Schmallenberg Virus Infection Research Articles

About the Paper ‘First Report of Schmallenberg Virus Infection in Cattle in Poland’ by Larska et al

About the Paper ‘First Report of Schmallenberg Virus Infection in Cattle in Poland’ by Larska et al

Survey of Schmallenberg virus (SBV) infection in German goat flocks

Animal losses due to abortion and malformed offspring during the lambing period 2011/2012 amounted to 50% in ruminants in Europe. A new arthropod-borne virus, called Schmallenberg virus (SBV), was identified as the cause of these losses. Blood samples were obtained from 40 goat flocks and tested for antibodies against SBV by ELISA, with 95% being seropositive. The calculated intra-herd seroprevalence (median 36·7%, min-max 0-93·3%) was smaller than in cattle or sheep flocks. Only 25% of the farmers reported malformations in kids. Statistical analysis revealed a significantly lower risk of goats housed indoors all year-round to be infected by SBV than for goats kept outside day and night. The low intra-herd seroprevalence demonstrates that German goat flocks are still at risk of SBV infection. Therefore, they must be protected during the next lambing seasons by rescheduling the mating period, implementing indoor housing, and continuous treatment with repellents or vaccination.

Reemerging Schmallenberg Virus Infections, Germany, 2012

To the Editor: In 2011, Schmallenberg virus, a novel orthobunyavirus of the Simbu serogroup, emerged in Germany and the Netherlands and spread rapidly over large parts of central and western Europe (1–5). The infection primarily affects ruminants but affects camelids as well (1,6). So far, evidence has not shown that humans are susceptible to Schmallenberg virus infection (7). Although the infection in adult animals causes only mild symptoms (1) or remains clinically inapparent, in pregnant animals, transplacental transmission during a limited period can lead to the birth of severely malformed progeny (1,2). Acute infections of adult ruminants or malformed Schmallenberg virus–positive offspring have been detected on >5,000 farms in Austria, Belgium, Denmark, Finland, France, Ireland, Germany, Italy, Luxembourg, Norway, Poland, Spain, Sweden, Switzerland, the Netherlands, and the United Kingdom. Also, a high proportion of adult ruminants were seropositive for antigens of the virus in the core region affected by Schmallenberg virus in the Netherlands, Germany, and Belgium (2,4,5). Schmallenberg virus caused the first known outbreak of an infection with a virus of the Simbu serogroup in Europe. Schmallenberg virus infections are notifiable in Germany. Biting midges seem to play a key role in the transmission of the infection (8), and this transmission led to seasonal spread of the infection in summer and autumn 2011.

Schmallenberg virus – Is it present in South Africa?

In July 2006, a case of two out of three lambs born to one ewe in a flock of 45 had signs that, in retrospect, were possibly consistent with Schmallenberg virus infection. This occurred in the Onderstepoort area (Gauteng Province) but a definitive diagnosis was not made. Then, in May 2008, a farmer in the Delmas area (Mpumalanga Province) reported that deformed lambs had been born to several ewes in the flock. Six of the approximately 50 mated ewes gave birth to lambs showing varying degrees of arthrogryposis, torticollis, kyphosis, mandibular brachygnathia and hydrocephalus. Of these, only two were born alive but they died within a few hours. Blood was collected from the ewes with deformed lambs, a random sample of ewes that had given birth to normal lambs and a lamb that was normal but had a twin that was deformed. The samples were tested for Wesselsbron and Akabane antibodies using a complement fixation test and a haemagglutination/haemagglutination inhibition test that were available at that time. Bluetongue virus antibodies were also tested for using a commercial Enzyme-linked immunosorbent assay (ELISA) test. All samples showed negative results for all diseases tested. At the time Rift Valley fever virus had not been diagnosed in that region for many years and so it was not included in the testing. It is unlikely that this was the cause as no liver pathology was detected on postmortem examination of the lambs and no adult ewes had died. The farmer reported that another farm just a few kilometres away experienced the same deformities in some of their lambs but this farm was not investigated. During investigation it was thought that the cause was possibly a new strain of Akabane virus, although there was no way to confirm it. However, with the recent discovery of the Schmallenberg virus, it is possible that this virus has been present in South Africa for at least the last four years without being identified.

