Emergence Of Anthelmintic Resistance Research Articles

Medicinal plants as alternative to anthelmintics for livestock : An overview with particular reference to Indian subcontinent

In livestock farming helminthiasis remains a major constraint to productivity, performance and profitability. Anthelmintics have been in use since long to combat the problem, but the emergence of anthelmintic resistance, particularly in gastrointestinal (g.i.) parasites has compelled a relook at alternative control strategies. The application of ethno-veterinary practices and plant derivatives as deworming agents is gaining popularity worldwide. The acceptability of this approach depends on the scientific validation of the plant products for their anthelmintic properties. Several controlled studies recently carried out in the Indian subcontinent, generated a large volume of data on in vitro, in vivo and clinical efficacies of plants and herbs singly and in combination. Most have used internationally accepted guidelines as parameters for evaluation of the candidate plants. The target helminths in these studies belonged to 3 major classes, but gastrointestinal (g.i.) nematodes, liver flukes of ruminants and intestinal worms of poultry were predominant. Active principles and mode of action were identified in majority of plants, which have proven anthelmintic potential. Lately, the use of forages containing condensed tannins, is finding favour in the management of g.i. nematodes in ruminants. A cross-section of recent studies, an overview of the current scenario, and the road ahead, are presented in this review.

Survey on anthelmintic resistance to gastrointestinal nematodes in unorganized goat farms of Tamil Nadu.

One of the major problems in small ruminant farms is emergence of anthelmintic resistance (AR) to commonly used dewormers. This study investigated AR to gastrointestinal nematodes affecting goats in 27 unorganized farms in three different agro-climatic zones (Cauvery delta zone, high altitude zone and high rainfall zone) of Tamil Nadu, India. Two anthelmintics viz., albendazole (AZ) and levamisole (LEV) were used in this study as per the dose recommended by the manufacturer. Status of AR was detected by using the faecal egg count reduction test. Results revealed the presence of high level of resistance to both AZ and LEV. In the high rainfall and high altitude zones, all the farm flocks were found to be resistant to LEV. In the Cauvery delta zone, 13 farm flocks were resistant and four farm flocks showed suspect resistance to AZ. Fifteen farm flocks showed resistance and two showed suspect resistance to LEV. Further, morphological characterization of the infective larvae derived from faecal cultures indicated that by far the most predominant gastrointestinal nematode species found in goats was Haemonchus contortus.

SvSXP: a Strongylus vulgaris antigen with potential for prepatent diagnosis

BackgroundStrongyle parasites are ubiquitous in grazing horses. Strongylus vulgaris, the most pathogenic of the large strongyles, is known for its extensive migration in the mesenteric arterial system. The lifecycle of S. vulgaris is characterised by a long prepatent period where the migrating larvae are virtually undetectable as there currently is no test available for diagnosing prepatent S. vulgaris infection. Presence of S. vulgaris larvae in the arterial system causes endarteritis and thrombosis with a risk of non-strangulating intestinal infarctions. Emergence of anthelmintic resistance among cyathostomins has led to recommendations of reduced treatment intensity by targeting horses that exceed a predetermined strongyle faecal egg count threshold. One study suggests an apparent increase in prevalence of S. vulgaris on farms where reduced anthelmintic treatment intensity has been implemented. These issues highlight the need for an accurate and reliable assay for diagnosing prepatent S. vulgaris infection.MethodsImmunoscreening of a larval S. vulgaris cDNA library using hyperimmune serum raised against S. vulgaris excretory/secretory antigens was performed to identify potential diagnostic antigens. Immunoreactive clones were sequenced, one potential antigen was characterised, expressed as a recombinant protein, initially evaluated by western blot (WB) analysis, the diagnostic potential of the IgG subclasses was evaluated by ELISA, and the diagnostic accuracy evaluated using serum from 102 horses with known S. vulgaris infection status.ResultsThe clone expressing the potential antigen encoded a S. vulgaris SXP/RAL2 homologue. The recombinant protein, rSvSXP, was shown to be a potential diagnostic antigen by WB analysis, and a target of serum IgGa, IgG(T) and total IgG in naturally infected horses, with IgG(T) antibodies being the most reliable indicator of S. vulgaris infection in horses. Evaluation of diagnostic accuracy of the ELISA resulted in a sensitivity of 73.3%, a specificity of 81.0%, a diagnostic odds ratio of 11.69; a positive likelihood ratio (LR) of 3.85 and a negative LR was 0.33. The area under the ROC curve was 0.820.ConclusionIgG(T) antibodies to recombinant SvSXP show potential for use as an antigen for prepatent diagnosis of migrating stages of S. vulgaris with moderate to good diagnostic accuracy.

