The global diversity of Haemonchus contortus is shaped by human intervention and climate.

Haemonchus contortus is a haematophagous parasitic nematode of veterinary interest. We have performed a survey of its genome-wide diversity using single-worm whole genome sequencing of 223 individuals sampled from 19 isolates spanning five continents. We find an African origin for the species, together with evidence for parasites spreading during the transatlantic slave trade and colonisation of Australia. Strong selective sweeps surrounding the ß-tubulin locus, a target of benzimidazole anthelmintic drug, are identified in independent populations. These sweeps are further supported by signals of diversifying selection enriched in genes involved in response to drugs and other anthelmintic-associated biological functions. We also identify some candidate genes that may play a role in ivermectin resistance. Finally, genetic signatures of climate-driven adaptation are described, revealing a gene acting as an epigenetic regulator and components of the dauer pathway. These results begin to define genetic adaptation to climate in a parasitic nematode.

Climate influences assemblages of abomasal nematodes of sheep on steppe pastures in the east of Algeria.

It is a common view that assemblages of parasitic nematodes are influenced by climatic conditions; however, there are only a few articles available regarding those that infect farm animals. We investigated the relationship between climate variables and infection with abomasal trichostrongyles in 335 1-year-old rams grazed on steppe pastures in Eastern Algeria. Abomasa were collected from 12 local slaughterhouses located in four climatic areas (from humid to arid) and the worms extracted, identified and counted. The abundance was low and the fauna composed primarily of Teladorsagia circumcincta, Marshallagia marshalli and Trichostrongylus sp. The high percentage of M. marshalli is typical of steppe areas. Ostertagia ostertagi and Haemonchus contortus were present in low numbers. Rainfall was the most important climatic variable related to the main species. This relationship was not linear for M. marshalli but an optimal rainfall was detected (350-400 mm/year). The more complex climatic indicators used in the study did not demonstrate a more significant correlation than rainfall. The predictive value of rainfall on the abundance or proportion of species in the assemblage was modest but highly significant. The seasonality of assemblages was different between the two main sub-climates (sub-humid and semi-arid).

Are sainfoin or protein supplements alternatives to control small strongyle infection in horses?

The spread of anthelmintic resistance in equine strongyle nematodes has become a major problem, advocating for the development of alternative control for strongyles. Our study consisted of both in vivo and in vitro experiments. We investigate for the first time the efficacy of a short-term consumption of tannin-rich sainfoin (Onobrychis viciifolia) or extra proteins in naturally infected horses. We used 30 horses allocated into three groups of 10 individuals that received for 18 days either (i) a tannin-rich diet with 70% DM sainfoin pellets (Sd), (ii) a protein-rich diet with 52% DM Italian rye-grass pellets and 18% DM grinded linseed expeller (Pd), or (iii) a control diet with 45% DM barley and 25% DM cereal-based pellets (Cd). The three diets were isoenergetic, covering 94% of animal energy requirements on average, and the Sd and Pd diets were isoproteic and provided extra proteins (227% of protein requirements v. 93% for the Cd diet). Pd and Cd were compared to test for benefits of receiving extra proteins, while Sd and Pd were compared to account for the effect of sainfoin secondary metabolites. There were no between-diet differences in faecal egg counts (FEC) or in worm burden evaluated from worm counts in faeces of drenched horses at the end of the experiment. However, coprocultures from the faeces collected in each group at the beginning and at the end of the experiment suggested a lower rate of strongyle larval development in the Sd group at the end of the experiment (Sd=8.1%, Pd=30.5%, Cd=22.6%). In vitro tests using sainfoin solutions evidenced the influence of sainfoin on strongyle larval development: adding 29% of sainfoin pellets to faeces reduced the strongyle egg development into infective larvae by 82% (P<0.001) and using solutions with sainfoin concentrations higher than 7.5 mg/ml reduced egg hatching by 37% (P<0.05). The short-term use of tannin-rich plants in horse diet could thus constitute a promising strategy to reduce the risk of infection by strongyles at pasture.

Nonlinear Hysteretic Torsional Waves.

