Anthelmintic resistance in nematode parasites of cattle: a global issue?

Acceptable performance of grazing cattle frequently depends on the availability of effective broad-spectrum anthelmintics to remove, or prevent infection with, gastrointestinal nematodes. This control is increasingly threatened by populations of nematodes resistant to the most commonly used anthelmintics. Although this appears to have developed more slowly than in nematodes infecting small ruminants, the number of reports in the literature over the past five years suggests a rapidly escalating problem. This review discusses this literature, several issues unique to cattle parasitism and anthelmintics, and how previous research in small ruminants can improve the management of anthelmintic resistance in cattle.     

Environmental control of gastrointestinal strongylosis in sheep and goats

Gastrointestinal strongylosis are the dominant parasitic infections of sheep and goats. The successful control of these parasites cannot be done exclusively with anthelmintics, but the first step is an integrated program for environmental prophylaxis. The correct planning of the prophylaxis program has to be preceded by the analysis of the related problems: (1) the parasitological status of farm livestock; (2) knowledge of the farm management; (3) hydrogeological, pedological and climatic-environmental aspects. The environmental control strategies can be resumed as follows: avoiding animals from different farms to share the same pasture; avoiding animals of different age classes to graze together; parcel the pastures to permit a rational rotation; rotational grazing of pastures according to the seasonal development of parasites; stocking rate; young animals grazing ahead of the older animal ones; crop management practices (draining, ploughing, harrowing, scrub clearing, fertilizing, etc.). These measures make the habitat less suitable for the free-living stages of gastrointestinal strongyles, reducing the potential of infection of the same pastures.     

The role of epidemiological knowledge and grazing management for helminth control in small ruminants

There is no single requirement more crucial to the rational and sustainable control of helminth parasites in grazing animals than a comprehensive knowledge of the epidemiology of the parasite as it interacts with the host in a specific climatic, management and production environment. In its absence, anthelmintic treatment is either given suppressively, which provokes resistance, or therapeutically, which risks clinical disease and production losses. Sustainable parasite-control programmes require knowledge of seasonal larval availability, origin of larvae contributing to any peaks and climatic requirements for worm egg hatching, larval development and survival. Control measures based on this knowledge include strategic anthelmintic treatments and various forms of grazing management. While these measures can reduce the frequency of anthelmintic treatment required, their effect on selection for drench resistance is more problematical, unless they can be combined with other forms of control to reduce our current dependence on anthelmintics.     

Gastrointestinal nematode parasites and the stability and productivity of intensive ruminant grazing systems

This paper uses mathematical models, describing the transmission dynamics of directly transmitted gastrointestinal nematode parasites of sheep and cattle, to examine the impact of these parasites on the stability and productivity of ruminant grazing systems. Current models of the ecology of grass growth under grazing, and the epidemiology of trichostrongylid nematode parasites of ruminants, are combined in a formulation that captures the general features of the plant - (ruminant) herbivore - parasite interaction. The simplest case, in which herbivore numbers are constant and not food limited (the norm for many agricultural systems) is considered in detail. The effect of gastrointestinal parasitism in reducing herbivore feeding rates is shown to act as a potential density-dependent constraint on the parasite's infection rate. The process is manifested in the model as a progressive linearization of the relation between herbivore feeding rate and plant density at the parasite equilibrium. This effect acts to stabilize the dynamics of the model grazing system and significantly affects its predictions about the impact of parasite control and the pattern of host productivity. Model predictions are discussed in the light of relevant field observations, and areas for future research are identified.     

Influence of host nutrition on the development and consequences of nematode parasitism in ruminants.

Control of gastrointestinal nematodes of ruminants is based largely on use of anthelmintics combined, where practical, with pasture management. The increasing prevalence of resistance to anthelmintics has led to the search for alternative sustainable control strategies. Here, we consider how nutrition, as a short-term alternative, can influence the host--parasite relationship in ruminants, using gastrointestinal nematode infections of sheep as the model system. Nutrition can affect the ability of the host to cope with the consequences of parasitism and to contain and eventually to overcome parasitism. It can also affect the parasite population through the intake of antiparasitic compounds.     

