Kaare Græsbøll

The range of attraction for light traps catching Culicoides biting midges (Diptera: Ceratopogonidae)

BackgroundCulicoides are vectors of e.g. bluetongue virus and Schmallenberg virus in northern Europe. Light trapping is an important tool for detecting the presence and quantifying the abundance of vectors in the field. Until now, few studies have investigated the range of attraction of light traps.MethodsHere we test a previously described mathematical model (Model I) and two novel models for the attraction of vectors to light traps (Model II and III). In Model I, Culicoides fly to the nearest trap from within a fixed range of attraction. In Model II Culicoides fly towards areas with greater light intensity, and in Model III Culicoides evaluate light sources in the field of view and fly towards the strongest. Model II and III incorporated the directionally dependent light field created around light traps with fluorescent light tubes. All three models were fitted to light trap collections obtained from two novel experimental setups in the field where traps were placed in different configurations.ResultsResults showed that overlapping ranges of attraction of neighboring traps extended the shared range of attraction. Model I did not fit data from any of the experimental setups. Model II could only fit data from one of the setups, while Model III fitted data from both experimental setups.ConclusionsThe model with the best fit, Model III, indicates that Culicoides continuously evaluate the light source direction and intensity. The maximum range of attraction of a single 4W CDC light trap was estimated to be approximately 15.25 meters. The attraction towards light traps is different from the attraction to host animals and thus light trap catches may not represent the vector species and numbers attracted to hosts.

How Fitness Reduced, Antimicrobial Resistant Bacteria Survive and Spread: A Multiple Pig - Multiple Bacterial Strain Model

More than 30% of E. coli strains sampled from pig farms in Denmark over the last five years were resistant to the commonly used antimicrobial tetracycline. This raises a number of questions: How is this high level sustained if resistant bacteria have reduced growth rates? Given that there are multiple susceptible and resistant bacterial strains in the pig intestines, how can we describe their coexistence? To what extent does the composition of these multiple strains in individual pigs influence the total bacterial population of the pig pen? What happens to a complex population when antimicrobials are used? To investigate these questions, we created a model where multiple strains of bacteria coexist in the intestines of pigs sharing a pen, and explored the parameter limits of a stable system; both with and without an antimicrobial treatment. The approach taken is a deterministic bacterial population model with stochastic elements of bacterial distributions and transmission. The rates that govern the model are process-oriented to represent growth, excretion, and uptake from environment, independent of herd and meta-population structures. Furthermore, an entry barrier and elimination process for the individual strains in each pig were implemented. We demonstrate how competitive growth between multiple bacterial strains in individual pigs, and the transmission between pigs in a pen allow for strains of antimicrobial resistant bacteria to persist in a pig population to different extents, and how quickly they can become dominant if antimicrobial treatment is initiated. The level of spread depends in a non-linear way of the parameters that govern excretion and uptake. Furthermore, the sampling of initial distributions of strains and stochastic transmission events give rise to large variation in how homogenous and how resistant the bacterial population becomes. Most important: resistant bacteria are demonstrated to survive with a disadvantage in growth rate of well over 10%.

Pharmacokinetic-Pharmacodynamic Model To Evaluate Intramuscular Tetracycline Treatment Protocols To Prevent Antimicrobial Resistance in Pigs

ABSTRACT High instances of antimicrobial resistance are linked to both routine and excessive antimicrobial use, but excessive or inappropriate use represents an unnecessary risk. The competitive growth advantages of resistant bacteria may be amplified by the strain dynamics; in particular, the extent to which resistant strains outcompete susceptible strains under antimicrobial pressure may depend not only on the antimicrobial treatment strategies but also on the epidemiological parameters, such as the composition of the bacterial strains in a pig. This study evaluated how variation in the dosing protocol for intramuscular administration of tetracycline and the composition of bacterial strains in a pig affect the level of resistance in the intestine of a pig. Predictions were generated by a mathematical model of competitive growth of Escherichia coli strains in pigs under specified plasma concentration profiles of tetracycline. All dosing regimens result in a clear growth advantage for resistant strains. Short treatment duration was found to be preferable, since it allowed less time for resistant strains to outcompete the susceptible ones. Dosing frequency appeared to be ineffective at reducing the resistance levels. The number of competing strains had no apparent effect on the resistance level during treatment, but possession of fewer strains reduced the time to reach equilibrium after the end of treatment. To sum up, epidemiological parameters may have more profound influence on growth dynamics than dosing regimens and should be considered when designing improved treatment protocols.

