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Sample records for managing anthelmintic resistant

  1. Anthelmintic resistance.

    PubMed

    Waller, P J

    1997-11-01

    simple commercial fact that by far the greatest anthelmintic sales are associated with the cattle industry. However, this market is specific and sectoral, with by far the greatest sales in North America and Western Europe, where the prevalence of resistance is likely to be low and remain so, more-or-less indefinitely. So the chances of the above scenario occurring must be considered low. Remarkable developments have recently occurred in non-chemotherapeutic parasite control options, for example worm vaccines, host selection and biological control. Also, there seems to be greater acceptance of various grazing management practices designed to reduce the frequency of anthelmintic treatment. However, they collectively cannot be expected to offer immediate salvation to farmers now faced with chemotherapeutic failure to control nematode parasites in their flocks. The future for these farmers must be considered bleak, because compounded with these problems are the poor commodity prices for sheep and goat meat and fibre, resulting in relentless reductions in funding for research to support these industries. Perhaps the major social issues associated with re-structuring and possibly abandonment of sheep and goat farming in affected areas may precipitate action? As veterinary parasitologists, who in general have an interest and expertise in parasite control, we must promote the importance of the problem of anthelmintic resistance and ways to tackle it.

  2. Managing anthelmintic resistance: is it feasible in New Zealand to delay the emergence of resistance to a new anthelmintic class?

    PubMed

    Leathwick, D M; Hosking, B C; Bisset, S A; McKay, C H

    2009-08-01

    The recent registration in New Zealand of the first new class of broad-spectrum anthelmintic, for use against nematode parasites of ruminants, in nearly three decades has raised the possibility that parasite management practices could be improved to minimise the emergence of resistance to the new drug. A review of knowledge pertaining to the selection of anthelmintic resistance in nematode parasites of sheep highlights a number of management practices which could be altered to achieve this. A number of previously common practices such as whole-flock treatment of adult ewes around lambing, and treatment of lambs as they are moved onto pastures with low parasite contamination have been clearly identified as high risk for selecting resistant parasites. Once high-risk practices have been identified steps can be taken to either eliminate their use or mitigate the associated risk. Much of the focus on the management of resistance around the world is on the retention of susceptible genotypes in refugia. While approaches to retaining unselected parasites are likely to vary around the world, empirical studies indicate that the practice is likely to be effective at slowing the development of resistance. The challenge for farmers and advisors will be to strike a balance between retaining sufficient susceptible parasites to usefully delay the development of resistance while not unduly compromising animal performance and farm profitability. The merits of combining different classes of anthelmintic in order to slow the development of resistance remains somewhat contentious in some countries. However, the attributes of oral anthelmintics are such that they seem likely to meet most, if not all, of the criteria for combinations to be highly effective at slowing the build-up of resistance in nematode parasites. It is evident that considerable progress has been made in understanding the factors involved in selecting anthelmintic-resistant nematodes since the last broad

  3. Evidence for reversion towards anthelmintic susceptibility in Teladorsagia circumcincta in response to resistance management programmes.

    PubMed

    Leathwick, Dave M; Ganesh, Siva; Waghorn, Tania S

    2015-04-01

    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

  4. Evidence for reversion towards anthelmintic susceptibility in Teladorsagia circumcincta in response to resistance management programmes

    PubMed Central

    Leathwick, Dave M.; Ganesh, Siva; Waghorn, Tania S.

    2015-01-01

    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

  5. The management of anthelmintic resistance in grazing ruminants in Australasia--strategies and experiences.

    PubMed

    Leathwick, D M; Besier, R B

    2014-07-30

    In many countries the presence of anthelmintic resistance in nematodes of small ruminants, and in some cases also in those infecting cattle and horses, has become the status quo rather than the exception. It is clear that consideration of anthelmintic resistance, and its management, should be an integral component of anthelmintic use regardless of country or host species. Many years of research into understanding the development and management of anthelmintic resistance in nematodes of small ruminants has resulted in an array of strategies for minimising selection for resistance and for dealing with it once it has developed. Importantly, many of these strategies are now supported by empirical science and some have been assessed and evaluated on commercial farms. In sheep the cost of resistance has been measured at about 10% of the value of the lamb at sale which means that losses due to undetected resistance far outweigh the cost of testing anthelmintic efficacy. Despite this many farmers still do not test for anthelmintic resistance on their farm. Many resistance management strategies have been developed and some of these have been tailored for specific environments and/or nematode species. However, in general, most strategies can be categorised as either; identify and mitigate high risk management practices, maintain an anthelmintic-susceptible population in refugia, choose the optimal anthelmintic (combinations and formulations), or prevent the introduction of resistant nematodes. Experiences with sheep farmers in both New Zealand and Australia indicate that acceptance and implementation of resistance management practices is relatively easy as long as the need to do so is clear and the recommended practices meet the farmer's criteria for practicality. A major difference between Australasia and many other countries is the availability and widespread acceptance of combination anthelmintics as a resistance management tool. The current situation in cattle and horses

  6. Managing anthelmintic resistance in Parascaris spp.: A modelling exercise.

    PubMed

    Leathwick, Dave M; Sauermann, Christian W; Geurden, Thomas; Nielsen, Martin K

    2017-06-15

    A previously described model for the dynamics of the parasitic stages of Parascaris spp. was modified to include eggs outside the host and the genetics of anthelmintic resistance before being used to address questions regarding the development of resistance. Three broad questions were addressed; i) How sustainable is the current common practice of treating foals monthly for their first year of life (i.e. 12 treatments/year)? ii) Does the timing of treatments have an effect on resistance development? (i.e. do certain treatments select for resistance more strongly than others?), and iii) How sustainable is the currently recommended strategy of targeting ascarid infections in foals with two treatments applied during the first five months of life? A range of variations within these broad questions were considered, such as the value in rotational deworming, whether larvicidal treatments are more selective for resistance, and whether combination anthelmintics should be introduced. Twelve anthelmintic treatments at monthly intervals resulted in the development of resistance to all the anthelmintics used, regardless of how they were used, indicating that such intensive treatment frequency is unlikely to be sustainable. The timing of a single annual treatment influenced resistance development with treatments at 3 and 4 months of age being more selective than treatments at other times. Treatments administered to foals older than 6 months of age did not select for resistance within the timeframe of these simulations. Treatments with activity against migrating third stage larvae (ivermectin and a programme of 5 daily treatments with fenbendazole) were more selective for resistance than those which only killed worms in the intestine. Restricting the number of treatments to young foals to two, administered at 2 and 5 months of age slowed the development of resistance by allowing a small contribution from susceptible genotype worms to subsequent generations. If the interval

  7. Recent developments in the management of anthelmintic resistance in small ruminants - an Australasian perspective.

    PubMed

    Sutherland, I A

    2015-07-01

    There have been a number of significant advances in recent years to the theory and practice of managing anthelmintic resistance in sheep in Australasia. The general principles of resistance management are, firstly identification and mitigation of high-risk practices, secondly using effective anthelmintics, and thirdly maintaining a refuge of unselected parasites. The first of these principles has been updated recently with the findings from a series of farm-based trials in New Zealand, in which the economic benefits of both short- and long-acting anthelmintic treatments in ewes pre-lambing were found to be inconsistent and not always positive. There have also been significant changes to the second principle, particularly given the introduction of new active families onto the market. Evidence continues to favour the use of combination products to maximise efficacy and delay the onset of treatment-failure. Many farmers have readily accepted the effectiveness of maintaining a refuge of unselected parasites; the challenge for researchers and advisers is now to improve adoption of properly designed and implemented resistance management programmes. A recently completed education programme in New Zealand has demonstrated that when this is achieved, then anthelmintic resistance can be controlled, and in many cases reduced in severity.

  8. Anthelmintics Resistance; How to Overcome it?

    PubMed Central

    Shalaby, Hatem A.

    2013-01-01

    Many parasitic helminthes of veterinary importance have genetic features that favor development of anthelmintic resistance, this becoming a major worldwide constrain in livestock production. The development of anthelmintic resistance poses a large threat to future production and welfare of grazing animals. Development of variable degrees of resistance among different species of gastrointestinal nematodes has been reported for all the major groups of anthelmintic drugs. It has been observed that frequent usage of the same group of anthelmintic; use of anthelmintics in sub-optimal doses, prophylactic mass treatment of domestic animals and frequent and continuous use of a single drug have contributed to the widespread development of anthelmintic resistance in helminthes. The degree and extent of this problem especially with respect to multidrug resistance in nematode populations is likely to increase. Maintaining parasites in refugia and not exposed to anthelmintics, seems to be a key point in controlling and delaying the development of resistance, because the susceptible genes are preserved. Targeted selective treatments attract the interest of scientists towards this direction. Additionally, adoption of strict quarantine measures and a combination drug strategy are two important methods of preventing of anthelmintic resistance. Experience from the development of anthelmintic resistance suggests that modern control schemes should not rely on sole use of anthelmintics, but employ other, more complex and sustainable recipes, including parasite resistant breeds, nutrition, pasture management, nematode-trapping fungi, antiparasitic vaccines and botanical dewormers. Most of them reduce reliance on the use of chemicals and are environmental friendly. Finally, if new anthelmintic products are released, an important question will be raised about how they should be used. It is suggested that slowing the development of resistance to a new class are likely to be gained by

  9. Managing anthelmintic resistance--parasite fitness, drug use strategy and the potential for reversion towards susceptibility.

    PubMed

    Leathwick, Dave M

    2013-11-15

    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

  10. Anthelmintic resistance: markers for resistance, or susceptibility?

    PubMed Central

    BEECH, R. N.; SKUCE, P.; BARTLEY, D. J.; MARTIN, R. J.; PRICHARD, R. K.; GILLEARD, J. S.

    2010-01-01

    SUMMARY The Consortium for Anthelmintic Resistance and Susceptibility (CARS) brings together researchers worldwide, with a focus of advancing knowledge of resistance and providing information on detection methods and treatment strategies. Advances in this field suggest mechanisms and features of resistance that are shared among different classes of anthelmintic. Benzimidazole resistance is characterized by specific amino acid substitutions in beta-tubulin. If present, these substitutions increase in frequency upon drug treatment and lead to treatment failure. In the laboratory, sequence substitutions in ion-channels can contribute to macrocyclic lactone resistance, but there is little evidence that they are significant in the field. Changes in gene expression are associated with resistance to several different classes of anthelmintic. Increased P-glycoprotein expression may prevent drug access to its site of action. Decreased expression of ion-channel subunits and the loss of specific receptors may remove the drug target. Tools for the identification and genetic analysis of parasitic nematodes and a new online database will help to coordinate research efforts in this area. Resistance may result from a loss of sensitivity as well as the appearance of resistance. A focus on the presence of anthelmintic susceptibility may be as important as the detection of resistance. PMID:20825689

  11. Managing anthelmintic resistance-Variability in the dose of drug reaching the target worms influences selection for resistance?

    PubMed

    Leathwick, Dave M; Luo, Dongwen

    2017-08-30

    The concentration profile of anthelmintic reaching the target worms in the host can vary between animals even when administered doses are tailored to individual liveweight at the manufacturer's recommended rate. Factors contributing to variation in drug concentration include weather, breed of animal, formulation and the route by which drugs are administered. The implications of this variability for the development of anthelmintic resistance was investigated using Monte-Carlo simulation. A model framework was established where 100 animals each received a single drug treatment. The 'dose' of drug allocated to each animal (i.e. the concentration-time profile of drug reaching the target worms) was sampled at random from a distribution of doses with mean m and standard deviation s. For each animal the dose of drug was used in conjunction with pre-determined dose-response relationships, representing single and poly-genetic inheritance, to calculate efficacy against susceptible and resistant genotypes. These data were then used to calculate the overall change in resistance gene frequency for the worm population as a result of the treatment. Values for m and s were varied to reflect differences in both mean dose and the variability in dose, and for each combination of these 100,000 simulations were run. The resistance gene frequency in the population after treatment increased as m decreased and as s increased. This occurred for both single and poly-gene models and for different levels of dominance (survival under treatment) of the heterozygote genotype(s). The results indicate that factors which result in lower and/or more variable concentrations of active reaching the target worms are more likely to select for resistance. The potential of different routes of anthelmintic administration to play a role in the development of anthelmintic resistance is discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. F200Y polymorphism of the β-tubulin isotype 1 gene in Haemonchus contortus and sheep flock management practices related to anthelmintic resistance in eastern Amazon.

    PubMed

    Chagas, Alexandre Moura; Sampaio Junior, Francisco Dantas; Pacheco, Adlilton; da Cunha, Amanda Batista; Cruz, Juliana Dos Santos; Scofield, Alessandra; Góes-Cavalcante, Gustavo

    2016-08-15

    The objective of the present study was to determine the frequency of the F200Y polymorphism in the β-tubulin isotype 1 gene of Haemonchus contortus from various sheep flocks in eastern Amazon, and to identify management practices that may favor the emergence of resistance to anthelmintic drugs in the same area. In total, 305 specimens of H. contortus were collected from sheep at 12 farms located in the state of Pará. An allele-specific PCR was performed to detect the F200Y polymorphism, and questionnaires were used to obtain information about the farms and flocks. All genotypes were detected as follows: 31% of the parasites were RR, 37% of the parasites were SR, and 32% were SS. The completed questionnaires revealed that all farms employed semi-intensive farming systems, performed suppressive anthelmintic treatment, and based their choice of drug on cost and availability rather than on any knowledge regarding drugs that remained effective on their property. It can thus be concluded that the SNP in codon 200 of the β-tubulin isotype 1 gene is present in the H. contortus populations from eastern Amazon, and that a series of management practices that favor the emergence of anthelmintic resistance are employed on these farms.

  13. Anthelmintics: From discovery to resistance II (San Diego, 2016).

    PubMed

    Martin, Richard J; Wolstenholme, Adrian J; Caffrey, Conor R

    2016-12-01

    The second scientific meeting in the series: "Anthelmintics: From Discovery to Resistance" was held in San Diego in February, 2016. The focus topics of the meeting, related to anthelmintic discovery and resistance, were novel technologies, bioinformatics, commercial interests, anthelmintic modes of action and anthelmintic resistance. Basic scientific, human and veterinary interests were addressed in oral and poster presentations. The delegates were from universities and industries in the US, Europe, Australia and New Zealand. The papers were a great representation of the field, and included the use of C. elegans for lead discovery, mechanisms of anthelmintic resistance, nematode neuropeptides, proteases, B. thuringiensis crystal protein, nicotinic receptors, emodepside, benzimidazoles, P-glycoproteins, natural products, microfluidic techniques and bioinformatics approaches. The NIH also presented NIAID-specific parasite genomic priorities and initiatives. From these papers we introduce below selected papers with a focus on anthelmintic drug screening and development. Copyright © 2016. Published by Elsevier Ltd.

  14. Gastrointestinal nematodes and anthelmintic resistance in Danish goat herds.

    PubMed

    Holm, Signe A; Sörensen, Camilla R L; Thamsborg, Stig M; Enemark, Heidi L

    2014-01-01

    The prevalence of gastrointestinal parasites in Danish goats and the presence of anthelmintic resistance (AR) in 10 selected herds were investigated during April-September 2012. All Danish herds (n = 137) with 10 or more adult goats were invited to participate, and of these 27 herds met the inclusion criterion of more than 10 young kids never treated with anthelmintics. Questionnaire data on management were collected, and faecal samples from 252 kids were analysed by the McMaster technique. From all herds with a mean faecal egg count (FEC) above 300 eggs per g of faeces, pooled samples were stained with peanut agglutinin (PNA) for specific detection of Haemonchus contortus. Strongyle eggs were detected with an individual prevalence of 69%, including Nematodirus battus (3.6%) and other Nematodirus species (15.0%). Eimeria spp. were observed in 99.6% of the kids. H. contortus was found in 11 of 12 (92%) tested herds. Anthelmintics were used in 89% of the herds with mean treatment frequencies of 0.96 and 0.89 treatments per year for kids and adults, respectively. In 2011, new animals were introduced into 44% of the herds of which 25% practised quarantine anthelmintic treatments. In 10 herds the presence of AR was analysed by egg hatch assay and FEC reduction tests using ivermectin (0.3 mg/kg) or fenbendazole (10.0 mg/kg). AR against both fenbendazole and ivermectin was detected in seven herds; AR against fenbendazole in one herd, and AR against ivermectin in another herd. In conclusion, resistance to the most commonly used anthelmintics is widespread in larger goat herds throughout Denmark.

  15. Gastrointestinal nematodes and anthelmintic resistance in Danish goat herds☆

    PubMed Central

    Holm, Signe A.; Sörensen, Camilla R. L.; Thamsborg, Stig M.; Enemark, Heidi L.

    2014-01-01

    The prevalence of gastrointestinal parasites in Danish goats and the presence of anthelmintic resistance (AR) in 10 selected herds were investigated during April–September 2012. All Danish herds (n = 137) with 10 or more adult goats were invited to participate, and of these 27 herds met the inclusion criterion of more than 10 young kids never treated with anthelmintics. Questionnaire data on management were collected, and faecal samples from 252 kids were analysed by the McMaster technique. From all herds with a mean faecal egg count (FEC) above 300 eggs per g of faeces, pooled samples were stained with peanut agglutinin (PNA) for specific detection of Haemonchus contortus. Strongyle eggs were detected with an individual prevalence of 69%, including Nematodirus battus (3.6%) and other Nematodirus species (15.0%). Eimeria spp. were observed in 99.6% of the kids. H. contortus was found in 11 of 12 (92%) tested herds. Anthelmintics were used in 89% of the herds with mean treatment frequencies of 0.96 and 0.89 treatments per year for kids and adults, respectively. In 2011, new animals were introduced into 44% of the herds of which 25% practised quarantine anthelmintic treatments. In 10 herds the presence of AR was analysed by egg hatch assay and FEC reduction tests using ivermectin (0.3 mg/kg) or fenbendazole (10.0 mg/kg). AR against both fenbendazole and ivermectin was detected in seven herds; AR against fenbendazole in one herd, and AR against ivermectin in another herd. In conclusion, resistance to the most commonly used anthelmintics is widespread in larger goat herds throughout Denmark. PMID:25076056

  16. P-glycoproteins and other multidrug resistance transporters in the pharmacology of anthelmintics: Prospects for reversing transport-dependent anthelmintic resistance

    PubMed Central

    Lespine, Anne; Ménez, Cécile; Bourguinat, Catherine; Prichard, Roger K.

    2011-01-01

    Parasitic helminths cause significant disease in animals and humans. In the absence of alternative treatments, anthelmintics remain the principal agents for their control. Resistance extends to the most important class of anthelmintics, the macrocyclic lactone endectocides (MLs), such as ivermectin, and presents serious problems for the livestock industries and threatens to severely limit current parasite control strategies in humans. Understanding drug resistance is important for optimizing and monitoring control, and reducing further selection for resistance. Multidrug resistance (MDR) ABC transporters have been implicated in ML resistance and contribute to resistance to a number of other anthelmintics. MDR transporters, such as P-glycoproteins, are essential for many cellular processes that require the transport of substrates across cell membranes. Being overexpressed in response to chemotherapy in tumour cells and to ML-based treatment in nematodes, they lead to therapy failure by decreasing drug concentration at the target. Several anthelmintics are inhibitors of these efflux pumps and appropriate combinations can result in higher treatment efficacy against parasites and reversal of resistance. However, this needs to be balanced against possible increased toxicity to the host, or the components of the combination selecting on the same genes involved in the resistance. Increased efficacy could result from modifying anthelmintic pharmacokinetics in the host or by blocking parasite transporters involved in resistance. Combination of anthelmintics can be beneficial for delaying selection for resistance. However, it should be based on knowledge of resistance mechanisms and not simply on mode of action classes, and is best started before resistance has been selected to any member of the combination. Increasing knowledge of the MDR transporters involved in anthelmintic resistance in helminths will play an important role in allowing for the identification of markers

  17. F200Y polymorphism in the β-tubulin gene in field isolates of Haemonchus contortus and risk factors of sheep flock management practices related to anthelmintic resistance.

    PubMed

    Niciura, Simone Cristina Méo; Veríssimo, Cecília José; Gromboni, Juliana Gracielle Gonzaga; Rocha, Marina Ibelli Pereira; de Mello, Suelen Scarpa; Barbosa, Cristina Maria Pacheco; Chiebao, Daniela Pontes; Cardoso, Daniel; Silva, Giane Serafim; Otsuk, Ivani Pozar; Pereira, José Roberto; Ambrosio, Luis Alberto; Nardon, Romeu Fernandes; Ueno, Tatiana Evelyn Hayama; Molento, Marcelo Beltrão

    2012-12-21

    Haemonchus contortus is the most prevalent and pathogenic nematode of sheep in tropical areas. The objectives of this study were to assess the frequency of the F200Y polymorphism on the β-tubulin gene in third-stage larvae of H. contortus from 33 sheep flocks in São Paulo state, Brazil, and to associate this frequency to risk factors based on farm management practices. The resistance allele frequency varied from 9 to 74%, and the resistance genotype frequency varied from 0 to 66.7%. Resistance genotype frequencies higher than 40% were associated with multiple risk factors - new sheep farming enterprises, the absence of farm records, the use of Dorper and Suffolk breeds, rotational grazing, the lack of wetlands on farms, pasture sharing with cattle or horses, frequent incorporation of animals into the flock, semi-intensive farming systems, whole-flock treatment, failure to use the FAMACHA method, lack of the dose-and-move practice, anthelmintic rotation after each application, visual estimation of animal weight for treatment, and lack of drug combination use. It can be concluded that genotyping the F200Y polymorphism can be used to monitor the resistance in sheep flocks and the knowledge of management strategies at the farm level is important to identify drug resistance related factors. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Anthelmintic resistance of nematode parasites of small ruminants in eastern Ethiopia: exploitation of refugia to restore anthelmintic efficacy.

    PubMed

    Sissay, Menkir M; Asefa, Asmare; Uggla, Arvid; Waller, Peter J

    2006-02-18

    Faecal egg count reduction tests (FECRT) were conducted in May 2003 to determine the efficacy of anthelmintics used for treatment against nematode parasites in separately managed sheep and goat flocks at Alemaya University in eastern Ethiopia. These tests revealed high levels of anthelmintic resistance to albendazole, tetramisole, the combination of these two drugs, and to ivermectin in the goat flock (predominantly infected by Haemonchus contortus and Trichostrongylus spp.), whereas all drugs were highly efficacious in the sheep flock. A second FECRT confirmed these observations. Following this, a new management system was implemented on the goat flock for a period of 9 months (January-September 2004) in an attempt to restore the anthelmintic efficacy. This involved a combination of measures: eliminating the existing parasite infections in the goats, exclusion from the traditional goat pastures, and introducing communal grazing of the goats with the university sheep flock and livestock owned by neighbouring small-holder farmers. A second series of FECRTs (Tests 3 and 4) conducted 7 months after this change in management, showed high levels of efficacy to all three drugs (albendazole, tetramisole and ivermectin) in the goat flock. This is the first field study to demonstrate that anthelmintic efficacy in the control of nematode parasites of small ruminants can be restored by exploiting refugia.

  19. An inconvenient truth: global worming and anthelmintic resistance.

    PubMed

    Kaplan, Ray M; Vidyashankar, Anand N

    2012-05-04

    Over the past 10-15 years, we have witnessed a rapid increase in both the prevalence and magnitude of anthelmintic resistance, and this increase appears to be a worldwide phenomenon. Reports of anthelmintic resistance to multiple drugs in individual parasite species, and in multiple parasite species across virtually all livestock hosts, are increasingly common. In addition, since the introduction of ivermectin in 1981, no novel anthelmintic classes were developed and introduced for use in livestock until recently with the launch of monepantel in New Zealand. Thus, livestock producers are often left with few options for effective treatment against many important parasite species. While new anthelmintic classes with novel mechanisms of action could potentially solve this problem, new drugs are extremely expensive to develop, and can be expected to be more expensive than older drugs. Thus, it seems clear that the "Global Worming" approach that has taken hold over the past 40-50 years must change, and livestock producers must develop a new vision for parasite control and sustainability of production. Furthermore, parasitologists must improve methods for study design and data analysis that are used for diagnosing anthelmintic resistance, especially for the fecal egg count reduction test (FECRT). Currently, standards for diagnosis of anthelmintic resistance using FECRT exist only for sheep. Lack of standards in horses and cattle and arbitrarily defined cutoffs for defining resistance, combined with inadequate analysis of the data, mean that errors in assigning resistance status are common. Similarly, the lack of standards makes it difficult to compare data among different studies. This problem needs to be addressed, because as new drugs are introduced now and in the future, the lack of alternative treatments will make early and accurate diagnosis of anthelmintic resistance increasingly important.

  20. [Resistance to anthelmintics in nematodes in sheep and goats].

    PubMed

    Praslicka, J; Corba, J

    1995-08-01

    The article offers a brief view on the most important theoretical knowledge of resistance of gastrointestinal nematodes to anthelmintic drugs in sheep and goats. Besides the definition and basic terms, factors of development and occurrence of resistance on farm are analyzed. Furthermore, methods for detection of resistant nematodes as well as complex of recommended preventive measures are given.

  1. Multiple anthelmintic resistance on a goat farm in Hawassa (southern Ethiopia).

    PubMed

    Kumsa, Bersissa; Abebe, Girma

    2009-04-01

    A study was conducted to determine the presence of anthelmintic resistance on Hawassa University goat farm in southern Ethiopia. The 180 goats were stratified by age and sex and randomly assigned to treatment groups (albendazole, tetramisole and ivermectin and untreated control). Each treatment group included 15 goats and treatments were administered according to weight of each goat with 7.5 mg/kg bw albendazole, 22.5 mg/kg bw tetramisole and 0.2 mg/kg bw ivermectin dose rates recommended by scientists. Faecal samples were collected on day 0 before treatment, and again on day 12 post treatment. Efficacy of all the drugs was assessed on day 12 post treatment by faecal egg count reduction test (FECRT). Multiple anthelmintic resistance in Haemonchus spp. against albendazole, tetramisole and ivermectin was recorded in all age categories of the goats. Likewise, Trichostrongylus/Teladorsagia spp. showed resistance against ivermectin. Coprocultures from all pre- and post-treatments revealed the predominance of Haemonchus spp. Resistance against anthelmintics is attributed to the high frequency of treatment and low dosage of treatment practices on the farm. Large scale studies, however, are needed to assess the current status of anthelmintic resistance against the most commonly used anthelmintics in different agroecology, species of animals and management systems in Ethiopia.

  2. Anthelmintic resistance in a herd of alpacas (Vicugna pacos)

    PubMed Central

    Galvan, Noe; Middleton, John R.; Nagy, Dusty W.; Schultz, Loren G.; Schaeffer, Josh W.

    2012-01-01

    A herd of alpacas was examined because of a history of severe endoparasitism, anemia, hypoproteinemia, and weight loss. Resistance of gastrointestinal nematodes to albendazole, fenbendazole, and doramectin was documented. This report suggests that anthelmintic resistance may be an emerging problem in South American camelids in North America. PMID:23729829

  3. First report of anthelmintic resistance in Haemonchus contortus in alpacas in Australia.

    PubMed

    Jabbar, Abdul; Campbell, Angus J D; Charles, Jennifer A; Gasser, Robin B

    2013-08-22

    Parasitic nematodes can cause substantial clinical and subclinical problems in alpacas and anthelmintics are regularly used to control parasitic nematodes in alpacas. Although anthelmintic resistance has been reported in ruminants worldwide, very little is known about anthelmintic resistance in alpacas. The present study was carried out to confirm a suspected case of anthelmintic resistance in Haemonchus contortus in alpacas in Australia. Post mortem examination of an alpaca was conducted to determine the cause of its death. To confirm a suspected case of macrocyclic lactone (ML) resistance in H. contortus in alpacas, a faecal egg count reduction test (FECRT) was performed using closantel (7.5 mg/kg) and ivermectin (0.2 mg/kg). Nematode species were identified by morphological and molecular methods. Post mortem examination of a 1-year-old female alpaca that had died following a brief period of lethargy, anorexia and recumbency revealed severe anaemia, hypoproteinaemia and gastric parasitism by adult Haemonchus contortus, despite recent abamectin (0.2 mg/kg) treatment. Based on these findings and the exclusive use of MLs in the herd over the preceding six years, ML resistance in parasitic nematodes of alpacas on this farm was suspected. FECRT revealed that the efficacy of closantel was 99% (95% CI 93-100), whereas that of ivermectin was 35% (95% CI 0-78), indicating that the treatment failure was likely due to the presence of ML-resistant nematodes. Larval culture of faecal samples collected following ivermectin treatment consisted of 99% H. contortus and 1% Cooperia oncophora, a result confirmed using a PCR assay. This study provides the first evidence of ML resistance in H. contortus in alpacas in Australia. Based on the extent of anthelmintic resistance in sheep gastrointestinal nematodes in Australia, veterinarians and alpaca owners should be encouraged to implement integrated parasite management strategies to improve nematode control in alpacas.

  4. First report of anthelmintic resistance in Haemonchus contortus in alpacas in Australia

    PubMed Central

    2013-01-01

    Background Parasitic nematodes can cause substantial clinical and subclinical problems in alpacas and anthelmintics are regularly used to control parasitic nematodes in alpacas. Although anthelmintic resistance has been reported in ruminants worldwide, very little is known about anthelmintic resistance in alpacas. The present study was carried out to confirm a suspected case of anthelmintic resistance in Haemonchus contortus in alpacas in Australia. Methods Post mortem examination of an alpaca was conducted to determine the cause of its death. To confirm a suspected case of macrocyclic lactone (ML) resistance in H. contortus in alpacas, a faecal egg count reduction test (FECRT) was performed using closantel (7.5 mg/kg) and ivermectin (0.2 mg/kg). Nematode species were identified by morphological and molecular methods. Results Post mortem examination of a 1-year-old female alpaca that had died following a brief period of lethargy, anorexia and recumbency revealed severe anaemia, hypoproteinaemia and gastric parasitism by adult Haemonchus contortus, despite recent abamectin (0.2 mg/kg) treatment. Based on these findings and the exclusive use of MLs in the herd over the preceding six years, ML resistance in parasitic nematodes of alpacas on this farm was suspected. FECRT revealed that the efficacy of closantel was 99% (95% CI 93-100), whereas that of ivermectin was 35% (95% CI 0-78), indicating that the treatment failure was likely due to the presence of ML-resistant nematodes. Larval culture of faecal samples collected following ivermectin treatment consisted of 99% H. contortus and 1% Cooperia oncophora, a result confirmed using a PCR assay. Conclusions This study provides the first evidence of ML resistance in H. contortus in alpacas in Australia. Based on the extent of anthelmintic resistance in sheep gastrointestinal nematodes in Australia, veterinarians and alpaca owners should be encouraged to implement integrated parasite management strategies to improve

  5. Anthelmintic resistance in equine helminth parasites - a growing issue for horse owners and veterinarians in New Zealand?

    PubMed

    Scott, I; Bishop, R M; Pomroy, W E

    2015-07-01

    There is growing concern that given the high frequency with which anthelmintics are being administered to many horses, anthelmintic resistance amongst equine helminth populations will be an increasing problem, rendering many of the currently available products unusable with little prospect of new products becoming available, at least in the near future. Worldwide, much reliance has been placed on the macrocyclic lactone (ML) group of anthelmintics, but resistance has been reported to these products as well as to the two other major anthelmintic classes used in this species, the benzimidazoles (BZ) and the tetrahydropyrimidines (e.g. pyrantel). In New Zealand, resistance has been reported to the ML and BZ groups, but not yet to pyrantel. As an alternative to interval-based anthelmintic regimens, the highly overdispersed nature of parasite populations in horses can be utilised to decide whether treatment is required, based on whether or not animals exceed a predetermined level of shedding of parasite eggs. If well managed, such a targeted and selective approach can be utilised to eliminate the majority of egg output whilst still providing a refuge for susceptible parasites to persist. Such a system would require that an adequate standard of monitoring be in place and cognisance needs to be taken of parasites or their lifecycle stages that cannot be diagnosed by routine methods. At the same time, using anthelmintics with high levels of efficacy, avoiding practices such as under-dosing, as well as utilising non-chemical means of parasite control when possible, e.g. regular removal of faeces from pasture, should all be considered. Combinations of anthelmintics, specifically of anthelmintics that target the same or a similar spectrum of parasite species, should play an important role in parasite control in horses. As well as providing arguably the highest levels of efficacy, combinations may also slow the rate at which anthelmintic resistance develops.

  6. Evolution of high-level, multiple anthelmintic resistance on a sheep farm in Malaysia.

    PubMed

    Chandrawathani, P; Waller, P J; Adnan, M; Höglund, J

    2003-02-01

    Anthelmintic resistance in nematode parasites of sheep and goats on a government farm in north Malaysia was monitored over a 3-year period (1997-2000). The faecal egg count reduction test (FECRT) was conducted on young sheep at the beginning and end of this period. Changes in management, designed to reduce the selection pressure for the development of anthelmintic resistance, were also implemented during this time. By far the most important parasite problem was Haemonchus contortus. In 1997, this nematode was found to be resistant to levamisole, with suspected resistance to closantel and moxidectin. However, when the FECRT was repeated 3 years later, its resistance status had become much more severe, with resistance to benzimidazole, levamisole and ivermectin, and suspected resistance to moxidectin. This rapid evolution to multiple anthelmintic resistance is a major concern that needs to be arrested. There is an urgent need to evaluate other control strategies that incorporate livestock management, the 'smart' use of drugs and non-chemotherapeutic approaches, such as biological control agents.

  7. Minimising the development of anthelmintic resistance, and optimising the use of the novel anthelmintic monepantel, for the sustainable control of nematode parasites in Australian sheep grazing systems.

    PubMed

    Dobson, R J; Hosking, B C; Besier, R B; Love, S; Larsen, J W A; Rolfe, P F; Bailey, J N

    2011-05-01

    To compare the risk of different treatment scenarios on selecting for anthelmintic resistance on Australian sheep farms. A computer simulation model predicted populations of Trichostrongylus colubriformis, Haemonchus contortus or Teladorsagia (Ostertagia) circumcincta, and the frequency of anthelmintic resistance genes. Nematode populations and the progression of drug resistance for a variety of treatment options and management practices in sheep-rearing areas of Western Australia (WA), Victoria (VIC) and New South Wales (NSW) were simulated. A scoring system was devised to measure the success of each option in delaying resistance to each anthelmintic and in controlling nematode populations. The best option at all sites was combining the new anthelmintic (monepantel) with a triple mixture of benzimidazole, levamisole and abamectin (COM). The next best option was: in NSW, rotation at each treatment between monepantel, moxidectin and COM; in VIC, rotation at each treatment between monepantel and COM; and in WA, rotation at each treatment between monepantel (used in winter) and COM or moxidectin (used in summer-autumn). In WA, rapid selection for resistance occurred as a consequence of summer-autumn treatments; however, if a small percentage of adult stock were left untreated then this selection could be greatly reduced. Despite purposely assuming relatively high resistance to benzimidazole and levamisole, COM was still effective in controlling worms and delaying resistance. Because of cost constraints, it may not be feasible or profitable for producers to always use the combination of all drugs. However, the second- and third-best options still considerably slowed the development of anthelmintic resistance. © 2011 The Authors. Australian Veterinary Journal © 2011 Australian Veterinary Association.

  8. Anthelmintic resistance in cattle nematodes in the US.

    PubMed

    Gasbarre, Louis C

    2014-07-30

    The first documented case of macrocyclic lactone resistance in gastrointestinal (GI) nematodes of cattle was seen in the US approximately 10 years ago. Since that time the increase incidence of anthelmintic resistance has continued at an alarming rate. Currently parasites of the genera Cooperia and/or Haemonchus resistant to generic or brand-name macrocyclic lactones have be demonstrated in more than half of all operations examined. Both of these parasite genera are capable of causing economic losses by decreasing food intake and subsequently animal productivity. Currently, there are no easy and quick means to detect anthelmintic resistant GI nematodes. Definitive identification requires killing of cattle. The most commonly used field detection method is the fecal egg count reduction test (FECRT). This method can be adapted for use as a screening agent for Veterinarians and producers to identify less than desired clearance of the parasites after anthelmintic treatment. Further studies can then define the reasons for persistence of the egg counts. The appearance of anthelmintic resistance is largely due to the development of very effective nematode control programs that have significantly improved the productivity of the US cattle industry, but at the same time has placed a high level of selective pressure on the parasite genome. The challenges ahead include the development of programs that control the anthelmintic resistant nematodes but at the same time result in more sustainable parasite control. The goal is to maintain high levels of productivity but to exert less selective pressures on the parasites. One of the most effective means to slow the development of drug resistance is through the simultaneous use of multiple classes of anthelmintics, each of which has a different mode of action. Reduction of the selective pressure on the parasites can be attained through a more targeted approach to drug treatments where the producer's needs are met by selective

  9. Anthelmintic resistance in gastrointestinal nematodes in goats and evaluation of FAMACHA diagnostic marker in Uganda.

    PubMed

    Nabukenya, Immaculate; Rubaire-Akiiki, Chris; Olila, Deogracious; Muhangi, Denis; Höglund, Johan

    2014-10-15

    Gastrointestinal nematodes (GIN) are a challenge to goat production globally causing reduced growth, morbidity and mortality. We report here results of the first nation-wide anthelmintic resistance (AR) study and validation of assessment of clinical anaemia with FAMACHA eye scores in goats in Uganda. From August to December 2012 the efficacy of albendazole (7.5mg/kg), levamisole (10.5mg/kg) and ivermectin (0.3mg/kg) against strongyle nematodes was tested on 33 goat farms in Soroti, Gulu, Mpigi, Mbarara and Ssembabule districts of Uganda. Altogether 497 goats were subjected to a total of 45 different faecal egg count reduction tests (FECRT), each involving 5-20 goats. On one farm all substances were tested. Faecal and blood samples were collected and FAMACHA eye scores evaluated on the day of treatment and 15 days later. A questionnaire survey was conducted on frequency, type and dose of anthelmintics used, farm size and grazing management system. Examination of infective third stage larvae (L3) from pooled faecal cultures demonstrated Haemonchus to be the predominant genus (>75%). Resistance to at least one anthelmintic group was detected on 61% of the 33 farms and in 49% of the 45 test groups. Prevalence of resistance to ivermectin, levamisole and albendazole was respectively 58%, 52% and 38%. Correlation between pre-treatment packed cell volume determinations and FAMACHA scores (r(498) = -0.89) was significant. Paddock grazing system (Odds ratio 4.9, 95% CI 1.4-17.3) and large farm size of >40 goats (odds ratio 4.4, 95% CI 1.2-16.1) were significant predictors of AR. In all districts, resistance to all three anthelmintics was higher on large-scale goat farms practising mostly paddock grazing. Interestingly, resistance to albendazole, the most commonly used anthelmintic in Uganda, was lower than that to ivermectin and levamisole. We recommend adaptation of FAMACHA to goats to help restrict anthelmintic treatment to heavily infected individuals. This will limit

  10. Anthelmintic Resistance of Strongyle Nematodes to Ivermectin and Fenbendazole on Cart Horses in Gondar, Northwest Ethiopia

    PubMed Central

    Zewdu, Alemu; Dagnachew, Shimelis; Bogale, Basazinew

    2017-01-01

    A study was conducted from November 2015 to April 2016 to determine fenbendazole and ivermectin resistance status of intestinal nematodes of cart horses in Gondar, Northwest Ethiopia. Forty-five strongyle infected animals were used for this study. The animals were randomly allocated into three groups (15 horses per group). Group I was treated with fenbendazole and Group II with ivermectin and Group III was left untreated. Faecal samples were collected from each cart horse before and after treatment. Accordingly, the reduction in the mean fecal egg count at fourteen days of treatment for ivermectin and fenbendazole was 97.25% and 79.4%, respectively. It was significantly different in net egg count between treatment and control groups after treatment. From the study, resistance level was determined for fenbendazole and suspected for ivermectin. In addition, a questionnaire survey was also conducted on 90 selected cart owners to assess their perception on anthelmintics. In the survey, the most available drugs in the study area used by the owners were fenbendazole and ivermectin. Most respondents have no knowledge about drug management techniques. Hence, animal health extension services to create awareness regarding anthelmintic management that plays a key role in reducing the anthelmintic resistance parasites. PMID:28265572

  11. Anthelmintic Resistance of Strongyle Nematodes to Ivermectin and Fenbendazole on Cart Horses in Gondar, Northwest Ethiopia.

    PubMed

    Seyoum, Zewdu; Zewdu, Alemu; Dagnachew, Shimelis; Bogale, Basazinew

    2017-01-01

    A study was conducted from November 2015 to April 2016 to determine fenbendazole and ivermectin resistance status of intestinal nematodes of cart horses in Gondar, Northwest Ethiopia. Forty-five strongyle infected animals were used for this study. The animals were randomly allocated into three groups (15 horses per group). Group I was treated with fenbendazole and Group II with ivermectin and Group III was left untreated. Faecal samples were collected from each cart horse before and after treatment. Accordingly, the reduction in the mean fecal egg count at fourteen days of treatment for ivermectin and fenbendazole was 97.25% and 79.4%, respectively. It was significantly different in net egg count between treatment and control groups after treatment. From the study, resistance level was determined for fenbendazole and suspected for ivermectin. In addition, a questionnaire survey was also conducted on 90 selected cart owners to assess their perception on anthelmintics. In the survey, the most available drugs in the study area used by the owners were fenbendazole and ivermectin. Most respondents have no knowledge about drug management techniques. Hence, animal health extension services to create awareness regarding anthelmintic management that plays a key role in reducing the anthelmintic resistance parasites.

  12. Repurposing Salicylanilide Anthelmintic Drugs to Combat Drug Resistant Staphylococcus aureus

    PubMed Central

    Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Conery, Annie L.; Kim, Wooseong; Jayamani, Elamparithi; Kwon, Bumsup; Ausubel, Frederick M.; Mylonakis, Eleftherios

    2015-01-01

    Staphylococcus aureus is a Gram-positive bacterium that has become the leading cause of hospital acquired infections in the US. Repurposing Food and Drug Administration (FDA) approved drugs for antimicrobial therapy involves lower risks and costs compared to de novo development of novel antimicrobial agents. In this study, we examined the antimicrobial properties of two commercially available anthelmintic drugs. The FDA approved drug niclosamide and the veterinary drug oxyclozanide displayed strong in vivo and in vitro activity against methicillin resistant S. aureus (minimum inhibitory concentration (MIC): 0.125 and 0.5 μg/ml respectively; minimum effective concentration: ≤ 0.78 μg/ml for both drugs). The two drugs were also effective against another Gram-positive bacteria Enterococcus faecium (MIC 0.25 and 2 μg/ml respectively), but not against the Gram-negative species Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter aerogenes. The in vitro antimicrobial activity of niclosamide and oxyclozanide were determined against methicillin, vancomycin, linezolid or daptomycin resistant S. aureus clinical isolates, with MICs at 0.0625-0.5 and 0.125-2 μg/ml for niclosamide and oxyclozanide respectively. A time-kill study demonstrated that niclosamide is bacteriostatic, whereas oxyclozanide is bactericidal. Interestingly, oxyclozanide permeabilized the bacterial membrane but neither of the anthelmintic drugs exhibited demonstrable toxicity to sheep erythrocytes. Oxyclozanide was non-toxic to HepG2 human liver carcinoma cells within the range of its in vitro MICs but niclosamide displayed toxicity even at low concentrations. These data show that the salicylanilide anthelmintic drugs niclosamide and oxyclozanide are suitable candidates for mechanism of action studies and further clinical evaluation for treatment of staphylococcal infections. PMID:25897961

  13. Anthelmintic resistant Haemonchus contortus in a giraffe (Giraffa camelopardalis) in Florida.

    PubMed

    Garretson, Pamela D; Hammond, Elizabeth E; Craig, Thomas M; Holman, Patricia J

    2009-03-01

    A young male giraffe (Giraffa camelopardalis) recently acquired by the Lion Country Safari in Loxahatchee, Florida, was diagnosed and successfully treated for Haemonchus infection while in quarantine. Seven weeks after introduction into a group of resident giraffes, this giraffe presented with diarrhea. Fecal evaluation revealed an extremely high count of 16,700 eggs/g, with larval identification of the parasite as Haemonchus. A larval development assay showed resistance to the three classes of anthelmintics currently used to treat Haemonchus contortus: the benzimidazoles, imidazothiazoles, and macrocyclic lactones. The giraffe was treated with a combination of moxidectin topically and fenbendazole orally, and follow-up fecal examination 2 wk later showed a marked reduction in strongyle-type eggs. However, within 2 mo the giraffe had a packed cell volume of 22% and an eggs per gram count of 11,900. The animal was then treated with moxidectin topically and copper oxide wire particles orally and removed from the contaminated area. Because of the unusual host, molecular analysis of the parasite was employed, which confirmed the nematode as H. contortus. It is likely that the monthly rotational deworming schedule first implemented more than 5 yr earlier contributed to the development of multiple anthelmintic resistance in this H. contortus population. The proper use of anthelmintics and good pasture management are crucial to reducing the parasite burden in captive giraffe.

  14. Microfluidic bioassay to characterize parasitic nematode phenotype and anthelmintic resistance.

    PubMed

    Chen, Baozhen; Deutmeyer, Alex; Carr, John; Robertson, Alan P; Martin, Richard J; Pandey, Santosh

    2011-01-01

    With increasing resistance to anti-parasitic drugs, it has become more important to detect and recognize phenotypes of resistant isolates. Molecular methods of detecting resistant isolates are limited at present. Here, we introduce a microfluidic bioassay to measure phenotype using parameters of nematode locomotion. We illustrate the technique on larvae of an animal parasite Oesophagostomum dentatum. Parameters of sinusoidal motion such as propagation velocity, wavelength, wave amplitude, and oscillation frequency depended on the levamisole-sensitivity of the isolate of parasitic nematode. The levamisole-sensitive isolate (SENS) had a mean wave amplitude of 135 μm, which was larger than 123 μm of the levamisole-resistant isolate (LEVR). SENS had a mean wavelength of 373 μm, which was less than 393 μm of LEVR. The mean propagation velocity of SENS, 149 μm s-1, was similar to LEVR, 143 μm s-1. The propagation velocity of the isolates was inhibited by levamisole in a concentration-dependent manner above 0.5 μm. The EC50 for SENS was 3 μm and the EC50 for LEVR was 10 μm. This microfluidic technology advances present-day nematode migration assays and provides a better quantification and increased drug sensitivity. It is anticipated that the bioassay will facilitate study of resistance to other anthelmintic drugs that affect locomotion.

  15. Microfluidic bioassay to characterize parasitic nematode phenotype and anthelmintic resistance

    PubMed Central

    CHEN, BAOZHEN; DEUTMEYER, ALEX; CARR, JOHN; ROBERTSON, ALAN P.; MARTIN, RICHARD J.; PANDEY, SANTOSH

    2010-01-01

    SUMMARY With increasing resistance to anti-parasitic drugs, it has become more important to detect and recognize phenotypes of resistant isolates. Molecular methods of detecting resistant isolates are limited at present. Here, we introduce a microfluidic bioassay to measure phenotype using parameters of nematode locomotion. We illustrate the technique on larvae of an animal parasite Oesophagostomum dentatum. Parameters of sinusoidal motion such as propagation velocity, wavelength, wave amplitude, and oscillation frequency depended on the levamisole-sensitivity of the isolate of parasitic nematode. The levamisole-sensitive isolate (SENS) had a mean wave amplitude of 135 μm, which was larger than 123 μm of the levamisole-resistant isolate (LEVR). SENS had a mean wavelength of 373 μm, which was less than 393 μm of LEVR. The mean propagation velocity of SENS, 149 μm s−1, was similar to LEVR, 143 μm s−1. The propagation velocity of the isolates was inhibited by levamisole in a concentration-dependent manner above 0.5 μM. The EC50 for SENS was 3 μM and the EC50 for LEVR was 10 μM. This microfluidic technology advances present-day nematode migration assays and provides a better quantification and increased drug sensitivity. It is anticipated that the bioassay will facilitate study of resistance to other anthelmintic drugs that affect locomotion. PMID:20663251

  16. The Role of Xenobiotic-Metabolizing Enzymes in Anthelmintic Deactivation and Resistance in Helminths.

    PubMed

    Matoušková, Petra; Vokřál, Ivan; Lamka, Jiří; Skálová, Lenka

    2016-06-01

    Xenobiotic-metabolizing enzymes (XMEs) modulate the biological activity and behavior of many drugs, including anthelmintics. The effects of anthelmintics can often be abolished by XMEs when the drugs are metabolized to an inefficient compound. XMEs therefore play a significant role in anthelmintic efficacy. Moreover, differences in XMEs between helminths are reflected by differences in anthelmintic metabolism between target species. Taking advantage of the newly sequenced genomes of many helminth species, progress in this field has been remarkable. The present review collects up to date information regarding the most important XMEs (phase I and phase II biotransformation enzymes; efflux transporters) in helminths. The participation of these XMEs in anthelmintic metabolism and their possible roles in drug resistance are evaluated. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. A survey on anthelmintic resistance in nematode parasites of sheep in the Slovak Republic.

    PubMed

    Cernanská, D; Várady, M; Corba, J

    2006-01-15

    The prevalence of anthelmintic resistance on 27 sheep farms in Slovakia was investigated in 2003 and 2004 using the faecal egg count reduction test (FECRT) according to the WAAVP guidelines. Resistance to albendazole was detected on one farm (3.7%) and suspected on two farms (7.4%) out of 27 sheep flocks. Resistance to ivermectin was tested on 26 farms. On six (23.1%) farms, results indicated the presence of ivermectin resistance. Resistance to ivermectin was suspected on eight farms (30.8%). However, it is also possible that generic ivermectin anthelmintics used in survey have a lower efficacy against sheep nematodes.

  18. Anthelmintic resistance on sheep and goat farms in the southeastern United States

    USDA-ARS?s Scientific Manuscript database

    Anthelmintic resistance in gastrointestinal nematodes (GIN) is recognized as a severe problem for small ruminant production worldwide. In the United States, a high prevalence of drug resistance to multiple drug classes was reported in GIN of goats in Georgia, but no studies have examined the prevale...

  19. Assessment of anthelmintic resistance in nematode parasites of sheep and goats owned by smallholder farmers in eastern Ethiopia.

    PubMed

    Sissay, M M; Asefa, A; Uggla, A; Waller, P J

    2006-04-01

    The anthelmintic resistance status was investigated of nematode parasites of sheep and goats owned by smallholder farmers in communities that received breeding stock from a source where a high level of anthelmintic resistance has been reported. The investigation used the faecal egg count reduction technique, whereby suitable animals within each of eight separate communities were pooled to achieve the numbers required to conduct separate tests for both sheep and goats. Anthelmintics tested were albendazole (ABZ), tetramisole (TET), a combination (ABZ + TET) and ivermectin (IVM), at the manufacturers' recommended dose rates. Results showed that there was no evidence of anthelmintic resistance in nematode parasites of either sheep an goats in any community. This indicates that dilution of resistant parasites imported with introduced breeding stock, and the low selection pressure imposed by the smallholder farmers themselves, has prevented anthelmintic resistance from emerging in nematode parasites of small ruminants in these communities.

  20. Gastrointestinal nematode control practices on lowland sheep farms in Ireland with reference to selection for anthelmintic resistance.

    PubMed

    Patten, Thomas; Good, Barbara; Hanrahan, James P; Mulcahy, Grace; de Waal, Theo

    2011-03-31

    Gastrointestinal parasitism is a widely recognised problem in sheep production, particularly for lambs. While anthelmintics have a pivotal role in controlling the effects of parasites, there is a paucity of data on how farmers use anthelmintics. A representative sample of Irish lowland farmers were surveyed regarding their parasite control practices and risk factors that may contribute to the development of anthelmintic resistance. Questionnaires were distributed to 166 lowland Irish sheep producers. The vast majority of respondents treated their sheep with anthelmintics. Lambs were the cohort treated most frequently, the majority of farmers followed a set programme as opposed to treating at sign of disease. A substantial proportion (61%) administered four or more treatments to lambs in a 'normal' year. Departures from best practice in anthelmintic administration that would encourage the development of anthelmintic resistance were observed. In conclusion, in the light of anthelmintic resistance, there is a need for a greater awareness of the principles that underpin the sustainable use of anthelmintics and practices that preserve anthelmintic efficacy should be given a very high priority in the design of helminth control programmes on each farm. To this end, given that veterinary practitioners and agricultural advisors were considered to be the farmer's most popular information resource, the capacity of these professions to communicate information relating to best practice in parasite control should be targeted.

  1. Anthelmintic resistance of intestinal nematodes to ivermectin and pyrantel in Estonian horses.

    PubMed

    Lassen, B; Peltola, S-M

    2015-11-01

    There is evidence of resistance in horses to anthelmintic treatment using ivermectin and pyrantel. However, little information is available about the parasites, treatment practices or anthelmintic resistance in the horse population in Estonia. In the present study, we examined 41 trotting and riding horses aged < 3 years from four stables in Estonia. Faecal samples were collected, and horses were selected for treatment if the nematode egg count per gram faeces exceeded 200. Horses (n= 32) that shed strongyle-type eggs were treated with pyrantel, whereas Parascaris equorum-positive animals received ivermectin. Up to 78% of horses required anthelmintic treatment and the efficiency of the anthelmintics was evaluated using a faecal egg count reduction test. Resistance of P. equorum was observed in 50% of horses treated with ivermectin and of strongyles in 27% of horses treated with pyrantel. Ivermectin treatment resulted in a mean reduction of 100% for strongyle eggs and an 89% reduction in P. equorum, and pyrantel-treated horses exhibited an 88% reduction in strongyle eggs. These results are considered to be the first indication of resistance to pyrantel, but further studies of ivermectin resistance are required. According to questionnaires completed by the owners of horses, resistance might be explained by a lack of evidence-based strategies, a strong preference for using ivermectin and possibly a subjective evaluation of the body weight of horses.

  2. Gastrointestinal nematodes of dairy goats, anthelmintic resistance and practices of parasite control in Northern Italy

    PubMed Central

    2014-01-01

    Background Gastrointestinal nematodes (GINs) are one of the main constraints to ruminant production worldwide. Anthelmintic resistance (AR) has been reported in goats throughout Europe, yet little is known about the AR status in Italy. The aims of the study were: i) determine the frequency of AR in GINs in goat flocks in Northern Italy, Italy, ii) survey goat farmers on the current practices of parasite control, iii) update the species composition of the gastrointestinal helminthofauna. Thirty three flocks were enrolled and 1288 individual fecal samples were collected. Based on the egg per gram (EPG), 15 flocks were selected to evaluate the presence of AR in GINs with the Fecal Egg Count Reduction Test (FECRT). A questionnaire surveyed 110 dairy goat farmers to acquire information about farm management and drenching practices against GINs. Further, the gastrointestinal tracts of 42 goats were analyzed. Results The FECRs indicated that five of the 15 flocks had problems of AR, which was identified in all two of the anthelmintic classes tested. Resistance and suspected resistance was found in 40% of the flocks selected for AR testing that were treated with benzimidazoles while 20% of the flocks treated with eprinomectin had resistant GINs. Teladorsagia/Trichostrongylus L3 were isolated from the post-treatment coprocultures of all flocks with resistance but not from the flock with suspected oxfendazole resistance. Treatments against helminths were performed once annually in 73.63% of the flocks, but 20.00% of farmers declared not regularly treating their goats every year. Annual treatments usually occurred in autumn or winter at dose rate for sheep. Te. circumcincta, H. contortus, Tr. colubriformis, Skrjabinema caprae and Oesophagostomum venulosum were the most abundant and prevalent species of the gastrointestinal tract. Conclusions Strategies to prevent the development of AR should be widely adopted in Northern Italy. Further, farmers and practitioners should be

  3. Gastrointestinal nematodes of dairy goats, anthelmintic resistance and practices of parasite control in Northern Italy.

    PubMed

    Zanzani, Sergio Aurelio; Gazzonis, Alessia Libera; Di Cerbo, Annarita; Varady, Marian; Manfredi, Maria Teresa

    2014-05-19

    Gastrointestinal nematodes (GINs) are one of the main constraints to ruminant production worldwide. Anthelmintic resistance (AR) has been reported in goats throughout Europe, yet little is known about the AR status in Italy. The aims of the study were: i) determine the frequency of AR in GINs in goat flocks in Northern Italy, Italy, ii) survey goat farmers on the current practices of parasite control, iii) update the species composition of the gastrointestinal helminthofauna. Thirty three flocks were enrolled and 1288 individual fecal samples were collected. Based on the egg per gram (EPG), 15 flocks were selected to evaluate the presence of AR in GINs with the Fecal Egg Count Reduction Test (FECRT). A questionnaire surveyed 110 dairy goat farmers to acquire information about farm management and drenching practices against GINs. Further, the gastrointestinal tracts of 42 goats were analyzed. The FECRs indicated that five of the 15 flocks had problems of AR, which was identified in all two of the anthelmintic classes tested. Resistance and suspected resistance was found in 40% of the flocks selected for AR testing that were treated with benzimidazoles while 20% of the flocks treated with eprinomectin had resistant GINs. Teladorsagia/Trichostrongylus L3 were isolated from the post-treatment coprocultures of all flocks with resistance but not from the flock with suspected oxfendazole resistance. Treatments against helminths were performed once annually in 73.63% of the flocks, but 20.00% of farmers declared not regularly treating their goats every year. Annual treatments usually occurred in autumn or winter at dose rate for sheep. Te. circumcincta, H. contortus, Tr. colubriformis, Skrjabinema caprae and Oesophagostomum venulosum were the most abundant and prevalent species of the gastrointestinal tract. Strategies to prevent the development of AR should be widely adopted in Northern Italy. Further, farmers and practitioners should be educated about the importance of

  4. Flow cytometry analysis of drug transport mechanisms in Haemonchus contortus susceptible or resistant to anthelmintics.

    PubMed

    Kerboeuf, D; Chambrier, P; Le Vern, Y; Aycardi, J

    1999-02-01

    The role of membrane drug-transport mechanisms in resistance to anthelmintics was examined using a flow cytometry method. This method was adapted from assays developed for the study of similar mechanisms in tumor cells. Rhodamine 123, a P-glycoprotein transport probe, associated with the reversal agent verapamil gave a significantly higher level of green fluorescence in Haemonchus contortus-resistant eggs as compared with that of susceptible eggs. In the same way, verapamilbodipy, a new fluorescent probe for the detection of multidrug resistance in cells, showed a significantly higher degree of binding to resistant eggs. The results confirm those obtained with biological drug assays using both anthelmintics and verapamil and provide a quantitative and effective methodology for the functional study of multidrug resistance in nematodes.

  5. An in vitro assay utilising parasitic larval Haemonchus contortus to detect resistance to closantel and other anthelmintics.

    PubMed

    Rothwell, J T; Sangster, N C

    1993-08-01

    A new assay for detecting resistance to anthelmintics in vitro is described. The assay uses a simple culture system in which the ability of anthelmintics to kill or inhibit the migration of parasitic third and fourth stage Haemonchus contortus larvae through a 50 microns aperture mesh is assessed. The assay detects 2-10-fold resistance to closantel. Resistance to benzimidazoles, levamisole and ivermectin can also be detected.

  6. Efficacy of commonly used anthelmintics: first report of multiple drug resistance in gastrointestinal nematodes of sheep in Trinidad.

    PubMed

    George, N; Persad, K; Sagam, R; Offiah, V N; Adesiyun, A A; Harewood, W; Lambie, N; Basu, A K

    2011-12-29

    In Trinidad, small ruminant farms are semi-intensively managed under tropical conditions which support the development and survival of the infective stages of the helminths. Local farmers use anthelmintics to control gastrointestinal nematodes frequently. Frequent use of anthelmintics has the potential to select for populations of nematodes resistance to those chemicals. Hence, an attempt was made to study the efficacy of commonly used drugs on gastrointestinal nematodes of sheep. Three farms situated in different counties in Trinidad were selected. Sheep aged 6-15 months and not treated with anthelmintics for a minimum of six months previous and with faecal egg count (FEC)>150 eggs per gram were selected for study. They were allocated into 5 groups, each consisting 10 animals. The Group TA animals were treated once with albendazole (5mg/kg. b.wt.), group TF with fenbendazole (5mg/kg.b.wt.), group TI animals with ivermectin (200 μg/kg b.wt.), group TL with levamisol (7.5mg/kg b.wt.). The group NTC animals were not given any drug and served as control. The number of nematode eggs per gram of faeces from each animal was determined before treatment and at 14 days after treatment. The anthelmintic susceptibility to different drugs was detected by FECRT (in vivo) with EPG recorded at 14 day post-treatment. The data analysis using FECRT revealed that efficacy of albendazole (46-62%), fenbendazole (44-61%) and levamisol (53-81%) were reduced compared to ivermectin (95-97%). An attempt has also been made to find a suitable method for calculation of FECR (%).

  7. First Report of Anthelmintic Resistance in Gastrointestinal Nematodes of Sheep from Costa Rica

    PubMed Central

    Maroto, R.; Jiménez, A. E.; Romero, J. J.; Alvarez, V.; De Oliveira, J. B.; Hernández, J.

    2011-01-01

    As the prevalence and severity of anthelmintic resistance continue to rise, nematode infections in sheep correspondingly reduce the profitability of the sheep industry. In Costa Rica, sheep production systems are increasing in both number and importance. A field trial study was carried out to detect the level of anthelmintic resistance to albendazole and ivermectin in gastrointestinal nematodes (GIN) of sheep from seven farms in Costa Rica. Resistance was determined using the fecal egg count reduction test (FECRT). Three treatment groups were assessed on each farm: control, albendazole, and ivermectin. Haemonchus spp. (71%), Strongyloides sp. (57%), and Trichostrongylus spp. (43%) presented resistance levels to albendazole, whereas Strongyloides sp. (43%), Haemonchus spp. (29%), and Trichostrongylus spp. (29%) were resistant to ivermectin. Haemonchus spp., Strongyloides sp., and Trichostrongylus spp. were the most resistant GIN to both products. This study suggests that frequency of treatment, exclusive chemical control, and visual estimation of animal weight to calculate dosage may contribute to the high levels of anthelmintic resistance that were observed on the farms analyzed herein. PMID:21772962

  8. Anthelmintic Avermectins Kill Mycobacterium tuberculosis, Including Multidrug-Resistant Clinical Strains

    PubMed Central

    Lim, Leah E.; Vilchèze, Catherine; Ng, Carol; Jacobs, William R.; Thompson, Charles J.

    2013-01-01

    Avermectins are a family of macrolides known for their anthelmintic activities and traditionally believed to be inactive against all bacteria. Here we report that members of the family, ivermectin, selamectin, and moxidectin, are bactericidal against mycobacterial species, including multidrug-resistant and extensively drug-resistant clinical strains of Mycobacterium tuberculosis. Avermectins are approved for clinical and veterinary uses and have documented pharmacokinetic and safety profiles. We suggest that avermectins could be repurposed for tuberculosis treatment. PMID:23165468

  9. Risk factors for anthelmintic resistance development in cattle gastrointestinal nematodes in Argentina.

    PubMed

    Suarez, Víctor Humberto; Cristel, Silvina Lujan

    2014-01-01

    Risk factors for anthelmintic resistance (AR) on bovine ranches were studied. Data were derived from a survey made to 50 ranch owners, who had conducted a faecal egg-count-reduction test. The questionnaire contained descriptors of bovine ranch management and nematode control. A case-control design study was undertaken and AR cases were present in 26 herds. Associations between the binary outcome variable (AR versus not AR) and risk factors recorded in the questionnaire were evaluated. Variables associated with the presence of AR at P< 0.15 and/or odds ratio (OR) > 2 were subjected to a multivariable logistic regression model. The main effects contributing to general AR (avermectin AVM and/or benzimidazole) in the final model were total number of annual treatments (OR 7.68; 95% CI 2.4 to 28.3) and use of more than 75% of AVM in the past (OR= 18.6; 95% CI 1.3 to 97.3), whereas for AVM resistance alone were total number of AVM annual treatments (OR= 11.5; 95% CI 2.9 to 45.5) and number of AVM Nov-Jan treatments (OR= 5.8; 95% CI 1.71 to 47.9). The results showed that treatment frequency, date of treatment and frequency of treatment in the past with a single drug were the main risk factors involved in AR development.

  10. A microlarval development assay for the detection of anthelmintic resistance in sheep nematodes.

    PubMed

    Hubert, J; Kerboeuf, D

    1992-05-16

    A microlarval development test for the detection of anthelmintic resistance in nematodes is described. Haemonchus contortus, Teladorsagia circumcincta and Trichostrongylus colubriformis eggs were cultured to third stage larvae in the presence of Earle's balanced salt solution, yeast extract and bacteria in a total volume of 150 microliters. Good dose-response data were obtained with thiabendazole, levamisole, pyrantel tartrate and ivermectin allowing the determination of the 50 per cent lethal concentration and of resistance factors when resistant strains were available. The test was found to be accurate, sensitive, easy to carry out and applicable to the routine detection of resistance.

  11. Prevalence of anthelmintic resistance in gastrointestinal nematodes of sheep and goats in Norway.

    PubMed

    Domke, Atle V Meling; Chartier, Christophe; Gjerde, Bjørn; Höglund, Johan; Leine, Nils; Vatn, Synnøve; Stuen, Snorre

    2012-07-01

    In the period of 2008–2009, the efficacies of the benzimidazole (BZ) albendazole and the macrocyclic lactone (ML) ivermectin against gastrointestinal nematodes (GIN) of small ruminants were evaluated by means of the fecal egg count reduction (FECR) test and by post-treatment identification of surviving third stage (L3) larvae after coproculture. Sheep (n=28) and goat (n=28) flocks from three areas of Norway were randomly selected to assess the prevalence of anthelmintic resistance (AR), whereas only lambs from non-randomly selected sheep flocks (n=32) with a farm management that could select for AR were investigated the second year. Only flocks with a mean excretion of nematode eggs per gram feces (EPG) ≥ 150 at time of treatment were included in the survey. In total, 48 (80%) and 13 (46.4%) of the selected sheep and goat flocks, respectively, fulfilled the inclusion criteria. The proportions of flocks classified as resistant (i.e., FECR <95% and with a lower 95% confidence interval of <90%) for the BZ drug albendazole were 10.5% and 31.0% in the randomly and non-randomly selected sheep flocks, respectively. When restricting the area to Rogaland County, eight flocks out of ten (80%) non-randomly selected sheep flocks showed BZ resistance. The efficacy of ML was 100% in all surveyed sheep and goat flocks. In post-treatment coprocultures from the non-randomly selected flocks, the main nematode genera were Teladorsagia/Trichostrongylus in five flocks, Haemonchus in two flocks, and a mixture of these genera in the remaining two flocks. In the goat flocks, the pre-treatment infection levels of GIN were low compared to what was found in the sheep flocks. Still, in one flock, AR against BZ in Teladorsagia/Trichostrongylus was found. New strategies and recommendations to face the emerging AR situation in Rogaland County in order to limit the spread of resistant nematodes within and into other areas are urgently needed.

  12. Comparison of two versions of larval development test to detect anthelmintic resistance in Haemonchus contortus.

    PubMed

    Várady, Marián; Corba, Július; Letková, Valéria; Kovác, Gabriel

    2009-03-23

    Larval development (LDT) and micro-agar larval development tests (MALDT) were used to compare the reliability and sensitivity of two methods for detecting anthelmintic resistance in Haemonchus contortus. The tests were conducted using three resistant and four susceptible isolates of H. contortus. Both versions of the tests provided comparable results with regard to the characterization of benzimidazole and levamisole susceptibility but neither test was sufficiently sensitive to discrimination between an ivermectin (IVM) susceptible and an IVM resistant isolate. Each test has its own merits with the LDT having the advantage of being less time-consuming.

  13. P-glycoprotein in helminths: function and perspectives for anthelmintic treatment and reversal of resistance.

    PubMed

    Kerboeuf, Dominique; Blackhall, William; Kaminsky, Ronald; von Samson-Himmelstjerna, Georg

    2003-09-01

    Infestation with parasitic helminths is a common problem in human populations of third world countries and is ubiquitous in livestock and other domestic animals. The cell-membrane efflux pump, P-glycoprotein (Pgp), appears to contribute to anthelmintic resistance. Pgp have been identified from both phyla of parasitic helminths, Platyhelmintha and Nematoda, and alterations in expression levels and allele frequencies of Pgp in anthelmintic-resistant populations have been observed in nematodes. Localisation of Pgp has been studied in the free-living nematode Caenorhabditis elegans and in the sheep parasite Haemonchus contortus using specific monoclonal antibodies or lectins. Reversing agents used in human studies, such as the calcium-channel blocker verapamil (VPL), appear to have similar effects in helminths as they do in human cancer cells: the efficacy of drug treatment is increased in drug-resistant parasites when reversing agents are co-administered with the anthelmintic. The functional role of the Pgp glycosylation was also studied using a lectin specific for the alpha-mannosyl residues and showed that resistance can be associated with a decreased affinity of the lectin for Pgp sites and that up to 50% reversion in the resistance to benzimidazoles (BZ) can be obtained using this lectin. Furthermore, the current knowledge on the role of Pgp in molecular mechanisms of drug resistance in the parasitic protozoan genus Trypanosoma is discussed. In some Trypanosoma species it was shown that drug resistance was associated with reduced uptake and in other ones with increased efflux. Several trypanosome Pgp-coding sequences have been described. In contrast to earlier data, most recent observations, based on experimentally overexpressed Pgp in Trypanosoma brucei, indicate a possible involvement in the mechanism of drug resistance in this parasite.

  14. Wild deer as potential vectors of anthelmintic-resistant abomasal nematodes between cattle and sheep farms.

    PubMed

    Chintoan-Uta, C; Morgan, E R; Skuce, P J; Coles, G C

    2014-04-07

    Gastrointestinal (GI) nematodes are among the most important causes of production loss in farmed ruminants, and anthelmintic resistance is emerging globally. We hypothesized that wild deer could potentially act as reservoirs of anthelmintic-resistant GI nematodes between livestock farms. Adult abomasal nematodes and faecal samples were collected from fallow (n = 24), red (n = 14) and roe deer (n = 10) from venison farms and areas of extensive or intensive livestock farming. Principal components analysis of abomasal nematode species composition revealed differences between wild roe deer grazing in the areas of intensive livestock farming, and fallow and red deer in all environments. Alleles for benzimidazole (BZ) resistance were identified in β-tubulin of Haemonchus contortus of roe deer and phenotypic resistance confirmed in vitro by an egg hatch test (EC50 = 0.149 µg ml(-1) ± 0.13 µg ml(-1)) on H. contortus eggs from experimentally infected sheep. This BZ-resistant H. contortus isolate also infected a calf experimentally. We present the first account of in vitro BZ resistance in wild roe deer, but further experiments should firmly establish the presence of phenotypic BZ resistance in vivo. Comprehensive in-field studies should assess whether nematode cross-transmission between deer and livestock occurs and contributes, in any way, to the development of resistance on livestock farms.

  15. Wild deer as potential vectors of anthelmintic-resistant abomasal nematodes between cattle and sheep farms

    PubMed Central

    Chintoan-Uta, C.; Morgan, E. R.; Skuce, P. J.; Coles, G. C.

    2014-01-01

    Gastrointestinal (GI) nematodes are among the most important causes of production loss in farmed ruminants, and anthelmintic resistance is emerging globally. We hypothesized that wild deer could potentially act as reservoirs of anthelmintic-resistant GI nematodes between livestock farms. Adult abomasal nematodes and faecal samples were collected from fallow (n = 24), red (n = 14) and roe deer (n = 10) from venison farms and areas of extensive or intensive livestock farming. Principal components analysis of abomasal nematode species composition revealed differences between wild roe deer grazing in the areas of intensive livestock farming, and fallow and red deer in all environments. Alleles for benzimidazole (BZ) resistance were identified in β-tubulin of Haemonchus contortus of roe deer and phenotypic resistance confirmed in vitro by an egg hatch test (EC50 = 0.149 µg ml−1 ± 0.13 µg ml−1) on H. contortus eggs from experimentally infected sheep. This BZ-resistant H. contortus isolate also infected a calf experimentally. We present the first account of in vitro BZ resistance in wild roe deer, but further experiments should firmly establish the presence of phenotypic BZ resistance in vivo. Comprehensive in-field studies should assess whether nematode cross-transmission between deer and livestock occurs and contributes, in any way, to the development of resistance on livestock farms. PMID:24552838

  16. A real-time PCR approach to identify anthelmintic-resistant nematodes in sheep farms.

    PubMed

    Milhes, M; Guillerm, M; Robin, M; Eichstadt, M; Roy, C; Grisez, C; Prévot, F; Liénard, E; Bouhsira, E; Franc, M; Jacquiet, P

    2017-03-01

    Resistance to fenbendazole, ivermectin, and moxidectin was explored by a fecal egg count reduction test in four meat sheep flocks in southwestern France where anthelmintic resistance was suspected. The FECR test results of the present study confirmed the presence of benzimidazole resistance in three out of the four farms and the presence of ivermectin resistance in one flock. In addition, a suspicion of moxidectin resistance was shown in this latter farm. Both conventional morphological and molecular identifications were performed on larval cultures before and after the treatment in the studied farms. A high positive correlation was found between the number of larvae counted under binocular microscope and the number of larvae estimated by the qPCR analysis (R (2) = 0.88) and a high Cohen's Kappa value (0.91) in the detection of strongylid larvae in larval cultures. According to qPCR results, Trichostrongylus species demonstrated high levels of BZ resistance and Teladorsagia circumcincta was involved in the IVM resistance in one farm. The molecular procedures used in this study have the potential to be beneficial for anthelmintic resistance surveillance in sheep industry.