Modelling the short- and long-term impacts of drenching frequency and targeted selective treatment on the performance of grazing lambs and the emergence of anthelmintic resistance

Refugia-based treatment strategies aim to prolong anthelmintic efficacy by maintaining a parasite population unexposed to anthelmintics. Targeted selective treatment (TST) achieves this by treating only animals that will benefit most from treatment, using a determinant criterion (DC). We developed a mathematical model to compare various traits proposed as DC, and investigate impacts of TST and drenching frequency on sheep performance and anthelmintic resistance. Short term, decreasing the proportion of animals drenched reduced benefits of anthelmintic treatment, assessed by empty body weight (EBW), but decreased the rate of anthelmintic resistance development; each consecutive drenching had a reduced impact on average EBW and an increased impact on the rate of anthelmintic resistance emergences. The optimal DC was fecal egg count, maintaining the highest average EBW when reducing the proportion of animals drenched. Long-term, reducing the proportion of animals drenched had little impact on total weight gain benefits, across animals and years, whilst reducing drenching frequency increased it. Decreasing the frequency and proportion of animals drenched were both predicted to increase the duration of anthelmintic efficacy but reduce the total number of drenches administered before resistance was observed. TST and frequency of drenching may lead to different benefits in the short versus long term.

Pharmaceutical treatments of gastrointestinal nematode infections of sheep—Future of anthelmintic drugs

Various interacting factors have been identified to explain why health plans for nematode parasite control, based on conventional epidemiological knowledge and involving pharmaceutical treatments of their sheep hosts have become unsustainable. Of these, the emergence of anthelmintic resistance has had a major impact on the economics of sheep farming, necessitating fundamental managemental changes. This review focusses on the use of anthelmintic drugs for the control of gastrointestinal nematode infections in sheep, emphasising the need to develop sustainable strategies in the face of inevitable parasite evolution in response to exposure to anthelmintic drugs and other noxious stimuli, or favourable opportunities resulting from changing animal management and climatic factors.

Potential of diagnostic markers in sustainable control of cattle parasites

PASTURE-BORNE infections with gastrointestinal nematodes are ubiquitous and they constitute a major challenge to health, welfare and productivity wherever livestock are grazing. Since the advent of the first modern broad-spectrum...

Benzimidazole resistance in Trichostrongylus axei in sheep: Long-term monitoring of affected sheep and genotypic evaluation of the parasite

This is the first report of benzimidazole (BZ) resistance in the nematode Trichostrongylus axei in sheep. Trichostrongylus axei infects several species of herbivores including sheep, cattle and horses, and the emergence of anthelmintic resistance could lead to significant problems in its control. Benzimidazole resistance in two sheep flocks in central France was detected by post-treatment worm counts. The sequencing of a central region of the isotype 1 beta-tubulin gene from adult T. axei recovered post-mortem revealed only one, non-synonymous single nucleotide polymorphism at position 200 (Phe200Tyr), which had already been reported for other nematodes. Seven years after BZ treatment ceased, T. axei helminths present were still resistant to BZ suggesting these parasites do not revert to susceptibility to this anthelmintic, even when the selection pressure had been removed for many years. The findings also highlight major changes in the make-up of the nematode burden in sheep flocks that accompanies the emergence of BZ resistance.

