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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. 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

  5. Anthelmintic resistance in equine nematodes

    PubMed Central

    Matthews, Jacqueline B.

    2014-01-01

    Anthelmintics have been applied indiscriminately to control horse nematodes for over 40 years. Three broad-spectrum anthelmintic classes are currently registered for nematode control in horses: benzimidazoles (fenbendazole, oxibendazole), tetrahydropyrimidines (pyrantel) and macrocyclic lactones (ivermectin, moxidectin). Generally, control strategies have focused on nematode egg suppression regimens that involve the frequent application of anthelmintics to all horses at intervals based on strongyle egg reappearance periods after treatment. The widespread use of such programmes has substantially reduced clinical disease, especially that associated with large strongyle species; however, high treatment frequency has led to considerable selection pressure for anthelmintic resistance, particularly in cyathostomin species. Field studies published over the last decade indicate that benzimidazole resistance is widespread globally in cyathostomins and there are also many reports of resistance to pyrantel in these worms. Cyathostomin resistance to macrocyclic lactone compounds is emerging, principally measured as a reduction in strongyle egg reappearance time observed after treatment. Ivermectin resistance is a further concern in the small intestinal nematode, Parascaris equorum, an important pathogen of foals. These issues indicate that horse nematodes must now be controlled using methods less dependent on anthelmintic use and more reliant on management practices designed to reduce the force of infection in the environment. Such strategies include improved grazing management integrated with targeted anthelmintic administration involving faecal egg count (FEC)-directed treatments. The latter require that the supporting diagnostic tests available are robust and practically applicable. Recent research has focused on maximising the value of FEC analysis in horses and on optimizing protocols for anthelmintic efficacy testing. Other studies have sought to develop diagnostics

  6. 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.

  7. 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

  8. 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

  9. 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. PMID:27514894

  10. 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.

  11. 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

  12. 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.

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

    PubMed

    Kaplan, Ray M; Vidyashankar, Anand N

    2012-05-01

    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.

  14. [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.

  15. Anthelmintic Resistance in Haemonchus contortus: History, Mechanisms and Diagnosis.

    PubMed

    Kotze, A C; Prichard, R K

    2016-01-01

    Haemonchus contortus has shown a great ability to develop resistance to anthelmintic drugs. In many instances, resistance has appeared less than 10years after the introduction of a new drug class. Field populations of this species now show resistance to all major anthelmintic drug classes, including benzimidazoles (BZs), imidazothiazoles and macrocyclic lactones. In addition, resistance to the recently introduced amino-acetonitrile derivative class (monepantel) has already been reported. The existence of field populations showing resistance to all three major drug classes, and the early appearance of resistance to monepantel, threatens the sustainability of sheep and goat production systems worldwide. This chapter reviews the history of the development of resistance to the various anthelmintics in H. contortus and examines the mechanisms utilized by this species to resist the effects of these drugs. Some of these mechanisms are well understood, particularly for BZ drugs, while our knowledge and understanding of others are increasing. Finally, we summarize methods available for the diagnosis of resistance. While such diagnosis currently relies largely on the faecal egg count reduction test, which suffers from issues of expense and sensitivity, we describe past and current efforts to utilize cheaper and less laborious phenotypic assays with free-living life stages, and then describe progress on the development of molecular assays to provide sensitive resistance-detection tests. PMID:27238009

  16. 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.

  17. Climatic influences on development and survival of free-living stages of equine strongyles: implications for worm control strategies and managing anthelmintic resistance.

    PubMed

    Nielsen, Martin K; Kaplan, Ray M; Thamsborg, Stig M; Monrad, Jesper; Olsen, Susanne N

    2007-07-01

    Development of resistance to anthelmintic drugs by horse strongyles constitutes a growing threat to equine health because it is unknown when new drug classes can be expected on the market. Consequently, parasite control strategies should attempt to maintain drug efficacy for as long as possible. The proportion of a parasite population that is not exposed to anthelmintic treatment is described as being "in refugia" and although many factors affect the rate at which resistance develops, levels of refugia are considered the most important as these parasites are not selected by treatment and so provide a pool of sensitive genes in the population. Accordingly, treatment should be avoided when pasture refugia are small because such treatments will place significant selection pressure for resistance on worm populations. Given this new paradigm for parasite control, it has become important to identify seasons and circumstances wherein refugia are diminished. Free-living stages of equine strongyles are highly dependent on climatic influences, and this review summarises studies of strongyle development and survival under laboratory and field conditions in Northern (cool) temperate, Southern (warm) temperate and subtropical/tropical climates. In Northern temperate climates, refugia are smallest during the winter. In contrast, refugia are lowest during the summer in warm temperate and subtropical/tropical climates. Although adverse seasonal changes clearly have significant effects on the ability of free living stages of strongyle nematode parasites to survive and develop, available data suggest that climatic influences cannot effectively "clean" pastures from one grazing season to the next. PMID:16815051

  18. 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

  19. 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. PMID:19368252

  20. Anthelmintic resistance on goat farms in Georgia: efficacy of anthelmintics against gastrointestinal nematodes in two selected goat herds.

    PubMed

    Terrill, T H; Kaplan, R M; Larsen, M; Samples, O M; Miller, J E; Gelaye, S

    2001-06-28

    Gastrointestinal nematode (GIN) parasitism is a major constraint to production of goats in the southeastern United States. The conventional method of control used by producers in this region is frequent use of anthelmintics during the warm season. Overuse of anthelmintics has led to an increase in the incidence of anthelmintic resistance in many parts of the world, but data on prevalence of anthelmintic resistance in GIN of goats in the southeastern United States are very limited. To address this issue, anthelmintic efficacy was determined in goat herds at the Fort Valley State University, Agricultural Research Station (FVSU-ARS) and the University of Georgia, College of Veterinary Medicine (UGA-CVM) using fecal egg count reduction (FECR) tests and DrenchRite((R)) larval development assays (LDA). At FVSU-ARS, 2-year-old Spanish goat does were randomly allocated to one of nine different treatment groups (n = 10): albendazole (ABZ; 20mg/kg body weight (BW)), fenbendazole (FBZ; 20mg/kg BW), ivermectin (IVM; 0.4 mg/kg BW), doramectin (DRM; 0.4 mg/kg BW), moxidectin (MOX; 0.4 mg/kg BW), levamisole (LEV; 12 mg/kg BW), morantel tartrate (MOR; 10mg/kg BW), a combination of IVM (0.4 mg/kg BW) and ABZ (20 mg/kg BW), and untreated controls. At UGA-CVM, goats were randomly allocated to one of five different treatment groups (n = 8): ABZ (20 mg/kg BW), IVM (0.4 mg/kg BW), MOX (0.4 mg/kg BW), LEV (12 mg/kg BW), and untreated controls. All drugs in both experiments were administered orally. Anthelmintic efficacy was calculated by comparing 14-day post-treatment FEC of treated and control animals, and percent reductions were interpreted using the World Association for the Advancement of Veterinary Parasitology guidelines for resistance. For the LDA, nematode eggs were isolated from pooled fecal samples of untreated control goats in each herd and used to perform DrenchRite((R)) assays. In the FVSU-ARS herd, MOX, LEV, the combination of IVM and ABZ, IVM, DRM, ABZ, MOR, and FBZ

  1. Multiple anthelmintic resistance and the possible contributory factors in Beetal goats in an irrigated area (Pakistan).

    PubMed

    Saeed, Muhammad; Iqbal, Zafar; Jabbar, Abdul; Masood, Sabiqaa; Babar, Wasim; Saddiqi, Hafiz A; Yaseen, Muhammad; Sarwar, Muhammad; Arshad, Muhammad

    2010-04-01

    This paper presents the first report of multiple anthelmintic resistance in the gastrointestinal nematodes of goats and its possible contributory factors in an irrigated area (Pakistan). A total of 18 privately owned Beetal goat flocks were selected in order to determine the anthelmintic resistance against commonly used anthelmintics. Forty to 48 animals from each flock were selected according to their weight and egg count. The three anthelmintics viz., oxfendazole, levamisole and ivermectin, were given to three groups at manufacturer's recommended dose while one group was kept as untreated control. Anthelmintic resistance was determined through faecal egg count reduction and egg hatch tests while assessment of the contributory factors of anthelmintic resistance was measured through the rural participatory approach. Faecal egg count reduction test revealed high prevalence of anthelmintic resistance (83.3%) and it was either single (levamisole) or multiple (oxfendazole and levamisole). Egg hatch test confirmed the resistance against oxfendazole as detected with faecal egg count reduction test. None of the goat flocks was resistant to ivermectin. Copro-cultures revealed that Haemonchus contortus, Trichostrongylus colubriformis and Teladorsagia circumcincta were the most common species exhibiting resistance to levamisole and oxfendazole. Step-wise logistic regression of the data on worm control practices revealed significant role of under-dosing, low-protein diets, healthcare supervision by the traditional healers and mass treatments.

  2. 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

  3. Overview of anthelmintic resistance of gastrointestinal nematodes of small ruminants in Brazil.

    PubMed

    Salgado, Jordana Andrioli; Santos, Clóvis de Paula

    2016-01-01

    Frequent and inappropriate use of all classes of antiparasitic drugs in small ruminants has led to failures in their effectiveness, culminating in a global problem of anthelmintic resistance. Brazil stands out as one of the world's leaders in publications about anthelmintic resistance, and for having the most numerous reports of this resistance in small ruminants in the Americas. These studies have involved mainly the fecal egg count reduction test (FECRT) and its correlation with field management practices. In vivoeffectiveness testing is conducted in areas where livestock is of greater economic significance, e.g., in the South (sheep) and Northeast (goats), or is important for research and economic centers, such as the Southeast (sheep). The most widely studied species is sheep, for which the widest range of drugs is also evaluated. Despite significant advances achieved in molecular research, laboratory analyses should include knowledge about the reality in the field so that they can become feasible for the producer. Moreover, molecular studies can be underpinned by the analysis of field studies, such as the maintenance of antiparasitic effectiveness over time and the mechanisms involved in this process. PMID:26982560

  4. Combination anthelmintics effectively control ML-resistant parasites; a real-world case history.

    PubMed

    Smith, L L

    2014-07-30

    Routine investigation into an ill-thrift situation with grazing cattle led to the discovery of the first reported case of macrocyclic lactone (ML) resistance in cattle in the USA. Research revealed that resistant parasites were originating on pastures in southeastern USA and were not an anomalous resident population on Wisconsin pastures. Prior to using anthelmintics in combination, ML-resistant Cooperia and Haemonchus spp. were shown to survive treatment with single-active MLs and were being transported in shipped cattle and seeding summer grazing pastures. Treatment and management strategies implemented in 2011 and 2012 suggested that ML-surviving parasites were introduced into the conditioning facility and surviving treatment with ML. Data also demonstrated the use of combination ML+oral levamisole was highly effective in minimizing the transport of ML-surviving parasites from southeastern USA to Wisconsin pastures. The value of fecal egg count monitoring and PCR evaluation of nematode species under production conditions are confirmed.

  5. 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.

  6. Effect of Heterogeneous Mixing and Vaccination on the Dynamics of Anthelmintic Resistance: A Nested Model

    PubMed Central

    Sabatelli, Lorenzo

    2010-01-01

    Anthelmintic resistance is a major threat to current measures for helminth control in humans and animals. The introduction of anthelmintic vaccines, as a complement to or replacement for drug treatments, has been advocated as a preventive measure. Here, a computer-based simulation, tracking the dynamics of hosts, parasites and parasite-genes, shows that, depending on the degree of host-population mixing, the frequency of totally recessive autosomes associated with anthelmintic resistance can follow either a fast dynamical regime with a low equilibrium point or a slow dynamical regime with a high equilibrium point. For fully dominant autosomes, only one regime is predicted. The effectiveness of anthelminthic vaccines against resistance is shown to be strongly influenced by the underlying dynamics of resistant autosomes. Vaccines targeting adult parasites, by decreasing helminth fecundity or lifespan, are predicted to be more effective than vaccines targeting parasite larvae, by decreasing host susceptibility to infection, in reducing the spread of resistance. These results may inform new strategies to prevent, monitor and control the spread of anthelmintic resistance, including the development of viable anthelmintic vaccines. PMID:20502690

  7. Import and efflux of flubendazole in Haemonchus contortus strains susceptible and resistant to anthelmintics.

    PubMed

    Bártíková, Hana; Vokřál, Ivan; Kubíček, Vladimír; Szotáková, Barbora; Prchal, Lukáš; Lamka, Jiří; Várady, Marián; Skálová, Lenka

    2012-07-01

    Drug entry into the body of a helminth is a key factor in the efficacy of anthelmintics. The present project was designed to study the ex vivo uptake and efflux of the benzimidazole anthelmintic flubendazole (FLU) in four strains of H. contortus: the ISE strain (fully susceptible to anthelmintics), the ISE-S strain (resistant to ivermectin), the BR strain (resistant to benzimidazoles) and the WR strain (multi-resistant). The transport of FLU between dead and living nematodes was also compared as well as the effect of verapamil, an inhibitor of the main efflux ABCB1 transporter (P-glycoprotein), on FLU accumulation in nematodes. The obtained results showed that FLU is able to effectively enter H. contortus adults due to high FLU lipophilicity. Passive diffusion is probably the only mechanism in both FLU import and efflux from nematodes. No differences in FLU transport were found among four H. contortus strains with different sensitivity to anthelmintics. No active FLU efflux from H. contortus and no effect of verapamil were observed, indicating that H. contortus cannot protect itself against FLU by the active removal of this anthelmintic from its body.

  8. Haemonchus contortus as a paradigm and model to study anthelmintic drug resistance.

    PubMed

    Gilleard, John S

    2013-10-01

    Anthelmintic resistance is a major problem for the control livestock parasites and a potential threat to the sustainability of community-wide treatment programmes being used to control human parasites in the developing world. Anthelmintic resistance is essentially a complex quantitative trait in which multiple mutations contribute to the resistance phenotype in an additive manner. Consequently, a combination of forward genetic and genomic approaches are needed to identify the causal mutations and quantify their contribution to the resistance phenotype. Therefore, there is a need to develop genetic and genomic approaches for key parasite species identified as relevant models. Haemonchus contortus, a gastro-intestinal parasite of sheep, has shown a remarkable propensity to develop resistance to all the drugs used in its control. Partly because of this, and partly because of its experimental amenability, research on this parasite has contributed more than any other to our understanding of anthelmintic resistance. H. contortus offers a variety of advantages as an experimental system including the ability to undertake genetic crosses; a prerequisite for genetic mapping. This review will discuss the current progress on developing H. contortus as a model system in which to study anthelmintic resistance. PMID:23998513

  9. 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.

  10. Efficacy of monepantel and anthelmintic combinations against multiple-resistant Haemonchus contortus in sheep, including characterisation of the nematode isolate.

    PubMed

    Baker, K E; George, S D; Stein, P A; Seewald, W; Rolfe, P F; Hosking, B C

    2012-05-25

    Three experiments defined the resistance profile of a population of Haemonchus contortus, which was shown to express multiple resistances to the benzimidazole, levamisole, macrocyclic lactone and salicylanilide anthelmintic classes when given as a registered combination. Study 1 was a faecal egg count reduction (FECR) test and the efficacies for the anthelmintics were monepantel, 100%; abamectin+levamisole+oxfendazole, 40.0%; and abamectin+levamisole+oxfendazole+naphthalophos, 100%. No larvae were recovered from the post-treatment cultures for monepantel or the 4-way treatment, and for the 3-way treatment the culture was 100% Haemonchus spp. Efficacies in Study 2 were calculated from mean post-mortem nematode burdens of H. contortus and were levamisole+oxfendazole, 3.1%; abamectin+levamisole+oxfendazole, 5.0%; ivermectin, 0.4%; moxidectin, 28.4% and closantel, 70.2%. Study 3 was also a FECR test that resulted in efficacies of 100% for monepantel and 83.0% for a formulated 4-way combination of abamectin+levamisole+albendazole+closantel. Larvae recovered from the post-treatment culture for the combination-treated sheep were all Haemonchus spp. Multi-resistant parasites such as examined in these studies are a continuing challenge to be managed by farmers and their advisors. Control programs must be planned and well-managed, and should include on-farm testing for anthelmintic resistance, monitoring of nematode burdens (by FEC and larval culture) to determine appropriate treatment times and the management of pastures to reduce the overall parasite challenge. This should be in balance with the generation, use and maintenance of drug-susceptible nematode populations in refugia.

