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Bovine Ephemeral Fever (Three Day Sickness)
- 1. BOVINE EPHEMERAL FEVER: What you need to know and What you need to do? Dr. Muhammad Avais, DVM, PhD Associate Professor Department of Veterinary Medicine University of Veterinary & Animal Sciences, Lahore
- 2. Synonyms of BEF • Three-day sickness or three-day fever • Bovine influenza • Bovine epizootic fever • Dengue of cattle • Three-day stiffsickness Vernacular name • Vil (Akakpo 2015)
- 3. What is BEF? • Acute febrile viral disease • Noncontagious arthropod borne • Affects cattle and buffalo • widespread in tropical and semitropical areas • cause severe economic loss • affected animals are only sick for a few days • alternative name - Three Day Sickness (Momtaz et al. 2012; oie 2016)
- 4. Why BEF is important? • largely economic in nature • does not cause significant mortality (1-2%) • high case fatality rate in recent outbreaks • main impact is on productivity • decreased milk yield (at least 50%) • rise in somatic cell count • loss of condition • reproductive losses (abortion, infertility) • Recovery is prolonged • Culling • Trade restrictions (oie 2016)
- 5. Who causes BEF? • Bovine ephemeral fever virus • member of genus Ephemerovirus • family Rhabdoviridae • exist as a single serotype worldwide • VN tests on isolates from Australia, China, Japan, Kenya, Nigeria and South Africa have demonstrated strong antigenic cross-reactions (Walker and Klement, 2015; Constables et al. 2017)
- 6. • vaccines developed in several countries using BEFV strains isolated more than 40 years ago remain effective against currently circulating strains • vaccines developed against a strain of the virus from one region are effective against viruses currently circulating in other regions of the world • homologous neutralisation titres are typically higher than heterologous titres Walker and Klement, 2015 Who causes BEF?
- 7. Temporal and phylogenetic relationships between bovine ephemeral fever outbreaks of Asian countries (Lee, 2019)
- 8. Species affected with BEF • Cattle and yaks (both mem. of genus Bos) • Water buffaloes (Bubalus bubalis) • Antibodies found in sheep, goat and wild animals • All age groups susceptible • Calves <3-6m not affected • Bulls & High producing cows at greater risk • no evidence of humans infections (oie, 2016)
- 9. Geographic distribution • Tropical and subtropical areas of: – Africa – Asia – Middle East – Australia • BEFV is not found in: – Europe – North or South America – New Zealand (Walker and Klement, 2015) Countries in which BEF is known to occur or from which the disease has been reported historically
- 10. Morbidity and Mortality • localized or seasonal epizootics • spread influenced by prevailing winds • mostly seen in summer and early fall • outbreaks associated with high rainfall • morbidity variable (80% or 1-10%) • varies with age, condition and immunity • mortality rate is 1-2% in most outbreaks • but can be 20-30% in cattle (oie, 2016)
- 11. How BEFV is transmitted? • Arthropods / hematophagus insects • BEFV isolated from mosquitoes and Culicoides • Mosquitoes primary biological vectors • Culicoides significant vectors in Africa (Keynya) • Wind-borne carriage of infected vector • Intravenous inoculation of small amounts of blood (oie, 2016)
- 12. How BEFV is transmitted? • No transmission between animals • Not transmitted by – Close contact – body secretions – aerosol droplets • Not transmitted in semen • Rapidly inactivated in meat • no evidence of animal becomes carrier (oie, 2016)
- 13. How BEF Develops? • virus inoculation by vector (mosquitoes) • Vascular System (Virus Multiplication) • Pyrogen and neutrophils influx in bulk (Fever) • Vasculitis and thrombosis • Increased endothelial permeability • Synovial cavities (Sero-fibrinous inflammation) • Generalized Inflammation
- 15. Clinical Signs • IP; most cases b/t 2-4d, Max. 10-11d • signs vary in individual animals • classic course begins with fever (biphasic to polyphasic) • Sharp fall in milk production • depressed, stiff or reluctant to move • increased heart rate, tachypnea • serous or mucoid nasal discharges • Profuse salivation, muscle twitching • waves of shivering or lacrimation
- 16. Clinical Signs • Shifting lameness, stiffness and joint pain • joints may or may not be swollen • submandibular or periorbital edema • Dyspnea, pulmonary emphysema and rales in severe cases • Recombancy • Bloat, ruminal stasis, or lose swallowing reflex • Temporary lose reflexes/unable to rise • Exacerbate by environmental stress or forced exercise • Video
