Toltrazuril Treatment Research Articles

The effect of an injectable toltrazuril – gleptoferron (Forceris®) on Cystoisospora suis oocyst excretion and growth of neonatal piglets pre- and post-weaning

In this study the efficacy of an intramuscular formulation of toltrazuril combined with gleptoferron for the control of porcine cystoisosporosis caused by Cystoisospora suis was investigated. The study was carried out on three Belgian farms with a confirmed history of C. suis infections. As none of the farms implemented a standardized toltrazuril treatment regimen for their piglets, the presence of resistant C. suis strains seems improbable. In total 90 litters, representing 1249 piglets, were included in the study and randomly allocated to either the treatment or control group. Piglets in the treatment group received a single intramuscular injection, containing 45 mg toltrazuril and 200 mg gleptoferron, between 1 and 3 days of age. Piglets in the control group received a single injection with only 200 mg gleptoferron. The effect of treatment on oocyst excretion, expressed in oocysts per gram of feces (OPG), average daily weight gain (ADG) and mortality was determined both pre- and post-weaning. A significant decrease in OPG as well as a decrease in the number of litters (pre-weaning) and pens (post-weaning) that tested positive for cystoisosporosis, was observed in the treated animals compared to the controls. Furthermore, treatment resulted in an increased ADG during the period from day 1 to day 21 (p-value: 0.03881). There was no significant difference in mortality observed between the treatment group to the control group (p-value: 0.2167). To our knowledge, this is the first report on the effect of toltrazuril on oocyst excretion after weaning. This finding highlights the potential long-term benefits of the treatment beyond the initial administration.

Ponazuril: Clinical efficacy, ultrastructure, and histopathology studies of in vivo anticoccidial action against Eimeria tenella

Ponazuril, a novel antiprotozoal drug in the class of triazine, has shown a promising application on apicomplexan infections in poultry and livestock. However, the effect and mechanism of action of ponazuril against Eimeria tenella (E. tenella) are unclear. The efficacy against E. tenella was initially studied by administering different doses of ponazuril in drinking water. The treated stage and site of ponazuril on E. tenella were observed through ultrastructural and histopathological analyses. Chicks were orally treated with a dose of 15 mg/kg body weight of ponazuril at different endogenous stages of E. tenella post-infection. According to the clinical study, the values of anticoccidial indices (ACI) were 157.0, 162.3, 196.9, 194.5, and 190.9, respectively, when the ponazuril was administered in drinking water at doses of 5, 10, 20, 40, and 50 mg/L for two consecutive days after infection. Among them, the 20 mg/L ponazuril group showed the best anticoccidial effect, which was superior to that of the toltrazuril treatment group, with an ACI value of 191.7. Histological analysis indicated that ponazuril effectively relieved cecal lesions, and decreased the number of merozoites. Transmission electron micrographs (TEM) observed that merozoites became irregular in shape, and some apparent protrusions of the outer membrane were presented especially the second-generation merozoites. Additionally, abnormalities in the development of WFBI and WFBII in the macrogametocyte were observed, which may affect the formation of the ovule wall. Moreover, merozoites in the treated group showed uneven and marginalized chromatin and mitochondrial swelling. These results suggested ponazuril is a potential anticoccidial drug, providing information on the mechanism of anticoccidial effects.

In Vitro Transcriptional Response of Eimeria tenella to Toltrazuril Reveals That Oxidative Stress and Autophagy Contribute to Its Anticoccidial Effect.

Intestinal coccidiosis is a common parasitic disease in livestock, caused by the infection of Eimeria and Cystoisospora parasites, which results in great economic losses to animal husbandry. Triazine compounds, such as toltrazuril and diclazuril, are widely used in the treatment and chemoprophylaxis of coccidiosis. Unfortunately, widespread drug resistance has compromised their effectiveness. Most studies have focused on prophylaxis and therapeutics with toltrazuril in flocks, while a comprehensive understanding of how toltrazuril treatment alters the transcriptome of E. tenella remains unknown. In this study, merozoites of E. tenella were treated in vitro with 0.5 μg/mL toltrazuril for 0, 1, 2 and 4 h, respectively. The gene transcription profiles were then compared by high-throughput sequencing. Our results showed that protein hydrolysis genes were significantly upregulated after drug treatment, while cell cycle-related genes were significantly downregulated, suggesting that toltrazuril may affect parasite division. The expression of redox-related genes was upregulated and elevated levels of ROS and autophagosomes were detected in the parasite after toltrazuril treatment, suggesting that toltrazuril may cause oxidative stress to parasite cells and lead to its autophagy. Our results provide basic knowledge of the response of Eimeria genes to toltrazuril and further analysis of the identified transcriptional changes can provide useful information for a better understanding of the mechanism of action of toltrazuril against Eimeria.

