Automated local lockdowns for SARS-CoV-2 epidemic control-assessment of effect by controlled interrupted time series analysis.

Objectives: During the COVID-19 pandemic, broad non-pharmaceutical interventions such as national lockdowns were effective but had significant drawbacks, prompting targeted approaches, such as Denmark's localized lockdowns, based on specific epidemiological criteria. This study evaluates the effect of Denmark's automated local lockdown strategy on epidemic control to inform future response. Methods: This was a register-based controlled interrupted time series analysis, examining SARS-CoV-2 infection rates in Danish parishes from March to September 2021. The matching of control parishes was based on location, time, and pre-lockdown infection trends, with the lockdown's start defined as the day after a parish exceeded the lockdown criteria. Follow-up included 3-week pre-lockdown and 2-week post-lockdown. Results: A total of 30 parishes were mandated to lockdown, approximately 3.5% of the population of Denmark. A total of 94 control parishes were used as 109 controls. The decrease in the incidence during the 2-week follow-up period after the initiation of the lockdown was 13% points higher in case parishes: in case parishes, the incidence was reduced by 78% compared with 65% in control parishes. Conclusions: Our findings demonstrate that local lockdowns did have a positive effect in mitigating the spread of the SARS-CoV-2 virus, making them valuable in the fight against the COVID-19 pandemic and an important alternative to national lockdowns.

First cases of SARS-CoV-2 BA.2.86 in Denmark, 2023.

We describe 10 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant BA.2.86 detected in Denmark, including molecular characteristics and results from wastewater surveillance that indicate that the variant is circulating in the country at a low level. This new variant with many spike gene mutations was classified as a variant under monitoring by the World Health Organization on 17 August 2023. Further global monitoring of COVID-19, BA.2.86 and other SARS-CoV-2 variants is highly warranted.

Predicting COVID-19 Incidence Using Wastewater Surveillance Data, Denmark, October 2021-June 2022.

Analysis of wastewater is used in many settings for surveillance of SARS-CoV-2, but it remains unclear how well wastewater testing results reflect incidence. Denmark has had an extensive wastewater analysis system that conducts 3 weekly tests in ≈200 sites and has 85% population coverage; the country also offers free SARS-CoV-2 PCR tests to all residents. Using time series analysis for modeling, we found that wastewater data, combined with information on circulating variants and the number of human tests performed, closely fitted the incidence curve of persons testing positive. The results were consistent at a regional level and among a subpopulation of frequently tested healthcare personnel. We used wastewater analysis data to estimate incidence after testing was reduced to a minimum after March 2022. These results imply that data from a large-scale wastewater surveillance system can serve as a good proxy for COVID-19 incidence and for epidemic control.

Estimating true prevalence through questionnaire data.

We present a general analytical method for obtaining unbiased prevalence estimates based on data from regional or national testing programs, where individual participation in the testing program is voluntary but where additional questionnaire data is collected regarding the individual-level reason/motivation for being tested. The approach is based on re-writing the conditional probabilities for being tested, being infected, and having symptoms, so that a series of equations can be defined that relate estimable quantities (from test data and questionnaire data) to the result of interest (an unbiased estimate of prevalence). The final estimates appear to be robust based on prima-facie examination of the temporal dynamics estimated, as well as agreement with an independent estimate of prevalence. Our approach demonstrates the potential strength of incorporating questionnaires when testing a population during an outbreak, and can be used to help obtain unbiased estimates of prevalence in similar settings.

The ALEX algorithm - estimating average lifetime antimicrobial exposure of danish slaughter pigs in a fast, automated and robust way.

Calculating and estimating antimicrobial exposure at specific batch level is key to understanding consumption patterns of antimicrobials in the Danish pig sector. Understanding consumption and trading patterns can assist in developing treatment plans at national levels and might lead to reducing antimicrobial resistance levels. The ALEX algorithm is a fast, automated and robust algorithm developed to estimate the average lifetime antimicrobial exposure of Danish slaughter pigs. The algorithm estimates antimicrobial exposure in the different life stages of the pig (piglet, weaner and finisher) together with the type of production network (the number of farms within a network and ownership of these). We present the algorithm and give two examples of usage. Furthermore, we compare the ALEX algorithm with an acknowledged exposure estimation algorithm, and we present a sensitivity analysis.

