Classical Swine Fever

Description

Classical swine fever is a highly contagious, haemorrhagic disease of swine which is caused by a Togavirus. Presentation may be actue, sub-acute, chronic or persistent, and the disease is indistinguishable in the field from African Swine Fever. Acutely, classical swine fever is characterised by severe depression, high fever and superficial and internal haemorrhages, with many cases resulting in death. Depression, anorexia and pyrexia are seen in chronic classical swine fever. Transplacental infection is also possible and results in persistently infected piglets.

Aetiology

The causative agent of classical swine fever is a small, enveloped virus of around 40nm diameter. The genome is comprised of single stranded RNA, which is positive sense and contains about 12,300 bases. The sequence of the genome is known, and codes four structural and seven non-structural proteins. The classical swine fever virus is relatively stable in excretions and in fresh meat products including ham, salami and other similar sausages. It is, however, easily inactivated by detergents, common disinfectants and heat.

Classical swine fever virus is a Togavirus within the Pestivirus genus of the Flaviviridae. As such, it is closely related to the bovine viral diarrhoea (BVD) virus of cattle, and the border disease virus of sheep.

Signalment

Domestic pigs and other swine of any age may become infected with classical swine fever.

Transmission and Pathogenesis

In field cases of CSFV, transmission is mainly oronasal by direct or indirect contact with infected pigs. Infected feed or pork products may also cause spread of disease, and transmission in semen can occur. Once the virus gains entry to the host an incubation period of around 7 days ensues, but this may vary from 4-10 days. Initially, virus infects the epithelial cells of the tonsillar crypts before spreading via the lymphatics to regional lymph nodes. From here, classical swine fever virus enters the blood stream and then replicates in the spleen, bone marrow and lymph nodes before spreading to further tissues. Replication in the endothelial cells of blood vessels leads to apoptosis, causing superficial and internal haemorrhages. CSFV also causes a thrombocytopenia which contributes to haemorrhage by impairing primary haemostasis. In acute CSF this angiopathy causes pig death in association with shock and the febrile response. Surviving swine go on to develop a chronic form of the disease where joint and enteric lesions are seen resulting from tissue infarction.

The outcome of transplacental infection of foetuses depends largely on the point of gestation and may result in abortions, stillbirths, mummifications, malformations or the birth of weak or persistently viraemic piglets. Although persistently infected piglets may be clinically normal at birth, they grow poorly, excrete virus over long periods and invariably die from CSF.

Diagnosis

Diagnosis is made on the basis of history, clinical signs and gross pathological lesions. In Britain, classical swine fever is notifiable to the local Animal Health Office. Following notification, the State Veterinary Service is responsible for visiting the suspect premises to confirm the diagnosis by laboratory testing.

Clinical Signs

Although the incubation period for classical swine fever is generally less than ten days, in the field it may take up to four weeks for clinical signs to become apparent in a population. Disease severity varies with virulence, immune status and the age of the animal: this means that although acute, chronic and congenital forms of the disease can be appreciated, there is no "classic" disease presentation.

In the acute form, animals are almost always pyrexic. In piglets the fever may exceed 40°, but in adults temperatures may be no higher than 39.5°. Lethargy, conjunctivitis, lymphomegaly may be seen, as well as respiratory signs and diarrhoea. Neurological signs such as gait abnormalities, incoordination and convulsions are also common. The most telling sign of classical swine fever is haemorrhage of the skin. These arise in the second or third week post-infection on the ear, tail, abdomen and medial aspect of the limbs and persist until death. CSF virus also causes severe leukopenia and immunosuppression, which can to secondary enteric or respiratory infections which may cause confusion by masking or overlapping the more typical signs of CSF. With increasing age of infected animals, the clinical signs of acute CSF become less specific and diagnosis more difficult. Alao, acute classical swine fever is indistinguishable from African swine fever and so care must be taken when formulating a diagnosis. Other differential diagnoses for acute CSF are erysipelas, PRRS, purpura haemorragica, PWMS, PDNS, Salmonellosis and Pasteurellosis. Classical swine fever should also be considered in any pyrexic enteric or respiratory disease case that is not responsive to antibiotics.

The chronic form of classical swine fever develops when pigs fail to mount an effective immune response to viral infection. Initially, the signs are similar to the acute form of the disease, but symptoms become less specific as the course progresses. For example, pigs may display chronic enteritis, loss of condition, lameness or intermittent pyrexia. In a herd, mortality may be increased or there may be large numbers of runty pigs. Although animals may survive some months after contracting chronic CSF, the disease is always eventually fatal and animals continue to shed virus until death.

