Crystal-associated cholangiohepatopathy and photosensitisation in lambs

Four outbreaks of hepatogenous photosensitisation occurred in weaned lambs in north eastern Victoria during the summers of 1985 and 1986. Attack rates varied between 7% and 43% and case fatality rates between 60% and 71%. Clinical signs included photosensitisation and jaundice. Serum biochemistry suggested hepatobiliary and hepatoparenchymal damage with impaired renal function. At necropsy livers were an ochre colour and kidneys a mottled brown to khaki. Histopathologically, needle-shaped to lenticular clefts were observed in and around bile ducts and in hepatocytes, hepatic sinusoidal macrophages and renal tubules. Optically active rhomboidal crystals were present in bile sediments. Panicum schinzii was identified as a possible cause in 2 of the 4 outbreaks. The clinical disease was reproduced in 2 of 6 lambs grazed on a toxic paddock. The disease was indistinguishable from geeldikkop except for the fact that Tribulus terrestris was not present on any of the 4 farms.     

Photosensitisation induced by clofazimine in a cat

A pale ginger cat was treated with clofazimine for feline leprosy. During the course of treatment, photosensitisation by clofazimine led to a dermatological disease resembling actinic dermatitis. The mycobacterial disease was eventually cured with clofazimine and the photosensitisation was managed by regulating sunlight exposure. Upon review of the literature, this appears to be the first documented case of drug-induced photosensitisation in the cat.     

Effects of low dose rates of sporidesmin given orally to sheep

Aim: To examine clinical and subclinical effects of sporidesmin administered orally to sheep at very low daily dose rates for periods of 3 to 48 days.

Methods: Two experiments were conducted. In Experiment A, sporidesmin-A was administered orally to groups of 16 sheep at daily dose rates of approximately 0.0042, 0.0083 and 0.0167 mg/kg bodyweight for 48 days. In Experiment B, the highest of these doses was administered orally for 3, 6, 12, 24 or 48 consecutive days. Parameters of production, clinical findings, organ weights and pathological findings were recorded.

Results: In Experiment A, severe liver lesions and photosensitisation were evident as early as 18 days after commencement of daily low-dose administration of sporidesmin, and were associated with significant bodyweight loss. Significant bodyweight loss also occurred in non-photosensitised sporidesmin-treated sheep. Bodyweight reductions were associated with reduced carcass weights and skin weights in treated animals. Sporidesmin administration was also associated with reduced bodyweight gains and pathological changes of the liver, kidney, hepatic lymph nodes, thymus, adrenal gland, heart and spleen. In Experiment B, only moderate changes occurred in a few sheep in the groups dosed with sporidesmin at 0.0167 mg/kg for 3 or 6 days, but major changes were frequently recorded in animals dosed at this rate for 12 days or longer. These comprised changes in the liver and other organs, and photosensitisation typical of the disease, facial eczema. Results are discussed in relation to animal welfare and economic issues associated with this disease.

Conclusions: Sporidesmin caused significant clinical and sub-clinical disease and reduced animal production at relatively low daily dose rates. The effects of repeated daily low-dose administration of sporidesmin appear to be cumulative. There was considerable variation in susceptibility between individual animals.These results emphasise the considerable production losses and animal welfare effects associated with sporidesmin toxicity in sheep.     

Effects of low dose rates of sporidesmin given orally to sheep

AIM: To examine clinical and subclinical effects of sporidesmin administered orally to sheep at very low daily dose rates for periods of 3 to 48 days. METHODS: Two experiments were conducted. In Experiment A, sporidesmin-A was administered orally to groups of 16 sheep at daily dose rates of approximately 0.0042, 0.0083 and 0.0167 mg/kg bodyweight for 48 days. In Experiment B, the highest of these doses was administered orally for 3, 6, 12, 24 or 48 consecutive days. Parameters of production, clinical findings, organ weights and pathological findings were recorded. RESULTS: In Experiment A, severe liver lesions and photosensitisation were evident as early as 18 days after commencement of daily low-dose administration of sporidesmin, and were associated with significant bodyweight loss. Significant bodyweight loss also occurred in non-photosensitised sporidesmin-treated sheep. Bodyweight reductions were associated with reduced carcass weights and skin weights in treated animals. Sporidesmin administration was also associated with reduced bodyweight gains and pathological changes of the liver, kidney, hepatic lymph nodes, thymus, adrenal gland, heart and spleen. In Experiment B, only moderate changes occurred in a few sheep in the groups dosed with sporidesmin at 0.0167 mg/kg for 3 or 6 days, but major changes were frequently recorded in animals dosed at this rate for 12 days or longer. These comprised changes in the liver and other organs, and photosensitisation typical of the disease, facial eczema. Results are discussed in relation to animal welfare and economic issues associated with this disease. CONCLUSIONS: Sporidesmin caused significant clinical and sub-clinical disease and reduced animal production at relatively low daily dose rates. The effects of repeated daily low-dose administration of sporidesmin appear to be cumulative. There was considerable variation in susceptibility between individual animals. These results emphasise the considerable production losses and animal welfare effects associated with sporidesmin toxicity in sheep.     

