Search

A series of 4 floor pen studies was conducted to evaluate the effects of environmental temperature modification on nicarbazin (NIC) responses in broiler chickens raised to 28 d of age. Birds were reared at either standard temperatures (recommended by the primary breeder for ages zero to 28 d) or at 3°C below this level. From placement to 28 d, birds were provided feeds containing zero, 100, or 125 ppm NIC, comprising a 2 × 3 factorial arrangement in each test. Two of the trials were conducted in the presence of an imposed coccidial challenge and 2 were conducted in healthy animals. At 18 and 28 d of age, performance was recorded; cloacal temperatures were measured at 7, 14, 21, and 26 days. Mortality data were collected daily and coccidial lesions were scored at 6 d post challenge. Results of these studies revealed that NIC improved coccidial lesion scores regardless of environmental temperature. In the absence of coccidial challenge, NIC depressed performance, but reductions in environmental temperature diminished the magnitude of these responses. Under conditions of coccidial challenge, NIC significantly improved body weight gains in both temperature environments. Compared to standard temperature conditions, lower environmental temperatures exerted a positive effect on feed conversion rates of NIC-fed broilers. Birds reared in the low temperature environment exhibited lower cloacal temperatures than standard environment groups throughout the test period. Irrespective of coccidial challenge, lower environmental temperatures significantly reduced nicarbazin mortality compared to standard temperature groups, resulting in a significant nicarbazin x temperature interaction. This finding indicates that temperature modification is a practical method for minimizing mortality over the course of 28-day nicarbazin usage., (© 2017 Poultry Science Association Inc.)

This manuscript provides an overview of past wildlife contraception efforts and discusses the current state of research. Two fertility control agents, an avian reproductive inhibitor containing the active ingredient nicarbazin and an immunocontraceptive vaccine, have received regulatory approval with the Environmental Protection Agency and are commercially available in the USA. OvoControl G Contraceptive Bait for Canada Geese and Ovo Control for pigeons are delivered as oral baits. An injectable immunocontraceptive vaccine (GonaCon Immunocontraceptive Vaccine) was registered with the Environmental Protection Agency for use in female white-tailed deer in September 2009. An injectable product (GonaCon Immunocontraceptive Vaccine) is registered for use in female white-tailed deer. Both products are labeled for use in urban/suburban areas where these species are overabundant. Several other compounds are currently being tested for use in wildlife in the USA, Europe, Australia and New Zealand that could have promise in the future. The development and use of reproductive inhibitors for resolving human-wildlife conflicts will depend on a number of factors, including meeting the requirements of regulatory agencies for use in the environment and on the biological and economical feasibility of their use. Use will also be dependent on health and safety issues and on public acceptance of the techniques., (© 2010 ISZS, Blackwell Publishing and IOZ/CAS.)

Anticoccidial vaccine and an anticoccidial drug rotation program were compared to determine which program was more effective in producing coccidia populations sensitive of 1 ppm diclazuril. The study used an anticoccidial drug-sensitivity battery test (AST) to determine the baseline level of diclazuril sensitivity to field isolates of Eimeria spp. from seven broiler complexes that had used diclazuril. Based on percentage reduction in weight gain and lesion scores, 25% or fewer of the isolates were effectively controlled by diclazuril. Following the baseline sampling, four of the complexes switched to a nondiclazuril in-feed anticoccidial drug program and three of the complexes switched to a vaccination program for two broiler grow-out cycles as the sole coccidiosis-control program. This study demonstrated that the vaccine used (Coccivac-B) contained anticoccidial drug-sensitive strains. Eimeria isolates were subsequently collected from the identical houses and diclazuril AST results were compared with the baseline AST results. Following the two grow-out cycles, sensitivity of the isolates to diclazuril from the four complexes that continued to use in-feed anticoccidial drugs remained essentially unchanged. The isolates from the three complexes that switched to the vaccination program demonstrated a marked increase in diclazuril sensitivity, with 60%-100% of the isolates from each complex effectively controlled by diclazuril. Vaccination with the anticoccidial drug-sensitive strains produced a measurable increase in the level of sensitivity to diclazuril.

