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Efficacy of toltrazuril as a metaphylactic and therapeutic treatment of coccidiosis in first-year grazing calves.

A multicentric, placebo-controlled, randomised, blinded and blocked field study was conducted to evaluate the efficacy and safety of toltrazuril (Baycox, Bayer AG, Leverkusen, Germany) in the treatment of coccidiosis in first-year grazing calves naturally infected with Eimeria spp. Three-hundred and thirty-one calves were enrolled in the study and allocated to one of two treatments at a ratio of 1:1. One hundred and sixty-seven animals were treated once orally with 15 mg/kg toltrazuril, and 164 animals served as placebo-treated controls. Two treatment regimes were compared, a metaphylactic (treatment on the day, or 1 day after, turn out) and a therapeutic treatment (4 or 7 days after turn out). During an observation period of 14 days after treatment the animals were clinically examined for diarrhoea and faecal samples were regularly assessed for Eimeria oocysts. Other possible causes of diarrhoea were excluded on the basis of microbiological and virological examination. Animals were predominantly infected with Eimeria alabamensis. Number of days with diarrhoea in animals treated with toltrazuril was significantly lower compared to the placebo-treated group (therapeutic treatment: P=0.0024; metaphylactic treatment: P<0.0001). Furthermore, the number of animals with diarrhoea during the observation period for a minimum of at least 3 days, the number of animals positive for Eimeria oocysts, and the number of animals with both diarrhoea for a period of at least 3 days and positive for Eimeria oocysts, were significantly lower (P<0.01), in the toltrazuril- compared to the placebo-treated animals. Body weight in the toltrazuril-treated animals significantly exceeded that of the placebo-treated animals at the end of the observation period. Mean difference in body weight was higher in the metaphylactic (+7.3 kg) compared to the therapeutic treatment group (+3.4 kg). No adverse reactions were observed. The results indicate that toltrazuril is highly efficacious and safe in the metaphylactic and therapeutic treatment of coccidiosis caused by E. alabamensis in first-year grazing calves.

Animals↗

Control of clinical coccidiosis of calves due to Eimeria bovis and Eimeria zuernii with toltrazuril under field conditions.

The efficacy of metaphylactic treatment with toltrazuril (Baycox 5% suspension) against natural infections with Eimeria bovis and/or Eimeria zuernii in calves was investigated. The study was conducted with 208 calves on five calf-rearing farms in Germany and the Czech Republic. All participating farms had a notable incidence of coccidiosis. Animals were treated 14 days after stabling in the respective facility. One group was treated with 15 mg toltrazuril/kg body weight, and a second group served as the sham-treated control. Assessment of efficacy was based on faecal consistency and oocyst excretion of E. bovis and E. zuernii, both investigated throughout the study. Duration and rate of oocyst excretion as well as number of scour days with E. bovis or E. zuernii oocyst shedding and the severity of diarrhoea were significantly lower in the toltrazuril-treated groups. It is concluded that a single metaphylactic treatment with toltrazuril controls coccidiosis of housed calves under various field conditions.

Animals↗

Experimental bovine coccidiosis: control with monensin.

Young Holstein-Friesian bull calves were used in a controlled experiment to evaluate the efficacy of monensin against coccidiosis. The calves were given oocysts of Eimeria bovis and/or E. zurnii. Medication was started 3 days prior to inoculation and continued during the 30-day experimental period. Oocyst shedding was quantified prior to and throughout the experiment and demonstrated that monensin at the rate of 20 or 30 g ton-1 of feed significantly reduced oocyst shedding and clinical coccidiosis. Clinical infection with E. zurnii was very difficult to establish, even when calves were treated with 20 mg dexamethasone IM on Days 12, 15, and 16 post-inoculation.

Animals↗

A descriptive epidemiological study of coccidiosis in early lambing housed flocks.

Infection with Eimeria sp. was studied in 135 lambs born to 79 ewes in four early lambing housed flocks. In three of these flocks two different coccidiostats (monensin and decoquinate) were administered in the feed. Cohort lambs were examined clinically and a rectal faeces sample taken once a week. Samples with more than 300 oocyts per gram were speciated by morphology. Nine species were identified and Eimeria crandallis was the most prevalent. One of the flocks developed clinical coccidiosis before the introduction of coccidiostats. On the remaining farms no differences in the oocyst excretion rate of infected lambs were found between medicated and non-medicated lambs until Visit 6 nor in the proportion of lambs infected until Visit 8. It is suggested that cocciodiosis may be controlled without coccidiostats, by identification of the risk factors associated with disease. Morphological variation of species and collection of large enough faeces samples from young lambs constitute limiting components for further epidemiological studies of coccidiosis.