The course of infection in older, breeding-age animals is often subclinical; however, CSFV is able to cross the placenta at any stage of pregnancy. The outcome of transplacental infection is highly dependent on the stage of gestation, and also virulence. During early pregnancy, transplacental CSFV infection may cause abortions, mummifications, congenital malformations or stillbirths. Infection occuring after 50-70 days gestation can lead to the birth of persistently viraemic piglets. These may appear clinically normal at birth, but grow poorly and occasionally show congenital tremor. Persistently infected piglets also shed virus until their inevitable death, acting as a reservoir for virus and making major contributions to the maintenance of infection in the population. It is therefore important to consider classical swine fever as a differential diagnosis of reduced fertility in addition to parvovirus, PRRS, leptospirosis and Aujeszky's disease.

Pathology

In acute classical swine fever, the major pathological change is multiple haemorrhages. This is seen as many purple blotches in the skin, and as sub-capsular bleeding in association with swelling and oedema in all lymph nodes. A "turkey egg" appearance to the kidneys is displayed, with haemorrhage varying from petechiae to ecchymoses. Haemorrhage may also be seen on any mucosal or serosal surface, including the urinary bladder and the larynx and epiglottis. The heart can be affected, and haemorrhage between other muscles is possible. The lungs are congested and haemorrhagic and often show bronchopneumonia, and straw-coloured fluid accumulates in the thoracic and abdominal cavities and the pericardial sac. A non-suppurative encephalitis can also feature.

The pathological changes of chronic classical swine fever are generally less typical, and organs and serosae usually lack haemorrhages. Necrotic, ulcerative lesions known as "button ulcers" are commonly seen in the ileum and rectum and at the ileocaecal valve in animals suffering chronic diarrhoea. Joint pathology is another frequent finding. However, the clinical signs of chronic CSF are non-specific and may vary according to secondary infections, and this is reflected in the pathological presentation of the disease.

The most common finding in cases of congenital classical swine fever is CNS pathology, particularly cerebellar hypoplasia.

Laboratory Tests

Laboratory testing is required to confirm a diagnosis of classical swine fever. As well as collection of tissues for histopathology, samples of tonsils, spleen, lymph nodes, kidney and distal ileum are taken for virus detection. Virus may be detected by fluorescent antibody detection, in situ hybridisation, PCR, immunoperoxidase staining or virus isolation. Several of these methods are reviewed by Moennig¹, and are briefly summarised here.

The gold standard laboratory test for CSFV is virus isolation in cell culture. In viraemic animals, virus may be isolated both from buffy coat cells and from supsensions of spleen, lymph node, tonsil, kidney or parotid salivary glands. Samples are incubated on cultures of porcine cells, and since classical swine fever virus is non-cytopathogenic, anti-CSFV antibodies are used to detect virus. Depsite good specificity and sensitivity, the virus isolation process takes around three days and is labour intesive and therefore costly. Fluorescent antibody testing is less sensitive but more rapid than virus isolation, and involves the used of fluoresecently-labelled anti-CSFV antibodies to demonstrate the presence of virus antigen in tissue. A virus anitigen capture ELISA also established the presence of antigen through the used of specific antibodies, and is useful for screening large numbers of animals. In the last ten years, it has become possible to detect CSF virus RNA by RT-PCR, usually of the 5' untranslated region. As well as confirming infection, this allows subsequent genetic sequening and differentiation between isolates.

Although antigen detection methods have largely replaced serology in the diagnosis of acute classical swine fever outbreaks, CSFV serology is important for disease surveillance, particularly in wild boar. A virus neutralisation test is the most sensitive and specific form of CSFV serology, and involved incubation of test sera with a CSFV to neutralise any anti-CSFV antibodies present. However, the virus neutralisation test takes several days, and so an ELISA test may be used when large numbers of samples must be processed.

Treatment

Classical swine fever is controlled rather than treated. The policy for control depends on the prevalence of infection in the pig population of a particular country: where CSF is endemic vaccination strategies are commonly used, but outbreaks in the normally CSF-free of the EU are controlled by a slaughter policy. This policy aims for eradication of CSFV by "stamping out" infected and neighbouring herds and contacts, imposing movement restrictions and investigating the source and spread of the outbreak. Equipment, footwear and other fomites must be disinfected, and once a herd is depopulated farm buildings and other areas are throughly cleaned and disinfected. Effective disinfectants include sodium hyrdoxide, formalin and washing soda.