We theoretically study and experimentally report the propagation of nonlinear hysteretic torsional pulses in a vertical granular chain made of cm-scale, self-hanged magnetic beads. As predicted by contact mechanics, the torsional coupling between two beads is found to be nonlinear hysteretic. This results in a nonlinear pulse distortion essentially different from the distortion predicted by classical nonlinearities and in a complex dynamic response depending on the history of the wave particle angular velocity. Both are consistent with the predictions of purely hysteretic nonlinear elasticity and the Preisach-Mayergoyz hysteresis model, providing the opportunity to study the phenomenon of nonlinear dynamic hysteresis in the absence of other types of material nonlinearities. The proposed configuration reveals a plethora of interesting phenomena including giant amplitude-dependent attenuation, short-term memory, as well as dispersive properties. Thus, it could find interesting applications in nonlinear wave control devices such as strong amplitude-dependent filters.

Storage of gastrointestinal nematode infective larvae for species preservation and experimental infections.

Techniques to preserve the infective third-stage larvae (L3) of gastrointestinal nematodes are of considerable interest to preserve rare species and to maintain a stable source for routine experimental infections. This study compares the relative pros and cons of the two most common techniques, cryopreservation and refrigeration by comparing how they influence consequent infection outcome parameters in terms of life-history traits and fitness as a function of time using the gastrointestinal nematode of sheep Haemonchus contortus as a study species. Establishment capacity was found to be significantly reduced in cryopreserved stocks of L3 compared to refrigerated stocks, but this was followed by significant increases in their fecundity. Refrigeration did not affect L3 stocks consequent fitness by 16 months (the maximum examined) although they did incur a significant reduction in establishment, followed once again by an augmentation in fecundity. The study highlights potential areas for bias in comparing studies using L3 larvae maintained for different periods of time under different techniques.

Exploring the limitations of pathophysiological indicators used for targeted selective treatment in sheep experimentally infected with Haemonchus contortus.

Identifying which sheep to treat as part of a Targeted Selective Treatment approach to gastro-intestinal nematode control relies entirely on the efficacy of the indicators. Indicators such as FAMACHA© (anaemia), DISCO (diarrhea) and reductions in weight gains were designed specifically to reflect those sheep experiencing symptomatic consequences of infection. Using the gastro-intestinal nematode Haemonchus contortus as a model species, this study explored the utility and sensitivity of these indicators under controlled experimental conditions on 63 adult sheep. The potential effect of sheep with different H. contortus resistance phenotypes on indicator efficacy was compared in three different phenotypes, i.e. high (Blackbelly females), medium (Blackbelly rams) and low resistance (Romane rams). The potential effect of the H. contortus isolate on indicator efficacy was also explored by using four different isolates, with varying anthelmintic resistance capacities, to infect the sheep. We limited the study to the first month of infection to evaluate the interest of these indicators as an early predictive means for controlling infection. The pathophysiological indicators FAMACHA© and DISCO do not reflect infection intensity based on Faecal Egg Counts, nor do reductions in weight gains. FAMACHA© was however a good indicator of anaemia with strong correlations to haematocrit. There was little agreement among the three indicators to identify the same animals in need of treatment and even combining them did not increase their predictive value of infection intensity or relative host damage from infection. The indicator sensitivity was influenced by the H. contortus isolate and sheep resistance phenotype in which they were tested. One isolate was poorly infective but induced high levels of anaemia (FAMACHA©) and diarrhea (DISCO) compared to the three others. The FAMACHA© and DISCO had higher values in the sheep group with a medium resistance phenotype (Blackbelly rams) indicating higher levels of damage compared to the high and low resistance phenotypes. We conclude that there is no 'one size fits all' approach to the use of indicators for Targeted Selective Treatment and the indicators should be calibrated to farm-specific conditions to increase their efficacy.

How does the suppression of energy supplementation affect herbage intake, performance and parasitism in lactating saddle mares?

