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Also known as: BTV, Bluetongue.
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Also known as: '''''BTV Bluetongue
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==Description==
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==Introduction==
 
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Bluetongue is a non-contagious, [[:Category:Arthropods|arthropod]]-borne disease of ruminants, caused by bluetongue virus (BTV). The clinical severity of disease is variable, but is characterised by inflammation of mucous membranes, haemorrhages and oedema<sup>1</sup>. Although cattle are the main reservoir of infection, sheep are more severely affected and can suffer a cyanotic tongue, lending the disease name. The virus has been isolated from hosts and vectors on all continents (excluding Antartica)<sup>2</sup>, despite being initially recognised in Africa in the late 19th and early 20th centuries<sup>3</sup>. Originally thought to be a disease of tropical and sub-tropical regions, bluetongue has shown a propensity to become established in temperate areas, and in recent years has spread North, through the Mediterranean Basin, to become endemic in many European countries including the UK. Although BTV's transmission and epidemiology is dependent on insect vectors, bluetongue greatly influences the global trade of ruminants as it is included on the Office International des Epizooties List A of animal diseases<sup>4</sup>.
Bluetongue is a non-contagious, arthropod-borne disease of ruminants, caused by bluetongue virus (BTV). The clinical severity of disease is variable, but is characterised by inflammation of mucous membranes, haemorrhages and oedema<sup>1</sup>. Although cattle are the main reservoir of infection, sheep are more severely affected and can suffer a cyanotic tongue, lending the disease its name. The virus has been isolated from hosts and vectors on all continents(excluding Antartica)<sup>2</sup>, despite being initially recognised in Africa in the late 19th and early 20th centuries<sup>3</sup>. Originally thought to be a disease of tropical and sub-tropical regions, bluetongue has shown a propensity to become established in temperate areas, and in recent years has spread North, through the Mediterranean Basin, to become endemic in many European countries including the UK. Although BTV's transmission and epidemiology is dependent on insect vectors, bluetongue greatly influences the global trade of ruminants as it is included on the Office International des Epizooties List A of animal diseases<sup>4</sup>.
      
==Virus Characteristics==
 
==Virus Characteristics==
 
[[Image:Bluetongue Virus.gif|thumb|right|150px|Bluetongue virus particle. Source: Wikimedia Commons; Author: CDC (2007)]]
 
[[Image:Bluetongue Virus.gif|thumb|right|150px|Bluetongue virus particle. Source: Wikimedia Commons; Author: CDC (2007)]]
Bluetongue virus is a species of the genus Orbivirus, within the Reoviridae family. The Reoviridae are non-enveloped and possess a double-stranded RNA genome contained in an outer-shelled icosohedral capsid. The BTV genome is arranged into 10 segments and encodes 7 structural and 4 non-structural viral proteins<sup>2</sup>. The BTV receptor is currently unknown, but is proposed to included sialic acid and junctional adhesion molecules. After interaction with this receptor, the virus enters an endolysosome where the capsid is partially digested to allow the genome into the cell. Replication begins at this partially uncoated stage since the virus particles contain all the necessary enzymes<sup>5</sup>. First, the dsRNA is transcribed to form positive sense RNA, of which some is delivered to cytoplasm for ribosomal translation and the remainder is packaged into partially assembled virions. Complementary negative sense RNA is then formed in the virions, to give a dsRNA genome. Complete virus particles are released from the cell.
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Bluetongue virus is a species of the genus Orbivirus, within the [[:Category:Reoviridae|Reoviridae]] family. The Reoviridae are non-enveloped and possess a double-stranded RNA genome contained in an outer-shelled icosohedral capsid. The BTV genome is arranged into 10 segments and encodes 7 structural and 4 non-structural viral proteins<sup>2</sup>. The BTV receptor is currently unknown, but is proposed to included sialic acid and junctional adhesion molecules. After interaction with this receptor, the virus enters an endolysosome where the capsid is partially digested to allow the genome into the cell. Replication begins at this partially uncoated stage since the virus particles contain all the necessary enzymes<sup>5</sup>. First, the dsRNA is transcribed to form positive sense RNA, of which some is delivered to cytoplasm for ribosomal translation and the remainder is packaged into partially assembled virions. Complementary negative sense RNA is then formed in the virions, to give a dsRNA genome. Complete virus particles are released from the cell.
    
All BTVs share group antigens, which can be demonstrated by agar gel diffusion tests, fluorescent antibody tests and the group
 
All BTVs share group antigens, which can be demonstrated by agar gel diffusion tests, fluorescent antibody tests and the group
reactive ELISA<sup>1</sup>. There are 24 distinct serotypes, which are are distinguished by epitopes on the outer capsid protein VP2<sup>4</sup>, encoded by L2, the only serotype-specific BTV gene. Serotypes are differentiated using serum neutralisation tests, although there is some degree of cross-reactivity between serotypes<sup>1</sup>. Numerous strains of bluetongue virus also exist, and these are characterised by molecular analysis.
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reactive [[ELISA testing|ELISA]]<sup>1</sup>. There are 24 distinct serotypes, which are distinguished by epitopes on the outer capsid protein VP2<sup>4</sup>, encoded by L2, the only serotype-specific BTV gene. Serotypes are differentiated using serum neutralisation tests, although there is some degree of cross-reactivity between serotypes<sup>1</sup>. Numerous strains of bluetongue virus also exist, and these are characterised by molecular analysis.
    
