Louping ill virus
I. Organism Information
A. Taxonomy Information
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Species:
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Louping ill virus
(Website 1):
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Ontology: UMLS:C0024026
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GenBank Taxonomy No.:
11086
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Description:
The Flaviviridae are a family of over 60 viruses transmitted mainly by mosquito or tick vectors and causing many diseases of man and animals including yellow fever, Japanese encephalitis, dengue, louping ill and tick-borne encephalitis (TBE). Louping ill virus (LIV), which is endemic in upland areas of the UK and Ireland, causes non-suppurative meningoencephalomyelitis in sheep, cattle, horses, pigs, dogs, deer, red grouse, other wildlife species and occasionally man. The natural vector is the tick, Ixodes ricinus. Transmission of LIV to laboratory workers by aerosol infection has been reported (Sheahan et al., 2002).
The name 'louping ill' is derived from the old Scots language describing the effect of encephalitis in sheep causing them to 'loup' or spring into the air (Davidson et al., 1991).
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Variant(s):
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Louping ill virus (strain Negishi 3248/49/P10)
(Website 4):
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GenBank Taxonomy No.:
36388
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Parent:
Louping ill virus
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Description:
Negishi virus (NEG) was originally isolated from a fatal case of encephalitis during and epidemic of Japanese encephalitis in Japan in 1948 and at this time no other tick-borne flaviviruses were being used in the laboratory. NEG virus is serologically related to Russian spring summer encephalitis (RSSE) virus. Subsequent antigenic studies confirmed the close relationship of NEG virus with LI virus and the central European subtype of TBE virus. This relationship has now been investigated more precisely using monoclonal antibodies and nucleotide sequencing. Results are presented suggesting that NEG virus is a strain of LI virus (Venugopal et al., 1992).
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Louping ill virus (strain Norway)
(Website 5):
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Louping ill virus (strain SB 526)
(Website 6):
B. Lifecycle Information:
No lifecycle information is currently available here.
C. Genome Summary:
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Genome of
Louping ill virus
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Description:
The genome of LI virus and other flaviviruses comprises a single open reading frame (ORF) approximately 11 kb in length. This ORF encodes a polyprotein consisting of three structural (capsid, premembrane and envelope) and seven nonstructural proteins. The envelope (E) protein is the major structural protein and plays an important role in membrane binding and inducing a protective immune response following virus infection (McGuire et al., 1998).
The genomic RNA of flaviviruses is single-stranded and approximately 11 kilobases in length. The genomic RNA is infectious, and thus of poisitive polarity encoding the viral proteins necessary for RNA replication. Genome-length RNAs appear to be the only virus-specific mRNA molecules in flaivirus-infected cells (Chambers et al., 1990).
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Single RNA strand (Website 7):
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GenBank Accession Number:
NC_001809
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Size:
10871 bp ss-RNA (Website 7)
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Gene Count:
The virion RNA is translated into a polyprotein from which structural and non-structural proteins are processed by cellular and viral proteases (Gritsun et al., 1997).
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Description:
Sequence analysis of the genomic RNAs of several flaviviruses has revealed that they are organized similarly. The viruses are enveloped particles about 50 nm in diameter containing a single stranded RNA molecule, approximately 11 kb in length, of positive sense coding for three structural proteins, designated capsid (C), membrane (M), envelope (E), and seven non-structural proteins designated NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5. The virion RNA is translated into a polyprotein from which structural and non-structural proteins are processed by cellular and viral proteases (Gritsun et al., 1997).
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Picture(s):
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Louping ill virus, complete genome (Website 8):
II. Epidemiology Information
Louping ill is best known as a disease of sheep reared on rough hill pastures in Scotland, northern England, Wales and Ireland. These are the areas which will support the vector, Ixodes ricinus the sheep tick which has three hosts and a life span of 3 years (Davidson et al., 1991).
A similar disease in sheep, reported in Norway, is caused by LIV-infected sheep/ticks introduced from mainland Britain (Gritsun et al., 1997).
A. Outbreak Locations:
No epidemic outbreak information is currently available here.
B. Transmission Information:
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From:
Ixodes ricinus To:
Vertebrates
Mechanism:
Ticks that find a host attach with their mouth parts and, following an initial period when saliva is injected, remove and concentrate blood over a period of 3-10 days (Reid, 1984).
Only nymphs and adults that have become infected by ingesting virus with a previous blood meal can transmit virus (Reid, 1984).
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From:
Vertebrates To:
Ixodes ricinus
Mechanism:
The infection of ticks with virus is complex. Blood is ingested for several days during which the titre of viraemia in the vertebrate will change, and the tick feeds in two distinct phases. Furthermore, not only does virus have to establish in the tick but it must also find its way to the salivary gland of the succeeding instar. Initial investigations in which larvae were fed on laboratory mice infected with louping ill indicated that although viraemias in excess of 10(4) plaque-forming units (p.f.u.) per 0.2 ml of blood occurred, this was insufficient to establish infection in larval ticks. However, experiments with day-old domestic chicks met with greater success and the incidence of infection in freshly engorged larvae approached 100%, the incidence of infection rapidly declined to 10% and remained at this level throughout the moulting process and for the succeeding 2 months. It was subsequently shown that the virus concentration in the blood during the initial feeding phase was directly related to the proportion of the ticks in which infection became established and that this proportion approached 40% as viraemias of 10(6) p.f.u. per 0.2 ml of blood were attained (Reid, 1984).
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From:
Vertebrates To:
Vertebrates
Mechanism:
Experimentally, LI virus has been shown to be shed in the milk of goats and ewes following infection with the virus. While titers of a virus in the milk of both species were similar, virus was shed for a longer period in goats. Transmission of virus presumably through the ingestion of infective mild was demonstrated in kids that suckled infected goats. Similar attempts to transmit the virus in sheep were unsuccessful (Timoney, 1992).
Louping-ill has been transmitted experimentally to various animal species by several parenteral routes of inoculation and following exposure to infective aerosols. Accidental infection of man has occurred following tick-bite, penetration of the virus through skin wounds or by aerosol (Timoney, 1992).
C. Environmental Reservoir:
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Sheep
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Description:
Of the mammalian species experimentally infected, only sheep consistently developed viremias of a sufficient intensity to infect the vector and are thus the only species that is likely to have a significant role in the maintenance of louping-ill virus (Reid, 1988).
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Survival Information:
In experimental studies, 22 of 33 six month-old sheep inoculated subcutaneously (s.c.) with 10(7) mouse LD(50), or cell culture plaque-forming unit (p.f.u.) doses of virus were moribund within 6 to 11 days (mean 8 days). Ataxia rapidly progressed to complete flaccid paralysis within 3 to 5 hr. Two of eleven which survived were 'chronically debilitated' (Smith and Varma, 1981).
