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A novel approach to the control of anthelmintic-resistant Haemonchus contortus in sheep.

This paper reports attempts to control a resistant strain of Haemonchus contortus on pasture by replacing it with a susceptible strain. By making use of artificially infected donor sheep, six camps (paddocks) were seeded with a resistant field strain of H. contortus until it was confirmed by means of worm-free tracer lambs that the grazing had become infective. Thereafter, using donor sheep infected with a susceptible laboratory strain of H. contortus for seeding the pasture, attempts were made at various times of the year to replace the resistant strain on the pasture with the susceptible strain in five of the camps. The sixth remained as a control camp, in which no attempt was made to replace the resistant strain. In two of the five test camps, the susceptible strain was introduced in the autumn after 8-10 weeks of nil grazing; in the remaining three camps the introduction was made in spring (two camps) or summer without having a period of nil grazing. The susceptibility of the worm strains introduced initially, as well as of those that developed in the various camps, was gauged both by controlled non-parametric anthelmintic slaughter trials at the beginning and at the conclusion of the trial, and by an in vitro egg hatch test. A reversion to susceptibility occurred in three of the five camps. These included both of the camps infested with the susceptible strain in the spring and one of the two infested in the autumn. Possible reasons for the failure to replace the resistant strain in the remaining two test camps are discussed.

Animals↗

Milk yield increase after anthelmintic treatment of dairy cattle related to some parameters estimating helminth infection.

On 81 farms blood samples were taken from adult dairy cattle, on pasture in October 1986 and after stabling in December 1986, to measure antibody titres against the nematodes Dictyocaulus viviparus, Cooperia spp. and Ostertagia spp., and the trematode Fasciola hepatica, and serum pepsinogen values. Faecal samples, collected in October, were examined to confirm the presence of parasites by means of egg counts and larval identifications. From December until the end of the stabling period, dry cows were either treated with albendazole or left untreated in alternate sequence of calving date. Treated cows produced 132.9 kg milk per cow per lactation more than untreated cows (P less than 0.01). Fat and protein percentage were not significantly influenced by anthelmintic treatment. The mean herd milk yield response to treatment varied from -889 to +1231 kg milk per cow per lactation. There was a significant between-herd variation in antibody titres against nematodes and in pepsinogen values. However no significant correlations between these parameters and the mean herd milk yield response to treatment were found.

Albendazole↗

The efficacy and persistent anthelmintic effect of ivermectin in sheep.

The direct efficacy and the long-term persistent anthelmintic effect of an oral suspension and an injectable formulation of ivermectin at a dose rate of 0.2 mg kg-1 was studied in sheep. Lambs were infected experimentally with Haemonchus contortus, Trichostrongylus vitrinus and Cooperia curticei. After 3 weeks they were treated with an oral suspension or with an injection, and reinfected with the same dose of larvae 3, 6 or 10 days after treatment. Post-mortem worm counts showed no persistent effect of the oral suspension. The injectable formulation showed an excellent persistent effect for up to 10 days against H. contortus. Reinfection with C. curticei 3 days after treatment resulted in a 64% reduction of the worm burden, but reinfection after 6 and 10 days was 100% reduced. The reduction of T. vitrinus was 46% after 3 days and 92% after 6 and 10 days.

Administration, Oral↗

Interaction of anthelmintic benzimidazoles with Ascaris suum embryonic tubulin.

The ability of mebendazole and fenbendazole to bind to tubulin in cytosolic fractions from 8-day Ascaris suum embryos was determined by inhibition studies with [3H]colchicine. Colchicine binding in the presence of 1 . 10(-6) M mebendazole was completely inhibited during a 6 h incubation period at 37 degrees C. Inhibition of colchicine binding to A. suum embryonic tubulin by mebendazole and fenbendazole appeared to be noncompetitive. The inhibition constants of mebendazole and fenbendazole for A. suum embryonic tubulin were 1.9 . 10(-8) M and 6.5 . 10(-8) M, respectively. Mebendazole and fenbendazole appeared to be competitive inhibitors of colchicine binding to bovine brain tubulin. The inhibition constants of mebendazole and fenbendazole for bovine brain tubulin were 7.3 . 10(-6) M and 1.7 . 10(-5) M, respectively. These values are 250-400 times greater than the inhibition constants of fenbendazole and mebendazole for A. suum embryonic tubulin. Differential binding affinities between nematode tubulin and mammalian tubulin for benzimidazoles may explain the selective toxicity. The importance of tubulin as a receptor for anthelmintic benzimidazoles in animal parasitic nematodes is discussed.

