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During February 2018–January 2019, we conducted large-scale surveillance for the presence and prevalence of tick-borne encephalitis virus (TBEV) and louping ill virus (LIV) in sentinel animals and ticks in the United Kingdom. Serum was collected from 1,309 deer culled across England and Scotland. Overall, 4% of samples were ELISA-positive for the TBEV serocomplex. A focus in the Thetford Forest area had the highest proportion (47.7%) of seropositive samples. Ticks collected from culled deer within seropositive regions were tested for viral RNA; 5 of 2,041 ticks tested positive by LIV/TBEV real-time reverse transcription PCR, all from within the Thetford Forest area. From 1 tick, we identified a full-length genomic sequence of TBEV. Thus, using deer as sentinels revealed a potential TBEV focus in the United Kingdom. This detection of TBEV genomic sequence in UK ticks has important public health implications, especially for undiagnosed encephalitis.

In Norway, the Willow Ptarmigan (Lagopus lagopus lagopus) is experiencing population declines and is nationally Red Listed as Near Threatened. Although disease has not generally been regarded as an important factor behind population fluctuations for Willow Ptarmigan in Norway, disease occurrence has been poorly investigated. Both louping-ill virus (LIV) and the closely related tick-borne encephalitis virus are found along the southern part of the Norwegian coast. We assessed whether and where Norwegian Willow Ptarmigan populations have been infected with LIV. We expected to find infected individuals in populations in the southernmost part of the country. We did not expect to find infected individuals in populations further north and at higher altitudes because of the absence of the main vector, the sheep tick (Ixodes ricinus). We collected serum samples on Nobuto filter paper and used a hemagglutination inhibition assay for antibodies against LIV. We collected data at both local and country-wide levels. For local sampling, we collected and analyzed 87 hunter-collected samples from one of the southernmost Willow Ptarmigan populations in Norway. Of these birds, only three positives (3.4%) were found. For the country-wide sampling, we collected serum samples from 163 Willow Ptarmigan carcasses submitted from selected locations all over the country. Of these birds, 32% (53) were seropositive for LIV or a cross-reacting virus. Surprisingly, we found seropositive individuals from locations across the whole country, including outside the known distribution of the sheep tick. These results suggest that either LIV or a cross-reacting virus infects ptarmigan in large parts of Norway, including at high altitudes and latitudes. Lagopus lagopus, louping-ill virus, ptarmigan, serosurvey, tick-borne viruses.

Fifty-three of a mixed flock of 180 one-year-old lambs (hoggs) and older, barren ewes (ewes that were non-pregnant or had not lambed that spring) died in May 2019 following introduction to 30 acres of unimproved hill pasture. The flock was moved onto this pasture in early May, and clinical signs and deaths were observed 14 days later. Clinical signs included dyspnoea, lethargy, and sternal and lateral recumbency; the majority were found dead. The flock was removed from the hill the day after the first deaths were discovered. Deaths continued for a further 14 days until a total of 53 animals had died. Three hoggs were submitted for postmortem examination to the Wales Veterinary Science Centre. Anaplasma phagocytophilum, the causal organism of tickborne fever, was detected by PCR testing. Coinfection with louping ill virus was also suspected and later confirmed. The laboratory findings are described, and the risk of these diseases to grazing sheep in upland areas is discussed, as well as the measures being taken to reduce the risk of infection.

Flaviviruses are globally distributed pathogens causing millions of human infections every year. Flaviviruses are arthropod-borne viruses and are mainly transmitted by either ticks or mosquitoes. Mosquito-borne flaviviruses and their interactions with the innate immune response have been well-studied and reviewed extensively, thus this review will discuss tick-borne flaviviruses and their interactions with the host innate immune response.

