The history of decoquinate in the control of coccidial infections in ruminants.

Decoquinate is a quinolone derivative that has been used for over 20 years in the control of coccidiosis in domestic ruminants. Decoquinate treats coccidiosis in lambs and calves and prevents coccidiosis in lambs when administered in feed at a dosage of 1 mg decoquinate/kg bodyweight (b.w.) daily for at least 28 days. It prevents coccidiosis in calves and aids in the prevention of coccidiosis in lambs when administered in calf and ewe feed, respectively, at a dosage of 0.5 mg/kg b.w. daily for at least 28 days. Decoquinate also aids in the prevention of abortions and perinatal losses owing to toxoplasmosis by medication of ewe feed at a dosage of 2 mg/kg b.w. daily, fed continuously for 14 weeks prior to lambing. Several field studies have reported reductions in cryptosporidial oocyst shedding. Decoquinate acts early in the life cycle of Eimeria on sporozoites, released from ingested oocysts, and on first-generation meronts, arresting development and release of merozoites and thus preventing further damage to the intestines owing to the gametocyte stages. Production benefits associated with the use of decoquinate are due mainly to its action as a coccidiostat rather than any effects on diet utilization or ruminal fermentation.

Evaluation of optimum conditions for decoquinate nanoliposomes and their anticoccidial efficacy against diclazuril-resistant Eimeria tenella infections in broilers.

Decoquinate (DQ) is used for prophylaxis against coccidian infections within the digestive tract of chickens, but DQ is extremely insoluble in water. Hence, improving the water solubility of DQ is extremely important. First, decoquinate nanoliposomes (DQNLs) were prepared by the thin-film dispersion-ultrasonic method. The preparation conditions of DQNLs were optimized using the orthogonal test. The optimal preparation conditions of DQNLs were: a ratio of egg-yolk lecithin:drug (w/w) of 10:1, ratio of egg-yolk lecithin:cholesterol (w/w) of 5:1, rotary-evaporation temperature of 50 ℃, and ultrasound duration of 15 min. The encapsulation efficiency of DQNLs prepared under these conditions reached 99.24 % and drug loading was 5.67 %. The characterization of optimized DQNLs was also done. Transmission electron microscopy of DQNLs showed that they had the characteristic structure of liposomes. The mean particle size was 115.6 nm. The polydispersity index was 0.175. The zeta potential was -39.1 mV. The stability of DQNLs was high upon storage at 4 ℃. In vivo studies demonstrated that the lower dose (5 mg/L) of DQNLs in drinking water obtained the similar anticoccidial efficacy to that of 40 mg/kg DQ in feed against diclazuril-resistance Eimeria tenella isolate. The in vitro inhibitory effect of DQNLs on the sporulation of Eimeria tenella oocysts was dose-dependent. Therefore, the anticoccidial efficacy of DQ was enhanced significantly after being encapsulated into nanoliposomes.

Ovine toxoplasmosis: transmission, clinical outcome and control.

Toxoplasma gondii is a significant cause of abortion in sheep. Infection is picked up from the environment and if initiated during pregnancy may cause fetal mortality. Infected sheep remain persistently infected with tissue cysts in brain and muscle (meat), and are also immune and would not be expected to abort again. The live tachyzoite vaccine (Toxovax) protects against abortion and this allows the suggestion that it may also reduce or prevent tissue cyst development in muscle. If this were so it raises the question of whether the vaccine could be used to make meat safer for human consumption.

Tracing the emergence of drug-resistance in coccidia (Eimeria spp.) of commercial broiler flocks medicated with decoquinate for the first time in the United Kingdom.