Piglet coccidiosis in Belgium and the Netherlands: Prevalence, management and potential risk factors.

Piglet coccidiosis caused by Cystoisospora suis is one of the most important causes of diarrhea in suckling piglets. The parasite has a fast development and multiplies quickly and effectively under the conditions of a farrowing unit. Control measures include cleaning and disinfection and anticoccidial treatment. In Europe, toltrazuril-based products are authorized for this purpose and are applied to piglets on affected farms in the first week of life. To observe the effect of treatment and disinfection on the control of piglet coccidiosis in the field, 23 farms (11 from Belgium, 12 from the Netherlands, mean number of sows=1413) were sampled twice by litter in the second and third week of life and fecal scores and the presence of C. suis oocysts were determined. A questionnaire was used to collect data on farm sizes, management and hygiene measures as well as treatment (product, dose and piglet age). Thirteen farms regularly treated with toltrazuril (treatment age: 1-6days, mean 4.3days) and 19 applied disinfection. Parasite excretion was documented on 60.9% and diarrhea on 78.3% of farms and in 34.3%/15.7% of the litters. Only 2.4% of the litters showed both, so subclinical infection appeared to be common. No significant differences between farms that did not treat against coccidiosis and farms that applied toltrazuril was observed with regard to C. suis oocysts shedding and/or diarrhea. However, in litters that were treated within the first three days of life, oocyst excretion was significantly less often observed than in litters with later treatment (p = 0.033). No significant effect of disinfection could be shown, but most farms applied disinfectants that have no proven effect against coccidia (oxygen-releasing agents or glutaraldehyde + ammonia) while the only farm that used chlorocresols (which are effective against coccidia) did not show oocyst shedding. Current control measures thus appear to be insufficient on most of the examined farms. It is therefore recommended to treat piglets timely and to apply effective disinfectants to reduce C. suis infections. Furthermore, regular evaluation of sustained efficacy of all implemented measures are necessary.

Suckling piglet coccidiosis on farms in the Czech Republic - A pilot study

Suckling piglet coccidiosis is a common diarrhoeal disease of unweaned pigs caused by Cystoisospora suis with previously reported herd prevalences of 60% and more. The parasite quickly spreads in affected herds and causes malabsorption and a reduced and uneven body weight gain. The only drug currently licenced for the control of porcine cystoisosporiasis is toltrazuril, which suppresses parasite development and the corresponding diarrhoea. A recent study detected high prevalences of C. suis on swine farms in Austria, Germany, Spain and the Czech Republic independent of the treatment. Here, the situation in the Czech Republic is evaluated in more detail. In total, faecal samples from 161 litters (two samples/litter in the second and third week of life) from 17 farms (250–2 000 sows) were examined for the presence of C. suis oocysts by autofluorescence and for faecal consistency. An accompanying questionnaire revealed details on the herd management and treatments. Eight farms applied toltrazuril on the 3<sup>rd</sup>, 4<sup>th</sup> or 5<sup>th</sup> day of life. Overall, 70.6% of the farms and 32.2% of the litters were positive for C. suis at least once, 39.4% in the untreated litters (n = 76) and 24.8% in the treated litters (n = 85). Diarrhoea occurred on eight farms (six with the toltrazuril treatment) in 11.9% of the untreated and 2.5% of the treated litters. This study shows that coccidiosis is still common in Czech swine farms and that treatment in the recommended time frame may reduce the diarrhoea, but cannot interrupt the parasite’s life cycle. Some type of effective disinfection, which may have contributed to a more effective parasite control, was not in place in any of the farms.

Shifts in the Fecal Microbial Community of Cystoisospora suis Infected Piglets in Response to Toltrazuril.

