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This study investigated the comparative susceptibility of indigenous Moo Laat and improved Large White/Landrace pig breeds to infection with classical swine fever virus (CSFV) under controlled conditions in the Lao People's Democratic Republic (Lao PDR). The Moo Laat (ML) and Large White/Landrace cross-breed (LWC) pigs were inoculated with a standard challenge strain designated Lao/Kham225 (infectivity titre of 10(2.75) TCID50/ml). The results demonstrated that both the native breed and an improved pig breed are fully susceptible to CSFV infection and the mortality rate is high. LWC pigs demonstrated lower (or shorter) survival times (50% survival time: 11 days), earlier and higher pyrexia and earlier onset of viraemia compared to ML pigs (50% survival time: 18 days). In the context of village-based pig production, the longer time from infection to death in native ML pigs means that incubating or early sick pigs are likely to be sold once an outbreak of CSF is recognized in a village. This increased longevity probably contributes to the maintenance and spread of disease in a population where generally the contact rate is low.

The ability to discriminate between different classical Swine fever virus (CSFV) isolates is a prerequisite for identifying the possible origin of an outbreak. To determine the relatedness between Colombian isolates from different geographical regions, genetic sequences of the glycoprotein E2 and the 5'UTR of CSFV were amplified by PCR, sequenced and compared with reference strains of different genetic grouping. The viruses originated from classical swine fever (CSF) outbreaks in Colombia during 1998-2002. All viruses characterized belonged to genogroup 1 and were members of the subgroup 1.1. The results indicate that the outbreaks from the year 2002 are caused by a strain related to the virus CSF/Santander, isolated in 1980, suggesting that the current CSF outbreaks are the consequence of a single strain that continues to circulate in the field. For the first time, an association between isolates from outbreaks in Colombia in the 1990s was established with a virus isolate from Brazil, indicating a possible origin of the virus causing the outbreak.

A report of the Scientific Committee on Animal Health and Animal Welfare of the European Commission (CEC, 1999.) includes recommendations for setting up monitoring programmes for classical swine fever (CSF) infection in a wild-boar population, based on the assumption that one would detect at least 5% prevalence in a CSF-infected wild-boar population. This assumption, however, is not science based. We propose an alternative method to provide evidence for a wild-boar population being free of CSF and evaluate the efficiency of a surveillance programme that was implemented in Belgium in 1998. In our study, the probability of freedom of CSF-virus was estimated based on 789 samples; these were collected from wild-boars within the surveillance programme (within the three provinces which include 95% of the Belgian wild-boar population) and examined by three diagnostics methods (antibody detection, virus detection and virus RNA detection). A Bayesian framework was used for the estimation, accounting for the diagnostic test characteristics without the assumption of the presence of a gold standard. The median probability of freedom of CSF-virus was estimated at 0.970, with a 95% credibility interval of 0.149-1.000. Independent on the choice of the prior information, the posterior distributions for the probability of freedom of CSF-virus were always skewed close to the upper boundary of 1. This represents a big gain of knowledge since we did not use any prior information for the probability of freedom of CSF-virus and took the uncertainty about the accuracy of the diagnostic methods into account.

We have analyzed the origin and evolution of viruses from the classical swine fever (CSF) epidemic that affects Cuba since 2001 by nucleotide sequencing of regions within the E2 glycoprotein and the NS5B (polymerase) genes. The sequence of 190 nucleotides from E2 gene was determined for 10 CSF viruses isolated at different locations of the island, and used for phylogenetic analyses, including sequences from viruses of the 1993--1997 epizootic, previously determined, as well as those from representatives of the different CSFV genotypes. The phylogenetic tree obtained indicates that viruses circulating at present belong to the subgroup 1.2 and are closely related to those isolated during the 1993--1997 epizootic, including the strain Margarita used for vaccine potency tests in Cuba. However, the pattern of evolution revealed by these analyses was different than that observed previously, in which western isolates were almost identical to Margarita strain, while eastern isolates showed a higher level of genetic diversification. In this case, all the viruses analyzed grouped in an independent, define cluster that is closely related, albeit distinguishable, from that of Margarita-related viruses that previously circulated in the western part of Cuba. In addition, the 2001--2003 viruses showed a branched pattern with a level of sequence diversification similar to that observed in the eastern 1993--1997 viruses. Interestingly, a significant fraction (about 54%) of the mutations found in the E2 sequence led to amino acid replacements. This high rate of non-synonymous mutations was not found in the previous Cuban epizootic and has not been reported for other CSF outbreaks. In spite of these amino acid replacements, no antigenic changes were observed in the reactivity of different isolates with CSFV-specific MAbs and polyclonal sera. The phylogenetic tree derived from 409 nucleotides of NS5B gene of seven isolates and Margarita strain, was consistent with that obtained from E2 sequences. In this region, encoding a non-structural protein, a low level of fixation of non-synonymous mutations was observed. The results obtained suggests that epidemiological factors affecting CSFV spread during the current epizootic in Cuba can favour the fixation of non-synonymous mutation in the E2 gene, which could be associated with a lower severity in the clinical signs developed by most of the affected animals.

A Monte Carlo simulation has been developed to describe the spread of classical swine fever virus between farms within a certain region. The data of the farms can be imported and considered individually. Transmission occurs via the infection routes direct animal and indirect person and vehicle contact, as well as by contaminated sperm and local spread. Parameters, such as incubation period and probability of detection, can be varied by the user and their impact on disease spread can be studied. The control measures stamping-out, movement control and pre-emptive slaughter in circular restriction areas as well as contact tracing can be applied and their effect on disease spread can thus be analysed. The numbers of culled and restricted farms and animals per epidemic and per day within an epidemic, the epidemic duration and the total length of restrictions per restricted farm are given. In an example, simulation runs were performed under the condition of application of all four-control measures. Because no real farm data were available, a test area was generated stochastically with a farm density of 1.3 farms/km(2). The distributions of the number of infected farms per epidemic and the epidemic length are shown.