Analysis of nematode infection levels among indoor pigs in Thika District, Kenya

The infection levels of various species of nematode infection were studied in 35 indoor pig herds in Thika district, Kenya. Faecal samples were collected from 830 pigs of all ages and examined for nematode eggs per gram (EPG) of faeces using a modified McMaster technique. The infection intensity exhibited a binomial distribution with a majority of animals having only a light infection (EPG range = 0-500). The level of nematode infections was associated with the age of pigs. Thus, the highest mean EPG levels of Oesophagostomum spp. was 218 (SE = ±34), Ascaris suum 215 (SE = ±62), Trichuris suis 155(SE = ±66) and Strongyloides ransomi 24(SE = ±6) were found in adults, weaners, porkers and piglets respectively. The widest individual nematode species range of EPG values was found in T. suis (0 - 10,000) and A. suum (0 - 5300) infections. It is possible that the low EPG levels could be due to aggressive helminth control by local farmers. This could increase costs and possibly lead to the emergence of anthelmintic resistance. To reduce these costs, it is recommended that animals should be treated after faecal examination and laboratory determination of the EPG levels.. Kenya Veterinarian Vol. 31 (2) 2007: pp. 54-58

Drenching adult ewes: Implications of anthelmintic treatments pre- and post-lambing on the development of anthelmintic resistance

AIMS: To test the hypothesis that peri-parturient anthelmintic treatment of adult ewes, either pre-lambing with a control- led-release capsule (CRC) or at tail-docking with a short-acting oral formulation, would increase the rate of development of anthelmintic resistance, as compared to not drenching ewes and giving an additional drench to lambs in the autumn. Also, to evaluate the potential of routinely leaving 15% of the heaviest lambs untreated when drenching, as a means of slowing the development of anthelmintic resistance. METHODS: A replicated farmlet trial was run from 1999– 2004. Eleven farmlets, each consisting of five paddocks, were initially seeded with Ostertagia (Teladorsagia) circumcincta and Trichostrongylus colubriformis parasites, these being a mixture of albendazole-susceptible and -resistant isolates to yield a 96% reduction in faecal nematode egg count (FEC) on drenching. Four prescriptive drenching regimes were applied; Treatments 1–3 were replicated three times and Treatment 4 twice. Treatments were as follows. Treatment 1: Ewes were given an albendazole CRC pre-lambing, and any ewes exceeding 65 kg liveweight were given two capsules simultaneously; lambs were given a five-drench preventive programme of treatments, orally, of albendazole on Days 0, 21, 42, 70 and 98 after weaning. Treatment 2: Ewes were given a single oral treatment of albenda- zole at docking (2–3 weeks after lambing), and lambs were given the same five-drench preventive programme as in Treatment 1. Treatment 3: Ewes remained untreated, while lambs were given a six-drench preventive programme of treatments, orally, of al- bendazole on Days 0, 21, 42, 70, 98 and 126 after weaning. Treatment 4: Ewes remained untreated, while lambs were given the same six-drench preventive programme as in Treatment 3, but the heaviest 15% of lambs were left untreated each time. Albendazole-resistance status was measured at least twice-yearly, using faecal egg count reduction tests (FECRTs) and larval development assays (LDA). In addition, controlled slaughter of drenched and undrenched tracer lambs was undertaken in the last 3 years. RESULTS: Resistance to albendazole increased most rapidly in Treatment 1, as measured by FECRT and LDA results, and worm burdens in tracer lambs. In Treatment 2, resistance developed slower than in Treatment 1 but faster than in Treat- ments 3 and 4, as measured by LDA; resistance in Treatment 2 developed more quickly than in Treatment 4, as measured by FECRTs. There was no significant difference between Treatments 3 and 4, although this approached significance in Ostertagia spp, as measured by LDA. CONCLUSIONS: Anthelmintic treatments to adult ewes around lambing time are likely to be more selective for resistance than additional treatments administered to lambs in the autumn. Farmers wishing to slow the emergence of anthelmintic resistance on their farms should look to minimise the administration of peri-parturient treatment of ewes. A trend to slower development of resistance where a proportion of lambs were left untreated at each drench suggests further work on this aspect of management of resistance is warranted.