Oral exposure, reinfection and cellular immunity to Schmallenberg virus in cattle

Schmallenberg virus (SBV), a novel orthobunyavirus, was discovered in Germany in 2011. In adult ruminants SBV causes mild transient disease, but foetal infection can lead to severe malformations. Owing to its recent discovery, the knowledge about the pathogenesis is limited. In this study, two heifers seroconverted after a previous SBV infection and five SBV antibody-negative calves were subcutaneously inoculated, another two animals received SBV orally and three were kept as controls. In naïve cattle infected subcutaneously viral RNA was detected in serum and blood samples for several days. Seropositive or orally inoculated animals as well as the uninfected controls remained negative throughout the study. Seroconversion was observed only after subcutaneous exposure of the naïve animals to SBV. In lymphocytes from peripheral blood SBV genome was not detected, but the lymphocyte homeostasis in blood was influenced.

First report of Schmallenberg Virus Infection in Cattle and Midges in Poland

Two outbreaks of Schmallenberg virus (SBV) infection that coincided with the introduction of two bulls imported from France into two herds located in West Pomerania and Silesia provinces in Poland are described in detail. The first SBV real-time RT-PCR-positive result was obtained during routine testing of one of the imported bulls. The second bull and the affected farms were tracked by further investigation. Transmission of SBV into Polish cattle herds where the bulls were imported was confirmed by viral RNA detection in real-time RT-PCR, virus isolation followed by immunoperoxidase (IPX) staining and seroconversion. SBV RNA was detected also in Culicoides obsoletus pools caught in a trap located 5 km from one of the outbreaks. Testing nearly 900 samples collected prior to the two outbreaks from the same areas or provinces neighbouring with Germany where SBV cases had previously been detected gave negative results for the presence of SBV or specific antibodies. These cases are the first ones detected in cattle in Poland and provide evidence of recent transmission of the pathogen into the country and involvement of midge vectors.

Schmallenberg Virus Pathogenesis, Tropism and Interaction with the Innate Immune System of the Host

Schmallenberg virus (SBV) is an emerging orthobunyavirus of ruminants associated with outbreaks of congenital malformations in aborted and stillborn animals. Since its discovery in November 2011, SBV has spread very rapidly to many European countries. Here, we developed molecular and serological tools, and an experimental in vivo model as a platform to study SBV pathogenesis, tropism and virus-host cell interactions. Using a synthetic biology approach, we developed a reverse genetics system for the rapid rescue and genetic manipulation of SBV. We showed that SBV has a wide tropism in cell culture and “synthetic” SBV replicates in vitro as efficiently as wild type virus. We developed an experimental mouse model to study SBV infection and showed that this virus replicates abundantly in neurons where it causes cerebral malacia and vacuolation of the cerebral cortex. These virus-induced acute lesions are useful in understanding the progression from vacuolation to porencephaly and extensive tissue destruction, often observed in aborted lambs and calves in naturally occurring Schmallenberg cases. Indeed, we detected high levels of SBV antigens in the neurons of the gray matter of brain and spinal cord of naturally affected lambs and calves, suggesting that muscular hypoplasia observed in SBV-infected lambs is mostly secondary to central nervous system damage. Finally, we investigated the molecular determinants of SBV virulence. Interestingly, we found a biological SBV clone that after passage in cell culture displays increased virulence in mice. We also found that a SBV deletion mutant of the non-structural NSs protein (SBVΔNSs) is less virulent in mice than wild type SBV. Attenuation of SBV virulence depends on the inability of SBVΔNSs to block IFN synthesis in virus infected cells. In conclusion, this work provides a useful experimental framework to study the biology and pathogenesis of SBV.

Preliminary Survey on the Impact of Schmallenberg Virus on Sheep Flocks in South of Belgium

Between late February and May 2012, a preliminary anonym survey was conducted among sheep farmers in south of Belgium in order to contribute to future estimations of the economic losses caused by Schmallenberg virus (SBV). Based on clinical signs consistent with SBV infection, this survey involved 13 meat sheep flocks considered as positive flocks with subsequent SBV detection by RT-qPCR [SBV-positive flocks (PF); total of 961 animals], and 13 meat sheep flocks considered as negative flocks (NF; total of 331 animals). These preliminary results indicated several significant characteristics that were more present in PF than in NF. These include an increased rate of abortions (6.7% in PF versus 3.2% in NF), of lambs born at term but presenting malformations (10.1% in PF versus 2.0% in NF) and of dystocia (10.1% in PF versus 3.4% in NF). Lamb mortality during the first week of life was reported more frequently in PF (8 of 13 PF, 61.5%) than in NF (1 of 13 NF, 7.7%). In PF, the observed prolificacy rate was 2-fold lower (93%) than expected (186%). The implementation of a survey at larger scale, including a high number of breeders, is necessary to allow a more detailed analysis of the SBV impact in the sheep sector.

