Conf. OIE 1998, 289-302 STRATEGIES FOR THE CONTROL OF CLASSICAL SWINE FEVER, INCLUDING THE APPLICATION OF MODERN VACCINES V. Moennig Institute of Virology, School of Veterinary Medicine, Buenteweg 17, D-30559 Hannover, Germany Original: English Summary: Classical swine fever (CSF) is an infectious viral disease which has severe economic impact on the pig industry of several European countries. Whereas European Union (EU) Member States and other Western European countries are almost free of the disease in domestic pigs, the CSF situation in many Central and Eastern European countries remains unclear. The number of outbreaks in domestic pigs decreased in the EU in the 1990s, but financial losses increased greatly due to changes in the structure of the pig industry and control policy. The concentration of pigs and farms in some regions of Europe and long distance trade increased the risk of spreading the disease and the number of pigs affected by control measures. Primary CSF outbreaks are mostly due to (illegal) swill feeding. In some areas of Europe, CSF has become endemic in the wild boar population. This poses a constant risk for domestic pigs. Knowledge about the epidemiological situation of CSF in wild boar is insufficient in many countries. Laboratory diagnosis has improved markedly during the last decade. Most European countries are equipped for CSF diagnosis and participate in international inter-laboratory comparison tests in order to standardise CSF diagnosis. Molecular typing of CSF virus isolates has become a valuable tool for epidemiology. Diagnostic capacities for emergency situations must be considered in national contingency plans. Since the prevalence of infected animals has decreased, the EU pursues a non-vaccination policy to control CSF. This facilitates the internal market and fulfils the requirements of the international market. Several other European countries have adopted this policy. Although this control strategy is widely accepted today, legislation needs some amendment based on the scientific evaluation of the recent CSF epidemics in Europe. Currently, two subunit marker vaccines are undergoing the licencing procedure. These vaccines might be a future option for restricted use in emergency situations. Essentially, the success of control programmes depends on education and awareness of all parties involved, i.e. farmers, practitioners and Veterinary Services. 1. INTRODUCTION Classical Swine Fever (CSF) is one of the most economically important viral infectious diseases of domestic and wild pigs and is classified as an OIE List A disease. After implementation of consequent control measures, several countries, including Australia, Canada, New Zealand, United States of America (USA), and some Member States of the European Union (EU), succeeded in eradicating the virus. In most other parts of the world the CSF virus is present, causing considerable economical damage. The manifestation of the infection may vary greatly depending on the age of the animal and the virus virulence. Young animals often display the acute classical form, with high fever, haemorrhages and high mortality. Alternatively, the chronic and ultimately fatal form may obscure the characteristic classical picture in young animals. Older animals often show only mild clinical symptoms. Like all pestiviruses, CSF virus may pass through the placenta of pregnant animals, infecting foetuses and leading incidentally to the birth of persistently viremic piglets. The latter develop late onset CSF later in life and die from CSF. The multitude of possible clinical signs very often hampers prompt diagnosis of primary outbreaks (photo 1). - 289 - Conf. OIE 1998 In order to compile information about occurrence, diagnosis and eradication in OIE Member Countries, a questionnaire was prepared and sent to each country. Out of 50 countries, 33 provided the requested information to OIE. Seventeen countries did not respond. The following countries made information available: Andorra, Armenia, Austria, Belarus, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Moldavia, Netherlands, Norway, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Ukraine, United Kingdom and Uzbekistan. 