The protozoan parasite Cystoisospora suis causes diarrhea and reduced weight gain in suckling piglets. Infections occur in the first days of life; it is transient but can lead to dysbiosis, exacerbating disease and increasing mortality. Cystoisosporosis is effectively controlled by toltrazuril treatment; however, alterations of the gut microbial composition upon infection and treatment have not been investigated. This study evaluated the development of fecal microbiota of C. suis infected piglets in response to treatment with toltrazuril. Thirty-eight conventional piglets were infected with C. suis on the first day of life (dol 1). Twenty-six of them received either parenteral or oral toltrazuril 2 days later. Fecal samples were collected pre- and post-weaning (dol 1–15 and 31–38) for microbiota analysis using 16S rRNA amplicon sequencing and during dol 5–18 to determine fecal consistency and parasite excretion. All control animals shed parasites at least once and the majority developed diarrhea, while toltrazuril-treated piglets did not excrete parasites and only had low levels of diarrhea. Age-related shifts in the fecal microbiota composition and increase in diversity and species richness were seen until after weaning. Parasite infection disrupted bacterial maturation 2 weeks after infection. Irrespective of the route of administration, fecal communities of piglets in the treated groups clustered separately and were more diverse compared to that of control piglets during the acute phase of infection on dol 11. Control piglet feces showed higher levels of Fusobacteriaceae and Veillonellaceae, while Ruminococcaceae, Lachnospiraceae, S24-7, Clostridiaceae, and Erysipelotrichaceae were more abundant in feces of treated piglets on dol 11. Thereafter, treatment-related effects on the microbial communities were small and mainly detectable on dol 34 (5 days post-weaning), potentially indicating that the oral toltrazuril treatment might have had long-term effects on host physiological responses post-weaning. Irrespective of the administration route, toltrazuril prevented C. suis-related dysbiosis and maintained species richness and diversity on dol 11. In addition to cystoisosporosis prevention, toltrazuril seems to contribute to the stabilization of the gut microbial development during the suckling phase and thus may reduce the need for antibiotics to control infections with secondary bacterial enteropathogens in C. suis-infected suckling piglets.

The efficacy of toltrazuril treatment for reducing the infection intensity of Theileria orientalis Ikeda type in dairy calves

The aim of this study was to test the hypothesis that toltrazuril administered at 4 weeks post-turnout reduces the infection intensity of Theileria orientalis Ikeda type in dairy calves and so prevents serious clinical disease in these animals at 2–3 months of age.Two groups of 40 dairy calves on two separate dairy farms in the Waikato were followed for 16 weeks post-turnout onto pasture. On each farm, 20 calves were randomly selected and orally treated with toltrazuril (15 mg/kg) at 4 weeks post-turnout, whilst the remaining 20 calves were left untreated. All 40 calves were blood sampled and weighed at 2, 4, 6, 8, 12, and 16 weeks post-turnout i.e. 6 samplings per calf. A random subset of 10 calves from each treatment group on each farm were faecal sampled at each visit.The blood samples were used to estimate the T. orientalis Ikeda type infection intensity and haematocrit for each calf and the faecal samples were used to estimate the number of coccidia oocysts per gram of faeces. Three linear mixed effects models, to evaluate the effect of toltrazuril treatment on infection intensity, haematocrit (HCT) and weight respectively were fitted to the data. No calves on either farm developed clinical theileriosis or coccidiosis and the three mixed effects linear models, controlling for the effect of farm and days from turnout, showed that there was no effect of treatment on infection intensity (p = 0.81), on HCT (p = 0.99) and on weight gain (p = 0.79).In conclusion, this study showed no evidence supporting the use of toltrazuril to control T. orientalis Ikeda type infection levels and prevent disease.

Anticoccidial activity of novel triazine compounds in broiler chickens

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.

INVESTIGATION OF THE PRESENCE OFATOXOPLASMASPP. IN BLUE-CROWNED LAUGHINGTHRUSH (DRYONASTES COURTOISI) ADULTS AND NEONATES

Between 1996 and 2013, 71 blue-crowned laughingthrush (Dryonastes courtoisi) chicks, a small passerine bird endemic to China, were born at Mulhouse Zoo in northeast France. None of them survived past 1 yr, and 82% died between 0 and 6 days old of an unidentified cause and despite an attempt to establish an artificial breeding protocol. Atoxoplasma spp., causing a disease known as systemic isosporosis, is a coccidian parasite that can infect several species of birds. Mulhouse's adult birds were suspected to be infected with Atoxoplasma spp. and to transmit this parasite to their offspring. A treatment with toltrazuril (Baycox® 2.5%) was implemented in the four adult birds. Coprologic examinations were performed before, during, and after the treatment to quantify the parasite load in feces. Polymerase chain reaction (PCR) assays were used to test blood samples from the adult and liver, lung, gizzard, and kidney samples from 10 chicks to detect Atoxoplasma spp. Five of the 10 chicks had some tissue samples positive for Atoxoplasma spp. in at least one of the three repeats of the atoxoplasmosis PCR. An average of 181 Isospora spp. oocysts per gram of feces were found in the group of adults before treatment. This number was reduced to zero 1 wk after the beginning of the toltrazuril treatment. The PCR results suggest a transovarian transmission of Atoxoplasma spp., but further investigation is needed for confirmation. The treatment with toltrazuril appears to allow a significant reduction of the parasite excretion.