Agroecology opens up new perspectives for the design of sustainable farming systems by using the stimulation of natural processes to reduce the inputs needed for production. In horse farming systems, the challenge is to maximize the proportion of forages in the diet, and to develop alternatives to synthetic chemical drugs for controlling gastrointestinal nematodes. Lactating saddle mares, with high nutritional requirements, are commonly supplemented with concentrates at pasture, although the influence of energy supplementation on voluntary intake, performance and immune response against parasites has not yet been quantified. In a 4-month study, 16 lactating mares experimentally infected with cyathostome larvae either received a daily supplement of barley (60% of energy requirements for lactation) or were non-supplemented. The mares were rotationally grazed on permanent pastures over three vegetation cycles. All the mares met their energy requirements and maintained their body condition score higher than 3. In both treatments, they produced foals with a satisfying growth rate (cycle 1: 1293 g/day; cycle 2: 1029 g/day; cycle 3: 559 g/day) and conformation (according to measurements of height at withers and cannon bone width at 11 months). Parasite egg excretion by mares increased in both groups during the grazing season (from 150 to 2011 epg), independently of whether they were supplemented or not. This suggests that energy supplementation did not improve mare ability to regulate parasite burden. Under unlimited herbage conditions, grass dry matter intake by supplemented mares remained stable around 22.6 g DM/kg LW per day (i.e. 13.5 kg DM/al per day), whereas non-supplemented mares increased voluntary intake from 22.6 to 28.0 g DM/kg LW per day (13.5 to 17.2 kg DM/al per day) between mid-June and the end of August. Hence total digestible dry matter intake and net energy intake did not significantly differ between supplemented and non-supplemented mares during the second and third cycles. In conclusion, supplementing lactating mares at pasture should not be systematic because their adaptive capacities enable to increase herbage intake and ensure foal growth. Further research is needed to determine the herbage allowance threshold below which supplementation is required.

Desiccation tolerance of gastrointestinal nematode third-stage larvae: exploring the effects on survival and fitness.

The free-living third-stage larvae (L3) of gastrointestinal nematodes are able to tolerate extreme weather conditions such as desiccation, but little is known about the consequent effects this has on their fitness. This study explored how the desiccation of Haemonchus contortus L3 larvae affected their absolute fitness by examining their success at consequent life cycle stages for a complete generation, and comparing them against a control. The stages examined include establishment, fecundity, larval development and pathogenicity. The results show that while desiccation greatly reduced the survival of the L3 prior to infection in sheep, their absolute fitness was not negatively impacted. Instead, it appears desiccation slightly augmented H. contortus fitness by triggering increases in fecundity. The study further explored what influence different gastrointestinal nematode (GIN) species (H. contortus, Trichostrongylus colubriformis, Teladorsagia circumcincta), isolates and age of L3 had on their capacity to revive following various periods of desiccation. The results showed desiccation tolerance varied as a function of each of these variables. The greatest L3 survival was found in Te. circumcincta followed by Tr. colubriformis and finally H. contortus. Significant variation was observed between individual species isolates and as a function of age. The results of this study carry important practical implications for the epidemiological understanding of gastrointestinal nematode species of economic importance.

The production of mammalian trematode infective stages by the snail Galba truncatula.

Several experiments on the breeding of trematode-infected Galba truncatula for obtaining and packaging Fasciola hepatica and Paramphistomum daubneyi metacercariae were carried out to determine the more convenient methods to use for commercial production of these infective stages. Compared to the breeding of infected snails in aquaterraria, the use of 14-cm Petri dishes allowed a greater prevalence of snail infection and a higher number of metacercariae. The production of these larvae was still 2.3-3.4 times greater if infected snails were dissected during the patent period. The aspiration of these metacercariae at the extremity of a Pasteur pipette significantly shortens the time necessary for their transfer from Petri dishes to Eppendorf tubes. Using 14-cm Petri dishes, snail dissection and metacercarial aspiration for their transfer strongly reduce the cost price for metacercarial production of the trematodes Fasciola hepatica and Paramphistomum daubneyi.

Comparative strategies and success of sympatric and allopatric Fasciola hepatica infecting Galba truncatula of different susceptibilities.

Allopatric infections of French Galba truncatula with an Argentinean isolate of Fasciola hepatica were carried out to determine the infectivity of foreign miracidia in three snail populations differing by their susceptibility to French miracidia (two highly and one poorly susceptible populations). Sympatric infections of G. truncatula with French miracidia were used as controls. Compared to sympatric infections of G. truncatula, snail survival at day 30 post-infection in allopatric groups was significantly lower in a highly susceptible population and significantly greater in the other two. Prevalence in snails infected with the allopatric isolate was significantly lower (16.4-34.5 % instead of 58.6-72.1 %), whereas their patent period was significantly longer (a mean of 69.9-85.9 days instead of 6.4-20.7 days). The mean number of metacercariae was also higher in allopatric groups (236.5-897.3 per cercariae-shedding snail instead of 70.7-222.1). Owing to longer patent periods, the Argentinean isolate of F. hepatica was less pathogenic for these snails. The lower prevalence of infection, the longer patent period and the higher number of metacercariae noted in allopatric groups might be the consequence of an adaptive mechanism used by this digenean introduced to the New World to infect new populations of unusual intermediate hosts.