- 17. Causes of death – Aspiration pneumonia & Pneumonia from secondary infection – Pulmonary emphysema – Muscle damaged and inflammation from long period lying down
- 18. Complications • temporary or permanent paralysis • gait impairment • aspiration pneumonia • Pulmonary and subcut Emphysema • mastitis • Temporary infertility in bulls (up to 6 months) • abortions in pregnant cows • In recovered animals, milk production is generally decreased for the rest of the lactation • but usually returns to normal after subsequent pregnancies • Cows that become ill late in lactation may not return to production
- 19. Postmortem lesions • Small amounts of fibrin-rich fluid in: – pleural, peritoneal, pericardial cavities – joint capsules • Serofibrinous: – Polysynovitis, polyarthritis – polytendinitis and cellulitis • Emphysematous lungs • Enlarged edematous lymph nodes • Focal necrosis in major muscle groups
- 20. How to diagnose BEF? Clinical • usually diagnosed clinically during outbreaks in endemic areas • This disease should be suspected in cattle herds that develop severe but transient symptoms including fever, lameness, temporary paralysis or recumbency • Difficult to diagnose when a single animal is affected
- 21. How to diagnose BEF? Hematology/Biochemistry • absolute rise in leukocyte in acute cases • A rapid fall in circulating lymphocytes • A return to normal levels after 3-4 days • Low total serum calcium, Zn and Fe • Plasma fibrinogen elevated • CK elevated
- 22. How to diagnose BEF? Laboratory tests • Most cases of BEF are confirmed by serology • A rising titer should be demonstrated with ELISA -- Paired samples • CFT can also be used • RT-PCR
- 23. Differential Diagnosis • Foot-and-mouth disease • Traumatic pericarditis/reticuloperitonitis: • Milk fever • Pneumonia/Pasteurellosis • Laminitis
- 24. CONTROL MEASURES (I) Vaccination • All animals on the farms above 6-months of age may be primed using live attenuated BEF vaccine at the start of summer • Make sure vaccine is not expired and the storage and handling requirements are strictly adhered • Booster dose of vaccine 4 weeks post-priming • Annual booster of vaccine
- 25. (II) Vector Control • BEF virus spreads through biting flies, mosquitoes • Fly repellents such as Cypermethrin mixed with liquid paraffin • Apply on Pouron method from head to tail. Repeat after every 7 days • Spray of Seguvon / Neguvon @ 0.1% on breeding places of vectors (floors, walls, manure, slurry, etc) • Remove stagnant water from the dairy farm • Proper disposal of manure / slurry CONTROL MEASURES
- 26. Control of Ticks • Weekly spray of cypermethrin on farm • Application of lime on dry floors • Filling of crevices (Breeding sites) on floors / walls, etc • Elimination of wooden structures on floors CONTROL MEASURES
- 27. Monitoring and control for blood parasites • Animals are often having subclinical form of blood parasites that may be the prime cause of vaccination failure • Monitor the herd for hemoparasites through random selected samples • If a herd or particular group of cows is positive for blood parasites, treat as per nature of the disease. CONTROL MEASURES
- 28. III. Movement restriction • Movement of cattle from infected herd or area should be strictly banned during the outbreak/epidemic • Avoid new purchases and introduction of new animals into the herd. (if necessary, put all new purchases to strict quarantine) CONTROL MEASURES
- 29. IV. Herd Monitoring • Feed and water consumption and production should be carefully monitored at all times • Typical sounds and behaviors of individual animals should be monitored • Temperature of randomly selected animals should be monitored CONTROL MEASURES
- 30. V. Biosecurity • Strictly adhere to all farm biosecurity measures • Do not allow visitors during the outbreak • Restrict the entry of service personals and vendors • • Disinfect farm and farm premises using disinfectants (Virkon or 2% pyodine or 5% Bleach) CONTROL MEASURES
- 31. TREATMENT STRATEGY (I) Therapeutics • Early detection of the clinically sick cases through continuous monitoring • Administration of NSAIDs • Immune boosters such as Vitamin E and Selenium • Calcium therapy (calcium borogluconate / Milfone-C, I/V) • Antibiotics to control secondary bacterial infection like Ceftiofur sodium • Cold water therapy to lower body temperature • Follow single needle use policy when treating or vaccinating the cows.
