1. General
2. Symptoms
3. Diagnosis
4. Prevalence
5. Approach to infected farm
6. Prevention
7. Regulations
8. Websites and literature

---

General

Definition

It is not known to what extent and under what conditions the virus can be re-shed. The disease was first described in cattle in 1813, with the main symptom being extreme pruritus ("mad itch"). In 1849, the term pseudorabies was used in Switzerland because of its similarity to rabies. Dogs and ruminants develop paralysis of the throat muscles due to the infection, causing difficulty in swallowing. The animals salivate, hence the resemblance to rabies. Only infected pigs (including wild boar) can transmit the virus. Almost all other mammals are susceptible to infection, but do not shed the virus (end hosts).

The causative agent

Aujeszky's disease virus (ADV) is an alpha herpes virus and is 150-180 nm in size. It is closely related to BHV-1 (IBR) and EHV-1 (respiratory disease and abortion in horses) and to varicella-zoster virus (human herpesvirus type 3; chickenpox and shingles). ADV isolates are serologically indistinguishable, but can vary widely in virulence and degree of shedding. Todd (1985) proposed a classification of NIA-1, -2, -3 and -4 strains. A modified live vaccine (MLV) has been produced based on the pathogenic NIA-3 virus (Northern Ireland strain from the 1970s). The genome consists of a linear double-stranded DNA molecule surrounded by an envelope. The envelope contains both essential and non-essential glycoproteins for replication. Detection of antibodies to the gE glycoprotein or PCR detection of genes for the gE glycoprotein can be used as markers for naturally infected animals. Important virulence factors:

• The enzyme thymidine kinase (TK), which is important for viral replication in the central nervous system. 
• The gE glycoprotein plays a role in the release of virions from infected cells, fusion between infected and non-infected cells, and cell-to-cell spread of virions in the nervous system. 

Removal of gE and TK from the genome leads to a reduction in virulence and the vaccine virus is no longer potent or virulent. (Mettenleiter, van Oirschot).

Sensitive species

In addition to pigs, other susceptible species include ruminants (100% lethality with symptoms of pruritus and encephalitis), dogs, cats, rodents and foxes. These are "dead-end hosts" (EFSA, 2017) that do not shed the virus. Horses are unlikely to be susceptible. There have been a few cases in horses that always ended in death, and it has been experimentally possible to fulfil Koch's postulates after infection with a high dose of virus (Kimman et al. 1991). Humans and poultry are not susceptible.

Public health

Humans are nog susceptible to the virus.

Survival 

The virus is stable at pH 5 to 9, sensitive to disinfectants and very sensitive to desiccation and sunlight. The virus survives well in cold and humid conditions. If meat has a pH above 5 after slaughter, it may still contain the virus. In manure, the virus survives for a long time: weeks to months, especially at lower temperatures. The virus is inactivated at 60°C in 30-60 minutes, at 80°C in 3 minutes and at 100°C in 1 minute.

Table 1: period that Aujeszky virus remains infectious 

Matrix	Survival
Inside the animal
Nose swabs	Up to 12 days
Oropharyngeal swabs	Up to 25 days
Vaginal secretions	Up to 12 days
Preputial secretions	Up to 12 days
Milk	Up to 2-3 days
Rectal swabs and urine (not manure)	Up to 10 days
Environment
Hay (summer)	30 days
Hay (winter)	40 days
(Floating) manure (summer)	1 month
(Floating) manure (winter)	2 months
Soil	5-6 weeks

Disinfection

Common disinfectants are effective against Aujeszky's virus (e.g. 2% NaOH, chlorhexidine, quaternary ammonium compounds), provided the correct concentration, temperature and exposure time are observed. 

---

Symptoms

Clinical picture 

General

The incubation period is 1-8 days, but may be up to 3 weeks. Young animals have the shortest incubation period. In species other than pigs, the clinical picture may be peracute and the incubation period is 2-3 days. In the body, the virus is spread through the blood, lymph and nervous system. Pigs can be carriers and become virus shedders without showing clinical signs. 

Clinical signs

Clinical signs depend on the virulence of the virus and the age of the pig and range from subclinical to severe. High fever, lethargy, respiratory distress, salivation, vomiting and tremors are common symptoms that may be associated with the disease.

