J.A. Backer

Vaccination against foot-and-mouth disease I: Epidemiological consequences

An epidemic of foot-and-mouth disease (FMD) can have devastating effects on animal welfare, economic revenues, the export position and society as a whole, as occurred during the 2001 FMD epidemic in the Netherlands. Following the preemptive culling of 260,000 animals during this outbreak, the Dutch government adopted emergency vaccination as preferred control policy. However, a vaccination-to-live strategy has not been applied before, posing unprecedented challenges for effectively controlling the epidemic, regaining FMD-free status and minimizing economic losses. These three topics are covered in an interdisciplinary model analysis. In this first part we evaluate whether and how emergency vaccination can be effectively applied to control FMD epidemics in the Netherlands. For this purpose we develop a stochastic individual-based model that describes FMD virus transmission between animals and between herds, taking heterogeneity between host species (cattle, sheep and pigs) into account. Our results in a densely populated livestock area with >4 farms/km(2) show that emergency ring vaccination can halt the epidemic as rapidly as preemptive ring culling, while the total number of farms to be culled is reduced by a factor of four. To achieve this reduction a larger control radius around detected farms and a corresponding adequate vaccination capacity is needed. Although sufficient for the majority of simulated epidemics with a 2 km vaccination zone, the vaccination capacity available in the Netherlands can be exhausted by pig farms that are on average ten times larger than cattle herds. Excluding pig farms from vaccination slightly increases the epidemic, but more than halves the number of animals to be vaccinated. Hobby flocks - modelled as small-sized sheep flocks - do not play a significant role in propagating the epidemic, and need not be targeted during the control phase. In a more sparsely populated livestock area in the Netherlands with about 2 farms/km(2) the minimal control strategy of culling only detected farms seems sufficient to control an epidemic.

Transmission and Control of African Horse Sickness in The Netherlands: A Model Analysis

African horse sickness (AHS) is an equine viral disease that is spread by Culicoides spp. Since the closely related disease bluetongue established itself in The Netherlands in 2006, AHS is considered a potential threat for the Dutch horse population. A vector-host model that incorporates the current knowledge of the infection biology is used to explore the effect of different parameters on whether and how the disease will spread, and to assess the effect of control measures. The time of introduction is an important determinant whether and how the disease will spread, depending on temperature and vector season. Given an introduction in the most favourable and constant circumstances, our results identify the vector-to-host ratio as the most important factor, because of its high variability over the country. Furthermore, a higher temperature accelerates the epidemic, while a higher horse density increases the extent of the epidemic. Due to the short infectious period in horses, the obvious clinical signs and the presence of non-susceptible hosts, AHS is expected to invade and spread less easily than bluetongue. Moreover, detection is presumed to be earlier, which allows control measures to be targeted towards elimination of infection sources. We argue that recommended control measures are euthanasia of infected horses with severe clinical signs and vector control in infected herds, protecting horses from midge bites in neighbouring herds, and (prioritized) vaccination of herds farther away, provided that transport regulations are strictly applied. The largest lack of knowledge is the competence and host preference of the different Culicoides species present in temperate regions.