  17. Survey on anthelmintic resistance to gastrointestinal nematodes in unorganized goat farms of Tamil Nadu.

    PubMed

    Manikkavasagan, I; Binosundar, S T; Raman, M

    2015-06-01

    One of the major problems in small ruminant farms is emergence of anthelmintic resistance (AR) to commonly used dewormers. This study investigated AR to gastrointestinal nematodes affecting goats in 27 unorganized farms in three different agro-climatic zones (Cauvery delta zone, high altitude zone and high rainfall zone) of Tamil Nadu, India. Two anthelmintics viz., albendazole (AZ) and levamisole (LEV) were used in this study as per the dose recommended by the manufacturer. Status of AR was detected by using the faecal egg count reduction test. Results revealed the presence of high level of resistance to both AZ and LEV. In the high rainfall and high altitude zones, all the farm flocks were found to be resistant to LEV. In the Cauvery delta zone, 13 farm flocks were resistant and four farm flocks showed suspect resistance to AZ. Fifteen farm flocks showed resistance and two showed suspect resistance to LEV. Further, morphological characterization of the infective larvae derived from faecal cultures indicated that by far the most predominant gastrointestinal nematode species found in goats was Haemonchus contortus.

  18. The identification of cattle nematode parasites resistant to multiple classes of anthelmintics in a commercial cattle population in the US.

    PubMed

    Gasbarre, Louis C; Smith, Larry L; Lichtenfels, J Ralph; Pilitt, Patricia A

    2009-12-23

    Resistance to modern anthelmintics by ruminant nematode parasites is an increasing problem throughout the world. To date the problem has largely been reported in parasites of small ruminants, but there are increasing reports of such resistance in nematodes recovered from cattle. Until now there have been no published reports of drug resistant parasites from cattle in North America. In 2002 a producer in the upper Midwest who backgrounds young cattle acquired from the southeastern US experienced lower than expected weight gain as well as apparent parasitic gastroenteritis in his cattle during the fall. Fecal sample results supported the suspicion that decreased productivity and diarrhea were the result of GI nematode parasitism. The operation used intensive grazing management and practiced strategically timed deworming for >17 year. In 2003, all animals were dewormed the first week of May with Ivomec Plus, then with Dectomax Injectable on 4 June and 17 July. On 31 July, 10 randomly taken fecal samples showed EPG values from 0 to 55. To assess whether the apparent decreased drug efficacy was the result of drug resistance in the nematode population, on 18 August approximately 150 heads, previously strategic timed dewormed, of 9-11 month old cattle from one pasture were selected for study. The calves were randomly assigned to 1 of 6 treatment groups: untreated (U), ivermectin injectable (I), moxidectin pour-on (M), doramectin injectable (D), eprinomectin pour-on (E), albendazole oral (A). Cattle were weighed prior to treatment and the drug was dosed according to label directions. Seven days later, 3 calves from each group were slaughtered for worm recovery. Fecal samples taken from the remaining animals at 14 days after treatment showed that the reduction of mean fecal EPG value for each group was: U-46%, I-52%, M-72%, D-61%, E-8%, and A-68%. Worm recovery from the slaughter calves showed that all groups harbored significant numbers of Haemonchus placei and H

  19. [Two cases of Ostertagia spp. in sheep showing resistance to benzimidazole anthelmintics].

    PubMed

    Van Schalkwyk, P C; Geyser, T L; Rezin, V S

    1983-06-01

    Two field isolates of Ostertagia spp. of sheep from the Swellendam and Malmesbury districts in the south-western Cape were shown to be resistant to benzimidazole anthelmintics. At therapeutic dosage rates albendazole was 32,5%, thiabendazole 0%, oxfendazole 14,9% and morantel 91,4% effective against the adult stage of Ostertagia spp. in naturally infested lambs at Swellendam. Efficacy against the adult stage of the same isolate of Ostertagia spp. in artificially infested sheep in the laboratory was tested at dosage rates of albendazole 3,8% mg/kg or 7,6 mg/kg, mebendazole 15 mg/kg, levamisole 7,5 mg/kg and morantel 14,5 mg/kg and varied from 0%, 0%, 1,9% 53,9% and 87,0% respectively. Albendazole, the only anthelmintic tested against the Malmesbury strain of Ostertagia spp. was 9,8% effective against the adult stage in naturally infested lambs. Trichostrongylus spp. and Nematodirus spp. simultaneously present in these animals were fully susceptible to all the anthelmintics tested.

  20. [The resistance status of gastrointestinal strongyles against anthelmintics in three Estonian sheep flocks].

    PubMed

    Anupöld, Ann Mari; Hinney, Barbara; Joachim, Anja

    2014-01-01

    Poor efficacy of anthelmintic drugs in sheep due to infections with resistant gastrointestinal strongyles is reported worldwide. The aim of this pilot study was to gain an insight into the current situation of anthelmintic efficacy in Estonian sheep flocks. From September to November 2012, faecal egg count reduction tests (FECRT) were carried out in three Estonian sheep farms, evaluating the efficacy of albendazole and ivermectin. Individual faecal samples were taken at the day of treatment and 10 to 14 days later and examined by a modified McMaster technique. Anthelmintic treatment was carried out with ivermectin (Bimectin 10 mg/ml, Bimeda Chemicals Export) subcutaneously with a dose rate of 0.2 mg/kg of body weight in the IVM group (n = 20 animals/farms 1 and 2; n = 5 for farm 3) or albendazol (Endospec 10%, Bimeda Chemicals Export) orally in the dose of 5 mg/kg of body weight in the ALB group (n = 20 animals/ farm); animals in the control group (n = 20 animals for farms 1 and 3, n = 18 for farm 2) were left untreated. The FECRT was carried out according to the WAAVP guidelines. On farm 1 the efficacy of albendazole and ivermectin was reduced with 66% and 65% FECR, respectively. With a FECR of 26% the results of farm 2 showed a pronounced albendazole resistance while ivermectin was still sufficiently efficient (99% reduction). Farm 3 showed nearly 100% efficacy of albendazole and ivermectin, but earlier problems with high endoparasite burden and mortality may indicate a possible developing albendazole resistance which could not be detected with the FECRT yet. The results of this study show that in Estonia resistance against benzimidazoles and macrocyclic lactones does occur, indicating that close countrywide monitoring is advisable.

  1. Recent advances in candidate-gene and whole-genome approaches to the discovery of anthelmintic resistance markers and the description of drug/receptor interactions.

    PubMed

    Kotze, Andrew C; Hunt, Peter W; Skuce, Philip; von Samson-Himmelstjerna, Georg; Martin, Richard J; Sager, Heinz; Krücken, Jürgen; Hodgkinson, Jane; Lespine, Anne; Jex, Aaron R; Gilleard, John S; Beech, Robin N; Wolstenholme, Adrian J; Demeler, Janina; Robertson, Alan P; Charvet, Claude L; Neveu, Cedric; Kaminsky, Ronald; Rufener, Lucien; Alberich, Melanie; Menez, Cecile; Prichard, Roger K

    2014-12-01

    Anthelmintic resistance has a great impact on livestock production systems worldwide, is an emerging concern in companion animal medicine, and represents a threat to our ongoing ability to control human soil-transmitted helminths. The Consortium for Anthelmintic Resistance and Susceptibility (CARS) provides a forum for scientists to meet and discuss the latest developments in the search for molecular markers of anthelmintic resistance. Such markers are important for detecting drug resistant worm populations, and indicating the likely impact of the resistance on drug efficacy. The molecular basis of resistance is also important for understanding how anthelmintics work, and how drug resistant populations arise. Changes to target receptors, drug efflux and other biological processes can be involved. This paper reports on the CARS group meeting held in August 2013 in Perth, Australia. The latest knowledge on the development of molecular markers for resistance to each of the principal classes of anthelmintics is reviewed. The molecular basis of resistance is best understood for the benzimidazole group of compounds, and we examine recent work to translate this knowledge into useful diagnostics for field use. We examine recent candidate-gene and whole-genome approaches to understanding anthelmintic resistance and identify markers. We also look at drug transporters in terms of providing both useful markers for resistance, as well as opportunities to overcome resistance through the targeting of the transporters themselves with inhibitors. Finally, we describe the tools available for the application of the newest high-throughput sequencing technologies to the study of anthelmintic resistance.

  2. Recent advances in candidate-gene and whole-genome approaches to the discovery of anthelmintic resistance markers and the description of drug/receptor interactions

    PubMed Central

    Kotze, Andrew C.; Hunt, Peter W.; Skuce, Philip; von Samson-Himmelstjerna, Georg; Martin, Richard J.; Sager, Heinz; Krücken, Jürgen; Hodgkinson, Jane; Lespine, Anne; Jex, Aaron R.; Gilleard, John S.; Beech, Robin N.; Wolstenholme, Adrian J.; Demeler, Janina; Robertson, Alan P.; Charvet, Claude L.; Neveu, Cedric; Kaminsky, Ronald; Rufener, Lucien; Alberich, Melanie; Menez, Cecile; Prichard, Roger K.

    2014-01-01

    Anthelmintic resistance has a great impact on livestock production systems worldwide, is an emerging concern in companion animal medicine, and represents a threat to our ongoing ability to control human soil-transmitted helminths. The Consortium for Anthelmintic Resistance and Susceptibility (CARS) provides a forum for scientists to meet and discuss the latest developments in the search for molecular markers of anthelmintic resistance. Such markers are important for detecting drug resistant worm populations, and indicating the likely impact of the resistance on drug efficacy. The molecular basis of resistance is also important for understanding how anthelmintics work, and how drug resistant populations arise. Changes to target receptors, drug efflux and other biological processes can be involved. This paper reports on the CARS group meeting held in August 2013 in Perth, Australia. The latest knowledge on the development of molecular markers for resistance to each of the principal classes of anthelmintics is reviewed. The molecular basis of resistance is best understood for the benzimidazole group of compounds, and we examine recent work to translate this knowledge into useful diagnostics for field use. We examine recent candidate-gene and whole-genome approaches to understanding anthelmintic resistance and identify markers. We also look at drug transporters in terms of providing both useful markers for resistance, as well as opportunities to overcome resistance through the targeting of the transporters themselves with inhibitors. Finally, we describe the tools available for the application of the newest high-throughput sequencing technologies to the study of anthelmintic resistance. PMID:25516826

  3. The development of anthelmintic resistance with best practice control of nematodes on commercial sheep farms in the UK.

    PubMed

    Learmount, Jane; Stephens, Nathalie; Boughtflower, Valerie; Barrecheguren, Alba; Rickell, Kayleigh

    2016-10-15

    Antimicrobial resistance threatens the effective prevention and treatment of an ever-increasing range of infections. The widespread development of anthelmintic resistance is a major global issue affecting the effective control of parasite diseases in grazing livestock production. Sustainable control strategies that reduce dependence on antimicrobials have the potential to slow the further development of resistance but there is little data on the effect of control strategies on resistance development in the field. This report documents a study undertaken to measure the temporal effect of the UK sustainable control of parasites in sheep (SCOPS) guidelines on the development of anthelmintic resistance. Farms carrying out SCOPS or traditional worm control (TRADITIONAL) were tested for resistance to the benzimidazole and imidazothiazole anthelmintics in vitro using a discriminating dose (dd) larval development test (LDT) in year 1 and then 7 years later. In years 5 and 7, resistance was also measured using a dose-response LDT assay. There was a significant increase in Teladorsagia survivors at the benzimidazole dd assay between year 1 and year 7 for both treatment groups, but the increase in survivors was greater for the farms carrying out their traditional worm control compared to the SCOPS farms. There was also a significant difference between benzimidazole dd results generated across years for Trichostrongylus, but the year and treatment interaction was not significant. Only one of the farm Teladorsagia populations had survivors in the imidazothiazole dd assay in years 1 and 7 and none of the Trichostrongylus populations survived in year 1 compared to isolates from three of the farms in year 7. Dose-response data showed a significant effect for time for both the benzimidazole and imidazothiazole anthelmintics and the increase was again significantly higher for the Teladorsagia populations in the TRADITIONAL group compared to the SCOPS group. This data suggests an

  4. Efficacy of an anthelmintic combination in sheep infected with Fasciola hepatica resistant to albendazole and clorsulon.

    PubMed

    Martínez-Valladares, M; Cordero-Pérez, C; Rojo-Vázquez, F A

    2014-01-01

    In the current study, we identified five sheep flocks with fasciolosis in the province of León (northwestern Spain) in order to determine the anthelmintic resistance status to three commonly used anthelmintics, namely albendazole (ABZ), triclabendazole (TCBZ) and clorsulon (CLOR). The identification of one flock resistant to ABZ and CLOR was shown after the faecal egg count reduction test (FECRT). The reductions in eggs per gram values were -17.6% and -68% against immature and adult flukes, respectively, after ABZ treatment; 85.15% and 44.91% against immature and adult flukes, respectively, after CLOR treatment; and 97.06% against both stages, after the administration of TCBZ. As an alternative to control the infection, two combinations of ABZ and CLOR were tested. In the first, both drugs were administered at the recommended dose of each; in this case, the efficiency reached values above 95% against both immature and adult flukes. However, when the combined drugs were administered at half the recommended dose of each, the efficiency of the combination was very low, i.e. 16.67% and -11.11% against mature and immature flukes, respectively. In conclusion, this preliminary report suggests a possible interaction between ABZ and CLOR after their joint administration. However, these results should be confirmed in other flocks. Copyright © 2014. Published by Elsevier Inc.

  5. Anthelmintic resistance to ivermectin and moxidectin in gastrointestinal nematodes of cattle in Europe.

    PubMed

    Geurden, Thomas; Chartier, Christophe; Fanke, Jane; di Regalbono, Antonio Frangipane; Traversa, Donato; von Samson-Himmelstjerna, Georg; Demeler, Janina; Vanimisetti, Hima Bindu; Bartram, David J; Denwood, Matthew J

    2015-12-01

    Anthelmintic resistance has been increasingly reported in cattle worldwide over the last decade, although reports from Europe are more limited. The objective of the present study was to evaluate the efficacy of injectable formulations of ivermectin and moxidectin at 0.2 mg per kg bodyweight against naturally acquired gastro-intestinal nematodes in cattle. A total of 753 animals on 40 farms were enrolled in Germany (12 farms), the UK (10 farms), Italy (10 farms), and France (8 farms). Animals were selected based on pre-treatment faecal egg counts and were allocated to one of the two treatment groups. Each treatment group consisted of between 7 and 10 animals. A post-treatment faecal egg count was performed 14 days (±2 days) after treatment. The observed percentage reduction was calculated for each treatment group based on the arithmetic mean faecal egg count before and after treatment. The resistance status was evaluated based on the reduction in arithmetic mean faecal egg count and both the lower and upper 95% confidence limits. A decreased efficacy was observed in half or more of the farms in Germany, France and the UK. For moxidectin, resistance was confirmed on 3 farms in France, and on 1 farm in Germany and the UK. For ivermectin, resistance was confirmed on 3 farms in the UK, and on 1 farm in Germany and France. The remaining farms with decreased efficacy were classified as having an inconclusive resistance status based on the available data. After treatment Cooperia spp. larvae were most frequently identified, though Ostertagia ostertagi was also found, in particular within the UK and Germany. The present study reports lower than expected efficacy for ivermectin and moxidectin (based on the reduction in egg excretion after treatment) on European cattle farms, with confirmed anthelmintic resistance on 12.5% of the farms.

  6. Anthelmintic resistance to ivermectin and moxidectin in gastrointestinal nematodes of cattle in Europe

    PubMed Central

    Geurden, Thomas; Chartier, Christophe; Fanke, Jane; di Regalbono, Antonio Frangipane; Traversa, Donato; von Samson-Himmelstjerna, Georg; Demeler, Janina; Vanimisetti, Hima Bindu; Bartram, David J.; Denwood, Matthew J.

    2015-01-01

    Anthelmintic resistance has been increasingly reported in cattle worldwide over the last decade, although reports from Europe are more limited. The objective of the present study was to evaluate the efficacy of injectable formulations of ivermectin and moxidectin at 0.2 mg per kg bodyweight against naturally acquired gastro-intestinal nematodes in cattle. A total of 753 animals on 40 farms were enrolled in Germany (12 farms), the UK (10 farms), Italy (10 farms), and France (8 farms). Animals were selected based on pre-treatment faecal egg counts and were allocated to one of the two treatment groups. Each treatment group consisted of between 7 and 10 animals. A post-treatment faecal egg count was performed 14 days (±2 days) after treatment. The observed percentage reduction was calculated for each treatment group based on the arithmetic mean faecal egg count before and after treatment. The resistance status was evaluated based on the reduction in arithmetic mean faecal egg count and both the lower and upper 95% confidence limits. A decreased efficacy was observed in half or more of the farms in Germany, France and the UK. For moxidectin, resistance was confirmed on 3 farms in France, and on 1 farm in Germany and the UK. For ivermectin, resistance was confirmed on 3 farms in the UK, and on 1 farm in Germany and France. The remaining farms with decreased efficacy were classified as having an inconclusive resistance status based on the available data. After treatment Cooperia spp. larvae were most frequently identified, though Ostertagia ostertagi was also found, in particular within the UK and Germany. The present study reports lower than expected efficacy for ivermectin and moxidectin (based on the reduction in egg excretion after treatment) on European cattle farms, with confirmed anthelmintic resistance on 12.5% of the farms. PMID:26448902

  7. Use of two in vitro methods for the detection of anthelmintic resistant nematode parasites on Slovak sheep farms.

    PubMed

    Várady, Marián; Cernanská, Dana; Corba, Július

    2006-02-18

    A survey of the prevalence of anthelmintic resistant nematode populations was conducted on 32 sheep farms in the Slovak Republic. In vitro egg hatch test and larval development tests were used for the detection of resistance to benzimidazole anthelmintics and they were compared with in vivo faecal egg count reduction tests. There was agreement in the declaration of resistance between the faecal egg count reduction test and both in vitro tests. The presence of resistant populations was determined on two farms using egg hatch test. In both farms, the LD(50) values were higher than 0.1 microg TBZ/ml, indicating resistance. By using LD(99) values it might be possible to reveal relatively small proportion of resistant larvae in the population. The prevalence of benzimidazole resistance has not change on Slovak sheep farms during last decade.

  8. Biotransformation of albendazole and activities of selected detoxification enzymes in Haemonchus contortus strains susceptible and resistant to anthelmintics.

    PubMed

    Vokřál, Ivan; Jirásko, Robert; Stuchlíková, Lucie; Bártíková, Hana; Szotáková, Barbora; Lamka, Jiří; Várady, Marián; Skálová, Lenka

    2013-09-23

    The increased activity of drug-metabolizing enzymes can protect helminths against the toxic effect of anthelmintics. The aim of this study was to compare the metabolism of the anthelmintic drug albendazole (ABZ) and the activities of selected biotransformation and antioxidant enzymes in three different strains of Haemonchus contortus: the ISE strain (susceptible to common anthelmintics), the BR strain (resistant to benzimidazole anthelmintics) and the WR strain (multi-resistant). H. contortus adults were collected from the abomasum of experimentally infected lambs. In vitro (subcellular fractions of H. contortus homogenate) as well as ex vivo (living nematodes cultivated in flasks with medium) experiments were performed. HPLC with spectrofluorimetric and mass-spectrometric detection was used in the analysis of ABZ metabolites. The in vitro activities of oxidation/antioxidation and conjugation enzymes toward model substrates were also assayed. The in vitro data showed significant differences between the susceptible (ISE) and resistant (BR, WR) strains regarding the activities of peroxidases, catalase and UDP-glucosyltransferases. S-oxidation of ABZ was significantly lower in BR than in the ISE strain. Ex vivo, four ABZ metabolites were identified: ABZ sulphoxide and three ABZ glucosides. In the resistant strains BR and WR, the ex vivo formation of all ABZ glucosides was significantly higher than in the susceptible ISE strain. The altered activities of certain detoxifying enzymes might partly protect the parasites against the toxic effect of the drugs as well as contribute to drug-resistance in these parasites. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Diagnosis of anthelmintic resistance in cattle in Brazil: a comparison of different methodologies.

    PubMed

    das Neves, José Henrique; Carvalho, Nadino; Rinaldi, Laura; Cringoli, Giuseppe; Amarante, Alessandro F T

    2014-12-15

    The occurrence of anthelmintic resistance to levamisole, albendazole, ivermectin and moxidectin was investigated in cattle from 10 farms located in São Paulo State, Brazil, using two techniques for counting eggs in faeces: McMaster with a sensitivity of 50 eggs per gram (EPG) and FLOTAC with a sensitivity of two EPG. We also evaluated the use of different mathematical and test design approaches to determine the efficacy of the anthelmintic treatments: one formula/design that compares post-treatment arithmetic mean EPG counts for the treated and control groups (FECRT1) and two methods to analyse data from pre- and post-treatment EPG counts in the same group (FECRT2 and FECRT3, respectively). Treatment groups received either ivermectin (0.2 mg/kg of body weight (BW); moxidectin (0.2 mg/kg BW); albendazole (2.5 mg/kg BW); levamisole (4.7 mg/kg BW); or no treatment (control group). The number of animals in each group ranged from 8 to 11. Faecal samples from each animal were collected 2 days before the treatment and again 10 and 28 days post-treatment. The FEC reduction (FECR) confidence intervals were usually wider when based on data obtained using the McMaster method than when data were obtained using the FLOTAC method. Efficacy estimated from pre- and post-treatment EPG counts in the same group presented smaller confidence intervals. Ivermectin proved to be totally ineffective in all herds evaluated. Cooperia spp. was the major parasite displaying resistance, followed by Haemonchus spp. The results also indicated the presence of Oesophagostomum spp. and Trichostrongylus spp., meaning they, too, were resistant to ivermectin. Resistance to moxidectin was found on nine of the 10 farms investigated; however, only three farms had previously used moxidectin. In contrast, albendazole and levamisole demonstrated high efficacy on the majority of farms. In surveys for anthelmintic resistance in cattle, the use of a diagnostic method with higher sensitivity to detect eggs is

  10. Anthelmintic resistance in gastrointestinal nematodes of beef cattle in the state of Rio Grande do Sul, Brazil.

    PubMed

    Ramos, Fernanda; Portella, Luiza Pires; Rodrigues, Fernando de Souza; Reginato, Caroline Zamperete; Pötter, Luciana; Cezar, Alfredo Skrebsky; Sangioni, Luís Antônio; Vogel, Fernanda Silveira Flores

    2016-04-01

    Gastrointestinal nematodes resistant to anthelmintics have been reported in several regions of Brazil, and they may be associated with economic losses for the cattle industry. This study aimed to evaluate the resistance status of gastrointestinal nematodes from naturally infected beef cattle to several commercially available anthelmintics, as well as to test the efficacy of combinations of anthelmintics against multi-resistant gastrointestinal nematodes. Ten farms located in Rio Grande do Sul state were selected by: farmers' consent; extensive raising system; availability of calves aged from 7 to 9 months naturally infected by gastrointestinal nematodes; absence of anthelmintic treatment for 60 days before the study; and presence of 70-100 calves or more of both genders with ≥ 200 eggs per gram of feces (EPG) (sensitivity of 50 EPG). These calves were distributed into 10 groups (of 7-10 animals) per farm and treated with ivermectin, doramectin, eprinomectin, fenbendazole, closantel, nitroxynil, disophenol, levamisole, albendazole, or moxidectin. Feces were collected 2 days before treatment and 14 days after treatment. Additional groups of 7-10 calves were used to test six different two-drug combinations at four of the studied farms. In general terms, fenbendazole was the most effective drug, followed by levamisole, disophenol, and moxidectin. However, parasite resistance to multiple drugs was found in all herds, especially in the genera Cooperia spp., Trichostrongylus spp., and Haemonchus spp.. Some of the two-drug combinations were effective against nematode populations identified as resistant to the same compounds when used as single drugs. The most effective combinations were moxidectin + levamisole, doramectin + fenbendazole, and levamisole + closantel. In this study, parasites resistant to the main commercially available anthelmintics were found in all herds, and some combinations of two active components belonging to different chemical groups were effective

  11. Anthelmintic resistance in gastrointestinal nematodes of beef cattle in the state of Rio Grande do Sul, Brazil

    PubMed Central

    Ramos, Fernanda; Portella, Luiza Pires; Rodrigues, Fernando de Souza; Reginato, Caroline Zamperete; Pötter, Luciana; Cezar, Alfredo Skrebsky; Sangioni, Luís Antônio; Vogel, Fernanda Silveira Flores

    2016-01-01

    Gastrointestinal nematodes resistant to anthelmintics have been reported in several regions of Brazil, and they may be associated with economic losses for the cattle industry. This study aimed to evaluate the resistance status of gastrointestinal nematodes from naturally infected beef cattle to several commercially available anthelmintics, as well as to test the efficacy of combinations of anthelmintics against multi-resistant gastrointestinal nematodes. Ten farms located in Rio Grande do Sul state were selected by: farmers' consent; extensive raising system; availability of calves aged from 7 to 9 months naturally infected by gastrointestinal nematodes; absence of anthelmintic treatment for 60 days before the study; and presence of 70–100 calves or more of both genders with ≥200 eggs per gram of feces (EPG) (sensitivity of 50 EPG). These calves were distributed into 10 groups (of 7–10 animals) per farm and treated with ivermectin, doramectin, eprinomectin, fenbendazole, closantel, nitroxynil, disophenol, levamisole, albendazole, or moxidectin. Feces were collected 2 days before treatment and 14 days after treatment. Additional groups of 7–10 calves were used to test six different two-drug combinations at four of the studied farms. In general terms, fenbendazole was the most effective drug, followed by levamisole, disophenol, and moxidectin. However, parasite resistance to multiple drugs was found in all herds, especially in the genera Cooperia spp., Trichostrongylus spp., and Haemonchus spp.. Some of the two-drug combinations were effective against nematode populations identified as resistant to the same compounds when used as single drugs. The most effective combinations were moxidectin + levamisole, doramectin + fenbendazole, and levamisole + closantel. In this study, parasites resistant to the main commercially available anthelmintics were found in all herds, and some combinations of two active components belonging to different chemical groups

  12. Prevalence of gastrointestinal helminths and anthelmintic resistance on small-scale farms in Gauteng Province, South Africa.

    PubMed

    Tsotetsi, Ana Mbokeleng; Njiro, Stephen; Katsande, Tendai Charles; Moyo, Gugulethu; Baloyi, Faculty; Mpofu, Jaison

    2013-03-01

    The present study was conducted to determine the prevalence and distribution of gastrointestinal helminths, to detect the presence of anthelmintic resistance in livestock from small-scale farms and to determine the level of helminthosis awareness among small-scale farmers in Gauteng Province, South Africa. Blood and faecal samples were collected from cattle (n = 314), sheep (n = 256) and goats (n = 311). Faecal egg counts and cultures were done, helminth genera identified and packed cell volume was assessed to detect anaemia. A faecal egg count reduction test was used to determine anthelmintic resistance against albendazole (7.5 mg/kg), levamisole (5 mg/kg) and ivermectin (0.2 mg/kg) on five small ruminant farms. A high prevalence of both nematodes and trematodes was observed; however, only 1 % of cattle had high nematode egg counts compared to goats (30 %) and sheep (32 %). Only 5 % of the animals were anaemic. Haemonchus and Calicophoron were the most dominant helminth genera in the studied ruminants. Anthelmintic resistance was detected against the three tested drugs on all the screened farms, except against albendazole and levamisole in sheep from Hammanskraal and Nigel, respectively. About 88 % of interviewed farmers were aware of veterinary helminthosis, 67 % treated against helminths and 83 % provided their livestock with nutritional supplements. This study showed that a high prevalence of helminthosis and anthelmintic resistance does occur in the study area, thus relevant strategic interventions are recommended.

  13. Anthelmintic resistance in gastrointestinal nematodes from grazing beef cattle in Campeche State, Mexico.

    PubMed

    Muñiz-Lagunes, Abel; González-Garduño, Roberto; López-Arellano, Maria Eugenia; Ramírez-Valverde, Rodolfo; Ruíz-Flores, Agustín; García-Muñiz, Guadalupe; Ramírez-Vargas, Gabriel; Mendoza-de Gives, Pedro; Torres-Hernández, Glafiro

    2015-08-01

    Production of beef cattle is one of the most important economic activities in Mexico. However, anthelmintic resistance (AR) has affected animal productivity. The aim of this study was to determine the presence of AR in gastrointestinal nematodes (GIN) of beef cattle in Candelaria Municipality of Campeche State, Mexico. Sixty-five-month-old beef calves were selected for the faecal egg count reduction test (FECRT) and the inhibition of egg hatch (IEH) assay. These parameters were determined using albendazole (benzimidazole, BZ), ivermectin (IVM, Macrocyclic lactone, ML) and levamisole (LEV, imidazothiazole, IMZ). Allele-specific PCR (AS-PCR) confirmed polymorphisms at codon 200 of isotype 1 of the β-tubulin gene of Haemonchus placei. The results showed 32 % IVM toxicity by FECRT, indicating problems of AR in the GIN population. In contrast, BZ and LEV showed 95 and 100 % toxicity, respectively, against GIN from infected beef calves. The infective larvae (L3) of Cooperia, Haemonchus and Oesophagostomum were identified before anthelmintic treatment, and Cooperia L3 larvae were identified after treatment with IVM. The IEH assays had lethal dose 50 (LD50) of 187 nM to BZ, confirming the ovicidal effect of BZ. In contrast, the LD50 for LEV and IVM were 3.3 and 0.4 mM, respectively. The results obtained by AS-PCR confirmed two DNA fragments of 250 and 550 bp, corresponding to the resistant and susceptible alleles in the H. placei population. The nematode Cooperia showed AR against IVM, while the toxicity effect of BZ against GIN with both FECRT and IEH was confirmed.

  14. Anthelmintic closantel enhances bacterial killing of polymyxin B against multidrug-resistant Acinetobacter baumannii

    PubMed Central

    Tran, Thien B.; Cheah, Soon-Ee; Yu, Heidi H.; Bergen, Phillip J.; Nation, Roger L.; Creek, Darren J.; Purcell, Anthony; Forrest, Alan; Doi, Yohei; Song, Jiangning; Velkov, Tony; Li, Jian

    2015-01-01

    Polymyxins, an old class of antibiotics, are currently used as the last resort for the treatment of multidrug-resistant (MDR) Acinetobacter baumannii. However, recent pharmacokinetic and pharmacodynamic data indicate that monotherapy can lead to the development of resistance. Novel approaches are urgently needed to preserve and improve the efficacy of this last-line class of antibiotics. This study examined the antimicrobial activity of novel combination of polymyxin B with anthelmintic closantel against A. baumannii. Closantel monotherapy (16 mg/L) was ineffective against most tested A. baumannii isolates. However, closantel at 4–16 mg/L with a clinically achievable concentration of polymyxin B (2 mg/L) successfully inhibited the development of polymyxin resistance in polymyxin-susceptible isolates, and provided synergistic killing against polymyxin-resistant isolates (MIC ≥4 mg/L). Our findings suggest that the combination of polymyxin B with closantel could be potentially useful for the treatment of MDR, including polymyxin-resistant, A. baumannii infections. The re-positioning of non-antibiotic drugs to treat bacterial infections may significantly expedite discovery of new treatment options for bacterial ‘superbugs’. PMID:26669752

  15. Anthelmintic closantel enhances bacterial killing of polymyxin B against multidrug-resistant Acinetobacter baumannii.

    PubMed

    Tran, Thien B; Cheah, Soon-Ee; Yu, Heidi H; Bergen, Phillip J; Nation, Roger L; Creek, Darren J; Purcell, Anthony; Forrest, Alan; Doi, Yohei; Song, Jiangning; Velkov, Tony; Li, Jian

    2016-06-01

    Polymyxins, an old class of antibiotics, are currently used as the last resort for the treatment of multidrug-resistant (MDR) Acinetobacter baumannii. However, recent pharmacokinetic and pharmacodynamic data indicate that monotherapy can lead to the development of resistance. Novel approaches are urgently needed to preserve and improve the efficacy of this last-line class of antibiotics. This study examined the antimicrobial activity of novel combination of polymyxin B with anthelmintic closantel against A. baumannii. Closantel monotherapy (16 mg l(-1)) was ineffective against most tested A. baumannii isolates. However, closantel at 4-16 mg l(-1) with a clinically achievable concentration of polymyxin B (2 mg l(-1)) successfully inhibited the development of polymyxin resistance in polymyxin-susceptible isolates, and provided synergistic killing against polymyxin-resistant isolates (MIC ⩾4 mg l(-1)). Our findings suggest that the combination of polymyxin B with closantel could be potentially useful for the treatment of MDR, including polymyxin-resistant, A. baumannii infections. The repositioning of non-antibiotic drugs to treat bacterial infections may significantly expedite discovery of new treatment options for bacterial 'superbugs'.

  16. A Novel High Throughput Assay for Anthelmintic Drug Screening and Resistance Diagnosis by Real-Time Monitoring of Parasite Motility

    PubMed Central

    Smout, Michael J.; Kotze, Andrew C.; McCarthy, James S.; Loukas, Alex

    2010-01-01

    Background Helminth parasites cause untold morbidity and mortality to billions of people and livestock. Anthelmintic drugs are available but resistance is a problem in livestock parasites, and is a looming threat for human helminths. Testing the efficacy of available anthelmintic drugs and development of new drugs is hindered by the lack of objective high-throughput screening methods. Currently, drug effect is assessed by observing motility or development of parasites using laborious, subjective, low-throughput methods. Methodology/Principal Findings Here we describe a novel application for a real-time cell monitoring device (xCELLigence) that can simply and objectively assess anthelmintic effects by measuring parasite motility in real time in a fully automated high-throughput fashion. We quantitatively assessed motility and determined real time IC50 values of different anthelmintic drugs against several developmental stages of major helminth pathogens of humans and livestock, including larval Haemonchus contortus and Strongyloides ratti, and adult hookworms and blood flukes. The assay enabled quantification of the onset of egg hatching in real time, and the impact of drugs on hatch rate, as well as discriminating between the effects of drugs on motility of drug-susceptible and –resistant isolates of H. contortus. Conclusions/Significance Our findings indicate that this technique will be suitable for discovery and development of new anthelmintic drugs as well as for detection of phenotypic resistance to existing drugs for the majority of helminths and other pathogens where motility is a measure of pathogen viability. The method is also amenable to use for other purposes where motility is assessed, such as gene silencing or antibody-mediated killing. PMID:21103363

  17. Analysis of putative inhibitors of anthelmintic resistance mechanisms in cattle gastrointestinal nematodes.

    PubMed

    AlGusbi, Salha; Krücken, Jürgen; Ramünke, Sabrina; von Samson-Himmelstjerna, Georg; Demeler, Janina

    2014-08-01

    Effects of the cytochrome P450 inhibitor piperonyl butoxide and the P-glycoprotein inhibitor verapamil on the efficacy of ivermectin and thiabendazole were studied in vitro in susceptible and resistant isolates of the cattle parasitic nematodes Cooperia oncophora and Ostertagia ostertagi. The effects of combined use of drug and piperonyl butoxide/verapamil, respectively, were investigated in the Egg Hatch Assay, the Larval Development Assay and the Larval Migration Inhibition Assay. The effects of piperonyl butoxide and verapamil as inhibitors of thiabendazole and ivermectin responses were particularly marked for larval development, where both inhibitors were able to completely eliminate all differences between susceptible and resistant isolates. Even the lowest concentrations of anthelmintics used in combination with inhibitors caused complete inhibition of development. Differences and/or similarities among responses in different isolates were only obtained in the two other assays: in the Egg Hatch Assay piperonyl butoxide caused a shift in concentration-response curves obtained with thiabendazole to the left for all isolates tested, changing relative differences between isolates. In contrast, an effect of verapamil in the Egg Hatch Assay was only apparent for benzimidazole-resistant isolates. In the Larval Migration Inhibition Assay only ivermectin was tested and piperonyl butoxide shifted the concentration-response curves for all isolates to the left, again eliminating differences in EC50 values between susceptible and resistant isolates. This was not the case using verapamil as an inhibitor, where curves for both susceptible and benzimidazole-resistant isolates shifted to the left in Ostertagia isolates. In Cooperia the picture was more complex with ivermectin-resistant isolates showing a larger shift than the susceptible isolate. Single nucleotide polymorphisms in the β-tubulin isotype 1 gene were investigated. Significantly increased frequencies of

  18. Drug Repurposing of the Anthelmintic Niclosamide to Treat Multidrug-Resistant Leukemia

    PubMed Central

    Hamdoun, Sami; Jung, Philipp; Efferth, Thomas

    2017-01-01

    Multidrug resistance, a major problem that leads to failure of anticancer chemotherapy, requires the development of new drugs. Repurposing of established drugs is a promising approach for overcoming this problem. An example of such drugs is niclosamide, a known anthelmintic that is now known to be cytotoxic and cytostatic against cancer cells. In this study, niclosamide showed varying activity against different cancer cell lines. It revealed better activity against hematological cancer cell lines CCRF-CEM, CEM/ADR5000, and RPMI-8226 compared to the solid tumor cell lines MDA-MB-231, A549, and HT-29. The multidrug resistant CEM/ADR5000 cells were similar sensitive as their sensitive counterpart CCRF-CEM (resistance ration: 1.24). Furthermore, niclosamide caused elevations in reactive oxygen species and glutathione (GSH) levels in leukemia cells. GSH synthetase (GS) was predicted as a target of niclosamide. Molecular docking showed that niclosamide probably binds to the ATP-binding site of GS with a binding energy of -9.40 kcal/mol. Using microscale thermophoresis, the binding affinity between niclosamide and recombinant human GS was measured (binding constant: 5.64 μM). COMPARE analyses of the NCI microarray database for 60 cell lines showed that several genes, including those involved in lipid metabolism, correlated with cellular responsiveness to niclosamide. Hierarchical cluster analysis showed five major branches with significant differences between sensitive and resistant cell lines (p = 8.66 × 105). Niclosamide significantly decreased nuclear factor of activated T-cells (NFAT) activity as predicted by promoter binding motif analysis. In conclusion, niclosamide was more active against hematological malignancies compared to solid tumors. The drug was particularly active against the multidrug-resistant CEM/ADR5000 leukemia cells. Inhibition of GSH synthesis and NFAT signaling were identified as relevant mechanisms for the anticancer activity of niclosamide

  19. Multiple resistance to anthelmintics by Haemonchus contortus and Trichostrongylus colubriformis in sheep in Brazil.

    PubMed

    Almeida, F A; Garcia, K C O D; Torgerson, P R; Amarante, A F T

    2010-12-01

    The objective of this study was to determine the level of resistance of Haemonchus contortus and Trichostrongylus colubriformis in sheep to levamisole, albendazole, ivermectin, moxidectin, closantel and trichlorfon. The parasites were isolated from sheep naturally infected by gastrointestinal nematodes and were then kept in monospecifically-infected lambs for production of infective larvae (L3) of both species. Forty-two lambs, at three months of age, were simultaneously artificially infected with 4000 L3 of H. contortus and 4000 L3 of T. colubriformis. The animals were allocated into seven groups with six animals each that received one of the following treatments: Group 1--control, no treatment; Group 2--moxidectin (0.2mg/kg body weight (BW)); Group 3--closantel (10mg/kg BW); Group 4--trichlorfon (100mg/kg BW); Group 5--levamisole phosphate (4.7 mg/kg BW); Group 6--albendazole (5.0mg/kg BW); and Group 7--ivermectin (0.2mg/kg BW). Nematode fecal egg counts (FEC) were carried out on the day of treatment and again at 3, 7, 10 and 14 days post-treatment. On the same occasions, composite fecal cultures were prepared for each group for production of L3, which were identified into genus. The animals were sacrificed for worm counts at 14 days after treatment. The efficacy of each treatment was calculated from the arithmetic mean of the FEC or worm burden of the treated group, compared with the values of the control group. Only trichlorfon and moxidectin treatments resulted in a significant reduction of H. contortus recorded at necropsy (73% and 45% respectively). Moxidectin reduced T. colubriformis worm burdens by 82% and albendazole by 19%. All other anthelmintics resulted in no significant reduction in the numbers of worms found at necropsy. In conclusion, the isolates of H. contortus and T. colubriformis showed multiple resistance to all groups of anthelmintics tested. This is the first report, based on the controlled efficacy test, to show resistance of T

  20. Managing Resistance.

    ERIC Educational Resources Information Center

    Maag, John W.

    2000-01-01

    This article presents some considerations and ideas for managing students' resistance. They are organized around four topics: the impact of context on behavior, the importance of being comprehensive and nonrestrictive in behavior, the adaptive function of resistant behavior, and the benefit of joining children in their frame of reference.…

  1. Managing Resistance.

    ERIC Educational Resources Information Center

    Maag, John W.

    2000-01-01

    This article presents some considerations and ideas for managing students' resistance. They are organized around four topics: the impact of context on behavior, the importance of being comprehensive and nonrestrictive in behavior, the adaptive function of resistant behavior, and the benefit of joining children in their frame of reference.…

  2. Anthelmintic resistance impact on tropical beef cattle productivity: effect on weight gain of weaned calves.

    PubMed

    Borges, Fernando A; Almeida, Gabriel D; Heckler, Rafael P; Lemes, Raul T; Onizuka, Marcel K V; Borges, Dyego G L

    2013-03-01

    The performance of grazing cattle in tropical areas is deeply influenced by parasitism, and the increasing reports of resistance are a threat to effective nematode control. The present study aimed to evaluate the effect of avermectins on the performance of weaned calves naturally infected by ivermectin-resistant gastrointestinal nematodes. The effect of four commercial endectocides (ivermectin 2.25 % + abamectin 1.25 %, ivermectin 3.15 %, doramectin 3.15 %, and doramectin 1 %) on parasitism and performance of a hundred weaned Nellore calves were evaluated during 112 days. The most effective anthelmintic showed efficacy of 84 % and resulted in an increase (P < 0.05) of live weight gain of 11.85 kg, compared to untreated group, 9.05 and 9.41 kg compared to those treated with more ineffective avermectins which showed efficacy of 0 and 48.2 %, respectively. A significant (P < 0.05) and weak negative correlation (r = -0.22) between the eggs per gram (EPG) and body weight was observed, indicating that even the low mean EPG (175 ± 150) observed at day 0 in the control group, with predominance of Haemonchus sp., was responsible for production losses. These results indicate that control of nematode parasites in beef cattle in the weaning phase may not result in increased productivity when carried out without technical criteria.

  3. Tannin rich peanut skins lack anthelmintic properties

    USDA-ARS?s Scientific Manuscript database

    Gastrointestinal nematode (GIN) resistance to synthetic anthelmintics in small ruminants has led to the evaluation of feed sources containing naturally occurring bioactive secondary metabolites that lessen parasite activity. Plants rich in condensed tannins (CT) can have beneficial anthelmintic pro...

  4. The efficacy of trichlorphon and naphthalophos against multiple anthelmintic-resistant nematodes of naturally infected sheep in Argentina.

    PubMed

    Fiel, César; Guzmán, Maricel; Steffan, Pedro; Rodriguez, Edgardo; Prieto, Olegario; Bhushan, Chandra

    2011-08-01

    An anthelmintic efficacy trial was conducted in sheep harbouring anthelmintic-resistant worms in Argentina. Seventy lambs were selected from a flock that had been grazed on pastures infected with trichostrongyles previously shown to be resistant to the main anthelmintic groups. Lambs were allocated to comparable groups of ten animals each and treated with trichlorphon (50 mg/kg body weight (b.w.) orally); naphthalophos (50 mg/kg b.w. orally); ivermectin (0.2 mg/kg b.w. subcutaneously); fenbendazole (5 mg/kg b.w. orally); levamisole (8 mg/kg b.w. subcutaneously) and closantel (10 mg/kg b.w. orally). There was also an untreated group. The dose selection was based on manufacturer's recommendations.Faecal samples were collected 0 and 10 days post treatment to estimate efficacy (faecal egg count reduction). Six animals from each group were necropsied at day 10 for enumeration/identification of worms from the abomasum, small and large intestines to determine the absolute efficacy of each agent (controlled efficacy test). Trichlorphon and naphthalophos were effective (> 99 %) against Haemonchus contortus (p < 0.05).Naphthalophos also showed efficacy against Trichostrongylus axei (99.3 %), Teladorsagia circumcincta (97.8 %), Trichostrongylus colubriformis (99.2 %), Cooperia punctata/curticei/pectinata (90.4 %), Nematodirus spathiger (89.2 %) and Oesophagostomum venulosum/columbianum (93.7 %). Fenbendazole and levamisole showed efficacy (> 95 %) against all nematodes except T. colubriformis. The efficacy of ivermectin was low against H. contortus (23 %) and Cooperia spp. (46.3 %). Closantel showed low efficacy against T. axei (64.4 %), H. contortus (80.6 %) and T. colubriformis (59.5 %).When anthelmintic resistance is widespread, trichlorphon treatment is appropriate if H. contortus is present; however, naphthalophos represents an effective therapeutic alternative for incorporation into worm control programmes.

  5. Anthelmintic metabolism in parasitic helminths: proteomic insights.

    PubMed

    Brophy, Peter M; MacKintosh, Neil; Morphew, Russell M

    2012-08-01

    Anthelmintics are the cornerstone of parasitic helminth control. Surprisingly, understanding of the biochemical pathways used by parasitic helminths to detoxify anthelmintics is fragmented, despite the increasing global threat of anthelmintic resistance within the ruminant and equine industries. Reductionist biochemistry has likely over-estimated the enzymatic role of glutathione transferases in anthelmintic metabolism and neglected the potential role of the cytochrome P-450 superfamily (CYPs). Proteomic technologies offers the opportunity to support genomics, reverse genetics and pharmacokinetics, and provide an integrated insight into both the cellular mechanisms underpinning response to anthelmintics and also the identification of biomarker panels for monitoring the development of anthelmintic resistance. To date, there have been limited attempts to include proteomics in anthelmintic metabolism studies. Optimisations of membrane, post-translational modification and interaction proteomic technologies in helminths are needed to especially study Phase I CYPs and Phase III ABC transporter pumps for anthelmintics and their metabolites.

  6. Anthelmintic resistance in Northern Ireland (III): uptake of 'SCOPS' (Sustainable Control of Parasites in Sheep) recommendations by sheep farmers.

    PubMed

    McMahon, C; McCoy, M; Ellison, S E; Barley, J P; Edgar, H W J; Hanna, R E B; Malone, F E; Brennan, G P; Fairweather, I

    2013-03-31

    Reports of anthelmintic resistance to multiple drugs in individual parasite species, and in multiple parasite species across virtually all livestock hosts, are increasingly common. A working group of UK researchers and practitioners devised a set of guidelines in 2003 (Sustainable Control of Parasites in Sheep, 'SCOPS') aimed at maintaining anthelmintic efficacy on farms. Over the years that followed, these guidelines were promoted through meetings, promotional literature and the agricultural press. Results from questionnaires conducted in Northern Ireland (NI) in 2005 (covering 1999-2004) and 2011 (covering 2008-2011) have provided an opportunity to examine the extent to which these campaigns have influenced parasite control on sheep farms. The percentage of flocks at risk of under-dosing through inaccurate weight estimation in NI has increased by 15.9% since 2005. The number of flocks at risk of under-dosing through non-calibrated equipment has increased by 14.3% since 2005. The size of the in refugia population may have potentially doubled, as indicated by an increased compliance with the recommendation (wherever possible) to leave a portion of the flock untreated. However, whether this is indeed the case cannot be explicitly determined without a measure of the impact of various factors, including host immunity, environment/climate, previous anthelmintic treatment and the species of parasite present. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Anthelmintic effect of Psidium guajava and Tagetes erecta on wild-type and Levamisole-resistant Caenorhabditis elegans strains.

    PubMed

    Piña-Vázquez, Denia M; Mayoral-Peña, Zyanya; Gómez-Sánchez, Maricela; Salazar-Olivo, Luis A; Arellano-Carbajal, Fausto

    2017-04-18

    Psidium guajava and Tagetes erecta have been used traditionally to treat gastrointestinal parasites, but their active metabolites and mechanisms of action remain largely unknown. To evaluate the anthelmintic potential of Psidium guajava and Tagetes erecta extracts on Levamisole-sensitive and Levamisole-resistant strains of the model nematode Caenorhabditis elegans. Aqueous extracts of Psidium guajava (PGE) and Tagetes erecta (TEE) were assayed on locomotion and egg-laying behaviors of the wild-type (N2) and Levamisole-resistant (CB193) strains of Caenorhabditis elegans. Both extracts paralyzed wild-type and Levamisole-resistant nematodes in a dose-dependent manner. In wild-type worms, TEE 25mg/mL induced a 75% paralysis after 8h of treatment and PGE 25mg/mL induced a 100% paralysis after 4h of treatment. PGE exerted a similar paralyzing effect on N2 wild-type and CB193 Levamisole-resistant worms, while TEE only partially paralyzed CB193 worms. TEE 25mg/mL decreased N2 egg-laying by 65% with respect to the untreated control, while PGE did it by 40%. Psidium guajava leaves and Tagetes erecta flower-heads possess hydrosoluble compounds that block the motility of Caenorhabditis elegans by a mechanism different to that of the anthelmintic drug Levamisole. Effects are also observable on oviposition, which was diminished in the wild-type worms. The strong anthelmintic effects in crude extracts of these plants warrants future work to identify their active compounds and to elucidate their molecular mechanisms of action. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  8. A single amino acid substitution in isozyme GST mu in Triclabendazole resistant Fasciola hepatica (Sligo strain) can substantially influence the manifestation of anthelmintic resistance.

    PubMed

    Fernández, V; Estein, S; Ortiz, P; Luchessi, P; Solana, V; Solana, H

    2015-12-01

    The helminth parasite Fasciola hepatica causes fascioliasis in human and domestic ruminants. Economic losses due to this infection are estimated in U$S 2000-3000 million yearly. The most common method of control is the use of anthelmintic drugs. However, there is an increased concern about the growing appearance of F. hepatica resistance to Triclabendazole (TCBZ), an anthelmintic with activity over adult and young flukes. F. hepatica has eight Glutathione S-Transferase (GST) isozymes, which are enzymes involved in the detoxification of a wide range of substrates through chemical conjugation with glutathione. In the present work we identified and characterized the GST mu gene isolated from the TCBZ-susceptible and TCBZ-resistant F. hepatica strains. Total RNA was transcribed into cDNA by reverse transcription and a 657 bp amplicon corresponding to the GST mu gene was obtained. The comparative genetic analysis of the GST mu gene of the TCBZ susceptible strain (Cullompton) and TCBZ resistant strain (Sligo) showed three nucleotide changes and one amino acid change at position 143 in the GST mu isozyme of the TCBZ-resistant strain. These results have potential relevance as they contribute better understand the mechanisms that generate resistance to anthelmintics. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Pharmaceutical treatments of gastrointestinal nematode infections of sheep--future of anthelmintic drugs.

    PubMed

    Sargison, N D

    2012-09-30

    Various interacting factors have been identified to explain why health plans for nematode parasite control, based on conventional epidemiological knowledge and involving pharmaceutical treatments of their sheep hosts have become unsustainable. Of these, the emergence of anthelmintic resistance has had a major impact on the economics of sheep farming, necessitating fundamental managemental changes. This review focusses on the use of anthelmintic drugs for the control of gastrointestinal nematode infections in sheep, emphasising the need to develop sustainable strategies in the face of inevitable parasite evolution in response to exposure to anthelmintic drugs and other noxious stimuli, or favourable opportunities resulting from changing animal management and climatic factors.

  10. Is anthelmintic resistance a concern for heartworm control? What can we learn from the human filariasis control programs?

    PubMed

    Prichard, R K

    2005-10-24

    Heartworm prophylaxis is currently largely dependent on the ability of avermectins and milbemycins to arrest the development of third and fourth stages of Dirofilaria immitis for prolonged periods, without producing adulticidal effects. Major control programs, dependent on the activity of ivermectin, are being implemented for human onchocerciasis and lymphatic filariasis. The avermectins and milbemycins act on glutamate-gated and gamma-aminobutyrate-gated chloride channel subunit proteins in nematodes. Ivermectin resistance has been widely described in trichostrongylid nematodes of ruminants. There is evidence that when ivermectin resistance occurs in nematodes, there may be selection on some, but not all of the genes that code for ligand-gated chloride channel subunit proteins as well as on some ABC-transporter genes, whose products may be involved in regulating macrocyclic lactone drug concentrations at receptors, and on some structural protein genes of amphidial neurones. Although ivermectin resistance has not been reported in filarial nematodes, there have recently been reports of suboptimal responses to ivermectin in Onchocerca volvulus. Evidence has been found of ivermectin selection on at least ABC-transporter genes and some neuronal structural protein genes in O. volvulus. To date, there is no evidence of avermectin/milbemycin resistance in D. immitis, also a filarial nematode. Chemotherapy against trichostrongylids of animals, human filariae, and D. immitis, relies on avermectins or milbemycins. However, control involves targeting different stages or processes in the nematode life cycles, different control strategies, different proportions of the nematode population in refugia, and different drug dosage rates. Consideration of the proportion of the D. immitis population normally in refugia, the life cycle stage targeted, and the anthelmintic dosages used suggest that it is unlikely that significant avermectin/milbemycin resistance will be selected in D

  11. Haemonchotolerance in West African Dwarf goats: contribution to sustainable, anthelmintics-free helminth control in traditionally managed Nigerian dwarf goats.

    PubMed

    Chiejina, Samuel N; Behnke, Jerzy M; Fakae, Barineme B

    2015-01-01

    West African Dwarf (WAD) goats are extremely important in the rural village economy of West Africa, but still little is known about their biology, ecology and capacity to cope with gastrointestinal nematode (GIN) infections. Here, we summarise the history of this breed and explain its economic importance in rural West Africa. We review recent work showing that Nigerian WAD goats are highly trypanotolerant and resist infections with Haemonchus contortus more effectively than other breeds of domestic goat (haemonchotolerance). We believe that haemonchotolerance is largely responsible for the generally low level GIN infections and absence of clinical haemonchosis in WADs under field conditions, and has contributed to the relatively successful and sustainable, anthelmintics-free, small-scale system of goat husbandry in Nigeria's humid zone, and is immunologically based and genetically controlled. If haemonchotolerance can be shown to be genetically controlled, it should be possible to exploit the underlying genes to improve GIN resistance among productive fibre and milk producing breeds of goats, most of which are highly susceptible to nematode infections. Genetic resistance to GIN and trypanosome infections would obviate the need for expensive chemotherapy, mostly unaffordable to small-holder farmers in Africa, and a significant cost of goat husbandry in more developed countries. Either introgression of resistance alleles into susceptible breeds by conventional breeding, or transgenesis could be used to develop novel parasite-resistant, but highly productive breeds, or to improve the resistance of existing breeds, benefitting the local West African rural economy as well as global caprine livestock agriculture.

  12. The present status of anthelmintic resistance in gastrointestinal nematode infections of sheep in the northwest of Spain by in vivo and in vitro techniques.

    PubMed

    Martínez-Valladares, M; Martínez-Pérez, J M; Robles-Pérez, D; Cordero-Pérez, C; Famularo, M R; Fernández-Pato, N; Castañón-Ordóñez, L; Rojo-Vázquez, F A

    2013-01-16

    The aim of this study was to update the anthelmintic resistance (AR) status in sheep flocks infected by gastrointestinal nematodes (GIN) by means of in vivo and in vitro methods in the northwest of Spain. With this objective, we studied the efficacy of benzimidazoles (BZs), imidazothiazoles (IMs) and macrocyclic lactones (MLs), between 2006 and 2011. The sampling area was the Autonomous Community of Castilla y León but the majority of the flocks were located in the province of León. When the mean of GIN eggs per gram (epg) in faeces in a flock was higher than 150, the in vivo Faecal Egg Count Reduction Test (FECRT) was carried out. According to this test, AR was present in 63.6% of flocks, independently of the anthelmintic used. Flocks were mainly resistant to levamisole (LEV) (59.0%), followed by ivermectin (IVM) (27.3%) and albendazole (13.6%). Multidrug-resistance was also observed in 27.2% of the flocks, one of them being resistant to all anthelmintic families, including long-acting moxidectin. Comparing the evolution of AR in the last decade, between 1999 and 2011, the level of resistance to BZs and MLs was fairly constant throughout the time by means of the FECRT. However, the resistance to LEV increased significantly in only one decade since during the period 1999-2003 the percentage was 38.5%. The AR status was also measured by in vitro techniques in those flocks with an egg output lower than 150 epg. The prevalence of AR to BZs reached the 35.3% by Egg Hatch Assay. However, the level of resistance reported for LEV and IVM was 61.5% and 23.5%, respectively, by using the Larval Feeding Inhibition Assay, percentages very similar to those reported with the FECRT. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Efficacy of a combined oral formulation of derquantel-abamectin against the adult and larval stages of nematodes in sheep, including anthelmintic-resistant strains.

    PubMed

    Little, Peter R; Hodge, Andrew; Maeder, Steven J; Wirtherle, Nicole C; Nicholas, David R; Cox, George G; Conder, George A

    2011-09-27

    Derquantel (DQL), a semi-synthetic member of a novel anthelmintic class, the spiroindoles, in combination with abamectin (ABA) [as the combination product STARTECT(®)] is a new entry for the treatment and control of parasites in sheep. The 19 studies reported herein were conducted in Australia, New Zealand, South Africa and the United Kingdom to demonstrate the efficacy of derquantel-abamectin (DQL-ABA) against a broad spectrum of gastrointestinal and respiratory nematodes of sheep, and to support registration of the combination product. Eleven studies were conducted using natural or experimental parasite infections with unknown or unconfirmed resistance, while eight studies utilised isolates/strains with confirmed or well characterised resistance to one or more currently available anthelmintics, including macrocyclic lactones. All studies included DQL-ABA and negative control groups, and in selected studies one or more reference anthelmintic groups were included. In all studies the commercial formulation of DQL-ABA was administered orally at 2mg/kg DQL and 0.2mg/kg ABA; placebo was administered in the same volume as DQL-ABA; and reference anthelmintics were administered as per label recommendations, except in one instance where levamisole was administered at twice the label dose. Infection, necropsy, worm collection and worm counting procedures were performed using standard techniques. Efficacy was calculated based on the percentage reduction in geometric mean worm count relative to negative control for each nematode species and lifecycle stage targeted. Twenty-two isolates/strains used in the eight studies targeting resistant worms had proven resistance: three to one anthelmintic class, eleven to two classes and eight to three or more classes; of these resistant strains, 16 demonstrated resistance to a macrocyclic lactone anthelmintic. Regardless of resistance status in the 19 studies, DQL-ABA controlled a broad range of economically important gastrointestinal

  14. Haemonchotolerance in West African Dwarf goats: contribution to sustainable, anthelmintics-free helminth control in traditionally managed Nigerian dwarf goats

    PubMed Central

    Chiejina, Samuel N.; Behnke, Jerzy M.; Fakae, Barineme B.

    2015-01-01

    West African Dwarf (WAD) goats are extremely important in the rural village economy of West Africa, but still little is known about their biology, ecology and capacity to cope with gastrointestinal nematode (GIN) infections. Here, we summarise the history of this breed and explain its economic importance in rural West Africa. We review recent work showing that Nigerian WAD goats are highly trypanotolerant and resist infections with Haemonchus contortus more effectively than other breeds of domestic goat (haemonchotolerance). We believe that haemonchotolerance is largely responsible for the generally low level GIN infections and absence of clinical haemonchosis in WADs under field conditions, and has contributed to the relatively successful and sustainable, anthelmintics-free, small-scale system of goat husbandry in Nigeria’s humid zone, and is immunologically based and genetically controlled. If haemonchotolerance can be shown to be genetically controlled, it should be possible to exploit the underlying genes to improve GIN resistance among productive fibre and milk producing breeds of goats, most of which are highly susceptible to nematode infections. Genetic resistance to GIN and trypanosome infections would obviate the need for expensive chemotherapy, mostly unaffordable to small-holder farmers in Africa, and a significant cost of goat husbandry in more developed countries. Either introgression of resistance alleles into susceptible breeds by conventional breeding, or transgenesis could be used to develop novel parasite-resistant, but highly productive breeds, or to improve the resistance of existing breeds, benefitting the local West African rural economy as well as global caprine livestock agriculture. PMID:25744655

  15. Resistance of gastrointestinal nematodes to the most commonly used anthelmintics in sheep, cattle and horses in Spain.

    PubMed

    Martínez-Valladares, M; Geurden, T; Bartram, D J; Martínez-Pérez, J M; Robles-Pérez, D; Bohórquez, A; Florez, E; Meana, A; Rojo-Vázquez, F A

    2015-07-30

    The objective of this study was to evaluate the status of anthelmintic resistance (AR) in ruminants and horses in Spain. The efficacy of commonly used macrocyclic lactones (MLs) - ivermectin (IVM) and moxidectin (MOX) - was measured in sheep, cattle and horses. In addition, albendazole (ABZ) and levamisole (LEV) were evaluated in sheep and oxibendazole (OXI) and pyrantel (PYR) in horses. Efficacy was evaluated based on the difference between the arithmetic mean pre- and post-treatment faecal egg count (in cattle and horses), or compared to an untreated control group (in sheep). AR was present when the percentage reduction in egg count was <95% and the lower 95% confidence interval (CI) was <90%; if only one of these two criteria was met, the finding was recorded as suspected AR (SAR). In horses, AR-PYR and OXI was considered when the percentage reduction in egg count was ≤ 90% and the lower 95% CI was ≤ 80%. For each animal species, at least 10 study sites were selected. AR to at least one of the drugs was detected in all 10 sheep flocks; the main parasite identified after treatment was Teladorsagia circumcincta. Moreover, in 5 flocks multidrug resistance was identified, on 4 farms to drugs from different families, on one farm to both MOX and IVM and on another farm to all drugs tested. In cattle, the efficacy of both MOX and IVM was 100% on 4 and 3 farms, respectively, and therefore 60% of these farms were considered to have AR or SAR to both MLs. The most frequent parasite identified after treatment was Trichostrongylus spp., although Ostertagia ostertagi was also identified after treatment on one farm. In contrast to ruminants, the 4 drugs evaluated in horses were highly efficacious against strongyles, with efficacies for the MLs and OXI between 95 and 100% and between 94 and 100% for PYR, although 3 herds were SAR against PYR. In conclusion, AR to at least one of the commonly used drugs was identified on all sheep flocks investigated in the northwest of

  16. Comparative efficacy of different anthelmintics against fenbendazole-resistant nematodes of pashmina goats.

    PubMed

    Ram, H; Rasool, T J; Sharma, A K; Meena, H R; Singh, S K

    2007-08-01

    A trial using albendazole, albendazole plus rafoxanide combination, ivermectin and doramectin was conducted in Pashmina goats having history of fenbendazole resistance to Haemonchus spp. and maintained at high altitude (>2350 m above sea level). Day 0 infection level was variable in different groups of animals and their larval cultures indicated Haemonchus, Trichostrongylus, Ostertagia and Oesophagostomum spp. infection, in addition to Nematodirus spp. as observed in egg counts. Efficacy of drugs was calculated on day 14 post treatment by faecal egg count reduction test (FECRT). Albendazole was least effective (14%) followed by its combination with rafoxanide (54%). However, ivermectin and doramectin were 96% and 94% effective against gastrointestinal nematodes of Pashmina goats. It was concluded that use of albendazole and its combination with rafoxanide are ineffective in controlling the nematodes of goats at this farm; hence, future use must be avoided. However, regular monitoring of the efficacy of ivermectin and doramectin is needed.

  17. Modelling the benefits of a new class of anthelmintic in combination.

    PubMed

    Leathwick, D M

    2012-05-04

    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

  18. Field efficacy of four anthelmintics and confirmation of drug-resistant nematodes by controlled efficacy test and pyrosequencing on a sheep and goat farm in Denmark.

    PubMed

    Peña-Espinoza, Miguel; Thamsborg, Stig M; Demeler, Janina; Enemark, Heidi L

    2014-12-15

    We describe a case of anthelmintic resistance on one of the largest organic small ruminant farms in Denmark. The flock was established in 2007 by purchase of animals from other Danish farms and had history of clinical parasitism, high mortality of young stock and anthelmintic treatment failure. In October 2011, 40 lambs and 40 kids were selected for a faecal egg count reduction test (FECRT) with fenbendazole (FBZ), ivermectin (IVM), moxidectin (MOX) and levamisole (LEV). Lambs were treated with the recommended sheep dose of each product while kids received the sheep dose of IVM, 1.5× sheep dose of MOX and 2× sheep dose of FBZ and LEV. Untreated lambs and kids were also included and three methods for calculating faecal egg count (FEC) reduction were compared. In a subsequent investigation, a controlled efficacy test (CET) with FBZ and IVM was performed in lambs infected with Haemonchus contortus and Trichostrongylus colubriformis isolated from adult goats on the farm. Recovered specimens of H. contortus were subjected to pyrosequencing for detection of single nucleotide polymorphisms (SNPs) related to benzimidazole (BZ) resistance. During the FECRT, FECs in untreated lambs dropped significantly by 47%. No FEC reduction was detected in untreated kids. After FBZ treatments, FEC reductions in lambs and kids ranged from 15 to 54% and 49-56%, respectively, according to the different calculation methods. Post IVM treatments, FEC reductions in lambs and kids varied between 71-90% and 81-83%, correspondingly. LEV and MOX reduced FECs by 98-100% in both species. In the CET, FBZ reduced H. contortus worm counts by 52-56% and no reduction in T. colubriformis counts were detected after treatment. IVM eliminated 100% of H. contortus and reduced T. colubriformis counts by 84-92%, according to different calculation methods. Pyrosequencing of isolated H. contortus revealed increased frequencies of the BZ resistance-related SNP in codon 200 of the β-tubulin isotype 1 gene

  19. Management of drug-resistant cyathostominosis on a breeding farm in central North Carolina.

    PubMed

    Little, D; Flowers, J R; Hammerberg, B H; Gardner, S Y

    2003-05-01

    Possible anthelmintic resistance on a breeding farm where a rapid rotation anthelmintic programme had been implemented for 9 years was investigated. Cyathostomins resistant to fenbendazole and pyrantel were documented by faecal worm egg count reduction test (FWECRT). To 1) manage small strongyle transmission in a herd of horses in which resistance to both pyrantel pamoate and fenbendazole was identified and thereby reduce the risk of clinical disease in the individual animal, 2) monitor the change in resistance patterns over time and 3) monitor the efficacy of ivermectin over the study period. Targeted ivermectin treatment of horses on the farm was instituted for mature horses with faecal worm egg counts (FWEC) > 200 eggs/g (epg) and for horses < age 2 years with FWEC > 100 epg. Over a 30 month period, targeted ivermectin treatment achieved acceptable control in mares, as judged by FWEC, and improved control of patent cyathostome infection in consecutive foal crops. Egg reappearance time (ERT) after treatment with ivermectin was < 8 weeks in mares and foals more frequently in the second year of the study than in the first year. Numbers of anthelmintic treatments were reduced by 77.6 and 533% in the mare and foal group, respectively. Targeted ivermectin treatment may be an economically viable method of managing multiple drug resistant cyathostominosis. Use of ivermectin should be monitored closely for development of resistance.

  20. In silico exploration of the impact of pasture larvae contamination and anthelmintic treatment on genetic parameter estimates for parasite resistance in grazing sheep.

    PubMed

    Laurenson, Y C S M; Kyriazakis, I; Bishop, S C

    2012-07-01

    A mathematical model was developed to investigate the impact of level of Teladorsagia circumcincta larval pasture contamination and anthelmintic treatment on genetic parameter estimates for performance and resistance to parasites in sheep. Currently great variability is seen for published correlations between performance and resistance, with estimates appearing to vary with production environment. The model accounted for host genotype and parasitism in a population of lambs, incorporating heritable between-lamb variation in host-parasite interactions, with genetic independence of input growth and immunological variables. An epidemiological module was linked to the host-parasite interaction module via food intake (FI) to create a grazing scenario. The model was run for a population of lambs growing from 2 mo of age, grazing on pasture initially contaminated with 0, 1,000, 3,000, or 5,000 larvae/kg DM, and given either no anthelmintic treatment or drenched at 30-d intervals. The mean population values for FI and empty BW (EBW) decreased with increasing levels of initial larval contamination (IL(0)), with non-drenched lambs having a greater reduction than drenched ones. For non-drenched lambs the maximum mean population values for worm burden (WB) and fecal egg count (FEC) increased and occurred earlier for increasing IL(0), with values being similar for all IL(0) at the end of the simulation. Drenching was predicted to suppress WB and FEC, and cause reduced pasture contamination. The heritability of EBW for non-drenched lambs was predicted to be initially high (0.55) and decreased over time with increasing IL(0), whereas drenched lambs remained high throughout. The heritability of WB and FEC for all lambs was initially low (∼0.05) and increased with time to ∼0.25, with increasing IL(0) leading to this value being reached at faster rates. The genetic correlation between EBW and FEC was initially ∼-0.3. As time progressed the correlation tended towards 0, before

  1. Management practices and use of anthelmintics on dairy cattle farms in The Netherlands: results of a questionnaire survey.

    PubMed

    Borgsteede, F H; Sol, J; van Uum, A; de Haan, N; Huyben, R; Sampimon, O

    1998-07-17

    In December 1996, a questionnaire about farm management and parasite control measures in calves was sent to 956 randomly chosen dairy cattle farmers in The Netherlands. Another 150 farmers in the vicinity of Deventer who had vaccinated their calves in 1995 against lungworm were approached with the same questions. Our object was to investigate the consequences on worm control of the withdrawal of the lungworm vaccine from the market for reasons of possible BSE contamination of the vaccine. OF the returned questionnaires, 411 (43%) of the 'at random' group and 89 (59.3%) of the 'Deventer' group were valid. The most important data with regard to the farms of the 'at random' group (41) were: mean area 31.6 ha, mean number of calves 23, heifers 23 and milking cows 53. Sheep (mean 37) were present on 18.3% of the farms. With regard to management: 74.5% of the farmers turned the calves in their first year onto pasture, 25.5% kept them indoors. The average time on pasture was ca. 5 months. Rational grazing was practise on 81.4% of the farms, on 18.6% calves were set stocked. The first pasture of the calves was mown before turn-out on 72.9% of the farms. On 48.2% of these farms, calves were always moved to mown pastures. With regard to treatments: 33.8% of the farmers vaccinated their calves against lungworm in the years 1993, 1994 and 1995. Despite the withdrawal of the vaccine from the market in 1996, 7.2% of the farmers vaccinated their calves as recommended, with two doses, and 13.1% with a single dose. At turn-out, 41.5% of the farmers gave the calves a preventive anthelmintic treatment. Of these treatments, 66.9% were sustained of pulse release long acting device. During the grazing season, 36.6% of the farmers treated their calves. After housing 50.3% of the farmers gave a treatment. Signs of lungworm infection were noticed on 18.6% of the farms. Of the 'Deventer' group (89 farmers), 96.6% turned the calves out, Of these farmers, 86.0% had used the lungworm vaccine

  2. [ANTHELMINTIC SUBSTANCES: MAIN CLASSES, PROBLEMS, TRENDS IN DEVELOPMENT AND PROSPECTS].

