- Research progress in some important problems in sheep and goats: ...
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Research progress in some important problems in sheep and goats:
2. Elucidation of enzootic icterus (geelsiekte)
EM van Tonder
Regional Veterinary Laboratory
Private Bag X528
Grootfontein College of Agriculture
MIDDELBURG C P
According to accounts of earlier inhabitants enzootic icterus has almost certainly been known from the earliest times of sheep farming in the central and south-western areas of the Cape Province under the name of geelsiekte (Brown & De Boom, 1966).
The disease was however first noticed and studied at Onderstepoort in 1924 when it occurred in sheep introduced from Middelburg Cape, for the purpose of bluetongue vaccine production (De Kock, 1928a, 1928b). It was also experienced in sheep subsequently obtained from Carnarvon, Philipstown, Colesberg and Beaufort West and usually made its appearance shortly after the arrival of the animals.
Losses up to the figure of 10% were generally accepted until 1949 since when only sporadic cases were seen. The marked decline in incidence amongst sheep introduced to Onderstepoort was considered to be due to the fact that since that time most of the animals emanated from Barkley East and the Transvaal Highveld (Brown & De Boom, 1966).
On the strength of his observations, De Kock (1928a, 1928b) considered enzootic icterus to be some intoxication or auto-intoxication in these sheep, which resulted from a variety of predisposing factors such as fatigue from being herded and railed, exposure, insufficiency of food and water whilst in transit and the provision of unaccustomed food at their destination. This assumption prevailed until his retirement in 1949, particularly since it was found that by changing the diet regime losses were reduced to below 5% (Groenewald cited by Brown and De Boom, 1966).
Although enzootic icterus appeared to have been well-known to farmers and many veterinarians in the field and has formed the subject of numerous unpublished reports, there is a remarkable void in the literature regarding the disease until 1959.
It would appear however that the first field investigations into enzootic icterus took place at the end of 1946 on a farm in the Murraysburg area (Brown & De Boom, 1966). This work was followed up on the same farm and on properties in De Aar and Aliwal North in 1947. Apart from a detailed description of the disease and its association in these cases with overgrazed veld dominated by unpalatable and undesirable bushes, no specific underlying cause was however identified (De Boom, 1947).
Uncertainty with regard to the aetiology of the disease seems to have continued until the second half of the nineteen-fifties when apparently influenced by overseas reports (Anonymous, 1956; Pearson, 1956), copper poisoning was incriminated as the likely cause of enzootic icterus in at least some of the cases which showed jaundice during outbreaks of heavy mortality in sheep in the Middelburg district (Belonje, 1958).
However the consideration of copper poisoning as a possible causative factor of geelsiekte seems to have been short-lived and overshadowed by the prominence given to overgrazing and intrusion of undesirable plants, a common feature observed in outbreaks subsequently investigated (Skinner, 1959, 1960; Hugo, 1959, 1962; Van der Riet, 1960).
During the course of extensive investigations to unravel the problem of geeldikkop, Brown and his co-workers in a series of comparative chemical pathological studies came to the belief that enzootic icterus and geeldikkop were related to some extent (Brown, 1959a, 1959b, 1962; Brown, Le Roux and Tustin, 1960; Brown & De Wet, 1962). In subsequent work evidence was also forwarded and the conclusion arrived at, that despite some incompatible and inexplicable differences, the two diseases were indeed related, being two different manifestations of the same basic disease entity caused by an underlying subclinical selenium toxicity (Brown, 1964, 1966, 1968; Brown & De Boom, 1966; Brown & De Wet, 1967). The possible role of an infectious agent in the production of the acute manifestations of both conditions was also envisaged (Brown, 1968).
As a result of numerous discrepancies and conflicting epizootological considerations the proposed relationship of enzootic icterus and geeldikkop, and the incrimination of subclinical selenium toxicity as the primary aetiological factor, particularly in the case of the formerly mentioned condition, never really gained popularity amongst workers in the field and elsewhere.
In view of earlier observations that overgrazing and the intrusion of undesirable plants were constant features associated with the occurrence of enzootic icterus (Skinner 1959, 1960; Hugo 1959,1962; Van der Riet, 1960), Louw, Steenkamp & Steenkamp (1963) conducted a comparative study on the chemical composition of the Karoo shrubs involved. These workers found that the ether extract of some Karoo shrubs, notably the invading undesirable types, was exceptionally high, being from 8 to 23% on a dry basis. This led them to suspect some or other alkaloid or resin in these plants to be responsible for the liver changes and high blood copper levels in enzootic icterus subjects rather than a form of copper poisoning per se, which at that stage was favoured as a possible cause.