==Hosts==
 
==Hosts==
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All ruminants are susceptible to bluetongue virus infection, including sheep, goats, cattle, deer, buffaloes, camels and antelopes. Sheep are most severely affected, and disease is occasionally seen in goats. Although cattle BTV infection is significant in the epidemiology of disease, the condition is generally subclinical in this host. Mortalities in white-tailed deer due to bluetongue have been reported in the USA<sup>1</sup>.
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All ruminants are susceptible to bluetongue virus  infection, including sheep, goats, cattle, deer, buffaloes, camels and antelopes. Sheep are most severely affected, and disease is occasionally seen in goats. Although cattle BTV infection is significant in the epidemiology of disease, the condition is generally subclinical in this host. Mortalities in white-tailed deer due to bluetongue have been reported in the USA<sup>1</sup>.
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Pigs and horses do not become infected with BTV, but may act as a food source for the [[Ceratopogonidae|''Culicoides'']] midges that transmit bluetongue virus to ruminants. Their habitats may also provide areas suitable for vector breeding.
 
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Pigs and horses do not become infected with BTV, but may act as a food source for the ''Culicoides'' midges that transmit bluetongue virus to ruminants. Their habitats may also provide areas suitable for vector breeding.
      
==Transmission and Epidemiology==
 
==Transmission and Epidemiology==
   
BTV is transmitted by biting insects. Although vertical and venereal transmission between ruminant hosts can occur, it is insignificant in the overall epidemiology of bluetongue.
 
BTV is transmitted by biting insects. Although vertical and venereal transmission between ruminant hosts can occur, it is insignificant in the overall epidemiology of bluetongue.
    
===Vectors===
 
===Vectors===
 
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The arthropod vector for bluetongue virus is the [[Ceratopogonidae|''Culicoides'']] biting midge. These are biological vectors of BTV, so the virus replicates in insect tissue after feeding on an infected host<sup>6</sup>. It takes 10-14 days for the virus to disseminated from the insect's gut to its salivary glands, after which bluetongue virus may be transmitted to a new, susceptible ruminant host. This incubation period may be reduced when ambient temperatures are higher<sup>2</sup> and once infected, midges maintain BTV infection for life.
The arthropod vector for bluetongue virus is the ''Culicoides'' biting midge. These are biological vectors of BTV, so the virus replicates in insect tissue after feeding on an infected host<sup>6</sup>. It takes 10-14 days for the virus to dissminated from the insect's gut to its salivary glands, after which bluetongue virus may be transmitted to a new, susceptible ruminant host. This incubation period may be reduced when ambient temperatures are higher<sup>2</sup> and once infected, midges maintain BTV infection for life.
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''Culicoides'' take blood meals from vertebrate hosts and breed in damp, dung-enriched soil, and so are abdunant in the vicinity of domestic livestock. Once eggs are laid in the soil, ''Culicoides'' larvae progress through four stages and pupate before becoming an adult midge. The lifecycle is greatly influenced by temperature: in temperate regions such as Britain, the adult midge population declines in October and is absent by December. The fourth larval stage overwinters, and adults re-appear the following April. The environmental conditions also affect the activity of midges in several ways. ''Culicoides'' survive around 10 days in warm weather but up to one month when conditions are cooler and are most active at night, from an hour before sunset to an hour after sunrise. Activity is decreased by windy conditions, and increased during the day when the weather is dull. Bluetongue virus replicates more rapidly in vector species when temperatures are warmer.  
      
Classically, the major vector for BTV is ''Culicoides imicola''. This midge is found throughout Africa, the
 
Classically, the major vector for BTV is ''Culicoides imicola''. This midge is found throughout Africa, the
Middle East, southern Asia, Portugal, Greece, Corsica, Sardinia, Sicily and areas of Italy<sup>1</sup>, and its distribution appears to be extending northwards. However, ''C. imicola'' has not yet been demonstrated in the United Kingdom. The ''Culicoides'' species found in the British Isles are ''C. pulicaris'' and ''C. obsoletus'', which are also common across central and northern Europe. Knowledge of the distribution of these species in the UK is incomplete but the insects tend to gather where breeding sites and hosts occur in tandem, with the highest midge concentrations in areas containing cattle, horses and pigs. Removal of livestock decreases populations of ''Culicoides'' by a factor of 10 to 20<sup>1</sup>, but some persist by feeding on wild animals and man. Hill sites have fewer midges as climatic conditions are less favourable, and the presence of sheep encourages the midge population less than that of cattle.
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Middle East, southern Asia, Portugal, Greece, Corsica, Sardinia, Sicily and areas of Italy<sup>1</sup>, and its distribution appears to be extending northwards. However, ''C. imicola'' has not yet been demonstrated in the United Kingdom.  
 
