Drug resistance in ostertagiasis

Benzimidazole- and levamisole-resistant Ostertagia circumcincta from sheep have been reported from several countries, but there are no reports of anthelmintic-resistant O. ostertagi in cattle, where resistance has been confirmed in controlled trials. The reasons for this may include (1) the biology of the worm, (2) avoidance of drug action by inhibition, (3) host metabolism of drugs, (4) less anthelmintic used in cattle than in sheep, (5) high costs of controlled trials, (6) lack of adequate in vitro tests to detect resistant worms and (7) lack of reporting of anthelmintic failures. Reduced efficacy of the anthelmintics levamisole and thiabendazole to adult O. ostertagi and of modern benzimidazoles to the inhibited L4 larvae has been reported in cattle. This latter effect might, in part, represent a stage-specific expression of resistance. Although anthelmintic resistance in O. ostertagi is not known to be a problem at present, it could potentially become a serious issue.     

Condensed tannins act against cattle nematodes

The use of natural plant anthelmintics was suggested as a possible alternative control of gastrointestinal nematodes (GIN) in ruminants. Direct anthelmintic effects of tannin-containing plants have already been shown in sheep and goat GIN. These anthelmintic properties are mainly associated with condensed tannins. In the present study, we evaluated possible in vitro effects of three tannin-containing plants against bovine GIN. Effects of Onobrychis viciifolia, Lotus pedunculatus and Lotus corniculatus condensed tannin (CT) extracts on Cooperia oncophora and Ostertagia ostertagi were determined by a larval feeding inhibition assay (LFIA) and a larval exsheathment assay (LEA). In the LFIA, all three plant extracts significantly inhibited larval feeding behaviour of both C. oncophora and O. ostertagi first stage larvae in a dose-dependent manner. The L. pedunculatus extract, based on EC(50) (effective concentration for 50% inhibition), was the most effective against both nematodes, followed by O. viciifolia and L. corniculatus. The effect of CT extracts upon larval feeding behaviour correlates with CT content and procyanidin/prodelphidin ratio. Larval exsheathment of C. oncophora and O. ostertagi L3 larvae (third stage larvae) was also affected by CT extracts from all three plants. In both in vitro assays, extracts with added polyvinylpolypyrrolidone, an inhibitor of tannins, generated almost the same values as the negative control; this confirms the role of CT in the anthelmintic effect of these plant extracts. Our results, therefore, indicated that tannin-containing plants could act against cattle nematodes.     

Persistence of dead Ostertagia ostertagi in the abomasal mucosa following anthelmintic treatment

Anthelmintic trails, conducted with albendazole, fenbendazole and ivermectin for efficacy against gastrointestinal nematodes, principally inhibited early fourth larval stages of Ostertagia ostertagi in naturally infected cattle. Cattle wee slaughtered seven to 20 days after treatment. O ostertagi was the predominant abomasal nematode recovered with occasional small numbers of Haemonchus species and Trichostrongylus axei. Control calves uniformly had very large O ostertagi infections, primarily early fourth stage larvae. Viable surviving worms and variable numbers of dead and degenerate worms were recovered in abomasal contents and washings. These O ostertagi larvae and adults were characterised by adherent debris or proteinaceous material, degenerated cuticles and distortion of internal structures. This study demonstrated the necessity for proper timing of slaughter for anthelmintic trial evaluation to allow clearance of dead nematodes, specifically O ostertagi larvae which are sequestered in the abomasal glandular tissue. Nematode collection within seven to 12 days after treatment will include dead and degenerate larval nematodes. The peripheral coating of larvae was suggestive of the Splendore-Hoeppli effect which has been associated with immunological responsiveness. The antigenic stimulus for this material and the lymphocyte and eosinophil infiltration was suspected to be early fourth stage O ostertagi larvae within the mucosa but was not identified definitively.     

