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Comparison of selective and systematic treatments to control nematode infection of the digestive tract in dairy goats
Veterinary Parasitology 106 (2002) 345–355
Comparison of selective and systematic treatments to control nematode infection of the digestive tract in dairy goats H. Hoste a,∗ , Y. Le Frileux b , A. Pommaret b a
Unité Mixte de Recherche, 959 INRA/DGER, Physiopathologie des Maladies Infectieuses et Parasitaires des Ruminants, ENV Toulouse, 23 Chemin des Capelles, F31076 Toulouse, France b Station du Pradel, Ferme Expérimentale Caprine, 07170 Mirabel, France Received 29 October 2001; received in revised form 20 February 2002; accepted 2 April 2002
Abstract Resistance to anthelmintics in nematode parasite of the digestive tract is a major concern in small ruminants and particularly in goats. One possible solution to limit the development and spread of resistance is to give treatments on a selective basis, i.e. by targeting the most susceptible animals within a flock rather than treating all the animals. In dairy goats, epidemiological studies have shown that, within a flock, goats in first lactation and the multiparous ones with the highest level of milk production were highly receptive to parasite infection. The objective of the study was to assess whether selective treatments could achieve a level of control of nematodes similar to systematic drenching. A similar experimental design was applied for two successive years. An experimental flock of 120 dairy goats was divided into two groups. All the goats from group SYS (systematic treatment) were drenched at mid-grazing season (July). In contrast, anthelmintics in group SEL (selective treatment) were restricted to the goats in first lactation plus the high producers. Overall, these treated goats represented 48% of the flock in year 1 and 66% in year 2. After treatments, both groups grazed on separate pastures. Parasitological and pathophysiological measurements were performed monthly. The results indicate a similar level of egg excretion in the two groups. The pathophysiological parameters (pepsinogen and phosphate concentrations) were also similar in the two groups, as well as the milk production for the 2 years. These results suggest that a targeted use of anthelmintics may allow efficient control of gastrointestinal nematodes whilst resulting in a predicted reduction in the selection pressure for the development of anthelmintic resistance. © 2002 Elsevier Science B.V. All rights reserved. Keywords: Trichostrongylidae; Goat; Control methods-Nematoda; Drug resistance
∗ Corresponding author. Tel.: +33-561-19-38-75; fax: +33-561-19-39-44. E-mail address: [email protected] (H. Hoste).
0304-4017/02/$ – see front matter © 2002 Elsevier Science B.V. All rights reserved. PII: S 0 3 0 4 - 4 0 1 7 ( 0 2 ) 0 0 0 8 4 - 5
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1. Introduction The control of gastrointestinal trichostrongylosis in small ruminants is now severely impaired by the increasing development of anthelmintic resistance (Sangster, 1999, 2001). The emergence of anthelmintic resistance is particularly rapid and the prevalence particularly high in goats (Cabaret, 2000; Jackson and Coop, 2000). This is due to: (i) the high frequency of treatments required because of the poor ability of goats to develop an immune response to nematodes; (ii) the restricted choice of anthelmintic family during lactation in order to avoid milk residues; and (iii) the specificity of drug metabolization in goats which made ovine dose unadapted and lead to underdosing for a long time. All these factors, i.e. frequent treatments, lack of alternation between molecules and underdosing, are known to favour the development of anthelmintic resistance (Jackson and Coop, 2000). Therefore, there is an urgent need in goats for alternative or complementary solutions to anthelmintics, as well as for improvement in the use of the drugs currently available in order to conserve efficacy. In countries from the southern hemisphere, several programs have been developed to reduce the selection pressure for anthelmintic resistance in trichostrongyle populations. The main recommendations included a reduction in frequency of treatments, the respect of appropriate doses, the alternation of drug families, and the preferred use of narrow spectrum anthelmintics when possible (Dash et al., 1985; Waller et al., 1995). Another recommended approach is to use selective treatments instead of systematic ones. The principle of selective treatment is to target and treat exclusively the most infected animals within a flock. By diluting the alleles of resistance in the nematode populations, the approach should contribute to slow down the rate of selection of resistance (Barnes et al., 1995; Sangster, 1999). The key point of the method lays in the identification of the most susceptible animals within a flock, i.e. those which are responsible for the largest part of pasture contamination. Assays of targeted application of anthelmintics have been previously conducted in horses, based on regular coproscopical examinations (Krecek et al., 1994; Gomez and Georgi, 1991). In South Africa, the FAMACHA system, based on clinical signs of anaemia, has also been developed in sheep and goats to reduce resistance to anthelmintics in Haemonchus contortus (Van Wyk et al., 1997, Vatta et al., 2001). In dairy goats, previous studies have demonstrated an aggregated distribution of worm infection with significant repeatabilities from one year to another (Hoste et al., 2001a,b). Moreover, epidemiological data were available which provided a means of identifying categories at risk within flocks. These studies have repeatedly shown a relationship between the level of milk production and the receptivity to trichostrongyle infection. Both in experimental and in farm conditions, goats with the highest level of milk production within flocks have been found to be more susceptible and more infected with gastrointestinal nematodes of the digestive tract than the low producing ones (Hoste and Chartier, 1993; Chartier et al., 2000; Hoste et al., 1999). In addition, goats during their first lactation appear to be more susceptible to infection than multiparous goats (Hoste et al., 1999). These observations hence provided the rationale for the design of a selective application of anthelmintic treatments restricted to high producers and goats in first lactation. The current study was, therefore, performed in controlled conditions in order to verify the feasibility of such a method in a dairy goat flock and to examine its consequences on production and pasture contamination.