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In Britain, studies are ongoing to determine midge distribution, seasonal incidence and the competency of the various ''Culicoides'' species to act as BTV vectors.
      
===Vector Competence===
 
===Vector Competence===
 
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Certain information can help inferences be made regarding BTV vectors in Britain. Both ''C. obsoletus'' and ''C. pulicaris'' have been implicated in transmission before. Previously, BTV has been isolated from ''C. obsoletus'' in Cyprus, and [[African Horse Sickness|African horse sickness virus]] (another Orbivirus) in Spain. ''C. obsoletus'' and ''C. pulicaris'' were also the most abundant ''Culicoides'' species detected in the 1999 BTV epizootic in Greece and Bulgaria, and so are strongly suspected of acting as vectors in this case. They may also have mediated outbreaks in Serbia, FYR Macedonia, Croatia and Bosnia in 2001-2002, where ''C. imicola'' has not been recorded. Both species are therefore contenders to transmit bluetongue virus in the UK<sup>1</sup>.
Certain information can help inferences be made regarding BTV vectors in Britain. Both ''C. obsoletus'' and ''C. pulicaris'' have been implicated in transmission before. Previously, BTV has been isolated from ''C. obsoletus'' in Cyprus, and African horse sickness virus (another Orbivirus) in Spain. ''C. obsoletus'' and ''C. pulicaris'' were also the most abundant ''Culicoides'' species detected in the 1999 BTV epizootic in Greece and Bulgaria, and so are strongly suspected of acting as vectors in this case. They may also have mediated outbreaks in Serbia, FYR Macedonia, Croatia and Bosnia in 2001-2002, where ''C. imicola'' has not been recorded. Both species are therefore contenders to transmit bluetongue virus in the UK<sup>1</sup>.
      
A British population of ''C. obsoletus'' has been shown to have and oral susceptibility rate of less than 2%<sup>1</sup>, suggesting that ''C. obsoletus'' is likely to be an inefficient or minor vector of BTV in the UK. However, it is possible that a high abundance or survival rate may compensate for this low vector competence. Indeed, ''C. brevitarsis'', the major Australian vector of BTV, has an extremely low experimental competency yet is an effective vector in the field.
 
A British population of ''C. obsoletus'' has been shown to have and oral susceptibility rate of less than 2%<sup>1</sup>, suggesting that ''C. obsoletus'' is likely to be an inefficient or minor vector of BTV in the UK. However, it is possible that a high abundance or survival rate may compensate for this low vector competence. Indeed, ''C. brevitarsis'', the major Australian vector of BTV, has an extremely low experimental competency yet is an effective vector in the field.
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===Epidemiology===
 
===Epidemiology===
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Although bluetongue virus is capable of infecting any ruminant, cattle are the main amplifying and maintenance hosts and are most abundantly fed on by ''Culicoides'' vectors. Infection of sheep with BTV is therefore usually preceded by widespread infection of cattle and an increase in vector density<sup>1</sup>.
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Althbough bluetongue virus is capable of infecting any ruminant, cattle are the main amplifying and maintenance hosts and are most abundantly fed on by ''Culicoides'' vectors. Infection of sheep with BTV is therefore usually preceded by widespread infection of cattle and an increase in vector density<sup>1</sup>.
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Although vertical and venereal transmission of bluetongue is possible, only to the presence of competent insect vectors influences the epidemiology of BTV<sup>2</sup>. This is illustrated by the fact that bluetongue virus is limited to geographical areas where competent vectors are present and that transmission only occurs at times of the year when conditions are favourable for vector activity<sup>1</sup>. In Britain, transmission occurs mainly in late summer and autumn. Once bluetongue virus is transmitted to a vertebrate host, there are two possible outcomes: either the host dies, or an immune response is mounted against the virus and the host is rendered resistant to re-infection. Either way, animals quickly become "unavailable" for BTV infection as the virus spreads, particularly where livestock populations are small. This presents a hurdle that must be surmounted if bluetongue virus is to persist in an area. By movement of infected vectors or viraemic animals, BTV can become established in new locations with naive hosts in order to overcome this obstacle. This means that even in zones where bluetongue virus is endemic, persistence is dynamic and comprises perpetually shifting "hot spots" of infection<sup>1</sup>. Creation of an enzootic zone is only possible in locations where adult midges are present throughout the year since bluetongue cannot be maintained through vertebrate-vertebrate or vector transovarial transmission. Any points where vectors are absent from the system must not exceed the maximum duration of viraemia in the ruminant host, otherwise the last infected vertebrate will have died or recovered by the time new vectors are available for onwards transmission.
 