  11. 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

  12. Decline in faecal worm egg counts in lambs suckling ewes treated with lipophilic anthelmintics: implications for hastening development of anthelmintic resistance.

    PubMed

    Dever, M L; Kahn, L P

    2015-04-30

    The aim for this experiment was to look for evidence of milk transfer of anthelmintic actives from ewes to their suckling lambs by reference to lambs' faecal worm egg count (WEC). The hypothesis was that WEC will decline in lambs suckling ewes treated with anthelmintics known to be lipophilic. One group of lactating Border Leicester×Merino ewes were treated (TX) with a combination of short (2.5mg/kg monepantel) and long-acting (1mg/kg moxidectin long-acting injection and a sustained release of 4.62g albendazole over 100 days) anthelmintics to remove gastrointestinal nematode (GIN) burden on day 0. The other group of lactating ewes (UTX) and all lambs (White Suffolk sires) were not treated. Ewes and lambs grazed as a single group and were exposed to GIN (predominately Haemonchus contortus) infection from pasture. Measurements were taken on days 0 and 7. WEC of lambs suckling UTX ewes increased from 6441 to 10,341 eggs per gram (epg) between days 0 and 7, while there was a 51% reduction in WEC for lambs suckling TX ewes. Packed cell volume (PCV) was significantly higher for lambs suckling TX ewes on day 7 compared to lambs suckling UTX ewes (28.5% vs. 24.9%, p=0.039). These results suggest that lambs suckling ewes treated with lipophilic anthelmintics received a sub-therapeutic dose via milk which would increase selection within the GIN (H. contortus) population for anthelmintic resistance.

  13. 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 (%).

  14. 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

  15. 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.

  16. 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

  17. 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

    2014-04-01

    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.

  18. In Vitro Anthelmintic Assay.

    PubMed

    2016-01-01

    Nematodes are believed to have originated 1000 million years ago as free living anaerobic benthic organisms. Modern anthelmintic drugs have been in use but the worms have created resistance to most of the broad spectrum anthelmintics such as benzimidazoles, levamisole, avermectins, etc. However, these drugs cause side effects. More recently, plant extracts have been reported as having developed resistance against anthelmintics. A study using earthworms to determine the activity has been developed and explained in a well-defined manner in this chapter.

  19. Is anthelmintic resistance a concern for the control of human soil-transmitted helminths?

    PubMed Central

    Vercruysse, Jozef; Albonico, Marco; Behnke, Jerzy M.; Kotze, Andrew C.; Prichard, Roger K.; McCarthy, James S.; Montresor, Antonio; Levecke, Bruno

    2011-01-01

    The major human soil-transmitted helminths (STH), Ascaris lumbricoides, hookworms (Necator americanus and Ancylostoma duodenale) and Trichuris trichiura have a marked impact on human health in many parts of the world. Current efforts to control these parasites rely predominantly on periodic mass administration of anthelmintic drugs to school age children and other at-risk groups. After many years of use of these same drugs for controlling roundworms in livestock, high levels of resistance have developed, threatening the sustainability of these livestock industries in some locations. Hence, the question arises as to whether this is likely to also occur in the human STH, thereby threatening our ability to control these parasites. This is particularly important because of the recent increase in mass control programmes, relying almost exclusively on benzimidazole anthelmintics. It will be important to ensure that resistance is detected as it emerges in order to allow the implementation of mitigation strategies, such as use of drug combinations, to ensure that the effectiveness of the few existing anthelmintic drugs is preserved. In this review we address these issues by firstly examining the efficacy of anthelmintics against the human STH, and assessing whether there are any indications to date that resistance has emerged. We then consider the factors that influence the effect of current drug-use patterns in selecting for resistant parasite populations. We describe the tools currently available for resistance monitoring (field-based coprological methods), and those under development (in vitro bioassays and molecular tests), and highlight confounding factors that need to be taken into account when interpreting such resistance-monitoring data. We then highlight means to ensure that the currently available tools are used correctly, particularly with regard to study design, and we set appropriate drug-efficacy thresholds. Finally, we make recommendations for monitoring

  20. [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.

  1. [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. PMID:6631911

  2. [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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. The metabolism of flubendazole and the activities of selected biotransformation enzymes in Haemonchus contortus strains susceptible and resistant to anthelmintics.

    PubMed

    Vokřál, Ivan; Bártíková, Hana; Prchal, Lukáš; Stuchlíková, Lucie; Skálová, Lenka; Szotáková, Barbora; Lamka, Jiří; Várady, Marián; Kubíček, Vladimír

    2012-09-01

    Haemonchus contortus is one of the most pathogenic parasites of small ruminants (e.g. sheep and goat). The treatment of haemonchosis is complicated because of recurrent resistance of H. contortus to common anthelmintics. The aim of this study was to compare the metabolism of the anthelmintic drug flubendazole (FLU) and the activities of selected biotransformation enzymes towards model xenobiotics in 4 different strains of H. contortus: the ISE strain (susceptible to common anthelmintics), ISE-S (resistant to ivermectin), the BR strain (resistant to benzimidazole anthelmintics) and the WR strain (resistant to all common anthelmintics). H. contortus adults were collected from the abomasums from experimentally infected lambs. The in vitro as well as ex vivo experiments were performed and analysed using HPLC with spectrofluorimetric and mass-spectrometric detection. In all H. contortus strains, 4 different FLU metabolites were detected: FLU with a reduced carbonyl group (FLU-R), glucose conjugate of FLU-R and 2 glucose conjugates of FLU. In the resistant strains, the ex vivo formation of all FLU metabolites was significantly higher than in the susceptible ISE strain. The multi-resistant WR strain formed approximately 5 times more conjugates of FLU than the susceptible ISE strain. The in vitro data also showed significant differences in FLU metabolism, in the activities of UDP-glucosyltransferase and several carbonyl-reducing enzymes between the susceptible and resistant H. contortus strains. The altered activities of certain detoxifying enzymes might protect the parasites against the toxic effect of the drugs as well as contribute to drug-resistance in these parasites.

  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.

  9. 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

  10. 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

  11. 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

  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. In Vitro Anthelmintic Assay.

    PubMed

    2016-01-01

    Nematodes are believed to have originated 1000 million years ago as free living anaerobic benthic organisms. Modern anthelmintic drugs have been in use but the worms have created resistance to most of the broad spectrum anthelmintics such as benzimidazoles, levamisole, avermectins, etc. However, these drugs cause side effects. More recently, plant extracts have been reported as having developed resistance against anthelmintics. A study using earthworms to determine the activity has been developed and explained in a well-defined manner in this chapter. PMID:26939269

  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. 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

  16. Modelling the short- and long-term impacts of drenching frequency and targeted selective treatment on the performance of grazing lambs and the emergence of anthelmintic resistance.

    PubMed

    Laurenson, Yan C S M; Bishop, Stephen C; Forbes, Andrew B; Kyriazakis, Ilias

    2013-05-01

    Refugia-based treatment strategies aim to prolong anthelmintic efficacy by maintaining a parasite population unexposed to anthelmintics. Targeted selective treatment (TST) achieves this by treating only animals that will benefit most from treatment, using a determinant criterion (DC). We developed a mathematical model to compare various traits proposed as DC, and investigate impacts of TST and drenching frequency on sheep performance and anthelmintic resistance. Short term, decreasing the proportion of animals drenched reduced benefits of anthelmintic treatment, assessed by empty body weight (EBW), but decreased the rate of anthelmintic resistance development; each consecutive drenching had a reduced impact on average EBW and an increased impact on the rate of anthelmintic resistance emergences. The optimal DC was fecal egg count, maintaining the highest average EBW when reducing the proportion of animals drenched. Long-term, reducing the proportion of animals drenched had little impact on total weight gain benefits, across animals and years, whilst reducing drenching frequency increased it. Decreasing the frequency and proportion of animals drenched were both predicted to increase the duration of anthelmintic efficacy but reduce the total number of drenches administered before resistance was observed. TST and frequency of drenching may lead to different benefits in the short versus long term.

  17. 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.…

  18. 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.

  19. Tannin rich peanut skins lack anthelmintic properties

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  20. Methods to determine resistance to anthelmintics when continuing larval development occurs.

    PubMed

    Lyndal-Murphy, M; Swain, A J; Pepper, P M

    2014-01-31

    The in vivo faecal egg count reduction test (FECRT) is the most commonly used test to detect anthelmintic resistance (AR) in gastrointestinal nematodes (GIN) of ruminants in pasture based systems. However, there are several variations on the method, some more appropriate than others in specific circumstances. While in some cases labour and time can be saved by just collecting post-drench faecal worm egg counts (FEC) of treatment groups with controls, or pre- and post-drench FEC of a treatment group with no controls, there are circumstances when pre- and post-drench FEC of an untreated control group as well as from the treatment groups are necessary. Computer simulation techniques were used to determine the most appropriate of several methods for calculating AR when there is continuing larval development during the testing period, as often occurs when anthelmintic treatments against genera of GIN with high biotic potential or high re-infection rates, such as Haemonchus contortus of sheep and Cooperia punctata of cattle, are less than 100% efficacious. Three field FECRT experimental designs were investigated: (I) post-drench FEC of treatment and controls groups, (II) pre- and post-drench FEC of a treatment group only and (III) pre- and post-drench FEC of treatment and control groups. To investigate the performance of methods of indicating AR for each of these designs, simulated animal FEC were generated from negative binominal distributions with subsequent sampling from the binomial distributions to account for drench effect, with varying parameters for worm burden, larval development and drench resistance. Calculations of percent reductions and confidence limits were based on those of the Standing Committee for Agriculture (SCA) guidelines. For the two field methods with pre-drench FEC, confidence limits were also determined from cumulative inverse Beta distributions of FEC, for eggs per gram (epg) and the number of eggs counted at detection levels of 50 and 25. Two

  1. 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.

  2. 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. PMID:26542261

  3. 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.

  4. Evaluation of anthelmintic resistance of intestinal parasitic nematodes in heifers in south central Nebraska

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Internal parasitic nematodes impact the livestock industry through losses in reproductive efficiency, rate of gain, carcass quality, milk production, or immune response. The frequent use of anthelmintics with drug formulations in which chemical activity persists for long periods selects for worm re...

  5. Comparison of calculation methods used for the determination of anthelmintic resistance in sheep in a temperate continental climate.

    PubMed

    Falzon, L C; van Leeuwen, J; Menzies, P I; Jones-Bitton, A; Sears, W; Jansen, J T; Peregrine, A S

    2015-04-01

    This study compared results obtained with five different fecal egg count reduction (FECR) calculation methods for defining resistance to ivermectin, fenbendazole, and levamisole in gastrointestinal nematodes of sheep in a temperate continental climate: FECR1 and FECR2 used pre-and posttreatment fecal egg count (FEC) means from both treated and control animals, but FECR1 used arithmetic means, whereas FECR2 used geometric means; FECR3 used arithmetic means for pre- and posttreatment FECs from treated animals only; FECR4 was calculated using only arithmetic means for posttreatment FECs from treated and control animals; and FECR5 was calculated using mean FEC estimates from a general linear mixed model. The classification of farm anthelmintic resistance (AR) status varied, depending on which FECR calculation method was used and whether a bias correction term (BCT, i.e., half the minimum detection limit) was added to the zeroes or not. Overall, agreement between all methods was higher when a BCT was used, particularly when levels of resistance were low. FECR4 showed the highest agreement with all the other FECR methods. We therefore recommend that small ruminant clinicians use the FECR4 formula with a BCT for AR determination, as this would reduce the cost of the FECRT, while still minimizing bias and allowing for comparisons between different farms. For researchers, we recommend the use of FECR1 or FECR2, as the inclusion of both pre- and posttreatment FECs and use of randomly allocated animals in treatment and control groups makes these methods mathematically more likely to estimate the true anthelmintic efficacy.

  6. Evaluation of a larval development assay (DrenchRite) for the detection of anthelmintic resistance in cyathostomin nematodes of horses.

    PubMed

    Tandon, R; Kaplan, R M

    2004-05-01

    A larval development assay (LDA, DrenchRite) was evaluated to determine the effectiveness of this method in detecting anthelmintic resistance in cyathostomin nematodes of horses. A total of 15 horse farms from Georgia and South Carolina (USA) and Population S ponies from the University of Kentucky (USA) were included in this study. Nematode eggs were extracted from pooled fecal samples and placed into the wells of a DrenchRite plate for testing against thiabendazole (TBZ), levamisole (LEV) and 2 ivermectin (IVM) analogs (IVM-1, IVM-2). After a 7-day incubation larvae in each well were counted and data were analyzed by logistic regression. Resistance status of each farm for different drugs was determined in a separate study using a fecal egg count reduction test. LDA were performed on the 15 farms once, however, the Population S cyathostomins were assayed on 3 separate occasions to estimate the consistency of results between assays. Mean TBZ LC50 for oxibendazole resistant, suspected resistant and sensitive farms were 0.2015, 0.1625, and 0.1355 microM, respectively. For LEV, mean LC50 for PYR resistant, suspected resistant and sensitive farms were 1.590, 1.8018 and 1.4219 microM, respectively. All 15 farms had worms susceptible to IVM; mean LC50 for IVM-1 and for IVM-2 were 7.5727 and 87.9718 nM, respectively. A linear mixed model was fitted to the data to determine the relationship between LC50 and LC95 and resistance status for each farm. No meaningful relations were found. Consistency of assays varied between drugs, being best for TBZ and worst for LEV and IVM-1. All farms in this study had benzimidazole-resistant nematodes; therefore usefulness of DrenchRite for discriminating susceptibility versus resistance to this drug class could not be accurately assessed. Moreover, since all farms tested were sensitive to IVM and resistance to this drug class has not yet been reported in cyathostomins, it is not possible to assess accurately the usefulness of Drench

  7. Anthelmintic resistance in Northern Ireland. II: Variations in nematode control practices between lowland and upland sheep flocks.

    PubMed

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

    2013-02-18

    A questionnaire to obtain information on nematode control practices and sheep management was sent to over 1000 farmers in Northern Ireland. Replies were received from 305 flock owners, and data from 252 of them were analysed. Farms were divided into lowland and upland areas. Sizes of pasture and stocking rates on lowland and upland farms were 59.5 hectares, 6.99 sheep/hectare and 62.9 hectares and 10.01 sheep/hectare, respectively. Mean drenching rates for lambs and adults were 2.33 and 2.44, respectively, in lowland flocks and 2.73 and 2.71, respectively, in upland flocks. Between 2008 and 2011, the most frequently identified compounds in use were benzimidazoles and moxidectin in lowland flocks, and benzimidazoles and avermectins in upland flocks. Over the same period the most frequently identified commercial formulations were Tramazole(®), Panacur(®) and Allverm(®) (white drench), Levacide(®) (yellow drench), Oramec(®) (clear drench; avermectin), Cydectin(®) (clear drench; moxidectin) and Monepantel(®) (orange drench). Most respondents (56.35%) treated their lambs at weaning and the most common time to treat ewes was identified to be pre-mating (67.86% of respondents). The results of the questionnaire survey revealed that lowland annual drench frequency was 2.33 and 2.44 in lambs and ewes, respectively, although drench frequencies were higher in upland flocks: 2.73 and 2.71 for lambs and ewes, respectively. Annual drench rotation was practiced by 43.96% of flock owners, but whether this was true rotation or pseudo-rotation (i.e., substitution of one anthelmintic product by another product belonging to the same chemical group of anthelmintics) could not be explicitly determined. PMID:23228496

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. [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. PMID:27405218

  14. [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.

  15. 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.

  16. 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. PMID:23583362

  17. 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.

  18. Caenorhabditis elegans is a useful model for anthelmintic discovery.

    PubMed

    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

    2015-06-25

    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.

  19. Genetic evidence for hybridisation between Haemonchus contortus and Haemonchus placei in natural field populations and its implications for interspecies transmission of anthelmintic resistance.

    PubMed

    Chaudhry, Umer; Redman, Elizabeth M; Abbas, Muhammad; Muthusamy, Raman; Ashraf, Kamran; Gilleard, John S

    2015-02-01

    introgression of drug resistance loci. We believe this is the first definitive genetic evidence of hybridisation between H. contortus and H. placei in the field and represents the most comprehensive genetic evidence of F1 hybrids between any human or livestock parasitic nematode species to date. Further, it suggests that interspecies transmission of anthelmintic resistance mutations warrants further investigation. PMID:25449043

  20. 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. PMID:26220023

  1. 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.