A novel laboratory anticestode assay was developed using Hymenolepis diminuta in the hamster. The commercial anticestode compounds, praziquantel, bunamidine, and niclosamide were active against patent infections of Hymenolepis diminuta in golden hamsters (Mesocricetus auratus) when given orally at 3.125, 100, and 200 mg/kg, respectively. The gastrointestinal nematode anthelmintics, cambendazole and mebendazole, were active at 50 mg/kg. Rafoxanide (fasciolicide) was active at 25 mg/kg, the lowest level tested. The coccidiostat, nicarbazin, was active at experimental levels (800 mg/kg and up). The anthelmintic-ectoparasiticide (endectocide), ivermectin, was inactive against the tapeworm at 0.5 mg/kg, as expected.

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.

A 42-day broiler floor pen study was conducted comparing the anticoccidial efficacy of toltrazuril (Baycox) as a stand alone treatment and as an additional treatment to in-feed anticoccidial programs. Toltrazuril was administered on days 18 and 19 in the drinking water at 7 mg/kg of body weight. The treatments were 125 ppm nicarbazin (days 0-14) to 66 ppm salinomycin (SAL) (days 15-35) with and without toltrazuril, SAL (days 0-35) with and without toltrazuril, nonmedicated (NM) to SAL with toltrazuril, and NM with and without toltrazuril. The controls were NM noninfected and infected. The treatments were replicated in five blocks of eight pens each in a randomized complete block design. All withdrawal feed was nonmedicated. On day 14, birds, except noninfected, were exposed to coccidial oocysts (Eimeria acervulina, Eimeria maxima, and Eimeria tenella) seeded litter. On days 21, 28, 35, and 42, birds and feed were weighed, four birds per pen were coccidial lesion scored, and litter oocyst counts were performed. The coccidial infection in the NM infected treatment caused a significant (P < 0.05) coccidiosis infection. Coccidiosis was moderately controlled in the anticoccidial treatment birds without toltrazuril. Performance in the NM with toltrazuril was equal to or better (P < 0.05) than the anticoccidial programs without toltrazuril. Toltrazuril was equal to the noninfected birds in performance. Toltrazuril most completely eliminated all coccidial lesions and dramatically reduced oocyst shedding. The performance data, lesion scores, and oocyst counts showed that a 2-day treatment with toltrazuril successfully controlled the coccidiosis with no relapse of infection. Toltrazuril can thus be used for supplemental control with in-feed anticoccidials or as a primary anticoccidial with nonmedicated feed.

A live attenuated anticoccidial vaccine (Paracox) was compared with a nicarbazin-monensin anticoccidial drug shuttle programme in three crops of Italian broilers, comprising a total of 290,405 chickens. All birds received the antibiotic growth promoter avilamycin. No coccidiosis was evident during the trials, but the occurrence of oocysts in the litter demonstrated that a natural challenge was present. Vaccinated birds consistently performed at least as well as those treated with the anticoccidial drug shuttle. The final mean weights of vaccinated birds were significantly greater (P < 0.001) than those of birds treated with anticoccidial drugs, both for females at 36/37 days and males at 56 days. Feed conversion ratios, total mortality including culls, the proportion of rejects at the processing plant, and the moisture content of the litter were not significantly different between the two control methods. Growth curves showed that there was no post-vaccinal growth check in the vaccinated birds and no intolerance of the anticoccidial drug treatment. There was no overall seasonal effect, regardless of treatment, on the performance of the three crops reared from November 1997 to July 1998. These findings suggest that the use of this vaccine is likely to enable the replacement of anticoccidial drug shuttle programmes in broilers reared under conditions similar to those used in these Italian flocks.