Animals↗

Hepato-biliary coccidiosis in a dairy goat.

Hepato-biliary coccidiosis is reported in a diary goat that died of liver failure. Two types of lesions were seen in the liver. In the biliary type, coccidial oocysts, schizonts, gametes and gametocytes were seen in the epithelium of the bile duct, the wall of which was highly fibrosed. The hepatic type was in the form of granuloma, composed of oocysts and macrophages encapsulated in a fibrous capsule. Hepatic lymph nodes were diffusely scattered with oocysts and macrophages. Liver coccidiosis was found to be unresponsive to oral sulphamethazine treatment.

Animals↗

In ovo vaccination with the Eimeria tenella EtMIC2 gene induces protective immunity against coccidiosis.

An Eimeria tenella microneme recombinant gene (EtMIC2) and encoded protein were evaluated as potential vaccines against avian coccidiosis. In ovo inoculation with the EtMIC2 gene increased anti-EtMIC2 antibody titers at days 10 and 17 following E. tenella infection. In addition, vaccinated birds developed protective immunity against infection by E. tenella as assessed by significantly increased body weight gain and decreased fecal oocyst shedding compared with non-vaccinated controls. Vaccination with the EtMIC2 gene also led to protective immunity against infection by E. acervulina, but not E. maxima. Combined in ovo DNA vaccination plus post-hatch boosting with EtMIC2 DNA or protein did not improve antibody titers or protective immunity beyond that achieved with in ovo vaccination alone. These results provide evidence that in ovo immunization with a recombinant Eimeria microneme gene stimulates protective intestinal immunity against coccidiosis.

Animals↗

Use of live oocyst vaccines in the control of avian coccidiosis: experimental studies and field trials.

Areas addressed in this study on the use of live oocyst vaccines to control coccidiosis include: the influence of immunocompetency of the strains and sex of the birds used; methods of delivery of vaccine; immunological variation between different strains of the same coccidial species; and the effects of combining vaccine with anticoccidial medication. The results show that vaccination with live oocysts elicited significant protection against coccidiosis, both with experimentally induced and naturally acquired coccidial infection, resulting in average bird weight gains and feed efficiency similar to that obtained with conventional anticoccidial medication.

Animals↗

Progress in recombinant vaccine development against coccidiosis. A review and prospects into the next millennium.

The increasing problems encountered by the poultry industry, despite the extensive use of drugs, have emphasised the need for an immunological solution for the economic damage caused by the Eimeria parasite. Although immunity develops relatively fast following a natural infection, to induce protection by using parasite extracts or single antigens appears more difficult. Nevertheless, the development of a vaccine based on defined antigens seems the best solution in the long run. At the VIth International Coccidiosis Conference in 1993 the first promising results were reported from small-scale experiments using recombinant antigens. This review summarises the advances in this field of research from 1993 onwards. Although since then not many reports have been published about the effects of using recombinant. antigens as a vaccine against coccidiosis, a number of interesting new proteins which could be considered good targets for such a vaccine have been described and are referred to herein. Proteins involved in the process of invasion of the host cell by the extracellular parasite are regarded as key components in the developmental cycle of the parasite. These components possibly bind to receptors on the host cell. Interference with this process could be a target of the protective immune response. Progress has also been made in characterising the immune mechanisms activated by infection with the parasite. From experimental mouse models and from studies in chickens, a better insight has been obtained towards the involvement of CD4- and CD8-type T cells in, respectively, the inductor and the effector branch of the immune response, although not all questions have been answered. Several antigens have been selected using T-cell stimulation and cytokine assays and these are reviewed. In a third section, mostly unpublished results of our own experiments dealing with the use of live vectors to present defined antigens such as Ea1A and EaSC2, a parasite refractile body transhydrogenase and a lactate dehydrogenase, respectively, are summarised. Partial protection could be induced using Salmonella typhimurium as a carrier for these antigens, in that the oocyst output was reduced by up to 50% after challenge and weight gain could be improved by 5-10% over non-vaccinated challenged chickens, when tested in a floor-pen trial. Similar results were obtained when these antigens were presented by viral vectors such as Fowlpox virus or Herpes virus of turkey. These data seem to offer good prospects for the accomplishment of a safe and efficaceous vaccine based on recombinant DNA technology. These expectations are corroborated by recent breakthrough in transfection of related parasites such as Plasmodium and Toxoplasma gondii, and by the increasing amount of genomic information becoming available every day, the impact of which cannot even be estimated yet. These new technologies will allow us to solve the complex problems that we once created ourselves.

