Akabane and Related Simbu Serogroup Virus Infections in Ruminants

Akabane virus and Schmallenberg virus are members of the Simbu antigenic group in the Orthobunyavirus genus of the family Peribunyaviridae, order Bunyavirales, which comprises approximately 25 antigenically different viruses (1).

The causative agent of Akabane infection is Akabane virus. It is transmitted by biting midges (Culicoides spp) in Australia, Japan, and Kenya.

Infections by Simbu serogroup viruses have been identified in all domestic ruminant species (cattle, sheep, goats), horses, buffalo, deer, camelids, and pigs in endemic areas. In Africa, antibodies against these viruses have been detected in a wide range of native wildlife.

Akabane virus has been widely detected in the tropical, subtropical, and adjacent temperate regions of Africa and the Middle East; throughout Asia; and south to Australia. A number of other viruses belonging to the Simbu serogroup have not usually been associated with disease but have a similar distribution.

Schmallenberg virus was first discovered in 2011, when it emerged in western Europe. It has been detected in various countries throughout continental Europe and the UK. Seropositivity to Schmallenberg virus has been demonstrated in other countries, including Ethiopia and China, but viral presence has not been confirmed.

None of the Simbu serogroup viruses that affect animals have been detected in North America. However, Oropouche virus, which causes a febrile illness in humans, is found in South America and the Caribbean.

The Simbu serogroup viruses are usually transmitted very efficiently by their insect vectors, which are predominantly Culicoides spp. These are true arboviruses; that is, after the insect takes a blood meal from its mammalian host, the virus replicates in the insect and, after an incubation period of approximately 8–10 days, is excreted in the saliva when the insect takes another blood meal.

Although there can be limited animal-to-animal transmission of some Simbu serogroup viruses, they are transmitted mainly by their insect vectors. Consequently, the geographical distribution of these viruses is defined exclusively by the habitat and range of the biting midge.

Akabane virus is common in most tropical and subtropical areas between approximately 35° N and 35° S. In these endemic areas, most herbivores become infected at an early age and develop a long-lasting immunity by the time of breeding. Thus, congenital abnormalities rarely occur.

Under favorable environmental conditions, such as an extended, humid summer, the Akabane virus vector (and hence the virus itself) can spread beyond its usual range into new areas, and outbreaks of congenital infection can be expected. These outbreaks usually occur at the northern or southern limits of the vector distribution or in areas of higher altitude. Similarly, pregnant ruminants from virus- and vector-free areas that are moved to virus-infected areas are at risk.

The midges that have been associated with the transmission of Schmallenberg virus in Europe have a greater tolerance to cooler temperatures, resulting in more northern limits to spread of the virus and detection of low-level transmission as temperatures rise soon after winter.

The development of disease induced by Akabane and Schmallenberg viruses is influenced by the time of gestation at which infection occurs and by the virus strain.

Akabane virus infections in cattle during the final 3 months of pregnancy result in a relatively low rate of disease (5–10% of calves are affected). With infections in the third and fourth months of pregnancy, up to 40% of calves are born with defects.

Some Akabane virus strains produce a very low incidence of abnormalities (< 20%) even at the most susceptible stages of gestation. The most severe strains, however, can cause disease in up to 80% of infected animals. In contrast, Schmallenberg virus causes a much lower incidence of disease (2).

In sheep and goats, disease induced by Akabane and Schmallenberg viruses occurs after infection of susceptible, pregnant animals; however, the distinct sequential manifestation of different abnormalities observed in cattle does not occur, because of the shorter period of gestation and therefore shorter period of susceptibility in sheep and goats.

Most Akabane and Schmallenberg virus–induced abnormalities in sheep or goats develop after infection between days 28 and 56 of gestation. Few, if any, abnormalities occur after infection at other times. However, it is not known whether infection in large or small ruminants very early in gestation results in lethal disease and subsequent embryonic or fetal death.

The clinical signs and pathological lesions of Akabane virus infection depend on the species of animal and time of infection.

In a herd of cattle with an extended or year-round calving period, the full range of Akabane virus–induced abnormalities can occur. The most severe defects occur when susceptible cows are infected between approximately 80 and 150 days of gestation; however, calves can be affected by infection at most times after the first 2 months of gestation.

Calves infected by Akabane virus late in pregnancy are sometimes born alive but unable to stand, and they might have flaccid paralysis of the limbs or might be uncoordinated.

Calves infected earlier (120–180 days of gestation) have rigid fixation of limbs, usually in flexion (arthrogryposis), and sometimes also torticollis, kyphosis, and scoliosis. These abnormalities usually cause dystocia and can result in severe obstetric complications, sometimes resulting in infertility and even death of cows.