Vaccination against foot-and-mouth disease II: regaining FMD-free status

An epidemic of foot-and-mouth disease (FMD) can have devastating effects on animal welfare, economic revenues, the export position and society as a whole. The preferred control strategy in the Netherlands has recently changed to vaccination-to-live, but - not have been applied before - this poses unprecedented challenges for effectively controlling an epidemic, regaining FMD-free status and minimizing economic losses. These three topics are addressed in an interdisciplinary model analysis. In this second part we evaluate whether vaccination-to-live poses a higher risk for regaining FMD-free status than non-vaccination strategies and whether the final screening can be improved to reduce this risk. The FMD transmission model that was developed in the first part, predicted the prevalence of infected animals in undetected herds for 1000 hypothetical epidemics per control strategy. These results serve as input for the final screening model that was developed in this part. It calculates the expected number of undetected infected herds and animals per epidemic after final screening, as well as the number of herds and animals to be tested. Our results show that vaccination strategies yield a larger number of undetected infected animals in the whole country per epidemic before final screening than preemptive culling (median values and 5-95% interval): 8 (0-42) animals for 1 km preemptive culling, 50 (7-148) for 2 km vaccination and 35 (6-99) for 5 km vaccination. But the final screening reduced these to comparably low numbers: 1.0 (0-9.1) for 1 km preemptive culling, 3.5 (0.3-15) for 2 km vaccination and 2.1 (0.3-9.4) for 5 km vaccination. Undetected infected animals were mainly found in non-vaccinated sheep herds and vaccinated cattle and sheep herds. As a consequence, testing more non-vaccinated cattle and pig herds will not reduce the expected number of undetected infected animals after the final screening by much, while the required testing resources drastically increase. However, testing only a sample instead of all animals in vaccinated pig herds will not increase the expected number of undetected infected animals by much, while the required testing resources reduce by half. In conclusion, vaccination and preemptive culling strategies yield comparable numbers of undetected infected animals after final screening and the final screening costs can be reduced by testing a sample instead of all vaccinated pigs.

Transmission of classical swine fever virus depends on the clinical course of infection which is associated with high and low levels of virus excretion

Infection with moderately virulent strains of classical swine fever virus (CSFV) can lead to different courses of disease: either (sub)acute, resulting in death or recovery, or chronic disease. The virus excretion dynamics between these courses are quite dissimilar, but it is not known if this also results in differences in virus transmission. In this study, the excretion and transmission dynamics of the moderately virulent Paderborn strain were studied in 15 one-to-one experiments. In these experiments, a single inoculated pig was housed with a single susceptible contact pig from day 1 post-inoculation (p.i.). Each contact pig that became infected was removed and replaced by a new contact pig at day 17 p.i. and day 26 p.i. Infection of contact pigs was monitored by reverse transcription quantitative real-time PCR on oropharyngeal fluid samples. Five of the inoculated pigs developed the chronic form or died during the acute phase (high excreting pigs), while 10 pigs recovered from the infection (low excreting pigs). In the first contact period, there was no significant difference in virus excretion between the high and low excreting pigs, while in the second and third contact period, high excreting pigs excreted significantly higher quantities of virus. Over the entire study period, the reproduction ratio differed significantly between the high (143 [56.3-373]) and low excreting pigs (23.1 [11.5-45.0]). This indicates the importance of high excreting pigs in transmission of CSFV. Furthermore, this study showed the rate of CSFV infections from a contaminated environment.

Using mortality data for early detection of Classical Swine Fever in The Netherlands

Early detection of the introduction of an infectious livestock disease is of great importance to limit the potential extent of an outbreak. Classical Swine Fever (CSF) often causes non-specific clinical signs, which can take considerable time to be detected. Currently, the disease can be detected by three main routes, that are all triggered by clinical signs. To improve the early detection of CSF an additional program, based on mortality data, aims to routinely perform PCR tests on ear notch samples from herds with a high(er) mortality. To assess the effectiveness of this new early detection system, we have developed a stochastic model that describes the virus transmission within a pig herd, the development of disease in infected animals and the different early detection programs. As virus transmission and mortality (by CSF and by other causes) are different for finishing pigs, piglets and sows, a distinction is made between these pig categories. The model is applied to an extensive database that contains all unique pig herds in The Netherlands, their herd sizes and their mortality reports over the CSF-free period 2001-2005. Results from the simulations suggest that the new early detection system is not effective in piglet sections, due to the high mortality from non-CSF causes, nor in sow sections, due to the low CSF-mortality. In finishing herds, the model predicts that the new early detection system can improve the detection time by two days, from 38 (27-53) days to 36 (24-51) days after virus introduction, when assuming a moderately virulent virus strain causing a 50% CSF mortality. For this result up to 5 ear notch samples per herd from 8 (0-13) finishing herds must be tested every workday. Detecting a source herd two days earlier could considerably reduce the number of initially infected herds. However, considering the variation in outcome and the uncertainty in some model assumptions, this two-day gain in detection time is too small to demonstrate a substantial effect of the new early detection system based on mortality data. But when the alertness of herd-owners and veterinarians diminishes during long CSF-free periods, the new early detection system might gain in effectiveness.

