Anthelmintic resistance: Management of parasite refugia for Haemonchus contortus through the replacement of resistant with susceptible populations (original) (raw)
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Role of Refugia in Management of Anthelmintic Resistance in Nematodes of Small Ruminants -A Review
Helminth parasitism is globally considered the most important form of transmissible disease in sheep and goats. Mortalities, ill thrift and the cost of treatments impose a massive annual burden on livestock owners. Despite the availability of highly effective anthelmintic compounds initially resistance in nematodes compromises their effectiveness. The alternative approaches that potentially reduce the reliance on anthelmintics have found limited adoption. Sustainable worm control strategies based largely on ensuring that a source of worms not exposed to anthelmintics (in refugia) remains, so that resistant worms do not become a dominant part of the total population. This may require withholding treatments from a proportion of animals when the whole group would normally be treated. The "targeted selective treatment" approach involves using anthelmintics on an individual animal basis according to indications of parasitic effects, regardless of parasite burdens. For Haemonchus contortus, the FAMACHA system, based on the easily visualized index of anaemia, has proved effective provided that labour is available for frequent inspections. Continuing investigations are necessary to indicate the most appropriate indices for different situations, so that the refugia effect is maximized for the least risk of disease and production loss. Of prime importance, targeted selective treatment strategies must be practical to implement if they are to achieve widespread adoption.
PARASITE-PARIS-, 2007
Haemonchosis, with its very wide distribution, has become a very important production constraint in sheep farms in tropical, subtropical and temperate regions worldwide. Various intrinsic and extrinsic factors determine the survival of Haemonchus contortus and hence the development of the disease in the animal. In general, control of gastrointestinal nematode infestation in sheep relies heavily on anthelmintic treatments. However, the indiscriminate use of these drugs has led to the widespread emergence of drug resistant strains of parasites, that has necessitated the development and use of various parasite control methods such as grazing management, biological agents and vaccines and the selection of resistant breeds of animals, with or without moderate use of anthelmintics. The ultimate goal of such control programs is to enhance productivity, while minimising risks regarding drug resistance and consumer and environmental concerns. This review attempts to highlight the different methods employed in the control of haemonchosis in sheep and the practical limitations associated with both control programs and the internal and external factors associated with the parasite and its microenvironment. Résumé : MOYENS DE LUTTE CONTRE HAEMONCHUS CONTORTUS CHEZ LE MOUTON. REVUE BIBLIOGRAPHIQUE L'hémonchose est une infestation parasitaire très répandue chez les petits ruminants et est un facteur limitant important de la production aussi bien dans les régions tropicales que subtropicales, voire tempérées. Divers facteurs intrinsèques ou extrinsèques déterminent la survie d'Haemonchus contortus et donc l'épidémiologie de l'infestation. La lutte contre les nématodoses gastro-intestinales du mouton repose principalement sur l'emploi d'anthelminthiques. Cependant, leur emploi à grande échelle a abouti au développement de résistances qui obligent à recourir à d'autres méthodes de lutte par la gestion du pâturage, par l'utilisation de champignon nématophage, ou par la sélection de souches ovines naturellement résistantes à H. contortus. L'objectif de ces moyens de contrôle est d'augmenter la productivité, tout en limitant les risques de résistance et les risques potentiels pour l'environnement ou les consommateurs. Cette revue présente les différentes méthodes utilisées pour la lutte contre l'hémonchose et souligne leurs limites, en particulier dans la pratique de l'élevage.
2013
Despite the increasing economic importance of the small ruminant production, parasite resistance continues to stand out as the main constraint to this activity. Haemonchus contortus, the most prevalent and pathogenic nematode in tropical areas, is responsible for economic losses and health problems. The purpose of this review is to present the current knowledge about H. contortus genetics, anthelmintic resistance and management practices in sheep flocks associated with parasite resistance. We present the main results of our team obtained in sheep flocks from São Paulo state, Brazil, in recent years regarding efficiency assessment of five anthelmintics by the fecal egg count reduction test (FECRT); genotyping of two genes related to anthelmintic resistance (βtubulin and P-glycoprotein); and risk factors in management practices associated with anthelmintic resistance. We aim to provide useful information to improve control, maintain the effectiveness of chemical groups, slow the emergence of anthelmintic resistance in sheep and help farmers deal with parasitic resistance.