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2. Materials and methods 2.1. Experimental design The study was conducted during two successive years (1998 and 1999) on a flock of 120 Alpine grazing dairy goats. The flock contained 96 multiparous adults and 24 first lactation animals. The survey was performed during the second half of the grazing season from July to the beginning of December, as the only anthelmintic treatment per grazing season was given at the end of July. The experimental period corresponded to the second half of lactation as kiddings occurred at the end of January and in February. The same experimental design was applied during the 2 years. The flock was divided into two groups of 60 goats, according to the mode of anthelmintic administration. The two groups were balanced according to the level of milk production; the age composition and the mean level of previous nematode infection as assessed by faecal egg counts in June. In group SYS (systematic treatment), all the animals were drenched at the end of July; in group SEL (selective treatment), the anthelmintic was given only to some of the goats within the group. The animals which were drenched in group SEL were all the goats in first lactation plus a proportion of the adult goats corresponding to those with the highest level of milk production. In each group, the treatment was composed of oxfendazole (Synanthic ND), used at the recommended ovine dose rate of 5 mg/kg, repeated at 24 h interval. The full efficiency of benzimidazoles on the farm has been evaluated in previous years and no evidence of anthelmintic resistance was detected. Classification of the adult goats, according to their level of milk production, was based on the records of milk production during the first 2 months of lactation, i.e. at a time when the animals were housed and nematode infections were absent or at a very low level. In year 1, the aim was to drench the goats in first lactation plus one-third of the high producing multiparous goats; in year 2, the proportion was increased to first lactation animals plus 60% of the multiparous goats with the highest level of production. Therefore, the total proportion of the flock drenched in group SEL was 47% in year 1 (12 first lactations plus 16 high producers ) and 66% in year 2 (12 first lactations plus 28 high producers). After treatment, the animals were kept indoors for 3 weeks, due to the lack of grass. Thereafter, the two groups were maintained on separate pastures, but with similar surfaces (4.3 ha) and plant composition. The pastures were previously used by the goats and their level of contamination was similar. 2.2. Parasitological and pathophysiological measurements During both years, the 120 goats were individually sampled at monthly intervals from July (before treatments) to the end of the grazing seasons (beginning of December). Faecal samples were used to assess the nematode egg excretion and were performed using a modified McMaster method (Raynaud, 1970). Blood samples were taken by venipuncture into vacutainers and were used to determine the pepsinogen and inorganic phosphate concentrations according to the methods described by Kerboeuf (1975) and Robinson et al. (1971). These measurements are considered to reflect indirectly the lesions provoked by the worms to the abomasal and to the intestinal mucosae. In addition, the individual
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milk production was recorded each week and the milk yield, fat and protein contents were assessed. 2.3. Statistical analyses One-way variance analysis (SYSTAT Software Science Ltd.) were used to compare on each date the difference between the two experimental groups for the parasitological, pathophysiological, and milk production measurements. Eggs per gram were log(x + 1) transformed before being analysed. 3. Results 3.1. Faecal egg excretion Egg excretion in the two groups of goats for the 2 years are illustrated in Fig. 1A and B. During year 1, a drop in the egg output was observed after treatment which was more prominent in the group SYS. As a consequence, significant differences between the two groups were observed in September and in October. However, at the end of the season, no difference occurred between both groups. The pattern of egg output was similar in year 2, although the level of egg output at the beginning of the assay (July) was low in both groups. No differences were observed in egg output at the beginning of autumn between both groups, but in November and December a lower egg excretion was measured in goats from group SEL. These differences in egg excretion were further analysed depending on subgroups within group SEL and SYS. The comparisons of egg excretion were, therefore, firstly conducted between the low producers from group SYS and SEL, which were, respectively, treated or not; and secondly, between high producers plus first lactation goats from each group, which were treated, whatever their experimental group. Differences in egg excretions between low producers from group SEL (untreated goats) or SYS (treated low producing goats) corresponded to what was observed for the whole groups of animals (Fig. 2A and B). In addition, differences were also observed in egg output from high producers plus first lactation goats at the end of the grazing season for the two successive years, although these goats received a similar treatment in the two experimental groups (Fig. 2C and D). In November (years 1 and 2) and December (year 2), egg excretions from these subgroups were significantly lower in group SEL. 3.2. Pathophysiological parameters Overall, only minor differences were observed between the two groups for both the pepsinogen and phosphate values during the two successive studies. Higher concentrations of pepsinogen were observed in year 1 compared to year 2, but no statistical differences were found between the two groups except in September from year 1 when higher values were recorded in group SEL (Fig. 3). The evolution of phosphate concentrations were similar during the 2 years with a slow decrease of values towards the end of surveys. The mean values were, respectively, 71 mg/l
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Fig. 1. Comparison of egg excretion in groups of goats receiving the anthelmintic treatment on a systematic or a selective basis during the grazing season in: year 1 (A), and year 2 (B) of the study. The arrows indicate the moment of treatment. Statistical comparisons: ∗ P < 0.05.