Symptoms by age group: 

• Suckling piglets: Rapid onset, severe neurological signs (tremors, ataxia, seizures, paralysis, cycling, opisthotonus, nystagmus due to encephalitis), fever, high mortality (up to 100%). 
• Weaned piglets: Slower than suckling pigs, significantly reduced feed intake, lethargy and drowsiness, (mild) fever, sneezing, coughing, nasal discharge, respiratory distress, neurological signs, high mortality (5 - 30%). 
• Fattening pigs: High fever (41°C), markedly reduced feed intake, lethargy and drowsiness are the main symptoms. Respiratory problems (coughing, sneezing, dyspnoea, nasal discharge) and mortality (up to 5%) may also occur. 
• Sows: Clinical signs include fever, reduced feed intake, lethargy and drowsiness. Abortion may occur in pregnant sows. 
• Boars: Fever, mild respiratory symptoms and sometimes infertility and primary morphological abnormalities of spermatozoa.
• Other susceptible species: Symptoms are neurological in nature. The most prominent symptom in cattle and sheep is severe pruritus, manifested by vigorous licking or rubbing, often leading to self-mutilation. Intense pruritus usually occurs near the site where the virus entered the animal. Cats on a pig farm tend to hide. In dogs, itching with vigorous rubbing may be observed. Mortality after initial pruritus is a notable occurrence in species other than pigs. In horses, in addition to high fever, severe neurological symptoms have been reported, including excessive sweating, muscle tremors, ataxia, spastic movements, blindness, manic phases, agitation or depression, unresponsiveness to stimuli, exhaustion and disorientation leading to euthanasia. 

In contrast to other end hosts, itching has not been reported in horses (van den Ingh 1990, Kimman 1991).

Morbidity/mortality

Depending on the age of the pigs, mortality ranges from less than 5% (fattening pigs) to 100% (suckling pigs). In older animals, mortality depends on the presence of co-infections.In other susceptible animals, morbidity and mortality are close to 100% and death usually occurs within a few days. In two horses experimentally infected through the nose and conjunctiva, fever was observed 7 days after infection, followed by the rapid development of the neurological symptoms described above, leading to death or euthanasia 9 and 10 days after inoculation, respectively (Kimman 1991).

Virus shedding

Infection is easily transmitted by direct contact between pigs and through the air (over several kilometres, especially in foggy and cold weather). Infection is mainly by the oro-nasal route, by airborne transmission or by ingestion of contaminated material. Infection via the reproductive system (contaminated semen) is also possible. Vertical transmission is also possible.

Indirect transmission of the virus is possible via manure, materials, visitors and livestock transport vehicles. The virus can be detected in nervous tissue, tonsils, milk (colostrum) and semen. After recovery from the disease, pigs can shed the virus for months. Pigs can become latent carriers of the virus and become active shedders during periods of stress (transport, heat, etc.) or hormonal changes (pregnancy, farrowing). The virus is then reactivated. Other infected species do not shed the virus.

Differential Diagnosis

• Suckling piglets: PRRS, hypoglycemia, ASF/CSF, EMC, PCV2
• Weaned piglets: Influenza, PRRS, stable gases, ASF/CSF, salt intoxication
• Fattening/growing pigs: Influenza, PRRS, stable gases, ASF/CSF, salt intoxication
• Sows: Influenza, Parvo, erysipelas, ASF/CSF, salt intoxication

Differentiation from DDx in other species

In distinguishing Aujeszky’s Disease (AD) from rabies in other species, carnivores do not show aggression and ruminants do not show hydrophobia. Respiratory symptoms in AD are not typical of rabies. In AD, hosts are often thirsty, whereas rabid animals show hydrophobia (fear of water).

---

Diagnosis

Pathology

Macroscopically, a full bladder is often observed in pigs later found to have AD. The virus typically causes minimal macroscopic lesions. In cases where diffusely distributed miliary necrotic foci are found in the liver, AD should be considered. Histologically, lesions (necrotic foci, small white patches) may be seen in the central nervous system, keratoconjunctivitis, serous to fibrino-necrotic rhinitis/laryngitis/tracheitis or necrotic tonsillitis. Placentitis has also been observed in aborted sows. In cattle, post-mortem examination typically reveals oedema, congestion and haemorrhage in the spinal cord, often in the region innervating the pruritic area. Microscopic lesions of cellular infiltration and neuronal degeneration may also be observed. In horses described in the literature, extensive neuronal necrosis, gliosis, mononuclear perivascular cuffing and endothelial cell proliferation have been observed, particularly in the cortex of the central nervous system, in addition to trauma resulting from severe neurological symptoms. Astrocytes frequently contained eosinophilic intranuclear inclusion bodies. In addition, PRV antigen was detected in various cells of the central nervous system by immunohistochemistry, and PRV DNA was identified in various cells of the central nervous system by in situ hybridisation.