Animals↗

High-performance liquid chromatographic method for the determination of the anthelmintic nitroxynil in cattle muscle tissue with on-line anion-exchange clean-up.

A high-performance liquid chromatographic method for the determination of the anthelmintic nitroxynil has been developed. The drug was extracted from cattle muscle tissue with 1% triethylamine in acetonitrile. The extract was evaporated to dryness and taken up in 0.1 M ammonium acetate-acetonitrile (50:50, v/v). The extract was then injected onto a polymeric anion-exchange precolumn. After clean-up with 0.1 M ammonium acetate-acetonitrile (50:50, v/v) for 5 min, the precolumn was eluted with 1% aqueous trifluoroacetic acid-acetonitrile (50:50, v/v) onto a PLRP-S polymer column and chromatographed with a mobile phase of 0.01 M phosphate pH 7-acetonitrile (80:20, v/v). Detection was by ultraviolet at 273 nm. Average recoveries at four levels from 0.005 to 1.000 mg kg-1 were > 88%. The limit of determination was 0.005 mg kg-1.

Animals↗

Marine pharmacology in 2001--2002: marine compounds with anthelmintic, antibacterial, anticoagulant, antidiabetic, antifungal, anti-inflammatory, antimalarial, antiplatelet, antiprotozoal, antituberculosis, and antiviral activities; affecting the cardiovascular, immune and nervous systems and other miscellaneous mechanisms of action.

During 2001--2002, research on the pharmacology of marine chemicals continued to be global in nature involving investigators from Argentina, Australia, Brazil, Canada, China, Denmark, France, Germany, India, Indonesia, Israel, Italy, Japan, Mexico, Netherlands, New Zealand, Pakistan, the Philippines, Russia, Singapore, Slovenia, South Africa, South Korea, Spain, Sweden, Switzerland, Thailand, United Kingdom, and the United States. This current article, a sequel to the authors' 1998, 1999 and 2000 marine pharmacology reviews, classifies 106 marine chemicals derived from a diverse group of marine animals, algae, fungi and bacteria, on the basis of peer-reviewed preclinical pharmacology. Anthelmintic, antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antiprotozoal, antituberculosis or antiviral activities were reported for 56 marine chemicals. An additional 19 marine compounds were shown to have significant effects on the cardiovascular, immune and nervous system as well as to possess anti-inflammatory and antidiabetic effects. Finally, 31 marine compounds were reported to act on a variety of molecular targets and thus may potentially contribute to several pharmacological classes. Thus, during 2001--2002 pharmacological research with marine chemicals continued to contribute potentially novel chemical leads for the ongoing global search for therapeutic agents for the treatment of multiple disease categories.

Animals↗

An inventory of the ethnobotanicals used as anthelmintics in the southern Punjab (Pakistan).

A survey was conducted in southern Punjab, Pakistan, in order to document existing ethnobotanical knowledge by the herdsmen/key respondents about anthelmintics in ruminants. A 3-satge process was used to document the plants being used to treat and/or control helminthes. This paper describes 29 plants to treat helminthosis in ruminants. The main plants used were Lamium amplexicaule L., Mallotus philippinensis Muell., Withania somnifera (L.) Dunal., Azadirachta indica A. Juss., and Citrullus colocynthis (L.) Schrad. A few of these plants have been scientifically validated for their claim by herdsmen on modern lines while majority of them still needs investigations. This documentation could provide a foundation for the scientific study and verification of those plants which merit such study.

Animals↗

Voltammetric assay of the anthelmintic veterinary drug nitroxynil in bulk form and formulation at a mercury electrode.