Pithomycotoxicosis (facial eczema) in ruminants in the Azores, Portugal

Outbreaks of pithomycotoxicosis (facial eczema), a hepatogenous photosensitisation caused by the mycotoxin sporidesmin, have affected ruminants in the Azores Islands of Portugal after warm, humid periods during late summer and autumn. Twenty-two outbreaks were recorded in cattle between 1999 and 2001, affecting 11.4 per cent of the animals in the affected herds, and in 2000 there was an outbreak in one sheep flock in which more than 20 per cent of the sheep died. The clinical signs included decreases in milk production, weight loss, photosensitisation and its sequelae, including death. The animals had high activities of gamma glutamyltransferase in their serum, and icterus and severe liver disease, including biliary hyperplasia and fibrosis, were found postmortem. The characteristic spores of the toxigenic saprophytic fungus Pithomyces chartarum were found on grass; all 381 isolates of the fungus were toxigenic for sporidesmin by elisa, and the results were confirmed by high-performance liquid chromatography analysis. Cattle from farms at greatest risk of pithomycotoxicosis were protected by supplementing their concentrate feed with zinc oxide, or using a slow-release intraruminal zinc bolus.     

Competition of a sporidesmin-producing Pithomyces strain with a non-toxigenic Pithomyces strain

Sporidesmin, a mycotoxin produced by some strains of Pithomyces chartarum, is responsible for the hepatogenous photosensitisation disease facial eczema, which causes severe losses in agricultural revenue in New Zealand. A sporidesmin-producing strain of P. chartarum, isolated in New Zealand, was grown in co-culture with a South African strain that does not produce the mycotoxin. Competition occurred between the two strains when grown both on agar plates and on dried ryegrass, with a significant decrease in the total amount of sporidesmin produced. Biological control of toxigenic P. chartarum can thus occur under laboratory conditions, raising the possibility of similar control in the field situation.     

Measurement of phylloerythrin (phytoporphyrin) in plasma or serum and skin from sheep photosensitised after ingestion of Narthecium ossifragum

AIM: To establish a method for measuring phylloerythrin in plasma or serum and skin from lambs photosensitised after ingestion of the plant, Narthecium ossifragum, which induces an hepatogenous photosensitisation similar to the disease known as facial eczema in sheep. METHODS: For two successive summers, lambs were grazed on uncultivated pastures containing N. ossifragum. Clinical photosensitisation was deemed to have occurred when symptoms such as restlessness, scratching, oedema and reddening of the skin were observed. Sixteen lambs that exhibited signs of photosensitisation were included in this study in the first year and five in the following year. A total of 16 clinically healthy lambs served as controls. Fluorescence emission and excitation spectra of phylloerythrin were measured in plasma or serum samples from the 21 photosensitised and 16 non-photosensitised lambs. In the first year of the study, skin samples were collected post mortem from the ear, lip, neck, nose, leg, belly, udder, back, vulva and perineal region, from all photosensitised and from seven non-photosensitised lambs, and examined by fixing them between two glass plates (each of 1 mm thickness) and placing them at a fixed angle in front of a fluorescence spectrofluorometer. RESULTS: All plasma or serum samples obtained from the photosensitised lambs exhibited strong phylloerythrin-like fluorescence of identical spectra; maximum fluorescence was at 650 and 711 nm, and maximum excitation at 425 nm. Emission spectra obtained from plasma or sera from non-photosensitised sheep grazing the same N. ossifragum-containing pastures exhibited either no or only minor fluorescence. Phylloerythrin concentration in plasma or serum exceeded 0.3 microg/ml before clinical photosensitisation occurred, whereas the concentration in samples from clinically healthy lambs was <0.05 microg/ml. Fluorescence from skin samples from the photosensitised lambs showed emission peaks at 650, 670 and 711 nm, whereas the phylloerythrin emission peaks at 650 and 711 nm were not observed in skin from clinically healthy lambs. CONCLUSION: Plasma concentrations of phylloerythrin in healthy sheep were <0.05 microg/ml. Clinical signs of photosensitisation were not observed until the concentration of phylloerythrin in plasma exceeded 0.3 microg/ml. This is the first reported spectroscopic method for analysis of phylloerythrin and the only one which does not involve exposure of the analyst to hazardous chemicals. It has the additional benefit of distinguishing between hepatogenous and primary photosensitisation.     

