Anthelmintic efficacy of Achillea millifolium against gastrointestinal nematodes of sheep: in vitro and in vivo studies

Achillea millifolium Linn., commonly called 'Pehl-ghasa', is used by farmers in traditional animal health care as a vermifuge. The objective of this study was to evaluate the anthelmintic efficacy of crude aqueous extracts and crude ethanolic extracts of entire A. millifolium against the gastrointestinal nematodes of sheep. The worm motility inhibition assay was used for in vitro studies and faecal egg count reduction assay was used for in vivo studies. In vitro studies revealed significant anthelmintic effects of aqueous extracts and ethanolic extracts on live Haemonchus contortus worms (P < 0.05) as evident from their paralysis and/or death at 8 h post exposure. Aqueous extracts of A. millifolium resulted in a mean worm motility inhibition of 94.44%, while ethanolic extracts resulted in mean worm motility inhibition of 88.88%. The mean mortality index of aqueous extracts was 0.95 while for ethanolic extracts it was 0.9. The lethal concentration 50 was 0.05 mg ml(-1) for aqueous extracts and 0.11 mg ml(-1) for ethanolic extracts. The in vivo anthelmintic activity of aqueous and ethanolic extracts of A. millifolium demonstrated a maximum (88.40%) nematode egg count reduction in sheep treated with aqueous extracts at 2 g kg(-1) body weight on day 15 after treatment. Ethanolic extracts resulted in a maximum of 76.53% reduction in faecal egg counts on day 15 after treatment with 2 g kg(-1) body weight. Thus, the aqueous extracts exhibited greater anthelmintic activity under both in vitro and in vivo conditions, and could be due to the presence of water-soluble active principle/s in A. millifolium. It is concluded that the entire plant of A. millifolium possesses significant anthelmintic activity and could be a potential alternative for treating cases of helminth infections in ruminants.     

Contrasting views of animal healthcare providers on worm control practices for sheep and goats in an arid environment

A questionnaire survey was conducted to determine the worm control practices and anthelmintic usage of 150 key respondents involved in sheep and goat production in the arid Thal area of Pakistan. The information was collected by visiting farms, and interviewing the key respondents which included veterinary officers (n = 15), veterinary assistants (n = 51), traditional practitioners (n = 24), and small and large scale sheep/goat farm herders and owners (n = 60). Among all interviewed animal healthcare providers, the veterinary officers had the highest level of awareness of parasitic infection and advocated the use of modern available anthelmintics according to the predefined schedule. The farmers on the other hand, had the lowest level of knowledge about parasitic infections. They used modern anthelmintics at low frequencies (every six months) following an unusual practice of diluting the medicine. Veterinary assistants had a medium level of awareness about the parasitic infections using anthelmintic treatments when they deemed necessary rather than following a predefined treatment schedule. Traditional practitioners were also aware of parasitic infections and used traditional anthelmintics or a combination of the traditional and modern anthelmintics. The animal health providers had a different awareness and knowledge of parasitic infections which resulted in contrasting proposals for its' control. The farmers used worm control measures in accordance with their own views and those of animal healthcare advisors, combining modern and traditional treatments. This study provides the first insight into the differing views of those animal healthcare providers who form the basis for effective parasitic control within the sheep and goat industry of an arid region.     

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?     

Macrocyclic lactone resistance in nematodes of cattle in Brazil: Blame it to the ticks!

Strategic helminth control in adult cattle would hardly impose sufficient selection pressure to parasite populations but reports of resistance against macrocyclic lactone (ML) based-products have been confirmed worldwide. The objective of this study was to evaluate the scientific literature of ML resistance (< 90.0% efficiency) in helminths of cattle from 2001 (the first report) to 2020 in Brazil. Additional to the data, we studied the correlation of parasite control practices based on a questionnaire given to 32 farmers. The search returned 246 reports and 21 full articles were selected. From these, a Wordcloud and a Keyword Co-occurrence Network graph were created. The published data revealed that most of the studies (19/21) reported multi-species (Cooperia spp., Haemonchus sp., Oesophagostomum radiatum, Trichostrongylus sp.) resistance to ML. None of the reports described the treatment frequency in the tested farms. As for the questionnaire, the majority of farmers (> 70.0%) responded that they rotate products after treatment, animals are treated monthly or biweekly (58.0%), treatments are based on visual evaluation (coat condition, ectoparasite infestation), and that in 94.0% of the times farmers treat all animals. Moreover, farmers use ML in association with potent acaricides (cypermethrin, chlorpyriphos, fluazuron) in more than 90.0% of the times (15/16). It was observed that this regimen was used to prevent and control the cattle-tick Rhipicephalus microplus (90.0%) and the horn-fly, Haematobia irritans (30.0%) infestations. We conclude that the most important factor for nematode resistance was the high level of ML exposure of up to 16 times/year, in combination with acaricides to control ticks and to a lesser extent to control horn-flies. Therefore, selection of helminth populations in cattle in Brazil can be considered secondary to ectoparasite control. The present analysis is critical, as one the most widespread recommendations to avoid drug resistance is to reduce the use of long-acting compounds, due to their extended persistent periods, increasing parasite selection. Moreover, a more serious attitude must be taken regarding parasite control strategies for livestock, reinforcing that health protocols should be based on single acaricidal products whenever possible. Complementary, selective evaluations based on transient threshold population abundance must be enforced to reduce treatment frequency, reducing parasite selection and animal distress.     

