diclazuril and toltrazuril

Triazines are relatively new antiprotozoal drugs that have successfully controlled coccidiosis and equine protozoal myeloencephalitis. These drugs have favorably treated other protozoal diseases such as neosporosis and toxoplasmosis. In this article, we discuss the pharmacological characteristics of five triazines, toltrazuril, ponazuril, clazuril, diclazuril, and nitromezuril which are used in veterinary medicine to control protozoal diseases which include coccidiosis, equine protozoal myeloencephalitis, neosporosis, and toxoplasmosis.

Topics: Acetonitriles; Animals; Antiprotozoal Agents; Coccidiosis; Encephalomyelitis, Equine; Horses; Nitriles; Protozoan Infections, Animal; Toxoplasmosis, Animal; Triazines

A blinded, controlled, randomised field study was undertaken on two commercial dairy farms in Germany to compare the efficacy of the anticoccidials, diclazuril and toltrazuril in the prevention of bovine coccidiosis. A total of 86 calves aged between five and six weeks were randomly allocated to two treatment and one untreated control groups. Calves were monitored for 78 days post-treatment by clinical observation, bodyweight gain, faecal oocyst counts (FOCs) and coccidia species differentiation. Strategic treatments had no significant effect on bodyweight gains (P>0.05). Whilst the number of diarrhoea days was similar for all three groups from days 1 to 41, there was a significant difference in the number and percentage of diarrhoea days from day 42 with the diclazuril-treated group showing only one diarrhoea day compared with 9 days (P=0.0195) and 18 days (P=0.0027) for the control and toltrazuril-treated groups, respectively. FOCs in control calves fluctuated throughout the period of study indicating continued coccidia challenge. FOCs in the diclazuril-treated calves declined to low levels post-treatment, increasing to occasional counts >500 oocysts per gram of faeces (OPG) between days 27 and 42, but thereafter remained low. Calves treated with toltrazuril also showed low FOCs until day 40 but then showed several peaks of oocyst output >500 OPG coinciding with days of diarrhoea.

Topics: Animals; Cattle; Cattle Diseases; Coccidiosis; Coccidiostats; Diarrhea; Double-Blind Method; Feces; Germany; Nitriles; Treatment Outcome; Triazines

Five controlled field trials were conducted in southern Italy to evaluate the effect of metaphylactic treatment strategies of toltrazuril and diclazuril for the control of coccidiosis in water buffaloes naturally infected by Eimeria spp. The 5 farms were divided into two types (A and B) according to their management system (individual or collective breeding of buffalo calves). In the farms of type A (no. 3), the buffalo calves were bred in individual boxes from the birth to the 7th/8th week of age and then transferred to concrete based pens; in the farms of type B (no. 2) the calves were bred in groups on concrete based pens from the birth. On each farm, 36 calves aged 5 weeks were divided at random into three similar groups of 12. One group was treated with toltrazuril (TOL), the second group was treated with diclazuril (DIC) and the third group was remained as untreated control group (CONT). On each farm the calves were weighed weekly and clinically examined. In the 5 buffalo farms the average oocyst excretion decreased significantly in both the treated groups (TOL and DIC), however the TOL groups had significantly low counts than the DIC groups. The body-weight gains recorded fortnightly were significantly higher in the TOL groups (range=5.4-8.1 kg) compared to the DIC (range=1.7-3.1 kg).

Topics: Animals; Buffaloes; Coccidiosis; Coccidiostats; Eimeria; Nitriles; Triazines

The effect of different treatment protocols using the triazinone compounds diclazuril and toltrazuril on Eimeria oocyst excretion, diarrhoea and weight gain was evaluated in the present study. The protocols were designed in order to best fit to common management practices in dairy production systems as applied in Greece. During the first two trials comparative preventive (11 days after birth) and therapeutic (18 days after birth) single treatments using either drug were performed on an intensive farm. In Trial 3 the efficacy of a repeated diclazuril treatment after weaning (at the start and 4 weeks later) of the animals in a semi-intensive farm was tested. The last trial was performed in order to assess the effect of a single oral dose of toltrazuril after weaning of the animals on the same farm. During an observation period of 6-7 weeks after treatment animals in all trials were clinically examined for diarrhoea and faecal samples were regularly monitored for Eimeria oocysts at weekly intervals. Body weight was also determined at the start and end of each trial. A single treatment with toltrazuril resulted in a significant reduction of oocyst excretion over the study period compared to the control, with very high efficacy values during the first 2-3 weeks after treatment, irrespective of the treatment protocol and the management system applied. This in general could not be confirmed in the protocols using diclazuril, which showed a much lower and mostly variable efficacy pattern.