in year 1 and 60.5 mg/ l in year 2 at the start of the assay; and 53 mg/l (year 1) and 45 mg/l (year 2) at the end in December (data not shown). Again, no statistical difference was observed between group SEL and SYS during the 2 years. 3.3. Milk production The curves of milk yield for the 2 years showed a similar pattern in both groups of goats. No statistical difference was detected between the two groups in year 1 and in year 2. Overall, the mean production for the second half of lactation (from July to December) in
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Fig. 3. Serum pepsinogen concentrations in the two groups of goats receiving the systematic or the selective anthelmintic treatment during the grazing season in: year 1 (A), and year 2 (B) of the study. Statistical comparisons: ∗ P < 0.05.
year 1 was 258 kg in group SEL versus 267 kg in group SYS. In year 2, these production records were, respectively, 290 and 294 kg (Fig. 4). 4. Discussion Most strategies designed to manage anthelmintic resistances aimed at decreasing the selection pressure and at keeping alleles of susceptibility to antiparasitic drugs in worm populations in order to dilute the resistance genes (Jackson, 2000; Jackson and Coop, 2000; Sangster, 1999, 2001). Proposed measures to maintain genes of susceptibility have included a reduced frequency of treatments, administration of anthelmintics at times when parasite populations on pastures (i.e. at the suprapopulation level) are high compared to the populations of treated worms in animals (i.e. at the infrapopulation level) (Jackson, 1993; Sangster, 1999) and even reintroduction of susceptible strains of trichostrongyles (Van Wyk and Van Schalwyck, 1990). Strategic computer models have also predicted that one efficient way to delay the onset of resistance is to let a proportion of the flock undrenched (Leathwick et al., 1995; Barnes et al., 1995). The feasibility and validity of such selective chemotherapy to control nematode has been previously assessed in horses, based on results from individual faecal egg counts (Krecek
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Fig. 4. Milk yields in the groups of goats treated on a systematic or selective basis during year 1 (A), and year 2 (B) of the study. Overall, the milk production for the second half of lactation were 267 and 258 kg in year 1, and 294 and 290 kg in year 2, in group SYS and SEL, respectively.
et al., 1994; Gomez and Georgi, 1991) and in small ruminants infected with Haemonchus spp. based on clinical diagnosis of anaemia signs associated with this nematode species (Van Wyk et al., 1997; Vatta et al., 2001). Unfortunately, this last method has little relevance for infections with other non-haematophagous nematode species, such as Teladorsagia circumcincta or Trichostrongylus colubriformis, which are the most prevalent species found in dairy goats in France (Chartier and Reche, 1992). An original aspect of the current study was that selective treatment was given not on the basis of diagnosed individual susceptibility to infection, but to subgroups of goats that previous studies had shown to be particularly vulnerable to nematode infection (Hoste and Chartier, 1993; Chartier and Hoste, 1997; Hoste et al., 1999; Chartier et al., 2000). The objectives of the present study were to answer the
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following two questions. (1) How efficient is a selective treatment compared to a systematic one to control nematode infection? (2) What are the costs in terms of productivity associated with a selective treatment? Results of the current study demonstrated that anthelmintic treatments restricted to 50 to 66% of the flock allowed a control of gastrointestinal parasitism similar to that achieved with systematic administration. This conclusion is supported both by comparisons of the dynamics of parasitological (egg excretion) and pathophysiological measurements in the two groups of goats. Comparisons of milk yields between the two experimental groups for both years also indicated that, overall, targeted administration of anthelmintics did not induce any detrimental consequences on mean milk production from the flock. In contrast, some economic benefits were derived from selective treatments due to the reduced number of drenchings. Nevertheless, the main interest of the method remains associated with the predicted delay in anthelmintic resistance, according to mathematical models (Barnes et al., 1995). To date, modelling and experimental studies have not provided any indications of the proportion of the flock that should be left untreated whilst maintaining treatment efficiency and delaying the onset of anthelmintic resistance. Since results from the current study did not indicate any major difference between treatments given either to approximately 50 or 66% of the flock, further studies will be required to identify the optimal proportions. One of the key question to implement the strategy of selective treatment is to understand why no overall difference was found in parasitism between group SEL and group SYS, despite the fact that 33–50% of the goats remained undrenched in group SEL and, consequently contributed continuously to pasture contamination. Separate analysis of egg excretion in the different subgroups (i.e. low producers on one side, and high producers and goats in first lactation on the other side) provided some insights to this question. The design of the experiment ensured that there were groups of low producers that were either treated (group SYS) or not treated (group SEL) with anthelmintic. The dynamics of egg excretion in these low producers showed that, after the initial effect of treatment, the increase in egg excretion was more dramatic in animals from group SYS. These results suggest that the presence of an established worm population could contribute to modulate the response to new incoming larvae. Some previous results obtained in goats (Hosking and Watson, 1993; Hadas and Stankiewicz, 1997; Hoste and Chartier, 1998) or in sheep (Barger, 1988; Luffau et al., 1985) after experimental or natural infections also strongly evoked negative interactions between anthelmintic drenches and the regulation of nematode infections through the host immune response. The present results tend to confirm these observations and to underline their epidemiological significance in natural conditions. The level of egg excretion observed in this study corresponded to intensities described in goat farms from previous epidemiological surveys in France (Etter et al., 2000; Vallade et al., 2000). In addition, the two main species occurring on the farm were also the most prevalent ones in France (Chartier and Reche, 1992). However, despite such similarities, it is difficult to generalise the conclusions from this unique study, obtained in the particular conditions of the site, to the various epidemiological situations encountered in the different areas of goat production. Further studies are clearly needed to verify the validity and feasibility of selective chemotherapy for goats under diverse farm conditions.