Competition of a sporidesmin-producing Pithomyces strain with a non-toxigenic Pithomyces strain

Sporidesmin, a mycotoxin produced by some strains of Pithomyces chartarum, is responsible for the hepatogenous photosensitisation disease facial eczema, which causes severe losses in agricultural revenue in New Zealand. A sporidesmin-producing strain of P. chartarum, isolated in New Zealand, was grown in co-culture with a South African strain that does not produce the mycotoxin. Competition occurred between the two strains when grown both on agar plates and on dried ryegrass, with a significant decrease in the total amount of sporidesmin produced. Biological control of toxkenic P. chartarum can thus occur under laboratory conditions, raising the possibility of similar control in the field situation.     

Suspected photosensitisation in lambs grazing birdsfoot trefoil (Lotus corniculatus)

Suspected photosensitisation occurred in three groups of lambs grazing birdsfoot trefoil (Lotus corniculatus c.v. Grasslands Goldie). In one group, sucking lambs aged about 10 weeks, grazing birdsfoot trefoil, developed skin lesions while lambs of a similar age and from the same flock grazing lucerne (Medicago sativa) or a mixed sward of both species showed no signs of photosensitisation. Affected lambs had lesions on their backs and ears. In a few animals the tips of the ears were shortened by 2-3 cm. In the affected lambs, serum liver enzymes (gamma-glutamyltransferase, glutamate dehydrogenase), bilirubin and serum Vitamin B12 levels were within the normal range. At necropsy, no significant pathological changes were detected in the liver and histological changes in the skin were consistent with primary photosensitisation. In the second group, three of 80 weaned lambs grazing the same birdsfoot trefoil at a restricted intake were affected in the same manner as the first group. In the third group, 15 animals from 28 sets of sucking twin lambs were also affected. In only two sets of twins were both lambs affected. None of the ewes grazing with the lambs in the first or third groups showed any clinical signs of photosensitisation.     

Hepatogenous photosensitisation in Scottish sheep casued by Dicrocoelium dendriticum

Dicrocoeliosis was identified as the probable predisposing cause of weight loss and hepatogenous photosensitisation affecting half of a group of 14month-old ewe lambs on a farm on the Inner Hebridean island of Coll. Oral dosing of the ewe lambs with 15mg/kg albendazole only achieved a 79.2% reduction in Dicrocoelium dendriticum egg count, 21day post treatment. Thus, this report of dicrocoeliosis differs from the disease that occurs elsewhere, both in the severity and nature of its clinical signs, and in the response of the parasite to anthelmintic drug treatment. These differences could indicate the existence of a genetically divergent D. dendriticum population, which may have evolved within the unique and isolated biotope afforded by the machair on the island of Coll. Better understanding of these factors is a prerequisite for effective and sustainable disease control.     

The impact of malnutrition and other causes of losses of adult sheep in 12 flocks during drought

OBJECTIVE: To establish the range and cost of losses in Merino flocks in southern New South Wales during drought conditions by determining the cause of death, morbidity or wasting in adult sheep. DESIGN AND POPULATION: Pathological studies were performed on 392 dead or moribund adult sheep from 12 Ovine Johne's disease (OJD)-infected flocks during 2002 and a further 58 sheep culled due to wasting from one of these flocks in 2003. Flocks ranged between 3,500 and 20,000 sheep. METHOD: The most likely cause of death, morbidity or wasting was determined following consideration of the environment in which the animal was found, clinical and gross pathological findings, plus histopathology of tissues collected during necropsy. RESULTS: A most likely cause of death, morbidity or wasting was determined for 362 sheep in 2002 and 58 sheep in 2003. OJD contributed to the death of 250 sheep in 2002, and wasting of 48 sheep in 2003. Of the sheep that died or were euthanased due to other causes, malnutrition was a contributing factor in the death of 70 sheep (63%) in 2002 and 2 sheep (20%) in 2003. Losses were not evenly distributed across flocks, with 57% of mortalities caused by malnutrition in 2002 occurring in one flock. Malnutrition accounted for 18% of the annual cost of all deaths among adult sheep in 2002 with an average cost of $16,882 per farm. Losses not attributed to malnutrition included a range of infectious and non-infectious disorders. These included balanoposthitis, clostridial enterotoxaemia, cutaneous myiasis, endoparasitism, enteritis, intestinal adenocarcinoma, misadventure, peritonitis, periparturient death of ewes, photosensitisation, pneumonia, post-shearing stress and squamous cell carcinoma of the perineum. CONCLUSION: Almost one third of mortalities in OJD-infected flocks during drought were unrelated to OJD and could be reduced by improving nutritional and disease management practices. The importance of close supervision of the flock is highlighted so that early management intervention can be instituted, including the culling of cases of welfare concern.     

