Although classical swine fever (CSF), also known as hog cholera, does not infect humans, it does cause large economic losses in the pig industry. Canada, the U.S., New Zealand, Australia, Japan and parts of Europe have eradicated CSF while the rest of the world vaccinates but still experiences losses from acute and chronic infection.
CSF emerged in Ohio and France in the early 1800s and quickly spread around the world. At that time, there were few railways in the U.S., and 1.5 times as many pigs as humans. CSF killed up to 13 percent of the U.S. pig population in outbreak years in the late 1800’s. There were few losses observed in some areas, but CSF was devastating in others. One Indiana distillery lost 11,000 pigs in an 1856 outbreak. U.S. experts thought it reasonable that "hog cholera" had originated in Europe, while Europeans considered "swine fever" to be yet another American malady. Molecular genetics suggest that CSF is an Old World pestivirus, since all three CSF genotypes exist on the Eurasian continent, while the New World strains cluster into genotype 1.
Immunologic innovations instituted in 1913 provided significant control, yet H. W. Dunne, author of "Diseases of Swine," stated in 1961 that "... it cannot be denied that hog cholera is still the biggest killer of swine of any specific disease now known in that species." The Paderborn genotype 2.1 CSF outbreak in the Netherlands in 1997-98 spread to 400 farms, resulting in the killing of 12 million pigs and a clean-up cost exceeding USD$2 billion. A panel of Chinese academicians and field experts at a January 2017 symposium generally agreed that CSF is the No. 1 disease concern in the Chinese swine industry among a legion of pathogens.
Transmission of CSF
CSF is highly contagious and is caused by a Pestivirus that moves from pig to pig by direct and indirect contact. CSF can be spread by contaminated feedstuffs, trucks and implements used in animal husbandry. CSF virus survives 10 weeks in muscle at room temperature, in cured uncooked pork for up to 6 months and for years in frozen pork. The feeding of raw garbage to pigs is major means of spread. Airborne pig to pig transmission is generally not important, but mosquitoes, flies and wildlife can transmit the virus mechanically. Pressure-washing can spread CSF short distances. Vertical transmission by persistently infected sows to their piglets represents the biggest headache in CSF control. Feedback of CSF virus material in unconfirmed cases of porcine epidemic diarrhea (PED) can amplify the CSF virus, producing unusually high piglet mortality. Immunosuppression from common, concurrent viral diseases, such as PRRS and PCV-2, may trigger CSF problems and new outbreaks.
Clinical signs
Incubation varies from a few days up to one month. Mortality in naive pigs can exceed 90 percent and can, at times, approach 30 percent even in the face of vaccination programs that often control the disease well. Growing pigs with CSF express lethargy, anorexia, depression, huddling, high fever greater than 40 to 42 C, purple extremities, and diarrhea and/or constipation. Sows may go off feed, abort, fail to farrow, or produce mummified or stillborn pigs. Sows may have diarrhea and occasionally may die. Piglets may be weak and spraddle-legged and show central nervous system signs including fine tremoring, incoordination and backwards-walking. Congenital deformities such as cyclops, cerebral encephalocele, jaw and limb deformities, hydrocephalus and cerebellar hypoplasia may occur. Piglets may look normal but have a mild to severe diarrhea and fail to grow and thrive. Pigs may seem to recover and then die suddenly weeks later. Piglets infected in-utero may be immunosuppressed and spread the virus to other pigs.
Necropsy findings
Typical gross lesions of CSF are hemorrhages on the heart, stomach, intestine, epiglottis, tonsils, urinary bladder and kidney. The “turkey-egg” kidney is the classical lesion of CSF but can be mimicked by other diseases. Hemorrhages in the epiglottis and urinary bladder are rather pathognomonic. There may be focal to patchy hemorrhagic/necrotic lesions in the intestines. The ileocecal tonsil may have ulcerative “cigarette burn” lesions. The lungs do not collapse normally, indicating interstitial (viral) pneumonia. The meninges are congested, and lymphnodes may be hemorrhagic. Pigs that linger may develop ulcerative lesions in the tonsil and “button ulcers” in the cecum and colon. Infarcts are sometimes seen in spleen and kidney. Significant strain differences exist. Low-pathogenicity CSF pigs succumb to secondary infections, and CSF is often a complex of coexisting diseases. Sometimes no specific CSF lesions are seen.