2. ETIOLOGY The causative agent of CSF is a small (40-60 nm) enveloped ribonucleic acid (RNA) virus with a single stranded RNA genome with positive polarity. CSF virus belongs to the pestivirus genus of the Flaviviridae family (29). It is related to the bovine viral diarrhoea (BVD) virus and the border disease (BD) virus of sheep. The genomic sequence of about 12,000 bases is known and infectious copy deoxyribonucleic acid (cDNAs) have been produced in several laboratories (16, 19, 20). The viral RNA codes for four structural and seven nonstructural proteins (17, 18). The virus is relatively stable in moist excretions and fresh meat products, including ham and salami type sausages (22). However, it is readily inactivated by detergents, lipid solvents, proteases and common disinfectants. 3. CLINICAL SIGNS The incubation period is seven to ten days. The clinical signs of CSF are extremely variable (18, 26). Infected pigs develop pyrexia and leukopenia. Petechial haemorrhages of the outer skin and mucosae are the most typical sign although they are not seen consistently (photos 2 & 3). Central nervous system disorders and obstipation followed by diarrhoea may also be characteristic clinical findings. The severity of clinical signs largely depends on the age of the animal and viral virulence. Usually young animals are affected more severely than older animals. In older breeding pigs the course of the infection is often mild or even subclinic. Acute and chronic courses of CSF are known. All courses of the infection have in common that the animals are viremic at least as long as they show clinical signs. Deaths occurs two to three weeks after infection (acute course) or after up to three months (chronic course). The outcome of transplacental infection of foetuses depends largely on the time of gestation (26) and may result in abortions and stillbirths, mummifications, malformations or the birth of weak or persistently viremic piglets (15) (photo 4). Although persistently infected offspring may be clinically normal at birth, they invariably die from CSF. Survival periods of 11 months after birth have been observed. This course of infection is referred to as 'late onset CSF' (25). 4. PATHOLOGY AND PATHOGENESIS Under natural conditions the most frequent route by which the CSF virus enters its host is oronasal. Major target cells for the virus are endothelial cells, lymphoreticular cells, macrophages, and some kinds of epithelial cells. Pathological findings vary according to clinical signs (18, 25). Prenatally, at the early phases of ontogenesis, the virus affects organ differentiation and leads to malformations. In postnatal infections, lesions are generally caused by widespread thrombosis and/or endothelial damage, inducing haemorrhagic diathesis and petechiation. Bronchopneumonia is another regular feature. In a high proportion of fatal cases, histopathology of the brain shows a non-suppurative encephalitis with severe vasculitis. Severe thrombocytopenia is a consistent finding. The terminal stage of acute infection is associated with a marked depletion of B lymphocytes in the circulatory system as well as in lymphoid tissues (24). - 290 - Conf. OIE 1998 Photo 1: Pox-like skin lesions Lésions cutanées varioliformes Оспоподобные кожные поражения Photo 2: Skin haemorrhages and necroses on the ear edges Hémorragies et nécroses cutanées au bord des oreilles Кожные геморрагии и некрозы по краям уха - 291 - Conf. OIE 1998 5. IMMUNOLOGY Like all pestiviruses, the CSF virus is immuno-suppressive during acute infection. Pigs that have recovered are protected against CSF for several years or even for their lifetime. Neutralising antibodies are detectable two weeks after infection at the earliest. In pigs with chronic CSF, neutralising antibodies are detectable at the end of the first month postinfection for a few days and disappear afterwards. Persistently viremic, in utero infected pigs seldom produce specific antibodies. Maternal antibodies have a half-life of approximately 14 days. Passive immunity generally protects piglets against mortality during the first five weeks of life, but not against virus replication and shedding. Little is known about cellmediated immunity against CSF. 6. DIAGNOSIS OF CSF AND LABORATORY FACILITIES Clinical diagnosis is of prime importance for the detection of CSF. However, it may prove difficult and many primary outbreaks are initially not recognised as CSF, because clinical signs are often variable and non specific. This applies especially for older animals in breeding herds. In general, CSF should be considered whenever a disease with high body temperature that does not react to treatment is diagnosed. This is especially relevant in regions where CSF has occurred during the last 12 months in domestic