Overview of Classical Swine Fever

CSF is caused by a small, enveloped RNA virus in the genus Pestivirus of the family Flaviviridae. Classical swine fever virus (CSFV) is antigenically related to the other pestiviruses, mainly to bovine viral diarrhea virus (BVDV, see Bovine Viral Diarrhea and Mucosal Disease Complex) of cattle and to border disease virus (BDV, see Border Disease) of sheep. These viruses are highly prevalent in bovine and ovine populations and can infect pigs. Although infections of pigs with ruminant pestiviruses in most cases do not lead to clinical disease and are rapidly cleared, infections with both BVDV and BVD induce an antibody response in swine. Therefore, antibody discrimination tests must be applied to differentiate CSF infections from infections caused by ruminant pestiviruses. Transmission of ruminant pestiviruses to pigs usually requires direct contact with cattle, sheep, or goats. CSFV naturally infects members of the Suidae family, ie, domestic and wild pigs.

In the laboratory, CSFV is cultured in cells of porcine origin, notably in the PK-15 cell line (porcine kidney), but does not generally cause a visible cytopathic effect. The virus has only one serotype, although some minor antigenic variability between strains is seen. Strains can be typed for epidemiologic mapping purposes by sequencing the entire viral genome or specific regions of the viral genome (ie, 5′UTR, E2, and NS5B regions) combined with phylogenetic analysis.

CSFV is moderately fragile and does not persist in the environment or spread long distances by the airborne route. However, it can survive for prolonged periods in a moist, protein-rich environment such as pork tissues or body fluids, particularly if kept cold or frozen. Virus survival times up to several years have been observed in frozen pork meat. CSFV may also survive months in chilled or cured cuts.

CSF has a worldwide distribution. It is considered endemic in certain countries of Central and South America, in the Caribbean basin, and in many pork-producing countries in Asia. Australia, New Zealand, Canada, and the USA are free of the disease, as well as most countries of western and central Europe, although sporadic outbreaks occur in Europe. CSF is considered endemic in several countries in eastern Europe. The main source of CSFV infection is the pig, either via infected live animals or via uncooked pork products. In areas where CSF is endemic, the major concern relates to the spread of disease through movement of infected animals, which may lead to widespread outbreaks, particularly in areas where there is large-scale transport of pigs among farms or to slaughter houses. In Europe, CSFV is considered endemic in wild boar populations, and infected wild boars are a source for CSF outbreaks among domestic pigs. However, the most probable source of CSFV infection for wild boars is contaminated garbage or even “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 of wild boars living within natural confines, such as valleys, tend to be self-limiting, and the disease fades away over time. In contrast, infections leading to outbreaks in large areas densely populated with wild boars often become endemic.

Another major risk for CSF outbreaks is the accidental introduction of CSFV into herds through illegally imported pork meat or pork products that often find their way into the porcine food chain via swill feeding. However, CSFV is readily inactivated by heat (ie, cooking), which emphasizes the importance of enforcing regulations for heat treatment of swill feed. In addition, many countries have completely banned swill feeding practices.

Mechanical transmission by vehicles and equipment, as well as by personnel (notably veterinarians) travelling between pig farms, are also significant means of spread of CSF within infected areas. The persistence of CSFV within herds for long periods has been observed. Infections of sows during pregnancy with low to moderately virulent strains of CSFV may lead to in utero infections of fetuses. These infections lead to litters born persistently infected with CSFV that are carriers of the virus and source for new infections. Persistently infected carrier pigs usually do not show clinical signs but constantly shed CSFV into the environment. Therefore, it is particularly important to consider CSFV infections while investigating herds presenting with unexplained reproductive failures that include clinical manifestations in piglets such as congenital tremor or congenital abnormalities.

