Spread Of Schmallenberg Virus Research Articles

Metaviromics Reveals Unknown Viral Diversity in the Biting Midge Culicoides impunctatus.

Biting midges (Culicoides species) are vectors of arboviruses and were responsible for the emergence and spread of Schmallenberg virus (SBV) in Europe in 2011 and are likely to be involved in the emergence of other arboviruses in Europe. Improved surveillance and better understanding of risks require a better understanding of the circulating viral diversity in these biting insects. In this study, we expand the sequence space of RNA viruses by identifying a number of novel RNA viruses from Culicoides impunctatus (biting midge) using a meta-transcriptomic approach. A novel metaviromic pipeline called MetaViC was developed specifically to identify novel virus sequence signatures from high throughput sequencing (HTS) datasets in the absence of a known host genome. MetaViC is a protein centric pipeline that looks for specific protein signatures in the reads and contigs generated as part of the pipeline. Several novel viruses, including an alphanodavirus with both segments, a novel relative of the Hubei sobemo-like virus 49, two rhabdo-like viruses and a chuvirus, were identified in the Scottish midge samples. The newly identified viruses were found to be phylogenetically distinct to those previous known. These findings expand our current knowledge of viral diversity in arthropods and especially in these understudied disease vectors.

Schmallenberg virus: a cyclical problem

Whether Schmallenberg virus (SBV) is a serious threat to ruminant breeding in Europe or is just another of the transboundary and emerging pathogens becoming popular recently due to changes in...

N-terminal domain of Schmallenberg virus envelope protein Gc delivered by recombinant equine herpesvirus type 1 and modified vaccinia virus Ankara: Immunogenicity and protective efficacy in cattle

Schmallenberg virus (SBV), which emerged in 2011 in Central Europe and subsequently spread very rapidly throughout the continent, affects predominantly ruminants. SBV is transmitted by insect vectors, and therefore vaccination is one of the major tools of disease control. Only recently, a domain connected to virus neutralization has been identified at the amino-terminal part of the viral envelope protein Gc. Here, this Gc domain delivered by recombinant EHV-1 or MVA vector viruses was tested in a vaccination-challenge trial in cattle, one of the major target species of SBV.The EHV-1-based vaccine conferred protection in two of four animals, whereas immunization using the MVA vector vaccine efficiently induced an SBV-specific antibody response and full protection against SBV challenge infection in all the vaccinated animals. Moreover, due to the absence of antibodies against SBVs N-protein, both vector vaccines enable the differentiation between vaccinated and field-infected animals making them to a promising tool to control SBV spread as well as to prevent disease in domestic ruminants.

Schmallenberg Virus: A Novel Virus of Veterinary Importance.

In late 2011, unspecific clinical symptoms such as fever, diarrhea, and decreased milk production were observed in dairy cattle in the Dutch/German border region. After exclusion of classical endemic and emerging viruses by targeted diagnostic systems, blood samples from acutely diseased cows were subjected to metagenomics analysis. An insect-transmitted orthobunyavirus of the Simbu serogroup was identified as the causative agent and named Schmallenberg virus (SBV). It was one of the first detections of the introduction of a novel virus of veterinary importance to Europe using the new technology of next-generation sequencing. The virus was subsequently isolated from identical samples as used for metagenomics analysis in insect and mammalian cell lines and disease symptoms were reproduced in calves experimentally infected with both, this culture-grown virus and blood samples of diseased cattle. Since its emergence, SBV spread very rapidly throughout the European ruminant population causing mild unspecific disease in adult animals, but also premature birth or stillbirth and severe fetal malformation when naive dams were infected during a critical phase of gestation. In the following years, SBV recirculated regularly to a larger extend; in the 2014 and 2016 vector seasons the virus was again repeatedly detected in the blood of adult ruminants, and in the following winter and spring months, a number of malformed calves and lambs was born. The genome of viruses present in viremic adult animals showed a very high sequence stability; in sequences generated between 2012 and 2016, only a few amino acid substitutions in comparison to the initial SBV isolate could be detected. In contrast, a high sequence variability was identified in the aminoterminal part of the glycoprotein Gc-encoding region of viruses present in the brain of malformed newborns. This mutation hotspot is independent of the region or host species from which the samples originated and is potentially involved in immune evasion mechanisms.