A stochastic and spatial simulation model was developed to simulate the spread of classical swine fever virus among herds in a certain area. A model is a simplification of a real system. The mechanisms and parameters are often not exactly known. Validation is necessary to gain insight into model behaviour and to identify risk factors with great impact on the response variables. Several risk factors such as incubation period, number of daily farm contacts, probability of detection, probability of infection after contact, probability of local spread and time from infection to infectivity were considered in the model as probability distributions in order to take the stochastic component of disease dynamics into account. In order to estimate the effects of the risk factors on the response variables mean size and duration of epidemics, a sensitivity analysis was performed. A fractional factorial design with two-level factors (2(7-2) design) was developed to gain the maximum strength with minimum demand on the calculating capacity. The main factors were unconfounded with any other main factor and also unconfounded with two-factor interactions. Apart from the time from infection to infectivity, all risk factors had a significant effect on the mean size and duration of epidemics (p<0.05). Eight two-factor interactions had a significant influence as well (p<0.05). Mainly, two-factor interactions with probability of detection were significant thus emphasising the impact of a rapid detection of outbreaks. The reaction of the simulation responses to changing of the parameter values was consistent with the expected reaction.

Two envelope glycoprotein (Erns and E2) regions of the classical swine fever virus (CSFV) were amplified by RT-PCR and sequenced directly from 158 specimens collected between 1989 and 2003 in Taiwan. Phylogenetic analysis of the two regions revealed a similar tree topology and the Erns region provided better discrimination than the E2 region. One hundred and fifteen isolates out of the 158 isolates were clustered within subgroup 2.1 (further classified as 2.1a and 2.1b) and 2.2, which were considered to be likely of the introduced strains, whereas the remaining 43 isolates were clustered within subgroup 3.4 and were considered to be of the endemic strains. The subgroup 2.1a viruses were first detected in 1994 and predominated from 1995 onwards. However, subgroup 3.4 viruses were prevalent in the early years, not being isolated after 1996. We have observed a dramatic switch in genotype from subgroup 3.4 to 2.1a. The subgroup 2.1a isolates are closely related to the Paderborn and Lao isolates, whereas 2.1b isolates have a close relationship to the Chinese Guangxi isolates. The phylogenetic tree of 27 CSFV sequences based on the complete envelope glycoprotein gene (Erns-E2) displayed better resolution than that based on the complete open reading frame.

Although veterinary authorities aim to limit persistence of classical swine fever (CSF) in wild boar (Sus scrofa), to avoid potential transmission to pigs, factors influencing CSF transmission and persistence are not clearly understood. Here we analyse incidence and persistence in a CSF epidemic that occurred in the French Vosges Forest. Higher incidence was found in large forests compared to smaller isolated ones, being highest near the starting point of the epidemic, but poorly related to the local density. We hypothesize that the spatial and social structure of wild boar populations may be responsible for this variability of incidence over space. Persistence was highest near the starting point of the epidemic and where initial density was highest. We hypothesize that persistence was favoured by the abundance of young wild boar, itself encouraged by CSF. Our results allow us to propose management measures aimed at limiting CSF persistence.

To date, there is little information concerning the epidemiological situation of classical swine fever (CSF) in the Americas. Besides summarizing the available data, genotyping of isolates from outbreaks in domestic pigs in several countries of South and Central America was performed. For this, a 190 base fragment of the E2 envelope glycoprotein gene was used. European strains and isolates, and historical isolates from the United States (US) were included for comparison. In contrast to the situation in most parts of Europe, where group 2 isolates predominate, it was found that all the isolates from the American continent analyzed belonged to group 1 and were further resolved into three subgroups. The Cuban isolates clustered in subgroup 1.2, whereas the isolates from Honduras and Guatemala clustered in subgroup 1.3. The remaining isolates from Argentina, Brazil, Colombia and Mexico generated four poorly resolved clusters in subgroup 1.1, together with the vaccine strains, with historical European and US isolates, and with a recent Russian isolate. While the vaccine strains and the historical European isolates formed a relatively distinct cluster, one of the US isolates clustered together with the Mexican, and another one with Colombian isolates. Historically, CSF (hog cholera) was observed almost simultaneously in the US and in Europe in the first half of the 19th century, and its origin remains a matter of discussion. Our results showed that the US isolates are closely related to isolates from South America, while appearance of isolates in Cuba on one hand and in Honduras and Guatemala on the other hand, seems to have been due to unrelated events. This allows to speculate that at least in the American continent, CSF virus may have appeared independently in several regions, and spreading may have been a secondary effect.

Summary Surveillance plans were carried out in Italy from 1995 to 2003, with the main aim of controlling the possible circulation of low-virulence classical swine fever viral strains. The repetition of a serological monitoring programme over several years, with constantly negative results, can prove the absence of the infection while increasing the degree of confidence. In our case, in 2003, after eight repetitions of the surveillance plan, the probability that there was at least one infected farm reached 0.006%. Therefore, on the basis of the results of the sampling carried out from 1995 to 2003, we may state that there is no endemic infection, even because of a low virulence virus, in continental Italy.

Thirty-four pregnant wild sows and their unborn progeny derived from an endemically infected population in the district of Nordvorpommern (Mecklenburg-Western Pomerania) were investigated for classical swine fever virus (CSFV) and antibodies. During the last 2.5 years of the epidemic, 20 out of 34 pregnant wild sows investigated were serologically positive. No CSFV or viral RNA was detected in organs derived from these animals and their progeny. This indicates that young wild boars persistently infected by transplacental virus transmission do not play a crucial role in the perpetuation of CSFV in wild boar. Other factors seem to be more important for the establishment of CSF as well as for virus perpetuation in the population.

