Louping ill, caused by louping ill virus and transmitted by ticks, causes a frequently fatal encephalitis that results in highly variable neurologic signs and has no specific treatment or available vaccine. Antemortem diagnosis is usually by serology using hemagglutination inhibition, which can also identify acute infections by differentiating IgM from IgG predominance. Postmortem, diagnosis is by histologic and immunohistochemical examination of the brain and also by PCR.
Louping ill is an acute, tick-transmitted viral disease of the CNS that primarily affects sheep and red grouse, but cattle, goats, horses, dogs, pigs, South American camelids, and people also can be affected; people can be infected by tick bites or exposure to tissues or instruments contaminated with virus. The disease is seen throughout the British Isles wherever the vector tick, Ixodes ricinus, is prevalent but especially in rough hill grazing. Diseases of sheep and goats indistinguishable from louping ill and caused by similar viruses have been reported in Norway, Spain, Turkey, and Bulgaria, which suggests that the condition may not be restricted to the British Isles.
Etiology and Transmission of Louping Ill in Animals
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. Although different strains of louping ill virus have been identified by genome sequencing, none appear specific to any of the susceptible species.
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 years 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 red 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.
Pathogenesis, Clinical Findings, and Lesions of Louping Ill in Animals
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 with few histologic lesions present. 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) 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 (lymphocytic) polioencephalomyelitis with lesions throughout the brain but predominantly in the brain stem.
Diagnosis of Louping Ill in Animals
Neurologic clinical signs in association with exposure to ticks is suspicious of disease
Antemortem diagnosis is by serologic testing, differentiating IgM from IgG predominance by hemagglutination inhibition to show recent infection
Louping ill 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 and immunohistochemistry using a specific monoclonal antibody, virus detection in CNS tissue by PCR, and serology.
Whole brain should be fixed in formaldehyde solution (10% in saline), and sections should be examined for the characteristic lesions, which can provide a presumptive diagnosis that is confirmed by immunohistochemistry. For routine diagnosis, virus isolation is now seldom undertaken and has been replaced by RT-PCR. This requires a piece of brain stem or proximal spinal cord 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 by comparison with a heat-inactivated aliquot of serum or plasma, provides good evidence that the animal was infected within the preceding 10 days.
Treatment and Control of Louping Ill in Animals
No specific treatments or vaccines are currently available
No specific treatment for louping ill is available, but nursing, hand-feeding, minimizing external stimuli, and sedation may be helpful.
An inactivated, tissue culture–propagated vaccine has successfully protected sheep, cattle, and goats but is no longer available, and development of a recombinant vaccine is only in the early experimental phase. Colostrum from the vaccinated, and presumably recovered and now immune, ewes prevents infection of lambs in their first months. Ideally, all animals to be retained for breeding would be vaccinated at 6–12 months 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.
Zoonotic Risk of Louping Ill in Animals
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, and development of a new vaccine is paramount.
Key Points
Louping ill is a viral infection that often causes fatal encephalitis.
The disease primarily affects sheep and red grouse, but cattle, goats, horses, dogs, pigs, South American camelids, and people also can be affected.
No specific treatments or vaccines are currently available.