Risk of reinfection, vaccine protection, and severity of infection with the BA.5 omicron subvariant: a nation-wide population-based study in Denmark.

BACKGROUND: Estimates of immunity and severity for the SARS-CoV-2 omicron subvariant BA.5 are important to assess the public health impact associated with its rapid global spread despite vaccination. We estimated natural and vaccine immunity and severity of BA.5 relative to BA.2 in Denmark, a country with high mRNA-vaccination coverage and free-of-charge RT-PCR testing. METHODS: This nation-wide population-based study in Denmark included residents aged 18 years or older who had taken an RT-PCR test between 10 April and 30 June, 2022 (ie, the outcome period), and who the national COVID-19 surveillance system identified as having information since February 2020 on RT-PCR tests, whole-genome sequencing, vaccinations, and hospitalisation with a positive RT-PCR test and COVID-19 as the main diagnosis. First, we used a case-control design, in which cases were people infected with BA.5 or BA.2 during the outcome period and controls were people who tested negative for SARS-CoV-2 infection during the outcome period. We calculated the protection provided by a previous PCR-confirmed omicron infection against BA.5 and BA.2 infection and hospitalisation among triple-vaccinated individuals. Second, we compared vaccination status in people infected with BA.5 versus BA.2 and estimated relative vaccine protection against each subvariant. Third, we compared rates of hospitalisation for COVID-19 among people infected with BA.5 versus BA.2. We estimated effects using logistic regression with adjustment for sex, age, region, PCR-test date, comorbidity and, as appropriate, vaccination and previous infection status. FINDINGS: A total of 210 (2·4%) of 8678 of BA.5 cases, 192 (0·7%) of 29 292 of BA.2 cases, and 33 972 (19·0%) of 178 669 PCR-negative controls previously had an omicron infection, which was estimated in the adjusted analyses to offer 92·7% (95% CI 91·6-93·7) protection against BA.5 infection and 97·1% (96·6-97·5) protection against BA.2 infection. We found similarly high amounts of protection against hospitalisation owing to infection with BA.5 (96·4% [95% CI 74·2-99·5]) and BA.2 (91·2% [76·3-96·7]). Vaccine coverage (three mRNA doses vs none) was 9307 (94·2%) of 9878 among BA.5 cases and 30 581 (94·8%) of 32 272 among BA.2 cases, although in the adjusted analysis, there was a trend towards slightly higher vaccination coverage among BA.5 cases than BA.2 cases (OR 1·18 [95% CI 0·99-1·42]; p=0·064), possibly suggesting marginally poorer vaccine protection against BA.5. The rate of hospitalisation due to COVID-19 was higher among the BA.5 cases (210 [1·9%] of 11 314) than among the BA.2 cases (514 [1·4%] of 36 805), with an OR of 1·34 (95% CI 1·14-1·57) and an adjusted OR of 1·69 (95% CI 1·22-2·33), despite low and stable COVID-19 hospitalisation numbers during the study period. INTERPRETATION: The study provides evidence that a previous omicron infection in triple-vaccinated individuals provides high amounts of protection against BA.5 and BA.2 infections. However, protection estimates greater than 90% might be too high if individuals with a previous infection were more likely than those without one to come forward for a test for reasons other than suspicion of COVID-19. Our analysis also showed that vaccine protection against BA.5 infection was similar to, or slightly weaker than, protection against BA.2 infection. Finally, there was evidence that BA.5 infections were associated with an increased risk of hospitalisation compared with BA.2 infections. FUNDING: There was no funding source for this study.

Estimating transmission dynamics of African swine fever virus from experimental studies.