By analyzing the E2 sequences of classical swine fever virus from field outbreaks in Taiwan during 1993-2001, three virus populations with distinct genotypes were determined including one historical (subgroup 3.4) and two exotic (subgroup 2.1) strains. The first subgroup 2.1 virus was isolated in 1994 and further sporadic outbreaks occurred after 1996. Phylogenetic analysis using the E2 region has segregated the Taiwanese strains of 2.1 virus into two different genotypes (termed 2.1a and 2.1b). The 2.1b viruses were only isolated in 2001 and shared approximately 94.8% nucleotide identities to the 2.1a viruses in the total genomic sequences. The results suggest that the 2.1a and 2.1b viruses may be introduced from different origins.

The herd sensitivity (HSe) and herd specificity (Hsp) of clinical diagnosis of an infection with classical swine fever (CSF) virus during veterinary inspection of breeding sows in a herd was evaluated. Data gathered from visits to herds during the CSF outbreak in 1997-1998 in The Netherlands were used for the analysis. Herds were visited one or more times by the same or by different veterinarians. On the basis of the veterinarians' reports, each visit was coded as 0 (negative clinical diagnosis) or 1 (positive clinical diagnosis). The HSe for clinical diagnosis of CSF was modelled as a function of days elapsed since introduction of the virus. The moment of introduction of the CSF virus in the CSF-positive herds was unknown, so for each herd, a probability distribution for the unknown number of days since introduction was derived from serum samples collected at depopulation. The information from the reports of the veterinarians and from the test results of the serum samples at depopulation was combined in a Bayesian analysis. Data from CSF-negative herds were analysed to estimate HSp of clinical diagnosis of CSF. The HSe of clinical diagnosis was 0.5 at 37 days after virus introduction (95% CI: 31, 45) and reached 0.9 at 47 days after virus introduction (95% CI: 41, 54). The estimated herd specificity was 0.72 (95% CI: 0.64, 0.79). Dependence of HSe and HSp on characteristics of the veterinarians and the herds also was studied. Specialisation of the veterinarian significantly, although not markedly, affected the HSe.

In the European Community, epizootics of classical swine fever (CSF) in the wild boar (Sus scrofa) are compulsorily monitored because transmission may occur between wild boars and domestic pigs, causing heavy economic losses to the pork industry. The estimation of incidence in populations of wild boars is generally based on viroprevalence. However, viral isolation becomes rare when the incidence is low because the virus cannot be detected for more than a few weeks following infection. On the contrary, seroprevalence is detectable at low incidence levels, because antibodies can be detected for the lifetime of the infected animal. We thus attempted to analyse the long-term evolution of CSF incidence using serological data. The data came from France, where CSF had been monitored from 1992 to 2002, and where the virus has not been detected since 1997. We assumed that the overall seroprevalence would estimate the proportion of immune wild boars, that seroprevalence in juveniles would approximate incidence and that seroprevalence in different age classes would show the evolution of incidence in a given cohort. Spatial and temporal trends of incidence and seroprevalence were explored using logistic modelling and the spatial trend was analysed using polynomial regression. In 1992, incidence peaked in the northern area. After 1993, incidence decreased but remained the highest in the northern area. After 2000, no seropositive juvenile was observed, suggesting the extinction of the epizootic. Our results support the reliability of serological monitoring since it allowed a longer detection of viral transmission and provided more information on the spatio-temporal evolution of incidence than did viral isolation. We advocate that the highest persistence of infection in northeastern France is not independent from infection persistence in Reinland-Pfalz (Germany). Such persistence may be due to favourable local conditions and/or the social organisation of wild boars.

Consequences of classical swine fever (CSF) epidemics depend on the control measures, but also on the number of infected herds at the end of the high-risk period (HRP). Surveillance programmes aim to keep this number as low as possible, so the effectiveness of surveillance programmes can be measured by the number of infected herds at the end of the HRP. In this paper, an evaluation of the effectiveness of the following five Dutch CSF surveillance programmes is presented: (1) routine gross pathology of severely diseased pigs; (2) routine virological tests of tonsils of all pigs, submitted under 1; (3) daily clinical observation by the farmer; (4) periodic clinical inspection by a veterinarian; (5) leucocyte counts in blood samples from diseased animals on a herd where antimicrobial 'group therapy' is started. The evaluation was done by a modelling study, in which virus transmission, disease development, and actions and diagnostic tests in surveillance programmes were simulated. Also, the yearly costs of the programmes were calculated, and direct costs of CSF epidemics were related to the number of infected herds at the end of the HRP. It appeared that the current Dutch surveillance programmes, without the leucocyte counts, keep the number of infected herds at the end of the HRP below 20 with 95% probability. Leaving out the most-expensive programme of periodic inspection (12.5M per year) does not change this result - indicating that (for CSF surveillance) the programme could well be stopped. If the leucocyte programme, which is currently not effective due to the low sample submission rate, optimally were applied, the 95th percentile could be reduced to 10 infected herds. However, whether application is beneficial is unclear, because of uncertainty of the economic benefits due to the many expected false-positive herds each year.

Clinical signs recorded in a classical swine fever (CSF)-suspect situation and the results of the subsequent post-mortem examination (PME) from swine submitted to post-mortem during the 1997-1998 CSF epidemic in the Netherlands, were presented in an experiment as anonymous cases (without knowledge of the actual infection status of the submission) to five veterinary pathologists for their judgment: CSF-suspect or non-suspect. It was presented to them in two hypothetical situations: country was free of CSF for 5 years and CSF was detected in the country 2 weeks ago. Subsequently, their judgment was compared to the gold standard (infection status of the submission on the basis of an immunofluoresence assay on tissue samples) and the sensitivity (Se) and specificity (Sp) of clinical diagnosis was estimated. Furthermore, intra- and inter-pathologist agreement on pathological diagnosis was measured. Adding information on clinical signs to information on PME resulted in a significant increase in median Se and a significant decrease in median Sp for a clinical judgment by pathologists. Also, median Se was significantly higher-and Sp significantly lower-for a clinical judgment by pathologists in a situation in which CSF was detected 2 weeks ago in the country compared to the situation in which the country had been free of CSF for 5 years. Apparently, the internal threshold of pathologists is severely adjusted depending on the actual disease situation in a country. Intra-rater agreement ranged from fair to almost perfect for a clinical diagnosis on the basis of PME. There was considerable variation between pathologists, especially if clinical diagnosis was based on the combined information on PME and clinical signs observed in the herd. Inter-rater agreement was substantial for the diagnosis based on information on PME. Inter-rater agreement was considerably lower for the diagnosis based on the combined information on PME and clinical signs observed in the herd.