Intermediate snail hosts of French Fasciola hepatica: Lymnaea neotropica and Lymnaea viatrix are better hosts than local Galba truncatula.

Allopatric and sympatric infections of Lymnaea neotropica and Lymnaea viatrix var. ventricosa with Argentinean and French isolates of Fasciola hepatica were carried out to determine the capacity of these snails to produce metacercariae and to verify if this capacity changed with snail generation. The same process was also made with a French population of Galba truncatula known to be highly susceptible to French isolates of the parasite. In each lymnaeid species separately considered, the survival rate at day 30 post-exposure and prevalence of F. hepatica infection in the group infected with Argentinean miracidia were significantly greater than those recorded in the corresponding French one. Compared to infected G. truncatula, both South American lymnaeids had longer patent periods and produced a higher number of metacercariae. The highest infections were noted with L. v. ventricosa. In the three snail species, metacercarial production was more important with the Argentinean isolate of miracidia than with the French one. If three successive generations of L. v. ventricosa are exposed to the same French isolate of miracidia, cercarial production significantly increased from parents to the F2 generation, while the other characteristics of infection only showed insignificant variations. L. neotropica and L. v. ventricosa are better intermediate hosts for French F. hepatica than local G. truncatula. The numerical increase of shed cercariae in the F1 and F2 generations of L. v. ventricosa demonstrates a rapid adaptation of this species to the French isolate of the parasite.

Can efficient management of sheep gastro-intestinal nematodes be based on random treatment?

Targeted selective treatment has been proposed as a method to reduce gastro-intestinal nematode infections in ruminants and lower the selective pressure that leads to anthelmintic resistance. Since nematodes are highly aggregated within their host population, treating only the most heavily infected hosts offers an efficient and sustainable strategy to reduce infection within the flock and slow the spread of anthelmintic resistance. Although effective methods to correctly identify such hosts are available, their feasibility is often limited in the field conditions. Instead, treating part of the flock at random may prove to be a useful and practical alternative. This study examined whether such random treatment could be relevant in controlling nematode infections and delaying the selection of anthelmintic resistance compared to targeted selective treatment. Firstly, an individual based model was used to evaluate the sustainability of random treatment according to several parasitic distributions in the host population (negative binomial, uniform and normal distributions). Anthelmintic resistance was modelled based on benzimidazoles, as a monogenic trait. Anthelmintic treatment was done twice a year, week 23 and 41, corresponding to beginning of June and of October. The model was run over a five-year period corresponding to the minimum delay for anthelmintic resistance to be observed following its initial use. The model outputs show an increase in the proportion of treated hosts led to an increase in the frequency of the resistance allele for both treatment regimes. Random treatment was shown to be slightly less efficient than targeted selective treatment in controlling for the infection intensity regardless of the percentage of hosts treated. Random treatment was however more efficient than targeted selective treatment in counter-selecting for anthelmintic resistance in both the aggregated and uniformly distributed models. Secondly, a one grazing season experiment was conducted to compare a random treatment flock (20% of flock was treated at random monthly) against a mass treatment flock (the whole flock was treated monthly). Both treatment regimes produced similar pasture infectivity, similar mean infection intensity and similar final host live weight. This is the first time random treatment of a subset of hosts has been demonstrated to be a sustainable alternative to mass treatment.

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.

Towards finding effective indicators (diarrhoea and anaemia scores and weight gains) for the implementation of targeted selective treatment against the gastro-intestinal nematodes in lambs in a steppic environment.