Australian Veterinary Journal, 2011
Develop a computer simulation model that uses daily meteorological data and farm management practices to predict populations of Trichostrongylus colubriformis, Haemonchus contortus and Teladorsagia (Ostertagia) circumcincta and the evolution of anthelmintic resistance within a sheep flock. Use the model to explore if increased refugia, provided by leaving some adult sheep untreated, would delay development of anthelmintic resistance without compromising nematode control.
Sheep and goat nematode resistance to anthelmintics: pro and cons among breeding management factors
Veterinary Research, 2002
Although the molecular bases of resistance to anthelmintic families have been intensively studied, the contributing factors for the development of anthelmintic resistance are less well known. Clear recommendations must be given to farmers in order to delay the onset of anthelmintic resistance. Until now, the main advice has concerned the reduction of treatment frequency in order to slow down the spread of resistance. Anthelmintic resistance development depends mostly on an efficient selection pressure. This means that a high treatment frequency is neither necessary nor sufficient to select for resistance. The contribution of resistant worms, which have survived an anthelmintic treatment, to the subsequent generation is the key factor that controls resistance spread. This point is illustrated by five surveys conducted on sheep and goat farms from France and Morocco. In the 52 farms studied, less than three anthelmintic treatments were given each year. Three characteristics of breeding management can be identified in the build up of anthelmintic resistance: (1) the introduction of resistant worms through the purchase of sheep/goats or the use of common pastures, grazed by several herds/flocks, (2) under-dosing of hosts and the repeated use of one class of drugs, (3) the size of the population in refugia (infective larvae on pastures) at the time of the treatment. The role played by these breeding management factors in selecting for resistance is discussed. The most efficient way to limit the increase of anthelmintic resistance remains the reduction of the selection pressure by drugs, and optimal timing to maximise their efficacy.
1993
A computer model developed to study Ostertagia circumcincta resistance to anthelmintics in UK sheep flocks has been adapted for use with Haemonchus contortus under southern Brazilian conditions. The model simulates the effect of different anthelmintic control regimens on the year-to-year pattern of resistance in breeding ewes. The nematode control regimen most used by Brazilian sheep farmers was found to increase the frequency of genes which confer resistance from approximately 3% to 14% in an H. contortus population over a 20 year period. The effect of early versus late season anthelmintic treatment was investigated. This indicated that early season treatment would select for resistance rapidly, whereas late season treatments would not, owing to large numbers of untreated parasites accumulating at the beginning of the season. A model which can predict the development of anthelmintic resistance in parasites of ewes is a valuable tool in the understanding of the effect of different strategies on nematode control programmes and merits further consideration.
Anthelmintic resistance in Haemonchus contortus
ProQuest Dissertations & Theses,, 1991
Studies were carried out on possible control measures using different drugs or management procedures which could help in the control of anthelmintic resistance in sheep nematodes, particularly that of ivermectin (IVM) resistance in Haemonchus contortus. Other aspects such as selection for IVM resistance, the effect of IVM on susceptible and resistant larval stages of H. contortus and the survival of their free-living stages under laboratory or field conditions were also investigated. In addition, a computer model to simulate the development of anthelmintic resistance in breeding ewes was examined incorporating Brazilian field data. Isoenzyme profiles of susceptible and resistant strains were also analysed. Three strains of H. contortus were mainly used in these studies: one susceptible to all of the common anthelmintics; the same strain selected for resistance to IVM under laboratory conditions and a field strain resistant to a wide range of anthelmintics, including IVM, which was isolated from a farm in South Africa. The IVM selected strain was derived experimentally from the susceptible strain serially passaged in lambs and submitted to successive doses of IVM at 0.02mg/kg. Although the drug was highly efficient until the seventh passage and treatment, the progeny of the adult worms which survived this treatment were highly resistant. Under controlled laboratory