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Acknowledgements This work received the financial support from the European Union (DG VI FAIR3 Project CT96-1485) and is part of a collaboration between UK, Greece, Spain, and France. References Barger, I.A., 1988. Resistance of young lambs to Haemonchus contortus infection and its loss following anthelmintic treatment. Int. J. Parasitol. 8, 1107–1109. Barnes, E.H., Dobson, R.J., Barger, I.A., 1995. Worm control and anthelmintic resistance: adventures with a model. Parasitol. Today 11, 56–63. Cabaret, J., 2000. Anthelmintic resistance in goats: from fictions to facts. In: Proceedings of the Seventh International Conference on Goats, Tours, 15–21 May 2000, pp. 793–794. Chartier, C., Reche, B., 1992. Gastrointestinal helminths and lungworms of French dairy goats: prevalence and geographical distribution in Poitou Charentes. Vet. Res. Commun. 16, 327–335. Chartier, C., Hoste, H., 1997. Response to challenge infection with Haemonchus contortus and Trichostrongylus colubriformis in dairy goats: differences between high and low producers. Vet. Parasitol. 73, 267–276. Chartier, C., Etter, E., Hoste, H., Pors, I., Mallereau, M.P., Broqua, C., Mallet, S., Koch, C., Massé, A., 2000. Effects of the initial level of milk production and of the dietary protein intake on the course of natural nematode infection in dairy goats. Vet. Parasitol. 92, 1–13. Dash, K.M., Newman, R.J., Hall E., 1985. Recommendations to minimise selection for anthelmintic resistance in nematode control programmes. In: Anderson, N., Waller, P.J. (Eds.), Resistance in Nematodes to Anthelmintic Drugs. Australian Wool Corporation Technical Publication, Melbourne, pp. 161–169. Etter, E., Chartier, C., Hoste, H., Pors, I., Le Frileux, Y., Broqua, C., Vallade, S., Goudeau, C., 2000. Parasitisme par les nématodes du tube digestif et utilisation du pˆaturage: epidémiologie de l’infestation dans les troupeaux caprins laitiers en France. Epidémiologie et Santé Animale 37, 75–86. Gomez, H.H., Georgi, J.R., 1991. Equine helminth infections: control by selective chemotherapy. Equine Vet. J. 23, 198–200. Hadas, E., Stankiewicz, M., 1997. The results of abbreviated infections of Trichostrongylus colubriformis and Teladorsagia circumcincta on faecal egg counts in goats on pasture. J. Parasitol. 83, 532–533. Hosking, B.C., Watson, T.G., 1993. Development of resistance to Haemonchus contortus by Saanen goats. In: Proceedings of the 14th WAAVP Conference, Cambridge, p. 111. Hoste, H., Chartier, C., 1993. Comparison of the effects on milk production of concurrent infection with Haemonchus contortus and Trichostrongylus colubriformis in high- and low-producing dairy goats. Am. J. Vet. Res. 54, 1886–1893. Hoste, H., Chartier, C., 1998. Response to challenge infection with Haemonchus contortus and Trichostrongylus colubriformis in dairy goats. Consequences on milk production. Vet. Parasitol. 74, 43–54. Hoste, H., Le Frileux, Y., Pommaret, A., Gruner, L., Van Quackebeke, E., Koch, C., 1999. Importance du parasitisme par des strongles gastrointestinaux chez les chèvres laitières dans le Sud Est de la France. INRA Prod. Anim. 12, 377–389. Hoste, H., Le Frileux, Y., Pommaret, A., 2001a. The distribution and repeatability of faecal egg counts and blood parameters in dairy goats following natural infection with nematodes of the digestive tract. Res. Vet. Sci. 70, 57–60. Hoste, H., Le Frileux, Y., Goudeau, C., Chartier, C., Broqua, C., Bergeaud, J.P., 2001b. Distribution and repeatability of nematode faecal egg counts in dairy goats: results from a farm survey and implications for worm control, Res. Vet. Sci., submitted for publication. Jackson, F., 1993. Anthelmintic resistance—the state of play. Br. Vet. J. 149, 123–138. Jackson, F., Coop, R.L., 2000. The development of anthelmintic resistance in sheep nematodes. Parasitology 120, S95–S107. Jackson, F., 2000. Options for the sustainable control of gastrointestinal nematode infections in goat production systems in Europe. In: Proceedings of the Seventh International Conference on Goats, Tours, 15–21 May 2000, pp. 789–792.
