Classical Swine Fever (CSF)

Last updated June 26, 2003

Agent
Hosts
Epidemiology
CSF As a Biological Weapon
Clinical Features
Differential Diagnosis
Laboratory Diagnosis
Treatment
Prevention
Outbreak Control
Public Health
References

Agent

Classical swine fever (CSF), also known as hog cholera and swine fever, is a highly contagious viral disease of swine with acute, chronic, and persistent presentations (see References: Moennig 2000, Murphy 1999). Characteristics include the following:

First described in 1810 in North America and shortly thereafter on the European continent
Caused by a lipid-enveloped virus in the family Flaviviridae, genus Pestivirus
Single-stranded, linear, positive-sense RNA
One serotype, although minor antigenic variations have been reported
Closely related antigenically to bovine viral diarrhea and border disease viruses
Virus can be destroyed by drying, heating, exposure to a pH outside the range of 3 to 11, or exposure to agents such as lipid solvents, inonic detergents, chlorine disinfectants, or strong iodophores (see References: Edwards: Survival and inactivation of CSF)

Hosts

Members of the family Suidae are susceptible. The only natural hosts of CSF include the domestic pig and wild boar–type animals. Experimental infections can be induced in other species.

Source: Edwards 1998 (see References).

Epidemiology

Transmission

Transmission occurs by several means:

Direct contact with infected animals (oral route most important)
Mechanical fomites (personnel, vehicles, instruments, feed, animals)
Feeding of waste food that has been improperly handled
Transplacental infection
Artificial insemination with contaminated semen (1997 Netherlands epidemic) (see References: Stegeman 2000)
Biting insects (under certain conditions)
Mechanical ventilation between production units located close to one another (within 6 km); this is not known to be important in the epidemiology of the virus

Sources: Dewulf 2000, Kleiboeker 2002 (see References).

Occurrence

The last outbreak of CSF in North America occurred in the United States in 1976 after a 14-year eradication program.
CSF has also been eradicated in some European Union member states, as well as in Australia, Japan, and New Zealand.
The disease is present in Asia, Southern Mexico, South and Central America, the Caribbean, and parts of Africa (Madagascar, Mauritius).

Brazil has an active eradication program for CSF. The southern part of the country is disease-free.
Mexico is divided into three control zones. The northern zone (including the Yucatan peninsula) is CSF-free; the middle zone uses stamping-out protocols without vaccination and the southern zone uses vaccination alone for control.
In Central America, Belize and Panama are reported to be CSF-free.
In South America, Uruguay and Chile are disease-free, with Argentina, Columbia, Paraguay, Ecuador, and Costa Rica implementing control programs.
CSF is present in Cuba, Haiti, and the Dominican Republic.
Many Eastern European nations have control programs with a goal of eradication.

CSF is enzootic in some feral pig populations (population estimated at 800,000 to 1 million animals) on the European continent (See References: Laddomada 2000). Within the last decade, efforts have been made to manage the population and adopt control measures to limit CSF in feral pigs (see References: Kaden 2000).

Animals less likely to take up oral vaccine and having a high likelihood of infection (such as young boars) are depopulated through hunting.
Oral vaccination programs have been shown to reduce spread of the virus, but the effectiveness in eradication programs is unknown.

The following outbreaks have occurred recently:

1997-98 in the Netherlands, Germany, Belgium, Spain, Austria, and Switzerland, costing an estimated $2.3 billion; 12.4 million animals were slaughtered
2000 in the United Kingdom
2001 in Germany, Slovakia, Spain, and Romania

The most recent updates on outbreaks and world animal health status of CSF can be viewed at the OIE Web site (see References: OIE: Disease information).

Further source: Edwards: Classical swine fever (see References).

Communicability

The CSF virus is found in all tissues, blood, secretions, and excretions of affected animals.
The virus is highly stable and can survive for long periods in protein-rich environments such as meat (up to 4 years in frozen meat).
Congenitally infected piglets are persistently viremic and shed the virus for months.
Virulence can range from low to high, but most field viruses today are of moderate virulence.

Sources: Edwards: Survival and inactivation of CSF; Kleiboeker 2002 (see References).

CSF As a Biological Weapon

CSF is considered a potential bioweapon because of the following factors:

The disease can have high rates of morbidity and mortality, especially in animal populations with no immunity.
Intensification in the swine industry, including a large number of animals per site and increased movement and distance between sources, increases the possibility of widespread dispersion of the disease (see References: Kleiboeker 2002).
The economic impact would be severe if CSF were intentionally introduced into US production systems. Pork exports in 1997 totaled $1 billion; CSF infection would eliminate most US export markets.