D. Intentional Releases:
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Intentional Release information
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Description:
Tick-borne flaviviruses are excreted in the urine and faeces of experimentally infected animals but it is unlikely that this form of virus would provide an efficient route of infection for humans. Perhaps their greatest weakness as biological weapons is the fact that they are normally transmitted to vertebrate hosts via the bite of an infected tick, and the natural habitat of ticks is the forest or moist thick grassy vegetation as found on uplands. Under most circumstances this means that humans and even most animals would be a dead-end for virus transmission because few humans are exposed to the bite of a tick. Another important factor is that these viruses are all antigenically closely related. Therefore, immunity against one strain is likely to produce cross-immunity against the others. Moreover, in endemic regions there is a reasonably high level of immunity amongst the indigenous viruses (Gritsun et al., 2003).
These viruses are unlikely to be the most effective front line weapons in biological warfare but they might be capable of causing significant problems on a small scale (Gritsun et al., 2003).
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Delivery mechanism:
In the con of bioterrorism, we have shown that the tick-borne flaviviruses are pathogenic for humans and some animals. Some strains are more virulent than others but even the most virulent viruses are unlikely to produce high fatality rates. These viruses can infect via the alimentary tract and also when inoculated intranasally into experimental animals. Presumably, therefore concentrated aerosols would be infectious or high virus concentrations delivered as a powder contaminating food might infect a significant proportion of people eating the food (Gritsun et al., 2003).
One can ask the question whether or not it is feasible to spread the virus by infecting large numbers of ticks with the virus. This would not be a logical approach for the following reasons: (a) very large numbers of infected ticks would be required and logistically this would be technically extremely difficult; (b) ticks only feed three times, at very critical stages of their life cycle and it would be extremely difficult to arrange for them to be infected and ready to feed when delivered as weapons; (c) the production of a sufficiently large number of ticks to pose a threat to human or animal populations would also be a difficult technical exercise (Gritsun et al., 2003).
III. Infected Hosts
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Human:
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Taxonomy Information:
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Species:
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Human
(Website 25):
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Ontology: UMLS:C0086418
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GenBank Taxonomy No.:
9606
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Scientific Name:
Homo sapiens (Website 25)
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Description:
The first report of human infection was made in 1934, and described four cases in laboratory personnel directly involved with louping ill virus. Subsequently seven other groups reported 22 instances of illness in laboratory workers, the last in 1972. Naturally occurring infection in man was first reported in 1948. Two cases of encephalitis, one in a veterinary surgeon and one in a farmer were described. Nine further cases were reported between 1948 and 1962 but none since (Davidson et al., 1991).
At least 26 laboratory acquired human cases have been reported. Nine naturally acquired human cases have been described, five of them probably exposed to tick bites, and four in which the source of infection could not be determined. One person had been skinning tick-infested sheep prior to his onset of illness. Serological evidence exists of subclinical human infections (Smith and Varma, 1981).
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Infection Process:
No infection process information is currently available here.
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Disease Information:
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Louping ill
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Incubation Period:
The incubation period is 4 to 7 days (Burke and Monath, 2001).
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Prognosis:
There have been no fatalities, but convalescence may take up to 3 months (Shope, 2003).
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Diagnosis Overview:
The earliest cases of louping ill in man were confirmed by isolation of virus or neutralization tests in animals. These were cumbersome methods and carried considerable risk to laboratory personnel. The development of complement fixation tests (CFT) and haemagglutination inhibition tests (HAI) for arboviruses allowed easier laboratory regimes but neither of these tests were highly sensitive and small amounts of antibody could be missed. Over the years improvements in antigen preparation and laboratory techniques have led to more sensitive diagnostic methods. Today enzyme-linked immunosorbent assay (ELISA) using commercially prepared TBE antigen is available. This avoids the use of in-house antigen preparations, leads to better standardization of tests and reduces the risk of laboratory-acquired infection. Rising titers or repeated high titers are regarded as indicative of current or recent infection. Falling titers or small amounts of antibody should ideally be complemented by additional evidence such as the presence of specific IgM antibody (Davidson et al., 1991).
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Symptom Information
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Syndrome --
Louping ill:
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Description:
The disease in human patients is characteristically biphasic, closely resembling the biphasic meningoencephalitis caused by the very closely related Central European tick-borne encephalitis virus which is also transmitted by I. ricinus. After an incubation period estimated as 4 to 7 days, the first "influenzal" phase lasts 2 to 11 days, followed by an asymptomatic interval of 5 to 15 days (usually 5 to 6 days), and then by the second meningoencephalomyelitis phase, with a febrile period lasting 4 to 10 days. Either phase may be completely unapparent, or so mild as to go unrecognized (Smith and Varma, 1981).
The most commonly reported syndrome has been an influenza-like illness which has resolved in about a week. This illness is characterized by fever up to 39.5 C, headache, anorexia, dizziness and muscle stiffness. This has been described most often in laboratory-acquired infections, but appears to be less common in naturally-acquired disease. It is possible that this febrile syndrome may occur often but is not detected (Davidson et al., 1991).
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Observed:
Fourteen of the 37 published cases have had only this short febrile episode (Davidson et al., 1991).
Symptoms Shown in the Syndrome:
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Fever (Davidson et al., 1991):
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Description:
The first phase is characterized by fever, headache (sometimes severe), weakness and anorexia with various combinations of muscle or joint pains or tenderness (often lumbar, also legs, neck), retro-orbital pain, photophobia, conjunctivitis, diplopia, excessive sweating (sometimes without fever), insomnia, drowsiness, nausea, vomiting (sometimes projectile), and tender lymphadenitis (cervical except in one case where axillary glands were also involved), with or without pharyngitis (Smith and Varma, 1981).
After the symptomless interval, the second phase is characterized by severe headache, fever, vomiting, bradycardia, drowsiness (which may develop into coma), confusion, and sometimes delirium, tremors, nystagmus, or ataxia. Some patients develop diplopia, blurred vision, slurred speech, and excessive sweating in the absence of fever (Smith and Varma, 1981).
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Headache (Davidson et al., 1991):
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Description:
The first phase is characterized by fever, headache (sometimes severe), weakness and anorexia with various combinations of muscle or joint pains or tenderness (often lumbar, also legs, neck), retro-orbital pain, photophobia, conjunctivitis, diplopia, excessive sweating (sometimes without fever), insomnia, drowsiness, nausea, vomiting (sometimes projectile), and tender lymphadenitis (cervical except in one case where axillary glands were also involved), with or without pharyngitis (Smith and Varma, 1981).
