Schmallenberg Virus Infection: An Emerging Vector-Borne Disease in Europe

Schmallenberg virus (SBV) is the first orthobunyavirus of the Simbu serogroup detected in Europe. It was first identified by metagenomic analysis in Germany (1) and in the Netherlands in autumn 2011 (2) and spread rapidly over large parts of Central and Western Europe (1-5), affecting primarily ruminants, but also new-world camelids such as alpacas (1,6). The disease recurred in 2012 (7).There is serological evidence for infection of wildlife ruminants (roe deer, fallow deer, red deer, mouflon).

The Simbu serogroup comprises of more than 24 viruses, most of which have been detected in ruminants. A number of these agents, e.g. Akabane and Aino virus, can cause disease in these animals, while human infections with orthobunyaviruses are rare and have only been described for two viruses (Oropouche and Iquitos virus). There is no evidence that humans are susceptible to SBV infection (8).

The genome of orthobunyaviruses consists of three single stranded RNA molecules (segments), designated as S(mall), M(edium) and L(arge). Exchange of segments by reassortment is possible between members of a group. As the M segment codes for the viral glycoproteins that induce neutralising antibodies in infected hosts, there is selection pressure leading to frequent reassortment events involving this segment. Molecular analyses have shown that Douglas virus, which was first isolated in Australia (9), Sathuperi and Shamonda virus represent close relatives of SBV, but can clearly by distinguished (10,11). 

Within little more than one year, SBV spread over large parts of Europe (12). Acute infections of adult ruminants or malformed SBV-positive offspring were detected in more than 5000 farms at least in Austria, Belgium, the Czech Republic, Denmark, Estonia, Finland, France, Ireland, Germany, Italy, Luxembourg, Norway, Poland, Spain, Sweden, Switzerland, the Netherlands and the United Kingdom. Suspect cases were also reported from Hungary and Slovenia.

Serological studies were conducted in Belgium (3) and The Netherlands (4). Further serological surveys were done at least in Germany, France, Austria and Switzerland, but the results have not yet been published. In Belgium, serum samples obtained from cattle during spring 2010 and in spring 2011 were seronegative for SBV. The testing of sera from cattle randomly sampled on 209 farms in April 2012 revealed an apparent seroprevalence among adult cows of 90.8 % (95 percent CI 88.3–93.2 %). In the Netherlands, the estimated seroprevalence in cattle was 72.5 percent (95 % CI 69.7–75.1 %). in winter 2012. It was significantly higher in the central-eastern part of the country than in the northern and southern regions, but there were no regional clusters. High (70–100 %) within-herd seroprevalences were observed in two SBV-infected dairy herds and two affected sheep flocks. Similar within-herd prevalences were observed in cattle herds and sheep flocks in Germany. The seroprevalence observed in cattle during winter 2012 in Germany, correlated with the spatial distribution of virus detection in malformed lambs and calves. In the core region of the epidemic in Germany, up to 98 % of the tested animals had seroconverted, while the numbers of seropositive animals decline with the spatial gradient. Examination of sera collected before 2011 from susceptible species provided no evidence that SBV had been present in the affected area before 2011. 

The epidemiological data existing so far is in accord with the hypothesis that SBV is transmitted by arthropods. This view is further supported by the fact that the virus has been detected in biting midges (Culicoides spp.) in Belgium, Denmark, Italy, the Netherlands and Germany (12-14). It seems likely that biting midges play a central role in the transmission of the infection.

Recently, infectious SBV has also been detected in the bull semen. It remains to be clarified, however, whether the infection can be transmitted to dams by inseminating them with semen containing infectious SBV and, if so, whether this route is of epidemiological importance.

Available evidence obtained from limited experimental infections suggests that direct horizontal transmission of SBV infection by contact does not occur. Oro-nasal inoculation of two calves at the Friedrich-Loeffler-Institut did not lead to infection and in several animal trials, contact animals remained seronegative (15). 

It is obvious, however, that SBV can be vertically transmitted from the dam to its offspring by transplacental infection (3,16). 

In adult cattle, mild symptoms such as transient decrease in milk production, fever and diarrhoea were observed already in the index cases in August/September 2012. The animals recovered within a period of one or two weeks. There were no specific reports on clinical cases in adult sheep which may suggest that the infection remained subclinical in these animals. It seems likely that a large number of adult cattle failed to show clinical signs upon infection with SBV or the clinical signs were not noticed by the farmers.

However, transplacental infection of the embryos or fetuses occurred after pregnant dams had been acutely infected. Depending on the gestational stage, SBV caused more or less severe damage to the embryo or fetus, leading to the birth of malformed lambs and calves that were normally unable to survive, for example because they were unable to suckle (“dummy lambs”) or stillborn. Most animals were born at full term, but abortions were also reported. SBV was also detected in mummified fetuses. Shepherds reported that several ewes had returned to service which may suggest that embryos had been aborted or resorbed in early stages of gestation. It seems that the affected ewes became pregnant normally and gave birth to healthy lambs when mated again after these events. It should be emphasized that most of the information reported here is not yet based on systematic studies but often anecdotal. Nevertheless, the available data on the clinical picture show a high degree of similarity of SBV with Akabane virus infections.