  2. 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.

  3. 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...

  4. 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

  5. Effects of three anthelmintic schedules on the incidence of colic in horses.

    PubMed

    Uhlinger, C

    1990-07-01

    Four privately owned herds (25 to 49 animals per herd) were used in a five-year trial designed to evaluate the effect of anthelmintic schedules on the incidence of colic. These herds had been treated bi-monthly with non-ivermectin, non-benzimidazole drugs for two years before the trial. Prior parasitological studies showed that they had substantial pre-treatment faecal egg counts (900 to 2200 eggs per gramme), and that they were infected with benzimidazole-resistant cyathostomes. In Years 1 and 2 of the trial, all herds (A, B, C, D) were treated bi-monthly with non-ivermectin anthelmintics (Schedule I). In Years 3 to 5, Herd A received monthly non-ivermectin anthelmintics (Schedule II) and Herd C was treated with bi-monthly ivermectin (Schedule III). Herd B was treated with Schedule II in Years 3 and 4 and Schedule III in Year 5. Herd D was maintained on Schedule I throughout the study period. In each herd, the incidence of colic, while on Schedule I, was compared to the incidence while on Schedule II or III. The risk of colic for horses on Schedule I was 2.61 to 13.04 times that of the same horses while on Schedule II and 2.27 to 9.64 times that of the same horses while on Schedule III. In Herd D, treated according to Schedule I for five years, the incidence of colic did not vary significantly throughout the study period. More effective anthelmintic treatment schedules decreased the incidence of colic in these herds, supporting the conclusion that bimonthly treatment with non-ivermectin drugs may not maximise horses' health in all management conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. 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

  7. 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

    2016-01-01

    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. PMID:27543148

  8. 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

  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

    2014-01-01

    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. PMID:25517625

  11. Reprofiled anthelmintics abate hypervirulent stationary-phase Clostridium difficile.

    PubMed

    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

  12. Reprofiled anthelmintics abate hypervirulent stationary-phase Clostridium difficile.

    PubMed

    Gooyit, Major; Janda, Kim D

    2016-09-16

    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.

  13. 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

  14. 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

  15. 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

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

    PubMed

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

    2015-07-01

    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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  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. The in vitro motility response to various anthelmintics of third-stage larvae of Oesophagostomum spp. from pigs.

    PubMed

    Várady, M; Corba, J; Hrcková, G

    1998-07-01

    The in vitro activities of thiabendazole, levamisole, pyrantel, morantel and ivermectin against Oesophagostomum spp., the nodular worm of pigs, were determined and compared. The study was carried out using isolates of O. dentatum and O. quadrispinulatum, which had been defined in vivo. Infective larvae were exposed to the anthelmintics for 24 h and then placed in a micromotility meter. All the treatments significantly reduced the motility of the ensheathed L3 larvae, but the micromotility meter was not able to differentiate between anthelmintic resistant and anthelmintic susceptible isolates.

  20. 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

  1. Medical Management of Drug-Resistant Tuberculosis

    PubMed Central

    2015-01-01

    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. PMID:26175768

  2. 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.

  3. 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

  4. 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. PMID:23768565

  5. 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. PMID:20980034

  6. Non-interventional management of resistant hypertension

    PubMed Central

    Doumas, Michael; Tsioufis, Costas; Faselis, Charles; Lazaridis, Antonios; Grassos, Haris; Papademetriou, Vasilios

    2014-01-01

    Hypertension is one of the most popular fields of research in modern medicine due to its high prevalence and its major impact on cardiovascular risk and consequently on global health. Indeed, about one third of individuals worldwide has hypertension and is under increased long-term risk of myocardial infarction, stroke or cardiovascular death. On the other hand, resistant hypertension, the “uncontrollable” part of arterial hypertension despite appropriate therapy, comprises a much greater menace since long-standing, high levels of blood pressure along with concomitant debilitating entities such as chronic kidney disease and diabetes mellitus create a prominent high cardiovascular risk milieu. However, despite the alarming consequences, resistant hypertension and its effective management still have not received proper scientific attention. Aspects like the exact prevalence and prognosis are yet to be clarified. In an effort to manage patients with resistant hypertension appropriately, clinical doctors are still racking their brains in order to find the best therapeutic algorithm and surmount the substantial difficulties in controlling this clinical entity. This review aims to shed light on the effective management of resistant hypertension and provide practical recommendations for clinicians dealing with such patients. PMID:25349652

  7. 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

  8. 21 CFR 357.110 - Anthelmintic active ingredient.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Anthelmintic active ingredient. 357.110 Section 357.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Anthelmintic Drug Products § 357.110 Anthelmintic active ingredient. The active ingredient of the product...

  9. 21 CFR 357.110 - Anthelmintic active ingredient.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Anthelmintic active ingredient. 357.110 Section 357.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Anthelmintic Drug Products § 357.110 Anthelmintic active ingredient. The active ingredient of the product...

  10. 21 CFR 357.110 - Anthelmintic active ingredient.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Anthelmintic active ingredient. 357.110 Section 357.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Anthelmintic Drug Products § 357.110 Anthelmintic active ingredient. The active ingredient of the product...

  11. 21 CFR 357.110 - Anthelmintic active ingredient.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Anthelmintic active ingredient. 357.110 Section 357.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Anthelmintic Drug Products § 357.110 Anthelmintic active ingredient. The active ingredient of the product...

  12. 21 CFR 357.110 - Anthelmintic active ingredient.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Anthelmintic active ingredient. 357.110 Section 357.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Anthelmintic Drug Products § 357.110 Anthelmintic active ingredient. The active ingredient of the product...

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

    PubMed

    Ouzir, M; Berrag, B; Benjouad, A; Cabaret, J

    2011-08-25

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

  14. Efficacy of major anthelmintics against horse cyathostomins in France.

    PubMed

    Traversa, Donato; Castagna, Giuseppe; von Samson-Himmelstjerna, Georg; Meloni, Silvana; Bartolini, Roberto; Geurden, Thomas; Pearce, Michael C; Woringer, Emmanuel; Besognet, Bruno; Milillo, Piermarino; D'Espois, Melanie

    2012-09-10

    This paper reports a survey conducted in France during 2011 to evaluate the efficacy of commonly used anthelmintics against horse cyathostomins. A total of 40 farms and 1089 horses were screened for the presence of cyathostomins. All farms but one were positive, with an overall animal infection rate of 53.7%, ranging from 9% to 83% on individual farms. On 445 horses from 30 of these farms, a faecal egg count reduction test (FECRT) was performed to evaluate the efficacy of oral formulations of fenbendazole (FBZ), pyrantel embonate (PYR), ivermectin (IVM) and moxidectin (MOX). Calculation of the mean FECR and 95% confidence intervals (95% CI) around the mean was performed using bootstrap analysis. Resistance to FBZ was found on 17 of 18 farms investigated, with a mean reduction of 57% (95% CI: 38.5-71.2%). Suspected resistance for PYR was found on 6 of 30 farms, and confirmed on another 3 of 30 farms, with a mean reduction for PYR of 94.7% (95% CI: 88.9-98.5%). Reduced efficacy simultaneously of FBZ and PYR was found in 7 farms. Reduced efficacy of IVM was found in one animal on one farm and of MOX in one animal on another farm, and was combined with resistance against FBZ and/or PYR. These results indicate that single and multiple drug resistance and reduced efficacy in equine cyathostomins is present in France. Macrocylic lactones proved to be highly effective compounds against cyathostomins, with reduced efficacy for IVM and MOX in two farms only. These results extend present knowledge on the occurrence of drug resistant cyathostomins in Europe, and illustrate the necessity to use anthelmintics in appropriate worm control programmes.

  15. 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.

  16. Discovery of a highly synergistic anthelmintic combination that shows mutual hypersusceptibility

    PubMed Central

    Hu, Yan; Platzer, Edward G.; Bellier, Audrey; Aroian, Raffi V.

    2010-01-01

    The soil-transmitted helminths or nematodes (hookworms, whipworms, and Ascaris) are roundworms that infect more than 1 billion of the poorest peoples and are leading causes of morbidity worldwide. Few anthelmintics are available for treatment, and only one is commonly used in mass drug administrations. New anthelmintics are urgently needed, and crystal (Cry) proteins made by Bacillus thuringiensis are promising new candidates. Combination drug therapies are considered the ideal treatment for infectious diseases. Surprisingly, little work has been done to define the characteristics of anthelmintic combinations. Here, by means of quantitative assays with wild-type and mutants of the roundworm Caenorhabditis elegans, we establish a paradigm for studying anthelmintic combinations using Cry proteins and nicotinic acetylcholine receptor (nAChR) agonists, e.g., tribendimidine and levamisole. We find that nAChR agonists and Cry proteins, like Cry5B and Cry21A, mutually display what is known in the HIV field as hypersusceptibility—when the nematodes become resistant to either class, they become hypersensitive to the other class. Furthermore, we find that when Cry5B and nAChR agonists are combined, their activities are strongly synergistic, producing combination index values as good or better than seen with antitumor, anti-HIV, and insecticide combinations. Our study provides a powerful means by which anthelmintic combination therapies can be examined and demonstrate that the combination of nAChR agonists and Cry proteins has excellent properties and is predicted to give improved cure rates while being recalcitrant to the development of parasite resistance. PMID:20231450

  17. Best management practices for herbicide resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  18. Statistical approach to measure the efficacy of anthelmintic treatment on horse farms.

    PubMed

    Vidyashankar, A N; Kaplan, R M; Chan, S

    2007-12-01

    Resistance to anthelmintics in gastrointestinal nematodes of livestock is a serious problem and appropriate methods are required to identify and quantify resistance. However, quantification and assessment of resistance depend on an accurate measure of treatment efficacy, and current methodologies fail to properly address the issue. The fecal egg count reduction test (FECRT) is the practical gold standard for measuring anthelmintic efficacy on farms, but these types of data are fraught with high variability that greatly impacts the accuracy of inference on efficacy. This paper develops a statistical model to measure, assess, and evaluate the efficacy of the anthelmintic treatment on horse farms as determined by FECRT. Novel robust bootstrap methods are developed to analyse the data and are compared to other suggested methods in the literature in terms of Type I error and power. The results demonstrate that the bootstrap methods have an optimal Type I error rate and high power to detect differences between the presumed and true efficacy without the need to know the true distribution of pre-treatment egg counts. Finally, data from multiple farms are studied and statistical models developed that take into account between-farm variability. Our analysis establishes that if inter-farm variability is not taken into account, misleading conclusions about resistance can be made.

  19. Lack of Cyathostomin sp. reduction after anthelmintic treatment in horses in Brazil.

    PubMed

    Canever, Ricardo J; Braga, Pollyana R C; Boeckh, Albert; Grycajuck, Marcelly; Bier, Daniele; Molento, Marcelo B

    2013-05-01

    The increase of anthelmintic resistance in the last years in the nematode population of veterinary importance has become a major concern. The objective of the present study was to evaluate the efficacy of the main anthelmintic drugs available in the market against small strongyles of horses in Brazil. A total of 498 horses from 11 horse farms, located in the states of Paraná, São Paulo, Rio de Janeiro and Minas Gerais, in Brazil, were treated with ivermectin, moxidectin, pyrantel and fenbendazole, orally at their recommended doses. The fecal egg count reduction test (FECRT) was used to determine the product's efficacy and fecal culture was used to determine the parasite genus. Reduction on anthelmintic efficacy was found for fenbendazole in all horse farms (11/11), pyrantel in five yards (5/11) and ivermectin had low efficacy in one of the yards studied (1/11). Multidrug resistance of up to 3 drugs classes was found in one of the tested farms (1/11). Cyathostomin were the most prevalent parasite. The results showed that resistance to fenbendazole is widespread; the efficacy of pyrantel is in a critical situation. Although the macrocyclic lactones compounds still showed high efficacy on most farms, suspected resistance to macrocyclic lactones is of great concern.

  20. 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

  1. 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. PMID:11237142

  2. High level of treatment failure with commonly used anthelmintics on Irish sheep farms

    PubMed Central

    2014-01-01

    Background In 2013 a Technology Adoption Program for sheep farmers was established to encourage the implementation of best management practices on sheep farms in Ireland. There were 4,500 participants in this programme in 2013. As part of this programme, farmers had the option to carry out a drench test to establish the efficacy of their anthelmintic treatment. Results Flock faecal samples were collected before and after treatment administration and gastrointestinal nematode eggs enumerated. In total there were 1,893 participants in the task, however only 1,585 included both a pre- and post-treatment faecal sample. Of those, 1,308 provided information on the anthelmintic product that they used with 46%, 23% and 28% using a benzimidazole (BZ), levamisole (LEV) and macrocyclic lactone (ML) product respectively. The remaining farmers used a product inapplicable for inclusion in the task such as a flukicide or BZ/LEV combination product. Samples were included for analysis of drench efficacy if the pre-treatment flock egg count was ≥200 eggs per gram and the interval post-sampling was 10–14 days for BZ products, 4–7 days for LEV products and 14–18 days for ML products. These criteria reduced the number of valid tests to 369, 19.5% of all tests conducted. If the reduction post-treatment was ≥95% the treatment was considered effective. Only 51% of treatments were considered effective using this criterion. There was a significant difference in efficacy between the anthelmintic drug classes with BZ effective in only 30% of treatments, LEV effective in 52% of cases and ML effective in 76% of cases. Conclusions Gastrointestinal nematode anthelmintic treatments, as practiced on Irish farms, have a high failure rate. There was a significant difference between the efficacies of the anthelmintic classes with BZ the least effective and ML the most effective. PMID:25140223

  3. 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

  4. 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.

  5. 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. PMID:27238006

  6. Substitution of benzimidazole-resistant nematodes for susceptible nematodes in grazing lambs.

    PubMed

    Moussavou-Boussougou, M-N; Silvestre, A; Cortet, J; Sauve, C; Cabaret, J

    2007-04-01

    Multi-drug-resistant gastrointestinal nematode parasite populations are becoming more and more prevalent. Since anthelmintic treatments are of limited effectiveness, one solution could be to replace the anthelmintic-resistant population by a susceptible population, in order to re-establish the possibility of drug-based anthelmintic control. We investigated this substitution strategy in 4 paddocks of 0.7 ha, each of which was seeded with a benzimidazole-resistant Teladorsagia circumcincta population. The proportion of benzimidazole-resistant worms in these paddocks ranged from 20% to 89%. A 2-step replacement was performed: first, the paddocks were not grazed for 6 months (from December to July), and then the grass was cut to eliminate any residual infective larvae, before contaminating each of the paddocks with 10 seeder lambs experimentally infected with a benzimidazole-susceptible strain of T. circumcincta (from July to November). At the end of the experiment, all the populations on the 4 paddocks were phenotypically benzimidazole-susceptible, but genotyping indicated that 2 populations harboured 1% and 3% resistant worms respectively. This study demonstrates that nematode replacement is feasible in temperate areas, using semi-intensive stock management, even when the initial levels of benzimidazole-resistance are very high. Further research should next assess replacing the whole community to cope with the species diversity observed under field conditions. PMID:17096872

  7. IN VITRO ANTHELMINTIC EFFICACY OF NATIVE PLANTS AGAINST HAEMONCHUS CONTORTUS.

    PubMed

    Jabeen, Nyla; Anwar, Sadaf; Mahmood, Qaisar; Zia, Muhammad Abid; Murtaza, Ghulam

    2015-01-01

    The current study aimed to investigate in vitro anthelmintic efficacy of two medicinally important plants against Haemonchus contortus in small ruminants. Fruit peel of Punica granatum Linn. (vern. Anar), leaves and roots of Berberis lycium Royle (vern. Sumbal) were tested for their anthelmintic efficacy. Methanolic extracts of the test plants from various plant parts were tested for anthelmintic efficacy against the Haemonchus contortous using albendazole as a reference standard. The results revealed that both the plant extracts exhibited potent anthelmintic activity at concentrations higher than 50 mg/mL when tested against their respective standard drug. In case of Berberis lycium Royle when the results were compared, methanolic roots extracts showed more potent activity as compared to leaves extracts at the same concentration. It was observed that the in vitro anthelmintic potential of Punica granatum Linn. fruit peel and Berberis lyceium Royale root can be used to treat helminth infections after in vivo trails. PMID:26665413

  8. IN VITRO ANTHELMINTIC EFFICACY OF NATIVE PLANTS AGAINST HAEMONCHUS CONTORTUS.

    PubMed

    Jabeen, Nyla; Anwar, Sadaf; Mahmood, Qaisar; Zia, Muhammad Abid; Murtaza, Ghulam

    2015-01-01

    The current study aimed to investigate in vitro anthelmintic efficacy of two medicinally important plants against Haemonchus contortus in small ruminants. Fruit peel of Punica granatum Linn. (vern. Anar), leaves and roots of Berberis lycium Royle (vern. Sumbal) were tested for their anthelmintic efficacy. Methanolic extracts of the test plants from various plant parts were tested for anthelmintic efficacy against the Haemonchus contortous using albendazole as a reference standard. The results revealed that both the plant extracts exhibited potent anthelmintic activity at concentrations higher than 50 mg/mL when tested against their respective standard drug. In case of Berberis lycium Royle when the results were compared, methanolic roots extracts showed more potent activity as compared to leaves extracts at the same concentration. It was observed that the in vitro anthelmintic potential of Punica granatum Linn. fruit peel and Berberis lyceium Royale root can be used to treat helminth infections after in vivo trails.

