The Experts below are selected from a list of 7542 Experts worldwide ranked by ideXlab platform

Jozef Vercruysse - One of the best experts on this subject based on the ideXlab platform.

  • modelling cooperia oncophora quantification of key parameters in the parasitic phase
    Veterinary Parasitology, 2016
    Co-Authors: Sien Verschave, Jozef Vercruysse, Eric R. Morgan, Hannah Rose, Edwin Claerebout, Johannes Charlier
    Abstract:

    Cooperia oncophora is one of the most common intestinal nematodes in cattle. It is also the dose-limiting species for the most frequently used Anthelmintics, and consequently, the species usually involved in reports of anthelmintic resistance. However, little information is available on its population dynamics, hindering the parameterisation of transmission models to support understanding of the impact of anthelmintic resistance, climate change and alternative control strategies on nematode epidemiology. This systematic review and meta-analysis provides estimates for key life history traits of the parasitic phase of C. oncophora and investigates potential influences of acquired immunity on these traits.

  • world association for the advancement of veterinary parasitology w a a v p guideline anthelmintic combination products targeting nematode infections of ruminants and horses
    Veterinary Parasitology, 2012
    Co-Authors: Timothy G. Geary, Peter Holdsworth, Steven J Maeder, W E Pomroy, Barry C. Hosking, P. J. Skuce, Georg Von Samsonhimmelstjerna, Jozef Vercruysse
    Abstract:

    Increasing threats from anthelmintic resistant nematode populations warrant and motivate a reappraisal of chemotherapeutic strategies for nematode control in ruminant livestock and horses. The objective of this paper is to present a guideline for the evaluation of products containing two or more constituent anthelmintic actives in a single dosage form for the treatment of nematode infections in these animals. At present, regulatory policies on the approval of such products vary across jurisdictions, and this World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guideline should enable the harmonization of the requirements. This guideline makes clear recommendations on the minimal standards needed, but stresses that registration dossiers for combination anthelmintic products submitted for approval must conform to the standards and practices already established in existing guidelines for Anthelmintics.

  • international harmonisation of anthelmintic efficacy guidelines part 2
    Veterinary Parasitology, 2002
    Co-Authors: Jozef Vercruysse, Pa Holdsworth, T Letonja, K. Okano, K. Hamamoto, George A. Conder, Steffen Rehbein
    Abstract:

    Abstract The “International Co-operation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH)” is an international programme of co-operation between regulatory authorities and the animal health industries of the European Union, Japan and the United States of America which aims to harmonise the technical requirements for the registration of veterinary medicinal products. Australia and New Zealand participate as active observers. The objective of this second paper is to present additional guidelines established by the Working Group on anthelmintic guidelines: (1) efficacy of Anthelmintics: specific recommendations for equine (VICH GL15), (2) efficacy of Anthelmintics: specific recommendations for porcine (VICH GL16), (3) efficacy of Anthelmintics: specific recommendations for canine (VICH GL19), (4) efficacy of Anthelmintics: specific recommendations for feline (VICH GL20) and (5) efficacy of Anthelmintics: specific recommendations for poultry (VICH GL21). These guidelines do not consist of rigid stipulations, but make clear recommendations on the minimal standards needed. To the veterinary profession, livestock producers and animal owners, harmonisation should mean quicker access to safer and more effective veterinary Anthelmintics. In general, products should be relatively more affordable because of the reduction in registration costs and efficient use of resources by the regulatory authorities.

  • international harmonisation of anthelmintic efficacy guidelines
    Veterinary Parasitology, 2001
    Co-Authors: Jozef Vercruysse, Pa Holdsworth, T Letonja, D. Barth, K. Hamamoto, George A. Conder, K. Okano
    Abstract:

    Abstract The “International Co-operation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH)” is an international programme of co-operation between regulatory authorities and the animal health industries of the European Union, Japan, and the United States of America which aims to harmonise the technical requirements for the registration of veterinary medicinal products. Australia and New Zealand participate as active observers. The objective of the present paper is to present the guidelines established by the working group on Anthelmintic Efficacy Guidelines: (1) efficacy of Anthelmintics: general requirements (VICH GL7); (2) efficacy of Anthelmintics: specific recommendations for bovines (VICH GL12); (3) efficacy of Anthelmintics: specific recommendations for ovines (VICH GL13); (4) efficacy of Anthelmintics: specific recommendations for caprines (VICH GL14). These guidelines do not consist of rigid stipulations, but make clear recommendations on the minimal standards needed. To the veterinary profession, livestock producers and animal owners, harmonisation should mean quicker access to safer and more effective veterinary Anthelmintics. In general, products should be relatively more affordable because of the reduction in registration costs and efficient use of resources by the regulatory authorities.