Hematological and histopathological assessment of pacu (Piaractus mesopotamicus) after treatment of pathogens with veterinary medicinal products

Fish species are impacted by multiple pathogens, and they are exposed to the chemicals used to treat these diseases at several stages during the aquaculture production cycle. This study performed hematological and histopathological evaluations of pacu (Piaractus mesopotamicus) that had been naturally infected with Aeromonas sp., Streptococcus sp., Ichthyophthirius multifiliis, Trichodina heterodentata, and Anacanthorus penilabiatus and treated with enrofloxacin and toltrazuril or with florfenicol and thiamethoxam. After 7 days of treatment from nine fishes were collected blood, via caudal puncture, and samples of the gills, liver, and kidneys. Following toltrazuril and enrofloxacin treatment, fish exhibited leukocytosis with lymphocytosis. With thiamethoxam and florfenicol treatment, the fish showed an increase in hematocrit, hemoglobin level, mean corpuscular volume, and mean corpuscular hemoglobin concentration and a decrease in red blood cells. The infected control fish presented aneurysms and a disruption of the secondary lamellae, which can cause death. The drugs used in this study stimulated the immune systems in the fish or caused electrolyte imbalances, which were temporary.

Significance of Timing on Effect of Metaphylactic Toltrazuril Treatment against Eimeriosis in Calves

In this multicentric, randomised, blinded and placebo-controlled field study, the effect of treatment with toltrazuril (Baycox(®) Bovis, Bayer) on oocyst excretion, diarrhoea score and weight gain was studied in Danish dairy herds with confirmed history of eimeriosis (coccidiosis) and prevalence of Eimeria bovis and Eimeria zuernii. Three commercial herds and a total of 71 calves, aged 48 - 135 days, were included. Treatment with a single oral dose of toltrazuril (15 mg/kg) was given after relocation to common pens and one week before expected outbreak of eimeriosis. The effect of treatment was followed by weekly faecal sampling and weighing initially and at the end of a study period of 8 weeks. In Herd 2 and 3 toltrazuril treated calves gained on average 7.95 kg more than placebo treated calves (p = 0.007), and both oocyst excretion and prevalence of Eimeria spp. were significantly reduced the first weeks post treatment. In Herd 1, by contrast, the farmer made some unforeseen changes in the management which entailed relocation to large deep-litter pens 3 - 6 weeks post treatment. In addition, many calves were not treated metaphylactically while few calves excreted oocysts when the trial was initiated. Thus, no significant difference in weight gain was found between toltrazuril and placebo treated calves (p = 0.523), and the oocyst excretion of toltrazuril treated calves was significantly higher during week 7 and 8. Significant differences in faecal scores were observed between the herds (p<0.002) but not between treatment groups in any of the herds. In conclusion, timing of treatment is crucial for optimal effect of metaphylactic toltrazuril treatment on weight gain and oocyst excretion.

Toltrazuril (Baycox) treatment against coccidiosis caused by Eimeria sp. in Japanese quails (Coturnix coturnix japonica).

Coccidiosis is the most predominant parasitic disease affecting Japanese quails (Coturnix coturnix japonica) in commercial farms. Coccidiosis as a subclinical infection is difficult to diagnose without parasitological examinations. Oocysts of two Eimeria species, E. bateri and E. tsunodai, were determined in the analysed quail flock. Infected birds were administered Baycox 2.5% at the dose of: group I--7 mg toltrazuril/kg BW per day provided in drinking water (1.5 ml/0.5 1 H2O) that was available 24 h for 2 days, group II--14 mg/kg BW (3 ml/0.5 1 H2O), and group III-- 24.5 mg/kg BW (5 ml/0.5 1 H2O); in groups II and III, the solutions were available 8 h/24 h for 2 days. After the first day of the treatment, the number of excreted oocysts (OPG - oocysts per gram) increased, a steady decrease in oocyst counts began on the second day of Baycox administration and lasted until a three-day period when no oocyst were determined in faecal samples. Regardless of the dose applied, toltrazuril (Baycox) completely eliminated E. bateri coccidia and led to a highly significant reduction in the number of E. tsunodai oocysts. The results suggest that the effectiveness of toltrazuril varies depending on coccidia species and developmental stages of the parasite. From the clinical point of view, the treatment applied significantly reduces the number of coccidia oocysts in commercial flocks of Japanese quails.

