Emodepside targets SLO-1 channels of Onchocerca ochengi and induces broad anthelmintic effects in a bovine model of onchocerciasis.

Onchocerciasis (river blindness), caused by the filarial worm Onchocerca volvulus, is a neglected tropical disease mostly affecting sub-Saharan Africa and is responsible for >1.3 million years lived with disability. Current control relies almost entirely on ivermectin, which suppresses symptoms caused by the first-stage larvae (microfilariae) but does not kill the long-lived adults. Here, we evaluated emodepside, a semi-synthetic cyclooctadepsipeptide registered for deworming applications in companion animals, for activity against adult filariae (i.e., as a macrofilaricide). We demonstrate the equivalence of emodepside activity on SLO-1 potassium channels in Onchocerca volvulus and Onchocerca ochengi, its sister species from cattle. Evaluation of emodepside in cattle as single or 7-day treatments at two doses (0.15 and 0.75 mg/kg) revealed rapid activity against microfilariae, prolonged suppression of female worm fecundity, and macrofilaricidal effects by 18 months post treatment. The drug was well tolerated, causing only transiently increased blood glucose. Female adult worms were mostly paralyzed; however, some retained metabolic activity even in the multiple high-dose group. These data support ongoing clinical development of emodepside to treat river blindness.

[Cortisol concentration before, during and after sham foot trimming in German Holstein cows - the suitability of different matrices]. / Kortisolkonzentration bei Deutsch-Holstein-Kühen vor, während und nach der Klauenbehandlung im Durchtreibestand ­ Eignung verschiedener Matrizes.

OBJECTIVE: The objective of this study was to determine whether changes in cortisol concentration measured in blood serum (KoB) of cows exposed to an acute stressor shows a correlation to cortisol concentrations in saliva (KoS), tears (KoT) and milk (KoM) as well as the concentration of cortisol metabolites in feces (KoK). MATERIALS AND METHODS: In 10 healthy German Holstein cows, sham foot trimming (sKB) including the movement/fixation of the cows through/in a foot trimming chute was used as a model for acute stress. KoB, KoS, KoT, KoM and KoK were measured once a day for 10 days. During sKB, performed on day 4, KoB and KoT were measured at the initiation of foot trimming (minute 0) as well as 15, 25, 30, 40, 50, 60 and 80 minutes later. Additionally, KoK was measured 480, 540, 600 and 660 minutes after the start of sKB. RESULTS: KoB and KoT increased during sKB and reached a maximum at 60 minutes followed by a decrease. KoK increased after sKB and reached a maximum at 660 minutes. There was a significant correlation between KoB and KoT, KoK and KoB and a trend towards a significant correlation between KoK and KoT during sKB. KoB and KoT were significantly correlated (area under the curve, minute 0-10, p = 0.04). KoB decreased significantly from day 1 to day 4 (p < 0.01). On day, 5 KoB (p = 0.03) and KoK (p < 0.01) were significantly higher. KoS and KoT served as good proxies for KoB throughout the study, and KoK and KoB exhibited similar profiles. There were several differences between the profiles of KoM and KoB. During the 10-day measurement period, a significant positive correlation was detected between KoB and KoS (p = 0.002) as well as between KoB and KoT (p = 0.002). CONCLUSIONS AND CLINICAL RELEVANCE: The collection of tear fluid and saliva for determination of cortisol concentrations are non-invasive alternatives to blood sampling. Calm handling of cows may reduce their stress reaction and thus improve animal welfare.

[Assessment of different pain management methods for the treatment of claw lesions in Meat Merino ewes]. / Bewertung verschiedener Methoden des Schmerzmanagements während der Behandlung von Klauenlederhaut-Läsionen bei weiblichen Merinofleischschafen.

OBJECTIVE: Pain management during veterinary procedures is a significant component of animal welfare and has legal as well as ethical implications. Even though regional intravenous anaesthesia (RIVA) is an accepted method for painful procedures involving the distal digits of sheep, this anaesthetic technique is rarely applied in the field. The primary goal was to investigate the feasibility, safety and efficacy of RIVA in sheep. A secondary goal was to examine whether the anaesthetic procedure can be improved by combining RIVA with sedation and whether these methods have a positive effect on the postoperative wellbeing of the animals. METHODS: A total of 36 Meat Merino sheep with contagious interdigital dermatitis and 12 healthy control sheep were used. Behaviour was observed during treatment of the lame sheep using various pain management protocols and during routine claw trimming of the healthy sheep, and all the sheep were observed after the procedures. The observed behaviours were assessed using scores and the scores compared among the animals of the 4 study groups (RIVA, sedation with xylazine hydrochloride + RIVA, placebo, control). RESULTS: RIVA was successfully conducted in sheep. Local reactions at the application sight and in the tourniquet area in 2 animals resolved completely. A significant reduction in defensive movements during the painful procedure confirmed the efficacy of RIVA. Stress-associated behaviours, including head shaking and idle chewing, occurred with a similar frequency in RIVA and placebo animals, leading to the conclusion that stress levels due to the handling in dorsal recumbency were comparable between these 2 groups. Sedation reduced the frequency of pain- and stress-associated behaviours, including guarding, favouring limbs, vocalisation, idle chewing and bruxism. Xylazine hydrochloride-RIVA animals displayed better weight-bearing in the affected limb, better food uptake and ruminated more postoperatively than sheep from the other study groups. CONCLUSION: RIVA in sheep is straightforward, safe and effective. Additional sedation reduces the stress and pain response. This pain and stress management has a positive effect on the postoperative wellbeing of sheep.

[Detection and assessment of acute and chronic pain in Meat Merino ewes using ethological parameters]. / Erfassung und Bewertung von akutem und chronischem Schmerz anhand ethologischer Merkmale bei weiblichen Merinofleischschafen.

OBJECTIVE: The assessment of pain in sheep is a clinical challenge, because being a prey species, they tend to mask it. Since pain in animals cannot be measured directly, various methods are applicable to detect its effects on physiological, biochemical and ethological processes. Clinicians experienced in behavioural assessment are able to reliably determine the level of pain endured by an animal. The objective of this study was to identify behaviours that reflect acute and chronic pain as well as stress in sheep. METHODS: The behaviour of 36 Meat Merino ewes with contagious footrot (contagious interdigital dermatitis) was analysed during normal activities in the flock and during footrot treatment, which included claw trimming to remove abnormal horn. The behaviour during treatment was compared with that of 12 healthy control sheep of the same breed during routine foot trimming. Grading of the observed behaviours was made using a numerical score. The occurrence of footrot was defined as, and equated with, chronic pain, and treatment was equated with acute pain. For the assessment of stress induced by the manipulative treatment, the data of the healthy sheep were taken as a comparison. RESULTS: The strongest indications of chronic pain were non-weight bearing lameness of an affected limb, shifting of weight and abnormal gait patterns. Additionally, sheep with footrot urinated more frequently than healthy animals. Stress-related bruxism occurred in healthy and ill sheep during foot trimming, but not during normal activities in the flock. Tail wagging and strong defensive movements of all limbs commonly occurred during footrot treatment. Head shaking appeared to be primarily stress-related in association with dorsal recumbency on the tilt table, but was exacerbated by pain elicited by hoof trimming. CONCLUSION: The behaviours selected in this study were useful for the identification of chronic and acute pain in sheep; however, correct interpretation of behavioural changes requires an experienced individual.