Pseudorabies is an acute, frequently fatal disease with a worldwide distribution that affects swine primarily and other domestic and wild animals incidentally. The pseudorabies virus has emerged as a significant pathogen in the USA since the 1960s, probably because of the increase in confinement swine housing or perhaps because of the emergence of more virulent strains. Clinical signs in nonporcine animals are similar to those of rabies, hence the name “mad itch” (pigs do not display this sign). Pseudorabies is a reportable disease and has been successfully eradicated from the vast majority of the USA.

1. AUJESKY’S DISEASE
Pseudo Rabies, Mad itch
Dr. Ranjini Manuel

2. HISTORY
Pseudorabies (PR) was first described in 1813 in cattle suffering with extreme pruritus. Based on the
clinical signs, the disease was called “mad itch” (Baskerville et al. 1973).
The term “pseudorabies” was first used in Switzerland in 1849 because the clinical signs in cattle were
considered similar to those of rabies.

3. HISTORY
 Aladar Aujeszky, the Hungarian for whom the disease is named,
determined that the etiologic agent was filterable, i.e., not bacterial,
and also conducted research on the disease in the dog and cat.
 The agent was first recovered from swine in 1909 by Weiss and from
sheep in (1910 by Schmiedhoffer)
 In 1934, Sabin and Wright identified the virus as a herpesvirus, later
called swine herpes virus 1 (SHV-1) or pseudorabies virus (PRV).
PRV virion attached
to a bovine kidney
cell (MDBK) in culture

4. ETIOLOGY
Pseudorabies is caused by porcine herpesvirus-
1 , Aujeszky’s disease virus, or pseudorabies
virus (PRV)
Genus --Varicellovirus
Family- Herpesviridae
subfamily - Alphaherpesvirinae.
Four major genome types
Type 1 -United States and Europe
Type 2 -central Europe
Type 3 -Eastern Europe
Type 4 -only in Asia.

5. Methods of Transmission
 Larger doses of virus are needed for oral infection than nasal infection.
 In feral pig and wild boar populations- venereal transmission is more
 Virus shedding starts 1 to 2 days after infection, reaches a peak at 2 to 5 days, and may last up to
17 days.
 Virus can be transmitted for up to 12 days in semen
 It can be transmitted transplacentally, especially in the last third of gestation.
 It can also be passed through the colostrum.
 In milk excretion of virus takes place for 2 to 3 days

6. Methods of Transmission
 Pigs and rodents -primary host for the virus.
 The virus is present in the nasal discharge and in the mouth of affected pigs from the first day
of illness
 This suggests that short-length aerosol transmission is a common occurrence within buildings
or units but long distance transmission is still doubted.
 After infection and recovery pigs may be regarded as carriers

7. Methods of Transmission
Within Herds
 Direct oral–nasal contact between infected and susceptible pigs
 Aerosols from projection of discharges during sneezing
 Contaminated drinking water and feed.

8. Methods of Transmission
Within an Area
 Transmission within an area is a major problem and not well understood.
 Some evidence indicates that area spread may be associated with markets and the
frequency of delivery of pigs to market per year.
 Infection is spread by airborne transmission. Sneezing probably generates the airborne
virus.
 An epidemic in Denmark in 1987 to 1988, associated with foreign strains of the virus,
suggests that airborne transmission occurred across the German–Danish border, especially as
a southerly wind was blowing during the period of transmission.

9. LATENCY
 Pigs that recover from infection are latent carriers of the virus for life.
 Reactivation, followed by shedding and spreading the virus, may occur following stress such as
transport or farrowing, or by the administration of corticosteroids
 Serologic testing of latent carriers detects the antibody response to the whole virus or to a
PRV virus glycoprotein.
 The virus can be isolated from tissue fragments of pigs clinically recovered from disease for up
to 13 months
 Latent infection can also occur in vaccinated pigs.