The effective application of targeted selective treatment (TST) against gastro-intestinal nematodes depends on the accurate identification of those animals in need of anthelmintic treatment. Finding cost and labour effective measures to identify such animals is paramount. This study tested the efficacy of three indicators on lambs in a farm in Eastern Algeria: anaemia score (FAMACHA(©)), diarrhoea score (DISCO) and weight gain. These were contrasted against traditional parasitological infection measures (nematode eggs per gram of faeces: EPG). Thirty lambs were used in the study; every second month they were sampled (FAMACHA(©), faecal samples for EPG and DISCO, weight gains) and two of the original 30 lambs were necropsied for adult worm counts. The main gastro-intestinal nematodes were Teladorsagia circumcincta, Marshallagia marshalli, Nematodirus helvetianus, Trichostrongylus vitrinus, and Haemonchus contortus. DISCO proved to be the most effective indicator correctly identifying 80% of the sheep in need of treatment. This was followed by FAMACHA(©) with a 50% accuracy level and finally weight gains, which were not found to be a useful indicator at all.

The steppe species of gastrointestinal nematodes of small ruminants, with a focus on Marshallagia: climate as a key determinant.

We intended to relate the geographic distribution of ruminant gastrointestinal nematodes in relation to steppe climate (and vegetation). Data are either from literature or from newly acquired/available results. Simple or more sophisticated meteorological indices were used to characterize the climate. Regression analyses were used to correlate climatic factors and presence of endoparasites from steppe areas. The distribution of one (Marshallagia) out of five endoparasite genera was concentrated mostly in steppic areas whereas other species were found also in other areas. In wild hosts the distribution of Marshallagia was much larger from Sptizberg to New World (northern territories in Canada or extreme south of America). In domestic small ruminants the presence of Marshallagia was identified more frequently and constantly in the area of original domestication and its early diffusion (from Northern Africa to Kashmir, Caucasia). The distribution of this parasite was correlated to low rainfalls which were not the case for all other endoparasites. After host switch (reindeer or south America camelids), it has expanded in other climatic areas, either colder or dryer.

Functional reconstitution of Haemonchus contortus acetylcholine receptors in Xenopus oocytes provides mechanistic insights into levamisole resistance.

BACKGROUND AND PURPOSE: The cholinergic agonist levamisole is widely used to treat parasitic nematode infestations. This anthelmintic drug paralyses worms by activating a class of levamisole-sensitive acetylcholine receptors (L-AChRs) expressed in nematode muscle cells. However, levamisole efficacy has been compromised by the emergence of drug-resistant parasites, especially in gastrointestinal nematodes such as Haemonchus contortus. We report here the first functional reconstitution and pharmacological characterization of H. contortus L-AChRs in a heterologous expression system. EXPERIMENTAL APPROACH: In the free-living nematode Caenorhabditis elegans, five AChR subunit and three ancillary protein genes are necessary in vivo and in vitro to synthesize L-AChRs. We have cloned the H. contortus orthologues of these genes and expressed them in Xenopus oocytes. We reconstituted two types of H. contortus L-AChRs with distinct pharmacologies by combining different receptor subunits. KEY RESULTS: The Hco-ACR-8 subunit plays a pivotal role in selective sensitivity to levamisole. As observed with C. elegans L-AChRs, expression of H. contortus receptors requires the ancillary proteins Hco-RIC-3, Hco-UNC-50 and Hco-UNC-74. Using this experimental system, we demonstrated that a truncated Hco-UNC-63 L-AChR subunit, which was specifically detected in a levamisole-resistant H. contortus isolate, but not in levamisole-sensitive strains, hampers the normal function of L-AChRs, when co-expressed with its full-length counterpart. CONCLUSIONS AND IMPLICATIONS: We provide the first functional evidence for a putative molecular mechanism involved in levamisole resistance in any parasitic nematode. This expression system will provide a means to analyse molecular polymorphisms associated with drug resistance at the electrophysiological level.

Use of pathophysiological indicators for individual decision of anthelmintic treatment of ewes against gastro-intestinal nematodes in Morocco.

The targeted selective treatments (TST) aim at reducing the number of anthelmintic treatments but also to maintain productivity of animals. The aim of this work was to assess the validity of pathophysiological indicators for detecting individually ewes in need for treatments in two regions of Morocco with different management and climatic environment (Chaouia plain-seven farms, and Middle-Atlas-three farms). Although resistance to benzimidazoles was already present the same drug was used for TST. The indicators tested were: FAMACHA(©) (associated with anaemia), DISCO (diarrhoea score), and BODCON (body condition score). Only FAMACHA(©) and DISCO indicators were well correlated to the EPGs. DISCO only did permit a substantial reduction (up to 85%) of the number of treatment and EPG (nematode eggs per gramme) remained low on average (less than 160).