Data collected by Agri Stats Inc. in the US for the years 1995 to 1999 was evaluated to determine the types of anticoccidial drug programs used by broiler plants, their frequency and duration, and whether there was any correlation with performance of the birds. Information was available for five feed types (prestarter, starter, grower, first withdrawal, and final withdrawal). The most popular program was an ionophore (ION; principally salinomycin) in starter and grower feeds. A chemical (principally nicarbazin) was also used in the starter feed followed by an ION in the grower feed, or two different ION in the starter and grower feeds. Seasonal differences were apparent in the type of program and in the frequency of program changes. There was no consistent pattern in the sequence with which different programs were employed. There were no significant differences in calorie conversion or the number of days to produce a 2.27 kg bird, whether a single ION or a chemical followed by an ION was used, but mortality was significantly higher for the latter. For 1999, calorie conversion and mortality were higher in plants where chemical-ION programs had been used for more than 40% of the time during the previous 4 yr. The duration and frequency with which different programs were employed were similar whether birds were raised to final weights of 1.5 to 2.0 kg, 2.0 to 2.5 kg, or more than 2.5 kg. There were significant differences in the use of salinomycin and nicarbazin in different regions of the US.

Coccidia were isolated from a commercial broiler farm with a history of suspected drug resistance. The sensitivity profiles of the Eimeria spp. isolates against the anticoccidial drugs nicarbazin (NIC), narasin (NAR), halofuginone (HAL), salinomycin (SAL), meticlorpindol plus methylbenzoquate (MET), and monensin (MON) at the recommended dose levels were followed in three battery trials (B1, B2, B3) corresponding to a field study over three periods of commercial broiler keeping (F1, F2, F3). Shuttle programs were performed in F1 (NIC/MON) and in F2 (MET/MON) while only SAL was used in F3. Eimeria acervulina and E. tenella were isolated from indicator birds in F1 while only E. acervulina could be found during F2 and F3. In trial B1 the isolate from F1 was identified as resistant against HAL and partly resistant against NIC and MON, the two drugs that were used in F1. Following the replacement of NIC in the starter feed by MET the respective isolate from F2 showed no resistance against ionophores (trial B2) while partial resistance against HAL was still present. Since SAL was the most efficient drug in B1 and B2 only this drug was applied in F3. Apart from a resistance against HAL no resistance against any of the other tested anticoccidials was found in the isolate from F3. SAL controlled coccidiosis efficiently in the field and best productivity was recorded in F3. This study shows that battery trials have a good predictive value in respect to the efficacy of anticoccidials under the conditions of commercial broiler production.

Seven anticoccidial drugs commonly used in poultry (diclazuri), monensin, salinomycin, halofuginone, nicarbazin, robenidine, amprolium, and lasalocid) were tested for residual activity after withdrawal. In each test, the products were given at the recommended level to cages of 10 broiler chickens. Oral inoculation with coccidia was given after withdrawal of medication. Birds pretreated with 1 ppm of diclazuril and inoculated with Eimeria tenella after drug withdrawal had normal weight gain and very low lesion scores. Residual activity depleted gradually over several days, as shown by higher lesion scores when medication was withdrawn for up to 3 days before inoculation. Similar results were observed when young birds were inoculated with a mixture of E. tenella, E. maxima and E. acervulina, and also when birds were given diclazuril to market weight (6 weeks of age) and inoculated with a mixture of six species of Eiméria (The above species plus E. brunetti, E. mitis, and E. necatrix) after withdrawal of medication for 2 days. In contrast, there was no evidence of residual anticoccidial activity with nicarbazin, halofuginone, lasalocid, amprolium, salinomycin or monensin. Overall, the residual activity was unique to diclazuril.

The performances of three different strains of male and female broiler or roaster chickens immunized at 1 day of age with a drug-resistant field isolate of Eimeria maxima were evaluated in battery and floorpen immunization trials. No difference in immunization potential was seen between these strains or sexes of day-old chickens immunized with 2500 oocysts/bird of E. maxima and challenged at 10 days of age with 25,000 oocysts/bird of the same isolate in two separate battery trials. All immunized birds showed significant protection for the parameters of weight gain and midintestinal lesion scores at 7 days post challenge (PC) when compared with nonimmunized challenged controls. In two separate floorpen trials, one broiler bird strain (designated strain 2) immunized by the same procedure and challenged at 21 days of age with the equivalent of 25,000 oocysts/bird of the same isolate showed significant protection for weight gain and lesion scores at 7 days PC when compared with nonimmunized controls. Birds in these same floorpen experiments immunized with E. maxima and then fed three different anticoccidial shuttle diets (narasin and nicarbazin 90 grams/ton (g/t) in starter feed and narasin 72 g/t + roxarsone 45.4 g/t in grower feed; nicarbazin 113 g/t in starter feed and narasin 72 g/t + roxarsone 45.4 g/t in grower feed; and monensin 100 g/t in starter and grower feed) showed no interference with elicited immunity with E. maxima challenge for the same parameters measured. No significant difference was seen between any floorpen immunized bird groups for total weight gain at trial terminations (49 days of age).