pigs or wild boar. Veterinarians, farmers and hunters should be highly aware of the risk. A modern and efficient laboratory diagnosis is an essential tool for CSF control. Monitoring of the status of the pig population in 'peace time' and early detection of CSF depend on reliable diagnostic methods and adequate laboratory facilities. In order to discover CSF infected herds at an early stage, it is important to identify the right animals for laboratory investigation. These are clinically sick animals and should be tested virologically. Random sampling is not suitable for CSF diagnosis. It may be used for epidemiological purposes, such as monitoring and serological prevalence studies. 6.1. Virology The 'gold standard' for CSF diagnosis is virus isolation. CSF virus can be isolated from buffy coat cells or organ suspensions of viremic animals. Suitable organs are spleen, tonsils, lymphnodes, parotid glands and kidneys (1, 3). The samples are incubated on susceptible cell cultures of porcine origin. As the CSF virus is non-cytopathogenic, CSF specific antibodies are a prerequisite for detection of the virus in cell culture. Differentiation of the CSF virus from ruminant pestiviruses can be achieved using monoclonal antibodies (1, 3, 6). The virus isolation protocol requires at least three days and is labour intensive. A rapid diagnostic test for CSF is based on the demonstration of viral antigen in organ tissue sections using conjugated antibodies for direct immunofluorescence (fluorescent antibody test, FAT). To screen large numbers of animals in herds suspect of being recently infected by CSF, virus antigen capture enzyme-linked immunosorbent assays (AgC-ELISAs) can be used for the detection of viral antigen in blood samples. However, the latter tests are less sensitive than virus isolation. Recently, detection of viral RNA has become an additional option for laboratory diagnosis. In particular, the 5'-nontranslated region of the genome has been used for amplification by the reverse transcriptase polymerase chain reaction (RT-PCR). Subsequent nucleotide sequencing of the respective region allows discrimination between different CSF virus isolates (9, 14). The OIE Reference Laboratory for CSF in Hannover, Germany, keeps an extensive computer data base on CSF virus isolates including epidemiological and virus type information data. The 'molecular epidemiology' based on the above technique has become a useful tool and may well support epidemiological investigations (tracing on/back). Typing of CSF virus isolates of at least each primary outbreak in domestic pigs and isolates originating from wild boar is desirable. OIE Member Countries are encouraged to send respective materials to the above-mentioned OIE Reference Laboratory. - 292 - Conf. OIE 1998 Photo 3: Multiple petechial haemorrhages on different wild boar organs (acute CSF) Pétéchies multiples de différents organes chez un sanglier (peste porcine aiguë) Множественные петехии в различных органах дикого кабана (острая чума свиней) Photo 4: Aborted and mumified fetuses Avortons momifiés Мумифицированные выкидыши - 293 - Conf. OIE 1998 6.2. Serology Serological diagnosis of CSF is important for the detection of hidden clusters of CSF, such as breeding herds with subclinical infection or reconvalescent animals. Furthermore, it is useful for epidemiological surveys in wild boar. The virus neutralisation test is the safest and most reliable method for CSF antibody detection. Porcine serum samples are incubated with a CSF reference virus. If the serum contains antibodies for CSF the test virus will be neutralised. However, cross-neutralising antibodies specific for ruminant pestivirus infections of pigs are sometimes registered by this test. Differential diagnosis for ruminant pestiviruses should therefore be carried out using a second neutralising test with ruminant pestiviruses. The neutralisation test requires two to three days and is labour intensive. Large numbers of serum samples are therefore processed using ELISA tests. Positive or unclear results should be retested using the neutralisation test, which is usually more sensitive and more specific. 