Managing anthelmintic resistance in small ruminant livestock of resource-poor farmers in South Africa : review article

Gastrointestinal parasitism is one of the most important disease complexes of sheep and goats impacting on the resource-poor livestock farmer. Of the responsible nematodes, Haemonchus contortus, a blood-sucking worm of the abomasum, poses possibly the greatest threat. Over the past several decades, the worm has been controlled through the use of anthelmintics, but the emergence of anthelmintic resistance has threatened this chemotherapeutic approach. In Africa, the overall prevalence of anthelmintic resistance has not been extensively investigated, particularly within the resource-poor farming sector, but resistance has been reported from at least 14 countries with most of the reports emanating from Kenya and South Africa and the majority concerning H. contortus. While levels of resistance under commercial sheep farming systems in South Africa is considered to be amongst the worst in the world, resistance has also been reported from the resource-poor farming sector. Increases in productivity and reproduction of livestock and the development of markets for sale of animals are seen by international funding bodies as a way out of poverty for communities that keep livestock. This must lead to the greater need for parasite control. At such times, the risk of levels of anthelmintic resistance escalating is much greater and there is therefore a need to look at alternatives to their use. Proposed strategies include the appropriate, but judicious use of anthelmintics by application of the FAMACHA system and the use of alternatives to anthelmintics such as strategic nutrient supplementation. It is also very clear that there is a strong demand for knowledge about animal diseases, including helminthosis, and their effective management in the resource-poor livestock farming communities. This is an important challenge to meet.

Efficacy of benzimidazole anthelmintics in goats and sheep in the Philippines using a larval development assay

The negative effects of nematodes in small ruminants can be reduced by use of dewormers but their effectiveness is increasingly limited by the emergence of anthelmintic resistance. The efficacy of benzimidazole (BZ) anthelmintics in the Philippines was estimated by an in vitro larval development assay using worm eggs recovered from faeces collected from goats and sheep. Two hundred and eighteen farms were selected to represent areas of the country with high goat and sheep populations and the full range of farm sizes, from smallholders with just a few animals to commercial and institutional farms with several hundred. Initial surveys of worm control advisers indicated that BZs have been in continuous widespread use for up to 20 years with little use of other chemical groups. A larval development assay (LDA: DrenchRite ®) was modified for use with BZs alone to allow up to five samples to be analysed on a single microtitre plate. The assay was validated by comparison with the faecal egg count reduction test (FECRT). The dominant nematode genera were Haemonchus and Trichostrongylus with small numbers of Oesophagostomum. The range of BZ efficacy estimated from the LDA results was 0–100% and the distribution of efficacy levels was continuous, with mean efficacy of 82 and 64% for goats and sheep, respectively. There were significant associations between efficacy and parameters measured to characterize the sampled farms: size of animal management group, FEC of sample, recent importation of stock and no access to common grazing were all correlated with decreased efficacy. Likewise, low efficacy was associated with reported frequency and number of years that BZ drenches had been used. The LDA was found to be highly suited to estimate efficacy in nematode populations from small farms where performance of a FECRT for even one chemical would be impractical. Using a larval development assay, we have demonstrated a wide efficacy range for BZs against nematodes from all sizes of goat and sheep farms in the tropics.

Variation and immunity to intestinal worms.

Genetically determined variation in host capacity to express resistance to a given parasite plays a major role in determining the outcome of infection. It can be assumed that the same is true of variation in parasites, but very much less is known of its influence on the host-parasite relationship. Phenotypic and genotypic variation within species of intestinal worms is now well documented, detailed studies having been made of parasites such as Ascaris in humans and trichostrongyles in domestic animals. However, the extent to which this variation affects the course of infection or the host immune response in these hosts is limited. Of the nematodes used as experimental models in laboratory rodents, detailed data on phenotypic or genotypic variation are limited to Strongyloides and Trichinella. Parasite variation is known to be subject to host-mediated selection, the emergence of anthelmintic resistance being a good example. Repeated passage has been used to select lines of parasite that survive in abnormal hosts or which show adaptation to host immunity. Experimental studies with Trichinella genotypes in mice have demonstrated the extent to which parasite variation influences the nature and degree of the host's immune and inflammatory responses, the complex interplay between immunogenicity and pathogenicity influencing both partners in the relationship. Recent studies with isolates of Trichuris muris have shown how parasite variation influences the capacity of mice to express the T helper cell responses necessary for resistance. Molecular differences between T. muris isolates have been shown in their excreted/secreted products as well as at the level of their DNA. Knowledge of the functional consequences of parasite variation will add to our understanding of host-parasite evolution as well as providing a rational basis for predicting the outcome of controls strategies that rest on the improvement of host resistance through vaccination or selective breeding.