Decoquinate is a quinolone coccidiostat introduced during 1967 as an in-feed prophylactic for broiler chickens. Despite early drug-resistance problems and its age, the drug is still used commercially worldwide. Decoquinate here serves as a valuable model in a field study that addresses the dynamics and economic impact of the development of coccidial resistance to potent synthetic anticoccidial drugs. The results of this unique, hitherto unpublished, study on the initial emergence of resistance of avian coccidia (Eimeria spp.) to a new drug in the field may be of strategic value in the continued use of decoquinate or the introduction of new drugs. The commercial performance of the first 3-5 crops of broilers to be medicated with decoquinate on each of six farms was monitored during 14 months in 1968-1969, supplemented by assessments of the species, population dynamics and decoquinate-resistance of coccidia isolated from each farm. During the rearing of each flock in a single shed on each farm, oocysts were counted in fresh faecal samples collected on three occasions, and the species were identified by their morphology if possible, supported if necessary by the biological characteristics of infections in chickens. E. acervulina was the most common species, followed by E. mitis, E. maxima, E. tenella and E. praecox. E. brunetti occurred rarely, and E. necatrix was not found. Decoquinate-resistance was evident in several species during the rearing of the first decoquinate-medicated crop on each farm, although clinical coccidiosis did not occur. It was concluded that inherently resistant mutants of E. acervulina, E. brunetti, E. maxima, E. tenella, and probably also E. mitis and E. praecox, were selected from field populations by 6 weeks during their first exposure to decoquinate. During up to four more subsequent crops, cycling of resistant parasites stimulated host immunity, which had no obvious adverse impact on commercial performance. There was no apparent seasonal effect. A hypothesis is proposed to explain the sudden and rapid emergence of quinolone-resistance in the coccidia, and why bird health was not thereby compromised in these circumstances.

Field study of the efficacy of halofuginone and decoquinate in the treatment of cryptosporidiosis in veal calves.

Ninety, seven- to 10-day-old calves were allocated to three groups of 30 and treated daily for seven days with either 100 microg/kg halofuginone hydrobromide or 2.5 mg/kg decoquinate orally or left untreated as controls. The levels of diarrhoea and dehydration were monitored daily for 28 days from the first day of treatment (day 0) and samples of faeces were collected on days 0, 7, 14, 21 and 28, to quantify the excretion of Cryptosporidium parvum oocysts. The calves were weighed on days 3 and 28. The treatments had no effect on the levels of diarrhoea or dehydration, the proportions of diarrhoeic calves or the proportions of calves shedding oocysts. However, unlike decoquinate, halofuginone significantly reduced the excretion of oocysts on day 7 (P<0.0001), and decoquinate increased the average daily weight gain of the calves (P=0.049).

The mode of action of anticoccidial quinolones (6-decyloxy-4-hydroxyquinoline-3-carboxylates) in chickens.

The anticoccidial mode of action of quinolones (6-decyloxy-4-hydroxyquinoline-3-carboxylates) against Eimeria tenella and E. acervulina in chickens has been investigated, using decoquinate and M&B 15,584 as examples. The well known static effect on sporozoites of relatively high continuous drug concentrations in the food masked other components of the mode of action, newly described here. Lower concentrations of quinolones allowed sporozoites to continue their development. First-stage schizonts were susceptible to a secondary cidal effect, although later schizonts seemed to be rather refractory. Furthermore, the sporulation of oocysts produced by E. tenella that completed its life cycle in the presence of suboptimal concentrations of quinolones was inhibited: this probably reflects a drug effect on gametocytes. Quinolones were absorbed rapidly from the chicken intestine, probably in less than 1 h. Drug withdrawal experiments showed that quinolones persisted in chicken tissues at active concentrations for up to 48 h. Despite their static effect on sporozoites, they may nevertheless be expected to exert a therapeutic effect against drug-sensitive coccidia in interrupted regimes that allow the later cidal effect to come into play. This allows immunity to coccidiosis to develop in the presence of drug. These new results, with the previously available data have been combined in an updated account of the anticoccidial mode of action of quinolones in the chicken.

Evaluation of decoquinate to treat experimental cryptosporidiosis in kids.