Virus Isolation

Virus detection (PCR) allows rapid diagnosis. The virus can be detected in experimental infections:

• Serum: 1-7 days after infection (low level)
• Nasal swabs: 8-17 days after infection
• Throat swabs: 18-25 days after infection
• Milk: 2 - 3 days after infection
• Rectal swabs: up to 10 days after infection
• Ejaculate and vaginal fluid: up to 12 days after infection

For the detection of latent carriers, virus isolation (PCR) in the trigeminal ganglion, olfactory bulb and tonsils is the best option. In species other than pigs, virus isolation can also be used for diagnosis. In cattle, it is useful to sample the part of the spinal cord that innervates the pruritic area or the skin and subcutaneous tissue of the pruritic area itself.

Serology

In the Netherlands, the most common tests for the detection of antibodies are the gE-ELISA for the detection of antibodies against the field virus and the gB-ELISA or VNT (virus neutralisation test) for the detection of antibodies against the field virus and the vaccine. Antibodies can be detected 7-10 days after infection. DIVA vaccines are available to distinguish between vaccinated and infected animals. The WBVR is the designated laboratory for AD diagnostics in the Netherlands. Latent carrier animals will not show a serological response. In species other than pigs, serology is usually not useful because of the rapid course of the disease, as death occurs in almost all cases before a serological response can be measured. However, two experimentally infected horses lived long enough to develop a neutralising antibody response to PRV.

Table 2: Available methods for the diagnosis of AD

Test	Sensitivity (95%Cl)	Specificity (95% Cl)	Objective	Matrix	References
Virus isolation	NA	100%	Diagnostics at clinic	Secretions or organs	OIE, 2012
gB PCR	94.6% (92.3-96.4)	71% (64-77.3)c	Diagnostics at clinic	Secretions or organs	Zanella et al., 2012*
gE PCR	94.6% (92.3-96.4)	79.3% (79.2-84.7)c	Diagnostics at clinic	Secretions or organs	Zanella et al., 2012*
VNT	NA	NA	Mandatory for international trade. Diagnostics in latent cases	Reference method for serology	OIE, 2012
I- or C-ELISAa,b	96-99%	96-99%	Mandatory for international trade. Diagnostics in latent cases	Serum, blood, milk, meat exudate	Le Potier, 2016
gE LAT	95.76%	96.77%	Screening	Serum	Yong et al., 2005
ADV LAT	97.17%	95.16%	Screening	Serum	Yong et al., 2005

• PCR = polymerase chain reaction
• VN = virus neutralisation test
• I- or C-ELISA = indirect/competitive enzyme-linked immunosorbent assay
• LAT = latex agglutinatie test
• NA = not available.
• a In regions where pigs are vaccinated with gE-deletion vaccines, the gE-PCR, -ELISA and -LAT gE kits show differences between infected and vaccinated animals. In the Netherlands, only the gE-ELISA and gB-ELISA are used
• b formation of antibodies after 7-14 days
• c Depending on the type of PCR (gB or gE PCR)
• * only from nasal swabs in experimental studies.

---

Prevalence

The Netherlands

The Netherlands are free of Aujeszky's disease. Vaccination is not authorised (Article 10 status).

Other European countries

In 2021, antibodies against Aujeszky's disease have been detected in feral pigs in two locations in France and one location in Finland. This does not change the status of these countries. In France, an outbreak in feral pigs was detected on 6 April 2020 in central France (Auvergne-Rhône-Alpes region). Two wild boars tested positive for Aujeszky's disease antibodies. A total of 108 wild boars were kept for hunting purposes: 3 boars, 15 sows and 90 piglets. The probable source of infection was wild boars that had come into contact with the captive boars through a fence. Previous cases of Aujeszky's disease have been found in France; in December 2019, an infection was found on a farm with outdoor domestic pigs in southwest France, likely infected through contact with wild boars. The same was observed on two interconnected farms with outdoor pigs in the south of France in April 2019.

Two further outbreaks were reported in wild boar in January and February 2022, and a case of Aujeszky's disease was reported on a farm with indoor pigs in March 2022. In January 2023, Aujeszky's disease was reported to the OIE in southern France on a farm with domestic pigs.

In Europe, 19 Member States now have Aujeszky's disease free status for the whole territory and three Member States (France, Italy, Poland) have free status in several regions (EU 2021/620, Annex VI). The Aujeszky's disease free status also implies a vaccination ban. Five Member States (Italy, Lithuania, Poland, Spain and Portugal) are working on an eradication programme (at regional level).
Source: Official Journal of the European Union, 28 November 2019, pages L307/52 and 53, and EU Implementing Regulation 2021/620.

