Bovine ephemeral fever

18/11/2021

18/11/2021

Bovine ephemeral fever (or 3-day sickness) is an acute febrile illness of cattle and water buffaloes. Caused by an arthropod-borne rhabdovirus, bovine ephemeral fever virus (BEFV), the disease occurs seasonally over a vast expanse of the globe encompassing much of Africa, the Middle East, Asia and Australia. Although mortality rates are typically low, infection prevalence and morbidity rates during outbreaks are often very high, causing serious economic impacts through loss of milk production, poor cattle condition at sale and loss of traction power at harvest. There are also significant impacts on trade to regions in which the disease does not occur, including the Americas and most of Europe. In recent years, unusually severe outbreaks of bovine ephemeral fever have been reported from several regions in Asia and the Middle East, with mortality rates through disease or culling in excess of 10–20%. There are also concerns that, like other vector-borne diseases of livestock, the geographic distribution of bovine ephemeral fever could expand into regions that have historically been free of the disease. Here, we review current knowledge of the virus, including its molecular and antigenic structure, and the epidemiology of the disease across its entire geographic range. We also discuss the effectiveness of vaccination and other strategies to prevent or control infection.

Introduction
Bovine ephemeral fever virus (BEFV) an arthropod-borne rhabdovirus which is classified as the type species of the genus Ephemerovirus. It causes an acute febrile illness of cattle and water buffalo known as bovine ephemeral fever (BEF) or various other local names such as 3-day sickness, bovine enzootic fever, bovine influenza or stiffseitke. It occurs over a vast expanse of the globe from the southern tip of Africa to the Nile River Delta, across the Middle East through South and South-East Asia, into northern and eastern Australia, and throughout most of China, extending into Taiwan, the Korean Peninsula and southern Japan (Figure 1). BEFV does not occur in the islands of the Pacific, Europe (other than in the western regions of Turkey) or in the Americas where, for quarantine purposes, it is considered as an important exotic pathogen. Infection may be clinically unapparent or result in mild to severe clinical signs including a bi-phasic fever, salivation, ocular and nasal discharge, recumbency, muscle stiffness, lameness and anorexia. Sternal and lateral recumbency in cattle with clinical BEF are shown in Additional file 1. Usually, the disease is characterised by rapid onset and rapid recovery, lasting only 1–3 days, but there are reports of prolonged paralysis and ataxia in some animals following the acute phase of infection. The most severe cases can result in mortality which may be due to exposure, starvation or pneumonia, but little is currently known about the direct cause of death. Morbidity rates can be very high (approaching 100%) and mortality rates are typically low (

18/11/2021

Bovine Ephemeral Fever (BEF = ‘three day sickness’) causes a short but significant fever, drooling, shivering, a discharge from eyes and nose, lameness and muscular soreness. Animals may become recumbent for a day or two. For the most part, BEF is a mild transient illness hence the name ‘three day sickness’. But some animals can be more significantly affected and cattle deaths can result. Thus the disease and the
need to manage cases shouldn’t be underestimated.
In particular heavy animals such as bulls and big cows may be most severely affected. A transient infertility in bulls can occur and a small proportion of pregnant cows can abort, presumably from the high fever.
Early veterinary treatment can mediate these impacts and prevent animals from becoming recumbent. Good nursing care can be the difference between affected cattle recovering in the normal three-day window or succumbing to secondary health effects from dehydration, particularly in hot weather, or sustained recumbency.
For information on vaccinating your herd or managing BEF, please contact your private veterinarian or discuss with our team at LLS by calling 1300 795 299.

18/11/2021

01/07/2021

29/06/2021

29/06/2021

26/06/2021

Nature of the disease
Bovine ephemeral fever (BEF or Bovine Epizootic Fever) is a non contagious arthropod-borne disease (arbovirus from the Rhabdoviridae family) of cattle, characterised by an acute fever of short duration, with high morbidity and low mortality.
Classification
SPC List D disease
Susceptible species
Cattle and buffalo are believed to be the only significant hosts.
Distribution
BEF occurs widely across Africa and Asia, and in areas of northern and eastern Australia. It does not occur in Europe or the Americas.
Clinical signs
Onset of clinical signs is usually rapid. Bulls and fat cows or bullocks tend to be worst affected, with calves usually only mildly affected. Clinical signs include:
Fever usually lasting only 1-2 days
Stiffness, with a shifting lameness affecting one or more legs. Some animals become recumbent and may remain down for up to a week
Subcutaneous swelling in the sub-mandibular area or around limb joints
Elevated respiratory rate and sometimes dyspnoea
Nasal and ocular discharges
Drooling of saliva
Periorbital swelling
Increased excitability and agitation.
Severely affected animals lose condition, milking cows suffer a severe drop in production and cows in advanced pregnancy may abort. In most cases the infection has a short duration with a rapid recovery. However, occasional cases die and relapses can occur.

