Aujeszky's disease

Pictures

Picture	Title	Caption	Copyright
Title Piglet with rhinitis and conjunctivitis Caption These lesions in a young piglet with such severity are characteristic of Aujesky's disease virus infection. Copyright Janet Owen	Piglet with rhinitis and conjunctivitis	These lesions in a young piglet with such severity are characteristic of Aujesky's disease virus infection.	Janet Owen
Title Aujeszky's disease Caption Only this disease is associated with this degree of necrosis in the nose. Copyright Janet Owen	Aujeszky's disease	Only this disease is associated with this degree of necrosis in the nose.	Janet Owen
Title Aujeszky's disease Caption Severe bronchiolar necrosis with inclusions in the remaining bronchiolar cells is a feature of Aujeszky's disease. Copyright Stan H. Done	Aujeszky's disease	Severe bronchiolar necrosis with inclusions in the remaining bronchiolar cells is a feature of Aujeszky's disease.	Stan H. Done

Identity

Preferred Scientific Name

• Aujeszky's disease

International Common Names

• English: Aujeszky disease; infectious bulbar paralysis; mad itch; paralysis, infectious bulbar; pseudorabies; pseudorabies, aujeszky's disease; pseudorabies, suid herpesvirus-1, aujeszky's disease in swine

English acronym

• AD
• PR

Overview

Aujeszky’s disease (also known as pseudorabies) is a viral disease of pigs that is endemic in most parts of the world. It is caused by Suid herpesvirus 1 (also known as Aujeszky's disease virus and pseudorabies virus), a member of the subfamily Alphaherpesvirinae and the family Herpesviridae. The virus infects the central nervous system and other organs, such as the respiratory tract, of a variety of mammals, but only pigs are able to survive a productive infection and are thus considered the natural host.

According to the World Organisation for Animal Health (OIE) Aujeszky’s disease is listed as a notifiable disease. Please see the AHPC library for further information on this disease from OIE, including the International Animal Health Code and the Manual of Standards for Diagnostic Tests and Vaccines. Also see the website: www.oie.int.

The information in this datasheet is partly taken from:
Mettenleiter TC, Ehlers B, Müller T, Yoon K-J, Teifke JP, 2012. Herpesviruses. In: Zimmerman JJ, Karriker LA, Ramirez A, Schwartz KJ, Stevenson GW, eds. Diseases of Swine, 10th edition. Chichester, UK: John Wiley & Sons, 412-446.

Hosts/Species Affected

Both domestic pigs and wild swine are the only natural reservoir hosts of Aujeszky’s disease virus (ADV) and able to survive a productive infection. It remains unexplained whether other members of the artiodactyl suborder Suina are susceptible to ADV. The virus can infect a wide range of other mammals, in particular animals in close contact with pigs such as sheep, cattle, goats cats and dogs. In those species the disease caused is nearly always fatal, but the virus is rarely shed and transmitted from such animals. Reports of horses contracting ADV are very rare (Mettenleiter et al., 2012).

Distribution

Aujeszky’s disease (AD) is spread in domestic or wild swine and has an almost worldwide distribution, particularly in regions with high population densities of domestic swine. There are only a few regions where the disease has never been endemic in the domestic pig population, such as Norway, Australia, and most of the Southeast Asian islands. In recent years, strict implementation of national eradication programmes has resulted in virtual disappearance of the infection from domestic pigs in several parts of the world, e.g. Europe, North America and New Zealand.

The current dimension of the regional occurrence of AD in eastern and southeastern Europe, Latin America, Africa, and Asia is difficult to assess as information from those countries is often fragmentary, incomplete or even lacking. Recently, severe clinical outbreaks with high morbidity and lethality have been reported from China.

The distribution in the summary table is mainly based on information available from OIE or the European Union (EU). For current information on disease incidence, see OIE's WAHID database.

Distribution Table

The distribution in this summary table is based on all the information available. When several references are cited, they may give conflicting information on the status. Further details may be available for individual references in the Distribution Table Details section which can be selected by going to Generate Report.

Pathology

The following is partly taken from:
Mettenleiter TC, Ehlers B, Müller T, Yoon K-J, Teifke JP, 2012. Herpesviruses. In: Zimmerman JJ, Karriker LA, Ramirez A, Schwartz KJ, Stevenson GW, eds. Diseases of Swine, 10th edition. Chichester, UK: John Wiley & Sons, 412-446.