In a more comprehensive investigation into the chemical composition of the plant species commonly found in the traditional enzootic icterus areas, Louw et al (1968a, 1968b) came to the conclusion that the respective values recorded for copper and molybdenum did not betray any possibility of copper poisoning or deficiency, either directly or through interaction between these elements to occur in these areas. The likelihood of these minerals playing a role in the aetiology of enzootic icterus was therefore discarded.
Since at the same time Brown and his co-workers (Brown, 1962, 1964, 1966, 1968; Brown & De Wet, 1962, 1967; Brown & De Boom, 1966) advanced the theory that enzootic icterus and geeldikkop were related and caused by subclinical selenium toxicity, Louw et al (1967) also investigated this possibility. On account of the interference by iron in the codein-phosphate method for the determination of selenium used by Brown and his collaborators (Brown, 1962, Brown & De Wet 1962), Louw et al (1967) conducted comparative determinations on plant and liver specimens and evaluated this method against the di-aminobenzidine (DAB) technique. These workers not only raised serious doubts as to the accuracy of the former method used by Brown and his co-workers, but also showed that no selenium value which they obtained from the large number of plant species subsequently examined by the DAB method, exceeded the maximum safety margin for animals. From these findings it was concluded that selenium toxicity was most unlikely to occur and to playa role in the aetiology of geeldikkop and enzootic icterus. Furthermore it was also shown that the selenium values of the grazing in the enzootic icterus areas were generally lower than those in the geeldikkop areas in contrast to the fact that Brown (1968) considered enzootic icterus to be the more severe form of subclinical selenium toxicity. The evidence produced by Louw et al (1967) therefore not only disproved the selenium theory but also the validity of any possible relationship between the two disease entities. In conclusion these researchers once more favoured the opinion that some substance present in the elevated ether extracted portions of the plants commonly found in the enzootic icterus areas was responsible for the production of the disease.
Since the Regional Veterinary Laboratory, Middelburg, Cape, came into operation at the end of 1966, enzootic icterus featured on the list of disease problems considered for investigation or re-examination.
One of the first steps deemed necessary in the approach towards these investigations was to identify each disease entity as accurately as possible at the hand of prominent epizootological and clinical-pathological features normally associated with it. This was done in order to avoid confusion between apparently similar syndromes and the interpretation of conflicting research results.
Once characterized, it soon became evident from the results of routine analyses done that the liver copper values of sheep that succumbed to enzootic icterus were consistently much higher than the accepted normal values or the values obtained in non-related deaths (Erasmus & De Vry, 1969).
In the first of two subsequent surveys, the liver copper values of clinically healthy aged Merino wethers and ewes from a known enzootic icterus farm were compared to those obtained from clinically healthy Transvaal sheep and it was found that the levels of 600;0 of these cases were far beyond the range of their Transvaal counterparts (Erasmus 1970).
In a second survey the liver copper values of a group of sheep from farms where both enzootic icterus and geeldikkop were unknown were compared to those of another group of sheep, which came from farms with a known history of enzootic icterus. All sheep were dependent on the natural Karoo vegetation on the farms of origin as their only source of nourishment. Although all these farms were situated in the same area, the mean value for liver copper in the sheep from the known enzootic icterus farms was significantly higher than that obtained for sheep from the farms where both this disease and geeldikkop were unknown (Erasmus, 1970).
Following these initial indications that harmful liver copper levels of a dietary origin could be associated with the development of enzootic icterus, a pilot experiment was carried out where the diet of milled lucerne of weaner lambs in the treatment groups were supplemented with copper sulphate at increasing levels. Cases, resembling enzootic icterus in most details were produced when a total amount of approximately 28 to 32 grams of copper was consumed over an extended period of up to 600 days (Van Tonder & De Vry, 1971).
Further developments took place when during severe outbreaks, the problem of geeldikkop was re-investigated in its entirety and ovine diseases involving icterus and photosensitisation were reappraised. During these studies it was shown that in both the aetiology and pathology geeldikkop and enzootic icterus were completely unrelated (Van Tonder, Basson & Van Rensburg, 1972).