Effect of strain and inoculation dose of classical swine fever virus on within-pen transmission

To improve the understanding of the dynamics and options for control of classical swine fever (CSF), more quantitative knowledge is needed on virus transmission. In this study, virus excretion and within-pen transmission of a strain of low, moderate and high virulence were quantified. Furthermore, the effect of inoculation dose on excretion and transmission were studied. The transmission was quantified using a stochastic susceptible-exposed-infectious-recovered (SEIR) model. Five transmission trials were conducted with ten pigs each. In each trial, three pigs were inoculated with the low virulent strain Zoelen, a low (10(2) TCID(50)), middle (10(3.5) TCID(50)), or high dose (10(5) TCID(50)) of the moderately virulent strain Paderborn, or the highly virulent strain Brescia. The other seven pigs in each trial served as contact pigs. None of the pigs inoculated with the low dose of the Paderborn strain were infected. When it was assumed that the infectiousness of the pigs coincided with virus isolation positive oropharyngeal fluid and/or faeces, no significant differences in transmission rate beta and basic reproduction ratio R(0) between the high inoculation dose of the Paderborn strain (beta= 1.62/day, R(0) = 35.9) and the Brescia strain (beta= 2.07/day, R(0)= 17.5) were observed. When the middle dose of the Paderborn strain was used for inoculation, the beta (5.38/day) was not significantly higher than the Brescia strain or the high inoculation dose of the Paderborn strain, but the R(0) (148) was significantly higher. Infection with the Zoelen strain resulted in a significantly lower beta and R(0) (beta= 0/day, R(0) = 0) than the other strains.

The potential of antiviral agents to control classical swine fever: A modelling study.

Classical swine fever (CSF) represents a continuous threat to pig populations that are free of disease without vaccination. When CSF virus is introduced, the minimal control strategy imposed by the EU is often insufficient to mitigate the epidemic. Additional measures such as preemptive culling encounter ethical objections, whereas emergency vaccination leads to prolonged export restrictions. Antiviral agents, however, provide instantaneous protection without inducing an antibody response. The use of antiviral agents to contain CSF epidemics is studied with a model describing within- and between-herd virus transmission. Epidemics are simulated in a densely populated livestock area in The Netherlands, with farms of varying sizes and pig types (finishers, piglets and sows). Our results show that vaccination and/or antiviral treatment in a 2 km radius around an infected herd is more effective than preemptive culling in a 1 km radius. However, the instantaneous but temporary protection provided by antiviral treatment is slightly less effective than the delayed but long-lasting protection offered by vaccination. Therefore, the most effective control strategy is to vaccinate animals when allowed (finishers and piglets) and to treat with antiviral agents when vaccination is prohibited (sows). As independent control measure, antiviral treatment in a 1 km radius presents an elevated risk of epidemics running out of control. A 2 km control radius largely eliminates this risk.

Analysis of Q fever in Dutch dairy goat herds and assessment of control measures by means of a transmission model