There are no AD-specific gross lesions in pigs, and changes are often absent or minimal. Gross lesions may occur in non-neural tissues, including lymphoid organs, and respiratory, digestive, and reproductive tracts. Particularly in young suckling pigs lacking passive immunity, multifocal necrosis is observed in these tissues, as well as in the liver, spleen, and adrenal glands. Typically, exudative keratoconjunctivitis, serous to fibrinonecrotic rhinitis, laryngitis, tracheitis, and necrotizing tonsillitis may be present. The CNS is free of gross lesions except for leptomeningeal hyperemia. Gross lesions in the upper respiratory tract are most common, including rhinitis with patchy epithelial necrosis and necrotizing laryngotracheitis, often in conjunction with multifocal tonsillar necrosis. Lesions in the lower respiratory tract may be pulmonary edema and scattered small foci of necrosis, hemorrhage, or bronchointerstitial pneumonia. However, the pulmonary lesions are less consistent and are composed of areas of reddening and consolidation scattered throughout the lungs, especially focused on the cranioventral lung lobes. Multiple, small foci (1-3 mm in diameter) of acute hemorrhagic necrosis characteristic of alphaherpesviral infections may be seen in the liver, spleen, lungs, intestines, adrenals, and placenta.

In sows, necrotizing placentitis and endometritis with thickened, edematous wall of the uterus are observed after abortion. Aborted fetuses may be macerated or, occasionally, mummified (stillbirth, mummified fetuses, embryonic death, infertility [SMEDI]). In fetuses or neonatal pigs, necrotic foci in the liver and spleen, lungs, and tonsils are common. ADV infection may also cause edema of the scrotal region.

Diagnosis

The following is partly taken from:
Mettenleiter TC, Ehlers B, Müller T, Yoon K-J, Teifke JP, 2012. Herpesviruses. In: Zimmerman JJ, Karriker LA, Ramirez A, Schwartz KJ, Stevenson GW, eds. Diseases of Swine, 10th edition. Chichester, UK: John Wiley & Sons, 412-446.

Clinical diagnosis

The presence and severity of clinical signs, as well as morbidity and mortality, depend on the age and immunological status of the pig. Furthermore, the route of infection and the virulence of the Aujeszky's disease virus (ADV) strain are important factors. In general, clinical signs manifest as neurological signs in young (sucking and weaned) and respiratory signs in older pigs. The disease is therefore more easily diagnosed in herds with both weaning or sucking and older pigs. Sow aborting is often one of the earlier signs of a herd being affected.

ADV infections in fully susceptible swine result in high morbidity and mortality, especially in juvenile animals in which meningoencephalitis and viremia-associated signs predominate. In neonatal pigs less than 7 days of age, the disease may be characterized by sudden death with few, if any, clinical signs. In 2- to 3-week-old piglets, severe signs of central nervous system (CNS) involvement, for example, trembling, incoordination, nystagmus, oposthotonos, epileptiform-like seizures, convulsion, tremor, ataxia, and paralysis, are seen with mortality up to 100%. Suckling pigs with neurological signs usually die within 24-36 h of onset of disease.

Older animals (3-6 weeks of age) may show neurological signs, but usually develop age-dependent resistance. Mortality may decrease to 50% by the fourth week of age and to less than 5% in 5-month-old pigs and even lower as the age of the infected pigs increases. Clinical signs can be present for 6-10 days. Animals may recover within a few days, but lose weight over the course of the disease. In finishing and fattening pigs, because of the population density, clinical signs can amplify and animals often die from secondary bacterial pneumonia. Signs in gilts and sows depend on the phase of gestation and include embryonic death, resorption of fetuses, mummified fetuses, abortion, or stillbirth, in addition to respiratory signs and fever. Pigs surviving a ADV infection become latently infected.

In the case of coinfections with other swine viruses, for example, porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus type 2 (PCV2), and swine influenza virus (SIV), a severe and often fatal proliferative and necrotizing pneumonia (PNP) may develop in weaning and postweaning pigs.

Laboratory diagnosis

Rapid detection of viral infection is essential for the effective control of AD. Clinical observations are only sufficient to lead to a suspicion of AD because the infection produces no pathognomonic clinical signs or gross post-mortem lesions in swine. Therefore, laboratory confirmation is required.

Viral antigen can be detected using immunoperoxidase and/or immunofluorescence staining with polyclonal or mAbs on impression smears and cryosections of tissues, for example, brain, lungs, and tonsils. Diagnosis is confirmed by virus isolation in conventional cell cultures requiring about 2-5 days. In the absence of any obvious CPE, blind passages should be performed. ADV can be isolated from secretions and excretions and from tissues, for example, brain, tonsils, lungs, and spleen, of infected animals. In latently infected pigs, the trigeminal ganglion and tonsils are the most consistent sites for virus isolation. As there is no CPE characteristic of ADV, and CPE may vary with the prevailing ADV strain and the cell line used, virus identity is confirmed by immunofluorescence, immunoperoxidase, or neutralization assays using specific antisera or mAbs.

