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Overview of Classical Swine Fever

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Classical swine fever is a contagious febrile disease of pigs. It was first described in the early 19th century in the USA. Later, a condition in Europe termed swine fever was recognized to be the same disease. Both names continue in use, although in Europe it is now called classical swine fever to distinguish it from African swine fever (see African Swine Fever), which is clinically indistinguishable but caused by an unrelated virus. Due to their severe economic impact, outbreaks of classical swine fever are notifiable to the OIE.

Classical swine fever has the potential to cause devastating epidemics, particularly in countries that are free of the disease. In these countries, vaccination is generally only allowed in emergency cases. In case of a new outbreak, strict measures are enforced to control the spread of the disease, eg, culling of infected and suspect pigs and movement restrictions. This can have severe consequences for the pig industry, especially in densely populated livestock areas. For example, during the epidemic in the Netherlands in 1997–98 a total of 429 herds were infected, and ~700,000 pigs were culled. Further control and welfare measures made it necessary to slaughter almost 12 million pigs. Awareness and vigilance are essential so that outbreaks are detected early and control measures are instituted rapidly to prevent further spread.The “high risk period”, ie, the time between introduction of the virus and detection of the outbreak, must be kept as short as possible.

Classical swine fever is caused by a small, enveloped RNA virus in the genus Pestivirus of the family Flaviviridae. Classical swine fever virus is antigenically related to the other pestiviruses, namely bovine viral diarrhea virus of cattle (see Intestinal Diseases in Ruminants: Bovine Viral Diarrhea and Mucosal Disease Complex) and border disease virus of sheep (see Congenital and Inherited Anomalies: Border Disease), which are widespread in ruminant populations and can occasionally infect pigs. Although they do not cause disease in pigs and are eliminated after a few days, antibody discrimination tests must be done to differentiate classical swine fever from infection with ruminant pestiviruses.

Classical swine fever virus infects only Suidae, ie, pigs and wild boar, although experimental infections can be induced in other species. It will grow in porcine cell cultures, notably the PK15 cell line, but does not generally cause a visible cytopathic effect. The virus has only one serotype, although some minor antigenic variability between strains can be shown. Strain typing for epidemiologic mapping purposes can be done by sequencing the viral genome or its fragments combined with phylogenetic analysis.

The virus is moderately fragile and does not persist in the environment or spread long distances by the airborne route. It can survive for prolonged periods in a moist, protein-rich medium such as meat, other tissues, and body fluids, particularly if kept cold or frozen. Viral survival times of several years in frozen pig meat, or months in chilled or cured meat, have been reported.

Classical swine fever is distributed worldwide. It is endemic in parts of Latin America, some Caribbean islands, and pig-producing countries of Asia. In 2005, South Africa reported its first occurrence of classical swine fever since 1918. Australia, New Zealand, Canada, and the USA are free of classical swine fever, as is most of western and central Europe, although sporadic outbreaks occur in a number of European countries. The disease is endemic in several countries in eastern Europe.

The main source of infection is the pig—either live animals or uncooked pig products. In endemic areas, the major concern is spread of disease by movement of infected pigs, which can be a cause of remote outbreaks where there is large-scale transport of pigs for finishing. In parts of Europe, the wild boar population may harbor the virus.

Another major risk is accidental introduction of the virus through illegally imported pig meat and meat products that find their way into the porcine food chain through the feeding of waste food. The virus is readily inactivated by cooking, which emphasizes the importance of enforcing regulations on heat treatment of swill. Many countries have completely banned swill feeding.

Mechanical transmission on vehicles and equipment, as well as by personnel (notably veterinarians) travelling between pig farms, are also significant means of spread within an infected area.

If sows are infected with low to moderately virulent strains of virus during pregnancy and then recover, there is a high risk that their offspring may be carriers. Not all such persistently infected carriers will always show clinical signs of disease, but they will permanently shed the virus. Therefore, it is particularly important to investigate herds with high levels of unexplained reproductive failure, congenital tremor, or other congenital abnormalities.

Probable transmission routes to wild boars are contaminated garbage or “spillover” from infected domestic pigs. The outcome of such infections mainly depends on the size and density of the wild boar populations affected. Outbreaks in small populations living within natural confines, such as valleys, tend to be self-limiting. In contrast, infections leading to outbreaks in large areas and dense populations often become endemic.

The disease has acute and chronic forms, and virulence varies from severe, with high mortality, to mild or even subclinical. Low virulence strains are a special diagnostic problem; the only expression may be poor reproductive performance and the birth of piglets with neurologic defects (eg, congenital tremor, see Congenital and Inherited Anomalies of the Nervous System: Large Animals).

The severe acute form is characterized by fever, inappetence, and depression. The incubation period is typically 3–7 days, with death at 10–20 days after infection. Fever (>41°C) persists until the terminal stage of disease, when body temperature may become subnormal. Constipation is common, followed by diarrhea. The principal lesion is a generalized vasculitis, seen in live pigs as hemorrhages and cyanosis in the skin, notably of the extremities. There may also be a generalized erythema. Vasculitis in the CNS may produce incoordination or even convulsions. At necropsy, the principal findings are widespread petechial and ecchymotic hemorrhages, especially in lymph nodes, kidneys, spleen, bladder, and larynx. Infarction may be seen, notably in the spleen. Most pigs show a nonsuppurative encephalitis with vascular cuffing.

