Effect of a one-off sporidesmin challenge on the milk production of dairy cows

Abstract

AIMS To investigate the effects on milk yield in lactating dairy cows of a single dose of sporidesmin, and to categorise the responses based on clinical signs and differing degrees of liver damage, as assessed by activities of γ-glutamyl transferase (GGT) and post-mortem liver histopathology. METHODS Adult lactating dairy cows (n=17) were given a single intra-ruminal dose of 0.24 mg/kg of sporidesmin dissolved in ethanol and diluted in water on Day 0; an additional three cows served as untreated controls. Weekly serum samples were collected between Days -14 and 42 and analysed for activities of GGT. Milk yields were measured daily over the same period. Cows were subjected to euthanasia due to severe clinical signs (n=2) or were slaughtered at the end of the trial. Samples of livers were examined histologically and were scored for lesions on a scale from 0 (normal) to 3 (severe). Based on GGT activities and clinical observations, cows that were treated with sporidesmin were categorised as non-responders (no clinical signs and normal GGT), subclinical (elevated GGT and no clinical signs) or clinical. Outcomes were compared between these three groups and control cows using generalised additive models. RESULTS Seven cows were classified as clinical, and had median liver scores of 22 (95% CI=20.6-23.4), six were subclinical with median liver scores of 8.7 (95% CI=3.8-13.5) and four were non-responders with median liver scores of 2.5 (95% CI=1.2-4.3). Median liver scores for the three control cows were 1 (95% CI=-0.8-2.1). Activities of GGT increased in subclinical and clinical cows around Day 7. The milk yield of all cows treated with sporidesmin, including non-responder cows, started to decrease on Day 1, and reached a nadir (a drop of between 9 and 85%) on Day 7. CONCLUSIONS AND CLINICAL RELEVANCE It is likely that the overall effects of sporidesmin consumption on milk production by the national herd in New Zealand are hugely underestimated, especially considering its effects on non-responder and subclinical cows as shown in this trial. In view of the results presented here, the authors are suggesting a change to the definition of response to sporidesmin from non-responder, subclinical, and clinical, to subclinical-low, subclinical-high, and clinical, when measuring a combination of GGT activities, clinical signs and milk yields during facial eczema-risk seasons (summer-autumn).

Biomarker identification and development of aptamers for the diagnosis of sub-clinical facial eczema

“…This specificity has been confirmed by later studies that sought to assess false positive and false negative rates, in comparison with alternative methods of screening that had been piloted, such as measuring cholesterol, aspartate aminotransferase, or albumin levels (Moreira et al, 2012). The characteristic rise in GGT levels, observed as a result of facial eczema, occurs 2-3 weeks after exposure to sporidesmin (Matthews, 2015;Smith & Embling, 1991). This increase is variable and can rise up to five-fold higher concentrations in serum.…”

“…In particular, it causes increased permeability of mitochondrial membranes (Gallagher, 1964), and cell-to-cell detachment due to disruption of microfilaments (Jordan & Pedersen, 1986). Sporidesmin is recycled within cells, causing continuing damage to tissue by the same molecule, even after exposure to sporidesmin has ceased (Matthews, 2015). The overall effect is the development of scarring, necrosis, and inflammation of the hepatobiliary system, as well as the build-up of compounds that would normally be processed by the liver in a healthy system (Bonnefoi et al, 1989).…”

“…One such compound is phytoporphyrin, a chlorophyll breakdown product that when left unprocessed causes the characteristic photosensitive dermatitis of the animal's skin observed in facial eczema (Morris et al, 2004). The increase of phytoporphyrin circulating in the blood causes the compound to aggregate in tissues, particularly in the skin, and it fluoresces on exposure to sunlight, releasing energy into the cells and damaging them (Matthews, 2015). The skin is irritated and suffers sunburn more easily, causing trauma to the affected animal and opening the path for secondary complications (Di Menna et al, 2009).…”

“…Levels increase in the blood around 10-20 days after exposure to sporidesmin and remain high over the course of the disease (Smith & Embling, 1991). A comprehensive study in cattle showed that while GDH can distinguish between clinical and non-clinical animals, it is not consistently able to distinguish subclinical animals (Matthews, 2015). GDH is underutilised in the diagnosis of facial eczema and more research would be required for it to be employed outside of research circles.…”

“…Bilirubin is often measured in animals to assess their liver health and increases in bilirubin are correlated with the progress of facial eczema in sheep, deer, and goats (FlÅøyen & Smith, 1992;Ozmen et al, 2008;Smith et al, 1997;Smith & Embling, 1991) but not in cattle (Matthews, 2015). This lack of consistency across species reduces the value of bilirubin for diagnosis of facial eczema, as it does not cover one of the species most in need of a new test method.…”