The purpose of this trial was to evaluate the effects of decoquinate at 2.5 mg/kg/day for 21 days to prevent an experimental cryptosporidiosis in kids. Twenty 1-day-old male kids (French Alpin), fed initially goat colostrum heated 1 h at 56 degrees C and fed twice daily with nonmedicated milk replacer, were assigned into 2 groups. Kids of both groups were orally inoculated with 10(6) Cryptosporidium parvum (D0 = inoculation day). Group A kids were kept as nonmedicated controls and group B kids were orally medicated with 2.5 mg/kg/day of decoquinate (Deccox L. Rhône Poulenc Animal Nutrition) for 21 days from D-3 to D17. The studied criteria were body weight gain, oocyst shedding and specific anti-C. parvum immune response. In group A, the inoculation was not followed by mortality; but only by diarrhea and high oocyst shedding. Decoquinate reduced the severity of cryptosporidiosis in group B kids. The treatment prevented episodes of diarrhea and weight gain decrease for the D0-D7 and D0-D14 disease periods but did not allow a better final weight gain. The oocyst shedding was decreased in number and in duration. This parasitic development has induced a specific anti-C. parvum immune response. This drug is well-tolerated by animals and may be recommended in the prevention of ruminant cryptosporidiosis, a disease which has very limited treatment options.

The extraintestinal stages of Eimeria tenella and E. maxima in the chicken.

Donor chickens given feed medicated with one or two levels of decoquinate or given non-medicated feed were infected with oocysts of Eimeria tenella or E. maxima per os. Twelve hours after inoculation with oocysts liver, mid-intestine or ceca homogenates were fed to previously uninfected recipient chickens. The results showed that continuous medication with decoquinate was effective in preventing the transfer of sporozoites from the intestine to the liver. Oocysts were detected in the feces of all recipients of tissue from non-medicated donors, showing that some sporozoites of E. maxima and E. tenella are normally transferred to liver. Young broiler chickens were immunized by oral inoculation of E. maxima oocysts. The immune status of similar chickens inoculated with sporozoites of the same species directly into the liver or spleen were assessed. During the experimental period half of the chicks were provided with non-medicated food and the remainder were given feed supplemented with decoquinate; decoquinate was effective in arresting the development of the sporozoites. Two weeks after initial infection the birds were challenged with oocysts of E. maxima per os. Injection of sporozoites into the spleen did not protect against challenge. Birds inoculated with sporozoites into the liver were unable to develop a significant level of immunity. When the drug pressure was removed from these birds, parasitism of the intestine occurred and immunity developed.

Reduction of anticoccidial drug resistance by massive introduction of drug-sensitive coccidia.

Massive introduction of a drug-sensitive attenuated strain of Eimeria tenella in a floor-pen heavily contaminated with a drug-resistant strain produced a marked reduction in the proportion of drug-resistant oocytsts in the litter. This provides a useful adjunct to planned immunization programs since the procedure protects the birds against subsequent challenge through immunity imparted by the introduced strain while restoring the effectiveness of the anticoccidial drug which was previously ineffective because of the predominance of drug-resistant coccidia.

Efficacy of selected oral chemotherapeutants against Ichthyophthirius multifiliis (Ciliophora: Ophyroglenidae) infecting rainbow trout Oncorhynchus mykiss.

The chemotherapeutic efficacy of 6 in-feed compounds against Ichthyophthirius multifiliis Fouquet, 1876 was assessed using experimental infections of rainbow trout Oncorhynchus mykiss (Walbaum) fingerlings. Trial doses of 104 ppm amprolium hydrochloride or 65 ppm clopidol fed to fish for 10 d prior to infection significantly reduced the number of trophonts establishing in trout fingerlings by 62.0 and 35.2% respectively. In-feed treatments of infected trout with either 63 or 75 ppm amprolium hydrochloride, 92 ppm clopidol, or 38, 43 or 47 ppm salinomycin sodium for 10 d also significantly reduced the number of surviving trophonts by 77.6 and 32.2% for amprolium, 20.1% for clopidol and 80.2, 71.9 and 93.3% respectively for salinomycin sodium.