Given that the timing of infection during gestation is important in the expression of teratogenic effects, in an outbreak of Akabane virus infection in a herd, the first calves born with arthrogryposis are less severely affected than those born during the next 4–6 weeks. Initially, affected calves might have only one or two joints affected on a single limb; later in the outbreak, affected calves might have severe fixation of multiple joints on several or all limbs.

Calves infected by Akabane virus at 80–120 days of gestation are usually born alive and, if able to stand, walk poorly and are depressed and blind. These calves have either porencephaly or hydranencephaly. Sometimes calves with severe hydranencephaly are aborted partway through gestation.

Infrequently, certain strains of Akabane virus cause disease when neonatal calves are infected in the first few weeks of life. A range of neurological signs and pathological changes consistent with acute viral encephalitis can occur.

In Japan, strains of Akabane virus that cause disease in adult cattle have also been described.

In small ruminants, arthrogryposis and hydranencephaly often occur concurrently. In lambs and kids, a range of other defects can occur, including pulmonary hypoplasia and spinal cord hypoplasia. Most Akabane-infected lambs or kids are stillborn or die soon after birth. Abortions also occur.

Akabane virus–induced congenital abnormalities (especially arthrogryposis and hydranencephaly) have been suspected in horses; however, this has not been confirmed in laboratory tests.

Clinical signs very similar to those observed with Akabane virus infection in ruminants have been observed in ruminants infected with Schmallenberg virus or with the Shamonda and Aino viruses, which are also members of the Simbu serogroup of orthobunyaviruses.

Compared with Akabane virus infection, with Schmallenberg, Shamonda, and Aino virus infections, the rate of disease development is usually much lower, unless infection occurs in a herd or flock that is managed under an intensively managed breeding program with rigorous synchronization that results in many animals simultaneously at similar stages of pregnancy.

When Schmallenberg virus first emerged in Europe, affected adult animals had mild fever and diarrhea; however, these effects have not been observed since that time.

In Africa, Shuni virus (Simbu serogroup) has also been described as a cause of acute encephalitis in horses. Shuni virus has also been an occasional cause of congenital defects in cattle in Israel and causes severe, fatal encephalitis in calves.

• Gross CNS lesions

• Serological testing

• RT-PCR assay

A presumptive diagnosis of Akabane virus infection can be based on gross CNS lesions; however, the disease must be differentiated from other infectious and genetic conditions. Infection can be confirmed by testing sera or body fluids (eg, pericardial or pleural fluid) from unsuckled affected offspring and their dams for antibodies against Akabane and other Simbu serogroup viruses.

Although the detection of antibodies in maternal serum does not confirm Akabane virus as an etiological agent, the absence of these antibodies is definitive for exclusion of the virus. Molecular tests such as RT-PCR assays occasionally can be used to detect residual viral RNA in the tissues of affected animals at term, or with greater success in aborted fetuses.

Other vector-borne viruses (and also non–vector-borne viruses such as BVDV) can cause congenital defects identical to those of Akabane and the related Simbu serogroup viruses. In Japan, Chuzan virus, a reovirus, is transmitted by Culicoides oxystoma and causes congenital infection in calves similar to Akabane virus infection.

In the US, Cache Valley virus, another vector-borne orthobunyavirus unrelated to Akabane virus, has been associated with congenital defects in small ruminants and, in some states, in cattle.

• Vaccination where available

There is no specific treatment for animals infected by Akabane or Schmallenberg virus. Measures should be directed at preventing infection of susceptible animals by these viruses during pregnancy and at controlling vectors. Introduction of stock from nonendemic to endemic areas should be done well before first breeding.

Effective vaccines against Akabane virus are available in Japan, and vaccines against Schmallenberg virus have been produced in Europe.

Infections in humans with teratogenic orthobunyaviruses from the Simbu serogroup have not been recorded, apart from oropouche virus in South America and the Caribbean.

Oropouche virus infection can cause meningitis and meningoencephalitis and is also transmitted by Culicoides midges. In some areas, wild animals are the reservoir; in others, there is human-to-human transmission via midge bites.

• Hecker YP, González-Ortega S, Cano S, Ortega-Mora LM, Horcajo P. Bovine infectious abortion: a systematic review and meta-analysis. Front Vet Sci. 2023;10:1249410.

1. Brenner J, Behar A. Simbu viruses' infection of livestock in Israel–a transient climatic land. Viruses. 2021;13(11):2149. doi:10.3390/v13112149

2. Kirkland PD, Barry RD, Harper PA, Zelski RZ. The development of Akabane virus-induced congenital abnormalities in cattle. Vet Rec. 1988;122(24):582-586. doi:10.1136/vr.122.24.582