Angela J Russell - One of the best experts on this subject based on the ideXlab platform.

  • an automated high throughput system for phenotypic screening of chemical libraries on c elegans and parasitic nematodes
    International Journal for Parasitology-Drugs and Drug Resistance, 2018
    Co-Authors: Frederick A Partridge, Anwen E Brown, Steven D Buckingham, Nicky J Willis, Graham Michael Wynne, Ruth Forman, Jacqueline B Matthews, Kathryn J. Else, Alison A. Morrison, Angela J Russell
    Abstract:

    Parasitic nematodes infect hundreds of millions of people and farmed livestock. Further, plant parasitic nematodes result in major crop damage. The pipeline of therapeutic compounds is limited and parasite resistance to the existing anthelmintic compounds is a global threat. We have developed an INVertebrate Automated Phenotyping Platform (INVAPP) for high-throughput, plate-based chemical screening, and an algorithm (Paragon) which allows screening for compounds that have an effect on motility and development of parasitic worms. We have validated its utility by determining the efficacy of a panel of known Anthelmintics against model and parasitic nematodes: Caenorhabditis elegans, Haemonchus contortus, Teladorsagia circumcincta, and Trichuris muris. We then applied the system to screen the Pathogen Box chemical library in a blinded fashion and identified compounds already known to have anthelmintic or anti-parasitic activity, including tolfenpyrad, auranofin, and mebendazole; and 14 compounds previously undescribed as Anthelmintics, including benzoxaborole and isoxazole chemotypes. This system offers an effective, high-throughput system for the discovery of novel Anthelmintics.

  • An automated high-throughput system for phenotypic screening of chemical libraries on C. elegans and parasitic nematodes
    Elsevier, 2018
    Co-Authors: Frederick A Partridge, Anwen E Brown, Steven D Buckingham, Nicky J Willis, Graham Michael Wynne, Ruth Forman, Jacqueline B Matthews, Kathryn J. Else, Alison A. Morrison, Angela J Russell
    Abstract:

    Parasitic nematodes infect hundreds of millions of people and farmed livestock. Further, plant parasitic nematodes result in major crop damage. The pipeline of therapeutic compounds is limited and parasite resistance to the existing anthelmintic compounds is a global threat. We have developed an INVertebrate Automated Phenotyping Platform (INVAPP) for high-throughput, plate-based chemical screening, and an algorithm (Paragon) which allows screening for compounds that have an effect on motility and development of parasitic worms. We have validated its utility by determining the efficacy of a panel of known Anthelmintics against model and parasitic nematodes: Caenorhabditis elegans, Haemonchus contortus, Teladorsagia circumcincta, and Trichuris muris. We then applied the system to screen the Pathogen Box chemical library in a blinded fashion and identified compounds already known to have anthelmintic or anti-parasitic activity, including tolfenpyrad, auranofin, and mebendazole; and 14 compounds previously undescribed as Anthelmintics, including benzoxaborole and isoxazole chemotypes. This system offers an effective, high-throughput system for the discovery of novel Anthelmintics. Keywords: Parasitic nematodes, C. elegans, Chemical library screening, Automated phenotyping, Anthelmintic, Benzoxaborol

  • an automated high throughput system for phenotypic screening of chemical libraries on c elegans and parasitic nematodes
    bioRxiv, 2017
    Co-Authors: Frederick A Partridge, Anwen E Brown, Steven D Buckingham, Nicky J Willis, Graham Michael Wynne, Ruth Forman, Jacqueline B Matthews, Kathryn J. Else, Alison A. Morrison, Angela J Russell
    Abstract:

    Parasitic nematodes infect hundreds of millions of people and farmed livestock. Further, plant parasitic nematodes result in major crop damage. The pipeline of therapeutic compounds is limited and parasite resistance to the existing anthelmintic compounds is a global threat. We have developed an INVertebrate Automated Phenotyping Platform (INVAPP) for high-throughput, plate-based chemical screening, and an algorithm (Paragon) which allows screening for compounds that have an effect on motility and development of parasitic worms. We have validated its utility by determining the efficacy of a panel of known Anthelmintics against model and parasitic nematodes: Caenorhabditis elegans, Haemonchus contortus, Teladorsagia circumcincta, and Trichuris muris. We then applied the system to screen the Pathogen Box chemical library in a blinded fashion and identified known Anthelmintics, including tolfenpyrad, auranofin, and mebendazole and 14 compounds previously undescribed as Anthelmintics, including benzoxaborole and isoxazole chemotypes. This system offers an effective, high-throughput system for the discovery of novel Anthelmintics.

D M Leathwick - One of the best experts on this subject based on the ideXlab platform.

  • evidence for reversion towards anthelmintic susceptibility in teladorsagia circumcincta in response to resistance management programmes
    International Journal for Parasitology-Drugs and Drug Resistance, 2015
    Co-Authors: D M Leathwick, Siva Ganesh, T S Waghorn
    Abstract:

    Maintaining production and economic viability in the face of resistance to multiple anthelmintic actives is a challenge for farmers in many countries. In this situation, most farmers in New Zealand rely on the use of combination products, containing multiple actives with similar spectra of activity, in order to maintain control. However, there are concerns that use of combinations, once resistance has already developed to the individual actives, could rapidly lead to complete failure of all actives. This study followed seven farms, previously diagnosed with resistance to at least two classes of anthelmintic, which were implementing a tailored programme of ‘best practice parasite management’. The aim was to ascertain whether the programmes, which included the almost exclusive use of combination Anthelmintics, were able to prevent resistance from developing further. Strategies implemented on each farm varied, but had consistent underlying principles i.e. to avoid over-use of Anthelmintics; to minimise parasite challenge to susceptible stock; to maintain refugia of susceptibility and to ensure that only effective Anthelmintics were used. Annual faecal egg count reduction tests (FECRT) were undertaken in lambs on all farms to monitor anthelmintic efficacy over 5 years. The efficacy of albendazole, ivermectin and levamisole was calculated and the changes in efficacy against Teladorsagia circumcincta assessed. Overall, there was a significant improvement in the effectiveness of both levamisole and ivermectin against T. circumcincta, and a positive but non-significant trend in efficacy of albendazole, i.e. there was evidence for reversion towards susceptibility. Hence, the almost exclusive use of combination Anthelmintics, integrated with other resistance management strategies, did not result in further resistance development despite all farms exhibiting resistance to multiple actives at the outset. What-is-more, the measured increases in anthelmintic efficacy suggests that adoption of best practice management strategies may extend the useful life of Anthelmintics even after resistance has been diagnosed.

  • managing anthelmintic resistance parasite fitness drug use strategy and the potential for reversion towards susceptibility
    Veterinary Parasitology, 2013
    Co-Authors: D M Leathwick
    Abstract:

    Abstract The rotation of different anthelmintic classes, on an approximately annual basis, has been widely promoted and adopted as a strategy to delay the development of anthelmintic resistance in nematode parasites. Part of the rationale for recommending this practice was the expectation that resistant genotype worms have a lower ecological fitness than susceptible worms, at least in the early stages of selection, and so reversion towards susceptibility could be expected in those years when an alternative class of anthelmintic was used. The routine use of combination Anthelmintics might be expected to negate this opportunity for reversion because multiple classes of anthelmintic would be used simultaneously. A simulation model was used to investigate whether the optimal strategy for use of multiple drug classes (i.e. an annual rotation of two classes of anthelmintic or continuous use of two classes in combination) changed with the size of the fitness cost associated with resistance. Model simulations were run in which the fitness cost associated with each resistance gene was varied from 0% to 15% and the rate at which resistance developed was compared for each of the drug-use strategies. Other factors evaluated were the initial frequency of the resistance genes and the proportion of the population not exposed to treatment (i.e. in refugia). Increasing the proportion of the population in refugia always slowed the development of resistance, as did using combinations in preference to an annual rotation. As the fitness cost associated with resistance increased, resistance developed more slowly and this was more pronounced when a combination was used compared to a rotation. If the fitness cost was sufficiently high then resistance did not develop (i.e. the resistance gene frequency declined over time) and this occurred at lower fitness costs when a combination was used. The results, therefore, indicate that the optimal drug-use strategy to maximise the benefit of any fitness cost associated with resistance is the use of combinations of different anthelmintic classes. Manual calculations confirmed that, within the model, the only resistant genotypes capable of surviving treatment with a combination are those carrying multiple resistance genes. These individuals are less fit, resulting in the worm population surviving treatment having a lower overall ecological fitness. This is a previously unreported perspective on the use of combination Anthelmintics and strengthens the argument that any new class of anthelmintic, for which resistance genes can be expected to be rare, should be brought to market in combination.

  • the role of combination anthelmintic formulations in the sustainable control of sheep nematodes
    Veterinary Parasitology, 2012
    Co-Authors: David Bartram, Ma Taylor, D M Leathwick, Thomas Geurden, Steven J Maeder
    Abstract:

    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.

  • modelling the benefits of a new class of anthelmintic in combination
    Veterinary Parasitology, 2012
    Co-Authors: D M Leathwick
    Abstract:

    Since 2009 two new classes of Anthelmintics have been registered for use in sheep in New Zealand. This raises challenging questions about how such new actives should be used, not only to minimise the development of resistance to them, thereby ensuring their availability as effective treatments for as long as possible, but also to minimise the further development of resistance to the other anthelmintic classes. One strategy which appears to offer considerable potential for slowing the development of resistance is the use of combinations of different anthelmintic classes, although this approach remains contentious in some countries. The potential benefit of using Anthelmintics in combination is particularly relevant to two recently released anthelmintic compounds because one, monepantel, is presently only available as a single active product while the other, derquantel, is only available in combination with abamectin. A simulation modelling approach was used to investigate the potential benefits of using Anthelmintics in combination. The rate at which resistance develops to a new 'active' when used alone was compared to an equivalent compound used in combination with a second compound from an alternative class (in this case, abamectin), when various levels of resistance occur to the second active. In addition, the potential of a new active to reduce further development of resistance to the second compound in the combination was evaluated. Finally, the use of combinations as compared to sequential or rotational use patterns, in the presence of side resistance between two actives was investigated. The modelling simulations suggest a significant advantage to both compounds when they are used in combination, especially if both initially have high efficacy. The development of resistance to the new active was delayed, although to a lesser extent, even when the efficacy of the second active in the combination was only 50%. Under a 'low-refugia' management environment resistance to all actives developed more rapidly, and the advantage of using actives in combination was reduced. When used in conjunction with other resistance management strategies, a combination containing a new active prevented further development of resistance to the older class. Using actives in combination was superior to using them individually either sequentially or in rotation, even in the presence of side-resistance between the two anthelmintic classes.

  • anthelmintic resistance in nematode parasites of cattle a global issue
    Trends in Parasitology, 2011
    Co-Authors: I A Sutherland, D M Leathwick
    Abstract:

    Acceptable performance of grazing cattle frequently depends on the availability of effective broad-spectrum Anthelmintics to remove, or prevent infection with, gastrointestinal nematodes. This control is increasingly threatened by populations of nematodes resistant to the most commonly used Anthelmintics. Although this appears to have developed more slowly than in nematodes infecting small ruminants, the number of reports in the literature over the past five years suggests a rapidly escalating problem. This review discusses this literature, several issues unique to cattle parasitism and Anthelmintics, and how previous research in small ruminants can improve the management of anthelmintic resistance in cattle.

Abdul S. Shawl - One of the best experts on this subject based on the ideXlab platform.

