Evaluation Of The Effectiveness Of Ponazuril Suspension On Isospora Suis Infection

Porcine coccidiosis is a parasitic protozoan disease caused by Isospora suis and some species of Eimeria coccidian which characterized by mucosal bleeding,diarrhea and wasting.Most of them parasitized in the intestinal mucosal epithelial cells of pigs and were distributed worldwide.Among them,I.suis had the highest infectivity and the strongest pathogenicity to Suckling piglets.In recent years,With the development of intensive pig industry,the disease has gradually become a rising trend,and cause great economic losses to the breeding industry.As an active metabolite of Toltrazuril,Ponazuril has a slow elimination rate and a long half-life in pigs,which can continue to play a clinical role in the treatment of coccidiosis.In this study,a disease model of porcine coccidiosis was established through artificial infection of piglets,and the effectiveness of Ponazuril suspension on porcine coccidiosis was evaluated to determine the optimal dose,so as to provide reference and basis for the rational use of Ponazuril in pigs and the reduction of toxic and side effects,and lay a foundation for further clinical field trials.1.Establishment of artificial disease model of Isospora in pigletsIn order to establish the artificial infection model of I.suis,16 5-day-old piglets were randomly divided into four groups and inoculated with 103,104,2×104 isospora oocysts,respectively.The optimal inoculation amount of oocysts was determined by observing clinical symptoms,weight gain,fecal viscosity and oocysts output.The results showed that the piglets inoculated with 103 oocysts had no obvious clinical symptoms and no significant difference in weight gain from the control group.The piglets inoculated with 104 and 2×104 oocysts all had diarrhea on the fourth day after inoculation,and the diarrhea degree was intensified with the increase of inoculation amount.The diarrhea ended on the 12th day post infection,and the piglets' mental state and appetite became normal.Piglet weight gain in the two groups inoculated with 104 and 2×104 oocysts was significantly lower than that in the control group(P<0.05).The results showed that 104 or more oocysts inoculated with healthy piglets could reproduce the model of I.suis infection2.Efficacy of Ponazuril Suspensions against Isospora piglets2.1 Dose determination studiesIn order to preliminarily evaluate the efficacy of Ponazuril suspension in preventing piglet isospora infection,the dose determination studies was conducted in 5 dose groups of 40 mg/kg,20 mg/kg,15 mg/kg,10 mg/kg and 5 mg/kg,with a single oral administration.A approved drug control group,a blank control group and an infection-free group were respectively set up.The observation period was 28 days.The pharmacodynamics of Ponazuril suspension in preventing isospora infection in piglets was evaluated by the parameters of fecal viscosity,diarrhea rate,ovulatory sac volume,oocysts loss rate and weight gain.The experimental results showed that the piglets in the 40 mg/kg bw dose group,20 mg/kg bw dose group,15 mg/kg bw dose group,the drug control group and the blank control group did not show diarrhea in the whole experimental period,and there was no significant difference in piglets' weight gain between the groups.In the 5 mg/kg bw group and the 10 mg/kg bw group,the piglets started to have diarrhea on the 5th day after inoculation of the oocysts,and the diarrhea rate was 87.5%and 58.3%,The diarrhea stops 12 days after infection,and the stool begins to take shape,but there are still oocysts excreted in fecal examination.The weight gain of the piglets in the two dose groups was significantly different from that in the other drug groups(P<0.05).In the control group,all piglets had diarrhea on the 4th day after oocysts inoculation,and the diarrhea rate was 100%.Compared with the control group,the diarrhea time was delayed,but the difference of weight gain was not significant.The results showed that when the single oral dose of Ponazuril suspension reached 15 mg/kg bw or above,it could effectively prevent the infection of piglets with isospora,reduce the diarrhea rate,reduce the incidence of coccidiosis and improve the weight gain.2.2 Dose confirmation studiesOn the basis of dose determination studies,to further determine the optimal dose of Ponazuril suspension for the prevention of piglet coccidiosis,three dose groups of high(20 mg/kg),medium(15 mg/kg)and low(7.5 mg/kg)were set.At the same time,a drug control group,a negative control group and a positive control group were respectively set up.The test period is 28 days,the effectiveness evaluation index is the same as the dose determination studies.The results showed that the piglets in the high-dose and medium-dose groups did not show any clinical symptoms of coccidiosis infection,and the oocysts were not excreted by fecal examination.The average weight gain of piglets in the high-dose group and the medium-dose group was 5.75 kg and 5.80 kg,respectively,with no significant difference from that in the blank control group.Diarrhea occurred in 6 piglets in the observation period in the low-dose group,and the average weight gain was only 4.29 kg,which was significantly different from that in the high-dose and medium-dose groups(P<0.05).Microscopic examination by electron microscopy showed that the villi of piglets in the low-dose group showed partial atrophy,fusion,and local erosion of small intestinal epithelial cells.The experimental results showed that Ponazuirl suspension could effectively control the clinical symptoms of piglet isospora infection and reduce the intestinal damage caused by coccidioides infection when administered orally at 15 to 20 mg/kg for 48 hours after piglets were artificially infected with swine isospora at 5 days of age.For the prevention and treatment of isospora infection in piglets with Ponazuirl suspension,the recommended dose is 15-20 mg/kg bw for single oral administration.