    PubMed

    Dzhafarov, M Kh; Vasilevich, F; Dovgalev, A S; Imamkuliev, K D; Pautova, E A

    2016-01-01

    The review chronologically considers the main classes of the currently available anthelminthic substances: early anthelmintic compounds, benzimidazoles, imidazolthiazoles, tetrahydropyrimidines, avermectins and milbemycins, and salicylanilides. Great attention is paid to novel substances (emodepside, monepantel, derquantel, tribendimidine) and promising developments. Some aspects of the molecular mechanisms of action of anthelmintics, their resistance, and alternative dehelmintization methods are discussed.

  3. β-Tubulin genotypes in six species of cyathostomins from anthelmintic-naive Przewalski and benzimidazole-resistant brood horses in Ukraine.

    PubMed

    Blackhall, William J; Kuzmina, Tetyana; von Samson-Himmelstjerna, Georg

    2011-10-01

    Resistance to benzimidazoles (BZ) in the gastrointestinal nematodes of livestock is characterised by the presence of specific polymorphisms in the β-tubulin isotype 1 protein, a component of microtubules. The most prevalent polymorphism associated with resistance in nematodes infecting cattle, sheep, and goats is found at codon 200, with minor occurrences of polymorphisms at codons 167 and 198. In the cyathostomins that infect horses, however, a polymorphism at codon 167 appears to be more common than the codon 200 polymorphism. In the present study, a focussed analysis of PCR-amplified β-tubulin fragments incorporating the above-mentioned three polymorphic sites in isotype 1 and 2 genes in worms of six species of cyathostomins, Cylicocyclus nassatus, Cylicocyclus ashworthi, Cyathostomum catinatum, Cylicostephanus goldi, Cylicostephanus longibursatus, and Coronocyclus coronatus, was performed. Worms were collected from two distinct horse populations, i.e. they were collected from Przewalski horses of the Askania-Nova Biosphere Reserve that had never received any anthelmintic treatment and from brood horses of the Dubrovsky farm where benzimidazole resistance had become established. DNA was extracted and sequenced from three worms of each species and population as well as from pools of 50 male C. nassatus and C. catinatum from both populations. The vast majority of putatively BZ resistance-associated TAC alleles were found at codon 167, compared to codon 200. The former allele occurred in isotype 1 in all six species of the supposedly benzimidazole-resistant cyathostomins from Dubrovsky horses. None of the polymorphisms associated with resistance was found in the corresponding isotype 2 codons nor at codon 198 in any of the six species of cyathostomins (neither single nor pooled worm DNA) from either of the two populations. These findings further support the predominant association of β-tubulin isotype 1 and therein codon 167 with BZ resistance in cyathostomins.

  4. Anthelmintic treatment strategies: current status and future.

    PubMed

    Williams, J C

    1997-11-01

    Despite the array of anthelmintics and endectocides and delivery systems available for use in the prevention and control of nematode parasites of ruminants, the number of highly effective control programs that have been developed and even the number of such programs that have been successfully implemented in commercial animal production, there have been no recent innovations or discoveries in regard to strategies, new anthelmintics, or systems for controlling nematode parasites through anthelmintic use. In the traditional sense of chemotherapy-chemoprophylaxis, we have probably achieved the maximum effect of what is possible from excellent anthelmintics developed by the pharmaceutical industry over the last 35 years, i.e. from thiabendazole through levamisole and morantel tartrate, to more advanced benzimidazoles and to the avermectins and milbemycins. At the core of all anthelmintic treatment-related problems is the lingering conception among a large body of animal producers that anthelmintic treatment is the only effort needed to control parasitism and its effects on host animals. This concept has given rise to the long-standing difficulty of drug resistance in sheep nematodes and the not remote possibility of its development in nematodes of cattle. Along with this are serious concerns over environmental toxicity, tissue residues and enormous financial investment to develop new and novel anthelmintic compounds. Progress is being made in current and intensive searches for development and testing of control approaches alternative to anthelmintics, e.g. helminth vaccines, biological control agents such as fungi, selection of resistant sires, alternative chemicals and nematode growth regulators. A timetable for when alternative controls can be developed fully and put into practical use cannot be predicted. It is universally acknowledged among parasitologists that existing anthelmintics must be preserved and utilized judiciously to ensure continued effectiveness. A

  5. The maintenance of anthelmintic efficacy in sheep in a Mediterranean climate.

    PubMed

    Rinaldi, Laura; Morgan, Eric R; Bosco, Antonio; Coles, Gerald C; Cringoli, Giuseppe

    2014-06-16

    To determine how far management practices on small ruminant dairy flocks in southern Italy have influenced the development of anthelmintic resistance (AR), faecal egg count (FEC) reduction tests were run on 54 sheep farms using the FLOTAC technique with a sensitivity of 2 eggs per gram of faeces. Tests were run on groups of sheep (12-20 animals per group) using six anthelmintics administered orally: levamisole on 8 farms, ivermectin (half and full dose) on 8 farms, moxidectin on 3 farms, monepantel on 8 farms, netobimin on 22 farms (pooled samples) and albendazole on 5 farms (pooled samples). Different formulae and statistics were used to calculate FEC reductions and confidence intervals based on the presence of a control group and/or the use of pooled samples. A very high average efficacy was obtained with all anthelmintics tested as follows: levamisole 99.3% (range across farms 98-100%), ivermectin half dose 99.5% (98.0-100%), ivermectin full dose 99.9% (99.3-100%), moxidectin 100% (99.9-100%), monepantel 99.4% (97-100%), netobimin 99.1% (92-100%) and albendazole 100%. The results suggest that the development of AR in small ruminants could be limited in countries with a Mediterranean type of climate provided that refugia of the nematode populations are maintained, anthelmintic use is restricted and movement of animals is not permitted to spread resistance.

  6. Alternatives to anthelmintics for the control of nematodes in livestock.

    PubMed

    Stear, M J; Doligalska, M; Donskow-Schmelter, K

    2007-02-01

    Efficient and welfare-friendly livestock production demands the control of nematode infection. Current control measures rely upon anthelmintic treatment but are threatened by the widespread evolution of drug-resistance in parasite populations. Several methods have been advocated to control nematodes without relying on effective anthelmintics. These include grazing management, biological control, nutritional supplementation, vaccination, and genetic approaches. Each method has its advantages and disadvantages. There are several grazing management schemes that can reduce the severity of infection but they are insufficient on their own to control infection. Biological control includes the use of predatory fungi to control nematode populations and the use of pasture species that can reduce the intensity of infection. Fungi can control nematodes but the current requirement for daily feeding means that this approach will be most useful for animals that are handled daily. Feeding supplementary protein can control nematode infection. The method is simple but can be expensive and may not be cost-effective for some marginal enterprises. Genetic approaches include the use of resistant breeds and selective breeding. Some breeds will thrive in conditions that kill animals from other breeds but substitution of resistant breeds is not always feasible. Selective breeding is effective and inexpensive but requires a high level of expertise. The most appropriate method or set of methods to minimize the adverse consequences of nematode infection may vary among farms.

  7. Selection for anthelmintic resistant Teladorsagia circumcincta in pre-weaned lambs by treating their dams with long-acting moxidectin injection

    PubMed Central

    Leathwick, D.M.; Miller, C.M.; Fraser, K.

    2015-01-01

    Administration of long-acting anthelmintics to pregnant ewes prior to lambing is a common practice in New Zealand. Today, most of these products contain macrocyclic lactone (ML) actives, which because of their lipophilic nature, are detectable in the milk of treated animals and in the plasma of their suckling offspring. This study was conducted to confirm the transfer of ML actives to lambs in the ewe's milk, and to assess whether this could result in selection for ML resistant nematodes in the lamb. Ninety, twin bearing Romney ewes were treated before lambing with a long-acting injectable formulation of moxidectin, a 100-day controlled release capsule (CRC) containing abamectin and albendazole, or remained untreated. After lambing, seven ewes from each treatment group were selected for uniformity of lambing date and, along with their twin lambs, relocated indoors. At intervals, all ewes and lambs were bled, and samples of ewe's milk were collected, for determination of drug concentrations. Commencing 4 weeks after birth all lambs were dosed weekly with 250 infective larvae (L3) of either an ML-susceptible or –resistant isolate of Teladorsagia circumcinta. At 12 weeks of age all lambs were slaughtered and their abomasa recovered for worm counts. Moxidectin was detected in the plasma of moxidectin-treated ewes until about 50 days after treatment and in their lambs until about day 60. Abamectin was detected in the plasma of CRC-treated ewes until the last sample on day 80 and in the plasma of their lambs until about day 60. Both actives were detectable in milk of treated ewes until day 80 after treatment. Establishment of resistant L3 was not different between the treatment groups but treatment of ewes with moxidectin reduced establishment of susceptible L3 by 70%, confirming the potential of drug transfer in milk to screen for ML-resistance in the suckling lamb. PMID:27120068

  8. Prevalence of anthelmintic resistance on sheep and goat farms in the mid-Atlantic region and comparison of in vivo and in vitro detection methods

    USDA-ARS?s Scientific Manuscript database

    Despite strong economic opportunities and incentives for small ruminant production, their health and productivity are often severely affected by parasitic disease. To combat these effects, most farms administer anthelmintics to their animals at frequent intervals, and without consideration to princ...

  9. In vitro anthelmintic activity of aqueous leaf extract of Annona muricata L. (Annonaceae) against Haemonchus contortus from sheep.

    PubMed

    Ferreira, L E; Castro, P M N; Chagas, A C S; França, S C; Beleboni, R O

    2013-07-01

    Despite the overall progress of sheep farming in Brazil, infections with the gastrointestinal parasite Haemonchus contortus represent one the most important problems in sheep production, aggravated by the increasing resistance of nematodes to traditional anthelmintic drugs caused by inadequate sheep flock management by breeders. Ethnopharmacological data indicate Annona muricata as a promising alternative for the control of gastrointestinal nematodes because of its general anthelmintic properties. The aim of this work was to evaluate the in vitro anthelmintic effects of A. muricata aqueous leaf extract against eggs, infective larvae and adult forms of parasitic nematode H. contortus. At higher doses, A. muricata extract showed 84.91% and 89.08% of efficacy in egg hatch test (EHT) and larval motility test (LMT), respectively. In the adult worm motility test, worms were completely immobilized within the first 6-8h of nematode exposition to different dilutions of extract. Phytochemical analysis indicated the presence of phenolic compounds in A. muricata aqueous leaf extract that may be responsible for the anthelmintic effects observed. Moreover those results validate the traditional use of A. muricata as a natural anthelmintic and then the pharmacological potential of its compounds for future in vivo investigations.

  10. Basic and clinical pharmacology contribution to extend anthelmintic molecules lifespan.

    PubMed

    Lanusse, Carlos; Lifschitz, Adrian; Alvarez, Luis

    2015-08-15

    The correct use of pharmacology-based information is critical to design successful strategies for the future of parasite control in livestock animals. Integrated pharmaco-parasitological research approaches have greatly contributed to optimize drug activity. In an attempt to manage drug resistance in helminths of ruminants, combinations of two or more anthelmintics are being used or promoted, based on the fact that individual worms may have a lower degree of resistance to a multiple component formulation, when each chemical has a different mode of action compared to that observed when a single compound is used. However, as emphasized in the current review, the occurrence of potential pharmacokinetic and/or pharmacodynamic interactions between drug components highlights the need for deeper and integrated research to identify the advantages or disadvantages associated with the use of combined drug preparations. This review article provides integrated pharmacokinetic/pharmacodynamic and clinical pharmacology information pertinent to preserve the traditional and modern active ingredients as practical tools for parasite control. Novel pharmacological data on derquantel and monepantel, as representatives of modern anthelmintics for use in livestock, is summarized here. The article also summarizes the pharmaco-parasitological knowledge considered critical to secure and/or extend the lifespan of the recently available novel molecules. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Investigating interactions between UK horse owners and prescribers of anthelmintics.

    PubMed

    Easton, Stephanie; Pinchbeck, Gina L; Tzelos, Thomas; Bartley, David J; Hotchkiss, Emily; Hodgkinson, Jane E; Matthews, Jacqueline B

    2016-12-01

    Helminths are common pathogens of equids and anthelmintic resistance is a major issue in cyathostomin species and Parascaris equorum. At the heart of mitigating the impact of increasing anthelmintic resistance levels, is the responsible dissemination and use of these medicines following best practice principles. There is a paucity of information on interactions between horse owners and anthelmintic prescribers and how this shapes control. Here, a study was undertaken to determine opinions and experiences of horse owners as they relate to anthelmintics purchase and implementation of best practice control. An online survey was distributed via email and social media to explore owners' experiences of purchasing anthelmintics from United Kingdom prescribers, these being veterinarians, suitably qualified persons (SQPs) and pharmacists. Owner responses (n=494) were analysed statistically to compare answers of respondents grouped according to: (i) from whom they bought anthelmintics (Veterinarians n=60; SQPs n=256; Pharmacists n=42; More than one channel n=136), and (ii) by which route (Face-to-face n=234; Telephone n=31; Online n=226) they purchased. Owners who purchased from veterinarians predominantly did so face-to-face (81.3%), whilst those that bought from SQPs purchased via face-to-face (48.8%) and online (46.0%) interactions. Those who purchased from pharmacists predominantly bought anthelmintics online (76.2%). Participants who bought from veterinarians were more likely to view certain factors (i.e. time to talk to the supplier, supplier knowledge) as more important than those who purchased from other prescribers. Those who purchased from veterinarians were more likely to be recommended faecal egg count (FEC) test analysis; however, there was high uptake of FEC testing across all groups. There was a low uptake of anthelmintic efficacy testing; regardless of the prescriber type from whom anthelmintics were purchased. Those who purchased from veterinarians were more

  12. Comparative anthelmintic activity investigation of selected ethno-medicinal weeds

    NASA Astrophysics Data System (ADS)

    Pueblos, Kirstin Rhys S.; Bajalla, Mark; Pacheco, Dixie; Ganot, Sheila; Paig, Daisy; Tapales, Radyn; Lagare, Jeanne; Quimque, Mark Tristan J.

    2017-01-01

    Helminth infections are one of the seriously neglected potent diseases in many parts of the world. The problems of parasitic helminthes becoming resistant to currently available anthelmintic drugs pose a challenge for the search - relying on natural products - for new and better anthelmintics. In this paper, four abundant Philippine weeds: Chrysopogon aciculatus Trin. Cyperus brevifolius Rottb., Ruellia tuberosa Linn. and Saccharum spontaneum Linn. were investigated for their anthelmintic activities to establish basis of their folkloric claim. The hexane-soluble and chloroform-soluble extracts were obtained through sequential solvent partitioning of the crude ethanolic extract of the air-dried aerial part of each plant sample. Meanwhile, the decoction was obtained from fresh aerial part of the plant samples. All extracts were then subjected to in vitro anthelmintic screening at different concentration as per method of Ghosh, et al. against African nightcrawler earthworms (Eudrillus euginiae) in which the activity of the extracts was determined by correlation with time. The anthelmintic bioassay results revealed a dose-dependent toxicity relationship. It indicated relatively low anthelmintic activities of the decoction of the four plant samples as compared to their corresponding crude ethanol extracts. Among the crude ethanol extracts, C. brevifolius (CBE) gave fastest time to bring about paralysis and death to the test organisms at all concentrations tested. For the hexane extracts, R. tuberosa (RTH) gave better activity among other plant samples. Lastly, among the chloroform-soluble extracts, both that of C. brevifolius (CBC) and R. tuberosa (RTC) comparably showed strongest anthelmintic activities at all tested concentrations, thus, exhibited best anthelmintic activity that is remarkably comparable to the positive control, Mebendazole at the highest concentration tested. In fact, CBC and RTC showed highest anthelmintic potential compared to all extracts tested in

  13. Anthelmintic activity of KSI-4088 against Caenorhabditis elegans.

    PubMed

    Kaewintajuk, Kusuma; Cho, Pyo Yun; Kim, Sung Yeon; Lee, Eun Sil; Lee, Hyeon-Kyu; Choi, Eun Bok; Park, Hyun

    2010-06-01

    Anthelmintic resistance is a serious global problem because of the worldwide spread of resistant nematodes in animals and humans. This has triggered increasing investment in research for new anthelmintics. Over the past decade, Caenorhabditis elegans has become a popular model organism for parasitic nematode research, and many examples have been published to illustrate its use. In this study, we investigated the effect of KSI-4088 on the egg hatching, larval development, and migration of the nematode worm C. elegans compared with ivermectin and levamisole (well-known anthelmintic drugs). KSI-4088 demonstrated anthelmintic activity on all assays of C. elegans. The anthelmintic activity of KSI-4088 on egg hatching and larval development showed especially strong activity, but assays showed that ivermectin and levamisole had no effects on C. elegans. In addition, KSI-4088 was capable of producing a change in the timing of the development of the worms at the L1-L3 and L4 stage. Also, we demonstrate that C. elegans L3-4 are more sensitive than adults to KSI-4088 in assay of migration. Our results indicate that KSI-4088 is an active anthelmintic compound that should be further investigated with the aim of developing a potent drug against nematodes.

  14. Management of resistant depression.

    PubMed Central

    Warneke, L.

    1996-01-01

    Treatment-resistant depression is a relative concept. It has been formally defined as a mood disorder that fails to respond to three adequate trials of antidepressants. However, treatment resistance is relative to the expertise and knowledge of the treating physician and the availability of resources, such as electroconvulsive therapy. Only about 7% of patients show absolute treatment resistance, and even they can be helped. PMID:8894244

  15. Insecticide Resistance Management

    DTIC Science & Technology

    2013-01-01

    been a side effect of insect vector control programs since 1914, and insect disease vectors in over 45 countries are resistant to at least one...the CDC and WHO bioassays can be performed on various insects , the remainder of the guide will focus specifically on how to detect resistance in...mosquito vector populations. For a description of how to develop a bioassay for resistance testing in other groups of insects , refer to the following

  16. Understanding and managing resistance.

    PubMed

    Berger, D S

    1998-01-01

    As many as 25 to 45 percent of patients using triple therapy with protease inhibitors will develop resistance due to a change in the genetic HIV code. However, patients who develop resistance may still benefit clinically when protease inhibitors are used in combination with other antiretrovirals. These patients may not have undetectable viral loads although they may have stable T4-cell counts. Resistance does not always lead to disease progression. Newer drugs under development or available through compassionate track programs may benefit people with resistance. DMP-266 (Sustiva) is a non-nucleoside reverse transcriptase inhibitor that shows promise for these patients. Other drugs in development include Compound 141, 1592, and adefovir.

  17. Anthelmintic efficacy in captive wild impala antelope (Aepyceros melampus) in Lusaka, Zambia.

    PubMed

    Nalubamba, King S; Mudenda, Ntombi B

    2012-05-25

    There has been an increase in the number of wild ungulates kept in captivity for ecotourism and conservation in Zambia and these animals are susceptible to a number of diseases including gastrointestinal helminth infections. Surveys to determine anthelmintic efficacy to gastrointestinal nematodes in captive-wildlife are not common and there have been no reports of anthelmintic resistance in captive-wildlife in Zambia. This study was carried out to determine the efficacy of the benzimidazole anthelmintic fenbendazole in captive wild impala (Aepyceros melampus) in Zambia. During the month of April 2011, at the end of the rainy season, the faecal egg count reduction test was performed at a private game facility for assessing anthelmintic efficacy of oral fenbendazole and the anthelmintic treatment showed an efficacy of 90%. Haemonchus spp. and Trichostrongylus spp. were the predominant genera present before treatment, but Haemonchus spp. larvae were the only genus recovered from the faecal cultures after anthelmintic treatment. This represents the first documentation of anthelmintic treatment failure in captive wild-antelopes in Zambia. It also demonstrated the ineffectiveness of the common traditional practice of deworming captive-wild antelopes at the end of the rainy season due to the rapid re-infection of impala that occurs due to high pasture infectivity. Suggestions on changes to current anthelmintic use/practices that will make them more efficacious and reduce the possibility of development of anthelmintic resistance in captive wild game in Zambia are also made.

  18. Resistance Management Research Status

    EPA Science Inventory

    Long-term sustainability of genetically modified corn expressing Bt relies on the validity of assumptions underlying IRM models used by the EPA and the ability of EPA to monitor, detect and react to insect resistance when it develops. The EPA is developing a multi-tiered approac...

  19. Resistance Management Research Status

    EPA Science Inventory

    Long-term sustainability of genetically modified corn expressing Bt relies on the validity of assumptions underlying IRM models used by the EPA and the ability of EPA to monitor, detect and react to insect resistance when it develops. The EPA is developing a multi-tiered approac...

  20. Geminivirus Management: Disease Resistance

    USDA-ARS?s Scientific Manuscript database

    Begomoviruses are a major constraint for tomato production in many parts of the subtropic and tropics; and the most efficient way to increase tomato production is to use resistant cultivars in association with an IPM program. The Middle East (MERC) and a Guatemalan (CDR) project involved involved d...

  1. Phytochemical analysis and in vitro anthelmintic activity of Lophira lanceolata (Ochnaceae) on the bovine parasite Onchocerca ochengi and on drug resistant strains of the free-living nematode Caenorhabditis elegans.

    PubMed

    Kalmobé, Justin; Ndjonka, Dieudonné; Boursou, Djafsia; Vildina, Jacqueline Dikti; Liebau, Eva

    2017-08-14

    Onchocerciasis is one of the tropical neglected diseases (NTDs) caused by the nematode Onchocerca volvulus. Control strategies currently in use rely on mass administration of ivermectin, which has marked activity against microfilariae. Furthermore, the development of resistance to ivermectin was observed. Since vaccine and safe macrofilaricidal treatment against onchocerciasis are still lacking, there is an urgent need to discover novel drugs. This study was undertaken to investigate the anthelmintic activity of Lophira lanceolata on the cattle parasite Onchocerca ochengi and the anthelmintic drug resistant strains of the free living nematode Caenorhabditis elegans and to determine the phytochemical profiles of the extracts and fractions of the plants. Plant was extracted in ethanol or methanol-methylene chloride. O. ochengi, C. elegans wild-type and C. elegans drug resistant strains were cultured in RPMI-1640 and NGM-agar respectively. Drugs diluted in dimethylsulphoxide/RPMI or M9-Buffer were added in assays and monitored at 48 h and 72 h. Worm viability was determined by using the MTT/formazan colorimetric method. Polyphenol, tannin and flavonoid contents were determined by dosage of gallic acid and rutin. Acute oral toxicity was evaluated using Swiss albino mice. Ethanolic and methanolic-methylene chloride extracts killed O. ochengi with LC50 values of 9.76, 8.05, 6.39 μg/mL and 9.45, 7.95, 6.39 μg/mL respectively for leaves, trunk bark and root bark after 72 h. The lowest concentrations required to kill 50% of the wild-type of C. elegans were 1200 and 1890 μg/mL with ethanolic crude extract, 1000 and 2030 μg/mL with MeOH-CH2Cl2 for root bark and trunk bark of L. lanceolata, respectively after 72 h. Leave extracts of L. lanceolata are lethal to albendazole and ivermectin resistant strains of C. elegans after 72 h. Methanol/methylene chloride extracted more metabolites. Additionally, extracts could be considered relatively safe. Ethanolic and

  2. Ion channels and drug transporters as targets for anthelmintics

    PubMed Central

    Greenberg, Robert M.

    2014-01-01

    Infections with parasitic helminths such as schistosomes and soil-transmitted nematodes are hugely prevalent and responsible for a major portion of the global health and economic burdens associated with neglected tropical diseases. In addition, many of these parasites infect livestock and plants used in agriculture, resulting in further impoverishment. Treatment and control of these pathogens rely on anthelmintic drugs, which are few in number, and against which drug resistance can develop rapidly. The neuromuscular system of the parasite, and in particular, the ion channels and associated receptors underlying excitation and signaling, have proven to be outstanding targets for anthelmintics. This review will survey the different ion channels found in helminths, focusing on their unique characteristics and pharmacological sensitivities. It will also briefly review the literature on helminth multidrug efflux that may modulate parasite susceptibility to anthelmintics and may prove useful targets for new or repurposed agents that can enhance parasite drug susceptibility and perhaps overcome drug resistance. PMID:25554739

  3. Ion channels and drug transporters as targets for anthelmintics.

    PubMed

    Greenberg, Robert M

    2014-12-01

    Infections with parasitic helminths such as schistosomes and soil-transmitted nematodes are hugely prevalent and responsible for a major portion of the global health and economic burdens associated with neglected tropical diseases. In addition, many of these parasites infect livestock and plants used in agriculture, resulting in further impoverishment. Treatment and control of these pathogens rely on anthelmintic drugs, which are few in number, and against which drug resistance can develop rapidly. The neuromuscular system of the parasite, and in particular, the ion channels and associated receptors underlying excitation and signaling, have proven to be outstanding targets for anthelmintics. This review will survey the different ion channels found in helminths, focusing on their unique characteristics and pharmacological sensitivities. It will also briefly review the literature on helminth multidrug efflux that may modulate parasite susceptibility to anthelmintics and may prove useful targets for new or repurposed agents that can enhance parasite drug susceptibility and perhaps overcome drug resistance.

  4. Anthelmintic efficacy and dose determination of Albizia anthelmintica against gastrointestinal nematodes in naturally infected Ugandan sheep.

    PubMed

    Gradé, J T; Arble, B L; Weladji, R B; Van Damme, P

    2008-11-07

    Weight loss, stunted growth, and death caused by gastrointestinal parasites are major constraints to livestock productivity, especially in tropical and developing countries where regular use, and misuse, of anthelmintics has led to nematode resistance. Albizia anthelmintica Brong. (Fabaceae) is traditionally employed throughout East Africa to treat helminth parasitosis in livestock. Reported efficacy has varied from 90% against mixed nematodes to just 19% against Haemonchus contortus alone. The objective of this study was to assess the anthelmintic effect of A. anthelmintica against naturally occurring infections of mixed gastrointestinal parasites, and to establish an effective treatment dose, in sheep under pastoral field conditions of northern Uganda. A. anthelmintica bark was collected and prepared according to local custom and packed into gel capsules. Fifty-five young female local mixed-breed lambs were randomly assigned to six groups, including a positive control group that received levamisole (synthetic anthelmintic) and a negative control group that received no treatment. Following the World Association for the Advancement of Veterinary Parasitology (WAAVP) dose determination guidelines, the other four groups were treated with varying doses of A. anthelmintica. Statistical analyses (using generalized linear models) were performed to assess treatment effect. There was a significant treatment (group) effect on parasite egg/oocyte counts per gram (EPG) for nematodes, but not for coccidia. The most effective dose against nematodes (0.8g, 58.7mg/kg) closely approximates what is usually given by traditional healers, 0.9g/adult sheep. It provided major and significant reduction in EPG as compared to the negative control. Anthelmintic efficacy was estimated using percent faecal egg count reduction (FECR). Other than the positive control, animals in the standard dose group showed the greatest decline in shedding of nematode eggs, with an FECR of 78%. This study

  5. Anthelmintic activity of Indigofera tinctoria against gastrointestinal nematodes of sheep

    PubMed Central

    Meenakshisundaram, Ambalathaduvar; Harikrishnan, Tirunelveli Jayagopal; Anna, Thavasi

    2016-01-01

    Aim: Gastrointestinal (GI) nematodes are considered as a major constraint for successful sheep production. Control of these parasites heavily relies on the use of chemical anthelmintics. Over the past decades, the development of anthelmintic resistance to various groups of anthelmintics and problem of drug residues in animal products has awakened interest in medicinal plants as an alternative source of anthelmintics. Hence, this study was undertaken to evaluate the anthelmintic efficacy of Indigofera tinctoria by scientifically validated in vitro and in vivo tests approved by the World Association for the Advancement of Veterinary Parasitology. Materials and Methods: In vitro assays such as egg hatch assay for ovicidal and larval migration inhibition and larval development assay for larvicidal properties were used to investigate in vitro effect of extracts on strongyle egg and larvae, respectively. Fecal egg count reduction test was conducted in vivo to evaluate the therapeutic efficacy of the extracts administered orally at dose rates of 125, 250, 500 mg/kg to sheep naturally infected with mixed GI nematodes. Results: Ethanolic extract of I. tinctoria demonstrated significant (p<0.01) inhibition on egg hatching at concentrations of 40 mg/ml and 80 mg/ml. In in vivo assay, the ethanolic extract of I. tinctoria reduced the fecal egg count ranging between 30.82% and 47.78% at various doses (125, 250 and 500 mg/kg). Although there was a slight variation, all the hematological parameters were within the normal range reported for sheep. Except for alanine transaminase, the overall mean of all the serum biochemical profile was within the normal range for sheep. Conclusion: Based on the results obtained by in vitro and in vivo assay, the ethanolic extract of I. tinctoria possesses anthelmintic activity and could replace the chemical anthelmintics used presently. PMID:27051192

  6. Anthelmintic activity of acetone extracts from South African plants used on egg hatching of Haemonchus contortus.

    PubMed

    Fouche, Gerda; Sakong, Bellonah M; Adenubi, Olubukola T; Pauw, Elizabeth; Leboho, Tlabo; Wellington, Kevin W; Eloff, Jacobus N

    2016-07-29

    The nematode, Haemonchus contortus, is responsible for major economic losses in the livestock industry. The management of parasites such as H. contortus has been through the use of synthetic parasiticides. This has resulted in the presence of residues in meat and milk, which affects food safety. The development of resistance to available anthelmintics coupled with their high cost has further complicated matters. This has led to the investigation of alternative methods to manage nematodes, including the use of plants and plant extracts as a potential source of novel anthelmintics. Acetone extracts were prepared from 15 South African plant species and their anthelmintic activity determined using the egg hatch assay (EHA). The leaf extract of Cleome gynandra had the best inhibitory activity (68% ± 3%) at a concentration of 2.5 mg/mL, followed by the stem extract of Maerua angolensis (65% ± 5%). The extracts had a relatively low toxicity on Vero cells determined by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) cellular assay.

  7. Caenorhabditis elegans is a useful model for anthelmintic discovery

    PubMed Central

    Burns, Andrew R.; Luciani, Genna M.; Musso, Gabriel; Bagg, Rachel; Yeo, May; Zhang, Yuqian; Rajendran, Luckshika; Glavin, John; Hunter, Robert; Redman, Elizabeth; Stasiuk, Susan; Schertzberg, Michael; Angus McQuibban, G.; Caffrey, Conor R.; Cutler, Sean R.; Tyers, Mike; Giaever, Guri; Nislow, Corey; Fraser, Andy G.; MacRae, Calum A.; Gilleard, John; Roy, Peter J.

    2015-01-01

    Parasitic nematodes infect one quarter of the world's population and impact all humans through widespread infection of crops and livestock. Resistance to current anthelmintics has prompted the search for new drugs. Traditional screens that rely on parasitic worms are costly and labour intensive and target-based approaches have failed to yield novel anthelmintics. Here, we present our screen of 67,012 compounds to identify those that kill the non-parasitic nematode Caenorhabditis elegans. We then rescreen our hits in two parasitic nematode species and two vertebrate models (HEK293 cells and zebrafish), and identify 30 structurally distinct anthelmintic lead molecules. Genetic screens of 19 million C. elegans mutants reveal those nematicides for which the generation of resistance is and is not likely. We identify the target of one lead with nematode specificity and nanomolar potency as complex II of the electron transport chain. This work establishes C. elegans as an effective and cost-efficient model system for anthelmintic discovery. PMID:26108372

  8. Anthelmintic constituents of Clonostachys candelabrum.

    PubMed

    Ayers, Sloan; Zink, Deborah L; Mohn, Kenneth; Powell, Joanne S; Brown, Christine M; Bills, Gerald; Grund, Alan; Thompson, Donald; Singh, Sheo B

    2010-03-01

    Five diastereomeric polyketide glycosides, roselipins 3A-3E (1-5), have been isolated from the acetone extract of Clonostachys candelabrum on the basis of their positive anthelmintic activity. The structures of these compounds were elucidated by comparison of their NMR and MS data to those of previously reported roselipins and related structures, and were confirmed by 2D-NMR spectral analysis. Known compounds linoleic acid (6) and aurantiogliocladin (7) were also isolated as active anthelmintic components, although much less potent than the roselipins.

  9. Developing novel anthelmintics from plant cysteine proteinases

    PubMed Central

    Behnke, Jerzy M; Buttle, David J; Stepek, Gillian; Lowe, Ann; Duce, Ian R

    2008-01-01

    Intestinal helminth infections of livestock and humans are predominantly controlled by treatment with three classes of synthetic drugs, but some livestock nematodes have now developed resistance to all three classes and there are signs that human hookworms are becoming less responsive to the two classes (benzimidazoles and the nicotinic acetylcholine agonists) that are licensed for treatment of humans. New anthelmintics are urgently needed, and whilst development of new synthetic drugs is ongoing, it is slow and there are no signs yet that novel compounds operating through different modes of action, will be available on the market in the current decade. The development of naturally-occurring compounds as medicines for human use and for treatment of animals is fraught with problems. In this paper we review the current status of cysteine proteinases from fruits and protective plant latices as novel anthelmintics, we consider some of the problems inherent in taking laboratory findings and those derived from folk-medicine to the market and we suggest that there is a wealth of new compounds still to be discovered that could be harvested to benefit humans and livestock. PMID:18761736

  10. Anthelmintic drugs and nematicides: studies in Caenorhabditis elegans.

    PubMed

    Holden-Dye, Lindy; Walker, Robert J

    2014-12-16

    Parasitic nematodes infect many species of animals throughout the phyla, including humans. Moreover, nematodes that parasitise plants are a global problem for agriculture. As such, these nematodes place a major burden on human health, on livestock production, on the welfare of companion animals and on crop production. In the 21st century there are two major challenges posed by the wide-spread prevalence of parasitic nematodes. First, many anthelmintic drugs are losing their effectiveness because nematode strains with resistance are emerging. Second, serious concerns regarding the environmental impact of the nematicides used for crop protection have prompted legislation to remove them from use, leaving agriculture at increased risk from nematode pests. There is clearly a need for a concerted effort to address these challenges. Over the last few decades the free-living nematode Caenorhabditis elegans has provided the opportunity to use molecular genetic techniques for mode of action studies for anthelmintics and nematicides. These approaches continue to be of considerable value. Less fruitful so far, but nonetheless potentially very useful, has been the direct use of C. elegans for anthelmintic and nematicide discovery programmes. Here we provide an introduction to the use of C. elegans as a 'model' parasitic nematode, briefly review the study of nematode control using C. elegans and highlight approaches that have been of particular value with a view to facilitating wider-use of C. elegans as a platform for anthelmintic and nematicide discovery and development.

  11. Anthelmintic activity of plant extracts from Brazilian savanna.

    PubMed

    Oliveira, Andreia F; Costa Junior, Livio M; Lima, Aldilene S; Silva, Carolina R; Ribeiro, Maria N S; Mesquista, José W C; Rocha, Cláudia Q; Tangerina, Marcelo M P; Vilegas, Wagner

    2017-03-15

    Helminth infections represent a serious problem for the production of small ruminants that is currently aggravated by resistance to anthelmintic products and has induced a search for control alternatives, such as natural products. In this study, extracts of Turnera ulmifolia L. (leaves and roots), Parkia platycephala Benth. (leaves and seeds) and Dimorphandra gardneriana Tul. (leaves and bark), which have been cited in ethnoveterinary studies and selected naturally by goats in the cerrado (Brazilian savanna), were tested in vitro against Haemonchus contortus. Hydroacetonic (ACT) and hydroalcoholic (ETH) extracts were evaluated using an Egg Hatching Assay (EHA), a Larval Exsheathment Inhibition Assay (LEIA) and a Larval Development Assay (LDA). A second set of incubations was performed using polyvinylpolypyrrolidone (PVPP) to determine the influence of polyphenols on the anthelmintic effects of EHA and LEIA. Data from each extract were used to calculate inhibition concentrations (IC50). All tested extracts showed activity against at least one life stage of H. contortus. The use of PVPP revealed that the tannins are not the only extracts of secondary metabolites responsible for the anthelmintic effects. The results showed clear in vitro anthelmintic activities against H. contortus at different stages and indicated the potential use of these species as a promising alternative approach to control helminthic infections of small ruminants.

  12. Reprofiled anthelmintics abate hypervirulent stationary-phase Clostridium difficile

    PubMed Central

    Gooyit, Major; Janda, Kim D.

    2016-01-01

    Prolonged use of broad-spectrum antibiotics disrupts the indigenous gut microbiota, which consequently enables toxigenic Clostridium difficile species to proliferate and cause infection. The burden of C. difficile infections was exacerbated with the outbreak of hypervirulent strains that produce copious amounts of enterotoxins and spores. In recent past, membrane-active agents have generated a surge of interest due to their bactericidal property with a low propensity for resistance. In this study, we capitalized on the antimicrobial property and low oral bioavailability of salicylanilide anthelmintics (closantel, rafoxanide, niclosamide, oxyclozanide) to target the gut pathogen. By broth microdilution techniques, we determined the MIC values of the anthelmintics against 16 C. difficile isolates of defined PCR-ribotype. The anthelmintics broadly inhibited C. difficile growth in vitro via a membrane depolarization mechanism. Interestingly, the salicylanilides were bactericidal against logarithmic- and stationary-phase cultures of the BI/NAP1/027 strain 4118. The salicylanilides were poorly active against select gut commensals (Bacteroides, Bifidobacterium and Lactobacillus species), and were non-hemolytic and non-toxic to mammalian cell lines HepG2 and HEK 293T/17 within the range of their in vitro MICs and MBCs. The salicylanilide anthelmintics exhibit desirable properties for repositioning as anti-C. difficile agents. PMID:27633064

  13. Using C. elegans Forward and Reverse Genetics to Identify New Compounds with Anthelmintic Activity

    PubMed Central

    Mathew, Mark D.; Mathew, Neal D.; Miller, Angela; Simpson, Mike; Au, Vinci; Garland, Stephanie; Gestin, Marie; Edgley, Mark L.; Flibotte, Stephane; Balgi, Aruna; Chiang, Jennifer; Giaever, Guri; Dean, Pamela; Tung, Audrey; Roberge, Michel; Roskelley, Calvin; Forge, Tom; Nislow, Corey; Moerman, Donald

    2016-01-01

    Background The lack of new anthelmintic agents is of growing concern because it affects human health and our food supply, as both livestock and plants are affected. Two principal factors contribute to this problem. First, nematode resistance to anthelmintic drugs is increasing worldwide and second, many effective nematicides pose environmental hazards. In this paper we address this problem by deploying a high throughput screening platform for anthelmintic drug discovery using the nematode Caenorhabditis elegans as a surrogate for infectious nematodes. This method offers the possibility of identifying new anthelmintics in a cost-effective and timely manner. Methods/Principal findings Using our high throughput screening platform we have identified 14 new potential anthelmintics by screening more than 26,000 compounds from the Chembridge and Maybridge chemical libraries. Using phylogenetic profiling we identified a subset of the 14 compounds as potential anthelmintics based on the relative sensitivity of C. elegans when compared to yeast and mammalian cells in culture. We showed that a subset of these compounds might employ mechanisms distinct from currently used anthelmintics by testing diverse drug resistant strains of C. elegans. One of these newly identified compounds targets mitochondrial complex II, and we used structural analysis of the target to suggest how differential binding of this compound may account for its different effects in nematodes versus mammalian cells. Conclusions/Significance The challenge of anthelmintic drug discovery is exacerbated by several factors; including, 1) the biochemical similarity between host and parasite genomes, 2) the geographic location of parasitic nematodes and 3) the rapid development of resistance. Accordingly, an approach that can screen large compound collections rapidly is required. C. elegans as a surrogate parasite offers the ability to screen compounds rapidly and, equally importantly, with specificity, thus

  14. The Conqueror Worm: recent advances with cholinergic anthelmintics and techniques excite research for better therapeutic drugs

    PubMed Central

    Martin, R.J.; Puttachary, S.; Buxton, S.K.; Verma, S.; Robertson, A.P.

    2014-01-01

    The following account is based on a review lecture given recently at the British Society of Parasitology. We point out that nematode parasites cause very widespread infections of humans, particularly in economically underdeveloped areas where sanitation and hygiene are not adequate. In the absence of adequate clean water and effective vaccines, control and prophylaxis relies on anthelmintic drugs. Widespread use of anthelmintics to control nematode parasites of animals has given rise to the development of resistance and so there is a concern that similar problems will occur in humans if mass drug administration is continued. Recent research on the cholinergic anthelmintic drugs has renewed enthusiasm for the further development of cholinergic anthelmintics. Here we illustrate the use of three parasite nematode models, Ascaris suum, Oesophagostomum dentatum and Brugia malayi, microfluidic techniques and the Xenopus oocyte expression system for testing and examining the effects of cholinergic anthelmintics. We also show how the combination of derquantel, the selective nematode cholinergic antagonist and abamectin produce increased inhibition of the nicotinic acetylcholine receptors on the nematode body muscle. We are optimistic that new compounds and combinations of compounds can limit the effects of drug resistance, allowing anthelmintics to be continued to be used for effective treatment of human and animal helminth parasites. PMID:24871674

  15. Anthelmintic activity of Cymbopogon martinii, Cymbopogon schoenanthus and Mentha piperita essential oils evaluated in four different in vitro tests

    USDA-ARS?s Scientific Manuscript database

    Anthelmintic resistance is a worldwide concern in small ruminant industry and new plant derived compounds are being studied for their potential use against gastrointestinal nematodes. Mentha piperita, Cymbopogon martinii and Cymbopogon schoenanthus essential oils were evaluated against developmenta...

  16. Control of helminthosis in lambs by strategic treatment with closantel and broad-spectrum anthelmintics.

    PubMed

    Dash, K M

    1986-01-01

    Treatment of ewes with broad-spectrum anthelmintic in August (pre-lambing) and early November, and of lambs in early November and early February, was effective in controlling infections with Trichostrongylus spp in lambs reared on contaminated pastures under set-stocked conditions. It was ineffective in controlling infections with Haemonchus contortus; 82% of lambs had to be withdrawn from the experiment because of severe haemonchosis. Treatment with closantel (7.5 mg/kg) at the same times was very effective against H. contortus but ineffective against Trichostrongylus spp; 25% of lambs had to be withdrawn because of severe trichostrongylosis. The same schedule using broad spectrum anthelmintic and closantel administered concurrently was effective against both parasites; no lambs had to be withdrawn and the bodyweight gain of lambs was higher than in lambs treated with broad-spectrum anthelmintic or closantel alone. The results provide a basis on which to develop a preventive anthelmintic treatment program to control haemonchosis and trichostrongylosis in sheep which will allow the current high frequency of treatment with broad-spectrum anthelmintics to be reduced. Such a program may retard selection for anthelmintic resistance in Trichostrongylus spp.

  17. USEPA Resistance Management Model development

    EPA Science Inventory

    The US EPA requires registrants of plant incorporated protectant (PIP) crops to provide information relating to the time frame for pest resistance development related to the control traits of the crop. Simulation models are used to evaluate the future conditions for resistance de...

  18. USEPA Resistance Management Model development

    EPA Science Inventory

    The US EPA requires registrants of plant incorporated protectant (PIP) crops to provide information relating to the time frame for pest resistance development related to the control traits of the crop. Simulation models are used to evaluate the future conditions for resistance de...

  19. Anthelmintic efficacy against cyathostomins in horses in Southern England.

    PubMed

    Lester, H E; Spanton, J; Stratford, C H; Bartley, D J; Morgan, E R; Hodgkinson, J E; Coumbe, K; Mair, T; Swan, B; Lemon, G; Cookson, R; Matthews, J B

    2013-10-18

    Cyathostomins are considered to be the most important group of helminths to affect equids due to their high prevalence, potential pathogenicity and ability to develop anthelmintic resistance. Their control relies almost exclusively on frequent anthelmintic use. Currently, fenbendazole (FBZ), pyrantel embonate (PYR), ivermectin (IVM) and moxidectin (MOX) are licensed for use in horses in the UK. With no new anthelmintics likely to be licensed in the near future, it is essential that investigations into the efficacy of current anthelmintics in different locations are performed to help inform control programmes. Here, efficacy of FBZ, PYR, IVM and MOX in horse populations in the South of England was investigated. Horses with a strongyle faecal egg count (FEC) of ≥50 eggs per gram (EPG) were enrolled onto a faecal egg count reduction test (FECRT) study. Efficacy was determined by calculating the percentage reduction in FEC between the group mean at Day 0 and 14 days post-treatment. Efficacy was indicated when a group arithmetic faecal egg count reduction (FECR) of ≥90% was recorded for FBZ and PYR, and ≥95% for IVM and MOX. Between March and December 2012, 404 FECRT were performed on 12 yards examining 101, 110, 93 and 100 equids for FBZ, PYR, IVM, and MOX, respectively. FBZ resistance was identified on all yards (mean FECR range 0-65.8%). On 10 of 12 yards, PYR efficacy was >90% (91.0-99.4%) and on two yards, PYR resistance was suspected (86.8-87.2%). IVM (96.4-100%) and MOX (99.9-100%) were >95% efficacious on all yards. As the prevalence of FBZ resistance was 100%, the future use of this anthelmintic for the control of strongyles should be questioned. PYR should be used strategically to reduce reliance on the macrocyclic lactone class products. Over-dispersion of FEC between horses was observed (average k=0.21) with 80% of the strongyle eggs counted measured in 15% of horses tested, strongly supporting the application of targeted helminth control programmes in

  20. A survey of anthelmintic use and internal parasite control in farmed deer in New Zealand.

    PubMed

    Castillo-Alcala, F; Wilson, P R; Pomroy, W E; Hoskin, S O

    2007-04-01

    To survey parasite control programmes and anthelmintic usage over a 12-month period on deer farms in New Zealand. A questionnaire of general farm data, policy and procedures for anthelmintic use, anthelmintic programmes for weaner and older deer, general information and understanding of parasite management practices was posted to 500 deer farmers in November 2004. Two hundred and twenty-seven (45.4%) replies were received, and 198 (39.6%) were suitable for analysis. Ninety four percent of respondents used anthelmintics at least once in the 12-month period; 53% treated all classes of deer and 22% treated only weaners. Seventy-four percent based anthelmintic dose on weight of the heaviest animal, and 36% used a weigh scale. Weaner deer (n=175 farms) were treated 1-13 (mean 3.2) times in their first 12 months, at the earliest commencing in January and at the latest in November. The mean interval between treatments ranged from 41 to 46 days. Yearling and adult hinds and stags were treated at least once (range 1-7 times) on 55-64% of farms, depending on class of animal. Moxidectin was the anthelmintic most commonly used (46-58%, depending on class of animal), followed by abamectin, eprinomectin, oxfendazole, ivermectin, albendazole, levamisole and doramectin. Perceived efficacy was the most common reason for choosing a type of anthelmintic. Weight gain and body condition were the most common measures used for monitoring parasitism in weaners and older deer, respectively, and few respondents used faecal egg and/or larval counts. Coughing and/or scouring were associated with parasitism in weaners on 13-14% of farms, and deaths associated with lungworm and gastrointestinal parasites were recorded on 5% and 3% of farms, respectively. Veterinary input to diagnosis was involved in 23% of events. Production losses and/or death of yearling and/or adult deer due to parasitism were reported by 27% of respondents. When planning anthelmintic treatment programmes, 63% of respondents

  1. A survey of UK prescribers' experience of, and opinions on, anthelmintic prescribing practices for livestock and equines.

    PubMed

    Easton, Stephanie; Pinchbeck, Gina L; Bartley, David J; Hotchkiss, Emily; Hodgkinson, Jane E; Matthews, Jacqueline B

    2016-11-01

    The aim of this study was to determine practices, attitudes and experiences of UK prescribers of anthelmintics for horses and livestock. A questionnaire was sent by direct email to groups licenced to prescribe these medicines. These were veterinarians, Suitably Qualified Persons (SQPs, registered with the Animal Medicines Training Regulatory Authority) and veterinary pharmacists. The survey was also advertised through social media. It comprised questions relating to demographics, training experiences, current prescribing practices, as well as personal opinions on anthelmintic selection, diagnostics and anthelmintic resistance. A total of 193 veterinarians and 326 SQPs were included in final analysis. Pharmacists were excluded from detailed analysis due to the low numbers that responded (n=3). The results indicated that SQP participants were more likely to receive post-certification parasitology training than the veterinarians, and that both channels consulted similar sources for information about helminths and their control (paper articles in journals, online sources). The SQP participants stated a higher frequency of face-to-face interactions with clients/customers (96.1%) than the veterinarians (76.4%), who stated a higher frequency of telephone interactions (55.1% and 73.5%, respectively). Veterinarians were more likely to state that there were specific factors that limited interactions with their clients (54.1%) than SQPs (19.6%), such as competition from other suppliers. SQP participants considered a wider range of factors as important when deciding on which anthelmintic to recommend (i.e. knowledge of specific parasites, knowledge of specific anthelmintics, discussion of measures to avoid anthelmintic resistance and time to talk with clients/customers); however, the veterinarian participants were more likely to consider the results of diagnostic tests. While discussions about anthelmintic resistance were stated with similar frequency in both groups, less

  2. Anthelmintics Are Substrates and Activators of Nematode P Glycoprotein▿

    PubMed Central

    Kerboeuf, Dominique; Guégnard, Fabrice

    2011-01-01

    P glycoproteins (Pgp), members of the ABC transporter superfamily, play a major role in chemoresistance. In nematodes, Pgp are responsible for resistance to anthelmintics, suggesting that they are Pgp substrates, as they are in mammalian cells. However, their binding to nematode Pgp and the functional consequences of this interaction have not been investigated. Our study showed that levamisole and most of the macrocyclic lactones (MLs) are Pgp substrates in nematodes. Ivermectin, although a very good substrate in mammalian cells, is poorly transported. In contrast to their inhibitory effect on mammalian Pgp, these drugs had a stimulatory effect on the transport activity of the reference Pgp substrate rhodamine 123 (R123) in the nematode. This may be due to a specific sequence of nematode Pgp, which shares only 44% identity with mammalian Pgp. Other factors, such as the affinity of anthelmintics for Pgp and their concentration in the Pgp microenvironment, could also differ in nematodes, as suggested by the specific relationship observed between the octanol-water partition coefficient (log P) of MLs and R123 efflux. Nevertheless, some similarities were also observed in the functional activities of the mammalian and nematode Pgp. As in mammalian cells, substrates known to bind the H site (Hoechst 33342 and colchicine) activated the R site, resulting in an increased R123 efflux. Our findings thus show that ML anthelmintics, which inhibit Pgp-mediated efflux in mammals, activate transport activity in nematodes and suggest that several substituents in the ML structure are involved in modulating the stimulatory effect. PMID:21300828

  3. Present-day anthelmintics and perspectives on future new targets.

    PubMed

    Taman, Amira; Azab, Manar

    2014-07-01

    In absence of vaccines for the majority of helminths, chemotherapy is still the mainstay for controlling human helminthiases. However, a limited number of drugs are available in the market to combat parasitic helminths in human. Besides, the development and spread of drug resistance have declined the use of most currently available anthelmintics. Clearly, availability of new anthelmintic agents will be essential in the next few years. More research into the mechanisms of drug actions and their targets are eminent for the discovery and development of novel anthelmintic agents. Recent drug discovery techniques mostly rely on mechanism-based screening of compounds on heterologously expressed targets in bacterial, mammalian or yeast cells. Although this is usually a successful approach, it is money- and time-consuming; meanwhile, pharmaceutical companies prefer the tested target that is chosen based on basic research. The nervous system is the site of action of several chemotherapeutics including pesticides and antinematode drugs; accordingly, the nervous system continues to be a promising target. Recent advances in exploring helminths' nervous system, neurotransmitters and receptors have paved the way for the development of potential agents targeting the nervous system and its components.

  4. Clinical Management of HIV Drug Resistance

    PubMed Central

    Cortez, Karoll J.; Maldarelli, Frank

    2011-01-01

    Combination antiretroviral therapy for HIV-1 infection has resulted in profound reductions in viremia and is associated with marked improvements in morbidity and mortality. Therapy is not curative, however, and prolonged therapy is complicated by drug toxicity and the emergence of drug resistance. Management of clinical drug resistance requires in depth evaluation, and includes extensive history, physical examination and laboratory studies. Appropriate use of resistance testing provides valuable information useful in constructing regimens for treatment-experienced individuals with viremia during therapy. This review outlines the emergence of drug resistance in vivo, and describes clinical evaluation and therapeutic options of the individual with rebound viremia during therapy. PMID:21994737

  5. Medical Management of Drug-Resistant Tuberculosis.

    PubMed

    Jeon, Doosoo

    2015-07-01

    Drug-resistant tuberculosis (TB) is still a major threat worldwide. However, recent scientific advances in diagnostic and therapeutic tools have improved the management of drug-resistant TB. The development of rapid molecular testing methods allows for the early detection of drug resistance and prompt initiation of an appropriate treatment. In addition, there has been growing supportive evidence for shorter treatment regimens in multidrug-resistant TB; and for the first time in over 50 years, new anti-TB drugs have been developed. The World Health Organization has recently revised their guidelines, primarily based on evidence from a meta-analysis of individual patient data (n=9,153) derived from 32 observational studies, and outlined the recommended combination and correct use of available anti-TB drugs. This review summarizes the updated guidelines with a focus on the medical management of drug-resistant TB.

  6. Managing the evolution of herbicide resistance.

    PubMed

    Evans, Jeffrey A; Tranel, Patrick J; Hager, Aaron G; Schutte, Brian; Wu, Chenxi; Chatham, Laura A; Davis, Adam S

    2016-01-01

    Understanding and managing the evolutionary responses of pests and pathogens to control efforts is essential to human health and survival. Herbicide-resistant (HR) weeds undermine agricultural sustainability, productivity and profitability, yet the epidemiology of resistance evolution - particularly at landscape scales - is poorly understood. We studied glyphosate resistance in a major agricultural weed, Amaranthus tuberculatus (common waterhemp), using landscape, weed and management data from 105 central Illinois grain farms, including over 500 site-years of herbicide application records. Glyphosate-resistant (GR) A. tuberculatus occurrence was greatest in fields with frequent glyphosate applications, high annual rates of herbicide mechanism of action (MOA) turnover and few MOAs field(-1) year(-1) . Combining herbicide MOAs at the time of application by herbicide mixing reduced the likelihood of GR A. tuberculatus. These findings illustrate the importance of examining large-scale evolutionary processes at relevant spatial scales. Although measures such as herbicide mixing may delay GR or other HR weed traits, they are unlikely to prevent them. Long-term weed management will require truly diversified management practices that minimize selection for herbicide resistance traits. © 2015 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

  7. EVALUATION OF ANTHELMINTIC FISHMEAL POLYMER BAITS FOR THE CONTROL OF BAYLISASCARIS PROCYONIS IN FREE-RANGING RACCOONS (PROCYON LOTOR).

    PubMed

    Smyser, Timothy J; Johnson, Shylo R; Stallard, Melissa D; McGrew, Ashley K; Page, L Kristen; Crider, Nikki; Ballweber, Lora R; Swihart, Robert K; VerCauteren, Kurt C

    2015-07-01

    Baylisascaris procyonis is a common gastrointestinal parasite of raccoons (Procyon lotor) and is a zoonotic helminth with the potential to cause severe or fatal infection. Raccoons thrive in human-dominated landscapes, and the fecal-oral transmission pathway and lack of effective treatment make B. procyonis a serious threat to public health. The distribution of medicinal baits has emerged as a socially acceptable and cost-effective method for managing disease in free-ranging wildlife. We assessed the suitability of a mass-producible anthelmintic bait for B. procyonis mitigation by evaluating the willingness of free-ranging raccoons to consume anthelmintic baits and determining whether bait consumption successfully cleared B. procyonis infections from raccoons. Anthelmintic baits were modified from standard fishmeal polymer baits, the food attractant commonly used in oral rabies vaccine baits, with the introduction of 220 mg of pyrantel pamoate into the fishmeal mixture. We captured 16 naturally infected raccoons, presented one anthelmintic bait, and monitored B. procyonis infection over 90 d by screening feces for eggs. Treatment cleared B. procyonis infections for nine of 12 raccoons that consumed >10 g of the 15 g bait. We used remote cameras to monitor in situ patterns of bait consumption for anthelmintic baits relative to standard baits. Both anthelmintic and standard baits were rapidly consumed, with no differences in the rate of consumption between bait types. However, after bait contact, raccoons demonstrated a greater willingness to consume standard baits while ignoring anthelmintic baits more frequently (P = 0.06). Initial trials of anthelmintic baits show promise, although refinement in both dose and palatability is needed. At mass production scales, the addition of pyrantel pamoate to fishmeal polymer baits would be inexpensive, potentially making anthelmintic baits a viable management option when coupled with an oral rabies vaccine or used independently

  8. Thymus capitatus from Tunisian arid zone: chemical composition and in vitro anthelmintic effects on Haemonchus contortus.

    PubMed

    Boubaker Elandalousi, Ramzi; Akkari, Hafidh; B'chir, Fatma; Gharbi, Mohamed; Mhadhbi, Moez; Awadi, Soufia; Darghouth, Mohamed Aziz

    2013-10-18

    The increasing prevalence of anthelmintic resistant strains of helminths, the drug residues in animal products and the high cost of conventional anthelmintics has created an interest in studying medicinal plants as an alternative source of anthelmintics. Thymus capitatus (Lamiales: Lamiaceae) is used traditionally by people as spices and reported to possess some biological effects. The objective of this study is to evaluate the anthelmintic efficacy of T. capitatus in comparison to albendazole against the gastrointestinal nematodes of sheep. To fulfil the objectives, in vitro anthelmintic activities of crude aqueous and crude ethanolic extracts of aerial parts of T. capitatus were investigated on the eggs and adults of the nematode parasite Haemonchus contortus. Both extract types of T. capitatus completely inhibited egg hatching at a concentration close to 2 mg/ml. LC₅₀ of ethanolic extract of T. capitatus was 0.368 mg/ml while that of aqueous extract was 6.344 mg/ml (p<0.05). The ethanolic extract showed higher in vitro activity against adult parasites than the aqueous one in terms of the paralysis and/or death of the worms at different hours post-treatment. Dose dependent effect was observed for both extracts. Chemical analyses revealed that the overall profile of both extracts was dominated by oxygenated constituents. In addition, ethanolic extract is mainly composed of phenols among which thymol (71.22%) and camphor (17.18%). As far as the literature could be ascertained, this is the first publication on anthelmintic activity of T. capitatus. The results of the present study suggest that T. capitatus extracts are a promising alternative to the commercially available anthelmintics like albendazole for the treatment of small ruminants' gastrointestinal nematodes.

  9. Host pharmacokinetics and drug accumulation of anthelmintics within target helminth parasites of ruminants.

    PubMed

    Lifschitz, A; Lanusse, C; Alvarez, L

    2017-07-01

    pharmacokinetic behaviour and identification of different factors affecting drug activity is important for achieving optimal parasite control and avoiding selection for drug resistance. The search for novel alternatives to deliver enhanced drug concentrations within target helminth parasites may contribute to avoiding misuse, and prolong the lifespan of existing and novel anthelmintic compounds in the veterinary pharmaceutical market.

  10. Anthelmintic activity of leaves of justicia beddomei.

    PubMed

    Srinivasa, U; Rao, J Venkateshwara; Krupanidhi, A M; Shanmukhappa, S

    2007-01-01

    Ethanolic and Chloroform extract of leaves of Justicia beddomei were evaluated separately for anthelmintic activity on adult Indian earthworms Pheretima posthuma, using Piperazine citrate as reference standard. The results indicated that ethanolic extract was more potent than the chloroform extract.

  11. Strategies to manage antifungal drug resistance.

    PubMed

    Tseng, Hsiang-Kuang; Perfect, John R

    2011-02-01

    Invasive fungal infections continue to cause significant morbidity and mortality in immunocompromised hosts. From more than half a million deaths from cryptococcosis in sub-Saharan Africa to an unchanging death rate from invasive candidiasis, despite three antifungal classes of drugs, insights into better strategies to reduce therapeutic failures or resistance are needed. This review examines the issues around antifungal drug resistance from both a basic description of the failures and how they are detected to the variety of issues that need to be addressed to help prevent failures for successful management. The reader will gain an understanding of the clinical complexities in this patient population for management of invasive fungal infections. Throughout the review, principles of management are given along with some specific clinical examples to illustrate the issues and frame the knowledge base. From this discussion it is hoped that the clinician can use the insights provided to manage individual patients and find links to the evidence-based material that support its conclusions. Also, this review specifically identifies the limitations of present management and directs clinicians to gather additional information and provide even better treatment strategies. Invasive fungal infections are life-threatening complications of serious underlying diseases. Their management can be complicated by both direct and clinical drug resistance and by understanding these possibilities and correcting them; most patients can be successfully managed with present antifungal drugs if the underlying diseases can be controlled.

  12. In vitro screening of six anthelmintic plant products against larval Haemonchus contortus with a modified methyl-thiazolyl-tetrazolium reduction assay.

    PubMed

    Hördegen, P; Cabaret, J; Hertzberg, H; Langhans, W; Maurer, V

    2006-11-03

    Because of the increasing anthelmintic resistance and the impact of conventional anthelmintics on the environment, it is important to look for alternative strategies against gastrointestinal nematodes. Phytotherapy could be one of the major options to control these pathologies. Extracts or ingredients of six different plant species were tested against exsheathed infective larvae of Haemonchus contortus using a modified methyl-thiazolyl-tetrazolium (MTT) reduction assay. Pyrantel tartrate was used as reference anthelmintic. Bromelain, the enzyme complex of the stem of Ananas comosus (Bromeliaceae), the ethanolic extracts of seeds of Azadirachta indica (Meliaceae), Caesalpinia crista (Caesalpiniaceae) and Vernonia anthelmintica (Asteraceae), and the ethanolic extracts of the whole plant of Fumaria parviflora (Papaveraceae) and of the fruit of Embelia ribes (Myrsinaceae) showed an anthelmintic efficacy of up to 93%, relative to pyrantel tartrate. Based on these results obtained with larval Haemonchus contortus, the modified MTT reduction assay could be a possible method for testing plant products with anthelmintic properties.

  13. Identification of the amino-acetonitrile derivative monepantel (AAD 1566) as a new anthelmintic drug development candidate

    PubMed Central

    Gauvry, N.; Schorderet Weber, S.; Skripsky, T.; Bouvier, J.; Wenger, A.; Schroeder, F.; Desaules, Y.; Hotz, R.; Goebel, T.; Hosking, B. C.; Pautrat, F.; Wieland-Berghausen, S.; Ducray, P.

    2008-01-01

    Anthelmintic resistance has become a global phenomenon in gastro-intestinal nematodes of farm animals, including multi-drug resistance against the three major classes of anthelmintics. There is an urgent need for an anthelmintic with a new mode of action. The recently discovered amino-acetonitrile derivatives (AADs) offer a new class of synthetic chemicals with anthelmintic activity. The evaluation of AADs was pursued applying in vitro assays and efficacy and tolerability studies in rodents, sheep, and cattle. Amongst various suitable compounds, AAD 1566 eliminated many tested pathogenic nematode species, both at larval and adult stages, at a dose of 2.5 mg/kg bodyweight in sheep and 5.0 mg/kg bodyweight in cattle. The same doses were sufficient to cure animals infected with resistant or multi-drug-resistant nematode isolates. These findings, complemented by the good tolerability and low toxicity to mammals, suggest that AAD 1566, monepantel, would be a suitable anthelmintic drug development candidate. PMID:18594861

  14. Mixtures as a fungicide resistance management tactic.

    PubMed

    van den Bosch, Frank; Paveley, Neil; van den Berg, Femke; Hobbelen, Peter; Oliver, Richard

    2014-12-01

    We have reviewed the experimental and modeling evidence on the use of mixtures of fungicides of differing modes of action as a resistance management tactic. The evidence supports the following conclusions. 1. Adding a mixing partner to a fungicide that is at-risk of resistance (without lowering the dose of the at-risk fungicide) reduces the rate of selection for fungicide resistance. This holds for the use of mixing partner fungicides that have either multi-site or single-site modes of action. The resulting predicted increase in the effective life of the at-risk fungicide can be large enough to be of practical relevance. The more effective the mixing partner (due to inherent activity and/or dose), the larger the reduction in selection and the larger the increase in effective life of the at-risk fungicide. 2. Adding a mixing partner while lowering the dose of the at-risk fungicide reduces the selection for fungicide resistance, without compromising effective disease control. The very few studies existing suggest that the reduction in selection is more sensitive to lowering the dose of the at-risk fungicide than to increasing the dose of the mixing partner. 3. Although there are very few studies, the existing evidence suggests that mixing two at-risk fungicides is also a useful resistance management tactic. The aspects that have received too little attention to draw generic conclusions about the effectiveness of fungicide mixtures as resistance management strategies are as follows: (i) the relative effect of the dose of the two mixing partners on selection for fungicide resistance, (ii) the effect of mixing on the effective life of a fungicide (the time from introduction of the fungicide mode of action to the time point where the fungicide can no longer maintain effective disease control), (iii) polygenically determined resistance, (iv) mixtures of two at-risk fungicides, (v) the emergence phase of resistance evolution and the effects of mixtures during this phase

  15. Anthelmintic Potential of Thymoquinone and Curcumin on Fasciola gigantica

    PubMed Central

    Ullah, Rizwan; Rehman, Abdur; Zafeer, Mohd Faraz; Rehman, Lubna; Khan, Yasir A.; Khan, M. A. Hannan; Khan, Shahper N.; Khan, Asad U.; Abidi, S. M. A.

    2017-01-01

    Fasciolosis an economically important global disease of ruminants in the temperate and tropical regions, caused by Fasciola hepatica and F. gigantica, respectively, also poses a potential zoonotic threat. In India alone it causes huge losses to stakeholders. Anthelmintics including triclabendazole have been used to control this menace but the emerging resistance against the available compounds necessitates identification of novel and alternative therapeutic measures involving plant derived natural compounds for their anthelmintic potential. Thymoquinone (T) and curcumin (C), the active ingredients of Nigella sativa and Curcuma longa respectively have been used as antiparasitic agents but the information on their flukicidal effect is very limited. Adult flukes of F. gigantica were in vitro exposed to different concentrations of thymoquinone and curcumin separately for 3h at 37+ 1°C. A significant (p<0.05) reduction in the worm motility at 60 μM concentration of both T and C was observed though all the worms remained alive after 3h exposure, whereas the effect on egg shedding was statistically insignificant. Pronounced tegumental disruptions and erosion of spines in the posterior region and around the acetabulum was evident. A significant (p<0.05) decrease in glutathione-S-transferase and superoxide dismutase activity and reduced glutathione (GSH) level was observed, while protein carbonylation increased differentially. A significant inhibition of CathepsinL (CatL) gene expression in thymoquinone treated worms was also evident. Further, in silico molecular docking of T and C with CatL revealed a stronger interaction of curcumin with the involvement of higher number of amino acids as compared to thymoquinone that could be more effective in inhibiting the antioxidant enzymes of F. gigantica. It is concluded that both the compounds understudy will decrease the detoxification ability of F. gigantica, while inhibition of CatL will significantly affect their virulence

  16. Anthelmintic Potential of Thymoquinone and Curcumin on Fasciola gigantica.

    PubMed

    Ullah, Rizwan; Rehman, Abdur; Zafeer, Mohd Faraz; Rehman, Lubna; Khan, Yasir A; Khan, M A Hannan; Khan, Shahper N; Khan, Asad U; Abidi, S M A

    2017-01-01

    Fasciolosis an economically important global disease of ruminants in the temperate and tropical regions, caused by Fasciola hepatica and F. gigantica, respectively, also poses a potential zoonotic threat. In India alone it causes huge losses to stakeholders. Anthelmintics including triclabendazole have been used to control this menace but the emerging resistance against the available compounds necessitates identification of novel and alternative therapeutic measures involving plant derived natural compounds for their anthelmintic potential. Thymoquinone (T) and curcumin (C), the active ingredients of Nigella sativa and Curcuma longa respectively have been used as antiparasitic agents but the information on their flukicidal effect is very limited. Adult flukes of F. gigantica were in vitro exposed to different concentrations of thymoquinone and curcumin separately for 3h at 37+ 1°C. A significant (p<0.05) reduction in the worm motility at 60 μM concentration of both T and C was observed though all the worms remained alive after 3h exposure, whereas the effect on egg shedding was statistically insignificant. Pronounced tegumental disruptions and erosion of spines in the posterior region and around the acetabulum was evident. A significant (p<0.05) decrease in glutathione-S-transferase and superoxide dismutase activity and reduced glutathione (GSH) level was observed, while protein carbonylation increased differentially. A significant inhibition of CathepsinL (CatL) gene expression in thymoquinone treated worms was also evident. Further, in silico molecular docking of T and C with CatL revealed a stronger interaction of curcumin with the involvement of higher number of amino acids as compared to thymoquinone that could be more effective in inhibiting the antioxidant enzymes of F. gigantica. It is concluded that both the compounds understudy will decrease the detoxification ability of F. gigantica, while inhibition of CatL will significantly affect their virulence

  17. Potential problems associated with the controlled release of anthelmintics in grazing animals.

    PubMed

    Herd, R P

    1984-11-01

    A high, constant and sustained release of drug appears to be a major requirement to avoid a late season rise in pasture infectivity that may result in production losses in calves in autumn or Type II osteragiasis in the following spring. The timing of administration is of crucial importance and will vary in regions of different epidemiology, such as between northern and southern United States. Lack of a standard and reliable technique for pasture larval counts has resulted in some negative or erratic results which are open to question. Although controlled release anthelmintics offer advantages of convenience, a comparison of the economic benefits at present favours prophylactic treatment of dairy heifers with conventional anthelmintics 3 and 6 weeks after spring turnout in northern regions of the Northern Hemisphere. There is a serious risk that boluses based on controlled release by diffusion will behave like slow decaying insecticides and select strongly for drug resistance, especially if farmers administer them in succession throughout the grazing season. There are, however, 2 features in the design of a controlled release device that in theory may minimize the risk of rapid selection for resistance: a high and constant release of anthelmintic followed by a rapid decline to zero as the device becomes exhausted. Under these conditions, the device may even prolong the useful life of an anthelmintic to which resistance has already developed. This paper was presented at Pfizer Symposium on The Application of Sustained Release Anthelmintic Dosage Forms in the Control of Parasites in Grazing Animals at the World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) 10th International Conference, 18-20 August 1983, Perth, W.A., Australia.

  18. Exploration of the epidemiological consequences of resistance to gastro-intestinal parasitism and grazing management of sheep through a mathematical model.

    PubMed

    Laurenson, Yan Christian Stephen Mountfort; Kyriazakis, Ilias; Forbes, Andrew Barnet; Bishop, Stephen Christopher

    2012-10-26

    Predicting the impacts of selection for decreased faecal egg count (FEC) (i.e. host resistance) in grazing ruminants is difficult, due to complex interactions between parasite epidemiology, management and host responses. A mathematical model including heritable between lamb variation in host-parasite interactions, Teladorsagia circumcincta epidemiology and anthelmintic drenching, was developed and used to (i) address such interactions and their impact on outcomes including FEC, live weight (LW, kg) and pasture larval contamination (PC, larvae/kg DM), and (ii) investigate how grazing management strategies, aimed at reducing host exposure to infective larvae via pasture moves at 40 day intervals, affect these outcomes. A population of 10,000 lambs was simulated and resultant FEC predictions used to assign the 1,000 lambs with the highest and lowest predicted FEC to 'susceptible' (S) and 'resistant', (R) groups, respectively. The predicted average FEC of the S group was ∼8.5-fold higher than the R group across a grazing season. The R and S groups were then simulated to graze separate pastures (R(sep) and S(sep)); and repeated for 3 grazing seasons to allow predictions to diverge and stabilize. Further, different grazing strategies were superimposed on all groups. PC and average FEC were affected by whether lambs of different resistance genotype grazed together or separately, with differences increasing across grazing seasons. By the third grazing season the average PC of the R(sep) group was reduced by ∼83%, and the S(sep) group was increased by ∼240%, in comparison to the whole population average. Average FEC of the R(sep) group was reduced by ∼40%, and the S(sep) group increased by ∼46% in comparison to the R and S groups, respectively, whilst drenching had little impact on the proportional differences in FEC between groups. Predicted LW was similar for the R and R(sep) groups irrespective of anthelmintic treatment, whilst LW of the S(sep) group was

  19. Efficacy of anthelmintics on South American camelid (llama and alpaca) farms in Georgia.

    PubMed

    Gillespie, Rose-Ann M; Williamson, Lisa H; Terrill, Thomas H; Kaplan, Ray M

    2010-08-27

    The number of South American camelid (SAC; llama and alpaca) farms is growing in the southeastern United States, and infection with gastrointestinal nematodes (GIN) is a major health concern in this region. There is widespread resistance to anthelmintic remedies in small ruminants (sheep and goats), but a paucity of information on llamas and alpacas. Anthelmintic resistance was evaluated on three SAC farms (two llama; one alpaca) in Georgia in the southern United States using fecal egg count reduction (FECR) tests. For each farm, animals were randomly assigned to 1 of 5 treatment groups based on initial fecal egg count (FEC) and number of animals available (2-5 groups, n=9-11 per treatment). Ivermectin (IVM, subcutaneous injection; 0.3mg/kg body weight (BW)) and a control group were tested on an alpaca farm, and fenbendazole (FBZ, oral; 10mg/kg BW; two farms), moxidectin (MOX oral; 0.2mg/kg BW; two farms), and levamisole (LEV, oral; 8 mg/kg BW; one farm) were added for the llama farms. Anthelmintic efficacy was determined by comparing FEC of treatment and control animals 14 days post-treatment, with resistance evaluated using the World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines. Based upon these guidelines, there was GIN resistance to IVM in both llamas and alpacas in Georgia and to FBZ on both llama farms where this drug was tested. There was MOX resistance on one llama farm using the FECR test, while there was no resistance to LEV detected in this study. These data demonstrate a serious emerging problem in the United States of llama and alpaca GIN resistant to drugs from two of the three major anthelmintic classes.