The incidence of oocysts was monitored in the litter at two broiler farms where birds were reared to 8 wk of age using a shuttle program involving nicarbazin (from 0 to 21 days of age) and salinomycin (from 21 to 44 days of age). Some birds from these farms were challenged with three species of Eimeria to see whether immunity had developed as a result of prior exposure to infection. Oocysts of at least three species of Eimeria were present in small numbers in the litter. Birds from both farms were immune to Eimeria acervulina and Eimeria maxima (judged by weight gain) although the immunity was incomplete as evidenced by oocyst production. Birds from one farm were immune to Eimeria tenella (judged by weight gain) but birds from the other farm were susceptible to this species.

The influence of coccidiosis on colonization of Salmonella typhimurium in broiler chickens under floor pen conditions was studied by semiquantitative methods. Chickens of two groups, unmedicated and medicated with nicarbazin (125 ppm via the feed), were exposed to three species of Eimeria (Eimeria tenella, Eimeria maxima, and Eimeria acervulina) at 2, 3, and 4 wk of age and given S. typhimurium in the feed 2 days later. Salmonella typhimurium was isolated most often (100%) from ceca of chickens exposed at 3 wk of age. Birds in the unmedicated group were positive for S. typhimurium at a higher rate than those in the medicated group. Salmonella typhimurium was detected in livers only in a few unmedicated birds.

One study was conducted utilizing 192 male broilers, at 4 to 7 wk posthatching, to evaluate a narasin-nicarbazin drug combination (Maxiban) for effects on bird growth rate, feed efficiency, and survivability during cycling ambient temperature (24 to 35 C) distress. Maxiban did not impact (P greater than .1) live weight gain, but reduced (P less than .05) gain:feed ratio (unadjusted for mortality), from .29 for controls to .21 as bird survivability declined (P less than .05) from 87.5 to 69.8%. Adjusting feed efficiency by adding the gain of birds dying of heat prostration to that for birds surviving the experiment resulted in feed efficiency for Maxiban-supplemented birds being similar (P = .48) to birds not consuming Maxiban. Under the conditions of the present study, Maxiban increased the mortality rate of male broilers exposed to cycling ambient temperature of 24 to 35 C during 4 to 7 wk posthatching.

Continuous programs of a combination of narasin (40 ppm) and nicarbazin (40 ppm) (NaNi), narasin at levels of 60 and 70 ppm, and a 2 by 2 factorial shuttle design (NaNi or nicarbazin at 125 ppm, each for 27 or 28 days, followed by narasin at 60 or 70 ppm to termination), were compared with unmedicated controls for their anticoccidial efficacy and growth performance in nine broiler trials conducted in seven countries outside the United States. Cecal coccidial lesions were reduced only by treatments that incorporated nicarbazin either at the 40-ppm level in NaNi or at 125 ppm, whereas total intestinal lesion scores were reduced by all the anticoccidial programs tested. At Day 28, the three treatments containing NaNi and the treatment containing narasin at 60 ppm significantly improved weight gain and feed efficiencies over the two treatments containing nicarbazin at 125 ppm and the unmedicated controls. At termination all the anticoccidial programs significantly decreased the mortality rate and improved bird weights and feed efficiencies. Birds on the treatments containing NaNi either in the two shuttle programs or in the continuous program were significantly heavier than those on the two treatments containing nicarbazin at 125 ppm in shuttle programs.