After the symptomless interval, the second phase is characterized by severe headache, fever, vomiting, bradycardia, drowsiness (which may develop into coma), confusion, and sometimes delirium, tremors, nystagmus, or ataxia. Some patients develop diplopia, blurred vision, slurred speech, and excessive sweating in the absence of fever (Smith and Varma, 1981).
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Weakness (Smith and Varma, 1981):
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Description:
The first phase is characterized by fever, headache (sometimes severe), weakness and anorexia with various combinations of muscle or joint pains or tenderness (often lumbar, also legs, neck), retro-orbital pain, photophobia, conjunctivitis, diplopia, excessive sweating (sometimes without fever), insomnia, drowsiness, nausea, vomiting (sometimes projectile), and tender lymphadenitis (cervical except in one case where axillary glands were also involved), with or without pharyngitis (Smith and Varma, 1981).
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Anorexia (Davidson et al., 1991):
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Description:
The first phase is characterized by fever, headache (sometimes severe), weakness and anorexia with various combinations of muscle or joint pains or tenderness (often lumbar, also legs, neck), retro-orbital pain, photophobia, conjunctivitis, diplopia, excessive sweating (sometimes without fever), insomnia, drowsiness, nausea, vomiting (sometimes projectile), and tender lymphadenitis (cervical except in one case where axillary glands were also involved), with or without pharyngitis (Smith and Varma, 1981).
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Dizziness (Davidson et al., 1991):
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Description:
This illness is characterized by fever up to 39.5 C, headache, anorexia, dizziness, and muscle stiffness (Davidson et al., 1991).
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Muscle or Joint pain (Smith and Varma, 1981):
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Ontology: UMLS:C0231528, C0003862
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Description:
The first phase is characterized by fever, headache (sometimes severe), weakness and anorexia with various combinations of muscle or joint pains or tenderness (often lumbar, also legs, neck), retro-orbital pain, photophobia, conjunctivitis, diplopia, excessive sweating (sometimes without fever), insomnia, drowsiness, nausea, vomiting (sometimes projectile), and tender lymphadenitis (cervical except in one case where axillary glands were also involved), with or without pharyngitis (Smith and Varma, 1981).
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Retro-orbital pain (Smith and Varma, 1981):
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Description:
The first phase is characterized by fever, headache (sometimes severe), weakness and anorexia with various combinations of muscle or joint pains or tenderness (often lumbar, also legs, neck), retro-orbital pain, photophobia, conjunctivitis, diplopia, excessive sweating (sometimes without fever), insomnia, drowsiness, nausea, vomiting (sometimes projectile), and tender lymphadenitis (cervical except in one case where axillary glands were also involved), with or without pharyngitis (Smith and Varma, 1981).
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Photophobia (Smith and Varma, 1981):
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Description:
The first phase is characterized by fever, headache (sometimes severe), weakness and anorexia with various combinations of muscle or joint pains or tenderness (often lumbar, also legs, neck), retro-orbital pain, photophobia, conjunctivitis, diplopia, excessive sweating (sometimes without fever), insomnia, drowsiness, nausea, vomiting (sometimes projectile), and tender lymphadenitis (cervical except in one case where axillary glands were also involved), with or without pharyngitis (Smith and Varma, 1981).
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Conjunctivitis (Smith and Varma, 1981):
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Description:
The first phase is characterized by fever, headache (sometimes severe), weakness and anorexia with various combinations of muscle or joint pains or tenderness (often lumbar, also legs, neck), retro-orbital pain, photophobia, conjunctivitis, diplopia, excessive sweating (sometimes without fever), insomnia, drowsiness, nausea, vomiting (sometimes projectile), and tender lymphadenitis (cervical except in one case where axillary glands were also involved), with or without pharyngitis (Smith and Varma, 1981).
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Diplopia:
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Description:
The first phase is characterized by fever, headache (sometimes severe), weakness and anorexia with various combinations of muscle or joint pains or tenderness (often lumbar, also legs, neck), retro-orbital pain, photophobia, conjunctivitis, diplopia, excessive sweating (sometimes without fever), insomnia, drowsiness, nausea, vomiting (sometimes projectile), and tender lymphadenitis (cervical except in one case where axillary glands were also involved), with or without pharyngitis (Smith and Varma, 1981).
After the symptomless interval, the second phase is characterized by severe headache, fever, vomiting, bradycardia, drowsiness (which may develop into coma), confusion, and sometimes delirium, tremors, nystagmus, or ataxia. Some patients develop diplopia, blurred vision, slurred speech, and excessive sweating in the absence of fever (Smith and Varma, 1981).
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Excessive sweating (Smith and Varma, 1981):
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Description:
The first phase is characterized by fever, headache (sometimes severe), weakness and anorexia with various combinations of muscle or joint pains or tenderness (often lumbar, also legs, neck), retro-orbital pain, photophobia, conjunctivitis, diplopia, excessive sweating (sometimes without fever), insomnia, drowsiness, nausea, vomiting (sometimes projectile), and tender lymphadenitis (cervical except in one case where axillary glands were also involved), with or without pharyngitis (Smith and Varma, 1981).
After the symptomless interval, the second phase is characterized by severe headache, fever, vomiting, bradycardia, drowsiness (which may develop into coma), confusion, and sometimes delirium, tremors, nystagmus, or ataxia. Some patients develop diplopia, blurred vision, slurred speech, and excessive sweating in the absence of fever (Smith and Varma, 1981).
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Insomnia (Smith and Varma, 1981):
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Description:
The first phase is characterized by fever, headache (sometimes severe), weakness and anorexia with various combinations of muscle or joint pains or tenderness (often lumbar, also legs, neck), retro-orbital pain, photophobia, conjunctivitis, diplopia, excessive sweating (sometimes without fever), insomnia, drowsiness, nausea, vomiting (sometimes projectile), and tender lymphadenitis (cervical except in one case where axillary glands were also involved), with or without pharyngitis (Smith and Varma, 1981).
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Drowsiness (Davidson et al., 1991):
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Description:
The first phase is characterized by fever, headache (sometimes severe), weakness and anorexia with various combinations of muscle or joint pains or tenderness (often lumbar, also legs, neck), retro-orbital pain, photophobia, conjunctivitis, diplopia, excessive sweating (sometimes without fever), insomnia, drowsiness, nausea, vomiting (sometimes projectile), and tender lymphadenitis (cervical except in one case where axillary glands were also involved), with or without pharyngitis (Smith and Varma, 1981).
After the symptomless interval, the second phase is characterized by severe headache, fever, vomiting, bradycardia, drowsiness (which may develop into coma), confusion, and sometimes delirium, tremors, nystagmus, or ataxia (Smith and Varma, 1981).