Schmallenberg virus: on its way out or due for a comeback?

SCHMALLENBERG virus (SBV) emerged during the summer of 2011 in north-western Europe and was identified for the first time in dairy cattle herds in Germany (Hoffmann and others 2012). The...

S segment variability during the two first years of the spread of Schmallenberg virus.

A large sheep flock screened over a two-year period showed active spreading of Schmallenberg virus (SBV) during the summers of 2011 and 2012. Transplacental infections were observed during the two associated lambing periods (the winters of 2012 and 2013). Analysis of small (S) segment sequences of 38 SBV-positive samples, collected during periods of viral spreading and lambing revealed intra-herd sequences diversity and sub-consensus variability occurring after transplacental infections. In comparison with the nucleoprotein (N), which appeared to be conserved, the non-structural protein (NSs) showed the highest level of variability at the time of viral emergence and over the two-year analysis period.

Exposure of Wildlife to the Schmallenberg Virus in France (2011-2014): Higher, Faster, Stronger (than Bluetongue)!

The Schmallenberg virus (SBV) has recently emerged in Europe, causing losses to the domestic livestock. A retrospective analysis of serodata was conducted in France for estimating seroprevalence of SBV among six wildlife species from 2011-2012 to 2013-2014, that is during the three vector seasons after the emergence of the SBV in France. Our objective was to quantify the exposure of wildlife to SBV and the potential protective effect of elevation such as previously observed for bluetongue. We also compared the spatiotemporal trends between domestic and wild animals at the level of the departments. We tested 2050 sera using competitive ELISA tests. Individual and population risk factors were further tested using general linear models among 1934 individuals. All populations but one exhibited positive results, seroprevalence up to 30% being observed for all species. The average seroprevalence did not differ between species but ranged from 0 to 90% according to the area and period, due to the dynamic pattern of infection. Seroprevalence was on average higher in the lowlands compared to areas located up to 800m. Nevertheless, seroprevalence above 50% occurred in areas located up to 1500m. Thus, contrary to what had been observed for bluetongue during the late 2000s in the same areas, SBV could spread to high altitudes and infect all the studied species. The spatial spread of SBV in wildlife did not fully match with SBV outbreaks reported in the domestic livestock. The mismatch was most obvious in mountainous areas where outbreaks in wildlife occurred on average oneyear after the peak of congenital cases in livestock. These results suggest a much larger spread and vector capacity for SBV than for bluetongue virus in natural areas. Potential consequences for wildlife dynamics are discussed.

Genetic stability of Schmallenberg virus in vivo during an epidemic, and in vitro, when passaged in the highly susceptible porcine SK-6 cell line

Schmallenberg virus (SBV), an arthropod-borne orthobunyavirus was first detected in 2011 in cattle suffering from diarrhea and fever. The most severe impact of an SBV infection is the induction of malformations in newborns and abortions. Between 2011 and 2013 SBV spread throughout Europe in an unprecedented epidemic wave. SBV contains a tripartite genome consisting of the three negative-sense RNA segments L, M, and S. The virus is usually isolated from clinical samples by inoculation of KC (insect) or BHK-21 (mammalian) cells. Several virus passages are required to allow adaptation of SBV to cells in vitro. In the present study, the porcine SK-6 cell line was used for isolation and passaging of SBV. SK-6 cells proved to be more sensitive to SBV infection and allowed to produce higher titers more rapidly as in BHK-21 cells after just one passage. No adaptation was required. In order to determine the in vivo genetic stability of SBV during an epidemic spread of the virus the nucleotide sequence of the genome from seven SBV field isolates collected in summer 2012 in Switzerland was determined and compared to other SBV sequences available in GenBank. A total of 101 mutations, mostly transitions randomly dispersed along the L and M segment were found when the Swiss isolates were compared to the first SBV isolated late 2011 in Germany. However, when these mutations were studied in detail, a previously described hypervariable region in the M segment was identified. The S segment was completely conserved among all sequenced SBV isolates. To assess the in vitro genetic stability of SBV, three isolates were passage 10 times in SK-6 cells and sequenced before and after passaging. Between two and five nt exchanges per genome were found. This low in vitro mutation rate further demonstrates the suitability of SK-6 cells for SBV propagation.