Post-mortem findings
Gross pathology of affected animals is usually unremarkable, with the main findings being:
Oedema of lymph nodes
Increased fluid in body cavities and joint cavities, often containing fibrin.
Differential diagnosis
BEF can be suspected on the basis of its transient nature and rapid spread. In individuals it may resemble conditions such as:
Traumatic reticulitis
Acute laminitis
Parturient paresis
In early stage

Specimens required for diagnosis
Diagnosis is usually made on clinical grounds during major epidemics. Sporadic cases, or those occurring early in a possible epidemic can be confirmed by virus isolation or serology. Paired blood samples should be collected — one during the acute phase, with the second taken 2-3 weeks later.
Transmission
BEF is spread by infected insects. The virus has been isolated from a range of potential insect vectors, including a number of species of Culicoides and several species of mosquito. There may be a range of vectors involved in spreading the disease, including some that have not yet been identified.
Risk of introduction
As virus is only present in the blood for short periods during the acute stage of the diseases and as cattle and buffalo are not considered to become carriers, BEF is unlikely to be introduced through the importation of healthy cattle. Infected vectors are an important potential source of introduction. Strong winds can transport vectors long distances, over land and water. Establishment of the disease depends on suitable environmental conditions for the vector to increase and spread.
Control / vaccines
Animals generally recover quickly without treatment, however the disease is responsive to anti-inflammatory drugs. These drugs must be given for the expected course of the clinical disease. During fever, the paresis or paralysis responds to injected calcium borogluconate in the same manner as parturient paresis (milk fever).
An effective vaccine is available, and can be used to protect animals in the face of an advancing outbreak, or as a routine in endemic areas.

26/06/2021

The disease is enzootic in Australia. It was first reported in 1936 when an outbreak occurred 450 km south of Darwin in the Northern Territory [67]. The remoteness of this location suggests that BEFV was likely present but undetected prior to the outbreak which occurred 60 years after the establishment of large cattle holdings in the north of the continent. Prior to the late 1970s, BEF occurred primarily as large epizootics that swept southwards in a wave-like fashion out of the northern tropical zone into sub-tropical and warm temperate regions of Western Australia, Queensland and New South Wales, occasionally reaching northern Victoria. Such epizootics occurred in 1936–37, 1955–56, 1967–68, and then in succession in 1970–71, 1972–74 and 1974–76 corresponding to periods of unusually high annual rainfall associated with the La Niña phase of the Southern Oscillation Index [6, 68–70]. Since that time, the epidemiological pattern changed from an advancing north-south wave to annual outbreaks during the summer and autumn months over a wide area of northern and eastern Australia [71]. Regular monitoring of sentinel herds has indicated that there are marked differences in seasonality between different geographic regions [72]. Sero-conversions occur perennially in the northern tropical zone of the Northern Territory but seasonality increases gradually with increasing latitude in eastern Australia where transmission may cease during the winter months, particularly during periods of prolonged drought. BEFV sero-conversions also occur annually in the Kimberley region in the far north of Western Australia and are detected regularly in the Pilbara region approximately 1000 km to the south-west.

Molecular epidemiological studies using G gene ectodomain sequences have shown that all BEFV strains isolated in Australia since 1956 have a single common ancestor indicating that, unless earlier lineages have become extinct, the virus has entered Australia on only a single occasion [18]. The phylogenetic data also indicate that BEFV is evolving as a single clade across the continent at the relatively high evolutionary rate of ~10−3 nucleotide substitutions/site/year [18]. This suggests that most adaptive evolution occurs in the perennial enzootic focus in the north where strains are continually selected for optimum fitness and regularly move south with the onset of summer and autumn rains, displacing the scattered remnants of enzootic infection. There is also evidence that the evolution of BEFV in Australia is being driven by cross-reactive neutralising antibody to Kimberley virus [18] which has a similar geographic distribution and ecology to BEFV but has not been associated with clinical disease (see below).