Clinical Features

The clinical features of CSF are outlined in the table below. Clinical signs and lesions, caused by degeneration of endothelial cells and changes in fibrinogen synthesis, are highly variable. Signs are loosely classified as acute, chronic, and persistent (see References: Giles 1998; Kleiboeker 2002; OIE: Manual of standards).

Clinical Features of Classical Swine Fever
*Feature*	*Characteristics*
General clinical signs*	—Pyrexia with huddling and piling for warmth in all age-groups —Nonspecific signs of anorexia, malaise, conjunctivitis —Constipation during initial fever followed by diarrhea —Purple discoloration of ears, abdomen, and inner thighs several days later —Unsteady gait progressing to paralysis, convulsions, and death
Complications	Secondary bacterial infection of tonsils
ACUTE FORM†
Incubation period‡	3-4 days
Clinical signs	—Pigs found dead or moribound —Intially, systemic vasculitis with petechial to ecchymotic hemorrhages; in late stages there will be skin hemorrhage and cyanotic areas in axilla, abdomen, and ears —Severe anorexia and depression —Pyrexia from 41°C-42°C (106°F-108°F) —Constipation at intial onset of fever, followed by profuse diarrhea —Severe leukopenia in initial stages —Conjunctivitis (seen with heavy crusting and streaking around eyes) (see Figure 65 from The Gray Book [References: Giles 1998]) —Severe tonsillitis with areas of necrosis —Progressive wasting and finally ataxia and paralysis prior to death
Case-fatality rate	High mortality rate (up to 100% in piglets) with death in 10-20 days with virulent strains
CHRONIC FORM§
Incubation period‡	3-4 days
Clinical signs	—Pyrexia for 2-3 wk reaching 40.5°C-41°C (105°F-106°F) —Virus spreads slowly and induces lower titers —Intially; pigs present with anorexia, depression, pyrexia, diarrhea, and leukopenia for a period of several weeks —Pigs then seem to recover and have generally normal appearance —Following normal period, pigs become anorexic, depressed, and febrile again —Animals have poor hair growth, retarded growth rates, and skin problems
Case-fatality rate	Lower mortality rate (30%-70%), with death in 1-3 mo
PERSISTENT FORM**
Incubation period‡	3-4 days in sows
Clinical signs	—Infected sows often exhibit minimal signs; these include transient pyrexia and inappetence —Infection can cause fetal death, resorption, mummification, birth defects, stillbirth, or (rarely) abortion —Birth defects include hypoplasia of lungs and cerebellum and hypomyeogenesis —Sow can give birth to live, congenitally affected piglets leading to: ~Piglets that are persistently infected and have congenital tremors with generalized weakness ~Piglets that eventually develop clinical chronic disease signs as listed above ~Signs that manifest between6 mo and 1 yr of age ~Animals that never generate an antibody response and shed organism continuously
Case-fatality rate	100% mortality rate, with death in 6 mo–1 yr in persistently infected animals
Clinical disease course and associated lesions at necropsy depend on virulence of strain and susceptibility of host. †Caused by virulent strains of CSF. ‡Ranges from 3 to 15 days, depending on infective dose, host susceptibility, and viral strain. §Occurs in vaccinated herds or herds with low-virulence CSF virus strains. *Pigs congenitally infected with ruminant pestiviruses (bovine viral diarrhea) will have clinical signs indistinguishable from those of congenital CSF.

Pathology

Although there are no pathognomonic lesions for CSF, some characteristic lesions can be present on necropsy of an affected animal (see References: Giles 1998; Kleiboeker 2002; OIE: Manual of standards).

Necropsy Lesions of CSF*

Acute Form

—No gross lesions on necropsy if death soon after infection.
—Widespread petechia and ecchymoses, especially in the skin, lymph nodes, larynx, bladder, kidney, ileocecal junction (see Figure 69 from The Gray Book [References: Giles 1998])
—Multifocal infarction of the margin of the spleen is considered highly characteristic but not always present
—Infarction and hemorrhage in lungs
—Edematous to hemorrhagic lymph nodes common (see Figure 67 from The Gray Book [References: Giles 1998])
—Histopathologic lesions: encephalomyelitis with perivascular cuffing most common, may see endotheial cell proliferation, focal necrosis, and microgliosis

Chronic Form

—Button ulcers in cecum and large intestine (see Figure 70 from The Gray Book [References: Giles 1998])
—Generalized depletion of lymphoid tissue
—Hemorrhagic and inflammatory lesions often absent