Was the French clinical surveillance system of bovine brucellosis influenced by the occurrence and surveillance of other abortive diseases?

The bovine brucellosis clinical surveillance system implemented in France aims to detect early any case of bovine brucellosis, a disease of which the country has been declared free since 2005. It relies on the mandatory notification of every bovine abortion. Following the spread of the Schmallenberg virus (SBV) in France in 2012 and 2013, and the implementation in 2012 of a clinical surveillance programme of Q fever based on abortion notifications in ten pilot départements, our objective was to study whether these two events influenced the brucellosis clinical surveillance system. The proportion of notifying farmers was analyzed over each semester from June 1, 2009 to June 30, 2013 according to the size and production type of herds, SBV status of départements and the implementation of the Q fever surveillance. Our analysis showed a slight increase in the proportion of notifying farmers as départements became infected by SBV, and after the implementation of Q fever surveillance (during the first semester of 2013). These variations might be explained by an increase in abortion occurrence (congenital deformities in newborns, due to SBV) and/or by an increase in farmers’ and veterinarians’ awareness (due to the spread of SBV and the implementation of the Q fever surveillance). These results highlight the difficulties in interpreting variations in the proportion of notifying farmers as a consequence of an increase in abortion occurrence. As bovine abortion surveillance can play an important role in the early warning for several diseases, there is a need to explore other ways to monitor abortions in cattle, such as syndromic surveillance using the dates of artificial insemination or calving data.

Spread and impact of the Schmallenberg virus epidemic in France in 2012-2013.

BackgroundThe Schmallenberg virus (SBV) emerged in Europe in 2011 and caused a widespread epidemic in ruminants.In France, SBV emergence was monitored through a national multi-stakeholder surveillance and investigation system. Based on the monitoring data collected from January 2012 to August 2013, we describe the spread of SBV in France during two seasons of dissemination (vector seasons 2011 and 2012) and we provide a large-scale assessment of the impact of this new disease in ruminants.ResultsSBV impact in infected herds was primarily due to the birth of stillborns or deformed foetuses and neonates. Congenital SBV morbidity level was on average moderate, although higher in sheep than in other ruminant species. On average, 8% of lambs, 3% of calves and 2% of kids born in SBV-infected herds showed typical congenital SBV deformities. In addition, in infected herds, farmers reported retrospectively a lower prolificacy during the vector season, suggesting a potential impact of acute SBV infection during mating and early stages of gestation.ConclusionsDue to the lack of available control and prevention measures, SBV spread quickly in the naive ruminant population. France continues to monitor for SBV, and updated information is made available online on a regular basis [http://www.plateforme-esa.fr/]. Outbreaks of congenital SBV are expected to occur sporadically from now on, but further epidemics may also occur if immunity at population level declines.

Impact of temperature, feeding preference and vaccination on Schmallenberg virus transmission in Scotland.

First identified in 2011, Schmallenberg virus (SBV) is principally transmitted by Culicoides midges and affects ruminants. Clinical presentation is typified by foetal abnormalities, but despite very high infection rates, relatively few animals present with clinical signs. In this paper we further develop a previously published stochastic mathematical model of SBV spread to investigate the optimal deployment of a vaccine for SBV in Scotland, a country that has experienced only sporadic and isolated cases of SBV. We consider the use of the vaccine under different temperatures and explore the effects of a vector preference for feeding on cattle. We demonstrate that vaccine impact is optimised by targeting it at the high risk areas in the south of Scotland, or vaccinating only cattle. At higher than average temperatures, and hence increased transmission potential, the relative impact of vaccination is considerably enhanced. Vaccine impact is also enhanced if vectors feed preferentially on cattle. These findings are of considerable importance when planning control strategies for SBV and also have important implications for management of other arboviruses such as Bluetongue virus. Environmental determinants and feeding preferences should be researched further to inform development of effective control strategies.

A bulk milk tank study to detect evidence of spread of Schmallenberg virus infection in the south-west of Ireland in 2013.