Anthelmintics for ruminants

There is now a wide range of potent broad-spectrum anthelmintics for cattle and small ruminants, including the benzimidazoles, the avermectins, tetrahydropyrimidines and imidothiazoles which are highly efficacious against parasite gastroenteritis and bronchitis. Fascioliasis can be controlled with the salicy-lanilide and related phenolic compounds, the benzimidazoles, albendazole and triclabendazole the latter being the first flukicide with excellent activity against all stages of liver fluke infestation.The major developments for anthelmintic therapy have been and will be in the use of intraruminal boluses with either sustained release or pulse release of anthelmintic and other methods for group medication. The implications of such strategies for helminth resistance and individual immunity require further evaluation.     

Understanding the role of wild ruminants in anthelmintic resistance in livestock

Wild ruminants are susceptible to infection from generalist helminth species, which can also infect domestic ruminants. A better understanding is required of the conditions under which wild ruminants can act as a source of helminths (including anthelmintic-resistant genotypes) for domestic ruminants, and vice versa, with the added possibility that wildlife could act as refugia for drug-susceptible genotypes and hence buffer the spread and development of resistance. Helminth infections cause significant productivity losses in domestic ruminants and a growing resistance to all classes of anthelmintic drug escalates concerns around helminth infection in the livestock industry. Previous research demonstrates that drug-resistant strains of the pathogenic nematode Haemonchus contortus can be transmitted between wild and domestic ruminants, and that gastro-intestinal nematode infections are more intense in wild ruminants within areas of high livestock density. In this article, the factors likely to influence the role of wild ruminants in helminth infections and anthelmintic resistance in livestock are considered, including host population movement across heterogeneous landscapes, and the effects of climate and environment on parasite dynamics. Methods of predicting and validating suspected drivers of helminth transmission in this context are considered based on advances in predictive modelling and molecular tools.     

Phylogenetic Characterization of β-Tubulins and Development of Pyrosequencing Assays for Benzimidazole Resistance in Cattle Nematodes

Control of helminth infections is a major task in livestock production to prevent health constraints and economic losses. However, resistance to established anthelmintic substances already impedes effective anthelmintic treatment in many regions worldwide. Thus, there is an obvious need for sensitive and reliable methods to assess the resistance status of at least the most important nematode populations. Several single nucleotide polymorphisms (SNPs) in the β-tubulin isotype 1 gene of various nematodes correlate with resistance to benzimidazoles (BZ), a major anthelmintic class. Here we describe the full-length β-tubulin isotype 1 and 2 and α-tubulin coding sequences of the cattle nematode Ostertagia ostertagi. Additionally, the Cooperia oncophora α-tubulin coding sequence was identified. Phylogenetic maximum-likelihood analysis revealed that both isotype 1 and 2 are orthologs to the Caenorhabditis elegans ben-1 gene which is also associated with BZ resistance upon mutation. In contrast, a Trichuris trichiura cDNA, postulated to be β-tubulin isotype 1 involved in BZ resistance in this human parasite, turned out to be closely related to C. elegans β-tubulins tbb-4 and mec-7 and would therefore represent the first non-ben-1-like β-tubulin to be under selection through treatment with BZs. A pyrosequencing assay was established to detect BZ resistance associated SNPs in β-tubulin isotype 1 codons 167, 198 and 200 of C. oncophora and O. ostertagi. PCR-fragments representing either of the two alleles were combined in defined ratios to evaluate the pyrosequencing assay. The correlation between the given and the measured allele frequencies of the respective SNPs was very high. Subsequently laboratory isolates and field populations with known resistance status were analyzed. With the exception of codon 167 in Cooperia, increases of resistance associated alleles were detected for all codons in at least one of the phenotypically resistant population. Pyrosequencing provides a fast, inexpensive and sensitive alternative to conventional resistance detection methods.     

