Progress 10/01/03 to 09/30/05
Outputs
Ivermectin and moxidectin are closely related avermectin/milbemycin anthelmintics and available data suggest that side resistance occurs with these two drugs. However, moxidectin remains effective against many species of ivermectin-resistant worms due to its higher potency. The larval development assay (LDA) is routinely used to diagnose ivermectin resistance in Haemonchus contortus but laboratory diagnosis of moxidectin resistance is hampered by the lack of any validated in vitro tests. The objective of this study was to measure the relative susceptibility/resistance of H. contortus to moxidectin on goat farms in Georgia, and to validate the DrenchRite LDA for detecting resistance to moxidectin. Fecal egg count reduction tests (FECRT) were performed at five different moxidectin dose levels and DrenchRite LDAs were performed in duplicate on nine meat goat farms in Georgia, USA. To improve our ability to make inferences on the relative levels of resistance between
farms, FECRT data were first analyzed using a linear mixed model, and then Tukey's sequential trend test was used to evaluate the trend in response across dose levels. LDA data were analyzed using log-dose logit-response and probit models. Using these statistical results, we were able to rank the nine farms from the least to the most resistant, and to develop a set of criteria for interpreting DrenchRite LDA results so that this assay can be used to diagnose both clinically-apparent moxidectin resistance, as well as sub-clinical emerging resistance. These results suggest that our novel approach for examining these types of data provides a method for obtaining an increased amount of information, thus permitting a more sensitive detection of resistance. Based on results of the LDA, moxidectin-resistant farms had resistance ratios, compared with an ivermectin-sensitive farm, ranging from 32-128, and had resistance ratios of 6-24 compared with an ivermectin-resistant/moxidectin naive
farm. Moxidectin resistance was diagnosed both in Haemonchus and Trichostrongylus on almost half of the farms tested, despite this drug only being used on these farms for 2 to 3 years.
Impacts
Prior to this study the prevalence of moxidectin resistance was unknown, and even more importantly, there was no laboratory test to determine if moxidectin resistance was even present on a farm. In this study we took a novel approach for investigating the presence of anthelmintic resistance by combining in vitro drug efficacy data with in vivo field data to make inferences on the relative sensitivity/resistance to moxidectin on individual farms. Using novel statistical methods, we were able to analyze our data in a new way that offers an improved method for measuring the relative levels of resistance on different farms. Using this approach, it should be possible to better measure the impact of using different management schemes and treatment strategies for delaying the development of resistance to anthelmintics. We also present parameters for interpreting DrenchRite LDA results for ivermectin so that this assay can also be used to diagnose both clinically-apparent
moxidectin resistance, as well as sub-clinical emerging resistance. Though the number of farms was small, the high prevalence of resistance to moxidectin we observed portends a very serious situation for control of both H. contortus and T. colubriformis in the southern US. It is expected that the results of this research will provide better tools for researching anthelmintic resistance, and will provide improved diagnostic tools to measure resistance. This will enable earlier detection of resistance which will lead to improved parasite control.
Publications
- Kaplan, R.M., A. N. Vidyashankar, S.B. Howell, J.M. Neiss, L.H. Williamson, and T.H. Terrill. 2007. A novel approach for combining the use of in vitro and in vivo data to measure and detect emerging moxidectin resistance in gastrointestinal nematodes of goats. International Journal for Parasitology, in press. (2007), doi:10.1016/j.ijpara.2007.01.001
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Progress 01/01/04 to 12/31/04
Outputs
Fecal egg count reduction tests (FECRT) performed on 18 goat farms in Georgia, USA in 2001 demonstrated an alarming prevalence of multiple-resistant gastrointestinal nematode (GIN) parasites, and greater than 90% of all farms tested had worms resistant to ivermectin (IVM) (mean FECR=54%). Moxidectin (MOX) (400 mcg/kg) was the only drug tested that was highly effective on all farms (mean FECR=99%). However, IVM and MOX are closely related drugs with very similar or the same mechanisms of action. Therefore, it is expected that IVM-resistant (IVM-R) worms will rapidly develop resistance to MOX. To test this hypothesis we recently repeated the FECRT with MOX on 7 of these same farms, plus 2 additional farms. Two farms served as controls: 1 farm had worms known to be IVM-sensitive (IVM-S), and another farm had worms known to be IVM-R, but neither farm had ever used MOX and were MOX-sensitive (MOX-S). All other farms (N=7) had a history of using MOX as the primary
anthelmintic over the past 2-3 years. On each farm goats were stratified by pretreatment FEC, blocked, and within each block were allocated randomly to treatment with MOX at 100 or 400 mcg/kg (Cydectin cattle pour-on administered PO) or were left untreated as controls. Data were analyzed using the RESO program and WAAVP guidelines. On the IVM-S and IVM-R/MOX-S control farms, 100 mcg/kg MOX reduced FEC by 100 and 98%, respectively, and on both farms 400 mcg/kg reduced FEC by 100%. In contrast, on farms with a history of MOX use, at the 100 mcg/kg dose, 7/7 had resistant Haemonchus contortus (mean FECR = 44%) and 6/7 had resistant Trichostrongylus colubriformis (mean FECR = 57%). At the 400 mcg/kg dose, 3/7 had resistant H. contortus (mean FECR = 75%) and 3/7 had resistant T. colubriformis (mean FECR = 82%). Within a period of 2 years, multiple species of GIN have developed resistance to MOX on goat farms in Georgia. The statistical analysis correlating the results of in vitro and in
vivo methods for the detection of moxidectin resistance is in progess and will be completed in the near future. At that time a publication will be prepared and submitted
Impacts
Resistance to moxidectin on goat farms is much more prevalent and severe than what was expected. If MOX is to remain effective on goat farms that do not yet have resistance, it must be used sparingly, preferably in a selective treatment program based on the FAMACHA method. Results of this study now make it possible to diagnose moxidectin resistance using the DrenchRite in vitro larval development assay. When statistical analysis is completed, it should be possible to predict the efficacy of moxidectin based on results obtained with the DrenchRite test.
Publications
- Kaplan, R.M., J. Neiss, L.H. Williamson, and T.H. Terrill, 2004 "Moxidectin resistance in gastrointestinal nematodes of goats in Georgia", American Association of Veterinary Parasitologists, 49th Annual Meeting, Philadelphia, PA July 24-28, 2004.
- Kaplan, R.M., J. Neiss, L.H. Williamson, and T.H. Terrill, 2005 "Moxidectin resistance in gastrointestinal nematodes of goats in Georgia, USA", Novel Approaches to the Control of Helminth Parasites of Livestock: 4th International workshop, Merida, Yucatan, Mexico January 10-12, 2005.
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