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Kerboeuf, D., 1975. Le dosage du pepsinogène sanguin. Pfizer Actualités 16, 9–16. Krecek, R.C., Guthrie, A.J., van Nieuwenhuizen, L.C., Booth, L.M., 1994. A comparison between the effects of conventional and selective antiparasitic treatments on nematode parasites of horses from two management schemes. J. South Africa Vet. Assoc. 65, 97–100. Leathwick, D.M., Vlassoff, A., Barlow, N.D., 1995. A model for nematodiasis in New Zealand lambs: the effect of drenching regime and grazing management on the development of anthelmintic resistance. Int. J. Parasitol. 25, 1479–1490. Luffau, G., Pery, P., Carrat, C., 1985. Interférence entre vermifugation et immunité dans les strongyloses gastrointestinales du mouton. Ann. Rech. Vet. 16, 17–23. Raynaud, J.P., 1970. Etude de l’efficacité d’une technique de coproscopie quantitative pour le diagnostic de routine et le contrˆole des infestations parasitaires des bovins, ovins, équins et porcins. Ann. Parasitol. Hum. Comp. 45, 321–342. Robinson, R., Roughan, M.E., Wagstaff, D.F., 1971. Measuring inorganic phosphate without using a reducing agent. Ann. Clin. Biochem. 8, 168–170. Sangster, N.C., 1999. Anthelmintic resistance: past, present and future. Int. J. Parasitol. 29, 115–124. Sangster, N.C., 2001. Managing parasiticide resistance. Vet. Parasitol. 98, 89–109. Vallade, S., Hoste, H., Broqua, C., Lazare, K., Le Frileux, Y., Chartier, C., Etter, E., 2000. Relationships between nematode infection and farm characteristics in dairy goats in two French regions. Rev. Med. Vet. 151, 1131– 1138. Van Wyk, J.A., Van Schalwyck, P.C., 1990. A novel approach to the control of anthelmintic-resistant Haemonchus contortus in sheep. Vet. Parasitol. 35, 61–69. Van Wyk, J.A., Malan, F.S., Bath, G.F., 1997. Rampant anthelmintic resistance in sheep in South Africa: what are the options? In: Van Wyk, J.A, Van Schalwyk, P.C. (Eds.), Managing Anthelmintic Resistance in Endoparasites, Workshop of the 16th WAAVP Conference, Sun City, South Africa, August 1997. Vatta, A.F., Letty, B.A., van der Linde, M.J., van Wijk, E.F., Hansen, J.W., Krecek, R.C., 2001. Testing for clinical anaemia caused by Haemonchus spp. in goats farmed under resource-poor conditions in South Africa using an eye colour chart developed for sheep. Vet. Parasitol. 99, 1–14. Waller, P.J., Dash, K.M., Barger, I.A., Le Jambre, L.F., Plant, J., 1995. Anthelmintic resistance in nematode parasites of sheep—learning from the Australian experience. Vet. Rec. 136, 411–413.
Comparison of selective and systematic treatments to control nematode infection of the digestive tract in dairy goats H. Hoste a,∗ , Y. Le Frileux b , A. Pommaret b a
Unité Mixte de Recherche, 959 INRA/DGER, Physiopathologie des Maladies Infectieuses et Parasitaires des Ruminants, ENV Toulouse, 23 Chemin des Capelles, F31076 Toulouse, France b Station du Pradel, Ferme Expérimentale Caprine, 07170 Mirabel, France Received 29 October 2001; received in revised form 20 February 2002; accepted 2 April 2002
Abstract Resistance to anthelmintics in nematode parasite of the digestive tract is a major concern in small ruminants and particularly in goats. One possible solution to limit the development and spread of resistance is to give treatments on a selective basis, i.e. by targeting the most susceptible animals within a flock rather than treating all the animals. In dairy goats, epidemiological studies have shown that, within a flock, goats in first lactation and the multiparous ones with the highest level of milk production were highly receptive to parasite infection. The objective of the study was to assess whether selective treatments could achieve a level of control of nematodes similar to systematic drenching. A similar experimental design was applied for two successive years. An experimental flock of 120 dairy goats was divided into two groups. All the goats from group SYS (systematic treatment) were drenched at mid-grazing season (July). In contrast, anthelmintics in group SEL (selective treatment) were restricted to the goats in first lactation plus the high producers. Overall, these treated goats represented 48% of the flock in year 1 and 66% in year 2. After treatments, both groups grazed on separate pastures. Parasitological and pathophysiological measurements were performed monthly. The results indicate a similar level of egg excretion in the two groups. The pathophysiological parameters (pepsinogen and phosphate concentrations) were also similar in the two groups, as well as the milk production for the 2 years. These results suggest that a targeted use of anthelmintics may allow efficient control of gastrointestinal nematodes whilst resulting in a predicted reduction in the selection pressure for the development of anthelmintic resistance. © 2002 Elsevier Science B.V. All rights reserved. Keywords: Trichostrongylidae; Goat; Control methods-Nematoda; Drug resistance
∗ Corresponding author. Tel.: +33-561-19-38-75; fax: +33-561-19-39-44. E-mail address: [email protected] (H. Hoste).