A research agenda for helminth diseases of humans: intervention for control and elimination

Recognising the burden helminth infections impose on human populations, and particularly the poor, major intervention programmes have been launched to control onchocerciasis, lymphatic filariasis, soil-transmitted helminthiases, schistosomiasis, and cysticercosis. The Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to review helminthiases research and identify research priorities and gaps. A summary of current helminth control initiatives is presented and available tools are described. Most of these programmes are highly dependent on mass drug administration (MDA) of anthelmintic drugs (donated or available at low cost) and require annual or biannual treatment of large numbers of at-risk populations, over prolonged periods of time. The continuation of prolonged MDA with a limited number of anthelmintics greatly increases the probability that drug resistance will develop, which would raise serious problems for continuation of control and the achievement of elimination. Most initiatives have focussed on a single type of helminth infection, but recognition of co-endemicity and polyparasitism is leading to more integration of control. An understanding of the implications of control integration for implementation, treatment coverage, combination of pharmaceuticals, and monitoring is needed. To achieve the goals of morbidity reduction or elimination of infection, novel tools need to be developed, including more efficacious drugs, vaccines, and/or antivectorial agents, new diagnostics for infection and assessment of drug efficacy, and markers for possible anthelmintic resistance. In addition, there is a need for the development of new formulations of some existing anthelmintics (e.g., paediatric formulations). To achieve ultimate elimination of helminth parasites, treatments for the above mentioned helminthiases, and for taeniasis and food-borne trematodiases, will need to be integrated with monitoring, education, sanitation, access to health services, and where appropriate, vector control or reduction of the parasite reservoir in alternative hosts. Based on an analysis of current knowledge gaps and identification of priorities, a research and development agenda for intervention tools considered necessary for control and elimination of human helminthiases is presented, and the challenges to be confronted are discussed.     

Egg excretion indicators for the measurement of soil-transmitted helminth response to treatment

BackgroundPeriodic administration of anthelmintic drugs is a cost-effective intervention for morbidity control of soil-transmitted helminth (STH) infections. However, with programs expanding, drug pressure potentially selecting for drug-resistant parasites increases. While monitoring anthelmintic drug efficacy is crucial to inform country control program strategies, different factors must be taken into consideration that influence drug efficacy and make it difficult to standardize treatment outcome measures. We aimed to identify suitable approaches to assess and compare the efficacy of different anthelmintic treatments.MethodologyWe built an individual participant-level database from 11 randomized controlled trials and two observational studies in which subjects received single-agent or combination therapy, or placebo. Eggs per gram of stool were calculated from egg counts at baseline and post-treatment. Egg reduction rates (ERR; based on mean group egg counts) and individual-patient ERR (iERR) were utilized to express drug efficacy and analyzed after log-transformation with a linear mixed effect model. The analyses were separated by follow-up duration (14–21 and 22–45 days) after drug administration.Principal findingsThe 13 studies enrolled 5,759 STH stool-positive individuals; 5,688 received active medication or placebo contributing a total of 11,103 STH infections (65% had two or three concurrent infections), of whom 3,904 (8,503 infections) and 1,784 (2,550 infections) had efficacy assessed at 14–21 days and 22–45 days post-treatment, respectively. Neither the number of helminth co-infections nor duration of follow-up affected ERR for any helminth species. The number of participants treated with single-dose albendazole was 689 (18%), with single-dose mebendazole 658 (17%), and with albendazole-based co-administrations 775 (23%). The overall mean ERR assessed by day 14–21 for albendazole and mebendazole was 94.5% and 87.4%, respectively on Ascaris lumbricoides, 86.8% and 40.8% on hookworm, and 44.9% and 23.8% on Trichuris trichiura. The World Health Organization (WHO) recommended criteria for efficacy were met in 50%, 62%, and 33% studies of albendazole for A. lumbricoides, T. trichiura, and hookworm, respectively and 25% of mebendazole studies. iERR analyses showed similar results, with cure achieved in 92% of A. lumbricoides-infected subjects treated with albendazole and 93% with mebendazole; corresponding figures for hookworm were 70% and 17%, and for T. trichiura 22% and 20%.Conclusions/significanceCombining the traditional efficacy assessment using group averages with individual responses provides a more complete picture of how anthelmintic treatments perform. Most treatments analyzed fail to meet the WHO minimal criteria for efficacy based on group means. Drug combinations (i.e., albendazole-ivermectin and albendazole-oxantel pamoate) are promising treatments for STH infections.     