CSF is characterized by fever, hemorrhages, ataxia, and purple discoloration of the skin; however, the clinical presentation varies, depending on host characteristics and the particular virus strain causing the infection. CSF occurs in several forms, including highly lethal, acute, chronic, or subclinical. Acute forms of CSF, associated with highly virulent CSFV strains, are characterized by an incubation period that is typically 3–7 days, with death occurring within 10 days after infection. Fever >41°C (105.8°F) is usually seen and persists until terminal stages of the disease when body temperature drops and becomes subnormal. Constipation followed by diarrhea and vomiting is common.

The principal lesion produced by CSFV infection is a generalized vasculitis, clinically manifested as hemorrhages and cyanosis of the skin, notably at the ears, lower abdomen, and extremities. There may also be a generalized erythema of the skin. Vasculitis in the CNS leads to incoordination (ie, staggering gait) or even convulsions. Histologically, nonsuppurative encephalitis with a characteristic vascular cuffing is common. At necropsy, the principal findings are widespread petechial and ecchymotic hemorrhages, especially in lymph nodes (eg, mandibular and retropharyngeal), tonsils, larynx, kidneys, spleen, urinary bladder, and ileum. Infarction may be seen, particularly in the periphery of the spleen. Subacute and chronic forms of the disease are also characterized by high fever, staggering gait, cough, diarrhea, purple discoloration of the skin, and death. In the subacute form, death generally happens within 20–30 days after infection; in the chronic form, death may occur much later. Subacute and chronic forms of the disease are associated with CSFV strains of moderate to low virulence, respectively. Low virulence strains can be difficult to detect; the only clinical expression may be poor reproductive performance of sows and the birth of piglets with neurologic defects (eg, congenital tremor). In chronic forms of CSF after an initial acute febrile phase, infected animals may show an apparent recovery but then relapse, with anorexia, depression, fever, and progressive loss of condition (ie, marked weight loss). Macroscopically, in addition to the lesions described above, “button” ulcers may develop in the intestine, particularly near the ileocecal junction. Histologically, atrophy of the thymus and depletion of lymphoid follicles in lymph nodes are seen.

CSF is first detected by veterinarians in the field. Because clinical signs manifested by CSFV-infected pigs are also seen with other diseases of swine, laboratory confirmation is always required. Clinically, the differential diagnosis varies according to the course of the disease, and primarily includes African swine fever. Hemorrhagic lesions must also be distinguished from those seen in porcine dermatitis and nephropathy syndrome and postweaning multisystemic wasting syndrome. Hemolytic disease of the newborn, porcine reproductive and respiratory syndrome, Aujeszky disease, parvovirus, thrombocytopenic purpura, anticoagulant poisoning (eg, warfarin), and salt poisoning should also be considered as possible differential diagnoses. Septicemic diseases, including salmonellosis, erysipelas, pasteurellosis, actinobacillosis, Haemophilus suis infections, and eperythrozoonosis may resemble CSF. Congenital infections with ruminant pestiviruses can resemble CSF reproductive failures caused by low virulence strains of CSFV. Poor reproductive performance in sows can also be associated with pseudorabies, parvovirus, and other noninfectious causes.

Virologic tests are essential to confirm the diagnosis of CSF. Advice on sample submission should be sought from the laboratory. Suitable tissues to detect the presence of the virus are tonsils, lymph nodes (mandibular, retropharyngeal, gastrohepatic, and mesenteric), spleen, kidney, and ileum. Whole blood collected with EDTA as anticoagulant can be used for virus isolation or virus detection, particularly during the viremic phase of the infection. Clotted blood samples (serum) are taken when serologic tests for detection of CSFV antibodies are pursued. Nasal swabs and/or tonsil scrapings are commonly collected clinical samples used to detect the virus (ie, viral RNA).

