Managing anthelmintic resistance--use of a combination anthelmintic and leaving some lambs untreated to slow the development of resistance to ivermectin

A field study was conducted to test the hypotheses that use of a combination anthelmintic and/or increasing the pool of unselected worms 'in refugia' by leaving a proportion of lambs untreated would slow the development of resistance to ivermectin. Twelve suites of four paddocks (farmlets) were seeded with a mixture of resistant and susceptible isolates of both Trichostrongylus colubriformis and Teladorsagia (Ostertagia) circumcincta calculated to yield a 95% reduction in faecal nematode egg count (FEC) after treatment with ivermectin. Each year for three years the farmlets were stocked in the spring with mobs of lambs which were treated five times at 28-day intervals with either ivermectin or an ivermectin+levamisole combination. In addition, in half the mobs the heaviest 10% of lambs remained untreated at each treatment occasion, resulting in a 2 × 2 factorial treatment structure (i.e. two drench types × two percentage treated) with three complete replicates. The development of resistance to ivermectin, and at the end to levamisole, was measured by larval development assays (LDA) and worm counts from treated and untreated tracer lambs. For T. colubriformis the development of resistance to ivermectin, as measured by tracer lamb worm burdens, was delayed by treatment with the combination and by leaving 10% of lambs untreated. In addition, the interaction between these factors approached significance (p=0.052). Similarly, results of the LDAs indicated a slower development of resistance when lambs were treated with the combination and when 10% of lambs were left untreated. For T. circumcincta, results were compromised by the rapid development of resistance, which appears to be the result of low viability in the field of the susceptible isolate used to contaminate the pastures. Although a small delay in the development of resistance to ivermectin was indicated, this was off-set by an increase in the level of resistance to levamisole. A post-study modelling experiment simulating the conditions of the field study and the starting efficacies for the two nematode species produced equivalent outputs to those measured in the field. Overall, results support the conclusions that use of combination anthelmintics and deliberately increasing 'refugia' of unselected genotypes will slow the development of anthelmintic resistance. However, as indicated in modelling studies, once resistance to all the constituent actives is well developed (efficacy<70%) the value of combinations for slowing the development of resistance is largely lost.     

Managing anthelmintic resistance: Modelling strategic use of a new anthelmintic class to slow the development of resistance to existing classes

AIM: To test the hypothesis that a single strategic treatment with a new class of anthelmintic could slow the development of resistance to existing classes of anthelmintic.

METHODS: An existing model was used to simulate nematode parasite dynamics and the development of anthelmintic resistance. Variations on a five-drench preventive programme of treatments for lambs, in which either zero, the first, third or fifth treatment was substituted with a different class of drug, were compared for the time to reach treatment failure (defined as efficacy <95%). The sensitivity to variations in the death rate of adult worms, that varied from 1 to 5%, and the dominance of resistance genes were also assessed.

RESULTS: Replacing one of the five treatments with a different class of anthelmintic almost always slowed the development of resistance, and was never worse than using the same drug for all treatments. Further, there were large differences in the relative time to treatment failure depending on which treatment was substituted. Changing the first treatment always had the least benefit, whereas changing the fifth treatment always had the greatest. This pattern was independent of the daily death rate of adult worms, and was not influenced by the dominance of resistance under treatment.

CONCLUSIONS: The results indicated that strategic substitution of a single treatment with a new class of anthelmintic, at the end of a series of preventive treatments to lambs using an existing class, could slow the further development of resistance to the latter. This strategic use of a new anthelmintic class has the potential to greatly extend the life of existing anthelmintics if these are still effective.     

A survey on anthelmintic resistance in nematode parasites of sheep in Lusaka,Zambia

While surveys in Southern Africa indicate anthelmintic resistance of gastrointestinal nematodes to be common in small ruminants in South Africa, Kenya and Zimbabwe there have been no reports of resistance in Zambia. The objective of this study was to determine whether anthelmintic resistance occurs in Zambia, and to obtain information on nematode control practices in the country. During the rainy season six commercial sheep farms were selected in and around Lusaka and Chisamba. Worm control practices were gauged by means of a questionnaire, and the Faecal Egg Count Reduction Test was performed for assessing anthelmintic efficacy of albendazole, levamisole and ivermectin. On all farms anthelmintic treatment was the only approach used to control nematode infections. Frequency of treatment varied from twice a year to every 6 weeks and drugs of different anthelmintic groups were alternated within the same year. There was a wide range in faecal egg counts of individual sheep before treatment, with some individual counts of up to 87000. Larval identification showed that Haemonchus was almost the only genus recovered from the faecal cultures before and after treatment. Albendazole resistance was found on five of the six farms. On each of the four farms where ivermectin gave less than 95% reduction in egg counts, there was resistance to albendazole as well. Levamisole showed an efficacy of 95% or higher on all six farms.     