This paper is concerned with a stochastic model, describing outbreaks of infectious diseases that have potentially great animal or human health consequences, and which can result in such severe economic losses that immediate sets of measures need to be taken to curb the spread. During an outbreak of such a disease, the environment that the infectious agent experiences is therefore changing due to the subsequent control measures taken. In our model, we introduce a general branching process in a changing (but not random) environment. With this branching process, we estimate the probability of extinction and the expected number of infected individuals for different control measures. We also use this branching process to calculate the generating function of the number of infected individuals at any given moment. The model and methods are designed using important infections of farmed animals, such as classical swine fever, foot-and-mouth disease and avian influenza as motivating examples, but have a wider application, for example to emerging human infections that lead to strict quarantine of cases and suspected cases (e.g. SARS) and contact and movement restrictions.

Classical swine fever (CSF) is a viral transboundary animal disease that is highly contagious among domestic and wild pigs, such as boars and peccaries. Today, far from being what was classically described historically, the disease is characterized as having a varied clinical picture, and its diagnosis depends on resorting to proper sample collection and prompt dispatch to a laboratory that can employ several techniques to obtain a definitive diagnosis. Laboratory findings should be complemented with a field analysis of the occurrence of disease to have a better understanding of its epidemiology. The disease is still present in various regions and countries of Latin America and the Caribbean, thus hindering production, trade, and the livestock economy in the region. Consequently, it is among the diseases included in List A of the Office International des Epizooties (OIE). Currently, there are epidemiologic and ecologic aspects that characterize its geographical distribution in the region such as: continued trends in the demand for pork and pork products; an increase in swine investment with low production costs which are able to compete advantageously in international markets; the convention of associating CSF in the syndrome of "swine hemorrhagic diseases" owing to the historical description of its acute presentation and not to the new and more frequent subacute presentations or the diseases with which it may be confused (notably, porcine reproductive and respiratory syndrome and porcine dermopathic nephropathy syndrome, among others); dissemination of the virus through asymptomatic hosts such as piglets infected in utero; frequent lack of quality control and registration of vaccines and vaccinations; feeding of swine with contaminated food waste (swill); the common practice of smuggling animals and by-products across borders; the backyard family production system or extensive open field methods of swine rearing with minimal input in care and feeding; poor understanding of the epidemiologic role that boars and peccaries could have in the transmission and maintenance of the disease in the Americas; and new procedures in animal welfare that some countries are adopting for the production, transport, and slaughter of domestic animals. Consequently, many countries (i.e., Canada, USA, Chile, Belize, Costa Rica, Panama, and Mexico, where 13 of 32 States are disease free) have given priority to the control and progressive eradication of CSF. In other parts of the Americas, the disease appears under control, as is the case of the five countries of the Andean Region and the 12 northern States of Brazil. In South America, Chile, Uruguay and 13 States in Brazil are disease free. Argentina has mounted a national campaign and is in the process of eradicating the disease. No recent information on its presence or distribution in Paraguay is available. With no master strategy to harmoniously progress in the control and eradication of the disease, 17 countries of the region, jointly led by the Food and Agriculture Organization of the United Nations, developed the Continental Plan for the Eradication of CSF whose objective is expected to be reached by 2020.

The E2 genes of 21 classical swine fever viruses (CSFV) were genetically characterized and compared with reference CSF viruses. The viruses originated from CSF outbreaks that occurred in the Lao People's Democratic Republic (Lao PDR) during 1997 though to 1999. All viruses characterized belonged to genogroup 2 and were members of subgroups 2.1 and 2.2. Results demonstrated a geographic delineation between subgroups 2.1 that was only found in the North-Central region, and subgroup 2.2 that was mostly found in the South-Central regions of Lao PDR. Although it was not possible to determine the origin of these viruses, it is probable that they may have been introduced to Lao PDR following cross-border trade. Alternatively, they have evolved independently of other viruses in the region.

The introduction of classical swine fever virus (CSFV) into a country free of disease without vaccination may have huge consequences in terms of both disease spread and economic losses. More quantitative insight into the main factors determining the probability of CSFV introduction (PCSFV) is needed to optimally use resources for the prevention of CSFV introduction. For this purpose a spreadsheet model was constructed that calculates the annual PCSFV into member states of the European Union (EU). The scenario pathway approach was used as most probabilities in the model are very small. Probability distributions were used to take into account inherent variability of input parameters. The model contained pathways of CSFV introduction including the import of pigs and pork products, returning livestock trucks, and contacts with wild boar. All EU member states were included as possible sources of CSFV. Default results for the Netherlands showed a mean overall annual PCSFV of approximately 0.06, indicating that the Netherlands can expect CSFV introduction on average once every 18 years from the pathways and countries included in the model. Almost 65% of this probability could be attributed to the pathway of returning livestock trucks. The most likely sources of CSFV introduction were Germany, Belgium, and the United Kingdom. Although the calculated probabilities were rather low when compared with expert estimates and recent history, the most likely causes of CSFV introduction indicated by the model were considered to be realistic. It was therefore concluded that the model is a useful tool to structure and analyze information for decision making concerning the prevention of CSFV introduction.