Persistent Form

—Central dysmyelinogenesis, cerebellar hypoplasia, microencephaly, pulmonary hypoplasia, hydrops and other malformations

Differential Diagnosis

CSF is indistinguishable clinically or pathologically from African swine fever. It is essential to send samples for laboratory examination. Conditions to consider in differential diagnosis include:

Infection with bovine viral diarrhea (BVD) virus, pestivirus
Salmonellosis (Salmonella typhimurium or Salmonella choleraesuis)
Erysipelas (Erysipelothrix rhusiopathiae)
Acute pasteurellosis (Pasteurella multocida)
Atypical porcine reproductive and respiratory syndrome (PRRS) (PRRS virus of the family Arteriviridae)
Pseudorabies (pseudorabies virus, family Herpesviridae)
Haemophilus suis infection
Leptospirosis (Leptospira pomona or Leptospira bratislava)
Coumarin poisoning
Water-deprivation sodium ion toxicosis (salt poisoning)

Sources: Edwards: Hog cholera; Giles 1998; OIE: Manual of standards (see References).

Laboratory Diagnosis

Diagnosis is based on virus isolation or detection of viral antigen, antibody, or genome (see References: Kleiboeker 2002; OIE: Manual of standards).

Agent Identification

Antigen detection by direct immunofluorescence using specfic monoclonal antibodies on tissue specimens

Characterization with virus-specific monoclonal antibodies can be done to differentiate from BVD (up to 5% of US pigs are BVD-seropositive) and Border's disease

Antigen detection by enzyme-linked immunosorbent assay (ELISA)
Virus isolation in cell culture (PK-15) tested daily with immunofluorescent antibodies
Nucleic acid detection through reverse transcriptase polyermase chain reaction (RT-PCR)

May provide epidemiologic data and strain-identification information as well

Serologic Tests

Antibody detection through neutralization peroxidase-linked assay
Antibody detection through fluorescent antibody virus neutralization
Antibody detection through ELISA
Serologic tests are the prescribed methods in the OIE Manual of Standards for Diagnostic Tests and Vaccines (see References) and are suited for large-scale monitoring and surveillance programs.

Neutralizing antibodies are detectable a minimum of 2 weeks post infection (see References: Moennig 2000).

Specimen Collection and Submission for CSF Diagnosis
*Animal Status*	*Sample Type*
Live animals	Whole blood in ethylenediaminetetraacetate (EDTA) Serum from recovered and affected animals
Necropsy specimens*	—Tonsil is most important specimen if CSF is suspected, as it is first tissue to be positive for viral antigen —Lymph nodes (pharyngeal, mesenteric, maxillary, renal) —Spleen —Kidney —Distal ileum
Should be shipped refrigerated, not frozen or fixed, to allow for isolation and immunofluorescence. Sources: Kleiboeker 2002; OIE: Technical disease cards (see References).*

Treatment

There is no specific treatment for animals with CSF.

Prevention

Following are the best methods of prevention:

Protection of CSF-free areas by control of animal movement and surveillance
Quarantine and import restrictions on feed, animal products, and livestock from non–CSF-free areas
Sterilization or prohibition of waste-food feed for pigs
Serologic surveillance program at slaughter and breeding facilities
The World Organization for Animal Health definition of CSF-free areas requires:

No CSF cases for 2 years
At least 1 year since control of an outbreak by stamping out/vaccination
At least 6 months since control of an outbreak by stamping out/no vaccination

Sources: Kleiboeker 2002; Moennig 2000; OIE: Manual of standards (see References).

Outbreak Control

Control can be by stamping out, vaccination, or a combination of the two (see References: Saatkamp 2000).

The stamping-out method is best used in outbreaks that are detected early and that involve areas with low pig density.
Vaccination programs (alone or combined with stamping out) are best used in enzootic regions or areas with high pig density.

Stamping Out

This method has several components:

Quarantine of premises
Slaughter of affected, recovered, and exposed animals
Trace-back to source of the infection and other potential exposures
Movement restriction around affected premises
Disinfection of premises and all infected materials with iononic detergents and strong iodophores
Destruction of carcasses and animal products in the area

Sources: Giles 1998; OIE: Manual of standards (see References).