0304-4017/02/$ – see front matter © 2002 Elsevier Science B.V. All rights reserved. PII: S 0 3 0 4 - 4 0 1 7 ( 0 2 ) 0 0 0 8 4 - 5
346
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1. Introduction The control of gastrointestinal trichostrongylosis in small ruminants is now severely impaired by the increasing development of anthelmintic resistance (Sangster, 1999, 2001). The emergence of anthelmintic resistance is particularly rapid and the prevalence particularly high in goats (Cabaret, 2000; Jackson and Coop, 2000). This is due to: (i) the high frequency of treatments required because of the poor ability of goats to develop an immune response to nematodes; (ii) the restricted choice of anthelmintic family during lactation in order to avoid milk residues; and (iii) the specificity of drug metabolization in goats which made ovine dose unadapted and lead to underdosing for a long time. All these factors, i.e. frequent treatments, lack of alternation between molecules and underdosing, are known to favour the development of anthelmintic resistance (Jackson and Coop, 2000). Therefore, there is an urgent need in goats for alternative or complementary solutions to anthelmintics, as well as for improvement in the use of the drugs currently available in order to conserve efficacy. In countries from the southern hemisphere, several programs have been developed to reduce the selection pressure for anthelmintic resistance in trichostrongyle populations. The main recommendations included a reduction in frequency of treatments, the respect of appropriate doses, the alternation of drug families, and the preferred use of narrow spectrum anthelmintics when possible (Dash et al., 1985; Waller et al., 1995). Another recommended approach is to use selective treatments instead of systematic ones. The principle of selective treatment is to target and treat exclusively the most infected animals within a flock. By diluting the alleles of resistance in the nematode populations, the approach should contribute to slow down the rate of selection of resistance (Barnes et al., 1995; Sangster, 1999). The key point of the method lays in the identification of the most susceptible animals within a flock, i.e. those which are responsible for the largest part of pasture contamination. Assays of targeted application of anthelmintics have been previously conducted in horses, based on regular coproscopical examinations (Krecek et al., 1994; Gomez and Georgi, 1991). In South Africa, the FAMACHA system, based on clinical signs of anaemia, has also been developed in sheep and goats to reduce resistance to anthelmintics in Haemonchus contortus (Van Wyk et al., 1997, Vatta et al., 2001). In dairy goats, previous studies have demonstrated an aggregated distribution of worm infection with significant repeatabilities from one year to another (Hoste et al., 2001a,b). Moreover, epidemiological data were available which provided a means of identifying categories at risk within flocks. These studies have repeatedly shown a relationship between the level of milk production and the receptivity to trichostrongyle infection. Both in experimental and in farm conditions, goats with the highest level of milk production within flocks have been found to be more susceptible and more infected with gastrointestinal nematodes of the digestive tract than the low producing ones (Hoste and Chartier, 1993; Chartier et al., 2000; Hoste et al., 1999). In addition, goats during their first lactation appear to be more susceptible to infection than multiparous goats (Hoste et al., 1999). These observations hence provided the rationale for the design of a selective application of anthelmintic treatments restricted to high producers and goats in first lactation. The current study was, therefore, performed in controlled conditions in order to verify the feasibility of such a method in a dairy goat flock and to examine its consequences on production and pasture contamination.
