Modelling the continental-scale spread of Schmallenberg virus in Europe: Approaches and challenges

Following its emergence in northern Europe in 2011 Schmallenberg virus (SBV), a vector-borne disease transmitted by the bites of Culicoides midges, has spread across much of the continent. Here we develop simple models to describe the spread of SBV at a continental scale and, more specifically, within and between NUTS2 regions in Europe. The model for the transmission of SBV between regions suggests that vector dispersal is the principle mechanism for transmission, even at the continental scale. The within-region model indicates that there is substantial heterogeneity amongst regions in the force of infection for cattle and sheep farms. Moreover, there is considerable under-ascertainment of SBV-affected holdings, though the level of under-ascertainment varies between regions. We contrast the relatively simple approach adopted in this study with the more complex continental-scale micro-simulation models which have been developed for pandemic influenza and discuss the strengths, weaknesses and data requirements of both approaches

Inferences about the transmission of Schmallenberg virus within and between farms

In the summer of 2011 Schmallenberg virus (SBV), a Culicoides-borne orthobunyavirus, emerged in Germany and The Netherlands and subsequently spread across much of Europe. To draw inferences about the transmission of SBV we have developed two models to describe its spread within and between farms. The within-farm model was fitted to seroprevalence data for cattle and sheep farms in Belgium and The Netherlands, with parameters estimated using approximate Bayesian computation. Despite the short duration of viraemia in cattle and sheep (mean of 3–4 days) the within-farm seroprevalence can reach high levels (mean within-herd seroprevalence >80%), largely because the probability of transmission from host to vector is high (14%) and SBV is able to replicate quickly (0.03 per day-degree) and at relatively low temperatures (threshold for replication: 12.3 °C). Parameter estimates from the within-farm model were then used in a separate between-farm model to simulate the regional spread of SBV. This showed that the rapid spread of SBV at a regional level is primarily a consequence of the high probability of transmission from host to vector and the temperature requirements for virus replication. Our results, obtained for a region of the UK in a typical year with regard to animal movements, indicate that there is no need to invoke additional transmission mechanisms to explain the observed patterns of rapid spread of SBV in Europe. Moreover, the imposition of movement restrictions, even a total movement ban, has little effect on the spread of SBV at this scale

Choice of units of analysis and modeling strategies in multilevel hierarchical models

Hierarchical models are common in complex surveys, psychometric applications, as well as agricultural and biomedical applications, to name but a few. The context of interest here is meta-analysis, with emphasis on the use of such an approach in the evaluation of surrogate endpoints in randomized clinical trials. The methodology rests on the ability to replicate the effect of treatment on both the true endpoint, as well as the candidate surrogate endpoint, across a number of trials. However, while a meta-analysis of clinical trials in the same indication seems the natural hierarchical structure, some authors have considered center or country as the unit, either because no meta-analytic data were available or because, even when available, they might not allow for a sufficient level of replication. This leaves us with two important, related questions. First, how sensible is it to replace one level of replication by another one? Second, what are the consequences when a truly three- or higher-level model (e.g., trial, center, patient) is replaced by a coarser two-level structure (either trial and patient or center and patient). The same or similar questions may occur in a number of different settings, as soon as interest is placed on the validity of a conclusion at a certain level of the hierarchy, such as in sociological or genetic studies. Using the framework of normally distributed endpoints, these questions will be studied, using both analytic calculation as well as Monte Carlo simulation. © 2003 Elsevier B.V. All rights reserved.status: publishe

Impact of a short period of pre-enrichment on detection and bacterial loads of methicillin-resistant Staphylococcus aureus from screening specimens

We compared the impacts of direct plating on a chromogenic medium and of plating after enrichment (4 h and overnight) on the detection of methicillin-resistant Staphylococcus aureus (MRSA) from 52 patient screening samples. MRSA colony counts for approximately 70% of samples after overnight pre-enrichment were >20-fold higher than the counts after the other two treatments. The qualitative differences (sample was MRSA positive/negative) between the results of the direct plating and 4-h pre-enrichment treatments were not significant, indicating no advantage of the latter; however, the number of samples positive for MRSA increased significantly after an overnight sample pre-enrichment (P < 0.005)

Impact of human interventions on the spread of Bluetongue virus serotype 8 during the 2006 epidemic in north-western Europe