  9. 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

  10. 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…

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

    PubMed

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

    2015-09-01

    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

  13. Efficacy of selected anthelmintic drugs against cyathostomins in horses in the federal state of Brandenburg, Germany.

    PubMed

    Fischer, Juliane K; Hinney, Barbara; Denwood, Matthew J; Traversa, Donato; von Samson-Himmelstjerna, Georg; Clausen, Peter-Henning

    2015-12-01

    Cyathostomins are currently the most common internal parasites of horses. With the intensive use of anthelmintic drugs over the past decades, resistance of cyathostomins to anthelmintics is becoming a growing problem in many countries. The aim of this study was to assess the current situation on horse farms in the German federal state of Brandenburg. A pre-selected population of horses from 24 premises that had shown a prevalence of cyathostomins higher than the average in a previous study was examined for anthelmintic efficacy. Faecal egg count reduction tests (FECRTs) were performed for ivermectin (IVM) and pyrantel (PYR). For IVM, the egg reappearance period (ERP) was also examined, as a shortened ERP can be indicative of developing resistance. The efficacy of IVM on cyathostomins was high: 99.1 % of 224 horses had a zero egg count 14 days after treatment. No shortening of the ERP was detected. For the data of the FECRT for PYR, three different methods of calculation were employed: (a) the method as recommended by the World Association for the Advancement of Veterinary Parasitology (WAAVP), (b) a bootstrapping method and (c) a Markov chain Monte Carlo method. Two methods of interpretation for these data were used: Resistance was declared (a) when FECR was <90 % and the lower 95 % confidence interval (LCL) <80 % and (b) when additionally the upper 95 % confidence level (UCL) was <95 %. When applying the first interpretation, resistance against PYR was found on four yards, while, when considering the UCL, all three methods for calculation only detected resistance on one single yard. Twelve species of cyathostomins were detected in larval cultures derived from strongyle egg positive faecal samples collected 14 days after treatment with PYR by reverse line blot hybridization (RLB). In order to generate comparable data, it is suggested to establish international standards for the calculation of FECRT data. PMID:26337266

  14. Efficacy of selected anthelmintic drugs against cyathostomins in horses in the federal state of Brandenburg, Germany.

    PubMed

    Fischer, Juliane K; Hinney, Barbara; Denwood, Matthew J; Traversa, Donato; von Samson-Himmelstjerna, Georg; Clausen, Peter-Henning

    2015-12-01

    Cyathostomins are currently the most common internal parasites of horses. With the intensive use of anthelmintic drugs over the past decades, resistance of cyathostomins to anthelmintics is becoming a growing problem in many countries. The aim of this study was to assess the current situation on horse farms in the German federal state of Brandenburg. A pre-selected population of horses from 24 premises that had shown a prevalence of cyathostomins higher than the average in a previous study was examined for anthelmintic efficacy. Faecal egg count reduction tests (FECRTs) were performed for ivermectin (IVM) and pyrantel (PYR). For IVM, the egg reappearance period (ERP) was also examined, as a shortened ERP can be indicative of developing resistance. The efficacy of IVM on cyathostomins was high: 99.1 % of 224 horses had a zero egg count 14 days after treatment. No shortening of the ERP was detected. For the data of the FECRT for PYR, three different methods of calculation were employed: (a) the method as recommended by the World Association for the Advancement of Veterinary Parasitology (WAAVP), (b) a bootstrapping method and (c) a Markov chain Monte Carlo method. Two methods of interpretation for these data were used: Resistance was declared (a) when FECR was <90 % and the lower 95 % confidence interval (LCL) <80 % and (b) when additionally the upper 95 % confidence level (UCL) was <95 %. When applying the first interpretation, resistance against PYR was found on four yards, while, when considering the UCL, all three methods for calculation only detected resistance on one single yard. Twelve species of cyathostomins were detected in larval cultures derived from strongyle egg positive faecal samples collected 14 days after treatment with PYR by reverse line blot hybridization (RLB). In order to generate comparable data, it is suggested to establish international standards for the calculation of FECRT data.

  15. Nematode cys-loop GABA receptors: biological function, pharmacology and sites of action for anthelmintics.

    PubMed

    Accardi, Michael V; Beech, Robin N; Forrester, Sean G

    2012-06-01

    Parasitic nematode infection of humans and livestock is a major problem globally. Attempts to control nematode populations have led to the development of several classes of anthelmintic, which target cys-loop ligand-gated ion channels. Unlike the vertebrate nervous system, the nematode nervous system possesses a large and diversified array of ligand-gated chloride channels that comprise key components of the inhibitory neurotransmission system. In particular, cys-loop GABA receptors have evolved to play many fundamental roles in nematode behaviour such as locomotion. Analysis of the genomes of several free-living and parasitic nematodes suggests that there are several groups of cys-loop GABA receptor subunits that, for the most part, are conserved among nematodes. Despite many similarities with vertebrate cys-loop GABA receptors, those in nematodes are quite distinct in sequence similarity, subunit composition and biological function. With rising anthelmintic resistance in many nematode populations worldwide, GABA receptors should become an area of increased scientific investigation in the development of the next generation of anthelmintics. PMID:22430311

  16. Gaining Insights Into the Pharmacology of Anthelmintics Using Haemonchus contortus as a Model Nematode.

    PubMed

    Lanusse, C E; Alvarez, L I; Lifschitz, A L

    2016-01-01

    Progress made in understanding pharmacokinetic behaviour and pharmacodynamic mechanisms of drug action/resistance has allowed deep insights into the pharmacology of the main chemical classes, including some of the few recently discovered anthelmintics. The integration of pharmaco-parasitological research approaches has contributed considerably to the optimization of drug activity, which is relevant to preserve existing and novel active compounds for parasite control in livestock. A remarkable amount of pharmacology-based knowledge has been generated using the sheep abomasal nematode Haemonchus contortus as a model. Relevant fundamental information on the relationship among drug influx/efflux balance (accumulation), biotransformation/detoxification and pharmacological effects in parasitic nematodes for the most traditional anthelmintic chemical families has been obtained by exploiting the advantages of working with H. contortus under in vitro, ex vivo and in vivo experimental conditions. The scientific contributions to the pharmacology of anthelmintic drugs based on the use of H. contortus as a model nematode are summarized in the present chapter. PMID:27238011

  17. Nematode cys-loop GABA receptors: biological function, pharmacology and sites of action for anthelmintics.

    PubMed

    Accardi, Michael V; Beech, Robin N; Forrester, Sean G

    2012-06-01

    Parasitic nematode infection of humans and livestock is a major problem globally. Attempts to control nematode populations have led to the development of several classes of anthelmintic, which target cys-loop ligand-gated ion channels. Unlike the vertebrate nervous system, the nematode nervous system possesses a large and diversified array of ligand-gated chloride channels that comprise key components of the inhibitory neurotransmission system. In particular, cys-loop GABA receptors have evolved to play many fundamental roles in nematode behaviour such as locomotion. Analysis of the genomes of several free-living and parasitic nematodes suggests that there are several groups of cys-loop GABA receptor subunits that, for the most part, are conserved among nematodes. Despite many similarities with vertebrate cys-loop GABA receptors, those in nematodes are quite distinct in sequence similarity, subunit composition and biological function. With rising anthelmintic resistance in many nematode populations worldwide, GABA receptors should become an area of increased scientific investigation in the development of the next generation of anthelmintics.

  18. Insect resistance management in GM crops: past, present and future.

    PubMed

    Bates, Sarah L; Zhao, Jian-Zhou; Roush, Richard T; Shelton, Anthony M

    2005-01-01

    Transgenic plants expressing insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) were first commercialized in 1996 amid concern from some scientists, regulators and environmentalists that the widespread use of Bt crops would inevitably lead to resistance and the loss of a 'public good,' specifically, the susceptibility of insect pests to Bt proteins. Eight years later, Bt corn and cotton have been grown on a cumulative area >80 million ha worldwide. Despite dire predictions to the contrary, resistance to a Bt crop has yet to be documented, suggesting that resistance management strategies have been effective thus far. However, current strategies to delay resistance remain far from ideal. Eight years without resistance provides a timely opportunity for researchers, regulators and industry to reassess the risk of resistance and the most effective strategies to preserve Bt and other novel insect-resistant crops in development.

  19. Management of multidrug-resistant tuberculosis.

    PubMed

    Iseman, M D

    1999-01-01

    Drug-resistant tuberculosis (TB) originally is the product of inadequate therapy; this may entail noncompliance with treatment, interrupted drug supplies, or inappropriate prescription. Patients may sequentially acquire resistance to several drugs through repetition of this process. Loss of activity of the major drugs greatly compromises the treatment process; most problematic is resistance to both isoniazid and rifampicin, so-called 'multidrug-resistant tuberculosis' (MDR-TB). Recent evidence indicates that MDR-TB is being transmitted to others, and particularly to persons with HIV infection/AIDS. Other situations in which epidemic spread of MDR-TB occurs include hospitals and prisons. In several areas of the world, ominous levels of MDR-TB have been identified in a recent WHO survey. Treatment of MDR-TB entails the use of poorly tolerated, second-line medications that are often toxic, and the duration of treatment must be extended to the range of two years. Resectional surgery may be required to effect cures in patients with advanced disease in which most of the first-line agents have been lost to resistance.

  20. Framing the issues of resistance management in soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  1. 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...

  2. [Management of multidrug-resistant tuberculosis].

    PubMed

    Tritar, F; Daghfous, H; Ben Saad, S; Slim-Saidi, L

    2015-01-01

    The emergence of drug-resistant TB in many countries has become a major public health problem and an obstacle to effective tuberculosis control. Multidrug-resistant tuberculosis (MDR-TB), which is most often the result of poor adherence, is a particularly dangerous form of tuberculosis because it is caused by bacilli resistant to at least isoniazid and rifampicin, the two most effective anti-tuberculosis drugs. Techniques for rapid diagnosis of resistance have greatly improved the care of patients by allowing early treatment which remains complex and costly establishment, and requires skills and resources. The treatment is not standardized but it includes in all cases attack phase with five drugs (there must be an injectable agent and a fluoroquinolone that form the basis of the regimen) for eight months and a maintenance phase (without injectable agent) with a total duration of 20 months on average. Surgery may be beneficial as long as the lesions are localized and the patient has a good cardiorespiratory function. Evolution of MDR-TB treated is less favorable than tuberculosis with germ sensitive. The cure rate varies from 60 to 75% for MDR-TB, and drops to 30 to 40% for XDR-TB. Mortality remains high, ranging from 20 to 40% even up to 70-90% in people co-infected with HIV.

  3. Managing the evolution of herbicide resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  4. 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

  5. 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

  6. Echinocandin resistance, susceptibility testing and prophylaxis: implications for patient management.

    PubMed

    Perlin, David S

    2014-09-01

    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

  7. 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)

  8. 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.

  9. 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. PMID:21548004

  10. Factors affecting pharmacokinetics of benzimidazole anthelmintics in food-producing animals: the consequences and potential risks.

    PubMed

    Křížová-Forstová, V; Lamka, J; Cvilink, V; Hanušová, V; Skálová, L

    2011-12-01

    Benzimidazoles are frequently and widely used veterinary anthelmintics. Unfortunately, an administration of these anthelmintics does not always result in the expected therapeutic success. Many host-related factors modify pharmacokinetic behavior and efficacy of a chosen anthelmintic. Pharmacokinetics of anthelmintics varies among animals of different species, sex and age. Also diseases, medication, feed and environmental conditions can significantly affect behavior of anthelmintics and resultant drug efficacy in animals. The presented review gathers information, gained in last 20 years, on factors which bring about the variability in performance of benzimidazole anthelmintics in food-producing animals. It is focused particularly on differences in absorption and metabolism of these anthelmintics as these stages of the pharmacokinetic process seem to be the most important for the overall anthelmintic efficacy. The consequences of abnormalities and alterations in pharmacokinetics of benzimidazole anthelmintics are summarized and discussed.

  11. [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.

  12. 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.

  13. 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. PMID:27089119

  14. 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

  15. 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.

  16. 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.

  17. CREATING INVASION RESISTANT SOILS VIA NITROGEN MANAGEMENT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Invasion by annual grasses, such as cheatgrass, into the western USA sagebrush steppe and the associated increase in fire frequency are major concerns of ecologists and resource managers. Maintaining or improving ecosystem health depends on our ability to protect or re-establish functioning, desire...

  18. SOIL NITROGEN MANAGEMENT AND INVASION RESISTANCE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  19. 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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  1. 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. PMID:11197758

  2. 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.

  3. Concept and Management of Treatment Resistant Schizophrenia (TRS)

    PubMed Central

    Painuly, Nitesh; Gupta, Nitin; Avasthi, Ajit

    2004-01-01

    Treatment resistance in schizophrenia is a fairly common problem faced by psychiatrists worldwide. The concept and definition of Treatment Resistant Schizophrenia (TRS) is still far from satisfactory. Data suggests the presence of biological factors underlying TRS. Second generation antipsychotics are advocated for patients with TRS. However, till date, clozapine remains the treatment of choice. Evidence for other pharmacological measures and ECT is accumulating. Psychosocial interventions do form an integral component of management of TRS. It can be concluded that, with advances in sychopharmacology, TRS needs to be better researched and managed in the future. PMID:21408038

  4. 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

  5. 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

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

    PubMed

    Green, Jerry M; Owen, Micheal D K

    2011-06-01

    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.

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

    PubMed

    Green, Jerry M; Owen, Micheal D K

    2011-06-01

    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

  8. 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 ...

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. Insecticide Resistance and Management Strategies in Urban Ecosystems.

    PubMed

    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

  15. 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

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

    PubMed

    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

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

    PubMed

    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.

  18. 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.

  19. 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. PMID:26470382

  20. Molecular and biochemical mining of heat-shock and 14-3-3 proteins in drug-induced protoscolices of Echinococcus granulosus and the detection of a candidate gene for anthelmintic resistance.

    PubMed

    Pan, D; Das, S; Bera, A K; Bandyopadhyay, S; Bandyopadhyay, S; De, S; Rana, T; Das, S K; Suryanaryana, V V; Deb, J; Bhattacharya, D

    2011-06-01

    Cystic echinococcosis (CE) caused by the larval stage of Echinococcus granulosus is a disease that affects both humans and animals. In humans the disease is treated by surgery with a supplementary option of chemotherapy with a benzimidazole compound. During the present study heat-shock protein 60 (HSP 60) was identified as one of the most frequently expressed biomolecules by E. granulosus after albendazole treatment. Data were correlated with 14-3-3 protein signature, and overexpression of this molecule after albendazole induction was an indicator of cell survival and signal transduction during in vitro maintenance of E. granulosus for up to 72 h. This observation was further correlated with a uniform expression pattern of a housekeeping gene (actin II). Out of three β-tubulin gene isoforms of E. granulosus, β-tubulin gene isoform 2 showed a conserved point mutation indicative of benzimidazole resistance.

