Bluetongue active again near the Belgian coast

The Belgian veterinary authorities reported on 17 July to the OIE (World Organisation for Animal Health) their suspicion that bluetongue had re-emerged in Belgium.

http://www.oie.int/wahid-prod/reports/en_imm_0000005744_20070717_170418.pdf

The notification was based on clinical signs and increasing amounts of antibody in a single sheep that subsequently died near Antwerp. Later that day they confirmed the outbreak, having detected the genetic material of the virus in that sheep. Taken together the evidence indicates that the infection of the sheep had occurred recently. As bluetongue virus (BTV) is only spread by biting midges when they take a blood meal, this demonstrates that bluetongue-infected midges are active in Belgium, not far from the coast. It is possible that easterly winds could bring infected midges to the south-east coast of Britain.

The disease occurred in northern Europe for the first time last summer (Belgium, France, Germany, Luxembourg and the Netherlands).

Further outbreaks in Germany reported on 20 July

In June the German veterinary authorities reported that bluetongue had re-emerged on a cattle farm, infection probably having occurred during April. (BT_Germany_25jun07.htm)

On 20 July, six more cases were reported in Germany, four in cattle and two in sheep, in the provinces of Nordrhein-Westfalen and Rheinland-Pfalz.

http://www.oie.int/wahid-prod/reports/en_imm_0000005769_20070720_120950.pdf

In addition to the observation of clinical signs, the genetic material of the virus was detected in the sheep (by the PCR test), and live virus was recovered from the cattle and grown in the laboratory. These findings confirm that the infection was active at the time of sampling.

For further information and links on the 2006 and 2007 outbreaks in northern Europe, for general background information on the disease and the causative virus, and an indication of the role of the IAH in bluetongue research, go to Bluetongue pages

To speak to our bluetongue experts, contact Dr Dave Cavanagh at the Institute for Animal Health’s press office: mobile 07789 941568 (messages can be recorded); office 01635 577241 (messages can be recorded: please repeat your telephone number twice); dave.cavanagh@bbsrc.ac.uk.

Bluetongue in northern Europe

Bluetongue was unknown in northern Europe until last summer, when bluetongue virus serotype 8 was introduced by means unknown. The successful spread of this serotype to domestic animals in Belgium, France, Germany, Luxembourg and the Netherlands is believed to have been helped by higher than normal temperatures (John_Gloster_3apr07.htm). The virus is spread by biting Culicoides midges, in which the virus replicates. Warm temperatures increase the rate at which the virus grows in the midges (reducing the time to them becoming infectious) and increase the number of times that the midges bite. A few years earlier other serotypes of bluetongue virus had spread to southern Europe, where they became established.

Bluetongue virus incursions into Europe since 1998

Summary of the molecular epidemiology of Bluetongue virus in Europe since 1998:

introductions, origins and movements of individual virus strains:  

Peter Mertens, Institute for Animal Health

By combining data from disease surveillance and diagnostic testing, with the results of molecular epidemiology studies, it is possible to build up a picture of the recent colonisation of Europe by bluetongue virus and its subsequent spread in the region. Genome segment 2 encodes the virus outer coat protein VP2, which is the most variable virus protein and is the primary determinant of virus serotype. The majority of the data regarding the molecular epidemiology of European BTV strains were generated for genome segment 2, although data was also produced for segments 5, 6, 8 and 10.

BTV-1:

There have been two separate introductions of BTV-1 into the Mediterranean region which have occurred in 2001 and 2006.   These are represented in the reference collection by the Greek isolate GRE2001/01 and by Algerian and Moroccan isolates ALG2006/01 and MOR2006/06.

Phylogenetic analyses of segment 2 sequences not only identified these strains as BTV serotype 1 but also showed that they are distinct, belonging to different ‘eastern’ and ‘western’ lineages respectively. The initial strain of BTV-1 in Greece is related to eastern viruses from India and Malaysia and is thought to have entered Europe from the east, most probably from Turkey. This strain only persisted for a relatively short period in Greece and did not spread to other European Countries.