The electrochemical behavior of the anthelmintic veterinary drug nitroxynil at the mercury electrode was studied in a series of Britton-Robinson universal buffer of pH 1.9-11 containing 20% (v/v) ethanol using dc-polarography cyclic voltammetry and controlled-potential coulometry. The voltammograms exhibited two irreversible cathodic steps over the pH range 1.9-10.2; the height of the first step is double that of the second one. Controlled-potential coulometry in the B-R universal buffer of pH 1.9-10 at a mercury pool working electrode revealed the consumption of four and two electrons via the first and second reduction steps, respectively, which attributed to reduction of the NO2 group to the hydroxylamine stage (first step), and then to the amine stage (second step). Three voltammetric analytical procedures including dc-polarography, differential-pulse adsorptive stripping voltammetry and square-wave adsorptive stripping voltammetry were optimized for the direct determination of bulk nitroxynil. The three proposed procedures were applied for analysis of bulk nitroxynil with limits of detection of 3 x 10(-5), 1.31 x 10(-8) and 8.4 x 10(-10)M and limits of quantification of 1 x 10(-5), 4.36 x 10(-8) and 2.80 x 10(-9)M, respectively. The three procedures were successfully applied to the determination of nitroxynil in formulation (Dovenix, 25% nitroxynil injection solution) without the necessity for sample pretreatment and/or time-consuming extraction steps prior to the analysis.

Antiplatyhelmintic Agents↗

Evaluation of a larval development assay (DrenchRite) for the detection of anthelmintic resistance in cyathostomin nematodes of horses.

A larval development assay (LDA, DrenchRite) was evaluated to determine the effectiveness of this method in detecting anthelmintic resistance in cyathostomin nematodes of horses. A total of 15 horse farms from Georgia and South Carolina (USA) and Population S ponies from the University of Kentucky (USA) were included in this study. Nematode eggs were extracted from pooled fecal samples and placed into the wells of a DrenchRite plate for testing against thiabendazole (TBZ), levamisole (LEV) and 2 ivermectin (IVM) analogs (IVM-1, IVM-2). After a 7-day incubation larvae in each well were counted and data were analyzed by logistic regression. Resistance status of each farm for different drugs was determined in a separate study using a fecal egg count reduction test. LDA were performed on the 15 farms once, however, the Population S cyathostomins were assayed on 3 separate occasions to estimate the consistency of results between assays. Mean TBZ LC50 for oxibendazole resistant, suspected resistant and sensitive farms were 0.2015, 0.1625, and 0.1355 microM, respectively. For LEV, mean LC50 for PYR resistant, suspected resistant and sensitive farms were 1.590, 1.8018 and 1.4219 microM, respectively. All 15 farms had worms susceptible to IVM; mean LC50 for IVM-1 and for IVM-2 were 7.5727 and 87.9718 nM, respectively. A linear mixed model was fitted to the data to determine the relationship between LC50 and LC95 and resistance status for each farm. No meaningful relations were found. Consistency of assays varied between drugs, being best for TBZ and worst for LEV and IVM-1. All farms in this study had benzimidazole-resistant nematodes; therefore usefulness of DrenchRite for discriminating susceptibility versus resistance to this drug class could not be accurately assessed. Moreover, since all farms tested were sensitive to IVM and resistance to this drug class has not yet been reported in cyathostomins, it is not possible to assess accurately the usefulness of DrenchRite LDA for detecting IVM resistance at this time. Assay results for LEV suggest that LEV in a LDA does not yield data that is useful in estimating PYR efficacy in vivo. Based on results for PYR/LEV, the current high prevalence of benzimidazole resistance, no known cases of IVM resistance, and the sometimes extreme variation in results seen in many of the assays, DrenchRite LDA cannot be considered a useful tool for the diagnosis of resistance in cyathostomins of horses at present.

Animals↗

Anthelmintic resistance in cattle nematode in the western Pampeana Region of Argentina.

During the past three years there have been several reports of cattle anthelmintic resistance (AR) in Argentina. Twenty-five cattle herds in the west fattening area of the Pampeana Region were surveyed to assess the prevalence of AR and the species of nematode involved. The survey involved fattening and cow-calf systems with a mean of 6760 bovines. Resistance was determined in vivo by a faecal egg count reduction test (FECRT). Efficacies from the World Association for the Advancement of Veterinary Parasitology (WAAVP) formula were compared with those obtained from the Abbott formula. Sixty 6-12-month-old calves were selected from each property and divided into four groups, namely, IVM (ivermectin, 0.2mg/kg), BZD (fenbendazole, 5mg/kg or albendazole 7.5mg/kg), LVM (levamisole, 7.5mg/kg) and Control (untreated group). Nematode larvae were identified by four pooled faecal cultures for each group. Cooperia and Ostertagia were the predominant nematode larvae in pre-treatment cultures. The mean FECRT efficacies for IVM, BZD and LVM were 81.0+/-21%, 93.3+/-8% and 97.6+/-4%, respectively. AR was detected in 16 (64%) herds. IVM resistance was present in 15 herds and BZD resistance in eight herds (32%). Resistance to both ivermectin and fenbendazole was present in seven herds. LVM resistance was not detected. Cooperia was the predominant post-treatment nematode in all the herds with IVM resistance. In one herd with IVM resistance, Ostertagia counts were slightly increased over pretreatment counts. Ostertagia was the prevalent post-treatment genera in herds with BZD resistance. A high level of resistance to ivermectin was recorded in this fattening region of Argentina. Also several herds with resistance to benzimidazole were observed. These results show the importance of AR in Argentinian cattle production. High correlation between WAAVP and Abbott formulae was observed. However, under some uncertain diagnosis, both formulae could be applied as complementary to help result interpretations.