Significant amounts of CSFV are shed from infected animals into the environment via the oronasal route, particularly early during infection. Detection of CSFV antigen can be performed using direct immunofluorescence on frozen tissue sections, particularly in tonsil samples using specific antibodies. Antigen detection can also be done using ELISA; however, this assay has low sensitivity and is only useful for screening for the presence of CSFV at the herd level. More commonly, viral nucleic acid detection is done using reverse transcriptase (RT)-PCR. The assay is highly specific and can differentiate CSFV from BVDV and BDV. Standardized methods such as RT-PCR can be scaled up to screen large numbers of samples, giving rapid results while retaining high sensitivity. This is particularly useful to screen herds during an outbreak of CSF.

For virus isolation, cell cultures are inoculated with tissue suspensions or WBCs, fixed after 2–3 days, and the virus is detected using specific antibodies directed against CSFV (eg, fluorescent or enzymatic methods). Final results may not be available for 4–7 days. This method is labor intensive and time consuming. Virus characterization using virus-specific monoclonal antibodies or RT-PCR is performed to differentiate CSFV from the other pestiviruses. Positive results of antigen detection or virus isolation are not confirmed until virus identification is completed. Virus neutralization tests and ELISA tests are available to detect antibodies against CSFV. Because the virus is noncytopathogenic in culture, the neutralization test requires an additional immunostaining step to reveal the presence of neutralizing antibodies. ELISA tests are suitable for large-scale serology when large number of samples are processed, ie, for surveillance purposes. Cross-reactions between pestivirus antibodies are seen in diagnostic tests. The presence of antibodies against ruminant pestiviruses in pigs may hamper the serologic diagnosis of CSF. BVDV or BDV-specific antibodies are sporadically detected in pig populations. Risk factors related with ruminant pestivirus antibodies in pigs are associated with the presence of cattle on the same farm and high density of sheep and/or goats in the area. Some commercial ELISAs can distinguish CSF from BVDV or BDV antibodies, although confirmatory testing is advised usually via neutralizing peroxidase-linked assays.

New generations of CSFV marker vaccines have been developed to make emergency vaccination compatible with control of CSF. The application of a marker vaccine is possible if tests such as ELISA can distinguish between antibodies produced in response to a natural infection and those produced by vaccination. This is the DIVA principle (differentiation of infected from vaccinated animals) that is based on detection of CSFV-specific antibodies that develop in the host only with CSFV infection but not on vaccination with a marker vaccine. These assays have been developed as necessary companion tests for CSF marker vaccines.

CSF is a notifiable disease. Control is usually strictly regulated by local laws that establish strict sanitary measures. No treatment is available. Outbreaks in countries free of CSF are controlled rapidly via culling of infected animals and preemptive slaughter of susceptible animals within determined distances from the focus. Restriction of movement within a well-defined radius from the outbreak is applied to contain spread of the infection. Eventually, emergency vaccination can be authorized to control the further spread of CSFV. Countries will regain their CSF-free status (no antibodies or virus detected) after establishing that CSFV is no longer present in the national pig herd.

Countries free of CSF usually implement preventive measures to avoid outbreaks of CSF by controlling movement of live animals and pork products at borders. Countries free of CSF forbid the use of prophylactic vaccination. In countries where CSF is endemic, prophylactic vaccination is regularly practiced and is mandatory in some cases. Prophylactic vaccination has been used worldwide as a tool to control and eradicate CSF. In these countries, herds affected by an outbreak are quarantined and if possible eliminated. Emergency ring vaccination around the outbreak is done to prevent further spread of CSFV. CSF live attenuated vaccines are safe and highly efficient, being able to induce protection shortly after vaccination (within 3 days after vaccination). Several live attenuated vaccines, such as the Chinese lapinized vaccine (C-strain), the Japanese GPE-strain, and the French Thiverval strain, have been developed and used in different countries. More recently, subunit CSFV vaccines containing only the major viral surface glycoprotein of the virus have been licensed. Although these vaccines have DIVA capabilities, they lack the efficiency of live attenuated vaccines. Oral vaccination of wild boars has been used successfully within the European Union using a live attenuated vaccine delivered via baits. Oral vaccination has been a key strategy to control CSF, particularly where parenteral vaccine delivery is not feasible.