M. F. Uren

Studies on the pathogenesis of bovine ephemeral fever in experimental cattle III. Virological and biochemical data

In an attempt to define the nature of the response of cattle to ephemeral fever infection, a number of indicators of inflammation were monitored during clinical disease. The total Ca, Zn, Fe, Cu, glucose and phosphate in plasma, together with blood ammonia, were assayed relative to changes in the rectal temperature. CaT levels fluctuated markedly and hypocalcaemia occurred in 4 of 8 cattle. Plasma Zn and Fe values fell while plasma Cu levels rose markedly in all cattle. Mean levels of serum NH3 of 20-30 mumol l-1 rose to a peak value of 56 mumoll-1. Plasma glucose levels rose to a peak of 4.6 +/- 0.5 mMl-1 and the plasma phosphate levels fell from 2.4 +/- 0.1 mMl-1 to 1.17 +/- 0.2 mMl-1 during fever. Values of pCO2 fell from a mean of 46.9 +/- 3.6 mmHg to 36.4 +/- 3.1 mmHg and coincided with a rise in pH. Virus was isolated 73 h (+/- 23) after inoculation and persisted until 130 h (+/- 21). The common role of these parameters in generalised inflammation and ephemeral fever is discussed.

Effective vaccination of cattle using the virion G protein of bovine ephemeral fever virus as an antigen.

In a series of experiments, the envelope glycoprotein (G protein) of bovine ephemeral fever virus (BEFV) induced immunity against challenge with virulent virus. Protection correlated with the level of specific serum antibodies to G protein measured by a blocking ELISA test and with the level of neutralizing antibody. The optimum vaccination regimen consisted of two injections given 21 days apart at a dose rate of 0.32 microgram per cow of purified G protein emulsified in the adjuvant Quil A. This schedule conferred immunity for the duration of the preliminary experiment (46 days). Immunity to severe disease, but not to infection, remained for at least 12 months after vaccination, although BEFV could not be reisolated from vaccinated cattle following challenge. Unvaccinated cattle used as controls exhibited typical signs of clinical ephemeral fever and BEFV was recovered from all control animals following challenge.

The effect of anti-inflammatory agents on the clinical expression of bovine ephemeral fever

The effect of two anti-inflammatory drugs on the development and persistence of clinical signs in cattle experimentally infected with bovine ephemeral fever (BEF) virus was investigated by their administration, either before or after the commencement of fever. A total of 16 cattle was given phenylbutazone sodium (PBZ). The drug prevented fever and other clinical signs in six cattle when given daily during the incubation period, and at 8-h intervals for 5 days when clinical disease might be expected. When treatment with PBZ was deferred until 2-4 h after the commencement of fever, the rectal temperature returned to normal within 4 h in four of six cattle and the development of other clinical signs was suppressed. Clinical signs of ephemeral fever occurred in four untreated cattle infected at the same time. Viraemia, the development of neutralizing antibodies (at 8-11 days), resistance to subsequent challenge with BEF virus, neutrophilia, lymphopenia and a rise in plasma fibrinogen occurred in all BEF-infected animals whether treated or untreated, despite different clinical appearances. The mean peak of plasma fibrinogen in the untreated cattle was 6.9 g l-1; 3.2 g l-1 when treated 2-4 h after fever developed and 3.8 g l-1 when treated from 18-h post-infection. BEF virus was isolated from leucocytes of each of the cattle, but the frequency of isolation was lower in the treated group. The results indicate that treatment with PBZ blocked the host response which produces the clinical signs and did not have an anti-viral effect. In a similar experiment, a long-acting anti-inflammatory drug, flunixin meglumine, failed to prevent BEF or to modify the clinical signs once they had developed, except for the rectal temperature which returned to normal within 2-4 h of the administration of the drug. The efficacy of this drug was not improved by increasing the dosage to two or three times the recommended level.

Epidemiology of bovine ephemeral fever in Australia 1981-1985

Bovine ephemeral fever is an important viral disease of cattle in Australia. The disease occurred each year, principally in summer and autumn, between 1981 and 1985. Queensland and the northern half of New South Wales were areas of greatest activity with only sporadic cases being reported from the Northern Territory and the northern third of Western Australia. Since 1981, the disease has been endemic in an extensive area of eastern Australia and has tended to occur in widely scattered outbreaks rather than the north-south advancing wave form of the epidemics of 1936-37, 1967-68, 1970-71 and 1972-74. The southernmost outbreaks between 1981 and 1985 were well within the limits of these earlier epidemics. The pattern of disease appears to have become seasonally endemic rather than periodically endemic in the northern two-thirds of eastern Australia. Ephemeral fever was not recorded in Victoria, Tasmania, South Australia or the southern part of Western Australia between 1981 and 1985. The disease was most frequently reported in cattle under 3 years of age, but also occurred in older cattle.