Data of the 1997-1998 epidemic of classical swine fever (CSF) in The Netherlands were analysed in survival analysis to identify risk factors that were associated with the rate of neighbourhood infections. The study population consisted of herds within 1000 m of exclusively one previously infected herd. Dates of virus introduction into herds were drawn randomly from estimated probability distributions per herd of possible weeks of virus introduction. (To confirm the insensitivity of the results for this random data-selection procedure, the procedure was repeated 9 times (resulting in 10 different data sets).) The data set had 906 non-infected and 59 infected neighbour herds, which were distributed over 215 different neighbourhoods. Neighbour herds that never became infected were right-censored at the last date of the infectious period of the infected source herd. Neighbour herds that became empty within the infectious period or within the following 21 days due to preventive depopulation or due to the implemented buying-out programme were right-censored 21 days before the moment of becoming empty. This was done as a correction for the time a herd could be infected without being noticed as such. The median time to identified infection of neighbour herds was 2 weeks, whereas the median time to right censoring of non-infected neighbour herds was 3 weeks. The risk factors, radial distance < or =500 m, cattle present on source herd and increasing herd size of the neighbour herd were associated multivariably with the hazard for neighbour herds to become infected. We did not find an association between time down wind and infection risk for neighbour herds. Radial dispersion of CSFV seemed more important in neighbourhood infections than dispersion along the road on which the infected source herd is situated. The results of this study support the strategy of preventive depopulation in the neighbourhood of an infected herd. Recommendations are presented to adapt the applied control strategy for neighbourhood infections.

The effects of additional measures adopted during a classical swine fever (CSF) epidemic to reduce piglet supply, namely, an insemination ban, abortion of sows and killing of young piglets, are studied using a stochastic, spatial, dynamic epidemiological simulation model of the pig sector in The Netherlands. The piglet supply derived from the epidemiological model is used as input for a sector-level market and trade model that simulates the pig market in The Netherlands. Changes in the economic welfare of different stakeholders are measured, as is the net welfare effect for the economy in The Netherlands. Sensitivity analysis is performed on parameters such as destruction capacity constraints and the duration of the high-risk period. Additional measures to reduce piglet supply are found to have no epidemiological impact, but they do involve larger economic welfare changes for stakeholders and a larger net welfare loss for the economy in The Netherlands. These findings do not support the use of the additional measures. Moreover, sensitivity analysis shows that such measures do not solve the problem of a shortage in rendering capacities.

Classical swine fever (CSF) is a serious and contagious viral disease of pigs and wild boar with a widespread worldwide distribution. The immunopathology of the disease is poorly understood, but the ability of the CSF virus to infect cells without triggering apoptosis and to kill uninfected cells is probably highly significant. The virus may be spread by various direct and indirect methods, but in most cases the exact mechanisms involved in local spread between farms are not known. Excellent diagnostic tools and typing methods are available, but tests that could be performed on-farm, in pre-clinically infected pigs or on meat would also be advantageous. A more complete picture of the viruses circulating in different parts of the world is needed. There is great interest to develop and use marker vaccines for the control of CSF in domestic pigs and in wild boar. Epidemiological modelling is increasingly used to evaluate control options.

The virulence of classical swine fever virus (CSFV) strains including established laboratory strains as well as field isolates ranges from avirulent to highly virulent. Here, we describe the construction and characterisation of two cDNA-derived CSFV strains, each corresponding to one of these extremes. The recombinant virus vEy-37 caused acute disease indistinguishable from that provoked by infection with the highly virulent parent strain Eystrup. In contrast, vRiems-3, a molecular clone of the CSFV vaccine strain Riems, was avirulent and induced protective immunity in pigs. After repeated passage of vEy-37 in porcine kidney SK-6 cells adaptive mutations in the E(rns) gene were observed. The respective reconstructed mutant virus grew to titres that were almost 4log units higher when compared to vEy-37. The mutation in the E(rns) gene had only a minor effect on the virulence of the virus. The complete genomic sequences of the two CSFV strains, Eystrup and Riems, have been deposited in GenBank (accession number AF326963 for CSFV Eystrup, AY259122 for CSFV Riems/IVI).

Emergency vaccination during an epidemic of classical swine fever virus (CSFV) has become a serious option because of the ethical problems of strategies with massive culling and the availability of a marker vaccine that reduces virus transmission. Here we present a model of between-herd CSFV transmission, which quantifies the effect of control strategies with and without vaccination. We estimate the model parameters from data of the Dutch CSFV epidemic of 1997/1998. With the model, a set of control strategies is compared, consisting of five control measures in several combinations. Consequently, the following general requirements of successful strategies can be formulated. First, to achieve extinction of a CSFV epidemic, transmission through transport should be prevented and the indirect virus transmission, i.e. all transmission not through animal contacts, should at least be halved, either by vaccination or by culling of the susceptible pig population. Second, to minimize the size and duration of an epidemic, the extinction requirements should be met quickly and indirect virus transmission should be reduced by far more than a half. Although the origin of the model parameters let the requirements in fact be only applicable for the south-eastern part of the Netherlands, it is argued that epidemics in other areas will not need stricter control strategies.

Recent classical swine fever (CSF) epidemics in the European Union (EU) have clearly shown that preventing the introduction of CSF virus (CSFV) deserves high priority. Insight into all the factors contributing to the risk of CSFV introduction is a prerequisite for deciding which preventive actions are cost-effective. The relations between virus introduction and spread, prevention and control, and economic losses have been described using the conceptual framework presented in this paper. A pathway diagram provides insight into all the pathways contributing to the likelihood of CSFV introduction (LVI&#95;CSF) into regions of the EU. A qualitative assessment based on this pathway diagram shows that regions with high pig densities generally have a higher LVI&#95;CSF, although this cannot be attributed to pig density only. The pathway diagram was also used to qualitatively assess the reduction in LVI&#95;CSF achieved by restructuring the pig production sector. Especially integrated chains of industrialised pig farming reduce the LVI&#95;CSF considerably, but are also difficult and costly to implement. Quantitative assessment of the LVI&#95;CSF on the basis of the pathway diagram is needed to support the results of the qualitative assessments described.