  1. Cyclooctadepsipeptides--an anthelmintically active class of compounds exhibiting a novel mode of action.

    PubMed

    Harder, Achim; Schmitt-Wrede, Hans-Peter; Krücken, Jürgen; Marinovski, Predrag; Wunderlich, Frank; Willson, James; Amliwala, Kiran; Holden-Dye, Lindy; Walker, Robert

    2003-09-01

    There are three major classes of anthelmintics for veterinary use: the benzimidazoles/prebenzimidazoles, the tetrahydropyrimidines/imidazothiazoles, and the macrocyclic lactones. In nematodes, there are five targets for the existing anthelmintics: the nicotinergic acetylcholine receptor which is the target of tetrahydropyrimidines/imidazothiazoles and indirectly that of the acetylcholineesterase inhibitors; the GABA receptor which is the target of piperazine, the glutamate-gated chloride channel as the target of the macrocyclic lactones, and beta-tubulin as the target of prebenzimidazoles/benzimidazoles. All these anthelmintics are now in serious danger because of the worldwide spread of resistant nematodes in sheep, cattle, horses and pigs. The class of cyclooctadepsipeptides has entered the scene of anthelmintic research in the early 1990s. PF1022A, the first anthelmintically active member, is a natural compound from the fungus Mycelia sterilia that belongs to the microflora of the leaves of the Camellia japonica. PF1022A contains 4 N-Methyl-L-leucines, 2 D-lactic acids and 2-D-phenyllactic acids arranged as a cyclic octadepsipeptide with an alternating L-D-L-configuration. Emodepside is a semisynthetic derivative of PF1022A with a morpholine ring at each of the two D-phenyllactic acids in para position. The anthelmintic activity is directed against gastrointestinal nematodes in chicken, mice, rats, meriones, dogs, cats, sheep, cattle and horses. Moreover, emodepside is active against Trichinella spiralis larvae in muscles, microfilariae and preadult filariae and Dictyocaulus viviparus. PF1022A and emodepside are fully effective against benzimidazole-, levamisole or ivermectin-resistant nematodes in sheep and cattle. In Ascaris suum both cyclooctadepsipeptides lead to paralysis indicating a neuropharmacological action of these compounds. Using a PF1022A-ligand immunoscreening of a cDNA library from Haemonchus contortus a cDNA clone of 3569 base pairs could be

  2. 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. PMID:26887285

  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. 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

  5. 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.

  6. Efficacy of major anthelmintics for reduction of fecal shedding of strongyle-type eggs in horses in the Mid-Atlantic region of the United States.

    PubMed

    Smith, M A; Nolan, T J; Rieger, R; Aceto, H; Levine, D G; Nolen-Walston, R; Smith, B I

    2015-11-30

    In the last decade there have been numerous reports of anthelmintic resistant cyathostomins in many parts of the world. The objective of the present study was to evaluate the efficacy of the commercially available anthelmintics against cyathostomin egg shedding in the Mid-Atlantic region of the United States. A total of 989 horses from 67 different farms located in southeastern Pennsylvania, northern Delaware, and northeastern Maryland were treated with fenbendazole, oxibendazole, pyrantel pamoate, ivermectin, or moxidectin at their recommended dosages. Fecal egg count reduction testing was used to determine the efficacy of each anthelmintic on those horses with fecal egg counts of ≥ 200 eggs per gram on the day of treatment (272 horses). Decreased efficacy (reduction of strongyle-type fecal egg counts by less than 90%) was found for fenbendazole, oxibendazole, and pyrantel pamoate, with only 6%, 21% and 43% of horses showing reductions of greater than 90%, respectively. The macrocyclic lactones showed high efficacy in all horses sampled in this study. The decreased anthelmintic efficacy detected in this study adds further evidence for the existence of resistant cyathostomins throughout much of the eastern United States. Findings from this study can be used to create a more sustainable approach for parasite control programs.

  7. 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. PMID:27436741

  8. Brazilian experience in the management of multidrug-resistance.

    PubMed

    de Melo, Fernando Augusto Fiuza

    2010-01-01

    In this article the author reviews the evolution of the approach to multidrug-resistant tuberculosis (MDR-TB) in Brazil following the introduction of rifampicin associated to isoniazid and pyrazinamide (RHZ). It shows Brazil was one of the world's first countries to use the RHZ regimen within a treatment system, with a first line regimen, another one specific for meningo-encephalic forms, for re-treatment of recurrences or of patients who returned with active tuberculosis after abandoning treatment, and a reserve regimen. The system was applied nationwide with guaranteed cost-free provision of medication, and self-administered. The author evaluates the growth of drug resistance, the emergence of multidrug-resistance and how management of this form of the disease has been organised.

  9. Studies on the Anthelmintic Property of Aminobenzylated Mannich Bases

    PubMed Central

    Chaluvaraju, KC; Bhat, KI

    2011-01-01

    Studies were conducted on the anthelmintic property of about 15(e-h, 1e-1h, 2d-2f and 3e-3h) synthesized aminobenzylated Mannich bases bearing N-methyl piperazine using Indian earthworms Pheritima Posthuma against piperazine citrate as standard reference. Three concentrations of each compound (0.1, 0.2, 0.3% w/v) were studied, which involved the determination of paralysis and death time of the worms. The compound 1g exhibited the most significant anthelmintic activity among all the compounds screened against the worms as compared to standard drug. PMID:21897666

  10. 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

  11. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26424910

  13. 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.

  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.

  16. 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

  17. Anthelmintic activity of saikosaponins a and d from radix bupleuri against Dactylogyrus spp. infecting goldfish.

    PubMed

    Zhu, Song; Ling, Fei; Zhang, Qizhong; Liu, Guanglu; Tu, Xiao; Jiang, Chao; Wang, Gaoxue

    2014-09-30

    Disease caused by the parasitic helminths Dactylogyrus spp. results in significant economic damage to the aquaculture industry. Treatment using common chemicals (e.g. formalin) is usually dissatisfactory due to environmental problems, risk of residues, toxicity to fish, and the possibility of anthelmintic resistance. The search for an alternative drug is thus becoming more urgent. This study was designed to evaluate in vivo the anthelmintic efficacy of total saponin (TS), saikosaponin a (SSa), and saikosaponin d (SSd) from radix bupleuri (i.e. the dried root of Bupleurum sp.) based on our previous screening works, with the aim of determining which has commercial potential. Results showed that median effective concentration (EC₅₀) values for TS, SSa, and SSd were 2.01, 1.46, and 0.74 mg l⁻¹, respectively. The acute toxicities against goldfish Carassius auratus for TS, SSa, and SSd were also determined, with median lethal concentration (LC₅₀) of 8.99, 11.20, and 1.54 mg l-1, respectively. The resulting therapeutic indices (TIs) indicated that SSa (TI = 7.67) is a potential therapeutic agent for treating Dactylogyrus infection.

  18. 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.

  19. In vitro anthelmintic effect of Tobacco (Nicotiana tabacum) extract on parasitic nematode, Marshallagia marshalli.

    PubMed

    Nouri, Fatemeh; Nourollahi-Fard, Saeid R; Foroodi, Hamid R; Sharifi, Hamid

    2016-09-01

    Because of developing resistance to the existing anthelmintic drugs, there is a need for new anthelmintic agents. Tobacco plant has alkaloid materials that have antiparasitic effect. We investigated the in vitro anthelminthic effect of aqueous and alcoholic extract of Tobacco (Nicotiana tabacum) against M. marshalli. For investigating this effect, we prepared three dilutions of aqueous and alcoholic extract of Tobacco (25, 50 and 75 mg/ml). The worms exposed to extracts for 10 h at 25-30 °C. The buffer PBS used as negative control and 50 mg/ml dilution of Levamisole used as standard reference. In each group, 50 worms were examined. We used an inhibition mobility test for our study. Survival analysis with Cox proportional hazard model was used for data analysis. The result showed that compared with Levamisole 50 mg/ml, dilution of 25 and 50 mg/ml of the aqueous extract had the same anthelminthic effects (P > 0.05), but 75 mg/ml dilution of the aqueous extract and dilution of 25, 50 and 75 mg/ml of alcoholic extract had more anthelminthic effect (P < 0.05). Overall, extracts of Tobacco possess considerable anthelminthic activity and more potent effects were observed with the highest concentrations. Therefore, the in vivo study on Tobocco in animal models is recommended. PMID:27605759

  20. In vitro anthelmintic effect of Tobacco (Nicotiana tabacum) extract on parasitic nematode, Marshallagia marshalli.

    PubMed

    Nouri, Fatemeh; Nourollahi-Fard, Saeid R; Foroodi, Hamid R; Sharifi, Hamid

    2016-09-01

    Because of developing resistance to the existing anthelmintic drugs, there is a need for new anthelmintic agents. Tobacco plant has alkaloid materials that have antiparasitic effect. We investigated the in vitro anthelminthic effect of aqueous and alcoholic extract of Tobacco (Nicotiana tabacum) against M. marshalli. For investigating this effect, we prepared three dilutions of aqueous and alcoholic extract of Tobacco (25, 50 and 75 mg/ml). The worms exposed to extracts for 10 h at 25-30 °C. The buffer PBS used as negative control and 50 mg/ml dilution of Levamisole used as standard reference. In each group, 50 worms were examined. We used an inhibition mobility test for our study. Survival analysis with Cox proportional hazard model was used for data analysis. The result showed that compared with Levamisole 50 mg/ml, dilution of 25 and 50 mg/ml of the aqueous extract had the same anthelminthic effects (P > 0.05), but 75 mg/ml dilution of the aqueous extract and dilution of 25, 50 and 75 mg/ml of alcoholic extract had more anthelminthic effect (P < 0.05). Overall, extracts of Tobacco possess considerable anthelminthic activity and more potent effects were observed with the highest concentrations. Therefore, the in vivo study on Tobocco in animal models is recommended.

  1. 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.

  2. Potential environmental consequences of administration of anthelmintics to sheep.

    PubMed

    Beynon, S A

    2012-09-30

    Anthelmintics, veterinary medicines for the control of endoparasites, enter into the environment largely through faeces of the treated animals. Sheep dung is a patchily distributed, ephemeral resource, with a functionally important decomposer community. The nature of this community and the pharmacokinetics of anthelmintics in sheep mean that the ecotoxic impacts of these drugs in sheep dung may differ markedly from those in cattle dung, where most research has been focussed. The period of maximum residue excretion is generally more transient in sheep than cattle dung, but low-level excretion may continue for longer, giving the potential for extended sub-lethal effects. Here, the environmental impacts of sheep anthelmintics, as well as alternative endoparasite control methods are reviewed. Impacts are discussed in terms of the potential for residues to enter into the environment, the toxicity and the impact on ecosystem functioning at an appropriate scale. Future research priorities are also discussed; these include the need for studies of the functional contributions of dung-colonising species, as well as the development of higher-tier ecotoxicological methods bridging the gap between laboratory and field experiments. Large-scale and long-term studies, including the development of appropriate models, are necessary to allow the consequences of anthelmintic administration to be assessed, particularly within the remit of sustainable animal production.

  3. 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.

  4. 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. PMID:27208642

  5. [Biological assay of anthelmintic drugs. Determination of DE 50].

    PubMed

    Luffau, G; Carrat, C; Borgaonkar, P W

    1982-01-01

    Experiments on ivermectine, thiabendazole and levamisole were performed by using the Nippostrongylus brasiliensis rat model. The aim of the experiments was to study the 50% as well as 99.5% doses of the above anthelmintics. Besides this a relative evaluation of drugs was also carried out and different dose efficiencies were compared by keeping one anthelmintic as a standard. The results were obtained on the following experimental conditions: homogeneity of the group of rats (age, weight and sex), uniform infestation in all the animals (3000 larvae at day zero), administration of anthelmintics was done on day 6 and autopsy was performed on the 9th day of infection. The effectivity of anthelmintic is essentially based on the mortality of the adult worms. The mathematical expression is obtained on the basis of logarithmic values of the doses and probit percentage analysis. The graph obtained between dose vs efficiency is a straight line, so the value of DE 50 can be calculated using this straight line. The normal distribution of worms exposed to a dose was verified which justifies the statistical interpretation. PMID:6985244

  6. 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.

  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. 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.

  9. 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

  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. Anthelmintic activity of the essential oil of artemisia pallens wall.

    PubMed

    Nakhare, S; Garg, S C

    1991-01-01

    Helminthic infections are now being recognized as the cause of much chronic ill health and sluggishness among the tropical people. More than half of the world populations suffers from worm infections of one type or the other. Traditional system of medicine reports the efficacy of chenopodiul oil, Embelia ribes (Via-Varang), Trachyspermum ammi Ajwain and Biper betle (Pan) oils etc. for eliminating helminthes. The present study reports the strong anthelmintic activity of the essential oil of Artemisia pallens Wall. Against Pheritima posthuma (earth worm), Taenia solium (tape worm) and Ascaris lumbricoides (round worm). The helminthes have been found to be more susceptible to the oil than to piperazine phosphate of similar concentration. Artemisia pallens has been ascribed to possess anthelmintic and stomachic properties in indigenous system of medicine. The present screening not only confirms the correct usage of the plant by the rurals but also enhances the creditability of ethnobotanical explorations.

  12. ANTHELMINTIC ACTIVITY OF AERIAL PARTS OF MELOTHRIA HETEROPHYLLA LOUR

    PubMed Central

    Pal, Dilip Kumar; Mondal, Arijit; Mandal, Uttam

    2006-01-01

    Petroleum ether (60-80°C), chloroform, ethyl acetate, ethanol and aqueous extract of aerial parts of Melothria heterophylla Lour. were evaluated separately for anthelmintic activity on adult Indian earthworms (Pheretima posthuma), using albandazole and piperazine citrate as reference standards. The results indicated that the ethanol extract of M. heterophylla Lour (EEMH) was more potent than the other four extracts of it. PMID:22557229

  13. Antifungal and anthelmintic activities of Cleistopholis patens (Annonaceae).

    PubMed

    Akendengué, Blandine; Champy, Pierre; Nzamba, Joseph; Roblot, François; Loiseau, Philippe M; Bories, Christian

    2009-08-01

    Basic CH2Cl2 extract of the trunk bark of Cleistopholis patens (Annonaceae) exhibited antifungal activities against Candida albicans, C. parapsilosis, and C. glabrata using an agar well-diffusion assay method. Bioassay-guided fractionation of the extract led to the isolation of 8-hydroxysampangine. The methanolic extract displayed anthelmintic activity against Rhabditis pseudoelongata. Purification of the neutral CH2Cl2 extract yielded bornyl-p-transcoumarate and bornyl-p-cis-coumarate.

  14. Direct and indirect anthelmintic effects of condensed tannins in sheep.

    PubMed

    Iqbal, Zafar; Sarwar, Muhammad; Jabbar, Abdul; Ahmed, Shahbaz; Nisa, M; Sajid, Muhammad Sohail; Khan, Muhammad Nisar; Mufti, Kamran Aftab; Yaseen, Muhammad

    2007-03-15

    Anthelmintic activity of condensed tannins (CT) was evaluated both in vitro and in vivo. In vitro tests included egg hatch test and paralysis/mortality assay on adult Haemonchus contortus. In vivo anthelmintic effect was determined by faecal egg count reduction test in lambs. To this end, 18 lambs were divided into three groups (low tannin, high tannin and control). The lambs of low and high tannin groups were fed diets containing 2 and 3% CT while the control group was fed on diets without CT. In vitro trials showed a dose-dependent inhibition of nematode egg hatching; whereas, there was no effect of CT on adult H. contortus. In vivo trials indicated reduction in faecal egg counts in lambs fed diets containing CT. Feed intake and nutrient digestibility of CT-fed sheep was lower and nitrogen balance was higher as compared to control. Maximum weight gain was observed in animals fed diets containing 3% CT. The direct anthelmintic effect of CT, therefore, was evidenced by inhibited egg hatching; whereas, faecal egg counts reduction in sheep was through improved nutrient utilization.

  15. 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.

  16. 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

  17. Relationship among particle size distribution, dissolution profile, plasma values, and anthelmintic efficacy of oxfendazole.

