Border disease (Britain) or hairy shaker disease (Australia and New Zealand) is a congenital disorder of lambs characterized by low birth weight and viability, poor conformation, tremor, and an excessively hairy birth coat resulting from in-utero infection with a pestivirus. The disease has been recognized in most sheep-rearing areas of the world, including the western USA. Surviving lambs are persistently infected with border disease virus, and no effective treatment is known.
Border disease is caused by infection of the fetus in early pregnancy with border disease virus (Pestivirus D), a pestivirus (Flaviviridae) closely related to the viruses of classical swine fever (Pestivirus C) and bovine viral diarrhea/mucosal disease (Pestivirus A and B).
Surviving lambs are persistently viremic, and the virus is present in their excretions and secretions, including semen. Cattle, goats, and pigs are also susceptible to infection with border disease virus. Persistently infected individuals have been demonstrated in all of the aforementioned species from natural in-utero infection. Transmission of border disease virus to cattle can occur from commingled grazing with persistent or acutely infected sheep. Acute infections in immunocompetent animals are usually transient and subclinical and result in immunity to challenge with homologous but not heterologous strains of virus.
Virus acquired in early pregnancy by previously unexposed animals crosses the placenta and invades the fetus. Placentitis occurs 10–30 days after infection and may cause fetal death with expulsion, resorption, or mummification. Abortion may occur at any stage of pregnancy and may pass unnoticed because there is little maternal malaise.
In sustained pregnancies, the virus becomes widely distributed in fetal tissues, but pathologic changes are most obvious in the skin, skeleton, and CNS. Affected lambs may be born 2–3 days early, and many die before or at weaning. In survivors, the clinical signs gradually regress, but such animals remain persistently infected and excrete virus for the remainder of their lives, exposing their progeny and flockmates. Death from a syndrome similar to bovine mucosal disease may occur in these clinically “recovered” hairy-shaker sheep at any time.
In naive flocks exposed to border disease virus, up to 50% or more of lambs born may be affected with clinical disease associated with border disease. Thereafter, the prevalence declines, although the disease may become endemic when “recovered” lambs are retained for breeding. The virus is most commonly introduced into susceptible flocks by the addition of persistently infected sheep or pregnant ewes carrying an infected fetus. However, sheep can also acquire infection from transiently or persistently infected cattle. For practical purposes, it should be assumed that sheep and cattle are equally susceptible to all strains of border disease virus and BVDV 1 and 2, even though at least seven species in the genus Pestivirus have been identified in domestic ruminants.
Flocks affected by border disease probably are recognized first at lambing time by an increase in the number of barren ewes and in the birth of undersized lambs with excessively hairy and sometimes excessively pigmented fleece. Skeletal abnormalities that may be seen in newborn lambs include a decreased crown-rump length, shortened tibia and radius, and a shortened longitudinal axis of the cranium. Some lambs exhibit involuntary muscular tremors, particularly of the trunk and hindlegs. The tremors are reduced at rest and exacerbated by purposeful movement. In others, skeletal defects such as dropped pasterns and mandibular brachygnathia may predominate. Affected lambs have a poor survival rate. In survivors, nervous signs gradually disappear within 3–4 months. Even in the absence of typical hairy-shaker lambs, outbreaks of low fertility in ewes and poor viability and ill-thrift in lambs may be associated with border disease virus infection. Goat kids may also be affected, and a similar condition occasionally occurs in calves. Other clinical signs include infertility, abortions, and stillbirths.
In severe cases, abnormal development of the cerebrum may be seen at necropsy, resulting in hydrocephalus, hydranencephaly, porencephaly, or microcephaly. Cerebellar hypoplasia or cerebellar dysplasia may also occur. Otherwise, the characteristic lesions are microscopic and involve the white matter of the CNS. There is a deficiency of myelin and an increase in interfascicular glial cells, in which myelin-like lipid droplets may accumulate. These changes are most obvious in the newborn and gradually resolve.
Clinical findings usually allow a diagnosis of border disease, although abnormal hairiness of the birth coat may not be apparent in rough-coated breeds of sheep. The diagnosis can be confirmed by histologic demonstration of the pathognomonic lesions in the CNS and with immunocytochemical staining of the virus. In typical hairy-shaker lambs, the virus or viral antigen may be demonstrated readily in blood and tissues by virus isolation, fluorescent antibody tests, immunohistochemistry, or PCR. When testing blood in newborn lambs, precolostral blood is ideal because colostral antibody can mask virus for up to 2 months. Virus can be isolated from serum or buffy coat cells in cell cultures, but a viral antigen detection ELISA using heparinized or EDTA blood is available. Reverse transcriptase-PCR can also be used to detect viral RNA in clinical specimens and to differentiate between ruminant pestiviruses.
Differential diagnoses in live-born lambs include:
Other causes of ovine abortion include:
There is no effective treatment for lambs persistently infected with border disease. Bulk tank milk samples can be tested for antibodies to border disease virus to screen for the presence of virus within dairy sheep flocks. Serology should be performed on the dams of affected lambs. Most should have high circulating concentrations of antibody, providing immunity to the same strain of virus in subsequent pregnancies. Those that do not have antibody titers should be screened for virus to identify any that are persistently infected. Recovered lambs should not be retained for breeding but can be mixed with replacement stock well before breeding season to maximize opportunities for the latter to become infected and develop immunity before subsequent matings. There is no effective vaccine.
Border disease virus infection in pregnant ruminants results in embryonic loss/abortion or birth of congenitally infected offspring.
Lambs born after in-utero border disease virus infection are characterized by low birth weight and viability, poor conformation, tremor, and an excessively hairy coat.
Surviving offspring remain persistently infected and are the primary reservoir for the virus in a susceptible population.