Topics: Animals; Coccidiosis; Coccidiostats; Dairying; Eimeria; Female; Male; Nitriles; Sheep; Sheep Diseases; Triazines; Weight Gain

Sheep coccidiosis is a pathology caused by protozoan parasites of the genus Eimeria spp. with clinical and economic effect especially in young animals (Ambrosi 1995; Pellérdy 1974). A field study was conducted to evaluate the efficacy of a metaphylactic treatment with toltrazuril 5 % suspension (Baycox®, Bayer) in comparison with diclazuril (Vecoxan®, Janssen-Cilag) and untreated controls against naturally acquired Eimeria infections in housed lambs. A total of 170 animals, aged 24 to 34 days and randomly divided in three homogeneous groups, were included in the study. The assessment of treatment efficacy was based on total faecal oocyst excretion (opg) and count reduction (FOCR) in the two groups of animals treated with toltrazuril (TOLT) and diclazuril (DICL) compared with untreated control group (C). The animals treated with toltrazuril showed a considerably lower mean opg to that of group C (5.78 opg versus 144.62 opg) (p < 0.05) and a FOCR of 97.7 %. The higher efficacy (99.23 %) was observed at 15 days post treatment; however, the average efficacy of the drug remained extremely high (> 90 %) for all the study. The lambs treated with diclazuril showed an intense, persistent oocyst excretion with average levels of 97.54 opg, (p < 0.05). This study demonstrates the good efficacy of toltrazuril administered orally to lambs in the prepatent period in subclinical natural Eimeria infections in housed lambs.

Topics: Administration, Oral; Animals; Antiprotozoal Agents; Asymptomatic Infections; Coccidiosis; Eimeria; Feces; Humans; Nitriles; Parasite Egg Count; Sheep; Sheep Diseases; Treatment Outcome; Triazines

The long-term effects of a toltrazuril treatment against natural Eimeria bovis and/or Eimeria zuernii infections were investigated in comparison with diclazuril and untreated controls on two dairy (Italian Friesian breed) and two beef (Chianina breed) farms. At each trial site, 30 calves were allocated into three groups of 10 calves each: T (treated with toltrazuril), D (treated with diclazuril) and C (left untreated). For 40 weeks post-treatment, the calves were weighed and examined clinically and parasitologically. The oocyst counts as well as the number of scour days were significantly lower in the T group than in the D and C groups. Final bodyweights and body condition scores of the T group exceeded those of groups C and D. The results confirmed that toltrazuril was highly efficacious, safe and provided productive benefits in dairy and beef calves.

Topics: Animals; Cattle; Cattle Diseases; Coccidiosis; Coccidiostats; Double-Blind Method; Drug Administration Schedule; Eimeria; Feces; Growth; Linear Models; Nitriles; Treatment Outcome; Triazines