    PubMed

    Shastri, S; Mroszczak, E; Prichard, R K; Parekh, P; Nguyen, T H; Hennessey, D R; Schiltz, R

    1980-12-01

    Three mean particle sizes of oxfendazole raw material (1.65 micron, lot A; 3.2 micron, 10t B; 12.0 micron, lot C) were prepared and identically formulated as corresponding (A, B, and C) suspensions at 2.26% (W/V) concentration. Studies involving microscopic examination, scanning electron microscope analysis, particle size distribution, and surface area measurement were carried out on raw materials. In vitro dissolution profiles were obtained for the suspensions. A comparative bioavailability study of these 3 suspensions was performed in 12 sheep with each sheep given each formulation in a Latin square crossover study design; oxfendazole was dosed at rate of 5 mg/kg of body weight. Plasma-value measurements were made followed by an analysis of various bioavailability studies. Plasma area values indicated that suspension C (dw = 12.0 micron) was significantly (P less than 0.05) less bioavailable than was suspension A (dw = 1.65 micron); there was no difference between suspension A and suspension B. Significant differences were not seen in biological half-life and maximum plasma concentrations. The term dw refers to that particle diameter (determined by Coulter counting) at which 50% of the oxfendazole mass was in the form of particles having a lesser diameter and 50% was in the form of particles having a greater diameter. In a separate study involving 20 Merino weaner sheep infected with benzimidazole-resistant Haemonchus contortus larvae, oxfendazole's anthelmintic efficacy was demonstrated in the 2.26% suspension dosage form (90% particles less than 10 micron) at a dosing rate of 5 mg/kg. A correlation was found between its anthelmintic activity and plasma area values when compared in individual sheep. Data demonstrated that substantial differences in particle size distribution of oxfendazole could influence its dissolution rate, plasma concentrations, and absorption characteristics, thus indicating that oxfendazole's absorption could be dissolution-rate limited.

  18. 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

  19. 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

  20. 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. PMID:26388864

  1. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  3. 21 CFR 500.25 - Anthelmintic drugs for use in animals.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 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 SERVICES... § 500.25 Anthelmintic drugs for use in animals. (a) The Commissioner of Food and Drugs has...

  4. 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

  5. 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.

  6. 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.

  7. 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. PMID:26025191

  8. Anthelmintics: The best way to predict the future is to create it.

    PubMed

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

    2015-08-15

    '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.

  9. 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

  10. Potential resistance management for the sustainable use of insect-resistant genetically modified corn and rice in China.

    PubMed

    Han, Lanzhi; Jiang, Xingfu; Peng, Yufa

    2016-06-01

    Many lines of insect-resistant genetically modified (IRGM) corn and rice containing Bacillus thuringiensis (Bt) insecticidal genes have been developed and undergone different environmental biosafety assessments stages in China, showing robust application prospects. The potential of targeted pests to develop resistance to Bt crops is widespread, which threatens the sustainable utility of IRGM corn and rice. In this study, the potential risks of target pest complexes developing resistance to IRGM corn and rice are evaluated. Theoretical and empirical studies implementing precautionary insect resistance management (IRM) strategies to delay resistance evolution are summarized and challenges to IRM are discussed. Additionally, solutions facing these challenges are proposed. Finally, directions for future studies in developing IRGM corn and rice and IRM plans are discussed. PMID:27436744

  11. 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.

  12. 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.

  13. 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. PMID:7310792

  14. 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

  15. 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

  16. Renal denervation for the management of resistant hypertension

    PubMed Central

    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. PMID:26672761

  17. Clinical management of resistance evolution in a bacterial infection

    PubMed Central

    Woods, Robert J.; Read, Andrew F.

    2015-01-01

    We report the case of a patient with a chronic bacterial infection that could not be cured. Drug treatment became progressively less effective due to antibiotic resistance, and the patient died, in effect from overwhelming evolution. Even though the evolution of drug resistance was recognized as a major threat, and the fundamentals of drug resistance evolution are well understood, it was impossible to make evidence-based decisions about the evolutionary risks associated with the various treatment options. We present this case to illustrate the urgent need for translational research in the evolutionary medicine of antibiotic resistance. PMID:26454762

  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. 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

  20. 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

  1. Characterization of Haemonchus contortus P-glycoprotein-16 and its interaction with the macrocyclic lactone anthelmintics.

    PubMed

    Godoy, P; Che, H; Beech, R N; Prichard, R K

    2015-11-01

    Anthelmintic resistance in veterinary nematodes, including Haemonchus contortus, has become a limitation to maintaining high standards of animal health. Resistance in this parasite, to all drug families including the macrocyclic lactones (MLs) is a serious issue worldwide. Mechanisms of resistance to the MLs appear to be complex and to include the elimination of these compounds by ABC transporter-like proteins present in nematodes. In order to investigate the potential involvement of ABC transporters in ML resistance in H. contortus, we have characterized the functionality of the ABC transporter H. contortus P-glycoprotein-16 (Hco-PGP-16) expressed in mammalian cells. This has included a study of its interaction with different MLs, including the avermectins, abamectin (ABA) and ivermectin (IVM), and the milbemycin, moxidectin (MOX). Hco-PGP-16 transport activity was studied using the fluorophore Rhodamine 123 (Rho 123). Transfected cells expressing Hco-PGP-16 accumulated less than 50% of Rho 123 than control cells, suggesting an active transport of this tracer dye by Hco-PGP-16. The influence of the MLs on the Rho123 transport by Hco-PGP-16 was then investigated. A marked inhibition of Rho123 transport by ABA and IVM was observed. In contrast, MOX showed less effect on inhibition of Rho123 transport by Hco-PGP-16, and the inhibition was not saturable. The difference in the interaction of the avermectins and MOX with Hco-PGP-16 may help explain the slower rate of development of resistance to MOX compared with the avermectins in H. contortus.

  2. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  4. Carbapenem-resistant Acinetobacter baumannii: epidemiology, surveillance and management.

    PubMed

    Pogue, Jason M; Mann, Tal; Barber, Katie E; Kaye, Keith S

    2013-04-01

    Carbapenem-resistant Acinetobacter baumannii pose a significant threat to hospitalized patients, as therapeutic options are scarse. Alarmingly, rates of carbapenem-resistance in A. baumannii are on the rise and are slowly becoming a routine phenotype for this organism. This review focuses on infection control strategies for identification and control of A. baumannii, as well the available therapeutic options.

  5. 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…

  6. 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. PMID:27605841

  7. Use of a multiple choice questionnaire to assess UK prescribing channels' knowledge of helminthology and best practice surrounding anthelmintic use in livestock and horses.

    PubMed

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

    2016-06-01

    Grazing livestock and equines are at risk of infection from a variety of helminths, for which the primary method of control has long been the use of anthelmintics. Anthelmintic resistance is now widespread in a number of helminth species across the globe so it is imperative that best practice control principles be adopted to delay the further spread of resistance. It is the responsibility of all who prescribe anthelmintics (in the UK, this being veterinarians, suitably qualified persons (SQPs) and pharmacists) to provide adequate information on best practice approaches to parasite control at the point of purchase. Poor uptake of best practice guidelines at farm level has been documented; this could be due to a lack of, or inappropriate, advice at the point of anthelmintics purchase. Therefore, the aim here was to evaluate levels of basic knowledge of helminthology, best practice guidelines and dispensing legislation among veterinarians and SQPs in the UK, through a Multiple Choice Question (MCQ) test, that was distributed online via targeted emails and social media sites. For each respondent, the percentage correct was determined (for the MCQ test overall and for subsections) and the results analysed initially using parametric and non-parametric statistics to compare differences between prescribing channels. The results showed that channels generally performed well; veterinarians achieved a mean total percentage correct of 79.7% (range 34.0-100%) and SQPs, a mean total percentage correct of 75.8% (range 38.5-100%) (p=0.051). The analysis indicated that veterinarians performed better in terms of knowledge of basic helminthology (p=0.001), whilst the SQP group performed better on legislation type questions (p=0.032). There was no significant difference in knowledge levels of best practice between the two channels. Multivariable linear regression analysis showed that veterinarians and those answering equine questions only performed significantly better than those

  8. Determination of anthelmintic activity of the leaf and bark extract of tamarindus indica linn.

    PubMed

    Das, S S; Dey, Monalisha; Ghosh, A K

    2011-01-01

    The aim of the present study was to evaluate the anthelmintic activity of ethanolic and aqueous extract of leaves and bark of Tamarindus indica Linn using Pheretima posthuma and Tubifex tubifex as test worms. The time of paralysis and time of death were studied and the activity was compared with piperazine citrate as reference standard. The alcohol and aqueous extract of bark of Tamarindus indica exhibited significant anthelmintic activity as evidenced by decreased paralyzing time and death time. The results thus support the use of Tamarindus indica as an anthelmintic agent.

  9. Evaluation of Anthelmintic Activities of Aerial Parts of Cynodon dactylon Pers

    PubMed Central

    Pal, Dilipkumar; Pandab, Koushik

    2010-01-01

    The Anthelmintic activities of different extracts of aerial parts of Cynodon dactylon Pers were evaluated separately on adult Indian earthworm (Pheritima posthuma). It was found that petroleum ether (PECD), chloroform (CECD), ethanol (EECD), aqueous extract (AECD) of C. dactylon showed anthelmintic activities at the concentration of 5 mg/ml of each. The anthelmintic effects of PECD, CECD, EECD and AECD at 10-mg/ml concentrations were comparable with that of the effects produced by the reference standards, albendazole (10 mg/ml) and piperazine citrate (10 mg/ml). PMID:22557417

  10. Resistance management in chronic hepatitis B complicated by renal failure.

    PubMed

    Wiegand, J; Karlas, T; Schiefke, I; Krasselt, U; Bock, T; Mössner, J; Tillmann, H L

    2010-07-01

    Therapy of chronic hepatitis B has improved by the invention of the potent nucleos(t)ide analogues entecavir, telbivudine and tenofovir disoproxil. Due to increasing prevalence of lamivudine resistance the appropriate first line therapy may prevent emergence of any new resistance and avoid combination therapy. The present case describes a complex history of chronic hepatitis B in the setting of renal failure after two renal transplants illustrating why lamivudine should not be used as first line treatment option any more. Instead, entecavir offers high antiviral potency, low risk for resistance and possible individual dose titration by an oral solution.

  11. 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

  12. 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)

  13. Application of pyramided traits against Lepidoptera in insect resistance management for Bt crops.

    PubMed

    Storer, Nicholas P; Thompson, Gary D; Head, Graham P

    2012-01-01

    Since initial launch of insect protected transgenic crops, the most effective strategy to manage the potential for target pests to evolve resistance has been the use of a single mode of action with "high dose" and structured refuge. However, the effectiveness of this strategy is limited if mortality of certain pests does not reach "high dose" criteria, inconsistent implementation of refuges and non-rare resistance alleles. More recently, several pyramided trait products, which include multiple modes of action against key target pests, have been developed. These products offer the potential for dramatically improved resistance management with smaller refuges and less dependence on high mortality of susceptible and heterozygous insects and rare resistance alleles. We show that products such as SmartStax and PowerCore offer compelling resistance management benefits compared with single mode of action products and allow for the option of products containing refuge seed mixtures rather than structured refuges to effectively delay resistance. We conclude that all stakeholders, including technology developers, growers, crop advisors, extensions services and regulatory authorities should continue to encourage the development, deployment and adoption of pyramided trait products for improved pest management and improved resistance management.

  14. 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.

  15. 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.

  16. 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

  17. In vivo anthelmintic activity of ginger against gastrointestinal nematodes of sheep.

    PubMed

    Iqbal, Zafar; Lateef, Muhammad; Akhtar, Muhammad Shoaib; Ghayur, Muhammad Nabeel; Gilani, Anwarul Hassan

    2006-06-30

    This paper describes the anthelmintic activity of Zingiber officinale Roscoe (family Zingiberaceae) rhizome, commonly known as ginger, to justify its traditional use in veterinary medicine. Crude powder (CP) and crude aqueous extract (CAE) of dried ginger (1-3 g/kg) were administered to sheep naturally infected with mixed species of gastrointestinal nematodes. Both CP and CAE exhibited a dose- and a time-dependent anthelmintic effect with respective maximum reduction of 25.6% and 66.6% in eggs per gram (EPG) of faeces on day 10 of post-treatment. Levamisole (7.5 mg/kg), a standard anthelmintic agent, exhibited 99.2% reduction in EPG. This study shows that ginger possesses in vivo anthelmintic activity in sheep thus justifying the age-old traditional use of this plant in helminth infestation. PMID:16443342

  18. Epidemiology. Opposite effects of anthelmintic treatment on microbial infection at individual versus population scales.

    PubMed

    Ezenwa, Vanessa O; Jolles, Anna E

    2015-01-01

    Parasitic worms modulate host immune responses in ways that affect microbial co-infections. For this reason, anthelmintic therapy may be a potent tool for indirectly controlling microbial pathogens. However, the population-level consequences of this type of intervention on co-infecting microbes are unknown. We evaluated the effects of anthelmintic treatment on bovine tuberculosis (BTB) acquisition, mortality after infection, and pathogen fitness in free-ranging African buffalo. We found that treatment had no effect on the probability of BTB infection, but buffalo survival after infection was ninefold higher among treated individuals. These contrasting effects translated into an approximately eightfold increase in the reproductive number of BTB for anthelmintic-treated compared with untreated buffalo. Our results indicate that anthelmintic treatment can enhance the spread of microbial pathogens in some real-world situations.

  19. A new approach for anthelmintic discovery for humans.

    PubMed

    Geary, Timothy G; Chibale, Kelly; Abegaz, Berhanu; Andrae-Marobela, Kerstin; Ubalijoro, Eliane

    2012-05-01

    Natural product-based drug discovery has been deemphasized by the pharmaceutical industry. This situation is discordant with the fact that most people in developing countries rely on traditional medicines derived from local biodiversity for healthcare. Despite economic growth in the past 10 years, Africa remains plagued by parasitic infections, out of reach of eradication. Limited regional funding for drug discovery complicates the situation. Novel models are needed to bring sustainability to local drug discovery programs. This Opinion describes an innovative partnership that promotes local leadership to harness a recombinant yeast-based assay to screen for novel anthelmintic candidates in collections of African natural products. Implementation of this strategy in biodiversity-rich but resource-constrained settings can help build sustainable local capacity for drug discovery. PMID:22424638

  20. 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. PMID:24709006

  1. 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.

  2. 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

  3. 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

  4. Potential shortfall of pyramided Bt cotton for resistance management

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  5. 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

  6. The management of fluid and wave resistances by whirligig beetles.

    PubMed

    Voise, Jonathan; Casas, Jérôme

    2010-02-01

    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.

  7. Identification of blast resistance genes for managing rice blast disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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,...

  8. 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…

  9. 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. PMID:22730379

  10. BR 04-1MANAGEMENT OF TREATMENT-RESISTANT HYPERTENSION.

    PubMed

    Webb, David John

    2016-09-01

    Treatment-resistant hypertension (TRH) is defined as the failure to achieve an office BP target of <140/90 mmHg (<130/80 mmHg in patients with chronic kidney disease (CKD) or diabetes) in patients with hypertension (HT), despite adherence to at least 3 antihypertensive medications at optimal tolerated doses, ideally including a diuretic (Calhoun et al., Circulation 2008). TRH identifies patients with hard-to-treat HT, who might benefit from specialist investigation and treatment. Although some studies put the prevalence of TRH as >10%, these levels may be inflated by white-coat hypertension and poor adherence. Indeed, PATHWAY-2 (Williams et al., Lancet 2016) and SYMPLICITY HNT-3 (Bhatt et al., NEJM 2014) suggest that true TRH is rarer than generally thought. Risk factors for TRH (which themselves increase cardiovascular risk) include obesity, older age, African ethnicity, CKD and diabetes. Although not fully addressed, evidence suggests that prolonged poorly controlled BP in TRH has a poor outcome.Before diagnosing TRH, pseudo-resistant HT must be excluded. Poor adherence to treatment - which may be caused by side-effects, complicated dosing schedules, pill burden, poor doctor-patient relationship, poor understanding or acceptance of the need for treatment, and medication cost -is common, with up to 40% of newly diagnosed hypertensive patients discontinuing medications within a year. Directly observed therapy and urine drug screens can be very helpful in its detection. Poor office BP measurement technique is another common problem. Sufficient rest, use of the right cuff, and repeated automated measurement in a quiet setting, is critical. ABPM (or at least home BP measurement) is crucial to excluding 'white coat' HT. In those diagnosed with true TRH, modifiable causes must be excluded, including diet, drugs, secondary endocrine and renal causes, and sleep apnoea. In most cases, however, the aetiology of TRH is multifactorial and treatment aimed at multiple targets

  11. 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

  12. 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.