The performance of pathological findings as a diagnostic tool for the detection of classical swine fever (CSF) outbreaks during the 1997/1998 CSF-epidemic in The Netherlands was evaluated by constructing and analysing receiver operating characteristic (ROC) curves. This was done at the individual pig level and at the submission level (a group of pigs from the same herd submitted together for post-mortem investigation). At post-mortem examination, the tonsils, spleen, ileo-caecal valve and renal pelvis were sampled, sent to the reference laboratory, and tested by means of a CSF-specific fluorescent antibody test in combination with a confirmatory test. This resulted in an infection status at the individual pig level. The infection status and pathological findings of 1072 individual pigs from a total of 230 infected herds were included in this analysis. We also included submissions of pigs from herds that were sent to post-mortem examination because of a clinically CSF-suspect situation but afterwards were concluded to be from non-infected herds. Infection status and pathological findings of 1224 individual pigs from a total of 241 non-infected herds were included in the analysis. Pneumonia, pleuritis, chronic bronchitis, pulmonary oedema, chronic gastric ulceration, dry faecal contents in the colon, conjunctivitis, haemorrhages in the renal pelvis, renal haemorrhages, splenic enlargement, haemorrhages in the urinary bladder, haemorrhagic and enlarged lymph nodes were the most frequently recorded pathological findings during a post-mortem examination of pigs submitted in a CSF-suspect clinical situation. However, some of these pathological findings (e.g. pneumonia, pleuritis) were almost evenly distributed in infected and in non-infected pigs, resulting in a high sensitivity combined with a low specificity. The area under the ROC curve of pathological findings at the individual pig level and at the submission level was 0.720 and 0.782, respectively, which was significantly (P<0.0001) larger than the area under the random ROC curve. It was concluded that, although gross pathology is a legitimate test, its quantitative contribution to the detection of CSF is limited.

During a period of 5 years (1997-2001) several outbreaks of classical swine fever (CSF) were recorded in Croatia. For genetic typing, fragments of 150 nucleotides within the 5'-non-translated region (5'-NTR) and 190 nucleotides within the E2 glycoprotein coding gene of nine field isolates that were derived from domestic pigs and wild boars were used. For better epizootiological understanding, isolates from other European countries were included in the study. The results show that the isolates belong to subgroups 2.1 and 2.3 of CSF virus. Isolates from subgroup 2.1 were collected from domestic pigs during sporadic outbreaks in June 1997 and are genetically closely related. A genomic similarity between these isolates and CSF virus isolates from pigs in other European countries from the same year could also be confirmed. In contrast, the isolate from October 1997 was found to be a member of subgroup 2.3, and is closely related to European CSF virus isolates from outbreaks in the last decade in Western and Central European countries. These results show that two different sources of CSF virus caused outbreaks in Croatia during the same year. Furthermore, a close relationship was found between an isolate from a domestic pig in 1999 and isolates of subgroup 2.3 that originated from Croatian wild boars.

The ability to discriminate between various classical swine fever virus (CSFV) strains and isolates is a prerequisite for following the spread of the virus after an outbreak. To determine the relatedness between Russian CSFV isolates from different geographical regions, three fragments of the viral genome (5' NTR, the variable region of the E2 gene and a fragment of the NS5B gene) were sequenced and used for genetic typing. Thirty-one field isolates were obtained from CSF outbreaks which occurred between 1994 and 1999. In addition, three attenuated strains were included in the study, namely the LK and CS vaccine strains, and the moderately virulent 238H isolate. The vaccine strains have been used in Russia for more than 30 years. Our results showed that all field isolates are in subgroup 1.1 together with Alfort 187 and with the highly virulent strain Shimen. In contrast, the CS and LK vaccine strains belong to subgroup 1.2. While there is no evidence for the reversion of the two vaccine strains to wild type, it is feasible that the highly virulent Shimen strain, which has been used as a challenge strain for many years, contributed to field strain generation. The Russian field isolates from the 1990s can be distinguished from the CSF virus isolates which occurred in the EU Member States in the same decade, as here all outbreaks were caused by CSF viruses belonging to subgroup 2.

Risk factors associated with the occurrence of "neighbourhood infections" [Epidemiology of classical swine fever. In: Truszczynski, M. (Ed.), Proceedings of the Workshop on Diagnostic Procedures and Measures to Control Classical Swine Fever in Domestic Pigs and the European Wild Boar. Pulaway, Poland, pp. 119-130] during classical swine fever (CSF) outbreaks were examined based on information collected during a CSF-epidemic, which occurred in the East Flanders Province of Belgium in 1994. The only risk factor that was associated with the occurrence of "neighbourhood infections" was a kernel estimation of the intensity of neighbouring herds (P=0.055) [Interactive spatial data analysis. Pearson Education Limited, Harlow, Essex], i.e. the higher the kernel estimation, the higher the risk for the occurrence of neighbourhood infections. In a second part of the study, the likelihood for the occurrence of neighbourhood infections within an area with a 1 km radius was predicted for every Belgian pig herd, assuming that the herd was infected with CSF-virus. For the prediction of these likelihoods, the model resulting from the risk assessment was used. Finally, the predicted likelihoods were transformed into a raster map after applying a smoothing technique. As a result, different areas in Belgium of higher or lower risk for CSF-virus spread through "neighbourhood infections" could be identified on the map. The areas in Belgium where CSF-outbreaks including "neighbourhood infections" occurred in the past decades were all predicted by the model to be of high risk.

Chile eradicated classical swine fever (CSF) in April 1998, following a 17-year eradication programme. The authors describe biosecurity levels of pig farms in Chile after the eradication of CSF. A formal survey was administered to 50 large integrated pig farms, which represented almost 60% of the swine population. The main topics on the questionnaire were production, health management, biosecurity, insurance and information about CSF outbreaks in the past. Biosecurity practices were analysed according to the criteria stated by Barcelo and Marco in 1998. A scoring system to measure biosecurity was designed and pig farms were classified according to this score. An adjusted specific measure is discussed as a potential indicator of risk for disease infections. The authors explore associations between biosecurity herd size and insurance policy against CSF.