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Nausea, Vomiting (Smith and Varma, 1981):
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Ontology: UMLS:C0027497, C0042963
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Description:
The first phase is characterized by fever, headache (sometimes severe), weakness and anorexia with various combinations of muscle or joint pains or tenderness (often lumbar, also legs, neck), retro-orbital pain, photophobia, conjunctivitis, diplopia, excessive sweating (sometimes without fever), insomnia, drowsiness, nausea, vomiting (sometimes projectile), and tender lymphadenitis (cervical except in one case where axillary glands were also involved), with or without pharyngitis (Smith and Varma, 1981).
After the symptomless interval, the second phase is characterized by severe headache, fever, vomiting, bradycardia, drowsiness (which may develop into coma), confusion, and sometimes delirium, tremors, nystagmus, or ataxia (Smith and Varma, 1981).
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Tender lymphadenitis (Smith and Varma, 1981):
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Description:
The first phase is characterized by fever, headache (sometimes severe), weakness and anorexia with various combinations of muscle or joint pains or tenderness (often lumbar, also legs, neck), retro-orbital pain, photophobia, conjunctivitis, diplopia, excessive sweating (sometimes without fever), insomnia, drowsiness, nausea, vomiting (sometimes projectile), and tender lymphadenitis (cervical except in one case where axillary glands were also involved), with or without pharyngitis (Smith and Varma, 1981).
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Pharyngitis (Smith and Varma, 1981):
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Description:
The first phase is characterized by fever, headache (sometimes severe), weakness and anorexia with various combinations of muscle or joint pains or tenderness (often lumbar, also legs, neck), retro-orbital pain, photophobia, conjunctivitis, diplopia, excessive sweating (sometimes without fever), insomnia, drowsiness, nausea, vomiting (sometimes projectile), and tender lymphadenitis (cervical except in one case where axillary glands were also involved), with or without pharyngitis (Smith and Varma, 1981).
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Bradycardia (Smith and Varma, 1981):
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Description:
After the symptomless interval, the second phase is characterized by severe headache, fever, vomiting, bradycardia, drowsiness (which may develop into coma), confusion, and sometimes delirium, tremors, nystagmus, or ataxia (Smith and Varma, 1981).
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Coma (Smith and Varma, 1981):
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Description:
After the symptomless interval, the second phase is characterized by severe headache, fever, vomiting, bradycardia, drowsiness (which may develop into coma), confusion, and sometimes delirium, tremors, nystagmus, or ataxia (Smith and Varma, 1981).
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Confusion (Smith and Varma, 1981):
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Description:
After the symptomless interval, the second phase is characterized by severe headache, fever, vomiting, bradycardia, drowsiness (which may develop into coma), confusion, and sometimes delirium, tremors, nystagmus, or ataxia (Smith and Varma, 1981).
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Delirium (Smith and Varma, 1981):
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Description:
After the symptomless interval, the second phase is characterized by severe headache, fever, vomiting, bradycardia, drowsiness (which may develop into coma), confusion, and sometimes delirium, tremors, nystagmus, or ataxia (Smith and Varma, 1981).
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Tremor of head and limbs (Davidson et al., 1991):
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Ontology: UMLS:C0239882, C0235081
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Description:
After the symptomless interval, the second phase is characterized by severe headache, fever, vomiting, bradycardia, drowsiness (which may develop into coma), confusion, and sometimes delirium, tremors, nystagmus, or ataxia (Smith and Varma, 1981).
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Nystagmus (Smith and Varma, 1981):
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Description:
After the symptomless interval, the second phase is characterized by severe headache, fever, vomiting, bradycardia, drowsiness (which may develop into coma), confusion, and sometimes delirium, tremors, nystagmus, or ataxia (Smith and Varma, 1981).
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Ataxia (Smith and Varma, 1981):
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Description:
After the symptomless interval, the second phase is characterized by severe headache, fever, vomiting, bradycardia, drowsiness (which may develop into coma), confusion, and sometimes delirium, tremors, nystagmus, or ataxia (Smith and Varma, 1981).
Like the symptoms, physical signs have been highly variable, including neck stiffness, Kernig's sign, loss of reflexes, papilloedema, retrobular neuritis, ataxia, and pyramidal signs (Smith and Varma, 1981).
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Blurred vision (Smith and Varma, 1981):
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Description:
Some patients develop diplopia, blurred vision, slurred speech, and excessive sweating in the absence of fever (Smith and Varma, 1981).
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Slurred speech (Smith and Varma, 1981):
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Description:
Some patients develop diplopia, blurred vision, slurred speech, and excessive sweating in the absence of fever (Smith and Varma, 1981).
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Papular abdominal rash (Smith and Varma, 1981):
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Description:
Other less commonly seen symptoms include papular abdominal rash, vesicles on the palate, subconjunctival hemorrhages, deafness, severe diarrhea, and incontinence (Smith and Varma, 1981).
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Vesicles on the palate (Smith and Varma, 1981):
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Description:
Other less commonly seen symptoms include papular abdominal rash, vesicles on the palate, subconjunctival hemorrhages, deafness, severe diarrhea, and incontinence (Smith and Varma, 1981).
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Subconjunctival hemorrhages (Smith and Varma, 1981):
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Description:
Other less commonly seen symptoms include papular abdominal rash, vesicles on the palate, subconjunctival hemorrhages, deafness, severe diarrhea, and incontinence (Smith and Varma, 1981).
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Deafness (Smith and Varma, 1981):
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Description:
Other less commonly seen symptoms include papular abdominal rash, vesicles on the palate, subconjunctival hemorrhages, deafness, severe diarrhea, and incontinence (Smith and Varma, 1981).
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Diarrhea (Smith and Varma, 1981):
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Description:
Other less commonly seen symptoms include papular abdominal rash, vesicles on the palate, subconjunctival hemorrhages, deafness, severe diarrhea, and incontinence (Smith and Varma, 1981).
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Incontinence (Smith and Varma, 1981):
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Description:
Other less commonly seen symptoms include papular abdominal rash, vesicles on the palate, subconjunctival hemorrhages, deafness, severe diarrhea, and incontinence (Smith and Varma, 1981).
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Neck stiffness (Smith and Varma, 1981):
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Description:
After the symptomless interval, the second phase is characterized by severe headache, fever, vomiting, bradycardia, drowsiness (which may develop into coma), confusion, and sometimes delirium, tremors, nystagmus, or ataxia. Some patients develop diplopia, blurred vision, slurred speech, and excessive sweating in the absence of fever. Other less commonly seen symptoms include papular abdominal rash, vesicles on the palate, subconjunctival hemorrhages, deafness, severe diarrhea, and incontinence. Paralysis may involve one or both lower limbs or may be limited to ptosis of one eyelid or strabismus. Like the symptoms, physical signs have been highly variable, including neck stiffness, Kernig's sign, loss of reflexes, papilloedema, retrobular neuritis, ataxia, and pyramidal signs (Smith and Varma, 1981)
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Kernig's sign (Smith and Varma, 1981):
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Description:
Like the symptoms, physical signs have been highly variable, including neck stiffness, Kernig's sign, loss of reflexes, papilloedema, retrobular neuritis, ataxia, and pyramidal signs (Smith and Varma, 1981).