  13. Hypertension Management and Microvascular Insulin Resistance in Diabetes

    PubMed Central

    Ko, Seung-Hyun; Cao, Wenhong; Liu, Zhenqi

    2011-01-01

    Type 2 diabetes is in essence a vascular disease and is frequently associated with hypertension, macrovascular events, and microvascular complications. Microvascular dysfunction, including impaired recruitment and capillary rarefaction, has been implicated in the pathogenesis of diabetic complications. Microvascular insulin resistance and renin-angiotensin system upregulation are present in diabetes, and each contributes to the development of hypertension and microvascular dysfunction. In the insulin-sensitive state, insulin increases microvascular perfusion by increasing endothelial nitric oxide production, but this effect is abolished by insulin resistance. Angiotensin II, acting via the type 1 receptors, induces inflammation and oxidative stress, leading to impaired insulin signaling, reduced nitric oxide availability, and vasoconstriction. Conversely, it acts on the type 2 receptors to cause vasodilatation. Because substrate and hormonal exchanges occur in the microvasculature, antihypertensive agents targeted to improve microvascular insulin sensitivity and function may have beneficial effects beyond their capacity to lower blood pressure in patients with diabetes. PMID:20582734

  14. Will antimicrobial resistance of BRD pathogens impact BRD management in the future?

    PubMed

    Brumbaugh, Gordon W

    2014-12-01

    Resistance is a qualitative interpretation of antimicrobial activity in vitro. Critical to management of bovine respiratory disease (BRD) is the clinical response in vivo. Attempts to connect activity in vitro to response in vivo have been complicated by the complexity of BRD, interpretation of antimicrobial activity in vitro, and inconsistent measures of clinical success or failure. During recent history, the discovery, development, and commercialization of antimicrobials have decreased. In response to resistance, voluntary and imposed restrictions on use of antimicrobials have been implemented. Resistance can be reversed using technology and knowledge of mechanisms of resistance. Perhaps approaches that reverse resistance will be used in clinical management of BRD in the future. The short answer to the question posed in the title is, 'yes.' Since antimicrobial drugs were discovered, resistance has been a consideration for selection of treatment of any infectious disease and BRD is not unique. In the opinion of the author, the more important question is, 'How will antimicrobial resistance of BRD pathogens impact BRD management in the future?'

  15. International expert opinion on the management of infection caused by azole-resistant Aspergillus fumigatus.

    PubMed

    Verweij, Paul E; Ananda-Rajah, Michelle; Andes, David; Arendrup, Maiken C; Brüggemann, Roger J; Chowdhary, Anuradha; Cornely, Oliver A; Denning, David W; Groll, Andreas H; Izumikawa, Koichi; Kullberg, Bart Jan; Lagrou, Katrien; Maertens, Johan; Meis, Jacques F; Newton, Pippa; Page, Iain; Seyedmousavi, Seyedmojtaba; Sheppard, Donald C; Viscoli, Claudio; Warris, Adilia; Donnelly, J Peter

    2015-01-01

    An international expert panel was convened to deliberate the management of azole-resistant aspergillosis. In culture-positive cases, in vitro susceptibility testing should always be performed if antifungal therapy is intended. Different patterns of resistance are seen, with multi-azole and pan-azole resistance more common than resistance to a single triazole. In confirmed invasive pulmonary aspergillosis due to an azole-resistant Aspergillus, the experts recommended a switch from voriconazole to liposomal amphotericin B (L-AmB; Ambisome(®)). In regions with environmental resistance rates of ≥10%, a voriconazole-echinocandin combination or L-AmB were favoured as initial therapy. All experts recommended L-AmB as core therapy for central nervous system aspergillosis suspected to be due to an azole-resistant Aspergillus, and considered the addition of a second agent with the majority favouring flucytosine. Intravenous therapy with either micafungin or L-AmB given as either intermittent or continuous therapy was recommended for chronic pulmonary aspergillosis due to a pan-azole-resistant Aspergillus. Local and national surveillance with identification of clinical and environmental resistance patterns, rapid diagnostics, better quality clinical outcome data, and a greater understanding of the factors driving or minimising environmental resistance are areas where research is urgently needed, as well as the development of new oral agents outside the azole drug class. PMID:26282594

  16. Strategies for the management of resistance in mosquitoes to the microbial control agent Bacillus sphaericus.

    PubMed

    Zahiri, Nayer S; Su, Tianyun; Mulla, Mir S

    2002-05-01

    Bacillus sphaericus (B.spi) strain 2362 has been recognized as a promising mosquito larvicide, and various preparations of this strain have been tested and used in mosquito control programs worldwide. This control agent has advantages of high efficacy, specificity, persistence, and environmental safety. However, resistance in Culex pipiens complex mosquitoes to Bsph has occurred in both laboratory and field populations, necessitating development of resistance management strategies. Studies were initiated aiming at reversing previously established Bsph resistance in a laboratory colony of Culex quinque fasciatus Say by selections with Bti alone, Bti and Bsph in rotation, or mixture. Partial restoration of susceptibility to Bsph was achieved by selection of resistant colony for 10 generations with Bti alone at LC80). After this colony was switched back to Bsph selection for 20 generations, resistance to Bsph partially increased to a stable level. Selections of Basph-resistant colonies with Bti and Bsph in rotation or mixture resulted in steady decline of resistance over 30 generations, with rapid decline in resistance noted in the initial 10-15 generations. It is interesting to note that selections with Bti and Bsph in rotation increased susceptibility to Bti in Bsph-resistant colony. It is promising that selection with Bti alone, Bsph and Bti in rotation, or mixture have a potential for developing practical strategies to overcome acquired resistance to Bsph in Cx. quinquefasciatus populations.

  17. 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...

  18. 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...

  19. Resistance and resilience: the final frontier in traumatic stress management.

    PubMed

    Everly, George S; Welzant, Victor; Jacobson, Jodi M

    2008-01-01

    This paper asserts that the constructs of resistance and resilience represent a domain rich in potential for a wide variety of applications in the field of traumatic stress. Resilience holds great potential for those working in applied settings such as public health planning and preparedness, Employee Assistance Programs (EAPs) and business continuity, as well as transportation, law enforcement, fire suppression, emergency medical services, pre-deployment training for military and other high risk professional groups. Additionally, its application to "the war on terrorism" cannot be denied. Finally, the construct of resilience may have direct applicability to businesses and organizations wherein there is perceived value in preparing a workforce to effectively function under adverse or high stress conditions. The putative value of resistance and resiliency in such applied settings resides in their ability to protect against stress-related behavioral morbidity, as well as counterproductive behavioral reactions. Given its importance, the question arises as to whether resilience is an innate trait or an acquired skill. This paper will report on preliminary data suggesting resiliency may be an attribute that can be acquired through participation in a relatively brief training program. PMID:19278142

  20. 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.

  1. 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

  2. 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

  3. Management of chronic, resistive scabies: a case study.

    PubMed

    Morris Hicks, L E; Lewis, D J

    1995-01-01

    It took about 9 months of diligent effort to resolve Mr. C's chronic, highly resistive case of scabies. In all, Mr. C. had a total of seven treatments with a scabicidal lotion or cream. In addition, other medications were prescribed in an attempt to resolve his skin condition. The treatment of scabies is costly to an institution, in medications, supplies, and additional nursing time required to treat the patient, as well as other patients prophylactically. Therefore it behooves nurses to do a thorough skin assessment on all nursing home care patients at least monthly, recognize early signs of scabies, and be cognizant of the fact that scabies in the elderly patient may have an atypical distribution.

  4. 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

  5. Selective Toxicity of the Anthelmintic Emodepside Revealed by Heterologous Expression of Human KCNMA1 in Caenorhabditis elegansS⃞

    PubMed Central

    Crisford, Anna; Murray, Caitriona; O'Connor, Vincent; Edwards, Richard J.; Kruger, Nina; Welz, Claudia; von Samson-Himmelstjerna, Georg; Harder, Achim; Walker, Robert J.

    2011-01-01

    Emodepside is a resistance-breaking anthelmintic of a new chemical class, the cyclooctadepsipeptides. A major determinant of its anthelmintic effect is the calcium-activated potassium channel SLO-1. SLO-1 belongs to a family of channels that are highly conserved across the animal phyla and regulate neurosecretion, hormone release, muscle contraction, and neuronal network excitability. To investigate the selective toxicity of emodepside, we performed transgenic experiments in which the nematode SLO-1 channel was swapped for a mammalian ortholog, human KCNMA1. Expression of either the human channel or Caenorhabditis elegans slo-1 from the native slo-1 promoter in a C. elegans slo-1 functional null mutant rescued behavioral deficits that otherwise resulted from loss of slo-1 signaling. However, worms expressing the human channel were 10- to 100-fold less sensitive to emodepside than those expressing the nematode channel. Strains expressing the human KCNMA1 channel were preferentially sensitive to the mammalian channel agonists NS1619 and rottlerin. In the C. elegans pharyngeal nervous system, slo-1 is expressed in neurons, not muscle, and cell-specific rescue experiments have previously shown that emodepside inhibits serotonin-stimulated feeding by interfering with SLO-1 signaling in the nervous system. Here we show that ectopic overexpression of slo-1 in pharyngeal muscle confers sensitivity of the muscle to emodepside, consistent with a direct interaction of emodepside with the channel. Taken together, these data predict an emodepside-selective pharmacophore harbored by SLO-1. This has implications for the development of this drug/target interface for the treatment of helminth infections. PMID:21415309

  6. Mixed methods evaluation of targeted selective anthelmintic treatment by resource-poor smallholder goat farmers in Botswana.

    PubMed

    Walker, Josephine G; Ofithile, Mphoeng; Tavolaro, F Marina; van Wyk, Jan A; Evans, Kate; Morgan, Eric R

    2015-11-30

    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. Mixed methods evaluation of targeted selective anthelmintic treatment by resource-poor smallholder goat farmers in Botswana.

    PubMed

    Walker, Josephine G; Ofithile, Mphoeng; Tavolaro, F Marina; van Wyk, Jan A; Evans, Kate; Morgan, Eric R

    2015-11-30

    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.

  8. 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

  9. The compatibility of a nucleopolyhedrosis virus control with resistance management for Bacillus thuringiensis: co-infection and cross-resistance studies with the diamondback moth, Plutella xylostella.

    PubMed

    Raymond, B; Sayyed, A H; Wright, D J

    2006-10-01

    The use of genetically modified crops expressing Bacillus thuringiensis (Bt) toxins can lead to the reduction in application of broad-spectrum pesticides and an increased opportunity for supplementary biological control. Bt microbial sprays are also used by organic growers or as part of integrated pest management programs that rely on the use of natural enemies. In both applications the evolution of resistance to Bt toxins is a potential problem. Natural enemies (pathogens or insects) acting in combination with toxins can accelerate or decelerate the evolution of resistance to Bt. In the present study we investigated whether the use of a nucleopolyhedrovirus (AcMNPV) could potentially affect the evolution of resistance to the Bt toxin Cry1Ac in Plutella xylostella. At low toxin doses there was evidence for antagonistic interactions between AcMNPV and Cry1Ac resistant and susceptible insects. However, this antagonism was much stronger and more widespread for susceptible larvae; interactions were generally not distinguishable from additive for resistant larvae. Selection for resistance to Cry1Ac in two populations of P. xylostella with differing resistance mechanisms did not produce any correlated changes in resistance to AcMNPV. Stronger antagonistic interactions between Bt and AcMNPV on susceptible rather than resistant larvae can decrease the relative fitness between Bt-resistant and susceptible larvae. These interactions and the lack of cross-resistance between virus and toxin suggest that the use of NPV is compatible with resistance management to Bt products.

  10. Insect Resistance Development Models as Tools for Determining Resistance Management Strategies (Final)

    EPA Science Inventory

    The work presented here was done as part of the biotechnology risk assessment research program in the U.S. EPA Office of Research and Development. A major goal of this program is to provide guidance for the use of science based tools that aid in the effective management of insec...

  11. Resistance to Gastrointestinal nematodse of cattle: Identification of genomic regions affecting resistance and potential mechanisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gastrointestinal nematode infections remain a major economic drain on the efficient raising of cattle throughout the world. The recent demonstrations of the appearance of drug resistance in these parasites underscores the problems associated with a complete reliance on anthelmintics to control econ...

  12. Susceptibility assay of Haemonchus contortus to commonly used anthelmintics in Jimma, southwest Ethiopia.

    PubMed

    Belew, Sileshi; Hussien, Jemal; Regassa, Feyesa; Belay, Kumilachew; Tolosa, Tadele

    2012-10-01

    An experimental study to investigate the susceptibility pattern of Haemonchus contortus to commonly used anthelmintics (albendazole, tetramisole, ivermectin, and triclobendazole) was conducted between June and September 2009. Adult H. contortus parasites were collected from a total of 30 sheep slaughtered at Jimma municipal abattoir. The anthelmintics were assessed for egg hatch inhibition ability against H. contortus eggs. The eggs (500 eggs/ml) were incubated with different concentrations (0.25, 0.125, 0.0625, 0.03125, and 0.015625 μg/ml) at 26°C for 48 h. Egg hatching inhibition of different anthelmintics at different concentrations was recorded. The overall mean percent inhibition showed that there was a significant difference (p < 0.05) among the different concentrations. Mean egg hatch inhibition of ivermectin showed the highest result (84.90 %) at 0.25 μg/ml, followed by albendazole (78.77 %), triclobendazole (76.66 %), and tetramisole (78.98 %), respectively. The overall mean percent inhibition showed a significant difference (p < 0.05) among the different anthelmintics. Further evaluation of these anthelmintics was recommended.

  13. 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.

  14. Determination of benzimidazole anthelmintics in animal-derived biological matrices.

    PubMed

    Neri, Bruno; Bidolli, Gentilina; Felli, Marialinda; Cozzani, Roberto

    2002-04-01

    This paper describes an easy multiresidue procedure for the determination of 8 benzimidazole anthelmintics (Albendazole, Albendazole sulphone, Albendazole sulphoxide, Ox-bendazole, Ossibendazole, p-OH-Fenbendazole, Fenbendazole, Flubendazole) in foodstuffs of animal origin for human consumption. According to the proposed procedure, 10 g of homogenised sample were extracted with acetonitrile in ultrasonic bath, the organic layer was evaporated to dryness and the residue dissolved in HCl 0.005 M. After an initial washing with hexane to remove fats, the aqueous layer was purified on SPE C2 column and the analytes were eluted with methanol, evaporated to dryness and reconstituted with phosphate buffer/acetonitrile (50/50). The solution obtained was analysed by HPLC with diode array detector (DAD); this detector provides useful information about the peaks present in routine samples, because it gains not only retention times of analytes, as well as their UV-spectra. Benzthiazuron was used as internal standard and the method was validated in the range 10-100 ppb, as requested by the imposed limits. The mean recoveries in spiked samples ranged between 70% and 95%, for 10 and 100 ppb respectively. The developed method resulted sensitive, simple and fast. It is particularly suitable for laboratories that execute screening analysis on a great number of samples, observing the EC regulations that establish the benzimidazole Maximum Residue Limits (MRLs) in food.

  15. [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.

  16. 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.

  17. Biotransformation of benzimidazole anthelmintics in reed (Phragmites australis) as a potential tool for their detoxification in environment.

    PubMed

    Podlipná, Radka; Skálová, Lenka; Seidlová, Helena; Szotáková, Barbora; Kubíček, Vladimír; Stuchlíková, Lucie; Jirásko, Robert; Vaněk, Tomáš; Vokřál, Ivan

    2013-09-01

    Benzimidazole anthelmintics, the drugs against parasitic worms, are widely used in human as well as veterinary medicine. Following excretion, these substances may persist in the environment and impact non-target organisms. In order to test phytoremediation as a possible tool for detoxification of anthelmintics in environment, the biotransformation pathways of albendazole (ABZ) and flubendazole (FLU) were studied in reed (Phragmites australis) in vitro. Reed cells were able to uptake and biotransform both anthelmintics. Ten ABZ metabolites and five FLU metabolites were found. Some atypical biotransformation reactions (formation of glucosylglucosides, acetylglucosides and xylosylglucosides), which have not been described previously, were identified. Based on the obtained results, the schemes of metabolic pathways of ABZ and FLU in reed were proposed. Most of ABZ and FLU metabolites can be considered as anthelmintically less active; therefore uptake and biotransformation of these anthelmintics by reed could be useful for decrease of their toxicity in environment.