6.3. Laboratory facilities Most European countries are equipped for CSF diagnosis, except for Andorra, Armenia, Iceland, Malta, Ukraine and Uzbekistan, which use laboratories in other countries. Laboratories in some countries are only equipped for ELISA testing. Almost all European countries with CSF laboratory facilities participate in annual international inter-laboratory comparison tests in order to standardise and improve diagnosis. These tests are organised by the reference laboratories and the results are discussed at international conferences. The number of samples tested in individual countries depends largely on the country's CSF status and the CSF monitoring programme of the pig population. Countries with CSF outbreaks usually test a large number of samples. Monitoring programmes vary significantly within European countries. Likewise, investigation for CSF in wild boar populations is variable and the available information is insufficient. Diagnostic capacities are crucial for the control of CSF in case of an epidemic. Past experience shows that capacities were often insufficient to handle large numbers of samples. The realistic assessment of emergency situations and provision of diagnostic capacities must be part of the national contingency plan. 7. VACCINES Immunoprophylaxis has been an important instrument to control CSF. From the beginning of the century attempts have been made to develop vaccines against CSF using simultaneous vaccination, i.e. where live field virus and hyperimmune serum were applied simultaneously. This procedure was efficacious but its safety was poor. The second generation of CSF vaccines was produced from virus propagated in pigs with subsequent inactivation, e.g., using crystal violet or formalin. These vaccines were safe but the immune response was delayed and weak, and lasted only a few months. Vaccinated animals usually showed good clinical resistance to challenge with virulent virus, but they were not effectively protected against infection. This was proven by the observation that virulent virus was found in foetuses after challenge of vaccinated pregnant sows (11, 13). In the 1940s the first experiments were made to attenuate the CSF virus by adapting it to rabbits (5, 12). After initial setbacks, this development ultimately led to a very efficient and safe generation of live vaccines. Most of these vaccines are based on the China-strain (C-strain) of lapinized CSF virus. C-strain vaccines were and are still being used worldwide for the control of CSF. Currently the C-strain is used in an oral immunisation field trial to control CSF in German wild boars. C-strain vaccines induce high titres of neutralising antibodies and they are safe when used on pregnant animals. Their efficacy is demonstrated by the observation that vaccinated pigs are protected against infections with virulent CSF virus as early as five days after vaccination. The animals are immune throughout their economic life. However, in light of today´s global trade policy there is a severe disadvantage in using live attenuated vaccines against CSF: vaccinated and field-virus-infected animals cannot be distinguished. The antibody pattern induced by the vaccine virus resembles that of reconvalescent animals; thus field virus infections may be masked by vaccination. For this reason, the European Union (EU) pursues a non-vaccination policy. Due to the recent series of CSF epidemics in several Member States, notably Belgium, Germany, Netherlands and Spain, it became apparent that the nonvaccination policy is expensive and difficult to enforce in regions with high pig densities. Emergency vaccination using conventional vaccines would result in prolonged and thereby prohibitive trade restrictions. The use of a marker vaccines against CSF could overcome this dilemma, and a first generation of such vaccines has been developed in recent years. These vaccines are under final investigation in order to determine their value under - 294 - Conf. OIE 1998 field conditions. A marker vaccine should induce protective immunity. The immune response must be distinguishable from field virus infection and the companion diagnostic test must detect all infected animals. Immunity should be induced rapidly (e.g. two weeks) and be long lasting (e.g., six months). Vaccinated pigs must be protected against natural challenge and must not show clinical signs or shed field virus. Sows should be protected against transplacental infection of foetuses. The vaccine should be safe and effective for young piglets and one administration should be sufficient. Subunit vaccines consist of single viral surface proteins, which are sufficient for the induction of protective immunity. Both current vaccines containing viral glycoprotein E2 are produced using recombinant DNA technology. The respective gene is expressed