Helminth parasites of intermingling axis deer, wild swine and domestic cattle from the island of Molokai, Hawaii

Helminth infections of axis deer (Cervus axis), wild swine (Sus scrofa) and domestic cattle (Bos taurus) were studied among intermingling herds on the Puu-O-Hoku Ranch, Molokai, Hawaii. Twenty-four species of helminths were collected from the 10 deer, 10 swine and 10 cattle. Capillaria bovis, Cooperia punctata, Haemonchus contortus and Trichostrongylus axei infected both axis deer and cattle, whereas Gongylonema pulchrum infected both axis deer and wild swine. None of the species of helminths occurred in both wild swine and cattle nor was any species found in all three hosts. Wild swine and domestic cattle supported separate and distinct helminth communities. In contrast, the helminth community of axis deer appeared to be derived from the helminth communities of cattle and wild swine and consisted only of those species capable of parasitizing either a broad range of ruminants or many mammalian taxa.     

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.     

Clinical use of praziquantel in China

Praziquantel, a broad-spectrum anthelmintic developed by E. Merck and Bayer AG in Germany in the early 1970s, was synthesized in the People's Republic of China in 1977 and given the Chinese name Pyquiton. After a series of pharmacological and toxicological studies in China, praziquantel was released for clinical use in 1978. The drug is now available for treatment of human schistosome and other trematode infections as well as the treatment of cestode infections including cysticercosis. However, much of the clinical work has been published in Chinese journals that may not be universally familiar. This article summarizes some of the key aspects of these reports, dealing with the clinical use of praziquantel against schistosomiasis japonica and other helminth infections in China.     

Estimating roundworm burdens and group sizes in anthelmintic trials with sheep and cattle

Results from controlled anthelmintic trials against roundworms in sheep and cattle have demonstrated that the variability in worm burdens within a group of animals is made up of the variation introduced in the sampling and counting of worms from the gut contents of an individual animal, and the variation in worm burdens from animal to animal within the group. These two factors are examined in detail and a procedure for counting worms from animals in anthelmintic trials proposed. A method is also suggested for determining the number of animals to be used in the untreated (control) and treated groups in anthelmintic tests, depending upon the degree of precision required in the evaluation of anthelmintic activity.     

Species-specific treatment effects of helminth/HIV-1 co-infection: a systematic review and meta-analysis

In sub-Saharan Africa, over 22 million people are estimated to be co-infected with both helminths and HIV-1. Several studies have suggested that de-worming individuals with HIV-1 may delay HIV-1 disease progression, and that the benefit of de-worming may vary by individual helminth species. We conducted a systematic review and meta-analysis of the published literature to determine the effect of treatment of individual helminth infections on markers of HIV-1 progression (CD4 count and HIV viral load). There was a trend towards an association between treatment for Schistosoma mansoni and a decrease in HIV viral load (Weighted mean difference (WMD)=-0·10; 95% Confidence interval (CI): -0·24, 0·03), although this association was not seen for Ascaris lumbricoides, hookworm or Trichuris trichiura. Treatment of A. lumbricoides, S. mansoni, hookworm or T. trichiura was not associated with a change in CD4 count. While pooled data from randomized trials suggested clinical benefit of de-worming for individual helminth species, these effects decreased when observational data were included in the pooled analysis. While further trials are needed to confirm the role of anthelmintic treatment in HIV-1 co-infected individuals, providing anthelmintics to individuals with HIV-1 may be a safe, inexpensive and practical intervention to slow progression of HIV-1.     

Nematode parasite control practices of sheep and goat farmers in the region of Trikala, Greece

Information concerning worm control practices of sheep and goat farmers in the region of Trikala (central Greece) was collected through a questionnaire survey by visiting farms and interviewing farmers. Questionnaires from 57 farmers residing in 23 rural communities were collected. Anthelmintics were used by 89% of the farmers. On average, lambs, kids and goats were treated once annually, while sheep were treated either once or twice annually. Only 2% of farmers reported treatment of animals with anthelmintics when moving to new pastures. The most common broad-spectrum anthelmintics used were those belonging to the benzimidazoles and probenzimidazoles. Fifty nine percent of the farmers used the same anthelmintic group for 3 or more years and 34% used two or more anthelmintic groups in the same year. Almost all farmers reported estimating live weights for calculating anthelmintic doses through visual perception on the basis of an average weight (96%). Tablets and boluses were the most preferred anthelmintic formulation used by 96% of farmers. The selection of an anthelmintic was based for 58% of farmers on recommendation by a veterinarian and for 39% of farmers on the cost of the drug. The most common occasions for deworming the animals were at turn out (86%) and after parturition (31%). Only 6% of farmers reported deworming new animals before introducing them onto the farm. Farmers preferred to seek information about the use of anthelmintics and worm control strategies from veterinarians (63%) and other farmers (37%).     