Parasitism in llamas

Llamas in North America are infected with a number of helminth parasites, including: gastrointestinal nematodes, lungworms, meningeal worms, tapeworms, and flukes. Most of these helminths can be treated with the anthelmintic currently used to treat cattle and sheep. At least two protozoan parasites, coccidia and toxoplasma, have been reported in the llamas in North America. Coccidia can be controlled with the anticoccidial drugs used to control these organisms in other domestic animals. Toxoplasma has been reported uncommonly in llamas in North America and control is very difficult. Several external parasites occur in llamas in North America, including lice, mites, ticks, and the deer nasal bot. Except for the deer nasal bot, the other external parasites in the llama can be treated with pesticides approved for use in cattle.     

Probable multigeneric resistance to macrocyclic lactone anthelmintics in cattle in New Zealand

AIM: To establish the efficacy of topical formulations of eprinomectin and abamectin against naturally acquired abomasal and small intestinal nematode infections in cattle purchased from a North Island bull-beef property. METHODS: A controlled slaughter trial, involving eighteen 6-8-month-old mixed breed calves, was conducted in May 2002.The animals were randomly allocated on the basis of faecal egg count to one of three equal-sized groups (n=6), consisting of an untreated control group and two treatment groups. One of the treatment groups was treated with a topical formulation of eprinomectin, the other with abamectin. Both anthelmintics were administered as a single topical treatment on an individual liveweight basis, at the manufacturer's recommended dose rates of 0.5 mg/kg. All calves were housed in separate groups with no access to pasture throughout the entire trial and were slaughtered 7-10 days after treatment. RESULTS: Both anthelmintic treatments were highly effective(worm count reduction >98%) against Ostertagia ostertagi, Trichostrongylus axei and Cooperia punctata, but were not effective at reducing worm counts significantly of either Cooperia oncophora or Trichostrongylus longispicularis. Against these latter two parasites, worm count reductions of only 72% and 79%, and 81% and 76%, respectively, were recorded following treatment with eprinomectin or abamectin, respectively (all p>0.05). CONCLUSIONS: These results demonstrate evidence of resistance to macrocyclic lactone anthelmintics by C. oncophora and probably T. longispicularis also. CLINICAL RELEVANCE: As well as perhaps providing the first record of resistance to any anthelmintic by T. longispicularis, the present findings may also represent the first case of resistance to macrocyclic lactone anthelmintics exhibited by more than one parasite species at a time in cattle in New Zealand. KEYWORDS: Eprinomectin, abamectin, macrocyclic lactone, anthelmintic resistance, cattle, Cooperia, Trichostrongylus.     

Control of gastrointestinal parasitism with nematodes in dairy goats by treating the host category at risk

Infections of the gastrointestinal tract with parasitic nematodes remain one of the main limiting factors in grazing dairy goats. The usual mode of control of these parasitic diseases has up to now been based on the repeated use of anthelmintics. However, the prevalence rates of anthelmintic resistances, in particular to benzimidazoles, are now particularly high in the French dairy goat production. This situation makes it mandatory to reconsider the usual mode of control of these nematodes and to look for short term, alternative solutions which combine the control of gastrointestinal infections and management of anthelmintic resistances. One of the possible options is to leave a part of the flock without treatment during the grazing season in order to maintain alleles of susceptibility to anthelmintics within the worm populations. Previous epidemiological observations identifying the categories of host populations at risk are presented which provide the rationale for targeted applications of treatments. The results of assays on experimental flocks and from farm surveys examining the advantages and drawbacks of selective treatments are presented. The value of these results in combination with other alternative solutions of control are discussed in order to use minimum treatments with maximum benefits.     

Efficacy of topically administered doramectin against eyeworms, lungworms, and gastrointestinal nematodes of cattle.

