Arne Flåøyen:  

STUDIES ON THE AETIOLOGY AND PATHOLOGY OF ALVELD  
with some comparisons to sporidesmin intoxication 

Introduction
Alveld (other names: alvella, hudbrand, yla, håvesot, den galne sotten, lyngsyke, lyngsot) is a hepatogenous photosensitivity disease of sheep in Norway which has been known for several hundred years (Ender, 1955; Flåøyen, 1990; FIåøyen, 1992).  The name alveld, literally elf-fire, indicates what people thought was the cause of the disease. When the sheep were grazing in the light summer nights, elves shot the sheep with their arrows, a way elves are known to cause diseases in both animals and humans (Ronald Grambo, personal communication).
Alveld was first reported in the Veterinary Statistics for Norway in 1891 (Jessen, 1893).  From the early reports we know that it was a typical disease of lambs, that adult sheep were rarely affected, that white animals were more frequently affected than black (Kjoss-Hansen, 1910; Tillier, 1910) and that the old Norwegian breed was more resistant to the disease than introduced sheep like Cheviot (Fusk, 1934). The disease occurred sporadically, but only when the lambs grazed particular pastures (Kjoss-Hansen, 1910; Tillier, 1910).  It was first reported from the Stavanger area on the South-western coast of Norway and later from the west coast from Agder to Troms County (Ulvund, 1984; see FIåøyen, 1992).
The first known study of the disease was made in 1908 by Jens J. Kjoss-Hansen (1910) and Sigurd Tillier (1910), who visited farms in Dalane in Rogaland County (FIåøyen, 1992).  Clinically, they found it to be similar to fagopyrism, but they stated that "the question of cause seems to be rather complicated".  They stated that it occurred more frequently in cold and rainy summers than in warm and dry summers, as was later noted by Ulvund (1984).
Bacteria, as well as elves, have been suspected to cause alveld.  In one area it was thought that the disease was caused by spiders crawling in to the ears of the lambs (Jensen, 1918).  However, since the disease occurred only when lambs were grazing particular pastures, a search was made for toxic plants.  As early as 1916 Narthecium ossifragum (Bog asphodel) was the chief suspect (Kjoss-Hansen, 1918; Tillier, 1918).  At that time alveld was reported to be the disease causing the greatest losses for sheep farmers in Western Norway, and a systematic botanical investigation was carried out in 1919 (Wille, 1919).  The results supported the hypothesis that N. ossifragum was the cause of the disease, but Wille (1919) thought that neither bacteria nor protozoa could be excluded from the aetiology.  A difficulty with the N . ossifragum hypothesis was, and still is, that lambs do not always develop alveld when they graze the plant, and that some N. ossifragum pastures are known to be non-toxic (Tillier, 1921; Slagsvold, 1928).  This caused Lars M. Slagsvold (1928) to suggest that the toxicity of N. ossifragum was dependent on where the plants were grown or whether they were parasitized.
In the late nineteen twenties Slagsvold tried to prove that N ossifragum was toxic by feeding fresh N. ossifragum to lambs, but none of the lambs developed alveld (Ender, 1955).  However, lambs which grazed a typical alveld-pasture, from which all plants other than N. ossifragum had been removed, developed alveld.  Lambs which grazed a similar pasture from which all N. ossifragum plants but no others were removed, did not develop alveld.
Photosensitization of sheep grazing pastures containing N . ossifragum is also reported to occur in Scotland and Northern England (Ford, 1964).  "Plochteach", "saut" and "yellowses" are names of similar diseases to alveld on the British Isles.
N. ossifragum is a loosely to densely clonal, perennial herb, 5-30(-40) cm tall with a creeping rhizome.  The plant occurs on oligotrophic, mesotrophic and eutrophic peat deposits in Scandinavia to 69°42' N, in the British Isles, in the Netherlands, Belgium, north-west Germany, west and central France, northern Spain and east Portugal (Summerfield, 1974).  In Norway the plant is most common on bogs and heathery moors which are low in calcium, on the western coast up to Troms County and up to Ringerike in eastern Norway (Ender, 1955; Fægri, 1960; Høeg, 1974).  Grazing of the plant has for several hundred years been associated with osteomalacia in cattle and thereby the specific name ossifragum (Hoeg, 1974).
Rimington and Quin revolutionized the research on photosensitivity diseases when they reported that retention of phylloerythrin, a metabolic product of chlorophyll produced by rumen microorganisms, caused geeldikkop, a photosensitization of sheep in South Africa (Rimington and Quin, 1933; Quin et al., 1935).  The phylloerythrin retention is caused by liver damage or liver dysfunction and reduced excretion capacity of the liver (Flåøyen, 1990).  Traditionally the hepatogenous photosensitivity diseases have been divided into two groups on the basis of histological changes in the liver, either photosensitivity resulting from damage primarily to the liver parenchyma, or photosensitivity resulting from damage primarily to the biliary system (Kellerman and Coetzer, 1984).  However, functional changes may occur before histological changes can be seen, and the mechanisms causing phylloerythrin retention in alveld as well as in other photosensitivity diseases are still not clearly understood.

Some years after Rimington and Quin presented their results, Mathews (1937) reported that saponins could cause liver lesions and photosensitization of sheep grazing Agave lecheguilia in Texas, USA.  Fifteen years later Henrici (1952) reported from South Africa that Tribulus terrestris, the plant known to be associated with geeldikkop, contains saponins, and soon after Ender (1955) found saponins in N. ossifragum.  By dosing crude saponins to lambs, Ender produced photosensitization, and he concluded that saponins could cause alveld, but did not exclude that other factors could be involved in the aetiology of the disease (Ender, 1955).  Results from work of Abdelkader et al. (1984), supported the findings of Ender that saponins might cause alveld.  However, Abdelkder et al. obtained their results by dosing crude saponins to rats, and to the knowledge of the author, it has not been reported that sheep dosed pure saponins have become photosensitized.
In the early works on alveld, liver lesions were not reported to be seen.  Ulvund (1984) was the first to describe the liver lesions, and to compare the findings with results from work on geeldikkop.  The finding of so called "cholesterol clefts" in the liver of alveld cases as well as in geeldikkop cases, made her suggest that the aetiology of alveld and geeldikkop could be similar.  By then it was known that sheep administered sporidesmin, a toxin produced by the saprophytic fungus Pithomyces chartarum, in combination with grazing T. terrestris, developed histological changes in the liver typical of geeldikkop, while sheep dosed sporidesmin solely developed lesions typical of facial eczema (Henrici, 1952; Kellerman et al., 1980).  Ingestion of sporidesmin in combination with grazing of T. terrestris was therefore suggested to be the cause of geeldikkop.  From Norway, Aas and Ulvund (1989) reported the finding of spores of P. chartarum on N. ossifragum pasture, and they suggested that mycotoxins, and possibly sporidesmin, could be involved in the aetiology of alveld as well.
On the background of earlier reports and previous studies the present work was undertaken to:
 

- study the involvement of saponins from N. ossifragum in the aetiology of alveld

- study the involvement of sporidesmin and other possible mycotoxins in the aetiology of alveld

- study the cause of differences in susceptibility to alveld between adult sheep and lambs

- study the differences in susceptibility to alveld between lambs of
different breeds

- study the liver pathology of lambs with alveld and compare it with the liver lesions seen in sporidesmin intoxicated lambs in order to better understand the mechanisms causing phylloerythrin retention.