In the years that now followed parallel studies of geeldikkop and enzootic icterus were pursued by the Regional Veterinary Laboratory at Middelburg. Thus a detailed systematic and comparative investigation of enzootic icterus in all its various facets was made, supplemented by a comprehensive study of the relevant literature and appropriate specific surveys and experiments (Bath, 1979). This work has unequivocally shown that uncomplicated forms of geeldikkop and enzootic icterus are unrelated in all respects but that their concurrent appearance in the same animal explains their apparent clinical congruence in some cases. Furthermore Bath (1979) concluded that the symptomatology, pathology, haematology, chemical pathology, histopathology and epizootology of enzootic icterus and chronic copper poisoning are indeed so similar that any interpretation other than that they are essentially the same disease, must be rejected.
In dealing with the mechanism of copper accumulation under natural circumstances, particularly in the face of the conclusion of Louw et al (1968a, 1968b) that the copper and molybdenum values they obtained for the various plants sampled in known enzootic icterus areas were such that neither deficiency nor toxicity could be expected, Bath (1979) examined some possible discrepancies in their approach. These included a disregard of the relative contribution of the dominant plant species in an enzootic area to the volume and mineral composition of the everyday diet of the animals concerned and the selective grazing habits of sheep, as proved by the significant differences in samples collected by hand as opposed to those obtained by oesophageal fistula. In a limited survey on a farm where enzootic icterus occurred at the time, the apparently dominant plants in the relevant camps growing on dolerite ridges, sandy alluvial soil and the areas in-between, were selected and the tiny leaves and growing tips carefully stripped by hand for copper analysis. Distinctly higher values than those of Louw et al (1968a, 1968b) for each of the plants concerned were generally obtained while markedly higher mean values occurred in samples of plants from dolerite ridges, and the lowest values in those plants derived from the sandy flats (Bath, 1979). These findings proved that chronic copper poisoning could certainly not be excluded as a possible cause of enzootic icterus and indeed supported the contention that enzootic icterus, which in its typical natural form mainly affects older sheep, results from a gradual low level build-up of copper in the liver. Once the threshold value for liver copper storage is exceeded or even approached, liver copper either spontaneously or triggered by stress is suddenly released into the circulatory system where it becomes responsible for the so-called haemolytic crisis. This in turn, depending on the degree of severity, is responsible for the typical range of symptoms normally associated with enzootic icterus. The correlation between the incidence of enzootic icterus and overgrazing or poor veld management found by Skinner (1960) could be explained by the fact that the plants which become dominant under these conditions supply a diet which is conducive to copper accumulation and which in any case affords nutritional stress which is a commonly experienced predisposing factor in the occurrence of enzootic icterus.
On account of the apparent similarity between chronic copper poisoning as was described overseas (Anonymous, 1956; Albiston, 1929; Albiston, Bull & Dick, 1940; Bull, 1952; Bull, Dick & Keast, 1956; Chamberlain, 1933; Ogilvie, 1954; Pearson, 1956; Rose & Edgar, 1936, Ross, 1964) and enzootic icterus (geelsiekte) experienced in certain areas of the Cape Province and the consistently high liver copper values found in typical cases of enzootic icterus examined at the Regional Veterinary Laboratory, Middelburg Cape (Erasmus, 1970; Erasmus & De Vry, 1969; Van Tonder & De Vry, 1971), the treatment of sheep in flocks where losses owing to this condition occurred with ammonium or sodium molybdate (Dick & Bull, 1949; Pierson & Aanes, 1958; Ross, 1966, 1970) was advised. At first this was done on a tentative and experimental basis but the results were so encouraging that it soon became a standard procedure. As a result of the fact that further deaths and clinical cases are dramatically arrested this preventative measure has since become widely known and practised even outside the enzootic area where cases have occurred in sheep coming from these regions.
The sustained efforts of research into the problem of enzootic icterus at the Regional Laboratory have thus been rewarded not only through elucidation of the problem but also by the introduction of highly effective preventative treatments. Although less dramatic and even poor results are occasionally reported, these are invariably due to the postponement of preventative treatment until outbreaks occur, when the additional stress of dosing and handling the already stressed animals does hamper success to a greater or lesser extent.
As the basic treatment consists of dosing of sheep above a certain age with ammonium or sodium molybdate at set intervals, other means of administration such as licks or drinking water have already been tried successfully and are still being investigated in order to define the recommendations more accurately.
The use of other supplements like sulphur and zinc to reduce liver copper accumulation is currently also under investigation.
In addition to the prevention of the chronic build-up of copper in the liver of sheep in the enzootic areas by supplementation of counteracting substances, avoidance of the problem in the long term by sound veld management procedures remains a basic recommendation.
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Karoo Agric 3 (8), 27-31