BackgroundSchmallenberg virus (SBV) was first detected in Germany in November 2011. Confirmation of infection in Ireland was reported on October 30th 2012. The results of a national serological survey carried out in early 2013 suggested that the first introduction of SBV into Ireland probably occurred in the south or southeast of Ireland in the spring or summer of 2012, with subsequent spread eastwards and northwards. It was unclear at that stage whether the virus had survived the winter period and would continue to spread in 2013. The purpose of this study was to monitor the spread of the virus in the mid-west region through the summer and autumn of 2013 using bulk tank milk from selected dairy herds.FindingsSeventy two dairy farmers were recruited to participate in the bulk milk tank study. Each farmer agreed to collect a bulk tank milk sample on a weekly basis from early June. A total of 988 samples were received between June 5th and December 3rd 2013 and these were analysed using an indirect ELISA test. Of the initial set of 72 samples received between June 5th and July 16th, nine were positive, one was inconclusive and 62 were negative. By the end of the study in early December 2013 only one new farm turned positive. This was the farm that had initially tested inconclusive.ConclusionThe study results suggest that the anticipated spread of SBV across Ireland from the south and south-east did not occur during 2013.

Inferences about the transmission of Schmallenberg virus within and between farms

In the summer of 2011 Schmallenberg virus (SBV), a Culicoides-borne orthobunyavirus, emerged in Germany and The Netherlands and subsequently spread across much of Europe. To draw inferences about the transmission of SBV we have developed two models to describe its spread within and between farms. The within-farm model was fitted to seroprevalence data for cattle and sheep farms in Belgium and The Netherlands, with parameters estimated using approximate Bayesian computation. Despite the short duration of viraemia in cattle and sheep (mean of 3–4 days) the within-farm seroprevalence can reach high levels (mean within-herd seroprevalence >80%), largely because the probability of transmission from host to vector is high (14%) and SBV is able to replicate quickly (0.03 per day-degree) and at relatively low temperatures (threshold for replication: 12.3°C). Parameter estimates from the within-farm model were then used in a separate between-farm model to simulate the regional spread of SBV. This showed that the rapid spread of SBV at a regional level is primarily a consequence of the high probability of transmission from host to vector and the temperature requirements for virus replication. Our results, obtained for a region of the UK in a typical year with regard to animal movements, indicate that there is no need to invoke additional transmission mechanisms to explain the observed patterns of rapid spread of SBV in Europe. Moreover, the imposition of movement restrictions, even a total movement ban, has little effect on the spread of SBV at this scale.

Serosurveillance of Schmallenberg virus in Switzerland using bulk tank milk samples

Infections with Schmallenberg virus (SBV), a novel Orthobunyavirus transmitted by biting midges, can cause abortions and malformations of newborns and severe symptoms in adults of domestic and wild ruminants. Understanding the temporal and spatial distribution of the virus in a certain territory is important for the control and prevention of the disease. In this study, seroprevalence of antibodies against SBV and the spatial spread of the virus was investigated in Swiss dairy cattle applying a milk serology technique on bulk milk samples. The seroprevalence in cattle herds was significantly higher in December 2012 (99.5%) compared to July 2012 (19.7%). This high between-herd seroprevalence in cattle herds was observed shortly after the first detection of viral infections. Milk samples originating from farms with seropositive animals taken in December 2012 (n=209; mean 160%) revealed significantly higher S/P% ratios than samples collected in July 2012 (n=48; mean 103.6%). This finding suggests a high within-herd seroprevalence in infected herds which makes testing of bulk tank milk samples for the identification farms with past exposures to SBV a sensitive method. It suggests also that within-herd transmission followed by seroconversion still occurred between July and December. In July 2012, positive bulk tank milk samples were mainly restricted to the western part of Switzerland whereas in December 2012, all samples except one were positive. A spatial analysis revealed a separation of regions with and without positive farms in July 2012 and no spatial clustering within the regions with positive farms. In contrast to the spatial dispersion of bluetongue virus, a virus that is also transmitted by Culicoides midges, in 2008 in Switzerland, the spread of SBV occurred from the western to the eastern part of the country. The dispersed incursion of SBV took place in the western part of Switzerland and the virus spread rapidly to the remaining territory. This spatial pattern is consistent with the hypothesis that transmission by Culicoides midges was the main way of spreading.