Wild boar act as a reservoir of CSF infection, and so control must also be aimed at this population. As well as adequate surveillance, this involves utilising knowledge about factors influencing CSF epidemiology such as wild boar behaviour and population dynamics, and the influence of hunting strategies. Wild boar vaccination schemes are currently being undertaken in parts of Europe using baits containing marker vaccines.

Vaccination

Where CSF is endemic vaccination is effective. there are now gene deletion marker vaccines available and ELISA tests an be used to differentiate vaccinated from infected animals.

In principle, emergency vaccination is in agreement with EU legislation (Anonymous, 1980). Requirements related to emergency vaccination campaigns against CSF virus have been de®ned in the document `Guidelines for a Classical Swine Fever Emergency Vaccination Programme' (Anonymous, 1994). However, by using conventional vaccines and applying the mentioned guidelines, the Scienti®c Veterinary Committee of the Commission has calculated that vaccinated animals would be excluded from the market for up to 600 days (Anonymous, 1997). This is economically unacceptable and so far emergency vaccination has never been used. With the development of a ®rst generation marker vaccine against CSF the possibility of an amendment of the existing EU emergency vaccination regulations seems feasible. A restricted application of a marker vaccine would require extensive serological testing in the vaccinated population in order to detect hidden ®eld virus infections. At present no marker vaccine has been licensed within the EU and EU Member States demand welldocumented data on the safety and ef®cacy of the vaccine before its 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 at least for pig products after a CSF outbreak (Anonymous, 1997). As soon as marker vaccines are suf®ciently investigated and licensed, the `Guidelines for a Classical Swine Fever Emergency Vaccination Programme' (Anonymous, 1994) are to be amended. The possible use of an emergency vaccination with marker vaccines is expected to avoid the ethically questionable and expensive large scale pre-emptive slaughter of pigs. Thereby, the public acceptance of the eradication policy will increase and costs will decrease. Under these circumstances the use of emergency vaccination using marker vaccines could be a useful tool of the non-vaccination policy.

From the beginning of the century attempts have been made to develop vaccines against CSF. However, the safety and ef®cacy of the ®rst generations of vaccines were poor. In the 1940s ®rst experiments were made to attenuate CSFV by adapting it to rabbits (Baker, 1946; Koprowski et al., 1946). After initial setbacks, this development ultimately led to a very ef®cient and safe generation of live vaccines. Most attenuated vaccines are based on the China-strain (C-strain) of lapinized CSF virus. C-strain vaccines were and are still being used world-wide for the control of CSF in domestic pigs. It is also used at least on an experimental basis for the oral immunisation to control CSF in wild boar (Kaden et al., 2000). C-strain vaccines induce high titres of neutralising antibodies and they are safe when used on pregnant animals. Their ef®cacy is demonstrated by the observation that vaccinated pigs are protected against infections with virulent CSF virus as early as ®ve days after vaccination. The animals are immune throughout their economic life. However, with respect to today's global trade policy there is a severe disadvantage in using live attenuated vaccines against CSF: Vaccinated and ®eld-virus-infected animals cannot be distinguished because the antibody pattern induced by the vaccine virus resembles that of reconvalescent animals. A way out of this dilemma may be the development and use of so-called marker vaccines, e.g., subunit vaccines consisting of single viral surface proteins, which are suf- ®cient for the induction of protective immunity. At present two subunit vaccines containing the viral glycoprotein E2 are under scrutiny. The respective gene is expressed in baculoviruses grown in insect cells (Van Rijn et al., 1996). 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, e.g., the surface glycoprotein Erns or the nonstructural protein NS2-3. However, not all criteria for the emergency use of marker vaccines are well de®ned yet, and the technical merits of these vaccines have not yet been established. More data are expected to be available during the year 1999. Technically there is the potential for further improving CSF marker vaccines by developing, e.g., viral vector vaccines (RuÈmenapf et al., 1991; Van Zijl et al., 1991; Hooft van Iddekinge et al., 1996), DNA vaccines and molecularly altered infectious cDNA clones of CSF virus (Meyers et al., 1996, Moormann et al., 1996, Ruggli et al., 1996).

Links

• Defra - Classical Swine Fever

References

1. Moennig, V (2000) Introduction to classical swine fever: virus, disease and control policy, Veterinary Microbiology, 73, 93-102.
2. Moennig, V et al (2003) Clinical Signs and Epidemiology of Classical Swine Fever: A Review of New Knowledge, The Veterinary Journal, 165, 11-20.
3. Paton, DJ and Greiser-Wilke, I (2003) Classical swine fever – an update, Research in Veterinary Science, 75, 169-178.