title: Dose-response effects of diclazuril against pathogenic species of ovine coccidia and the development of protective immunity.
abstract: Twin lambs at pasture with their ewes, were divided into seven groups of 10 lambs. One group of 10 lambs served as a non-infected, untreated control. Five groups of 10 lambs were infected with 10,000 oocysts of Eimeria crandallis and 10,000 oocysts of Eimeria ovinoidalis when they were 3 weeks old (day 21 of the study). This produced a good level of infection with high oocysts production and diarrhoea in the lambs. Fourteen days after the primary, artificial challenge (day 35) four of these groups were treated with oral diclazuril at 0.25, 1.0, 2.0 or 4.0mg/kg. Diclazuril treatment was highly effective, dramatically reducing symptoms of diarrhoea and reducing faecal oocyst output by 79.7%, 97.3%, 99.4% and 99.5% respectively in the treated groups within four days. Two weeks post-treatment, and 28 days after the primary coccidial challenge (day 49 of the study), five groups of lambs were re-challenged with 100,000 oocysts of E. crandallis and 100,000 oocysts of E. ovinoidalis (secondary challenge). A group of lambs which had received neither the primary coccidia infection, nor drug treatment (susceptible controls) were also given the secondary challenge. All lambs given the secondary challenge produced high numbers of coccidia and exhibited varying degrees of diarrhoeic faeces. The lambs, which had previously received the higher doses of diclazuril at 2.0 and 4.0mg/kg, developed clinical signs of coccidiosis. These lambs were completely susceptible despite having received the early primary immunising infection of coccidia on day 21. The effects of the secondary challenge were more severe in the groups dosed with the two highest levels of diclazuril than in the susceptible control lambs, which had presumably been exposed to continued low levels of pasture contamination and had acquired a limited degree of immunity from this exposure. It would appear that treatment at the higher dose levels not only eliminated most of the oocysts from the primary challenge but also adventitious infection derived from the grazing paddocks. In contrast, lambs which had received the two lower drug levels of diclazuril (0.25 and 1.0mg/kg) whilst producing large numbers of oocysts, had only transient diarrhoea following secondary challenge. It was concluded that when used as a metaphylactic treatment, diclazuril works rapidly and is effective within four days of administration. Overall, a single dose of diclazuril at either 0.25-1.0mg/kg appears to be highly effective in the control of coccidiosis in young lambs at pasture whilst allowing the development of protective immunity against subsequent heavy coccidia challenge.
authors.affiliation: Veterinary Laboratories Agency, Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK. mike.taylor@fera.gsi.gov.uk
authors.forename: M A
authors.initials: MA
authors.lastname: Taylor
authors.forename: R N
authors.initials: RN
authors.lastname: Marshall
authors.forename: J A
authors.initials: JA
authors.lastname: Marshall
authors.forename: J
authors.initials: J
authors.lastname: Catchpole
authors.forename: D
authors.initials: D
authors.lastname: Bartram
mesh_terms: D000818:Animals; D003049:Coccidiostats / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D009570:Nitriles / Q000008:administration & dosage / Q000627:therapeutic use*; D012756:Sheep; D012757:Sheep Diseases / Q000188:drug therapy* / Q000276:immunology; D014227:Triazines / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D003049:Coccidiostats; D009570:Nitriles; D014227:Triazines; C057884:diclazuril