Anthelmintic resistance in the field: Changes in resistance status of parasitic populations in response to anthelmintic treatment

Changes in anthelmintic resistance in nematode parasites were monitored in sheep grazing on 2 separate farms, but with the same anthelmintic treatment program, over 16 years. High levels of benzimidazole resistance emerged in Ostertagia and Trichostrongylus spp populations on both farms following 9 years of continuous use of this class of drug. Subsequently, variations in the levels of resistance occurred for the same species between farms and between species on the same farm. A change to levamisole for 2 years resulted in a significant reversion towards benzimidazole susceptibility, but a concomitant rise in levamisole resistance, in Ostertagia on one farm. However, benzimidazole resistance increased rapidly following the re-introduction of oxfendazole into the anthelmintic treatment program. Results from both farms illustrate the pitfalls of using one anthelmintic class for an extended period and provide indirect support for the alternation of anthelmintic classes at approximately yearly intervals.     

Survey of internal parasites in Western Australian pig herds 2. Relationship to anthelmintic usage and parasite control practices

The housing, management and internal parasite control practices used in piggeries in Western Australia was surveyed by interviewing the owner/manager of 100 randomly selected piggeries. At the time of the interview 20 faecal samples were collected from pigs and examined for evidence of internal parasites. Most herds (80%) in which anthelmintics were used, had evidence of nematode infection. Some pig producers were using an anthelmintic that was ineffective against nematode species present while some herds had nematodes that should have been controlled by the anthelmintic being used. Prevalence of nematode infection was higher in pigs run in paddocks than in pigs housed intensively. Washing sows prior to farrowing was associated with a lower prevalence of nematode infection. The findings suggested that pig producers should ensure that the anthelmintic used is effective against the nematodes present in their pigs. It was concluded that administering anthelmintics as a single dose in the feed may not be the most effective method of deworming pigs.     

Feline intestinal parasites in Finland: prevalence, risk factors and anthelmintic treatment practices

The aim of this study was to estimate the prevalence of feline intestinal parasites in Finland and to determine the possible risk factors for infection. Altogether 411 feline fecal samples were analyzed with a flotation method to reveal helminth eggs and protozoan oocysts. Of the samples, 402 were also screened for Giardia species antigens with a commercial enzyme-linked immunosorbent assay kit. The cat owners completed a questionnaire. Toxocara cati prevalence was 5.4% and Toxascaris leonina 0.2%. Taenia species eggs were found in 1.5% of the samples and Isospora felis in 0.7%, whilst 3.2% of the samples tested positive for Giardia species antigen. Risk factors for Toxocara/Toxascaris species infection included being a non-pedigree cat, having access to the outdoors, living outside of the cities and receiving home-made food. Pedigree cats were at greater risk of contracting Giardia duodenalis. The majority of the cat owners (62.4%) treated their cat with anthelmintics 2-4 times per year.     

Minimising the development of anthelmintic resistance, and optimising the use of the novel anthelmintic monepantel, for the sustainable control of nematode parasites in Australian sheep grazing systems

Objective To compare the risk of different treatment scenarios on selecting for anthelmintic resistance on Australian sheep farms. Design A computer simulation model predicted populations of Trichostrongylus colubriformis, Haemonchus contortus or Teladorsagia (Ostertagia) circumcincta, and the frequency of anthelmintic resistance genes. Method Nematode populations and the progression of drug resistance for a variety of treatment options and management practices in sheep‐rearing areas of Western Australia (WA), Victoria (VIC) and New South Wales (NSW) were simulated. A scoring system was devised to measure the success of each option in delaying resistance to each anthelmintic and in controlling nematode populations. Results The best option at all sites was combining the new anthelmintic (monepantel) with a triple mixture of benzimidazole, levamisole and abamectin (COM). The next best option was: in NSW, rotation at each treatment between monepantel, moxidectin and COM; in VIC, rotation at each treatment between monepantel and COM; and in WA, rotation at each treatment between monepantel (used in winter) and COM or moxidectin (used in summer–autumn). In WA, rapid selection for resistance occurred as a consequence of summer–autumn treatments; however, if a small percentage of adult stock were left untreated then this selection could be greatly reduced. Despite purposely assuming relatively high resistance to benzimidazole and levamisole, COM was still effective in controlling worms and delaying resistance. Conclusions Because of cost constraints, it may not be feasible or profitable for producers to always use the combination of all drugs. However, the second‐ and third‐best options still considerably slowed the development of anthelmintic resistance.     