Amino Acid Sequence↗

Prevalence of subclinical coccidiosis in broiler-chicken farms in the municipality of Mashhad, Khorasan, Iran.

A survey of the prevalence of subclinical coccidiosis in broiler-chickens was conducted in the municipality of Mashhad, Khorasan, Iran. Eighty-four chicken farms were randomly selected; from each farm, five birds per 106th week of age.6th week of age. The farm-level prevalence of subclinical coccidiosis was 38% (95% CI: 48 .47%). Uni- and multi-variable associations were tested between each va riable. An increased risk of infection in the broiler was associated wi th the larger farm, with older chickens, and if the chicken farm were sa mpled in the winter or spring, using coccidiostat in the food was not as sociated. The peak oocyst score in the litter occurred at >6th week age . Most farms (97%) had E. acervulina; (41%) had E. maxima and (12%) had E. tenella.

Animal Husbandry↗

Role of acquired immunity and natural age resistance on course of Isospora suis coccidiosis in nursing piglets.

Thirty-two piglets from three litters were experimentally inoculated with 200000 sporulated oocysts of Isospora suis at 3 days of age and/or rechallenged at 19 days of age or primary inoculated at 19 days of age, to compare the role of acquired immunity and natural age resistance on the course of coccidiosis. Twelve piglets were not inoculated and served as a control. Following challenge, the signs of coccidiosis characterised by clinical symptoms, oocysts shedding and weekly weights were similar to those which occurred in piglets primary inoculated at 19 days of age. This comparison suggests that maturation of non-specific components of the immune system plays a more important role in the resistance of neonatal piglets to I. suis infection than specific immune mechanisms.

Aging↗

Ileoileal intussusception associated with coccidiosis in sheep.

Postmortem examination of a 3-year-old male Iranian native sheep with a history of anorexia and severe colic, revealed an intussusception of the small intestine, 30 cm proximal to the ileocaecal junction. Scattered hyperplastic lesions were present in the jejunal and ileal mucosa especially in intussuscipien. Microscopic examination of these lesions showed severe papillary hyperplasia of the epithelium associated with developmental stages of coccidia in the epithelial cells. An unusual type of intussusception and the presence of the proliferative nodular form of coccidiosis in the intestinal wall of intussuscipien suggested that coccidiosis could be considered as the possible cause of the problem.

Animals↗

The effect of intestinal coccidiosis (Eimeria acervulina) on blood and tissue ascorbic acid concentrations.

1. Two experiments were conducted to investigate the effect of intestinal coccidiosis (Eimeria acervulina) on blood plasma and tissue ascorbic acid (AA) concentrations in chicks, and a third experiment was carried out to examine the role of dietary AA in this infection. 2. Experimental infection with intestinal coccidiosis (Eimeria acervulina) brought about a depletion in the concentration of AA in blood plasma, duodenum, jejunum, ileum, liver and the adrenal glands. Generally, these changes were obtained after the prepatent period of 4-5 d of the infection. 3. Dietary AA at 1000 mg/kg prevented the depletion in plasma and tissue AA levels but did not significantly affect adrenal weight.

Adrenal Glands↗

Effects of dietary supplementation with n-3 fatty acid ethyl esters on coccidiosis in chickens.

The ethyl esters of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids were added to a broiler starter diet singly or in combination [as bulk purified ethyl ester concentrate from menhaden oil (n3FAC)] in quantities similar to those found in a diet supplemented with 5% menhaden oil (MO). Diets were fed to chickens from 1 d of age through 3 wk of age. At 2 wk of age, the chickens were infected with Eimeria tenella, Eimeria acervulina, or Eimeria maxima. At 6 d postinfection (PI), the effects of the diets were assessed on weight gains, plasma carotenoids, gross lesion scores, and histological parasite scores in gut cross sections, or oocyst output. Significant ameliorating effects of diet on lesion scores and parasite scores were only seen in E. tenella infections and were only produced by the n3FAC and MO supplements. These two supplements, which contained higher molar concentrations of double bonds than the other supplements, also significantly reduced plasma carotenoids in uninfected chickens, indicating that they promoted a state of oxidative stress. These results are consistent with previous reports on the interaction of coccidiosis with dietary n-3 fatty acids and strengthen the hypotheses that dietary-induced oxidative stress is an effective deterrent against cecal coccidiosis in chickens.

Animals↗

Comparison of outbred lines of chickens for resistance to experimental infection with coccidiosis (Eimeria tenella).