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Although vertical and venereal transmission of bluetongue is possible, only to the presence of competent insect vectors influences the epidemiology of BTV<sup>2</sup>. This is illustrated by the fact that bluetongue virus is limited to geographical areas where competent vectors are present and that transmission only occurs at times of the year when conditions are favourable for vector activity<sup>1</sup>. In Britain, transmission occurs mainly in late summer and autumn. Once bluetongue virus is transmitted to a vertebrate host, there are two possible outcomes: either the host dies, or an immune response is mounted against the virus and the host is rendered resistant to re-infection. Either way, animals quickly become "unavailable" for BTV infection as the virus spreads, particularly where livestock populations are small. This presents a hurdle that must be surmounted if bluetongue virus is to persist in an area. By movement of infected vectors or viraemic animals, BTV can become established in new locations with naive hosts in order to overcome this obtascle. This means that even in zones where bluetongue virus is endemic, persistence is dynamic and comprises perpetually shifting "hot spots" of infection<sup>1</sup>. Creation of an enzootic zone is only possible in locations where adult midges are present throughout the year since bluetongue cannot be maintained through vertebrate-vertebrate or vector transovarial transmission. Any points where vectores are absent from the system must not exceed the maximum duration of viraemia in the ruminant host, otherwise the last infected vertebrate will have died or recovered by the time new vectors are availble for onwards transmission.
      
In some areas, bluetongue can occur in annual bouts. This may be due to new introduction of virus each year from adjacent areas where the disease is endemic, via the transportation of ''Culicoides'' on the wind for up to 100 kilometres. Alternatively, this could be the manifestation of low-level persistence.  
 
In some areas, bluetongue can occur in annual bouts. This may be due to new introduction of virus each year from adjacent areas where the disease is endemic, via the transportation of ''Culicoides'' on the wind for up to 100 kilometres. Alternatively, this could be the manifestation of low-level persistence.  
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==Pathogenesis==
 
==Pathogenesis==
   
The pathogenesis of BTV infection has been shown to be similar in sheep and cattle, and is assumed to be similar in other species of ruminants<sup>8, 9, 10</sup>. However, the severity of disease varies greatly with species and cattle in particular express very few signs.  
 
The pathogenesis of BTV infection has been shown to be similar in sheep and cattle, and is assumed to be similar in other species of ruminants<sup>8, 9, 10</sup>. However, the severity of disease varies greatly with species and cattle in particular express very few signs.  
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When a BTV-infected midge takes a blood meal from a ruminant host, innoculated virus spreads from the skin to replicate in the regional lymph nodes, tonsils and spleen<sup>11</sup>. A secondary cell-associated viraemia then carries the virus to many tissues where further replication occurs in macrophages and endothelial cells. In the process of reproducing, bluetongue virus causes endothelial cell injury and necrosis<sup>10</sup> which can increase vascular permeability to cause oedema. Endothelial damage can also give thrombosis, leading to tissue infarction. In sheep and deer a consumptive coagulopathy may occur<sup>2</sup>.
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When a BTV-infected midge takes a blood meal from a ruminant host, innoculated virus spreads from the skin to replicate in the regional lymph nodes, tonsils and spleen<sup>11</sup>. A secondary cell-associated viraemia then carries the virus to many tissues where further replication occurs in macrophages and endothelial cells. In the process of reproducing, bluetongue virus causes endothelial cell injury and necrosis<sup>10</sup> which can increase vascular permeability to cause oedema. Endothelial damage can also give thrombosis, leading to tissue infarction. In sheep and deer a [[Disseminated Intravascular Coagulation|consumptive coagulopathy]] may occur<sup>2</sup>.
    
Several factors can influence the presentation of disease. Firstly, each virus strain is associated with its own particular virulence and thus clinical manifestation<sup>10</sup>. Host factors are also important: breed<sup>3, 12</sup>, stress, nutritional status and age<sup>12, 13</sup> can all affect bluetongue presentation.
 
Several factors can influence the presentation of disease. Firstly, each virus strain is associated with its own particular virulence and thus clinical manifestation<sup>10</sup>. Host factors are also important: breed<sup>3, 12</sup>, stress, nutritional status and age<sup>12, 13</sup> can all affect bluetongue presentation.
    
==Diagnosis==
 
==Diagnosis==
   
Where animals present with clinical signs of bluetongue a presumptive diagnosis may be made, especially in regions where bluetongue is endemic. Post-mortem examination can be used to confirm the diagnosis. However, many cases of bluetongue are mild or subclinical and so laboratory confirmation of disease is required. Cattle in particular show few clinical signs.
 
Where animals present with clinical signs of bluetongue a presumptive diagnosis may be made, especially in regions where bluetongue is endemic. Post-mortem examination can be used to confirm the diagnosis. However, many cases of bluetongue are mild or subclinical and so laboratory confirmation of disease is required. Cattle in particular show few clinical signs.
    
