Emergence of Schmallenberg virus

Issue: April 2012

During the summer and autumn of 2011, farmers and veterinarians in the German state of North Rhine-Westphalia and the Netherlands reported to the animal health authorities and diagnostic laboratories a unidenti?ed disease in dairy cattle with clear, nonlethal clinical signs of short duration, including fever, decreased milk production and diarrhea.

All classical endemic and emerging viruses with such manifestations could be excluded as the causative agent. To identify the cause of the apparently new disease, Germany’s leading animal health research institute — the Friedrich Loeffler Institute (FLI) — applied metagenomic analysis in the testing of pooled blood samples from affected cattle with acute symptoms.

Arnon Shimshony, DVM

The analysis yielded six sequence fragments with homology to the L and the M segments of viruses from the genus Orthobunyavirus. This led to the detection of sequences homologous to Orthobunyavirus S-segment, related to genomic sequences of Shamonda, Aino and Akabane virus — viruses of serogroup Simbu in the genus Orthobunyavirus. The virus was provisionally named: Schmallenberg virus (SBV), according to the location where the samples originated.

Infection in German cattle

On Nov. 19, FLI submitted to ProMED-mail a short communication, titled “A novel Orthobunyavirus-infection in German cattle,” in which it reported that real-time reverse transcription-polymerase chain reaction (RT-PCR) targeting the L segment was developed and supplied to its Dutch counterparts.

Orthobunyavirus is a genus of the Bunyaviridae, which is prevalent in Africa, Asia, Australia and Oceania, but occurs almost worldwide. Those viruses are vector-borne; the main transmitters are gnats (Culicoides spp.), but mosquitoes have been incriminated as well. There are five serogroups: Bwamba, California, Simbu, Bunyamwera and Wyeomyia. Several members of the Simbu group, namely the Akabane, Aino and Shamonda virus, and one of the Bunyamwera serogroup, the Cache valley virus, are known for decades as teratogenic in animals, predominantly cattle, sheep and goats. In most cases, no clinical disease is observed in the infected animal, but if susceptible females are infected while pregnant, abortions, fetal resorption or congenital malformations — mainly arthrogryposis and hydranencephaly (A-H) — may occur.

Simbu group viruses have been isolated from hematophagous insects, fowls and mammals in Africa, Asia, Australia and North and South America.

Congenitally malformed lambs

Since Dec. 1, sheep farms in the Netherlands reported the birth of congenitally malformed lambs on a steadily growing number of farms throughout the country. Using the RT-PCR test obtained from FLI, the Dutch Veterinary Research Institute in Lelystad succeeded in detecting the SBV in tissues of malformed lambs and in the samples from cattle that had suffered from the clinical disease, enabling them to conclude that the same virus was involved in both syndromes and species. This conclusion was supported by preliminary experimental infection trial in cows, carried out by FLI in Germany, demonstrating viral propagation with a short-lived viremia (days 2 to 5 post-inoculation). The clinical signs observed included elevated temperature for 1 day and moderate diarrhea.

Malformed lambs, as well as calves and kids, appeared during December 2011 throughout Germany and Belgium extending since the beginning of 2012 to France, southern United Kingdom, Luxembourg and (a single case) in north Italy. Many of the cases were confirmed as SBV by the RT-PCR test.

As of mid-March, the total number of affected, PCR-confirmed farms in the eight countries was about 2,500, of which 81% were sheep, 16.5% cattle and 2.5% goat farms. The actual number of affected cattle farms is assumed to be much higher since malformed calves seem to have tested PCR-negative more than 5 months after infection. This is supported by the results of a Dutch representative serosurgery that suggests the prevalence of antibodies against SBV in the dairy cattle population in the Netherlands is about 70%.

It is assumed that the virus had spread during summer and autumn by infected gnats. The vector (Culicoides) season was terminated in December; taking into consideration that closely related viruses, such as Akabane, are known to cause hydranencephaly in cattle, particularly during the third month of pregnancy. Such cases may still occur until May (the average gestation in cattle is 280 days; in sheep, 147 days; and in goats, 150 days).

Main concerns

One of the main concerns of the EU animal- and public-health authorities was to exclude any potential health risk to humans from the emerging virus. The Dutch National Institute for Public Health and the Environment (RIVM) produced a richly referenced “Risk Profile Human Schmallenberg virus,” later endorsed by the European Center for Disease Prevention and Control (ECDC). The analysis indicated that other teratogenic viruses of the Simbu serogroup, namely Akabane, Aino and Shamonda, which are genetically most related to SBV, are only found in livestock. However, the zoonotic potential of this virus could not be excluded as:

Viruses within the Simbu serogroup (Oropouche virus and Iquitos virus) are known to be zoonotic and cause human outbreaks.
Genetic reassortment among members of the same serogroup within the Orthobunyavirus genus occurs in nature and has led to the emergence of new viruses, occasionally with increased pathogenicity. This may increase the zoonotic potential of reasserted viruses.
Viruses within other serogroups of the genus Orthobunyavirus are zoonotic. Examples: California encephalitis virus, La Crosse encephalitis virus, Tahyna virus, Batai virus, Inkoo virus and Snowshoe hare virus. Cache valley virus, member of the Bunyamwera serogroup, is known as the causative agent of fetal death, abortion and A-H in sheep. This virus, endemic in North America, incidentally can cause encephalitis in humans.

Oropouche virus, a member of the Simbu serogroup, causes febrile disease in humans, often associated with clinical meningitis signs and skin rash, sometimes relapsing 2 to 3 weeks after initial onset of symptoms. It is present mainly in the Amazonic region, the Caribbean and Panama. The very limited information available indicates that Oropouche virus infection is associated with viremia that declines quickly until day 5 or 6 of illness. The virus has been recovered from the cerebral spinal fluid (CSF) in association with clinical meningitis.

Iquitos virus, also a member of the Simbu serogroup, is regarded a novel reassortant Orthobunyavirus. Cases reported from Peru were characterized by signs of meningitis, myalgia, arthralgias and chills. Respiratory and gastrointestinal manifestations, including diarrhea, vomiting and nausea, have been observed as well.

It deserves to be stressed that, so far, there are no reports of unusual human illness from the regions in Europe where SBV has been identified. The veterinary health services indicate that farmers from affected farms have been specifically asked for symptoms of illness and have reported none.

The World Animal Health Organization (OIE), paying special attention to the emerging (though not notifiable) SBV epizootic, has recently summarized the human aspects as follows:

“No human disease related to SBV has been reported in the affected zone so far, and the genetically most related Orthobunyaviruses do not cause disease in humans. Thus, current risk assessments conclude that the virus is unlikely to cause disease in humans, even if it cannot be fully excluded at this stage. Nevertheless, close collaboration between public health and animal health services is recommended for the early detection of potential human cases, particularly in farmers and veterinarians in close contact with potentially infected animals, and especially during interventions for dystocia.”

Even if human infection is possible, this is not likely to happen during the non-vector season, namely until May. In the meantime, it is anticipated that a serological test will become available, enabling mass-testing of animals and screening of potential human contacts.