Salmonella Indiana as a cause of abortion in ewes: Genetic diversity and resistance patterns

Salmonella enterica subspecies enterica Indiana, a food-borne serovar uncommon in most countries, was responsible for an outbreak of abortion in a flock of Lacaune dairy ewes in southern Spain. Drinking water and feedstuff samples were analysed in an attempt to determine the source of the infection. Pigeons (Columba livia) and turtledoves (Streptopelia turtur) in close contact with the ewes were captured and examined for the bacterium. Seventeen S. Indiana strains were isolated from the ewes and wild birds and the genetic similarity among them analysed by Pulsed Field Gel Electrophoresis (PFGE) after the digestion of their genomic DNA with the restriction enzyme XbaI. The results suggest the wild birds might be responsible for the outbreak in the ewes. The strains recovered were fully susceptible to 15 out of the 16 antimicrobial agents tested: ampicillin, amoxycillin clavulanate, cephalothin, ceftriaxone, gentamicin, neomycin, streptomycin, tetracycline, ciprofloxacin, enrofloxacin, sulphonamides, trimethoprim-sulphamethoxazole, apramycin, colistin and chloramphenicol. Differences in the resistance pattern to nalidixic acid were observed; 11 strains (64.7%) were nalidixic acid resistant (R-Nx) and 6 (35.3%) sensitive (S-Nx). Among the R-Nx strains, a substitution of Gly to Cys at position 81 (Gly81àCys) of the gyrA gene in 10 strains isolated from wild birds and ovine foetuses, and of Asp to Tyr at position 87 (Asp87àTyr) in one strain isolated from ewe faeces, were revealed by sequencing the gene. To control the outbreak, enrofloxacin treatment was administered for 5 days. The same therapy was used to prevent infection during following gestation cycles, administering the antimicrobial agent at presentation and over 4 weeks before birth. Anti-bird meshes and closed drinking and feeding troughs were also installed to prevent further contact of the ewes with wild birds.     

Assessment of anthelmintic resistance in nematode parasites of sheep and goats owned by smallholder farmers in eastern Ethiopia

The anthelmintic resistance status was investigated of nematode parasites of sheep and goats owned by smallholder farmers in communities that received breeding stock from a source where a high level of anthelmintic resistance has been reported. The investigation used the faecal egg count reduction technique, whereby suitable animals within each of eight separate communities were pooled to achieve the numbers required to conduct separate tests for both sheep and goats. Anthelmintics tested were albendazole (ABZ), tetramisole (TET), a combination (ABZ $+$ TET) and ivermectin (IVM), at the manufacturers' recommended dose rates. Results showed that there was no evidence of anthelmintic resistance in nematode parasites of either sheep an goats in any community. This indicates that dilution of resistant parasites imported with introduced breeding stock, and the low selection pressure imposed by the smallholder farmers themselves, has prevented anthelmintic resistance from emerging in nematode parasites of small ruminants in these communities.     

Anthelmintic resistance of nematode parasites of small ruminants in eastern Ethiopia: exploitation of refugia to restore anthelmintic efficacy

Faecal egg count reduction tests (FECRT) were conducted in May 2003 to determine the efficacy of anthelmintics used for treatment against nematode parasites in separately managed sheep and goat flocks at Alemaya University in eastern Ethiopia. These tests revealed high levels of anthelmintic resistance to albendazole, tetramisole, the combination of these two drugs, and to ivermectin in the goat flock (predominantly infected by Haemonchus contortus and Trichostrongylus spp.), whereas all drugs were highly efficacious in the sheep flock. A second FECRT confirmed these observations. Following this, a new management system was implemented on the goat flock for a period of 9 months (January-September 2004) in an attempt to restore the anthelmintic efficacy. This involved a combination of measures: eliminating the existing parasite infections in the goats, exclusion from the traditional goat pastures, and introducing communal grazing of the goats with the university sheep flock and livestock owned by neighbouring small-holder farmers. A second series of FECRTs (Tests 3 and 4) conducted 7 months after this change in management, showed high levels of efficacy to all three drugs (albendazole, tetramisole and ivermectin) in the goat flock. This is the first field study to demonstrate that anthelmintic efficacy in the control of nematode parasites of small ruminants can be restored by exploiting refugia.     

