Louping ill virus: Infectious substances pathogen safety data sheet

Section I – Infectious agent


Louping ill virus

Agent type








Louping ill virus

Synonym or cross-reference

Louping ill disease, ovine encephalomyelitis, infectious encephalomyelitis of sheep, trembling-ill, British, Irish, Spanish, or Turkish sheep encephalitis virus, and Greek goat encephalitis virusFootnote 1 .


Brief description

Louping ill virus (LIV) is a positive-sense, single-stranded, enveloped RNA virus of 40-50 nmFootnote 2. Its genome is approximately 11 kbp in length, and as with other Flaviviridae, it has a conserved genome structure consisting of structural genes for the capsid, pre-membrane, and envelope, along with seven non-structural genesFootnote 3 .

Section II – Hazard identification

Pathogenicity and toxicity

In humans, LIV infections are most often asymptomatic or present with a mono- or biphasic courseFootnote 3Footnote 4. Influenza-like symptoms, including fever, headache and muscle stiffness, last 2 to 12 daysFootnote 2Footnote 4 . After an asymptomatic interval of approximately five days, disease progresses to an encephalitic phase in some patientsFootnote 2Footnote 4. Symptoms worsen (e.g., fever, severe headache, vomiting) and neurological signs (e.g., neck stiffness, tremor or head/limbs) of meningoencephalitis or paralytic poliomyelitis occurFootnote 2Footnote 4Footnote 5. There has been one confirmed fatal case in humansFootnote 6.

Sheep, the main host of the disease, are most susceptible to infection post-weaning when they are moved to pasture, due to the combination of initial exposure to ticks and drop-off in maternal antibody protectionFootnote 3. Louping ill disease is characterized by a mono- or biphasic feverFootnote 4, and initial signs are often non-specific leading to poor detection rates. The initial phase is associated with fever and viremiaFootnote 4. Many animals recover, while in others, the infection progresses to the secondary phase, which leads to neuroinvasion. At this stage, disease manifests as depression, panting, and nibbling. In extreme cases, the animal may uncontrollably leap, from which the virus is namedFootnote 3Footnote 7. Sheep may also present with muscle tremors, incoordination, circling, ataxia, and posterior paralysisFootnote 7. If the disease progresses further, animals will appear in a depressed state with no interest in food, and disease will eventually lead to paralysis and death. If sheep survive the encephalitic stage, most animals suffer from torticollis (twisted neck syndrome) and paraplegiaFootnote 3Footnote 8. Mortality rates range from 1-4% in adult sheep, and up to 60% in lambsFootnote 4.

Serological evidence indicates that cattle and horses in louping-ill-enzootic areas are naturally infected with LIV, but do not usually develop clinical signsFootnote 9. When present, neurological signs are similar to those in sheep, but animals may also experience lateral recumbency, convulsions hyperaesthesia, and hyperexitabilityFootnote 3. Death occurred within hours in one case of horse illness, otherwise disease is rarely fatalFootnote 3Footnote 9Footnote 10Footnote 11. Louping ill disease is rarely reported in pigs; however, neurological signs have been observed in LIV-infected pigsFootnote 12Footnote 13. Fatal cases of louping-ill disease have been reported in goats that showed fever and neurological signs (e.g., incoordination, hindleg lameness)Footnote 14.

Deer show no signs of infectionFootnote 3Footnote 15 . Red grouse chicks are highly susceptible to disease and develop high levels of viremiaFootnote 3Footnote 16. Experimental studies indicate the red grouse mortality rate can be as high as 80%Footnote 17.


LIV is a rare disease in humans; less than 50 cases have been reportedFootnote 2Footnote 3. In animals, LIV primarily affects sheep and is mainly restricted to upland grazing areas of the United Kingdom where it is enzooticFootnote 3; however, LIV cases in livestock have occurred in Norway, Denmark, and SpainFootnote 18. Between 1999-2012, there were 506 confirmed LIV cases in sheepFootnote 3.

In humans, laboratory and slaughterhouse workers, and shepherds are at highest risk due to their interaction with potentially infected sheepFootnote 2Footnote 4. Young animals are particularly susceptible to diseaseFootnote 3Footnote 9Footnote 12Footnote 16. Sheep have an increased risk of severe disease when co-infected with Anaplasma phagocytophilumFootnote 19Footnote 20Footnote 21.

Host range

Natural host(s)

SheepFootnote 3, cattleFootnote 9, deerFootnote 15, pigsFootnote 12, horsesFootnote 3, goatsFootnote 14, alpacaFootnote 22, llamaFootnote 23, dogFootnote 24, mountain haresFootnote 18, and small mammals, such as the common shrew and wood mouseFootnote 25. The red grouse is a natural dead-end hostFootnote 26.

