SimInf: An R package for Data-driven Stochastic Disease Spread Simulations

We present the R package SimInf which provides an efficient and very flexible framework to conduct data-driven epidemiological modeling in realistic large scale disease spread simulations. The framework integrates infection dynamics in subpopulations as continuous-time Markov chains using the Gillespie stochastic simulation algorithm and incorporates available data such as births, deaths and movements as scheduled events at predefined time-points. Using C code for the numerical solvers and OpenMP to divide work over multiple processors ensures high performance when simulating a sample outcome. One of our design goal was to make SimInf extendable and enable usage of the numerical solvers from other R extension packages in order to facilitate complex epidemiological research. In this paper, we provide a technical description of the framework and demonstrate its use on some basic examples. We also discuss how to specify and extend the framework with user-defined models.Comment: The manual has been updated to the latest version of SimInf (v6.0.0). 41 pages, 16 figure

Graph theory in veterinary epidemiology

One objective of this study has been to demonstrate how graph theory can be a useful tool for intervention in the case of an outbreak of a contagious disease. By using graph theory algorithms on data from the Swedish surveillance network system (Grisregistret) and combining this with the power of graph layout engines for visualization of interherd movements, valuable information can rapidly be provided from data that is easily available. Thus a clear line of priority in the strategy of fighting the outbreak can be established from day 0. This can be invaluable during the first couple of days, before more thorough information concerning all different types of contacts has been collected by veterinarians during farm visits. Thus rapid control measures can be implemented and this should increase the likelihood that possible infectious holdings are found during an early stage of the outbreak. Combining the information of the geographical location of an infectious holding and the interherd movements during the relevant time period on the same map can improve the understanding of the spread of the outbreak. It would also be possible to add information concerning other types of contacts, when such information becomes available, to make the picture clearer. Another objective has been to model a putative outbreak of classical swine fever without any interventions from authorities. The epidemiological model uses data from the Swedish surveillance network system of pig movements, Grisregistret, based on the reported flows of pigs between farms. The model includes all interherd pig movements that occurred within a community in southern Sweden during 6 months. Both a high virulent strain and a low virulent strain of classical swine fever virus have been modelled. The epidemiological model is based on a SEIRD model for each holding, which have been interconnected to each other through the reported movements of pigs.Ett syfte med den här studien har varit att visa hur grafteori skulle kunna vara ett användbart verktyg vid bekämpning av ett utbrott av en smittsam sjukdom. Genom att använda grafteori algoritmer på data från det svenska Grisregistret och kombinera detta med möjligheten att visualisera förflyttningar mellan gårdar kan man få fram värdefull information snabbt från data som är lätt tillgänglig. Därmed får man ett underlag för prioriteringar i bekämpningsstrategin redan dag 0. Detta är viktigt under de första dagarna, innan mer detaljerad information samlats in genom gårdsbesök av veterinär. På så sätt kan kontrollåtgärder snabbt sättas in och borde öka möjligheten att tidigt under utbrottet finna gårdar som kan vara smittade. Därutöver skulle det också vara användbart att markera gårdarnas läge och förflyttningar av djur mellan dem på samma karta för att ytterligare öka förståelsen för spridningen av sjukdomen. Det skulle också vara möjligt att komplettera med information avseende andra typer av kontakter, när sådan informationen finns tillgänglig, för att få en tydligare bild. Ett annat syfte med studien har varit att modellera ett tänkt utbrott av klassisk svinpest utan att några insatser görs för att begränsa spridningen. Den epidemiologiska modellen använder data från det svenska Grisregistret, innehållande rapporterade förflyttningar av grisar mellan gårdar. Modellen inkluderar grisförflyttningar under 6 månader från en kommun i södra Sverige. Både en hög- och lågvirulent stam av klassiskt svinpestvirus har modellerats. Den epidemiologiska modellen bygger på en SEIRD modell för varje gård som kopplats samman genom de förflyttningar som är rapporterade till Grisregistret