副结核分枝杆菌感染的免疫应答与检测方法研究进展北大核心CSCD

副结核分枝杆菌常引起感染牛的产奶量下降、持续性消瘦、顽固性下痢甚至死亡,给畜牧业带来了巨大的经济损失。牛通常在幼年期经口感染该菌并具有一个较长的亚临床期,后期才表现出临床症状,感染前期以细胞免疫为主并伴随着间歇排菌,经过一个2到5年的亚临床期后体液免疫应答增强,同时排菌量明显增加。目前对牛副结核病常用的检测方法有病原学检测方法,基于细胞免疫反应和基于体液免疫反应的检测方法。由于不同方法的反应原理不同,加之副结核分枝杆菌感染动物的特定免疫应答规律,在某一时间内各方法之间敏感性差异较大。本文简要阐述了牛副结核分枝杆菌的传播途径以及牛感染后的免疫应答特点,对牛副结核病的常见诊断方法进行了综述。     

Evaluation of the Egg Hatch Assay and the Larval Migration Inhibition Assay to detect anthelmintic resistance in cattle parasitic nematodes on farms

Resistance to anthelmintic drugs, particularly to the widely used benzimidazoles (BZs) and macrocyclic lactones (MLs) is an increasing problem in cattle industries worldwide. Reliable methods for the assessment of anthelmintic efficacy in the field are required in order to react before resistance becomes an obvious problem on individual properties. The ability of the Egg Hatch Assay (EHA) and the Larval Migration Inhibition Assay (LMIA) to detect anthelmintic resistance under field conditions was evaluated on cattle farms in Northern Germany. As published previously Faecal Egg Count Reduction Test (FECRT) was performed using oral albendazole (Valbazen®) or injectable ivermectin (Ivomec®). Herein the FECRT results described earlier were compared with data from EHAs or LMIAs, respectively, performed with eggs from fresh faeces or larvae from faecal cultures of the tested animals before and after treatment. The obtained EC₅₀ values allowed the assessment of efficacy of albendazole and ivermectin on farm level. The results of the FECRTs and the results of both in vitro assays were comparable. In comparison to the FECRT the in vitro assays are less time, labour and cost intensive and are able to assess the susceptibility status of a worm population without treatment. Therefore both are beneficial alternatives for the reliable detection of reduced efficacy of these two drug classes on farms.     

Supplemented nutrition decreases helminth burden and increases drug efficacy in a natural host–helminth system

Gastrointestinal (GI) helminths are common parasites of humans, wildlife, and livestock, causing chronic infections. In humans and wildlife, poor nutrition or limited resources can compromise an individual''s immune response, predisposing them to higher helminth burdens. This relationship has been tested in laboratory models by investigating infection outcomes following reductions of specific nutrients. However, much less is known about how diet supplementation can impact susceptibility to infection, acquisition of immunity, and drug efficacy in natural host–helminth systems. We experimentally supplemented the diet of wood mice (Apodemus sylvaticus) with high-quality nutrition and measured resistance to the common GI nematode Heligmosomoides polygyrus. To test whether diet can enhance immunity to reinfection, we also administered anthelmintic treatment in both natural and captive populations. Supplemented wood mice were more resistant to H. polygyrus infection, cleared worms more efficiently after treatment, avoided a post-treatment infection rebound, produced stronger general and parasite-specific antibody responses, and maintained better body condition. In addition, when applied in conjunction with anthelmintic treatment, supplemented nutrition significantly reduced H. polygyrus transmission potential. These results show the rapid and extensive benefits of a well-balanced diet and have important implications for both disease control and wildlife health under changing environmental conditions.     

The anthelmintic efficacy of papaya latex in a rodent-nematode model is not dependent on fasting before treatment

In earlier studies of the anthelmintic activity of plant cysteine proteinases (CPs), a period of food deprivation was routinely employed before administration of CPs, but there has been no systematic evaluation as to whether this does actually benefit the anthelmintic efficacy. Therefore, we assessed the effect of fasting on the efficacy of CPs from papaya latex (PL) against Heligmosomoides bakeri in C3H mice. We used a refined, supernatant extract of papaya latex (PLS) with known active enzyme content. The animals were divided into three groups (fasted prior to treatment with PLS, not fasted but treated with PLS and fasted but given only water). The study demonstrated clearly that although food deprivation had been routinely employed in much of the earlier work on CPs in mice infected with nematodes, fasting has no beneficial effect on the efficacy of PLS against H. bakeri infections. Administration of CPs to fed animals will also reduce the stress associated with fasting.     

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.