Other host(s)

MiceFootnote 27, black grouseFootnote 17.

Infectious dose


Incubation period

The incubation period averages 8-13 days in sheepFootnote 3Footnote 27 and approximately 1 week in humansFootnote 28.


In humans, flavivirus transmission can occur via bite from an infected tick, but the majority of cases result from inhalation, handling of infected animals and penetrative injury in a laboratory setting or slaughterhouseFootnote 1Footnote 28Footnote 29. LIV has been detected in the milk of infected sheep and goats, indicating that consumption of raw milk in enzootic areas is a possible mode of LIV transmission to humansFootnote 1Footnote 30Footnote 31; however, no human cases of LIV infection have been associated with consumption of raw milk. There are no reported human-to-human transmission.

In animals, transmission occurs primarily through the tick bites of Ixodes RicinusFootnote 2Footnote 3. One outbreak investigation of LIV in pigs identified the probable cause to be consumption of raw meat of sheep that were presumed to be infected with LIVFootnote 12, indicating that ingestion is a possible transmission route.

Section III – Dissemination


LIV is maintained in sheep, and mountain hares are possible reservoirsFootnote 25Footnote 32.


Close contact with infected animals or blood/tissue of infected animals may allow for transfer of the disease to humansFootnote 2Footnote 3Footnote 28.


Sheep, castor bean tick (Ixodes ricinus)Footnote 3Footnote 18.

Section IV – Stability and viability

Drug susceptibility/resistance


Susceptibility to disinfectants

Flaviviruses are sensitive to 1% sodium hypochlorite, 2% glutaraldehyde, 70% ethanol, paraformaldehyde, iodophors, and 3-6% hydrogen peroxideFootnote 33Footnote 34Footnote 35. Some flaviviruses are also susceptible to organic solvents and detergents, such as Triton-XFootnote 33.

Physical inactivation

Flaviviruses are completely inactivated within 30 minutes at 56°C and are susceptible to UV light and extreme pH (pH ≥ 9)Footnote 33.

Survival outside host

Flaviviruses are stable up to 6 hours in a liquid aerosol suspension at room temperature, and survive for long periods at room temperature when freeze-driedFootnote 33Footnote 36. Other tick-borne flaviviruses are stable in milk for 72 hours at refrigeration temperature, but are not detectable after 48 hours at room temperatureFootnote 37.

Section V – First aid/medical


In animals, initial assessment is done through surveillance of neurological symptomsFootnote 38. In both humans and animals, the virus can be isolated from bloodFootnote 4. Serologic testing for antibodies against LIV, including complement fixation, neutralization, hemagglutination inhibition and ELISA, is another alternative in diagnosing the diseaseFootnote 39; but histopathological examination provides the greatest accuracyFootnote 3Footnote 27. LIV can also be detected in clinical samples by reverse transcriptase PCRFootnote 3.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook (CBH).

First aid/treatment

There is no treatment available for louping ill disease; all care is supportiveFootnote 3. Infected animals may be sedated; however, this does not effect the outcome of the diseaseFootnote 3.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the CBH.


There is no human vaccine available. There is an animal vaccine given to sheep flocks in enzootic areasFootnote 3Footnote 18.

Note: More information on the medical surveillance program can be found in the CBH, and by consulting the Canadian Immunization Guide.



Note: More information on prophylaxis as part of the medical surveillance program can be found in the CBH.

Section VI – Laboratory hazard

Laboratory-acquired infections

From its discovery in 1934 to 1972 there were 22 cases of laboratory-acquired infectionFootnote 2. Most infections were caused by penetrative needle stick or cutting injury, or occurred after performing aerosol-generating procedures with infectious materialFootnote 2Footnote 3Footnote 28.

Note: Please consult the Canadian Biosafety Standard (CBS) and CBH for additional details on requirements for reporting exposure incidents. A Canadian biosafety guideline describing notification and reporting procedures is also available.


Blood, secretions (e.g., milk, saliva, nasal discharge), feces, infected tissue (especially brain), infected ticks.

Primary hazards

Autoinoculation with infectious material, inhalation of airborne or aerosolized infectious material, or exposure to infectious material in animal wasteFootnote 28Footnote 29.

Special hazards

Exposure to infected ticksFootnote 2Footnote 18.