Rapid spread and association of Schmallenberg virus with ruminant abortions and foetal death in Austria in 2012/2013

Schmallenberg virus (SBV) has emerged in summer–autumn 2011 in north-western Europe. Since then, SBV has been continuously spreading over Europe, including Austria, where antibodies to SBV, as well as SBV genome, were first detected in autumn 2012. This study was performed to demonstrate the dynamics of SBV spread within Austria, after its probable first introduction in summer 2012. True seroprevalence estimates for cattle and small ruminates were calculated to demonstrate temporal and regional differences of infection. Furthermore, the probability of SBV genome detection in foetal tissues of aborted or stillborn cattle and small ruminants as well as in allantoic fluid samples from cows with early foetal losses was retrospectively assessed.SBV first reached Austria most likely in July–August 2012, as indicated by retrospective detection of SBV antibodies and SBV genome in archived samples. From August to October 2012, a rapid increase in seroprevalence to over 98% in cattle and a contemporaneous peak in the detection of SBV genome in foetal tissues and allantoic fluid samples was noted, indicating widespread acute infections. Notably, foetal malformations were absent in RT-qPCR positive foetuses at this time of the epidemic. SBV spread within Austrian cattle reached a plateau phase as early as October 2012, without significant regional differences in SBV seroprevalence (98.4–100%). Estimated true seroprevalences among small ruminates were comparatively lower than in cattle and regionally different (58.3–95.6% in October 2012), potentially indicating an eastward spread of the infection, as well as different infection dynamics between cattle and small ruminants. Additionally, the probability of SBV genome detection over time differed significantly between small ruminant and cattle samples subjected to RT-qPCR testing.

The Schmallenberg virus epidemic in Europe—2011–2013

During the Schmallenberg virus (SBV) epidemic, the European Food Safety Authority (EFSA) collected data on SBV occurrence across Europe in order to provide an assessment of spread and impact. By May 2013, twenty-nine countries were reporting to EFSA and twenty-two countries had reported cases of SBV. The total number of SBV herds reported was 13,846 and the number of SBV laboratory confirmed herds was 8730. The surveillance activities were based on the detection of SBV clinical cases (either adults or newborns). Malformation in newborns was the most commonly reported clinical sign of SBV-infection. All countries were able to provide the date when the first suspicion of SBV in the herd was reported and nineteen could report the location of the herd at a regional level. This allowed the spread of SBV in Europe to be measured both temporally and spatially. The number of SBV confirmed herds started to increase in December 2011 and two peaks were observed in 2012 (February and May). Confirmed herds continued to be reported in 2012 and into 2013. An increase during winter 2012 and spring 2013 was again observed, but the number of confirmed herds was lower than in the previous year. SBV spread rapidly throughout Europe from the initial area of detection. SBV was detected above the latitude of 60° North, which exceeds the northern expansion observed during the bluetongue virus serotype 8 epidemic in 2006–2009. The impact of SBV was calculated as ratio of the number of herds with at least one malformed SBV positive foetus and the total number of herds in this region. The 75th percentile of the malformations ratio in the various affected countries for the whole reporting period was below 1% and 3% for cattle and sheep herds, respectively. International data collection on emerging diseases represents a challenge as the nature of available data, data quality and the proportion of reported cases may vary widely between affected countries. Surveillance activities on emerging animal diseases are often structured only for case detection making the estimation of infection/diseases prevalence and the investigation of risk factors difficult. The impact of the disease must be determined to allow risk managers to take appropriate decisions. Simple within-herd impact indicators suitable for emerging disease outbreaks should be defined that could be measured as part of routine animal health surveillance programmes and allow for rapid and reliable impact assessment of emerging animal health diseases.