  20. Clinical management of HIV-1 resistance.

    PubMed

    Paredes, Roger; Clotet, Bonaventura

    2010-01-01

    Antiretroviral drug resistance is a fundamental survival strategy for the virus that stems from its vast capacity to generate diversity. With the recent availability of new ARV drugs and classes, it is now possible to prescribe fully active ART to most HIV-infected subjects and achieve viral suppression even in those with multidrug-resistant HIV. It is uncertain, however, if this scenario will endure. Given that ART must be given for life, and new compounds other than second-generation integrase inhibitors may not reach the clinic soon, all efforts must be done to avoid the development of resistance to the new agents. Here, we discuss relevant aspects for the clinical management of antiretroviral drug resistance, leaving detailed explanations of mechanisms and mutation patterns to other articles in this issue. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, vol. 85, issue 1, 2010. Copyright 2009 Elsevier B.V. All rights reserved.

  1. Anthelmintic efficacy on Parascaris equorum in foals on Swedish studs

    PubMed Central

    2009-01-01

    Background In the last few years stud farms have experienced increasing problems with Parascaris equorum infections in foals despite intensive deworming programs. This has led to the question as to whether the anthelmintic drugs used against this parasite are failing. This study aimed to investigate the efficacy of ivermectin, fenbendazole and pyrantel on the faecal output of ascarid eggs of foals. Methods A Faecal Egg Count Reduction Test (FECRT) was performed on nine large studs in Sweden. Anthelmintic drugs were given orally and faecal samples were examined for ascarid eggs on the day of deworming and 14 days later. Faecal Egg Count Reductions (FECRs) were calculated on arithmetic means of transformed individual FECRs and on arithmetic means of individual FECRs. Results Seventy-nine (48%) out of a total of 165 foals sampled were positive for P. equorum eggs before deworming and 66 of these met the criteria for being used in the efficacy assessment. It was shown that there was no, or very low activity of ivermectin on the output of ascarid eggs in the majority of the foals, whereas for fenbendazole and pyrantel it was >90%. Conclusion Ivermectin resistance was shown in 5 out of 6 farms. Therefore, ivermectin should not be the drug of choice in the control of P. equorum infections in foals. According to the results of this study, fenbendazole or pyrantel are still effective and should be used against this parasite. PMID:19930608

  2. ANTHELMINTIC ACTIVITY OF LEAVES OF JUSTICIA BEDDOMEI

    PubMed Central

    Srinivasa, U.; Rao, J. Venkateshwara; Krupanidhi, A.M.; Shanmukhappa, S.

    2007-01-01

    Ethanolic and Chloroform extract of leaves of Justicia beddomei were evaluated separately for anthelmintic activity on adult Indian earthworms Pheretima posthuma, using Piperazine citrate as reference standard. The results indicated that ethanolic extract was more potent than the chloroform extract PMID:22557233

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

    PubMed

    Gaba, S; Cabaret, J; Sauvé, C; Cortet, J; Silvestre, A

    2010-08-04

    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.

  4. Anthelmintic activity of selected ethno-medicinal plant extracts on parasitic stages of Haemonchus contortus.

    PubMed

    Kumarasingha, Rasika; Preston, Sarah; Yeo, Tiong-Chia; Lim, Diana S L; Tu, Chu-Lee; Palombo, Enzo A; Shaw, Jillian M; Gasser, Robin B; Boag, Peter R

    2016-04-01

    Parasitic roundworms (nematodes) cause substantial morbidity and mortality in livestock animals globally, and considerable productivity losses to farmers. The control of these nematodes has relied largely on the use of a limited number of anthelmintics. However, resistance to many of these these anthelmintics is now widespread, and, therefore, there is a need to find new drugs to ensure sustained and effective treatment and control into the future. Recently, we developed a screening assay to test natural, plant extracts with known inhibitory effects against the free-living worm Caenorhabditis elegans. Using this assay, we assessed here the effects of the extracts on motility and development of parasitic larval stages of Haemonchus contortus, one of the most important nematodes of small ruminants worldwide. The study showed that two of five extracts from Picria fel-terrae Lour. have a significant inhibitory effect (at concentrations of 3-5 mg/ml) on the motility and development of H. contortus larvae. Although the two extracts originated from the same plant, they displayed different levels of inhibition on motility and development, which might relate to the presence of various active constituents in these extracts, or the same constituents at different concentrations in distinct parts of the plant. These results suggest that extracts from P. fel-terrae Lour. have promising anthelmintic activity and that more broadly, plant extracts are a potential rich source of anthelmintics to combat helminthic diseases.

  5. Licking behaviour induces partial anthelmintic efficacy of ivermectin pour-on formulation in untreated cattle.

    PubMed

    Bousquet-Mélou, Alain; Jacquiet, Philippe; Hoste, Hervé; Clément, Julien; Bergeaud, Jean-Paul; Alvinerie, Michel; Toutain, Pierre-Louis

    2011-04-01

    Licking behaviour in cattle has been reported to account for the disposition of topically administered macrocyclic lactones. However, its impact on anthelmintic efficacy remains to be established. Therefore, we evaluated the impact of ivermectin exchange between cattle on the reduction in the faecal egg count (FEC) after pour-on administration in a group of 10 heifers experimentally infected with Ostertagia ostertagi and Cooperia oncophora. Four treated (500 μg/kg, pour-on) and six untreated animals were put together after treatment and plasma and faecal exposure to ivermectin as well as the FECs were evaluated before and over 40 days after treatment. Ivermectin was detected in plasma and faeces of the six untreated heifers, with maximal exposures two- to three-fold lower than the minimal exposures in treated animals. The interindividual variability of exposure was very high in untreated animals, with a ten-fold difference between the upper and lower limits compared with treated heifers, where there was only a two-fold difference. Anthelmintic efficacy, expressed as an average reduction of the FECs over the experimental period, was maximal in the treated group. In untreated heifers, anthelmintic efficacies ranged from zero to maximal efficacy, with intermediary values between 30% and 80%. The use of a classical pharmacodynamic model demonstrated a clear relationship between exposure and efficacy and enabled us to define the critical plasma or faecal ivermectin concentrations delimiting an exposure window associated with partial anthelmintic efficacy. This range of ivermectin plasma concentrations (0.1-1 ng/mL) could be considered as a potential selection window for anthelmintic resistance. Finally, our results show that macrocyclic lactone exchange between cattle after pour-on administration, resulting from natural grooming behaviour, can significantly impact on anthelmintic efficacy. This raises several issues such as the design of comparative clinical trials and

  6. Treatment-resistant depression: managed care considerations.

    PubMed

    Tierney, John G

    2007-07-01

    Treatment-resistant depression (TRD) presents a unique challenge in managed care, requiring review of both the clinical and economic components of care. To review the TRD disease state as well as data supporting the various therapeutic options available for the treatment of persistent depression in managed care. While there is no consensus on the definition of TRD, persistent disease can generally be defined as depression that fails to respond to adequate treatment. When initial treatment is not effective or tolerable after 6 to 8 weeks of therapy, the American Psychiatric Association (APA) treatment guidelines recommend dose titration, augmentation, or switching. In the case of a therapy switch, the body of evidence suggests that selection of an agent with a different mechanism of action than the initial agent may be the most effective treatment. Furthermore, when patients maintain continuous therapy for the recommended treatment duration, outcomes are improved compared with patients who discontinue therapy early. As a result, the most effective treatment strategies promote improved patient compliance as well as the use of agents associated with a reduced incidence of premature discontinuation and therapy change early in the treatment program. While data supporting these clinically effective components of therapy exist, few data are available demonstrating the most cost-effective therapeutic options for TRD. This analysis suggests that managed care providers could benefit from a model that they can customize to evaluate the overall costeffectiveness of different strategies in the management of depression.

  7. Managing Resistance: An Essential Consulting Skill for Learning Disabilities Teachers.

    ERIC Educational Resources Information Center

    Friend, Marilyn; Bauwens, Jeanne

    1988-01-01

    The article explores characteristics of resistance by general educators to special education consultation programs. It offers teachers of learning disabled students strategies for managing specific types of resistance as well as a general plan for minimizing resistance as well as suggestions for evaluating the impact of resistance management…

  8. Managing Resistance: An Essential Consulting Skill for Learning Disabilities Teachers.

    ERIC Educational Resources Information Center

    Friend, Marilyn; Bauwens, Jeanne

    1988-01-01

    The article explores characteristics of resistance by general educators to special education consultation programs. It offers teachers of learning disabled students strategies for managing specific types of resistance as well as a general plan for minimizing resistance as well as suggestions for evaluating the impact of resistance management…

  9. Chemical composition, anthelmintic, antibacterial and antioxidant effects of Thymus bovei essential oil.

    PubMed

    Jaradat, Nidal; Adwan, Lina; K'aibni, Shadi; Shraim, Naser; Zaid, Abdel Naser

    2016-10-26

    It has been recently recognized that oxidative stress, helminth and microbial infections are the cause of much illness found in the underdeveloped, developing and developed countries. The present study was undertaken to identify the chemical composition, and to assess anthelmintic, antimicrobial and antioxidant effects of Thymus bovei essential oil. The chemical composition of the essential oil was analyzed using gas chromatography mass spectrometry (GC-MS). Antimicrobial activity was tested against the selected strains from American Type Culture Collection (ATCC) and clinical isolates such as Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Methicillin Resistant Staphylococcus aureus, Candida albicans using MIC assay. The anthelmintic assay was carried out on adult earthworm (Pheretima posthuma), while antioxidant activity was analyzed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method. Trans-geraniol (35.38 %), α-citral (20.37 %) and β-citral (14.76 %) were the major compounds comprising 70.51 % of the essential oil. Our results showed that T. bovei essential oil exhibited strong anthelmintic activity, even higher than piperazine citrate, the used reference standard, with potential antioxidant activity almost equal to the Trolox standard. Furthermore, T. bovei essential oil had powerful antibacterial and antifungal activities against the studied pathogens. Essential oil of T. bovei exerted excellent antioxidant, antimicrobial, and anthelmintic activities. Moreover, this study found that T. bovei volatile oil contains active substances that could potentially be used as natural preservatives in food and pharmaceutical industries, these substances could also be employed for developing new anthelmintic, antimicrobial and antioxidant agents.

  10. The Validation of Nematode-Specific Acetylcholine-Gated Chloride Channels as Potential Anthelmintic Drug Targets

    PubMed Central

    Wever, Claudia M.; Farrington, Danielle; Dent, Joseph A.

    2015-01-01

    New compounds are needed to treat parasitic nematode infections in humans, livestock and plants. Small molecule anthelmintics are the primary means of nematode parasite control in animals; however, widespread resistance to the currently available drug classes means control will be impossible without the introduction of new compounds. Adverse environmental effects associated with nematocides used to control plant parasitic species are also motivating the search for safer, more effective compounds. Discovery of new anthelmintic drugs in particular has been a serious challenge due to the difficulty of obtaining and culturing target parasites for high-throughput screens and the lack of functional genomic techniques to validate potential drug targets in these pathogens. We present here a novel strategy for target validation that employs the free-living nematode Caenorhabditis elegans to demonstrate the value of new ligand-gated ion channels as targets for anthelmintic discovery. Many successful anthelmintics, including ivermectin, levamisole and monepantel, are agonists of pentameric ligand-gated ion channels, suggesting that the unexploited pentameric ion channels encoded in parasite genomes may be suitable drug targets. We validated five members of the nematode-specific family of acetylcholine-gated chloride channels as targets of agonists with anthelmintic properties by ectopically expressing an ivermectin-gated chloride channel, AVR-15, in tissues that endogenously express the acetylcholine-gated chloride channels and using the effects of ivermectin to predict the effects of an acetylcholine-gated chloride channel agonist. In principle, our strategy can be applied to validate any ion channel as a putative anti-parasitic drug target. PMID:26393923

  11. Best management practices for herbicide resistance

    USDA-ARS?s Scientific Manuscript database

    In spite of the recent focus on herbicide resistant weeds, herbicide resistant weeds are not new to agriculture; the first herbicide resistant weed was documented in 1957, with the first widespread resistance occurring in common groundsel with atrazine in the early 1970’s. Glyphosate resistant weed...

  12. Evaluation of anthelmintic activity in captive wild ruminants by fecal egg reduction tests and a larval development assay.

    PubMed

    Young, K E; Jensen, J M; Craig, T M

    2000-09-01

    The effectiveness of anthelmintics was evaluated in four herds of captive ruminants, wapiti (Cervus elaphus), Armenian red sheep (Ovis orientalis), giraffe (Giraffa camelopardalis), and pronghorn (Antilocapra americana), by the use of fecal egg reduction tests (FERTs) and a commercial larval development assay (LDA) designed to evaluate susceptibility or resistance of nematodes to anthelmintics. Haemonchus sp. was the predominant nematode in the red sheep, giraffe, and pronghorn herds, whereas Ostertagia sp. and Trichostrongylus sp. were predominant in the wapiti. The LDA data indicated susceptibility by the worms to benzimidazoles except in the red sheep flock, which showed a high level of resistance. High levels of resistance to levamisole were seen in the worm populations from the wapiti and red sheep, moderate resistance in the pronghorn herd, and susceptibility in the giraffe herd. Worms were susceptible in all four herds to a combination of benzimidazole/levamisole. There was suspected avermectin resistance by Trichostrongylus sp. in the wapiti herd and by Haemonchus sp. in the giraffe. The FERTs agreed with the LDA in showing the Haemonchus in the giraffe was susceptible to fenbendazole and had suspected resistance to ivermectin, whereas Haemonchus in the red sheep and pronghorn were susceptible to ivermectin. There was correlation between the tests evaluating anthelmintics. The LDA is useful as a screening test in the selection of an anthelmintic for use in grazing ruminants, but the effectiveness of a drug in a host species may depend as much on the dose used, and the method of administration, as it does on the parasite's sensitivity to the anthelmintic.

  13. Zero-inflated hierarchical models for faecal egg counts to assess anthelmintic efficacy.

    PubMed

    Wang, Craig; Torgerson, Paul R; Höglund, Johan; Furrer, Reinhard

    2017-02-15

    The prevalence of anthelmintic resistance has increased in recent years, as a result of the extensive use of anthelmintic drugs to reduce the infection of parasitic worms in livestock. In order to detect the resistance, the number of parasite eggs in animal faeces is counted. Typically a subsample of the diluted faeces is examined, and the mean egg counts from both untreated and treated animals are compared. However, the conventional method ignores the variabilities introduced by the counting process and by different infection levels across animals. In addition, there can be extra zero counts, which arise as a result of the unexposed animals in an infected population or animals. In this paper, we propose the zero-inflated Bayesian hierarchical models to estimate the reduction in faecal egg counts. The simulation study compares the Bayesian models with the conventional faecal egg count reduction test and other methods such as bootstrap and quasi-Poisson regression. The results show the Bayesian models are more robust and they perform well in terms of both the bias and the coverage. We further illustrate the advantages of our proposed model using a case study about the anthelmintic resistance in Swedish sheep flocks.

  14. ANTHELMINTIC EFFECTS OF DRIED GROUND BANANA PLANT LEAVES (MUSA SPP.) FED TO SHEEP ARTIFICIALLY INFECTED WITH HAEMONCHUS CONTORTUS AND TRICHOSTRONGYLUS COLUBRIFORMIS.

    PubMed

    Gregory, Lilian; Yoshihara, Eidi; Silva, Leandro Kataoaka Fernandes; Marques, Eduardo Carvalho; Ribeiro, Bruno Leonardo Mendonça; de Souza Meira, Enoch Brandão; Rossi, Rodolfo Santos; do Amarante, Alessandro Francisco Talamini; Hasegawa, Marjorie Yumi

    2017-01-01

    Helminths is a endoparasites that cause the major losses for profitable sheep production in Brazil. The increased development of resistant strains of endoparasites have enforced the search for sustainable alternatives. The aim of this paper was to provide information about endoparasites control with banana leaves in infected sheep as alternative control strategies and see its viability. In this study, we performed two trials to investigate the anthelmintic properties of banana leaves on endoparasites in sheep. In Trial 1, twelve sheep were artificially infected with Trichostrongylus colubriformis; in Trial 2, eleven sheep were artificially infected with Haemonchus contortus. Clinical examinations, packed cell volume, total protein, faecal egg counts (FECs) and egg hatchability tests (EHTs) were performed. At the end of the trials, the sheep were humanely slaughtered, and total worm counts were performed. In Trial 1 and 2, no significant FEC decreases were note but significant diference in EHTs were observed. Total worm counts, clinical and haematological parameters did not reveal significant changes between the treatment and control groups. These results suggest that feeding dried ground banana plant leaves to sheep may reduce the viability of Trichostrongylus colubriformis eggs, and this anthelmintic activity is potentially exploitable as part of an integrated parasite management programme. However, further investigation is needed to establish the optimal dosage, develop a convenient delivery form and confirm the economic feasibility of using banana plantation byproducts as feed for ruminant species. Abbreviations: Coproculture test (CT)., Faecal egg count (FEC)., Egg hatchability test (EHT).

  15. Managing Resistance: Remembering How to Fly a Kite.

    ERIC Educational Resources Information Center

    Maag, John W.

    1997-01-01

    Describes a technique for managing resistance in which adults alter their responses to fit a child's perspective. Offers a cognitive perspective of reality and ways in which to create rapport through mirroring, postural congruence, and crossover mirroring. Provides techniques for managing resistance, such as acknowledging pessimistic beliefs and…

  16. Managing Resistance: Remembering How to Fly a Kite.

    ERIC Educational Resources Information Center

    Maag, John W.

    1997-01-01

    Describes a technique for managing resistance in which adults alter their responses to fit a child's perspective. Offers a cognitive perspective of reality and ways in which to create rapport through mirroring, postural congruence, and crossover mirroring. Provides techniques for managing resistance, such as acknowledging pessimistic beliefs and…

  17. Management of multiple drug-resistant tuberculosis.

    PubMed

    Hutchison, D C S; Drobniewski, F A; Milburn, H J

    2003-01-01

    There has been a worldwide increase in multiple drug-resistant tuberculosis (MDR-TB) which has in the past been associated with a poor prognosis. In the U.K., about half of the cases live in the London area and we have set out to obtain further information on their treatment and outcome. We examined the risk factors, drug resistance, drug treatment, sputum conversion, and outcome in patients with MDR-TB at three hospitals in South London and diagnosed during the period June 1995-January 1999. Human Immunodeficiency Virus (HIV)-positive patients were excluded. There were 760 patients resident in Lambeth, Southwark and Lewisham Health Authority (LSLHA) who were notified as tuberculosis (TB) during the time period and who were of negative or unknown HIV status. (The population of LSLHA is approx.750,000.) There was a total of 13 patients with MDR-TB, known or presumed to be HlV negative. Their median age was 28 years (range 15-53); nine (69%) were born outside the U.K. and 11 had pulmonary disease; they had organisms resistant to a median of two first-line drugs (range 2-4) and to a median of four of all drugs tested (range 2-10). They received treatment with a median of six drugs (range 3-9). Eight were followed up for at least 3 years (range 3-6) after the completion of treatment; at their last assessment none had features of active TB and all were sputum negative (smear and culture). Two returned to their countries of origin during treatment; they were sputum negative at that time. Two patients are well and continue on treatment in the U.K. One patient (known HIV negative) died following treatment failure. In conclusion, we obtained disease-free survival in eight cases of MDR-TB, known or presumed to be HIV negative and followed up for 3 years or more. The prognosis for patients treated at specialised centres is good (and better than is generally believed). We describe a new protocol for the detection and management of MDR-TB.

  18. Anthelmintic activity of Cocos nucifera L. against sheep gastrointestinal nematodes.

    PubMed

    Oliveira, L M B; Bevilaqua, C M L; Costa, C T C; Macedo, I T F; Barros, R S; Rodrigues, A C M; Camurça-Vasconcelos, A L F; Morais, S M; Lima, Y C; Vieira, L S; Navarro, A M C

    2009-01-22

    The development of anthelmintic resistance has made the search for alternatives to control gastrointestinal nematodes of small ruminants imperative. Among these alternatives are several medicinal plants traditionally used as anthelmintics. This work evaluated the efficacy of Cocos nucifera fruit on sheep gastrointestinal parasites. The ethyl acetate extract obtained from the liquid of green coconut husk fiber (LGCHF) was submitted to in vitro and in vivo tests. The in vitro assay was based on egg hatching (EHT) and larval development tests (LDT) with Haemonchus contortus. The concentrations tested in the EHT were 0.31, 0.62, 1.25, 2.5 and 5 mg ml(-1), while in the LDT they were 5, 10, 20, 40 and 80 mg ml(-1). The in vivo assay was a controlled test. In this experiment, 18 sheep infected with gastrointestinal nematodes were divided into three groups (n=6), with the following doses administered: G1-400 mg kg(-1) LGCHF ethyl acetate extract, G2-0.2 mg kg(-1) moxidectin (Cydectin) and G3-3% DMSO. The worm burden was analyzed. The results of the in vitro and in vivo tests were submitted to ANOVA and analyzed by the Tukey and Kruskal-Wallis tests, respectively. The extract efficacy in the EHT and LDT, at the highest concentrations tested, was 100% on egg hatching and 99.77% on larval development. The parameters evaluated in the controlled test were not statistically different, showing that despite the significant results of the in vitro tests, the LGCHF ethyl acetate extract showed no activity against sheep gastrointestinal nematodes.

  19. Phenotypic- and Genotypic-Resistance Detection for Adaptive Resistance Management in Tetranychus urticae Koch

    PubMed Central

    Kwon, Deok Ho; Kang, Taek-Jun; Kim, Young Ho; Lee, Si Hyeock

    2015-01-01

    Rapid resistance detection is necessary for the adaptive management of acaricide-resistant populations of Tetranychus urticae. Detection of phenotypic and genotypic resistance was conducted by employing residual contact vial bioassay (RCV) and quantitative sequencing (QS) methods, respectively. RCV was useful for detecting the acaricide resistance levels of T. urticae, particularly for on-site resistance detection; however, it was only applicable for rapid-acting acaricides (12 out of 19 tested acaricides). QS was effective for determining the frequencies of resistance alleles on a population basis, which corresponded to 12 nonsynonymous point mutations associated with target-site resistance to five types of acaricides [organophosphates (monocrotophos, pirimiphos-methyl, dimethoate and chlorpyrifos), pyrethroids (fenpropathrin and bifenthrin), abamectin, bifenazate and etoxazole]. Most field-collected mites exhibited high levels of multiple resistance, as determined by RCV and QS data, suggesting the seriousness of their current acaricide resistance status in rose cultivation areas in Korea. The correlation analyses revealed moderate to high levels of positive relationships between the resistance allele frequencies and the actual resistance levels in only five of the acaricides evaluated, which limits the general application of allele frequency as a direct indicator for estimating actual resistance levels. Nevertheless, the resistance allele frequency data alone allowed for the evaluation of the genetic resistance potential and background of test mite populations. The combined use of RCV and QS provides basic information on resistance levels, which is essential for choosing appropriate acaricides for the management of resistant T. urticae. PMID:26545209

  20. Anthelmintic activity of root bark of Carissa carandas.

    PubMed

    John, P P; Mazumder, Avijit; Mazumder, R; Bhatnagar, S P

    2007-07-01

    The anthelmintic activity of the Imethanolic extract of the root bark of Carissa carandas was evaluated on adult Indian earthworm (Pheretima posthuma) using albendazole as a reference standard. The extract caused paralysis followed by the death of worm at the tested dose level. The extract at the highest tested concentration has anthelmintic activity comparable with that of standard drug albendazole.

  1. Anthelmintic activity of root bark of Carissa carandas

    PubMed Central

    John, P.P.; Mazumder, Avijit; Mazumder, R.; Bhatnagar, S.P.

    2007-01-01

    The anthelmintic activity of the Imethanolic extract of the root bark of Carissa carandas was evaluated on adult Indian earthworm (Pheretima posthuma) using albendazole as a reference standard. The extract caused paralysis followed by the death of worm at the tested dose level. The extract at the highest tested concentration has anthelmintic activity comparable with that of standard drug albendazole. PMID:22557253

  2. Diagnosis, Treatment and Management of Haemonchus contortus in Small Ruminants.

    PubMed

    Besier, R B; Kahn, L P; Sargison, N D; Van Wyk, J A

    2016-01-01

    Haemonchus contortus is a highly pathogenic, blood-feeding nematode of small ruminants, and a significant cause of mortalities worldwide. Haemonchosis is a particularly significant threat in tropical, subtropical and warm temperate regions, where warm and moist conditions favour the free-living stages, but periodic outbreaks occur more widely during periods of transient environmental favourability. The clinical diagnosis of haemonchosis is based mostly on the detection of anaemia in association with a characteristic epidemiological picture, and confirmed at postmortem by the finding of large numbers of H. contortus in the abomasum. The detection of impending haemonchosis relies chiefly on periodic monitoring for anaemia, including through the 'FAMACHA' conjunctival-colour index, or through faecal worm egg counts and other laboratory procedures. A range of anthelmintics for use against H. contortus is available, but in most endemic situations anthelmintic resistance significantly limits the available treatment options. Effective preventative programmes vary depending on environments and enterprise types, and according to the scale of the haemonchosis risk and the local epidemiology of infections, but should aim to prevent disease outbreaks while maintaining anthelmintic efficacy. Appropriate strategies include animal management programmes to avoid excessive H. contortus challenge, genetic and nutritional approaches to enhance resistance and resilience to infection, and the monitoring of H. contortus infection on an individual animal or flock basis. Specific strategies to manage anthelmintic resistance centre on the appropriate use of effective anthelmintics, and refugia-based treatment schedules. Alternative approaches, such as biological control, may also prove useful, and vaccination against H. contortus appears to have significant potential in control programmes.

  3. Preventing and managing antiretroviral drug resistance.

    PubMed

    Kuritzkes, Daniel R

    2004-05-01

    Development of resistance to antiretroviral drugs (ARVs) is a major impediment to optimum treatment of HIV-1 infection. Although resistance testing can help to select subsequent regimens when virologic failure occurs, cross-resistance, which affects all classes of ARVs, may make it more difficult to achieve optimum control of HIV. We have known for some time that our first choice of antiretroviral therapy offers the best chance to control HIV replication and that initial therapy should be selected with an eye on future options. Potency is the first line of defense against the development of resistance. Other factors that affect resistance development include: tolerability, potential for optimum adherence, and genetic and pharmacologic barriers to development of resistance. If resistance emerges, only a single drug may be affected initially, and a rapid change in ARVs may preserve the efficacy of other components. One cautionary note is that we can no longer assume that a patient's HIV is fully susceptible to all ARVs even in the initial regimen. Transmission of drug-resistant HIV means that the genetic composition may be that of an "experienced" virus with reduced susceptibility to ARVs. Resistance testing at the time of transmission is most likely to reveal this resistance, but over time the dominant genetic pattern may revert to wild-type, and be missed by resistance testing. Because "archived" resistant HIV may emerge quickly once treatment is initiated, we need to keep this in mind when selecting initial therapy.

  4. Thymus vulgaris L. essential oil and its main component thymol: Anthelmintic effects against Haemonchus contortus from sheep.

    PubMed

    Ferreira, Luis E; Benincasa, Bruno I; Fachin, Ana L; França, Suzelei C; Contini, Silvia S H T; Chagas, Ana C S; Beleboni, Rene O

    2016-09-15

    Haemonchus contortus is an important gastrointestinal parasite on sheep farms in tropical regions. The resistance of the parasite against most anthelmintic drugs represents a great economic problem to sheep farming and is a major challenge that needs to be overcome. The searches for new anthelmintic agents that act on different stages of the parasite's life cycle are necessary for the development of new therapeutic options. The aim of this study was to evaluate the in vitro and in vivo anthelmintic activity of Thymus vulgaris essential oil against H. contortus and of its main component, the monoterpene thymol. Despite the relative ineffectiveness of the oil in the in vivo test, which may be corrected in the future after technical improvements to increase the oil's bioavailability, the in vitro results validated the popular use of T. vulgaris oil as an anthelmintic agent, at least against H. contortus. In fact, both the essential oil and thymol, which accounts for 50.22% of the oil composition, were effective against the three main stages of H. contortus. The oil and thymol were able to inhibit egg hatching by 96.4-100%, larval development by 90.8-100%, and larval motility by 97-100%. Similar to the positive control (levamisole 20mg/mL), the oil and thymol completely inhibited the motility of H. contortus adults within the first 8h of the experiment. Since thymol reproduces the anthelmintic effects of the oil and because it is the main component of the oil, it is reasonable to assume that thymol is the most important compound responsible for the anthelmintic effect of T. vulgaris. These results are of ethnopharmacological importance and may contribute to the development of new drugs and even herbal medicines, increasing treatment options for the farm breeding. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. The effectiveness of faecal removal methods of pasture management to control the cyathostomin burden of donkeys.

    PubMed

    Corbett, Christopher J; Love, Sandy; Moore, Anna; Burden, Faith A; Matthews, Jacqui B; Denwood, Matthew J

    2014-01-24

    The level of anthelmintic resistance within some cyathostomin parasite populations has increased to the level where sole reliance on anthelmintic-based control protocols is not possible. Management-based nematode control methods, including removal of faeces from pasture, are widely recommended for use in association with a reduction in anthelmintic use to reduce selection pressure for drug resistance; however, very little work has been performed to quantitatively assess the effectiveness of such methods. We analysed data obtained from 345 donkeys at The Donkey Sanctuary (Devon, UK), managed under three different pasture management techniques, to investigate the effectiveness of faeces removal in strongyle control in equids. The management groups were as follows: no removal of faeces from pasture, manual, twice-weekly removal of faeces from pasture and automatic, twice-weekly removal of faeces from pasture (using a mechanical pasture sweeper). From turn-out onto pasture in May, monthly faecal egg counts were obtained for each donkey and the dataset subjected to an auto regressive moving average model. There was little to no difference in faecal egg counts between the two methods of faecal removal; both resulted in significantly improved cyathostomin control compared to the results obtained from the donkeys that grazed pasture from which there was no faecal removal. This study represents a valuable and unique assessment of the effectiveness of the removal of equine faeces from pasture, and provides an evidence base from which to advocate twice-weekly removal of faeces from pasture as an adjunct for equid nematode control. Widespread adoption of this practice could substantially reduce anthelmintic usage, and hence reduce selection pressure for nematode resistance to the currently effective anthelmintic products.

  6. The effectiveness of faecal removal methods of pasture management to control the cyathostomin burden of donkeys

    PubMed Central

    2014-01-01

    Background The level of anthelmintic resistance within some cyathostomin parasite populations has increased to the level where sole reliance on anthelmintic-based control protocols is not possible. Management-based nematode control methods, including removal of faeces from pasture, are widely recommended for use in association with a reduction in anthelmintic use to reduce selection pressure for drug resistance; however, very little work has been performed to quantitatively assess the effectiveness of such methods. Methods We analysed data obtained from 345 donkeys at The Donkey Sanctuary (Devon, UK), managed under three different pasture management techniques, to investigate the effectiveness of faeces removal in strongyle control in equids. The management groups were as follows: no removal of faeces from pasture, manual, twice-weekly removal of faeces from pasture and automatic, twice-weekly removal of faeces from pasture (using a mechanical pasture sweeper). From turn-out onto pasture in May, monthly faecal egg counts were obtained for each donkey and the dataset subjected to an auto regressive moving average model. Results There was little to no difference in faecal egg counts between the two methods of faecal removal; both resulted in significantly improved cyathostomin control compared to the results obtained from the donkeys that grazed pasture from which there was no faecal removal. Conclusions This study represents a valuable and unique assessment of the effectiveness of the removal of equine faeces from pasture, and provides an evidence base from which to advocate twice-weekly removal of faeces from pasture as an adjunct for equid nematode control. Widespread adoption of this practice could substantially reduce anthelmintic usage, and hence reduce selection pressure for nematode resistance to the currently effective anthelmintic products. PMID:24460700

  7. In vitro anthelmintic efficacy of inhibitors of phosphoethanolamine Methyltransferases in Haemonchus contortus

    PubMed Central

    Witola, William H.; Matthews, Kwame; McHugh, Mark

    2016-01-01

    The essential phosphobase methylation pathway for synthesis of phosphocholine is unique to nematodes, protozoa and plants, and thus an attractive antiparasitic molecular target. Herein, we screened compounds from the National Cancer Institute (Developmental Therapeutics Program Open Chemical Repository) for specific inhibitory activity against Haemonchus contortus phosphoethanolamine methyltransferases (HcPMT1 and HcPMT2), and tested candidate compounds for anthelmintic activity against adult and third-stage larvae of H. contortus. We identified compound NSC-641296 with IC50 values of 8.3 ± 1.1 μM and 5.1 ± 1.8 μM for inhibition of the catalytic activity of HcPMT1 alone and HcPMT1/HcPMT2 combination, respectively. Additionally we identified compound NSC-668394 with inhibitory IC50 values of 5.9 ± 0.9 μM and 2.8 ± 0.6 μM for HcPMT1 alone and HcPMT1/HcPMT2 combination, respectively. Of the two compounds, NSC-641296 depicted significant anthelmintic activity against third-stage larvae (IC50 = 15 ± 2.9 μM) and adult stages (IC50 = 7 ± 2.9 μM) of H. contortus, with optimal effective in vitro concentrations being 2-fold and 4-fold, respectively, lower than its cytotoxic IC50 (29 ± 2.1 μM) in a mammalian cell line. Additionally, we identified two compounds, NSC-158011 and NSC-323241, with low inhibitory activity against the combined activity of HcPMT1 and HcPMT2, but both compounds did not show any anthelmintic activity against H. contortus. The identification of NSC-641296 that specifically inhibits a unique biosynthetic pathway in H. contortus and has anthelmintic activity against both larval and adult stages of H. contortus, provides impetus for the development of urgently needed new efficacious anthelmintics to address the prevailing problem of anthelmintic-resistant H. contortus. PMID:27054063

  8. In vitro anthelmintic efficacy of inhibitors of phosphoethanolamine Methyltransferases in Haemonchus contortus.

    PubMed

    Witola, William H; Matthews, Kwame; McHugh, Mark

    2016-04-01

    The essential phosphobase methylation pathway for synthesis of phosphocholine is unique to nematodes, protozoa and plants, and thus an attractive antiparasitic molecular target. Herein, we screened compounds from the National Cancer Institute (Developmental Therapeutics Program Open Chemical Repository) for specific inhibitory activity against Haemonchus contortus phosphoethanolamine methyltransferases (HcPMT1 and HcPMT2), and tested candidate compounds for anthelmintic activity against adult and third-stage larvae of H. contortus. We identified compound NSC-641296 with IC50 values of 8.3 ± 1.1 μM and 5.1 ± 1.8 μM for inhibition of the catalytic activity of HcPMT1 alone and HcPMT1/HcPMT2 combination, respectively. Additionally we identified compound NSC-668394 with inhibitory IC50 values of 5.9 ± 0.9 μM and 2.8 ± 0.6 μM for HcPMT1 alone and HcPMT1/HcPMT2 combination, respectively. Of the two compounds, NSC-641296 depicted significant anthelmintic activity against third-stage larvae (IC50 = 15 ± 2.9 μM) and adult stages (IC50 = 7 ± 2.9 μM) of H. contortus, with optimal effective in vitro concentrations being 2-fold and 4-fold, respectively, lower than its cytotoxic IC50 (29 ± 2.1 μM) in a mammalian cell line. Additionally, we identified two compounds, NSC-158011 and NSC-323241, with low inhibitory activity against the combined activity of HcPMT1 and HcPMT2, but both compounds did not show any anthelmintic activity against H. contortus. The identification of NSC-641296 that specifically inhibits a unique biosynthetic pathway in H. contortus and has anthelmintic activity against both larval and adult stages of H. contortus, provides impetus for the development of urgently needed new efficacious anthelmintics to address the prevailing problem of anthelmintic-resistant H. contortus.

  9. The economic effects of whole-herd versus selective anthelmintic treatment strategies in dairy cows.

    PubMed

    Charlier, J; Levecke, B; Devleesschauwer, B; Vercruysse, J; Hogeveen, H

    2012-06-01

    Current control practices against gastrointestinal nematodes in dairy cows rely strongly on anthelmintic use. To reduce the development of anthelmintic resistance or disposition of drug residues in the environment, novel control approaches are currently proposed that target anthelmintic treatment to individual animals instead of the whole herd. However, such selective treatment strategies come with additional costs for labor and diagnostics and, so far, no studies have addressed whether they could be economically sustainable. The objectives of this study were to (1) investigate the economic effects at farm level of whole-herd versus more selective anthelmintic treatment strategies in adult dairy cows, and (2) determine how these economic effects depend on level of infection and herd size. A Monte Carlo simulation, fed by current epidemiological and economical knowledge, was used to estimate the expected economic effects and possible variation of different control strategies under Belgian conditions. Four treatment strategies were compared with a baseline situation in which no treatments were applied: whole herd at calving (S1), selective at calving with (S2) or without (S3) treatment of the first-calf cows, and whole-herd when animals are moved from grazing to the barn in the fall (housing treatment, S4). The benefit per lactation for an average dairy herd varied between -$2 and $131 (average $64) for S1, between -$2 and $127 (average $62) for S2, between -$17 and $104 (average $43) for S3, and between -$41 and $72 (average $15) for S4. The farmer's risk associated with any treatment strategy, as indicated by the width of the 95% credible intervals of economic benefit of anthelmintic treatment, decreased with increasing level of exposure, as assessed by bulk tank milk ELISA. The order of the different strategies when sorted by expected benefit was robust to changes in economic input parameters. We conclude that, on average, strategies applying anthelmintic

  10. The effect of providing feed supplementation and anthelmintic to donkeys during late pregnancy and lactation on live weight and survival of dams and their foals in central Ethiopia.

    PubMed

    Mengistu, A; Smith, D G; Yoseph, S; Nega, T; Zewdie, W; Kassahun, W G; Taye, B; Firew, T

    2005-11-01

    Anthelmintic treatment (A), feed supplementation (F), anthelmintic and feed supplementation (A+F) or traditional management (Control) was given to 166 pregnant female donkeys in three localities (Holetta, Debre Zeit and Adami Tulu) in Ethiopia during an on-farm study. Treatments started during the last trimester of pregnancy and continued until 6 months after parturition when the foals were weaned. The same treatments were administered to foals once they reached 1 month of age. Live weights of adults and foals were measured throughout the study along with work output of adult donkeys and survival to weaning of the foals. Faecal worm egg counts (FEC) and blood packed cell volumes (PCV) were recorded monthly. When applied alone, anthelmintic treatment (A) or feed supplementation (F) had no significant effect on live weight gain or foal survival. However, when combined, anthelmintic and feed supplementation (A+F) significantly (p<0.05) improved both live weight gain in adults and foals and foal survival. Workout was not affected by any of the treatments. Treatments A and A+F resulted in a highly significant (p<0.001) reduction in FEC in all three localities during the course of study and for at least 6 months after the last dose of anthelmintic in one of the study areas (Holetta). None of the treatments had any significant effect on PCV. Donkey owners in Ethiopia should be encouraged to adopt both anthelmintic treatment and feed supplementation if they expect tangible benefits in animal performance.

  11. Parasite control in Canadian companion animal shelters and a cost-comparison of anthelmintics

    PubMed Central

    Schurer, Janna M.; McKenzie, Christina; Dowling, Patricia M.; Bouchard, Emilie; Jenkins, Emily J.

    2015-01-01

    Animal shelters have limited resources and must accommodate large numbers of animals at unpredictable intake rates. These dogs and cats are often parasitized, which can adversely affect the health of animals and expose shelter workers and adoptive owners to zoonoses. We analyzed survey responses from rural (n = 32) and urban (n = 50) companion animal shelters across Canada, and compared the wholesale cost of commercially available anthelmintics to identify cost-effective methods of managing parasites within shelters. Almost all shelters employed nematocides (98% to 99%), but cestocides and ectoparasiticides were used less frequently. Shelters identified cost as an important consideration in choosing to perform fecal diagnostic testing and administer anthelmintics, and this motivated many shelters to selectively perform testing (66%) or never to test (32%), and to use drugs extralabel (80%). PMID:26345387

  12. Modulation of porcine biotransformation enzymes by anthelmintic therapy with fenbendazole and flubendazole.

    PubMed

    Savlík, M; Fimanová, K; Szotáková, B; Lamka, J; Skálová, L

    2006-06-01

    Fenbendazole (FEN) and flubendazole (FLU) are benzimidazole anthelmintics often used in pig management for the control of nematodoses. The in vivo study presented here was designed to test the influence of FLU and FEN on cytochrome P4501A and other cytochrome P450 (CYP) isoforms, UDP-glucuronosyl transferase and several carbonyl reducing enzymes. The results indicated that FEN (in a single therapeutic dose as well as in repeated therapeutic doses) caused significant induction of pig CYP1A, while FLU did not show an inductive effect towards this isoform. Some of the other hepatic and intestinal biotransformation enzymes that were assayed were moderately influenced by FEN or FLU. Strong CYP1A induction following FEN therapy in pigs may negatively affect the efficacy and pharmacokinetics of FEN itself or other simultaneously or consecutively administered drugs. From the perspective of biotransformation enzyme modulation, FLU would appear to be a more convenient anthelmintic therapy of pigs than FEN.

  13. Resistance gene management: concepts and practice

    Treesearch

    Christopher C. Mundt

    2012-01-01

    There is now a very long history of genetics/breeding for disease resistance in annual crops. These efforts have resulted in conceptual advances and frustrations, as well as practical successes and failures. This talk will review this history and its relevance to the genetics of resistance in forest species. All plant breeders and pathologists are familiar with boom-...

  14. Patterns of Resistance in Managing Assessment Change

    ERIC Educational Resources Information Center

    Deneen, Christopher; Boud, David

    2014-01-01

    Achieving change in assessment practices in higher education is difficult. One of the reasons for this is resistance among those responsible for teaching and assessing. This paper seeks to explore this resistance through an analysis of staff dialogue during a major attempt to change the assessment practices at one institution. An institution-wide…

  15. Patterns of Resistance in Managing Assessment Change

    ERIC Educational Resources Information Center

    Deneen, Christopher; Boud, David

    2014-01-01

    Achieving change in assessment practices in higher education is difficult. One of the reasons for this is resistance among those responsible for teaching and assessing. This paper seeks to explore this resistance through an analysis of staff dialogue during a major attempt to change the assessment practices at one institution. An institution-wide…

  16. Efficacy of anthelmintic properties of medicinal plant extracts against Haemonchus contortus.

    PubMed

    Kamaraj, C; Rahuman, A Abdul

    2011-12-01

    The development of anthelmintic resistance has made the search for alternatives to control gastrointestinal nematodes of small ruminants imperative. Among these alternatives are several medicinal plants traditionally used as anthelmintics. This present work evaluated the efficacy of ethyl acetate, acetone, and methanol dried leaf and seed extracts of five medicinal plants were tested in vitro ovicidal and larvicidal activities on Haemonchus contortus. The in vitro assay was based on egg hatch assay (EHA) and larval development assay (LDA), all plant extracts were evaluated at five concentrations 50, 25, 12.5, 6.25 and 3.13 mg/ml. The leaf and seed ethyl acetate, acetone and methanol of Annona squamosa, Eclipta prostrata, Solanum torvum, Terminalia chebula, and Catharanthus roseus extracts were showed complete inhibition (100%) at the maximum concentration tested (50 mg/ml). The overall findings of the present study have shown that our experimental plant extracts contain possible anthelmintic compounds. Copyright © 2010 Elsevier Ltd. All rights reserved.

  17. Transcriptome analysis reveals molecular anthelmintic effects of procyanidins in C. elegans.

    PubMed

    Spiegler, Verena; Hensel, Andreas; Seggewiß, Jochen; Lubisch, Milena; Liebau, Eva

    2017-01-01

    Worldwide, more than 1 billion people are affected by infestations with soil-transmitted helminths and also in veterinary medicine helminthiases are a severe threat to livestock due to emerging resistances against the common anthelmintics. Proanthocyanidins have been increasingly investigated for their anthelmintic properties, however, except for an interaction with certain proteins of the nematodes, not much is known about their mode of action. To investigate the anthelmintic activity on a molecular level, a transcriptome analysis was performed in Caenorhabditis elegans after treatment with purified and fully characterized oligomeric procyanidins (OPC). The OPCs had previously been obtained from a hydro-ethanolic (1:1) extract from the leaves of Combretum mucronatum, a plant which is traditionally used in West Africa for the treatment of helminthiasis, therefore, also the crude extract was included in the study. Significant changes in differential gene expression were observed mainly for proteins related to the intestine, many of which were located extracellularly or within cellular membranes. Among the up-regulated genes, several hitherto undescribed orthologues of structural proteins in humans were identified, but also genes that are potentially involved in the worms' defense against tannins. For example, T22D1.2, an orthologue of human basic salivary proline-rich protein (PRB) 2, and numr-1 (nuclear localized metal responsive) were found to be strongly up-regulated. Down-regulated genes were mainly associated with lysosomal activity, glycoside hydrolysis or the worms' innate immune response. No major differences were found between the groups treated with purified OPCs versus the crude extract. Investigations using GFP reporter gene constructs of T22D1.2 and numr-1 corroborated the intestine as the predominant site of the anthelmintic activity. The current findings support previous hypotheses of OPCs interacting with intestinal surface proteins and provide the

  18. Management of treatment resistance in schizophrenia.

    PubMed

    Conley, R R; Kelly, D L

    2001-12-01

    A systematic approach to the evaluation and characterization of treatment resistance in schizophrenia has become increasingly important since the introduction of the second-generation antipsychotics. The need for accurate evaluation will increase further as other new antipsychotic medications are developed. Patients with schizophrenia may manifest poor response to therapy because of intolerance to medication, poor adherence, inappropriate dosing, as well as true resistance of their illness to antipsychotic drug therapy. Criteria for treatment-resistance are presented to help in standardizing treatment and clinical trials. As clinicians face the decision of when to change or augment antipsychotic medications, a clear understanding of the appropriate length of a treatment trial and which target symptoms respond to antipsychotic therapy is critical for maximizing response in patients with treatment-resistant schizophrenia.

  19. [Diagnosis and management of antibiotic-resistant bacteria].

    PubMed

    Yanagihara, Katsunori; Kamihira, Shimeru

    2012-06-01

    Antibiotic-resistant infections acquired in hospitals are of great concern, and have become a serious public issue. Antibiotic-resistant infections can be associated with a variety of bacteria, such as methicillin resistant Staphylococcus aureus(MRSA) and multidrug-resistant Pseudomonas aeruginosa (MDRP). Since clinical laboratories are responsible for detecting information regarding antibiotic-resistant bacteria, they are required to perform analysis and dissemination of the information. Currently, rapid methods for detecting antibiotic-resistant bacteria using molecular techniques are being developed in response to the problem of the conventional methods for bacteriological testing, which require a few days to obtain results. This article presents the diagnosis and management of antibiotic-resistant bacteria, which comprise a serious health care issue.

  20. In vitro anthelmintic activity of active compounds of the fringed rue Ruta chalepensis against dairy ewe gastrointestinal nematodes.

    PubMed

    Ortu, E; Sanna, G; Scala, A; Pulina, G; Caboni, P; Battacone, G

    2016-06-22

    Infections by gastrointestinal nematodes negatively affect small ruminant health and at the same time cause substantial economic losses worldwide. Because resistance to conventional anthelmintic compounds is growing, target studies evaluating the effectiveness of alternative ingredients of botanical origin on gastrointestinal nematodes are needed. In this study, we evaluated the in vitro anthelmintic activity of Ruta chalepensis L. extracts on the third-stage larvae of sheep gastrointestinal nematodes. A methanol extract showed the highest anthelmintic activity, with an EC50 = 0.10 ± 0.06 mg/ml after 96 h, while the essential oil had an EC50 = 1.45 ± 1.22 mg/ml after 48 h. Moreover, three secondary metabolites of the essential oil, i.e. 2-decanone, 2-nonanone and 2-undecanone, showed EC50 values of 0.07 ± 0.06, 0.25 ± 0.29 and 0.88 ± 0.73 mg/ml at 24 h, respectively. The present study indicated that the R. chalepensis methanol extract, the essential oil and its metabolites 2-decanone, 2-nonanone and 2-undecanone showed promising anthelmintic activity on gastrointestinal nematodes.

  1. An in vitro larval migration assay for assessing anthelmintic activity of different drug classes against Ascaris suum.

    PubMed

    Zhao, Jianguo; Williams, Andrew R; Hansen, Tina Vicky Alstrup; Thamsborg, Stig M; Cai, Jianping; Song, Shuaibao; Chen, Gang; Kang, Ming; Zhang, Zhuangzhi; Liu, Qun; Han, Qian

    2017-03-18

    In vitro methods have been developed for the detection of anthelmintic resistance in a range of nematode species. However, the life cycle of Ascaris suum renders the commonly used egg hatch assay and larval development assay unusable. In this study we developed a combined multi-well culture and agar gel larval migration assay to test the effect of benzimidazole and tetrahydropyrimidin/imidazothiazole anthelmintics against nine isolates of A. suum collected from locations in China and Denmark. Drugs tested were thiabendazole, fenbendazole, mebendazole, levamisole, and pyrantel. The percentages of larvae that migrated to the surface of each treated and control well were used to calculate the drug concentration which inhibits 50% of the larvae migration (EC50). The values of EC50 of thiabendazole, fenbendazole, mebendazole, levamisole, and pyrantel against A. suum isolates ranged 74-150, 4.9-13.9, 2.3-4.3, 358-1150 and 1100-4000nM, respectively. This combined multi-well culture and agar gel larval migration assay was a sensitive bioassay for anthelmintic activity and could serve as an in vitro method to detect for lowered drug efficacy against A. suum or possibly to screen for anthelmintic drug candidates.

  2. Framing the issues of resistance management in soybean

    USDA-ARS?s Scientific Manuscript database

    The soybean insect-pest complex consists of both long-established and new invasive pests. Management of these pests has been achieved by various means, but often relies heavily on the application of insecticides and the development of insect-resistant soybean varieties. Pest management practitione...

  3. Parasite management extension - challenging traditional practice through adoption of a systems approach.

    PubMed

    Wilson, L; Rhodes, A P; Dodunski, G

    2015-11-01

    The drivers for anthelmintic use today are substantial and anthelmintic use has become an embedded normalised behaviour. The cheapness and easy availability of anthelmintic products has meant that New Zealand farmers have had access to easy "solutions" for dealing with parasites and minimal forward planning or system redesign has been required. Despite 30 years of messaging about the emerging issue of anthelmintic resistance, management to reduce parasitism and the need to change behaviour, farmer practice has largely remained unchanged. Traditional approaches to extension, particularly around parasite management, appear to have been quite ineffective, apart from encouraging change in anthelmintic products and a switch to use of anthelmintics in combination. More effective approaches are required. The evolving nature of anthelmintic resistance and sustainable management of parasitism require attitudes, knowledge and behaviour to change. This is a challenge for all players in the industry; researchers, manufacturers and sellers, advisors and farmers. Looking beyond agriculture to the health sector provides some insight into models of decision making and behaviour change that can inform future strategies. Features in the health belief model including concepts of self-efficacy and cues to action appear to align with the issues, challenges and culture prevailing in farming, and parasite management in particular. Programmes through which farmers have made substantial beneficial behaviour change and the lessons learnt are discussed. Effecting consistent behaviour change around parasite management will involve new approaches by all participants in the process. And the process itself also needs to change. It requires an understanding of whole-farm systems, and the consideration of all the sources of influence on the farmer and the other participants in the process. The process of knowledge sharing involving the farmer should be based on equality; each person in the process

  4. Anthelmintic macrolactams from Nonomuraea turkmeniaca MA7364.

    PubMed

    Ayers, Sloan; Zink, Deborah L; Mohn, Kenneth; Powell, Joanne Staats; Brown, Christine M; Murphy, Terry; Grund, Alan; Genilloud, Olga; Salazar, Oscar; Thompson, Donald; Singh, Sheo B

    2007-08-01

    Two new macrolactams, 6-desmethyl-N-methylfluvirucin A1 (1) and N-methylfluvirucin A1 (2), have been isolated from the acetone extract of Nonomuraea turkmeniaca MA7364. These compounds were isolated by bioassay-guided fractionation as part of our search for new anthelmintics. The structures of these compounds were elucidated by comparison of their NMR and MS data to those of previously reported fluvirucins and confirmed by 2D NMR. Compound 1 exhibited in vitro activity (EC(90) 15 +/- 5 microg/mL) against Haemonchus contortus larvae, whereas compound 2, while a bit less active in vitro (EC(90) 29 +/- 8 microg/mL), showed modest in vivo activity against a surrogate organism, Heligmosomoides polygyrus in mice, at 50 mg/kg.

  5. Anthelmintic macrolactams from Nonomuraea turkmeniaca MA7381.

    PubMed

    Ayers, Sloan; Zink, Deborah L; Powell, Joanne Staats; Brown, Christine M; Grund, Alan; Genilloud, Olga; Salazar, Oscar; Thompson, Donald; Singh, Sheo B

    2008-02-01

    A new macrolactam, fluvirucin B0 (1), and two known macrolactams, Sch 38516/fluvirucin B1 (2) and Sch 39185/fluvirucin B3 (3), have been isolated from an acetone extract of a strain of Nonomuraea turkmeniaca. These compounds were isolated by bioassay-guided fractionation as part of our search for new anthelmintics. The structures of these compounds were elucidated by comparison of their NMR and MS data to those of previously reported fluvirucins, and confirmed by 2D-NMR. 1approximately 3 exhibited in vitro activity (EC90 <1.0 approximately 1.7 microg/ml) against Haemonchus contortus larvae, but were ineffective in reducing worm counts in vivo against Heligmosomoides polygyrus in mice at 50 mg/kg dosed intramuscularly.

  6. Field efficacy and safety of an oral formulation of the novel combination anthelmintic, derquantel-abamectin, in sheep in New Zealand

    PubMed Central

    Little, PR; Hodge, A; Watson, TG; Seed, JA; Maeder, SJ

    2011-01-01

    AIM: To evaluate the efficacy and safety of the novel anthelmintic combination, derquantel-abamectin, against gastrointestinal nematode populations in sheep, under field-use conditions. METHODS: Controlled faecal egg count reduction tests (FECRT) were conducted in New Zealand in 14 trials, covering a range of geographic locations, farming enterprises, breeds, nematode populations, and anthelmintic-resistance profiles. Enrolled animals were naturally infected with mixed populations of gastrointestinal nematodes. All trials included a group treated with derquantel-abamectin, and a negative control group. Nine trials included additional groups each treated with a single- or dual-active oral reference anthelmintic, selected from albendazole, levamisole, albendazole-levamisole, ivermectin, abamectin and moxidectin. A total of 838 animals were enrolled across all trials, and were randomly allocated to treatment groups within blocks defined by faecal nematode egg counts (FEC) pre-treatment. On Day 0 derquantel-abamectin was administered orally at 1 ml/5 kg bodyweight (2 mg/kg derquantel, 0.2 mg/ kg abamectin), and each reference anthelmintic was given at the recommended label dose. Faecal samples were collected on Day 14 (± 1 day), to determine the percentage reduction in mean FEC for each anthelmintic tested. Larval differentiation was also performed post-treatment, to estimate efficacy at the genus level. Animals were weighed on or before Day 0, and on Day 14 (± 1 day) in 13 trials. RESULTS: The efficacy of derquantel-abamectin against mixed strongyle populations was ≥99.2%, based on the percentage reduction in geometric mean FEC. Nematodirus sp. was present in six trials at a level sufficient for efficacy calculations to be conducted; in all cases, the efficacy of derquantel-abamectin was 100%. In those trials where the efficacy of at least one reference anthelmintic was <95% against strongyles and/or Nematodirus sp., derquantel-abamectin was 100% effective. In

  7. [Anthelmintic control of multiresistant nematodes in the gastrointestinal tract of imported goats].

    PubMed

    Corba, J; Várady, M; Praslicka, J; Veselý, L

    1993-01-01

    Multiple resistant strains of Ostertagia and Trichostrongylus were detected in a flock of cashmere and angora goats imported from New Zealand. The ED50 values detected by in vitro EHA test were from 0.27 to 0.36 micrograms/ml (while the reference value of sensitivity is 0.10 microgram/ml TBZ). Multiple resistance to all the types of currently used anthelmintics was confirmed by in vivo FECRT, when the efficacy of recommended doses was lower than 90% (albendazole 74%, levamisole 86%, ivermectin 83%). Two control schemes were investigated. In the simultaneous application of anthelmintics in the double or triple of recommended doses (0.4 mg/kg ivermectin s.c., 30 mg/kg levamisole and 20 mg/kg albendazole p.o.) was effective. Examination of goats 7 and 8 months after treatment revealed the repeated presence of multiple resistant gastrointestinal nematodes. It is the first published case of intercontinental transfer of resistant strains of nematodes when importing small ruminants.

  8. Anthelmintic efficiency of doramectin, fenbendazole, and nitroxynil, in combination or individually, in sheep worm control.

    PubMed

    Holsback, Luciane; Luppi, Pedro Alex Ramsey; Silva, Camile Sanches; Negrão, Gustavo Kremer; Conde, Gabriel; Gabriel, Hugo Vinícius; Balestrieri, João Vitor; Tomazella, Lucas

    2016-01-01

    The anthelmintic efficiency of doramectin, fenbendazole, and nitroxynil, used individually or in combination, was determined by the Fecal Egg Count Reduction (FECR) test and cultivation of larvae of anthelminthic-treated sheep grouped as follows: G1 (doramectin), G2 (fenbendazole), G3 (nitroxynil), G4 (doramectin + fenbendazole), G5 (doramectin + nitroxynil), G6 (fenbendazole + nitroxynil), G7 (doramectin + nitroxynil + fenbendazole), G8 (untreated). In addition to individually used doramectin and fenbendazole, the helminths were also resistant to the combination of doramectin + fenbendazole; nitroxynil + fenbendazole; and doramectin + nitroxynil + fenbendazole, with their FECR rates ranging from 62-83%. The helminths showed possible nitroxynil-resistance, but had low resistance when the drug was administered in combination with doramectin. The evaluation of individual helminth species revealed that fenbendazole was fully effective against Cooperia; doramectin (G1), moderately effective against Haemonchus and insufficiently active against Cooperia; nitroxynil, effective against Haemonchus and insufficiently active against Cooperia. It was concluded from the results that herd nematodes are resistant to doramectin, fenbendazole, and nitroxynil, and that the combined use of the drugs not only fails to significantly improve the anthelmintic efficiency against Haemonchus and Cooperia, but is also cost-ineffective.

  9. Resistance Management Research Status-May 2008

    EPA Science Inventory

    Long-term sustainability of genetically modified corn expressing Bt relies on the validity of assumptions underlying IRM models used by the EPA and the ability of EPA to monitor, detect and react to insect resistance when it develops. The EPA is developing a multi-tiered approac...

  10. Managing the evolution of herbicide resistance

    USDA-ARS?s Scientific Manuscript database

    Herbicide-resistant (HR) weeds are widespread threats to the sustainability, productivity, and profitability of many cropping systems. Efforts to combat their spread through herbicide rotation schedules have been marginally effective at best. Despite the scope of the problem, we lack sound empirical...

  11. Resistance Management Research Status-May 2008

    EPA Science Inventory

    Long-term sustainability of genetically modified corn expressing Bt relies on the validity of assumptions underlying IRM models used by the EPA and the ability of EPA to monitor, detect and react to insect resistance when it develops. The EPA is developing a multi-tiered approac...

  12. Sustainable management of insect-resistant crops

    USDA-ARS?s Scientific Manuscript database

    Crop genetically engineered to provide resistance to specific groups of insect pests have been adopted by millions of growers throughout the world. Here we document the effects of transgenic crops on pest population densities, beneficial insect densities and biological control services, insecticide ...

  13. Anthelmintic properties of extracts from Artemisia plants against nematodes.

    PubMed

    Khan, S; Afshan, K; Mirza, B; Miller, J E; Manan, A; Irum, S; Rizvi, S S R; Qayyum, M

    2015-06-01

    Artemisia plant genus, natural inhabitant of northern Punjab Pakistan, is well known for its anthelmintic properties; many Artemisia species have not been so far scientifically proved. The aim of this study was to assess in vitro anthelmintic activity of Artemisia indica and Artemisia roxburghiana against mixed infection of gastrointestinal nematodes in small ruminants. This study is first scientifically proven study on anthelmintic activity of A. indica and A. roxburghiana. Five different concentrations (50, 25, 12.5, 6.25 and 3.75 mg/mL) accompanied by negative control (PBS) and positive control (albendazole, 10%) were used to carry out the egg hatch inhibition assay, larval mortality assay and adult worm mortality assay. The Baermann technique was used first time in larval mortality assay and proved to be effective. The results revealed that methanolic extracts of both A. indica and A. roxburghiana, showed maximum anthelmintic activity at concentration of 50 mg/ml by egg hatch inhibition (85±21.2; 80±28.3), larvae mortality (18±2.8; 17±4.2) and adult worm mortality (8.5±2.1; 8±2.8) assays. However, at concentration of 50 mg/ml both plant extracts in comparison to albendazole showed statistically insignificant (p≤0.05) results. The A. indica showed higher anthelmintic activity at all concentrations as compared to A. roburghiana. It has been concluded both plants exhibit anthelmintic activity and further evaluation of these plants should be carried out to purify the active ingredients for anthelmintic activity. Moreover, the decoctions of these plants could be used to GINs after confirming anthelmintic properties through in vivo.

  14. The antimicrobial resistance crisis: management through gene monitoring

    PubMed Central

    2016-01-01

    Antimicrobial resistance (AMR) is an acknowledged crisis for humanity. Its genetic origins and dire potential outcomes are increasingly well understood. However, diagnostic techniques for monitoring the crisis are currently largely limited to enumerating the increasing incidence of resistant pathogens. Being the end-stage of the evolutionary process that produces antimicrobial resistant pathogens, these measurements, while diagnostic, are not prognostic, and so are not optimal in managing this crisis. A better test is required. Here, using insights from an understanding of evolutionary processes ruling the changing abundance of genes under selective pressure, we suggest a predictive framework for the AMR crisis. We then discuss the likely progression of resistance for both existing and prospective antimicrobial therapies. Finally, we suggest that by the environmental monitoring of resistance gene frequency, resistance may be detected and tracked presumptively, and how this tool may be used to guide decision-making in the local and global use of antimicrobials. PMID:27831476

  15. Herbicide-resistant weed management: focus on glyphosate.

    PubMed

    Beckie, Hugh J

    2011-09-01

    This review focuses on proactive and reactive management of glyphosate-resistant (GR) weeds. Glyphosate resistance in weeds has evolved under recurrent glyphosate usage, with little or no diversity in weed management practices. The main herbicide strategy for proactively or reactively managing GR weeds is to supplement glyphosate with herbicides of alternative modes of action and with soil-residual activity. These herbicides can be applied in sequences or mixtures. Proactive or reactive GR weed management can be aided by crop cultivars with alternative single or stacked herbicide-resistance traits, which will become increasingly available to growers in the future. Many growers with GR weeds continue to use glyphosate because of its economical broad-spectrum weed control. Government farm policies, pesticide regulatory policies and industry actions should encourage growers to adopt a more proactive approach to GR weed management by providing the best information and training on management practices, information on the benefits of proactive management and voluntary incentives, as appropriate. Results from recent surveys in the United States indicate that such a change in grower attitudes may be occurring because of enhanced awareness of the benefits of proactive management and the relative cost of the reactive management of GR weeds.

  16. Resistance to Change Reconsidered: Implications for Managers

    ERIC Educational Resources Information Center

    Powell, Gary; Posner, Barry Z.

    1978-01-01

    Managers should understand that people react to proposed changes in a variety of ways and make every effort to recognize what their employees' responses to change actually are and what factors are likely to affect their responses. (Author)

  17. Echinocandin Resistance, Susceptibility Testing and Prophylaxis: Implications for Patient Management

    PubMed Central

    Perlin, David S.

    2014-01-01

    This article addresses the emergence of echinocandin resistance among Candida species, mechanisms of resistance, factors that promote resistance and confounding issues surrounding standard susceptibility testing. Fungal infections remain a significant cause of global morbidity and mortality, especially among patients with underlying immunosupression. Antifungal therapy is a critical component of patient management for acute and chronic diseases. Yet, therapeutic choices are limited due to only a few drug classes available to treat systemic disease. Moreover, the problem is exacerbated by the emergence of antifungal resistance, which has resulted in difficult to manage multidrug resistant strains. Echinocandin drugs are now the preferred choice to treat a range of candidiasis. These drugs target and inhibit the fungal-specific enzyme glucan synthase, which is responsible for the biosynthesis of a key cell wall polymer. Therapeutic failures involving acquisition of resistance among susceptible organisms like Candida albicans is largely a rare event. However, in recent years, there is an alarming trend of increased resistance among strains of Candida glabrata, which in many cases are also resistant to azole drugs. Echinocandin resistance is always acquired during therapy and the mechanism of resistance is well established to involve amino acid changes in “hot-spot regions of the Fks subunits carrying the catalytic portion of glucan synthase. These changes significantly decrease the sensitivity of the enzyme to drug resulting in higher MIC values. A range of drug responses, from complete to partial refractory response, is observed depending on the nature of the amino acid substitution, and clinical responses are recapitulated in pharmacodynamic models of infection. The cellular processes promoting the formation of resistant Fks strains involve complex stress response pathways, which yield a variety of adaptive compensatory genetic responses. Stress-adapted cells

  18. Resistance to medical educational change: management and communication.

    PubMed

    Tsai, Tsuen-Chiuan

    2007-01-01

    Medical education in Taiwan is currently undergoing active renovation. Reform and changes always bring resistance from the levels of individuals, institution and even the society. As an educational leader, to be able to manage resistance is a key to successful reform. This review article provides management strategies and communication skills to solve the resistance problem. The best solution to the problem is "to prevent" resistance from happening through identifying those who may be reluctant to change, and the reasons behind the potential resistance. Some of the reasons for resistance are threatening of self-interest and a loss of face, excess uncertainty, conservatism, fear of personal-worth declination in the organization, and different assessment or perception. The management and communication strategies are suggested to adjust to fit reform process, i.e., recognizing the needs for change, planning process, implementation, and institutionalization innovation. Finally, it is only with respect, empathy, sincerity and support that the resistance to changes can be resolved and difficulties can be overcome.

  19. The effect of anthelmintic treatment on helminth infection and anaemia.

    PubMed

    Gilgen, D; Mascie-Taylor, C G

    2001-01-01

    A 24-week randomized double blind intervention trial was conducted on adult female tea pluckers from an estate in Bangladesh to investigate the impact of iron supplementation and anthelmintic treatment on changes in ferritin and haemoglobin levels as well as on prevalence and intensity of helminth infections. A total of 553 women were randomly assigned to 1 of 4 intervention groups: group 1 received iron supplementation on a weekly basis, group 2 received anthelmintic treatment at the beginning and half way through the trial, group 3 received both iron supplementation as group 1 and anthelmintic treatment as group 2, and group 4 was a control group and received placebos for both iron supplementation and anthelmintic treatment. Prevalence and intensity of helminth infections (egg counts/g stool) of Ascaris lumbricoides, Trichuris trichiura and hookworms significantly fell in the 2 groups receiving anthelmintic treatment and there were some reductions in the 2 groups not receiving anthelminthic treatment. Haemoglobin and haematocrit concentrations increased significantly in the iron supplemented groups with smaller increases in the anthelmintic only group. All women showed a decrease in serum ferritin levels post-trial with greater losses in the 2 dewormed groups. Significant negative associations were found between hookworm egg counts and ferritin levels and Trichuris trichiura egg counts and haemoglobin concentration.

  20. Characterization of Constituents and Anthelmintic Properties of Hagenia abyssinica

    PubMed Central

    Thomsen, Henrieke; Reider, Katrin; Franke, Katrin; Wessjohann, Ludger A.; Keiser, Jennifer; Dagne, Ermias; Arnold, Norbert

    2012-01-01

    The dried female flowers of Hagenia abyssinica (Bruce) J. F. Gmel. (Rosaceae) are traditionally used as an anthelmintic remedy in Ethiopia and formerly were incorporated into the European Pharmacopoeia. One-, two- and tricyclic phloroglucinol derivatives (kosins) were suggested to be the active principles. However, polar constituents may also contribute to the activity. Therefore, we investigated for the first time the polar constituents. We isolated typical Rosaceae constituents such as quercetin 3-O-β-glucuronide, quercetin 3-O-β-glucoside and rutin. Polar kosin glycosides or derivatives could not be detected. The anthelmintic activity of fractions of different polarity were tested against the blood fluke Schistosoma mansoni, the liver flukes Clonorchis sinensis and Fasciola hepatica and the intestinal fluke Echinostoma caproni. The anthelmintic activity decreased with increasing polarity of the tested fractions. ESI-MS investigations indicated the predominant occurrence of kosins in the active fractions. Using the anthelmintic active extracts of Hagenia abyssinica we developed a simple, inexpensive bioassay against the non-parasitic nematode Caenorhabditis elegans, which can be used as an initial screening procedure for anthelmintic properties of crude extracts of plants or fungi. The anthelmintic activity of test extracts against the model organism was determined in a microtiter plate assay by enumeration of living and dead nematodes under a microscope. PMID:22896828

  1. Management of multidrug resistant bacterial endemic.

    PubMed

    Zahar, J-R; Lesprit, P

    2014-09-01

    The fight against multi-drug resistant Gram-negative bacilli (MDRGNB), especially extended-spectrum β-lactamase producing Enterobacteriaceae, is about to be lost in our country. The emergence of new resistance mechanisms to carbapenems in these Enterobacteriaceae exposes patients to a risk of treatment failure without any other therapeutic options. This dramatic situation is paradoxical because we are well aware of the 2 major factors responsible for this situation: 1) MDRO cross-transmission, associated with a low compliance to standard precautions, especially hand hygiene, and 2) overexposure of patients to antibiotics. The implementation of a "search and isolate" policy, which was justified to control the spread of some MDRO that remained rare in the country, was not associated with a better adherence to standard precautions. The antibiotic policy and the measures implemented to control antibiotic consumptions have rarely been enforced and have shown inconsistent results. Notably, no significant decrease of antibiotic consumption has been observed. There is no excuse for these poor results, because some authors evaluating the effectiveness of programs for the control of MDRO have reported their positive effects on antimicrobial resistance without any detrimental effects. It is now urgent to deal with the 2 major factors by establishing an educational and persuasive program with quantified and opposable objectives. Firstly, we have to improve the observance of hand hygiene above 70%. Secondly, we have to define and reach a target for the reduction of antibiotic consumption both in community and in hospital settings.

  2. Anthelmintic activity of Artemisia annua L. extracts in vitro and the effect of an aqueous extract and artemisinin in sheep naturally infected with gastrointestinal nematodes

    USDA-ARS?s Scientific Manuscript database

    There is no effective natural alternative control for gastrointestinal nematodes (GIN) of small ruminants, with Haemonchus contortus being the most economically important GIN. Despite frequent reports of multidrug-resistant GIN, there is no new commercial anthelmintic to substitute failing ones. Alt...