The rapid succession of the pandemic of arbovirus diseases, such as dengue, West Nile fever, chikungunya, and Zika fever, has intensified research on these and other arbovirus diseases worldwide. Investigating the unique mode of vector-borne transmission requires a clear understanding of the roles of vertebrates. One major obstacle to this understanding is the ambiguity of the arbovirus definition originally established by the World Health Organization. The paucity of pertinent information on arbovirus transmission at the time contributed to the notion that vertebrates played the role of reservoir in the arbovirus transmission cycle. Because this notion is a salient feature of the arbovirus definition, it is important to reexamine its validity. This review addresses controversial issues concerning vertebrate reservoirs and their role in arbovirus persistence in nature, examines the genesis of the problem from a historical perspective, discusses various unresolved issues from multiple points of view, assesses the present status of the notion in light of current knowledge, and provides options for a solution to resolve the issue.

Spanish goat encephalitis virus (SGEV) is a recently described member of the genus Flavivirus belonging to the tick-borne encephalitis group of viruses, and is closely related to louping ill virus (LIV). Naturally acquired disease in goats results in severe, acute encephalitis and 100% mortality. Eighteen goats were challenged subcutaneously with SGEV; nine were vaccinated previously against LIV and nine were not. None of the vaccinated goats showed any clinical signs of disease or histological lesions, but all of the non-vaccinated goats developed pyrexia and 5/9 developed neurological clinical signs, primarily tremors in the neck and ataxia. All non-vaccinated animals developed histological lesions restricted to the central nervous system and consistent with a lymphocytic meningomyeloencephalitis. Vaccinated goats had significantly (P, This work was supported by a grant from Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), reference number E-RTA2013-00013-C04-04 (FEDER co-funded) and the Rural and Environment Science and Analytical Services (RESAS) division of the Scottish Government.

Throughout Europe interest in tick-borne agents is increasing, particularly with regard to those that can cause human disease. The reason for this is the apparent rise in the incidence of many tick-borne diseases (TBD's). While there has never been a national survey of ticks or TBD's in Ireland, the trend here appears to be the reverse with a decline in the incidence of some agents seemingly associated with decreasing tick numbers particularly on agricultural land. In the absence of robust baseline data, however, this development cannot be confirmed. This review collates the limited information available from several dated published records on tick species and a small number of studies focused on certain TBD's. Some pilot data on tick density and TBD agents collected in 2016 are also presented. The aim is to explore the particular situation in Ireland with regard to ticks and TBD's and to provide a reference for future workers in the field.

6 páginas.-- Mansfield, K. L. (et al.)., In 2011, a neurological disease was reported in a herd of goats (Capra hircus) in Asturias, Spain. Initial sequencing identified the causative agent as louping ill virus (LIV). Subsequently, with the application of whole genome sequencing and phylogenetic analysis, empirical data demonstrates that the LIV-like virus detected is significantly divergent from LIV and Spanish sheep encephalitis virus (SSEV). This virus encoded an amino acid sequence motif at the site of a previously identified marker for differentiating tick-borne flaviviruses that was shared with a virus previously isolated in Ireland in 1968. The significance of these observations reflects the diversity of tick-borne flaviviruses in Europe. These data also contribute to our knowledge of the evolution of tick-borne flaviviruses and could reflect the movement of viruses throughout Europe. Based on these observations, the proposed name for this virus is Spanish goat encephalitis virus (SGEV), to distinguish it from SSEV., C. G. acknowledges support from CYTEMA. This work was jointly funded from the European Commission Seventh Framework Programme under ANTIGONE (project 278976), the UK Department for Environment, Food and Rural Affairs (Defra) project SE4112 and the INIA grant E-RTA2013-00013-C04-04 (FEDER co-funded, Spain).