conditions, an experiment was set up to look at the development of eggs and larvae of the original susceptible strain in comparison to the selected strain. This showed that at 22°C the resistant strain had a higher percentage development v from eggs to the infective stage while at 27°C the results were reversed, i.e., a significantly higher percentage of larvae developed from eggs of the original susceptible strain. Under field conditions of Southern Brazil, eggs from two strains of H. contortus, one resistant and another susceptible to IVM, were seeded on to pasture plots during three summer months. The results of these field studies indicated that resistant larvae survived better after only one of the contamination periods; at other times there appeared to be no significant difference in development rates. In all cases the recovery rate was low, indicating that during the summer months in Southern Brazil there is limited survival and development of eggs and larvae on pasture and that most of the parasite population is present in sheep during this period. An experiment designed to exploit the residual anthelmintic effects of salicylanilide/substituted phenols, strategically administered during the summer in the conditions of Southern Brazil, was successful in controlling an IVM resistant population of H. contortus thus preventing the predictable outbreaks of haemonchosis in autumn. Of these drugs, nitroxynil gave the best results. Another approach examined as an alternative method in the control of sheep nematodes under Brazilian conditions was the use of "safe pastures", i.e., areas with a low level of infectivity where young susceptible sheep could be grazed with a low risk of infection. In this case an infected pasture, reseeded after a crop of soya bean, was tested for larval infectivity in spring using lamb and calf tracers. After harvesting a soya bean crop from this area, it was found to be virtually negative for H. contortus and other important vi viii LIST OF CONTENTS ACKNOWLEDGEMENTS DECLARATION SUMMARY LIST OF TABLES LIST OF FIGURES LIST OF APPENDICES CHAPTER 1-INTRODUCTION AND LITERATURE REVIEW CHAPTER 2-GENERAL MATERIAL AND METHODS CHAPTER 3-STUDIES ON FACTORS AFFECTING IVERMECTIN RESISTANT Haemonchus contortus IN SHEEP Exp. 3.1-Efficacy of other anthelmintics on ivermectin resistant adult Haemonchus contortus Exp. 3.2-The response to ivermectin treatment of parasitic stages of Haemonchus contortus resistant or susceptible to ivermectin Exp. 3.3-Could the strategic use of salicylanilides control an ivermectin resistant strain of Haemonchus contortus in grazing lambs in Brazil? Exp. 3.4-How effective are reseeded pastures as an aid in the control of gastrointestinal nematodes in sheep? CHAPTER 4-STUDIES ON THE BIOLOGY OF IVERMECTIN RESISTANT Haemonchus contortus Exp. 4.1-Laboratory selection for ivermectin resistance in Haemonchus contortus Exp. 4.2-The pattern of faecal egg output in lambs infected with a multiple resistant strain of Haemonchus contortus after treatment with albendazole Exp. 4.3-The survival and development of ivermectin resistant or susceptible strains of Haemonchus contortus under field and laboratory conditions Exp. 4.4-Isoenzyme analysis of Haemonchus contortus strains either resistant or susceptible to ivermectin CHAPTER 5-COMPUTER MODELLING FOR ANTHELMINTIC RESISTANCE i Exp. 5.1-A drug action model in genetic selection for anthelmintic resistance in Haemonchus contortus CHAPTER 6-GENERAL DISCUSSION AND CONCLUSIONS REFERENCES APPENDICES x 122 xii LIST OF FIGURES ig. 1.1 Life cycle of H. contortus 4 ig-1.2 Location of four epidemiological studies in Brazil 46 ig-1.3 Climatic conditions in Brazil-rainfall ig-1.4 Climatic conditions in Brazil-temperatures ig-1.5 Epidemiology in Bage-H. contortus ig-1.6 Epidemiology in Uruguaiana-H. contortus ig-1.7 Epidemiology in Guaiba-//. contortus ig. 1.8 Epidemiology in Itaqui-H. contortus ig-1.9 Epidemiology in Bage-other nematodes ig-1.10 Epidemiology in Uruguaiana-other nematodes ig-1.11 Epidemiology in Guaiba-other nematodes ig-1.12 Epidemiology in Itaqui-other nematodes ig. 3.3.1 Worm egg counts from permanent grazers in Zone 1 ig-3.3.2 Worm egg counts from permanent grazers in Zone 2 ig. 3.3.3 Packed cell volume (%) from permanent grazers in Zone 1 ig. 3.3.4 Packed cell volume (%) from permanent grazers in Zone 2 ig. 3.3.5 Body weights from permanent grazers in Zone 1 ig. 3.3.6 Body weights from permanent grazers in Zone 2 ig. 4.1.1 Worm egg counts after IVM treatment on R or S H. contortus ig. 4.2.1 Worm egg counts after ABZ treatment on a strain of H. contortus 131 ig. 4.2.2 Haemonchus infective larvae (L3) recoveries after albendazole treatment 131 ig. 4.3.1 Development of Haemonchus L3 at 22°C 146 x iii xiv
Veterinary Parasitology - VET PARASITOL, 1993