The epizootiology of gastrointestinal nematode parasites in Greek dairy breeds of sheep and goats

Gastrointestinal (GI) parasitism represents a severe health problem in small ruminant production systems world-wide. The objective of the present study was three-fold: (i) to assess the prevalence of GI parasitism in dairy breeds of sheep and goats in selected areas of Greece; (ii) to determine the species of existing gastrointestinal parasites; and (iii) to investigate the effect of climatic factors on the seasonal variation of parasite population dynamics in dairy sheep and goats reared in two different geographical areas of Greece. The study was conducted in four flocks of either sheep or goats that were equally allocated in northern and central Greece. In each flock, faecal samples were randomly collected from 30 animals at monthly intervals and were used for nematode egg counts and coprocultures. Two animals from each flock were slaughtered monthly and their GI tract were examined for adult worm population and identification. The study revealed that the parasitic burdens in sheep were significantly (P<0.05) higher than those in goats. Faecal egg counts for both sheep and goats were significantly (P<0.01) affected by the month of the year and there was also a significant interaction between month of the year and area of study (P<0.01). Teladorsagia, Haemonchus, Trichostrongylus and Chabertia were the most prevalent nematode genera in both sheep and goats. Such information could be useful for the development of strategic treatments when sheep and goats are reared under systems similar to those described in this study.     

The role of parasite epidemiology in the management of grazing cattle

Epidemiology of ruminant helminths is the foundation on which strategic parasite control programmes are designed. Without this information one is not able to use anthelmintics to provide the optimal benefits for controlling both the adult worm and the pasture larval populations. The absence of strategic programmes generally results in using anthelmintics at the convenience of the producer, which may have little if any impact on parasite populations. The design of a strategic parasite control programme requires a knowledge of the dynamics of egg shedding from the host and the resulting pasture larval populations. It is important to know if larvae are available when animals are turned out onto pasture, when larval populations reach their maximal numbers and when they are induced to become hypobiotic. The goal is to keep pasture larval populations as low as possible. The use of pasture rotation adds another dimension to control programmes. The longer a pasture is allowed to remain fallow, the lower the pasture larval burden will be when it is grazed next. However, when we use intensive rotational grazing, animals may return to the pasture about 28 days later, when the larvae resulting from the eggs shed in the previous grazing are infective. This practice forces cattle to eat all of the forage available, including the grass closest to the faecal pat, where most of the infective larvae are available. If we treated cattle before turning them onto a clean rotationally grazed pasture, we should be able to control parasitism. Using a long-acting anthelmintic should enhance helminth control in rotationally grazed pastures and actually help to clean the pastures. Another grazing management practice is to alternately graze different species. This programme with the strategic use of anthelmintics should reduce parasitism in both host species.     

Population density and phenotypic attributes influence the level of nematode parasitism in roe deer

The impact of parasites on population dynamics is well documented, but less is known on how host population density affects parasite spread. This relationship is difficult to assess because of confounding effects of social structure, population density, and environmental conditions that lead to biased among-population comparisons. Here, we analyzed the infestation by two groups of nematodes (gastro-intestinal (GI) strongyles and Trichuris) in the roe deer (Capreolus capreolus) population of Trois Fontaines (France) between 1997 and 2007. During this period, we experimentally manipulated population density through changes in removals. Using measures collected on 297 individuals, we quantified the impact of density on parasite spread after taking into account possible influences of date, age, sex, body mass, and weather conditions. The prevalence and abundance of eggs of both parasites in females were positively related to roe deer density, except Trichuris in adult females. We also found a negative relationship between parasitism and body mass, and strong age and sex-dependent patterns of parasitism. Prime-age adults were less often parasitized and had lower fecal egg counts than fawns or old individuals, and males were more heavily and more often infected than females. Trichuris parasites were not affected by weather, whereas GI strongyles were less present after dry and hot summers. In the range of observed densities, the observed effect of density likely involves a variation of the exposure rate, as opposed to variation in host susceptibility.     

Vaccines against gastrointestinal nematode parasites of ruminants

A consequence of intensive livestock production is an increase in the incidence and impact of gastrointestinal (GI) parasites. Farmers have sought to redress this shift in the natural host-parasite relationship by chemotherapy. However, with the widespread development of resistance to anthelmintics and the current impetus for sustainable agricultural practices, alternatives such as vaccines are being sought to maintain animal productivity. In this article, David Emery and Barry Wagland discuss recent advances in immunity to nematode infections of ruminants and the development of vaccines made possible by the dogged persistence and ingenuity of cadres of parasitologists who have done more than 'go through the motions'.     

Breeding cattle and sheep for resistance to gastrointestinal nematodes

Gastrointestinal nematodes are an important cause of reduced production of meat, milk and wool in domestic livestock. It is generally believed that problems caused by these parasites have increased owing to the intensification of animal husbandry(1-3) of resistance to anthelmintics, current research is focussed on alternative control strategies that do not rely on anthelmintics. Here, Bram Kloosterman, Henk Parmentier and Harm Ploeger review work on the genetic resistance of domestic ruminants to these nematodes and discuss the practicality of breeding programmes.     