Large-scale management systems and parasite populations prevalence and resistance of parasitic agents in animal effluents and their potential hygienic hazard

Keeping large numbers of animals in large-scale, pseudo-industrial units poses similar problems to the overstocking of small farms within any one area, as far as the disposal of animal effluents is concerned. The prevalence of parasites in pigs, poultry and cattle on large-scale farms is listed, and examples of the resistance of their exogenic stages are given. The possibilities of transmission to individuals of the same species or to other species including man are evaluated. Guidelines for safe or restricted disposal of the effluents as fertilizers for different plant crops are given. On recycling effluents as animal food, no problems should arise from the parasitologist's point of view if poultry manure is fed to pigs or cattle or if swine or cattle effluents are fed to poultry. Other combinations are hazardous.     

The effectiveness of copper oxide wire particles as an anthelmintic in pregnant ewes and safety to offspring

The objective of the experiment was to determine the effectiveness of copper oxide wire particles (COWP) in pregnant ewes and safety to lambs. COWP have been used recently as an anthelmintic in small ruminants to overcome problems associated with nematode resistance to chemical dewormers. Doses of COWP (相似文献   

Teladorsagia circumcincta resistance to moxidectin and multiple anthelmintic groups in ewes following use of the persistent drug before lambing

This paper describes the nematode control strategy adopted by a Scottish hill sheep farmer. It provides an example of the limited use of anthelmintic drugs, targeted towards control of the periparturient rise in faecal nematode egg output in ewes and exploitation of grazing management, resulting in limited exposure of naive sheep to infective larvae on pasture. Resistance to benzimidazole, imidazothiazole and macrocyclic lactone anthelmintics, and to a combination of a macrocyclic lactone and imidazothiazole anthelmintic drugs was diagnosed. The targeted use of a persistent anthelmintic drug to control a periparturient rise in faecal nematode egg output in ewes may be unnecessary and selects strongly for resistance when the reservoir of anthelmintic-susceptible nematodes in refugia is small at the time of treatment. However, the use of a persistent anthelmintic drug in a selective proportion of ewes can be important and probably does not select strongly for resistance when the reservoir of anthelmintic-susceptible nematodes in refugia is large at the time of treatment. The former circumstances might arise on many Scottish hill sheep farms, whereas the latter may occur on upland and lowground farms, depending on previous grazing management, anthelmintic use and winter weather conditions. These factors must be taken into account when preparing sustainable health plans for nematode parasite control in individual sheep flocks.     

Brave or gullible: testing the concept that leaving susceptible parasites in refugia will slow the development of anthelmintic resistance

AIM: To test the theory that creating a reservoir of unselected worms by leaving a proportion of lambs in a flock untreated with anthelmintic, i.e. in refugia, will slow the development of anthelmintic resistance in nematode parasite populations. METHODS: Newly weaned Romney lambs (n=180) were infected with two nematode parasite species, Teladorsagia (= Ostertagia) circumcincta and Trichostrongylus colubriformis. For each species, the challenge doses contained a mixture of infective larvae from benzimidazole-resistant and -susceptible isolates calculated to yield, from the combined population, a 95% reduction in faecal nematode egg counts (FEC) following treatment with albendazole. Once the infections were patent, the lambs were divided into nine groups of 20 animals, and each group was allocated to one of three treatments. In Treatments 1, 2 and 3, 100%, 90% and 80% of animals were treated with an anthelmintic, respectively. For treatments 2 and 3, the heaviest animals remained untreated. Following treatment, each group was moved to its own previously prepared low-contamination pasture. Lambs grazed this pasture for 7 weeks before again being treated and moved to new low-contamination pastures (Shift 1 and Shift 2). The parasite populations on pasture resulting from the different treatments were subsequently sampled using tracer lambs, and worm eggs derived from these were used in both egg-hatch assays (EHA) and larval development assays (LDA), to measure albendazole-resistance status. RESULTS: Treating all animals each time the groups were moved to new low-contamination pastures resulted in higher levels of albendazole resistance (p<0.05), measured using EHA and LDA, in subsequent parasite generations than when either 10 or 20% of animals were left untreated. However, higher FEC in the tracer lambs grazed on pastures in Treatments 2 and 3, compared with Treatment 1, indicated an increased level of pasture contamination as a result of leaving some animals untreated. CONCLUSIONS: The results demonstrate that creating a reservoir of unselected parasites slows the development of anthelmintic resistance, and emphasises the risk of treating all animals prior to a shift on to low-contamination pasture. However, higher levels of pasture contamination, resulting from untreated animals, indicate the difficulty in managing both worm control and resistance.