Modelling the continental-scale spread of Schmallenberg virus in Europe: Approaches and challenges

SummaryFollowing its emergence in northern Europe in 2011 Schmallenberg virus (SBV), a vector-borne disease transmitted by the bites of Culicoides midges, has spread across much of the continent. Here we develop simple models to describe the spread of SBV at a continental scale and, more specifically, within and between NUTS2 regions in Europe. The model for the transmission of SBV between regions suggests that vector dispersal is the principle mechanism for transmission, even at the continental scale. The within-region model indicates that there is substantial heterogeneity amongst regions in the force of infection for cattle and sheep farms. Moreover, there is considerable under-ascertainment of SBV-affected holdings, though the level of under-ascertainment varies between regions. We contrast the relatively simple approach adopted in this study with the more complex continental-scale micro-simulation models which have been developed for pandemic influenza and discuss the strengths, weaknesses and data requirements of both approaches.

Dynamics of Schmallenberg virus infection within a cattle herd in Germany, 2011

In late 2011, the insect-transmitted Schmallenberg virus (SBV) emerged in Europe. In this study, a cattle farm located in the core region of the epidemic was closely monitored between May 2011 and January 2012. Up to the end of September every tested serum sample was negative by an SBV-specific antibody ELISA, suggesting the absence of an infection before autumn 2011. Around the end of September/beginning of October SBV genome was detected in blood samples of some animals, and a few cows exhibited fever during that period. Starting at the end of September the first cows seroconverted; the within-herd prevalence reached 100% within barely 1 month. Consequently, SBV spread rapidly in the tested herd during the vector season of 2011.

Emergence and spread of Schmallenberg virus

IF the adage that the ‘retrospectoscope’ is a powerful tool is to be believed, it is useful to review the occurrence of the second epizootic viral vector borne disease to emerge in five years in Northern Europe: the emergence of Schmallenberg virus (SBV) illustrates a number of key principles in the control of such transboundary diseases. Globalisation and climate change are clearly drivers of changing patterns of vector borne disease (Saker and others 2004). Purse and others (2005) recognised the potential for bluetongue (BTV) to spread beyond its accustomed subtropical/Mediterranean distribution into more temperate climates, but the sudden occurrence of BTV-8 in 2006 and the speed and scale of its spread in Northern Europe was unprecedented. A similar pattern has been seen more recently with SBV. In the late summer of 2011, an unusual pattern of clinical disease (fever, milk drop and in some cases diarrhoea) was observed in dairy herds on both sides of the Dutch-German border (Promed 2011). The ability to recognise the occurence of something new and get an accurate picture of what is happening is the first step in disease control. Information on the emergence and spread of this, at first …

Schmallenberg virus epidemic in the Netherlands: Spatiotemporal introduction in 2011 and seroprevalence in ruminants

This study aimed at estimating the Schmallenberg virus (SBV) seroprevalence in dairy heifers, non-dairy adult cattle, sheep and goats in the Netherlands after cessation of SBV transmission at the end of 2011. Archived serum samples from ruminants submitted to the GD Animal Health Service for monitoring purposes between November 2011 and March 2012 were selected and tested for presence of SBV-specific antibodies using an in-house ELISA. Animal seroprevalences were estimated at 63.4% in dairy heifers, 98.5% in adult non-dairy cattle, 89.0% in sheep and 50.8% in goats. Multivariable analyses were carried out to describe the relationship between potential risk factors and the ELISA outcome S/P%. The overall SBV seroprevalence in ruminants and ruminant herds in the Netherlands at the end of 2011 was high, with considerable differences between species and farm types. No gradient spatial pattern in final seroprevalence could be detected and therefore no suggestions about the site of introduction and spread of SBV in the Netherlands in 2011 could be made. In dairy heifers, it was shown that S/P% increased with age. In sheep, S/P% was lower in animals located in the coastal area. Whether herds were located near the German border did not affect the S/P% in sheep nor in dairy heifers. An attempt was made to gain insight in the spatiotemporal introduction of SBV in the Netherlands in 2011, by testing sheep serum samples from 2011. A seroprevalence of about 2% was found in samples from April, June and July 2011, but the ELISA positive samples could not be confirmed in a virus neutralization test. A clear increase in seroprevalence started at August 2011. From mid-August 2011 onwards, seropositive samples were confirmed positive by virus neutralization testing. This indicated the start of the epidemic, but without a clear spatial pattern.