10. PATHOGENESIS
 The portal of entry is through abraded skin, oral mucosa, or via the intact nasal mucosa
 The virus is pantropic and affects tissues derived from all embryonic layers
 Spread to the brain occurs by way of the olfactory, glossopharyngeal, or trigeminal nerves, i.e., via
the autonomic nerves.
 It can pass across synapses and infect higher level neurons.
 Virus disappears from the brain by the eighth day, coinciding with the appearance of neutralizing
antibody in the blood

11. PATHOGENESIS
 When the virus gains entry through a skin abrasion, it quickly invades the local peripheral nerves,
passing along them centripetally and causing damage to nerve cells.
 It is this form of progression that causes local pruritus in the early stages of the disease, and
encephalomyelitis at a later stage when the virus has invaded the CNS.

12. CLINICAL FINDINGS
 The major signs are referable to infection of the respiratory, nervous, and reproductive systems.
 There is considerable variation in the clinical manifestation, depending on the virulence and tropism
of the infecting strain.
 Nervous system disease is the major manifestation, but with some strains, respiratory disease may be
the initial and prime presenting feature
 There is also strain variation in the pattern of age susceptibility.

13. CLINICAL FINDINGS
 Young pigs a few days to a month old are most susceptible
 Very young sucklings develop an indistinct syndrome, but prominent nervous signs occur in
older piglets
 A febrile reaction, with temperatures up to 41.5°C (107°F), occurs before the onset of nervous
signs
 Incoordination of the hind limbs causing sideways progression is followed by recumbency, fine
and coarse muscle tremors, and paddling movements.

14. CLINICAL FINDINGS
 Lateral deviation of the head, frothing at the mouth, nystagmus, slight ocular discharge, and
convulsive episodes appear in a few animals
 A snoring respiration with marked abdominal movement occurs in many, and vomiting and diarrhea
in some affected pigs
 Deaths occur about 12 hours after the first signs appear
 In California, a consistent sign has been blindness caused by extensive retinal degeneration

15. CLINICAL FINDINGS
 In growing and adult pigs, the disease is much less severe but there is considerable variation
depending on the virulence of the infecting strain
 In growing pigs, mortality falls with increasing age and is generally less than 5% in pigs at 4 to 6
months of age
 With some strains, fever is a prominent sign, whereas depression, vomiting, and sometimes
marked respiratory signs, including sneezing, nasal discharge, coughing, and severe dyspnea are
common
 Trembling, incoordination, and paralysis and convulsions follow, and precede death

16. CLINICAL FINDINGS
 In adults, fever may not be present, and the infection may cause only a mild syndrome of anorexia,
dullness, agalactia, and constipation.
 Infection in early pregnancy may result in embryonic death, or abortion, and early return to estrus.
 Abundant vaginal discharge may be seen.
 Infection in late pregnancy may result in abortion, or in the subsequent birth of mummified
fetuses, which may involve all or only part of the litter.
 Abortion may result from the effects of fever or from viral infection of the fetus.

17. DIAGNOSIS
Serology
 serum neutralization (SN) and ELISA tests.
Detection of Virus
 In infected pigs the virus is usually present in nasal secretions for up to 10 days
 A common method for the diagnosis of PRV in sows is to take swabs from the nasal mucosa
and vagina
 New PCR techniques have been used and they can differentiate between true and false
serologic positives

18. Virus may be detected by direct fluorescent antibody examination or by growth in tissue
culture.
 The immune peroxidase test can be used to study the distribution of the virus in different
tissues.
 Latent virus can be detected using a DNA hybridization dot blot assay

19. CULTIVATION
porcine cell lines PK-15 or SK-6 are generally used in cultivation (Toma et al. 2004).
PRV induces a cytopathic effect (CPE) that usually appears in 24–72 hours, but cell cultures may
be incubated for 5–6days (Figure 25.4).
The monolayer develops accumulations of birefringent cells, followed by complete detachment
of the cell sheet.
 Syncytia also develop, the appearance of which is variable.

20. NECROPSY FINDINGS
 Gross lesions in the upper respiratory tract are the most obvious and these include
necrotic rhinitis, conjunctivitis, laryngitis, and tracheitis. The lungs show congestion,
edema, and some hemorrhages.
 Hemorrhages may be present under the endocardium and excess fluid is often
present in the pericardial sac.
 Slight splenomegaly, meningitis, and excess pericardial fluid are observed, and
there may be small necrotic foci in the spleen and liver.