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Loss of Reflexes (Smith and Varma, 1981):
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Description:
Like the symptoms, physical signs have been highly variable, including neck stiffness, Kernig's sign, loss of reflexes, papilloedema, retrobular neuritis, ataxia, and pyramidal signs (Smith and Varma, 1981).
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Papilloedema (Smith and Varma, 1981):
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Description:
Like the symptoms, physical signs have been highly variable, including neck stiffness, Kernig's sign, loss of reflexes, papilloedema, retrobular neuritis, ataxia, and pyramidal signs (Smith and Varma, 1981).
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Retrobulbar neuritis (Smith and Varma, 1981):
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Description:
Like the symptoms, physical signs have been highly variable, including neck stiffness, Kernig's sign, loss of reflexes, papilloedema, retrobular neuritis, ataxia, and pyramidal signs (Smith and Varma, 1981).
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Pyramidal signs (Smith and Varma, 1981):
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Description:
Like the symptoms, physical signs have been highly variable, including neck stiffness, Kernig's sign, loss of reflexes, papilloedema, retrobular neuritis, ataxia, and pyramidal signs (Smith and Varma, 1981).
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Paralysis (Davidson et al., 1991):
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Syndrome --
Hemorrhagic fever:
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Description:
The most unusual manifestation of the disease was reported in 1963. This described a haemorrhagic fever in a laboratory technician working with Korean haemorrhagic fever samples. Two viruses were isolated from his blood, both of which were identified as louping ill virus at the Rockefeller Institute in New York. There have been no other reports of this type of illness associated with louping ill, although closely related viruses Omsk Haemorrhagic Fever virus and Kyasanur Forest Disease virus do cause haemorrhagic disease (Davidson et al., 1991).
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Observed:
One of 37 published cases (Davidson et al., 1991).
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LIV:
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Description:
The clinical picture of humans infected with LIV is very similar to that produced by European subtypes of TBEV. The first phase of disease is characterized by fever, lasting 2-11 days, followed by remission lasting 5-6 days, and then the reappearance of fever and meningoencephalitis lasting 4-10 days. There have been very few reported cases of encephalitis in humans, mostly among laboratory personnel. Although the virus is potentially a serious threat, human exposure to LIV is rare and probably most often results in subclinical infections (Gritsun et al., 1997).
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Treatment Information:
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Prevention:
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Tick control (Reid, 1988):
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Ontology: UMLS:C0040195
-
Description:
The major role that sheep have in the maintenance of I. ricinus suggests that the tick would be vulnerable to control by the systematic application of insecticidal sheep dips. No such study has been made, although it is the opinion of many sheep farmers that ticks have become a much greater problem since sheep dips incorporation dieldrin have been withdrawn. Most sheep dips currently available are effective against ticks for only a limited period. In addition, as the period of maximum tick activity alters according to weather, latitude, and altitude, the most appropriate time to dip for the control of ticks varies from year to year and between regions. Furthermore, problems with sheep management, such as abortion and mismothering of lambs following dipping, can render strategic dipping impractical. Thus, the use of sheep dips has only a limited role in tick control (Reid, 1988).
-
Efficacy:
-
Duration:
Most sheep dips currently available are effective against ticks for only a limited period (Reid, 1988).
-
Complication:
Furthermore, problems with sheep management, such as abortion and mismothering of lambs following dipping, can render strategic dipping impractical (Reid, 1988).
-
Sheep management (Reid, 1988):
-
Description:
A system of sheep management designed to provide areas of improved pasture and the use of hill grazing only during midsummer and winter, the periods when is minimal tick activity, can succeed in dramatically reducing tick infestation (Reid, 1988).
-
Chlorpyrifos application (Reid, 1988):
-
Ontology: UMLS: C0013328
-
Description:
The application of insecticide (chlorpyrifos) directly to pasture has been reported to reduce tick infestation markedly, but the economic considerations and environmental implications of this procedure make such a strategy both unfeasible and unacceptable (Reid, 1988).
-
Vaccine (Reid, 1988):
-
Ontology: UMLS:C0042210
-
Description:
Shortly after the discovery of the viral etiology of louping-ill, a vaccine consisting of homogenized, formalin treated brains from experimentally infected sheep was developed and widely deployed. It was considered that while this vaccine failed to induce a detectable immune reaction, it sensitized animals to viral antigens so that on exposure to natural challenge the immune response was accelerated and provided protection from clinical encephalitis (Reid, 1988).
This crude vaccine was subsequently replaced by one prepared from virus propagated in BHK-21 cell, inactivated with formalin, and incorporated in an oil-based adjuvant. This vaccine induced substantial titers of HI and neutralizing antibody and provided complete protection both from disease and from the establishment of infections. The systematic administration of such a vaccine to sheep, the one essential maintenance host, should interrupt the transmission of louping-ill virus, and over a period of 2 to 3 years eliminate it from an area. Militating against such a strategy is the possible introduction of virus-infected ticks from adjacent properties carried by wild or domestic animals and difficulties in ensuring that all sheep on an extensive grazing are vaccinated. Thus, to overcome these problems, a test site was selected on an island to which the lateral spread of ticks was considered to be insignificant (Reid, 1988).
-
Efficacy:
-
Duration:
Following 3 successive years when all sheep were vaccinated, the bovine calves employed as sentinels did not show evidence of infection. However, in the following years some cattle did seroconvert, indicating that virus had survived (Reid, 1988).
-
Complication:
It was considered that virus persistence on the island was due at least in part to problems with the shelf life of the vaccine which were experienced at the time, and thus all sheep may not have been fully protected (Reid, 1988).
-
Model System:
-
Sheep:
-
Ontology: UMLS:C1123019
-
Model Host:
Ovis aries
.
Ovis aires (Fleeton et al., 2000)
-
Model Pathogens:
-
Description:
Sheep represent a large animal model for experimentation, which is cheaper and easier to manipulate than other models, and it should be possible to conduct field trials of any recombinant vaccine produced for this virus, since outbreaks of louping ill occur in predictable isolated areas with sparse human populations (Fleeton et al., 2000).
-
Mice:
-
Ontology: UMLS:C0025929
-
Model Host:
Vertebrates.