Eimeria tenella: stability of resistance to halofuginone, decoquinate and arprinocid in the chicken.

The stability of experimentally induced resistance to halofuginone, decoquinate or arprinocid in lines of Eimeria tenella, was examined after 10 passages in unmedicated chickens. There was no loss of resistance to halofuginone or decoquinate. Resistance to arprinocid was unaffected in a line developed in the presence of 150 ppm of the drug but was unstable in a line developed with 60 ppm.

Evaluation of decoquinate, lasalocid, and monensin against experimentally induced sarcocystosis in calves.

Effects of decoquinate, lasalocid, and monensin against experimentally induced sarcocystosis (Sarcocystis bovicanis) were evaluated in 12 calves, 3 of which were inoculated, nontreated controls. Three additional calves were noninoculated, nontreated controls. Drugs were administered in the feed (33 mg/kg of feed) of the treated calves (3 calves/group) for 87 days. Eight of the 12 inoculated calves died from acute sarcocystosis during the experiment (the 3 inoculated, nontreated controls, the 3 calves given decoquinate, and 2 of the 3 calves given lasalocid). Large numbers of sarcocysts were found in tissues from inoculated calves that survived in the experiment (1 of the 3 calves given lasalocid and the 3 calves given monensin). Although large numbers of sarcocysts developed in the muscles of monensin-treated calves, monensin may have an ameliorating effect on acute sarcocystosis.

Decoquinate in the control of experimentally induced coccidiosis of calves.

Decoquinate administered orally in a grain mix at dosages of 0.5, 0.538, 0.7, and 0.8 mg/kg of body weight suppressed oocyst discharge and bloody diarrhea in calves inoculated 3 days later with 100,000 oocysts of Eimeria bovis (experiment 1, n = 12 calves) or with 100,000 oocysts each of E bovis and Eimeria zuernii (experiment 2, n = 16 calves). Doses of 0.1, 0.163, 0.243, 0.3, and 0.362 mg/kg of body weight gave only partial suppression of oocyst discharge and diarrhea. Clinical signs of coccidiosis did not recur for 23 days after the treatment was discontinued.

Bovine coccidiosis: protective effects of low-level infection and coccidiostat treatments in calves.

Twenty coccidia-free Holstein bull calves were allotted to groups to study effects of treatment with lasalocid and decoquinate on subsequent resistance to coccidiosis (Eimeria spp infections). Calves fed medicated rations of either drug at dosages of 50 mg/kg of feed (approx 1.2 mg/kg of body weight) had significantly fewer oocysts (P less than 0.01) than did nontreated controls regardless of other procedures used. Treated calves premunized with 2,000 oocysts/day for 5 days and later challenge inoculated with 200,000 oocysts did not develop diarrhea, unless the drugs were withdrawn from feed. Animals premunized (2,000 oocysts/day for 5 days) in absence of drug were no more resistant to the challenge inoculation than nonpremunized animals. These results indicated that lasalocid and decoquinate were efficacious coccidiostats and protected calves as long as they were administered. Cessation of drug treatment usually resulted in appearance of oocysts in feces and diarrhea. Premunization alone cannot be expected to prevent coccidiosis when animals are exposed to large numbers of oocysts.

Evaluation of lasalocid as a coccidiostat in calves: titration, efficacy, and comparison with monensin and decoquinate.