Simulating the Epidemiological and Economic Impact of Paratuberculosis Control Actions in Dairy Cattle

We describe a new mechanistic bioeconomic model for simulating the spread of Mycobacterium avium subsp. paratuberculosis (MAP) within a dairy cattle herd. The model includes age-dependent susceptibility for infection; age-dependent sensitivity for detection; environmental MAP build up in five separate areas of the farm; in utero infection; infection via colostrum and waste milk, and it allows for realistic culling (i.e., due to other diseases) by including a ranking system. We calibrated the model using a unique dataset from Denmark, including 102 random farms with no control actions against spread of MAP. Likewise, four control actions recommended in the Danish MAP control program were implemented in the model based on reported management strategies in Danish dairy herds in a MAP control scheme. We tested the model parameterization in a sensitivity analysis. We show that a test-and-cull strategy is on average the most cost-effective solution to decrease the prevalence and increase the total net revenue on a farm with low hygiene, but not more profitable than no control strategy on a farm with average hygiene. Although it is possible to eradicate MAP from the farm by implementing all four control actions from the Danish MAP control program, it was not economically attractive since the expenses for the control actions outweigh the benefits. Furthermore, the three most popular control actions against the spread of MAP on the farm were found to be costly and inefficient in lowering the prevalence when used independently.

Models to Estimate Lactation Curves of Milk Yield and Somatic Cell Count in Dairy Cows at the Herd Level for the Use in Simulations and Predictive Models

Typically, central milk recording data from dairy herds are recorded less than monthly. Over-fitting early in lactation periods is a challenge, which we explored in different ways by reducing the number of parameters needed to describe the milk yield and somatic cell count of individual cows. Furthermore, we investigated how the parameters of lactation models correlate between parities and from dam to offspring. The aim of the study was to provide simple and robust models for cow level milk yield and somatic cell count for fitting to sparse data to parameterize herd- and cow-specific simulation of dairy herds. Data from 610 Danish Holstein herds were used to determine parity traits in milk production regarding milk yield and somatic cell count of individual cows. Parity was stratified in first, second, and third and higher for milk, and first to sixth and higher for somatic cell count. Fitting of herd level parameters allowed for cow level lactation curves with three, two, or one parameters per lactation. Correlations of milk yield and somatic cell count were estimated between lactations and between dam and offspring. The shape of the lactation curves varied markedly between farms. The correlation between lactations for milk yield and somatic cell count was 0.2–0.6 and significant on more than 95% of farms. The variation in the daily milk yield was observed to be a source of variation to the somatic cell count, and the total somatic cell count was less correlated with the milk production than somatic cells per milliliter. A positive correlation was found between relative levels of the total somatic cell count and the milk yield. The variation of lactation and somatic cell count curves between farms highlights the importance of a herd level approach. The one-parameter per cow model using a herd level curve allows for estimating the cow production level from first the recording in the parity, while a two-parameter model requires more recordings for a credible estimate, but may more precisely predict persistence, and given the independence of parameters, these can be easily drawn for use in simulation models. We also conclude that using total somatic cell count may stabilize models, and therefore, the dilution factor is of importance in Danish Holstein.

Optimal vaccination strategies against vector-borne diseases.

Using a process oriented semi-agent based model, we simulated the spread of Bluetongue virus by Culicoides, biting midges, between cattle in Denmark. We evaluated the minimum vaccination cover and minimum cost for eight different preventive vaccination strategies in Denmark. The simulation model replicates both a passive and active flight of midges between cattle distributed on pastures and cattle farms in Denmark. A seasonal abundance of midges and temperature dependence of biological processes were included in the model. The eight vaccination strategies were investigated under four different grazing conditions. Furthermore, scenarios were tested with three different index locations stratified for cattle density. The cheapest way to vaccinate cattle with a medium risk profile (less than 1000 total affected cattle) was to vaccinate cattle on pasture. Regional vaccination displayed better results when index cases were in the vaccinated areas. However, given that the long-range spread of midge borne disease is still poorly quantified, more robust national vaccination schemes seem preferable.

Modeling the growth dynamics of multiple Escherichia coli strains in the pig intestine following intramuscular ampicillin treatment

BackgroundThis study evaluated how dosing regimen for intramuscularly-administered ampicillin, composition of Escherichia coli strains with regard to ampicillin susceptibility, and excretion of bacteria from the intestine affected the level of resistance among Escherichia coli strains in the intestine of nursery pigs. It also examined the dynamics of the composition of bacterial strains during and after the treatment. The growth responses of strains to ampicillin concentrations were determined using in vitro growth curves. Using these results as input data, growth predictions were generated using a mathematical model to simulate the competitive growth of E. coli strains in a pig intestine under specified plasma concentration profiles of ampicillin.ResultsIn vitro growth results demonstrated that the resistant strains did not carry a fitness cost for their resistance, and that the most susceptible strains were more affected by increasing concentrations of antibiotics that the rest of the strains. The modeling revealed that short treatment duration resulted in lower levels of resistance and that dosing frequency did not substantially influence the growth of resistant strains. Resistance levels were found to be sensitive to the number of competing strains, and this effect was enhanced by longer duration of treatment. High excretion of bacteria from the intestine favored resistant strains over sensitive strains, but at the same time it resulted in a faster return to pre-treatment levels after the treatment ended. When the duration of high excretion was set to be limited to the treatment time (i.e. the treatment was assumed to result in a cure of diarrhea) resistant strains required longer time to reach the previous level.ConclusionNo fitness cost was found to be associated with ampicillin resistance in E. coli. Besides dosing factors, epidemiological factors (such as number of competing strains and bacterial excretion) influenced resistance development and need to be considered further in relation to optimal treatment strategies. The modeling approach used in the study is generic, and could be used for prediction of the effect of treatment with other drugs and other administration routes for effect on resistance development in the intestine of pigs.