Feed additive anticoccidials currently used in Japan were examined for possible effects on oocyst sporulation of Eimeria tenella. Monensin, salinomycin, lasalocid, amprolium plus ethpabate, amporolium plus ethopabate plus sulfaquinoxaline, clopidol, or nicarbazin were given to chickens continuously via the feed at the recommended use level or one-half of that level. Oocysts discharged in feces 7-8 days post inoculation (PI) were collected and aerated for sporulation. Low sporulation rate was noted, when clopidol at 62.5 mg kg-1 was given from 4 to 7 days PI. These oocysts were as infective as oocysts from controls, based on weight gain, feed efficiency, gross lesion score of cecae, and oocyst count 7 days PI. The results of the study indicated that the second schizogony and gametogony are vulnerable to clopidol, as evidenced by oocyst sporulation, but infectivity of these sporulated oocysts was not affected.

(1) The efficacy of toltrazuril (Baycox) against coccidiosis was established on a broiler farm in an intermittent application during five consecutive growing periods. Treated birds were fed a broiler ration without anticoccidials. The efficacy of Baycox was compared with the nicarbazin-salinomycin shuttle. It was concluded that Baycox retarded the onset of Eimeria infection for several weeks. During the fifth rearing period coccidiosis problems emerged on the farm in all birds during medication, suggesting development of resistance. (2) During a laboratory experiment the efficacy of Baycox was studied in birds after inoculation with different numbers of oocysts at 7, 10 or 15 days of age. Baycox was applied at 10 and 11 days of age. In all cases medication with Baycox protected birds from coccidiosis during a period of at least 7 days. This effect of Baycox could be due to the long-existing tissue levels of the product and its metabolites as well as its specific effect on the second generation of schizonts. (3) In another laboratory experiment coccidia obtained from field trials were tested for sensitivity to Baycox in conjunction with two strains obtained from farms were coccidiosis emerged during application. The inoculation model developed in this study was used for sensitivity testing. One of the Eimeria strains tested was resistant to the product, one strain was tolerant and the remaining two strains, including the control strain, were fully sensitive to Baycox.

A floor-pen experiment conducted to study the anticoccidial efficacy of a number of drugs coincided with prolonged periods of hot weather and provided a good opportunity to study the interactions of anticoccidial drugs and environmental temperature. Six replicates of 60 day-old male chicks were fed one of the experimental diets for 48 days followed by a 5-day withdrawal period. The treatments consisted of unmedicated, salinomycin (60 ppm), monensin (100 ppm), arprinocid (60 ppm), halofuginone (3 ppm), amprolium/ethopabate (125/4 ppm), nicarbazin (125 ppm), and clopidol (125 ppm). Coccidiosis exposure was produced by mixing the suspensions of oocysts with the feed. Eleven heat related mortality episodes were recorded in the period of the experiment. All the mortality peaks were recorded at environmental temperatures at or above 37.8 C and relative humidity of 80 to 98%. Heat stress caused an excessive mortality in nicarbazin treated birds at an early age (18 to 29 days of age), while heat related mortality was low at this age with other drug treatments. Total heat related mortality with nicarbazin treated birds was significantly higher (59.2%) than the other treatments (8 to 18.6%). In order to investigate further the interaction of environmental temperature and nicarbazin, two battery trials were conducted in controlled environmental rooms. No heat stress mortality was recorded in the period of the first trial when nicarbazin treated birds were exposed to a constant environmental temperature of 32.2 C; however, their performance was affected. The results of the second trail showed that when nicarbazin treated birds were exposed to a constant environmental temperature of 37.8 C they suffered more severely from the heat stress than the unmedicated group in a short period of time. The results of these experiments confirmed that an interaction exists between high environmental temperatures and the anticoccidial drug nicarbazin.

Processed yields (percent hot carcass) and cooked meat flavor of broilers fed 100 ppm of an anticoccidial agent (a mixture of 50 ppm narasin and 50 ppm nicarbazin) were compared with yields of birds fed a ration without the anticoccidial agent. Broilers were processed at 7 wk of age (49 days) after a 4-day withdrawal from the anticoccidial agent for the treated birds. The flavor of meat was evaluated by a 12-member sensory panel. Meat was either deep fat-fried or oven roasted. Sensory evaluations were made on freshly cooked samples and on cooked meat refrigerated for 24 h and reheated. The anticoccidial agent did not produce a difference (P greater than .05) in the hot carcass yields of the broilers as compared with control birds fed the nonmedicated diet. Analyses of triangle test data for flavor evaluations by two statistical methods indicated that there were no detectable differences (P greater than .05) in flavor between broilers fed the anticoccidial agent in the diet and those fed the control diet.