In 2006 BTV was detected in northern Africa and was shown by RT-PCR and sequence analysis to be caused by BTV type 1. The strain involved is most closely related to other western type 1 isolates from sub-Saharan Africa, but is clearly distinct from the South African vaccine strain (RSAvvvv/01). It is also distinct from the earlier Greek isolates of BTV-1. There are subsequent reports of BTV-1 in Sardinia during 2006, suggesting that the virus had moved northwards into the western Mediterranean Islands.

BTV-2:

BT outbreaks were recorded in Tunisia during 2000. The virus was isolated and is represented in the IAH reference collection by TUN2000/01 and TUN2000/02. Phylogenetic analyses of Seg-2 sequences identified the virus as BTV serotype 2, belonging to a western lineage.

The virus is related to other BTV-2 strains from Nigeria and South Africa, although it is distinct from the South African BTV-2 vaccine strain (RSAvvvv/02). The initial Tunisian isolates of BTV-2 are also almost identical to subsequent isolates made in Corsica and Sardinia indicating that (like the BTV-1 strain from North Africa in 2006) BTV-2 managed to spread northwards, from north Africa into Italy and the western Mediterranean islands (represented by isolates from Corsica (FRA2001/01 to FRA2001/06), Sardinia (SAD2001/01 to SAD2002/03) and Sicily (ITL2002/01).  

However, there is evidence that some of the subsequent isolates of BTV-2 from mainland Italy, are similar to the BTV-2 vaccine strain that was also used in the region, indicating that it can be transmitted in the field.

BTV-4:

Widespread bluetongue outbreaks in Greece during 1999 and 2000 were caused by a strain of BTV-4 (represented in the collection by multiple isolates: GRE1999/01 to GRE2000/07). Phylogenetic analyses demonstrated that the virus is similar to earlier isolates from Cyprus and Turkey (CYP1969/01 and TUR1978/01). It is also closely related to the Reference strain of BTV-4, cited in the collection as RSArrrr/04, which is also believed to have been originally derived from Cyprus. This suggests that the BTV-4 strain which invaded Greece and the Eastern Mediterranean region since 1999, has been circulating in the region, on the borders of Europe, for some time. Indeed several isolates of BTV-4 have subsequently been made in Israel (represented by isolates ISR2002/01 to ISR2001/13, ISR2006/10 and ISR2006/12). Phylogenetic analyses show that these European BTV-4 strains belong to a western lineage but are distinct from the South African vaccine strain (represented in the collection by TURvvvv/04).

In 2003, BTV was detected in the Western Mediterranean islands, including Menorca (represented in the reference collection by isolates SPA2003/01 to SPA2003/04. Although phylogenetic analyses showed that this was also a western strain of BTV-4, it is clearly distinct from strains that had previously caused outbreaks in the eastern Mediterranean region. These conclusions were confirmed by Stephan Zientara et al, working with Corsican isolates at Maisons Alfort in France.  This virus is believed to have entered Europe from North Africa, possibly (like the earlier BTV-2 strain) from Tunisia. The same strain of BTV-4 subsequently caused outbreaks and was isolated in Morocco (represented by isolate MOR2004/02) and then spread to the Iberian peninsula in 2004 (represented by isolates SPA2004/01 and SPA2004/02), where it persisted through into 2005 (represented by isolates SPA2005/02 to SPA2005/05).

BTV-8:

In August 2006, BT was recognised for the first time in northern Europe. The disease was subsequently detected in Belgium (where the index case is thought to have occurred, possibly in May or June 2006), Luxemburg, Germany and north-east France. Multiple isolates of the virus were made from isolates across this region (represented in the collection by NET2006/01 to NET2006/04, GER2006/01 and BEL2006/01). Sequence analyses of Seg-2 from NET2006/01, demonstrated that the virus is from a western lineage from sub Saharan Africa, but is distinct from the BTV-8 vaccine strain (www.iah.bbsrc.ac.uk/dsRNA_virus_proteins/BTV-8-Seg-2-tree.htm). It is uncertain exactly how BTV-8 arrived in northern Europe, but the absence of BTV-8 outbreaks in southern Europe suggests that it did not involve simple linear extension of earlier outbreaks and is likely to reflect a distinct entry route and mechanism.