  3. Efficacy of an orange oil emulsion as an anthelmintic against Haemonchus contortus in gerbils (Meriones unguiculatus) and in sheep (Ovis aries)

    USDA-ARS?s Scientific Manuscript database

    Haemonchus contortus is a blood-sucking abomasal parasite responsible for major losses to small ruminant producers worldwide. The recent increase in populations of anthelmintic resistant parasites has produced a demand for alternative control methods. An orange oil emulsion that has shown activity...

  4. Managing Drug Resistance in Cancer: Role of Cancer Informatics.

    PubMed

    Gautam, Ankur; Chaudhary, Kumardeep; Kumar, Rahul; Gupta, Sudheer; Singh, Harinder; Raghava, Gajendra P S

    2016-01-01

    Understanding and managing cancer drug resistance is the main goal of the modern oncology programs worldwide. One of the major factors contributing to drug resistance in cancer cells is the acquired mutations in drug targets. Advances in sequencing technologies and high-throughput screening assays have generated huge information related to pharmaco-profiling of anticancer drugs and revealed the mutational spectrum of different cancers. Systematic meta-analysis of this complex data is very essential to make useful conclusions in order to manage cancer drug resistance. Bioinformatics can play a significant role to interpret this complex data into useful conclusions. In this chapter, the use of bioinformatics platforms, particularly CancerDR, in understanding the cancer drug resistance is described.

  5. An Operational Framework for Insecticide Resistance Management Planning.

    PubMed

    Chanda, Emmanuel; Thomsen, Edward K; Musapa, Mulenga; Kamuliwo, Mulakwa; Brogdon, William G; Norris, Douglas E; Masaninga, Freddie; Wirtz, Robert; Sikaala, Chadwick H; Muleba, Mbanga; Craig, Allen; Govere, John M; Ranson, Hilary; Hemingway, Janet; Seyoum, Aklilu; Macdonald, Michael B; Coleman, Michael

    2016-05-01

    Arthropod vectors transmit organisms that cause many emerging and reemerging diseases, and their control is reliant mainly on the use of chemical insecticides. Only a few classes of insecticides are available for public health use, and the increased spread of insecticide resistance is a major threat to sustainable disease control. The primary strategy for mitigating the detrimental effects of insecticide resistance is the development of an insecticide resistance management plan. However, few examples exist to show how to implement such plans programmatically. We describe the formulation and implementation of a resistance management plan for mosquito vectors of human disease in Zambia. We also discuss challenges, steps taken to address the challenges, and directions for the future.

  6. An Operational Framework for Insecticide Resistance Management Planning

    PubMed Central

    Chanda, Emmanuel; Thomsen, Edward K.; Musapa, Mulenga; Kamuliwo, Mulakwa; Brogdon, William G.; Norris, Douglas E.; Masaninga, Freddie; Wirtz, Robert; Sikaala, Chadwick H.; Muleba, Mbanga; Craig, Allen; Govere, John M.; Ranson, Hilary; Hemingway, Janet; Seyoum, Aklilu; Macdonald, Michael B.

    2016-01-01

    Arthropod vectors transmit organisms that cause many emerging and reemerging diseases, and their control is reliant mainly on the use of chemical insecticides. Only a few classes of insecticides are available for public health use, and the increased spread of insecticide resistance is a major threat to sustainable disease control. The primary strategy for mitigating the detrimental effects of insecticide resistance is the development of an insecticide resistance management plan. However, few examples exist to show how to implement such plans programmatically. We describe the formulation and implementation of a resistance management plan for mosquito vectors of human disease in Zambia. We also discuss challenges, steps taken to address the challenges, and directions for the future. PMID:27089119

  7. SOIL NITROGEN MANAGEMENT AND INVASION RESISTANCE

    USDA-ARS?s Scientific Manuscript database

    Invasion by annual grasses, such as medusahead (Taeniatherum. caput-medusae (L.) Nevski), into the Great Basin sagebrush steppe is a major concern of ecologists and resource managers. Maintaining or improving ecosystem health depends on our ability to protect or re-establish functioning, desired pl...

  8. Managing Resistance to EFGR- and ALK-Targeted Therapies.

    PubMed

    Lovly, Christine M; Iyengar, Puneeth; Gainor, Justin F

    2017-01-01

    Targeted therapies have transformed the management of non-small cell lung cancer (NSCLC) and placed an increased emphasis on stratifying patients on the basis of genetic alterations in oncogenic drivers. To date, the best characterized molecular targets in NSCLC are the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). Despite steady advances in targeted therapies within these molecular subsets, however, acquired resistance to therapy is near universal. Recent preclinical models and translational efforts have provided critical insights into the molecular mechanisms of resistance to EGFR and ALK inhibitors. In this review, we present a framework for understanding resistance to targeted therapies. We also provide overviews of the molecular mechanisms of resistance and strategies to overcome resistance among EGFR-mutant and ALK-rearranged lung cancers. To date, these strategies have centered on the development of novel next-generation inhibitors, rationale combinations, and use of local ablative therapies, such as radiotherapy.

  9. Insecticide Resistance: Challenge to Pest Management and Basic Research

    NASA Astrophysics Data System (ADS)

    Brattsten, L. B.; Holyoke, C. W.; Leeper, J. R.; Raffa, K. F.

    1986-03-01

    The agricultural use of synthetic insecticides usually protects crops but imposes strong selection pressures that can result in the development of resistance. The most important resistance mechanisms are enhancement of the capacity to metabolically detoxify insecticides and alterations in target sites that prevent insecticides from binding to them. Insect control methods must incorporate strategies to minimize resistance development and preserve the utility of the insecticides. The most promising approach, integrated pest management, includes the use of chemical insecticides in combination with improved cultural and biologically based techniques.

  10. Anthelmintic and nutritional effects of heather supplementation on Cashmere goats grazing perennial ryegrass-white clover pastures.

    PubMed

    Osoro, K; Mateos-Sanz, A; Frutos, P; García, U; Ortega-Mora, L M; Ferreira, L M M; Celaya, R; Ferre, I

    2007-03-01

    To investigate anthelmintic and nutritional effects of heather supplementation in goats grazing perennial ryegrass-white clover pastures, 40 dry Cashmere goats were randomly assigned to 4 treatments in a 2 x 2 factorial arrangement: 2 grazing management treatments (supplementation with heather vs. nonsupplementation) and 2 anthelmintic treatments (treatment vs. nontreatment). Goats grazed continuously from May to September 2004. At the end of the grazing period, the number of dead goats due to gastrointestinal parasitism was 1 in the group supplemented with heather and dosed with anthelmintic, 4 in the group that received neither supplementation nor anthelmintic, and 0 in the other 2 groups. For goats that did not receive anthelmintic treatment, the percentage of heather in the diet was negatively correlated with fecal egg count in August (r = -0.59, P < 0.05) and September (r = -0.49, P < 0.1) and positively correlated (r = 0.54, P < 0.05) with BW changes during the grazing season. Therefore, the correlation coefficient between BW change and fecal egg count was negative (r = -0.62, P < 0.05). Rumen ammonia concentrations were always lower in supplemented goats (P < 0.05). However, VFA concentrations were greater in goats consuming heather (58.9 vs. 50.9 mmol/L), which suggests that ruminal fermentation was not adversely affected by consumption of tannins. Heather availability in the vegetation might represent a valuable opportunity and sustainable method to control gastrointestinal nematode infections in a goat production system based on grazing perennial ryegrass-white clover pastures.

  11. Thyroid hormone resistance and its management

    PubMed Central

    Lado-Abeal, Joaquin

    2016-01-01

    The syndrome of impaired sensitivity to thyroid hormone, also known as syndrome of thyroid hormone resistance, is an inherited condition that occurs in 1 of 40,000 live births characterized by a reduced responsiveness of target tissues to thyroid hormone due to mutations on the thyroid hormone receptor. Patients can present with symptoms of hyperthyroidism or hypothyroidism. They usually have elevated thyroid hormones and a normal or elevated thyroid-stimulating hormone level. Due to their nonspecific symptomatic presentation, these patients can be misdiagnosed if the primary care physician is not familiar with the condition. This can result in frustration for the patient and sometimes unnecessary invasive treatment such as radioactive iodine ablation, as in the case presented herein. PMID:27034574

  12. Herbicide-Resistant Crops: Utilities and Limitations for Herbicide-Resistant Weed Management

    PubMed Central

    2010-01-01

    Since 1996, genetically modified herbicide-resistant (HR) crops, particularly glyphosate-resistant (GR) crops, have transformed the tactics that corn, soybean, and cotton growers use to manage weeds. The use of GR crops continues to grow, but weeds are adapting to the common practice of using only glyphosate to control weeds. Growers using only a single mode of action to manage weeds need to change to a more diverse array of herbicidal, mechanical, and cultural practices to maintain the effectiveness of glyphosate. Unfortunately, the introduction of GR crops and the high initial efficacy of glyphosate often lead to a decline in the use of other herbicide options and less investment by industry to discover new herbicide active ingredients. With some exceptions, most growers can still manage their weed problems with currently available selective and HR crop-enabled herbicides. However, current crop management systems are in jeopardy given the pace at which weed populations are evolving glyphosate resistance. New HR crop technologies will expand the utility of currently available herbicides and enable new interim solutions for growers to manage HR weeds, but will not replace the long-term need to diversify weed management tactics and discover herbicides with new modes of action. This paper reviews the strengths and weaknesses of anticipated weed management options and the best management practices that growers need to implement in HR crops to maximize the long-term benefits of current technologies and reduce weed shifts to difficult-to-control and HR weeds. PMID:20586458

  13. Herbicide-resistant crops: utilities and limitations for herbicide-resistant weed management.

    PubMed

    Green, Jerry M; Owen, Micheal D K

    2011-06-08

    Since 1996, genetically modified herbicide-resistant (HR) crops, particularly glyphosate-resistant (GR) crops, have transformed the tactics that corn, soybean, and cotton growers use to manage weeds. The use of GR crops continues to grow, but weeds are adapting to the common practice of using only glyphosate to control weeds. Growers using only a single mode of action to manage weeds need to change to a more diverse array of herbicidal, mechanical, and cultural practices to maintain the effectiveness of glyphosate. Unfortunately, the introduction of GR crops and the high initial efficacy of glyphosate often lead to a decline in the use of other herbicide options and less investment by industry to discover new herbicide active ingredients. With some exceptions, most growers can still manage their weed problems with currently available selective and HR crop-enabled herbicides. However, current crop management systems are in jeopardy given the pace at which weed populations are evolving glyphosate resistance. New HR crop technologies will expand the utility of currently available herbicides and enable new interim solutions for growers to manage HR weeds, but will not replace the long-term need to diversify weed management tactics and discover herbicides with new modes of action. This paper reviews the strengths and weaknesses of anticipated weed management options and the best management practices that growers need to implement in HR crops to maximize the long-term benefits of current technologies and reduce weed shifts to difficult-to-control and HR weeds.

  14. Resistant starches for the management of metabolic diseases.

    PubMed

    Bindels, Laure B; Walter, Jens; Ramer-Tait, Amanda E

    2015-11-01

    Recent clinical trials and animal studies indicate that resistant starches may be beneficial therapeutic tools for the management of metabolic diseases. The purpose of this review is to summarize these findings and discuss the established and proposed mechanisms by which resistant starches exert their benefits. We also examine open questions regarding how resistant starches improve metabolism and propose future research directions for the field. Data from both humans and animal models clearly support a role for resistant starches in improving a variety of metabolic features; however, discrepancies do exist regarding specific effects. Concomitant improvements in both insulin levels and body fat depots are often reported in rodents fed resistant starches, whereas resistant starch feeding in humans improves insulin sensitivity without having a major impact on fat mass. These differences could be explained by the coexistence of several mechanisms (both gut microbiota-dependent and gut microbiota-independent) underpinning the metabolic benefits of resistant starches. Together, the studies presented in this review offer new insights into the potential pathways by which resistant starches enhance metabolic health, including modulation of the gut microbiota, gut peptides, circulating inflammatory mediators, innate immune cells, and the bile acid cycle.

  15. IRAC: Mode of action classification and insecticide resistance management.

    PubMed

    Sparks, Thomas C; Nauen, Ralf

    2015-06-01

    Insecticide resistance is a long standing and expanding problem for pest arthropod control. Effective insecticide resistance management (IRM) is essential if the utility of current and future insecticides is to be preserved. Established in 1984, the Insecticide Resistance Action Committee (IRAC) is an international association of crop protection companies. IRAC serves as the Specialist Technical Group within CropLife International focused on ensuring the long term efficacy of insect, mite and tick control products through effective resistance management for sustainable agriculture and improved public health. A key function of IRAC is the continued development of the Mode of Action (MoA) classification scheme, which provides up-to-date information on the modes of action of new and established insecticides and acaricides and which serves as the basis for developing appropriate IRM strategies for crop protection and vector control. The IRAC MoA classification scheme covers more than 25 different modes of action and at least 55 different chemical classes. Diversity is the spice of resistance management by chemical means and thus it provides an approach to IRM providing a straightforward means to identify potential rotation/alternation options.

  16. Extensively Drug-Resistant Tuberculosis: Principles of Resistance, Diagnosis, and Management.

    PubMed

    Wilson, John W; Tsukayama, Dean T

    2016-04-01

    Extensively drug-resistant (XDR) tuberculosis (TB) is an unfortunate by-product of mankind's medical and pharmaceutical ingenuity during the past 60 years. Although new drug developments have enabled TB to be more readily curable, inappropriate TB management has led to the emergence of drug-resistant disease. Extensively drug-resistant TB describes Mycobacterium tuberculosis that is collectively resistant to isoniazid, rifampin, a fluoroquinolone, and an injectable agent. It proliferates when established case management and infection control procedures are not followed. Optimized treatment outcomes necessitate time-sensitive diagnoses, along with expanded combinations and prolonged durations of antimicrobial drug therapy. The challenges to public health institutions are immense and most noteworthy in underresourced communities and in patients coinfected with human immunodeficiency virus. A comprehensive and multidisciplinary case management approach is required to optimize outcomes. We review the principles of TB drug resistance and the risk factors, diagnosis, and managerial approaches for extensively drug-resistant TB. Treatment outcomes, cost, and unresolved medical issues are also discussed. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  17. Managing 'resistance': is adherence a target for treatment?

    PubMed

    Burnier, Michel

    2014-09-01

    Adherence to preventive measures and prescribed medications is the cornerstone of the successful management of hypertension. The role of adherence is particularly important when treatments are not providing the expected clinical results, for example, in patients with resistant hypertension. The goal of this article is to review the recent observations regarding drug adherence in resistant hypertension. Today, the role of drug adherence as a potential cause of resistant hypertension is largely underestimated. Most studies suggest that a low adherence to the prescribed medications can affect up to 50% of patients with resistant hypertension.A good adherence to therapy is generally associated with an improved prognosis. Nonetheless, adherence should probably not be a target for treatment per se because data on adherence should always be interpreted in the view of clinical results. In our opinion, the availability of reliable data on drug adherence would be a major help for physicians to manage patients apparently resistant to therapy. The actual development of new drugs for hypertension is slow. Thus, focusing on drug adherence to the drugs available is an important way to improve blood pressure control in the population. More emphasis should be put on measuring drug adherence in patients with resistant hypertension to avoid costly investigations and treatments.

  18. Governing principles can guide fungicide-resistance management tactics.

    PubMed

    van den Bosch, Frank; Oliver, Richard; van den Berg, Femke; Paveley, Neil

    2014-01-01

    Fungicide-resistance management would be more effective if principles governing the selection of resistant strains could be determined and validated. Such principles could then be used to predict whether a proposed change to a fungicide application program would decrease selection for resistant strains. In this review, we assess a governing principle that appears to have good predictive power. The principle states that reducing the product of the selection coefficient (defined as the difference between the per capita rate of increase of the sensitive and resistant strains) and the exposure time of the pathogen to the fungicide reduces the selection for resistance. We show that observations as well as modeling studies agree with the predicted effect (i.e., that a specific change to a fungicide program increased or decreased selection or was broadly neutral in its effect on selection) in 84% of the cases and that only 5% of the experimental results contradict predictions. We argue that the selection coefficient and exposure time principle can guide the development of resistance management tactics.

  19. HIV Drug-Resistant Patient Information Management, Analysis, and Interpretation

    PubMed Central

    Mars, Maurice

    2012-01-01

    Introduction The science of information systems, management, and interpretation plays an important part in the continuity of care of patients. This is becoming more evident in the treatment of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS), the leading cause of death in sub-Saharan Africa. The high replication rates, selective pressure, and initial infection by resistant strains of HIV infer that drug resistance will inevitably become an important health care concern. This paper describes proposed research with the aim of developing a physician-administered, artificial intelligence-based decision support system tool to facilitate the management of patients on antiretroviral therapy. Methods This tool will consist of (1) an artificial intelligence computer program that will determine HIV drug resistance information from genomic analysis; (2) a machine-learning algorithm that can predict future CD4 count information given a genomic sequence; and (3) the integration of these tools into an electronic medical record for storage and management. Conclusion The aim of the project is to create an electronic tool that assists clinicians in managing and interpreting patient information in order to determine the optimal therapy for drug-resistant HIV patients. PMID:23611761

  20. Integrated palmer amaranth management in glufosinate-resistant cotton

    USDA-ARS?s Scientific Manuscript database

    Two separate three year field experiments were conducted to evaluate: 1) the role of soil-inversion, cover crops and herbicide regimes for Amaranthus palmeri between-row (BR) and within-row (WR) management in glufosinate-resistant cotton and 2) the role of soil inversion, cover crops and spring til...

  1. Insecticide Resistance and Management Strategies in Urban Ecosystems

    PubMed Central

    Zhu, Fang; Lavine, Laura; O’Neal, Sally; Lavine, Mark; Foss, Carrie; Walsh, Douglas

    2016-01-01

    The increased urbanization of a growing global population makes imperative the development of sustainable integrated pest management (IPM) strategies for urban pest control. This emphasizes pests that are closely associated with the health and wellbeing of humans and domesticated animals. Concurrently there are regulatory requirements enforced to minimize inadvertent exposures to insecticides in the urban environment. Development of insecticide resistance management (IRM) strategies in urban ecosystems involves understanding the status and mechanisms of insecticide resistance and reducing insecticide selection pressure by combining multiple chemical and non-chemical approaches. In this review, we will focus on the commonly used insecticides and molecular and physiological mechanisms underlying insecticide resistance in six major urban insect pests: house fly, German cockroach, mosquitoes, red flour beetle, bed bugs and head louse. We will also discuss several strategies that may prove promising for future urban IPM programs. PMID:26751480

  2. Management of treatment-resistant depression.

    PubMed

    Keitner, Gabor I; Mansfield, Abigail K

    2012-03-01

    Given the limitations of evidence for treatment options that are consistently effective for TRD and the possibility that TRD is in fact a form of depression that has a low probability of resolving, how can clinicians help patients with TRD? Perhaps the most important conceptual shift that needs to take place before treatment can be helpful is to accept TRD as a chronic illness, an illness similar to many others, one that can be effectively managed but that is not, at our present level of knowledge, likely to be cured. An undue focus on remission or even a 50% diminution of symptoms sets unrealistic goals for both patients and therapists and may lead to overtreatment and demoralization. The focus should be less on eliminating depressive symptoms and more on making sense of and learning to function better in spite of them. It is important to acknowledge the difficult nature of the depressive illness, to remove blame from the patient and clinician for not achieving remission, to set realistic expectations, and to help promote better psychosocial functioning even in the face of persisting symptoms. The critical element when implementing such an approach is a judicious balance between maintaining hope for improvement without setting unrealistic expectations. It is important to reemphasize that following a disease management model with acceptance of the reality of a chronic illness is not nihilistic and does not mean the abandonment of hope for improvement. The first step in treating a patient with TRD is to perform a comprehensive assessment of the patient’s past and current treatment history to ensure that evidence-based treatment trials have in fact been undertaken, and if not, such treatment trials should be implemented. If the patient continues to have significant residual symptoms, it is important to determine the impact is of these symptoms on the patient’s quality of life and ability to function. It is also important to evaluate the factors that may be

  3. Toxocara canis: anthelmintic activity of quinone derivatives in murine toxocarosis.

    PubMed

    Mata-Santos, T; Mata-Santos, H A; Carneiro, P F; De Moura, K C G; Fenalti, J M; Klafke, G B; Cruz, L A X; Martins, L H R; Pinto, N F; Pinto, M C F R; Berne, M E A; Da Silva, P E A; Scaini, C J

    2016-04-01

    Human toxocarosis is a chronic tissue parasitosis most often caused by Toxocara canis. The seroprevalence can reach up to 50%, especially among children and adolescents. The anthelmintics used in the treatment have moderate efficacy. The aim of this study was to evaluate the in vitro and in vivo anthelmintic activity of quinones and their derivatives against T. canis larvae and the cytotoxicity of the larvicidal compounds. The compounds were evaluated at 1 mg mL(-1) concentration in microculture plates containing third stage larvae in an Roswell Park Memorial Institute (RPMI) 1640 environment, incubated at 37 °C in 5% CO2 tension for 48 h. Five naphthoxiranes were selected for the cytotoxicity analysis. The cell viability evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays using murine peritoneal macrophages isolated from C57BL/6 mice revealed that the naphthoxiranes (1 and 3) were less cytotoxic at a concentration of 0.05 mg mL(-1). The efficacy of naphthoxiranes (1 and 3) was examined in murine toxocarosis also. The anthelmintic activity was examined by evaluating the number of larvae in the brain, carcass, liver, lungs, heart, kidneys and eyes. Compound (3) demonstrated anthelmintic activity similar to that of albendazole by decreasing the number of larvae in the organs of mice and thus could form the basis of the development of a new anthelmintic drug.

  4. Anthelmintic properties of traditional African and Caribbean medicinal plants: identification of extracts with potent activity against Ascaris suum in vitro

    PubMed Central

    Williams, Andrew R.; Soelberg, Jens; Jäger, Anna K.

    2016-01-01

    Ascariasis affects more than 1 billion people worldwide, mainly in developing countries, causing substantial morbidity. Current treatments for Ascaris infection are based on mass drug administration (MDA) with synthetic anthelmintic drugs such as albendazole, however continual re-infection and the threat of drug resistance mean that complementary treatment options would be highly valuable. Here, we screened ethanolic extracts from 29 medicinal plants used in Africa (Ghana) and the Caribbean (US Virgin Islands) for in vitro anthelmintic properties against Ascaris suum, a swine parasite that is very closely related to the human A. lumbricoides. A wide variety of activities were seen in the extracts, from negligible to potent. Extracts from Clausena anisata, Zanthoxylum zanthoxyloides and Punica granatum were identified as the most potent with EC50 values of 74, 97 and 164 μg/mL, respectively. Our results encourage further investigation of their use as complementary treatment options for ascariasis, alongside MDA. PMID:27301442

  5. INDUCTION OF ALBENDAZOLE RESISTANCE IN GIARDIA LAMBLIA

    EPA Science Inventory

    Previous studies have shown that Giardia lamblia resistance to metronidazole can be induced in the laboratory, and treatment failures with this drug have also been documented. As replacement theraples, anthelmintic benzimidazoles have antigiardial activity with few clinical side ...

  6. INDUCTION OF ALBENDAZOLE RESISTANCE IN GIARDIA LAMBLIA

    EPA Science Inventory

    Previous studies have shown that Giardia lamblia resistance to metronidazole can be induced in the laboratory, and treatment failures with this drug have also been documented. As replacement theraples, anthelmintic benzimidazoles have antigiardial activity with few clinical side ...

  7. Novel AChE Inhibitors for Sustainable Insecticide Resistance Management

    PubMed Central

    Alout, Haoues; Labbé, Pierrick; Berthomieu, Arnaud; Djogbénou, Luc; Leonetti, Jean-Paul; Fort, Philippe; Weill, Mylène

    2012-01-01

    Resistance to insecticides has become a critical issue in pest management and it is particularly chronic in the control of human disease vectors. The gravity of this situation is being exacerbated since there has not been a new insecticide class produced for over twenty years. Reasoned strategies have been developed to limit resistance spread but have proven difficult to implement in the field. Here we propose a new conceptual strategy based on inhibitors that preferentially target mosquitoes already resistant to a currently used insecticide. Application of such inhibitors in rotation with the insecticide against which resistance has been selected initially is expected to restore vector control efficacy and reduce the odds of neo-resistance. We validated this strategy by screening for inhibitors of the G119S mutated acetylcholinesterase-1 (AChE1), which mediates insensitivity to the widely used organophosphates (OP) and carbamates (CX) insecticides. PyrimidineTrione Furan-substituted (PTF) compounds came out as best hits, acting biochemically as reversible and competitive inhibitors of mosquito AChE1 and preferentially inhibiting the mutated form, insensitive to OP and CX. PTF application in bioassays preferentially killed OP-resistant Culex pipiens and Anopheles gambiae larvae as a consequence of AChE1 inhibition. Modeling the evolution of frequencies of wild type and OP-insensitive AChE1 alleles in PTF-treated populations using the selectivity parameters estimated from bioassays predicts a rapid rise in the wild type allele frequency. This study identifies the first compound class that preferentially targets OP-resistant mosquitoes, thus restoring OP-susceptibility, which validates a new prospect of sustainable insecticide resistance management. PMID:23056599

  8. Nematode parasites of animals are more prone to develop xenobiotic resistance than nematode parasites of plants.

    PubMed

    Silvestre, A; Cabaret, J

    2004-06-01

    In this paper, we concentrate on a comparison of plant and animal-parasitic nematodes, to gain insight into the factors that influence the acquisition of the drug resistance by nematodes. Comparing nematode parasite of domestic animals and cultivated plants, it appears that drug resistance threatens only domestic animal production. Does the paucity of report on nematicide field resistance reflect reality or, is nematicide resistance bypassed by other management practices, specific to cultivated plants (i.e. agricultural control)? First, it seems that selection pressure by treatments in plants is not as efficient as selection pressure in ruminants. Agronomic practices (i.e. sanitation, early planting, usage of nematodes resistant cultivar and crop rotation) are frequently used to control parasitic-plant nematodes. Although the efficiency of such measures is generally moderate to high, integrated approaches are developing successfully in parasitic-plant nematode models. Secondly, the majority of anthelmintic resistance cases recorded in animal-parasitic nematodes concern drug families that are not used in plant-parasitic nematodes control (i.e. benzimidazoles, avermectines and levamisole). Thirdly, particular life traits of parasitic-plant nematodes (low to moderate fecundity and reproductive strategy) are expected to reduce probability of appearance and transmission of drug resistance genes. It has been demonstrated that, for a large number of nematodes such as Meloidogyne spp., the mode of reproduction by mitotic parthenogenesis reduced genetic diversity of populations which may prevent a rapid drug resistance development. In conclusion, anthelmintic resistance develops in nematode parasite of animals as a consequence of an efficient selection pressure. Early detection of anthelmintic resistance is then crucial: it is not possible to avoid it, but only to delay its development in farm animal industry.

  9. Development of novel valerolactam-benzimidazole hybrids anthelmintic derivatives: Diffusion and biotransformation studies in helminth parasites.

    PubMed

    Munguía, Beatriz; Michelena, Mauricio; Melian, Elisa; Saldaña, Jenny; Ures, Ximena; Manta, Eduardo; Domínguez, Laura

    2015-06-01

    In the search for new anthelmintics able to overcome the resistance problem against all available drugs in livestock, the synthesis of novel valerolactam-benzimidazole hybrid compounds was reported. This allowed us to obtain these in vitro and in vivo bioactive compounds using Nippostrongylus brasiliensis rat model by integrating physiology-based assays and ex vivo diffusion studies. In order to further study those novel hybrid molecules, Haemonchus contortus (a sheep gastrointestinal nematode of interest) and Mesocestoides vogae tetrathyridia (a useful system to study the efficacy of anthelmintic drugs against cestoda) were used as parasite models to compare the ex vivo patterns of diffusion and biotransformation of benzimidazoles and their valerolactam-benzimidazole hybrid derivatives. On average, a nine-fold higher intraparasitic concentration of compounds was found in M. vogae compared with H.contortus, with similarities regarding the order of entry of compounds, highlighting febendazole (FEB) and its hybrid compound 10, while valerolactam compound 2 practically did not penetrate the parasites. Interestingly, sulphoxidation drug metabolism was observed and measured, revealing percentages of oxidation of 8.2% and 14.5% for albendazole (ABZ) and febendazole respectively in M. vogae, while this effect was more relevant in H. contortus parasite. More importantly, significant differences were observed between anthelmintic-susceptible adult parasites (Hc S) and those from sheep farms (Hc U). In fact, the percentages of oxidation of FEB and the hybrid compound 8 were higher in Hc U (25.5%, 54.1%, respectively) than in Hc S (8.8%, 38.2%). Interestingly, sulphoxidation of hybrid compound 10 was neither observed in M. vogae nor in H. contortus parasites, suggesting that increased drug metabolism (oxidation reactions) could not be used by these parasites as a defense mechanism against this novel drug. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Discovery of Anthelmintic Drug Targets and Drugs Using Chokepoints in Nematode Metabolic Pathways

    PubMed Central

    Taylor, Christina M.; Wang, Qi; Rosa, Bruce A.; Huang, Stanley Ching-Cheng; Powell, Kerrie; Schedl, Tim; Pearce, Edward J.; Abubucker, Sahar; Mitreva, Makedonka

    2013-01-01

    Parasitic roundworm infections plague more than 2 billion people (1/3 of humanity) and cause drastic losses in crops and livestock. New anthelmintic drugs are urgently needed as new drug resistance and environmental concerns arise. A “chokepoint reaction” is defined as a reaction that either consumes a unique substrate or produces a unique product. A chokepoint analysis provides a systematic method of identifying novel potential drug targets. Chokepoint enzymes were identified in the genomes of 10 nematode species, and the intersection and union of all chokepoint enzymes were found. By studying and experimentally testing available compounds known to target proteins orthologous to nematode chokepoint proteins in public databases, this study uncovers features of chokepoints that make them successful drug targets. Chemogenomic screening was performed on drug-like compounds from public drug databases to find existing compounds that target homologs of nematode chokepoints. The compounds were prioritized based on chemical properties frequently found in successful drugs and were experimentally tested using Caenorhabditis elegans. Several drugs that are already known anthelmintic drugs and novel candidate targets were identified. Seven of the compounds were tested in Caenorhabditis elegans and three yielded a detrimental phenotype. One of these three drug-like compounds, Perhexiline, also yielded a deleterious effect in Haemonchus contortus and Onchocerca lienalis, two nematodes with divergent forms of parasitism. Perhexiline, known to affect the fatty acid oxidation pathway in mammals, caused a reduction in oxygen consumption rates in C. elegans and genome-wide gene expression profiles provided an additional confirmation of its mode of action. Computational modeling of Perhexiline and its target provided structural insights regarding its binding mode and specificity. Our lists of prioritized drug targets and drug-like compounds have potential to expedite the discovery

  11. Resistance Exercise to Prevent and Manage Sarcopenia and Dynapenia.

    PubMed

    Law, Timothy D; Clark, Leatha A; Clark, Brian C

    For well over twenty centuries the muscle wasting (sarcopenia) and weakness (dynapenia) that occurs with old age has been a predominant concern of mankind. Exercise has long been suggested as a treatment to combat sarcopenia and dynapenia, as it exerts effects on both the nervous and muscular systems that are critical to positive physiological and functional adaptations (e.g., enhanced muscle strength). For more than two decades scientists have recognized the profound role that progressive resistance exercise training can have on increasing muscle strength, muscle size and functional capacity in older adults. In this review article we discuss how resistance exercise training can be used in the management and prevention of sarcopenia and dynapenia. We first provide an overview of the evidence for this notion and highlight certain critical factors- namely exercise intensity, volume and progression- that are key to optimizing the resistance exercise prescription. We then highlight how many, if not most, of the commonly prescribed exercise programs for seniors are not the 'best practices', and subsequently present easy-to-read guidelines for a well-rounded resistance exercise training program designed for the management and prevention of sarcopenia and dynapenia, including example training programs for the beginner through the advanced senior resistance exerciser. These guidelines have been written for the academician as well as the student and health care provider across a variety of disciplines, including those in the long term care industry, such as wellness instructors or activity directors.

  12. Resistance Management for San Jose Scale (Hemiptera: Diaspididae).

    PubMed

    Buzzetti, K; Chorbadjian, R A; Nauen, R

    2015-12-01

    The San Jose scale Diaspidiotus perniciosus Comstock is one of the most important pests of deciduous fruit trees. The major cause of recent outbreaks in apple orchards is thought to be the development of insecticide resistance, specifically organophosphates. The first report was given in North America, and now, in Chile. In the present study, San Jose scale populations collected from two central regions of Chile were checked for their susceptibility to different mode of action insecticides in order to establish alternatives to manage this pest. No evidence of cross resistance between organophosphates insecticides and acetamiprid, buprofezin, pyriproxyfen, spirotetramat, sulfoxaflor, or thiacloprid was found. Baselines of LC50-LC95 for different life stages of San Jose scale are given, as reference to future studies of resistance monitoring. The systemic activity of acetamiprid, spirotetramat, and thiacloprid was higher than the contact residue effect of these compounds. For sulfoxaflor, both values were similar. Program treatments including one or more of these compounds are compared in efficacy and impact on resistance ratio values. In order to preserve new insecticides as an important tool to control San Jose scale, resistance management programs should be implemented, considering insecticide mode of action classes alternated or mixed.

  13. Resistance Exercise to Prevent and Manage Sarcopenia and Dynapenia

    PubMed Central

    Law, Timothy D.; Clark, Leatha A.; Clark, Brian C.

    2016-01-01

    For well over twenty centuries the muscle wasting (sarcopenia) and weakness (dynapenia) that occurs with old age has been a predominant concern of mankind. Exercise has long been suggested as a treatment to combat sarcopenia and dynapenia, as it exerts effects on both the nervous and muscular systems that are critical to positive physiological and functional adaptations (e.g., enhanced muscle strength). For more than two decades scientists have recognized the profound role that progressive resistance exercise training can have on increasing muscle strength, muscle size and functional capacity in older adults. In this review article we discuss how resistance exercise training can be used in the management and prevention of sarcopenia and dynapenia. We first provide an overview of the evidence for this notion and highlight certain critical factors— namely exercise intensity, volume and progression— that are key to optimizing the resistance exercise prescription. We then highlight how many, if not most, of the commonly prescribed exercise programs for seniors are not the ‘best practices’, and subsequently present easy-to-read guidelines for a well-rounded resistance exercise training program designed for the management and prevention of sarcopenia and dynapenia, including example training programs for the beginner through the advanced senior resistance exerciser. These guidelines have been written for the academician as well as the student and health care provider across a variety of disciplines, including those in the long term care industry, such as wellness instructors or activity directors. PMID:27134329

  14. Drug resistance in influenza A virus: the epidemiology and management

    PubMed Central

    Hussain, Mazhar; Galvin, Henry D; Haw, Tatt Y; Nutsford, Ashley N; Husain, Matloob

    2017-01-01

    Influenza A virus (IAV) is the sole cause of the unpredictable influenza pandemics and deadly zoonotic outbreaks and constitutes at least half of the cause of regular annual influenza epidemics in humans. Two classes of anti-IAV drugs, adamantanes and neuraminidase (NA) inhibitors (NAIs) targeting the viral components M2 ion channel and NA, respectively, have been approved to treat IAV infections. However, IAV rapidly acquired resistance against both classes of drugs by mutating these viral components. The adamantane-resistant IAV has established itself in nature, and a majority of the IAV subtypes, especially the most common H1N1 and H3N2, circulating globally are resistant to adamantanes. Consequently, adamantanes have become practically obsolete as anti-IAV drugs. Similarly, up to 100% of the globally circulating IAV H1N1 subtypes were resistant to oseltamivir, the most commonly used NAI, until 2009. However, the 2009 pandemic IAV H1N1 subtype, which was sensitive to NAIs and has now become one of the dominant seasonal influenza virus strains, has replaced the pre-2009 oseltamivir-resistant H1N1 variants. This review traces the epidemiology of both adamantane- and NAI-resistant IAV subtypes since the approval of these drugs and highlights the susceptibility status of currently circulating IAV subtypes to NAIs. Further, it provides an overview of currently and soon to be available control measures to manage current and emerging drug-resistant IAV. Finally, this review outlines the research directions that should be undertaken to manage the circulation of IAV in intermediate hosts and develop effective and alternative anti-IAV therapies. PMID:28458567

  15. Broad spectrum anthelmintic potential of Cassia plants

    PubMed Central

    Kundu, Suman; Roy, Saptarshi; Lyndem, Larisha Mawkhleing

    2014-01-01

    Objective To study the in vitro anthelmintic efficacy of Cassia alata (C. alata), Cassia angustifolia (C. angustifolia) and Cassia occidentalis (C. occidentalis). Methods Crude ethanol extract from leaves of the three plants were prepared in rotary evaporator and different concentrations (10, 20 and 40 mg/mL) of leaf extracts were used for treatment on different representatives of helminthes (Heterakis gallinarum, Raillietina tetragona and Catatropis sp.) from domestic fowl (Gallus gallus domesticus). Loss of motility and death were monitored frequently. Results C. alata showed early paralysis in all worms treated followed by C. angustifolia. C. occidentalis in combination with C. alata together caused early paralysis in all treated worms than the combination of C. alata with C. angustfolia. While Heterakis gallinarum in control survived for (81.33±2.07) h, treated worms lost their motility at (5.71±0.10) h, (6.60±0.86) h and (13.95±0.43) h with C. angustifolia, C. alata and C. occidentalis respectively at a concentration of 40 mg/mL which showed better efficacy than albendazole. Catatropis sp. survival period was (26.49±1.38) h in control, but with plant treatment, it lost its motility in just (0.57±0.08) h, (1.00±0.12) h and (1.47±0.40) h at 40 mg/mL concentration of C. alata, C. angustifolia and C. occidentalis respectively. Raillietina tetragona on the other hand became paralysed at (1.68±0.27) h, (2.95±0.29) h and (4.13±0.31) h with above concentrations treated with three plants respectively, however in control it survived up to (81.93±4.71) h. Conclusions This present study indicated broad spectrum vermifugal activity of all plants tested. PMID:25183125

  16. Nematode control in spring-born suckler beef calves using targeted selective anthelmintic treatments.

    PubMed

    O'Shaughnessy, J; Earley, B; Mee, J F; Doherty, M L; Crosson, P; Barrett, D; Macrelli, M; de Waal, T

    2014-09-15

    As anthelmintic resistance is increasingly being reported in cattle worldwide, there is a need to explore alternative approaches to gastrointestinal nematode control in cattle. A novel approach is the use of targeted selective treatments (TST) where only individual animals are treated instead of the entire group. The study objective was to determine if anthelmintic usage could be reduced using a TST-based approach in rotationally grazed first-grazing season suckler beef calves without affecting calf performance. Eighty-eight spring-born suckler beef calves, naïve to anthelmintics, with an initial mean (s.d.) age and live weight of 159 (22.4) days and 221 (42.4) kg, respectively, were used. All calves were vaccinated at pasture against dictyocaulosis at 8 and 12 weeks old. On August 9th 2013 (Week 0), when the trial began, calves were randomised by age, weight, sex, dam breed and sire breed to one of two treatments: (1) standard treatment (positive control) (n=44) and (2) TST (n=44). Samples collected one week prior to the start of the study were used as baseline covariates. Each treatment group was replicated once. All calves in the control groups were treated subcutaneously with levamisole on Week 0 and on Week 6. Individual calves in the TST groups were only eligible for treatment at pasture with the same product if predetermined thresholds were reached [plasma pepsinogen ≥ 2.0 international units of tyrosine/litre and faecal egg count ≥ 200 eggs per gram of faeces]. The trial concluded at housing on Week 13. Data were analysed using repeated measures mixed models ANOVA (PROC MIXED) (SAS 9.3). No calves in the TST groups were treated for gastrointestinal nematodes during the study period as they did not reach pre-determined treatment thresholds. Mean (sem) calf daily live weight gain for control and TST groups was 0.90 (±0.04) and 0.92 (±0.03) kg, respectively (P=0.68). Using an ELISA to detect antibodies to Dictyocaulus viviparus at Week 11, 81% of calves

  17. Management of gastrointestinal nematode parasites on sheep farms in New Zealand.

    PubMed

    Lawrence, K E; Lethwick, D M; Rhodes, A P; Jackson, R; Heuer, C; Pomroy, W E; West, D M; Waghorn, T S; Moffat, J R

    2007-10-01

    To report current farmer opinions and farming practices relating to control of gastrointestinal nematodes and anthelmintic resistance on sheep farms in New Zealand. An interview-based cross-sectional study of grazing management and anthelmintic usage was conducted by veterinarians on 80 randomly selected sheep farms in New Zealand. Useable data were returned by 74/80 (92%) farmers who participated in the study. However, despite contacting 400 farmers the target sample size of 100 farms was not reached. The results indicated that only 31% of farms had previously tested for drench resistance, that effective quarantine-drenching of imported stock was not always carried out, and that farmers were more likely to integrate cattle than ewes into their grazing management of lambs. Furthermore, the number of drenches given to lambs had changed little in 25 years. The use of faecal egg counting by farmers has increased. Dependence on anthelmintics continues to be high on sheep farms in New Zealand. Whilst the number of drench treatments has changed little, there is more widespread use of persistent or long-acting treatments. Farmers need to be encouraged to monitor the resistance status of nematode populations on their farms and use this information to develop strategies aimed at maintaining susceptible alleles within the parasite populations and conserving the efficacy of existing drug families.

  18. Detection and management of antiviral resistance for influenza viruses.

    PubMed

    Boivin, Guy

    2013-11-01

    Neuraminidase inhibitors (NAIs) are first-line agents for the treatment and prevention of influenza virus infections. As for other antivirals, the development of resistance to NAIs has become an important concern particularly in the case of A(H1N1) viruses and oseltamivir. The most frequently reported change conferring oseltamivir resistance in that viral context is the H275Y neuraminidase mutation (N1 numbering). Recent studies have shown that, in the presence of the appropriate permissive mutations, the H275Y variant can retain virulence and transmissibility in some viral backgrounds. Most oseltamivir-resistant influenza A virus infections can be managed with the use of inhaled or intravenous zanamivir, another NAI. New NAI compounds and non-neuraminidase agents as well as combination therapies are currently in clinical evaluation for the treatment for severe influenza infections. © 2013 Blackwell Publishing Ltd.

  19. Cry1F resistance among lepidopteran pests: a model for improved resistance management?

    PubMed

    Vélez, Ana M; Vellichirammal, Neetha Nanoth; Jurat-Fuentes, Juan Luis; Siegfried, Blair D

    2016-06-01

    The Cry1Fa protein from the bacterium Bacillus thuringiensis (Bt) is known for its potential to control lepidopteran pests, especially through transgenic expression in maize and cotton. The maize event TC1507 expressing the cry1Fa toxin gene became commercially available in the United States in 2003 for the management of key lepidopteran pests including the European corn borer, Ostrinia nubilalis, and the fall armyworm, Spodoptera frugiperda. A high-dose/refuge strategy has been widely adopted to delay evolution of resistance to event TC1507 and other transgenic Bt crops. Efficacy of this strategy depends on the crops expressing a high dose of the Bt toxin to targeted pests and adjacent refuges of non-Bt host plants serving as a source of abundant susceptible insects. While this strategy has proved effective in delaying O. nubilalis resistance, field-evolved resistance to event TC1507 has been reported in S. frugiperda populations in Puerto Rico, Brazil, and the southeastern United States. This paper examines available information on resistance to Cry1Fa in O. nubilalis and S. frugiperda and discusses how this information identifies opportunities to refine resistance management recommendations for Bt maize. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Critical Tests on Thiabendazole as an Anthelmintic in Sheep

    PubMed Central

    Gibbs, H. C.; Pullin, J. W.

    1963-01-01

    The results of critical tests on thiabendazole given at three dose levels, 50 mg/kg, 80 mg/kg and 100 mg/kg, to groups of naturally parasitized lambs are reported. While the compound appeared to be efficient at all levels, the best results were obtained at 100 mg/kg. The total percentage removals of all worms present in the gut at these three dosage levels were 79.1 per cent at the 50 mg/kg level, 96.3 per cent at the 80 mg/kg level and 99.5 per cent at the 100 mg/kg level. No activity against T. ovis, Capillaria or Moniezia was observed. Useful activity in a limited number of lambs was observed against Dictyocaulus filaria especially at the 100 mg/kg level. This drug appeared to be completely effective at the 100 mg/kg level in removing tissue-phase parasites. Inhibitory activity against developing larvae in faecal cultures obtained 24 hours after dosing was also shown. At levels up to 500 mg/kg the drug appeared relatively non-toxic. The result at 800 mg/kg was complicated by the death of the treated animal 22 days after dosing from a septicaemia. Dosage at a level of 1.6 mg/kg proved rapidly fatal to a ewe. No effect on pregnant ewes or the lambs therefrom was observed at a dose level of 160 mg/kg. The most efficient level for routine treatment of sheep under Canadian conditions of management would appear to be 100 mg/kg of body weight. This compound appears to be the best anthelmintic to have been tried to date at this laboratory against the internal parasites of sheep. PMID:17649418

  1. Anthelmintic activity of Cymbopogon martinii, Cymbopogon schoenanthus and Mentha piperita essential oils evaluated in four different in vitro tests.

    PubMed

    Katiki, L M; Chagas, A C S; Bizzo, H R; Ferreira, J F S; Amarante, A F T

    2011-12-29

    Anthelmintic resistance is a worldwide concern in small ruminant industry and new plant-derived compounds are being studied for their potential use against gastrointestinal nematodes. Mentha piperita, Cymbopogon martinii and Cymbopogon schoenanthus essential oils were evaluated against developmental stages of trichostrongylids from sheep naturally infected (95% Haemonchus contortus and 5% Trichostrogylus spp.) through the egg hatch assay (EHA), larval development assay (LDA), larval feeding inhibition assay (LFIA), and the larval exsheathment assay (LEA). The major constituent of the essential oils, quantified by gas chromatography for M. piperita oil was menthol (42.5%), while for C. martinii and C. schoenanthus the main component was geraniol (81.4% and 62.5%, respectively). In all in vitro tests C. schoenanthus essential oil had the best activity against ovine trichostrongylids followed by C. martini, while M. piperita presented the least activity. Cymbopogon schoenanthus essential oil had LC(50) value of 0.045 mg/ml in EHA, 0.063 mg/ml in LDA, 0.009 mg/ml in LFIA, and 24.66 mg/ml in LEA. The anthelmintic activity of essential oils followed the same pattern in all in vitro tests, suggesting C. schoenanthus essential oil could be an interesting candidate for nematode control, although in vivo studies are necessary to validate the anthelmintic properties of this oil.

  2. In vitro and in vivo anthelmintic activity of Murraya koenigii against gastro-intestinal nematodes of sheep.

    PubMed

    Molla, Sabir Hossen; Bandyopadhyay, Probir Kumar

    2016-06-01

    The present study have been conducted to evaluate the anthelmintic activity of crude aqueous and crude methanolic leaf extracts of Murraya koenigii. Infection of ruminants with gastro-intestinal (GI) parasite has become a worldwide problem. The parasite causes economic losses in a variety of ways. Previously sheep producers relied heavily on anti-parasitic drugs to control gastro-intestinal parasites of the flocks. But due to misuse of these drugs the parasites become resistant to drugs. Thus created interest in studying medicinal plants as an alternative source of controlling the GI parasites. Adult motility assay (AMA) and egg hatch assay (EHA) have been done for in vitro study, and faecal egg count reduction (FECR) assay have been done for in vivo study. The in vitro study revealed anthelmintic effects of M. koenigii on Haemonchus contortus as evident from their paralytic condition and/or death at eight hour post exposure in different concentrations (12.5, 25, 50 mg/ml) of aqueous and methanolic extracts which exhibit to be dose-dependent. Aqueous and methanolic extracts of M. koenigii were found to have low percent inhibitory effect on egg hatching. It may be concluded that M. koenigii showed significant anthelmintic activity.

  3. In vivo anthelmintic activity of Carex baccans and its active principle resveratrol against Hymenolepis diminuta.

    PubMed

    Giri, Bikash Ranjan; Bharti, Ravi Rao; Roy, Bishnupada

    2015-02-01

    Anthelmintic resistance against most of the commercial drugs is a great threat to humans as well as the veterinary live stocks. Hence, new treatment strategies to control helminth infections are essential at this hour. Carex baccans Nees has been traditionally used by Jaintia tribes in Northeast India to get rid of intestinal worm infections. Therefore, the present study was conducted to evaluate in vivo cestocidal activity of root tuber extract of C. baccans and its active component resveratrol against the zoonotic cestode Hymenolepis diminuta in the experimental model rat. The cestocidal activity was determined by monitoring the eggs per gram (EPG) counts in faeces of different treated groups. The result showed that the highest dose of the plant extract (50 mg/kg) and resveratrol (4.564 mg/kg body weight) has significant anthelmintic efficacy against H. diminuta. Crude extract of the plant as well as resveratrol reduced EPG count (56.012 and 46.049 %) and also resulted in decreased worm burden by 44.287 and 31.034 %, respectively. The efficacy of the crude extract and resveratrol can be compared to the reference drug praziquantel. The results exhibits considerable cestocidal potential of root tuber crude extract of C. baccans and resveratrol and justify its folklore use.

  4. Glutamate-gated chloride channels and the mode of action of the avermectin/milbemycin anthelmintics.

    PubMed

    Wolstenholme, A J; Rogers, A T

    2005-01-01

    The macrocyclic lactones are the biggest selling and arguably most effective anthelmintics currently available. They are good substrates for the P-glycoproteins, which might explain their selective toxicity for parasites over their vertebrate hosts. Changes in the expression of these pumps have been implicated in resistance to the macrocyclic lactones, but it is clear that they exert their anthelmintic effects by binding to glutamate-gated chloride channels expressed on nematode neurones and pharyngeal muscle cells. This effect is quite distinct from the channel opening induced by glutamate, the endogenous transmitter acting at these receptors, which produces rapidly opening and desensitising channels. Ivermectin-activated channels open very slowly but essentially irreversibly, leading to a very long-lasting hyperpolarisation or depolarisation of the neurone or muscle cell and therefore blocking further function. Molecular and genetic studies have shown that there are multiple GluCl isoforms in both free-living and parasitic nematodes: the exact genetic make-up and functions of the GluCl may vary between species. The known expression patterns of the GluCl explain most of the observed biological effects of treatment with the macrocyclic lactones, though the reason for the long-lasting inhibition of larval production in filarial species is still poorly understood.

  5. Automated imaging and other developments in whole-organism anthelmintic screening.

    PubMed

    Paveley, R A; Bickle, Q D

    2013-01-01

    Helminth infections still represent a huge public health problem throughout the developing world and in the absence of vaccines control is based on periodic mass drug administration. Poor efficacy of some anthelmintics and concerns about emergence of drug resistance has highlighted the need for new drug discovery. Most current anthelmintics were discovered through in vivo screening of selected compounds in animal models but recent approaches have shifted towards screening for activity against adult or larval stages in vitro. Larvae are normally available in greater numbers than adults, can often be produced in vitro and are small enough for microplate assays. However, the manual visualization of drug effects in vitro is subjective, laborious and slow. This can be overcome by application of automated readouts including high-content imaging. Incorporated into robotically controlled HTS platforms such methods allow the very large compound collections being made available by the pharmaceutical industry or academic organizations to be screened against helminths for the first time, invigorating the drug discovery pipeline. Here, we review the status of whole-organism screens based on in vitro activity against living worms and highlight the recent progress towards automated image-based readouts. © 2013 John Wiley & Sons Ltd.

  6. Effectiveness of current anthelmintic treatment programs on reducing fecal egg counts in United States cow-calf operations.

    PubMed

    Gasbarre, Louis C; Ballweber, Lora R; Stromberg, Bert E; Dargatz, David A; Rodriguez, Judy M; Kopral, Christine A; Zarlenga, Dante S

    2015-10-01

    During the United States Department of Agriculture (USDA) National Animal Health Monitoring System's (NAHMS) 2007-2008 beef study, producers from 24 states were offered the opportunity to evaluate their animals for internal parasites and for overall responses to treatment with anthelmintics. A lapse of 45 d was required between initial sampling and any previous treatments. Choice of anthelmintic (oral benzimidazoles, and both injectable and pour-on endectocides) was at the discretion of the producer so as not to alter the local control programs. Fresh fecal samples were collected from 20 animals, or from the entire group if less than 20, then randomly assigned to 1 of 3 participating laboratories for examination. Analyses consisted of double centrifugation flotation followed by enumeration of strongyle, Nematodirus, and Trichuris eggs (the presence of coccidian oocysts and tapeworm eggs was also noted). Where strongyle eggs per gram (epg) exceeded 30, aliquots from 2 to 6 animals were pooled for egg isolation and polymerase chain reaction (PCR) analysis for the presence of Ostertagia, Cooperia, Haemonchus, Oesophagostomum, and Trichostrongylus. Results from 72 producers (19 States) indicated that fecal egg count reductions were < 90% in 1/3 of the operations. All operations exhibiting less than a 90% reduction had used pour-on macrocyclic lactones as the anthelmintic treatment. While some of these less than expected reductions could have been the result of improper drug application, PCR analyses of the parasite populations surviving treatment, coupled with follow-up studies at a limited number of sites, indicated that less than expected reductions were most likely due to anthelmintic resistance in Cooperia spp. and possibly Haemonchus spp.

  7. Investigating anthelmintic efficacy against gastrointestinal nematodes in cattle by considering appropriate probability distributions for faecal egg count data.

    PubMed

    Love, J W; Kelly, L A; Lester, H E; Nanjiani, I; Taylor, M A; Robertson, C

    2017-04-01

    The Faecal Egg Count Reduction Test (FECRT) is the most widely used field-based method for estimating anthelmintic efficacy and as an indicator of the presence of anthelmintic resistant nematodes in cattle, despite never having been validated against the gold standard of controlled slaughter studies. The objectives of this study were to assess the normality of cattle faecal egg count (FEC) data and their transformed versions, since confidence intervals used to aid the interpretation of the FECRT, are derived from data assumed to be normally distributed, and violation of this assumption could potentially lead to the misclassification of anthelmintic efficacy. Further, probability distributions and associated parameters were evaluated to determine those most appropriate for representing cattle FEC data, which could be used to estimate percentage reductions and confidence limits. FEC data were analysed from 2175 cattle on 52 farms using a McMaster method at two different diagnostic sensitivities (30 and 15 eggs per gram (epg)) and a sensitive centrifugal flotation technique (SCFT) with a sensitivity of 1 epg. FEC data obtained from all egg count methods were found to be non-normal even upon transformation; therefore, it would be recommended that confidence or credible intervals be generated using either a Bootstrapping or Bayesian approach, respectively, since analyses using these frameworks do not necessarily require the assumption of normality. FEC data obtained using the SCFT method were best represented by distributions associated with the negative binomial and hence arithmetic means could be used in FECRT calculations. Where FEC data were obtained with less sensitive counting techniques (i.e. McMaster 30 or 15 epg), zero-inflated distributions and their associated central tendency were the most appropriate and would be recommended to use, i.e. the arithmetic group mean divided by the proportion of non-zero counts present; otherwise apparent anthelmintic efficacy

  8. A survey on parasite management by equine veterinarians highlights the need for a regulation change

    PubMed Central

    Sallé, Guillaume; Cabaret, Jacques

    2015-01-01

    Introduction In-depth knowledge of the use of anthelminthics in the field, especially by veterinarians, is required to design more sustainable parasite control strategies. Materials and methods An online survey was sent by e-mail to 940 equine veterinary practitioners to describe their equine practice, their awareness about parasites and the management strategies they apply. Results Gastrointestinal parasites were generally considered (68%) as an issue of moderate importance. Drug efficacy failure was a minor or moderate issue for 47% and 48% of responders, respectively. Parasite management mostly relied on the use of systematic calendar treatments across a wide variety of horse owners (ie, riding schools, studs or hobby horse owners). Almost half of the practitioners (42%) never performed Faecal Egg Count (FEC) before drenching. Horse owners or their employees in charge of equines were reported to be the only person managing drenching in 59% of the collected answers. This was associated with the report of many off-label uses of anthelmintics and the frequent buying of drugs using the internet. Conclusions Given the critical situation regarding anthelmintic resistance, it seems necessary for veterinarians to reclaim parasite management and prevention as a specific topic. Implementation of stricter regulations for use of anthelmintics, like the one applied in Denmark, may make parasitic management in equids more sustainable. PMID:26421153

  9. A survey on parasite management by equine veterinarians highlights the need for a regulation change.

    PubMed

    Sallé, Guillaume; Cabaret, Jacques

    2015-01-01

    In-depth knowledge of the use of anthelminthics in the field, especially by veterinarians, is required to design more sustainable parasite control strategies. An online survey was sent by e-mail to 940 equine veterinary practitioners to describe their equine practice, their awareness about parasites and the management strategies they apply. Gastrointestinal parasites were generally considered (68%) as an issue of moderate importance. Drug efficacy failure was a minor or moderate issue for 47% and 48% of responders, respectively. Parasite management mostly relied on the use of systematic calendar treatments across a wide variety of horse owners (ie, riding schools, studs or hobby horse owners). Almost half of the practitioners (42%) never performed Faecal Egg Count (FEC) before drenching. Horse owners or their employees in charge of equines were reported to be the only person managing drenching in 59% of the collected answers. This was associated with the report of many off-label uses of anthelmintics and the frequent buying of drugs using the internet. Given the critical situation regarding anthelmintic resistance, it seems necessary for veterinarians to reclaim parasite management and prevention as a specific topic. Implementation of stricter regulations for use of anthelmintics, like the one applied in Denmark, may make parasitic management in equids more sustainable.

  10. Childhood obesity and insulin resistance: how should it be managed?

    PubMed

    Ho, Mandy; Garnett, Sarah P; Baur, Louise A

    2014-12-01

    Concomitant with the rise in global pediatric obesity in the past decades, there has been a significant increase in the number of children and adolescents with clinical signs of insulin resistance. Given insulin resistance is the important link between obesity and the associated metabolic abnormalities and cardiovascular risk, clinicians should be aware of high risk groups and treatment options. As there is no universally accepted biochemical definition of insulin resistance in children and adolescents, identification and diagnosis of insulin resistance usually relies on clinical features such as acanthosis nigricans, polycystic ovary syndrome, hypertension, dyslipidemia, and nonalcoholic fatty liver disease. Treatment for reducing insulin resistance and other obesity-associated comorbidities should focus on changes in health behaviors to achieve effective weight management. Lifestyle interventions incorporating dietary change, increased physical activity, and decreased sedentary behaviors, with the involvement of family and adoption of a developmentally appropriate approach, should be used as the first line treatment. Current evidence suggests that the primary objective of dietary interventions should be to reduce total energy intake and a combination of aerobic and resistance training should be encouraged. Metformin can be used in conjunction with a lifestyle intervention program in obese adolescents with clinical insulin resistance to achieve weight loss and to improve insulin sensitivity. Ongoing evaluation and research are required to explore optimal protocol and long-term effectiveness of lifestyle interventions, as well as to determine whether the improvements in insulin sensitivity induced by lifestyle interventions and weight loss will lead to a clinical benefit including reduced cardiovascular morbidity and mortality.

  11. Metabolic pathways of benzimidazole anthelmintics in harebell (Campanula rotundifolia).

    PubMed

    Stuchlíková, Lucie; Jirásko, Robert; Skálová, Lenka; Pavlík, František; Szotáková, Barbora; Holčapek, Michal; Vaněk, Tomáš; Podlipná, Radka

    2016-08-01

    Benzimidazoles anthelmintics, which enter into environment primarily through excretion in the feces or urine of treated animals, can affect various organisms and disrupt ecosystem balance. The present study was designed to test the phytotoxicity and biotransformation of the three benzimidazole anthelmintics albendazole (ABZ), fenbendazole (FBZ) and flubendazole (FLU) in the harebell (Campanula rotundifolia). This meadow plant commonly grows in pastures and comes into contact with anthelmintics through the excrements of treated animals. Suspensions of harebell cells in culture medium were used as an in vitro model system. ABZ, FLU and FBZ were not found to be toxic for harebell cells, which were able to metabolize ABZ, FLU and FBZ via the formation of a wide scale of metabolites. Ultrahigh-performance liquid chromatography coupled with high mass accuracy tandem mass spectrometry (UHPLC-MS/MS) led to the identification of 24, 18 and 29 metabolites of ABZ, FLU and FBZ, respectively. Several novel metabolites were identified for the first time. Based on the obtained results, the schemes of the metabolic pathways of these anthelmintics were proposed. Most of these metabolites can be considered deactivation products, but a substantial portion of them may readily be decomposed to biologically active substances which could negatively affect ecosystems.

  12. Chronic Urticaria in Returning Travellers: The Role of Anthelmintic Treatment.

    PubMed

    Nahshoni, Avishai; Baum, Sharon; Barzilai, Aviv; Schwartz, Eli

    2016-01-01

    Chronic urticaria often poses a therapeutic challenge. The human immune response to helminths has a high degree of similarity to an allergic response in terms of skin manifestations, eosinophilia, and IgE elevation. Unfortunately, it is often complicated to diagnose such infections. We sought to assess the effect of empirical anthelmintic treatment among returning travellers diagnosed with chronic urticaria, without clear proof of helminthic infection. This is a retrospective case series of 19 returning travellers with chronic urticaria. All patients were treated with anthelmintic treatment given based on clinical suspicion only. A randomly selected control group of 20 patients with chronic urticaria, with no history of travel, was also enrolled. A positive clinical response was reported in 68.4% (13 patients) of the travellers' group within 3 months after treatment with anthelmintic therapy compared with 10% (2 patients) of chronic urticaria patients in the control group. No adverse effects from treatment were recorded. In patients with chronic urticaria, travel history to developing countries must be obtained. Empiric anthelmintic therapy might be beneficial, even in the absence of findings suggestive of helminthic infection. © 2016 S. Karger AG, Basel.

  13. Common errors in multidrug-resistant tuberculosis management.

    PubMed

    Monedero, Ignacio; Caminero, Jose A

    2014-02-01

    Multidrug-resistant tuberculosis (MDR-TB), defined as being resistant to at least rifampicin and isoniazid, has an increasing burden and threatens TB control. Diagnosis is limited and usually delayed while treatment is long lasting, toxic and poorly effective. MDR-TB management in scarce-resource settings is demanding however it is feasible and extremely necessary. In these settings, cure rates do not usually exceed 60-70% and MDR-TB management is novel for many TB programs. In this challenging scenario, both clinical and programmatic errors are likely to occur. The majority of these errors may be prevented or alleviated with appropriate and timely training in addition to uninterrupted procurement of high-quality drugs, updated national guidelines and laws and an overall improvement in management capacities. While new tools for diagnosis and shorter and less toxic treatment are not available in developing countries, MDR-TB management will remain complex in scarce resource settings. Focusing special attention on the common errors in diagnosis, regimen design and especially treatment delivery may benefit patients and programs with current outdated tools. The present article is a compilation of typical errors repeatedly observed by the authors in a wide range of countries during technical assistant missions and trainings.

  14. Antimicrobial resistance and management of invasive Salmonella disease

    PubMed Central

    Kariuki, Samuel; Gordon, Melita A.; Feasey, Nicholas; Parry, Christopher M

    2015-01-01

    Invasive Salmonella infections (typhoidal and non-typhoidal) cause a huge burden of illness estimated at nearly 3.4 million cases and over 600,000 deaths annually especially in resource-limited settings. Invasive non-typhoidal Salmonella (iNTS) infections are particularly important in immunosuppressed populations especially in sub-Saharan Africa, causing a mortality of 20–30% in vulnerable children below 5 years of age. In these settings, where routine surveillance for antimicrobial resistance is rare or non-existent, reports of 50–75% multidrug resistance (MDR) in NTS are common, including strains of NTS also resistant to flouroquinolones and 3rd generation cephalosporins. Typhoid (enteric) fever caused by Salmonella Typhi and Salmonella Paratyphi A remains a major public health problem in many parts of Asia and Africa. Currently over a third of isolates in many endemic areas are MDR, and diminished susceptibility or resistance to fluoroquinolones, the drugs of choice for MDR cases over the last decade is an increasing problem. The situation is particularly worrying in resource-limited settings where the few remaining effective antimicrobials are either unavailable or altogether too expensive to be afforded by either the general public or by public health services. Although the prudent use of effective antimicrobials, improved hygiene and sanitation and the discovery of new antimicrobial agents may offer hope for the management of invasive salmonella infections, it is essential to consider other interventions including the wider use of WHO recommended typhoid vaccines and the acceleration of trials for novel iNTS vaccines. The main objective of this review is to describe existing data on the prevalence and epidemiology of antimicrobial resistant invasive Salmonella infections and how this affects the management of these infections, especially in endemic developing countries. PMID:25912288

  15. Antimicrobial resistance and management of invasive Salmonella disease.

    PubMed

    Kariuki, Samuel; Gordon, Melita A; Feasey, Nicholas; Parry, Christopher M

    2015-06-19

    Invasive Salmonella infections (typhoidal and non-typhoidal) cause a huge burden of illness estimated at nearly 3.4 million cases and over 600,000 deaths annually especially in resource-limited settings. Invasive non-typhoidal Salmonella (iNTS) infections are particularly important in immunosuppressed populations especially in sub-Saharan Africa, causing a mortality of 20-30% in vulnerable children below 5 years of age. In these settings, where routine surveillance for antimicrobial resistance is rare or non-existent, reports of 50-75% multidrug resistance (MDR) in NTS are common, including strains of NTS also resistant to flouroquinolones and 3rd generation cephalosporins. Typhoid (enteric) fever caused by Salmonella Typhi and Salmonella Paratyphi A remains a major public health problem in many parts of Asia and Africa. Currently over a third of isolates in many endemic areas are MDR, and diminished susceptibility or resistance to fluoroquinolones, the drugs of choice for MDR cases over the last decade is an increasing problem. The situation is particularly worrying in resource-limited settings where the few remaining effective antimicrobials are either unavailable or altogether too expensive to be afforded by either the general public or by public health services. Although the prudent use of effective antimicrobials, improved hygiene and sanitation and the discovery of new antimicrobial agents may offer hope for the management of invasive salmonella infections, it is essential to consider other interventions including the wider use of WHO recommended typhoid vaccines and the acceleration of trials for novel iNTS vaccines. The main objective of this review is to describe existing data on the prevalence and epidemiology of antimicrobial resistant invasive Salmonella infections and how this affects the management of these infections, especially in endemic developing countries. Copyright © 2015. Published by Elsevier Ltd.

  16. Extensively drug-resistant tuberculosis: epidemiology and management.

    PubMed

    Matteelli, Alberto; Roggi, Alberto; Carvalho, Anna Cc

    2014-01-01

    The advent of antibiotics for the treatment of tuberculosis (TB) represented a major breakthrough in the fight against the disease. However, since its first use, antibiotic therapy has been associated with the emergence of resistance to drugs. The incorrect use of anti-TB drugs, either due to prescription errors, low patient compliance, or poor quality of drugs, led to the widespread emergence of Mycobacterium tuberculosis strains with an expanding spectrum of resistance. The spread of multidrug-resistant (MDR) strains (ie, strains resistant to both isoniazid and rifampicin) has represented a major threat to TB control since the 1990s. In 2006, the first cases of MDR strains with further resistance to fluoroquinolone and injectable drugs were described and named extensively drug-resistant TB (XDR-TB). The emergence of XDR-TB strains is a result of mismanagement of MDR cases, and treatment relies on drugs that are less potent and more toxic than those used to treat drug-susceptible or MDR strains. Furthermore, treatment success is lower and mortality higher than achieved in MDR-TB cases, and the number of drugs necessary in the intensive phase of treatment may be higher than the four drugs recommended for MDR-TB. Linezolid may represent a valuable drug to treat cases of XDR-TB. Delamanid, bedaquiline, and PA-824 are new anti-TB agents in the development pipeline that have the potential to enhance the cure rate of XDR-TB. The best measures to prevent new cases of XDR-TB are the correct management of MDR-TB patients, early detection, and proper treatment of existing patients with XDR-TB.

  17. Current management of advanced and castration resistant prostate cancer.

    PubMed

    Gomella, Leonard G; Petrylak, Daniel P; Shayegan, Bobby

    2014-04-01

    Newer approaches to the management of advanced prostate cancer have rapidly evolved. While basic androgen deprivation remains as the first line in newly diagnosed hormone naïve metastatic prostate cancer, the agents used and strategies followed have undergone significant changes. Numerous new agents such as sipuleucel-T, abiraterone, enzalutamide, cabazitaxel and radium 223 have all been approved since 2010 to treat metastatic castration resistant prostate cancer (CRPC). New imaging techniques to detect advanced disease such as F-18 PET, 11 C-choline PET and other modalities are becoming available. The concepts of "bone health" and the management of side effects related to androgen deprivation therapy are also gaining attention as men are being treated with longer courses of androgen deprivation. Understanding the theory behind these new agents and management approaches while focusing on the practical clinical considerations are essential to improve outcomes in advanced prostate cancer. A review of the current state of the art in the management of advanced and castration resistant prostate cancer presented in this Canadian Journal of Urology International supplement was performed. Key findings are summarized and presented along with critical updates based on recent publications and meeting presentations. Key concepts identified in the management of advanced prostate cancer included the new understanding of prostate cancer based on translational discoveries, applications of various hormonally based strategies in advanced disease including traditional and recently approved agents. The use of new imaging modalities to identify metastatic disease, immunotherapy approaches and discussions of sequencing and which new agents are likely to be available in the future in the management of CRPC were identified. Bone targeted strategies are also addressed in the setting of androgen deprivation and metastatic disease. The management of men with advanced prostate cancer has

  18. Insect resistance management for Syngenta's VipCot transgenic cotton.

    PubMed

    Kurtz, Ryan W; McCaffery, Alan; O'Reilly, David

    2007-07-01

    Syngenta is seeking commercial registration for VipCot cotton, a pyramided transgenic cotton trait that expresses two insecticidal proteins derived from Bacillus thuringiensis Vip3A and Cry1Ab. Both proteins are highly effective against two key cotton pests, Helicoverpa zea cotton bollworm; and Heliothis virescens, tobacco budworm. To investigate the role of VipCot cotton in delaying the development of resistance in these pests to transgenic Bt traits, Syngenta has performed studies to determine the dose of proteins expressed in VipCot and evaluate the potential for cross-resistance between the component proteins. Following United States Environmental Protection Agency (US EPA) high dose methods 1 and 4, VipCot was shown to express a high dose of proteins for H. zea and H. virescens. VipCot was also confirmed to express a high dose of proteins for H. zea through US EPA Method 5. Additionally, all the data collected to date verify a lack of cross-resistance between Vip3A and Cry proteins. These two key pieces of information indicate that VipCot cotton should be very durable under the currently mandated high dose plus refuge insect resistance management strategy.

  19. Extensively drug-resistant tuberculosis: epidemiology and management challenges.

    PubMed

    Dheda, Keertan; Warren, Robin M; Zumla, Alimuddin; Grobusch, Martin P

    2010-09-01

    Widespread global use of rifampin for 2 decades preceded the emergence of clinically significant multidrug-resistant tuberculosis (MDR-TB) in the early 1990s. The prevalence of MDR-TB has gradually increased such that it accounts for approximately 5% of the global case burden of disease (approximately half a million cases in 2007). Eclipsing this worrying trend is the widespread emergence of extensively drug-resistant TB (XDR-TB). This article reviews the insights provided by clinical and molecular epidemiology regarding global trends and transmission dynamics of XDR-TB, and the challenges clinicians have to face in diagnosing and managing cases of XDR-TB. The ethical and management dilemmas posed by recurrent defaulters, XDR-TB treatment failures, and isolation of incurable patients are also discussed. Given the past global trends in MDR-TB, if aggressive preventive and management strategies are not implemented, XDR-TB has the potential to severely cripple global control efforts of TB.

  20. Frequency of cattle farms with ivermectin resistant gastrointestinal nematodes in Veracruz, Mexico.

    PubMed

    Alonso-Díaz, M A; Arnaud-Ochoa, R A; Becerra-Nava, R; Torres-Acosta, J F J; Rodriguez-Vivas, R I; Quiroz-Romero, R H

    2015-09-15

    This study reports the percentage of cattle farms with ivermectin (IVM) resistant gastrointestinal nematodes (GINs) in Veracruz, Mexico, and identifies the GIN genera involved in the resistances. It also describes management practices of anthelmintic (AH) use on the surveyed farms. Twenty-one farms were assessed by means of the faecal egg count reduction test using the McMaster technique. Only two farms had GIN populations susceptible to IVM (9.5%). The proportion of farms with IVM resistant GIN was 71.4% (15/21). Seven of these farms had less than 80% egg count reductions. Haemonchus and Cooperia were the genera most commonly found in the resistant populations, followed by Oesophagostomum. Inappropriate AH treatment practices were identified from the completed questionnaires. Further management practices such as selective treatment and quarantine treatments are proposed to further reduce the spread of IVM resistance between farms.