Albendazole↗

Anthelmintic resistance revisited: under-dosing, chemoprophylactic strategies, and mating probabilities.

Deterministic and stochastic models are used to examine the evolution of anthelmintic resistance among trichostrongylid parasites of domestic ruminants. We find that the relative selection pressures exerted by chemoprophylactic (preventive) control strategies, chemotherapeutic (salvage) control strategies, and regimens involving "under-dosing" are critically dependent on a variety of host and parasite parameters (particularly host immunity and grazing behaviour, parasite fecundity, and the survival of the free-living stages on the pasture). Chemoprophylactic strategies are not necessarily more likely to exert a stronger selection pressure than chemotherapeutic strategies. Similarly, as one reduces dosage levels, there is a range of dose levels where under-dosing promotes resistance and a range of dose levels where under-dosing impedes resistance. The most dangerous dose is either that necessary to kill all the susceptible homozygotes, or that necessary to kill all the susceptible homozygotes and all the heterozygotes. Which one prevails depends upon model parameters. The stochastic formulation indicates that spatial heterogeneity in transmission may be a significant force in promoting the spread of resistant genotypes--at least when infection is at low levels.

Animals↗

Reproductive responses of beef heifers after concurrent administration of vaccines, anthelmintic and progestogen.

A study was conducted to determine whether concurrent administration of vaccines for reproductive diseases and an anthelmintic, given immediately prior to estrus synchronization with a progestogen, would affect subsequent estrous response and fertility in beef heifers. Two hundred ninety-five yearling crossbred beef heifers on 3 ranches in Oregon and Kansas were assigned to 1 of 2 treatments. Control heifers were vaccinated and dewormed 30 d prior to the anticipated breeding. Treated heifers received the same vaccination and deworming products 9 d prior to breeding. All heifers in both groups were treated with norgestomet (Syncro-Mate-B) for 9 d to synchronize estrus. The administered vaccine consisted of modified live virus for infectious bovine rhinotracheitis, parainfluenza and bovine viral diarrhea, with 5-way bacterin for leptospirosis and bacterin for vibriosis. Heifers were also administered ivermectin or fenbendazole for deworming. Heifers exhibiting synchronized estrus were artificially inseminated and subsequently exposed to fertile bulls. Pregnancy status was determined at a later date by palpation per rectum. Vaccination and deworming at the time of treatment with progestogen compared with immunizing and deworming 30 d prior to breeding did not impair the expression of behavioral estrus. The percentage of treated heifers conceiving to AI or natural service did not differ from that of the respective control heifers. These data suggest that vaccination, deworming and synchronization of estrus with norgestomet can be performed simultaneously without any detrimental effects upon occurrence of behavioral estrus or fertility.

Journal Article↗

Biannual anthelmintic treatments in village Djallonke sheep in The Gambia: effects on productivity and profitability.

An on-farm deworming trial was conducted between 1991 and 1995 on traditionally managed Djallonke sheep in The Gambia to assess the impact on productivity and profitability of prophylactic biannual anthelmintic treatments- Fifteen private flocks with an average of 25 animals per flock participated in the experiment. Half of each flock was dewormed twice a year while the other half served as the control group. The two productivity traits that were significantly improved by the treatment scheme tested were the number of lambs per lambing which increased from 1.11 +/- 0.31 (Mean +/- S.D.) to 1.19 +/- 0.39 and the number of lambings per year which improved from 1.04 +/- 0.53 to 1.22 +/- 0.47. The mortality and weight at 12 months were not significantly affected by the treatment. Monitoring of sheep sales in the flocks and on surrounding markets allowed the calculation of a rate of return to the treatment scheme tested of 246%. Despite large variations in returns. The scheme studied is recommended as over 90% of the adopting farmers would yield positive returns to their investment.