The European subtype of tick-borne encephalitis virus (TBEV-Eu) and louping-ill virus (LIV) are two closely related tick-borne flaviviruses. However, whereas the first is the cause of one of Europe's most important zoonoses, the latter most often only causes disease in sheep and grouse. TBEV-Eu is typically found in the forests of central and northeastern Europe, and LIV typically is found in sheep pastures in the British Isles. In the 1980s, however, LIV was isolated from sheep with encephalomyelitis in Norway. In the 1990s, the first cases of human TBEV were also detected in this country, but while Louping-ill in sheep is very rare, the number of human TBEV cases is increasing. No larger investigations of TBEV and/or LIV seroprevalence and distribution in Norway have been published. However, before such studies are initiated, it is pertinent to know if LIV and TBEV are potentially co-circulating. In the current study, we examined if antibodies against LIV and TBEV were found in wild cervids in one location (Farsund) in southern and one location (Molde) in northwestern Norway using a commercially available enzyme-linked immunosorbent assay for detection of anti-TBEV immunoglobulin G (IgG) and a hemagglutination inhibition test for anti-LIV IgG. Positive results were confirmed by serum neutralization tests. In Farsund, 22 of 54 cervids had antibodies against TBEV and 8 antibodies against LIV. In Molde, 1 of 64 cervids was confirmed positive for TBEV, whereas none were positive for LIV. This shows that TBEV and LIV may co-circulate in southern Norway and that virus(es) antigenetically very similar to TBEV may be found in northwestern Norway. The latter is intriguing, because the climatic conditions typical of TBEV locations should not be expected this far north.

Louping ill virus (LIV) is a zoonotic virus causing fatal encephalitis in young sheep and grouse. We have recovered the complete genome sequence from a spinal cord sample prepared from a lamb that was naturally infected with LIV. This is only the second LIV genome sequence reported and the first prepared from a clinical sample.

Blood samples were collected opportunistically at routine post mortem examination from 199 sheep which came from 152 flocks. The location of each submitting flock was mapped. Sera were tested using a goose blood haemagglutination inhibition assay for louping ill virus. There was an animal level prevalence of 8.5%, and a flock level prevalence of 9.8%. The greatest proportion of seropositive animals was identified among the animals older than 24 months of age. The elevation of the land associated with positive flocks was greater than that of negative flocks. Lesions of non-suppurative meningoencephalitis were observed in three of the 199 animals. Deposited by bulk import

3 páginas, 2 figuras.-- et al., Although louping ill affects mainly sheep, a 2011 outbreak in northern Spain occurred among goats. Histopathologic lesions and molecular genetics identified a new strain of louping ill virus, 94% identical to the strain from Britain. Surveillance is needed to minimize risk to domestic and wildlife species and humans., This article was partially funded by a grant from the Spanish National Institute for Agriculture and Food Research and Technology (INIA) (RTA2011-00010-00-00). A.B. is a recipient of a ‘Contrato de Investigación para Doctores’ grant from INIA. N.M. received a fellowship for prospective research from the Swiss National Science Foundation.

1. Japanese B encephalitis virus, obtained from Japanese investigators, has proved virulent for mice and monkeys, confirming the reports from Japan. It has also been found virulent for monkeys when instilled intranasally and for sheep when introduced intracerebrally or intranasally. 2. Japanese B encephalitis virus has been differentiated from St. Louis virus and found similar to louping ill virus according to its reactions in animal species. Serologically, however, it is distinct. 3. Japanese B encephalitis and its related group of primary virus encephalitides of man have been discussed with regard to their differentiation and mode of spread.

The results of the work presented in the present paper show that louping ill and poliomyelitis immunologically are not closely related. Although relatively few experiments were performed, the data obtained were sufficiently decisive for our purposes. Certainly nothing was found to indicate that one might be able to immunize human beings against poliomyelitis by the use of louping ill virus. In addition to the negative findings, a certain amount of useful information was also secured, namely, (1) monkeys can be solidly immunized against louping ill by intraperitoneal injections of virus and partially protected by intramuscular administrations of the active agent, (2) during the process of immunization no signs of involvement of the central nervous system are manifested, and (3) sera from monkeys immunized in the manner described contain antibodies capable of neutralizing the virus.