===Clinical Signs===
 
===Clinical Signs===
 
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Bluetongue is primarily a disease of '''sheep''', and in the face of infection these animals can display clinical signs ranging from acute to subclinical<sup>1, 14</sup>. Acute disease follows an incubation period of about one week, which may depend on the infectious dose of virus received.  Signs begin with pyrexia of around 40.5-42°C, and hyperaemia of the oral and nasal mucosa is seen 24-36 hours later accompanied by hypersalivation and a serous nasal discharge. The nasal discharge quickly becomes mucopurulent and potentially blood-tinged, and dries to form a crust around the nostrils. Oedema of the head occurs, which particularly affects the lips and tongue but may also spread to include the ears and submandibular areas. In a few cases the tongue becomes severely swollen and cyanotic, lending the disease its name. Petechial haemorrhages appear on the still-hyperaemic mucosae, and areas of necrosis appear on the gums, cheeks and tongue 5-8 days after the onset of fever. Covered by a diphtheritic membrane, these necrotic lesions heal slowly and contribute to inappetance, dysphagia and hypersalivation. In some cases, profuse bloody diarrhoea is seen. Erythema and petechiation of the coronary band can cause lameness, and sheep stand with an arched back, reluctant to move. In advanced disease, skeletal muscle is necrosed and contributes to rapid weight loss, along with inappetance. Animals in the late stage may also suffer torticollis. In pregnant ewes, infection with BTV may lead to abortions, foetal mummification, or the birth of stillborn or weak lambs, which may suffer congenital defects.
Bluetongue is primarily a disease of sheep, and in the face of infection these animals can display clinical signs ranging from acute to subclinical<sup>1, 14</sup>. Acute disease follows an incubation period of about one week, which may depend on the infectious dose of virus received.  Signs begin with pyrexia of around 40.5-42°C, and hyperaemia of the oral and nasal mucosa is seen 24-36 hours later accompanied by hypersalivation and a serous nasal discharge. The nasal discharge quickly becomes mucopurulent and potentially blood-tinged, and dries to form a crust around the nostrils. Oedema of the head occurs, which particularly affects the lips and tongue but may also spread to include the ears and submandibular areas. In a few cases the tongue becomes severely swollen and cyanotic, lending the disease its name. Petechial haemorrhages appear on the still-hyperaemic mucosae, and areas of necrosis appear on the gums, cheeks and tongue 5-8 days after the onset of fever. Covered by a diptheritic membrane, these necrotic lesions heal slowly and contribute to inappetance, dysphagia and hypersalivation. In some cases, profuse bloody diarrhoea is seen. Erythema and petechiation of the coronary band can cause lameness, and sheep stand with an arched back, reluctant to move. In advanced disease, skeletal muscle is necrosed and contributes to rapid weight loss, along with inappetance. Animals in the late stage may also suffer torticollis. In pregnant ewes, infection with BTV may lead to abortions, foetal mummification, or the birth of stillborn or weak lambs, which may suffer congenital defects.
      
Considering all cases, including those which are subclinical, mortality due to bluetongue in sheep ranges between 2% and 30%<sup>14</sup>. Death can occur up to a month after the onset of clinical signs, or a protracted recovery may follow acute infection. Recovery in mild cases is often much more rapid.  
 
Considering all cases, including those which are subclinical, mortality due to bluetongue in sheep ranges between 2% and 30%<sup>14</sup>. Death can occur up to a month after the onset of clinical signs, or a protracted recovery may follow acute infection. Recovery in mild cases is often much more rapid.  
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Disease is most often sub-clinical in cattle despite its epidemiological significance in this species: it has been reported that only 0.01% of infected cattle show signs of bluetongue<sup>1</sup>. Clinical signs, when seen, can include inflammation or erosions of the oral and nasal mucosae and a stiff gait. Similar signs to sheep may also occur: pyrexia, tachypnoea, lacrimation, salivation and an ulcerative dermatitis are all possibilities. In cattle in early gestation, embryonic death and resorption can result from BTV infection.
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Disease is most often sub-clinical in '''cattle''' despite its epidemiological significance in this species: it has been reported that only 0.01% of infected cattle show signs of bluetongue<sup>1</sup>. Clinical signs, when seen, can include inflammation or erosions of the oral and nasal mucosae and a stiff gait. Similar signs to sheep may also occur: pyrexia, tachypnoea, lacrimation, salivation and an ulcerative dermatitis are all possibilities. In cattle in early gestation, embryonic death and resorption can result from BTV infection.
    
===Laboratory Tests===
 
===Laboratory Tests===
   
In the United Kingdom, bluetongue is a notifiable disease and so samples from suspected cases should be submitted to the Institute for Animal Health (Pirbright) for laboratory diagnosis. Samples are collected from sheep with raised temperatures and include jugular blood collected into a plain tube to provide serum for an antibody test, and a heparinised blood sample to be used for PCR. Serum from in-contact ruminants is also submitted, as well as spleen and lymph node from all post-mortem cases. All samples should be stored at 4&deg;C and never frozen. Paired serology may be necessary.
 