Toxicity, pathophysiology and pathology in sheep following dosing of the nephrotoxic plant Nolletia gariepina (DC) Mattf

Ingestion of the plant Nolletia gariepina was confirmed as the cause of acute mortalities in cattle in the Kuruman area of the Northern Cape Province of South Africa. The aim of this trial was to investigate the toxic effects of this plant with respect to clinical signs, pathophysiology and pathology using the sheep as a model. At dosages of 1.5 g dried, milled plant material/kg body mass there were no detectable abnormal findings, while at dosages of 2.8-3.0 g/kg most of the animals died acutely. In subacutely affected sheep, depression, inappetance, teeth grinding, tachycardia, weak ruminal movements and recumbency were noticed. The most prominent pathophysiological changes observed, included a sharp rise in non-protein nitrogen substances in the plasma, remarkable decline in glomerular filtration rate, increase in sodium and potassium excretion, and a rise in urine gamma glutamyltransferase activity. Macroscopically a severe nephrosis was present in all the animals. The most important findings detected histologically were necrosis of the proximal convoluted tubular epithelium and large numbers of protein casts in the lumens.     

WHITE LIVER DISEASE IN LAMBS

An outbreak of white liver disease in lambs in Western Australia is described. The disease affected 2- to 3-month-old lambs and was characterised by liver damage, severe ill-thrift, depression, serous ocular discharge, photosensitisation, and a high mortality rate. Transient central nervous system signs occurred. A positive response to vitamin B₁₂ therapy was demonstrated.     

Adrenal-associated changes in experimental sporidesmin poisoning of sheep

Sporidesmin-dosed hoggets which developed photosensitisation were shown to have enlarged adrenal glands and premature involution of the thymus. These sheep also developed high concentrations of plasma cortisol after the onset of photosensitisation. Sporidesmin-dosed sheep which did not show photosensitisation showed less or no adrenal associated changes.     

Adrenal-associated changes in experimental sporidesmin poisoning of sheep

Sporidesmin-dosed hoggets which developed photosensitisation were shown to have enlarged adrenal glands and premature involution of the thymus. These sheep also developed high concentrations of plasma cortisol after the onset of photosensitisation. Sporidesmin-dosed sheep which did not show photosensitisation showed less or no adrenal associated changes.     

Spectrofluorometric analysis of phylloerythrin (phytoporphyrin) in plasma and tissues from sheep suffering from facial eczema