- 32. (II) Nutrition and Environmental Management • Increase level of calcium, selenium, vitamin C and vitamin E • • Reduce stock Density • Avoid overcrowding • Disease normally followed rainy season due to hot humid climate TREATMENT STRATEGY
- 33. (III) Isolation of sick cows • Keep the infected/diseases animals in isolation and don’t allow them to mix with healthy ones TREATMENT STRATEGY
- 34. (IV) Management of recumbent cows • Nursing care- Animals that have gone down should be provided with adequate shelter, water and food, as cattle left exposed in hot weather are much more likely to die • BEF can impair the swallowing reflex, so affected animals should not be drenched or force fed • Recumbent cows are rolled over several times a day to help avoid loss of circulation to the underside limbs, which will result in permanent muscle damage. TREATMENT STRATEGY
- 35. • Ensure that animal is in sternal position: Cattle that go into lateral recombancy (lying flat) can bloat and die or aspirate rumen fluid which can cause pneumonia • Place sand bags, hay bales to prop up animals that cannot remain sternal without assistance • Calcium injections- if given early in the course of the illness, can be very effective in helping an animal regain its footing. TREATMENT STRATEGY
- 36. Disinfection • BEFV is not thought to be transmitted directly between animals, and does not persist for long periods in the environment • If disinfection is needed, this virus is reported to be very susceptible to disinfectants, including sodium hypochlorite, and lipid solvents TREATMENT STRATEGY
- 37. Summary • BEF also know as three-day-sickness • Noncontagious arthropod borne viral disease caused by BEFV of genus ephemerovirus • Affects cattle and water buffalo • Economically important due to reduced milk yield, loss of condition, infertility, trade restriction • Transmitted by mosquitoes and biting flies • Prevalence in tropical and subtropical areas • High morbidity during outbreaks and high case fatality rate
- 38. • BEFV causes vasculitis and increases vascular permeability • Polyserositis and polyarthritis • Clinical signs are fever, shifting lameness, stiffness, joint pain and recombancy • Pulmonary emphysema is the complication • Diagnosis by clinical picture, serology and PCR • Control through vaccination, vector control and farm hygiene • Treat with NSAIDs, immune-boosters and calcium Summary
Editor's Notes
- Bovine ephemeral fever (BEF), also known as three-day sickness or three-day fever [1], is an arthropod-borne viral disease that mainly strikes cattle and water buffalo.. Historically, BEF has also been named bovine influenza, bovine, epizootic fever [2], styfsieket, or dengue of cattle [3], This disease was first recorded in the late 19th century
- Bovine Ephemeral Fever (BEF) is an acute febrile viral non-contagious arthropod borne disease of cattle and buffalo. Widespread in tropical and semitropical areas of the Eastern Hemisphere that can cause severe economic loss. Typically, affected animals are only sick for a few days, hence the alternative name - Three Day Sickness Bovine ephemeral fever is an economically important arboviral disease that affects cattle and water buffalo, and is widespread in tropical and semitropical areas of the Eastern Hemisphere. In most cases, the main impact is on productivity. While the illness is usually brief, it can result in decreased milk yield, loss of condition and reproductive losses, and recovery can be prolonged in some animals. Mortality is typically low (1-2%); however, significantly higher case fatality rates were reported in some recent outbreaks.
- The importance of BEF is largely economic in nature, however, it does not cause significant mortality (1-2%). In most cases, the main impact is on productivity. In recent outbreaks high case fatality rate of 25-30% was reposted in exotic dairy herds. The main impact of the disease is on productivity, with decreases milk production. Milk production usually drops by at least 50% in sick cows. In dairy herds it is the highest producing animals that are usually the most severely affected. Yield should return to normal after about three weeks. Bulls and fat cows tend to show more severe signs than other cattle. Such animals lose condition rapidly and are slow to regain their body weight. A proportion of bulls will suffer temporary infertility lasting from three to six months because of the high fever. Permanent infertility is uncommon but can occur. Recovery is prolonged and severe chronic cases may lead to increased culling.
- Bovine ephemeral fever is caused by bovine ephemeral fever virus (BEFV), a member of the genus Ephemerovirus in the family Rhabdoviridae. BEFV is considered to exist as a single serotype worldwide. Virus neutralisation tests conducted using isolates from Australia, China, Japan, Kenya, Nigeria and South Africa have demonstrated strong antigenic cross-reactions [25–29]. Structure and morphology of BEFV. A Structural organization of the 14.9 kb BEFV genome shown as arranged in negative sense. Structural protein genes (N, P, M, G and L) are shown in black and the various accessory genes are coloured. B Transmission electron micrograph showing BEFV virions and defective-interfering (DI) particles. Scale bar 100 nm. Reproduced from Walker [7] with permission from Springer-Verlag. C Structural model of a monomeric subunit of the BEFV G protein derived by homology modelling using the pre-fusion form of the VSV G protein as a template. The model illustrates the three major neutralization sites (G1, G2 and G3a/b) and amino acid residues shown to be under positive selection in Australia [18]. Adapted with permission from the American Society for Microbiology.