In chronic disease, pigs often survive for up to 3 mo. After an initial acute febrile phase, they may show apparent recovery but then relapse, with anorexia, depression, fever, and progressive loss of condition. Histologically, there is atrophy of the thymus and lymphoid depletion. Button ulcers may develop in the intestine, particularly near the ileocecal junction.

The first line of diagnosis is performed by the veterinarian in the field. As clinical signs are not necessarily typical, differential and laboratory diagnosis generally follow. Differential diagnoses include other febrile hemorrhagic diseases of pigs such as African swine fever, bacterial septicemias (eg, salmonellosis, erysipelas, etc), anticoagulant poisoning (coumarin derivatives), and hemolytic disease of the newborn. Hemorrhagic lesions must be distinguished from those seen in porcine dermatitis and nephropathy syndrome and postweaning multisystemic wasting syndrome (see Porcine Circovirus Diseases), which have become widespread in many pig-producing countries. With low virulence strains of classical swine fever virus, a variety of other cases of low reproductive performance and congenital tremors should be considered, including pseudorabies, parvovirus, bovine viral diarrhea virus, border disease virus, and noninfectious causes.

Virologic tests are essential to confirm a diagnosis. Advice on sample submission should be sought from the laboratory. Suitable tissues are tonsil, maxillary or submandibular lymph nodes, mesenteric lymph nodes, spleen, ileum, and kidney. Whole blood with EDTA as anticoagulant can be used for virus isolation from a live acute case, or for antigen or nucleic acid detection. Clotted blood samples are taken when serologic tests for antibody are required. Serology is the method of choice for testing sows that have given birth to congenitally affected litters and for screening to reveal the virus, in particular in wild boar and feral pig populations.

Antigen detection can be performed using direct immunofluorescence on frozen tissue sections, particularly of tonsil. Reading the sections requires highly skilled and experienced personnel. Its main advantage is a rapid result. Antigen detection can also be done using ELISA. However, this assay has low sensitivity and is only useful for screening pigs at the herd level. More commonly, viral nucleic acid detection is done using reverse transcriptase (RT) PCR. In addition, with the use of suitable primers, RT-PCR can differentiate the virus from bovine viral diarrhea and border disease virus. Standardized methods have been described that permit scale-up to screen large numbers of (pooled) blood samples, giving rapid results while retaining high sensitivity. This is particularly useful for screening herds during an outbreak.

For virus isolation, cell cultures are inoculated with tissue suspensions or WBC, fixed after 2–3 days, and virus detected after immunolabeling (using fluorescent or enzyme labels). Final results may not be available for 4–7 days. This method is labor- and time-intensive. However, due to its sensitivity and specificity it is the reference method in the case of a new outbreak.

Virus characterization using virus-specific monoclonal antibodies or RT-PCR is performed to differentiate classical swine fever virus from the other pestiviruses. Positive results of antigen detection or virus isolation tests should not be confirmed until virus characterization is done.

For serology, virus neutralization tests and ELISA are available. Because the virus is noncytopathogenic in culture, the neutralization test requires an additional immunolabeling stage. The ELISA is more suited to large-scale serology, ie, for surveillance. Some commercial ELISA can distinguish classical swine fever from bovine viral diarrhea virus antibodies, although confirmatory testing is advised in cases of doubt. Some ELISA methods can detect antibodies to a specific viral protein that is absent from so-called “marker vaccines.” Such a differentiating infected from vaccinated individuals (DIVA) ELISA was developed for identifying pigs infected with field virus among a population vaccinated with a commercially available subunit vaccine. The technique has not as yet found much acceptance for field use, and the DIVA ELISA has rather low sensitivity.

In most countries, classical swine fever is a notifiable disease. Control is strictly regulated by laws and health measures. No treatment is possible. Affected pigs must be slaughtered and the carcasses buried or incinerated. Confirmed cases and in-contact animals should be slaughtered, and measures taken to protect other pigs. This may involve herd slaughter combined with area restrictions on pig movements, or vaccination, depending on local disease control regulations.

In countries where the virus is endemic, infected animals are destroyed, and vaccination is used to prevent to prevent further spread of the virus. Countries free of classical swine fever usually implement measures to avoid outbreaks of the disease. Within the EU, where prophylactic vaccination is forbidden, emergency vaccination can be used for control in the event of severe outbreaks with a conventional modified live vaccine or a marker vaccine. The modified live vaccines are either derivatives of the lapinized “C” strain or strains adapted from cell cultures. They are effective and innocuous. A few years ago a subunit vaccine that contains only the major viral surface glycoprotein was licensed. Because naturally infected pigs develop antibodies to this protein, the combination of marker vaccine and specific diagnostic test (DIVA, see Classical Swine Fever: Diagnosis) enables the theoretical differentiation of vaccinated from infected pigs. The subunit vaccine has been used since 2006 in Romania for emergency vaccination. In wild boar outbreaks, emergency vaccination using baits with modified live vaccines has been used successfully in Germany and other European countries.

Last full review/revision March 2012 by Irene Greiser-Wilke, Dr rer nat

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