Studies on verotoxigenic Escherichia coli O157 in Swedish cattle

Verotoxigenic Escherichia coli O157:H7 (VTEC O157) is an important zoonotic pathogen capable of causing infections in humans, sometimes with severe symptoms such as hemorrhagic colitis and hemolytic uremic syndrome (HUS). Cattle are considered to be the main reservoir of the bacterium. In this thesis, sampling strategies to detect VTEC O157 in a cattle herd, risk factors for the introduction and the spread of VTEC O157 in Swedish cattle herds, as well as options for control, are studied. A spatial data-driven stochastic model was developed to explore the spread of VTEC O157 by livestock movements and local transmission among proximal holdings in the complete Swedish cattle population. Overshoe sampling alone or in combination with dust and/or pooled pat sampling were established to be reliable for identifying cattle herds with animals shedding VTEC O157. Results from field studies and computer simulations show that animal movements and local spread are important for the transmission of VTEC O157 in the Swedish cattle population. However, simulated control measures based on reducing the between-herd VTEC O157 transmission by animal movements and local spread, had marginal effect in decreasing the prevalence. On the other hand, simulated control measures based on reducing the shedding and susceptibility, efficiently decreased the prevalence of VTEC O157 in the Swedish cattle population

Modelling spread and surveillance of Mycobacterium avium subsp. paratuberculosis in the Swedish cattle trade network

To monitor a state of disease freedom and to ensure a timely detection of new introductions of disease, surveillance programmes need be evaluated prior to implementation. We present a strategy to evaluate surveillance of Mycobacterium avium subsp. paratuberculosis (MAP) using simulated testing of bulk milk in an infectious disease spread model. MAP is a globally distributed, chronic infectious disease with substantial animal health impact. Designing surveillance for this disease poses specific challenges because methods for surveillance evaluation have focused on estimating surveillance system sensitivity and probability of freedom from disease and do not account for spread of disease or complex and changing population structure over long periods. The aims of the study were to 1. define a model that describes the spread of MAP within and between Swedish herds; 2. define a method for simulation of imperfect diagnostic testing in this framework; 3. to compare surveillance strategies to support surveillance design choices. The results illustrate how this approach can be used to identify differences between the probability of detecting disease in the population based on choices of the number of herds sampled and the use of risk-based or random selection of these herds. The approach was also used to assess surveillance to detect introduction of disease and to detect a very low prevalence endemic state. The use of bulk milk sampling was determined to be an effective method to detect MAP in the population with as few as 500 herds tested per year if the herd-level prevalence was 0.2 %. However, detection of point introductions in the population was unlikely in the 13-year simulation period even if as many as 2000 herds were tested per year. Interestingly, the use of a risk-based selection strategy was found to be a disadvantage to detect MAP given the modelled disease dynamics

Infection prevention and control interventions in the first outbreak of methicillin-resistant Staphylococcus aureus infections in an equine hospital in Sweden

<p>Abstract</p> <p>Background</p> <p>The first outbreak of methicillin-resistant <it>Staphylococcus aureus </it>(MRSA) infection in horses in Sweden occurred in 2008 at the University Animal Hospital and highlighted the need for improved infection prevention and control. The present study describes interventions and infection prevention control in an equine hospital setting July 2008 - April 2010.</p> <p>Method</p> <p>This descriptive study of interventions is based on examination of policy documents, medical records, notes from meetings and cost estimates. MRSA cases were identified through clinical sampling and telephone enquiries about horses post-surgery. Prospective sampling in the hospital environment with culture for MRSA and genotyping of isolates by <it>spa</it>-typing and pulsed-field gel electrophoresis (PFGE) were performed.</p> <p>Results</p> <p>Interventions focused on interruption of indirect contact spread of MRSA between horses via staff and equipment and included: Temporary suspension of elective surgery; and identification and isolation of MRSA-infected horses; collaboration was initiated between authorities in animal and human public health, human medicine infection control and the veterinary hospital; extensive cleaning and disinfection was performed; basic hygiene and cleaning policies, staff training, equipment modification and interior renovation were implemented over seven months.</p> <p>Ten (11%) of 92 surfaces sampled between July 2008 and April 2010 tested positive for MRSA <it>spa</it>-type 011, seven of which were from the first of nine sampling occasions. PFGE typing showed the isolates to be the outbreak strain (9 of 10) or a closely related strain. Two new cases of MRSA infection occurred 14 and 19 months later, but had no proven connections to the outbreak cases.</p> <p>Conclusions</p> <p>Collaboration between relevant authorities and the veterinary hospital and formation of an infection control committee with an executive working group were required to move the intervention process forward. Support from hospital management and the dedication of staff were essential for the development and implementation of new, improved routines. Demonstration of the outbreak strain in the environment was useful for interventions such as improvement of cleaning routines and interior design, and increased compliance with basic hygienic precautions. The interventions led to a reduction in MRSA-positive samples and the outbreak was considered curbed as no new cases occurred for over a year.</p