OBJECTIVE: To evaluate efficacy of topically administered doramectin against eyeworms, lungworms, and gastrointestinal nematodes of cattle. ANIMALS: 400 cattle (20 cattle in each of 20 trials). PROCEDURE: Trials were conducted in North America; natural and experimentally induced infections were used. In each trial, cattle were allocated randomly to control (placebo [saline [0.9% NaCl] solution at 1 ml/10 kg of body weight] or untreated; n = 10) or doramectin-treated (500 microg/kg of body weight; 10) groups. Treatments were applied in a single passage along the midline of the back, from the withers to the tailhead. Cattle were euthanatized > or =14 days after treatment, and worm burdens were determined by use of standard techniques. RESULTS: Efficacy of doramectin was > or =95.3% against adults of Thelazia gulosa, T skrjabini, Dictyocaulus viviparus, Haemonchus contortus, H placei, Ostertagia lyrata, O ostertagi, Trichostrongylus axei, Bunostomum phlebotomum, Capillaria spp, Cooperia oncophora, C pectinata, C punctata, C spatulata, C surnabada, Nematodirus spathiger, Strongyloides papillosus, T colubriformis, Oesophagostomum radiatum, and Trichuris spp. Efficacy was 95.1% against fourth-stage larvae of D viviparus, H placei, O lyrata, O ostertagi, T axei, C oncophora, C punctata, C spatulata, C surnabada, N helvetianus, T colubriformis, O radiatum, and Trichuris spp. In addition, efficacy against inhibited fourth-stage larvae of O ostertagi and Ostertagia spp was > or =98.1%. CONCLUSIONS AND CLINICAL RELEVANCE: A single topical application of doramectin pour-on was efficacious against a broad range of nematode species in cattle.     

Efficacy of an albendazole feed formulation against bovine gastrointestinal nematodes including arrested larvae of Ostertagia ostertagi

The efficacy of an albendazole feed premix formulation was compared with that of an albendazole drench suspension for control of gastrointestinal nematodes in 31 beef cattle. The premix (11 cattle) and drench suspension (9 cattle) were found to have similar efficacies at a dosage of 7.5 mg/kg of body weight. When compared with controls (11 cattle), both formulations caused significant (P less than 0.05) reductions in worm counts with an efficacy of 98% or greater against adult Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, Cooperia punctata, and C pectinata. There was no significant effect against arrested 4th-stage larvae of O ostertagi. Adverse effects of albendazole treatment were not observed, and the premix formulation was readily consumed by cattle.     

The helminth fauna of the gastrointestinal tract of young cattle in northwest Germany

Ten unmedicated animals of a controlled anthelmintic trial were used to analyse the present gastrointestinal helminth fauna of young cattle from the northwest of Germany. This survey done in August revealed Ostertagia ostertagi to represent the most prevalent and abundant species followed by Cooperia oncophora and Nematodirus helvetianus. O. lyrata, O. leptospicularis, C. zurnabada, C. punctata, Trichostrongylus axei, Haemonchus contortus, Bunostomum phlebotomum, Capillaria bovis and Trichuris discolor were less prevalent and abundant. These findings are closely similar to findings from investigations more than 20 years ago although since that time anthelmintics have been used increasingly.     

牛羊线虫抗药性及其PC检测技术研究进展

牛羊线虫病是严重影响牛羊生产性能和经济效益的主要寄生虫病，化学药物是目前防治本病的主要手段，近年来线虫抗药性。已经成为世界各地牛羊线虫控制中的首要问题。建立线虫抗药早期检测技术可以时了解抗药性及其产生的条件等，便于采取有效对策，本文简要阐述牛羊线虫抗药性的分布与检测，现有抗药性检测方法的缺点以及PCR检测技术的最新进展。     

SCOPS and COWS--'worming it out of UK farmers'

Infections with gastrointestinal roundworms are an important cause of production losses in sheep and cattle. Worm control is a vital part of health and production management in sheep flocks and cattle herds in the UK, and good control is highly dependent on effective anthelmintics. Unfortunately, a direct and unavoidable consequence of using anthelmintics to control worm populations is selection for individuals that are resistant to the chemicals used. If left unchecked, anthelmintic resistance (AR) could prove to be one of the biggest challenges to sheep and cattle production and animal welfare within the UK. As a consequence of increasing reports of AR in sheep, a working group, "SCOPS" (sustainable control of parasites in sheep) was formed in 2003 with representatives from the UK sheep industry to promote practical guidelines for sheep farmers and their advisors. This led to the production of guidelines for 'sustainable worm control strategies for sheep' intended for veterinarians and sheep advisors, plus ongoing promotional literature aimed at farmers. Whilst there is some evidence of emerging resistance in roundworms of cattle, it appears to still be at a very low level in the UK. However the potential presence of such AR in cattle worms has been seen as a timely warning, which if ignored, could lead to a not dissimilar AR situation to that seen in sheep, and in other cattle areas around the world. Reports of AR in UK cattle nematodes have generally been limited to a small number of anecdotal reports of treatment failure with some macrocyclic lactone (ML) products, especially those formulated as pour-on preparations, and invariably involving the dose-limiting species, Cooperia oncophora. As a consequence of these observations, guidelines have been produced similar to those for sheep, for sustainable worm control strategies for cattle "COWS" (control of worms sustainably), and were launched in May 2010. Uptake and effectiveness of SCOPS recommendations are currently being monitored in collaboration with the UK animal health industry, and similar proposals are being considered for uptake of COWS guidelines following the launch this year.     