in baculoviruses grown in insect cells (27). Since these cells are able to glycosylate proteins, the resulting viral glycoprotein is expressed in a 'natural' way. CSF subunit vaccines are safe and so far their protective potency is promising, though inferior to live vaccines. Vaccinated animals may be distinguished from infected pigs using an ELISA based on a different viral protein as diagnostic antigen, for example, the surface glycoprotein Erns or the nonstructural protein NS2-3. However, not all criteria are well defined yet, and the technical merits of CSF subunit marker vaccines have not yet been confirmed. Data are expected to be available by the year 1999. CSF marker vaccines might be improved by future vaccine generations, e.g., viral vector vaccines (10, 21, 28), DNA vaccines and molecular altered infectious cDNA clones of CSF virus (17, 19, 20). 8. EPIDEMIOLOGY 8.1. Pig population and occurrence of CSF CSF occurs in nearly all continents and countries where pigs are kept except for Australia and North America (CSF eradicated) and some Western European countries (e.g. Denmark, England, Finland, Greece, Ireland, Norway and Sweden), which have been free of CSF for several decades. Both the structure and density of pig populations have a considerable influence on the epidemiology and control of CSF. In recent years high pig concentrations (animal and farm density) were built up in several European regions. The probability of spreading the disease in those areas is much higher than in lower density areas. Long distance animal trade was intensified and contributes to the problem. Therefore, it is very important to obtain quick, reliable and complete information about trade movements and contact farms. The structure of the European pig industry displays a wide variation between regions and countries (Table 1). In some countries domestic pigs are kept preferably in small farms (more than 50% of farms have less than 20 pigs in Andorra, Estonia, Germany, Latvia, Lithuania, Portugal, Romania, Slovenia, Spain, Sweden and Ukraine). In other countries, domestic pigs are kept preferably in bigger farms (more than 50% of farms with more than 500 pigs: Armenia, Cyprus, Czech Republic, Finland, France, Greece and Slovakia). The remaining countries show a high percentage of pig farms with between 20 and 500 pigs (Belarus, Croatia, Denmark, Iceland, Luxembourg, Malta, Netherlands, Norway, Switzerland, United Kingdom and Uzbekistan). Wild boar and domestic pigs are equally susceptible to CSF virus infection (7). The occurrence, density and behaviour of wild boar populations are important for the epidemiology of CSF. Wild boar populations appear to be increasing all over Europe. Present estimated populations of wild boar in European countries are shown in Table 2. If not disturbed, wild boar have a limited home-range and tend to be stationary, except for young boar which tend to move. In countries that are free of CSF in domestic pigs, epidemics in wild boar are typically initiated by swill feeding. Depending on viral virulence, the density and the size of the population, CSF epidemics in wild boar are not always self-limiting. The wild boar might represent a permanent virus reservoir that poses a constant threat to domestic pigs. - 295 - Conf. OIE 1998 Table 1: Domestic pig populations in European countries Country Andorra Armenia Austria Belarus Croatia Cyprus Czech Republic Denmark Estonia Finland France Germany Greece Iceland Ireland Italy Latvia Lithuania Luxembourg Malta Moldavia Netherlands Norway Portugal Romania Slovakia Slovenia Spain Sweden Switzerland United Kingdom Ukraine Uzbekistan Total pig population 103 54 297 3 680 000 3 680 000 1 200 000 400 000 3 900 000 11 300 000 300 000 1 400 000 14 000 000 24 700 000 1 500 000 3 537 1 700 000 8 000 000 429 400 1 120 000 77 149 80 000 776 264 15 000 000 647 000 2 230 000 6 490 000 1 800 000 583 000 18 000 000 3 800 000 1 400 000 7 350 000 9 400 000 70 000 * CSF occurrence during the last four years Number of pig herds % of herds <20 pigs % of herds >500 pigs CSF* occurrence 25 3 100 455 1 375 n.a. 158 5 700 24 738 5 462 6 500 28 000 192 239 52 000 70 3 000 44 085 86 269 426 389 120 498 21 000 5 800 10 150 2 590 000 1 148 89 301 000 10 700 17 800 12 202 2 740 000 112 100 0 n.a.