Two experiments were conducted to evaluate lasalocid as a coccidiostat in Holstein calves and to compare lasalocid with monensin and decoquinate. In experiment 1, calves in 3 groups (6 calves/group) were each inoculated with 500,000 sporulated oocysts, 88% of which were Eimeria bovis and 12% were E zuernii. Calves in each group were given lasalocid-medicated feed at 0.50 (group 3), 0.75 (group 4), or 1 mg/kg (group 5) of body weight/day for 45 days. Two control groups (6 calves/group) were also evaluated; calves in control group 2 were inoculated and nontreated, and calves in control group 1 were noninoculated and nontreated. At 0.50, 0.75, or 1 mg/kg/day, lasalocid was equally effective in preventing induced coccidiosis (E bovis and E zuernii) in calves. Compared with inoculated nontreated controls, treated calves had significantly (P less than 0.05) fewer oocysts in feces and had fewer clinical signs of coccidiosis from days 16 to 30 after inoculation. Experiment 2 was conducted to compare the effectiveness of monensin, lasalocid, and decoquinate for the prevention of experimentally induced coccidiosis. Calves (n = 48) were allotted into 4 groups (12 calves/group); each was inoculated orally with 275,000 sporulated oocysts, predominantly E bovis and E zuernii, and each was given nonmedicated feed (group 6) or feed medicated with 33 mg of lasalocid (group 7), decoquinate (group 8), or monensin (group 9)/kg of feed for 46 days. Calves given medicated rations had significantly (P less than 0.05) fewer oocysts in their feces and fewer clinical signs of coccidiosis than did calves given nonmedicated rations.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention and control of coccidiosis in goats with decoquinate.

Decoquinate was evaluated as a coccidiostat in domestic goats. Fifty goats less than 4 months of age were assigned to 5 groups (pens) of 10 goats each and were treated for 87 days with 0 (control), 0.3, 0.5, 1.0, or 4.0 mg of decoquinate in feed/kg of body weight. Goats were inoculated orally weight. Goats were inoculated orally with 30,000 oocysts, mainly Eimeria christenseni (74%) and E ninakohlyakimovae (20%) on day 19. Nontreated goats developed profuse watery diarrhea and tenesmus and gained weight poorly; 2 died. Treated goats did not develop clinical coccidiosis and gained significantly more weight (P less than 0.05), regardless of the dose used. Treated goats also had significantly fewer (P less than 0.05) oocysts in feces than did nontreated controls. Oocyst numbers were inversely related to dose; a more rapid decrease in oocyst numbers occurred as the dose was increased. At the doses used, decoquinate was safe in goats and was an effective drug for the prevention of clinical coccidiosis.

Effect of decoquinate on the control of coccidiosis in young ruminating calves.

Twenty-five 6-week-old Holstein male calves were each inoculated with 500,000 sporulated oocysts of Eimeria bovis. Two nontreated (control) and 3 treated calves (1.5 mg of decoquinate/kg of body weight in feed) were necropsied 7 days after inoculation. Similar groups of calves were necropsied at 12, 18, 22, and 28 days after inoculation. Treated calves were started on medicated feed 2 days before inoculation or at 7, 12, or 15 days after inoculation or were on continuous medication from the day of inoculation. Control calves were not given medication. Early schizonts were in the small intestines of control calves at 7 days after inoculation, but none was in the treated calves that were started on medicated feed 2 days before inoculation. Schizonts were present in the small intestine of both treated and control calves at 12 days after inoculation. At 18 days after inoculation, control calves had schizonts in the small intestine and gamonts and oocysts in the cecum and large intestines, but treated calves only had schizonts in the small intestine. At 22 days, control calves had schizonts in the small intestine and gamonts and oocysts in the large intestine; treated calves had schizonts in the small intestine. At 28 days, controls still had schizonts in the small intestine and gamonts and oocysts in the cecum and large intestine; the treated calves that had been on continuous medication did not have schizonts, gamonts, or oocysts in the tissues. Decoquinate apparently kills sporozoites or arrests development and release of merozoites from the schizonts when fed at 1.5 mg/kg of body weight in the feed.

Effects of inoculations with Eimeria zuernii on young calves treated with decoquinate or narasin with or without dexamethasone.