A computer model developed to study Ostertagia circumcincta resistance to anthelmintics in UK sheep flocks has been adapted for use with Haemonchus contortus under southern Brazilian conditions. The model simulates the effect of different anthelmintic control regimens on the year-to-year pattern of resistance in breeding ewes. The nematode control regimen most used by Brazilian sheep farmers was found to increase the frequency of genes which confer resistance from approximately 3% to 14% in an H. contortus population over a 20 year period. The effect of early versus late season anthelmintic treatment was investigated. This indicated that early season treatment would select for resistance rapidly, whereas late season treatments would not, owing to large numbers of untreated parasites accumulating at the beginning of the season. A model which can predict the development of anthelmintic resistance in parasites of ewes is a valuable tool in the understanding of the effect of different strategies on nematode control programmes and merits further consideration.
2011
Gastrointestinal parasitism is a widely recognised problem in sheep production, particularly for lambs. While anthelmintics have a pivotal role in controlling the effects of parasites, there is a paucity of data on how farmers use anthelmintics. A representative sample of Irish lowland farmers were surveyed regarding their parasite control practices and risk factors that may contribute to the development of anthelmintic resistance. Questionnaires were distributed to 166 lowland Irish sheep producers. The vast majority of respondents treated their sheep with anthelmintics. Lambs were the cohort treated most frequently, the majority of farmers followed a set programme as opposed to treating at sign of disease. A substantial proportion (61%) administered four or more treatments to lambs in a 'normal' year. Departures from best practice in anthelmintic administration that would encourage the development of anthelmintic resistance were observed. In conclusion, in the light of anthelmintic resistance, there is a need for a greater awareness of the principles that underpin the sustainable use of anthelmintics and practices that preserve anthelmintic efficacy should be given a very high priority in the design of helminth control programmes on each farm. To this end, given that veterinary practitioners and agricultural advisors were considered to be the farmer's most popular information resource, the capacity of these professions to communicate information relating to best practice in parasite control should be targeted.
The role of combination anthelmintic formulations in the sustainable control of sheep nematodes
Veterinary Parasitology, 2012
Combinations of anthelmintics with a similar spectrum of activity and different mechanisms of action and resistance are widely available in several regions of the world for the control of sheep nematodes. There are two main justifications for the use of such combinations: (1) to enable the effective control of nematodes in the presence of single or multiple drug resistance, and (2) to slow the development of resistance to the component anthelmintic classes. Computer model simulations of sheep nematode populations indicate that the ability of combinations to slow the development of resistance is maximised if certain prerequisite criteria are met, the most important of which appear to concern the opportunity for survival of susceptible nematodes in refugia and the pre-existing levels of resistance to each of the anthelmintics in the combination. Combinations slow the development of a resistant parasite population by reducing the number of resistant genotypes which survive treatment, because multiple alleles conferring resistance to all the component anthelmintic classes must be present in the same parasite for survival. Individuals carrying multiple resistance alleles are rarer than those carrying single resistance alleles. This enhanced efficacy leads to greater dilution of resistant genotypes by the unselected parasites in refugia, thus reducing the proportion of resistant parasites available to reproduce with other resistant adults that have survived treatment. Concerns over the use of anthelmintic combinations include the potential to select for resistance to multiple anthelmintic classes concurrently if there are insufficient parasites in refugia; the potential for shared mechanisms of resistance between chemical classes; and the pre-existing frequency of resistance alleles may be too high on some farms to warrant the introduction of certain combinations. In conclusion, anthelmintic combinations can play an important role in resistance management. However, they are not a panacea and should always be used in accordance with contemporary principles for sustainable anthelmintic use.