** 0 30 0 15 25 92 5 3 57 <5 10 n.a. n.a. 100 60 6 0 n.a. 8 50 70 100 13 75 86 66 47 10 99 0 0 100 n.a. 34 10 98 70 32 2 60 62 14 >80 50 n.a. n.a. 0 25 9 20 n.a. 32 5 30 0 59 10 4 10 0 30 0 18 no no yes yes yes no yes no no no no yes no no no yes yes no no no yes yes no no no yes yes yes no no no yes no ** data not available 8.1.1. EU Member States and other Western European countries At present the EU Member States are practically free of CSF in domestic pigs. However, sporadic or massive new outbreaks have been observed in domestic pigs in recent years (1990 - 1998). Outbreaks in areas with a high density of pigs have often led to extensive epidemics with most severe economic losses. During the last four years, CSF outbreaks in domestic pigs have been observed in Austria, Belgium, Germany, Italy, Netherlands, Spain and Switzerland (Table 1). The most recent and probably the most costly epidemic started at the end of 1996 in a pig herd in Western Germany due to illegal swill feeding. The virus subsequently spread to several regional pig farms (1997) and presumably from Germany to the Netherlands and subsequently to Spain, Italy and Belgium. More than 550 confirmed outbreaks could be attributed to this epidemic, which appears to have recently come to an end. - 296 - Conf. OIE 1998 Table 2: Wild boar populations in European countries and monitoring for CSF Wild boar population Country Estimated population Andorra Armenia Austria Belarus Croatia Cyprus Czech Rep. Denmark Estonia Finland France Germany n.a.* n.a. n.a. 26 643 10 200 0 38 000 n.a. 10 000 300 450 000 600 000 Greece Iceland Ireland Italy Latvia Lithuania Luxembourg 500 0 0 n.a. 17 274 19 400 15 000 Malta Moldavia Netherlands Norway Portugal 0 1137 3 000 0 60 000 Romania Slovakia Slovenia Spain Sweden Switzerland United Kingdom Ukraine Uzbekistan 16 800 19 536 5 000 n.a. 10 000 8 000 100 43 000 n.a. * data not available Investigation and choice of samples Distribution Random Sick wild boar Proximity to outbreaks** CSF occurrence overall regional n.a. overall overall no n.a. n.a. no yes no n.a. n.a. yes yes no n.a. n.a. no yes n.i.*** n.a. yes n.i. no overall regional overall regional regional overall yes no n.a. yes yes yes yes no n.a. yes yes yes yes no n.a. no no yes yes n.i. n.a. n.i. yes yes regional no no no n.i. regional overall overall overall yes yes yes yes yes no yes no yes no yes no yes yes no no overall regional yes yes no yes yes yes n.i. no n.a. yes no no no overall overall overall overall regional regional regional overall overall yes yes yes no no yes no no no yes yes yes no no yes no yes no yes yes yes no no yes no yes no no yes n.i. n.i. n.i. yes n.i. yes n.i. ** proximity to CSF outbreaks in domestic pigs *** not investigated In wild boar, CSF has been observed in Austria, France, Germany, Italy and Switzerland (Table 2). In some areas the infection has been endemic for several years. In Germany, many primary outbreaks have been linked to the occurrence of CSF in local wild boar populations. All Western European countries where CSF has occurred during the last few years run a monitoring programme for CSF in wild boar, except for Spain. Three of the seven other countries with wild boar populations (Finland, Luxembourg, Portugal) monitor wild boar for CSF (Table 2). In the other countries (Denmark, Greece, Sweden and United Kingdom), CSF infection in wild boar is unlikely to occur due to animal population size and geographic location. Since almost all Western European countries made information available, the epidemiological situation with respect to wild boar is clear in that part of Europe. - 297 - Conf. OIE 1998 8.1.2. Central and Eastern European countries The situation regarding CSF in both domestic and wild swine is less clear in these countries than it is in Western Europe. In most Central and Eastern European countries from which data are available CSF has been observed in domestic pigs during the last decade. Cyprus and Uzbekistan were free of CSF. With regard to the last four years, CSF occurred in Belarus, Croatia, Czech Republic, Latvia, Moldavia, Slovakia, Slovenia and Ukraine (Table 1). In Czech Republic, Latvia, Slovakia and Ukraine, CSF has been observed in wild boar. Croatia, Lithuania and Romania have not detected CSF infection in wild boar whereas data from the other 23 countries are not available (Table 2). The provided data shows that monitoring programmes for CSF in wild boar have been established in all countries except for Armenia, Estonia and Uzbekistan. However, results of the monitoring programmes have not been made available. In order to prevent the introduction of CSF by pig or meat imports, it is essential to obtain reliable and comprehensive information on the disease status of trade partners. Monitoring programmes are a useful tool to determine whether a pig population is free of CSF or affected by the disease. This is most important in the wild boar population because, compared with domestic pigs, wild boar are not under permanent control. There is a need to considerably strengthen information systems and reporting on epidemiology of CSF and particularly that of wild boar in Central and Eastern Europe. 