  1. The early drug selection of nematodes to anthelmintics: stochastic transmission and population in refuge.

    PubMed

    Gaba, S; Cabaret, J; Ginot, V; Silvestre, A

    2006-09-01

    We have developed an individual-based model to reflect the complexity of the early phase of drug resistance selection in a nematode/sheep model. The infection process consists of the stochastic ingestion of infective larvae spatially aggregated in clumps. Each clump corresponds to infective larvae, which are the offspring of the mature nematodes from a given sheep. We studied the dynamics of the parasitic population and the frequency of the recessive resistance alleles during selection by anthelmintic treatments. The interaction between genetic and demographic processes illustrated the trade-off between the control of the infection and the delay of resistance selection. We confirmed the importance of the number of treatments and their timing. The same treatment frequency may result in different outcomes on resistance selection in relation to the size of the refuge (infective larvae on pasture). Treatment applied during the summer (when the mortality of infective larvae on pasture was high), may lead to a rapid selection of drug resistance and a lack of control of sheep and pasture contamination. We showed that higher stocking rates were also a force in promoting the resistance allele selection.

  2. Our top 10 herbicide-resistant weed management practices.

    PubMed

    Beckie, Hugh J; Harker, K Neil

    2017-06-01

    Although proactive or reactive herbicide-resistant weed management (HRWM) practices have been recommended to growers in different agroecoregions globally, there is a need to identify and prioritise those having the most impact in mitigating or managing herbicide selection pressure in the northern Great Plains of North America. Our perspective on this issue is based on collaborative research, extension activities and dialogue with growers or farming experience (cereal, oilseed and pulse crop production) during the past 30 years. We list our top 10 HRWM practices, concluding with the number 1 practice which is the foundation of the other nine practices: crop diversity. Although our top 10 HRWM practices have broad applicability across agroecoregions, their ranking may vary widely. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  3. A theoretical examination of the relative importance of evolution management and drug development for managing resistance.

    PubMed

    McClure, Nathan S; Day, Troy

    2014-12-22

    Drug resistance is a serious public health problem that threatens to thwart our ability to treat many infectious diseases. Repeatedly, the introduction of new drugs has been followed by the evolution of resistance. In principle, there are two complementary ways to address this problem: (i) enhancing drug development and (ii) slowing the evolution of drug resistance through evolutionary management. Although these two strategies are not mutually exclusive, it is nevertheless worthwhile considering whether one might be inherently more effective than the other. We present a simple mathematical model that explores how interventions aimed at these two approaches affect the availability of effective drugs. Our results identify an interesting feature of evolution management that, all else equal, tends to make it more effective than enhancing drug development. Thus, although enhancing drug development will necessarily be a central part of addressing the problem of resistance, our results lend support to the idea that evolution management is probably a very significant component of the solution as well.

  4. A theoretical examination of the relative importance of evolution management and drug development for managing resistance

    PubMed Central

    McClure, Nathan S.; Day, Troy

    2014-01-01

    Drug resistance is a serious public health problem that threatens to thwart our ability to treat many infectious diseases. Repeatedly, the introduction of new drugs has been followed by the evolution of resistance. In principle, there are two complementary ways to address this problem: (i) enhancing drug development and (ii) slowing the evolution of drug resistance through evolutionary management. Although these two strategies are not mutually exclusive, it is nevertheless worthwhile considering whether one might be inherently more effective than the other. We present a simple mathematical model that explores how interventions aimed at these two approaches affect the availability of effective drugs. Our results identify an interesting feature of evolution management that, all else equal, tends to make it more effective than enhancing drug development. Thus, although enhancing drug development will necessarily be a central part of addressing the problem of resistance, our results lend support to the idea that evolution management is probably a very significant component of the solution as well. PMID:25377456

  5. Management of febrile neutropenia in the era of bacterial resistance

    PubMed Central

    Alp, Sehnaz

    2013-01-01

    Managing cancer patients with fever and neutropenia must be considered as a medical emergency since any delay in initiating appropriate empirical antibacterial therapy may result in high rates of mortality and morbidity. Emerging antibacterial resistance in bacterial pathogens infecting febrile neutropenic patients complicates management, and choosing the type of empirical antimicrobial therapy has become a challenge. To further complicate the decision process, not all neutropenic patients are in same category of susceptibility to develop severe infection. While low-risk patients may be treated with oral antibiotics in the outpatient setting, high-risk patients usually need to be admitted to hospital and receive parenteral broad-spectrum antibiotics until the neutrophil levels recover. These strategies have recently been addressed in two international guidelines from the Infectious Diseases Society of America (IDSA) and the European Conference on Infections in Leukaemia (ECIL). This review gives a brief overview of current antimicrobial resistance problems and their effects in febrile neutropenic cancer patients by summarizing the suggestions from the IDSA and ECIL guidelines. PMID:25165543

  6. Management of multidrug-resistant tuberculosis and patients in retreatment.

    PubMed

    Caminero, J A

    2005-05-01

    Retreatment of tuberculosis involves the management of entities as diverse as relapse, failure, treatment after default, and poor patient adherence to the previous treatment. The emergence of conditions for selection of resistance (failure and partial abandonment) is a matter of great concern. The development of a retreatment regimen for tuberculosis requires consideration of certain basic premises. The importance of a comprehensive and directed history of drugs taken in the past, and the limited reliability of susceptibility tests to many of these drugs, should be kept in mind. Taking this into account, and possessing a thorough knowledge of all anti-tuberculosis medications, it is possible to cure almost all patients with an appropriate retreatment regimen including a minimum of three or four drugs not previously used. Nonetheless, the treatment of these patients is so complex that it should only be carried out by experienced staff. Concern about treating tuberculosis patients with drug resistance varies greatly depending on the available resources. High-income countries should provide individual treatment regimens adapted to each patient; however, in other settings, restricted resources could justify the implementation of standardised therapeutic guidelines with second-line drugs in order to facilitate management and reduce costs.

  7. Managing drug-resistant epilepsy: challenges and solutions

    PubMed Central

    Dalic, Linda; Cook, Mark J

    2016-01-01

    Despite the development of new antiepileptic drugs (AEDs), ~20%–30% of people with epilepsy remain refractory to treatment and are said to have drug-resistant epilepsy (DRE). This multifaceted condition comprises intractable seizures, neurobiochemical changes, cognitive decline, and psychosocial dysfunction. An ongoing challenge to both researchers and clinicians alike, DRE management is complicated by the heterogeneity among this patient group. The underlying mechanism of DRE is not completely understood. Many hypotheses exist, and relate to both the intrinsic characteristics of the particular epilepsy (associated syndrome/lesion, initial response to AED, and the number and type of seizures prior to diagnosis) and other pharmacological mechanisms of resistance. The four current hypotheses behind pharmacological resistance are the “transporter”, “target”, “network”, and “intrinsic severity” hypotheses, and these are reviewed in this paper. Of equal challenge is managing patients with DRE, and this requires a multidisciplinary approach, involving physicians, surgeons, psychiatrists, neuropsychologists, pharmacists, dietitians, and specialist nurses. Attention to comorbid psychiatric and other diseases is paramount, given the higher prevalence in this cohort and associated poorer health outcomes. Treatment options need to consider the economic burden to the patient and the likelihood of AED compliance and tolerability. Most importantly, higher mortality rates, due to comorbidities, suicide, and sudden death, emphasize the importance of seizure control in reducing this risk. Overall, resective surgery offers the best rates of seizure control. It is not an option for all patients, and there is often a significant delay in referring to epilepsy surgery centers. Optimization of AEDs, identification and treatment of comorbidities, patient education to promote adherence to treatment, and avoidance of triggers should be periodically performed until further

  8. Antiparasitic drugs and lactation: focus on anthelmintics, scabicides, and pediculicides.

    PubMed

    Porto, Isabel

    2003-11-01

    Infections involving helminths or parasitic worms affect more than 25% of the population worldwide. Because lactating women and their infants are often affected by the complications of these infections such as iron deficiency anemia and malnutrition, they benefit the most from drug therapy. However, scientific literature offers little information regarding transfer of anthelmintics in breast milk and its effects in lactating infants. Scabies and pediculosis, or lice, are common skin infections affecting school-aged children. Close contacts of infected children, which often include lactating mothers, need treatment with one of the several topical products available in the market. This article will review the physicochemical properties and use of anthelmintics, pediculicides, and scabicides while breastfeeding.

  9. Effect of three anthelmintics on weight gain of feedlot cattle.

    PubMed

    Waldhalm, D G; Hall, R F

    1977-09-01

    Three groups of 50 heavy feedlot steers were treated with 1 of 3 anthelmintics (haloxon, tramisol, or thiabendazole). One group of 50 steers was not treated and served as a control. The initial degree of infection with gastrointestinal nematodes was light and decreased during the course of the study. There were no significant differences in weight gains among any of the groups at the end of a 113-day feeding period.

  10. Management Options For Reducing The Release Of Antibiotics And Antibiotic Resistance Genes To The Environment

    EPA Science Inventory

    Background: There is growing concern worldwide about the role of polluted soil and water - 77 environments in the development and dissemination of antibiotic resistance. 78 Objective: To identify management options for reducing the spread of antibiotics and 79 antibiotic resist...

  11. Management Options For Reducing The Release Of Antibiotics And Antibiotic Resistance Genes To The Environment

    EPA Science Inventory

    Background: There is growing concern worldwide about the role of polluted soil and water - 77 environments in the development and dissemination of antibiotic resistance. 78 Objective: To identify management options for reducing the spread of antibiotics and 79 antibiotic resist...

  12. Anthelmintic activity of the latex of Ficus species.

    PubMed

    de Amorin, A; Borba, H R; Carauta, J P; Lopes, D; Kaplan, M A

    1999-03-01

    The latex of some species of Ficus (Moraceae) has been traditionally used as vermifuge in Central and South America. It has been accepted that anthelmintic activity is due to a proteolytic fraction called ficin. In the present study, the anthelmintic activity of the latex of Ficus insipida Willd. and Ficus carica L. has been investigated in NIH mice naturally infected with Syphacia obvelata, Aspiculuris tetraptera and Vampirolepis nana. The latex of F. insipida, administered by intragastric route in doses of 4 ml/kg/day during three consecutive days, were effective in the removal of 38.6% of the total number of S. obvelata, being inexpressive in the removal of A. tetraptera (8.4%) and segments of V. nana (6.3%). The latex of F. carica, administered in doses of 3 ml/kg/day, during three consecutive days, was effective in the removal of S. obvelata (41.7%) and it did not produce significant elimination of A. tetraptera (2.6%) and V. nana (8.3%). The observed high acute toxicity with hemorrhagic enteritis, in addition to a weak anthelmintic efficacy, do not recommend the use of these lattices in traditional medicine.

  13. Comparative in vitro effects of closantel and selected beta-ketoamide anthelmintics on a gastrointestinal nematode and vertebrate liver cells.

    PubMed

    Bacon, J A; Ulrich, R G; Davis, J P; Thomas, E M; Johnson, S S; Conder, G A; Sangster, N C; Rothwell, J T; McCracken, R O; Lee, B H; Clothier, M F; Geary, T G; Thompson, D P

    1998-06-01

    PNU-87407 and PNU-88509, beta-ketoamide anthelmintics that are structurally related to each other and to the salicylanilide anthelmintic closantel, exhibit different anthelmintic spectra and apparent toxicity in mammals. The basis for this differential pharmacology was examined in experiments that measured motility and adenosine triphosphate (ATP) levels in larval and adult stages of the gastrointestinal nematode, Haemonchus contortus, and in a vertebrate liver cell line and mitochondria. PNU-87407 and PNU-88509 both exhibited functional cross-resistance with closantel in larval migration assays using closantel-resistant and -sensitive isolates of H. contortus. Each compound reduced motility and ATP levels in cultured adult H. contortus in a concentration- and time-dependent manner; however, motility was reduced more rapidly by PNU-88509, and ATP levels were reduced by lower concentrations of closantel than the beta-ketoamides. Tension recordings from segments of adult H. contortus showed that PNU-88509 induces spastic paralysis, while PNU-87407 and closantel induce flaccid paralysis of the somatic musculature. Marked differences in the actions of these compounds were also observed in the mammalian preparations. In Chang liver cells, ATP levels were reduced after 3 h exposures to > or = 0.25 microM PNU-87407, > or = 1 microM closantel or > or = 10 microM PNU-88509. Reductions in ATP caused by PNU-88509 were completely reversible, while the effects of closantel and PNU-87407 were irreversible. PNU-87407, closantel and PNU-88509 uncoupled oxidative phosphorylation in isolated rat liver mitochondria, inhibiting the respiratory control index (with glutamate or succinate as substrate) by 50% at concentrations of 0.14, 0.9 and 7.6 microM, respectively.

  14. Gastrointestinal nematode infection and performance of weaned stocker calves in response to anthelmintic control strategies.

    PubMed

    Walker, R S; Miller, J E; Monlezun, C J; LaMay, D; Navarre, C; Ensley, D

    2013-10-18

    Gastrointestinal nematode (GIN) parasite control recommendations are in a state of flux because of the increase in anthelmintic resistant cattle parasites, such as Cooperia spp. In addition, Cooperia spp. infection is typically high in warm-season grass pastures and can affect growth performance of grazing stocker calves in the Gulf Coast Region. This study evaluated the effects of moxidectin pour-on, oxfendazole oral suspension, or a combination of the two given at separate times on infection and performance of weaned beef calves grazing summer forages. Steers (n=42) and heifers (n=31) were stratified by sex, d-11 fecal egg count (FEC), and d-1 shrunk body weight (BW) to one of 10 pastures with four anthelmintic treatments and one control. Treatments included: (1) oxfendazole given on d 0 and moxidectin on d 73 (O+M), (2) moxidectin given on d 0 and oxfendazole on d 73 (M+O), (3) moxidectin given on d 0 (M), (4) oxfendazole given on d 0 (O) and (5) no anthelmintic given (CON). Calves grazed for d-110 beginning May 27th. Response variables were FEC (collected on d-11, 14, 31, 45, 59, 73, 87 and 108), coprocultures (evaluated for d 87 and 108), final shrunk BW, shrunk BW gain, average daily gain (ADG), and full BW gain (collected on d 31, 59, 73, 87, and 108). Calves treated with either oxfendazole (O+M and O) or moxidectin (M+O and M) on d 0 had significantly lower (P<0.001) FEC than the CON calves on d 14, 31 and 45. However, the M+O treated calves had significantly higher (P<0.001) FEC than both oxfendazole treated groups. In addition, calves treated with a second dewormer on d 73 (O+M and M+O) had significantly lower (P<0.001) FEC by d 87 than the CON or M treated calves. Shrunk BW gain and ADG were significantly greater (P=0.005) for the O+M compared to the M treated and CON calves, but comparable with the M+O and O treated calves, respectively. Coprocultures sampled on d 87 and 108 for calves not receiving a second dewormer were predominantly Cooperia spp. and

  15. Gene expression changes in a P-glycoprotein (Tci-pgp-9) putatively associated with ivermectin resistance in Teladorsagia circumcincta.

    PubMed

    Dicker, Alison J; Nisbet, Alasdair J; Skuce, Philip J

    2011-08-01

    Anthelmintic resistance in parasitic nematodes of small ruminants is widespread and, in some parts of the world, threatens the sustainability of sheep production. The genetic changes underlying resistance to anthelmintics, particularly ivermectin (IVM), remain to be determined. The majority of studies to date have investigated target site mutations; relatively little attention has been paid to the role of changes in gene expression. In this study, we investigated the expression of putative drug transporter molecules, P-glycoproteins (Pgps), in Teladorsagia circumcincta, the predominant parasitic nematode species of sheep in the UK and the major anthelmintic resistant species. Utilising a degenerate PCR approach, 11 partial Pgp sequences were identified. Constitutive differences in gene expression between an IVM-susceptible (MTci2) and a multidrug-resistant (MTci5) isolate were determined for 10 of the Pgps using the ΔΔCt TaqMan® real-time PCR method. Gene expression differences were particularly marked in one of these genes, namely Tci-pgp-9. In the MTci5 isolate, statistically significant increases in Tci-pgp-9 expression, at the mRNA level, were observed across all life-cycle stages and most notably in eggs (55-fold increase). Comparison of the partial Tci-pgp-9 nucleotide sequences from MTci2 and MTci5 also identified high levels of polymorphism. This work has shown that constitutively increased expression in Tci-pgp-9, coupled with increased sequence polymorphism, could play a role in allowing multidrug-resistant T. circumcincta to survive IVM exposure. The genetic changes underpinning these gene expression changes remain to be elucidated and need to be investigated in other isolates. These changes could form the basis of an IVM resistance marker to monitor the spread of resistance and to evaluate management practices aimed at delaying its spread.

  16. Faecal Cyathostomin Egg Count distribution and efficacy of anthelmintics against cyathostomins in Italy: a matter of geography?

    PubMed Central

    Milillo, Piermarino; Boeckh, Albert; Cobb, Rami; Otranto, Domenico; Lia, Riccardo P; Perrucci, Stefania; di Regalbono, Antonio Frangipane; Beraldo, Paola; von Samson-Himmelstjerna, Georg; Demeler, Janina; Bartolini, Roberto; Traversa, Donato

    2009-01-01

    Background In the framework of a trial carried out in 2008 in Europe to evaluate the efficacy of major parasiticides against horse cyathostomins, pre- and/or post-treatment Faecal Egg Counts (FEC) were evaluated in a total of 84 yards and 2105 horses from nine different regions from the South, the Center, the North-Center and North-East of Italy. Specifically, on the basis of FECs of the horses present in each property, 60 out of the 84 yards were enrolled for a Faecal Egg Count Reduction Test (FECRT) using fenbendazole, pyrantel, ivermectin and moxidectin. Results Of the 1646 horses bred in the 60 recruited yards, 416 animals had a FEC between 50 and 150 Eggs Per Gram (EPG) of faeces and 694 a FEC >150 EPG (i.e. with total of 1110 positive animals). Of the 1110 positive animals, those with the highest FECs (i.e. 988) were included in the FECRT. The FECRT for four anthelmintic compounds showed remarkable differences in terms of prevalence of reduced and equivocal efficacy against cyathostomins in the different areas of Italy. Administration of fenbendazole and pyrantel resulted in resistance present or suspected in about half of the yards examined while resistance to ivermectin was found in one yard from central Italy and suspected resistance was detected in three more yards, one in each the North, the Center and the South. Treatment with moxidectin was 100% effective in all yards examined. Conclusion Cyathostomin populations in the South and the Center of Italy were more susceptible to fenbendazole and pyrantel than the populations present in the Center-North and North-Eastern areas of Italy. Fenbendazole and/or pyrantel were ineffective in almost all properties from the North of Italy. The reasons for such a difference among the Italian regions in terms of FECs and efficacy of antiparasitic drugs are discussed, together with the role that veterinarians, and horse owners and managers should have for effective worm control programs in this country. PMID:19778465

  17. Evaluation of anthelmintic activity and in silico PASS assisted prediction of Cordia dichotoma (Forst.) root extract

    PubMed Central

    Jamkhande, Prasad G.; Barde, Sonal R.

    2014-01-01

    Background: Worm infection and associated complications are severe problems that afflict a large population worldwide. Failure of synthetic drugs in worm infections because of drug resistance has made alternative drug therapy desirable. Cordia dichotoma (Forst.) is an ethnomedicinal plant which is rich in several secondary metabolites. Traditionally, the plant has been claimed to have high medicinal properties including antimicrobial activity and cytotoxicity. Materials and Methods: The study begun with an aim to explore plant-based natural anthelmintic agents against Pheretima posthuma, an Indian earthworm. Methanol extract of the drug was obtained by successive soxhlet extraction. The extract was tested for different phytochemicals. Worms were exposed to 10 mg/ml, 25 mg/ml, 50 mg/ml, and 75 mg/ml concentrations of extract and standard drug, albendazole. A software-based tool, prediction of activity spectra for substances was used to estimate anthelmintic efficacy of plant metabolites. Result: The phytochemical analysis revealed presence of alkaloids, tannins, glycosides, saponins, flavonoids, and phenols. The extract showed dose-dependent effects, affecting worm motility, viability, and mortality. It was also found that the biological activity spectrum of the plant phytoconstituents such as octacosanol, lupeol, caffeic acid, and hentricontanol were >0.5 (probable activity > 0.5). Conclusion: The findings of the present work suggest that the extract of C. dichotoma significantly interferes with motility pattern of P. posthuma. The paralysis and mortality of P. posthuma might be due to the combined effects different phytoconstituents. The extract of C. dichotoma promises natural sources to control worm infection. PMID:25737609

  18. Bacillus thuringiensis-derived Cry5B Has Potent Anthelmintic Activity against Ascaris suum

    PubMed Central

    Miller, Melanie M.; Scheib, Ulrike; Yiu, Ying Y.; Aroian, Raffi V.

    2013-01-01

    Ascaris suum and Ascaris lumbricoides are two closely related geo-helminth parasites that ubiquitously infect pigs and humans, respectively. Ascaris suum infection in pigs is considered a good model for A. lumbricoides infection in humans because of a similar biology and tissue migration to the intestines. Ascaris lumbricoides infections in children are associated with malnutrition, growth and cognitive stunting, immune defects, and, in extreme cases, life-threatening blockage of the digestive tract and aberrant migration into the bile duct and peritoneum. Similar effects can be seen with A. suum infections in pigs related to poor feed efficiency and performance. New strategies to control Ascaris infections are needed largely due to reduced treatment efficacies of current anthelmintics in the field, the threat of resistance development, and the general lack of new drug development for intestinal soil-transmitted helminths for humans and animals. Here we demonstrate for the first time that A. suum expresses the receptors for Bacillus thuringiensis crystal protein and novel anthelmintic Cry5B, which has been previously shown to intoxicate hookworms and which belongs to a class of proteins considered non-toxic to vertebrates. Cry5B is able to intoxicate A. suum larvae and adults and triggers the activation of the p38 mitogen-activated protein kinase pathway similar to that observed with other nematodes. Most importantly, two moderate doses of 20 mg/kg body weight (143 nM/kg) of Cry5B resulted in a near complete cure of intestinal A. suum infections in pigs. Taken together, these results demonstrate the excellent potential of Cry5B to treat Ascaris infections in pigs and in humans and for Cry5B to work effectively in the human gastrointestinal tract. PMID:23818995

  19. Bacillus thuringiensis-derived Cry5B has potent anthelmintic activity against Ascaris suum.

    PubMed

    Urban, Joseph F; Hu, Yan; Miller, Melanie M; Scheib, Ulrike; Yiu, Ying Y; Aroian, Raffi V

    2013-01-01

    Ascaris suum and Ascaris lumbricoides are two closely related geo-helminth parasites that ubiquitously infect pigs and humans, respectively. Ascaris suum infection in pigs is considered a good model for A. lumbricoides infection in humans because of a similar biology and tissue migration to the intestines. Ascaris lumbricoides infections in children are associated with malnutrition, growth and cognitive stunting, immune defects, and, in extreme cases, life-threatening blockage of the digestive tract and aberrant migration into the bile duct and peritoneum. Similar effects can be seen with A. suum infections in pigs related to poor feed efficiency and performance. New strategies to control Ascaris infections are needed largely due to reduced treatment efficacies of current anthelmintics in the field, the threat of resistance development, and the general lack of new drug development for intestinal soil-transmitted helminths for humans and animals. Here we demonstrate for the first time that A. suum expresses the receptors for Bacillus thuringiensis crystal protein and novel anthelmintic Cry5B, which has been previously shown to intoxicate hookworms and which belongs to a class of proteins considered non-toxic to vertebrates. Cry5B is able to intoxicate A. suum larvae and adults and triggers the activation of the p38 mitogen-activated protein kinase pathway similar to that observed with other nematodes. Most importantly, two moderate doses of 20 mg/kg body weight (143 nM/kg) of Cry5B resulted in a near complete cure of intestinal A. suum infections in pigs. Taken together, these results demonstrate the excellent potential of Cry5B to treat Ascaris infections in pigs and in humans and for Cry5B to work effectively in the human gastrointestinal tract.

  20. Interaction between anthelmintic treatment and vaccine responses in ponies naturally infected with cyathostomins.

    PubMed

    Nielsen, M K; Rubinson, E F; Chambers, T M; Horohov, D W; Wagner, B; Betancourt, A; Reedy, S E; Jacobsen, S

    2015-04-15

    Anthelmintics and vaccines are commonly given concurrently in routine equine management, but it is unknown to what extent an interaction between the two exists. Cyathostomins can modulate the local immune response by stimulating a type 2 helper T cell (Th2) response. In addition, anti-inflammatory effects of ivermectin have been found in rodent models. It is unknown whether these anti-inflammatory effects affect the acute phase response elicited by commonly used vaccines. This study evaluated how the acute phase inflammatory response, leukocyte expression of pro-inflammatory cytokines, and vaccine-specific titers induced by simultaneous injection of three vaccines (West Nile Virus, Equine Herpes Rhinopneumonitis, and Keyhole Limpet Hemocyanin) were modulated by concurrent administration of ivermectin or pyrantel pamoate in ponies naturally infected with cyathostomins. Mixed-breed yearling ponies were blocked by gender and fecal strongyle egg count, then randomly assigned to three treatment groups: ivermectin (n=8), pyrantel pamoate (n=8), and control (n=7). All ponies received vaccinations intramuscularly on days 0 and 29, and anthelmintics were administered on the same days. Whole blood, serum and plasma samples were collected one, three and 14 days after each vaccination. Samples were analyzed for concentrations of acute phase reactants (haptoglobin, serum amyloid A, fibrinogen and iron), mRNA expression levels of cytokines (interleukin (IL)-1β, IL-4, IL-10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ) in leukocytes, and vaccine-specific antibody titers. A marked acute-phase response was noted following both vaccinations. In contrast, the pattern of change in cytokine expression was less pronounced and more variable. Statistical differences were observed between groups for haptoglobin, fibrinogen, IL-1β, IL-4, and IL-10, but differences were generally small and none of the vaccine titers were different between the groups. Taken together, the study

  1. Benzimidazole resistance in equine cyathostomins in India.

    PubMed

    Kumar, Sunil; Garg, Rajat; Kumar, Saroj; Banerjee, P S; Ram, Hira; Prasad, A

    2016-03-15

    Benzimidazole resistance is a major hindrance to the control of equine cyathostominosis throughout the world. There is a paucity of knowledge on the level of benzimidazole resistance in small strongyles of horses in India. In the present study, allele-specific PCR (AS-PCR) that detects F200Y mutation of the isotype 1 β-tubulin gene and faecal egg count reduction test (FECRT) were used for detecting benzimidazole resistance in equine cyathostomin populations in different agro-climatic zones of Uttar Pradesh, India. Results of the FECRT revealed prevalence of benzimidazole resistance in cyathostomins in an intensively managed equine farm in the mid-western plain (FECR=27.5%, LCI=0) and in working horses (extensively managed) at three locations in central plains of Uttar Pradesh (FECR=75.7-83.6%, LCI=29-57%). Post-treatment larval cultures revealed the presence of exclusively cyathostomin larvae. Genotyping of cyathostomin larvae by AS-PCR revealed that the frequency of homozygous resistant (rr) individuals and the resistant allele frequency was significantly higher (p<0.001) in the intensively managed farm in the mid-western plain and in working horses at two locations in central plains of the state. The resistant allele (r) frequency in cyathostomins was significantly higher (p<0.05) in Vindhyan and Tarai and Bhabar zones of Uttar Pradesh. The prevalence of benzimidazole resistant allele (r) was significantly higher (p<0.05) in cyathostomins of intensively managed horses (allelic frequency-0.35) as compared to extensively managed horses (allelic frequency-0.22). The widespread prevalence of benzimidazole resistant alleles in equine cyathostomins in Uttar Pradesh, India, necessitates immediate replacement of the drugs of benzimidazole group with other unrelated effective anthelmintics for management and control of equine cyathostomins.

  2. Psychological insulin resistance: patient beliefs and implications for diabetes management.

    PubMed

    Brod, Meryl; Kongsø, Jens Harald; Lessard, Suzanne; Christensen, Torsten L

    2009-02-01

    To define and understand patient psychological insulin resistance (PIR) and its impact on diabetes management. Systematic literature review of peer-refereed journals using the MEDLINE database, including all articles in English from 1985 to 2007. The population included patients with type 1 and type 2 diabetes, insulin naïve, and those currently using insulin. A total of 116 articles were reviewed. PIR is impacted by patients' beliefs and knowledge about diabetes and insulin, negative self-perceptions and attitudinal barriers, the fear of side effects and complications from insulin use, as well as lifestyle adaptations, restrictions required by insulin use, and social stigma. These etiological influences, both independently and in combination, constitute a patient's PIR and may result in the reluctance of patients to both initiate and intensify treatment, leading to delayed treatment initiation and compromised glucose control. PIR is complex and multifaceted. It plays an important, although often ignored, role in diabetes management. Assisting health care professionals in better understanding PIR from the patient's perspective should result in improved treatment outcomes. By tailoring treatments to patients' PIR, clinicians may be better able to help their patients begin insulin treatment sooner and improve compliance, thus facilitating target glycemic control.

  3. A dual validation approach to detect anthelmintic residues in bovine liver over an extended concentration range

    USDA-ARS?s Scientific Manuscript database

    This paper describes a method for the detection and quantification of 38 of the most widely used anthelmintics (including benzimidazoles, macrocyclic lactones and flukicides) in bovine liver at MRL and non-MRL level. A dual validation approach was adapted to reliably detect anthelmintic residues ov...

  4. ANTHELMINTICS: THE BEST WAY TO PREDICT THE FUTURE IS TO CREATE IT

    PubMed Central

    Martin, Richard J.; Verma, Saurabh.; Choudhary, Shivani; Kashyap, Sudhanva; Zheng, Melanie Abongwa Fudan; Robertson, Alan P.

    2015-01-01

    ‘The best way to predict the future is to create it.’ When we look at drugs that are used to control parasites, we see that new knowledge has been created (discovered) about their modes of action. This knowledge will allow us to predict combinations of drugs which can be used together rationally to increase the spectrum of action and to slow the development of anthelmintic resistance. In this paper we comment on some recent observations of ours on the modes of action of emodepside, diethylcarbamazine and tribendimidine. Emodepside increases the activation of a SLO-1 K+ current inhibiting movement, and diethylcarbamazine has a synergistic effect on the effect of emodepside on the SLO-1 K+ current, increasing the size of the response. The combination may be considered for further testing for therapeutic use. Tribendimidine is a selective cholinergic nematode B-subtype nAChR agonist, producing muscle depolarization and contraction. It has different subtype selectivity to levamisole and may be effective in the presence of some types of levamisole resistance. The new information about the modes of action may aid the design of rational drug combinations designed to slow the development of resistance or increase the spectrum of action. PMID:26138153

  5. Breeding Resistant Sugarcane for Managing the Stem Borer Diatraea saccharalis: Progress and Prospects for Louisiana

    USDA-ARS?s Scientific Manuscript database

    The stem borer, Diatraea saccharalis (F.), is an important insect pest of sugarcane in Louisiana. Growing resistant varieties is a component of the Integrated Pest Management Program as practiced in Louisiana for managing this insect; however, the release of stem borer resistant varieties is intermi...

  6. Applying the emergency risk management process to tackle the crisis of antibiotic resistance

    PubMed Central

    Dominey-Howes, Dale; Bajorek, Beata; Michael, Carolyn A.; Betteridge, Brittany; Iredell, Jonathan; Labbate, Maurizio

    2015-01-01

    We advocate that antibiotic resistance be reframed as a disaster risk management problem. Antibiotic-resistant infections represent a risk to life as significant as other commonly occurring natural disasters (e.g., earthquakes). Despite efforts by global health authorities, antibiotic resistance continues to escalate. Therefore, new approaches and expertise are needed to manage the issue. In this perspective we: (1) make a call for the emergency management community to recognize the antibiotic resistance risk and join in addressing this problem; (2) suggest using the risk management process to help tackle antibiotic resistance; (3) show why this approach has value and why it is different to existing approaches; and (4) identify public perception of antibiotic resistance as an important issue that warrants exploration. PMID:26388864

  7. Applying the emergency risk management process to tackle the crisis of antibiotic resistance.

    PubMed

    Dominey-Howes, Dale; Bajorek, Beata; Michael, Carolyn A; Betteridge, Brittany; Iredell, Jonathan; Labbate, Maurizio

    2015-01-01

    We advocate that antibiotic resistance be reframed as a disaster risk management problem. Antibiotic-resistant infections represent a risk to life as significant as other commonly occurring natural disasters (e.g., earthquakes). Despite efforts by global health authorities, antibiotic resistance continues to escalate. Therefore, new approaches and expertise are needed to manage the issue. In this perspective we: (1) make a call for the emergency management community to recognize the antibiotic resistance risk and join in addressing this problem; (2) suggest using the risk management process to help tackle antibiotic resistance; (3) show why this approach has value and why it is different to existing approaches; and (4) identify public perception of antibiotic resistance as an important issue that warrants exploration.

  8. Defining terms for proactive management of resistance to Bt crops and pesticides.

    PubMed

    Tabashnik, Bruce E; Mota-Sanchez, David; Whalon, Mark E; Hollingworth, Robert M; Carrière, Yves

    2014-04-01

    Evolution of pest resistance to pesticides is an urgent global problem with resistance recorded in at least 954 species of pests, including 546 arthropods, 218 weeds, and 190 plant pathogens. To facilitate understanding and management of resistance, we provide definitions of 50 key terms related to resistance. We confirm the broad, long-standing definition of resistance, which is a genetically based decrease in susceptibility to a pesticide, and the definition of "field-evolved resistance," which is a genetically based decrease in susceptibility to a pesticide in a population caused by exposure to the pesticide in the field. The impact of field-evolved resistance on pest control can vary from none to severe. We define "practical resistance" as field-evolved resistance that reduces pesticide efficacy and has practical consequences for pest control. Recognizing that resistance is not "all or none" and that intermediate levels of resistance can have a continuum of effects on pest control, we describe five categories of field-evolved resistance and use them to classify 13 cases of field-evolved resistance to five Bacillus thuringiensis (Bt) toxins in transgenic corn and cotton based on monitoring data from five continents for nine major pest species. We urge researchers to publish and analyze their resistance monitoring data in conjunction with data on management practices to accelerate progress in determining which actions will be most useful in response to specific data on the magnitude, distribution, and impact of resistance.

  9. The efficacy of anthelmintics against Thysaniezia giardi in South Africa.

    PubMed

    Van Schalkwyk, P C; Geyser, T L; Davies, P V; Récio, M

    1981-09-01

    Two field cases of apparent inefficacy of albendazole against cestodes in lambs were investigated. In both farms Thysaniezia giardi was identified and 2 critical controlled trials were conducted to determine the efficacy of 5 anthelmintics against T. giardi. Albendazole dosed at 3,8 mg/kg or 7,6 mg/kg live mass, mebendazole at 15 mg/kg were totally ineffective against T. giardi. Treatment with resorantel at 65 mg/kg or niclosamide at 50 mg/kg however, caused expulsion of the strobilae within 16--24 hours after treatment and at autopsy, lambs were free of scoleces of T. giardi.

  10. Dicamba resistance: enlarging and preserving biotechnology-based weed management strategies.

    PubMed

    Behrens, Mark R; Mutlu, Nedim; Chakraborty, Sarbani; Dumitru, Razvan; Jiang, Wen Zhi; Lavallee, Bradley J; Herman, Patricia L; Clemente, Thomas E; Weeks, Donald P

    2007-05-25

    The advent of biotechnology-derived, herbicide-resistant crops has revolutionized farming practices in many countries. Facile, highly effective, environmentally sound, and profitable weed control methods have been rapidly adopted by crop producers who value the benefits associated with biotechnology-derived weed management traits. But a rapid rise in the populations of several troublesome weeds that are tolerant or resistant to herbicides currently used in conjunction with herbicide-resistant crops may signify that the useful lifetime of these economically important weed management traits will be cut short. We describe the development of soybean and other broadleaf plant species resistant to dicamba, a widely used, inexpensive, and environmentally safe herbicide. The dicamba resistance technology will augment current herbicide resistance technologies and extend their effective lifetime. Attributes of both nuclear- and chloroplast-encoded dicamba resistance genes that affect the potency and expected durability of the herbicide resistance trait are examined.

  11. The antimicrobial resistance crisis: causes, consequences, and management.

    PubMed

    Michael, Carolyn Anne; Dominey-Howes, Dale; Labbate, Maurizio

    2014-01-01

    The antimicrobial resistance (AMR) crisis is the increasing global incidence of infectious diseases affecting the human population, which are untreatable with any known antimicrobial agent. This crisis will have a devastating cost on human society as both debilitating and lethal diseases increase in frequency and scope. Three major factors determine this crisis: (1) the increasing frequency of AMR phenotypes among microbes is an evolutionary response to the widespread use of antimicrobials; (2) the large and globally connected human population allows pathogens in any environment access to all of humanity; and (3) the extensive and often unnecessary use of antimicrobials by humanity provides the strong selective pressure that is driving the evolutionary response in the microbial world. Of these factors, the size of the human population is least amenable to rapid change. In contrast, the remaining two factors may be affected, so offering a means of managing the crisis: the rate at which AMR, as well as virulence factors evolve in microbial world may be slowed by reducing the applied selective pressure. This may be accomplished by radically reducing the global use of current and prospective antimicrobials. Current management measures to legislate the use of antimicrobials and to educate the healthcare world in the issues, while useful, have not comprehensively addressed the problem of achieving an overall reduction in the human use of antimicrobials. We propose that in addition to current measures and increased research into new antimicrobials and diagnostics, a comprehensive education program will be required to change the public paradigm of antimicrobial usage from that of a first line treatment to that of a last resort when all other therapeutic options have failed.

  12. The Antimicrobial Resistance Crisis: Causes, Consequences, and Management

    PubMed Central

    Michael, Carolyn Anne; Dominey-Howes, Dale; Labbate, Maurizio

    2014-01-01

    The antimicrobial resistance (AMR) crisis is the increasing global incidence of infectious diseases affecting the human population, which are untreatable with any known antimicrobial agent. This crisis will have a devastating cost on human society as both debilitating and lethal diseases increase in frequency and scope. Three major factors determine this crisis: (1) the increasing frequency of AMR phenotypes among microbes is an evolutionary response to the widespread use of antimicrobials; (2) the large and globally connected human population allows pathogens in any environment access to all of humanity; and (3) the extensive and often unnecessary use of antimicrobials by humanity provides the strong selective pressure that is driving the evolutionary response in the microbial world. Of these factors, the size of the human population is least amenable to rapid change. In contrast, the remaining two factors may be affected, so offering a means of managing the crisis: the rate at which AMR, as well as virulence factors evolve in microbial world may be slowed by reducing the applied selective pressure. This may be accomplished by radically reducing the global use of current and prospective antimicrobials. Current management measures to legislate the use of antimicrobials and to educate the healthcare world in the issues, while useful, have not comprehensively addressed the problem of achieving an overall reduction in the human use of antimicrobials. We propose that in addition to current measures and increased research into new antimicrobials and diagnostics, a comprehensive education program will be required to change the public paradigm of antimicrobial usage from that of a first line treatment to that of a last resort when all other therapeutic options have failed. PMID:25279369

  13. Antibiotic resistance to Propionobacterium acnes: worldwide scenario, diagnosis and management.

    PubMed

    Sardana, Kabir; Gupta, Tanvi; Garg, Vijay K; Ghunawat, Sneha

    2015-07-01

    Antibiotic resistance in cutaneous Propionobacterium is a global problem. As a general rule, resistance levels are high to macrolides, trimethoprim/sulfamethoxazole and clindamycin, while tetracyclines and levofloxacin have low resistance potential. Newer preparations like doxycycline MR and doxycycline 20 mg are subantimicrobial and may not lead to resistance. Sampling techniques are crucial to determine resistance. Genomic evaluation using 16S ribosomal RNA gene sequencing can be useful in diagnosing mutations and mapping phylotypes of Propionobacterium acnes. Resistance may lead to slow response and relapses. Apart from benzoyl peroxide, azelaic acid, topical dapsone, oral zinc and retinoids, novel molecules with little resistance potential include octadecenedioic acid, phytosphingosine, lauric acid, retapamulin, resveratrol, T-3912 and NB-003. The use of oral retinoids and non-antibiotics like zinc can prevent resistance and help reduce the dependence on antibiotics.

  14. Anti-inflammatory and anthelmintic activities of Solanum khasianum Clarke.

    PubMed

    Jarald, E Edwin; Edwin, S; Saini, V; Deb, L; Gupta, V B; Wate, S P; Busari, K P

    2008-02-15

    In order to scientifically appraise some of the folkloric uses of Solanum khasianum Clarke (Solanaceae), the present study was undertaken to examine the anti-inflammatory and anthelmintic properties of the berries of ethanol extract. Anti-inflammatory activity was tested in carrageenan induced rat hind paw edema method at three dose level of 200, 300, and 400 mg kg(-1) respectively, Diclofenac sodium (100 mg kg(-1)) was used as the reference standard. The anti-inflammatory activity of the extract was compared with standard and control. The anthelmintic activity of the extract was tested on tape worm, liver fluke, thread worm, and hook worm using two different concentrations, 100 and 200 mg mL(-1) respectively. Time taken for the inhibition of motility was noted and compared with the standard drug, Piperazine citrate 15 mg mL. The plant extract significantly (p < 0.01) reduced the inflammation of the rats when compared to the control group. Also, the ethanol extract of the plant paralyzed the worms followed by death, which was comparable with that of the standard. This study supports the folk claim.

  15. Anthelmintics. A comparative review of their clinical pharmacology.

    PubMed

    de Silva, N; Guyatt, H; Bundy, D

    1997-05-01

    Virtually all the important helminth infections in humans can be treated with one of 5 anthelmintics currently in use: albendazole, mebendazole, diethylcarbamazine, ivermectin and praziquantel. These drugs are vital not only for the treatment of individual infections, but also useful in controlling transmission of the more common infections. This article reviews briefly the pharmacology of these 5 drugs, and then discusses current issues in the use of anthelmintics in the treatment and/or control of soil-transmitted nematode infections, filariasis, onchocerciasis, schistosomiasis (and other trematode infections), neurocysticercosis and hydatidosis. Mebendazole and albendazole are most effective against intestinal nematodes, but are contraindicated during the first trimester of pregnancy. The efficacy of prolonged therapy with these 2 drugs for treatment of larval cestode infections has not yet been established. Diethylcarbamazine is widely used to treat and control lymphatic filariasis, but adverse effects related to death of microfilariae or damage to adult worms may be marked. While ivermectin has been used in the treatment of patients with onchocerciasis, it is also undergoing investigation against lymphatic filariae. Praziquantel, used to treat schistosome infections, is also effective in other trematode infections and adult cestode infections.

  16. Seeds of change: corn seed mixtures for resistance management and integrated pest management.

    PubMed

    Onstad, David W; Mitchell, Paul D; Hurley, Terrance M; Lundgren, Jonathan G; Porter, R Patrick; Krupke, Christian H; Spencer, Joseph L; DiFonzo, Christine D; Baute, Tracey S; Hellmich, Richard L; Buschman, Lawrent L; Hutchison, William D; Tooker, John F

    2011-04-01

    The use of mixtures of transgenic insecticidal seed and nontransgenic seed to provide an in-field refuge for susceptible insects in insect-resistance-management (IRM) plans has been considered for at least two decades. However, the U.S. Environmental Protection Agency has only recently authorized the practice. This commentary explores issues that regulators, industry, and other stakeholders should consider as the use of biotechnology increases and seed mixtures are implemented as a major tactic for IRM. We discuss how block refuges and seed mixtures in transgenic insecticidal corn, Zea mays L., production will influence integrated pest management (IPM) and the evolution of pest resistance. We conclude that seed mixtures will make pest monitoring more difficult and that seed mixtures may make IRM riskier because of larval behavior and greater adoption of insecticidal corn. Conversely, block refuges present a different suite of risks because of adult pest behavior and the lower compliance with IRM rules expected from farmers. It is likely that secondary pests not targeted by the insecticidal corn as well as natural enemies will respond differently to block refuges and seed mixtures.

  17. French vineyards provide information that opens ways for effective resistance management of Botrytis cinerea (grey mould).

    PubMed

    Walker, Anne-Sophie; Micoud, Annie; Rémuson, Florent; Grosman, Jacques; Gredt, Michel; Leroux, Pierre

    2013-06-01

    Resistance to fungicides is an evolutionary process resulting from the selection of advantageous genotypes in naturally diverse populations. Seven fungicide modes of action are authorised to control grey mould caused by Botrytis cinerea on grapevine in France, and five of them have encountered specific resistance, with variable frequencies in populations and possible consequences for field fungicide efficacy. Moreover, multidrug resistance is caused by fungicide efflux and allows a weak resistance towards six unrelated modes of action. Here, a review is given of the fungicide resistance status of B. cinerea in France, particularly in the vineyards of Champagne, which are the most affected. Recently developed resistance and recent findings concerning the associated resistance mechanisms are focused upon in particular. Finally, antiresistance strategies are presented, and examples of managed resistance are discussed in a more general manner with the aim of extending this knowledge to other crops and countries undergoing similar resistance problems.

  18. The 'Toolbox' of strategies for managing Haemonchus contortus in goats: What's in and what's out.

    PubMed

    Kearney, P E; Murray, P J; Hoy, J M; Hohenhaus, M; Kotze, A

    2016-04-15

    A dynamic and innovative approach to managing the blood-consuming nematode Haemonchus contortus in goats is critical to crack dependence on veterinary anthelmintics. H. contortus management strategies have been the subject of intense research for decades, and must be selected to create a tailored, individualized program for goat farms. Through the selection and combination of strategies from the Toolbox, an effective management program for H. contortus can be designed according to the unique conditions of each particular farm. This Toolbox investigates strategies including vaccines, bioactive forages, pasture/grazing management, behavioural management, natural immunity, FAMACHA, Refugia and strategic drenching, mineral/vitamin supplementation, copper Oxide Wire Particles (COWPs), breeding and selection/selecting resistant and resilient individuals, biological control and anthelmintic drugs. Barbervax(®), the ground-breaking Haemonchus vaccine developed and currently commercially available on a pilot scale for sheep, is prime for trialling in goats and would be an invaluable inclusion to this Toolbox. The specialised behaviours of goats, specifically their preferences to browse a variety of plants and accompanying physiological adaptations to the consumption of secondary compounds contained in browse, have long been unappreciated and thus overlooked as a valuable, sustainable strategy for Haemonchus management. These strategies are discussed in this review as to their value for inclusion into the 'Toolbox' currently, and the future implications of ongoing research for goat producers. Combining and manipulating strategies such as browsing behaviour, pasture management, bioactive forages and identifying and treating individual animals for haemonchosis, in addition to continuous evaluation of strategy effectiveness, is conducted using a model farm scenario. Selecting strategies from the Toolbox, with regard to their current availability, feasibility, economical cost

  19. In vitro anthelmintic assessment of selected phytochemicals against Hymenolepis diminuta, a zoonotic tapeworm.

    PubMed

    Vijaya; Yadav, Arun K

    2016-09-01

    A large number of medicinal plants are used as herbal remedy for the treatment of helminthic diseases in the developing countries, however, far too little attention has been paid to assess the anthelmintic potentials of chemical compounds that are present in these plants. This study was carried out to assess the in vitro anthelmintic effects of biochanin A, ursolic acid, betulinic acid and beta-sitosterol which are the major phytochemicals of Trifolium repens, Houttuynia cordata and Lasia spinosa, the traditionally used anthelmintic plants of Northeast India. The in vitro anthelmintic testing of these phytochemicals was undertaken against Hymenolepis diminuta, a zoonotic tapeworm, and their efficacy was compared with a reference drug, praziquantel. The results revealed that except beta-sitosterol, which showed a very weak anthelmintic effect, remaining all other tested compounds possess highly significant (p ≤ 0.001) and dose-dependent anthelmintic effects. Upon exposure to 0.25, 0.50 and 1 mg/ml concentrations of biochanin A, ursolic acid and betulinic acid, the test parasite H. diminuta, at first, showed a paralyzed state which later culminated into their mortality after short time periods. Of all the phytochemicals tested, betulinic acid (1 mg/ml) showed the best anthelmintic effect and caused the mortality of test parasites at 3.4 ± 0.66 h. In conclusion, the results of this study demonstrate for the first time that betulinic acid, biochanin A and ursolic acid possess significant in vitro anthelmintic effects against H. diminuta, a zoonotic tapeworm, and, therefore, these compounds may be exploited further for anthelmintic drug development.

  20. Insecticide resistance in vector Chagas disease: evolution, mechanisms and management.

    PubMed

    Mougabure-Cueto, Gastón; Picollo, María Inés

    2015-09-01

    Chagas disease is a chronic parasitic infection restricted to America. The disease is caused by the protozoa Trypanosoma cruzi, which is transmitted to human through the feces of infected triatomine insects. Because no treatment is available for the chronic forms of the disease, vector chemical control represents the best way to reduce the incidence of the disease. Chemical control has been based principally on spraying dwellings with insecticide formulations and led to the reduction of triatomine distribution and consequent interruption of disease transmission in several areas from endemic region. However, in the last decade it has been repeatedly reported the presence triatomnes, mainly Triatoma infestans, after spraying with pyrethroid insecticides, which was associated to evolution to insecticide resistance. In this paper the evolution of insecticide resistance in triatomines is reviewed. The insecticide resistance was detected in 1970s in Rhodnius prolixus and 1990s in R. prolixus and T. infestans, but not until the 2000s resistance to pyrthroids in T. infestans associated to control failures was described in Argentina and Bolivia. The main resistance mechanisms (i.e. enhanced metabolism, altered site of action and reduced penetration) were described in the T. infestans resistant to pyrethrods. Different resistant profiles were demonstrated suggesting independent origin of the different resistant foci of Argentina and Bolivia. The deltamethrin resistance in T. infestans was showed to be controlled by semi-dominant, autosomally inherited factors. Reproductive and developmental costs were also demonstrated for the resistant T. infestans. A discussion about resistance and tolerance concepts and the persistence of T. infestans in Gran Chaco region are presented. In addition, theoretical concepts related to toxicological, evolutionary and ecological aspects of insecticide resistance are discussed in order to understand the particular scenario of pyrethroid

  1. Renal denervation for the management of resistant hypertension.

    PubMed

    Patel, Hitesh C; Hayward, Carl; Vassiliou, Vassilis; Patel, Ketna; Howard, James P; Di Mario, Carlo

    2015-01-01

    Renal sympathetic denervation (RSD) as a therapy for patients with resistant hypertension has attracted great interest. The majority of studies in this field have demonstrated impressive reductions in blood pressure (BP). However, these trials were not randomized or sham-controlled and hence, the findings may have been overinflated due to trial biases. SYMPLICITY HTN-3 was the first randomized controlled trial to use a blinded sham-control and ambulatory BP monitoring. A surprise to many was that this study was neutral. Possible reasons for this neutrality include the fact that RSD may not be effective at lowering BP in man, RSD was not performed adequately due to limited operator experience, patients' adherence with their anti-hypertensive drugs may have changed during the trial period, and perhaps the intervention only works in certain subgroups that are yet to be identified. Future studies seeking to demonstrate efficacy of RSD should be designed as randomized blinded sham-controlled trials. The efficacy of RSD is in doubt, but many feel that its safety has been established through the thousands of patients in whom the procedure has been performed. Over 90% of these data, however, are for the Symplicity™ system and rarely extend beyond 12 months of follow-up. Long-term safety cannot be assumed with RSD and nor should it be assumed that if one catheter system is safe then all are. We hope that in the near future, with the benefit of well-designed clinical trials, the role of renal denervation in the management of hypertension will be established.

  2. A comparative trial of garlic, its extract and ammonium-potassium tartrate as anthelmintics in carp.

    PubMed

    Peña, N; Auró, A; Sumano, H

    1988-12-01

    While fish chemotherapy is not a common practice in México, folk medicine is usually well accepted by fish farmers. Empirical knowledge suggested that garlic should have anthelmintic properties. Various trials were carried out in Cyprinus carpio infested with Capillaria sp., using minced garlic and its extracts. An empirical concentration of 200 mg/l of minced garlic showed the greatest activity against the above mentioned worms (100%). The hexane extract in equivalent amounts showed a 75% effectiveness while the aqueous extract showed no anthelmintic effect. The addition of ammonium-potassium tartrate to the tanks (1.5 mg/l) gave a 86% anthelmintic effectiveness.

  3. An attempt to replace an ivermectin-resistant Cooperia spp. population by a susceptible one on grazing pastures based on epidemiological principles and refugia management.

    PubMed

    Fiel, C A; Steffan, P E; Muchiut, S M; Fernández, A S; Bernat, G; Riva, E; Lloberas, M M; Almada, A; Homer, D

    2017-11-15

    The maintenance of anthelmintic-susceptible parasite refugia to delay the onset of anthelmintic resistance is an almost impossible effort in many grazing livestock production countries given that current refugia consist of already resistant parasites. Rather, efforts could be focused on replacing the resistant parasite refugia by susceptible parasite ones and implementing sustainable parasite control measures from then on. To this purpose, a trial was conducted to attempt to establish a new population of ivermectin-susceptible Cooperia sp. on a beef cattle farm with proven problems of ivermectin-resistant Cooperia. During two consecutive years, 82 (Year 1) and 100 (Year 2) recently weaned and parasite-free heifers were inoculated with 40,000 or 30,000 susceptible Cooperia L3, respectively, at a time when levels of resistant parasite refugia were normally low. The animals were subsequently allowed to graze on the problem pastures during autumn until the end of spring. Levels of parasitism in the animals and on pasture were monitored monthly and animals were treated with levamisole when needed. The combination of parasitological monitoring and local epidemiological knowledge was essential to determine when treatments were to be administered. No clinical signs of gastrointestinal parasitosis in the herd were observed throughout the study and unnecessary treatments were avoided. Faecal egg counts reduction tests (FECRT) and controlled efficacy tests (CET) employing worm counts were carried out at different times throughout the study to determine the clinical efficacy (FECRT) and the absolute efficacy (CET) of ivermectin, respectively. The clinical efficacy of ivermectin increased from an initial 73% to 99.4%, while the absolute efficacy increased from 54.1% to 87.5% after just two animal production cycles. The switch from a resistant parasite population to a susceptible one requires knowledge of parasitological epidemiology, especially in relation to seasonal

  4. Emergence of resistance and resistance management in field populations of tropical Culex quinquefasciatus to the microbial control agent Bacillus sphaericus.

    PubMed

    Mulla, Mir S; Thavara, Usavadee; Tawatsin, Apiwat; Chomposri, Jakkrawarn; Su, Tianyun

    2003-03-01

    In recent years, highly potent mosquitocidal strains of the microbial agent Bacillus sphaericus (Bsph) have been isolated and developed for the control of mosquito larvae around the world. Laboratory selection experiments with the most active strains and their use in large-scale operational mosquito control programs resulted in the emergence of resistance in larvae of the Culex pipiens complex. This generated great concern among vector control agencies around the world, who feared reduced efficacy of this highly active larvicidal agent. To address this issue, the current studies were started to find practical strategies for controlling resistant mosquitoes and more importantly to develop resistance management strategies that would prevent or delay development of resistance. We initiated field studies in 3 low-income communities in Nonthaburi Province, Thailand. In 1 of the communities, larvae of Culex quinquefasciatus that were highly resistant (>125,000-fold) to Bsph strain 2362 were successfully controlled with applications of Bacillus thuringiensis var. israelensis (Bti) alone or in combination with Bsph. To prevent or delay resistance to Bsph, 2 other sites were selected, 1 treated with Bsph 2362 alone and the other treated with a mixture of Bsph 2362 and Bti. Mosquitoes treated with Bsph 2362 alone showed some resistance by the 9th treatment and almost complete failure of control occurred by the 17th treatment. After 9 treatments with the mixture over a 9-month period at another site, no noticeable change in susceptibility to Bsph was detected. During this period, the site treated with Bsph alone required 19 treatments, whereas the site treated with mixtures took only 9 treatments because of slower resurgence of larvae at the site treated with the mixture than at the site treated with Bsph alone. This is the 1st field evidence for delay or prevention of resistance to microbial agents in larval Cx. quinquefasciatus by using mixtures of Bti and Bsph. Further

  5. Herbicide-resistant weeds: Management strategies and upcoming technologies

    USDA-ARS?s Scientific Manuscript database

    Herbicides have contributed to substantial increase in crop yields over the past seven decades. Over reliance on herbicides for weed control has led to rapid evolution of herbicide-resistant (HR) weeds. Increased awareness of herbicide resistance and adoption of diversified weed control tactics by f...

  6. Integrating insect-resistant GM Crops in pest management systems

    USDA-ARS?s Scientific Manuscript database

    In 2006, GM cotton and maize with insect resistance were grown on 12.1 and 20.1 million hectares in 9 and 13 countries, respectively. These insect resistant GM crops produce various Cry toxins from Bacillus thuringiensis (Bt) and provide highly selective and effective control of lepidopteran and col...

  7. Managing Resistance to Instructional Modifications in Mainstreamed Environments.

    ERIC Educational Resources Information Center

    Margolis, Howard; McGettigan, James

    1988-01-01

    Classroom teachers serving handicapped students in the mainstream often need to make instructional modifications. This article discusses reasons for teacher resistance to instructional modifications and provides strategies that consultative staff can use to prevent or reduce resistance. Expectancy theory is used to provide a framework for…

  8. Designing the Recipient: Managing Advice Resistance in Institutional Settings

    ERIC Educational Resources Information Center

    Hepburn, Alexa; Potter, Jonathan

    2011-01-01

    In this paper we consider a collection of conversational practices that arise when a professional is faced with extended resistance to their offered advice. Our data is comprised of telephone calls to a UK child protection helpline. The practices we identify occur repeatedly across our corpus of advice resistance sequences and involve (1) the…

  9. Designing the Recipient: Managing Advice Resistance in Institutional Settings

    ERIC Educational Resources Information Center

    Hepburn, Alexa; Potter, Jonathan

    2011-01-01

    In this paper we consider a collection of conversational practices that arise when a professional is faced with extended resistance to their offered advice. Our data is comprised of telephone calls to a UK child protection helpline. The practices we identify occur repeatedly across our corpus of advice resistance sequences and involve (1) the…

  10. Managing Resistance to Instructional Modifications in Mainstreamed Environments.

    ERIC Educational Resources Information Center

    Margolis, Howard; McGettigan, James

    1988-01-01

    Classroom teachers serving handicapped students in the mainstream often need to make instructional modifications. This article discusses reasons for teacher resistance to instructional modifications and provides strategies that consultative staff can use to prevent or reduce resistance. Expectancy theory is used to provide a framework for…

  11. New oral anthelmintic intraruminal delivery device for cattle

    PubMed Central

    Vandamme, Thierry F.

    2014-01-01

    Background: The purpose of this work was to develop a new oral drug delivery system intended for cattle and that enables delayed and pulsed release of an anthelmintic agent. Materials: This new tailored dosage form, also called reticulo-rumen device (RRD) has been evaluated on grazing calves by means of measurements of milliunits of tyrosine concentration, number of eggs per gram of feces, mean number of infective larvae on cattle pasture and increase in mean weight of cattle. Methods: The in vivo evaluation was carried out during two grazing seasons on different groups of dairy cattle. During the first grazing season, Group 1 was designated as an untreated control group. The remaining two were assigned to different treatments as follows: Group 2, early season suppression with a marketed intraruminal slow release bolus (Chronomintic®, Virbac) administered immediately prior to turn-out and Group 3, mid-season suppression with a new RRD administered immediately prior to turn out. When the cattle were turned out at the start of the second grazing season, they were not given any anthelmintic treatment and were divided into two different groups, corresponding to the previous groups that received an anthelmintic treatment during the first grazing season, on that pasture that they had occupied as separate groups in the previous year. Furthermore, during the second season, samples of feces, blood and herbage were collected every month. Results and Conclusion: During the first grazing season, the results indicated that the fecal egg counts and the number of infective larvae in herbage samples were slightly lower for the group receiving the new RRDs. Regular weighing of the cattle receiving the new RRDs revealed no significant difference with cattle receiving marketed RRDs. Conversely, during the second grazing season, the results for the mean weights of the cattle demonstrated that the weights of animals having been administered new RRDs during the first grazing season

  12. Notification: Evaluation of Office of Pesticide Programs’ Genetically Engineered Corn Insect Resistance Management

    EPA Pesticide Factsheets

    Project #OPE-FY15-0055, July 09, 2015. The EPA OIG plans to begin preliminary research on the EPA's ability to manage and prevent increased insect resistance to genetically engineered Bacillus thuringiensis (Bt) corn.

  13. Notification: Evaluation of EPA's Management of Resistance Issues Related to Herbicide Tolerant Genetically Engineered Crops

    EPA Pesticide Factsheets

    Project #OPE-FY16-0023, March 25, 2016. The EPA OIG plans to begin preliminary research to assess the EPA's management and oversight of resistance issues related to herbicide tolerant genetically engineered crops.

  14. PRN 2001-5: Guidance for Pesticide Registrants on Pesticide Resistance Management Labeling

    EPA Pesticide Factsheets

    This pesticide registration notice describes purely voluntary pesticide resistance management labeling guidelines based on mode/target site of action for agricultural uses of herbicides, fungicides, bactericides, insecticides, and acaricides.

  15. Southern African Treatment Resistance Network (SATuRN) RegaDB HIV drug resistance and clinical management database: supporting patient management, surveillance and research in southern Africa.

    PubMed

    Manasa, Justen; Lessells, Richard; Rossouw, Theresa; Naidu, Kevindra; Van Vuuren, Cloete; Goedhals, Dominique; van Zyl, Gert; Bester, Armand; Skingsley, Andrew; Stott, Katharine; Danaviah, Siva; Chetty, Terusha; Singh, Lavanya; Moodley, Pravi; Iwuji, Collins; McGrath, Nuala; Seebregts, Christopher J; de Oliveira, Tulio

    2014-01-01

    Substantial amounts of data have been generated from patient management and academic exercises designed to better understand the human immunodeficiency virus (HIV) epidemic and design interventions to control it. A number of specialized databases have been designed to manage huge data sets from HIV cohort, vaccine, host genomic and drug resistance studies. Besides databases from cohort studies, most of the online databases contain limited curated data and are thus sequence repositories. HIV drug resistance has been shown to have a great potential to derail the progress made thus far through antiretroviral therapy. Thus, a lot of resources have been invested in generating drug resistance data for patient management and surveillance purposes. Unfortunately, most of the data currently available relate to subtype B even though >60% of the epidemic is caused by HIV-1 subtype C. A consortium of clinicians, scientists, public health experts and policy markers working in southern Africa came together and formed a network, the Southern African Treatment and Resistance Network (SATuRN), with the aim of increasing curated HIV-1 subtype C and tuberculosis drug resistance data. This article describes the HIV-1 data curation process using the SATuRN Rega database. The data curation is a manual and time-consuming process done by clinical, laboratory and data curation specialists. Access to the highly curated data sets is through applications that are reviewed by the SATuRN executive committee. Examples of research outputs from the analysis of the curated data include trends in the level of transmitted drug resistance in South Africa, analysis of the levels of acquired resistance among patients failing therapy and factors associated with the absence of genotypic evidence of drug resistance among patients failing therapy. All these studies have been important for informing first- and second-line therapy. This database is a free password-protected open source database available on

  16. Evaluation of Bacillus cereus and Bacillus pumilus metabolites for anthelmintic activity.

    PubMed

    Kumar, M L Vijaya; Thippeswamy, B; Kuppust, I L; Naveenkumar, K J; Shivakumar, C K

    2015-01-01

    To assess the anthelmintic acivity of Bacillus cereus and Bacillus pumilus metabolites. The successive solvent extractions with petroleum ether, ethyl acetate and methanol. The solvent extracts were tested for anthelmintic activity against Pheretima posthuma at 20 mg/ml concentration. The time of paralysis and time of death of the worms was determined for all the extracts. Albendazole was taken as a standard reference and sterile water as a control. All the sample extracts showed significant anthelmintic activity in paralyzing the worms comparable with that of the standard drug. The time of death exhibited by BP metabolites was close to the time exhibited by standard. The study indicates both bacteria Bacillus cereus and Bacillus pumilus have anthelmintic activity indicating potential metabolites in them.

  17. Evaluation of Bacillus cereus and Bacillus pumilus metabolites for anthelmintic activity

    PubMed Central

    Kumar, M. L. Vijaya; Thippeswamy, B.; Kuppust, I. L.; Naveenkumar, K. J.; Shivakumar, C. K.

    2015-01-01

    Objective: To assess the anthelmintic acivity of Bacillus cereus and Bacillus pumilus metabolites. Materials and Methods: The successive solvent extractions with petroleum ether, ethyl acetate and methanol. The solvent extracts were tested for anthelmintic activity against Pheretima posthuma at 20 mg/ml concentration. The time of paralysis and time of death of the worms was determined for all the extracts. Albendazole was taken as a standard reference and sterile water as a control. Results: All the sample extracts showed significant anthelmintic activity in paralyzing the worms comparable with that of the standard drug. The time of death exhibited by BP metabolites was close to the time exhibited by standard. Conclusion: The study indicates both bacteria Bacillus cereus and Bacillus pumilus have anthelmintic activity indicating potential metabolites in them. PMID:25598639

  18. Ambulatory Blood Pressure Monitoring in the Diagnosis, Prognosis, and Management of Resistant Hypertension: Still a Matter of our Resistance?

    PubMed

    Lazaridis, Antonios A; Sarafidis, Pantelis A; Ruilope, Luis M

    2015-10-01

    Resistant hypertension, commonly described as the failure to achieve goal blood pressure (BP) despite an appropriate regimen of three antihypertensive drugs at the maximal tolerated doses, one of which is diuretic, is increasingly recognized as an important problem of public health. Large population studies with office measurements suggest that the prevalence of resistance hypertension is approximately at 6-12 % of the general hypertensive population and 8-28 % of treated hypertensives. However, these estimations do not take into account factors of pseudo-resistance, most importantly, the white-coat effect that can be effectively ruled out with ambulatory blood pressure monitoring (ABPM). Recent studies have clearly shown that when ABPM is used, at least 30-35 % of patients labeled as "resistant hypertensives" turn out to have well-controlled BP on ambulatory basis, a finding changing entirely the estimates of prevalence of resistance hypertension and actual patient handling. Furthermore, current evidence suggests that ABPM is a much more accurate predictor of cardiovascular events in resistant hypertension compared to office BP and thus can offer a better risk stratification for these high-risk individuals. Finally, ABPM offers the potential of a better evaluation of the effect of pharmacologic and non-pharmacologic therapeutic interventions. This review attempts to summarize recent evidence on the advantages of ABPM in the diagnosis, prognosis, and management of resistant hypertension.

  19. Pharmacokinetic variability of anthelmintics: implications for the treatment of neurocysticercosis.

    PubMed

    Jung-Cook, Helgi

    2012-01-01

    Human neurocysticercosis is a severe disease caused by the installation of Taenia solium larvae in the CNS. A wide variety of clinical manifestations are related to neurocysticercosis. These are determined by a number of important factors, including the number and location of the cysts, the stage of cystercerci and the host response to the infection. Epilepsy, focal neurological signs and increased intracranial pressure are the most common clinical manifestations of the disease. Neurocysticercosis is still deeply rooted in Latin America, Africa and Asia. Albendazole and praziquantel are the drugs used in the treatment of cysticercosis. Both drugs have limited solubility and extensive metabolism, and thus great interindividual variability in plasma levels is found. This article focuses on current knowledge of the pharmacokinetics and the drug interactions of the anthelmintic drugs and the perspectives in the treatment of this parasitic disease.

  20. Managing Resistance to Bt Crops in a Genetically Variable Insect Herbivore, Ostrinia nubilalis

    USDA-ARS?s Scientific Manuscript database

    The "high-dose/refuge strategy" is central to the insect resistance management (IRM) plan adopted by the United States Environmental Protection Agency (EPA) to slow resistance evolution of European corn borer (ECB-Ostrinia nubilalis) to transgenic Bacillus thuringiensis (Bt) corn and organic Bt inse...

  1. Harnessing Resistance: Using the Theory of Constraints To Assist Change Management.

    ERIC Educational Resources Information Center

    Mabin, Victoria J.; Forgeson, Steve; Green, Lawrence

    2001-01-01

    Applies the Theory of Constraints, which views resistance to change as a necessary, positive force, to a case study of a bank merger. For each resistance factor, the theory provides tools for using it and managing change successfully. (Contains 46 references.) (SK)

  2. Harnessing Resistance: Using the Theory of Constraints To Assist Change Management.

    ERIC Educational Resources Information Center

    Mabin, Victoria J.; Forgeson, Steve; Green, Lawrence

    2001-01-01

    Applies the Theory of Constraints, which views resistance to change as a necessary, positive force, to a case study of a bank merger. For each resistance factor, the theory provides tools for using it and managing change successfully. (Contains 46 references.) (SK)

  3. In vitro anthelmintic and cytotoxicity activities the Digitaria insularis (Poaceae).

    PubMed

    Santos, Francianne Oliveira; de Lima, Hélimar Gonçalves; de Souza Santos, Nathália Silva; Serra, Taiane Menezes; Uzeda, Rosângela Soares; Reis, Isabella Mary Alves; Botura, Mariana Borges; Branco, Alexsandro; Batatinha, Maria José Moreira

    2017-10-15

    This study aimed to evaluate the in vitro activity of D. insularis extracts and fractions against gastrointestinal nematodes of goats and its cytotoxicity on Vero cells. The egg hatch (EHT) and larval motility (LMT) tests were conducted to investigate the anthelmintic effects of the crude hydroethanolic (CH), ethyl acetate (EA), butanolic (BT) and residual hydroethanolic (RH) extracts. The elution of the active extract (EA) on column chromatography (SiO2) using organic solvents furnished six fractions (FR1 to FR6), which were also tested. Cytotoxicity was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Trypan Blue exclusion assays. All extracts, FR2 and FR3, inhibited egg hatching in a concentration-dependent manner. The EHT led to EC50 values (effective concentration 50%) of 0.64; 0.69; 0.77; 0.96; 0.27 and 0.65mg/mL for CH, EA, BT, RH, FR2 and FR3, respectively. However, the extracts exhibited low effect on the motility of L3. In the cytotoxicity evaluation (MTT assay), the IC50 (inhibitory concentration 50%) was 1.18 (EA), 1.65 (FR2) and 1.59mg/mL (FR3), which was relatively high (low toxicity) in comparison to the EC50 values in EHT, mainly for FR2. The chemical analyses of most active fractions (FR2) by Liquid Chromatography coupled to Mass Spectrometry (LC-MS) led the characterization of the flavones tricin and diosmetin. These results showed the high anthelmintic effect and low cytotoxicity of D. insularis and also that the flavones can be probably responsible for the nematocidal activity of this plant. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Pharmacokinetics and anthelmintic efficacy of injectable eprinomectin in goats.

    PubMed

    Briqué-Pellet, C; Ravinet, N; Quenet, Y; Alvinerie, M; Chartier, C

    2017-07-15

    The objective of this study was to assess the pharmacokinetics and the anthelmintic efficacy of eprinomectin (Eprecis(®) 20mg/mL) following subcutaneous administration to goats. Forty non-lactating female Alpine goats aged between one and three years and weighing between 32.7 and 59.5kg, were randomly allocated to one of the following groups (8 animals per group): two groups were not infected and were treated at a dose of either 0.2 or 0.4mg/kg BW of eprinomectin, two groups were experimentally infected with nematodes and treated at 0.2 or 0.4mg/kg BW of eprinomectin similarly and one group was infected and left untreated (control). Infection consisted in a single and simultaneous administration of 5000 Haemonchus contortus and 12,500 Trichostrongylus colubriformis infective larvae. No local or general adverse reaction was visually observed whatever the dose rate. The maximal plasma concentrations (Cmax) were 20.68±12.85 vs 39.79±17.25μg/L and the plasma bioavailabilities (AUC) 83.45±34.75 vs 169.37±43.44μg*d/L for 0.2 vs 0.4mg/kg respectively. The efficacy against H. contortus and T. colubriformis was 97.8 and 98.7% at 0.2mg/kg and 98.4% and >99.9% at 0.4mg/kg respectively. The differences in worm burdens between the two dose rates were only significant for T. colubriformis. These results indicate that injectable eprinomectin is a potent anthelmintic against the two major gastrointestinal nematodes in goats. Additional information is needed regarding pharmacokinetics in lactating goats and milk residues. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Long-term medical management and complications of `resistant' ascites

    PubMed Central

    Summerskill, William H. J.; Clowdus, Bernard F.; Rosevear, John W.

