years of routine vaccination of nine-year olds at 80% coverage was sensitive to both the numerical value of vaccine efficacy and to the extent to which efficacy derives from blocking of DENV infection. Simulations of a vaccine resembling Dengvaxia(R) took into account that vaccine trial results substantially reduced statistical uncertainty but did not address biological uncertainty, resulting in the proportion of disease episodes averted being more sensitive to biological uncertainty than to statistical uncertainty. Taken together, our results indicate limitations associated with the use of symptomatic disease as the primary endpoint of dengue vaccine trials and highlight the importance of considering multiple forms of uncertainty in projections of a vaccines public health impact.

epidemiology↗