Louping ill in man: a forgotten disease.

Louping ill disease of sheep has been recognised in Scotland for centuries. It causes encephalitis and is transmitted by the sheep tick, Ixodes ricinus. Human infection was first reported in 1934. Thirty-one cases of human infection have now been described. Four clinical syndromes are seen, an influenza-like illness, a bi-phase encephalitis, a poliomyelitis-like illness and a hemorrhagic fever. Certain occupational groups, e.g. laboratory personnel working with the virus and those who kill injected sheep, are at increased risk of acquiring louping ill infection. In many instances, infection is subclinical. Eight new human cases are described. Six were in crofters or shepherds in the north and west of Scotland, one was in a general practitioner in the Western Isles and the eighth was in a butcher in Edinburgh. Louping ill disease should not be forgotten in cases of unexplained encephalitis in those whose lifestyle exposes them to the virus.

Response of sheep to experimental concurrent infection with tick-borne fever (Cytoecetes phagocytophila) and louping-ill virus.

The pathogenesis of concurrent Cytoecetes phagocytophila and louping-ill virus infection was studied in two experiments. In the first experiment 18 four- to seven-year-old rams were used. Ten were infected with C phagocytophila and five days later eight of these animals and the remaining eight sheep were infected with louping-ill virus. The two rams infected with C phagocytophila alone developed no clinical signs apart from a transient pyrexia, while only three of the eight rams infected with louping-ill virus alone showed mild clinical signs. In marked contrast, all eight dually infected sheep developed severe clinical signs with pronounced depression and dysentery and three died and five were killed in extremis. They developed higher titres of viraemia and the antibody response was depressed while necrotising lesions affecting a variety of organs were detected at post mortem examination. Rhizomucor pucillus was recovered from these lesions in seven of the eight sheep. A second experiment using 10 sheep, five aged seven months and five aged two to three years, confirmed the findings of the first experiment indicating that the age of the animal had not significantly influenced the initial result. It was concluded that C phagocytophila infection could enhance the pathogenicity of louping-ill virus and that, operating together, the two pathogens facilitated fungal invasion. It is postulated that sudden deaths in sheep recently transferred to tick-infested pastures may be due to this newly described syndrome.

Experimental louping-ill virus infection of black grouse (Tetrao tetrix).

Louping-ill virus was injected into the tarsal pads of four black grouse and the course of infection monitored. All developed viraemia of low intensity that lasted for four days and thereafter produced high titres of haemagglutination inhibiting antibody. No clinical signs were detected and mild neuropathological changes were present in only 1/4 brains collected on day 17 after inoculation. The mild response of black grouse to infection with louping-ill virus is thus similar to that found in other woodland and forest birds and contrasts with the generally fatal response of moorland and tundra grouse species. These findings give further support to the concept that louping-ill has been introduced to the moorland habitat only in the relatively recent past.

Immunosuppression in toxoplasmosis: further studies on mice infected with louping-ill virus.

Mice were infected with an avirulent cyst-producing strain of Toxoplasma gondii and given injections of louping-ill virus 7 days later; control mice were given virus but not Toxoplasma. Test and control mice were then killed, in groups, 2, 4, 6, 8 and 10 days later. In the dually infected mice viraemia was later, greater and more prolonged; titres of virus recovered from brain and spleen were greater; production and haemagglutinating antibody to louping-ill virus was later and less, and inflammation in the brain was more severe, than in mice given virus alone. We suggest that T. gondii suppressed the immunity of mice, making them more susceptible to the virus, and that a significant proportion of the increased number of inflammatory cells observed in the brain could have been toxoplasma specific and not virus-specific and hence contributed to the increased susceptibility of the dually infected mice to louping-ill virus.

Evaluation of the double immunodiffusion test for the diagnosis of louping ill infection.

The usefulness of the double immunodiffusion test for the diagnosis of louping ill infection was investigated. Whereas louping ill viral antigen was not detected in brain material from field cases of the infection, its presence was readily confirmed in suckling mouse brain isolates of the virus. The double immunodiffusion test was found to be unreliable as a serological test for the retrospective diagnosis of louping ill infection in the horse.

Virus infections in cattle and sheep in Scotland 1975-1978.

Over the four-year period 1975-78 attempts were made to identify virus in samples from 1231 outbreaks of disease in cattle, and 682 outbreaks of disease in sheep. A virus identification was possible in 26 per cent of these disease outbreaks. The nature and significance of these virus infections is discussed.

Effect of chronic Trypanosoma brucei infection on the course of louping ill virus infection in mice.

The course of louping-ill virus infection in mice chronically infected with Trypanosoma brucei was investigated. The mean survival time of mice infected with virus alone was 10.2 days, compared to 12.8 days in mice infected with T. brucei 14 days before virus challenge, and the cumulative mortality in the two groups was 62.5 and 90%, respectively. Virus was only inconsistently detected in the blood of mice given virus alone but was regularly present at high titers for up to 12 days in the blood of mice previously infected with T. brucei. Titers of virus in brains were also higher in dually infected mice, and encephalitis was of greater severity. These results indicate that the immunosuppressive effect of chronic trypanosomiasis may markedly increase susceptibility to acute virus infection. In addition, it is concluded that vector-vertebrate relationships of arthropod-transmitted viruses may be altered by concurrent trypanosome infection.