African swine fever virus (ASFV) continues to spread across the world, and currently, there are no treatments or vaccines available to combat this virus. Reliable estimates of transmission parameters for ASFV are therefore needed to establish effective contingency plans. This study used data from controlled ASFV inoculations of pigs to assess the transmission parameters. Three models were developed with (binary, piecewise-linear and exponential) time-dependent levels of infectiousness based on latency periods of 3-5 days derived from the analysis of 294 ethylenediamine tetraacetic acid-stabilized blood samples originating from 16 pigs with direct and 10 pigs with indirect contact to 8 inoculated pigs. The models were evaluated for three different discrete latency periods of infection. The likelihood ratio test showed that a binary model had an equally good fit for a latency period of 4 or 5 days as the piecewise-linear and exponential model. However, for a latency period of 3 days, the piecewise-linear and exponential models had the best fit. The modelling was done in discrete time as testing was conducted on specific days. The main contribution of this study is the estimation of ASFV genotype II transmission through the air in a confined space. The estimated transmission parameters via air are not much lower than for direct contact between pigs. The estimated parameters should be useful for future simulations of control measures against ASFV.

Seasonal variation in the transmission rate of covid-19 in a temperate climate can be implemented in epidemic population models by using daily average temperature as a proxy for seasonal changes in transmission rate.

From march 2020 to march 2022 covid-19 has shown a consistent pattern of increasing infections during the Winter and low infection numbers during the Summer. Understanding the effects of seasonal variation on covid-19 spread is crucial for future epidemic modelling and management. In this study, seasonal variation in the transmission rate of covid-19, was estimated based on an epidemic population model of covid-19 in Denmark, which included changes in national restrictions and introduction of the α -variant covid-19 strain, in the period March 2020 - March 2021. Seasonal variation was implemented as a logistic temperature dependent scaling of the transmission rate, and parameters for the logistic relationship was estimated through rejection-based approximate bayesian computation (ABC). The likelihoods used in the ABC were based on national hospital admission data and seroprevalence data stratified into nine and two age groups, respectively. The seasonally induced reduction in the transmission rate of covid-19 in Denmark was estimated to be 27 % , (95% CI [ 24 % ; 31 % ]), when moving from peak Winter to peak Summer. The reducing effect of seasonality on transmission rate per + 1 ∘ C in daily average temperature were shown to vary based on temperature, and were estimated to be - 2.2 % [ - 2.8 % ; - 1.7 % ] pr. 1  ∘ C around 2 ∘ C; 2 % [ - 2.3 % ; - 1.7 % ] pr. 1  ∘ C around 7 ∘ C; and 1.7 % [ - 2.0 % ; - 1.5 % ] pr. 1  ∘ C around a daily average temperature of 11  ∘ C.

Household transmission of SARS-CoV-2 Omicron variant of concern subvariants BA.1 and BA.2 in Denmark.

SARS coronavirus 2 (SARS-CoV-2) continues to evolve and new variants emerge. Using nationwide Danish data, we estimate the transmission dynamics of SARS-CoV-2 Omicron subvariants BA.1 and BA.2 within households. Among 22,678 primary cases, we identified 17,319 secondary infections among 50,588 household contacts during a 1-7 day follow-up. The secondary attack rate (SAR) was 29% and 39% in households infected with Omicron BA.1 and BA.2, respectively. BA.2 was associated with increased susceptibility of infection for unvaccinated household contacts (Odds Ratio (OR) 1.99; 95%-CI 1.72-2.31), fully vaccinated contacts (OR 2.26; 95%-CI 1.95-2.62) and booster-vaccinated contacts (OR 2.65; 95%-CI 2.29-3.08), compared to BA.1. We also found increased infectiousness from unvaccinated primary cases infected with BA.2 compared to BA.1 (OR 2.47; 95%-CI 2.15-2.84), but not for fully vaccinated (OR 0.66; 95%-CI 0.57-0.78) or booster-vaccinated primary cases (OR 0.69; 95%-CI 0.59-0.82). Omicron BA.2 is inherently more transmissible than BA.1. Its immune-evasive properties also reduce the protective effect of vaccination against infection, but do not increase infectiousness of breakthrough infections from vaccinated individuals.

Household transmission of the SARS-CoV-2 Omicron variant in Denmark.