Coccidiosis causes dramatic economic losses in the poultry industry. Next to the extensive use of anticoccidial drugs, improving genetic resistance of birds to this parasitic disease represents an attractive alternative. An experiment was run in order to identify lines of chickens resistant and susceptible to coccidiosis as a tool to search for genetic markers of resistance. Five outbred lines were used: two Egyptian lines (Mandarah and Fayoumi), a Rhode Island Red line, and two White Leghorn lines (WLB21 and WLDW). The WLDW line segregated for three MHC haplotypes, B15, B19, and B21, and for the sex-linked dwarf gene, DW. Chicks were challenged at 4 wk of age with a high dose of Eimeria tenella (150,000 oocysts) and slaughtered 8 d postinoculation. Innate resistance was assessed individually by measures of lesion score, mortality, and body weight gain at slaughter, and plasma coloration 4 d postinoculation. Large differences in resistance to E. tenella were observed between lines. The Fayoumi line appeared clearly as the most resistant line, showing no mortality, less severe lesions than other lines, and a 30% reduction of growth as compared to control birds. The WLDW line was the most susceptible, with 27% mortality and a 85% reduction in growth. No major effect of MHC or dwarfism on resistance to E. tenella was found.

Animals↗

Anticoccidial efficacy of drinking water soluble diclazuril on experimental and field coccidiosis in broiler chickens.

Prophylactic and curative capacity of water soluble formulation of Diclazuril (Diclosol 1%) and feed additive form (Clinacox, 0.5%) were tested against Eimeria infection in broiler chickens. Such testing was performed both experimentally and in the field. Toltrazuril (Baycox, 2.5%) was used as reference control drug. Water soluble formulation of Diclazuril induced a marked inhibitory effect on the different stages of the parasite life cycle in experimentally infected treated birds especially when applied on the day when blood first appeared in the faeces [fifth day post-infection (d.p.i.)] as well as on the second day of blood dropping (6 d.p.i.). Both tested dosage levels of Diclazuril water soluble formulation in drinking water (5 and 10 ppm) showed the same effect in controlling coccidial infection and reducing the total oocyst numbers, lesion and faecal scores. Moreover, there was no significant difference in the efficacy of water soluble form of Diclazuril and the reference control drug (Toltrazuril, 25 ppm). In addition, testing the water soluble formulation (5 ppm) in naturally infected poultry farm (20,000 birds), showed the same anticoccidial effect observed when using Toltrazuril, as a treatment for coccidiosis. In conclusion, addition of Diclazuril at the dose of 5 ppm in the drinking water of naturally coccidia infected bird induced the same effect as 25 ppm of Toltrazuril as a treatment for coccidiosis in chickens.

Administration, Oral↗

Nervous disease associated with coccidiosis in young cattle.

Four cases are described of nervous disease associated with coccidiosis in young cattle. Prodromal nystagmus, ventromedial strabismus, sternal or lateral recumbency with contortions of the head and neck, near normal interictal periods and palpable proctitis were common findings. Differentiation from other nervous disorders in young cattle and the pathogenesis of the nervous signs associated with coccidiosis are discussed. It is suggested that the clinical picture is sufficiently distinctive to allow a diagnosis to be made on clinical grounds alone.

Animals↗

The use of toltrazuril for the prevention of coccidiosis in piglets before weaning.

To determine the efficacy of toltrazuril as a prophylactic treatment for coccidiosis in piglets caused by Isospora suis (I suis), a single 1.0 mL dose of toltrazuril was administered orally to 1056 piglets between 3 and 6 days of age, in 5 piggeries. Prophylactic treatment of piglets reduced the occurrence of coccidiosis in litters from 71% to 22%. The number of antibacterial treatments given and the number of piglets affected per litter were also significantly reduced, resulting in some improvement in growth rates to weaning. The severity of diarrhoea was significantly reduced, as was the amount of oocyst excretion. The number of days that piglets excreted oocysts in the faeces was reduced from 4.9 days to 2.5 days. The detection of I suis in piglets with diarrhoea was reduced from 84% in the untreated piglets to 6% in the piglets given the prophylactic treatment.

Administration, Oral↗

Lesions associated with coccidiosis in nursing piglets.

Of 45 piglets with diarrhea, 28 had coccidiosis, with no evidence of concurrent viral infection. Villous atrophy and necrotic enteritis were the characteristic lesions, and were more severe in piglets with combined viral and coccidial infections than with coccidiosis alone. Necrotic enteritis presumably was caused by bacterial invasion of the villous lamina propria at foci denuded of epithelium by coccidia, viruses or both. Consistent lesions associated with coccidia in piglets not infected by other primary enteric pathogens suggest that coccidia are the cause of significant clinical disease in nursing piglets 6 to 15 days old.

Animals↗