Mus musculus BALB/C (Sheahan et al., 2002)
-
Model Pathogens:
-
Description:
Mice and lambs were infected with the LI/I, LI/31 or MA54 strain of louping ill virus (LIV) to provide information relevant to testing the efficacy and biosafety of a new generation of flavivirus vaccines based on a Semliki Forest virus (SFV) vector (Sheahan et al., 2002).
-
Rhesus monkey:
-
Ontology: UMLS:C0024400
-
Model Host:
Vertebrates.
Macaca mulatta (Zlontnik et al., 1976)
-
Model Pathogens:
-
Description:
Rhesus, patas and vervet monkeys were infected i.c. or i.n. with three viruses of the tick-borne encephalitis complex (TBE) as follows: Turkish tick-borne encephalitis virus (TTE), Louping-ill virus and Central European tick-borne encephalitis virus (CETE). The incidence of overt clinical signs of disease varied according to the virus that was used for the inoculations. TTE proved to be more pathogenic for monkeys than the other two members of the complex, whilst CETE was the least pathogenic (Zlontnik et al., 1976).
-
Patas monkey:
-
Ontology: UMLS:C0014763
-
Model Host:
Vertebrates.
Erythrocebus patas (Zlontnik et al., 1976)
-
Model Pathogens:
-
Description:
Rhesus, patas and vervet monkeys were infected i.c. or i.n. with three viruses of the tick-borne encephalitis complex (TBE) as follows: Turkish tick-borne encephalitis virus (TTE), Louping-ill virus and Central European tick-borne encephalitis virus (CETE). The incidence of overt clinical signs of disease varied according to the virus that was used for the inoculations. TTE proved to be more pathogenic for monkeys than the other two members of the complex, whilst CETE was the least pathogenic (Zlontnik et al., 1976).
-
Vervet monkey:
-
Ontology: UMLS:C0026438
-
Model Host:
Vertebrates.
Cercopithecus aethiops (Zlontnik et al., 1976)
-
Model Pathogens:
-
Description:
Rhesus, patas and vervet monkeys were infected i.c. or i.n. with three viruses of the tick-borne encephalitis complex (TBE) as follows: Turkish tick-borne encephalitis virus (TTE), Louping-ill virus and Central European tick-borne encephalitis virus (CETE). The incidence of overt clinical signs of disease varied according to the virus that was used for the inoculations. TTE proved to be more pathogenic for monkeys than the other two members of the complex, whilst CETE was the least pathogenic (Zlontnik et al., 1976).
-
Ixodes ricinus:
-
Taxonomy Information:
-
Species:
-
Castor bean tick
(Website 11):
-
Ontology: UMLS:C0282509
-
GenBank Taxonomy No.:
34613
-
Scientific Name:
Ixodes ricinus (Website 11)
-
Description:
Although a number of ixodid ticks have been shown to be capable of transmitting louping-ill virus, including Ripicephalus appendiculatus and Haemaphysalis anatolicum, it is unlikely that any arthropod other than Ixodes ricinus is involved in the natural transmission of this virus (Reid, 1984).
-
Infection Process:
No infection process information is currently available here.
-
Disease Information:
No disease information is currently available here.
-
Prevention:
No prevention information is currently available here.
-
Model System:
No model system information is currently available here.
-
Vertebrates:
-
Taxonomy Information:
-
Species:
-
Sheep
(Website 12):
-
Ontology: UMLS:C1123019
-
GenBank Taxonomy No.:
9940
-
Scientific Name:
Ovis aries (Website 12)
-
Description:
Louping ill is best known as a disease of sheep reared on rough hill pastures in Scotland, northern England, Wales and Ireland. These are the areas which will support the vector, I. ricinus the sheep tick which has three hosts and a life span of 3 years (Davidson et al., 1991).
Disease in sheep has a bi-phasic course, a primary febrile phase being followed by an encephalitic one, when the animals may exhibit the leaping which gives rise to the name 'louping ill'. Viraemia occurs in the primary phase when virus amounts are sufficiently high for 2 to 3 days to cause infection in a feeding tick. However many infections in sheep are subclinical. Most symptomatic infections are fatal and those animals which survive never regain full health, though they have protective antibody for life. Lambs born to immune animals have passive protection for the first year of life, but are then susceptible (Davidson et al., 1991).
-
Willow ptarmigan
(Website 13):
-
Ontology: UMLS:C1016821
-
GenBank Taxonomy No.:
52650
-
Scientific Name:
Lagopus lagopus (Website 13)
-
Description:
High and sustained viraemias were recorded in all experimentally infected red grouse injected with virus. However, as 79% died, the role of the red grouse in the maintenance of louping-ill was brought into question. A field study was made in an area in which virus had been isolated from the brains of free-living birds that had been found dead. The breeding success of birds in areas where ticks were numerous was compared with that of birds in areas where ticks were less abundant. It was found that in areas where ticks were abundant, very few birds were reared-indeed the rate of replacement was markedly below that required to sustain the grouse population. Sequential observation of broods of birds which were trapped every 7 to 10 days indicated that following infection with virus very few birds were seen again and were presumed dead. In this way much of the mortality detected could be attributed to louping-ill virus infection. Thus, both these experimental and field studies suggested that louping-ill viruses was highly pathogenic for red grouse (Reid, 1984).
-
European shrew
(Website 14):
-
Ontology: UMLS:C1010036
-
GenBank Taxonomy No.:
42254
-
Scientific Name:
Sorex araneus (Website 14)
-
Description:
The catholic host preference of the vector ensures that all vertebrates in endemic areas are likely to encounter infection. Antibody has been detected and/or virus isolated from a number of wild species including shrew (Sorex araneus), wood mouse (Apodemus sylvaticus), blue hare (Lepus timidus), badger (Meles meles), roe deer (Capreolus capreolus), red deer (C. elaphus), feral goats and red grouse (Lagopus scoticus) (Reid, 1984).
-
European woodmouse, long-tailed field mouse
(Website 15):
-
Ontology: UMLS:C0999696
-
GenBank Taxonomy No.:
10129
-
Scientific Name:
Apodemus sylvaticus (Website 15)
-
Description:
The catholic host preference of the vector ensures that all vertebrates in endemic areas are likely to encounter infection. Antibody has been detected and/or virus isolated from a number of wild species including shrew (Sorex araneus), wood mouse (Apodemus sylvaticus), blue hare (Lepus timidus), badger (Meles meles), roe deer (Capreolus capreolus), red deer (C. elaphus), feral goats and red grouse (Lagopus scoticus) (Reid, 1984).