Characterization of moxidectin resistant Trichostrongylus colubriformis and Haemonchus contortus

The development of moxidectin resistance (MOX-R) in sheep parasitic gastrointestinal nematodes already carrying multiple resistances to other anthelmintic groups has made control of these strains very difficult. The anthelmintic resistance patterns of MOX-R strains of Trichostrongylus colubriformis and Haemonchus contortus were characterized to provide an insight into the remaining role of anthelmintics in the control of such strains. Homozygous MOX-R individuals of both genera were unaffected by moxidectin. For MOX-R heterozygotes a dose rate of 200 microg/kg abamectin (ABA) given orally removed 25% of H. contortus while 200 microg/kg MOX given orally achieved a 72% reduction. Doubling the dose rate of ABA improved the mean efficacy to 37%. Consequently, in H. contortus, the degree of dominance differs markedly between the two anthelmintics. A dose rate of 8 mg/kg levamisole and 185 mg/kg napthalophos achieved >95% reduction in worm count of the MOX-R homozygous H. contortus but only 85 and 7%, respectively against the MOX-R homozygous T. colubriformis.     

Refugia--overlooked as perhaps the most potent factor concerning the development of anthelmintic resistance

Anthelmintic resistance involving particularly the gastrointestinal nematodes of small ruminants is escalating globally, to the extent that in certain countries, such as South Africa, it has already reached alarming proportions, and is affecting practically all the anthelmintics. In this paper it is argued that the high levels of resistance in nematodes of veterinary importance indicate that the drugs have been used incorrectly. It is suggested that the phenomenon of refugia plays a much more important role in the selection of anthelmintic resistance than other phenomena that are more frequently investigated and recommended for counteracting it, such as reduced drenching frequency and avoiding under-dosing. While refugia is commonly mentioned in passing in most papers on anthelmintic resistance, it is, almost without exception, not incorporated in the final control/ management proposals. On the strength of the conclusions arrived at in the present paper strategies such as the drench-and-move system in which all the animals in a flock are drenched before they are moved to pastures containing few or no worms in refugia, and the system of strategic drenching on safe pastures should be condemned and never recommended. If such strategies are indeed unavoidable, the farmer should be warned that the farming system would probably not be sustainable even in the short term, in view of the generally high levels of resistance already present in most of the important sheep-producing regions. Farmers should be educated to consider refugia above all else when designing worm management programmes. Finally there seems to be too much complacency concerning the possibility that anthelmintic resistance may also escalate in cattle, eventually to reach the proportions that it has in sheep.     

EFFICACY OF ANTHELMINTICS AGAINST CATTLE NEMATODES

The efficacies of fenbendazole and thiabendazole against artifically acquired cattle nematodes and the efficacies of fenbendazole, prabendazole and levamisole against naturally acquired cattle nematodes were studied in western Victoria. Fenbendazole significantly (P less than 0.05) reduced numbers of late and early fourth stage larvae (greater than 96%), artificially acquired Cooperla spp (100%) and naturally acquired adult Ostertagia ostertagi (98%) and Trichostrongylus axei (90%). Thiabendazole significantly reduced numbers of artificially acquired late fourth stage larvae (83%) and parbendazole significantly reduced numbers of adult O. ostertagi (72%) in one group of cattle. Fenbendazole was the most effective anthelmintic.     