Interestingly serological evidence for BTV-8 infection of sentinel animals was subsequently obtained from Bulgaria (during 2006), although since no virus was detected by virus isolation or by RT-PCR assays of blood samples, it is difficult to determine the likely timing of BTV infections involved or the relevance of these reports to northern Europe.

In April 2008 a sentinel animal in Germany seroconverted, becoming seropositive for BTV. This suggests that the virus had not 'died out' during the winter. The virus was identified in Germany by type specific RT-PCR , as BTV-8.

On July 17th 2007 the Belgian authorities also reported disease in a flock of sheep near Antwerp in which a single sheep had clinical signs of bluetongue and subsequently died. The detection of antibodies to BTV and viral RNA in blood samples indicated the presence of virus and new transmission.

BTV-9:

The first serotype to arrive in the Europe in 1998 was BTV-9 (represented by virus isolate GRE1998/01). Sequence data for genome segment 2 of this isolate compared to other isolates of BTV held in the reference collection at IAH Pirbright from around the world. The resulting analysis shows that this is an ‘eastern’ virus, related to strains from Indonesia and Australia). This strain of BTV is also closely related to BTV-9 subsequently isolated in Greece, Bulgaria, Turkey, Bosnia, Kosovo and Serbia, represented in the reference collection by multiple isolates from these regions. This indicates that the outbreak of BTV-9 in the eastern and central Mediterranean region stemmed from this eastern source. It also appears likely that BTV-9 in Italy originated from the same initial source (since no other introductions of BTV-9 field strains have been detected), although an isolate of BTV-9 was made in Sicily (ITL2003/01) which was identical to the BTV-9 vaccine strain. was

BTV15:

A sample of a virus-isolate that was made in Israel from outbreaks of disease in 2006 (represented in the collection by ISR2006/11) was typed as BTV-15, by RT-PCR assays using serotype specific primers targeting genome segment 2.  Subsequent phylogenetic analyses confirm the virus serotype and indicated that it belongs to a western lineage. The number of BTV-15 isolates that are available is very limited. So it is difficult to be more precise about the origins of this virus strain. However, the existing data suggest that it is new to the region and may therefore represent a further threat to Europe in the future.

BTV16:

The initial European strain of BTV-16 was isolated in Greece during 1999 (represented in the reference collection by isolate number GRE1999/13). Sequence analysis of Seg-2 and phylogenetic analysis show that this virus is from an eastern lineage and is very similar to strains of BTV-16 from Turkey and the South African reference strain of BTV-16. This may seem surprising but the reference strain (RSArrrr/16) was originally derived from an outbreak in Pakistan. This suggests that the virus arrived in Europe from the east, possibly via Turkey. Phylogenetic analyses have shown that the original European field strain of BTV-16 is closely related, although distinct from the BTV-16 vaccine strain. Its appearance in Europe may be related to the use of live BTV-16 for several years as part of an annual vaccination campaign in Israel. After its arrival in Europe the virus spread eastwards across Europe and BTV-16 eventually appeared in mainland Italy. Although BTV-16 caused an outbreak in Sardinia in 2004, the strain involved (represented by isolates SAD2004/01 to SAD2004/24) is identical to the BTV-16 vaccine strain that was used in mainland Italy, suggesting that this was a ‘vaccine’ outbreak and was not caused by the European field strain.

BTV 16 also appeared in Cyprus during 2004 (represented by CYP2004/01), which is similar to the earlier eastern Mediterranean isolates.