  • anthelmintic activity of extracts of artemisia absinthium against ovine nematodes
    Veterinary Parasitology, 2009
    Co-Authors: Khurshid Ahmad Tariq, Fayaz Ahmad, Muhammad Zubair Chishti, Abdul S. Shawl
    Abstract:

    Abstract The increasing prevalence of anthelmintic resistant strains of helminths, drug residues in animal products and high cost of conventional Anthelmintics has created an interest in studying medicinal plants as an alternative source of Anthelmintics. Artemisia absinthium Linn. (Tethwen) is used traditionally by people as a vermifuge in addition to its other livestock uses. The objective of this study was to evaluate the anthelmintic efficacy of crude aqueous extracts (CAE) and crude ethanolic extracts (CEE) of the aerial parts of A. absinthium in comparison to albendazole against the gastrointestinal (GI) nematodes of sheep. To fulfill the objectives, the worm motility inhibition assay was utilized in order to investigate the direct effects of plant extracts on the survival of the adult nematodes under in vitro conditions and faecal egg count reduction assay to investigate the effects on faecal egg output of GI nematodes under in vivo conditions. Significant anthelmintic effects of CAE and CEE on live adult Haemonchus contortus worms ( P −1 body weight on day 15 PT followed by 82.85% FECR at 1.0 g kg −1 bw on day 15 PT. The CAE showed less activity and resulted in maximum of 80.49% FECR at 2.0 g kg −1  bw. Dosage had a significant ( P A. absinthium . The better activity of CEE can be attributed to the greater concentration of alcohol soluble active anthelmintic principle/s and a more rapid transcuticular absorption of the CEE into the body of the worms when compared with the CAE. The results of the present study suggest that A. absinthium extracts are a promising alternative to the commercially available Anthelmintics for the treatment of GI nematodes of sheep.

  • anthelmintic activity of extracts of artemisia absinthium against ovine nematodes
    Veterinary Parasitology, 2009
    Co-Authors: Khurshid Ahmad Tariq, Fayaz Ahmad, Muhammad Zubair Chishti, Abdul S. Shawl
    Abstract:

    The increasing prevalence of anthelmintic resistant strains of helminths, drug residues in animal products and high cost of conventional Anthelmintics has created an interest in studying medicinal plants as an alternative source of Anthelmintics. Artemisia absinthium Linn. (Tethwen) is used traditionally by people as a vermifuge in addition to its other livestock uses. The objective of this study was to evaluate the anthelmintic efficacy of crude aqueous extracts (CAE) and crude ethanolic extracts (CEE) of the aerial parts of A. absinthium in comparison to albendazole against the gastrointestinal (GI) nematodes of sheep. To fulfill the objectives, the worm motility inhibition assay was utilized in order to investigate the direct effects of plant extracts on the survival of the adult nematodes under in vitro conditions and faecal egg count reduction assay to investigate the effects on faecal egg output of GI nematodes under in vivo conditions. Significant anthelmintic effects of CAE and CEE on live adult Haemonchus contortus worms (P < 0.005) were observed in terms of the paralysis and/or death of the worms at different hours post-treatment (PT), however, CEE were more efficacious than CAE. The oral administration of the extracts in sheep was associated with significant reduction in faecal egg output by the GI nematodes. The CEE was as effective as the reference drug-albendazole and demonstrated faecal egg count reduction (FECR) of 90.46% in sheep at 2.0 g kg(-1) body weight on day 15 PT followed by 82.85% FECR at 1.0 g kg(-1) bw on day 15 PT. The CAE showed less activity and resulted in maximum of 80.49% FECR at 2.0 g kg(-1)bw. Dosage had a significant (P < 0.05) influence on the anthelmintic efficacy of A. absinthium. The better activity of CEE can be attributed to the greater concentration of alcohol soluble active anthelmintic principle/s and a more rapid transcuticular absorption of the CEE into the body of the worms when compared with the CAE. The results of the present study suggest that A. absinthium extracts are a promising alternative to the commercially available Anthelmintics for the treatment of GI nematodes of sheep.

Frederick A Partridge - One of the best experts on this subject based on the ideXlab platform.