Animal Husbandry↗

The anthelmintic efficacy of the plant, Albizia anthelmintica, against the nematode parasites Haemonchus contortus of sheep and Heligmosomoides polygyrus of mice.

Albizia anthelmintica Brong., belongs to the plant family Mimosaceae. The plant is widely used in East Africa by poor smallholder farmers and pastoralists to treat their livestock against internal parasites. The anthelmintic effects of water extracts from the bark of A. anthelmintica, obtained from three different geographic areas in Kenya and using different methods of preparation, were tested at different doses in sheep and mice infected with the nematode parasites Haemonchus contortus and Heligmosomoides polygyrus, respectively. Lambs were infected with 3000 infective larvae of H. contortus and treated with the plant preparations 28 days later, while mice were infected with 200 infective larvae of H. polygyrus and treated 18 days later. Proximate analysis established high levels of crude proteins in A. anthelmintica bark. Two sheep out of the 45 treated with the plant preparations suffered from transient bloat, which was relieved by dosing with a surfactant. Significant reductions in faecal egg counts were observed in lambs treated with A. anthelmintica in two of the three experiments undertaken, but the efficacy levels achieved were well below the 70% reduction required. Similar values of packed red cell volume and live weight gain were observed for treated and control lambs. There was no overall significant effect of treatment with A. anthelmintica on faecal egg and total worm counts in mice. A dose rate of 1000 mg/kg bodyweight of A. anthelmintica preparation resulted in death of all mice. The results show that A. anthelmintica at the doses and preparations used is not efficacious against H. contortus in sheep or against H. polygyrus in mice.

Albizzia↗

Effects of three nematode anthelmintic treatment regimes on flock performance of sheep and goats under extensive management in semi-arid Kenya.

A study was undertaken in a semi-arid area of Kenya between August 1991 and June 1993 to evaluate the effects of anthelmintic treatment using ivermectin before or during the rains, on performance of mixed sheep and goat flocks, in comparison with an untreated flock. Performance parameters measured included age and weight of dams at first parturition, parturition intervals, body weights of dams and offspring, and birth weights, growth rates, and mortality rates of offspring. Among these parameters, birth weights and growth rates of offspring were found to be significantly improved by the treatment administered before the rains compared with the other two treatments. Mortality was lower in lambs and kids with high birth weights. Treatment, either before or during the rains, significantly reduced the faecal egg output and improved body weight, packed cell volume and flock fertility. Liveweight was confirmed to be a better measure of sexual maturity than age. It was further shown that lambs and kids, born of dams at their first lambing or kidding, experienced higher mortality rates than lambs and kids born of dams in their second and subsequent parturitions. Overall, treatment with ivermectin before the onset of rains was equal to or better, in terms of the performance parameters measured, than treatment during the rains, whilst treatment compared with no treatment increased performance in almost all of the parameters measured.

Albendazole↗

Multiple anthelmintic resistance on a goat farm in Kenya.

The anthelmintic efficacy of benzimidazoles, levamisole, rafoxanide and ivermectin was evaluated on an institutional farm in Kenya using faecal egg count reduction test, larval cultures and a controlled slaughter trial. The results of this study indicated simultaneous resistance of Haemonchus contortus against benzimidazoles, levamisole and rafoxanide and Trichostrongylus columbriformis and Oesophagostomum sp. against levamisole on the same farm. Injectable and orally administered ivermectin was effective against the benzimidazole and levamisole resistant H. contortus.

Albendazole↗

Estimation of anthelmintic compound 81/470 in cow's milk by high-performance liquid chromatography: method development and validation.

CDRI compound 81/470 is a new broad spectrum anthelmintic agent and is being developed for veterinary use. HPLC assay method for 81/470 in cow milk was developed and validated. The sample preparation consisted of protein precipitation, followed by extraction with ether. Separation was achieved on a C18 column using acetonitrile-buffer (pH 6, 50 mM) mobile phase and the compound was quantitated using fluorescence detector. The recovery of 81/470 was above 90% and was consistent over the calibration range of 10-1000 ng ml-1. Accuracy and precision were determined by analyzing replicate samples and were found to be within acceptable limits. Five freeze-thaw cycles of spiked milk and storage of processed dry residues at -30 degrees C for 7 days did not have any detrimental effect on the stability of 81/470.

Animals↗