Between 2006 and 2009 the largest human Q fever epidemic ever described occurred in the Netherlands. The source of infection was traced back to dairy goat herds with abortion problems due to Q fever. The first aim of control measures taken in these herds was the reduction of human exposure. To analyze Q fever dynamics in goat herds and to study the effect of control measures, a within-herd model of Coxiella burnetii transmission in dairy goat herds was developed. With this individual-based stochastic model we evaluated six control strategies and three herd management styles and studied which strategy leads to a lower Q fever prevalence and/or to disease extinction in a goat herd. Parameter values were based on literature and on experimental work. The model could not be validated with independent data. The results of the epidemiological model were: (1) Vaccination is effective in quickly reducing the prevalence in a dairy goat herd. (2) When taking into account the average time to extinction of the infection and the infection pressure in a goat herd, the most effective control strategy is preventive yearly vaccination, followed by the reactive strategies to vaccinate after an abortion storm or after testing BTM (bulk tank milk) positive. (3) As C. burnetii in dried dust may affect public health, an alternative ranking method is based on the cumulative amount of C. burnetii emitted into the environment (from disease introduction until extinction). Using this criterion, the same control strategies are effective as when based on time to extinction and infection pressure (see 2). (4) As the bulk of pathogen excretion occurs during partus and abortion, culling of pregnant animals during an abortion storm leads to a fast reduction of the amount of C. burnetii emitted into the environment. However, emission is not entirely prevented and Q fever will not be eradicated in the herd by this measure. (5) A search & destroy (i.e. test and cull) method by PCR of individual milk samples with a detection probability of 50% of detecting and culling infected goats - that excrete C. burnetii intermittently - will not result in eradication of Q fever in the herd. This control strategy was the least effective of the six evaluated strategies. Subject to model limitations, our results indicate that only vaccination is capable of preventing and controlling Q fever outbreaks in dairy goat farms. Thus, preventive vaccination should be considered as an ongoing control measure.

Controlling highly pathogenic avian influenza outbreaks : An epidemiological and economic model analysis

Outbreaks of highly pathogenic avian influenza (HPAI) can cause large losses for the poultry sector and for animal disease controlling authorities, as well as risks for animal and human welfare. In the current simulation approach epidemiological and economic models are combined to compare different strategies to control highly pathogenic avian influenza in Dutch poultry flocks. Evaluated control strategies are the minimum EU strategy (i.e., culling of infected flocks, transport regulations, tracing and screening of contact flocks, establishment of protection and surveillance zones), and additional control strategies comprising pre-emptive culling of all susceptible poultry flocks in an area around infected flocks (1 km, 3 km and 10 km) and emergency vaccination of all flocks except broilers around infected flocks (3 km). Simulation results indicate that the EU strategy is not sufficient to eradicate an epidemic in high density poultry areas. From an epidemiological point of view, this strategy is the least effective, while pre-emptive culling in 10 km radius is the most effective of the studied strategies. But these two strategies incur the highest costs due to long duration (EU strategy) and large-scale culling (pre-emptive culling in 10 km radius). Other analysed pre-emptive culling strategies (i.e., in 1 km and 3 km radius) are more effective than the analysed emergency vaccination strategy (in 3 km radius) in terms of duration and size of the epidemics, despite the assumed optimistic vaccination capacity of 20 farms per day. However, the total costs of these strategies differ only marginally. Extending the capacity for culling substantially reduces the duration, size and costs of the epidemic. This study demonstrates the strength of combining epidemiological and economic model analysis to gain insight in a range of consequences and thus to serve as a decision support tool in the control of HPAI epidemics.

Ensemble modelling and structured decision-making to support Emergency Disease Management.

Epidemiological models in animal health are commonly used as decision-support tools to understand the impact of various control actions on infection spread in susceptible populations. Different models contain different assumptions and parameterizations, and policy decisions might be improved by considering outputs from multiple models. However, a transparent decision-support framework to integrate outputs from multiple models is nascent in epidemiology. Ensemble modelling and structured decision-making integrate the outputs of multiple models, compare policy actions and support policy decision-making. We briefly review the epidemiological application of ensemble modelling and structured decision-making and illustrate the potential of these methods using foot and mouth disease (FMD) models. In case study one, we apply structured decision-making to compare five possible control actions across three FMD models and show which control actions and outbreak costs are robustly supported and which are impacted by model uncertainty. In case study two, we develop a methodology for weighting the outputs of different models and show how different weighting schemes may impact the choice of control action. Using these case studies, we broadly illustrate the potential of ensemble modelling and structured decision-making in epidemiology to provide better information for decision-making and outline necessary development of these methods for their further application.