Teratogenic Effects of Schmallenberg Virus Infection in Sheep and Cattle

Teratogenic Effects of Schmallenberg Virus Infection in Sheep and Cattle

Epidemiology, molecular virology and diagnostics of Schmallenberg virus, an emerging orthobunyavirus in Europe

After the unexpected emergence of Bluetongue virus serotype 8 (BTV-8) in northern Europe in 2006, another arbovirus, Schmallenberg virus (SBV), emerged in Europe in 2011 causing a new economically important disease in ruminants. The virus, belonging to the Orthobunyavirus genus in the Bunyaviridae family, was first detected in Germany, in The Netherlands and in Belgium in 2011 and soon after in the United Kingdom, France, Italy, Luxembourg, Spain, Denmark and Switzerland. This review describes the current knowledge on the emergence, epidemiology, clinical signs, molecular virology and diagnosis of SBV infection.

Diagnosis of Schmallenberg virus infection in malformed lambs and calves and first indications for virus clearance in the fetus

Since mid-December 2011, samples from malformed lambs and calves are sent to CODA-CERVA in Belgium for diagnosis of Schmallenberg virus (SBV), a novel Orthobunyavirus that was first detected by researchers of the Friedrich-Loeffler-Institut (FLI, Germany) in German cattle in autumn 2011 and was later shown to be involved in congenital malformations in lambs, goat kids and calves. Surprisingly, by making use of real time RT-PCR (rRT-PCR) assays developed by the FLI, presence of SBV RNA could only be confirmed in part of the SBV suspected newborns examined. To investigate possible causes for non-confirmation by rRT-PCR, a comparative analysis between different organs and tissues (cerebrum, cerebellum, brain stem, spinal cord, thymus, spleen, lymph nodes, meconium) originating from respectively 90 and 81 malformed lambs and calves was undertaken. Furthermore, thoracic fluids of respectively 55 malformed lambs and calves were examined by a virus neutralization test (VNT) to evaluate the presence of neutralizing anti-SBV antibodies in these animals. Our results show that among the different organs tested by rRT-PCR, brain stem material is the most appropriate tissue for SBV detection while it could also be detected in all other tissues but to a more variable degree. The VNT test showed that 95% of the malformed lambs were positive for anti-SBV neutralizing antibodies while this was only the case for 44% of malformed calves. These immunological data suggest that a humoral immune response could assist in the clearance of SBV from the fetus during gestation and that SBV specific antibody testing should be considered together with rRT-PCR analysis for confirmation of SBV infection.

Diagnostics for Schmallenberg virus

SCHMALLENBERG virus (SBV) was discovered in November 2011 in Germany and named after the village where the first definitive sample was derived from dairy cattle (Hoffmann and others 2012). Clinical...

Preliminary estimate of Schmallenberg virus infection impact in sheep flocks – France

Schmallenberg virus (SBV) infection is an emerging livestock disease caused by a novel Orthobunyavirus which was first identified in Germany in November 2011. Non-specific clinical signs such as fever, decreased...

Development of a virus neutralisation test to detect antibodies against Schmallenberg virus and serological results in suspect and infected herds

BackgroundAt the end of 2011, a new orthobunyavirus, tentatively named Schmallenberg virus (SBV), was discovered in Germany. This virus has since been associated with clinical signs of decreased milk production, watery diarrhoea and fever in dairy cows, and subsequently also with congenital malformations in calves, lambs and goat kids. In affected countries, initial surveillance for the infection was based on examination of malformed progeny. These suspicions were followed up by real-time reverse transcription polymerase chain reaction (RT-PCR) on brain tissue. For epidemiological purposes, a serological assay was, however, needed.ResultsA virus neutralisation test (VNT) was developed and optimized, and subsequently evaluated. This VNT has a specificity of >99% and the sensitivity is likely also very close to 100%. The assay is highly repeatable and reproducible. The final assay was used to test for antibodies in cows, ewes and does from herds known to be infected or suspected to be so. Targets for sampling in these herds were the mothers of malformed offspring. In herds with an RT-PCR confirmed SBV infection, more than 94% (190 out of 201) of the ewes and 99% (145 out of 146) of the cows were seropositive. In herds with suspicion of SBV infection based on birth of malformed offspring only (no or negative RT-PCR), more than 90% (231 out of 255) of the ewes and 95% (795 out of 834) of the cows were seropositive. In goats, on the other hand, only a low number of seropositives was found: overall 36.4%, being 16 out of 44 goats tested.ConclusionsGiven the characteristics of this VNT, it can be used at a relative high throughput for testing of animals for export, surveillance, screening and research purposes, but can also be used as a confirmation test for commercially available enzyme-linked immunosorbent assays (ELISA’s) and for (relative) quantification of antibodies.Suspicions of SBV infections that were confirmed by RT-PCR were almost always confirmed by serology in cows. Due to individual registration and identification of cows and calves, affected offspring could almost always be traced back to the mother. Ewes on the other hand were not always the mothers of affected lambs, but were in many cases herd mates with unaffected lambs. This indicated a high within-herd seroprevalence of antibodies against SBV.