-
Mountain hare
(Website 16):
-
Ontology: UMLS:C1023637
-
GenBank Taxonomy No.:
62621
-
Scientific Name:
Lepus timidus (Website 16)
-
Description:
The catholic host preference of the vector ensures that all vertebrates in endemic areas are likely to encounter infection. Antibody has been detected and/or virus isolated from a number of wild species including shrew (Sorex araneus), wood mouse (Apodemus sylvaticus), blue hare (Lepus timidus), badger (Meles meles), roe deer (Capreolus capreolus), red deer (C. elaphus), feral goats and red grouse (Lagopus scoticus) (Reid, 1984).
-
Eurasian badger
(Website 17):
-
Ontology: UMLS:C0325052
-
GenBank Taxonomy No.:
9662
-
Scientific Name:
Meles meles (Website 17)
-
Description:
The catholic host preference of the vector ensures that all vertebrates in endemic areas are likely to encounter infection. Antibody has been detected and/or virus isolated from a number of wild species including shrew (Sorex araneus), wood mouse (Apodemus sylvaticus), blue hare (Lepus timidus), badger (Meles meles), roe deer (Capreolus capreolus), red deer (C. elaphus), feral goats and red grouse (Lagopus scoticus) (Reid, 1984).
-
Roe deer
(Website 18):
-
Ontology: UMLS:C0325219
-
GenBank Taxonomy No.:
9858
-
Scientific Name:
Capreolus capreolus (Website 18)
-
Description:
The catholic host preference of the vector ensures that all vertebrates in endemic areas are likely to encounter infection. Antibody has been detected and/or virus isolated from a number of wild species including shrew (Sorex araneus), wood mouse (Apodemus sylvaticus), blue hare (Lepus timidus), badger (Meles meles), roe deer (Capreolus capreolus), red deer (C. elaphus), feral goats and red grouse (Lagopus scoticus) (Reid, 1984).
-
Red deer
(Website 19):
-
Ontology: UMLS:C0325228
-
GenBank Taxonomy No.:
9860
-
Scientific Name:
Cervus elaphus (Website 19)
-
Description:
The catholic host preference of the vector ensures that all vertebrates in endemic areas are likely to encounter infection. Antibody has been detected and/or virus isolated from a number of wild species including shrew (Sorex araneus), wood mouse (Apodemus sylvaticus), blue hare (Lepus timidus), badger (Meles meles), roe deer (Capreolus capreolus), red deer (C. elaphus), feral goats and red grouse (Lagopus scoticus) (Reid, 1984).
-
Goat
(Website 20):
-
Ontology: UMLS:C1265550
-
GenBank Taxonomy No.:
9925
-
Scientific Name:
Capra hircus (Website 20)
-
Description:
Disease caused by louping-ill virus has been described in a variety of domestic species including pig, sheep cattle, horse, dog and farmed deer as well as in man (Reid, 1984).
-
Pig
(Website 21):
-
Ontology: UMLS:C1135183
-
GenBank Taxonomy No.:
9823
-
Scientific Name:
Sus scrofa (Website 21)
-
Description:
Disease caused by louping-ill virus has been described in a variety of domestic species including pig, sheep cattle, horse, dog and farmed deer as well as in man (Reid, 1984).
-
Cow
(Website 22):
-
Ontology: UMLS:C1140701
-
GenBank Taxonomy No.:
9913
-
Scientific Name:
Bos taurus (Website 22)
-
Description:
Disease caused by louping-ill virus has been described in a variety of domestic species including pig, sheep cattle, horse, dog and farmed deer as well as in man (Reid, 1984).
-
Horse
(Website 23):
-
Ontology: UMLS:C0019944
-
GenBank Taxonomy No.:
9796
-
Scientific Name:
Equus caballus (Website 23)
-
Description:
Disease caused by louping-ill virus has been described in a variety of domestic species including pig, sheep cattle, horse, dog and farmed deer as well as in man (Reid, 1984).
-
Dog
(Website 24):
-
Ontology: UMLS:C0012984
-
GenBank Taxonomy No.:
9615
-
Scientific Name:
Canis familiaris (Website 24)
-
Description:
Disease caused by louping-ill virus has been described in a variety of domestic species including pig, sheep cattle, horse, dog and farmed deer as well as in man (Reid, 1984).
-
Infection Process:
No infection process information is currently available here.
-
Disease Information:
No disease information is currently available here.
-
Prevention:
No prevention information is currently available here.
-
Model System:
No model system information is currently available here.
IV. Labwork Information
A. Biosafety Information:
-
Biosafety information for
:
Louping ill virus
:
-
Biosafety Level:
3 (Website 9)
-
Precautions:
-
Biosafety Level 3 practices, safety equipment, and facilities are recommended for activities using potentially infectious clinical materials and infected tissue cultures, animals, or arthropods (Website 10).
B. Culturing Information:
-
Monolayer Tissue Culture of Pig Kidney
(Williams, 1958):
-
Description:
Virus was passaged serially in culture by transferring pooled undiluted or diluted infected medium from one group of four to six tube-cultures to each of a group of newly prepared ones. Passage virus was harvested on the sixth day of incubation and was titrated immediately in mice. By the fifth passage the original virus inoculum titer of 4 x 10(4) mouse LD(50) doses per ml was diluted 10(7) but yielded 3.9 x 10(7) mouse LD(50) doses per ml. Clearly, the cultures were supporting multiplication of the virus. Microscopic examination of live cultures inoculated with low dilutions of mouse brain virus revealed a cytopathogenic effect which commenced on the second to third day. The affected cells became granular, rounded up, and appeared to agglutinate. As the effect increased in severity, there was almost total cell necrosis and destruction of the monolayers. Fixed coverslip preparations of affected cells stained with Giemsa showed shrinking, pyknosis and disintegration. Uninfected cultures and culture inoculated with comparable dilutions of normal mouse brain remained unchanged (Williams, 1958).
-
Medium:
-
Earle's saline, 0.5 % lactalbumen hydrolysate (enzymatic) and 0.01 % yeast extract. To this mixture was added 10% normal cattle serum as well as antibiotics (Williams, 1958).
-
Optimal Temperature:
35 C (Williams, 1958)
C. Diagnostic Tests
:
-
Organism Detection Tests:
-
IFAT of cell culture assays or tick squashes (Gaunt et al., 1997):
-
Ontology:
UMLS:C0282647
-
Time to Perform:
2-to-7-days
-
Description:
Sterile glass coverslips were added aseptically to each well of a 24-well tissue culture plate. Porcine kidney (PS) cells were grown to confluence in each well prior to inoculation with the tick homogenates. Three days p.i. cells were washed in PBS and fixed in situ in a 3:2 solution of methanol:acetone at -20 C for 5 min. Infection of cells was confirmed by indirect immunofluorescence antibody test (IFAT) using a monoclonal antibody Mab 813 that binds to the E protein of all flaviviruses (Gaunt et al., 1997).