Vaccination

In instances where complete slaughter is not possible, vaccination should be relied upon:

Vaccination should be accomplished around and possibly within the infected premises to control CSF spread.
One available agent is a modified live vaccine with no residual virulence for pigs. A lapinized Chinese strain, a Japanese guinea pig strain, and a French thiverval strain are available for pregnant sows and piglets more than 2 weeks old (see References: Kleiboeker 2002; OIE: Manual of standards).
Marker vaccines have been developed using recombinant DNA technology based on envelope glycoproteins produced in insect cells. The antibodies generated by such "marker vaccines" can be distinguished from antibodies in naturally infected animals (see References: Moormann 2000)

Single-dose protection against clinical signs and against horizontal and vertical transmission is conferred 2 weeks after vaccination and lasts for 6 months (95% of cases, 95% confidence interval).

Oral vaccines have been developed and tested for use in feral pig populations. Efficacy in experimental settings has been proven, but application and use in wild populations is still being developed (see References: Kaden 2001).

Further sources: Giles 1998; OIE: Manual of standards (see References).

Public Health Issues

CSF does not cause infection in humans; therefore, there are no public health issues to be considered.

References

Dewulf J, Laevens H, Koenen F, et al. Airborne transmission of classical swine fever under experimental conditions. Vet Rec 2000 Dec;147(26):735-8 [Abstract]

Edwards S. Hog cholera. In Aeillo S, ed. Merck veterinary manual. Ed 8. Whitehouse Station, NJ: Merck & Co, 1998 [Full text]

Edwards S. Survival and inactivation of classical swine fever virus. Vet Microbiol 2000 Apr 13;73:175-81 [Abstract]

Edwards S, Fukusho A Lefevre PC, et al. Classical swine fever: the global situation. Vet Microbiol 2000 Apr 13;73(2-3):103-19 [Abstract]

Giles C. Hog cholera. In: US Animal Health Association, Committee on Foreign Animal Disease. Foreign animal diseases: the gray book. Ed 6. Part IV. Richmond, VA: US Animal Health Assoc, 1998 [Full text]

Kaden V, Lange B. Oral immunization against classical swine fever: onset and duration of immunity. Vet Microbiol 2001 Oct 1;(82):301-10 [Abstract]

Kaden V, Lange E, Fischer U, et al. Oral immunisation of wild boar for classical swine fever: evaluation of the first field study in Germany. Vet Microbiol 2000 Apr 13;73(2-3):239-52 [Abstract]

Kleiboeker SB. Swine fever: classical swine fever and African swine fever. Vet Clin North Am Food Anim Pract 2002 Nov;18(3):431-51 [Abstract]

Laddomada A. Incidence and control of CSF in wild boar in Europe. Vet Microbiol 2000 Apr 13;73(2-3):121-30 [Abstract]

Moennig V. Introduction to classical swine fever: virus, disease and control policy. Vet Microbiol 2000 Apr 13;73(2-3)93-102 [Abstract]

Moormann R, Bouma A, Kramps J, et al. Development of a classical swine fever subunit marker vaccine and companion diagnostic test. Vet Microbiol 2000 Apr 13;73(2-3):209-19 [Abstract]

Murphy FA, Gibbs EP, Horzinek MC, et al. Flaviviridae. In: Veterinary virology. Ed 3. San Diego, CA: Academic Press, 1999

OIE (Office International des Epizooties/World Organization for Animal Health). Classical swine fever (hog cholera). In: Manual of standards for diagnostic tests and vaccines. Ed 4. Chap 2.1.9. Paris: OIE, 2000 [Full text]

OIE (Office International des Epizooties/World Organization for Animal Health). Classical swine fever (hog cholera). Technical disease cards database. 2002 [Web page]

OIE (Office International des Epizooties/World Organization for Animal Health). Disease information published during the past 18 months (recent outbreaks) [Web page]

Saatkamp HW, Berentsen PM, Horst HS. Economic aspects of classical swine fever outbreaks in the European Union. Vet Microbiol 2000;73(2-3):221-37 [Abstract]

Stegeman A, Elbers A, de Smit H, et al. The 1997-1998 epidemic of classical swine fever in the Netherlands. Vet Microbiol 2000 Apr 13;73(2-3):183-96 [Abstract]

Other Resources of Interest

APHIS (Animal Health and Plant Inspection Service). Impact to United States of recent outbreaks (many diseases in addition to CSF) [Web site—click on Impact Worksheets and Impact Worksheet Archive]

OIE (Office International des Epizooties/World Organization for Animal Health). Reference experts and laboratories: classical swine fever [Web page]

Pig Disease Information Centre. Classical swine fever (CSF) facts [Web page]

Vetgate (United Kingdom). Swine fever [Web site]


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