Faecal samples were also collected from broiler farms presenting birds for autopsy. 126 Samples were examined, using two methods. Oocysts were detectable 3.5 days previously on an average before the presence of coccidiosis was determined at autopsy. Of the faecal samples 65.9 per cent were positive, and 46.0 per cent of the findings at autopsy were positive for coccidiosis. Examination of the faeces showed that more cases of mixed infection were present than could be concluded from autopsy. The largest number of oocysts was observed in E. acervulina infection, though large numbers of oocysts were also detected in cases of mixed infection. Treatment with nicarbazin during te first three weeks of life was found to delay the appearance of coccidiosis. The frequent use of withdrawal periods in the administration of anticoccidial drugs in view of 'thinning' showed high excretion rates.

Features of the anticoccidial activity of nicarbazin, amprolium, zoalene, sulphadimidine, diaveridine, Darvisul, spiramycin, chloramphenicol and oxytetracycline have been re-investigated both in vivo and in cell culture using Eimeria tenella. Of the drugs studied, only spiramycin was appreciably coccidiocidal, although nicarbazin and amprolium showed possibly slower coccidiocidal activity. In order to show activity against a particular stage in the life-cycle, higher concentrations of drug than those usually recommended for field usage had in most cases to be used. Under these conditions, parasites were usually inhibited as multinucleate 1st generation schizonts. With delayed medication, effects against 2nd generation parasites were in most cases found, and in many cases, although the parasites never matured to give viable merozoites, the large degenerating forms produced were able to cause extensive tissue destruction and haemorrhage. Methodology in this type of study is discussed in relation to more active and more recent anticoccidials, and some further experiments with robenidine reported.

The efficacy of mixtures of narasin and nicarbazin were evaluated by comparing broiler performance, susceptibility to heat stress, and the mode of action against Eimeria. In a floor pen trial, narasin (70 ppm) alone or in combination with nicarbazin at levels between 10/10 and 50/50 ppm gave significantly better performance than unmedicated birds or birds given nicarbazin at 125 ppm alone. Amelioration of nicarbazin-associated mortality with heat as a stressor was observed in birds given the 50/50 ppm mixture of narasin and nicarbazin: mortality in these birds was similar to that of unmedicated birds and was reduced by 15 to 20% of that occurring in birds in the nicarbazin (125 ppm) treatment. The narasin/nicarbazin mixture (50/50) appears primarily to prevent further development of sporozoites. However, in birds treated with 25/25 ppm of narasin and nicarbazin, both the deleterious action of nicarbazin on merogeny and the antisporozoite activity of narasin were observed.

A strain of the cecal coccidian of chickens, Eimeria tenella, was propagated serially in chickens fed mash containing amprolium, nicarbazin, Unistat, or zoalene. Each group of chickens received a different coccidiostat on a rotating basis. The strain was propagated through 40 groups of chickens; thus, the strain was intermittently exposed 10 times to each coccidiostat. The end product of this simulated shuttle program of prophylactic anticoccidial medication was a strain resistant to three of the four coccidiostats involved. Resistance to nicarbazin was not evident.

Nutritional encephalopathy was induced in young chicks by vitamin E-deficient diets containing either 4% methyl esters of safflower oil or 10% thermally oxidized safflower oil. The coccidiostat nicarbazin (an equimolecular complex of 4,4'-dinitrocarbanilide and 2-hydroxy 4,6-dimethylpyrimidine) reduced the incidence of encephalopathy, but zoalene (3,5-dinitro-o-toluamide) and amprolium [1-(4-amino-2-n-propyl-5-pyrimidinylmethyl)-2-picolinium chloride hydrochloride] did not. Neither of the two components of nicarbazin affected the rate of development of encephalopathy when fed separately, but when included together in the diet, they reduced the incidence of the disease.

Duocoxin, nicrazine and amprol plus showed no therapeutic effect in 50 mice each of which was infected with 25,000 organisms of a virulent Toxoplasma strain.