A field study was conducted to evaluate the effect of a single oral treatment with 20 mg/kg body weight (BW) of toltrazuril (Baycox 5% suspension)--TOL--in comparison to a single oral treatment with 1 mg/kg BW of diclazuril (Vecoxan suspension orale, 2.5 mg/ml)--DIC--and an untreated control group (CTRL) on naturally acquired Eimeria infections in lambs. On a French sheep farm with a known history of coccidiosis, 75 housed lambs aged 10-14 days were randomised and allocated to one of three groups. During an observation period of 60 days after treatment, clinical (faecal consistency, BW) and parasitological parameters (oocyst excretion) were evaluated. Excretion in the negative control group started 3 days after treatment and peaked on the 31st day with a prevalence of 80%. Animals were predominantly infected with Eimeria ovinoidalis. Treatment with toltrazuril, but not with diclazuril, resulted in significantly reduced numbers of excreting animals. The number of excretion days and the average oocyst excretion decreased significantly in both the TOL and the DIC groups compared to the CTRL, with the TOL group showing significantly fewer excretion days and excretion intensities than the DIC group. Changes in the faecal consistency were moderate throughout the study and not significantly different between the groups. Daily weight gains were higher in the TOL group compared to the DIC and CTRL groups which did not differ. This study demonstrates the good efficacy of toltrazuril administered orally to lambs in the prepatent period in subclinical natural Eimeria infections in housed lambs.

Topics: Administration, Oral; Animals; Animals, Newborn; Coccidiosis; Coccidiostats; Eimeria; Feces; Female; Male; Nitriles; Sheep; Sheep Diseases; Treatment Outcome; Triazines

A blinded, controlled and randomised field study was conducted on a sheep farm with a known history of coccidiosis and a high prevalence mainly of the pathogenic coccidium Eimeria ovinoidalis. The efficacy of treatment with toltrazuril (Baycox 5% suspension) against natural infections with Eimeria crandallis and/or Eimeria ovinoidalis in housed lambs was investigated in comparison with diclazuril and untreated controls. Both drugs were administered either metaphylactically (i.e., in the prepatency of Eimeria spp.) or therapeutically (after onset of oocyst excretion). A total of 145 animals aged 1 to 5 days at the start of the study were included. Examination of faecal samples was performed every second day between days 13 and 49 of the study. The assessment of treatment efficacy was based mainly on total oocyst excretion and the number of E. crandallis and E. ovinoidalis oocysts (OPG) shed throughout the study. Oocyst excretion was reduced significantly in both groups treated with toltrazuril compared with the untreated control group and with both diclazuril-treated groups. The most prevalent and most severe diarrhoea was observed in the untreated control group. In this study, toltrazuril proved to be highly effective in controlling ovine coccidiosis both metaphylactically and therapeutically. The efficacy of toltrazuril was significantly higher than the efficacy of the control substance with regard to the duration and amount of oocyst excretion, both for the comparison of metaphylactic as well as therapeutic treatment.

Topics: Animals; Antiprotozoal Agents; Coccidiosis; Diarrhea; Eimeria; Feces; Humans; Male; Nitriles; Parasite Egg Count; Severity of Illness Index; Sheep; Sheep Diseases; Treatment Outcome; Triazines

The efficacies of 20 mg/kg body weight (BW) of toltrazuril (Toltra) 2 days post-infection (dpi), 2 mg/kg BW of diclazuril 2 and 3 dpi and 200 mg/kg BW of sulphadimidine 2, 3 and 4 dpi were compared in a model for piglet isosporosis. Weight gain (first 4 weeks of life) and diarrhoea and oocyst excretion from 4 to 11 dpi were evaluated (10-12 piglets/group). Additionally, animals were killed and examined for pathohistological changes of the small intestines 5, 7, 11 and 14 dpi (n = 3 per group and time point) and lengths of the intestinal villi. Diarrhoea (semi-liquid or liquid faeces) was seen from 5 dpi in all groups except Toltra, and the differences in prevalence and intensity of diarrhoea were statistically significant (p < 0.05) between Toltra and the other groups, which were similar (trial 1). Oocyst excretion was greatly reduced in the Toltra group, which was also statistically significant for the mean and median excretion rates and the percentage of excreting piglets between Toltra and the other groups (p < 0.05). Weight gain was highest in Toltra (p < 0.05). Histopathology revealed mostly villous necrosis and atrophy in the small intestines except the duodenum, which peaked at 7 dpi, in all groups except Toltra. Between 5 and 11 dpi, the Toltra group had significantly longer villi than the other groups. Reduced weight gain and diarrhoea caused by Isospora suis was controlled by a single application of Toltra in the pre-patent period, while neither diclazuril nor sulphadimidine improved the clinical picture of isosporosis.