Section VII – Exposure controls/personal protection

Risk group classification

Louping ill virus is a Risk Group (RG)3 Human Pathogen, a Risk Group 3 Animal Pathogen, and a Security Sensitive Biological Agent (SSBA)Footnote 40Footnote 41.

Containment requirements

Containment Level 3 facilities, equipment and operational practices outlined in the CBS are required for work with infectious or potentially infectious materials, animals, or cultures.

Note: There are additional security requirements, such as obtaining a Human Pathogens and Toxins Act Security Clearance, for work involving SSBAs.

Protective clothing

The applicable Containment Level 3 requirements for personal protective equipment and clothing outlined in the CBS to be followed. At minimum, use of full body coverage dedicated protective clothing, dedicated protective footwear and/or additional protective footwear, gloves when handling infectious materials or animals, face protection when there is a known or potential risk of exposure to splashes or flying objects, respirators when there is a risk of exposure to infectious aerosols, and an additional layer of protective clothing prior to work with infectious materials or animals.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone must be documented.

Other precautions

All activities involving open vessels of pathogens are to be performed in a certified biological safety cabinet (BSC) or other appropriate primary containment device. The use of needles, syringes, and other sharp objects to be strictly limited. Additional precautions must considered with work involving animals or large scale activities.

Section VIII – Handling and storage


Allow aerosols to settle. Wearing protective clothing, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (CBH).


Regulated materials, as well as all items and waste to be decontaminated at the containment barrier prior to removal from the containment zone, animal room, animal cubicle, or post mortem room. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the infectious material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (CBH).


The applicable Containment Level 3 requirements for storage outlined in the CBS are to be followed. Primary containers of regulated materials removed from the containment zone to be stored in a labelled, leak-proof, impact-resistant secondary container, and kept either in locked storage equipment or within an area with limited access.
SSBA: Containers of security sensitive biological agents (SSBA) stored outside the containment zone must be labelled, leakproof, impact resistant, and kept in locked storage equipment that is fixed in place (i.e., non-movable) and within an area with limited access.
An inventory of RG3 and RG4 pathogens, and SSBA toxins in long-term storage, to be maintained and to include:

Section IX – Regulatory and other information

Canadian regulatory information

Controlled activities with LIV require a Human Pathogens and Toxins Licence, issued by the Public Health Agency of CanadaFootnote 40. LIV is a non-indigenous animal pathogen in Canada; therefore, importation of LIV requires an import permit, issued by the CFIAFootnote 42. Louping ill disease is an immediately notifiable disease in CanadaFootnote 43 and infection causing louping ill is a World Organisation for Animal Health (WOAH; founded as OIE)-listed disease. The following is a non-exhaustive list of applicable designations, regulation, or legislation:

Human Pathogen and Toxins Act and Human Pathogens and Toxins Regulations
Health of Animals Act and Health of Animals Regulations
Quarantine Act
Transportation of Dangerous Goods Regulations

Last file update

December, 2019

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.


The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

Copyright © Public Health Agency of Canada, 2023, Canada


Footnote 1

International Committee on the Taxonomy of Viruses. 2019. Virus Taxonomy. The ICTV Report on Virus Classification and Taxon Nomenclature. Flaviviridae.

Return to footnote 1 referrer

Footnote 2

Davidson, M. M., H. Williams, and J. A. J. Macleod. 1991. Louping ill in man: a forgotten disease. J. Infect. 23:241-249.

Return to footnote 2 referrer

Footnote 3

Jeffries, C. L., K. L. Mansfield, L. P. Phipps, P. R. Wakeley, R. Mearns, A. Schock, S. Bell, A. C. Breed, A. R. Fooks, and N. Johnson. 2014. Louping ill virus: an endemic tick-borne disease of Great Britain. J. Gen. Virol. 95:1005-1014.

Return to footnote 3 referrer

Footnote 4

Acha, P. N., and B. Szyfres. 2003. Zoonoses and communicable diseases common to man and animals. Pan American Health Org.

Return to footnote 4 referrer

Footnote 5

Lawson, J. H., W. G. Manderson, and E. W. Hurst. 1949. Louping-ill meningo-encephalitis; a further case and a serological survey. Lancet. 2:696-699.

Return to footnote 5 referrer

Footnote 6

Williams, H., and H. Thorburn. 1962. Serum antibodies to louping-ill virus. Scott. Med. J. 7:353-355.

Return to footnote 6 referrer

Footnote 7

Reid, H. 1991. Louping-ill. In Pract. 13:157-160.

Return to footnote 7 referrer

Footnote 8

Reid, H. W., and P. C. Doherty. 1971. Experimental louping-ill in sheep and lambs. I. Viraemia and the antibody response. J. Comp. Pathol. 81:291-298.