Comparison of the sensitivity of virus infectivity in cell culture and RT-PCR to detect LI virus in field-trapped ticks showed that there was little if any difference between the two methods. However, in terms of speed, simplicity and reliability, the RT-PCR method proved superior, taking only 8 h to demonstrate a cDNA product and a further 48 h to confirm virus identity by nucleotide and deduced amino acid sequence analysis. In contrast, IFAT relied upon a subjective analysis and in samples containing very small quantities of virus-specific antigen, was less reliable (Gaunt et al., 1997).
-
Virus Isolation (Timoney, 1992):
-
Ontology:
UMLS:C0201674
-
Description:
In the majority of cases, virus isolation is attempted on the brain and spinal cord of dead animals. While this is frequently successful in sheep, results in cattle have been variable. Fresh tissue is best transported to the laboratory in 50 percent glycerol/normal saline or frozen on dry ice and dispatched in a closed, insulated container using an overnight delivery service. Virus can be isolated in the PK1B/RS2 cell line or by the intracerebral inoculation of suckling or adult mice in which the virus produces a fatal encephalomyelitis. Isolates of LI virus can be preliminarily identified either by means of the complement fixation test using a crude mouse brain antigen or simpler still, in a double immunodiffusion test. Final verification of identity is accomplished by means of a neutralization test in cell culture (plaque-reduction or microneutralization) or in mice (Timoney, 1992).
-
Immunoassay Tests:
-
ELISA as Serological Confirmation of LI Infection (Timoney, 1992):
-
Ontology:
UMLS:C0014441
-
Description:
Serological confirmation of a diagnosis of LI virus infection is based on the demonstration of seroconversion or a significant (4 fold or greater) rise in antibody titer to the virus between acute and convalescent sera. Demonstration of specific IgM antibody in serum is also confirmatory of infection. Hemagglutination-inhibition, neutralization and most recently, the enzyme-linked immunosorbent assay (ELISA) tests have been used for the serological diagnosis of LI virus infection. Whereas HI antibodies appear 5 to 10 days after infection and decline after 6 to 12 months, SN antibodies persist for years. The complement fixation test is of very limited value in the diagnosis of this disease in sheep as these antibodies appear late in the course of infection and are transient in duration. A standardized Tick Borne Encephalitis virus antigen is now commercially available for use in an ELISA test for this disease, obviating the need to prepare in-house antigen reagents (Timoney, 1992).
-
Haemagglutination as Serological Confirmation of LI Infection (Timoney, 1992):
-
Ontology:
UMLS:C0018905
-
Description:
Serological confirmation of a diagnosis of LI virus infection is based on the demonstration of seroconversion or a significant (4 fold or greater) rise in antibody titer to the virus between acute and convalescent sera. Demonstration of specific 1gM antibody in serum is also confirmatory of infection. Hemagglutination-inhibition, neutralization and most recently, the enzyme-linked immunosorbent assay (ELISA) tests have been used for the serological diagnosis of LI virus infection. Whereas HI antibodies appear 5 to 10 days after infection and decline after 6 to 12 months, SN antibodies persist for years. The complement fixation test is of very limited value in the diagnosis of this disease in sheep as these antibodies appear late in the course of infection and are transient in duration. A standardized Tick Borne Encephalitis virus antigen is now commercially available for use in an ELISA test for this disease, obviating the need to prepare in-house antigen reagents (Timoney, 1992).
-
Neutralization as Serological Confirmation of LI Infection (Timoney, 1992):
-
Ontology:
UMLS:C0201677
-
Description:
Serological confirmation of a diagnosis of LI virus infection is based on the demonstration of seroconversion or a significant (4 fold or greater) rise in antibody titer to the virus between acute and convalescent sera. Demonstration of specific 1gM antibody in serum is also confirmatory of infection. Hemagglutination-inhibition, neutralization and most recently, the enzyme-linked immunosorbent assay (ELISA) tests have been used for the serological diagnosis of LI virus infection. Whereas HI antibodies appear 5 to 10 days after infection and decline after 6 to 12 months, SN antibodies persist for years. The complement fixation test is of very limited value in the diagnosis of this disease in sheep as these antibodies appear late in the course of infection and are transient in duration. A standardized Tick Borne Encephalitis virus antigen is now commercially available for use in an ELISA test for this disease, obviating the need to prepare in-house antigen reagents (Timoney, 1992).
-
Microneutralization Test in PK(15) Cells (Timoney et al., 1984):
-
Time to Perform:
2-to-7-days
-
Description:
A microneutralization test in PK(15) cells was developed to measure the neutralizing antibody response of a group of ponies experimentally challenged with louping ill virus. Viral cytopathic effect was maximal after 6 days of incubation, at which point titration endpoints were clear-cut and readily determinable. The assay compared favorably with the mouse neutralization test for accuracy and ease of performance (Timoney et al., 1984).
The microneutralization test for LI virus was simple and easy to perform and offered significant advantage over other currently available cell culture assay procedures in that the pig kidney line used was not contaminated with hog cholera virus. The CPE associated with LI virus infection of PK(15) cells was clearly discernible after incubation of cultures for 4 to 6 days and very similar to that previously reported in pig kidney secondary monolayers. Titration endpoints were clear-cut and could be readily determined. In addition to easy reading of test results, the microneutralization assay provides a rapid and relatively inexpensive means of detection and estimation of SN antibody levels to LI virus with satisfactory accuracy. It has considerable advantages over the mouse neutralization test and is less laborious than alternative cell culture procedures (Timoney et al., 1984).
-
Avidin-Biotin-complex Immunoperoxidase Technique (Krueger and Reid, 1994):
-
Ontology:
UMLS:C0200822
-
Time to Perform:
2-to-7-days
-
Description:
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 (Krueger and Reid, 1994).
Viral antigen was detected in all 10 experimentally infected mice, in two of the five sheep, and in the pig (Krueger and Reid, 1994).
-
False Negative:
As only two of the five presumptive cases of louping ill in sheep were shown to be positive by the technique it should not at present be the only means of diagnosis (Krueger and Reid, 1994).
-
Nucleic Acid Detection Tests:
:
-
RT-PCR:
-
Ontology:
UMLS:C0599161
-
Time to Perform:
1-hour-to-1-day
-
Description:
Rapid and precise virus detection procedures are an important component of any epizootiological study. An automated one tube reverse transcriptase and nested primer polymerase chain reaction (RT-PCR) followed by nucleotide sequencing of the cDNA product, was used for the rapid detection and identification of louping ill (LI) virus in field caught Ixodes ricinus and compared with a classical isolation method i.e. infectivity in cell culture. The results establish the gene