8.2. Transmission/spread of the virus In many countries the feeding of pigs with swill is strictly forbidden. Exceptions are made when handling and heat-treatment of swill are officially licensed. Despite these strict measures the typical source of infection in many if not most index cases in domestic pig herds or in wild boar populations is swill feeding. Sometimes the outbreaks are due to a failure in swill processing but in most cases swill is fed illegally without any previous treatment. Often the farmer´s awareness of the risk and knowledge of the legislation are not sufficient. Wild boar might pick up material contaminated with the CSF virus had been thrown away at rest places and garbage dumps. From wild boar the virus may be transmitted directly (animal contact) or more often indirectly to domestic pigs (contaminated equipment belonging to farmers who are hunters as well, feed contaminated by wild boar excretions or carcasses, illegal swill feeding, contact of pigs with wild boar excretions etc.). After introduction of the CSF virus into the first domestic pig herd (primary outbreak), the probability of the disease spreading depends primarily on the number of contacts with other pig holdings before the disease is noticed. In general, high risk factors are the pig and farm density in the affected region. Pig farms within a radius of approximately 500 metres face a higher relative risk of contracting the infection when compared with more distant farms surrounding an infected holding (23). The increasing long distance trade in the pig industry is an additional important risk factor. The most important routes of CSF virus transmission during epidemics are as follows: - trade with chronically or acutely infected pigs - transmission by persons via contaminated clothes or instruments - "undefined" contacts in the neighbourhood of infected farms (up to 500 metres) - indirect or direct contact with infected wild boar - insufficiently cleaned and disinfected vehicles (transport lorries) - (illegal) swill feeding 9. CONTROL STRATEGIES There are two major control strategies: the first is routine vaccination while the other is exclusively based on eradication measures without the use of vaccines. The use of conventional vaccines prevents the differentiation between of vaccinated and field virus infected animals. Thus the field virus may reside undetected in parts of the population. For this reason the EU banned vaccination against CSF at the end of the 1980s. CSF is an OIE List A disease. Every suspected case has to be investigated and once it is confirmed, the outbreak has to be notified. The preventive measures adopted for trade with third countries include that live pigs and fresh pig meat can only be imported from regions or countries where no CSF has occurred for 12 months and no vaccination against CSF was undertaken during the same period. Whereas the immediate neighbours of the EU - 298 - Conf. OIE 1998 have adopted the non vaccination policy, vaccination is allowed and mostly routinely applied by most other Central and Eastern European countries (Table 3). In Slovakia, only emergency vaccination is carried out. Most countries use modified live vaccines. In Armenia, Latvia, Lithuania and Slovakia, inactivated virus vaccines are used. In the EU, eradication measures are based on stamping out (depopulation) of infected pig herds and possibly infected contact or (partially) neighbouring herds, epidemiological investigations, clinical and virological investigations, movement restrictions for live pigs, pig meat and other vectors which can transmit CSF within zones surrounding the infected farm and restrictions on contact farms outside these zones (1). Especially in areas with dense pig populations, very high numbers of pigs had to be destroyed in the course of the eradication measures dealing with the outbreaks mentioned above. Only a minority of animals were killed due to direct involvement with the infection. Most of the pigs had to be killed because of welfare measures. Table 3: CSF Vaccination policy in non-EU European countries Country Vaccination allowed Routine vaccination Emergency vaccination Andorra Cyprus Czech Republic Iceland Malta Norway Switzerland Uzbekistan Lithuania no no no no no no no no yes no no no no no no no no no no no no no no no no n.a.