Summary

With the development of a molecular epidemiology database containing sequence data for large numbers of specific well documented BTV isolates, sequence analyses and comparisons of genome segment 2 can now be used to give a clear indication of the serotype and origins of individual BTV strains (Maan et al 2007).

These analyses for the European BTV strains isolated since 1998 have indicated that six serotypes of the virus have entered Europe, with at least 9 separate introductions, via at least 4 distinct routes. Indeed there have been new introductions in each year with the possible exception of 2002.

The use of live vaccine strains of BTV-2, 4, 9 and 16 in the region have added further strains to the European virus pool. With this number of distinct viruses co-circulating, it is perhaps not surprising that there is also conclusive evidence for genome segment exchange via ‘reassortment’ events between different virus strains and serotypes, and between vaccine and field strains, in the field.

There appears to have been a fundamental change in the European ecosystem since 1998, possibly linked to climate change which favours the introduction and survival of BTV in Europe. Based on these recent events, it considered likely that other BTV strains, and possibly other orbiviruses, will spread to the region in the immediate and foreseeable future.

Bluetongue virus causes disease in sheep, cattle, and other ruminants

Although all ruminant species can be infected by the bluetongue virus, clinical signs of the disease are usually restricted to domesticated breeds of sheep. Other animals such as goats and cattle rarely show any symptoms. Bluetongue may therefore spread into new areas without necessarily being noticed. However, a relatively high number of cattle have been affected during the current outbreak in Northern Europe.

In sheep, bluetongue disease is characterised by a fever that may last for several days. The virus mainly affects small blood vessels and this can lead to reddening and swelling of the lips, mouth, nasal linings and eyelids. Swelling of the tongue can lead to a restriction of the blood supply to the tongue, leading to a blue colouration, hence the name of the disease. Animals may have quickened breathing. Nasal discharges, excess salivation and frothing are common. Lameness may occur. Animals can lose condition rapidly, including muscle degeneration. BT_clinical.pdf

There is no treatment for bluetongue. Prevention may be possible by vaccination (but only if a vaccine of the appropriate serotype is available) and by controlling midge populations (with insecticides or, where practical, by control of breeding sites), but neither is totally successful.

Roles of the Institute for Animal Health

The Institute for Animal Health (IAH) is the largest research institute in the United Kingdom dedicated to the study of infectious diseases in farm animals. It has two sites: Compton Laboratory (Compton, near Newbury, Berkshire), and Pirbright Laboratory (Pirbright, near Guildford, Surrey) www.iah.bbsrc.ac.uk

IAH is one of seven research institutes sponsored by the Biotechnology and Biological Sciences Research Council (BBSRC; www.bbsrc.ac.uk).

The main programme of research at Compton Laboratory of the Institute for Animal Health is on diseases that commonly infect farm animals in the UK, principally poultry and cattle.  Compton Laboratory also supports the work of Pirbright Laboratory by its programme of research on bovine immunology, and by providing animals for research at both Compton and Pirbright Laboratories.

The Pirbright Laboratory (near Guildford, Surrey, UK) of the Institute for Animal Health contains world and regional laboratories for many major diseases of farm animals.  The viruses studied at Pirbright do not commonly infect animals in the UK, though they are potentially devastating when they do.  Pirbright Laboratory contains nine reference laboratories on behalf of various international agencies:

World Reference Laboratory of the UN’s Food and Agriculture Organisation (FAO)

Regional Reference Laboratory of the OIE (World Organisation for Animal Health

Community Reference Laboratory of the EU

Each reference laboratory specialises in one type of virus.  A reference laboratory maintains a collection of viruses and related reagents, and provides a diagnostic service.

Bluetongue: OIE, EU

African swine fever: OIE

African horse sickness: OIE, EU

Foot-and-mouth disease: FAO, OIE, EU

Swine vesicular disease: OIE, EU

Lumpy skin disease: OIE

Sheep and goat pox: IE

Peste de petits ruminants: FAO, OIE

Rinderpest: FAO, EU