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Pseudorabies: Introduction
(Aujeszky's disease, Mad itch)
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 are similar to those of rabies, hence the name "mad itch." Some researchers believe
that clinical problems have become more apparent secondary to the eradication of hog cholera. Pseudorabies is a reportable
disease.
Etiology:
Pseudorabies virus is a DNA herpesvirus. Although the pig is the only natural host, the
virus can infect cattle, sheep, cats, dogs, and goats as well as such feral animals as raccoons, opossums, skunks, and rodents.
Experimental studies in nonhuman primates indicate that rhesus monkeys and marmosets are susceptible but chimpanzees are not.
Reports of human infection are limited and are based on seroconversion rather than virus isolation. Infections in horses are
rare. Only one serotype of pseudorabies virus is recognized, but strain differences have been identified by using monoclonal
antibody preparations, restriction endonuclease assays, and heat and trypsin inactivation markers.
Epidemiology:
Transmission
of the virus can occur via nose-to-nose or fecal-oral contact. Indirect transmission commonly occurs via inhalation of aerosolized
virus. Infectious virus can persist for up to 7 hr in air with a relative humidity of ≥55%. Data from England
indicate that virus may travel via aerosols for up to 2 km in certain weather conditions. Other studies have demonstrated
that the virus can survive for up to 7 hr in nonchlorinated well water; for 2 days in anaerobic lagoon effluent and in green
grass, soil, feces, and shelled corn; for 3 days in nasal washings on plastic and pelleted hog feed; and for 4 days in straw
bedding. The virus is enveloped and, therefore, is inactivated by drying, sunlight, and high temperatures (37°C). Dead-end
hosts, such as dogs, cats, or feral animals, can transmit the virus between farms, but these animals survive only 2-3 days
after infection. The role of insects as potential vectors is being investigated. Birds do not seem to play a role in transmission.
Clinical Findings and Pathogenesis:
The clinical signs depend on the age of the affected animal. Young swine
are highly susceptible, and losses may reach 100% in piglets <7 days old. In general, signs of CNS disease (eg, tremors
and paddling) are seen. If weaned pigs are infected, respiratory disease is the primary clinical problem, especially if complicated
by secondary bacterial pathogens. It has been reported that pseudorabies virus inhibits the function of the alveolar macrophages,
thereby reducing the ability of these cells to process and destroy bacteria. A generalized febrile response (41-42°C), anorexia,
and weight loss are seen in infected pigs of all ages. Mortality can be very low (1-2%) in grower and finisher pigs but may
reach 50% in nursery pigs. Sneezing and dyspnea are frequently seen, and there are occasional reports of CNS involvement.
After natural infection, the primary site of viral replication is nasal, pharyngeal, or tonsillar epithelium. Lymphatic spread
carries the virus to regional lymph nodes, where replication continues. Virus also spreads via nervous tissue to the brain,
where it replicates, especially in neurons of the pons and medulla. In addition, virus has been isolated from alveolar macrophages,
bronchial epithelium, spleen, lymph nodes, trophoblasts, embryos, and luteal cells.
Viral excretion begins ~2-5 days after
infection, and virus can be recovered from nasal secretions, tonsillar epithelium, vaginal and preputial secretions, milk,
or urine for >2 wk. A latent state, in which virus is harbored in the trigeminal ganglia, may exist. Swine with latent
infections may resume shedding after periods of stress such as farrowing, crowding, or transport. Experimentally, corticosteroid
injections (dexamethasone, 2 mg/kg, IM) for 5 consecutive days has induced recrudescence.
Lesions:
Gross lesions
of pseudorabies virus infection are often undetectable. Serous rhinitis, necrotic tonsillitis, or hemorrhagic pulmonary lymph
nodes may be seen. Pulmonary edema, as well as pneumonic lesions of secondary bacterial pathogens may be present. Necrotic
foci (2-3 mm in diameter) may be scattered throughout the liver. Such lesions are typically found in young (< 7 days old)
piglets.