In the United Kingdom, bluetongue is a notifiable disease and so samples from suspected cases should be submitted to the Institute for Animal Health (Pirbright) for laboratory diagnosis. Samples are collected from sheep with raised temperatures and include jugular blood collected into a plain tube to provide serum for an antibody test, and a heparinised blood sample to be used for PCR. Serum from in-contact ruminants is also submitted, as well as spleen and lymph node from all post-mortem cases. All samples should be stored at 4&deg;C and never frozen. Paired serology may be necessary.
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===Pathology===
 
===Pathology===
 
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A haemorrhagic gross pathology of BTV infection reflects the endothelial damage responsible for disease pathogenesis<sup>1, 4, 10, 12</sup>. Certain lesions have been described as "pathognomic" for bluetongue: these include necrosis of the papillary muscle in the left ventricle, and haemorrhage in pulmonary arterial wall. However, these lesions may be difficult to visualise in mild or recovering cases and may occasionally occur in other diseases such as [[Pulpy Kidney|pulpy kidney]] disease or Rift Valley fever.  
A haemorrhagic gross pathology of BTV infection reflects the endothelial damage responsible for disease pathogenesis<sup>1, 4, 10, 12</sup>. Certain lesions have been describes as "pathognomic" for bluetongue: these include necrosis of the papillary muscle in the left ventricle, and haemorrhage in pulmonary arterial wall. However, these lesions may be difficult to visualise in mild or recovering cases and may occasionally occur in other diseases such as pulpy kidney disease or Rift Valley fever.  
      
In addition to these characteristic lesions, the oral mucosa is found to be hyperaemic and oedematous and occasionally cyanotic on post-mortem examination, and petechial or ecchymotic haemorrhages may be present. The ruminal pillars and omasal folds can also appear hyperaemic, and abrasions may be seen on the lips, dental pad, tongue and cheeks. These are sometimes covered by grey necrotic material. Moderate lymphomegaly and splenomegaly are apparent, and there are areas of necrosis in the skeletal musculature. Pulmonary oedema and catarrhal inflammation of the upper respiratory tract is seen in some cases.
 
In addition to these characteristic lesions, the oral mucosa is found to be hyperaemic and oedematous and occasionally cyanotic on post-mortem examination, and petechial or ecchymotic haemorrhages may be present. The ruminal pillars and omasal folds can also appear hyperaemic, and abrasions may be seen on the lips, dental pad, tongue and cheeks. These are sometimes covered by grey necrotic material. Moderate lymphomegaly and splenomegaly are apparent, and there are areas of necrosis in the skeletal musculature. Pulmonary oedema and catarrhal inflammation of the upper respiratory tract is seen in some cases.
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===Vaccination===
 
===Vaccination===
   
Vaccines against BTV are available, and in different situations may be used to prevent or control outbreaks of bluetongue. Initially, modified live BTV vaccines were used, particularly in Africa, the United States and southern Europe<sup>4</sup>. Although useful for the control of disease, these vaccines have the potential to introduce novel strains of virus into the environment, which could lead to vector infection and reversion to virulence by evolution or genome reassortment with wild-type viruses. Foetal infection and teratogenesis are also possible. Killed, adjuvanted vaccines for some serotypes are now available, which are much safer. It is this type of product that has been used in recent years for control of BTV-8 in the UK.
 
Vaccines against BTV are available, and in different situations may be used to prevent or control outbreaks of bluetongue. Initially, modified live BTV vaccines were used, particularly in Africa, the United States and southern Europe<sup>4</sup>. Although useful for the control of disease, these vaccines have the potential to introduce novel strains of virus into the environment, which could lead to vector infection and reversion to virulence by evolution or genome reassortment with wild-type viruses. Foetal infection and teratogenesis are also possible. Killed, adjuvanted vaccines for some serotypes are now available, which are much safer. It is this type of product that has been used in recent years for control of BTV-8 in the UK.
    
===Vector Control===
 
===Vector Control===
   
As the cycle of bluetongue transmission involves a ''Culicoides'' vector, elements of disease control can be targetted at controlling midges. This can involve the use of insecticides on ''Culicoides'' breeding grounds to reduce midge numbers, and insect repellants on livestock to limit feeding on potential BTV hosts. Animals can also be housed indoors at dawn and dusk, when midges are most active. So far, little evidence has supported the value of these control measures, and the practicalities of implementing these strategies may preclude them from widespread use.
 
As the cycle of bluetongue transmission involves a ''Culicoides'' vector, elements of disease control can be targetted at controlling midges. This can involve the use of insecticides on ''Culicoides'' breeding grounds to reduce midge numbers, and insect repellants on livestock to limit feeding on potential BTV hosts. Animals can also be housed indoors at dawn and dusk, when midges are most active. So far, little evidence has supported the value of these control measures, and the practicalities of implementing these strategies may preclude them from widespread use.
    