Horse infection with intestinal helminths in relation to age, sex, access to grass and farm system.

A 11-year survey on helminth intestinal infection of horses was done in seven provinces of southern Poland. 21,641 faecal samples were collected from horses of different age, sex, breed and management system originating from 84 farms. Age was the major factor influencing the cyathostome egg excretion, the maximum being observed in yearlings and second year horses. Parascaris was found mostly in foals and yearlings. The main factor for Anoplocephala was the access to pasture. The level of cyathostome egg shedding (EPG) could be related to sex (geldings had higher values of EPG), breed (Thoroughbred had higher EPG than other breeds), and type of farm (large farms had higher EPG than others). The change during the survey of anthelmintic treatment (from benzimidazole or pyrantel embonate to avermectins) was associated with lower cyathostome EPG, and this was probably due to partial resistance to benzimidazole. The seasonality of egg shedding (lowest from November to January included) was due to management (leaving the pasture to stable, anthelmintic treatment in October). The influence of climate on EPG was significant but small, annual rainfalls and average temperature being associated negatively and positively, respectively, with high cyathostome EPG.

Alternation of anthelmintic treatments: a molecular evaluation for benzimidazole resistance in nematodes.

The evolution of benzimidazoles (BZ) resistance in Teladorsagia circumcincta was investigated in a controlled trial with lambs, submitted to different treatment regimens. Four paddocks were seeded with a T. circumcincta strain constituted by 25% of BZ-resistant nematodes. Ten permanent lambs were allocated to each paddock, from April to November in order to renew the contamination of pasture. Monthly, three tracer lambs were allocated in each paddock. BZ-resistant nematode frequency was determined (PCR diagnosis). The faecal egg count reduction test (permanent lambs) and the number of nematodes in lambs were also determined (permanent and tracer lambs). Four different regimens of treatments were performed: control, levamisole (a non-BZ drug), fenbendazole (a BZ drug), and an alternation of levamisole and fenbendazole every second treatment. The same protocol was repeated on two consecutive grazing seasons, increasing the number of treatments (3 in first year and 5 in second year). The proportions of BZ-resistant nematodes did not change during all the study in both the control and the levamisole paddocks, supporting an equal global fitness of BZ-resistant and susceptible nematodes. Thus, no reversion of BZ resistance is to be expected. In the alternated drug group and in the BZ treated group, BZ-resistant nematodes increased from 25% to 47% and to 78%, respectively. BZ resistance increased proportionally to the selective pressure (number of BZ treatments). The drug alternation is not a good solution to delay importantly the evolution of resistance when more than 25% of nematodes are BZ-resistant. This study is the first evaluation of BZ-resistance evolution (using individual genotyping) in controlled conditions. It showed that when a monogenic anthelmintic resistance is established at 25% in a sexually reproducing nematode population, it seems to be impossible to prevent its increase even when using limited number of BZ treatments.

Experimental and modeling approaches to evaluate different aspects of the efficacy of Targeted Selective Treatment of anthelmintics against sheep parasite nematodes.

Maintaining a refugia i.e. a proportion of the population that is not exposed to selection by treatments has been suggested as an alternative to mass treatment in the management of nematode parasites of sheep. Three refugia have been identified: nematodes in untreated hosts, encysted larvae and free-living stages on pastures. Here we tested whether Targeted Selective Treatments (TST) could be relevant in controlling nematode infections and delaying anthelmintic resistance selection. We first conducted a one grazing season experiment to compare all flock treatment (the whole flock was treated monthly) and TST based on monthly excretion eggs and daily weight gain. Nematode burden was higher in TST group, but anthelmintic susceptibility of nematodes was preserved. We then used an individual-based model to evaluate the sustainability of TST on a longer period. The simulation approach indicated that TST20% and TST30% of the flock were efficient both at maintaining resistance at a low level and controlling nematode parasite infections on a mid-term period (i.e. simulation of five grazing seasons). However for an efficient TST, these percentages of treated hosts should be adapted to flock size since the number of nematode parasites exposed to selection increases in large flocks. Our results also showed a high dependence on the timing of treatment i.e. on the size of the refugia constituted by the free-living stages on the pasture.