Although various members of the genus Flavivirus have been associated with livestock and wildlife, the most significant veterinary viruses include mosquito-borne Wesselsbron and West Nile, and tick-borne louping ill. West Nile virus is widely distributed in Africa, Asia, and Europe, and more recently the Americas and Canada. There has been an increase in the frequency and severity of outbreaks of human disease, neurologic infections in horses and fatal infections in birds with the virus. Sporadic outbreaks of Wesselsbron virus have been recorded in southern Africa, resulting in death of young cattle, goats and sheep and abortion in pregnant animals. Serological evidence suggests the virus is widely spread throughout Africa, and it is possible that the extent and veterinary importance may be underestimated at this time. Louping ill virus infects sheep throughout the hill sheep farming areas of Scotland, northern and southwest England, Ireland, and north Wales. The virus causes a fatal encephalomyelitis in at least some of the infected sheep.

The authors thank Lord Landsdowne and the Hon Charles Pearson for funding and for access to the study sites. M. H. M. was the holder of a Small Grant from the Royal College of Veterinary Surgeons Trust. The Moredun Research Institute and the Macaulay Land Use Research Institute receive funding from the Scottish Executive Environment and Rural Affairs Department.

Several human diseases in Europe are caused by viruses transmitted by tick bite. These viruses belong to the genus Flavivirus, and include tick-borne encephalitis virus, Omsk haemorrhagic fever virus, louping ill virus, Powassan virus, Nairovirus (Crimean-Congo haemorrhagic fever virus) and Coltivirus (Eyach virus). All of these viruses cause more or less severe neurological diseases, and some are also responsible for haemorrhagic fever. The epidemiology, clinical picture and methods for diagnosis are detailed in this review. Most of these viral pathogens are classified as Biosafety Level 3 or 4 agents, and therefore some of them have been classified in Categories A–C of potential bioterrorism agents by the Centers for Disease Control and Prevention. Their ability to cause severe disease in man means that these viruses, as well as any clinical samples suspected of containing them, must be handled with specific and stringent precautions.

1. We investigated the effects of three types of host on the persistence of a tick-borne virus, using the grouse-hare-deer-tick-louping ill virus system of upland Britain. Each host differed in its interaction with the vector and pathogen. Grouse amplify virus only, deer amplify vector only and hares amplify both. Grouse alone suffer high virus-induced mortality. 2. An analytical model of the system was parameterized using empirical data from two wild populations with different community structures. By changing relative host densities we examined the conditions under which the virus would persist and considered the possibility of parasite-mediated competition between hosts. 3. Although deer alone and grouse alone were unable to maintain louping ill virus, a deer-grouse community usually allowed virus persistence because grouse transmitted virus while deer maintained the tick population. Since virus reduces grouse populations this is a type of apparent competition, and is unusual because deer do not amplify the virus. 4. At very high deer densities, the opposite effect could occur, whereby virus died out because of 'wasted' infected tick bites on deer, that do not transmit virus (the dilution effect). 5. In a hare-grouse two-host system virus usually persisted because hares amplified both the vector and virus (through non-viraemic transmission). Thus, apparent competition may occur between mountain hares and grouse. 6. The addition of a third host type increased the likelihood of disease persistence. Hares added to the deer-grouse system rendered the dilution effect unlikely because of additional virus amplifiers. Deer added to the hare-grouse system meant virus almost always persisted because they amplified the vector.

An immunohistochemical method for the detection of louping ill virus antigen in formalin-fixed, paraffin wax-embedded tissues by an avidin-biotin-complex (ABC) immunoperoxidase technique was established. The tissues examined were from the brains of 10 mice, five sheep and one pig. The mice were experimentally infected with louping ill virus whereas the sheep and the pig were field cases of louping ill confirmed by clinical examination, and by histological and serological methods.

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.

SUMMARYThe influence of colostrum-derived antibody to louping-ill virus on the course of experimental infection was investigated in lambs. Lambs that had high titres of antibody were refractory to infection. Lambs that had low titres of antibody did not develop a viraemia but either showed an antibody reaction or were sensitized as judged by the immune response, which was typical of an anamnestic response, after rechallenge. Animals that had no antibody 34–20 days before challenge had either no or very slight viraemia, but did develop an antibody response with titres as high as those of control lambs by day 21. Lambs that had been negative for longer periods responded in a similar fashion to controls.These findings are discussed in relation to the occurrence of disease in lambs kept in louping-ill endemic areas. It is concluded that in such areas infections of lambs are likely to be of minor importance as a cause of mortality and of little epidemiological significance.