The clinical diagnosis of classical swine fever (CSF) still caused problems to the veterinarians during the last decade. The primary CSF outbreak was often detected too late and, meanwhile, the virus had spread. Consequently, the recent classical swine fever virus isolates (CSFV) were suspected to be of low virulence. The purpose of the study was to quantify the virulence of four recent CSFV by evaluating the clinical and pathological signs caused by different CSFV. Pigs of the same breed and age group were inoculated intranasally with CSFV from recent epidemics in European Union (EU) member states. The CSFV used are registered in the data base of the EU Reference Laboratory for CSF and belong to different genotypes: 2.1, 2.2 and 2.3 respectively. Clinical signs of CSF were evaluated by using a score system suggested previously (Mittelholzer et al., 2000: Vet. Microbiol. 74, 293). For the evaluation of pathological lesions, a new pathological score was introduced. The four CSFV tested here were classified as moderately virulent in general, although one CSFV may cause different clinical courses, ranging from highly virulent to avirulent. This indicates the importance of additional factors in the host animal for virulence. Differences in the clinical and pathological signs between these four recent CSFV were rather minor, emphasizing that the genetic typing of CSFV is absolutely essential. Differences towards former CSFV (e.g. reference virus strain Alfort 187) were more pronounced, especially regarding the onset and duration of the disease, the occurrence of skin haemorrhages and pathological lesions of kidney, subcutis and serosae. It is concluded that clinical diagnosis of CSF is rather difficult in pigs up to 14 days post-CSFV infection using these four CSFV, emphasizing the need for careful differential diagnosis and the laboratory investigation for CSF at an early stage.

The classical swine fever (CSF) epidemic in the Netherlands in 1997-1998 lasted 14 months, during which 429 infected and 1300 at risk herds were culled, at an estimated economical cost of 2 billion US dollars. Despite the overwhelming scale of the epizootic, the CSF virus (CSFV) strain causing the outbreak has remained largely uncharacterized. The Dutch epizootic is epidemiologically linked to a small CSF outbreak in 1997, in Paderborn in Germany. E2 and partial 5' NTR sequencing has shown that the index Paderborn isolate, and several Dutch isolates taken during the 1997-1998 epizootic, are virtually identical, confirming that the Paderborn isolate triggered the Dutch outbreak, and furthermore showing that this single isolate was stable throughout the whole Dutch outbreak (the above reviewed in [C. Terpstra, A. J. de Smit, Veterinary Microbiol. 77 (2000) 3-15]). We determined the nucleotide sequence of the 5' NTR (by 5' RACE) and the complete open reading frame of the Paderborn isolate (GenBank AY072924). Our sequence was identical to previously published partial 5'NTR and E2 sequences for the index Paderborn 1997 and Dutch 1997 (Venhorst) isolates, confirming the identity of the virus we sequenced. Phylogenetic analysis based on the complete open reading frame showed that Paderborn is genetically very different from common European laboratory reference strains. Neutralization studies showed that Paderborn is also antigenically very different from common laboratory strains such as Alfort 187. Paderborn is the only recent European CSFV field isolate for which a complete sequence is available, and given Paderborns genetic and antigenic uniqueness, the Paderborn sequence may have practical use for diagnostic and vaccine antigen development.

In 1997, outbreaks of classical swine fever occurred in wild boar and domestic pigs in the Italian province of Varese (Lombardy region). Statutory animal health measures were imposed, and a control plan aimed at preventing the virus from spreading outside the infected hunting zone of 108 km2 was implemented. However, in 1998, virologically positive wild boar were found outside this zone, including within Swiss territory. The infected zone was then enlarged to include the three other hunting areas of the northern province of Varese and the neighbouring Swiss territory. Italian and Swiss veterinary services initiated a joint policy to control the disease by hunting young wild boar and conserving older, immune animals. The percentage of virologically positive animals gradually decreased, the last being found in July 2000. The seroprevalence initially increased, but in 2000 and 2001 it decreased from 42.2 per cent to 8.8 per cent, indicating that the wild boar population had had no further contact with the virus.

Although classical swine fever (CSF) has been well known for decades and epidemics still occur, clinical diagnosis continues to cause problems for veterinary practitioners. This is due to the extensive differential diagnosis, further complicated by the emergence of new diseases such as porcine reproductive and respiratory syndrome (PRRS) and porcine dermatitis and nephropathy syndrome (PDNS). In addition, acute, chronic and prenatal courses of CSF have to be distinguished. As a cause of considerable economical losses within the EU, control of CSF requires knowledge of the primary outbreaks and spread of the disease. Genetic typing of CSF virus isolates has proved to be a potent method of supporting epidemiological investigations. Phylogenetic analysis of CSF virus strains and isolates originating from different continents has allowed three genetic groups and several subgroups within these groups to be distinguished. Whereas isolates belonging to group 3 seem to occur solely in Asia, all CSF virus isolates of the 1990s isolated in the EU belonged to one of the subgroups within group 2 (2.1, 2.2, or 2.3) and were clearly distinct from former CSF reference viruses, which belong to group 1. Within the EU, different strategies are followed for the eradication of CSF in domestic pigs and in wild boar. While a strict non-vaccination policy is followed for domestic pigs, eradication of the disease in wild boar is more complex, and oral immunisation together with special hunting strategies have been applied. Recently, marker vaccines with a companion discriminatory test designed to allow differentiation between vaccinated animals and animals having recovered from field virus infection have been developed. Preliminary studies indicated that the discriminatory tests had a reduced sensitivity and specificity. Further improvements are therefore necessary before marker vaccines can be considered for emergency use in EU Member States. Prevention of CSF remains the main objective within the EU.