Danish holsteins favor bull offspring: biased milk production as a function of fetal sex, and calving difficulty.

In a previous study from 2014 it was found that US Holstein cows that gave birth to heifer calves produced more milk than cows having bull calves. We wanted to assess whether this is also true for Danish cattle. Data from 578 Danish Holstein herds were analysed with a mixed effect model and contrary to the findings in the US, we found that cows produced higher volumes of milk if they had a bull calf compared to a heifer calf. We found a significantly higher milk production of 0.28% in the first lactation period for cows giving birth to a bull calf, compared to a heifer calf. This difference was even higher when cows gave birth to another bull calf, so having two bull calves resulted in a difference of 0.52% in milk production compared to any other combination of sex of the offspring. Furthermore, we found that farmer assisted calvings were associated with a higher milk yield. Cows with no farmer assistance or with veterinary assistance during the most recent calving produced less milk. There were also indications that dams would favor a bull fetus by decreasing milk production during the second pregnancy if the calf born in the first parity was a heifer. We hypothesize that size of calves is a confounding factor for milk production. However, calving weight was not available in the present data set to test this hypothesis.

A Robust Statistical Model to Predict the Future Value of the Milk Production of Dairy Cows Using Herd Recording Data

The future value of an individual dairy cow depends greatly on its projected milk yield. In developed countries with developed dairy industry infrastructures, facilities exist to record individual cow production and reproduction outcomes consistently and accurately. Accurate prediction of the future value of a dairy cow requires further detailed knowledge of the costs associated with feed, management practices, production systems, and disease. Here, we present a method to predict the future value of the milk production of a dairy cow based on herd recording data only. The method consists of several steps to evaluate lifetime milk production and individual cow somatic cell counts and to finally predict the average production for each day that the cow is alive. Herd recording data from 610 Danish Holstein herds were used to train and test a model predicting milk production (including factors associated with milk yield, somatic cell count, and the survival of individual cows). All estimated parameters were either herd- or cow-specific. The model prediction deviated, on average, less than 0.5 kg from the future average milk production of dairy cows in multiple herds after adjusting for the effect of somatic cell count. We conclude that estimates of future average production can be used on a day-to-day basis to rank cows for culling, or can be implemented in simulation models of within-herd disease spread to make operational decisions, such as culling versus treatment. An advantage of the approach presented in this paper is that it requires no specific knowledge of disease status or any other information beyond herd recorded milk yields, somatic cell counts, and reproductive status.

Effect of Tetracycline Dose and Treatment Mode on Selection of Resistant Coliform Bacteria in Nursery Pigs

ABSTRACT This study describes the results of a randomized clinical trial investigating the effect of oxytetracycline treatment dose and mode of administration on the selection of antibiotic-resistant coliform bacteria in fecal samples from nursery pigs. Nursery pigs (pigs of 4 to 7 weeks of age) in five pig herds were treated with oxytetracycline for Lawsonia intracellularis-induced diarrhea. Each group was randomly allocated to one of five treatment groups: oral flock treatment with a (i) high (20 mg/kg of body weight), (ii) medium (10 mg/kg), or (iii) low (5 mg/kg) dose, (iv) oral pen-wise (small-group) treatment (10 mg/kg), and (v) individual intramuscular injection treatment (10 mg/kg). All groups were treated once a day for 5 days. In all groups, treatment caused a rise in the numbers and proportions of tetracycline-resistant coliform bacteria right after treatment, followed by a significant drop by the time that the pigs left the nursery unit. The counts and proportions of tetracycline-resistant coliforms did not vary significantly between treatment groups, except immediately after treatment, when the highest treatment dose resulted in the highest number of resistant coliforms. A control group treated with tiamulin did not show significant changes in the numbers or proportions of tetracycline-resistant coliforms. Selection for tetracycline-resistant coliforms was significantly correlated to selection for ampicillin- and sulfonamide-resistant strains but not to selection for cefotaxime-resistant strains. In conclusion, the difference in the dose of oxytetracycline and the way in which the drug was applied did not cause significantly different levels of selection of tetracycline-resistant coliform bacteria under the conditions tested. IMPORTANCE Antimicrobial resistance is a global threat to human health. Treatment of livestock with antimicrobials has a direct impact on this problem, and there is a need to improve the ways that we use antimicrobials in livestock production. We hypothesized that antibiotic resistance development following treatment of diarrhea in nursery pigs could be reduced either by lowering the dose of oxytetracycline or by replacing the commonly used practice of flock treatment with individual or small-group treatments, since this would reduce the number of pigs treated. However, the study showed no significant difference between treatment groups with respect to the number or proportion of tetracycline-resistant coliforms selected. The most important conclusion is that under practical field conditions, there will be no added value, in terms of lowering resistance development, by exchanging flock treatment for individual or small-group treatment of nursery pigs. The reason for the lack of an effect of single-animal treatment is probably that such animals share the environment with treated animals and take up resistant bacteria from the environment.