  • an automated high throughput system for phenotypic screening of chemical libraries on c elegans and parasitic nematodes
    International Journal for Parasitology-Drugs and Drug Resistance, 2018
    Co-Authors: Frederick A Partridge, Anwen E Brown, Steven D Buckingham, Nicky J Willis, Graham Michael Wynne, Ruth Forman, Jacqueline B Matthews, Kathryn J. Else, Alison A. Morrison, Angela J Russell
    Abstract:

    Parasitic nematodes infect hundreds of millions of people and farmed livestock. Further, plant parasitic nematodes result in major crop damage. The pipeline of therapeutic compounds is limited and parasite resistance to the existing anthelmintic compounds is a global threat. We have developed an INVertebrate Automated Phenotyping Platform (INVAPP) for high-throughput, plate-based chemical screening, and an algorithm (Paragon) which allows screening for compounds that have an effect on motility and development of parasitic worms. We have validated its utility by determining the efficacy of a panel of known Anthelmintics against model and parasitic nematodes: Caenorhabditis elegans, Haemonchus contortus, Teladorsagia circumcincta, and Trichuris muris. We then applied the system to screen the Pathogen Box chemical library in a blinded fashion and identified compounds already known to have anthelmintic or anti-parasitic activity, including tolfenpyrad, auranofin, and mebendazole; and 14 compounds previously undescribed as Anthelmintics, including benzoxaborole and isoxazole chemotypes. This system offers an effective, high-throughput system for the discovery of novel Anthelmintics.

  • An automated high-throughput system for phenotypic screening of chemical libraries on C. elegans and parasitic nematodes
    Elsevier, 2018
    Co-Authors: Frederick A Partridge, Anwen E Brown, Steven D Buckingham, Nicky J Willis, Graham Michael Wynne, Ruth Forman, Jacqueline B Matthews, Kathryn J. Else, Alison A. Morrison, Angela J Russell
    Abstract:

    Parasitic nematodes infect hundreds of millions of people and farmed livestock. Further, plant parasitic nematodes result in major crop damage. The pipeline of therapeutic compounds is limited and parasite resistance to the existing anthelmintic compounds is a global threat. We have developed an INVertebrate Automated Phenotyping Platform (INVAPP) for high-throughput, plate-based chemical screening, and an algorithm (Paragon) which allows screening for compounds that have an effect on motility and development of parasitic worms. We have validated its utility by determining the efficacy of a panel of known Anthelmintics against model and parasitic nematodes: Caenorhabditis elegans, Haemonchus contortus, Teladorsagia circumcincta, and Trichuris muris. We then applied the system to screen the Pathogen Box chemical library in a blinded fashion and identified compounds already known to have anthelmintic or anti-parasitic activity, including tolfenpyrad, auranofin, and mebendazole; and 14 compounds previously undescribed as Anthelmintics, including benzoxaborole and isoxazole chemotypes. This system offers an effective, high-throughput system for the discovery of novel Anthelmintics. Keywords: Parasitic nematodes, C. elegans, Chemical library screening, Automated phenotyping, Anthelmintic, Benzoxaborol

  • an automated high throughput system for phenotypic screening of chemical libraries on c elegans and parasitic nematodes
    bioRxiv, 2017
    Co-Authors: Frederick A Partridge, Anwen E Brown, Steven D Buckingham, Nicky J Willis, Graham Michael Wynne, Ruth Forman, Jacqueline B Matthews, Kathryn J. Else, Alison A. Morrison, Angela J Russell
    Abstract:

    Parasitic nematodes infect hundreds of millions of people and farmed livestock. Further, plant parasitic nematodes result in major crop damage. The pipeline of therapeutic compounds is limited and parasite resistance to the existing anthelmintic compounds is a global threat. We have developed an INVertebrate Automated Phenotyping Platform (INVAPP) for high-throughput, plate-based chemical screening, and an algorithm (Paragon) which allows screening for compounds that have an effect on motility and development of parasitic worms. We have validated its utility by determining the efficacy of a panel of known Anthelmintics against model and parasitic nematodes: Caenorhabditis elegans, Haemonchus contortus, Teladorsagia circumcincta, and Trichuris muris. We then applied the system to screen the Pathogen Box chemical library in a blinded fashion and identified known Anthelmintics, including tolfenpyrad, auranofin, and mebendazole and 14 compounds previously undescribed as Anthelmintics, including benzoxaborole and isoxazole chemotypes. This system offers an effective, high-throughput system for the discovery of novel Anthelmintics.