Gastrointestinal helminths of ponies in Louisiana: a comparison of species currently prevalent with those present 20 years ago

A survey in Louisiana of gastrointestinal helminths recovered at necropsy from 117 ponies with minimal exposure to anthelmintics between 1989 and 2000 is compared with a survey conducted 20 yr earlier in the same region. An objective of this study was to determine whether species diversity has been affected by the advent and use of the macrocyclic lactone (ML) parasiticides and by the increased anthelmintic pressure on the helminth species infecting the general equine population. Twenty-six cyathostome species and 8 strongyle species were recovered. Two cyathostome species that were not found before, Cylicostephanus asymetricus and C. bidentatus, and 1 species of large strongyle, Oesophagodontus robustus, were added to the list of species found in Louisiana. All cyathostome and large strongyle species found previously were still present. But prevalences and intensities were significantly reduced for almost all large and small strongyle species. Prevalences and intensities of Oxyuris equi adults and larvae were reduced, whereas the prevalence of Parascaris equorum remained constant. The tapeworm Paranoplocephala mamillana was added to the list of parasite species found in Louisiana. Anoplocephala perfoliata remained the most common cestode. This species was found at the same level of intensity but increased slightly in prevalence. Anoplocephala magna was found less frequently than previously. The overall diversity of species remained reatively unchanged. The reasons for the differences in intensity and prevalence of strongyles between these 2 periods are unknown but might be related to the development and use of the broad-spectrum ML anthelmintics in the intervening period, a difference in the population of equids surveyed, different techniques used to identify the parasites, or differences in numbers of parasites identified (or to all).     

Anthelmintic resistance: the state of play revisited

Helminthosis is one of the major constraints in the successful wool and mutton industry throughout the world. Anthelmintic Resistance (AR) is said to have been established when previously effective drug ceases to kill exposed parasitic population at the therapeutically recommended dosages. Anthelmintic resistance is almost cosmopolitan in distribution and it has been reported in almost all species of domestic animals and even in some parasites of human beings. Some of the most important species of parasites of small ruminants in which AR has been reported include: Haemonchus spp., Trichostrongylus spp. Teladorsagia spp., Cooperia spp. Nematodirus spp., and Oesophagostomum spp. All the major groups of anthelmintics have been reported for development of variable degrees of resistance in different species of gastrointestinal nematodes. This paper describes the global scenario of prevalence and methods used for detection of AR in small ruminants. Different mechanisms and contributory factors for the development of AR are discussed. Various options and alternate strategies for the control and/or delay in the onset of AR are suggested in the light of available information.     

Pro and cons of targeted selective treatment against digestive-tract strongyles of ruminants

The increasing prevalence of resistance to anthelmintics among gastrointestinal nematodes and the desire for lower input agriculture have promoted the idea that targeted selective treatment (treating the animals in need of such a treatment and only them) could be a sustainable solution for controlling internal parasites of ruminants. The pros are the slowing of resistance prevalence, lower residues of anthelmintics in meat and milk, and lower cost; the cons are the difficulty and time spent on selecting animals in need of treatment and the possibility of lower production. Using actual experiments and modelling we show that targeted selective treatment can be used to sustainably control gastrointestinal nematode infections in flock.     

Parasite control practices on Swedish horse farms

Background  

Virtually all horses are infected with helminth parasites. For some decades, the control of parasites of Swedish horses has been based on routine treatments with anthelmintics, often several times per year. Since anthelmintic resistance is becoming an increasing problem it is essential to develop more sustainable control strategies, which are adapted to different types of horse management. The aim of this study was to obtain information on practices used by Swedish horse owners for the control of endoparasites.     

Drug transfer into target helminth parasites

The pharmacokinetics of an anthelmintic drug includes the time course of drug absorption, distribution, metabolism and elimination from the host and determines the concentration of the active drug that reaches the location of the parasite. However, the action of the anthelmintic also depends on the ability of the active drug to reach its specific receptor within the target parasite. Thus, drug entry and accumulation in target helminths are important issues when considering how best to achieve optimal efficacy. Passive drug transfer through the external helminth surface is the predominant entry mechanism for most widely used anthelmintics and is discussed in this article. Despite the structural differences between the external surface of nematodes (the cuticle) and the external surface of cestodes and trematodes (the tegument), the mechanism of drug entrance into both types of helminth depends on the lipophilicity of the anthelmintic and this is the major physicochemical determinant for the drug to reach a therapeutic concentration in the target parasite. Understanding the processes that regulate drug transfer into helminth parasites is an important aspect in improving the control of parasites in human and veterinary medicine.     

Detection of benzimidazole resistance in trichostrongylid nematodes

Benzimidazole anthelmintics (Box 1) have an important role in the control of economically-important nematode parasites of sheep and other ruminants. But effective control and management strategies using such compounds require a clear appraisal of the resistance or susceptibility of the target worms. Currently available tests for benzimidozole resistance in trichostrongylid nematodes tend to be costly, time-consuming and technically-demanding - as a result, attention is now turning to biochemical assays.     