- There is also anecdotal evidence that vaccines developed in several countries using BEFV strains isolated more than 40 years ago remain effective against currently circulating strains and that vaccines developed against a strain of the virus from one region are effective against viruses currently circulating in other regions of the world. Nevertheless, homologous neutralisation titres are typically higher than heterologous titres amongst viruses isolated at different times or from different geographic regions [1, 27, 28].
- Only cattle and yaks (both members of the genus Bos) and water buffalo (Bubalus bubalis) are known to be affected by BEFV. Camels (Camelus dromedarius) can be seropositive, and a disease resembling ephemeral fever has been reported in this species, but its cause is still unknown. Antibodies to BEFV have also been found in asymptomatic sheep, goats and pigs, and in many wild animals including African buffalo (Syncerus caffer), hartebeest (Alcelaphalus buselaphus), waterbuck (Kobus ellipsiprymnus), wildebeest (Connochaetes taurinus), kudu (Tragelaphus strepsiceros), giraffe (Giraffa camelopardalis), elephant (Loxodonta africana), hippopotamus (Hippopotamus amphibius), warthog (Phacochoerus aethiopicus) and various species of deer and antelope. Seroprevalence can be high in some African wildlife, and some species might act as reservoir hosts. However, cross-reactivity with similar viruses complicates the interpretation of serological tests. Experimental infections have been established in sheep, but there is currently no evidence that this species plays any role in the epidemiology of bovine ephemeral fever in nature. Zoonotic potential There is no evidence that humans can be infected by BEFV.
- Geographic Distribution 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.
- Morbidity and Mortality Bovine ephemeral fever can occur as localized outbreaks or in seasonal epizootics. During epizootics, the pattern of spread seems to be influenced by the prevailing winds. Most cases are seen in the summer and early fall, and outbreaks are often associated with high rainfall. The morbidity rate is highly variable, and can be as high as 80% or as low as 1-10%. Morbidity varies with the age and condition of the animal, as well as any immunity it may have. The mortality rate is 1-2% in most outbreaks, but it can be as high as 30% in cattle.
- Transmission BEFV appears to be transmitted by arthropods, but the identity of the vector or vectors is not entirely clear. This virus has been isolated from various genera of mosquitoes, and from a number of Culicoides species (biting midges). Laboratory observations, together with epidemiological evidence from some locations, currently suggest that mosquitoes are the primary biological vectors. However, there are some indications that Culicoides might be significant vectors in parts of Africa (e.g., Kenya). Windborne transmission of infected vectors has been suspected in some outbreaks.
- There is no evidence that bovine ephemeral fever can be transmitted directly between animals in nature; BEFV is not spread by close contact, body secretions, or aerosol droplets. However, animals can be infected in the laboratory by intravenous inoculation of small amounts of blood. This virus does not seem to be transmitted in semen and it is rapidly inactivated in meat. There is no evidence that animals become carriers.