Viral DNA can be detected by direct filter hybridization, DNA hybridization dotblot assay, ADV-specific PCR, nested and real-time quantitative PCR (qPCR) assays with the latter ones being the method of choice for detection of ADV in secretions or organ samples under routine conditions. Several conventional PCRs targeting genes encoding gB, gC, gD, or gE have been established, but there is as yet no internationally agreed upon standard.

According to OIE for routine testing, the virus neutralization (VN) test and ELISAs are standard reference serological test to detect ADV specific antibodies. Robust and sensitive indirect or competitive ELISAs detect antibodies against the complete ADV or against distinct viral antigens. The latex agglutination test (LAT) and immunoblotting are alternatives. VN and LAT are highly reliable but cannot differentiate between antibodies resulting from natural infection or vaccination. The development of ELISAs able to detect serum antibodies against gE (or gC or gG) allowed for the differentiation of infection from vaccination and led to the “marker” or differentiating infected from vaccinated animal (DIVA) concept. These ELISAs became a key part of AD eradication programs.

For more information on diagnostic tests for international trade purposes see the relevant chapter in the World Organisation for Animals Health’s (OIE) ‘Manual of Diagnostic Tests and Vaccines for Terrestrial Animals’ (www.oie.int).

List of Symptoms/Signs

Disease Course

The following is partly taken from:
Mettenleiter TC, Ehlers B, Müller T, Yoon K-J, Teifke JP, 2012. Herpesviruses. In: Zimmerman JJ, Karriker LA, Ramirez A, Schwartz KJ, Stevenson GW, eds. Diseases of Swine, 10th edition. Chichester, UK: John Wiley & Sons, 412-446.

After oronasal infection of the natural host and primary replication in epithelial cells of the upper respiratory tract, the virus gains access to neurons innervating the facial and oropharyngeal area, in particular, the olfactory, trigeminal, and glossopharyngeal nerves. By fast axonal retrograde transport, it spreads centripetally and reaches the cell bodies of infected neurons, where either lytic or latent infection ensues. ADV is also able to cross synapses to infect neurons of higher order. Viremia disseminates it to many organs, where the virus replicates in epithelia, vascular endothelium, lymphocytes, and macrophages. Replication of ADV in the CNS is characterized by nonsuppurative meningoencephalitis causing severe central nervous disorders. Trigeminal ganglia, sacral ganglia, and tonsils are considered prime sites of latency in pigs. The demonstration of the sacral ganglia as the most common sites of ADV latency in feral swine supported the hypothesis that these viruses are primarily transmitted venereally and not by the respiratory route, as is common in domestic swine, in which the trigeminal ganglia are the predominant sites of virus latency. In nonporcine species, ADV is rather strictly neuroinvasive.

Epidemiology

Aujeszky’s disease virus (ADV) is shed via secretions (lachrymal fluid, preputial and vaginal secretions) and excretions (saliva, nasal discharge, urine, faeces). Hence, the disease can be transmitted by direct and indirect contact with infected animals. Oro-nasal, vertical (transplacental), and venereal (sexual encounters) transmission are a result of direct contact. Within non-domestic swine ADV appears to be preferentially transmitted by the venereal route (Mettenleiter et al., 2012).

Indirect contact due to exposure with ADV aerosol created by exhalation of infected animals and contaminated urine, faeces, water run-off, fomites, slurry and feed/carcasses as well as artificial insemination (virus contaminated semen). Transmission between herds is mainly through the introduction of infected animals into an uninfected herd. The virus can rapidly spread through a naive herd. The manifestation of disease in a pig herd is affected by the herd's demographics, stage of farrowing, immunological status and husbandry conditions.

Depending on age and virulence of the prevailing ADV strain, incubation period in pigs can range between 1-8 days up to 3 weeks. There is a short incubation period of about 2-4 days in suckling pigs, whereas clinical signs in grower-finisher pigs occur after 3-6 days. The capacity of ADV to persist for the lifetime in their host in a latent state is characteristic with trigeminal ganglia, sacral ganglia and tonsils as the most common sites of latency. Hence, pigs may remain permanently infected without exhibiting clinical signs. However, clinical signs may be caused in latently infected animals as a result of immunosuppression, e.g. after episodes of stress, such as transport, and in over-crowded housing.