SUMMARY An outbreak of LI infection in a group of free range horses is described. Three of 4 horses displayed signs of CNS disturbance and 2 of these died after illnesses ranging from 2–12 days duration. In both cases a variable degree of viral polioencephalomyelitis was observed. A virus antigenically indistinguishable from a reference strain of LI virus was isolated from the brain and cervical cord of a 3 y.o. draft mare. Serum samples obtained from 3 of the horses contained HI, CF, precipitating and neutralising antibodies to LI virus, with a rise in antibody titre being demonstrated in 2 animals. RESUME Un foyer d'infection par le virus Louping Ill sur divers chevaux est decrit. Trois des quatre chevaux montrerent des troubles cerebraux et deux d'entre eux moururent au terme d'une maladie evoluant en deux a douze jours. Dans ces deux cas, on observa une polioencephalomyelite virale. Un virus antigeniquement semblable a une souche de reference du virus Louping Ill fut isole du cerveau et de la moelle cervicale d'une jument de trait de trois ans. Les echantillons de serum recueillis sur trois chevaux renfermaient des anticorps fixant le complement, neutralisant et precipitant le virus du Louping Ill, avec une elevation du taux des anticorps, mise en evidence sur deux des animaux. ZUSAMMENFASSUNG Ein Ausbruch einer “Louping ill”-Infektion bei einer Gruppe von Weidepferden wird beschrieben. Drei von vier Pferden wiesen Zeichen einer ZNS-Storung auf und zwei starben nach 2–12 Tagen dauernder Krankheit. In beiden Fallen wurde eine virale Polioencephalomyelitis verschiedenen Grades beobachtet. Ein antigenetisch von LI-Virus nicht zu unterscheidendes Agens konnte aus dem Gehirn und dem Ruckenmark einer 3-jahrigen Zugpferdestute isoliert werden. Serumproben von drei Pferden wiesen haemag-glutinationshemmende, komplementbindende, praezipitierende und neutralisierende Antikorper gegen LI-Virus auf, wobei bei 2 Tieren ein Titeranstieg demonstriert werden konnte.

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.

Summary 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 of 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.

Sheep, after infection with louping ill virus and after re-infection with the same strain of virus 19–21 months later, were bled at intervals and their sera examined for neutralizing and haemagglutinin-inhibiting antibodies. Each antibody type was measured by the constant serum/variable virus and constant virus/variable serum methods. The persistence of each type of antibody and its significance in epidemiological studies is discussed. The relationship of antibody levels in ewes and their lambs was also examined.

Four instances of infection in man which are believed, because of the circumstances under which they occurred and in view of the results of neutralization tests, to represent cases of louping ill have been described. Evidence obtained by the neutralization tests is in favor of the idea that the antibodies against louping ill virus demonstrated in certain sera were most likely the result either of contact with or of infection with the active agent.

Ixodes ricinus (L.) ticks are more dispersed both in time and space in Ireland than in Britain. In Ireland louping ill virus may occur at lower altitudes involving a somewhat wider range of incidental maintenance hosts. Consequently, cattle and possibly man may be infected more frequently than in Britain.

SUMMARY Louping ill (LI) virus was isolated from a suspension of pooled liver and spleen tissue obtained from a red grouse (Lagopus lagopus scoticus). The grouse, a two-month-old hen, had been reared in captivity at Glenamoy, Co. Mayo, and was found dead without having shown any premonitory signs. Additional specimens of grouse dying in captivity have since been received but there have been no further virus isolations. Serologic comparison of the grouse isolate with a reference strain of LI virus, showed them to be identical. The grouse virus was pathogenic for sheep both by the intracerebral (i/c) and subcutaneous (s/c) routes.