Topics: Animals; Animals, Newborn; Coccidiostats; Female; Intestine, Small; Isosporiasis; Male; Nitriles; Sulfamethazine; Swine; Swine Diseases; Triazines

Topics: Animals; Coccidiostats; Isospora; Isosporiasis; Nitriles; Sulfamethazine; Swine; Swine Diseases; Treatment Outcome; Triazines

Topics: Animals; Cattle; Cattle Diseases; CD8-Positive T-Lymphocytes; Coccidiosis; Coccidiostats; Disease Models, Animal; Eimeria; Male; Mice; Mice, Inbred C57BL; Nitriles; Rodent Diseases; Triazines

The objective of present studies was to evaluate and compare the anticoccidial activity of triazine compounds in broiler chickens infected with E. tenella, E. necatrix, E. acervulina, E. maxima, and two field mixed Eimeria species. The anticoccidial efficacy was evaluated using the anticoccidial index (ACI). The results showed that Aminomizuril (AZL) and Ethanamizuril (EZL) were active metabolites of nitromezuril, which demonstrated excellent effectiveness against E. tenella, E. necatrix, E. acervulina, E. maxima, and the field Eimeria isolates in broiler chickens at a dosage of 10 mg/kg in feed. The anticoccidial activities of AZL and EZL at dose 10 mg/kg were roughly equivalent to the parent nitromezuril at a dosage of 3 mg/kg in feed. The decrease in metabolite anticoccidial activity is probably due to an increasing polarity of compounds in the metabolic processes. The sensitivity of two field Eimeria isolates to triazines EZL, diclazuril and toltrazuril was tested using 4 indices including anticoccidial index (ACI), percent of optimum anticoccidial activity (POAA), reduction of lesion scores (RLS) and relative oocysts production (ROP). Results showed that the sensitivity of EZL treatment against the two field Eimeria isolates were relatively superior to that of diclazuril and toltrazuril treatment. The field Eimeria isolates from Gansu Province was determined to be slightly, moderately and highly resistant to EZL, diclazuril and toltrazuril respectively. The field Eimeria isolates from Zhejiang Province was slightly, highly and slightly resistant to EZL, diclazuril and toltrazuril respectively. The results above indicated that the anticoccidial activity of metabolites was lower than that of the parent nitromezuril and there was partial cross-resistance among triazines EZL, diclazuril and toltrazuril. However the field Eimeria isolates had higher sensitive to EZL than the triazines diclazuril and toltrazuril. It was suggested that the site of C4 substituents of phenol of triazine anticoccidials may have important biological functions and the metabolite EZL would be a potential novel anticoccidial agent worthy of more attention.

Topics: Animals; Chickens; Coccidiosis; Drug Resistance; Eimeria; Nitriles; Oocysts; Poultry Diseases; Triazines

Ovine Eimeria spp. infections cause increased mortality, reduced welfare and substantial economic losses, and anticocccidials are important for their control. Recent reports of anticoccidial resistance against ovine Eimeria spp. necessitate the development of in vitro methods for the detection of reduced anticoccidial efficacy, especially since the in vivo methods are both expensive, time consuming and requires the use of otherwise healthy animals. The aim of the present study was therefore to approach a preliminary standardization of in vitro assays for evaluation of the efficacy of the most commonly used anticoccidials in ruminants. For this purpose, apart from the evaluation of inhibition of oocyst sporulation, most effort was concentrated on assessment of the capacity of the different anticoccidials to inhibit both the invasion and further development (up to the first schizogony) of E. ninakohlyakimovae sporozoites in bovine colonic epithelial cells (BCEC). For this purpose, infected cultures were monitored 1, 8 and 15 days post infection to determine the infection rate, number of immature schizonts and number, size and appearance of mature schizonts, respectively. No clear inhibitory effect was found with any of the anticoccidial formulations tested, and we could not identify why there were no measurable effects from the different anticoccidials. Despite the lack of positive results, further investigations should be encouraged, as this could decrease the need for animal experiments and could be used in the initial assessment of anticoccidial efficacy of new drugs.