Evaluation of efficacy of toltrazuril and diclazuril in the control of subclinical eimeriosis in weaned lambs

A field study was conducted to compare the effect of toltrazuril and diclazuril treatment against Eimeria infection in 142 naturally infected, weaned lambs aged 45–60 days. Lambs were divided into three groups of 48, 48 and 46 animals and treated with toltrazuril (20mg/kg b.w.) and diclazuril (1mg/kg b.w.). The last group of 46 lambs was left untreated as control. Oocyst faecal counts (OPG), Eimeria species and faeces consistency where assessed weekly from day 7 to day 63. In comparison with the control group, the OPG reduction on day 7 and 14 in toltrazuril-treated lambs was 99.1% and 97.4%, respectively, and 67% and 58% in lambs treated with diclazuril (p<0.005). On day 21, the percent of OPG reduction was still significant in toltrazuril-treated lambs (76.3%, p<0.05). Treatment with toltrazuril showed a decrease of Eimeria ahsata and E. crandallis oocysts at the time of maximum efficacy. The same effect was found in the diclazuril-treated group for E. ahsata only. No difference was found between the three groups regarding the consistency of the faeces (p>0.05). Body weight gains were determined at the start and the end of the study and showed a significant increase in the toltrazuril-treated lambs (p<0.001). These results suggested a greater efficacy of toltrazuril against subclinical eimeriosis in weaned lambs.

Effectiveness of therapeutic agents in disease treatment in Piaractus mesopotamicus

The use of drugs in aquaculture is necessary to combat pathogens responsible for causing the high rate of mortality in fish farming, such as infection by ectoparasites. The aim of this research was to evaluate the efficacy: (A) of toltrazuril (TOL) treatment against Ichthyophthirius multifiliis, Trichodina heterodentata and Anacanthorus penilabiatus; (B) of thiamethoxam (TH), in treating fish infected by A. penilabiatus and (C) of enrofloxacin (ENR) and florfenicol (FFC) against Aeromonas sp. and Streptococcus sp. The drugs TOL and TH were administered in therapeutic baths while ENR and FFC were mixed with the fish food. The drug concentrations were adjusted according to the experimental conditions (laboratory, microcosm or mesocosm). The drug TOL presented a treatment efficacy rate of 100% against I. multifiliis in microcosm and T. heterodentata in mesocosm. Moreover, ENR presented an efficacy rate of 100% in treating fish infected by Aeromonas sp. and Streptococcus sp. in mesocosm. Finally, TH efficacy rate in controlling A. penilabiatus infection was 81.86% in mesocosm and FFC decreased the overall bacterial load in infected fish. Aeromonas sp. and Streptococcus sp. strains were found in the samples collected for microbiological analysis. In conclusion, TH presented a high efficacy in treating fish against A. penilabiatus infection while TOL was better in controlling T. heterodentata. The antibiotics used in mecoscosm condition presented potential to be used against bacterial infection in aquaculture.

Treatment of atoxoplasmosis in the Blue-crowned Laughing Thrush (Dryonastes courtoisi)

Passerines are frequently parasitized by coccidia, especially species of the genus Isospora, with extra-intestinal stages that can be highly pathogenic causing serious clinical damage in young birds. Whilst there is still no effective treatment to completely clear isosporoid coccidia with extra-intestinal stages from a host species, our results showed that prolonged treatment with toltrazuril (BAYER AG, Leverkusen, Germany) can decrease the oocysts in faeces and thus reduce the extra-intestinal phase of the infection. The toltrazuril treatment is therefore probably indirectly effective against the systemic form of atoxoplasmosis.