===Surveillance===
 
===Surveillance===
   
Surveillance is a key component to controlling the spread of bluetongue. As well as vigilance in the face of a bluetongue outbreak to determine the extent of disease spread, ongoing surveillance is required to limit the possibility of BTV entering areas where the virus is not already circulating. The UK currently achieves ongoing surveillance through two mechanisms<sup>15</sup>. Firstly, bluetongue is a notifiable disease, and so it is a legal requirement for livestock holders to report all new cases of bluetongue on their premises. This allows new midge-transmission from the continent and any re-emergence of disease to be assessed. Secondly, every susceptible animal imported from Continental Europe, where bluetongue is currently circulating, is post-import tested for all serotypes of bluetongue virus. This ensures infected animals are not introduced to the country.
 
Surveillance is a key component to controlling the spread of bluetongue. As well as vigilance in the face of a bluetongue outbreak to determine the extent of disease spread, ongoing surveillance is required to limit the possibility of BTV entering areas where the virus is not already circulating. The UK currently achieves ongoing surveillance through two mechanisms<sup>15</sup>. Firstly, bluetongue is a notifiable disease, and so it is a legal requirement for livestock holders to report all new cases of bluetongue on their premises. This allows new midge-transmission from the continent and any re-emergence of disease to be assessed. Secondly, every susceptible animal imported from Continental Europe, where bluetongue is currently circulating, is post-import tested for all serotypes of bluetongue virus. This ensures infected animals are not introduced to the country.
    
===Controlling Spread of Bluetongue in Europe===
 
===Controlling Spread of Bluetongue in Europe===
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Although some factors influencing the introduction of bluetongue to an area are outwith human control, such as transportation of ''Culicoides'' on the wind, certain measures can be taken to help avoid BTV becoming established in an area. This involves designation of areas where bluetongue is circulating as restricted (or protection) zones for the specific serotype, and imposing movement limitations within and between these areas. Animals in protection zones may be moved within the zone, and to confluent protection zones for the same serotype. However, they may not be moved to free zones (BTV-free areas), although animals from free zones may be moved without restriction. A map of the current restriction/protection zones in Europe is available from the [http://ec.europa.eu/food/animal/diseases/controlmeasures/bt_restrictedzones-map.jpg European Commission Website].
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Although some factors influencing the introduction of bluetongue to an area are outwith human control, such as transportation of ''Culicoides'' on the wind, certain measures can be taken to help avoid BTV becoming established in an area. This involves designation of areas where bluetongue is circulating as restricted (or protection) zones for the specific serotype, and imposing movement limitations within and between these areas. Animals in protection zones may be moved within in the zone, and to confluent protection zones for the same serotype. However, they may not be moved to free zones (BTV-free areas), although animals from free zones may be moved without restriction. A map of the current restriction/protection zones in Europe is available from the [http://ec.europa.eu/food/animal/diseases/controlmeasures/bt_restrictedzones-map.jpg European Commission Website].
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Since animals may be moved freely between protection zones for the same serotype, a protection zone which does not currently have circulating BTV is at risk of becoming re-infected.  This fact has lead to the designation of lower risk zones. Vaccination is only normally permitted within protection zones, but livestock holders in lower risk zones are able to vaccinate their animals. There are also more stringent regulations on bringing in animals from confluent protection zones. Therefore, the risk of re-introducing bluetongue is reduced and the area can move towards BTV freedom more confidently. A further advantage of lower risk zones is that fewer limitations apply to the export of livestock to free zones or areas with other BTV serotypes.
 
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Since animals may be moved freely between protection zones for the same serotype, a protection zone which does not currently have circulating BTV is as risk of becoming re-infected.  This fact has lead to the designation of lower risk zones. Vaccination is only normally permitted within protection zones, but livestock holders in lower risk zones are able to vaccinate their animals. There are also more stringent regulations on bringing in animals from confluent protection zones. Therefore, the risk of re-introducing bluetongue is reduced and the area can move towards BTV freedom more confidently. A further advantage of lower risk zones is that fewer limitations apply to the export of livestock to free zones or areas with other BTV serotypes.
      
===Control in the UK===
 
===Control in the UK===
 
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In 2007, BTV-8 was confirmed in the UK and control measures implemented. However, the last BTV-8 infected premise was confirmed in the UK in November 2008, and since this date the situation has remained unchanged. No imported ruminants have tested positive for BTV-8 and there is no evidence that the disease has been circulating since this point. On 12th June 2010 the UK's status was changed from a protection zone for BTV-8 to a lower risk zone (LRZ). This status continues to allow vaccination against BTV, and imposes stricter restrictions on importing animals from zones with the same BTV serotype. The aim of this is to help prevent bluetongue re-entering the country. Up-to-date information on the current UK bluetongue situation can be found on the [http://www.defra.gov.uk/foodfarm/farmanimal/diseases/atoz/bluetongue/latest/index.htm DEFRA Bluetongue: Latest situation] webpage. At this point in time (Autumn 2010), vaccination is voluntary within the UK.
In 2007, BTV-8 was confirmed in the UK and control measures implemented. However, the last BTV-8 infected premise was confirmed in the UK in November 2008, and since this date the situation has remained unchanged. No imported ruminants have tested positive for BTV-8 and there is no evidence that the disease has been circulating since this point. On 12th June 2010 the UK's status was changed from a protection zone for BTV-8 to a lower risk zone (LRZ). This status allows continues to allow vaccination against BTV, and imposes stricter restrictions on importing animals from zones with the same BTV serotype. The aim of this is to help prevent bluetongue re-entering the country. Up-to-date information on the current UK bluetongue situation can be found on the [http://www.defra.gov.uk/foodfarm/farmanimal/diseases/atoz/bluetongue/latest/index.htm DEFRA Bluetongue: Latest situation] webpage. At this point in time, vaccination is voluntary within the UK.
      