    1961-01-01

    This paper reports the experience of treating patients with hepatic cirrhosis and ascites with an aldosterone inhibitor in addition to conventional therapy. Good results are demonstrated in 13 patients previously resistant to treatment. PMID:13918387

  6. Treatment-resistant panic disorder: clinical significance, concept and management.

    PubMed

    Chen, Mu-Hong; Tsai, Shih-Jen

    2016-10-03

    Panic disorder is commonly prevalent in the population, but the treatment response for panic disorder in clinical practice is much less effective than that in our imagination. Increasing evidence suggested existence of a chronic or remitting-relapsing clinical course in panic disorder. In this systematic review, we re-examine the definition of treatment-resistant panic disorder, and present the potential risk factors related to the treatment resistance, including the characteristics of panic disorder, other psychiatric and physical comorbidities, and psychosocial stresses. Furthermore, we summarize the potential pathophysiologies, such as genetic susceptibility, altered brain functioning, brain-derived neurotrophic factor, and long-term inflammation, to explain the treatment resistance. Finally, we conclude the current therapeutic strategies for treating treatment-resistant panic disorder from pharmacological and non-pharmacological views. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. The management of tuberculosis: epidemiology, resistance and monitoring.

    PubMed

    Bang, Didi

    2010-11-01

    This PhD thesis is based on 5 studies conducted in the period 2006-2010 during my employment at the International Reference Laboratory of Mycobacteriology, Statens Serum Institut. The overall aim was to assess tuberculosis (TB) treatment in Denmark with specific focus on the risk of relapse of TB disease, and to analyse treatment outcome of patients with multidrug-resistant (MDR) or isoniazid-resistant TB. The project established the need for rapid methods to detect resistance and follow-up of treatment. A rapid method to detect drug resistance was optimised and evaluated for use directly in clinical specimens. The studies were based on data from the Mycobacterial registry in the period 1992-2007, which included the results from microscopy, culture, drug-susceptibility and restriction fragment length polymorphism (RFLP). Information on dates of death/emigration were taken from the CPR-registry and treatment from surveillance data and patient records. The rate of recurrent TB was found to be low in Denmark, during 13.5 years of follow-up. Relapse accounted for 1.3% of the recurrent cases and reinfection was rare, only in 0.5% cases. The relapse hazard increased up to four years after diagnosis. Cavitary disease was associated with relapse as opposed to reinfection and may need prolonged treatment and closer monitoring. The incidence of MDR-TB and isoniazid resistance was confirmed to be low. Successful short- and long-term treatment outcome of MDR-TB and isoniazid-resistant TB was high. High- and low-level isoniazid resistance did not affect treatment outcome. A multiplex PCR hybridization mutation analysis, that simultaneously detects the most frequent rpoB and katG gene mutations conferring rifampin and high-level isoniazid resistance, was optimized for direct use and evaluated in smear-positive specimens as opposed to slow conventional drug-susceptibility testing (DST). The second-generation rifampin and isoniazid resistance mutation assay additionally included

  8. The Challenge of Antimicrobial Resistance in Managing Intra-Abdominal Infections.

    PubMed

    Sartelli, Massimo; Catena, Fausto; di Saverio, Salomone; Ansaloni, Luca; Coccolini, Federico; Tranà, Cristian; Kirkby-Bott, James

    2015-06-01

    In recent years, there has been a worldwide increase in infections caused by microorganisms resistant to multiple antimicrobial agents. In the past few decades, an increased prevalence of infections caused by antibiotic-resistant pathogens, including Enterococcus spp., carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii, extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella spp., carbapenemase-producing Klebsiella pneumoniae, and resistant Candida spp., also has been observed among intra-abdominal infections (IAIs). The increasing prevalence of multi-drug resistance is responsible for a substantial increase in morbidity and mortality rates associated with IAIs. It is necessary for every surgeon treating IAIs to understand the underlying epidemiology and clinical consequences of antimicrobial resistance. Emergence of drug resistance, combined with the lack of new agents in the drug development pipeline, indicates that judicious antimicrobial management will be necessary to preserve the utility of the drugs available currently.

  9. Anthelmintic efficacy of Santalum album (Santalaceae) against monogenean infections in goldfish.

    PubMed

    Tu, Xiao; Ling, Fei; Huang, Aiguo; Zhang, Qizhong; Wang, Gaoxue

    2013-08-01

    Dactylogyrus spp. and Gyrodactylus spp. are helminth ectoparasites that are a significant threat to the aquaculture industry. Existing treatments could cause the threats of anthelmintic resistance, risk of residues, environmental contamination, and toxicity to fish. Importantly, there is no report on a treatment against these two parasites. This study explored the possibility of using the extracts of Santalum album to treat Dactylogyrus sp. and Gyrodactylus sp. infections in goldfish. Results showed that among the four extracts (chloroform, methanol, ethyl acetate, and water) of S. album, the chloroform extract is the most effective and 40 mg/L is a safe and the lowest effective dosage. In addition, we found that Gyrodactylus elegans is more sensitive than Dactylogyrus intermedius when exposed to the extract of the medicinal plant. Finally, it is substantiated that bath treatment with long duration and multiple administrations could eliminate a greater proportion of monogenean infections. These findings show the potential for the development of effective and safe therapy to treat Dactylogyrus sp. and Gyrodactylus sp. infections of fishes.

  10. In vivo anthelmintic activity of Anogeissus leiocarpus Guill & Perr (Combretaceae) against nematodes in naturally infected sheep.

    PubMed

    Soro, Dramane; Koné, Witabouna Mamidou; Bonfoh, Bassirou; Dro, Bernadin; Toily, Kassédo Bénédicte; Kamanzi, Kagoyire

    2013-07-01

    The identification of new anthelmintic drugs becomes a priority because of the availability of a handful of drugs, cost of treatments, and recent emergence of drug resistance. Medicinal plants are a good source of bioactive compounds for development of drugs. In this study, in vivo efficacy of Anogeissus leiocarpus was assessed in sheep naturally infected with gastrointestinal nematodes. Fecal examination, serological analyses, and necropsy were carried out to determine the egg and worm-burden reduction. The administration of ethanolic extract (single oral dose of 80 mg/kg) of A. leiocarpus induced a moderate fecal egg reduction (81 %) and adult worm-burden reduction (87 %) against Haemonchus contortus and Trichostrongylus colubriformis (82 %). The plant exhibited high efficacy against adult Strongyloïdes papillosus (100 %), Gaigeria pachyscelis (90 %), Cooperia curticei (100 %), and Oesophagostomum columbianum (95 %) but low efficacy against Trichostrongylus axei (67 %) and Trichuris globulosa (79 %). All these helminthes were sensitive to fenbendazole, except O. columbianum which showed a decrease susceptibility (17 %). The plant extract also improved certain biological parameters by increasing bodyweight from 0.7 ± 2.9 to 3.3 ± 1.9 % and improving hematocrit of 6.9 ± 1.6 % 3-week posttreatment. It emerges from the results that the plant possesses significant effectiveness on diarrhea; all treated animals gave normal feces. This study has shown that A. leiocarpus could find an application in the control of multiparasitism in small ruminants.

  11. Modelling the impact of targeted anthelmintic treatment of cattle on dung fauna.

    PubMed

    Cooke, Andrew S; Morgan, Eric R; Dungait, Jennifer A J

    2017-10-01

    The insecticidal properties of many anthelmintics pose a risk to dung fauna through the effects of drug residues in dung on the activity, oviposition and development of dung-dwelling invertebrates. Reductions in dung fauna numbers can inhibit dung degradation, which may impact biodiversity and nutrient cycling on farms. A simulation model was created to predict the impact of antiparasitic drugs on cattle dung fauna, and calibrated using published data on the dung-breeding fly Scathophaga stercoraria. This model was then tested under different effective dung drug concentrations (EC) and proportions of treated cattle (PT) to determine the impact under different application regimens. EC accounted for 12.9% of the observed variation in S. stercoraria population size, whilst PT accounted for 54.9%. The model outputs indicate that the tendency within veterinary medicine for targeted selective treatments (TST), in order to attenuate selection for drug resistance in parasite populations, will decrease the negative impacts of treatments on dung fauna populations by providing population refugia. This provides novel evidence for the benefits of TST regimens on local food webs, relative to whole-herd treatments. The model outputs were used to create a risk graph for stakeholders to use to estimate risk of anthelminthic toxicity to dung fauna. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  12. A survey in Louisiana of intestinal helminths of ponies with little exposure to anthelmintics.

    PubMed

    Torbert, B J; Klei, T R; Lichtenfels, J R; Chapman, M R

    1986-12-01

    Ponies reared with minimal or no exposure to anthelmintics were surveyed for intestinal helminths in order to estimate prevalence and intensity of parasite populations unaltered by frequent exposure to anthelmintics. Thirty-seven mixed breed ponies of varying ages were examined. Thirty-four species of nematodes and 2 species of cestodes were found. Twenty-four of the nematode species (including 1 new species) were in the subfamily Cyathostominae (small strongyles). Eighty-seven percent of the total burden of adult small strongyles in the large intestine was composed of 10 species. By comparing the results of the present survey with those of recent surveys of horses from herds which had been subjected to treatments with anthelmintics, the effect of prolonged usage of anthelmintic treatment on the prevalence of individual species possibly can be estimated. The general ranking of the 10 most common cyathostome species was similar to those described in recent surveys of horses, suggesting that anthelmintic pressure does not affect the prevalence of most cyathostome species. The lack of anthelmintic treatment appeared not to affect prevalence rates for Anoplocephala perfoliata and Anoplocephala magna when compared to other studies. Conversely, prevalence rates for Strongylus spp., Triodontophorus spp., Craterostomum acuticaudatum, Oxyuris equi, and Parascaris equorum were higher than those reported for these species in recent studies of horses.

  13. Anthelmintic, Antibacterial and Cytotoxicity Activity of Imidazole Alkaloids from Pilocarpus microphyllus Leaves.

    PubMed

    Rocha, Jefferson A; Andrade, Ivanilza M; Véras, Leiz M C; Quelemes, Patrick V; Lima, David F; Soares, Maria J S; Pinto, Pedro L S; Mayo, Simon J; Ivanova, Galya; Rangel, Maria; Correia, Manuela; Mafud, Ana Carolina; Mascarenhas, Yvonne P; Delerue-Matos, Cristina; de Moraes, Josué; Eaton, Peter; Leite, José R S A

    2017-04-01

    Pilocarpus microphyllus Stapf ex Wardlew (Rutaceae), popularly known as jaborandi, is a plant native to the northern and northeastern macroregions of Brazil. Several alkaloids from this species have been isolated. There are few reports of antibacterial and anthelmintic activities for these compounds. In this work, we report the antibacterial and anthelmintic activity of five alkaloids found in P. microphyllus leaves, namely, pilosine, epiisopilosine, isopilosine, epiisopiloturine and macaubine. Of these, only anthelmintic activity of one of the compounds has been previously reported. Nuclear magnetic resonance, HPLC and mass spectrometry were combined and used to identify and confirm the structure of the five compounds. As regards the anthelmintic activity, the alkaloids were studied using in vitro assays to evaluate survival time and damaged teguments for Schistosoma mansoni adult worms. We found epiisopilosine to have anthelmintic activity at very low concentrations (3.125 μg mL(-1) ); at this concentration, it prevented mating, oviposition, reducing motor activity and altered the tegument of these worms. In contrast, none of the alkaloids showed antibacterial activity. Additionally, alkaloids displayed no cytotoxic effect on vero cells. The potent anthelmintic activity of epiisopilosine indicates the potential of this natural compound as an antiparasitic agent. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  14. Biotransformation of anthelmintics and the activity of drug-metabolizing enzymes in the tapeworm Moniezia expansa.

    PubMed

    Prchal, Lukáš; Bártíková, Hana; Bečanová, Aneta; Jirásko, Robert; Vokřál, Ivan; Stuchlíková, Lucie; Skálová, Lenka; Kubíček, Vladimír; Lamka, Jiří; Trejtnar, František; Szotáková, Barbora

    2015-04-01

    The sheep tapeworm Moniezia expansa is very common parasite, which affects ruminants such as sheep, goats as well as other species. The benzimidazole anthelmintics albendazole (ABZ), flubendazole (FLU) and mebendazole (MBZ) are often used to treat the infection. The drug-metabolizing enzymes of helminths may alter the potency of anthelmintic treatment. The aim of our study was to assess the activity of the main drug-metabolizing enzymes and evaluate the metabolism of selected anthelmintics (ABZ, MBZ and FLU) in M. expansa. Activities of biotransformation enzymes were determined in subcellular fractions. Metabolites of the anthelmintics were detected and identified using high performance liquid chromatography/ultra-violet/VIS/fluorescence or ultra-high performance liquid chromatography/mass spectrometry. Reduction of MBZ, FLU and oxidation of ABZ were proved as well as activities of various metabolizing enzymes. Despite the fact that the conjugation enzymes glutathione S-transferase, UDP-glucuronosyl transferase and UDP-glucosyl transferase were active in vitro, no conjugated metabolites of anthelmintics were identified either ex vivo or in vitro. The obtained results indicate that sheep tapeworm is able to deactivate the administered anthelmintics, and thus protects itself against their action.

  15. Pooling sheep faecal samples for the assessment of anthelmintic drug efficacy using McMaster and Mini-FLOTAC in gastrointestinal strongyle and Nematodirus infection.

    PubMed

    Kenyon, Fiona; Rinaldi, Laura; McBean, Dave; Pepe, Paola; Bosco, Antonio; Melville, Lynsey; Devin, Leigh; Mitchell, Gillian; Ianniello, Davide; Charlier, Johannes; Vercruysse, Jozef; Cringoli, Giuseppe; Levecke, Bruno

    2016-07-30

    In small ruminants, faecal egg counts (FECs) and reduction in FECs (FECR) are the most common methods for the assessment of intensity of gastrointestinal (GI) nematodes infections and anthelmintic drug efficacy, respectively. The main limitation of these methods is the time and cost to conduct FECs on a representative number of individual animals. A cost-saving alternative would be to examine pooled faecal samples, however little is known regarding whether pooling can give representative results. In the present study, we compared the FECR results obtained by both an individual and a pooled examination strategy across different pool sizes and analytical sensitivity of the FEC techniques. A survey was conducted on 5 sheep farms in Scotland, where anthelmintic resistance is known to be widespread. Lambs were treated with fenbendazole (4 groups), levamisole (3 groups), ivermectin (3 groups) or moxidectin (1 group). For each group, individual faecal samples were collected from 20 animals, at baseline (D0) and 14 days after (D14) anthelmintic administration. Faecal samples were analyzed as pools of 3-5, 6-10, and 14-20 individual samples. Both individual and pooled samples were screened for GI strongyle and Nematodirus eggs using two FEC techniques with three different levels of analytical sensitivity, including Mini-FLOTAC (analytical sensitivity of 10 eggs per gram of faeces (EPG)) and McMaster (analytical sensitivity of 15 or 50 EPG).For both Mini-FLOTAC and McMaster (analytical sensitivity of 15 EPG), there was a perfect agreement in classifying the efficacy of the anthelmintic as 'normal', 'doubtful' or 'reduced' regardless of pool size. When using the McMaster method (analytical sensitivity of 50 EPG) anthelmintic efficacy was often falsely classified as 'normal' or assessment was not possible due to zero FECs at D0, and this became more pronounced when the pool size increased. In conclusion, pooling ovine faecal samples holds promise as a cost-saving and efficient

  16. Comparing the refuge strategy for managing the evolution of insect resistance under different reproductive strategies.

    PubMed

    Crowder, David W; Carrière, Yves

    2009-12-07

    Genetically modified (GM) crops are used extensively worldwide to control diploid agricultural insect pests that reproduce sexually. However, future GM crops will likely soon target haplodiploid and parthenogenetic insects. As rapid pest adaptation could compromise these novel crops, strategies to manage resistance in haplodiploid and parthenogenetic pests are urgently needed. Here, we developed models to characterize factors that could delay or prevent the evolution of resistance to GM crops in diploid, haplodiploid, and parthenogenetic insect pests. The standard strategy for managing resistance in diploid pests relies on refuges of non-GM host plants and GM crops that produce high toxin concentrations. Although the tenets of the standard refuge strategy apply to all pests, this strategy does not greatly delay the evolution of resistance in haplodiploid or parthenogenetic pests. Two additional factors are needed to effectively delay or prevent the evolution of resistance in such pests, large recessive or smaller non-recessive fitness costs must reduce the fitness of resistance individuals in refuges (and ideally also on GM crops), and resistant individuals must have lower fitness on GM compared to non-GM crops (incomplete resistance). Recent research indicates that the magnitude and dominance of fitness costs could be increased by using specific host-plants, natural enemies, or pathogens. Furthermore, incomplete resistance could be enhanced by engineering desirable traits into novel GM crops. Thus, the sustainability of GM crops that target haplodiploid or parthenogenetic pests will require careful consideration of the effects of reproductive mode, fitness costs, and incomplete resistance.

  17. Nippostronglylus brasiliensis infection in the rat: effect of iron and protein deficiency and dexamethasone on the efficacy of benzimidazole anthelmintics.

    PubMed Central

    Duncombe, V M; Bolin, T D; Davis, A E; Kelly, J D

    1977-01-01

    Malnutrition, anaemia, and gut parasites are commonly interrelated. Using the Nippostrongylus brasiliensis-rat model, the effect of iron and protein deficiency on the efficacy of benzimidazole anthelmintics was studied. It was demonstrated that the anthelmintics mebendazole and fenbendazole were significantly less effective in eradicating parasites when animals were deficient in iron and protein. This decreased efficacy of anthelmintics in iron and protein deficiency could not be overcome by intraperitoneal administration of the drug. Since nutritional deficiencies may act via impairment of the immune response, anthelmintic efficacy was determined in adequately nourished rats treated with the immunosuppressive drug dexamethasone. A similar decrease in efficacy of mebendazole was shown when these animals were treated with dexamethasone. Thus it is possible that lowered anthelmintic efficacy in iron and protein deficient animals is mediated by immune deficiency. These findings may be relevant to anthelmintic programmes in malnourished communities. PMID:590849

  18. Country-level operational implementation of the Global Plan for Insecticide Resistance Management

    PubMed Central

    Hemingway, Janet; Vontas, John; Poupardin, Rodolphe; Raman, Jaishree; Lines, Jo; Schwabe, Chris; Matias, Abrahan; Kleinschmidt, Immo

    2013-01-01

    Malaria control is reliant on the use of long-lasting pyrethroid-impregnated nets and/or indoor residual spraying (IRS) of insecticide. The rapid selection and spread of operationally significant pyrethroid resistance in African malaria vectors threatens our ability to sustain malaria control. Establishing whether resistance is operationally significant is technically challenging. Routine monitoring by bioassay is inadequate, and there are limited data linking resistance selection with changes in disease transmission. The default is to switch insecticides when resistance is detected, but limited insecticide options and resistance to multiple insecticides in numerous locations make this approach unsustainable. Detailed analysis of the resistance situation in Anopheles gambiae on Bioko Island after pyrethroid resistance was detected in this species in 2004, and the IRS program switched to carbamate bendiocarb, has now been undertaken. The pyrethroid resistance selected is a target-site knock-down resistance kdr-form, on a background of generally elevated metabolic activity, compared with insecticide-susceptible A. gambiae, but the major cytochrome P450-based metabolic pyrethroid resistance mechanisms are not present. The available evidence from bioassays and infection data suggests that the pyrethroid resistance mechanisms in Bioko malaria vectors are not operationally significant, and on this basis, a different, long-lasting pyrethroid formulation is now being reintroduced for IRS in a rotational insecticide resistance management program. This will allow control efforts to be sustained in a cost-effective manner while reducing the selection pressure for resistance to nonpyrethroid insecticides. The methods used provide a template for evidence-based insecticide resistance management by malaria control programs. PMID:23696658

  19. Country-level operational implementation of the Global Plan for Insecticide Resistance Management.

    PubMed

    Hemingway, Janet; Vontas, John; Poupardin, Rodolphe; Raman, Jaishree; Lines, Jo; Schwabe, Chris; Matias, Abrahan; Kleinschmidt, Immo

    2013-06-04

    Malaria control is reliant on the use of long-lasting pyrethroid-impregnated nets and/or indoor residual spraying (IRS) of insecticide. The rapid selection and spread of operationally significant pyrethroid resistance in African malaria vectors threatens our ability to sustain malaria control. Establishing whether resistance is operationally significant is technically challenging. Routine monitoring by bioassay is inadequate, and there are limited data linking resistance selection with changes in disease transmission. The default is to switch insecticides when resistance is detected, but limited insecticide options and resistance to multiple insecticides in numerous locations make this approach unsustainable. Detailed analysis of the resistance situation in Anopheles gambiae on Bioko Island after pyrethroid resistance was detected in this species in 2004, and the IRS program switched to carbamate bendiocarb, has now been undertaken. The pyrethroid resistance selected is a target-site knock-down resistance kdr-form, on a background of generally elevated metabolic activity, compared with insecticide-susceptible A. gambiae, but the major cytochrome P450-based metabolic pyrethroid resistance mechanisms are not present. The available evidence from bioassays and infection data suggests that the pyrethroid resistance mechanisms in Bioko malaria vectors are not operationally significant, and on this basis, a different, long-lasting pyrethroid formulation is now being reintroduced for IRS in a rotational insecticide resistance management program. This will allow control efforts to be sustained in a cost-effective manner while reducing the selection pressure for resistance to nonpyrethroid insecticides. The methods used provide a template for evidence-based insecticide resistance management by malaria control programs.

  20. Grassland resistance and resilience after drought depends on management intensity and species richness.

    PubMed

    Vogel, Anja; Scherer-Lorenzen, Michael; Weigelt, Alexandra

    2012-01-01

    The degree to which biodiversity may promote the stability of grasslands in the light of climatic variability, such as prolonged summer drought, has attracted considerable interest. Studies so far yielded inconsistent results and in addition, the effect of different grassland management practices on their response to drought remains an open question. We experimentally combined the manipulation of prolonged summer drought (sheltered vs. unsheltered sites), plant species loss (6 levels of 60 down to 1 species) and management intensity (4 levels varying in mowing frequency and amount of fertilizer application). Stability was measured as resistance and resilience of aboveground biomass production in grasslands against decreased summer precipitation, where resistance is the difference between drought treatments directly after drought induction and resilience is the difference between drought treatments in spring of the following year. We hypothesized that (i) management intensification amplifies biomass decrease under drought, (ii) resistance decreases with increasing species richness and with management intensification and (iii) resilience increases with increasing species richness and with management intensification.We found that resistance and resilience of grasslands to summer drought are highly dependent on management intensity and partly on species richness. Frequent mowing reduced the resistance of grasslands against drought and increasing species richness decreased resistance in one of our two study years. Resilience was positively related to species richness only under the highest management treatment. We conclude that low mowing frequency is more important for high resistance against drought than species richness. Nevertheless, species richness increased aboveground productivity in all management treatments both under drought and ambient conditions and should therefore be maintained under future climates.

  1. Immunogenomics of gastrointestinal nematode infection in ruminants - breeding for resistance to produce food sustainably and safely.

    PubMed

    Sweeney, T; Hanrahan, J P; Ryan, M T; Good, B

    2016-09-01

    Gastrointestinal nematode (GIN) infection of ruminants represents a major health and welfare challenge for livestock producers worldwide. The emergence of anthelmintic resistance in important GIN species and the associated animal welfare concerns have stimulated interest in the development of alternative and more sustainable strategies aimed at the effective management of the impact of GINs. These integrative strategies include selective breeding using genetic/genomic tools, grazing management, biological control, nutritional supplementation, vaccination and targeted selective treatment. In this review, the logic of selecting for "resistance" to GIN infection as opposed to "resilience" or "tolerance" is discussed. This is followed by a review of the potential application of immunogenomics to genetic selection for animals that have the capacity to withstand the impact of GIN infection. Advances in relevant genomic technologies are highlighted together with how these tools can be advanced to support the integration of immunogenomic information into ruminant breeding programmes.

  2. Antibiotic resistance and transferable antibiotica resistance Escherichia coli isolated from calves on a modern farm with therapeutic problems and unsatisfactory management conditions.

    PubMed

    Farris, A S; Wierup, M; Jacobsson, S O

    1979-01-01

    On a farm with therapeutic problems and unsatisfactory management conditions, the occurrence of antibiotic resistance and transferable antibiotic resistance has been studied in E. coli isolated from calves which were 5 and 30 days old. Strains with resistance to up to seven antibiotics as well as transferable resistance against up to five antibiotics were recorded. On an average, 4.2 strains with different patterns and 4.0 different strains with transferable resistance were isolated from each calf. The corresponding figures previously found for healthy control calves were 1.6 and 1.1 strains, respectively. Resistance and transferable resistance were most common against sulphonamide and penicillin.

  3. Evaluation of clinical safety and anthelmintic efficacy of aurixazole administed orally at 24 mg/kg in cattle.

    PubMed

    Sakamoto, Claudio Alessandro M; Lopes, Welber Daniel Zanetti; Buzzulini, Carolina; Cruz, Breno Cayeiro; Felippelli, Gustavo; Teixeira, Weslen F; Silva, Helenara Machado; Santana, Luis Fernando; Soares, Vando Edésio; Henrique, Carlos Henrique; de Oliveira, Gilson Pereira; da Costa, Alvimar José

    2014-06-01

    The current study evaluated, in vivo, the clinical safety and the anthelmintic efficacy of 24% aurixazole (24 mg/kg), administered orally, in bovines. Two experiments were conducted: the first one evaluating the clinical safety of 24% aurixazole (24 mg/kg) in cattle, and a second one evaluating the anthelmintic efficacy of aurixazole (24 mg/kg) against gastrointestinal nematodes on naturally infected cattle. Based on the results of clinical safety, no alterations on clinical and haematological signs and on the biochemical values obtained in animals treated orally with aurixazole 24 mg/kg were observed. Regarding the results of reduction or efficacy, obtained by eggs per gram of faeces (EPG) counts, the formulation of aurixazole reached values superior to 99% (arithmetic means) in all post-treatment dates. In two occasions, this formulation reached maximum efficacy (100%). Comparing these results with the reduction percentages obtained by EPG counts, it is possible to verify that the values obtained by all three formulations were compatible with the efficacy results. Aurixazole reached maximum efficacy (100%) against Haemonchus placei, Cooperia spatulata and Oesophagostomum radiatum. Against Cooperia punctata, this formulation reached an efficacy index of 99.99%. Regarding aurixazole, no specific trials were conducted on the field in order to evaluate the behaviour of this molecule against helminths that are resistant to other molecules, specially isolated levamisole and disophenolat. Due to this fact, future studies will be necessary to assess the effectiveness of aurixazole against strains of nematodes that are resistant to levamisole and disophenolat, but the results of clinical safety and efficacy described in this study allow us to conclude that the aurixazole molecule, concomitantly with other measures and orally administered formulations, can be another important tool in the control of nematodes parasitizing bovines.

  4. Management of Antiviral Resistance in Chronic Hepatitis B

    PubMed Central

    Lim, Young-Suk

    2017-01-01

    The primary goal of therapy for chronic hepatitis B (CHB) is to prevent liver disease progression. Hepatitis B surface antigen (HBsAg) seroclearance or seroconversion is regarded as an optimal endpoint to discontinue treatment. However, HBsAg seroclearance occurs very rarely with nucleos(t)ide analog (NUC) treatment, and long-term, almost indefinite, NUC treatment is required for the majority of patients. In patients with drug-resistant hepatitis B virus (HBV), a combination of tenofovir disoproxil fumarate (TDF) and entecavir (ETV), which is currently regarded as the strongest combination therapy against HBV, would be potentially safe to prevent the emergence of additional HBV resistance mutations. However, long-term tolerance data are lacking, and cost may be an issue for combination therapies. Several recent, well-designed, randomized controlled trials have shown that TDF mono-therapy provides similar antiviral efficacy compared with the combination of TDF and ETV. Furthermore, no additional HBV resistance mutations emerged during TDF monotherapy for up to 96 weeks. Considering a comparable antiviral efficacy, extremely low risk of TDF-resistance, lower cost, and better safety potential, TDF monotherapy would be a reasonable choice for the treatment of drug-resistant patients with CHB. PMID:28183162

  5. Six Strategies for Breaking Out of Another HRD Box--Management's Resistance to Change Itself

    ERIC Educational Resources Information Center

    Bowen, Robert; Mok, Paul

    1976-01-01

    Many human resources development (HRD) people play out self-fulfilling roles of incongruency with top management, but when management resistance to change is real, the six strategies offered in the article can be used by HRD specialists to help themselves and their companies. (Author/AJ)

  6. Acaricide resistance in cattle ticks and approaches to its management: the state of play.

    PubMed

    Abbas, Rao Z; Zaman, Muhammad Arfan; Colwell, Douglas D; Gilleard, John; Iqbal, Zafar

    2014-06-16

    Cattle ticks are an important constraint on livestock production, particularly in tropical and subtropical areas. Use of synthetic acaricides is the primary method of tick control; therefore, it would be imperative to develop strategies to preserve the efficacy of existing acaricides. This paper summarizes the status of acaricide resistance in cattle ticks from different parts of the world and reviews modes of action of currently used acaricides, mechanism of resistance development, contributory factors for the development and spread of resistance, management of resistant strains and strategies to prolong the effect of the available acaricides. Use of vaccines, synthetic and botanical acaricides and educating farmers about recommended tick control practices are discussed, along with the integration of currently available options for the management of drug resistance and, ultimately, the control of cattle ticks. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Management of castrate-resistant prostate cancer in older men.

    PubMed

    Ged, Yasser; Horgan, Anne M

    2016-03-01

    Prostate cancer is the most common cancer diagnosed in men with the highest incidence in older men. Older men are more likely to present with metastatic disease compared with younger patients and eventually all will develop castrate resistant disease. In recent years, a number of new treatment options have demonstrated survival benefits for metastatic castrate resistant prostate cancer. However, the lack of randomized trials directly comparing the different available options results in some uncertainty on how best to choose and sequence therapy. In this paper, we outline the therapeutic options available to men with metastatic castrate-resistant prostate cancer, including cytotoxic therapy, hormonal agents and bone-directed therapy. We focus particularly on the evidence for specific treatment options and the challenges faced in choosing the appropriate therapy for the older patient. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Pyrantel resistance in two herds of donkey in the UK.

    PubMed

    Lawson, Edwina; Burden, Faith; Elsheikha, Hany M

    2015-01-30

    Resistance to currently available anthelmintics is a serious phenomenon which is prevalent globally. Cyathostomins are one of the major parasites, and are of primary concern in donkeys. There have been reports of emerging resistance to pyrantel, but the status of pyrantel resistance in donkey populations in the UK is largely unknown. This report investigates pyrantel resistance in two geographically isolated donkey herds in the South West of England. The first herd had suspected pyrantel resistance, with already established resistance to other anthelmintics. In the second herd the efficacy of pyrantel was not suspected at the time the study took place. Faecal Egg Count Reduction Test (FECRT) was carried out, revealing large scale resistance. Eighty one percent of the first herd and 73% of the second herd had a FEC of less than 95% after treatment, and anthelmintic resistance was confirmed using the World Association for the Advancement of Veterinary Parasitology guidelines. These findings indicate that anthelmintic resistance to pyrantel exists in both tested donkey populations and illustrate the continuing development of resistance through different classes of chemotherapeutics.

  9. Identification of blast resistance genes for managing rice blast disease

    USDA-ARS?s Scientific Manuscript database

    Rice blast, caused by the fungal pathogen Magnaporthe oryzae, is one of the most devastating diseases worldwide. In the present study, an international set of monogenic differentials carrying 24 major blast resistance (R) genes (Pia, Pib, Pii, Pik, Pik-h, Pik-m, Pik-p, Pik-s, Pish, Pit, Pita, Pita2,...

  10. Clinical management of infections caused by multidrug-resistant Enterobacteriaceae

    PubMed Central

    Delgado-Valverde, Mercedes; Sojo-Dorado, Jesús; Pascual, Álvaro

    2013-01-01

    Enterobacteriaceae showing resistance to cephalosporins due to extended-spectrum β-lactamases (ESBLs) or plasmid-mediated AmpC enzymes, and those producing carbapenemases have spread worldwide during the last decades. Many of these isolates are also resistant to other first-line agents such as fluoroquinolones or aminoglycosides, leaving few available options for therapy. Thus, older drugs such as colistin and fosfomycin are being increasingly used. Infections caused by these bacteria are associated with increased morbidity and mortality compared with those caused by their susceptible counterparts. Most of the evidence supporting the present recommendations is from in vitro data, animal studies, and observational studies. While carbapenems are considered the drugs of choice for ESBL and AmpC producers, recent data suggest that certain alternatives may be suitable for some types of infections. Combined therapy seems superior to monotherapy in the treatment of invasive infections caused by carbapenemase-producing Enterobacteriaceae. Optimization of dosage according to pharmacokinetics/pharmacodynamics data is important for the treatment of infections caused by isolates with borderline minimum inhibitory concentration due to low-level resistance mechanisms. The increasing frequency and the rapid spread of multidrug resistance among the Enterobacteriaceae is a true and complex public health problem. PMID:25165544

  11. The management of fluid and wave resistances by whirligig beetles.

    PubMed

    Voise, Jonathan; Casas, Jérôme

    2010-02-06

    Whirligig beetles (Coleoptera: Gyrinidae) are semi-aquatic insects with a morphology and propulsion system highly adapted to their life at the air-water interface. When swimming on the water surface, beetles are subject to both fluid resistance and wave resistance. The purpose of this study was to analyse swimming speed, leg kinematics and the capillarity waves produced by whirligig beetles on the water surface in a simple environment. Whirligig beetles of the species Gyrinus substriatus were filmed in a large container, with a high-speed camera. Resistance forces were also estimated. These beetles used three types of leg kinematics, differing in the sequence of leg strokes: two for swimming at low speed and one for swimming at high speed. Four main speed patterns were produced by different combinations of these types of leg kinematics, and the minimum speed for the production of surface waves (23 cm s(-1)) corresponded to an upper limit when beetles used low-speed leg kinematics. Each type of leg kinematics produced characteristic capillarity waves, even if the beetles moved at a speed below 23 cm s(-1). Our results indicate that whirligig beetles use low- and high-speed leg kinematics to avoid maximum drag and swim at speed corresponding to low resistances.

  12. Potential shortfall of pyramided Bt cotton for resistance management

    USDA-ARS?s Scientific Manuscript database

    To delay evolution of pest resistance to transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt), the "pyramid" strategy uses plants that produce two or more toxins that kill the same pest. In the United States, two-toxin Bt cotton has replaced one-toxin Bt cotton. Althou...

  13. Pharmacological Management of Treatment-Resistant Pediatric Depression

    ERIC Educational Resources Information Center

    Kratochvil, Christopher J.; Wagner, Karen Dineen; Emslie, Graham; March, John

    2005-01-01

    A 13-year-old boy presents with treatment-resistant symptoms of major depression. This is his first episode of depression, initially treated with 200 mg sertraline for 12 weeks with no significant benefit. The severe depression has shown a partial response to weekly cognitive-behavioral therapy (CBT) and fluoxetine, which was titrated up to 60 mg…

  14. Pharmacological Management of Treatment-Resistant Pediatric Depression

    ERIC Educational Resources Information Center

    Kratochvil, Christopher J.; Wagner, Karen Dineen; Emslie, Graham; March, John

    2005-01-01

    A 13-year-old boy presents with treatment-resistant symptoms of major depression. This is his first episode of depression, initially treated with 200 mg sertraline for 12 weeks with no significant benefit. The severe depression has shown a partial response to weekly cognitive-behavioral therapy (CBT) and fluoxetine, which was titrated up to 60 mg…

  15. Anticoagulant resistance in the United Kingdom and a new guideline for the management of resistant infestations of Norway rats (Rattus norvegicus Berk.).

    PubMed

    Buckle, Alan

    2013-03-01

    Anticoagulant resistance was first discovered in UK Norway rats (Rattus norvegicus Berk.) in 1958 and has been present ever since. The possible detrimental impact of resistance on effective rodent control was quickly recognised, and, for almost three decades, extensive research was conducted on the geographical distribution and severity of anticoagulant resistance in UK rats. Various schemes for the eradication of resistant rats were also implemented. At first, surveys showed resistance only to the first-generation anticoagulants, such as warfarin, chlorophacinone and coumatetralyl, but, later, resistance to the more potent second-generation anticoagulants, such as difenacoum and bromadiolone, was also discovered. Unlike some European countries, where only one or two resistance mutations occur, virtually all known rat resistance mutations occur in the United Kingdom, and five (Leu128Gln, Tyr139Ser, Tyr139Cys, Tyr139Phe and Leu120Gln) are known to have significant impacts on anticoagulant efficacy. Little is currently known of the geographical extent of anticoagulant resistance among Norway rats in the United Kingdom because no comprehensive survey has been conducted recently. At an operational level, anticoagulants generally retain their utility for Norway rat control, but it is impossible to control resistant rats in some areas because of restrictions on the use of the more potent resistance-breaking compounds. This paper reviews the development of resistance in Norway rats in the United Kingdom, outlines the present situation for resistance management and introduces a new resistance management guideline from the UK Rodenticide Resistance Action Group.

  16. A review of pharmacokinetic drug-drug interactions with the anthelmintic medications albendazole and mebendazole.

    PubMed

    Pawluk, Shane Ashley; Roels, Craig Allan; Wilby, Kyle John; Ensom, Mary H H

    2015-04-01

    Medications indicated for helminthes and other parasitic infections are frequently being used in mass populations in endemic areas. Currently, there is a lack of guidance for clinicians on how to appropriately manage drug interactions when faced with patients requiring short-term anthelmintic therapy with albendazole or mebendazole while concurrently taking other agents. The objective of this review was to systematically summarize and evaluate published literature on the pharmacokinetics of albendazole or mebendazole when taken with other interacting medications. A search of MEDLINE (1946 to October 2014), EMBASE (1974 to October 2014), International Pharmaceutical Abstracts (1970 to October 2014), Google, and Google Scholar was conducted for articles describing the pharmacokinetics of albendazole or mebendazole when given with other medications (and supplemented by a bibliographic review of all relevant articles). Altogether, 17 articles were included in the review. Studies reported data on pharmacokinetic parameters for albendazole or mebendazole when taken with cimetidine, dexamethasone, ritonavir, phenytoin, carbamazepine, phenobarbital, ivermectin, praziquantel, diethylcarbamazine, azithromycin, and levamisole. Cimetidine increased the elimination half-life of albendazole and maximum concentration (Cmax) of mebendazole; dexamethasone increased the area under the plasma concentration-time curve (AUC) of albendazole; levamisole decreased the Cmax of albendazole; anticonvulsants (phenytoin, phenobarbital, carbamazepine) decreased the AUC of albendazole; praziquantel increased the AUC of albendazole; and ritonavir decreased the AUC of both albendazole and mebendazole. No major interactions were found with ivermectin, azithromycin, or diethylcarbamazine. Future research is required to clarify the clinical relevance of the interactions observed.

  17. Breeding for resistance to gastrointestinal nematodes - the potential in low-input/output small ruminant production systems.

    PubMed

    Zvinorova, P I; Halimani, T E; Muchadeyi, F C; Matika, O; Riggio, V; Dzama, K

    2016-07-30

    The control of gastrointestinal nematodes (GIN) is mainly based on the use of drugs, grazing management, use of copper oxide wire particles and bioactive forages. Resistance to anthelmintic drugs in small ruminants is documented worldwide. Host genetic resistance to parasites, has been increasingly used as a complementary control strategy, along with the conventional intervention methods mentioned above. Genetic diversity in resistance to GIN has been well studied in experimental and commercial flocks in temperate climates and more developed economies. However, there are very few report outputs from the more extensive low-input/output smallholder systems in developing and emerging countries. Furthermore, results on quantitative trait loci (QTL) associated with nematode resistance from various studies have not always been consistent, mainly due to the different nematodes studied, different host breeds, ages, climates, natural infections versus artificial challenges, infection level at sampling periods, among others. The increasing use of genetic markers (Single Nucleotide Polymorphisms, SNPs) in GWAS or the use of whole genome sequence data and a plethora of analytic methods offer the potential to identify loci or regions associated nematode resistance. Genomic selection as a genome-wide level method overcomes the need to identify candidate genes. Benefits in genomic selection are now being realised in dairy cattle and sheep under commercial settings in the more advanced countries. However, despite the commercial benefits of using these tools, there are practical problems associated with incorporating the use of marker-assisted selection or genomic selection in low-input/output smallholder farming systems breeding schemes. Unlike anthelmintic resistance, there is no empirical evidence suggesting that nematodes will evolve rapidly in response to resistant hosts. The strategy of nematode control has evolved to a more practical manipulation of host-parasite equilibrium

  18. Anthelmintic and relaxant activities of Verbascum Thapsus Mullein

    PubMed Central

    2012-01-01

    Background Verbascum thapsus is used in tribal medicine as an antispasmodic, anti-tubercular agent and wormicide. In this study, we investigated the antispasmodic and anthelmintic activities of crude aqueous methanolic extract of the plant. Methods V. thapsus extracts were tested against roundworms (Ascaridia galli) and tapeworms (Raillietina spiralis). Each species of worm was placed into a negative control group, an albendazole treatment group, or a V. thapsus treatment group, and the time taken for paralysis and death was determined. In addition, relaxation activity tests were performed on sections of rabbit's jejunum. Plant extracts were tested on KCl-induced contractions and the relaxation activities were quantified against atropine. V. thapsus calcium chloride curves were constructed to investigate the mode of action of the plant extracts. Results We detected flavonoids, saponins, tannins, terpenoids, glycosides, carbohydrates, proteins, fats and fixed oils in V. thapsus. For both species of worm, paralysis occurred fastest at the highest concentration of extract. The relative index values for paralysis in A. galli were 4.58, 3.41 and 2.08, at concentrations of 10, 20 and 40 mg/ml of plant extract, respectively. The relative index for death in A. galli suggested that V. thapsus extract is wormicidal at high concentration. Similarly, the relative indexes for paralysis and death in R. spiralis suggested that the extract is a more potent wormicidal agent than albendazole. The mean EC50 relaxation activity values for spontaneous and KCl induced contractions were 7.5 ± 1.4 mg/ml (6.57-8.01, n = 6) and 7.9 ± 0.41 mg/ml (7.44-8.46, n = 6), respectively. The relaxation activity of the extract was 11.42 ± 2, 17.0 ± 3, 28.5 ± 4, and 128.0 ± 7% of the maximum observed for atropine at corresponding concentrations. The calcium chloride curves showed that V. thapsus extracts (3 mg/ml), had a mean EC50 (log molar [calcium]) value of -1.9 ± 0.06 (-1.87 - -1.98, n = 6

  19. Effective dominance of resistance of Spodoptera frugiperda to Bt maize and cotton varieties: implications for resistance management.

    PubMed

    Horikoshi, Renato J; Bernardi, Daniel; Bernardi, Oderlei; Malaquias, José B; Okuma, Daniela M; Miraldo, Leonardo L; Amaral, Fernando S de A E; Omoto, Celso

    2016-10-10

    The resistance of fall armyworm (FAW), Spodoptera frugiperda, has been characterized to some Cry and Vip3A proteins of Bacillus thuringiensis (Bt) expressed in transgenic maize in Brazil. Here we evaluated the effective dominance of resistance based on the survival of neonates from selected Bt-resistant, heterozygous, and susceptible (Sus) strains of FAW on different Bt maize and cotton varieties. High survival of strains resistant to the Cry1F (HX-R), Cry1A.105/Cry2Ab (VT-R) and Cry1A.105/Cry2Ab/Cry1F (PW-R) proteins was detected on Herculex, YieldGard VT PRO and PowerCore maize. Our Vip3A-resistant strain (Vip-R) exhibited high survival on Herculex, Agrisure Viptera and Agrisure Viptera 3 maize. However, the heterozygous from HX-R × Sus, VT-R × Sus, PW-R × Sus and Vip-R × Sus had complete mortality on YieldGard VT PRO, PowerCore, Agrisure Viptera, and Agrisure Viptera 3, whereas the HX-R × Sus and Vip-R × Sus strains survived on Herculex maize. On Bt cotton, the HX-R, VT-R and PW-R strains exhibited high survival on Bollgard II. All resistant strains survived on WideStrike, but only PW-R and Vip-R × Sus survived on TwinLink. Our study provides useful data to aid in the understanding of the effectiveness of the refuge strategy for Insect Resistance Management of Bt plants.

  20. Effective dominance of resistance of Spodoptera frugiperda to Bt maize and cotton varieties: implications for resistance management

    NASA Astrophysics Data System (ADS)

    Horikoshi, Renato J.; Bernardi, Daniel; Bernardi, Oderlei; Malaquias, José B.; Okuma, Daniela M.; Miraldo, Leonardo L.; Amaral, Fernando S. De A. E.; Omoto, Celso

    2016-10-01

    The resistance of fall armyworm (FAW), Spodoptera frugiperda, has been characterized to some Cry and Vip3A proteins of Bacillus thuringiensis (Bt) expressed in transgenic maize in Brazil. Here we evaluated the effective dominance of resistance based on the survival of neonates from selected Bt-resistant, heterozygous, and susceptible (Sus) strains of FAW on different Bt maize and cotton varieties. High survival of strains resistant to the Cry1F (HX-R), Cry1A.105/Cry2Ab (VT-R) and Cry1A.105/Cry2Ab/Cry1F (PW-R) proteins was detected on Herculex, YieldGard VT PRO and PowerCore maize. Our Vip3A-resistant strain (Vip-R) exhibited high survival on Herculex, Agrisure Viptera and Agrisure Viptera 3 maize. However, the heterozygous from HX-R × Sus, VT-R × Sus, PW-R × Sus and Vip-R × Sus had complete mortality on YieldGard VT PRO, PowerCore, Agrisure Viptera, and Agrisure Viptera 3, whereas the HX-R × Sus and Vip-R × Sus strains survived on Herculex maize. On Bt cotton, the HX-R, VT-R and PW-R strains exhibited high survival on Bollgard II. All resistant strains survived on WideStrike, but only PW-R and Vip-R × Sus survived on TwinLink. Our study provides useful data to aid in the understanding of the effectiveness of the refuge strategy for Insect Resistance Management of Bt plants.

  1. Effective dominance of resistance of Spodoptera frugiperda to Bt maize and cotton varieties: implications for resistance management

    PubMed Central

    Horikoshi, Renato J.; Bernardi, Daniel; Bernardi, Oderlei; Malaquias, José B.; Okuma, Daniela M.; Miraldo, Leonardo L.; Amaral, Fernando S. de A. e; Omoto, Celso

    2016-01-01

    The resistance of fall armyworm (FAW), Spodoptera frugiperda, has been characterized to some Cry and Vip3A proteins of Bacillus thuringiensis (Bt) expressed in transgenic maize in Brazil. Here we evaluated the effective dominance of resistance based on the survival of neonates from selected Bt-resistant, heterozygous, and susceptible (Sus) strains of FAW on different Bt maize and cotton varieties. High survival of strains resistant to the Cry1F (HX-R), Cry1A.105/Cry2Ab (VT-R) and Cry1A.105/Cry2Ab/Cry1F (PW-R) proteins was detected on Herculex, YieldGard VT PRO and PowerCore maize. Our Vip3A-resistant strain (Vip-R) exhibited high survival on Herculex, Agrisure Viptera and Agrisure Viptera 3 maize. However, the heterozygous from HX-R × Sus, VT-R × Sus, PW-R × Sus and Vip-R × Sus had complete mortality on YieldGard VT PRO, PowerCore, Agrisure Viptera, and Agrisure Viptera 3, whereas the HX-R × Sus and Vip-R × Sus strains survived on Herculex maize. On Bt cotton, the HX-R, VT-R and PW-R strains exhibited high survival on Bollgard II. All resistant strains survived on WideStrike, but only PW-R and Vip-R × Sus survived on TwinLink. Our study provides useful data to aid in the understanding of the effectiveness of the refuge strategy for Insect Resistance Management of Bt plants. PMID:27721425

  2. Potential shortfall of pyramided transgenic cotton for insect resistance management

    PubMed Central

    Brévault, Thierry; Heuberger, Shannon; Zhang, Min; Ellers-Kirk, Christa; Ni, Xinzhi; Masson, Luke; Li, Xianchiun; Tabashnik, Bruce E.; Carrière, Yves

    2013-01-01

    To delay evolution of pest resistance to transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt), the “pyramid” strategy uses plants that produce two or more toxins that kill the same pest. In the United States, this strategy has been adopted widely, with two-toxin Bt cotton replacing one-toxin Bt cotton. Although two-toxin plants are likely to be more durable than one-toxin plants, the extent of this advantage depends on several conditions. One key assumption favoring success of two-toxin plants is that they kill insects selected for resistance to one toxin, which is called “redundant killing.” Here we tested this assumption for a major pest, Helicoverpa zea, on transgenic cotton producing Bt toxins Cry1Ac and Cry2Ab. Selection with Cry1Ac increased survival on two-toxin cotton, which contradicts the assumption. The concentration of Cry1Ac and Cry2Ab declined during the growing season, which would tend to exacerbate this problem. Furthermore, analysis of results from 21 selection experiments with eight species of lepidopteran pests indicates that some cross-resistance typically occurs between Cry1A and Cry2A toxins. Incorporation of empirical data into simulation models shows that the observed deviations from ideal conditions could greatly reduce the benefits of the pyramid strategy for pests like H. zea, which have inherently low susceptibility to Bt toxins and have been exposed extensively to one of the toxins in the pyramid before two-toxin plants are adopted. For such pests, the pyramid strategy could be improved by incorporating empirical data on deviations from ideal assumptions about redundant killing and cross-resistance. PMID:23530245

  3. Multidrug-resistant Escherichia coli in Asia: epidemiology and management.

    PubMed

    Sidjabat, Hanna E; Paterson, David L

    2015-05-01

    Escherichia coli has become multiresistant by way of production of a variety of β-lactamases. The prevalence of CTX-M-producing E. coli has reached 60-79% in certain parts of Asia. The acquisition of CTX-M plasmids by E. coli sequence type 131, a successful clone of E. coli, has caused further dissemination of CTX-M-producing E. coli. The prevalence of carbapenemase-producing E. coli, especially Klebsiella pneumoniae carbapenemase, and New Delhi metallo-β-lactamase (NDM)-producing E. coli has been increasing in Asia. K. pneumoniae carbapenemase and NDM have now been found in E. coli sequence type 131. The occurrence of NDM-producing E. coli is a major concern particularly in the Indian subcontinent, but now elsewhere in Asia as well. There are multiple reasons why antibiotic resistance in E. coli in Asia has reached such extreme levels. Approaches beyond antibiotic therapy, such as prevention of antibiotic resistance by antibiotic stewardship and protecting natural microbiome, are strategies to avoid further spread of antibiotic resistance.

  4. Management strategies for recurrent platinum-resistant ovarian cancer.

    PubMed

    Naumann, R Wendel; Coleman, Robert L

    2011-07-30

    Although ovarian cancer is often a chemosensitive malignancy, patients who are resistant to platinum-based chemotherapy represent a therapeutic challenge. Currently, the only drugs that are US FDA approved to treat this subset of patients are paclitaxel, pegylated liposomal doxorubicin (PLD) and topotecan. The response rates with these agents is in the 10-15% range and overall survival is around 12 months. Other drugs that have shown some activity in platinum-resistant ovarian cancer include the taxane analogues, oral etoposide, pemetrexed and bevacizumab. Unfortunately, randomized phase III trials of second-line chemotherapy in patients with platinum-resistant ovarian cancer have not shown an advantage over existing therapy with respect to progression-free survival or overall survival. The only trial that has reported a significant progression-free survival advantage over standard therapy is a randomized phase II trial of PLD with or without EC145, a folate-linked vinca alkaloid. Final survival results of this trial are pending.

  5. A new enabling proteomics methodology to investigate membrane associated proteins from parasitic nematodes: case study using ivermectin resistant and ivermectin susceptible isolates of Caenorhabditis elegans and Haemonchus contortus.

    PubMed

    Hart, Elizabeth H; Brophy, Peter M; Prescott, Mark; Bartley, David J; Wolf, Basil T; Hamilton, Joanne V

    2015-01-30

    The mechanisms involved in anthelmintic resistance (AR) are complex but a greater understanding of AR management is essential for effective and sustainable control of parasitic helminth worms in livestock. Current tests to measure AR are time consuming and can be technically problematic, gold standard diagnostics are therefore urgently required to assist in combatting the threat from drug resistant parasites. For anthelmintics such as ivermectin (IVM), target proteins may be present in the cellular membrane. As proteins usually act in complexes and not in isolation, AR may develop and be measurable in the target associated proteins present in the parasite membrane. The model nematode Caenorhabditis elegans was used to develop a sub-proteomic assay to measure protein expression differences, between IVM resistant and IVM susceptible isolates in the presence and absence of drug challenge. Evaluation of detergents including CHAPS, ASB-14, C7BzO, Triton ×100 and TBP (tributyl phosphine) determined optimal conditions for the resolution of membrane proteins in Two Dimensional Gel Electrophoresis (2DE). These sub-proteomic methodologies were then translated and evaluated using IVM-susceptible and IVM-resistant Haemonchus contortus; a pathogenic blood feeding parasitic nematode which is of global importance in livestock health, welfare and productivity. We have demonstrated the successful resolution of membrane associated proteins from both C. elegans and H. contortus isolates, using a combination of CHAPS and the zwitterionic amphiphilic surfactant ASB-14 to further support the detection of markers for AR. Copyright © 2014. Published by Elsevier B.V.

  6. Mixed methods evaluation of targeted selective anthelmintic treatment by resource-poor smallholder goat farmers in Botswana

    PubMed Central

    Walker, Josephine G.; Ofithile, Mphoeng; Tavolaro, F. Marina; van Wyk, Jan A.; Evans, Kate; Morgan, Eric R.

    2015-01-01

    Due to the threat of anthelmintic resistance, livestock farmers worldwide are encouraged to selectively apply treatments against gastrointestinal nematodes (GINs). Targeted selective treatment (TST) of individual animals would be especially useful for smallholder farmers in low-income economies, where cost-effective and sustainable intervention strategies will improve livestock productivity and food security. Supporting research has focused mainly on refining technical indicators for treatment, and much less on factors influencing uptake and effectiveness. We used a mixed method approach, whereby qualitative and quantitative approaches are combined, to develop, implement and validate a TST system for GINs in small ruminants, most commonly goats, among smallholder farmers in the Makgadikgadi Pans region of Botswana, and to seek better understanding of system performance within a cultural context. After the first six months of the study, 42 out of 47 enrolled farmers were followed up; 52% had monitored their animals using the taught inspection criteria and 26% applied TST during this phase. Uptake level showed little correlation with farmer characteristics, such as literacy and size of farm. Herd health significantly improved in those herds where anthelmintic treatment was applied: anaemia, as assessed using the five-point FAMACHA© scale, was 0.44–0.69 points better (95% confidence interval) and body condition score was 0.18–0.36 points better (95% C.I., five-point scale) in treated compared with untreated herds. Only targeting individuals in greatest need led to similar health improvements compared to treating the entire herd, leading to dose savings ranging from 36% to 97%. This study demonstrates that TST against nematodes can be implemented effectively by resource-poor farmers using a community-led approach. The use of mixed methods provides a promising system to integrate technical and social aspects of TST programmes for maximum uptake and effect. PMID

  7. Targeting of Wnt/β-Catenin by Anthelmintic Drug Pyrvinium Enhances Sensitivity of Ovarian Cancer Cells to Chemotherapy

    PubMed Central

    Zhang, Chongyuan; Zhang, Zhenge; Zhang, Shuirong; Wang, Wenrong; Hu, Ping

    2017-01-01

    Background Aberrant activation of Wnt/β-catenin has been shown to promote ovarian cancer proliferation and chemoresistance. Pyrvinium, an FDA-approved anthelmintic drug, has been identified as a potent Wnt inhibitor. Pyrvinium may sensitize ovarian cancer cells to chemotherapy. Material/Methods The effect of pyrvinium alone and its combination with paclitaxel in ovarian cancer was investigated using an in vitro culture system and in vivo xenograft models. The mechanisms of its action were also analyzed, focusing on the Wnt/β-catenin pathway. Results Pyrvinium inhibited growth and induced apoptosis of paclitaxel- and cisplatin-resistant epithelial ovarian cancer cell lines A2278/PTX and SK-OV-3. Its combination with paclitaxel was synergistic in targeting ovarian cancer cells in vitro. In 3 independent ovarian xenograft mouse models, pyrvinium alone inhibited tumor growth. More importantly, we observed significant inhibition of tumor growth throughout the treatment when using pyrvinium and paclitaxel combined. Mechanistically, pyrvinium increased the Wnt-negative regulator axin and decreased the β-catenin levels in ovarian cancer cells. In addition, pyrvinium suppressed Wnt/β-catenin-mediated transcription, as shown by the decreased mRNA levels of MYC, cyclin D, and BCL-9. In contrast, the inhibitory effects of pyrvinium were reversed by β-catenin stabilization or overexpression, demonstrating that pyrvinium acted on ovarian cancer cells via targeting the Wnt/β-catenin signaling pathway. Conclusions We demonstrated that the anthelmintic drug pyrvinium targets ovarian cancer cells through suppressing Wnt/β-catenin signaling. Our work highlights the therapeutic value of inhibiting Wnt/β-catenin in ovarian cancer. PMID:28090074

  8. Management of community-associated methicillin-resistant Staphylococcus aureus skin abscesses in children

    PubMed Central

    Robinson, Joan L; Salvadori, Marina I

    2011-01-01

    Uncomplicated skin abscesses in previously well children are typically managed with drainage alone. An increasing percentage of such abscesses are due to methicillin-resistant Staphylococcus aureus infections. Although definitive data are lacking, drainage alone appears to be a reasonable strategy for methicillin-resistant S aureus skin abscesses, with antibiotics reserved for infants younger than three months of age, or for children who are systemically unwell, have underlying medical problems or have significant surrounding cellulitis. PMID:22294871

  9. ANALYSIS OF INSECT RESISTANCE MANAGEMENT OPTIONS FOR TRANSGENIC BT CORN,

    EPA Science Inventory

    Increasing interest in the responsible management of technology in the industrial and agricultural sectors of the economy has been met through the development of broadly applicable tools to assess the "sustainability" of new technologies. An arena ripe for application of such ana...

  10. ANALYSIS OF INSECT RESISTANCE MANAGEMENT OPTIONS FOR TRANSGENIC BT CORN,

    EPA Science Inventory

    Increasing interest in the responsible management of technology in the industrial and agricultural sectors of the economy has been met through the development of broadly applicable tools to assess the "sustainability" of new technologies. An arena ripe for application of such ana...

  11. SUSTAINABILITY OF INSECT RESISTANCE MANAGEMENT STRATEGIES FOR TRANSGENIC BT CORN

    EPA Science Inventory

    Increasing interest in the responsible management of technology in the industrial and agricultural sectors of the economy has been met through the development of broadly applicable tools to assess the "sustainability" of new technologies. An arena ripe for application of such ana...

  12. SUSTAINABILITY OF INSECT RESISTANCE MANAGEMENT STRATEGIES FOR TRANSGENIC BT CORN

    EPA Science Inventory

    Increasing interest in the responsible management of technology in the industrial and agricultural sectors of the economy has been met through the development of broadly applicable tools to assess the "sustainability" of new technologies. An arena ripe for application of such ana...

  13. Species differences in hepatic biotransformation of the anthelmintic drug flubendazole.

    PubMed

    Maté, M L; Geary, T; Mackenzie, C; Lanusse, C; Virkel, G

    2017-10-01

    Flubendazole (FLBZ) is a broad-spectrum benzimidazole anthelmintic used in pigs, poultry, and humans. It has been proposed as a candidate for development for use in elimination programmes for lymphatic filariasis and onchocerciasis in humans. Moreover, FLBZ has shown promise in cancer chemotherapy, particularly for neuroblastoma. This work investigated the hepatic carbonyl-reducing pathway of FLBZ in different species, including humans. Microsomal and cytosolic fractions were obtained from sheep, cattle, pig, hen, rat, and human liver. Both subcellular fractions of each species converted FLBZ into a reduced metabolite (red-FLBZ). The rate of microsomal red-FLBZ production was highest in sheep (1.92 ± 0.13 nmol/min.mg) and lowest in pigs (0.04 ± 0.02 nmol/min.mg); cytosolic red-FLBZ production ranged from 0.02 ± 0.01 (pig) to 1.86 ± 0.61 nmol/min.mg (sheep). Only subcellular fractions from sheep liver oxidized red-FLBZ to FLBZ in a NADP(+) -dependent oxidative reaction. Liver microsomes from both pigs and humans transformed FLBZ to red-FLBZ and a hydrolyzed metabolite. Very significant differences in the pattern of FLBZ metabolism were observed among the tested species and humans. These results reinforce the need for caution in extrapolating data on metabolism, efficacy, and safety of drugs derived from studies performed in different species. © 2017 John Wiley & Sons Ltd.

  14. The Anthelmintic Ingredient Moxidectin Negatively Affects Seed Germination of Three Temperate Grassland Species.

    PubMed

    Eichberg, Carsten; Wohde, Manuel; Müller, Kerstin; Rausch, Anja; Scherrmann, Christina; Scheuren, Theresa; Düring, Rolf-Alexander; Donath, Tobias W

    2016-01-01

    In animal farming, anthelmintics are regularly applied to control gastrointestinal nematodes. There is plenty of evidence that also non-target organisms, such as dung beetles, are negatively affected by residues of anthelmintics in faeces of domestic ungulates. By contrast, knowledge about possible effects on wild plants is scarce. To bridge this gap of knowledge, we tested for effects of the common anthelmintic formulation Cydectin and its active ingredient moxidectin on seed germination. We conducted a feeding experiment with sheep and germination experiments in a climate chamber. Three wide-spread plant species of temperate grasslands (Centaurea jacea, Galium verum, Plantago lanceolata) were studied. We found significant influences of both, Cydectin and moxidectin, on germination of the tested species. Across species, both formulation and active ingredient solely led to a decrease in germination percentage and synchrony of germination and an increase in mean germination time with the formulation showing a more pronounced response pattern. Our study shows for the first time that anthelmintics have the potential to negatively affect plant regeneration. This has practical implications for nature conservation since our results suggest that treatments of livestock with anthelmintics should be carefully timed to not impede endozoochorous seed exchange between plant populations.

  15. The Anthelmintic Ingredient Moxidectin Negatively Affects Seed Germination of Three Temperate Grassland Species

    PubMed Central

    Eichberg, Carsten; Wohde, Manuel; Müller, Kerstin; Rausch, Anja; Scherrmann, Christina; Scheuren, Theresa; Düring, Rolf-Alexander; Donath, Tobias W.

    2016-01-01

    In animal farming, anthelmintics are regularly applied to control gastrointestinal nematodes. There is plenty of evidence that also non-target organisms, such as dung beetles, are negatively affected by residues of anthelmintics in faeces of domestic ungulates. By contrast, knowledge about possible effects on wild plants is scarce. To bridge this gap of knowledge, we tested for effects of the common anthelmintic formulation Cydectin and its active ingredient moxidectin on seed germination. We conducted a feeding experiment with sheep and germination experiments in a climate chamber. Three wide-spread plant species of temperate grasslands (Centaurea jacea, Galium verum, Plantago lanceolata) were studied. We found significant influences of both, Cydectin and moxidectin, on germination of the tested species. Across species, both formulation and active ingredient solely led to a decrease in germination percentage and synchrony of germination and an increase in mean germination time with the formulation showing a more pronounced response pattern. Our study shows for the first time that anthelmintics have the potential to negatively affect plant regeneration. This has practical implications for nature conservation since our results suggest that treatments of livestock with anthelmintics should be carefully timed to not impede endozoochorous seed exchange between plant populations. PMID:27846249

  16. Challenges with managing insecticide resistance in agricultural pests, exemplisfied by the whitefly Bemisia tabaci

    PubMed Central

    Denholm, I.

    1998-01-01

    For many key agricultural pests, successful management of insecticide resistance depends not only on modifying the way that insecticides are deployed, but also on reducing the total number of treatments applied. Both approaches benefit from a knowledge of the biological characteristics of pests that promote or may retard the development of resistance. For the whitefly Bemisia tabaci (Gennadius), these factors include a haplodiploid breeding system that encourages the rapid selection and fixation of resistance genes, its breeding cycle on a succession of treated or untreated hosts, and its occurrence on and dispersal from high-value crops in greenhouses and glasshouses. These factors, in conjunction with often intensive insecticide use, have led to severe and widespread resistance that now affects several novel as well as conventional control agents. Resistance-management strategies implemented on cotton in Israel, and subsequently in south-western USA, have nonetheless so far succeeded in arresting the resistance treadmill in B. tabaci through a combination of increased chemical diversity, voluntary or mandatory restrictions on the use of key insecticides, and careful integration of chemical control with other pest-management options. In both countries, the most significant achievement has been a dramatic reduction in the number of insecticide treatments applied against whiteflies on cotton, increasing the prospect of sustained use of existing and future insecticides.

  17. Antimicrobial resistance in Helicobacter pylori: current situation and management strategy in Vietnam.

    PubMed

    Phan, Trung Nam; Tran, Van Huy; Tran, Thi Nhu Hoa; Le, Van An; Santona, Antonella; Rubino, Salvatore; Paglietti, Bianca

    2015-07-04

    Increasing antimicrobial resistance to key antibiotics in Helicobacter pylori has become a main cause of treatment failures in many countries, including Vietnam. For this reason it is advisable to perform antimicrobial sensitivity tests to provide more focused regimens for H. pylori eradication. However, this approach is generally unavailable for H. pylori in Vietnam and the selection of treatment regimens is mainly based on the trend of antibiotic use in the population, resistance development in the region, and history of H. pylori eradication of patients. The aim of this review is to examine the current situation of antimicrobial resistance in Vietnam and suggest management strategies for treatment selection.

  18. Treatment-resistant depression in adolescents: review and updates on clinical management.

    PubMed

    Maalouf, Fadi T; Atwi, Mia; Brent, David A

    2011-11-01

    Treatment-resistant depression (TRD) in adolescents is prevalent and impairing. We here review the definition, prevalence, clinical significance, risk factors, and management of TRD in adolescents. Risk factors associated with TRD include characteristics of depression (severity, level of hopelessness, and suicidal ideation), psychiatric and medical comorbidities, environmental factors (family conflict, maternal depression, and history of abuse), and pharmacokinetics and other biomarkers. Management options include review of the adequacy of the initial treatment, re-assessment for the above-noted factors that might predispose to treatment resistance, switching antidepressants, and augmentation with medication or psychotherapy. Other modalities, such as electroconvulsive therapy, vagal nerve stimulation, and repetitive transcranial magnetic stimulation, are also reviewed.

  19. Evolution, ecology and management of resistance in Helicoverpa spp. to Bt cotton in Australia.

    PubMed

    Downes, Sharon; Mahon, Rod

    2012-07-01

    Prior to the widespread adoption of two-gene Bt cotton (Bollgard II®) in Australia, the frequency of resistance alleles to one of the deployed proteins (Cry2Ab) was at least 0.001 in the pests targeted namely, Helicoverpa armigera and Helicoverpa punctigera. In the 7 years hence, there has been a statistically significant increase in the frequency of alleles conferring Cry2Ab resistance in field populations of H. punctigera. This paper reviews the history of deploying Bt cotton in Australia, the characteristics of the isolated Cry2Ab resistance that likely impact on resistance evolution, aspects of the efficacy of Bollgard IIχ, and the behavioural ecology of Helicoverpa spp. larvae as it pertains to resistance management. It also presents up-to-date frequencies of resistant alleles for H. punctigera and reviews the same information for H. armigera. This is followed by a discussion of current resistance management strategies. The consequences of the imminent release of a third generation product that utilizes the novel vegetative insecticidal protein Vip3A are then considered. The area planted to Bt-crops is anticipated to continue to rise worldwide and many biotechnical companies intend to add Vip3A to existing products; therefore the information reviewed herein for Australia is likely to be pertinent to other situations.

  20. Successes and challenges of managing resistance in Helicoverpa armigera to Bt cotton in Australia.

    PubMed

    Downes, Sharon; Mahon, Rod

    2012-01-01

    Bt cotton has been gradually released and adopted by Australian growers since 1996. It was initially deployed in Australia primarily to control the polyphagous pest Helicoverpa armigera (Hübner), which in the 1990s became increasingly difficult to control due to widespread resistance to synthetic chemical insecticides. Bt-cotton has become a key tool in a program of integrated pest management for the production system that reduces pesticide dependence and the problems associated with its use. Herein we overview the deployment of Bt cotton in Australia including its performance and the approaches used to prolong the evolution of resistance to it by H. armigera. An integral component of this approach is monitoring resistance in this pest. We outline resistance screening methods, as well as the characteristics of resistant strains of H. armigera that have been isolated from field populations, or selected in the laboratory. We then highlight the successes and challenges for Bt cotton in Australia by way of discussing adaptive resistance management in light of potential changes in resistance.

  1. Vasopressin for the management of catecholamine-resistant anaphylactic shock.

    PubMed

    Hussain, A M; Yousuf, B; Khan, M A; Khan, F H; Khan, F A

    2008-09-01

    Severe anaesthetic anaphylaxis is relatively uncommon. Oxygen, fluids and epinephrine are considered to be the mainstay for treatment of cardiovascular collapse and current guidelines for the management of anaphylaxis list only epinephrine as a vasopressor to use in the event of a cardiovascular collapse. Recently, evidence has emerged in the support of the use of vasopressin in cardiopulmonary resuscitation; it is also recommended for the treatment of ventricular fibrillation, septic shock and post-cardiopulmonary bypass distribution shock. Currently, there is no algorithm or guideline for the management of anaphylaxis that include the use of vasopressin. We report a 24-year-old woman who developed severe anaphylactic shock at induction of anaesthesia while undergoing laparoscopic cholecystectomy. Circulation shock was refractory to epinephrine and high doses of pure alpha-agonist phenylephrine and norepinephrine. Single intravenous dose of two units of vasopressin re-established normal circulation and blood pressure.

  2. A novel series of milbemycin antibiotics from Streptomyces strain E225. I. Discovery, fermentation and anthelmintic activity.

    PubMed

    Hood, J D; Banks, R M; Brewer, M D; Fish, J P; Manger, B R; Poulton, M E

    1989-11-01

    A novel series of milbemycin antibiotics were produced by soil isolate, strain E225 which was shown to be a Streptomyces species. The antibiotics displayed anthelmintic activity against Trichostrongylus colubriformis in the gerbil. Two of the compounds, VM 44857 and VM 44866 were shown to be potent anthelmintics against mixed nematode infections in sheep.

  3. Management options for reducing the release of antibiotics and antibiotic resistance genes to the environment.

    PubMed

    Pruden, Amy; Larsson, D G Joakim; Amézquita, Alejandro; Collignon, Peter; Brandt, Kristian K; Graham, David W; Lazorchak, James M; Suzuki, Satoru; Silley, Peter; Snape, Jason R; Topp, Edward; Zhang, Tong; Zhu, Yong-Guan

    2013-08-01

    There is growing concern worldwide about the role of polluted soil and water environments in the development and dissemination of antibiotic resistance. Our aim in this study was to identify management options for reducing the spread of antibiotics and antibiotic-resistance determinants via environmental pathways, with the ultimate goal of extending the useful life span of antibiotics. We also examined incentives and disincentives for action. We focused on management options with respect to limiting agricultural sources; treatment of domestic, hospital, and industrial wastewater; and aquaculture. We identified several options, such as nutrient management, runoff control, and infrastructure upgrades. Where appropriate, a cross-section of examples from various regions of the world is provided. The importance of monitoring and validating effectiveness of management strategies is also highlighted. Finally, we describe a case study in Sweden that illustrates the critical role of communication to engage stakeholders and promote action. Environmental releases of antibiotics and antibiotic-resistant bacteria can in many cases be reduced at little or no cost. Some management options are synergistic with existing policies and goals. The anticipated benefit is an extended useful life span for current and future antibiotics. Although risk reductions are often difficult to quantify, the severity of accelerating worldwide morbidity and mortality rates associated with antibiotic resistance strongly indicate the need for action.