Microscopically, nonsuppurative meningoencephalitis is a characteristic lesion that can be present in gray and
white matter. Mononuclear perivascular cuffing and neuronal necrosis may also be present. The meninges are thickened as a
result of mononuclear cell infiltration. Necrotic tonsillitis with the presence of intranuclear inclusion bodies, as well
as necrotic bronchitis, bronchiolitis, and alveolitis are commonly seen. Focal areas of necrosis are often found in the liver,
spleen, lymph nodes, and adrenal glands of macerated fetuses.
Diagnosis:
In addition to the gross and microscopic
lesions, other diagnostic aids include virus isolation, fluorescent antibody testing, and serologic testing. Brain, spleen,
and lung are the organs of choice for virus isolation. Nasal swabs can be used for isolation of virus from acutely infected
animals. The nasal specimens must be stored and transported in cold, sterile saline with antibiotics to suppress bacterial
growth. The fluorescent antibody test can be performed using tonsil or brain.
Many serologic tests are now available,
including serum neutralization, ELISA, and latex agglutination. Serum neutralization, which is the standard test, requires
48 hr to complete. Recently, an ELISA has been developed as a screening assay for large volumes of sera; however, specificity
may be poor. False-positive results are typically reassessed using the serum neutralization test. The latex agglutination
test, although highly sensitive and rapid, may also have poor specificity. After infection, antibodies can be detected within
6-7 days using the latex agglutination test, within 7-8 days using the ELISA, and within 8-10 days using the serum neutralization
test.
A differential ELISA has recently been used to differentiate antibodies produced as a result of vaccination from
those produced as a result of natural infection. The vaccines used in swine are based on the deletion of certain genes (gI,
gIII, or gX) from the vaccine virus. Swine vaccinated with a gene-deleted vaccine will not mount an antibody response to the
protein coded for by the deleted gene. In contrast, infection with field virus results in antibodies against proteins.
Colostral
antibodies to pseudorabies virus may be present until the pig is 4 mo old (similar to porcine parvovirus). Therefore, paired
samples or serologic profiles may be necessary in grower and finisher pigs to assess decreasing levels of maternal antibody
and to ensure that vaccination occurs at the appropriate time.
Treatment and Control:
Although there is no
specific treatment for acute infection with pseudorabies virus, vaccination can alleviate clinical signs in pigs of certain
ages. Typically, mass vaccination of all pigs on the farm with a modified live virus vaccine is recommended. Intranasal vaccination
of sows and neonatal piglets 1-7 days old, followed by IM vaccination of all other swine on the premises, helps reduce viral
shedding and improve survival. The modified live virus will replicate at the site of injection and in regional lymph nodes.
Vaccine virus is shed in such low levels that mucous transmission to other animals is minimal. In gene-deleted vaccines, the
thymidine kinase gene has also been deleted; thus, the virus cannot infect and replicate in neurons. It is recommended that
breeding herds be vaccinated quarterly, and that finisher pigs be vaccinated after levels of maternal antibody decrease. Use
of vaccines on a regular basis results in excellent control of disease. Concurrent antibiotic therapy via feed and IM injection
is recommended for controlling secondary bacterial pathogens.
Numerous programs have been developed for eradication of
pseudorabies virus and include whole-herd depopulation, a test and remove strategy, and offspring segregation. Although effective,
whole-herd depopulation can be costly and time consuming. Usually, problems other than pseudorabies virus (eg, genetic improvement)
need to be resolved before whole-herd depopulation can be cost effective.
The test and remove strategy consists of blood
testing all breeding swine, culling all positive animals, and repeating this procedure until the population tests negative.
Naturally infected animals can be culled when such a strategy is used in conjunction with a differential vaccination program.
A test and remove strategy can be effective, but it is laborious, and latently infected animals that do not exhibit an antibody
response on serologic testing may potentially resume shedding the virus at a later time. In an offspring segregation program,
young piglets (18-21 days old) are removed from vaccinated sows and raised to adulthood at another site. If enough gilts and
boars are raised in this manner, the original breeding herd may be depopulated and subsequently repopulated with seronegative
replacements. This method also allows seedstock producers to sell animals, even though the breeding herd is infected. In this
case, however, all offspring must be individually tested using the serum neutralization test and have negative results before
being sold.
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