The virus is highly environmentally resistant depending on pH, humidity, and temperature (for details see Mettenleiter et al., 2012). Bedding and water can remain infected for several days after contamination with the virus. It can remain viable for up to seven hours as an aerosol in humidities over 55% and can travel up to 2 km (CFSPH, 2006).

ADV infections are widespread in populations of non-domestic swine across the world, in particular Europe and North America (for review see Müller et al., 2011).

Impact: Economic

In a cost-benefit study of the USA Aujeszky virus eradication programme, productivity and economic impacts were calculated for infected and non infected herds, including preweaning, nursing, grower and finisher pig mortality, breeding-herd mortality, feed conversion, layout and veterinary and biologic/pharmaceutical expenses. The study calculated that there was a US$ 6.00/hundredweight reduction of profitability due to Aujeszky virus herd infection (Anderson et al., 1989; Miller et al., 1996; cited in Kluge et al., 1999).

Zoonoses and Food Safety

Humans and apes are considered resistant against natural ADV infection (Jentzsch and Apostoloff, 1970). Although isolated reports describe putative infections of humans with ADV, this has never been substantiated by virus isolation (Kluge et al., 1999).

Prevention and Control

Measures to prevent infection of a herd in an area where the disease is endemic include isolation of domestic pigs from ADV infected feral pigs or wild boar, prevention of entry onto the premises of contaminated fomites, and potentially infected people and animals.

Modern eradication programmes involve measures such as use of vaccines, removal of latently infected animals, and quarantine. The use of blanket vaccination with inactivated (particularly in breeding animals) and modified live virus vaccines (in finishers) to control of disease, but not infection is no longer practised.

Today, a combination of modern genetically modified live deletion (gE, gC or gG) marker vaccines against AD and differential ELISAs to discriminate between vaccinated, ADV-uninfected animals from wild-type ADV-infected animals (DIVA strategy - test and removal) is the method of choice for eliminating ADV from domestic pigs

Depopulation of infected herds can be applied in the final phase of an eradication programme to facilitate achieving an AD-free status.

For measures to be taken to determine the AD status of a country or zone, and recommendations for importation of pigs for breeding, rearing and slaughter from countries and zones with different AD statuses see chapter Chapter 8.2., Infection with Aujeszky's disease virus of the OIE Terrestrial Animal Health Code (http://www.oie.int/fileadmin/Home/eng/Health_standards/tahc/2010/en_chapitre_aujeszky.htm).

References

Anderson et al., 1989. The control and eradication of Aujeszky's disease in Denmark: epidemiological aspects. In: Vaccination and control of Aujeszky's disease. Ed. JT van Oirschot. Brussels and Luxembourg: ECSC, EEC, EAEC; Boston: Kluwer Academic Publishers, pp. 175-183.

CFSPH, 2006. Aujeszky's disease. Iowa, USA: Center for Food Security and Public Health, Iowa State University, 4 pp. http://www.cfsph.iastate.edu

Jentzsch KD; Apostoloff E, 1970. Susceptibility of man to Aujeszky's disease virus. 4. Serological findings in occupationally exposed persons. Zeitschrift fur die gesamte Hygiene und ihre Grenzgebiete, 16:692-696.

Kluge JP; Beran GW; Hill HT; Platt KB, 1999. Pseudorabies (Aujeszky's disease). In: BE Straw, S D'Allaire, WL Mengeling, DJ Taylor (Eds.), Diseases of swine. Eighth Edition. Ames, USA: Iowa State University Press, pp. 233-246.

Mettenleiter TC; Ehlers B; Müller T; Yoon K-J; Teifke JP, 2012. Herpesviruses. In: Diseases of Swine, 10th edition [ed. by Zimmerman, J. J. \Karriker, L. A. \Ramirez, A. \Schwartz, K. J. \Stevenson, G. W.]. Chichester, UK: John Wiley & Sons, 412-446.

Miller GY; Tsai JS; Forster DL, 1996. Benefit-cost analysis of the national pseudorabies virus eradication program. Journal of the American Veterinary Medical Association, 208(2):208-213; 23 ref.

Müller T; Hahn EC; Tottewitz F; Kramer M; Klupp BG; Mettenleiter TC; Freuling C, 2011. Pseudorabies virus in wild swine: a global perspective. Archives of Virology, 156(10):1691-1705. http://www.springerlink.com/content/g8t6424781l33150/

OIE Handistatus, 2005. World Animal Health Publication and Handistatus II (data set for 2004). Paris, France: Office International des Epizooties.

OIE, 2009. World Animal Health Information Database - Version: 1.4. World Animal Health Information Database. Paris, France: World Organisation for Animal Health. http://www.oie.int

Links to Websites

Distribution Maps