Lack of Evidence for Schmallenberg Virus Infection in Highly Exposed Persons, Germany, 2012

Schmallenberg virus, a novel orthobunyavirus, is spreading among ruminants, especially sheep, throughout Europe. To determine the risk for human infection, we conducted a survey among shepherds to assess possible exposure and symptoms. We also performed serologic and molecular assays. No evidence of transmission to humans was detected.

Schmallenberg Virus Infection of Adult Type I Interferon Receptor Knock-Out Mice

Schmallenberg virus (SBV), a novel orthobunyavirus, was discovered in Europe in late 2011. It causes mild and transient disease in adult ruminants, but fetal infection can lead to abortion or severe malformations. There is considerable demand for SBV research, but in vivo studies in large animals are complicated by their long gestation periods and the cost of high containment housing. The goal of this study was to investigate whether type I interferon receptor knock-out (IFNAR−/−) mice are a suitable small animal model for SBV. Twenty IFNAR−/− mice were inoculated with SBV, four were kept as controls. After inoculation, all were observed and weighed daily; two mice per day were sacrificed and blood, brain, lungs, liver, spleen, and intestine were harvested. All but one inoculated mouse lost weight, and two mice died spontaneously at the end of the first week, while another two had to be euthanized. Real-time RT-PCR detected large amounts of SBV RNA in all dead or sick mice; the controls were healthy and PCR-negative. IFNAR−/− mice are susceptible to SBV infection and can develop fatal disease, making them a handy and versatile tool for SBV vaccine research.

“Schmallenberg” virus: Analysis of the Epidemiological Data and Assessment of Impact

This scientific report provides an overall assessment of the impact of the infection on animal health, animal production and animal welfare of the provisionally named “Schmallenberg” virus (SBV) first detected in Germany. In Europe, 3745 holdings have been reported with SBV cases confirmed by laboratory testing across several Member States, mid May 2012. EFSA reviewed the epidemiological reports noting that SBV has been detected in cattle, sheep, goats and a bison. SBV antibodies have been detected in deer and no other species are known to be affected. EFSA also confirms that new studies support the initial assessment undertaken by the European Center for Disease Control and Prevention, that it is very unlikely that SBV poses a risk to humans. In terms of transmission routes, recent entomological investigations have identified SBV in field samples of biting midges of the Culicoides obsoletus group. Currently there is no evidence of any other route of transmission other than transplacental or vector borne routes. EFSA coordinated the collation of SBV epidemiological data during 2011–2012 in order to obtain comparable data for Europe. The maximum proportion of reported sheep holdings with SBV confirmed was 4% per country and 7.6% per region while for cattle less than 1.3 % of holdings were reported as SBV confirmed at both country and regional level. In order to assess the impact of SBV(spatial and temporal spread, proportion of affected holding and potential projection of arthrogryposis hydranencephaly syndrome cases) three models were used. In regions with SBV confirmed holdings, assuming a high prevalence of infection and post infection immunity, impact in the 2012–2013 calving and lambing season should be low. However, assuming SBV survived the winter of 2011, the models suggest that in unaffected regions with suitable temperatures for within herd transmission by vectors and high density of susceptible species (cattle and sheep) SBV infection is likely to spread. EFSA puts forward a number of recommendations to fill the knowledge gaps, these include but are not limited to: continuing serological investigations in affected regions and regions neighbouring affected areas, within herd and animal level impact investigation, monitoring putative vector population, setting SBV host vector transmission parameters, investigating other routes of transmission, host susceptibility, virulence and vulnerable period during gestation. Furthermore, the possible origins of the virus should be investigated as more information becomes available on the virus characteristics and infection epidemiology.

Schmallenberg Virus in Central Nervous System of Ruminants

Schmallenberg Virus in Central Nervous System of Ruminants