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2. Materials and methods 2.1. Experimental design The study was conducted during two successive years (1998 and 1999) on a flock of 120 Alpine grazing dairy goats. The flock contained 96 multiparous adults and 24 first lactation animals. The survey was performed during the second half of the grazing season from July to the beginning of December, as the only anthelmintic treatment per grazing season was given at the end of July. The experimental period corresponded to the second half of lactation as kiddings occurred at the end of January and in February. The same experimental design was applied during the 2 years. The flock was divided into two groups of 60 goats, according to the mode of anthelmintic administration. The two groups were balanced according to the level of milk production; the age composition and the mean level of previous nematode infection as assessed by faecal egg counts in June. In group SYS (systematic treatment), all the animals were drenched at the end of July; in group SEL (selective treatment), the anthelmintic was given only to some of the goats within the group. The animals which were drenched in group SEL were all the goats in first lactation plus a proportion of the adult goats corresponding to those with the highest level of milk production. In each group, the treatment was composed of oxfendazole (Synanthic ND), used at the recommended ovine dose rate of 5 mg/kg, repeated at 24 h interval. The full efficiency of benzimidazoles on the farm has been evaluated in previous years and no evidence of anthelmintic resistance was detected. Classification of the adult goats, according to their level of milk production, was based on the records of milk production during the first 2 months of lactation, i.e. at a time when the animals were housed and nematode infections were absent or at a very low level. In year 1, the aim was to drench the goats in first lactation plus one-third of the high producing multiparous goats; in year 2, the proportion was increased to first lactation animals plus 60% of the multiparous goats with the highest level of production. Therefore, the total proportion of the flock drenched in group SEL was 47% in year 1 (12 first lactations plus 16 high producers ) and 66% in year 2 (12 first lactations plus 28 high producers). After treatment, the animals were kept indoors for 3 weeks, due to the lack of grass. Thereafter, the two groups were maintained on separate pastures, but with similar surfaces (4.3 ha) and plant composition. The pastures were previously used by the goats and their level of contamination was similar. 2.2. Parasitological and pathophysiological measurements During both years, the 120 goats were individually sampled at monthly intervals from July (before treatments) to the end of the grazing seasons (beginning of December). Faecal samples were used to assess the nematode egg excretion and were performed using a modified McMaster method (Raynaud, 1970). Blood samples were taken by venipuncture into vacutainers and were used to determine the pepsinogen and inorganic phosphate concentrations according to the methods described by Kerboeuf (1975) and Robinson et al. (1971). These measurements are considered to reflect indirectly the lesions provoked by the worms to the abomasal and to the intestinal mucosae. In addition, the individual
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milk production was recorded each week and the milk yield, fat and protein contents were assessed. 2.3. Statistical analyses One-way variance analysis (SYSTAT Software Science Ltd.) were used to compare on each date the difference between the two experimental groups for the parasitological, pathophysiological, and milk production measurements. Eggs per gram were log(x + 1) transformed before being analysed. 3. Results 3.1. Faecal egg excretion Egg excretion in the two groups of goats for the 2 years are illustrated in Fig. 1A and B. During year 1, a drop in the egg output was observed after treatment which was more prominent in the group SYS. As a consequence, significant differences between the two groups were observed in September and in October. However, at the end of the season, no difference occurred between both groups. The pattern of egg output was similar in year 2, although the level of egg output at the beginning of the assay (July) was low in both groups. No differences were observed in egg output at the beginning of autumn between both groups, but in November and December a lower egg excretion was measured in goats from group SEL. These differences in egg excretion were further analysed depending on subgroups within group SEL and SYS. The comparisons of egg excretion were, therefore, firstly conducted between the low producers from group SYS and SEL, which were, respectively, treated or not; and secondly, between high producers plus first lactation goats from each group, which were treated, whatever their experimental group. Differences in egg excretions between low producers from group SEL (untreated goats) or SYS (treated low producing goats) corresponded to what was observed for the whole groups of animals (Fig. 2A and B). In addition, differences were also observed in egg output from high producers plus first lactation goats at the end of the grazing season for the two successive years, although these goats received a similar treatment in the two experimental groups (Fig. 2C and D). In November (years 1 and 2) and December (year 2), egg excretions from these subgroups were significantly lower in group SEL. 3.2. Pathophysiological parameters Overall, only minor differences were observed between the two groups for both the pepsinogen and phosphate values during the two successive studies. Higher concentrations of pepsinogen were observed in year 1 compared to year 2, but no statistical differences were found between the two groups except in September from year 1 when higher values were recorded in group SEL (Fig. 3). The evolution of phosphate concentrations were similar during the 2 years with a slow decrease of values towards the end of surveys. The mean values were, respectively, 71 mg/l
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Fig. 1. Comparison of egg excretion in groups of goats receiving the anthelmintic treatment on a systematic or a selective basis during the grazing season in: year 1 (A), and year 2 (B) of the study. The arrows indicate the moment of treatment. Statistical comparisons: ∗ P < 0.05.
in year 1 and 60.5 mg/ l in year 2 at the start of the assay; and 53 mg/l (year 1) and 45 mg/l (year 2) at the end in December (data not shown). Again, no statistical difference was observed between group SEL and SYS during the 2 years. 3.3. Milk production The curves of milk yield for the 2 years showed a similar pattern in both groups of goats. No statistical difference was detected between the two groups in year 1 and in year 2. Overall, the mean production for the second half of lactation (from July to December) in
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Fig. 3. Serum pepsinogen concentrations in the two groups of goats receiving the systematic or the selective anthelmintic treatment during the grazing season in: year 1 (A), and year 2 (B) of the study. Statistical comparisons: ∗ P < 0.05.