South and South-East Asia
Although the epidemiology is poorly defined, there is evidence of BEFV infection in an arc of countries in South and South-East Asia extending from the Indian sub-continent and Sri Lanka, eastwards to the Indonesian Archipelago and northwards to the Philippines. An ephemeral fever resembling BEF was first reported in Pakistan (then Punjab) in 1919 as a disease of cattle known locally as “Vil” [73]. It was noted that the disease occurred most commonly during the rainy season (July to October) and simultaneous outbreaks at widely separated locations suggested that it was insect-borne. The disease was also reported in Tamil Nadu in the south-east of India in 1924 [74]. More recently, BEF has been reported in cattle and water buffalo in Uttar Pradesh in the central north [75], Gujarat in the west [36] and Himachal Pradesh in the far north [76]. In Uttar Pradesh during 1973–1975, BEF was reported to occur from April to October with the highest incidence in July and August when the weather is hot and humid. Disease occurred more frequently in Bos taurus/Bos indicus cross-bred animals than in local breeds and the highest incidence occurred in older cattle [75]. In Nepal, BEF also occurs during the hot, humid months of June to October and is considered to be sporadic in some regions and enzootic in others [77]. In Sri Lanka, BEF occurs primarily from June to December and appears to follow periods of high rainfall [78, 79].

BEF was first reported in Indonesia in 1919 when an outbreak occurred in dairy cattle in West Java. The next reported epizootic occurred from 1928 to 1931 on the east coast of Sumatra [80]. Subsequent outbreaks were reported in East Java in 1978, where cases persisted at least until 1985 with sometimes quite high mortality rates, and in Kalimantan in 1991. A serological survey conducted in 1979 detected a high prevalence (78.9%) of BEFV-neutralising antibodies in cattle from Java and Bali [81]. Serological surveys conducted between 1987 and 1990 also detected a relatively high prevalence of BEFV-neutralising antibodies in sentinel cattle across much of the archipelago including Sumatra, Java, Bali, Timor, Kalimantan, Sulawesi and West Papua [80, 82]. Sero-conversions were seasonal, occurring primarily during the wet season from December to June. A BEF epizootic also occurred in Papua New Guinea in 1959 but subsequent serological surveys in sentinel herds between 1969 and 1975 failed to detect evidence of infection [68].

Less information is available from other countries in the region. A BEF-like illness was reported in water buffalo in the Philippines in 1936 and passed experimentally in water buffalo and cattle, resulting in a brief, non-fatal febrile illness [83]. BEF was also reported in the Philippines in 1975–1976 when it affected cattle and water buffalo in 44 provinces in 12 regions, with a case-fatality rate of 5% in water buffalo [84]. There were also local news reports in the Philippines of the disease in January 2011. A serological survey conducted in southern Thailand in 1982 revealed BEFV-specific neutralizing antibodies in 70% of cattle tested from 11 provinces and 47.5% of water buffalo sampled from four provinces [85]. The disease has also been reported to occur sporadically in cattle and water buffalo in Malaysia, especially following heavy rain after period of dry weather [86]. Mortality rates were reported to be low but higher in water buffalo than in cattle. There are also unconfirmed historical reports (1964–1969) of BEF in Laos and Singapore [66].

There have been no confirmed isolations of BEFV from South or South-East Asia and no molecular epidemiological data are available at this time.

China and East Asia
BEF is enzootic in mainland China [37]. It was first reported in Jiangsu Province (north of Shanghai) in 1934 when the disease was called bovine influenza [87]. Since 1955, BEF has been recorded in all provinces except Xinjiang and Qinghai in the west, Heilongjiang in the far north-east and the densely populated areas of Tianjin and Hebei [87]. In Guangdong Province in the south-east, outbreaks occur almost every year and large epizootics occur in the south every 2 years, usually commencing in June or July and lasting until November. Approximately every 4 years, the large epizootics move further northward in a wave-like fashion, affecting provinces such as Henan and Anhui in August and September [87]. An outbreak in Jilin Province in 1991 remains the most northerly latitude (44°N) at which the disease has ever been recorded [88]. A serological survey conducted in cattle, water buffalo and yak during 2011–2014 detected BEFV-neutralising antibody in 26 of 28 provinces across the country, including Heilongjiang in the far north-east and Xinjiang in the west [37]. Sero-prevalence varied by location and year with highest prevalence (81%) in cattle from Shaanxi Province in 2012. Although mortality rates due to BEF in China have been typically low (case fatality rates 4 were found to be resistant to challenge. The vaccine has been adopted for field use in China prior to predicted epizootics and, although no formal field evaluation has been reported, it appears to be safe and effective [147]. A G protein sub-unit vaccine administered in Quil A adjuvant has also been developed in Australia [16]. Two doses of the vaccine administered on days 0 and 21 or three doses administered on days 0, 7 and 36 resulted in 100% protection against experimental challenge on day 104. It was also shown that three doses of 0.32 μg of the purified G protein were required for effective protection against challenge at 46 days [16]. There has been no field evaluation of this vaccine and it has not been adopted commercially.

Vaccination experiments have also been conducted using the BEFV G protein delivered in recombinant virus vectors. Vaccination with four doses of the Neethling strain of lumpy skin disease virus expressing the BEFV G protein at 0, 3, 6 and 12 weeks induced a specific neutralising antibody and cell-mediated immune responses but failed to protect cattle challenged with BEFV 10 weeks after the last dose [148]. In the same experiment, a commercial South African live-attenuated BEFV vaccine induced a stronger neutralisating antibody response but provided incomplete protection. Similarly, vaccination of cattle at days 0 and 21 with recombinant BEFV G protein expressed from the NYBH strain of vaccinia virus has been shown to induce specific neutralising antibodies but a protection experiment was inconclusive due to the poor potency of the challenge virus [13].

In summary, although experimental and commercial BEF vaccines have been developed in various formulations, there are few reports of the evaluation of their efficacy in the field. Protective immunity for most of the vaccines appears to be of limited duration and so their efficacy may be poor unless additional booster doses are administered at intervals of 6 months to 1 year. There remains a need for further research to provide a more informed evaluation of performance in the field and to evaluate slow-release and other advanced technologies that may reduce the required number of doses and extend the duration of protection.

Control of cattle movements
As viraemia is brief (3–5 days) and occurs soon after infection, the risks associated with the movement of infected cattle pertains mostly to rapid transport across relatively short distances and a brief quarantine period in a vector-free area should be sufficient to eliminate the risk of introduction of BEFV with imported cattle [149]. However, recent phylogenetic evidence that BEFV strains of the East Asian lineage appear to be circulating in the Middle East [2, 8, 18, 32] suggest that the livestock trade has been responsible for the inter-continental transfer of the viruses, either in cattle or in vectors that may have accompanied them. Although BEF is not an OIE-listed disease, some countries require that live cattle or bovine semen to be imported are tested and shown to be free of BEFV-neutralising antibodies.

Treatment
BEF is rare amongst viral diseases in that rationally based treatment is possible [54]. Rest, protection from the elements and the provision of feed and water will assist recovery. Laterally recumbent animals should be rolled-over several times a day to prevent loss of circulation and muscle damage. Force-feeding is not advisable because of the risk of aspiration pneumonia due to an impaired swallowing reflex [149]. Non-steroidal anti-inflammatory drugs are effective in preventing the onset of clinical signs when given daily during the incubation period and can induce rapid recovery when given after the onset of clinical disease [150]. Clinical signs of hypocalcaemia (ruminal stasis, paresis, loss of reflex) can be treated by subcutaneous or intravenous injection of calcium borogluconate. Convalescent animals should not be stressed or worked for several days after clinical signs subside to ensure biochemical functions have returned to normal [54].

Conclusions
BEF is a disease for which the economic and social impacts are not always obvious and are frequently underestimated. Epizootics are now occurring more frequently in some parts of the world, there are increasing reports of alarmingly high case-fatality rates, and there is potential, under the influence of climate change and through the livestock trade, for spread of the disease to regions that are presently free. Although the epizootiology has been studied extensively in some regions, little is known of the distribution, prevalence and impacts over vast areas of Africa and Asia, relatively few virus isolates have been recovered and sequenced, and the specific vectors are not clearly defined anywhere in the world. This severely limits our ability to assess the relative importance and risk of spread by wind-borne dispersal of vectors and translocation through movement of livestock, and to assess the potential for establishment as an enzootic disease in Europe or the Americas through transmission by local vectors. Although a multitude of experimental and commercial vaccines have been developed, usage rates are often poor due to the irregular nature of epizootics and the need for multiple doses, and there are few published reports of the evaluation of vaccines under conditions in the field. The role of related viruses in the epizootiology of BEF is also unclear. This knowledge deficit provides a fertile field for future research.