Evaluation of farm-level parameters derived from animal movements for use in risk-based surveillance programmes of cattle in Switzerland

This study focused on the descriptive analysis of cattle movements and farm-level parameters derived from cattle movements, which are considered to be generically suitable for risk-based surveillance systems in Switzerland for diseases where animal movements constitute an important risk pathway.; A framework was developed to select farms for surveillance based on a risk score summarizing 5 parameters. The proposed framework was validated using data from the bovine viral diarrhoea (BVD) surveillance programme in 2013.; A cumulative score was calculated per farm, including the following parameters; the maximum monthly ingoing contact chain (in 2012), the average number of animals per incoming movement, use of mixed alpine pastures and the number of weeks in 2012 a farm had movements registered. The final score for the farm depended on the distribution of the parameters. Different cut offs; 50, 90, 95 and 99 %, were explored. The final scores ranged between 0 and 5. Validation of the scores against results from the BVD surveillance programme 2013 gave promising results for setting the cut off for each of the five selected farm level criteria at the 50th percentile. Restricting testing to farms with a score ≥ 2 would have resulted in the same number of detected BVD positive farms as testing all farms, i.e., the outcome of the 2013 surveillance programme could have been reached with a smaller survey.; The seasonality and time dependency of the activity of single farms in the networks requires a careful assessment of the actual time period included to determine farm level criteria. However, selecting farms in the sample for risk-based surveillance can be optimized with the proposed scoring system. The system was validated using data from the BVD eradication program. The proposed method is a promising framework for the selection of farms according to the risk of infection based on animal movements

Spatio-temporal evaluation of cattle trade in Sweden: description of a grid network visualization technique

Abstract. Understanding the intensity and spatial patterns of animal transfers is of prime importance as geographical moves play an important part in the spread and potential control of contagious animal diseases of veterinary importance. For the purpose of visualizing all registered between-herd animal movements in Sweden between 1 July 2005 and 31 December 2008 by map animation, a grid network technique based on the Bresenham line algorithm was developed. Potential spatio-temporal clustering of animals registered as sold or purchased based on location and month of trade was also detected and tested using a spatial scan statistic. Calculations were based on data from 31,375 holdings and 3,487,426 head of cattle. In total, 988,167 between-herd movements of individual bovines were displayed in a sequence of maps covering three and a half years by 2-week intervals. The maps showed that several cattle movements, both short- and long-distance, take place in Sweden each week of the year. However, most animals (75%) were only registered at one single holding during the study period and 23 % were sold to a different holding once. Spatial scan statistics based on data from the year 2008 indicated uneven distributions of purchased or sold animals in space and time. During each autumn, there was an increase in cattle movements and October and November showed significantly more cases of sold or purchased animals (relative risk ~1.7, p = 0.001). Based on the results, we conclude that cattle trade is constantly active at a considerable level. This, in combination with possibly insufficient biosecurity routines applied on many farms, constitutes a risk that contagious diseases are spread in the population. The grid network map

Bayesian epidemiological modeling over high-resolution network data

Mathematical epidemiological models have a broad use, including both qualitative and quantitative applications. With the increasing availability of data, large-scale quantitative disease spread models can nowadays be formulated. Such models have a great potential, e.g., in risk assessments in public health. Their main challenge is model parameterization given surveillance data, a problem which often limits their practical usage. We offer a solution to this problem by developing a Bayesian methodology suitable to epidemiological models driven by network data. The greatest difficulty in obtaining a concentrated parameter posterior is the quality of surveillance data; disease measurements are often scarce and carry little information about the parameters. The often overlooked problem of the model's identifiability therefore needs to be addressed, and we do so using a hierarchy of increasingly realistic known truth experiments. Our proposed Bayesian approach performs convincingly across all our synthetic tests. From pathogen measurements of shiga toxin-producing Escherichia coli O157 in Swedish cattle, we are able to produce an accurate statistical model of first-principles confronted with data. Within this model we explore the potential of a Bayesian public health framework by assessing the efficiency of disease detection and -intervention scenarios.eSSENC

The Inter-institutional Distribution of Power in EU Codecision

power measurement; European Union codecision procedure, bargaining, spatial voting, decision procedures