Read more: 6 most common pig diseases worldwide
Pathogenesis and microscopic lesions
CSF virus attacks blood vessels, the immune system and the nervous system. Microscopic lesions include lymphoid destruction, vasculitis, thrombosis, infarction, necrosis and hemorrhages. In the brain there is vasculitis with thrombosis, perivascular cuffing, neuronal degeneration and gliosis, and mononuclear cell meningitis. There is often tonsillar crypt necrosis and intestinal mucosa ulcerations. Histopathology can confirm necropsy results but molecular methods, immunohistochemistry and virus isolation are often used.
Active and passive immunity
Recovered pigs are immune, and serum antibodies from immune pigs can protect naive pigs. In 1913, simultaneous injection of serum and virulent virus (serum-virus) provided immunization that was used into the 1960s in the U.S. Killed vaccines enjoyed some popularity. In 1946, serial passage of CSF virus in rabbits (lapinization) produced the first modified live CSF vaccines. The Chinese C-strain vaccine produced in 1954 after over 400 passages induces protective immunity in 5 days in healthy pigs, and more than one billion rabbit and cell culture doses are administered annually. Disadvantages are thermal instability, interference from maternal antibodies in pigs less than 35 days of age and lack of booster effect. C-strain vaccine clusters with genotype 1.1, but some CSF problems result from subtypes such as 2.1 strains not covered well by C-strain vaccine.
Subunit and DIVA vaccines
Subunit vaccines against the CSF virus E2 protein can provide protective immunity. If the pigs are vaccinated but not infected, they will have antibody to E2 but not to E0 (also called Erns). Subunit vaccines can thus function as DIVA, differentiate infected from vaccinated animals, vaccines. Subunit vaccines function like CSF virus killed vaccine and require two injections and 14 to 21 days for immunity. Subunit vaccines are type- and strain-specific and may not protect against variant (heterologous) strains. Subunit vaccines can provide a strong booster effect.
Controlling vertical transmission
Standard vaccination programs do not break the sow to piglet cycle of vertical transmission. Prenatally and perinatally infected piglets lack immunocompetency and spread the virus to other piglets before and after weaning, well before immunization of the piglet himself is possible. The modified live vaccine does produce immunity in pigs 35 days or older, but as one waits for the pigs to become old enough to immunize it becomes too late to outmaneuver the insidiously spreading CSF virus. A common stop-gap strategy for problem herds is to mass vaccinate sows with 20x doses of high virus count cell culture vaccine and repeat in 3 weeks. This method is effective, but the problem can reemerge if this costly strategy is abandoned.
Neonatal intranasal vaccination and pre-colostral vaccination is also attempted in outbreak situations. Diagnosis is extremely important. Necropsy, PCR, gene sequencing, histopathology and immunohistochemical methods can be used for diagnosis. Virus isolation is seldom performed for routine diagnosis of CSF but is possible. Long-term strategy includes the identification and culling of chronic carrier gilts and sows and successful management of coexisting diseases such as PRRS, PCV2 and infectious anaemia.
Do we really want to live with this?
CSF is a nasty bedmate for a pig production enterprise. The first proposals to eradicate CSF from the U.S. and Canada were raised in the 1890s, but the U.S. program was abandoned in favor of the then emerging serum-virus control methods. Continuing losses from “hog cholera” in the face of vaccination, the desire to get rid of the disease rather than continue living with it and the loss of export opportunities drove the U.S. swine industry to press for eradication, which was completed by January 1978.
Eradicating CSF
A radical stamping-out policy seems unlikely to be successful in the CSF-infected world. It has been demonstrated that the removal of carrier sows could be part of a successful strategy for elimination of CSF from individual herds and production systems. PCR of the white cells (“buffy coat”) from the blood of persistently infected females may reveal the carrier state, but tonsil samples may also be used. The ELISA antigen test is not sensitive compared with PCR, but cheap isothermal molecular methods such as LAMP or RPA can be effective. Polyvalent and customized subunit vaccines and a DIVA strategy are possible alternatives to current vaccine programs for producing seronegative gilts and stabilization of herds with carrier sows, pending their speedy removal. Establishment and segregation of “clean” (CSF eliminated) and “dirty” (CSF not eliminated) geographical zones and the control of pig traffic into cleaned-up zones is required for eradication. Some nations eradicated CSF because their pig industries desired eradication, and the pig producers themselves pushed their leaders until eradication became a reality.