In late 2021, the Omicron SARS-CoV-2 variant overtook the previously dominant Delta variant, but the extent to which this transition was driven by immune evasion or a change in the inherent transmissibility is currently unclear. We estimate SARS-CoV-2 transmission within Danish households during December 2021. Among 26,675 households (8,568 with the Omicron VOC), we identified 14,140 secondary infections within a 1-7-day follow-up period. The secondary attack rate was 29% and 21% in households infected with Omicron and Delta, respectively. For Omicron, the odds of infection were 1.10 (95%-CI: 1.00-1.21) times higher for unvaccinated, 2.38 (95%-CI: 2.23-2.54) times higher for fully vaccinated and 3.20 (95%-CI: 2.67-3.83) times higher for booster-vaccinated contacts compared to Delta. We conclude that the transition from Delta to Omicron VOC was primarily driven by immune evasiveness and to a lesser extent an inherent increase in the basic transmissibility of the Omicron variant.

Effect of vaccination on household transmission of SARS-CoV-2 Delta variant of concern.

Effective vaccines protect individuals by not only reducing the susceptibility to infection, but also reducing the infectiousness of breakthrough infections in vaccinated cases. To disentangle the vaccine effectiveness against susceptibility to infection (VES) and vaccine effectiveness against infectiousness (VEI), we took advantage of Danish national data comprising 24,693 households with a primary case of SARS-CoV-2 infection (Delta Variant of Concern, 2021) including 53,584 household contacts. In this setting, we estimated VES as 61% (95%-CI: 59-63), when the primary case was unvaccinated, and VEI as 31% (95%-CI: 26-36), when the household contact was unvaccinated. Furthermore, unvaccinated secondary cases with an infection exhibited a three-fold higher viral load compared to fully vaccinated secondary cases with a breakthrough infection. Our results demonstrate that vaccinations reduce susceptibility to infection as well as infectiousness, which should be considered by policy makers when seeking to understand the public health impact of vaccination against transmission of SARS-CoV-2.

Communicate hope to motivate the public during the COVID-19 pandemic.

How should health authorities communicate to motivate the public to comply with health advice during a prolonged health crisis such as a pandemic? During the SARS-CoV-2 pandemic, for example, people have had to comply with successive restrictions as the world faced multiple races between controlling new waves of the virus and the development and implementation of vaccines. Here, we examine how health authorities and governments most effectively motivate the public by focusing on a specific race: between the Alpha variant and the implementation of the first generation of COVID-19 vaccinations in the winter of 2021. Following prior research on crisis communication, we focus on appeals to fear and hope using communicative aids in the form of visualizations based on epidemiological modelling. Using a population-based experiment conducted in United States ([Formula: see text]), we demonstrate that a hope-oriented visual communication aid, depicting the competing effects on the epidemic curve of (1) a more infectious variant and (2) vaccinations, motivates public action more effectively than a fear-oriented visual communication, focusing exclusively on the threat of the new variant. The importance of the implementation of such hope-oriented messages is further highlighted by cross-national representative surveys from eight countries ([Formula: see text]), which demonstrate that feelings of fear towards the Alpha variant alone were insufficient to activate strong compliance. Overall, these findings provide general insights into the importance of hope as a health communication strategy during the COVID-19 pandemic and beyond.

Increased transmissibility of SARS-CoV-2 lineage B.1.1.7 by age and viral load.

New lineages of SARS-CoV-2 are of potential concern due to higher transmissibility, risk of severe outcomes, and/or escape from neutralizing antibodies. Lineage B.1.1.7 (the Alpha variant) became dominant in early 2021, but the association between transmissibility and risk factors, such as age of primary case and viral load remains poorly understood. Here, we used comprehensive administrative data from Denmark, comprising the full population (January 11 to February 7, 2021), to estimate household transmissibility. This study included 5,241 households with primary cases; 808 were infected with lineage B.1.1.7 and 4,433 with other lineages. Here, we report an attack rate of 38% in households with a primary case infected with B.1.1.7 and 27% in households with other lineages. Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load.

Mixed effect modeling of tetracycline resistance levels in Danish slaughter pigs.

Mathematical and statistical modeling can be a very useful tool in understanding and fighting antimicrobial resistance (AMR). Here we present investigations of mixed effect models of varying complexity in order to identify and address possible management factors affecting the tetracycline AMR levels in Danish pig farms. Besides antimicrobial exposure during pigs life cycle, the type of production seems to also have an influence. The results concludes that not only fully integrated farms (CHR integrated) but also farms in a production network with a single ownership (CVR integrated) might have a preventive effect on levels of tetracycline AMR compared to more complex trading patterns.