Sixteen 7-week-old Holstein male calves were inoculated with sporulated oocysts of Eimeria zuernii. Four calves (controls) were euthanatized and necropsied at 14 and 20 days after inoculation (DAI). Two calves were treated with 20 mg of dexamethasone (IM) on 13, 14, and 15 DAI and euthanatized and necropsied 17 DAI and 2 calves were given similar treatments and necropsied 20 DAI. The 8 other calves were euthanatized and necropsied 20 DAI. Two were started on the anticoccidial drug decoquinate in feed 13 DAI; 2 others were given decoquinate on the same schedule plus dexamethasone on 13,14, and 15 DAI. Two calves were given the antibiotic narasin in feed beginning 13 DAI and 2 calves were given parasin on the same schedule plus dexamethasone on 13,14, and 15 DAI. All calves, except 2 controls necropsied 14 DAI and 4 calves given decoquinate, discharged moderate-to-large numbers of oocysts in feces and had moderate-to-serve changes in fecal consistency. Histologic examinations revealed large numbers of endogenous stages in tissues of calves treated or not treated with dexamethasone. Few endogenous stages were observed in tissues from calves that were given decoquinate or decoquinate plus dexamethasone. Calves given narasin or narasin plus dexamethasone had moderate-to-large numbers of endogenous stages in the tissues.

Evaluation of lasalocid and decoquinate against coccidiosis resulting from natural exposure in weaned dairy calves.

Eighteen female Holstein calves, raised as natural herd additions under conditions typical of a well-managed midwestern United States dairy farm, were used in a natural-exposure study to determine the anticoccidial efficacies of lasalocid and decoquinate. Calves were allotted to 6 treatment blocks of 3 calves each as they were weaned. Within each block, calves were randomly assigned to be given either lasalocid or decoquinate or to remain as a nonmedicated control. Calves were given medication for 90 days and remained separated from other calves for 120 days. Adjusted weight gains were consistently greater in calves that were given medication; however, differences were not statistically significant. Fecal specimens were obtained from calves at weekly intervals during the study. Overall, oocyst shedding was low. During the medication period, quantitative mean fecal shedding of oocysts was reduced eightfold in calves given decoquinate and four-fold in calves given lasalocid, as compared with nonmedicated control calves. During the period following the medication period, calves that had been controls shed fewer oocysts than did calves that had previously been given medication. A pairwise comparison of the proportion of specimens that were oocyst-positive was made to assess qualitative oocyst shedding among treatment groups. During the medication period, qualitative oocyst shedding (all species, Eimeria bovis, E zuernii, species other than E bovis and E zuernii) was greater in controls than in either lasalocid-or decoquinate-treated groups. Like-wise, lasalocid-medicated calves shed oocysts more frequently than did the decoquinate-medicated group. After medication, qualitative findings were reversed. Little diarrhea was noticed in treatment or control calves during the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of intermittent and continuous administration of decoquinate on bovine coccidiosis in male calves.

Male Holstein calves were each inoculated with 350,000 sporulated oocysts of Eimeria bovis. Two calves were given decoquinate (0.5 mg/kg of body weight) continuously in dry feed for 29 days, and 2 calves each were given 0.5, 1, or 1.5 mg of decoquinate/kg on an every 2nd-or 3rd-day schedule for 29 days. Calves given decoquinate continuously did not discharge oocysts but had slightly loose feces. In general, the number of oocysts discharged increased and fecal consistency decreased as the time between feeding of medicated feed increased. Calves given 0.5 or 1.5 mg of decoquinate/kg every 3rd day discharged more oocysts and had more diarrhea than did calves given 1 mg of decoquinate/kg every 3rd day. At postinoculation day 29, calves were euthanatized. At necropsy, intestinal tissues of calves given decoquinate were mostly normal. Apparently, reduced infections along with the elapsed time were sufficient to resolve most intestinal lesions caused by the coccidia. Decoquinate was most effective when fed continuously at 0.5 mg/kg. However, when fed at 1 or 1.5 mg of decoquinate/kg every 2nd day or 1.5 mg of decoquinate/kg every 3rd day, oocyst production was reduced and clinical coccidiosis was prevented.