Efficacy of early treatment with toltrazuril in prevention of coccidiosis and necrotic enteritis in chickens

In the present study, efficacy of the toltrazuril treatment for prevention of coccidiosis and necrotic enteritis was tested. Ninety-six 14-day-old commercial broiler chickens were caged and divided into eight groups (n=12), designated groups 1 to 8. Chickens of groups 1 to 6 were inoculated orally at 18 days of age with 25,000 oocysts of Eimeria tenella and 75,000 oocysts of Eimeria brunetti. At 22 days of age, chickens of groups 1 to 6 were infected with 109 colony-forming unit Clostridium perfringens. Chickens of group 1 were treated with 75 parts/106 toltrazuril in drinking water for 8 h on two consecutive days up to 12 h before Eimeria infection, while chickens of groups 2 to 5 were treated with the same dose of toltrazuril at 12 h, 36 h, 60 h and 84 h after Eimeria infection, respectively. The non-treated group 6 served as a positive control. Chickens in group 7 were treated with toltrazuril at 17 and 18 days of age, and those of group 8 remained uninfected and non-treated as a negative control. The feed conversion ratio was higher in the positive control compared with other groups. The mortality rates were 16.8% and 41.7% in the late toltrazuril-treated (at 84 h) and infected non-treated chickens, respectively. Lesions scores of necrotic enteritis or coccidiosis in infected, non-treated chickens were significantly more severe compared with negative controls (P<0.01) and late toltrazuril-treated (at 84 h) chickens (P<0.05). In conclusion, application of toltrazuril before Eimeria challenge protected chickens from coccidiosis and indirectly from successive necrotic enteritis caused by C. perfringens infection.

Influence of a metaphylactic treatment with Baycox® Bovis on the reproductive performances of Fresian heifers: a preliminary study

A blind, randomised, controlled, multicentric field trial was conducted to assess the influence of a metaphylactic treatment with an oral solution of toltrazuril on some reproductive parameters of Italian Fresian heifers during the first 18-20months of life. For this goal 40 calves were selected from two dairy farms and randomly divided into two homogeneous groups: MTol, treated with toltrazuril and NegC, left untreated. The calves were clinically and coprologically examined over the entire study period. The body condition scores, the body weights and the age at the first service were recorded and compared between the two groups, in addition to some other reproductive parameters including number of pregnancies, average service per pregnancy, conception rate, conception rate at first service and post first service conception rate. The analysis of the results showed that the metaphylactic treatment with toltrazuril influenced positively the average age of the first service (MTol 461.4days versus NegC 485.45days), the overall conception rate (MTol 95% versus NegC 85%), the success at first (MTol 60% versus NegC 45%) and second (MTol 75% versus NegC 45%) services and, consequently, the mean number of services to be carried out for each animal (MTol 1.4 ± 0.6 versus NegC 1.6 ± 0.79). Furthermore, the results confirmed that toltrazuril treatment, applied in accordance with the epidemiological aspects of each farm, is highly efficacious in persistent reduction of oocyst excretions with particular reference to Eimeria zuernii, Eimeria bovis, considered to be mainly responsible for clinical coccidiosis.

In-vivo efficacy of toltrazuril on experimentally induced Toxoplasma gondii tissue cysts in lambs: A novel strategy for prevention of human exposure to meat-borne toxoplasmosis