Effects of anthelmintic treatment and feed supplementation on grazing Tuli weaner steers naturally infected with gastrointestinal nematodes

A study was carried out to determine the epidemiology of gastrointestinal nematodes in indigenous Tuli cattle and the effect of dietary protein supplementation and anthelmintic treatment on productivity in young growing cattle. Forty steers with an average age of 18 months were divided into 4 groups; 1) fenbendazole (slow release bolus) and cottonseed meal (FCSM group), 2) fenbendazole (FBZ group), 3) cottonseed meal (CSM group) and 4) control (no cottonseed meal and no fenbendazole) (control group). Performance parameters measured included worm eggs per gram of faeces (EPG), packed cell volume (PCV), albumin and live-weight gain. Results showed that faecal worm egg counts were lower and PCV was higher in the FCSM and FBZ groups than in the CSM and control groups (P < 0.01). Weight gains were higher in the CSM and FCSM groups than in the FBZ and control groups (P < 0.05). The cost benefits of anthelmintic treatment and dietary supplementation were apparent in this study. The improved growth performance of the FCSM, FBZ and CSM groups reflected a financial gain over the controls on termination of the study. The dominant genera of gastrointestinal nematodes on faecal culture, pasture larval counts and necropsy were Cooperia and Haemonchus. The incidences of Trichostrongylus, Oesophagostomum and Bunostomum were low.     

ANTHELMINTIC EFFICIENCY OF OXFENDAZOLE, FENBENDAZOLE AND LEVAMISOLE AGAINST NATURALLY ACQUIRED INFECTIONS OF OSTERTAGIA OSTERTAGI AND TRICHOSTRONGYLUS AXEI IN CATTLE

The anthelmintic efficiencies of oxfendazole, fenbendazole and levamisole, each at 4 dose rates spanning the manufacturers' recommended dosages were compared in beef cattle with naturally acquired infections of Ostertagia ostertagi and Trichostrongylus axei. In 8 of the 9 cases tested there was no significant increase in anthelmintic efficiency due to increased dose rates of any of the drugs. Percentage efficiencies and their standard errors, calculated from mean worm counts of pooled data for adult worms, developing 4th stage and early 4th stage larvae of O. ostertagi, were respectively, 86.9+/-4.2, 77.4+/-6.1, 74.5+/-7.3 for oxfendazole, 93.7+/-2.0. 80.7+/-6.8, 59.6+/-13.9 for fenbendazole and 69.7+/-6.9, 39.4+/-14.8, 31.2+/-22.6 for levamisole. Counts of O. ostertagi from cattle treated with oxfendazole and fenbendazole were not significantly different, but both were significantly lower than those from cattle given levamisole. Efficiency against T. axei exceeded 99% for all drugs. Practical implications for therapy and preventative control of ostertagiasis are discussed.     

Use of diagnostic markers to monitor fasciolosis and gastrointestinal nematodes on an organic dairy farm

A 12-month study was conducted to assess and monitor gastrointestinal tract nematodes and liver fluke in cohorts of cattle on a Scottish organic dairy farm. Various diagnostic markers for helminth parasites of cattle from different age groups were assessed monthly from April 2007 to March 2008. First season grazing stock were subjected to significant challenge from Ostertagia ostertagi nematodes as reflected in serum pepsinogen concentrations, which rose markedly in the second half of the grazing season. In addition, plasma albumin concentrations decreased and faecal egg counts (FEC) increased moderately, indicating exposure to both O ostertagi and probably Cooperia oncophora. Second season grazing animals had a peak FEC early in the grazing period, suggestive of a potential carry-over of Ostertagia species infection ('Type 2') during housing. All classes of cattle showed evidence of fluke (Fasciola hepatica) infection. Adult cow exposure to O ostertagi and fluke was estimated via the use of ELISA testing to detect antibodies to O ostertagi and F hepatica and the high levels detected suggested a significant exposure response. Despite low stocking densities and sympathetic grazing management, there was a significant challenge to all grazing stock from gastrointestinal nematodes and liver fluke.     

Multispecies and multiple anthelmintic resistance on cattle nematodes in a farm in Argentina: the beginning of high resistance?