Integrated control of nematode infections in cattle: a reality? A need? A future?

Helminth infections are a major cause of production loss in cattle. Great progress has been achieved in the design of control strategies for these infections. Control is based mainly on the use of anthelmintics, and these have become more potent and easier to administer. However, the most effective control is possible only through the integration of different approaches. Moreover, an increasing number of disadvantages of chemotherapy/prophylaxis--biological, economical and environmental--have been suggested. In sheep, the high incidence of anthelmintic resistance has simply forced veterinarians/producers to adopt alternative control strategies; in cattle, no real need for deviation from the actual control programmes seems to exist. Therefore, the following questions are discussed: (1) Based on the distribution of cattle worldwide, what are the target parasites? (2) Can we continue to rely on control based mainly on the use of (highly effective) anthelmintics? (3) What are the prospects for non-chemical control? (4) Who will develop and implement integrated control systems? (5) In the case of parasite control in Western Europe, has it been efficient and can/need it be changed? (6) How can we integrate helminth control in the general design of herd disease control?     

To treat or not to treat: diagnostic thresholds in subclinical helminth infections of cattle

Helminth infections of cattle place significant burdens on livestock production and farm economic efficiency. Heavy infections are relatively easy to detect and treat with anthelmintics. However, subclinical infections have major but often hidden impacts on animals, necessitating more refined diagnostics to detect them and ideally inform farmers about the likely impact of anthelmintic treatment on animal and herd performance. Here, we review recent advances in diagnosing three major cattle helminth infections – gastrointestinal nematodes (GINs), liver flukes, and lungworms – and the search for subclinical infection thresholds to guide treatment decisions. Combining refined diagnostic thresholds with farm-specific information on grazing systems and animal history enables farmers to tailor helminth treatments to specific epidemiological circumstances, thereby limiting anthelmintic resistance (AR) and boosting agricultural efficiency and food security.     

Anthelmintics for horses

Modern equine anthelmintics can be divided into at least seven principal groups based on mode of action, i.e., benzimidazoles, pro-benzimidazoles, imidothiazoles, tetrahydropyrimidines, organophosphates, piperazines, and avermectins. The spectrum of activity of these drugs varies and resistance of cyathostomes to benzimidazole and pro-benzimidazole drugs has been observed in many areas. Cross resistance with other groups has not been reported in equines, however. Control is dependent upon understanding the capabilities of anthelmintics and the epizootiology of the important parasites, e.g., large strongyles, cyathostomes, ascarids and bots. Development of effective programs in a given region should be based on routine fecal analysis to ensure that treatment schedule and products selected are adequate for local climatic conditions and management methods.     

Using long-term averted goats for selective grazing in olive groves

Conditioned taste aversion (CTA) is a useful tool to modify animal feed preferences, allowing the implementation of selective grazing to control weeds in tree orchards without damaging the trees or affecting fruit production. LiCl is commonly used for inducing CTA. However, studies investigating the long-term persistence of CTA by LiCl in small ruminants are scarce. With this aim, we evaluated the efficiency of two LiCl doses (AV1 and AV2, 175 and 200 mg/kg BW, respectively) and a control (C, 0 mg/kg BW) for averting non-lactating dairy goats (n=15) to olive tree leaves. Aversion induction was reinforced on day 9 in those goats that consumed >10 g of olive leaves. Mid-term aversion effectiveness was assessed by five double-choice feeding tests (days 16, 24, 31, 38 and 53) of 30 min each, where 100 g of olive leaves were offered side-by-side with 390 g of Italian rye-grass (as-fed). Long-term aversion effectiveness was assessed in C, AV1 and AV2 goats by grazing for 30 min in paddocks with a simulated olive tree (days 59, 90, 121, 182 and 420). Moreover, C and AV2 goats were compared under on-field conditions (days 143, 211 and 363) in a commercial olive grove also for 30 min. The CTA proved to be established with a single LiCl dose in all goats and persisted for 4 and 55 days in AV1 and AV2 goats, respectively (P<0.001). However, 80% AV1 and 20% AV2 goats needed to be reinforced at day 9. When grazing under simulated olive tree and commercial olive grove conditions, the CTA goats, especially AV2 group, avoided the contact with the olive trees and minimally used a bipedal stance to feed leaves, than control goats. On average, time proportion spent consuming olive leaves and sprouts was much greater (P<0.05) for C (50.7±9.1%) than for AV1 (14.4±3.9%) and AV2 (3.1±0.9%). In conclusion, the 200 mg LiCl/kg BW dose was more effective than the 175 mg LiCl/kg BW dose for inducing an effective long-term CTA to olive tree leaves in goats.