Louping ill virus: Infectious substances pathogen safety data sheet

Section I – Infectious agent

Name

Louping ill virus

Agent type

Virus

Taxonomy

Family

Flaviviridae

Genus

Flavivirus

Species

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 virus^{Footnote 1} .

Characteristics

Brief description

Louping ill virus (LIV) is a positive-sense, single-stranded, enveloped RNA virus of 40-50 nm^{Footnote 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 genes^{Footnote 3} .

Section II – Hazard identification

Pathogenicity and toxicity

In humans, LIV infections are most often asymptomatic or present with a mono- or biphasic course^{Footnote 3Footnote 4}. Influenza-like symptoms, including fever, headache and muscle stiffness, last 2 to 12 days^{Footnote 2Footnote 4} . After an asymptomatic interval of approximately five days, disease progresses to an encephalitic phase in some patients^{Footnote 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 occur^{Footnote 2Footnote 4Footnote 5}. There has been one confirmed fatal case in humans^{Footnote 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 protection^{Footnote 3}. Louping ill disease is characterized by a mono- or biphasic fever^{Footnote 4}, and initial signs are often non-specific leading to poor detection rates. The initial phase is associated with fever and viremia^{Footnote 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 named^{Footnote 3Footnote 7}. Sheep may also present with muscle tremors, incoordination, circling, ataxia, and posterior paralysis^{Footnote 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 paraplegia^{Footnote 3Footnote 8}. Mortality rates range from 1-4% in adult sheep, and up to 60% in lambs^{Footnote 4}.

Serological evidence indicates that cattle and horses in louping-ill-enzootic areas are naturally infected with LIV, but do not usually develop clinical signs^{Footnote 9}. When present, neurological signs are similar to those in sheep, but animals may also experience lateral recumbency, convulsions hyperaesthesia, and hyperexitability^{Footnote 3}. Death occurred within hours in one case of horse illness, otherwise disease is rarely fatal^{Footnote 3Footnote 9Footnote 10Footnote 11}. Louping ill disease is rarely reported in pigs; however, neurological signs have been observed in LIV-infected pigs^{Footnote 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 infection^{Footnote 3Footnote 15} . Red grouse chicks are highly susceptible to disease and develop high levels of viremia^{Footnote 3Footnote 16}. Experimental studies indicate the red grouse mortality rate can be as high as 80%^{Footnote 17}.

Epidemiology

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

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

Host range

Natural host(s)

Sheep^{Footnote 3}, cattle^{Footnote 9}, deer^{Footnote 15}, pigs^{Footnote 12}, horses^{Footnote 3}, goats^{Footnote 14}, alpaca^{Footnote 22}, llama^{Footnote 23}, dog^{Footnote 24}, mountain hares^{Footnote 18}, and small mammals, such as the common shrew and wood mouse^{Footnote 25}. The red grouse is a natural dead-end host^{Footnote 26}.

Other host(s)

Mice^{Footnote 27}, black grouse^{Footnote 17}.

Infectious dose

Unknown.

Incubation period

The incubation period averages 8-13 days in sheep^{Footnote 3Footnote 27} and approximately 1 week in humans^{Footnote 28}.

Communicability

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 slaughterhouse^{Footnote 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 humans^{Footnote 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 Ricinus^{Footnote 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 LIV^{Footnote 12}, indicating that ingestion is a possible transmission route.

Section III – Dissemination

Reservoir

LIV is maintained in sheep, and mountain hares are possible reservoirs^{Footnote 25Footnote 32}.

Zoonosis

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

Vectors

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

Section IV – Stability and viability

Drug susceptibility/resistance

None.

Susceptibility to disinfectants

Flaviviruses are sensitive to 1% sodium hypochlorite, 2% glutaraldehyde, 70% ethanol, paraformaldehyde, iodophors, and 3-6% hydrogen peroxide^{Footnote 33Footnote 34Footnote 35}. Some flaviviruses are also susceptible to organic solvents and detergents, such as Triton-X^{Footnote 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-dried^{Footnote 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 temperature^{Footnote 37}.

Section V – First aid/medical

Surveillance

In animals, initial assessment is done through surveillance of neurological symptoms^{Footnote 38}. In both humans and animals, the virus can be isolated from blood^{Footnote 4}. Serologic testing for antibodies against LIV, including complement fixation, neutralization, hemagglutination inhibition and ELISA, is another alternative in diagnosing the disease^{Footnote 39}; but histopathological examination provides the greatest accuracy^{Footnote 3Footnote 27}. LIV can also be detected in clinical samples by reverse transcriptase PCR^{Footnote 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 supportive^{Footnote 3}. Infected animals may be sedated; however, this does not effect the outcome of the disease^{Footnote 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.

Immunization

There is no human vaccine available. There is an animal vaccine given to sheep flocks in enzootic areas^{Footnote 3Footnote 18}.

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

Prophylaxis

None.

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 infection^{Footnote 2}. Most infections were caused by penetrative needle stick or cutting injury, or occurred after performing aerosol-generating procedures with infectious material^{Footnote 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.

Sources/specimens

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 waste^{Footnote 28Footnote 29}.

Special hazards

Exposure to infected ticks^{Footnote 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

Spills

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).

Disposal

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).

Storage

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:

• specific identification of the regulated materials
• a mechanism that allows for the detection of a missing or stolen sample in a timely manner

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 Canada^{Footnote 40}. LIV is a non-indigenous animal pathogen in Canada; therefore, importation of LIV requires an import permit, issued by the CFIA^{Footnote 42}. Louping ill disease is an immediately notifiable disease in Canada^{Footnote 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.

Disclaimer

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.

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