Return to footnote 8 referrer

Footnote 9

Benavides, J., K. Willoughby, C. Underwood, B. Newman, G. Mitchell, and H. Carty. 2011. Encephalitis and neuronal necrosis in a 3-month-old suckled beef calf. Vet. Pathol. 48:E1-4.

Return to footnote 9 referrer

Footnote 10

Twomey, D. F., M. P. Cranwell, H. W. Reid, and J. F. Tan. 2001. Louping ill on Dartmoor. Vet. Rec. 149:687.

Return to footnote 10 referrer

Footnote 11

Reid, H. W., D. Buxton, and I. P. Finlayson. 1981. Experimental louping-ill virus infection of cattle. Vet. Rec. 108:497-498.

Return to footnote 11 referrer

Footnote 12

Bannatyne, C., R. Wilson, H. Reid, D. Buxton, and I. Pow. 1980. Louping-ill virus infection of pigs. Vet. Rec. 106 (1):13.

Return to footnote 12 referrer

Footnote 13

Ross, H. M., C. C. Evans, J. A. Spence, H. W. Reid, and N. Krueger. 1994. Louping ill in free-ranging pigs. Vet. Rec. 134:99-100.

Return to footnote 13 referrer

Footnote 14

Balseiro, A., L. J. Royo, C. P. Martínez, I. G. Fernández de Mera, Ú. Höfle, L. Polledo, N. Marreros, R. Casais, and J. F. Marín. 2012. Louping ill in goats, Spain, 2011. Emerg. Infect. Dis. 18:976-978.

Return to footnote 14 referrer

Footnote 15

Reid, H., R. Barlow, I. Pow, J. Maddox, and C. Evans. 1978. Isolation of louping-ill virus from red deer (Cervus elaphus). Vet. Rec. 102:463-464.

Return to footnote 15 referrer

Footnote 16

Hudson, P., E. Gould, K. Laurenson, M. Gaunt, H. Reid, L. Jones, R. Norman, K. MacGuire, and D. Newborn. 1997. The epidemiology of louping-ill, a tick borne infection of red grouse (Lagopus lagopus scoticus). Parassitologia. 39:319-323.

Return to footnote 16 referrer

Footnote 17

Reid, H. W., D. Buxton, I. Pow, and R. Moss. 1983. Experimental louping-ill virus infection of black grouse (Tetrao tetrix). Arch. Virol. 78:299-302.

Return to footnote 17 referrer

Footnote 18

Gilbert, L. 2016. Louping ill virus in the UK: a review of the hosts, transmission and ecological consequences of control. Experimental and Applied Acarology. 68:363-374.

Return to footnote 18 referrer

Footnote 19

Andersen, N. S., S. L. Larsen, C. R. Olesen, K. Stiasny, H. J. Kolmos, P. M. Jensen, and S. Skarphédinsson. 2019. Continued expansion of tick-borne pathogens: Tick-borne encephalitis virus complex and Anaplasma phagocytophilum in Denmark. Ticks and Tick-Borne Diseases. 10:115-123.

Return to footnote 19 referrer

Footnote 20

Daniel, R., B. A. M. Hopkins, M. S. Rocchi, M. Wessels, and T. Floyd. 2020. High mortality in a sheep flock caused by coinfection of louping ill virus and Anaplasma phagocytophilum. Vet Rec Case Rep. 8:e000980.

Return to footnote 20 referrer

Footnote 21

Reid, H. W., D. Buxton, I. Pow, T. A. Brodie, P. H. Holmes, and G. M. Urquhart. 1986. Response of sheep to experimental concurrent infection with tick-borne fever (Cytoecetes phagocytophila) and louping-ill virus. Res. Vet. Sci. 41:56-62.

Return to footnote 21 referrer

Footnote 22

Cranwell, M. P., M. Josephson, K. Willoughby, and L. Marriott. 2008. Louping ill in an alpaca. Vet. Rec. 162:28.

Return to footnote 22 referrer

Footnote 23

Macaldowie, C., I. A. Patterson, P. F. Nettleton, H. Low, and D. Buxton. 2005. Louping ill in llamas (Lama glama) in the Hebrides. Vet. Rec. 156:420-421.

Return to footnote 23 referrer

Footnote 24

Dagleish, M., J. Clark, C. Robson, M. Tucker, R. Orton, and M. Rocchi. 2018. A Fatal Case of Louping-ill in a Dog: Immunolocalization and Full Genome Sequencing of the Virus. J. Comp. Pathol. 165:23-32.