Nematodes and liver fluke in New Zealand

A general review of the epidemiology, significance and control of nematode parasitism of sheep, goats, cattle and deer in New Zealand, the emergence of anthelmintic resistance and its effects, and the search for parasite control strategies that reduce reliance on anthelmintic use, is provided. The research that has formed the basis for present levels of understanding of this complex and important topic is summarised and sources of further information are indicated. Aspects of nematode infections of horses, pigs, dogs and cats, and the history of the liver fluke, Fasciola hepatica, in New Zealand are also reviewed briefly.

10 μg cholecystokinin tetrapeptide reduces the reaction to a 35% carbon dioxide challenge

The limitations associated with the use of anthelmintic drugs in the control of gastrotintestinal nematodosis, such as the emergence of anthelmintic resistance, have stimulated the study of the immunological control of many parasites. In the case of Haemonchus contortus, several vaccination trials using native and recombinant antigens have been conducted. A group of antigens with demonstrated immunoprotective value are cathepsin B – like proteolytic enzymes of the cysteine proteinase type. These enzymes, which have been observed in both excretory-secretory products and somatic extracts of H. contortus, may vary among different geographic isolates and on strains isolated from different hosts, or even from the same host, as has been demonstrated in some comparative studies of genetic variability. In the present study, we evaluated the genetic variability of the worms that fully developed their endogenous cycle in immunised sheep and goat in order to identify the alleles of most immunoprotective value. To address these objectives, groups of sheep and goats were immunised with PBS soluble fractions enriched for cysteine proteinases from adult worms of H. contortus from either a strain of H. contortus isolated from goats of Gran Canaria Island (SP) or a strain isolated from sheep of North America (NA). The results confirmed the immunoprophylactic value of this type of enzyme against haemonchosis in both sheep and goats in association with increased levels of specific IgG. The genetic analysis demonstrated that the immunisation had a genetic selection on proteinase-encoding genes. In all the immunised animals, allelic frequencies were statistically different from those observed in non-immunised control animals in the four analysed genes. The reduction in the allelic frequencies suggests that parasites expressing these proteases are selectively targeted by the vaccine, and hence they should be considered in any subunit vaccine approach to control haemonchosis in small ruminants.

Sheep health: research developments and emerging problems

AbstractRelative to other livestock sectors sheep production has a high wastage through mortality, suboptimal husbandry practices and premature culling. A significant but unquantified component of this loss is attributable to infectious and parasitic disease. Some common infectious diseases (e.g. those caused byClostridia) are amenable to effective control but regular sporadic outbreaks indicate that, from time to time, control measures fail or are improperly applied. Other diseases, notably those causing abortion, continue to present problems, particularly chlamydial abortion and toxoplasmosis. Inability to diagnose infection before the onset of clinical signs hinders the control of scrapie and pulmonary adenomatosis (jaagsiekte) and the only vaccine against orf is of limited efficacy.However, the new information being generated by application of molecular biological techniques in some of these problem areas carries promise of improved control. Good examples are provided by research which has led to a blood test for discriminating between sheep that are genetically susceptible or resistant to scrapie and by studies onChlamydia psittaciwhich have identified essential protective antigens and which thereby improve prospects for significant vaccine enhancement.The world-wide importance of gastrointestinal parasitism and the emergence of anthelmintic resistance have spurred efforts, internationally, to develop an alternative biological control system. Evidence that protective vaccination may be feasible is accruing but the time scale to a real product may be long.Factors to be considered in assessing future disease trends include the impact of a ‘frontier-free’ Europe, changes in husbandry practices, introduction of new livestock species, altered land use and climatic change resulting from global warming. Some predictions are made.