21. In sows, there may be a necrotizing placentitis and endometritis.
 Foci of hepatic, splenic, or pulmonary necrosis may be seen in aborted fetuses.
 Pruritus -- Considerable damage to local areas of skin and extensive subcutaneous oedema.

22. NECROPSY FINDINGS
 Histologically -severe and extensive neuronal damage in the spinal cord, paravertebral ganglia,
and brain.
Intranuclear inclusion bodies occur infrequently in the degenerating neurons and astroglial
cells, particularly in cerebral cortex in the pig.
 Necrotizing lesions with inclusion-body formation in the upper respiratory tract and lungs is
strongly suggestive of porcine pseudorabies.

23. DIFFERENTIAL DIAGNOSIS
 Teschen disease occurs in similar forms in certain areas; the diagnosis is dependent on
serology and pathology.
 Rabies is rare in pigs and is usually accompanied by pruritus at the site of the bite.
 Streptococcal meningitis is restricted to sucking pigs of 2–6 weeks of age, the lesions are
usually obvious at necropsy, and the causative organism is readily cultured from the meninges.
 The response to treatment with penicillin is good and is of value as a diagnostic test.

24. DIFFERENTIAL DIAGNOSIS
 Encephalopathy associated with hog cholera, African swine fever, salmonellosis, Glasser’s
disease, Escherichia coli septicaemia and erysipelas are considerations, and are usually obvious
at necropsy
 Bowel edema causes typical edema of the head and eyelids in weaner pigs as well as a rapid
death.
 Salt poisoning causes typical intermittent nervous signs, with a typical history of water
deprivation.
 Respiratory form of pseudorabies should be considered in any outbreak of respiratory disease
that is poorly responsive to usually effective therapeutic measures.

25. DIFFERENTIAL DIAGNOSIS
 Reproductive inefficiency associated with enterovirus (SMEDI) and requires laboratory
differentiation by virus isolation and serologic testing.
The furious form of rabies and acute lead poisoning cause signs of mania, but pruritus does not
occur.

26. TREATMENT & CONTROL
 There is no treatment.
The methods of control or eradication include
 Depopulation and repopulation
 Test and removal
 Vaccination.

27. Susceptibility to Disinfectants
Effective disinfectants include orthophenolphenate
compounds, 5% phenol, 2% Na hydroxide, trisodium
phosphate iodine disinfectants, and chlorhexidine solutions
(Beran 1991). When disinfecting on a large scale, cheaper disinfectants
are adopted: calcium chloride milk, calcium
chloride preparations that dissolve in water, crude chloramines, and agents containing at
least 1% active
formaldehyde. For disinfecting slurry, lime (20 kg
Ca(OH)2 per cubic meter is recommended

28. The virus survives on hay for 30 days in summer and
46 days in winter. It is stable between pH 4 to 12. Stored
in 50% glycerol, it survives for 154 days with little loss of
virus titer at refrigerator temperatures. At low temperatures,
virus in tissue remains viable for many years.
Lyophilized virus survives at least 2 years. Ultraviolet
light and drying on glass inactivates the virus (Davies
and Beran 1981; Wittmann 1985).

29. PRV is relatively resistant to heat. It is inactivated at
60°C in 30–60 min, at 70°C in 10–15 min, at 80°C in 3
minutes and at 100°C within 1 minutes (Kunev 1978).
The virus is very stable at normal temperatures the virus is relatively unstable at 18°C
to 25°C, where inactivation occurs within 12 weeks
By combining low or high pH levels
with elevated temperatures, the inactivation time is significantly
reduced (Davies and Beran 1981).