* no inactivated virus 650 000 Slovakia Slovenia Armenia Belarus Croatia Latvia yes yes yes yes yes yes no no yes yes yes yes yes n.a. yes yes no yes modified live modified live inactivated virus modified live modified live inactivated virus 276 500 300 000 100 000 ca. 5.000.000 2 072 112 432 593 Moldavia Romania Ukraine yes yes yes yes yes yes yes yes yes modified live modified live modified live Vaccine type Number of vaccinated animals 1 200 000 6 500 000 12 200 000 * data not available In principle, emergency vaccination is not contradictory with EU directives (1). Requirements related to emergency vaccination campaigns against the CSF virus have been defined in the document 'Guidelines for a Classical Swine Fever Emergency Vaccination Programme' (2). However, by using conventional vaccines and applying the mentioned guidelines, the Scientific Veterinary Committee of the European Commission has calculated that vaccinated animals would be excluded from the market for up to 600 days (4). This is economically unacceptable and so far emergency vaccination has never been used. With the development of a first generation marker vaccine against CSF, the possibility of an amendment of the existing emergency vaccination regulations seems feasible. The implementation of a marker vaccine would require extensive serological testing in the vaccinated population in order to detect field infections. However, so far no marker vaccine has been licensed by the European Agency for Evaluation of Medicinal Products (EMEA) in London and EU Member States demand additional data on the safety and efficacy of the vaccine before a potential use in emergency situations. It is understood that the criteria for the use of the marker vaccine will be very stringent. Provided that all safety requirements are met, the period of exclusion from the market could be considerably shortened (4). As soon as marker vaccines are sufficiently investigated and licensed, the 'Guidelines for a Classical Swine Fever Emergency Vaccination Programme' (2) are to be amended. The possible use of an emergency vaccination with marker vaccines is expected to lower the costs incurred by current procedures, thereby adding an additional tool to the non-vaccination policy. - 299 - Conf. OIE 1998 In non-EU countries, CSF control measures are run by official veterinary authorities (with the exception of Uzbekistan), insofar as data are available. Not all countries follow a national eradication programme. In Latvia and Lithuania, voluntary programmes for pig farmers have been established. Several countries do not run a monitoring programme to establish whether the domestic pig population is free from CSF. In the case of an outbreak, all EU Member States and the other Western European countries execute eradication measures according to the Council Directive 80/217/EEC. Some of the Central and Eastern European countries apply similar measures. In some countries, only sick or clinically suspect animals are destroyed whereas all other animals of the infected herd, herds in the neighbouring area and contact herds are vaccinated. An unsolved problem is the control of CSF in wild boar. Both the prolonged persistence of the virus in wildlife populations and the constant threat to pig holdings in the areas concerned require an efficient control strategy. It is essential for veterinary officers and hunters to have profound knowledge of the structure and dynamics of the wild boar population in their local habitat. Wild boar meta-populations (subpopulations with very limited contacts with other ones) should be defined on the basis of their natural habitat and resources. Any kind of regulatory measures (including hunting) should be carried out on the entire meta-population, not just on parts of it. Young wild boars (< 1 year) are the most important virus target and play the most important role in virus spread. The average age of the wild boar population should be kept as high as possible (hunting: 80 % <one year old, 15 % 1-2 years old, 5 % >2 years old). In the early stage of an epidemic, animals should not be disturbed in order to keep them in their habitat. 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