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Also known as: '''''CSF — Hog Cholera — Pig Plague — CSFV

Also known as: '''''CSF — hog cholera — pig plague — CSFV

==Introduction==

==Introduction==

Classical swine fever is a highly contagious, haemorrhagic disease of swine which is caused by a [[:Category:Pestiviruses|Pestivirus]] from the family [[:Category:Flaviviridae|Flaviviridae]]. Presentation may be acute, 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.

Classical swine fever is a highly contagious, haemorrhagic disease of swine which is caused by a [[:Category:Pestiviruses|Pestivirus]] from the family Flaviviridae. Presentation may be acute, 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==

==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.

The causative agent of classical swine fever is a small, enveloped virus of around 40nm diameter. The genome is comprised of single stranded positive sense RNA 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 closely related to the [[Bovine Viral Diarrhoea Virus|bovine viral diarrhoea (BVD)]] virus of cattle, and the [[Border Disease Virus|border disease virus]] of sheep.

Classical swine fever virus is closely related to the [[Bovine Viral Diarrhoea Virus|bovine viral diarrhoea (BVD)]] virus of cattle, and the [[Border Disease Virus|border disease virus]] of sheep.

==Transmission and Pathogenesis==

==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 [[:Category:Haemostasis|haemostasis]]. In acute CSF this angiopathy, in association with shock and pyrexia, leads to death. Surviving swine go on to develop a chronic form of the disease where tissue infarction results in joint and enteric lesions.

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 occurs prior to the onset of clinical signs, 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, the virus enters the blood stream and then replicates in the spleen, bone marrow and lymph nodes before spreading to other tissues. Replication in the endothelial cells of blood vessels leads to apoptosis, causing superficial and internal haemorrhages. CSFV also induces a [[thrombocytopenia]] which contributes to haemorrhage by impairing primary [[Normal_Mechanisms_of_Haemostatic_Control#Introduction|haemostasis]]. In acute CSF this angiopathy, in association with shock and pyrexia, leads to death. Surviving swine go on to develop a chronic form of the disease where tissue infarction results in joint and enteric lesions.

The outcome of transplacental infection 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.

The outcome of transplacental infection 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 eventually from full blown CSF.

==Diagnosis==

==Diagnosis==

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.

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 40⁰C;, but in adults temperatures may be no higher than 39.5⁰C;. Lethargy, conjunctivitis and 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. Haemorrhages 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, leading 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. Also, acute classical swine fever is clinically indistinguishable from African swine fever and so care must be taken when formulating a diagnosis. Other differential diagnoses for acute CSF are [[Erysipelas - Pig|erysipelas]], [[Porcine Reproductive and Respiratory Syndrome|PRRS]], [[Haemorrhage - Pathology#Purpura|purpura haemorragica]], [[Porcine Circoviruses|PMWS, PDNS]], [[Salmonellosis]] and [[Pasteurellosis - Pigs|Pasteurellosis]]. Classical swine fever should also be considered in any pyrexic enteric or respiratory disease case that is not responsive to antibiotics.  

In the '''acute form''', animals are almost always pyrexic. In piglets the fever may exceed 40⁰C, but in adults temperatures may be no higher than 39.5⁰C. Lethargy, conjunctivitis and 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. Haemorrhages 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, leading to secondary enteric or respiratory infections which may cause confusion by masking or overlapping the more typical signs of CSF. The clinical signs of acute CSF become less specific and diagnosis more difficult as the age of onset increases. Also, acute classical swine fever is clinically indistinguishable from African swine fever and so care must be taken when formulating a diagnosis. Other differential diagnoses for acute CSF are [[Erysipelas - Pig|erysipelas]], [[Porcine Reproductive and Respiratory Syndrome|PRRS]], [[Haemorrhage#Purpura|purpura haemorragica]], [[Porcine Circoviruses|PMWS, PDNS]], [[Salmonellosis]] and [[Pasteurellosis - Pigs|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 '''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 occurring 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 [[Porcine Parvovirus|parvovirus]], [[Porcine Reproductive and Respiratory Syndrome|PRRS]], [[Leptospirosis - Pigs|leptospirosis]] and [[Suid Herpesvirus 1|Aujeszky's disease]].

The course of infection in older, breeding-age animals is often initially 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 viral virulence. During early pregnancy, transplacental CSFV infection may cause abortions, mummifications, congenital malformations or stillbirths. Infection occurring 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 shed virus and act as a reservoir for the virus, making a major contribution to the persistence of infection in the population. It is therefore important to consider classical swine fever as a differential diagnosis of reduced fertility in addition to [[Porcine Parvovirus|parvovirus]], [[Porcine Reproductive and Respiratory Syndrome|PRRS]], [[Leptospirosis - Pigs|leptospirosis]] and [[Suid Herpesvirus 1|Aujeszky's disease]].

===Pathology===

===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.

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 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 junction in animals suffering chronic diarrhoea. Joint pathology is another frequent finding. The clinical signs of chronic CSF are non-specific, however and may vary according to secondary infections; 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.

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

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.

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 suspensions 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. Despite good specificity and sensitivity, the virus isolation process takes around three days and is labour intensive and therefore costly. [[Immunofluorescence|'''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 antigen capture [[ELISA testing|'''ELISA''']] also established the presence of antigen through the use 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 sequencing and differentiation between isolates.

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 suspensions 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. Despite good specificity and sensitivity, the virus isolation process takes around three days and is labour intensive and therefore costly. [[Immunofluorescence|'''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 antigen capture [[ELISA testing|'''ELISA''']] also establishes the presence of antigen through the use 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 sequencing 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.

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 involves incubation of test sera with a CSFV to neutralise any anti-CSFV antibodies present. The virus neutralisation test takes several days, and so an ELISA test may be used when large numbers of samples must be processed urgently.

==Treatment==  

==Treatment==  

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 bait containing marker vaccines.

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 bait containing marker vaccines.

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==Links==

==Links==

#Paton, DJ and Greiser-Wilke, I (2003) '''Classical swine fever – an update''', ''Research in Veterinary Science'', 75, 169-178.

#Paton, DJ and Greiser-Wilke, I (2003) '''Classical swine fever – an update''', ''Research in Veterinary Science'', 75, 169-178.

[[Category:Expert_Review]]

[[Category:Flaviviridae]]

[[Category:Brian Aldridge reviewing]]

[[Category:Cardiology Section]]