There are very few resistance records on cattle nematodes. South American successive records have been increasing rapidly since the year 2000. In Argentina, increasing dissatisfaction based on the exclusive use of macrocyclic lactones has prompted the use of benzimidazoles in the Pampean region. The studied farm is located in the Argentina humid Pampas and had apparently poor results after anthelmintic treatments. Evaluation of resistance was firstly based on faecal egg reduction after treatment in November 2001 and June 2002 and was complemented with worm counts obtained by necropsy in June 2002. The study reports that the reduction of faecal egg excretion after benzimidazole (reduction 31-79%) or ivermectin treatments (76-97%) in November 2001 was insufficient and these poor results were confirmed in June 2002 (benzimidazoles (65-89%) and ivermectin (47-77%)). Several methods for evaluating faecal egg count reduction were performed and yielded different results. A new method based on the estimated faecal egg counts (corrected from the initial faecal egg counts and animal type using a general linear model) was used and gave higher flexibility in the interpretation of putative resistance to anthelmintics. From necropsy results, it could be concluded that Cooperia oncophora was resistant to avermectins and benzimidazoles and that Cooperia punctata, Ostertagia ostertagi and Haemonchus placei were resistant to benzimidazoles. This case of multispecies and multidrug resistance is probably not unique and could reflect the emergence of resistances in Argentina. This emergence is probably due to the intensive use of anthelmintics, the absence of refugia, and the frequent circulation of infected cattle.     

Anthelmintic treatment of dairy cows and its effect on milk production.

The results of more than 80 experiments on gastrointestinal parasitism and the impact of anthelmintic treatment on milk production in dairy cattle were reviewed. Abattoir surveys of culled dairy cows, faecal egg counts in milking cows, and serological tests and worm counts in cull cows in milk production studies were collated to assess the level of parasitism in dairy herds. The studies were divided into four general categories: induced infections in previously uninfected cattle; naturally infected cattle treated in mid-lactation; naturally infected cattle treated one to three times during the dry period and/or just before or just after parturition; and naturally infected cattle treated repeatedly from early lactation or given strategic treatments throughout the year. In most studies, the milk production of anthelmintic-treated cattle was compared with that of untreated controls. The anthelmintics investigated included members of the organophosphate, benzimidazole, imidazothiazole and macrocyclic lactone groups. The number of experiments in which the medicated (or uninfected) group had a higher milk yield was compared with the number of experiments in which the control (or infected) group had a higher yield. Overall, the studies demonstrated that grazing dairy cattle are likely to be infected with gastrointestinal nematode parasites, usually Ostertagia ostertagi and Cooperia species. These infections may be present as inhibited larvae, and a periparturient or spring rise is associated with their emergence. There is, at present, no reliable means of determining whether a cow or a herd may be parasitised subclinically at a level sufficient to interfere with milk production. In 70 of 87 experiments (80 per cent) there was an increase in milk production (P < 0.001) after anthelmintic treatment, with a median increase of 0.63 kg/day. In each of the four trial categories, a majority of the studies showed that anthelmintic treatment increased milk production. The yield of milk fat by the medicated cows was greater than by the controls in 26 of the 35 experiments in which that variable was studied (P < 0.01).     

Activity of fenbendazole against inhibited early fourth-stage larvae of Ostertagia ostertagi

The efficacy of fenbendazole (Panacur, Hoechst-Roussel) against inhibited early fourth-stage larvae of Ostertagia ostertagi and other nematodes of the abomasum and intestinal tract was investigated in naturally infected, yearling cattle in April 1978. The time when peak levels of inhibited larvae occurred was determined by epizootiologic study which began in November 1977. All animals were removed from pasture and maintained free from further helminth infection until slaughter (19 to 21 days). The fenbendazole liquid suspension was administered as an oral drench at dose level of 10 mg/kg to 10 animals and then at dose level of 15 mg/kg to an additional 10 animals at 10 days after removal from pasture. Eleven animals were maintained as untreated controls. In cattle given the dose of 10 mg/kg, the following reductions were observed: O ostertagi adults--100%, developing stages--80%, and inhibited larvae--97%; other worm genera in the abomasum and nematodes of the intestinal tract--100%. In the cattle given the larger dose, the following reductions were observed: O ostertagi adults--100%, developing stages--98%, and inhibited larvae--99%; other worm genera in the abomasum and nematodes of the intestinal tract--100%.