year 1 was 258 kg in group SEL versus 267 kg in group SYS. In year 2, these production records were, respectively, 290 and 294 kg (Fig. 4). 4. Discussion Most strategies designed to manage anthelmintic resistances aimed at decreasing the selection pressure and at keeping alleles of susceptibility to antiparasitic drugs in worm populations in order to dilute the resistance genes (Jackson, 2000; Jackson and Coop, 2000; Sangster, 1999, 2001). Proposed measures to maintain genes of susceptibility have included a reduced frequency of treatments, administration of anthelmintics at times when parasite populations on pastures (i.e. at the suprapopulation level) are high compared to the populations of treated worms in animals (i.e. at the infrapopulation level) (Jackson, 1993; Sangster, 1999) and even reintroduction of susceptible strains of trichostrongyles (Van Wyk and Van Schalwyck, 1990). Strategic computer models have also predicted that one efficient way to delay the onset of resistance is to let a proportion of the flock undrenched (Leathwick et al., 1995; Barnes et al., 1995). The feasibility and validity of such selective chemotherapy to control nematode has been previously assessed in horses, based on results from individual faecal egg counts (Krecek
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Fig. 4. Milk yields in the groups of goats treated on a systematic or selective basis during year 1 (A), and year 2 (B) of the study. Overall, the milk production for the second half of lactation were 267 and 258 kg in year 1, and 294 and 290 kg in year 2, in group SYS and SEL, respectively.
et al., 1994; Gomez and Georgi, 1991) and in small ruminants infected with Haemonchus spp. based on clinical diagnosis of anaemia signs associated with this nematode species (Van Wyk et al., 1997; Vatta et al., 2001). Unfortunately, this last method has little relevance for infections with other non-haematophagous nematode species, such as Teladorsagia circumcincta or Trichostrongylus colubriformis, which are the most prevalent species found in dairy goats in France (Chartier and Reche, 1992). An original aspect of the current study was that selective treatment was given not on the basis of diagnosed individual susceptibility to infection, but to subgroups of goats that previous studies had shown to be particularly vulnerable to nematode infection (Hoste and Chartier, 1993; Chartier and Hoste, 1997; Hoste et al., 1999; Chartier et al., 2000). The objectives of the present study were to answer the
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following two questions. (1) How efficient is a selective treatment compared to a systematic one to control nematode infection? (2) What are the costs in terms of productivity associated with a selective treatment? Results of the current study demonstrated that anthelmintic treatments restricted to 50 to 66% of the flock allowed a control of gastrointestinal parasitism similar to that achieved with systematic administration. This conclusion is supported both by comparisons of the dynamics of parasitological (egg excretion) and pathophysiological measurements in the two groups of goats. Comparisons of milk yields between the two experimental groups for both years also indicated that, overall, targeted administration of anthelmintics did not induce any detrimental consequences on mean milk production from the flock. In contrast, some economic benefits were derived from selective treatments due to the reduced number of drenchings. Nevertheless, the main interest of the method remains associated with the predicted delay in anthelmintic resistance, according to mathematical models (Barnes et al., 1995). To date, modelling and experimental studies have not provided any indications of the proportion of the flock that should be left untreated whilst maintaining treatment efficiency and delaying the onset of anthelmintic resistance. Since results from the current study did not indicate any major difference between treatments given either to approximately 50 or 66% of the flock, further studies will be required to identify the optimal proportions. One of the key question to implement the strategy of selective treatment is to understand why no overall difference was found in parasitism between group SEL and group SYS, despite the fact that 33–50% of the goats remained undrenched in group SEL and, consequently contributed continuously to pasture contamination. Separate analysis of egg excretion in the different subgroups (i.e. low producers on one side, and high producers and goats in first lactation on the other side) provided some insights to this question. The design of the experiment ensured that there were groups of low producers that were either treated (group SYS) or not treated (group SEL) with anthelmintic. The dynamics of egg excretion in these low producers showed that, after the initial effect of treatment, the increase in egg excretion was more dramatic in animals from group SYS. These results suggest that the presence of an established worm population could contribute to modulate the response to new incoming larvae. Some previous results obtained in goats (Hosking and Watson, 1993; Hadas and Stankiewicz, 1997; Hoste and Chartier, 1998) or in sheep (Barger, 1988; Luffau et al., 1985) after experimental or natural infections also strongly evoked negative interactions between anthelmintic drenches and the regulation of nematode infections through the host immune response. The present results tend to confirm these observations and to underline their epidemiological significance in natural conditions. The level of egg excretion observed in this study corresponded to intensities described in goat farms from previous epidemiological surveys in France (Etter et al., 2000; Vallade et al., 2000). In addition, the two main species occurring on the farm were also the most prevalent ones in France (Chartier and Reche, 1992). However, despite such similarities, it is difficult to generalise the conclusions from this unique study, obtained in the particular conditions of the site, to the various epidemiological situations encountered in the different areas of goat production. Further studies are clearly needed to verify the validity and feasibility of selective chemotherapy for goats under diverse farm conditions.
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