---

Approach to infected farms

Vaccination

Vaccination has been prohibited in the Netherlands since 1 January 2007.

Use of antibiotics

Other measures

If a case of Aujeszky's disease occurs in a free country/zone, the OIE recommends and the EU requires complete culling of the infected pig population. Alternatively, removal of infected animals with serological control by ELISA after 30 days. Serological screening of the immediate environment is also required.

An isolated case and if the prevalence between farms remains <1% should not affect the official disease-free status of a country. In endemically infected countries with an eradication programme, vaccination is carried out with a gE deletion vaccine. Serologically positive animals are then culled.

---

Prevention

Biosecurity

Prevention of introduction is only possible by purchasing Aujeszky's disease virus (ADV)-free animals. Given the airborne spread of the virus, treatment of incoming air (filtration) will also have an effect.

To prevent other species from being infected with Aujeszky's disease, contact with potentially infected pigs (including wild boar and pig tissues or carcasses) should be avoided. Raw meat from infected pigs should not be fed to carnivores.
Vaccination should be carried out with vaccines at least as effective as the gE TK-negative 783 strain dissolved in an oil-in-water adjuvant (gold standard). In countries with an Article 10 status, vaccination is not allowed.
There are no vaccines available for species other than pigs, and it has even been described that the attenuated viruses from the porcine vaccine can cause disease in some species.

Personal protective equipment for humans

Aujeszky's disease is harmless to humans. It is advisable to wear masks during farm visits in case of suspicion or outbreaks to reduce or prevent exposure to lung dust. If blood samples need to be taken, the use of hearing protection is necessary.

---

Regulations

Aujeszky's disease is listed in the Animal Health Regulation as a List C (+D+E) disease. Aujeszky's disease is a designated contagious animal disease in accordance with Annex 9 and Article 6.3 of the Ordinance on animal husbandry.

The Netherlands is free of Aujeszky's disease according to the EU implementing regulation 2021/620 (Annex VI page 23). Since 1 January 2007, vaccination is no longer allowed in the Netherlands due to the transition from Article 9 to Article 10 status (free without vaccination) (Article 3b.3 of the Animal Breeders' Ordinance).

Monitoring

Blood samples must be taken every 4 months using the gB-ELISA test. The number of samples required is given below.

B, D and F holdings (source: RVO website)

• 31 or more pigs: 3 samples per trimester
• 30 or less pigs: no testing required for Aujeszky's disease

A, C and E holdings

• 31 or more pigs: 12 samples per month
• 11 to 30 pigs: 9 samples per month
• 7 to 10 pigs: 7 samples per month
• 1 to 6 pigs: all pigs to be tested monthly

For A-farms it is also required that if they import pigs that have to be quarantined and no gB antibodies are detected before the animals are added to the rest of the herd (source: Staatsblad 2021, 169 | Overheid.nl > Officiële bekendmakingen (officialbekendmakingen.nl) art 2.27h).

On the basis of the Animal Health Decree, rules on control (transport, entry and exit, insemination, destruction, etc.) apply. Suspicions must be reported to the NVWA official. In addition, both pig farmers and veterinarians are obliged to report certain diseases. Under the reporting obligation, the farmer or his veterinarian is obliged to report a case of Aujeszky's disease to the central reporting office for animal disease control at the Ministry of Agriculture, Nature and Food Quality.

---

Websites and Literature

• OIE: www.oie.int
• World Organization Animal Health: www.woah.int
• EU: www.ec.europa.eu
• Center for Food Security and Public Health: www.cfsph.iastate.edu
• Ruminants
  www.cfsph.iastate.edu/Factsheets/pdfs/aujeszkys_disease
  www.cfsph.iastate.edu/Aujeszky’s Disease
• Horses: Virus infections of equines, 1996, edited by M.J. Studdert
• Sehl J and Teifke JP Comparative pathology of pseudorabies in different naturally and experimentally infected species – a review. Pathogens 2020; 9: 633
• Van den Ingh TS, Binkhorst GJ, Kimman TG et al. Aujeszky’s disease in a horse. Zentralbl Veterinarmed B 1990; 37: 532-538.
• Kimman TG, Binkhorst GJ, van den Ingh TS et al. Aujeszky’s disease in horses fulfils Koch’s postulates. Vet Rec 1991;128: 103-106.