Return to footnote 24 referrer

Footnote 25

Smith, C. E. G., M. G. R. Varma, and D. McMahon. 1964. Isolation of louping ill virus from small mammals in Ayrshire, Scotland. Nature. 203:992.

Return to footnote 25 referrer

Footnote 26

Williams, H., H. Thorburn, and G. Ziffo. 1963. Isolation of louping ill virus from the red grouse. Nature. 200:193-194.

Return to footnote 26 referrer

Footnote 27

Sheahan, B. J., M. Moore, and G. J. Atkins. 2002. The pathogenicity of louping ill virus for mice and lambs. J. Comp. Pathol. 126:137-146.

Return to footnote 27 referrer

Footnote 28

Reid, H. W., C. Gibbs, C. Burrells, and P. C. Doherty. 1972. Laboratory infections with louping-ill virus. The Lancet. 299:592-593.

Return to footnote 28 referrer

Footnote 29

US Centers for Disease Control and Prevention, and National Institutes of Health. 2020. Biosafety in Microbiological and Biomedical Laboratories.

Return to footnote 29 referrer

Footnote 30

Reid, H. W., and I. Pow. 1985. Excretion of louping-ill virus in ewes' milk. Vet. Rec. 117:470.

Return to footnote 30 referrer

Footnote 31

Reid, H. W., D. Buxton, I. Pow, and J. Finlayson. 1984. Transmission of louping-ill virus in goat milk. Vet. Rec. 114:163-165.

Return to footnote 31 referrer

Footnote 32

Laurenson, M. K., R. A. Norman, L. Gilbert, H. W. Reid, and P. J. Hudson. 2003. Identifying disease reservoirs in complex systems: mountain hares as reservoirs of ticks and louping‐ill virus, pathogens of red grouse. J. Anim. Ecol. 72:177-185.

Return to footnote 32 referrer

Footnote 33

Gritsun, T. S., V. A. Lashkevich, and E. A. Gould. 2003. Tick-borne encephalitis. Antiviral Research. 57:129-146.

Return to footnote 33 referrer

Footnote 34

Müller, J. A., M. Harms, A. Schubert, S. Jansen, D. Michel, T. Mertens, J. Schmidt-Chanasit, and J. Münch. 2016. Inactivation and Environmental Stability of Zika Virus. Emerg. Infect. Dis. 22:1685-1687.

Return to footnote 34 referrer

Footnote 35

Thomas, S. J., T. P. Endy, A. L. Rothman, and A. D. Barrett. 2015. Flaviviruses (Dengue, Yellow Fever, Japanese Encephalitis, West Nile Encephalitis, St. Louis Encephalitis, Tick-Borne Encephalitis, Kyasanur Forest Disease, Alkhurma Hemorrhagic Fever, Zika), p. 1881. J. E. Bennett, R. Dolin, and M. J. Blaser (eds.), Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 8th ed., . Elsevier.

Return to footnote 35 referrer

Footnote 36

Karabatsos, N. 1980. General characteristics and antigenic relationships. St.Louis Encephalitis. 105-158.

Return to footnote 36 referrer

Footnote 37

Offerdahl, D. K., N. G. Clancy, and M. E. Bloom. 2016. Stability of a Tick-Borne Flavivirus in Milk. Front. Bioeng. Biotechnol. 4:40.

Return to footnote 37 referrer

Footnote 38

Reid, H., S. Rodger, and I. Aitken. 2007. Orf Diseases of Sheep. Ed ID Aitken.

Return to footnote 38 referrer

Footnote 39

Laurenson, M. K., I. J. McKendrick, H. W. Reid, R. Challenor, and G. K. Mathewson. 2007. Prevalence, spatial distribution and the effect of control measures on louping-ill virus in the Forest of Bowland, Lancashire. Epidemiol. Infect. 135:963-973.

Return to footnote 39 referrer

Footnote 40

Public Health Agency of Canada. 2019. Human Pathogens and Toxins Act (HPTA) (S.C. 2009, c.24).

Return to footnote 40 referrer

Footnote 41

Government of Canada. Jan 2019. ePATHogen - Risk Group Database. Feb 2019.

Return to footnote 41 referrer

Footnote 42

Canadian Food Inspection Agency. 2018. Health of Animals Act (S.C. 1990, c21).

Return to footnote 42 referrer

Footnote 43

Canadian Food Inspection Agency. 2009. Health of Animals Regulations. C.R.C., c. 296.

Return to footnote 43 referrer

Page details

Date modified: