Three Days Sickness Disease
Key Points
Bovine ephemeral fever is a disease of cattle and water buffalo caused by a rhabdovirus and transmitted by flying, biting insects.
Because of the inflammatory nature of the disease, NSAIDs are very effective at relieving clinical signs and pain.
Vaccine effectiveness varies. Inactivated vaccines provide only short-term immunity and should be administered at least three times to gain some effectiveness in prevention of clinical signs.
Bovine ephemeral fever (also known as 3 days sickness disease) is an arthropod-borne viral disease of cattle and water buffalo that causes milk production losses, recumbency, and sometimes death.
Bovine ephemeral fever is an insect-transmitted, noncontagious, viral disease of cattle and water buffalo that is seen in Africa, the Middle East, Australia, and Asia. Inapparent infections can develop in Cape buffalo, hartebeest, water-buck, wildebeest, deer, and possibly goats, sheep, and gazelles. Low levels of antibody have been recorded in several other antelope species, giraffe, and even in pigs and elephants, but the specificity has not been confirmed.
Etiology and Epidemiology
Bovine ephemeral fever virus (BEFV) is classified as a member of the genus Ephemerovirus in the family Rhabdoviridae (single-stranded, negative sense RNA). The virus is ether-sensitive and readily inactivated at pH levels below 5 and above 10. Although BEFV is considered to exist as a single serotype worldwide, antigenic variation has been demonstrated by cross-neutralization tests, monoclonal antibody panels, and epitope mapping. Several closely related ephemeroviruses (including Berrimah virus, Kimberley virus, Malakal virus, Adelaide River virus, Obodhiang virus, Puchong virus, Kotonkan virus, Koolpinyah virus, and Mavingoni virus) have been identified. However, of these, only Kotonkan virus (isolated in Nigeria) has been associated with clinical ephemeral fever in cattle.
BEFV can be transmitted from infected to susceptible cattle by IV inoculation; as little as 0.005 mL of blood collected during the febrile stage is infective. To date, infection by virus obtained from virus culture has never succeeded. Although the virus has been recovered from several Culicoides species and from anopheline and culicine mosquito species collected in the field, the identity of the major vectors has not been proved. Transmission by contact or fomites does not occur. The virus does not appear to persist for long periods in recovered cattle, though it was detected in lymphoid tissue one week after cessation of viremia. Infection results in long term immunity.
The prevalence, geographic range, and severity of the disease vary from year to year, and epidemics occur periodically. During epidemics, onset is rapid; many animals are affected within days or 2–3 weeks. Bovine ephemeral fever is most prevalent in the wet season in the tropics and in summer to early autumn in the subtropics or temperate regions (when conditions favor multiplication of biting insects); it disappears abruptly in winter. Virus spread appears to be associated with winds and transportation of animals. Morbidity may be as high as 80%; overall mortality is usually 1%–2%, although it can be higher in lactating cows, bulls in good condition, and fat steers (10%–30%). However, reported overall mortality rates have exceeded 10% in outbreaks in several countries in recent years.
Clinical Findings
Bovine Ephemeral fever signs occur suddely and vary in severity, which include:
Clinical signs are generally milder in water buffalo. Affected cattle may become recumbent and paralyzed for 8 hours to >1 week. After recovery, milk production can fail to return to normal levels until the next lactation. There are anecdotal reports of abortions. This might be an indirect consequence of the disease, because the virus does not appear to cross the placenta or affect the fertility of the cow. Apparently, bulls, heavy cattle, and high-lactating dairy cows are the most severely affected, but spontaneous recovery usually occurs within a few days. More insidious losses may result from decreased muscle mass and lowered fertility in bulls.
Lesions
Diagnosis
Diagnosis of bovine ephemeral fever is based almost entirely on clinical signs in an epidemic. Whole blood should be collected from sick and apparently healthy cattle in affected herds and must be sufficient to provide two air-dried blood smears, 5 mL of whole blood in anticoagulant (not EDTA), and ~10 mL of serum. A differential WBC count on blood smears can either support or refute a presumptive field diagnosis. The majority of clinical cases have a neutrophilia with the presence of many immature forms, although this is not pathognomonic. Plasma fibrinogen rises on the day of peak fever and remains elevated for at least 7 days. Hypocalcemia may occur one day after fever onset.
Timely laboratory confirmation is mostly performed by PCR and rarely by virus isolation. Serum neutralization is diagnostic in retrospect. A 4-fold rise in antibody titer between paired sera collected 2–3 weeks apart confirms infection.
Virus is best isolated by inoculation of mosquito (Aedes albopictus) cell cultures with defibrinated blood, followed by transfer to baby hamster kidney (BHK-21 or BHK-BSR) or monkey kidney (Vero) cell cultures after 15 days. Suckling mice may also be used for primary isolation by intracerebral inoculation. Isolated viruses are identified by PCR and sequencing, neutralization tests using specific BEFV antisera, and ELISA using specific monoclonal antibodies.
Treatment and Control
Complete rest is the most effective treatment for bovine ephemeral fever, and recovering animals should not be stressed or worked because relapse is likely. Anti-inflammatory drugs given early and in repeated doses for 2–3 days are effective. Oral dosing should be avoided unless the swallowing reflex is functional. Signs of hypocalcemia are treated as for milk fever. Antibiotic treatment to control secondary infection and rehydration with isotonic fluids may be warranted.
There is conflicting evidence regarding the effectiveness of the commercially available attenuated or inactivated BEFV vaccines. Although an attenuated BEF vaccine showed high effectiveness in Australia, reports from other countries indicate lower effectiveness of the same vaccine. Inactivated virus vaccines have not produced longterm protection against experimental challenge with virulent virus and cannot guarantee lasting immunity. In field studies, they were 50% effective only after at least three vaccinations. Although a subunit vaccine that protects against field and laboratory challenge has been described, it is not commercially available. The efficacy of vector control remains uncertain, because the insect vectors have not been fully identified. There is no evidence that people can be infected.
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