Studies on the pathogenesis of bovine ephemeral fever in sentinel cattle. II. haematological and biochemical data

Twenty-two non-lactating dairy cattle from a sentinel herd previously described (St. George, 1985) were monitored daily during an outbreak of ephemeral fever. Nine developed clinical ephemeral fever between 25 December 1981 and 30 January 1982. There were no subclinical infections with bovine ephemeral fever virus in the group. There were, however, subclinical infections with CSIRO Village, Akabane, Aino, Tinaroo and Kimberley viruses as described by St. George et al. (1984). Six of the nine affected cattle showed a neutrophilia with a concurrent lymphopaenia on the day of pyrexia; however, the differential white cell profile had begun to change up to 24 h prior to leucocytosis. Serum carboxypeptidase values fell by 24 h following the febrile response. Plasma fibrinogen rose rapidly in all six cows. The peak concentration (15.6 +/- 2.70 g l-1) occurred 3 days after pyrexia with the highest individual increase being from 6.05 to 19.6 g l-1. Plasma fibrinogen levels remained elevated for at least 7 days. Serum calcium fell significantly during Day 1 of the disease, the mean decline being 0.22 +/- 0.08 mmol l-1. The greatest individual fall was from 2.33 to 1.92 mmol l-1. None of the affected cattle showed any compensatory change in serum magnesium. There was no change in the normal values of creatinine, urea, gamma-GT, AST and alkaline phosphatase. Bovine ephemeral fever virus was isolated from only four of the six cases, whereas specific antibody was detected in all cattle 3-4 days after recovery.

Studies on the pathogenesis of bovine ephemeral fever IV: A comparison with the inflammatory events in milk fever of cattle

The study of ephemeral fever in cattle has defined a range of haematological and biochemical changes in blood which are characteristic of an inflammatory response. One of the clinical signs of ephemeral fever, a temporary paralysis reversible by treatment with calcium borogluconate, is similar to that in milk fever (parturient paresis), a disease of multiparous dairy cows. Three separate groups of cows were studied. Four multiparous cows were observed and sampled repeatedly during calving, three similar cows and one cow calving for the first time in a dairy herd were sampled daily before and after calving; and, in other dairy herds, seven cows with milk fever were sampled during illness. One of the cows under repeated observation during calving developed milk fever. The results showed that all the inflammatory indicators in blood were present in the multiparous cows at calving and that these were essentially similar to those established in ephemeral fever. The similarities in the four cows sampled repeatedly during the periparturient period were: a rectal temperature rise of 1 to 1.2 degrees C; rise in circulating neutrophils to peaks between 5700 and 11200 l-6; disappearance of eosinophils for 1 day; hypocalcaemia (plasma Ca < 2.0 mM l-1); fall of plasma zinc to low levels immediately after calving (plasma Zn < 500 micrograms l-1); fall of inorganic phosphate (plasma P < 0.9 mM l-1); rises in copper (plasma Cu > 1000 micrograms l-1) and plasma fibrin to > 8.75 g l-1. Plasma glucose peaked at calving between 5.7 and 8.9 mM l-1 then fell to levels ranging between 3.4 and 3.8 mM l-1. Plasma iron rose in one cow to 1220 micrograms l-1, was unchanged in one cow and fell in the other two to 440 and 860 micrograms l-1 respectively. The three multiparous cows which were sampled daily and calved normally showed similar haematological, macro and micromineral changes and fibrin response as did the seven milk fever cases. In the periparturient period, milk fever cows differed from multiparous cows calving normally, in degree but not in kind, of inflammatory response. It is postulated that an inflammatory event occurs in the periparturient period of multiparous cows which partially accounts for the falls in plasma calcium. This can precipitate a paralysis and other hypocalcaemic signs similar to that seen in acute ephemeral fever.

Epidemiology of Ephemeral Fever of Cattle in Australia 1975?1981

Ephemeral fever occurred each year in Australia between 1975 and 1981. Since the 1974-75 epidemic, ephemeral fever outbreaks have changed markedly in character and pattern of spread from the previous pattern of spaced explosive epidemics. The outbreaks between 1975 and 1981 were typified by slower-moving epidemics with a general north-south sequential pattern in the eastern States of Queensland and New South Wales. The summer months of January to March were peak months for reports of the disease and quiescence occurred between May and August. Victoria, Tasmania, South Australia and the southern part of Western Australia were free of clinical and subclinical infection with bovine ephemeral fever virius between 1975 and 1981.

Trace element and macro electrolyte behaviour during inflammatory diseases in cattle and sheep

Ephemeral fever is a disease of cattle caused by bovine ephemeral fever (BEF) virus, a rhabdovirus. It occurs in a wide band of tropical and sub-tropical Asia, Africa and Australia and is spread by insect vectors (St. George et al., 1984). In susceptible cattle, BEF causes high morbidity and variable mortality. Effects are worst in prime, fat cattle and high producing cows. St. George et al. (1986) have argued that the viraemia should be considered as an inflammatory/toxic response as shown by the marked neutrophilia and elevated fibrinogen levels. We (Murphy et al., 1986) have provided physiological support for this hypothesis by measuring changes in circulating levels of Fe, Zn and Cu during the viraemia. As well, we have confirmed an earlier report (St. George et al., 1984) that in affected animals (a) uncompensated hypocalcaemia (plasma Ca < 2.0 mM L−1) is commonplace; and (b) the cardinal signs (tachycardia, tachypnea, ruminal stasis and sternal recumbency) are consistent with the gross disturbance of calcium homeostasis. More importantly, phenylbutazone treatment of BEF affected cattle has shown that the trace element changes and hypocalcaemia are independent of fever per se (Murphy et al., 1986). Overall, this physiological expression of BEF is consistent with an Interleukin-1 initiated sequence.