Bluetongue virus (BTV) can be spread by movement or migration of infected ruminants. Infected midges (Culicoides sp.) can be dispersed with livestock or on the wind. Transmissions of infection from host to host by semen and trans-placental infection of the embryo from the dam have been found. As for any infectious animal disease, the spread of BTV can be heavily influenced by human interventions preventing or facilitating the transmission pathways. This paper describes the results of investigations that were conducted on the potential role of the above-mentioned human interventions on the spread of BTV-8 during the 2006 epidemic in north-western Europe. Data on surveillance and control measures implemented in the affected European Union (EU) Member States (MS) were extracted from the legislation and procedures adopted by the national authorities in Belgium, France, Germany, and The Netherlands. The impact of the control measures on the BTV-incidence in time and space was explored. Data on ruminant transports leaving the area of first infection (AFI) to other areas within and beyond the affected MS were obtained from the national identification and registration systems of the three initially affected MS (Belgium, Germany, The Netherlands) and from the Trade Control and Expert System (TRACES) of the European Commission. The association between the cumulative number of cases that occurred in a municipality outside the AFI and the number of movements or the number of animals moved from the AFI to that municipality was assessed using a linear negative binomial regression model. The results of this study indicated that the control measures which were implemented in the affected MS (in accordance with EU directives) were not able to fully stop further spread of BTV and to control the epidemic. This finding is not surprising because BT is a vector-borne disease and it is difficult to limit vector movements. We could not assess the consequences of not taking control measures at all but it is possible, if not most likely, that this would have resulted in even wider spread. The study also showed an indication of the possible involvement of animal movements in the spread of BTV during the epidemic. Therefore, the prevention of animal movements remains an important tool to control BTV outbreaks. The extension of the epidemic to the east cannot be explained by the movement of animals, which mainly occurred in a north-western direction. This indicates that it is important to consider other influential factors such as dispersal of infected vectors depending on wind direction, or local spread

Evaluation of Chromogenic Media for Detection of Methicillin-Resistant Staphylococcus aureus▿†

Rapid laboratory diagnosis is critical for treating, managing, and preventing methicillin-resistant Staphylococcus aureus (MRSA) infections. We evaluated and compared the potential for MRSA detection of five chromogenic media, Brilliance MRSA agar (Oxoid), ChromID (bioMérieux), MRSASelect (Bio-Rad), CHROMagar (CHROMagar Microbiology), and BBL-CHROMagar (BD Diagnostics). Media were tested with log serial dilutions (100 to 106 CFU) of pure isolates of MRSA (n = 60), non-MRSA (n = 27), and defined mixtures thereof simulating clinical samples (n = 84). Further evaluations were done on pre-enriched nasal and groin screening swabs (n = 213) from 165 hospitalized patients. Randomized samples were spiral plated on each medium and independently scored by five investigators for characteristic colonies at 24 and 48 h of incubation. Confirmatory testing of up to five putative MRSA colonies recovered from each medium was done. The cumulative average sensitivity with isolates, mixtures, and clinical samples was the highest for Brilliance MRSA agar (97%) and similar for the other four media (≥92%). The cumulative average specificity was the highest for BBL-CHROMagar (99%), followed by MRSASelect (98%), CHROMagar (97%), ChromID (89%), and Brilliance MRSA agar (86%). All of the media detected MRSA at 10 and 1 CFU, although at these low loads, few MRSA samples harboring SCCmec type III or IV were misinterpreted as non-MRSA by investigators. False-positive results were mainly due to methicillin-resistant S. epidermidis. For an arbitrary MRSA prevalence of 5% and based on patient sample evaluations, the positive predictive values for BBL-CHROMagar and CHROMagar (∼84%) were the highest. The negative predictive values of all of the media were ≥92% for MRSA prevalences ranging from 5% to 30%. In conclusion, BBL-CHROMagar and CHROMagar gave the best overall results for detection of MRSA, irrespective of the sample concentration, investigator, or incubation period

Developing TK databases and tools to support food safety assessment

International audiencerequirements for pre-market authorisation of pesticides (regulation 283-284/2013) for which comparative in vitro metabolism (rat) human and in vivo rat TK data are required. As a consequence, EFSA has been involved in collaborative research to develop TK tools and databases for food safety in the human health, animal health and ecological area. After problem formulation, risk assessors may start at low tier (e.g. basic information and default values) under time and resource constraints, or use all data available for a particular chemical. In this situation, ADME and toxicity information may allow sound dose response modelling and a full quantitative assessment. In a broad context, developing generic tools and databases allow replacing default values with quantitative metrics for physiological, TK and toxicity parameters in any data situation. First, physiological parameters for species of interest are collected and integrated, within a set of differential equations, into generic models. These range from allometric scaling, one compartment model to full physiologically-based TK models (PB-TK). Third, databases reporting physico-chemical and ADME properties, TK parameters and bioaccumulation provide input data to run the models for predicting blood concentrations or elimination patterns. Applications are illustrated including modelling interspecies differences in renal elimination using allometric scaling, integrating variability in human metabolism into generic PB-TK models and development of a modelling platform: TKplate (Wiecek et al., 2018, Darney et al., 2018). Future perspectives include the development of guidance and case studies to use TK tools in routine risk assessment and training programmes