We examined the importance of pig-population density in the area of an outbreak of classical swine fever (CSF) for the spread of the infection and the choice of control measures. A spatial, stochastic, dynamic epidemiological simulation model linked to a sector-level market-and-trade model for The Netherlands were used. Outbreaks in sparsely and densely populated areas were compared under four different control strategies and with two alternative trade assumptions. The obligatory control strategy required by current EU legislation was predicted to be enough to eradicate an epidemic starting in an area with sparse pig population. By contrast, additional control measures would be necessary if the outbreak began in an area with high pig density. The economic consequences of using preventive slaughter rather than emergency vaccination as an additional control measure depended strongly on the reactions of trading partners. Reducing the number of animal movements significantly reduced the size and length of epidemics in areas with high pig density. The phenomenon of carrier piglets was included in the model with realistic probabilities of infection by this route, but it made a negligible contribution to the spread of the infection.

Because of the clinical and pathologic similarity to common endemic diseases, introduction of CSFV or ASFV strains of moderate to low virulence represents the greatest risk to North American swine herds. Producers, veterinarians, and diagnosticians should increase their awareness of these devastating diseases and request specific diagnostic testing whenever they are suspected. Production practices that improve biosecurity will reduce the risk of introduction of CSF and ASF and limit the spread if an incursion occurs. Additional resources. The following Web sites contain excellent color photographs that will assist producers and practitioners in identifying clinical signs and gross lesions associated with CSFV and ASFV: http://www.vet.uga.edu/vpp/gray&#95;book/FAD and http://www.pighealth.com. The latter Web site and the OIE Web site (http://www.oie.int) offer updated information on current worldwide epizootics of ASF and CSF and other swine diseases. Details of biosecurity procedures can be found at http://www.agebb.missouri.edu; see publication G2340.

Classical swine fever (CSF) is of increasing concern in Europe where wild boar appear to play an important epidemiological role. In most parts of the continent, demographic trends are on the increase, due to improvement in game management. As a result of higher densities, populations become more susceptible to various infectious diseases, among which CSF is cause for particular concern. Wild boar do not appear to be a classic reservoir in most cases, but nevertheless may perpetuate foci of infection over the long term, constituting a real threat for the pig farming industry. Since the infection does not appear to spread easily in natural populations of free-ranging wild boars, control of the disease may be feasible. However, most of the appropriate measures, such as banning hunting, are not considered acceptable. Consequently, the expertise of wildlife disease specialists is required to help solve the problem when it occurs.

During the hunting season in February 1999, a total of 44 blood samples were collected from wild boars shot in the area of Moslavacka gora. These blood samples were examined by enzyme immunoassay for the presence of antibodies to classical swine fever (CSFV), Aujeszky's disease (ADV), bovine viral diarrhoea (BVDV), and porcine reproductive and respiratory syndrome (PRRSV) viruses. Out of 44 serum samples examined, 17 (38.63%) were positive for CSFV, 24 (54.54%) were positive for ADV and two (4.54%) were positive for BVDV. All sera were negative for PRRSV. The results, recorded for the first time in Croatia, supported the hypothesis that wild boar act as a potential reservoir of CSFV, ADV and BVDV, and thus have a role in the epidemiology of these diseases.

The recent oral immunisation trials in wild boar against classical swine fever (CSF) in Germany are described and evaluated in summary. After the first field study in Lower Saxony from 1993-1995 further immunisation trials started in Mecklenburg-Western Pomerania, Brandenburg, Lower Saxony, Baden-Württemberg and Saxony-Anhalt. The immunisation strategies and the size of the vaccination zones were different in the individual federal states. In principle, the bait vaccine based on the CSF virus strain "C" were laid out by hand. Later also the aerial distribution was carried out in selected areas of Mecklenburg-Western Pomerania. The application of baits by plane was introduced at the beginning of the immunisation measures in Saxony-Anhalt apart from the manual distribution. Up to now, the field trials show that the oral immunisation can be an additional tool for CSF control by increasing of herd immunity and reduction of the CSFV prevalence. However, the immunisation was not sufficient enough for young boars in the most field studies. Based on the evaluation of the immunisation experiments an improved immunisation procedure is recommended.

The performance of clinical signs as a diagnostic test for the detection of classical swine fever (CSF) outbreaks during the 1997-1998 CSF epidemic in The Netherlands was evaluated by constructing and analysing a receiver operating characteristic (ROC) curve. This curve assesses the discriminating ability of a diagnostic test over a range of test signals. The cut-off values for a defined diagnostic test to detect CSF outbreaks were set by different combinations of clinical signs observed. The area under the ROC curve, which is a quantitative measure of test performance, was significantly (P<0.001) larger than the area under the random ROC curve. This indicates that clinical signs have a significantly higher performance as a diagnostic test for the detection of CSF than for flipping a coin. However, the gain in diagnostic performance compared to a random process is not as much as we would wish it to be. The optimal efficient diagnostic test combined a sensitivity of 72.7% with a specificity of 52.7%, with a combination of the following clinical signs: unsteady gait/ataxia, not eating, not reacting to antibiotic treatment, conjunctivitis, hard faecal pellets.

In this study we quantified the rate at which classical swine fever had been transmitted by several different types of inter-herd contact during the 1997-8 epidemic in The Netherlands. During that epidemic 428 CSFV-infected pig herds were detected, 403 of which were include in this study. The estimated rates of transmission were 0.065 per shipment of live pigs, 0.011 per contact by a pig transportation lorry, 0.0068 per person contact, 0.0007 per dose of semen, 0.0065 per contact with a potentially contaminated pig assembly point, 0.027 per week per infected herd within a radius of 500 metres and 0.0078 per week per infected herd at a distance between 500 and 1000 metres. These transmission rates can be used to optimize the strategy to stop future epidemics of CSF in The Netherlands. In addition, the analysis demonstrated in this paper, can be used to quantify CSFV transmission rates from other epidemics.

The outbreaks of classical swine fever in 1997-1998 and foot- and mouth-disease in 2001 provided a lot of experiences in the culling of animals. These experiences, as well as the aspects of animal welfare and public acceptance are described. In the future these experiences will help to carry out culling in a more efficient way including improved aspects of animal welfare and public acceptance.