  4. Management Options for Reducing the Release of Antibiotics and Antibiotic Resistance Genes to the Environment

    PubMed Central

    Pruden, Amy; Amézquita, Alejandro; Collignon, Peter; Brandt, Kristian K.; Graham, David W.; Lazorchak, James M.; Suzuki, Satoru; Silley, Peter; Snape, Jason R.; Topp, Edward; Zhang, Tong; Zhu, Yong-Guan

    2013-01-01

    Background: There is growing concern worldwide about the role of polluted soil and water environments in the development and dissemination of antibiotic resistance. Objective: Our aim in this study was to identify management options for reducing the spread of antibiotics and antibiotic-resistance determinants via environmental pathways, with the ultimate goal of extending the useful life span of antibiotics. We also examined incentives and disincentives for action. Methods: We focused on management options with respect to limiting agricultural sources; treatment of domestic, hospital, and industrial wastewater; and aquaculture. Discussion: We identified several options, such as nutrient management, runoff control, and infrastructure upgrades. Where appropriate, a cross-section of examples from various regions of the world is provided. The importance of monitoring and validating effectiveness of management strategies is also highlighted. Finally, we describe a case study in Sweden that illustrates the critical role of communication to engage stakeholders and promote action. Conclusions: Environmental releases of antibiotics and antibiotic-resistant bacteria can in many cases be reduced at little or no cost. Some management options are synergistic with existing policies and goals. The anticipated benefit is an extended useful life span for current and future antibiotics. Although risk reductions are often difficult to quantify, the severity of accelerating worldwide morbidity and mortality rates associated with antibiotic resistance strongly indicate the need for action. PMID:23735422

  5. Management of patients with multidrug-resistant/extensively drug-resistant tuberculosis in Europe: a TBNET consensus statement.

    PubMed

    Lange, Christoph; Abubakar, Ibrahim; Alffenaar, Jan-Willem C; Bothamley, Graham; Caminero, Jose A; Carvalho, Anna Cristina C; Chang, Kwok-Chiu; Codecasa, Luigi; Correia, Ana; Crudu, Valeriu; Davies, Peter; Dedicoat, Martin; Drobniewski, Francis; Duarte, Raquel; Ehlers, Cordula; Erkens, Connie; Goletti, Delia; Günther, Gunar; Ibraim, Elmira; Kampmann, Beate; Kuksa, Liga; de Lange, Wiel; van Leth, Frank; van Lunzen, Jan; Matteelli, Alberto; Menzies, Dick; Monedero, Ignacio; Richter, Elvira; Rüsch-Gerdes, Sabine; Sandgren, Andreas; Scardigli, Anna; Skrahina, Alena; Tortoli, Enrico; Volchenkov, Grigory; Wagner, Dirk; van der Werf, Marieke J; Williams, Bhanu; Yew, Wing-Wai; Zellweger, Jean-Pierre; Cirillo, Daniela Maria

    2014-07-01

    The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) substantially challenges TB control, especially in the European Region of the World Health Organization, where the highest prevalence of MDR/XDR cases is reported. The current management of patients with MDR/XDR-TB is extremely complex for medical, social and public health systems. The treatment with currently available anti-TB therapies to achieve relapse-free cure is long and undermined by a high frequency of adverse drug events, suboptimal treatment adherence, high costs and low treatment success rates. Availability of optimal management for patients with MDR/XDR-TB is limited even in the European Region. In the absence of a preventive vaccine, more effective diagnostic tools and novel therapeutic interventions the control of MDR/XDR-TB will be extremely difficult. Despite recent scientific advances in MDR/XDR-TB care, decisions for the management of patients with MDR/XDR-TB and their contacts often rely on expert opinions, rather than on clinical evidence. This document summarises the current knowledge on the prevention, diagnosis and treatment of adults and children with MDR/XDR-TB and their contacts, and provides expert consensus recommendations on questions where scientific evidence is still lacking.

  6. Management of patients with multidrug-resistant/extensively drug-resistant tuberculosis in Europe: a TBNET consensus statement

    PubMed Central

    Lange, Christoph; Abubakar, Ibrahim; Alffenaar, Jan-Willem C.; Bothamley, Graham; Caminero, Jose A.; Carvalho, Anna Cristina C.; Chang, Kwok-Chiu; Codecasa, Luigi; Correia, Ana; Crudu, Valeriu; Davies, Peter; Dedicoat, Martin; Drobniewski, Francis; Duarte, Raquel; Ehlers, Cordula; Erkens, Connie; Goletti, Delia; Günther, Gunar; Ibraim, Elmira; Kampmann, Beate; Kuksa, Liga; de Lange, Wiel; van Leth, Frank; van Lunzen, Jan; Matteelli, Alberto; Menzies, Dick; Monedero, Ignacio; Richter, Elvira; Rüsch-Gerdes, Sabine; Sandgren, Andreas; Scardigli, Anna; Skrahina, Alena; Tortoli, Enrico; Volchenkov, Grigory; Wagner, Dirk; van der Werf, Marieke J.; Williams, Bhanu; Yew, Wing-Wai; Zellweger, Jean-Pierre; Cirillo, Daniela Maria

    2014-01-01

    The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) substantially challenges TB control, especially in the European Region of the World Health Organization, where the highest prevalence of MDR/XDR cases is reported. The current management of patients with MDR/XDR-TB is extremely complex for medical, social and public health systems. The treatment with currently available anti-TB therapies to achieve relapse-free cure is long and undermined by a high frequency of adverse drug events, suboptimal treatment adherence, high costs and low treatment success rates. Availability of optimal management for patients with MDR/XDR-TB is limited even in the European Region. In the absence of a preventive vaccine, more effective diagnostic tools and novel therapeutic interventions the control of MDR/XDR-TB will be extremely difficult. Despite recent scientific advances in MDR/XDR-TB care, decisions for the management of patients with MDR/XDR-TB and their contacts often rely on expert opinions, rather than on clinical evidence. This document summarises the current knowledge on the prevention, diagnosis and treatment of adults and children with MDR/XDR-TB and their contacts, and provides expert consensus recommendations on questions where scientific evidence is still lacking. PMID:24659544

  7. The management of insulin resistance in polycystic ovary syndrome.

    PubMed

    Teede, Helena J; Hutchison, Samantha K; Zoungas, Sophia

    2007-09-01

    Polycystic ovary syndrome (PCOS) has reproductive and metabolic implications. Insulin resistance (IR), secondary to genetic and lifestyle factors, is integral in the pathogenesis, metabolic, clinical features and the long-term sequelae in the majority of people with PCOS. Therapeutic strategies targeting IR in PCOS ameliorate clinical features and might reduce long-term sequelae including diabetes. The mainstay for improving IR is lifestyle change; however, feasibility and sustainability remain concerns. In PCOS, metformin reduces IR, improves ovarian function, regulates cycles, lowers androgens, improves clinical hyperandrogenism and potentially improves fertility. Metformin is also likely to delay diabetes onset and has a role in PCOS in those at high risk of diabetes; however, further research is needed to clarify specific target subgroups and clinical indications.

  8. Positive and normative modeling for Palmer amaranth control and herbicide resistance management.

    PubMed

    Frisvold, George B; Bagavathiannan, Muthukumar V; Norsworthy, Jason K

    2017-06-01

    Dynamic optimization models are normative; they solve for what growers 'ought to do' to maximize some objective, such as long-run profits. While valuable for research, such models are difficult to solve computationally, limiting their applicability to grower resistance management education. While discussing properties of normative models in general, this study presents results of a specific positive model of herbicide resistance management, applied to Palmer amaranth control on a representative cotton farm. This positive model compares a proactive resistance management strategy to a reactive strategy with lower short-run costs, but greater risk of herbicide resistance developing. The proactive strategy can pay for itself within 1-4 years, with a yield advantage of 4% or less if the yield advantage begins within 1-2 years of adoption. Whether the proactive strategy is preferable is sensitive to resistance onset and yield losses, but less sensitive to cotton prices or baseline yields. Industry rebates to encourage residual herbicide use (to delay resistance to post-emergence treatments) may be too small to alter grower behavior or they may be paid to growers who would have used residuals anyway. Rebates change grower behavior over a relatively narrow range of model parameters. The size of rebates needed to induce a grower to adopt the proactive strategy declines significantly if growers extend their planning horizon from 1 year to 3-4 years. Whether proactive resistance management is more profitable than a reactive strategy is more sensitive to biological parameters than economic ones. Simulation results suggest growers with longer time horizons (perhaps younger ones) would be more responsive to rebate programs. More empirical work is needed to determine how much rebates increase residual use above what would occur without them. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  9. Anthelmintic administration to small ruminants in emergency drought responses: assessing the impact in two locations of northern Kenya.

    PubMed

    Okell, Claire Natasha; Mariner, Jeffrey; Allport, Robert; Buono, Nicoletta; Mutembei, Henry M'Ikiugu; Rushton, Jonathan; Verheyen, Kristien

    2016-03-01

    Internal parasites are a significant determinant of the productivity of ruminant species in the tropics. Provision of anthelmintics has become a predominant part of animal health interventions in emergency drought responses, aiming to maintain the food conversion efficiency of livestock when pasture is scarce. This study aimed to assess the owner-perceived impact of anthelmintic provision on the health and productivity of small ruminants in the drought-prone counties of Isiolo and Marsabit, northern Kenya. Participatory approaches were used to retrospectively measure differences in key indicators of livestock output before and after anthelmintic administration. Results showed that there was no perceived impact of anthelmintic administration during droughts on small ruminant health and productivity, but some benefit of anthelmintic administration during rainy season was perceived. The study also provided some evidence of potential differences in the epidemiology of internal parasites between the counties. These findings may be utilised to inform future livestock intervention programmes in drought-prone areas.

  10. Fire-resistant fuel program analysis and program management documentation. Final report, December 1985-January 1986

    SciTech Connect

    Dye, C.A.

    1986-01-31

    There was an urgent need to transition management of the Fire Resistant Fuel (FRF) Program from the Materials Fuels and Lubricants Laboratory (MFLL) to the Logistics Support Directorate (LSD). It is recommended that the LSD develop program management documentation (PMD) that supports a Milestone I review as soon as possible to include the following: System Concept Paper, Concept Formulation Package and a Test Evaluation Master Plan. This report describes programmatic analyses and subsequent programmatic recommendations.

  11. The anthelmintic efficacy of natural plant cysteine proteinases against the equine tapeworm, Anoplocephala perfoliata in vitro.

    PubMed

    Mansur, F; Luoga, W; Buttle, D J; Duce, I R; Lowe, A E; Behnke, J M

    2016-09-01

    Papaya latex has been demonstrated to be an efficacious anthelmintic against murine, porcine, ovine and canine nematode parasites, and even those infecting poultry, and it has some efficacy against rodent cestodes. The active ingredients of papaya latex are known to be cysteine proteinases (CPs). The experiments described in this paper indicate that CPs in papaya latex, and also those in pineapples, are highly efficacious against the equine cestode Anoplocephala perfoliata in vitro, by causing a significant reduction in motility leading to death of the worms. The susceptibility of A. perfoliata to damage by CPs was considerably greater than that of the rodent cestodes Hymenolepis diminuta and H. microstoma. Our results are the first to report anthelmintic efficacy of CPs against an economically important equine helminth. Moreover, they provide further evidence that the spectrum of activity of CPs is not restricted to nematodes and support the idea that these plant-derived enzymes can be developed into useful broad-spectrum anthelmintics.

  12. Low cost whole-organism screening of compounds for anthelmintic activity.

    PubMed

    Preston, Sarah; Jabbar, Abdul; Nowell, Cameron; Joachim, Anja; Ruttkowski, Bärbel; Baell, Jonathan; Cardno, Tony; Korhonen, Pasi K; Piedrafita, David; Ansell, Brendan R E; Jex, Aaron R; Hofmann, Andreas; Gasser, Robin B

    2015-04-01

    Due to major problems with drug resistance in parasitic nematodes of animals, there is a substantial need and excellent opportunities to develop new anthelmintics via genomic-guided and/or repurposing approaches. In the present study, we established a practical and cost-effective whole-organism assay for the in vitro-screening of compounds for activity against parasitic stages of the nematode Haemonchus contortus (barber's pole worm). The assay is based on the use of exsheathed L3 (xL3) and L4 stages of H. contortus of small ruminants (sheep and goats). Using this assay, we screened a panel of 522 well-curated kinase inhibitors (GlaxoSmithKline, USA; code: PKIS2) for activity against H. contortus by measuring the inhibition of larval motility using an automated image analysis system. We identified two chemicals within the compound classes biphenyl amides and pyrazolo[1,5-α]pyridines, which reproducibly inhibit both xL3 and L4 motility and development, with IC50s of 14-47 μM. Given that these inhibitors were designed as anti-inflammatory drugs for use in humans and fit the Lipinski rule-of-five (including bioavailability), they show promise for hit-to-lead optimisation and repurposing for use against parasitic nematodes. The screening assay established here has significant advantages over conventional methods, particularly in terms of ease of use, throughput, time and cost. Although not yet fully automated, the current assay is readily suited to the screening of hundreds to thousands of compounds for subsequent hit-to-lead optimisation. The current assay is highly adaptable to many parasites of socioeconomic importance, including those causing neglected tropical diseases. This aspect is of major relevance, given the urgent need to deliver the goals of the London Declaration (http://unitingtocombatntds.org/resource/london-declaration) through the rapid and efficient repurposing of compounds in public-private partnerships.

  13. Development of an in vitro bioassay for measuring susceptibility to macrocyclic lactone anthelmintics in Dirofilaria immitis☆

    PubMed Central

    Evans, Christopher C.; Moorhead, Andrew R.; Storey, Bobby E.; Wolstenholme, Adrian J.; Kaplan, Ray M.

    2013-01-01

    For more than 20 years, anthelmintics of the macrocyclic lactone (ML) drug class have been widely and effectively used as preventives against the canine heartworm, Dirofilaria immitis. However, in recent years an increased number of lack of efficacy (LOE) cases are being reported, in which dogs develop mature heartworm infections despite receiving monthly prophylactic doses of ML drugs. While this situation is raising concerns that heartworms may be developing resistance to MLs, compelling evidence for this is still lacking. Resolution of this dilemma requires validated biological or molecular diagnostic assays, but, unfortunately, no such tests currently exist. To address this need, we developed and optimized a larval migration inhibition assay (LMIA) for use with D. immitis third-stage larvae. The LMIA was used to measure the in vitro dose–response of two ML drugs (ivermectin and eprinomectin) on a known ML-susceptible laboratory strain of D. immitis. A nonlinear regression model was fit to the dose–response data, from which IC50 values were calculated; the mean IC50 and 95% confidence interval for IVM was 4.56 μM (1.26–16.4 μM), greater than that for EPR at 2.02 μM (1.68–2.42 μM), and this difference was significant (p = 0.0428). The R2 value for EPR assays (0.90) was also greater than that for IVM treatment (0.71). The consistency and reproducibility of the dose–response data obtained with this assay suggests that it may be a useful technique for investigating the relative susceptibilities to ML drugs in other D. immitis populations. PMID:24533299

  14. Melaleuca alternifolia anthelmintic activity in gerbils experimentally infected by Haemonchus contortus.

    PubMed

    Grando, Thirssa H; Baldissera, Matheus D; Gressler, Lucas T; de Sá, Mariângela Facco; Bortoluzzi, Bruna N; Schafer, Andressa S; Ebling, Rafael C; Raffin, Renata P; Santos, Roberto C V; Stefani, Lenita M; Vaucher, Rodrigo; Leal, Marta L R; Monteiro, Silvia G

    2016-11-01

    Gastrointestinal parasites are one of the biggest health problems faced in sheep, mainly due to their pathogenicity and resistance to drugs used to control these parasites. Thus, the following study aimed to assess the anthelmintic efficacy of Melaleuca alternifolia against Haemonchus contortus in gerbils (Meriones unguiculatus) experimentally infected. Three treatments were tested: M. alternifolia essential oil, popularly known as tea tree oil (TTO), a solid lipid nanocarrier made with essential oil of Melaleuca (nanoTTO), and terpinen-4-ol (terp-4-ol). In vivo studies were performed by determining the mean worm burden of H. contortus in gerbils TTO (0.75 mL/kg); nanoTTO (0.5 mL/kg) and terp-4-ol (0.5 mL l/kg) were able to reduce 46.36%; 48.64%, and 43.18% worm burden, respectively. H. contortus increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, as demonstrated by liver injury. It was found that the TTO, nanoTTO, and terp-4-ol were not toxic to liver and kidneys since hepatic and renal functions were not affected. Moreover, terp-4-ol was able to prevent increased levels of seric AST and ALT in infected animals, indicating a hepatoprotective effect. Thus, our results indicate that TTO, nanoTTO, and terp-4-ol are safe and efficient against H. contortus infection in gerbils, and possibly the terp-4-ol may be considered the compound present in the Melaleuca alternifolia responsible for parasitic action against H. contortus.

  15. Direct anthelmintic effects of condensed tannins from diverse plant sources against Ascaris suum.

    PubMed

    Williams, Andrew R; Fryganas, Christos; Ramsay, Aina; Mueller-Harvey, Irene; Thamsborg, Stig M

    2014-01-01

    Ascaris suum is one of the most prevalent nematode parasites in pigs and causes significant economic losses, and also serves as a good model for A. lumbricoides, the large roundworm of humans that is ubiquitous in developing countries and causes malnutrition, stunted growth and compromises immunity to other pathogens. New treatment options for Ascaris infections are urgently needed, to reduce reliance on the limited number of synthetic anthelmintic drugs. In areas where Ascaris infections are common, ethno-pharmacological practices such as treatment with natural plant extracts are still widely employed. However, scientific validation of these practices and identification of the active compounds are lacking, although observed effects are often ascribed to plant secondary metabolites such as tannins. Here, we extracted, purified and characterised a wide range of condensed tannins from diverse plant sources and investigated anthelmintic effects against A. suum in vitro. We show that condensed tannins can have potent, direct anthelmintic effects against A. suum, as evidenced by reduced migratory ability of newly hatched third-stage larvae and reduced motility and survival of fourth-stage larvae recovered from pigs. Transmission electron microscopy showed that CT caused significant damage to the cuticle and digestive tissues of the larvae. Furthermore, we provide evidence that the strength of the anthelmintic effect is related to the polymer size of the tannin molecule. Moreover, the identity of the monomeric structural units of tannin polymers may also have an influence as gallocatechin and epigallocatechin monomers exerted significant anthelmintic activity whereas catechin and epicatechin monomers did not. Therefore, our results clearly document direct anthelmintic effects of condensed tannins against Ascaris and encourage further in vivo investigation to determine optimal strategies for the use of these plant compounds for the prevention and/or treatment of

  16. Direct Anthelmintic Effects of Condensed Tannins from Diverse Plant Sources against Ascaris suum

    PubMed Central

    Williams, Andrew R.; Fryganas, Christos; Ramsay, Aina; Mueller-Harvey, Irene; Thamsborg, Stig M.

    2014-01-01

    Ascaris suum is one of the most prevalent nematode parasites in pigs and causes significant economic losses, and also serves as a good model for A. lumbricoides, the large roundworm of humans that is ubiquitous in developing countries and causes malnutrition, stunted growth and compromises immunity to other pathogens. New treatment options for Ascaris infections are urgently needed, to reduce reliance on the limited number of synthetic anthelmintic drugs. In areas where Ascaris infections are common, ethno-pharmacological practices such as treatment with natural plant extracts are still widely employed. However, scientific validation of these practices and identification of the active compounds are lacking, although observed effects are often ascribed to plant secondary metabolites such as tannins. Here, we extracted, purified and characterised a wide range of condensed tannins from diverse plant sources and investigated anthelmintic effects against A. suum in vitro. We show that condensed tannins can have potent, direct anthelmintic effects against A. suum, as evidenced by reduced migratory ability of newly hatched third-stage larvae and reduced motility and survival of fourth-stage larvae recovered from pigs. Transmission electron microscopy showed that CT caused significant damage to the cuticle and digestive tissues of the larvae. Furthermore, we provide evidence that the strength of the anthelmintic effect is related to the polymer size of the tannin molecule. Moreover, the identity of the monomeric structural units of tannin polymers may also have an influence as gallocatechin and epigallocatechin monomers exerted significant anthelmintic activity whereas catechin and epicatechin monomers did not. Therefore, our results clearly document direct anthelmintic effects of condensed tannins against Ascaris and encourage further in vivo investigation to determine optimal strategies for the use of these plant compounds for the prevention and/or treatment of

  17. Do we have the tools to manage resistance in the future?

    PubMed

    Hollomon, Derek W

    2012-02-01

    Pesticide resistance is a major factor affecting world food and fibre production, but that has been contained so far by the availability of diverse modes of action. Overcoming resistance by switching to a new mode of action is a concept easily grasped by growers but threatened by losses through resistance and new registration requirements. Opportunities for innovation and development of a diversity of novel modes of action exist through harnessing recent advances, fundamental to all eukaryotes and largely funded for medical rather than agricultural objectives, in understanding cell biology and development. The cystoskeleton, cell wall synthesis, signal transduction and RNAi are discussed as examples where new targets are now exposed. However, new modes of action will be delivered not only by sprayer or seed treatment but also through transgenic crops, although these still need to be transferred from experiment to practice. Improvements in modelling protein structures and target-site changes, supplemented by rapid diagnostics to detect resistance early, will improve resistance risk management and integrate chemical, biopesticide, transgenic and conventional breeding around the concept of diversity in modes of action. However, before agronomy can translate this into practical antiresistance strategies, there is a need to direct more resources to the biochemistry and cell biology of pests, diseases and weeds to translate these new discoveries into key tools needed to manage resistance in the future. Copyright © 2012 Society of Chemical Industry.

  18. [5,6-bis-(3-alkoxy-carbonyl thio-ureido) benzimidazoles with anthelmintic activity].

    PubMed

    Sluka, J; Zikán, V; Danĕk, J

    1989-04-01

    The reaction of potassium thiocyanate with the methyl- and ethyl esters of chloroformic acid (V-VI) in acetone resulted in methoxy- and ethoxycarbonylisothiocyanates which were converted without isolation by means of an addition reaction with 2-alkyl-5,6-diaminobenzimidazoles (I-IV) into the pertinent 2-alkyl-5,6-bis (3-alkoxycarbonyl-2-thioureido) benzimidazoles (VII-XV). The substances obtained were tested for anthelmintic and anticoccidial effectiveness. In anthelmintic screening, substances VIII, IX, XI, XII, XIV and XV were significantly effective against the taenia Hymenolepis nana.

  19. Anthelmintic activity of some Mediterranean browse plants against parasitic nematodes.

    PubMed

    Manolaraki, F; Sotiraki, S; Stefanakis, A; Skampardonis, V; Volanis, M; Hoste, H

    2010-04-01

    The anthelmintic properties of tannin-rich plants are being explored as an alternative to chemical drugs. Most data have been acquired on legume forages, but only few on browse plants. The present study aimed to (i) screen the in vitro effects of extracts from 7 Mediterranean plants on Haemonchus contortus, (ii) verify the role of tannins using an inhibitor, polyvinyl polypyrrolidone (PVPP) and (iii) verify the in vivo effects of extracts from 4 plants. Significant inhibition was shown in vitro using a larval migration inhibition (LMI) assay for all extracts except that from Olea europaea var. koroneiki. After adding PVPP, the LMI values were restored to control levels for all plants except Pistacia lentiscus and Ceratonia siliqua, confirming a role for tannins in the activity. In the in vivo experiment, 48 lambs composed 6 groups, depending on diet. On Day 0, groups G1-G5 received H. contortus and Trichostrongylus colubriformis larvae and G6 remained uninfected. The various diets were distributed from Days 14 to 45: P. lentiscus (G1), Quercus coccifera (G2), C. siliqua (G3), Onobrychis viciifolia (G4), or Medicago sativa for the 2 control groups (G5, G6). Egg excretion, packed cell volumes (PCVs) and inorganic phosphate were measured weekly throughout the entire experimental period. At slaughter, the worms were enumerated and their fecundity assessed. Consumption of the 4 browser plants did not provoke differences in pathophysiological measurements but there were significant decreases in egg excretion, mainly explained by significant decreases in worm fecundity for both species, without any statistical difference in worm numbers.

  20. Anthelmintic efficacy of Clerodendrum viscosum on fowl tapeworm Raillietina tetragona.

    PubMed

    Nandi, Suranjana; Ukil, Bidisha; Roy, Saptarshi; Kundu, Suman; Lyndem, Larisha Mawkhlieng

    2017-12-01

    Clerodendrum viscosum Vent. (Verbenaceae) is a shrub, widely used amongst the natives of India against various diseases. Crude extract of the plant was tested in vitro on a tapeworm Raillietina tetragona Molin (Davaineidae) to evaluate its potential anthelmintic efficacy and ultrastructural changes in the parasite. Parasites were exposed to different concentrations of ethanolic leaf extract (10-80 mg/mL) and praziquantel (0.0005-0.005 mg/mL) and incubated in phosphate-buffered saline (PBS). The pH was 7.4 at 37 °C, while one set of worms was incubated only with PBS as a control. Permanent immobilization of worms was determined visually when no motility occurred on physically disturbing them. The parasites exposed to high concentrations of leaf extract and praziquantel treatments were processed for histological and electron microscopic studies, as these concentrations took the least time for paralysis and death to occur. With an increase in the concentration of the leaf extract from 10 to 80 mg/mL and praziquantel from 0.0005 to 0.005 mg/mL, the time for the onset of paralysis and death was shortened. The treated parasites lost their spontaneous movement rapidly followed by death. Electron microscopic observations revealed disruptions in the tegument and parenchymal layer, accompanied by deformities in cell organelles. Extensive structural alterations in the tegument indicate that the plant-derived components cause permeability changes in the parasite leading to paralysis and subsequent death. These observations suggest that phytochemicals present in C. viscosum have vermifugal or vermicidal activity, and thus may be exploited as alternative chemotherapeutic agents.

  1. Integrated palmer amaranth management in glufosinate-resistant cotton: II. primary, secondary, and conservation tillage

    USDA-ARS?s Scientific Manuscript database

    A three-year field experiment was conducted to evaluate the role of inversion tillage, cover crops and spring tillage methods for Palmer amaranth between-row (BR) and within-row (WR) management in glufosinate-resistant cotton. Main plots were two inversion tillage systems: fall inversion tillage (IT...

  2. Cercospora leaf spot: monitoring and managing fungicide resistance in populations of Cercospora beticola in Michigan

    USDA-ARS?s Scientific Manuscript database

    Cercospora leaf spot (CLS, Cercospora beticola) is the most serious foliar disease of sugarbeet in Michigan and Ontario.Management of CLS depends on timely fungicide applications, disease forecasting prediction models and the use of CLS resistant sugar beet varieties. Fungicides have a dominant role...

  3. Report: EPA Can Strengthen Its Oversight of Herbicide Resistance With Better Management Controls

    EPA Pesticide Factsheets

    Report #17-P-0278, June 21, 2017. Billions of dollars in U.S. crop value are at risk due to the threat of herbicide-resistant weeds. With private and public partners, the EPA can establish better controls to manage and minimize the threat.

  4. Resilience and resistance of sagebrush ecosystems: Implications for state and transition models and management treatments

    Treesearch

    Jeanne C. Chambers; Richard F. Miller; David I. Board; David A. Pyke; Bruce A. Roundy; James B. Grace; Eugene W. Schupp; Robin J. Tausch

    2014-01-01

    In sagebrush ecosystems invasion of annual exotics and expansion of pinon (Pinus monophylla Torr. and Frem.) and juniper (Juniperus occidentalis Hook., J. osteosperma [Torr.] Little) are altering fire regimes and resulting in large-scale ecosystem transformations. Management treatments aim to increase resilience to disturbance and enhance resistance to invasive species...

  5. Crop advisor perceptions of giant ragweed distribution, herbicide-resistance, and management in the Corn Belt

    USDA-ARS?s Scientific Manuscript database

    Giant ragweed has been increasing as a major weed of row crops in North America. We conducted a web-based survey of Certified Crop Advisors in the Corn Belt to determine the current distribution of giant ragweed, the distribution of herbicide resistant populations, and management and ecological fact...

  6. Induced resistance – does it have potential as a tool in pecan disease management?

    USDA-ARS?s Scientific Manuscript database

    Pecan scab (Fusicladium effusum) causes losses of pecan nutmeat yield and quality in the southeastern US. New methods are needed to manage the disease. Plants possess resistance mechanisms that can be activated in response to infection with certain diseases (or damage from a pest). These mechanisms ...

  7. Seeds of change: corn seed mixtures for resistance management and IPM

    USDA-ARS?s Scientific Manuscript database

    The use of mixtures of insecticidal seed and non-toxic seed to provide an in-field refuge for susceptible insects in an insect-resistance-management (IRM) plan has been considered for at least two decades, but the US Environmental Protection Agency has only recently authorized their use in commercia...

  8. Overcoming resistance against managed care - insights from a bargaining model.

    PubMed

    Ehlert, Andree; Wein, Thomas; Zweifel, Peter

    2017-12-01

    Recent healthcare reforms have sought to increase efficiency by introducing managed care (MC) while respecting consumer preferences by admitting choice between MC and conventional care. This article proposes an institutional change designed to let German consumers choose between the two settings through directing payments from the Federal Health Fund to social health insurers (SHIs) or to specialized MC organizations (MCOs). To gauge the chance of success of this reform, a game involving a SHI, a MCO, and a representative insured (RI) is analyzed. In a "three-player/three-cake" game the coalitions {SHI, MCO}, {MCO, RI}, and {SHI, RI} can form. Players' possibility to switch between coalitions creates new outside options, causing the conventional bilateral Nash bargaining solution to be replaced by the so-called von Neumann-Morgenstern triple. These triples are compared to the status quo (where the RI has no threat potential) and related to institutional conditions characterizing Germany, the Netherlands, and Switzerland.

  9. The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis.

    PubMed

    Dheda, Keertan; Gumbo, Tawanda; Maartens, Gary; Dooley, Kelly E; McNerney, Ruth; Murray, Megan; Furin, Jennifer; Nardell, Edward A; London, Leslie; Lessem, Erica; Theron, Grant; van Helden, Paul; Niemann, Stefan; Merker, Matthias; Dowdy, David; Van Rie, Annelies; Siu, Gilman K H; Pasipanodya, Jotam G; Rodrigues, Camilla; Clark, Taane G; Sirgel, Frik A; Esmail, Aliasgar; Lin, Hsien-Ho; Atre, Sachin R; Schaaf, H Simon; Chang, Kwok Chiu; Lange, Christoph; Nahid, Payam; Udwadia, Zarir F; Horsburgh, C Robert; Churchyard, Gavin J; Menzies, Dick; Hesseling, Anneke C; Nuermberger, Eric; McIlleron, Helen; Fennelly, Kevin P; Goemaere, Eric; Jaramillo, Ernesto; Low, Marcus; Jara, Carolina Morán; Padayatchi, Nesri; Warren, Robin M

    2017-03-15

    Global tuberculosis incidence has declined marginally over the past decade, and tuberculosis remains out of control in several parts of the world including Africa and Asia. Although tuberculosis control has been effective in some regions of the world, these gains are threatened by the increasing burden of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. XDR tuberculosis has evolved in several tuberculosis-endemic countries to drug-incurable or programmatically incurable tuberculosis (totally drug-resistant tuberculosis). This poses several challenges similar to those encountered in the pre-chemotherapy era, including the inability to cure tuberculosis, high mortality, and the need for alternative methods to prevent disease transmission. This phenomenon mirrors the worldwide increase in antimicrobial resistance and the emergence of other MDR pathogens, such as malaria, HIV, and Gram-negative bacteria. MDR and XDR tuberculosis are associated with high morbidity and substantial mortality, are a threat to health-care workers, prohibitively expensive to treat, and are therefore a serious public health problem. In this Commission, we examine several aspects of drug-resistant tuberculosis. The traditional view that acquired resistance to antituberculous drugs is driven by poor compliance and programmatic failure is now being questioned, and several lines of evidence suggest that alternative mechanisms-including pharmacokinetic variability, induction of efflux pumps that transport the drug out of cells, and suboptimal drug penetration into tuberculosis lesions-are likely crucial to the pathogenesis of drug-resistant tuberculosis. These factors have implications for the design of new interventions, drug delivery and dosing mechanisms, and public health policy. We discuss epidemiology and transmission dynamics, including new insights into the fundamental biology of transmission, and we review the utility of newer diagnostic tools, including

  10. Anthelmintic activity of Artemisia annua L. extracts in vitro and the effect of an aqueous extract and artemisinin in sheep naturally infected with gastrointestinal nematodes.

    PubMed

    Cala, Aida C; Ferreira, Jorge F S; Chagas, Ana Carolina S; Gonzalez, Javier M; Rodrigues, Rodney A F; Foglio, Mary Ann; Oliveira, Marcia C S; Sousa, Ilza M O; Magalhães, Pedro M; Barioni Júnior, Waldomiro

    2014-06-01

    There is no effective natural alternative control for gastrointestinal nematodes (GIN) of small ruminants, with Haemonchus contortus being the most economically important GIN. Despite frequent reports of multidrug-resistant GIN, there is no new commercial anthelmintic to substitute failing ones. Although trematocidal activity of artemisinin analogs has been reported in sheep, neither artemisinin nor its plant source (Artemisia annua) has been evaluated for anthelmintic activity in ruminants. This study evaluated the anthelmintic activity of A. annua crude extracts in vitro and compared the most effective extract with artemisinin in sheep naturally infected with H. contortus. A. annua leaves extracted with water, aqueous 0.1% sodium bicarbonate, dichloromethane, and ethanol were evaluated in vitro by the egg hatch test (EHT) and with the bicarbonate extract only for the larval development test (LDT) using H. contortus. The A. annua water, sodium bicarbonate (SBE), ethanol, and dichloromethane extracts tested in vitro contained 0.3, 0.6, 4.4, and 9.8% of artemisinin, respectively. The sodium bicarbonate extract resulted in the lowest LC99 in the EHT (1.27 μg/mL) and in a LC99 of 23.8 μg/mL in the LDT. Following in vitro results, the SBE (2 g/kg body weight (BW)) and artemisinin (100 mg/kg BW) were evaluated as a single oral dose in naturally infected Santa Inês sheep. Speciation from stool cultures established that 84-91% of GIN were H. contortus, 8.4-15.6 % were Trichostrongylus sp., and 0.3-0.7% were Oesophagostomum sp. Packed-cell volume and eggs per gram (EPG) of feces were used to test treatment efficacy. The SBE tested in vivo contained no artemisinin, but had a high antioxidant capacity of 2,295 μmol of Trolox equivalents/g. Sheep dosed with artemisinin had maximum feces concentrations 24 h after treatment (126.5 μg/g artemisinin), which sharply decreased at 36 h. By day 15, only levamisole-treated sheep had a significant decrease of 97% in EPG

  11. Regulating insect resistance management: the case of non-Bt corn refuges in the US.

    PubMed

    Bourguet, Denis; Desquilbet, Marion; Lemarié, Stéphane

    2005-08-01

    In this paper, we analyze the insect resistance management (IRM) plan put in place by the US Environmental Protection Agency (EPA) to delay the evolution of resistance to Bt corn in natural populations of the European corn borer, Ostrinia nubilalis Hübner. This IRM plan is the most impressive mandatory IRM system ever developed. It forms a coherent whole and includes mandatory refuges, actions to increase growers' compliance and a program for monitoring the evolution of resistance. However, our analysis suggests that two components of this IRM plan are not entirely satisfactory: growers' compliance and monitoring of the evolution of resistance. Moreover, the implementation of these two components of IRM has been required of the registrants, whose incentives for IRM are probably lower than the social optimum. Our analysis suggests that alternatives to the IRM plan currently in place could improve these two components.

  12. Complex Interactions between Fungal Avirulence Genes and Their Corresponding Plant Resistance Genes and Consequences for Disease Resistance Management

    PubMed Central

    Petit-Houdenot, Yohann; Fudal, Isabelle

    2017-01-01

    During infection, pathogens secrete an arsenal of molecules, collectively called effectors, key elements of pathogenesis which modulate innate immunity of the plant and facilitate infection. Some of these effectors can be recognized directly or indirectly by resistance (R) proteins from the plant and are then called avirulence (AVR) proteins. This recognition usually triggers defense responses including the hypersensitive response and results in resistance of the plant. R—AVR gene interactions are frequently exploited in the field to control diseases. Recently, the availability of fungal genomes has accelerated the identification of AVR genes in plant pathogenic fungi, including in fungi infecting agronomically important crops. While single AVR genes recognized by their corresponding R gene were identified, more and more complex interactions between AVR and R genes are reported (e.g., AVR genes recognized by several R genes, R genes recognizing several AVR genes in distinct organisms, one AVR gene suppressing recognition of another AVR gene by its corresponding R gene, two cooperating R genes both necessary to recognize an AVR gene). These complex interactions were particularly reported in pathosystems showing a long co-evolution with their host plant but could also result from the way agronomic crops were obtained and improved (e.g., through interspecific hybridization or introgression of resistance genes from wild related species into cultivated crops). In this review, we describe some complex R—AVR interactions between plants and fungi that were recently reported and discuss their implications for AVR gene evolution and R gene management. PMID:28670324

  13. Greenhouse tests on resistance management of Bt transgenic plants using refuge strategies.

    PubMed

    Tang, J D; Collins, H L; Metz, T D; Earle, E D; Zhao, J Z; Roush, R T; Shelton, A M

    2001-02-01

    Experimental evaluation of the effectiveness of resistance management tactics is vital to help provide guidelines for the deployment of transgenic insecticidal crops. Transgenic broccoli expressing a Cry1Ac gene of Bacillus thuringiensis (Bt) and the diamondback moth, Plutella xylostella (L.), were used in greenhouse tests to evaluate the influence of size and placement of nontransgenic refuge plants on changes in resistance allele frequency and pest population growth. In the first test with an initial Cry1Ac-resistance (R) allele frequency of 0.007, P. xylostella were introduced into cages with the following treatments: 0, 3.3, 10, 20, and 100% refuge plants. Results after four generations showed that resistance could be delayed by increasing the proportion of refuge plants in the cage. Population growth was also influenced by refuge size with the highest populations occurring in treatments that had either no refuge plants or all refuge plants. In the second test, we evaluated the effect of refuge placement by comparing 20% separate and 20% mixed refuges. P. xylostella with an initial frequency of resistant alleles at 0.0125 were introduced into cages and allowed to cycle; later generations were evaluated for resistance and population growth. Separating the refuge had a pronounced effect on delaying resistance and slowing establishment of resistant larvae on Bt plants. Combining information from both trials, we found a strong negative correlation between the number of larvae on Bt plants and the mortality of the population in leaf dip bioassays. Results from larval movement studies showed that separate refuges delayed resistance better than mixed refuges because they conserved relatively more susceptible alleles than R alleles and did not increase the effective dominance of resistance.

  14. [Levamisole- and tetramisole-resistant gastrointestinal nematodes in sheep].

    PubMed

    Praslicka, J; Pilko, P; Várady, M; Corba, J

    1995-02-01

    Two experiments were carried out with sheep naturally infected with gastrointestinal nematodes to evaluate efficacy of anthelmintics using in vivo faecal egg count reduction (FECR) test. In experiment 1 with 28 ewes, the following efficacy of anthelmintics given at recommended dose rates was observed: albendazole 99.4%, ivermectin 99.3% and levamisole 81.8%. In experiment 2 with 18 ewes, tetramisole exhibited 71.3% efficacy. Suspected resistance to imidothiazole anthelmintics was confirmed by in vitro larval development test (LDT)--minimal inhibition concentration (MIC) values were estimated at 2.0 micrograms/ml. Infective larvae L3 cultivated from eggs produced by the population of resistant helminths were identified as Ostertagia and Trichostrongylus spp.

  15. Genotypic resistance tests in the management of the HIV-infected patient at virological failure.

    PubMed

    Aceti, Antonio; Carosi, Giampiero

    2003-01-01

    Witness for the prosecution: The IAS-USA and Euro-Resistance Group HIV guidelines recommend the use of resistance testing for all patients experiencing treatment failure for whom therapy change is being considered. However, these assays suffer from several limitations (problems in sensitivity, specificity, complexity of interpretation, cost) and the results of the prospective studies evaluating genotype-guided treatment in HIV patients failing antiretroviral treatment are inconclusive and partially contrasting (virological benefit is short-term). On this basis, incorporating genotypic resistance assays into the clinical management of HIV patients experiencing first treatment failure is not a sufficiently evidence-based practice. Witness for the defence: Highly active antiretroviral therapy (HAART) has markedly improved the prognosis of HIV-infected patients by controlling HIV replication. However, HAART fails to control HIV replication in an increasing number of patients as a result of a complex array of causes. There is now substantial evidence that the emergence of drug resistance is a leading cause (as well as consequence) of antiretroviral therapy failure. Moreover, HIV drug resistance can be transmitted and this can favour initial treatment failure. Several retrospective and prospective studies have indicated that both genotypic and phenotypic HIV-1 drug resistance testing results are associated with, or predictive of, the virological outcome. As a consequence, international guidelines have soundly recommended the use of resistance testing to guide treatment choices after virological failure. The rationale and advantages of using such testing after first virological failure will be discussed.

  16. Clinical Management of an Increasing Threat: Outpatient Urinary Tract Infections Due to Multidrug-Resistant Uropathogens.

    PubMed

    Walker, Emily; Lyman, Alessandra; Gupta, Kalpana; Mahoney, Monica V; Snyder, Graham M; Hirsch, Elizabeth B

    2016-10-01

    Urinary tract infections (UTIs) are among the most commonly treated bacterial infections. Over the past decade, antimicrobial resistance has become an increasingly common factor in the management of outpatient UTIs. As treatment options for multidrug-resistant (MDR) uropathogens are limited, clinicians need to be aware of specific clinical and epidemiological risk factors for these infections. Based on available literature, the activity of fosfomycin and nitrofurantoin remain high for most cases of MDR Escherichia coli UTIs. Trimethoprim-sulfamethoxazole retains clinical efficacy, but resistance rates are increasing internationally. Beta-lactam agents have the highest rates of resistance and lowest rates of clinical success. Fluoroquinolones have high resistance rates among MDR uropathogens and are being strongly discouraged as first-line agents for UTIs. In addition to accounting for local resistance rates, consideration of patient risk factors for resistance and pharmacological principles will help guide optimal empiric treatment of outpatient UTIs. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  17. Pest control and resistance management through release of insects carrying a male-selecting transgene.

    PubMed

    Harvey-Samuel, Tim; Morrison, Neil I; Walker, Adam S; Marubbi, Thea; Yao, Ju; Collins, Hilda L; Gorman, Kevin; Davies, T G Emyr; Alphey, Nina; Warner, Simon; Shelton, Anthony M; Alphey, Luke

    2015-07-16

    Development and evaluation of new insect pest management tools is critical for overcoming over-reliance upon, and growing resistance to, synthetic, biological and plant-expressed insecticides. For transgenic crops expressing insecticidal proteins from the bacterium Bacillus thuringiensis ('Bt crops') emergence of resistance is slowed by maintaining a proportion of the crop as non-Bt varieties, which produce pest insects unselected for resistance. While this strategy has been largely successful, multiple cases of Bt resistance have now been reported. One new approach to pest management is the use of genetically engineered insects to suppress populations of their own species. Models suggest that released insects carrying male-selecting (MS) transgenes would be effective agents of direct, species-specific pest management by preventing survival of female progeny, and simultaneously provide an alternative insecticide resistance management strategy by introgression of susceptibility alleles into target populations. We developed a MS strain of the diamondback moth, Plutella xylostella, a serious global pest of crucifers. MS-strain larvae are reared as normal with dietary tetracycline, but, when reared without tetracycline or on host plants, only males will survive to adulthood. We used this strain in glasshouse-cages to study the effect of MS male P. xylostella releases on target pest population size and spread of Bt resistance in these populations. Introductions of MS-engineered P. xylostella males into wild-type populations led to rapid pest population decline, and then elimination. In separate experiments on broccoli plants, relatively low-level releases of MS males in combination with broccoli expressing Cry1Ac (Bt broccoli) suppressed population growth and delayed the spread of Bt resistance. Higher rates of MS male releases in the absence of Bt broccoli were also able to suppress P. xylostella populations, whereas either low-level MS male releases or Bt broccoli

  18. Insecticide resistance in disease vectors from Mayotte: an opportunity for integrated vector management

    PubMed Central

    2014-01-01

    Background Mayotte, a small island in the Indian Ocean, has been affected for many years by vector-borne diseases. Malaria, Bancroftian filariasis, dengue, chikungunya and Rift Valley fever have circulated or still circulate on the island. They are all transmitted by Culicidae mosquitoes. To limit the impact of these diseases on human health, vector control has been implemented for more than 60 years on Mayotte. In this study, we assessed the resistance levels of four major vector species (Anopheles gambiae, Culex pipiens quinquefasciatus, Aedes aegypti and Aedes albopictus) to two types of insecticides: i) the locally currently-used insecticides (organophosphates, pyrethroids) and ii) alternative molecules that are promising for vector control and come from different insecticide families (bacterial toxins or insect growth regulators). When some resistance was found to one of these insecticides, we characterized the mechanisms involved. Methods Larval and adult bioassays were used to evaluate the level of resistance. When resistance was found, we tested for the presence of metabolic resistance through detoxifying enzyme activity assays, or for target-site mutations through molecular identification of known resistance alleles. Results Resistance to currently-used insecticides varied greatly between the four vector species. While no resistance to any insecticides was found in the two Aedes species, bioassays confirmed multiple resistance in Cx. p. quinquefasciatus (temephos: ~ 20 fold and deltamethrin: only 10% mortality after 24 hours). In An. gambiae, resistance was scarce: only a moderate resistance to temephos was found (~5 fold). This resistance appears to be due only to carboxyl-esterase overexpression and not to target modification. Finally, and comfortingly, none of the four species showed resistance to any of the new insecticides. Conclusions The low resistance observed in Mayotte’s main disease vectors is particularly interesting, because it leaves a

  19. Options for the management of antiviral resistance during hepatitis B therapy: reflections on battles over a decade

    PubMed Central

    2013-01-01

    Although much advancement has been achieved in the treatment of chronic hepatitis B, antiviral resistance is still a challenging issue. Previous generation antiviral agents have already developed resistance in a number of patients, and it is still being used especially in resource limited countries. Once antiviral resistance occurs, it predisposes to subsequent resistance, resulting in multidrug resistance. Therefore, prevention of initial antiviral resistance is the most important strategy, and appropriate choice and modification of therapy would be the cornerstone in avoiding treatment failures. Until now, management of antiviral resistance has been evolving from sequential therapy to combination therapy. In the era of tenofovir, the paradigm shifts again, and we have to decide when to switch and when to combine on the basis of newly emerging clinical data. We expect future eradication of chronic hepatitis B virus infection by proper prevention and optimal management of antiviral resistance. PMID:24133659

  20. Management of herbicide resistance in wheat cropping systems: learning from the Australian experience.

    PubMed

    Walsh, Michael J; Powles, Stephen B

    2014-09-01

    Herbicide resistance continues to escalate in weed populations infesting global wheat (Triticum aestivum L.) crops, threatening grain production and thereby food supply. Conservation wheat production systems are reliant on the use of efficient herbicides providing low-cost, selective weed control in intensive cropping systems. The resistance-driven loss of herbicide resources combined with limited potential for new herbicide molecules means greater emphasis must be placed on preserving existing herbicides. For more than two decades, since the initial recognition of the dramatic consequences of herbicide resistance, the challenge of introducing additional weed control strategies into herbicide-based weed management programmes has been formidable. Throughout this period, herbicide resistance has expanded unabated across the world's wheat production regions. However, in Australia, where herbicide resources have become desperately depleted, the adoption of harvest weed seed control is evidence, at last, of a successful approach to sustainable weed management in wheat production systems. Growers routinely including strategies to target weed seeds during crop harvest, as part of herbicide-based weed management programmes, are now realising significant weed control and crop production benefits. When combined with an attitude of zero weed tolerance, there is evidence of a sustainable weed control future for wheat production systems. The hard-learned lessons of Australian growers can now be viewed by global wheat producers as an example of how to stop the continual loss of herbicide resources in productive cropping systems. © 2013 Society of Chemical Industry.

  1. Quantifying immediate and delayed effects of anthelmintic exposure on ecosystem functioning supported by a common dung beetle species

    PubMed Central

    Beynon, Sarah A.; Lewis, Owen T.

    2017-01-01

    Dung beetles (Coleoptera: Scarabaeoidea) support numerous ecosystem functions in livestock-grazed pastures. Exposure to veterinary anthelmintic residues in livestock dung can have lethal and sublethal effects on dung beetles, and can reduce rates of dung removal, but the immediate and longer-term consequences for other dung beetle mediated functions have rarely been studied. We investigated the consequences of anthelmintic exposure on survival of the dung beetle Aphodius fossor and its delivery of four ecosystems functions that underpin pasture production: dung removal, soil fauna feeding activity, primary productivity, and reduction of soil compaction. We tested whether anthelmintic exposure had immediate or delayed effects on these functions individually and simultaneously (i.e., ecosystem multifunctionality). We found no evidence that ivermectin residues had a lethal effect on adult beetles. For dung removal, we found a significant interaction between the timing of exposure and functioning: while dung removal was impaired by concurrent exposure to high levels of ivermectin, functioning was unaffected when beetles that had been exposed previously to the same concentration of anthelmintic later interacted with untreated dung. Other ecosystem functions were not affected significantly by anthelmintic exposure, and there was no evidence to suggest any persistent impact of anthelmintic exposure on ecosystem multifunctionality. While anthelmintic residues remain a significant threat to dung beetle populations, for adult beetles, we found no evidence that residues have detrimental consequences for ecosystem functioning beyond the immediate point of exposure. PMID:28800623

  2. Quantifying immediate and delayed effects of anthelmintic exposure on ecosystem functioning supported by a common dung beetle species.

    PubMed

    Manning, Paul; Beynon, Sarah A; Lewis, Owen T

    2017-01-01

    Dung beetles (Coleoptera: Scarabaeoidea) support numerous ecosystem functions in livestock-grazed pastures. Exposure to veterinary anthelmintic residues in livestock dung can have lethal and sublethal effects on dung beetles, and can reduce rates of dung removal, but the immediate and longer-term consequences for other dung beetle mediated functions have rarely been studied. We investigated the consequences of anthelmintic exposure on survival of the dung beetle Aphodius fossor and its delivery of four ecosystems functions that underpin pasture production: dung removal, soil fauna feeding activity, primary productivity, and reduction of soil compaction. We tested whether anthelmintic exposure had immediate or delayed effects on these functions individually and simultaneously (i.e., ecosystem multifunctionality). We found no evidence that ivermectin residues had a lethal effect on adult beetles. For dung removal, we found a significant interaction between the timing of exposure and functioning: while dung removal was impaired by concurrent exposure to high levels of ivermectin, functioning was unaffected when beetles that had been exposed previously to the same concentration of anthelmintic later interacted with untreated dung. Other ecosystem functions were not affected significantly by anthelmintic exposure, and there was no evidence to suggest any persistent impact of anthelmintic exposure on ecosystem multifunctionality. While anthelmintic residues remain a significant threat to dung beetle populations, for adult beetles, we found no evidence that residues have detrimental consequences for ecosystem functioning beyond the immediate point of exposure.

  3. Monitoring and adaptive resistance management in Australia for Bt-cotton: current status and future challenges.

    PubMed

    Downes, Sharon; Mahon, Rod; Olsen, Karen

    2007-07-01

    In the mid-1990 s the Australian Cotton industry adopted an insect-resistant variety of cotton (Ingard) which expresses the Bt toxin Cry1Ac that is specific to a group of insects including the target Helicoverpa armigera. A conservative resistance management plan (RMP), that restricted the area planted to Ingard, was implemented to preserve the efficacy of Cry1Ac until two-gene transgenic cotton was available. In 2004/05 Bollgard II replaced Ingard as the transgenic cotton available in Australia. It improves on Ingard by incorporating an additional insecticidal protein (Cry2Ab). If an appropriate refuge is grown, there is no restriction on the area planted to Bollgard II. In 2004/05 and 2005/06 the Bollgard II acreage represented approximately 80 of the total area planted to cotton in Australia. The sensitivity of field-collected populations of H. armigera to Bt products was assayed before and subsequent to the widespread deployment of Ingard cotton. In 2002 screens against Cry2Ab were developed in preparation for replacement of Ingard with Bollgard II. There have been no reported field failures of Bollgard II due to resistance. However, while alleles that confer resistance to H. armigera in the field are rare for Cry1Ac, they are surprisingly common for Cry2Ab. We present an overview of the current approach adopted in Australia to monitor and adaptively manage resistance to Bt-cotton in field populations of H. armigera and discuss the implications of our findings to date. We also highlight future challenges for resistance management in Australia, many of which extend to other Bt-crop and pest systems.

  4. Organizational risk management of resistance to care episodes in health facilities.

    PubMed

    Kable, Ashley; Guest, Maya; McLeod, Mary

    2012-09-01

    This article reports a study of organizational risk management approaches to resistance to care episodes in specific clinical areas: prevention measures, provision of subsequent support and follow-up by management and resultant organizational change. Resistance to care describes a patient's unwillingness to be assisted by healthcare staff and is manifested in defensive behaviours ranging from minor non-compliance/dissent to aggression. It has previously been studied in aged care settings and focused on patient behaviours and appropriate responses. This was a cross-sectional survey of a representative sample of nurses (n = 5044) who were members of the New South Wales Nurses' Association in Australia, in 2008-2009. Of 1132 participants, 80% reported being involved in resistance to care episodes during the previous month and this was higher in some settings. Episodes were not routinely reported internally, and often did not lead to organizational change. Nurses reported that talking with other staff was the most effective action in dealing with the consequences of these episodes. Half of the respondents considered that they were provided with sufficient support and follow-up after a resistance to care episode. Prevention measures and follow-up strategies adopted by employers varied across clinical settings. Resistance to care is not confined to aged care settings, and risk management of resistance to care can increase safety in the workplace. Preventive strategies such as increased staff, training and security should be focused on high risk clinical areas; and appropriate support, follow-up and organizational change instituted in response to these episodes. © 2011 Blackwell Publishing Ltd.

  5. Epidemiology and Management of Emerging Drug-Resistant Gram-Negative Bacteria: Extended-Spectrum β-Lactamases and Beyond.

    PubMed

    Boyle, Daniel P; Zembower, Teresa R

    2015-11-01

    Worldwide prevalence of antimicrobial resistance is rapidly increasing, primarily a result of antibiotic misuse in the medical community. Resistant infections involving the urinary tract are typically caused by gram-negative bacteria. When treating these infections, clinicians have few effective antimicrobials to choose from and many are associated with significant adverse effects. There are now situations when clinicians are tasked with managing infections from pan-resistant organisms; thus, it is of paramount importance that spread of resistance be controlled. This review discusses common gram-negative resistance classes, highlighting the mechanisms of resistance, risk factors, type of infections, treatment, and outcomes associated with each class.

  6. Combining pest control and resistance management: synergy of engineered insects with Bt crops.

    PubMed

    Alphey, Nina; Bonsall, Michael B; Alphey, Luke

    2009-04-01

    Transgenic crops producing insecticidal toxins are widely used to control insect pests. Their benefits would be lost if resistance to the toxins became widespread in pest populations. The most widely used resistance management method is the high-dose/refuge strategy. This requires toxin-free host plants as refuges near insecticidal crops, and toxin doses intended to be sufficiently high to kill insects heterozygous for a resistant allele, thereby rendering resistance functionally recessive. We have previously shown by mathematical modeling that mass-release of harmless susceptible (toxin-sensitive) insects engineered with repressible female-specific lethality using release of insects carrying a dominant lethal ([RIDL] Oxitec Limited, United Kingdom) technology could substantially delay or reverse the spread of resistance and reduce refuge sizes. Here, we explore this proposal in depth, studying a wide range of scenarios, considering impacts on population dynamics as well as evolution of allele frequencies, comparing with releases of natural fertile susceptible insects, and examining the effect of seasonality. We investigate the outcome for pest control for which the plant-incorporated toxins are not necessarily at a high dose (i.e., they might not kill all homozygous susceptible and all heterozygous insects). We demonstrate that a RIDL-based approach could form an effective component of a resistance management strategy in a wide range of genetic and ecological circumstances. Because there are significant threshold effects for several variables, we expect that a margin of error would be advisable in setting release ratios and refuge sizes, especially as the frequency and properties of resistant alleles may be difficult to measure accurately in the field.

  7. Developing effective fumigation protocols to manage strongly phosphine-resistant Cryptolestes ferrugineus (Stephens) (Coleoptera: Laemophloeidae).

    PubMed

    Kaur, Ramandeep; Nayak, Manoj K

    2015-09-01

    The emergence of high levels of resistance in Cryptolestes ferrugineus (Stephens) in recent years threatens the sustainability of phosphine, a key fumigant used worldwide to disinfest stored grain. We aimed at developing robust fumigation protocols that could be used in a range of practical situations to control this resistant pest. Values of the lethal time to kill 99.9% (LT99 .9 , in days) of mixed-age populations, containing all life stages, of a susceptible and a strongly resistant C. ferrugineus population were established at three phosphine concentrations (1.0, 1.5 and 2.0 mg L(-1) ) and three temperatures (25, 30 and 35 °C). Multiple linear regression analysis revealed that phosphine concentration and temperature both contributed significantly to the LT99 .9 of a population (P < 0.003, R2 = 0.92), with concentration being the dominant variable, accounting for 75.9% of the variation. Across all concentrations, LT99.9 of the strongly resistant C. ferrugineus population was longest at the lowest temperature and shortest at the highest temperature. For example, 1.0 mg L(-1) of phosphine is required for 20, 15 and 15 days, 1.5 mg L(-1) for 12, 11 and 9 days and 2.0 mg L(-1) for 10, 7 and 6 days at 25, 30 and 35 °C, respectively, to achieve 99.9% mortality of the strongly resistant C. ferrugineus population. We also observed that phosphine concentration is inversely proportional to fumigation period in regard to the population extinction of this pest. The fumigation protocols developed in this study will be used in recommending changes to the currently registered rates of phosphine in Australia towards management of strongly resistant C. ferrugineus populations, and can be repeated in any country where this type of resistance appears. © 2014 Commonwealth of Australia. Pest Management Science © 2014 Society of Chemical Industry.

  8. Screening of plant extracts for anthelmintic activity against Dactylogyrus intermedius (Monogenea) in goldfish (Carassius auratus).

    PubMed

    Huang, Ai-Guo; Yi, Yang-Lei; Ling, Fei; Lu, Lin; Zhang, Qi-Zhong; Wang, Gao-Xue

    2013-12-01

    With the aim of finding natural anthelmintic agents against Dactylogyrus intermedius (Monogenea) in goldfish (Carassius auratus), 26 plants were screened for antiparasitic properties using in vivo anthelmintic efficacy assay. The results showed that Caesalpinia sappan, Lysima chiachristinae, Cuscuta chinensis, Artemisia argyi, and Eupatorium fortunei were found to have 100% anthelmintic efficacy at 125, 150, 225, 300, and 500 mg L(-1) after 48 h of exposure. Crude extract of the five plants were further partitioned with petroleum ether, chloroform, ethyl acetate, methanol, and water to obtain anthelmintically active fractions with various polarity. Among these fractions tested, the ethyl acetate extract of L. chiachristinae was found to be the most effective with a 50% effective concentration (EC50) value of 5.1 mg/L after 48 h of exposure. This was followed by ethyl acetate extract of C. chinensis (48 h-EC50 = 8.5 mg L(-1)), chloroform extracts of C. sappan (48 h-EC50 = 15.6 mg L(-1)), methanol extract of C. chinensis (48 h-EC50 = 15.9 mg L(-1)), and chloroform and petroleum ether extract of L. chiachristinae (EC50 values of 17.2 and 21.1 mg/L, respectively), suggesting that these plants, as well as the active fractions, provide potential sources of botanic drugs for the control of D. intermedius in aquaculture.

  9. Anthelmintic activity of Eucalyptus staigeriana encapsulated oil on sheep gastrointestinal nematodes.

    PubMed

    de Aquino Mesquita, Mayara; E Silva Júnior, João Batista; Panassol, Andressa Machado; de Oliveira, Erick Falcão; Vasconcelos, Ana Lourdes Camurça Fernandes; de Paula, Haroldo Cesar Beserra; Bevilaqua, Claudia Maria Leal

    2013-09-01

    The anthelmintic activity of Eucalyptus staigeriana essential oil has previously been inferred through both in vitro and in vivo tests. Thus, the encapsulation process generally improves oil stability, promotes controlled release in target organs, reduces dosage, and increases efficacy. The aims of this study were to analyze and encapsulate E. staigeriana essential oil and to verify its anthelmintic activity in sheep. The encapsulation process was accomplished through emulsion using a 4% chitosan solution as the matrix. Anthelmintic activity was established through controlled testing using 18 sheep that were separated into three groups: group 1 was treated with a single dose of 365 mg/kg of E. staigeriana encapsulated oil, group 2 was treated with 200 μg/kg of ivermectin, and group 3 was treated with a 4% chitosan solution as a negative control. The sheep were euthanized and necropsied 13 days posttreatment to evaluate worm burden. Limonene was the major oil component (72.91%). The final product was a hydrogel with 36.5% (m/m) E. staigeriana essential oil per gram. Its efficacy on gastrointestinal nematodes was 60.79%. The highest efficacy was against abomasal nematodes, with 83.75% efficacy. Further studies are necessary to explore the possibility of increasing the hydrogel efficacy; nevertheless, we can state that E. staigeriana encapsulated oil had anthelmintic activity and can be used in gastrointestinal nematode control.

  10. 21 CFR 357.152 - Package inserts for anthelmintic drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... the pinworm. (c) A commentary on the life cycle of the pinworm. (d) A commentary on the ways in which... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Package inserts for anthelmintic drug products... SERVICES (CONTINUED) DRUGS FOR HUMAN USE MISCELLANEOUS INTERNAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN...

  11. New Method for Analysis of Multiple Anthelmintic Residues in Animal Tissue

    USDA-ARS?s Scientific Manuscript database

    For the first time, 39 of the major anthelmintics can be detected in one rapid and sensitive LC-MS/MS method, including the flukicides, which have been generally overlooked in surveillance programs. Utilizing the QuEChERS approach, residues were extracted from liver and milk using acetonitrile, sod...

  12. Determination of anthelmintic drug residues in milk using UPLC-MS/MS with rapid polarity switching

    USDA-ARS?s Scientific Manuscript database

    A new UPLC-MS/MS (ultra-performance liquid chromatography coupled to tandem mass spectrometry) method was developed and validated to detect 38 anthelmintic drug residues, consisting of benzimidazoles, avermectins and flukicides. A modified QuEChERS-type extraction method was developed with an added...

  13. Phytochemical, Anti-oxidant and Anthelmintic activities of various leaf extracts of Flacourtia sepiaria Roxb

    PubMed Central

    Sreejith, M; Kannappan, N; Santhiagu, A; Mathew, Ajith P

    2013-01-01

    Objective The present study was carried out to investigate the phytochemical constituents, in vitro antioxidant potential and anthelmintic activities of Flacourtia sepiaria Roxb leaves. Methods The dried powdered leaves of Flacourtia sepiaria were extracted using petroleum ether, chloroform, ethyl acetate and methanol by a soxhlet extractor and preliminary phytochemical screening was performed using standard protocols. All the extract was evaluated for their potential antioxidant activities using test such as DPPH, superoxide anion radical, hydroxyl radical, nitric oxide radical scavenging abilities, ferrous chelating ability and total phenolic and flavanoid content. Anthelmintic activity of extract was screened in adult Indian earthworm model. Results Preliminary screening revealed the presence of bioactive compounds especially phenolics, tannins and terpenoids in all extracts. The phenolic and flavanoid content was highest in methanolic extract and lowest in petroleum ether extract. The paralytic (9.46±0.212) and death time (31.43±0.148) of methanolic extract was found to be significant (P<0.05) when compared with paralytic (7.33±0.206) and death time (18.60±0.229) of standard piperazine citrate at 100 mg/mL concentration. Conclusions The results of the present study indicate that the leaf extracts of Flacourtia sepiaria exhibited strong antioxidant activity and possess significant anthelmintic activity and thus it is a good source of antioxidant and anthelmintic constituents. PMID:24093785

  14. 21 CFR 500.25 - Anthelmintic drugs for use in animals.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... into effect without prior approval, as provided for in § 514.8(c)(3) of this chapter. For drugs listed... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Anthelmintic drugs for use in animals. 500.25 Section 500.25 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  15. 21 CFR 500.25 - Anthelmintic drugs for use in animals.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Anthelmintic drugs for use in animals. 500.25 Section 500.25 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS GENERAL Specific Administrative Rulings and...

  16. Anthelmintic potential of chicory forage is influenced by sesquiterpene lactone composition

    USDA-ARS?s Scientific Manuscript database

    The anthelmintic activity of chicory (Cichorium intybus L.) herbage has been attributed to sesquiterpene lactones (SLs). Chicory leaves contain lactucin (LAC), 8-deoxylactucin (DOL), and lactucopicrin (LPIC), but the amounts of these three SLs vary among cultivars. The objective of this study was...

  17. Anthelmintic constituents from ginger (Zingiber officinale) against Hymenolepis nana.

    PubMed

    Lin, Rong-Jyh; Chen, Chung-Yi; Lu, Chin-Mei; Ma, Yi-Hsuan; Chung, Li-Yu; Wang, Jiun-Jye; Lee, June-Der; Yen, Chuan-Min

    2014-12-01

    This study investigated the anthelmintic activity of gingerenone A, [6]-dehydrogingerdione, [4]-shogaol, 5-hydroxy-[6]-gingerol, [6]-shogaol, [6]-gingerol, [10]-shogaol, [10]-gingerol, hexahydrocurcumin, 3R,5S-[6]-gingerdiol and 3S,5S-[6]-gingerdiol, a constituent isolate from the roots of ginger, for the parasite Hymenolepis nana. The cestocidal activity or ability to halt spontaneous parasite movement (oscillation/peristalsis) in H. nana of above constituents was reached from 24 to 72h in a time- and dose-dependent manner, respectively. The [10]-shogaol and [10]-gingero1 have maximum lethal efficacy and loss of spontaneous movement than the others at 24-72h. In addition, worms treated with 1 and 10μM [10]-gingero1, more than 30% had spontaneous movement of oscillation at 72h but [10]-shogaol at 72h only about 15-20% of oscillation. This showing that [10]-gingero1 had less loss of spontaneous movement efficacy than [10]-shogaol. After exposure to 200μM [10]-shogaol, 100% of H. nana had died at 12h rather than died at 24h for [10]-gingerol, showing that [10]-gingero1 had less lethal efficacy than [10]-shogaol. In addition, these constituents of ginger showed effects against peroxyl radical under cestocidal activity. In order to evaluate the cestocidal activity and cytokine production caused by ginger's extract R0 in the H. nana infected mice, we carried out in vivo examination about H. nana infected mice BALB/c mice were inoculated orally with 500 eggs. After post-inoculation, R0 (1g/kg/day) was administered orally for 10 days. The R0 exhibited cestocidal activity in vivo of significantly reduced worms number and cytokines production by in vitro Con A-stimulated spleen cells showed that INF-γ and IL-2 were significantly increases by R0. IL-4, IL-5, IL-6, IL-10 and IL-13 were significantly decreases and Murine KC and IL-12 were not significantly changes by R0. Together, these findings first suggest that these constituents of ginger might be used as cestocidal

  18. Managing Pesticide Resistance in Potato Health Management, ed. D. Johnson. APS Press

    USDA-ARS?s Scientific Manuscript database

    Pesticides exert a selection pressure on pest populations and pests that are not controlled may produce progeny with genetic resistance to the pesticide. Pesticide classification systems based on site/mode of action have been developed and knowing a pesticides’s mode/site of action is key to planni...

  19. Anthelmintic activity of Trianthema portulacastrum L. and Musa paradisiaca L. against gastrointestinal nematodes of sheep.

    PubMed

    Hussain, Altaf; Khan, Muhammad Nisar; Iqbal, Zafar; Sajid, Muhammad Sohail; Khan, Muhammad Kasib

    2011-06-30

    Evaluation of anthelmintic effects of Trianthema (T.) portulacastrum L. (Aizoaceae) whole plant and Musa (M.) paradisiaca L. (Musaceae) leaves against prevalent gastrointestinal worms of sheep was done that may justify their traditional use in veterinary clinical medicine. In vitro anthelmintic activity of the crude aqueous methanolic extract (CAME) of both the plants was determined using mature female Haemonchus (H.) contortus and their eggs in adult motility assay (AMA) and egg hatch test (EHT), respectively. In vivo anthelmintic activity of crude powder (CP) and CAME in increasing doses (1.0-8.0 g kg(-1)) was determined in sheep naturally infected with mixed species of nematodes using fecal egg count reduction test (FECRT) and larval counts. The study design also included untreated as well as treated controls. Fecal egg count reduction and larval counts from coprocultures were performed pre- and post-treatments to assess the anthelmintic activity of the plants. CAME of T. portulacastrum and M. paradisiaca showed a strong in vitro anthelmintic activity and pronounced inhibitory effects on H. contortus egg hatching as observed through AMA and EHT, respectively. Both plants exhibited dose and time dependent anthelmintic effects on live worms as well as egg hatching. M. paradisiaca (LC(50)=2.13 μg mL(-1)) was found to be more potent than T. portulacastrum (LC(50)=2.41 μg mL(-1)) in EHT. However, in vivo, maximum reduction in eggs per gram (EPG) of faeces was recorded as 85.6% and 80.7% with CAME of T. portulacastrum and M. paradisiaca at 8.0 g kg(-1) on 15th day post-treatment, respectively as compared to that of Levamisole (7.5 mg kg(-1)) that caused 97.0% reduction in EPG. All the species of gastrointestinal nematodes (GINs), i.e. Haemonchus contortus, Trichostronglyus spp., Oesophagostomum columbianum and Trichuris ovis which were prevalent, found susceptible (P<0.01) to the different doses of CP and CAME of both plants. The data showed that both T

  20. [Anthelmintics as a risk factor in intestinal obstruction by Ascaris lumbricoides in children].

    PubMed

    Vásquez Tsuji, O; Gutiérrez Castrellón, P; Yamazaki Nakashimada, M A; Arredondo Suárez, J C; Campos Riveral, T; Martínez Barbosa, I

    2000-01-01

    In a retrospective study the authors analyzed the clinical records of 199 children ages one month to 16 years hospitalized, with the diagnosis of intestinal ascariasis, in the Instituto Nacional de Pediatria of Mexico from 1984 to 1999. The purpose of the study was to evaluate the use of anthelmintics drugs as a risk factor of intestinal obstruction by A. lumbricoides. Two groups were made for the study: Group A (n = 66) of children who presented intestinal obstruction, Group B (n = 133) children with no complications. A comparative analysis of clinical data of both groups was made by means of chi square with Yates correction and a stratified analysis by means of chi square. Possible confusing elements were overcrowding, age and the use of antiparasitic drugs. The calculus of risk factors for intestinal obstruction by A. lumbricoides was done by means of contingency tables of 2 x 2 and odds ratio with an IC of 95%. The significant risk factors were included in a model of logistics regression with an impact variable consting in the presence or absence of intestinal obstruction in order to establish a multivariate model of predictive risk at level of significance of p < 0.05. Twenty-seven patients (40.90%) in group A (n = 66) were given anthelmintics medications prior to the intestinal obstruction: mebendazol, 14 (51-85%); two, albedazol (7.4%); eight, a non-specified anthelmintic (29.6%). In addition, an anthelmintic medication without a specified time of ingestion: two with mebendazol and one with piperazine (11.3%). In the case of mebendazol, the drug most frequently associated with intestinal obstruction, seven patients received it on the same day of the obstruction; five patients received it between one and seven days prior to the obstruction; two received it seven days prior to the complication. In the control group, only 7% had taken the anthelmintic one to seven days before the diagnosis of uncomplicated intestinal ascariasis diagnosis was made. With the step