The aim of the present study was to investigate in vivo efficacy of toltrazuril on Toxoplasma gondii tissue cysts following induction of chronic toxoplasmosis in 4-week-old lambs (n=27) by inoculation of 1×105T. gondii ME 49 strain oocysts (day 0). Beginning at the 15th day after inoculation, lambs in Group T20 and Group T40 were given toltrazuril orally 2 times, once every week (Baycox 5%, Bayer Animal Health) at a dose of 20mg/kg and 40mg/kg, respectively. Positive control (PC) lambs were not given any therapy, and 2 clinically healthy non-infected lambs were used as negative controls (Group NC). Two out of 9 lambs in PC group (oocyst inoculated but non-treated) were killed on toltrazuril treatment days (day 15 and 22) to evaluate the tissue cyst presence in their muscles. On day 90, the remaining 25 lambs were necropsied, and samples from the brain and 11 different muscle groups were collected. The tissues were examined for the presence of tissue cysts by histopathology, immunohistochemistry, nested-PCR and percoll gradient centrifugation. Anti-T. gondii antibodies were screened by IFAT throughout the experiment. The increased T. gondii seropositivity beginning from the 15th day of inoculation remained steady at Day 45 and Day 90 in Groups PC while it was significantly lower at Day 90 in toltrazuril receiving groups. In toltrazuril treated groups, histopathological findings included degenerative changes in the cyst wall, complete macrophage invasion to the cysts, and reduction or removal of the cysts in toto. Four out of 9 lambs (44.4%) in both toltrazuril treated group (Group T20 and T40) did not contain tissue cyst in any examined tissues while all positive control animals had T. gondii tissue cysts at least in one muscle group. The toltrazuril treatment efficacy on the cyst presence was determined as 44.4%. The number of the cysts in the musculature was significantly different between non-treated and toltrazuril treated lambs (X2=6.613; p=0.037). For the total number of cysts, the positive control lambs had higher number of cysts compared to both toltrazuril treated lambs (T20 and T40) (X2=5.629; p=0.018 and X2=5.629; p=0.018, respectively) while there were no differences between Group T20 and Group T40 (X2=0.000; p=1.000). According to PCR results, the brain and M. semitendinosus were positive in all 7 control lambs while 12 out of 18 lambs were positive in toltrazuril treated lambs. In conclusion, the results are promising as the toltrazuril treated lambs had markedly less parasite counts compared to those of untreated lambs. Further research should be conducted to reveal if toltrazuril treatment in sheep could be used as a strategy to minimize the cyst exposure of humans through consumption of raw or undercooked mutton.

Effect of Isosporiasis Prevention with Toltrazuril on Long-Term Pig Performance

The efficacy of toltrazuril treatment was assessed in two experiments in Polish swine herds. Experiment 1 included a toltrazuril treatment group, Group A (n = 410), and untreated control, Group B (n = 386). Time to sale in Group A was 108 days versus 120 days for Group B, with average body weights at sale of 114.2 kg and 108.8 kg, respectively (P < 0.05). In experiment 2, the health status and body weight gain of 238 piglets treated with toltrazuril (Group D) were compared to 235 untreated piglets (Group K). A similar difference was observed in average body weights of slaughtered animals, being on average 104 kg in Group D and 101 kg in Group K (P < 0.01). Animals from Group D were slaughtered 5 days earlier than animals from Group K (day 166 versus day 171). Data from clinical trials suggest treatment of coccidiosis with toltrazuril offering potential for improved animal welfare and yields, however this has remained unproven in field conditions in large swine production facilities. The present study confirms the efficacy of toltrazuril treatment when used in the field and the subsequent positive impact on time to weaning, time to market, and on weight gain at all time points.

Factors associated with the occurrence and level of Isospora suis oocyst excretion in nursing piglets of Greek farrow-to-finish herds.

BackgroundPiglet isosporosis is one of the most common parasitic diseases in modern pig production. To prevent clinical disease, prophylactic treatment of piglets with toltrazuril (BAYCOX® 5%, Bayer HealthCare, Animal Health, Monheim, Germany) is widely practiced in the past 20 years. There are only very few reports documenting the likely effect of managerial practices, such as hygiene measures, all-in-all-out management of farrowing facilities and piglet manipulations, and/or farm-specific environment - i.e. design and materials of the farrowing pen and room - in the risk of disease occurrence and transmission. Therefore, in this cross-sectional study, we identified litter- and herd-level factors associated with the odds and the level of Isospora suis oocyst excretion in nursing piglets of Greek farrow-to-finish pig herds. Faecal samples were collected from 314 liters of 55 randomly selected herds. Oocyst counts were determined by a modified McMaster technique and possible risk-factor data were collected through a questionnaire. In the analysis, we employed a two-part model that simultaneously assessed the odds and the level of oocyst excretion.ResultsFactors associated with lower odds of oocyst excretion were: use of toltrazuril treatment, all-in all-out management of the farrowing rooms, no cross-fostering or fostering during the first 24 hours after farrowing, plastic flooring in the farrowing pens, farrowing rooms with more than fourteen farrowing pens and employment of more than two caretakers in the farrowing section. Factors associated with lower oocyst excretion level were: use of toltrazuril treatment and caretakers averting from entering into farrowing pens.ConclusionApart from prophylactic treatment with toltrazuril, the risk and the level of I. suis oocyst excretion from piglets in their second week of life, was associated with managerial and environmental factors. Changes in these factors, which may enhance prevention of piglet isosporosis – either alternatively or supplementary to medical control – are of increasing importance because of the likely development of resistant parasites under the currently widespread use of anticoccidial compounds.