- Incubation Period Based on natural and experimental infections, the incubation period is thought to be 2-4 days in most cases, with a maximum of 10-11 days. Clinical Signs Clinical signs vary in individual animals, but the classic course begins with a fever, which is often biphasic to polyphasic. The temperature peaks typically occur 12 to 18 hours apart. In lactating cows, milk production often drops dramatically during the first fever spike. There are often few other clinical signs at this time, although some animals may be depressed, stiff or reluctant to move. However, the illness soon becomes more obvious; most animals become inappetent and depressed, with an increased heart rate, tachypnea, and serous or mucoid discharges from the nose. Profuse salivation, muscle twitching, waves of shivering or lacrimation may also be seen. Some animals develop submandibular or periorbital edema, or patchy edema on the head
- Shifting lameness, stiffness and joint pain are common; the joints may or may not be swollen. The lameness can be severe enough to mimic a fracture or dislocation. Dyspnea, pulmonary emphysema and rales may be found in severe cases. Many animals, particularly cows in good condition and bulls, become recumbent for periods that range from 8 hours to several days or more. Most animals lie in sternal recumbency, but in severe cases, animals may become laterally recumbent. Some animals temporarily lose their reflexes and are unable to rise. Recumbent animals may be bloated, have ruminal stasis, or lose their swallowing reflex. These clinical signs can be exacerbated by severe environmental stress or forced exercise. Most animals begin to improve a day or two after the initial signs, and recover completely within another 1-2 days. Lactating cows, bulls and animals in good condition are usually affected more severely, and may take up to a week to recover. Generally, animals lose condition rapidly during the illness, and regain their weight only slowly. Complications are uncommon in most outbreaks, but can include temporary or (rarely) permanent paralysis, as well as gait impairment, aspiration pneumonia, emphysema, mastitis, and the subcutaneous accumulation of air along the back. Many of these complications may be the result of trauma or complications of recumbency. Temporary infertility (up to 6 months) can develop in bulls, and abortions sometimes occur in cows. Permanent infertility is rare. In recovered animals, milk production is generally decreased for the rest of the lactation, but usually returns to normal after subsequent pregnancies. Cows that become ill late in lactation may not return to production. Death is uncommon in most outbreaks, but may occur during either the febrile or the convalescent stage. During recent outbreaks in China, some severely ill cattle died with signs of dyspnea, 6-12 hours after they first became ill. Secondary complications such as pneumonia or trauma are thought to contribute significantly to the death rate. Subclinical infections are also seen. Water buffalo have similar signs. The disease is usually thought to be milder in this species; however, some severe outbreaks have been reported in the field. Experimentally infected sheep remained asymptomatic.
- Post Mortem Lesions The most obvious lesion is a small amount of fibrin-rich fluid in the pleural, peritoneal and pericardial cavities, resulting from polyserositis of the pleural, pericardial and peritoneal surfaces. Edema, lobular congestion and atelectasis may be apparent in the lungs, and emphysematous lesions are sometime detected in the lungs, mediastinum and subcutaneous connective tissue. Serofibrinous polysynovitis (with variable amounts of yellow to brown, typically gelatinous fluid), polyarthritis, polytendinitis, and cellulitis are common. Other lesions can include lymphadenitis, edema and petechial hemorrhages in the lymph nodes, and areas of focal necrosis in the major muscle groups.
- Diagnostic Tests Most cases of bovine ephemeral fever are confirmed by serology. A rising titer should be demonstrated, but single serum samples may be suggestive in areas where this disease does not normally occur. Anamnestic (rather than primary) responses to BEFV can occur during the first exposure, if the animal was previously exposed to another ephemerovirus. Virus neutralization or enzyme-linked immunosorbent assays (ELISAs) are the most commonly used serological tests. Some of these tests, including certain ELISAs, can distinguish BEFV from other members of the Ephemerovirus genus. Complement fixation was mainly used in the past, and identifies the antibodies only as Ephemerovirus-specific. Reverse transcription polymerase chain reaction (RT-PCR) assays are used regularly for diagnosis in some countries. These assays may be able to detect viral RNA in blood during the (typically short) febrile period, and from tissue samples such as the lung at necropsy. A real-time loop-mediated isothermal amplification (RT-LAMP) assay has been published. Virus isolation may occasionally be successful, especially during the first 24-48 hours. The virus is often recovered initially in Aedes albopictus (mosquito) cell lines, and propagated in BHK-21 or Vero cells. The identity of the virus can be confirmed by RT-PCR, virus neutralization and some ELISAs. Immunofluorescence has also been used, but may be able to identify the virus only as an Ephemerovirus. While animal inoculation is generally discouraged if there are alternatives, BEFV can be recovered by intracerebral inoculation into unweaned mice.
- Differential Diagnosis:
- (I) Therapeutics Early detection of the clinically sick cases through continuous monitoring (Cardinal signs such as drop in milk production, fever, dull, depressed, off feed, increased respiration, lameness and staggering gait to recombancy) Administration of non-steroidal anti-inflammatory drugs such as Phenylbutazone / ketoprofen / flunixin meglumine at recommended doses and route Immune boosters such as Vitamin E and Selenium preparations (E-sel / Selevit) Calcium therapy if needed (calcium borogluconate / Milfone-C, I/V at recommended dose) Antibiotics to control secondary bacterial infection like Ceftiofur sodium at recommended doses Cold water therapy on body to lower body temperature Follow single needle use policy when treating or vaccinating the cows.