Overview of Louping Ill

The virus belongs to the Flaviviridae family and is part of an antigenically closely related complex of viruses known as the tickborne encephalitides, which are primarily associated with disease in people and distributed throughout the northern temperate regions. Infection is transmitted transstadially by the tick vector; transovarial transmission of louping ill virus does not appear to occur. In sheep flocks, mortality ranges from 60% in newly introduced stock to 5%–10% in sheep acclimatized to the pasture. On farms where the disease is endemic, losses are mainly confined to animals <2 yr old; adults tend to be immune as a result of previous infection, and lambs are protected in their first season by colostral antibody. However, when the disease appears for the first time, or after a lapse of several years, all ages of sheep are susceptible. Mortality is variable in other species but tends to be high in red grouse. All species of vertebrates that come in contact with questing ticks may become parasitized and infected with louping ill virus, but only sheep and grouse develop titers of viremia sufficient to pass the infection to the vector tick. Infection also can be spread through contact with contaminated instruments or tissues. Infected lactating goats can excrete high titers of virus in their milk, which may cause fatal infection of their kids and be a potential human health hazard.

The course of infection in all species is similar, and varies only in the intensity of viremia and frequency with which clinical signs develop. After inoculation by an infected tick, virus initially replicates in lymphoid tissues, which gives rise to viremia that lasts 1–5 days. Only animals that develop high titers can transfer the virus to ticks. During viremia, a febrile reaction may be present, but overt clinical signs are generally absent until the virus enters the CNS and begins replication, even though the immune response has eliminated the virus from the extraneuronal tissues. The extent of neuronal damage consequent to viral replication determines the severity of signs, from none (subclinical) through varying degrees of neurologic dysfunction to sudden death. Histologic lesions may be present whether or not signs develop. Signs include fine muscular tremors, nervous nibbling, ataxia (particularly of the hindlimbs), weakness, and collapse; death may occur 1–3 days after onset of signs. Peracute deaths may also occur. In some recovered animals, residual paresis or torticollis may persist. All recovered animals are solidly immune for life.

The severity of clinical disease in animals recently infected with Anaplasma phagocytophilum (the cause of tickborne fever [see Tickborne Fever]) is markedly increased, presumably because of the immunosuppressive effect of this organism. The accompanying pathology may be complex and associated with secondary bacterial and mycotic infection, accounting for the high mortality experienced when naive flocks are introduced to tick-infested pasture.

No specific gross lesions are present, although secondary pneumonia may develop. Histologic examination of the CNS usually shows a nonsuppurative polioencephalomyelitis with lesions predominantly in the brain stem.

The disease normally is seen only in animals that have had access to tick-infested pasture; however, the variable clinical picture necessitates differentiation from other conditions that cause locomotor or neurologic dysfunction. Confirmation is by histologic examination of the brain, virus detection in CNS tissue, and serology. As much of the brain and brain stem as possible should be fixed in formaldehyde solution (10% in saline), and sections examined for the characteristic lesions, which can be useful in reaching a presumptive diagnosis. Diagnosis is confirmed by immunohistochemistry using an appropriate monoclonal antibody. For routine diagnosis, virus isolation is now seldom undertaken and has been replaced by reverse transcriptase PCR. This requires a piece of brain stem to be collected into virus transport medium and dispatched to a suitable diagnostic laboratory. Measurement of serum neutralizing and hemagglutination inhibition antibodies also can help reach a diagnosis and for surveys. The presence of IgM antibody in cattle and sheep serum, detected by the hemagglutination inhibition test, provides good evidence that the animal was infected within the preceding 10 days.

No specific treatment is available, but nursing, hand-feeding, and sedation may be helpful. An inactivated, tissue culture–propagated vaccine is available and has successfully protected sheep, cattle, and goats. A single injection induces an antibody response that provides protection for <2 yr. Colostrum from the vaccinated ewe prevents infection of lambs in their first months. Generally, all animals to be retained for breeding are vaccinated at 6–12 mo of age. Use of insecticidal dips to protect against exposure to ticks generally is inadequate, although pour-on preparations reduce exposure, and their systematic use may effectively reduce the abundance of ticks and prevalence of virus infection.

Louping ill virus infection of people can cause severe encephalomyelitis. Symptoms are biphasic; the initial, flu-like symptoms are replaced 4–5 days later with signs of encephalitis. People become infected through the bite of infected ticks or through contact with infected carcasses, sharp instruments, or aerosol. Only a few cases of natural transmission have been reported, most occurring in laboratory workers. Those engaged in the diagnosis or research of this virus should be vaccinated with a human vaccine against tickborne encephalitis virus. Because goats can excrete high titers of virus in their milk, goats kept for milk production in endemic areas must be vaccinated.