Akabane and some of the related Simbu serogroup viruses, including Schmallenberg, are insect-transmitted viruses that cause congenital abnormalities of the CNS and musculoskeletal system in ruminants. Disease due to Akabane virus has been recognized in Australia, Israel, Japan, and Korea, usually at the margins of endemic areas. Schmallenberg virus caused an outbreak of disease associated with congenital defects across the European continent when it first emerged in 2011. The disease affects fetuses and neonates of cattle, sheep, and goats, mostly after in utero exposure.
Etiology, Susceptibility, Host Range, and Distribution of Akabane and Related Simbu Virus Infections in Ruminants
The causal agent of Akabane infection, Akabane virus, is an orthobunyavirus and member of the Simbu serogroup of the family Peribunyaviridae, order Bunyavirales. It is spread by biting midges(Culicoides spp) in Australia, Japan, and Kenya.
Infections with the 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 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, 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, spreading throughout Europe, to the UK, and to the Scandinavian countries. None of the Simbu serogroup viruses that affect animals have been detected in North America, although Oropouche virus, which causes a febrile illness in humans, is found in South America and the Caribbean.
Akabane and Schmallenberg virus are members of the Simbu antigenic group in the Orthobunyavirus genus of the family Peribunyaviridae, order Bunyavirales.
The Simbu serogroup viruses are usually transmitted very efficiently by their insect vectors, which are predominantly Culicoides spp. They 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 about 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 of these viruses, they are mostly dependent on spread by their insect vectors. Consequently, the geographic distribution of these viruses is exclusively defined by the habitat and range of the biting midge.
Akabane virus is common in most tropical and subtropical areas between ~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 are seldom seen. However, under favorable environmental conditions, such as an extended, humid summer, the vector (and hence the virus) may spread beyond its usual range into new areas, and outbreaks of congenital infection may 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 incidence of disease induced by Akabane and Schmallenberg viruses, is influenced by the time of gestation at which infection occurs and by the strain of virus. Infections in cattle during the last 3 months of pregnancy result in a relatively low incidence of disease (5%–10% of calves are affected). The peak incidence is seen after infection in the third and fourth months, when up to 40% of calves may be born with defects after Akabane virus infection. Some strains of Akabane virus produce a very low incidence of abnormalities (<20%) even at the most susceptible stages of gestation, whereas the most severe strains can cause disease in up to 80% of infected animals. In contrast, Schmallenberg virus causes a much lower incidence of disease.
In sheep and goats, disease is seen after infection of susceptible, pregnant animals, but the distinct sequential manifestation of different abnormalities seen in cattle does not occur because of the shorter period of gestation and the shorter period of susceptibility. Most abnormalities develop after infection between days 28–56 of gestation. Few, if any, abnormalities are seen after infection at other times. However, it is not known whether infection in large or small ruminants very early in gestation results in lethal infection, with abortion of the fetus.
The clinical signs and pathology 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 abnormalities may be seen. The most severe defects are seen after susceptible cows have been infected between ~80–150 days of gestation; however, calves can be affected at most times after the first 2 months of gestation.
Calves infected late in pregnancy may be born alive but unable to stand and may have a flaccid paralysis of the limbs, or may be uncoordinated. Those 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.
The first calves born with arthrogryposis are less severely affected than those born during the next 4–6 weeks. Initially, only one or two joints may be affected on a single limb, but later cases can have severe fixation of multiple joints on several or all limbs. Calves infected 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. Some calves with severe hydranencephaly may be aborted mid-gestation.
Infrequently, strains of Akabane virus can cause disease when calves are infected in the first few weeks of life. A range of neurologic signs and pathology consistent with an acute viral encephalitis may be seen. In Japan, strains of Akabane virus that cause disease in adult cattle have also been described.
In small ruminants, the lesions of arthrogryposis and hydranencephaly are often seen concurrently and are common in the same animals. In lambs and kids, a range of other defects may occur, including pulmonary hypoplasia and hypoplasia of the spinal cord. Most Akabane-infected lambs or kids are stillborn or die soon after birth. Abortions are also seen.
Akabane virus–induced congenital abnormalities (especially arthrogryposis and hydranencephaly) have been suspected in horses, but laboratory confirmation has been inconclusive.
A very similar range of clinical signs to those observed with Akabane virus in ruminants have been observed with Schmallenberg, as well as Shamonda and Aino viruses which are also members of the Simbu serogroup of orthobunyaviruses. The incidence of disease has usually been much lower, unless infection occurs in a herd or flock with an intensively managed breeding program with rigorous synchronization that results in a large number of animals at similar stages of pregnancy. When Schmallenberg virus first emerged in Europe, adult animals suffered a mild febrile illness with diarrhea, but this has not been observed subsequently.
In Africa, Shuni virus (Simbu serogroup) has also been described as a cause of acute encephalitis in horses. This virus has also been an occasional cause of congenital defects in cattle in Israel and has caused a severe, fatal encephalitis in calves.
Calves infected late in gestation with Akabane virus may show a disseminated encephalomyelitis when tissues are examined by histology. A neurogenic muscle atrophy due to loss of spinal motor neurons is observed histologically after infection of calves between 120–180 days of gestation. These lesions are responsible for the varying degrees of arthrogryposis, torticollis, kyphosis, or scoliosis that are observed grossly.
When calves are infected at 80–120 days of gestation, although most are born alive, careful examination of the brain will show varying degrees of cavitation of the cerebral hemispheres, ranging from porencephaly to severe hydranencephaly, which can result in destruction of the entire cerebral hemispheres and leave a residual brain stem. These severe lesions are common among animals infected in the earlier stages of pregnancy. The severity of the gross lesions is remarkable when compared with the clinical state of affected calves.
A useful differential diagnostic feature is the virtual absence of either gross or histologic lesions in the cerebellum, distinguishing Akabane virus infection from other teratogenic viruses such as bovine viral diarrhea virus. However, other Simbu serogroup viruses appear to produce lesions throughout the brain.
Infection of fetal sheep and goats with Akabane or Schmallenberg virus produces the range of gross and histologic lesions observed in cattle, although a greater diversity and severity of pathology can be seen in the same animal, presumably due to the shorter length of gestation.
A presumptive diagnosis of Akabane virus can be made based on the gross CNS lesions, but the disease must be differentiated from other infectious and genetic conditions. Infection can be confirmed by testing sera or body fluids (e.g., 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 as an etiologic agent, absence is definitive for exclusion. Molecular tests such as RT-PCR assays can be used to occasionally 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 nonvector-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. In the USA, Cache Valley virus, another vector-borne orthobunyavirus unrelated to Akabane virus, has been associated with congenital defects in sheep and perhaps cattle in some states.
There is no specific treatment for animals affected by Akabane or Schmallenberg virus infection. Measures should be directed at the prevention of infection of susceptible animals with these viruses during pregnancy. Introduction of stock from nonendemic to endemic areas should be done well before first breeding. Effective vaccines for Akabane virus are available in Japan, and vaccines for Schmallenberg virus have been produced in Europe.
Human infections with the teratogenic orthobunyaviruses from the Simbu serogroup have not been recorded, apart from Oropouche virus in South America and the Caribbean. Oropouche virus can cause meningitis and meningoencephalitis and is also transmitted by Culicoides midges. In some areas wildlife are the reservoir, but in others there is human to human transmission via midge bites.
Akabane and several related orthobunyaviruses are transmitted by biting midges and can cause severe congenital defects in large and small ruminant species.
In endemic areas, domestic animals usually become infected before reaching breeding age.
There are no treatments for affected animals.
There is limited availability and use of vaccines in some countries.