Topics: Animals; Cattle; Cells, Cultured; Coccidiosis; Coccidiostats; Colon; Decoquinate; Drug Resistance; Eimeria; Epithelial Cells; Feces; Goat Diseases; Goats; Intestinal Mucosa; Nitriles; Oocysts; Schizonts; Sporozoites; Sulfonamides; Triazines

A blinded, randomized, controlled, multi-centric field study was conducted on French dairy farms (n = 9) to evaluate the long term efficacy of metaphylactic, single oral treatments with either 1 mg/kg body weight (BW) of diclazuril (Vecoxan®), or 15 mg/kg BW of toltrazuril (Baycox®) against natural infections with Eimeria zuernii and/or Eimeria bovis, compared to untreated control animals. A total of 199 calves from nine commercial farms aged between 21 and 55 days old at the start of study were included and randomly allocated to one of three groups. Calves on all farms were observed for a period of 78 days post treatment, using both parasitological (oocyst excretion), and clinical parameters (faecal score and body weight). The assessment of efficacy was based on both control of oocyst excretion, and on the average daily weight gains throughout the study. During the whole study period, the mean number of days with diarrhoea (≥ 2) was similar (0.7 days) between treated groups. Excretion in the untreated group peaked at 21 days after treatment. In both the diclazuril and toltrazuril-treated groups, mean oocyst excretion decreased dramatically in the five days following treatment. Thereafter, particularly towards the end of the study period, oocyst counts and percentage levels of E. zuernii were highest in the toltrazuril-treated group. In pooled data from all trial sites, the average daily weight gain was significantly (p = 0.01) higher (+ 0.057 kg/day) in the diclazuril group when compared to the toltrazuril group, and the average body weight gain of the diclazuril treated group was 4.4 kg higher than the toltrazuril group. On eight of the nine trial sites, the average daily gain was greater in the diclazuril group than in the toltrazuril group. This study demonstrates that, over an extended observation period of 78 days, metaphylactic treatment with both diclazuril and toltrazuril reduces the impact of coccidiosis, but greater performance benefits based on average daily weight gains, were achieved following the use of diclazuril.

Topics: Administration, Oral; Animals; Cattle; Cattle Diseases; Coccidiosis; Coccidiostats; Diarrhea; Eimeria; Feces; Female; Male; Nitriles; Oocysts; Triazines; Weight Gain

A new procedure has been described for the extraction of diclazuril (DIZ), toltrazuril (TOZ) and its two main metabolites toltrazuril sulphoxide (TZSO) and toltrazuril sulphone (TZS) from poultry tissues and eggs, using gel permeation chromatography (GPC). The analytes and the deuterated internal standard were extracted from the samples with ethyl acetate. The analytes were measured by LC coupled to an electrospray ionization tandem mass spectrometer operating in the negative ion mode. Excellent linear dynamic range was observed from 1 to 500 μg/L with the correlation coefficients (R(2)) better than 0.99 for all analytes. The method LOQ of the four analytes in real samples was 1.2 μg/kg for DIZ and TOZ, and 1.8 μg/kg for TZSO and TZS. These values are far lower than the maximum residue limits (MRLs) established by several control authorities. The developed method was accurate with overall recoveries in four matrices.

Topics: Animals; Chromatography, Gel; Coccidiostats; Drug Residues; Eggs; Linear Models; Nitriles; Poultry; Reproducibility of Results; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Triazines

A method for the determination of avermectin, ivermectin, doramectin, moxidectin, eprinomectin, diclazuril, toltrazuril and its two metabolite residues in pork was developed using QuEChERS method with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The sample was extracted with acetonitrile and purified through QuEChERS method using ODS as the sorbent. The target compounds were separated on a Venusil ASB C18 column (150 mm x 2.1 mm, 3.0 microm) and detected by HPLC-MS/MS. The linear ranges were 0.005 - 0.2 mg/L and the correlation coefficients were all above 0.990. The average recoveries and the relative standard deviations ranged from 73.2% to 91.5% and from 12% to 17% at the spiked levels of 0.005, 0.01 and 0.02 mg/kg for the 9 analytes in pork matrix. This method is reliable, and suitable for the determination of the residues of avermectin and related compounds in pork.