In the UK, Bluetongue is a notifiable disease and so cases must be reported to the local AHO. There are also further obligations for notification: within 24 hours of confirmation of bluetongue in the UK, the Chief Veterinary Officer must inform the European Commission and the OIE Central Bureau. There are several broad principles of disease control when a bluetongue outbreak occurs in the UK<sup>16</sup>. Firstly, premises suspected of having the disease are inspected by a veterinary surgeon, and a ban is placed on moving animals on and off the site. Once it has been confirmed that bluetongue is circulating (i.e. there is not a single, isolated case of disease, for example due to importation), a restricted zone is imposed around the infected premises. A restricted zone is the overall area where restrictions apply and is composed of a protection zone (100km radius) surrounded by a surveillance zone (50km radius). The sizes of these zones are dictated by EU legislation for bluetongue control. The restricted zone may also contain control zones of tighter restrictions in the immediate vicinity (20km) of infected premises. Movements are permitted within protection and suveillance zones, and from the surveillance zone to the protection zone. Animals from neighbouring BTV-free areas may move into either the surveillance or protected zones. However, the converse of any of these movements is not permitted unless animals are travelling to slaughter. No movements are permitted within, to, or from the control zone.  
 
In the UK, Bluetongue is a notifiable disease and so cases must be reported to the local AHO. There are also further obligations for notification: within 24 hours of confirmation of bluetongue in the UK, the Chief Veterinary Officer must inform the European Commission and the OIE Central Bureau. There are several broad principles of disease control when a bluetongue outbreak occurs in the UK<sup>16</sup>. Firstly, premises suspected of having the disease are inspected by a veterinary surgeon, and a ban is placed on moving animals on and off the site. Once it has been confirmed that bluetongue is circulating (i.e. there is not a single, isolated case of disease, for example due to importation), a restricted zone is imposed around the infected premises. A restricted zone is the overall area where restrictions apply and is composed of a protection zone (100km radius) surrounded by a surveillance zone (50km radius). The sizes of these zones are dictated by EU legislation for bluetongue control. The restricted zone may also contain control zones of tighter restrictions in the immediate vicinity (20km) of infected premises. Movements are permitted within protection and suveillance zones, and from the surveillance zone to the protection zone. Animals from neighbouring BTV-free areas may move into either the surveillance or protected zones. However, the converse of any of these movements is not permitted unless animals are travelling to slaughter. No movements are permitted within, to, or from the control zone.  
    
In addition to movement restrictions, surveillance for disease and vectors is implemented as necessary in an outbreak, and relevant communications are made to livestock owners and veterinary surgeons to advise of the measures in place. The aim at all times is to tightly control disease, with an aim to eradication, and vaccination will normally play a large part in this according to plans laid out by DEFRA. A test and slaugher policy is not used, because BTV is not transmitted directly between susceptible animals.
 
In addition to movement restrictions, surveillance for disease and vectors is implemented as necessary in an outbreak, and relevant communications are made to livestock owners and veterinary surgeons to advise of the measures in place. The aim at all times is to tightly control disease, with an aim to eradication, and vaccination will normally play a large part in this according to plans laid out by DEFRA. A test and slaugher policy is not used, because BTV is not transmitted directly between susceptible animals.
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==Literature Search==
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[[File:CABI logo.jpg|left|90px]]
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Use these links to find recent scientific publications via CAB Abstracts (log in required unless accessing from a subscribing organisation).
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<br><br><br>
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[http://www.cabdirect.org/search.html?rowId=1&options1=AND&q1=title:(Bluetongue)+OR+(%22Blue+tongue%22)&occuring1=freetext&rowId=2&options2=AND&q2=&occuring2=freetext&rowId=3&options3=AND&q3=&occuring3=freetext&publishedstart=2000&publishedend=yyyy&calendarInput=yyyy-mm-dd&la=any&it=any&show=all&x=42&y=4 Bluetongue publications since 2000]
    
==Links==
 
==Links==
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[[Category:Orbiviruses]][[Category:Cattle]][[Category:Sheep]][[Category:Pig]]
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[[Category:Orbiviruses]][[Category:Cattle]][[Category:Sheep]][[Category:Goat]][[Category:Camelids]]
[[Category:Tongue_-_Pathology]][[Category:To_Do_-_Lizzie]] [[Category:To_Do_-_Review]]
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[[Category:Tongue_-_Pathology]][[Category:To_Do_-_Lizzie]] [[Category:Expert_Review]]
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