AIMS: To study the increase in phylloerythrin concentration in plasma and the disposition of phylloerythrin in skin and other tissues of sheep in which the hepatogenous photosensitisation,facial eczema, had been experimentally induced by dosing with the mycotoxin, sporidesmin. Spectroscopic differences between plasma and skin measurements of animals kept inside and outside after dosing were also studied in order to establish whether phylloerythrin undergoes photodegradation when exposed to sunlight. METHODS: Twenty-six Romney x Polled Dorset (25-30 kg)weaned female lambs were purchased from a commercial flock in the Waikato region, New Zealand. Twenty-two of these lambs were dosed with 0.25 mg sporidesmin/kg liveweight on each of two consecutive days (Days -1 and 0); the remaining four lambs served as controls. Both sporidesmin-dosed lambs and controls were randomly divided into two penned groups, one group housed inside in a darkened room and the others outside, exposed to natural sunlight. The lambs were fed green lucerne pellets and lucerne chaff ad libitum for 10 days prior to dosing and until Day 12 after the first dose; thereafter, all the lambs were fed fresh, cut grass (mainly ryegrass) ad libitum, until the end of the experimental period on Day 26. Plasma samples collected on Days -2, 7, 10, 12, 14, 17, 20 and 25were analysed for gamma glutamyltransferase (GGT) activity, bilirubin concentration, and the fluorescence spectrum of phylloerythrin. Spectrofluorometric analysis of phylloerythrin in skin was performed in vivo on the same days, using an external fiber-optic probe. RESULTS: Eight of 11 lambs (73%) kept outside after sporidesmin dosing became photosensitised during the experimental period. None of the sporidesmin-dosed animals kept inside showed clinical signs of photosensitisation. The GGT activity in plasma increased exponentially during the experimental period in all sporidesmin-dosed animals until it reached a plateau. All plasma obtained from sporidesmin-dosed sheep had spectral characteristics similar to those of phylloerythrin, namely a peak in the excitation spectrum at 422 nm and strong emission band at 650 (SE 1) and 709 (SE 1) nm. The fluorescence under excitation at 422 nm of phylloerythrin added to plasma from control lambs had identical peaks. Emission spectra obtained from plasma from healthy sheep without addition of phylloerythrin showed either no fluorescence or minor fluorescence at around 671 nm. Fluorescence in skin of sporidesmin-dosed animals had similar spectra to that in plasma. The appearance of the phylloerythrin-like spectra occurred 2-3 days later in the skin than in plasma, and phylloerythrin in sunlight-exposed skin did not suffer photodegradation during the course of the study. CONCLUSION: Plasma concentrations of phylloerythrin in healthy sheep were <0.1 micromol/l, and clinical signs of photosensitisation were not evident until concentrations exceeded 0.3 micromol/l. Plasma concentrations of phylloerythrin rose as high as 4.9 micromol/l in some animals. The concentration of phylloerythrin in skin began increasing 2-3 days later than that in blood. Hepatogenous photosensitisation can be diagnosed by analysis of plasma phylloerythrin concentrations using a spectroscopic method.     

Hepatogenous photosensitisation in fallow deer (Dama dama) in New Zealand

An outbreak of hepatogenous photosensitisation occurred in fallow deer and was diagnosed as facial eczema on the basis of liver lesions and plasma enzyme changes over 56 weeks. Clinical signs of photosensitisation were not as obvious as they are in sheep and cattle. The condition occurred over autumn and in the following spring. Six of 23 deer died or were destroyed. Concentrations of plasma total bilirubin, total bile acids and cholesterol increased, as well as the activities of aspartate transaminase, glutamic dehydrogenase, lactic dehydrogenase, alkaline phosphatase and gamma glutamyltransferase. Albumin:globulin ratios declined due to moderate increases in globulin and minor reductions in albumin. Many of the plasma enzyme activities did not return to normal after autumn and increased to even higher values during the spring outbreak of photosensitisation. Minor plasma biochemical changes were also detected in non-photosensitive deer in the same herd.     

Encephalomyocarditis virus disease of pigs associated with a plague of rodents

An epizootic of encephalomyocarditis virus (EMCV) disease in pigs in the central west of New South Wales in association with a plague of mice (Mus musculus) in 1984 is described. The disease was confirmed in 47 outbreaks in 37 piggeries and 1152 pigs died, representing an overall death rate of 17.4% in pigs considered at risk. The disease was diagnosed in both intensively housed pigs and pigs farmed outdoors, with mortality rates higher in piggeries with less than 50 sows. The age at which pigs died ranged from 4 days to 24 weeks with higher death rates in younger pigs. Serological testing of pigs slaughtered at Blayney abattoir indicated EMCV infection to be more widespread than the disease reported. Mice were present in all piggeries reporting the disease while rats were present in 66% of the outbreaks. The role of rodents as natural reservoirs of EMCV and the possibility of variations in pathogenicity amongst strains of the virus are discussed.     

Analysis of the population structure of the South German coldblood in Bavaria, Germany

Gene contributions of foreign populations as well as coefficients of inbreeding and relationship were calculated in 1918 South German Coldblood horses registered in Bavaria in 2003. Based on nearly complete 8-generation-pedigrees (index of pedigree completeness: 76%) the mean coefficient of inbreeding was 23%. After considering missing pedigree data, the mean coefficient of inbreeding was 3%. The rates of inbreeding per generation in the current population amount to about 0.43% over the last eight generations and to about 0.15% in the forthcoming generation. In the total current population, the mean degree of relationship was 6%. The proportion of purebred South German Coldblood horses in the current population is about 43%. As the Noric horse is of same origin as the South German Coldblood, these two breeds can be considered as an entity and thus the proportion of purebred genes in the current Bavarian South German Coldblood population reaches more than 93%. The Suffolk Punch and Thoroughbred Horse were the most important contributors to the current South German Coldblood population, whereas the Rhenish-German and Black Forest Draught Horse as well as the Percheron had neglectable influences. The effective population size in the current Bavarian South German Coldblood population is Ne = 332.