Effect of tetracycline treatment regimens on antibiotic resistance gene selection over time in nursery pigs.

BACKGROUND: The majority of antimicrobials given during the production of pigs are given to nursery pigs. The influence of antimicrobial use on the levels of antimicrobial resistant (AMR) genes is important to quantify to be able to assess the impact of resistance on the food chain and risk to human and animal health. RESULTS: This study investigated the response on the levels of nine AMR genes to five different treatment strategies with oxytetracycline, and the dynamics of gene abundance over time by following 1167 pigs from five different farms in Denmark. The results showed no significant difference between treatments and an increase in abundance for the efflux pump encoding tet(A) gene and the genes encoding the ribosomal protection proteins tet(O) and tet(W) tetracycline resistant genes following treatment, while tet(M) showed no response to treatment. However, it was also observed that the levels of tet(O), tet(W), and ermB in some farms would drift more over time compared to a single treatment-course with antibiotic. CONCLUSION: This study underlines the large variation in AMR levels under natural conditions and the need for increased investigation of the complex interactions of antimicrobial treatment and other environmental and managerial practices in swine production on AMR gene abundance.

Effect of different oral oxytetracycline treatment regimes on selection of antimicrobial resistant coliforms in nursery pigs.

A major concern derived from using antimicrobials in pig production is the development of resistance. This study aimed to assess the impact of selected combinations of oral dose and duration of treatment with oxytetracycline (OTC) on selection of tetracycline resistant (TET-R) coliforms recovered from swine feces. The work encompassed two studies: 1) OTC 5mg/kg and 20mg/kg were administered to nursery pigs for 3 and 10days, respectively, under controlled experimental conditions, and 2) 10mg/kg, 20mg/kg and 30mg/kg OTC were given to a higher number of pigs for 6, 3 and 2days, respectively, under field conditions. Statistical modeling was applied to analyze trends in the proportion of TET-R coliforms. In the experimental study, no statistical difference in proportion of TET-R coliforms was observed between treatments at the end of the trial (day 18) and compared to day 0. In the field study, treatment had a significant effect on the proportion of TET-R bacteria two days after the end of treatment (2dAT) with the regimes "low dose-six days" and "medium dose-three days" yielding the highest and lowest proportions of TET-R strains, respectively. No indication of co-selection for ampicillin- and sulphonamide -R bacteria was observed for any treatment at 2dAT. By the end of the nursery period, the proportion of TET-R bacteria was not significantly different between treatments and compared to day 0. Our results suggest that similar resistance levels might be obtained by using different treatment regimes regardless of the combinations of oral dose-duration of treatment.

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

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.

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.

Adaptive Test Schemes for Control of Paratuberculosis in Dairy Cows.

Paratuberculosis is a chronic infection that in dairy cattle causes reduced milk yield, weight loss, and ultimately fatal diarrhea. Subclinical animals can excrete bacteria (Mycobacterium avium ssp. paratuberculosis, MAP) in feces and infect other animals. Farmers identify the infectious animals through a variety of test-strategies, but are challenged by the lack of perfect tests. Frequent testing increases the sensitivity but the costs of testing are a cause of concern for farmers. Here, we used a herd simulation model using milk ELISA tests to evaluate the epidemiological and economic consequences of continuously adapting the sampling interval in response to the estimated true prevalence in the herd. The key results were that the true prevalence was greatly affected by the hygiene level and to some extent by the test-frequency. Furthermore, the choice of prevalence that will be tolerated in a control scenario had a major impact on the true prevalence in the normal hygiene setting, but less so when the hygiene was poor. The net revenue is not greatly affected by the test-strategy, because of the general variation in net revenues between farms. An exception to this is the low hygiene herd, where frequent testing results in lower revenue. When we look at the probability of eradication, then it is correlated with the testing frequency and the target prevalence during the control phase. The probability of eradication is low in the low hygiene herd, and a test-and-cull strategy should probably not be the primary strategy in this herd. Based on this study we suggest that, in order to control MAP, the standard Danish dairy farm should use an adaptive strategy where a short sampling interval of three months is used when the estimated true prevalence is above 1%, and otherwise use a long sampling interval of one year.

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

BACKGROUND: This 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. RESULTS: In 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. CONCLUSION: No 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.