30. CONTROL
The selection of a strategy for the control or elimination of the disease depends on the
following:
(1) source of the herd infection
(2) method of transmission of the virus
(3) survival of the virus in the environment
(4) sensitivity and specificity of the diagnostic test
(5) risk factors in the herd

31. CONTROL
Depopulation and Repopulation
 When the prevalence of infection in the herd is over 50%, eradication can be
achieved by depopulation and repopulation with virus free breeding stock.
 The entire herd is depopulated over a period of months as the animals reach
market weight.
 After removal of the animals the entire premises are cleaned and disinfected.
 Repopulation should be delayed at least 30 days after the final disinfection
 Swine should be taken from a pseudorabies-free qualified herd
They should be isolated and tested 30 days after introduction.

32. CONTROL
Test and Removal
 The test and removal program is recommended when the prevalence of infection in the herd is
below 50%.
 This method requires testing of the entire breeding herd and immediate removal of all
seropositive animals;
 30 days after removal of seropositive animals, the herd is retested, and if necessary at 30-day
intervals, until the entire herd tests are negative.
 Seropositive animals are identified and culled.
 The test and removal method is superior to the vaccination system as a method of control.

33. CONTROL
Offspring Segregation
 The objective of this strategy is to raise a PRV-negative breeding herd to replace the infected
herd.
 Gilts are vaccinated at first breeding, and both sows and gilts are vaccinated 2 to 4 weeks
before farrowing to provide a high level of colostral immunity to their piglets.
 Offspring are removed at weaning and raised apart from the infected herd.
 At 4 months of age, and then again before breeding, the segregated replacements are tested
for antibody

34. CONTROL
 As the gilts reach reproductive maturity, the old sow herd is replaced.
 Segregation between the infected sow herd and the clean gilt herd is maintained until all
positive sows have been removed and the facilities disinfected.
 Groups of seronegative pigs are identified and combined into larger groups to establish a new
herd.
 The original herd is gradually depopulated and the premises cleaned and disinfected.
 The new herd is then monitored on a regular basis.

35. CONTROL
Vaccines and Vaccination
 Vaccination is used to reduce clinical disease when outbreaks occur or when the disease is
endemic in the herd.
 An effective immunity develops after natural infection or vaccination, and piglets from
immune sows are protected from clinical disease during the nursing period by colostral
immunity.
 However, vaccination reduces viral shedding after natural infection.
 On farms in which the disease is endemic or outbreaks have occurred, vaccination of the sows,
and management procedures to reduce the spread of infection, have markedly reduced pre-
weaning mortality and reproductive failures.

36. CONTROL
 Conventional modified live virus and inactivated virus vaccines have been available.
 Both vaccines will reduce the incidence rate and severity of clinical disease in an infected herd.
 They also reduce the field virus shedding and latency in the trigeminal ganglion after exposure
to field virus.
The vaccine efficiency is, however, markedly influenced by the modified live virus vaccine strain
and the route of administration.
 The vaccine genotype plays a very important role in the effectiveness of the vaccine program.

37. CONTROL
Pregnant Sows
 Vaccination of pregnant sows induces SN antibodies, which are transferred to the new-born
piglets and provide protection against infection.
 Vaccination during pregnancy produces more protection against PRV for piglets than sow
vaccination before mating.
 A better protection was observed in sows vaccinated with an attenuated virus than in sows
vaccinated with inactivated virus.
 Piglets rely on colostral and milk antibodies for protection, and the vaccination of piglets born
from vaccinated sows does not produce a significant serologic response until the piglets are
about 12 weeks of age

38. CONTROL
 Maternally derived antibodies may disturb or even block the development of active humoral
responses.
 Earlier vaccination of piglets from infected or vaccinated sows is ineffective because high levels
of maternal antibodies interfere with a serologic response stimulated by the vaccine.
 Maternal immunity interferes with the development of active immunity from vaccination until
at least 15 weeks of age, even when the colostral titers are low.
 Thus in a situation in which the majority of sows have been infected or immune vaccinated,
vaccination of weaned pigs may not yield desirable results.

39. CONTROL
Marker or Subunit Vaccines
 Introduction of genetically engineered live vaccine strains used to make marker or subunit
vaccines.
 Vaccination with modified live gene-deleted vaccines is now an integral part of pseudorabies
eradication programs worldwide.
 These vaccines, in conjunction with a companion diagnostic test, can distinguish between
naturally infected and vaccinated animals.

40. THANK YOU