Topics: Animals; Chromatography, High Pressure Liquid; Drug Residues; Food Contamination; Ivermectin; Meat; Nitriles; Swine; Tandem Mass Spectrometry; Triazines

The effects of four pretreatment methods (acetonitrile extraction-evaporation concentration, acetonitrile extraction-solid phase extraction (SPE), matrix solid-phase dispersion (MSPD) extraction and MSPD-SPE) for the simultaneous analysis of diclazuril and toltrazuril residues in chicken tissues were compared. The average recovery of 70% for the former three methods as achieved. In comparison with other methods, the MSPD method saved more than 60% in time and solvent. So, MSPD as the sample pretreatment method, an MSPD-high performance liquid chromatography with ultraviolet detection (MSPD-HPLC/UV) method was established for the analysis. Under the optimal chromatographic conditions, the linear range was between 50 and 1,000 microg/kg. At the added levels of 50, 500, 1,000 ng/g, the recoveries of diclazuril and toltrazuril in chicken tissues ranged from 71.13% - 84.02% with the relative standard deviations (RSD) in the range of 3.76% - 12.11%, and the RSDs of intra- and interday analyses ranged from 3.70% - 6.77%. The detection limits of diclazuril and toltrazuril were less than 10 microg/kg. The quantitative limits of diclazuril and toltrazuril were less than 20 microg/kg. The method meet the requirements of the residue analysis on accuracy and precision.

Topics: Animals; Chickens; Chromatography, High Pressure Liquid; Coccidiostats; Drug Residues; Food Contamination; Meat Products; Nitriles; Solid Phase Extraction; Triazines

Topics: Animals; Cat Diseases; Cats; Coccidiostats; Dog Diseases; Dogs; Isospora; Isosporiasis; Nitriles; Triazines

Three battery tests were conducted to study the anticryptosporidial efficacy of the 2 commercially available anticoccidial triazinone derivates, diclazuril and toltrazuril, and a garlic extract. At the recommended level, diclazuril reduced the oocyst output of birds by 14.6%. The efficacy of toltrazuril was 52.1% at the recommended level, which could be moderately increased using 5 or 10 times the recommended dose. However, these doses resulted in significant weight gain reduction. The efficacy of garlic extract was 24.4%. It is concluded that none of the drugs can be recommended for chemoprophylaxis or therapy of cryptosporidiosis in chickens.

Topics: Animals; Chickens; Coccidiostats; Cryptosporidiosis; Feces; Garlic; Male; Nitriles; Phytotherapy; Plant Extracts; Plants, Medicinal; Poultry Diseases; Triazines; Weight Gain

Ten Eimeria field isolates from North Germany were studied in battery tests for sensitivity to selected anticoccidials. A high percentage of the Eimeria field isolates (9 out of 10) showed resistance to anticoccidials, mostly multiple resistance. Partial or complete resistance to maduramicin was found in 7 field isolates, to monensin in 6, to salinomycin in 5, to nicarbazin in 8, to halofuginone in 7, to robenidine and toltrazuril in 1, and to diclazuril in 2 field isolates. Multiple resistance had developed in 7 of the 10 isolates. Cross-resistance between maduramicin, monensin, and salinomycin occurred in 5 Eimeria isolates. One isolate showed cross-resistance between diclazuril and toltrazuril. From the resistant isolates 15 pure E. acerculina and 5 pure E. brunetti strains were obtained by single oocyst infections. Seven of the E. acerculina and 4 of the E. brunetti strains showed resistance or partial resistance that was also present in the original isolate. Ten of 11 resistant strains were multiply resistant.

Topics: Animals; Chickens; Coccidiosis; Coccidiostats; Drug Resistance; Drug Resistance, Multiple; Eimeria; Germany; Lactones; Male; Monensin; Nicarbazin; Nitriles; Piperidines; Poultry Diseases; Pyrans; Quinazolines; Quinazolinones; Robenidine; Triazines