While the infection causes only mild symptoms (1) or remains clinically inapparent in adult animals, transplacental transmission during a limited period of time in pregnancy can lead to the birth of severely malformed progeny (1,2). 

Due to the mild and transient clinical signs and the seasonal occurrence in late summer/autumn 2011, when the etiology of the alterations was not yet known, our knowledge on the pathology of acute SBV infection in adult ruminants is still sparse. Experimentally infected calves and sheep failed to show any clinical signs or displayed only very mild symptoms such as fever and diarrhea. However, SBV can cause malformations in the embryo or fetus, respectively, if transplacentally transmitted during the teratogenic determination period, i.e. the ‘vulnerable’ phase for the embryo or fetus. For Akabane virus, this period ranges between approximately days 28 and 36 (56) in sheep and days 74 and 110 (150) in cattle (17,18). Infections that take place before or after this period might still result in embryonic/fetal death, but malformations are rare or do no occur. If the fetuses survive until birth, it is sometimes possible to detect SBV in meconium or amniotic fluid or to detect pre-colostral antibodies in the animals. 

In lambs, kids and calves, SBV-associated malformations include arthrogryposis, malformations of the vertebral column (kyphosis, lordosis, scoliosis, torticollis) and of the scull (deformation, macrocephaly, brachygnathia inferior) as well as variable malformations of the brain (hydranencephaly, porencephaly, cerebellar hypoplasia, hypoplasia of the brain stem) and of the spinal cord (19). These alterations, known as ‘arthrogryposis and hydranencephaly syndrome’ (AG/HE) resemble the pathological changes observed after infection with other viruses of the Simbu sero group. Arthrogryposis is caused by a neurogenic developmental disorder and degeneration of skeletal muscles and accompanied by the formation of replacing tissue. Neurons required for the normal development of the muscles lack in both the dorsal and ventral horn of the spinal cord.  

Infected animals mount a detectable antibody response to SBV within 12 to 14 days. In analogy to other infections with viruses of the Simbu serogroup and based on the results of initial re-infection experiments of two calves, it seems likely that infection with SBV induces an immune response that protects against challenge infection applied several weeks after primary infection. It is not yet known how long protection might last.                                

SBV genome can be most readily detected by PCR (1,20). SBV-specific antibodies can be demonstrated in serum samples by virus neutralisation test (VNT), indirect immunofluorescent antibody test (IFAT) or ELISA (21). Plasma samples can be tested by IFAT or ELISA, but confirmation by VNT is difficult with this material.

Acute SBV infection, which is expected to occur primarily during the vector active period (in central Europe April – November) can be detected by PCR in blood or serum samples (1). It is important to note that the extremely short viraemia observed in SBV infection (5 days maximum) requires that the affected animals are sampled when they show clinical signs, preferably during the very short phase when the animals develop fever.

PCR can also be used to demonstrate SBV in malformed neonates (1), preferably by testing brain samples from at least two different parts of the organ (cerebrum and cerebellum). Spleen and blood can also be used, but SBV is less frequently detected in these matrices. Amniotic/fetal fluid (e.g. swabs from the amniotic/fetal fluid in the fur of malformed neonates) and meconium may be suitable samples, which are readily accessible. A good correlation of SBV detection was shown in particular for samples of amniotic fluid relative to brain material (20), but further validation of the test performance with these matrices may be needed.

While SBV genome is regularly detectable by PCR in the brain and in other tissues from lambs with SBV-associated malformations, it is significantly less likely to find SBV genome in calves with typical malformations of the AG/HE type, as also observed for Akabane virus. A negative PCR result in a malformed calf does therefore not rule out SBV as the cause of the malformation. In these cases, antibody detection in pre-colostral blood samples or body liquids, e.g. obtained by cardial puncture in stillborn animals, may be performed. Detection of SBV-specific antibodies in these samples is indicative of transplacental SBV infection. 

The European Food Safety Authority has estimated that the maximum proportion of confirmed sheep herds per region was 6.6% and 4% for cattle herds (12). In Germany, approximately 0.8 % of the cattle farms and 4.2% of the sheep holdings were affected, but there were considerable regional differences. In North Rhine-Westphalia, for example, where SBV first occurred in 2011, the proportion of affected sheep flocks amounted to 11.8% (data as of 28/01/2013).

Although the losses caused by SBV infections were limited, the emergence of this new disease caused substantial trade disruptions. It remains to be seen, whether the infection will establish permanently in the affected region.