  18. Induced resistance – does it have potential as a tool in pecan disease management?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  19. Cercospora leaf spot: monitoring and managing fungicide resistance in populations of Cercospora beticola in Michigan

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  20. Crop advisor perceptions of giant ragweed distribution, herbicide-resistance, and management in the Corn Belt

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  1. Integrated palmer amaranth management in glufosinate-resistant cotton: II. primary, secondary, and conservation tillage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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. Ultrasound Doppler renal resistive index: a useful tool for the management of the hypertensive patient

    PubMed Central

    Viazzi, Francesca; Leoncini, Giovanna; Derchi, Lorenzo E.; Pontremoli, Roberto

    2014-01-01

    The Doppler-derived renal resistive index has been used for years in a variety of clinical settings such as the assessment of chronic renal allograft rejection, detection and management of renal artery stenosis, evaluation of progression risk in chronic kidney disease, differential diagnosis in acute and chronic obstructive renal disease, and more recently as a predictor of renal and global outcome in the critically ill patient. More recently, evidence has been accumulating showing that an increased renal resistive index not only reflects changes in intrarenal perfusion but is also related to systemic hemodynamics and the presence of subclinical atherosclerosis, and may thus provide useful prognostic information in patients with primary hypertension. On the basis of these results, the evaluation of renal resistive index has been proposed in the assessment and management of patients with primary hypertension to complement other signs of renal abnormalities. PMID:24172238

  3. The anthelmintic efficacy of natural plant cysteine proteinases against Hymenolepis microstoma in vivo.

    PubMed

    Mansur, F; Luoga, W; Buttle, D J; Duce, I R; Lowe, A; Behnke, J M

    2015-09-01

    Little is known about the efficacy of cysteine proteinases (CP) as anthelmintics for cestode infections in vivo. Hymenolepis microstoma is a natural parasite of house mice, and provides a convenient model system for the assessment of novel drugs for anthelmintic activity against cestodes. The experiments described in this paper indicate that treatment of H. microstoma infections in mice with the supernatant of papaya latex (PLS), containing active cysteine proteinases, is only minimally efficacious. The statistically significant effects seen on worm burden and biomass showed little evidence of dose dependency, were temporary and the role of cysteine proteinases as the active principles in PLS was not confirmed by specific inhibition with E-64. Worm fecundity was not affected by treatment at the doses used. We conclude also that this in vivo host-parasite system is not sensitive enough to be used reliably for the detection of cestocidal activity of compounds being screened as potential, novel anthelmintics.

  4. EVALUATION OF ANTHELMINTIC ACTIVITIES OF AERIAL PARTS of Celsia coromandeliane Vahl AND Mollugo pentaphylla Linn

    PubMed Central

    Pal, Dilip Kumar; Majumder, Avijit; Bandyopadhyay, Pranab Kumar; Jena, Anima; Panday, Rajesh

    2006-01-01

    The anthelmintic activities of different extracts of aerial parts of Celsia coromandeliane Vahl and Mollugo pentaphylla Linn were evaluated separately on adult Indian earthworm (Pheritima posthuma). It was found that petroleum ether (PECC), chloroform (CCC), ethanol (ECC) extract of C. coromandeliane and petroleum ether (PEMP), benzene (BMP), ethyl acetate (EAMP), ethanol (EMP) extract of M. pentaphylla showed anthelmintic activities at the concentration of 5 mg/ml of each. The anthelmintic effects of CCC, PEMP, BMP and EAMP at 5 mg/ml and PECC at 10-mg/ml concentrations are comparable with that of the effects produced by the reference standards albendazole (10 mg/ml) and piperazine citrate (10 mg/ml). PMID:22557204

  5. The Anthelmintic Triclabendazole and Its Metabolites Inhibit the Membrane Transporter ABCG2/BCRP

    PubMed Central

    Barrera, Borja; Otero, Jon A.; Egido, Estefanía; Prieto, Julio G.; Seelig, Anna; Álvarez, Ana I.

    2012-01-01

    ABCG2/BCRP is an ATP-binding cassette transporter that extrudes compounds from cells in the intestine, liver, kidney, and other organs, such as the mammary gland, affecting pharmacokinetics and milk secretion of antibiotics, anticancer drugs, and other compounds and mediating drug-drug interactions. In addition, ABCG2 expression in cancer cells may directly cause resistance by active efflux of anticancer drugs. The development of ABCG2 modulators is critical in order to improve drug pharmacokinetic properties, reduce milk secretion of xenotoxins, and/or increase the effective intracellular concentrations of substrates. Our purpose was to determine whether the anthelmintic triclabendazole (TCBZ) and its main plasma metabolites triclabendazole sulfoxide (TCBZSO) and triclabendazole sulfone (TCBZSO2) inhibit ABCG2 activity. ATPase assays using human ABCG2-enriched membranes demonstrated a clear ABCG2 inhibition exerted by these compounds. Mitoxantrone accumulation assays using murine Abcg2- and human ABCG2-transduced MDCK-II cells confirmed that TCBZSO and TCBZSO2 are ABCG2 inhibitors, reaching inhibitory potencies between 40 and 55% for a concentration range from 5 to 25 μM. Transepithelial transport assays of ABCG2 substrates in the presence of both TCBZ metabolites at 15 μM showed very efficient inhibition of the Abcg2/ABCG2-mediated transport of the antibacterial agents nitrofurantoin and danofloxacin. TCBZSO administration also inhibited nitrofurantoin Abcg2-mediated secretion into milk by more than 2-fold and increased plasma levels of the sulfonamide sulfasalazine by more than 1.5-fold in mice. These results support the potential role of TCBZSO and TCBZSO2 as ABCG2 inhibitors to participate in drug interactions and modulate ABCG2-mediated pharmacokinetic processes. PMID:22508302

  6. 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

  7. Development of an in vitro bioassay for measuring susceptibility to macrocyclic lactone anthelmintics in Dirofilaria immitis.

    PubMed

    Evans, Christopher C; Moorhead, Andrew R; Storey, Bobby E; Wolstenholme, Adrian J; Kaplan, Ray M

    2013-12-01

    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 R (2) 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.

  8. New life for an old drug: the anthelmintic drug niclosamide inhibits Pseudomonas aeruginosa quorum sensing.

    PubMed

    Imperi, Francesco; Massai, Francesco; Ramachandran Pillai, Cejoice; Longo, Francesca; Zennaro, Elisabetta; Rampioni, Giordano; Visca, Paolo; Leoni, Livia

    2013-02-01

    The need for novel antibacterial strategies and the awareness of the importance of quorum sensing (QS) in bacterial infections have stimulated research aimed at identifying QS inhibitors (QSIs). However, clinical application of QSIs identified so far is still distant, likely due to their unsuitability for use in humans. A promising way to overcome this problem is searching for anti-QS side activity among the thousands of drugs approved for clinical use in the treatment of different diseases. Here, we applied this strategy to the search for QSIs, by screening a library of FDA-approved compounds for their ability to inhibit the QS response in the Gram-negative pathogen Pseudomonas aeruginosa. We found that the anthelmintic drug niclosamide strongly inhibits the P. aeruginosa QS response and production of acyl-homoserine lactone QS signal molecules. Microarray analysis showed that niclosamide affects the transcription of about 250 genes, with a high degree of target specificity toward the QS-dependent regulon. Phenotypic assays demonstrated that niclosamide suppresses surface motility and production of the secreted virulence factors elastase, pyocyanin, and rhamnolipids, and it reduces biofilm formation. In accordance with the strong antivirulence activity disclosed in vitro, niclosamide prevented P. aeruginosa pathogenicity in an insect model of acute infection. Besides the finding that an FDA-approved drug has a promising antivirulence activity against one of the most antibiotic-resistant bacterial pathogens, this work provides a proof of concept that a lateral anti-QS activity can be detected among drugs already used in humans, validating a new approach to identify QSIs that could easily move into clinical applications.

  9. 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

  10. 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

  11. 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

  12. Large-scale management of insect resistance to transgenic cotton in Arizona: can transgenic insecticidal crops be sustained?

    PubMed

    Carrière, Y; Dennehy, T J; Pedersen, B; Haller, S; Ellers-Kirk, C; Antilla, L; Liu, Y B; Willott, E; Tabashnik, B E

    2001-04-01

    A major challenge for agriculture is management of insect resistance to toxins from Bacillus thuringiensis (Bt) produced by transgenic crops. Here we describe how a large-scale program is being developed in Arizona for management of resistance to Bt cotton in the pink bollworm, Pectinophora gossypiella (Saunders) (Lepidoptera: Gelechiidae), and other insect pests of cotton. Financial support from growers makes this program possible. Collaboration between the Arizona Cotton Research and Protection Council, the University of Arizona, and government agencies has led to development of resistance management guidelines, a remedial action plan, and tools for monitoring compliance with the proposed guidelines. Direct participation in development of resistance management policies is a strong incentive for growers to invest in resistance management research. However, more research, regularly updated regulations, and increased collaboration between stakeholders are urgently needed to maintain efficacy of Bt toxins in transgenic crops.

  13. Options for the management of antiviral resistance during hepatitis B therapy: reflections on battles over a decade.

    PubMed

    Yim, Hyung Joon; Hwang, Seong Gyu

    2013-09-01

    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.

  14. Treatment of multiple resistant field strain of Ostertagia spp. in Cashmere and Angora goats.

    PubMed

    Várady, M; Praslicka, J; Corba, J

    1994-05-01

    A multiple resistant field strain of gastro-intestinal nematodes was detected in Cashmere and Angora goats imported from New Zealand. Different treatments with three types of broad spectrum anthelmintics (albendazole, levamisole/tetramisole and ivermectin) at various dose rates are described. Satisfactory effect in Angora goats was not achieved until all three anthelmintics were administered simultaneously at twice the normal sheep dose. Post mortem worm counts and identification revealed that the resistant population consisted of 89% Ostertagia circumcincta, 6% Ostertagia ostertagi and 5% Ostertagia trifurcata. However, egg hatch assay carried out seven months later detected the presence of resistant nematodes again.

  15. Targeted therapies in CLL: mechanisms of resistance and strategies for management

    PubMed Central

    Johnson, Amy J.

    2015-01-01

    The therapy of relapsed chronic lymphocytic leukemia (CLL) has changed dramatically in the past year with the regulatory approval of idelalisib and ibrutinib, with other therapeutic small molecules likely to become widely available in the next few years. Although durable remissions are being seen in many patients with these agents, it is becoming apparent that some patients with high genomic risk disease will relapse. Next-generation sequencing in patients as well as in vitro models is affording us the opportunity to understand the biology behind these relapses, which is the first step to designing rational therapies to prevent and treat targeted therapy-resistant CLL. These strategies are critical, as these relapses can be very difficult to manage, and a coordinated effort to put these patients on clinical trials will be required to efficiently determine the optimal therapies for these patients. In this review, we will describe mechanisms of resistance, both proven and hypothesized, for idelalisib, ibrutinib, and venetoclax, describe patterns of resistance that have been described with ibrutinib, and discuss potential strategies for management of disease resistant to these drugs as well as potential strategies to prevent resistance. PMID:26065659

  16. 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.

  17. Epidemiology, Clinical Presentation, Laboratory Diagnosis, Antimicrobial Resistance, and Antimicrobial Management of Invasive Salmonella Infections.

    PubMed

    Crump, John A; Sjölund-Karlsson, Maria; Gordon, Melita A; Parry, Christopher M

    2015-10-01

    Salmonella enterica infections are common causes of bloodstream infection in low-resource areas, where they may be difficult to distinguish from other febrile illnesses and may be associated with a high case fatality ratio. Microbiologic culture of blood or bone marrow remains the mainstay of laboratory diagnosis. Antimicrobial resistance has emerged in Salmonella enterica, initially to the traditional first-line drugs chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole. Decreased fluoroquinolone susceptibility and then fluoroquinolone resistance have developed in association with chromosomal mutations in the quinolone resistance-determining region of genes encoding DNA gyrase and topoisomerase IV and also by plasmid-mediated resistance mechanisms. Resistance to extended-spectrum cephalosporins has occurred more often in nontyphoidal than in typhoidal Salmonella strains. Azithromycin is effective for the management of uncomplicated typhoid fever and may serve as an alternative oral drug in areas where fluoroquinolone resistance is common. In 2013, CLSI lowered the ciprofloxacin susceptibility breakpoints to account for accumulating clinical, microbiologic, and pharmacokinetic-pharmacodynamic data suggesting that revision was needed for contemporary invasive Salmonella infections. Newly established CLSI guidelines for azithromycin and Salmonella enterica serovar Typhi were published in CLSI document M100 in 2015.

  18. Insulin resistance and response to antiviral therapy in chronic hepatitis C: mechanisms and management.

    PubMed

    del Campo, José A; López, Reyes Aparcero; Romero-Gómez, Manuel

    2010-01-01

    Insulin resistance has been found to be an independent factor predicting sustained response to peginterferon plus ribavirin in patients with chronic hepatitis C. Insulin resistance seems to be involved in decreased sensitivity to interferon and could block interferon intracellular signaling. Insulin resistance promotes steatosis and fibrosis progression, induces pro-inflammatory cytokine secretion and increases adipose tissue, decreasing interferon availability. Moreover, suppressor of cytokines 3 and protein tyrosine-phosphatase seems to be able to block interferon and insulin signaling, building a feed-forward loop. Insulin resistance can be treated with exercise, diet or through the use of drugs that improve insulin sensitivity, like biguanides or glitazones. A recent controlled, randomized, double-blind clinical trial (TRIC-1) examined the effect of adding metformin to standard therapy in the treatment of hepatitis C. This study demonstrated that women infected with hepatitis C virus genotype 1 and HOMA >2 treated with metformin showed a greater drop in viral load during the first 12 weeks and a doubled sustained viral response in comparison with females receiving placebo. Pioglitazone has been used in previous nonresponders and naïve patients with disappointing results in two pilot trials. The mechanisms by which the virus promotes insulin resistance seems to be genotype-dependent and could explain, at least in part, the discrepancies between insulin sensitizers. Insulin resistance is a new target in the challenging management of chronic hepatitis C. PMID:20460925

  19. Epidemiology, Clinical Presentation, Laboratory Diagnosis, Antimicrobial Resistance, and Antimicrobial Management of Invasive Salmonella Infections

    PubMed Central

    Sjölund-Karlsson, Maria; Gordon, Melita A.; Parry, Christopher M.

    2015-01-01

    SUMMARY Salmonella enterica infections are common causes of bloodstream infection in low-resource areas, where they may be difficult to distinguish from other febrile illnesses and may be associated with a high case fatality ratio. Microbiologic culture of blood or bone marrow remains the mainstay of laboratory diagnosis. Antimicrobial resistance has emerged in Salmonella enterica, initially to the traditional first-line drugs chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole. Decreased fluoroquinolone susceptibility and then fluoroquinolone resistance have developed in association with chromosomal mutations in the quinolone resistance-determining region of genes encoding DNA gyrase and topoisomerase IV and also by plasmid-mediated resistance mechanisms. Resistance to extended-spectrum cephalosporins has occurred more often in nontyphoidal than in typhoidal Salmonella strains. Azithromycin is effective for the management of uncomplicated typhoid fever and may serve as an alternative oral drug in areas where fluoroquinolone resistance is common. In 2013, CLSI lowered the ciprofloxacin susceptibility breakpoints to account for accumulating clinical, microbiologic, and pharmacokinetic-pharmacodynamic data suggesting that revision was needed for contemporary invasive Salmonella infections. Newly established CLSI guidelines for azithromycin and Salmonella enterica serovar Typhi were published in CLSI document M100 in 2015. PMID:26180063

  20. Tackling antibiotic resistance in febrile neutropenia: current challenges with and recommendations for managing infections with resistant Gram-negative organisms.

    PubMed

    Nouér, Simone A; Nucci, Marcio; Anaissie, Elias

    2015-10-01

    Multidrug resistant (MDR) Gram-negative bacteria (GNB) have emerged as important pathogens and a serious challenge in the management of neutropenic patients worldwide. The great majority of infections are caused by the Enterobacteriaceae (especially Escherichia coli and Klebsiella spp.) and Pseudomonas aeruginosa, and less frequently Acinetobacter spp. and Stenotrophomonas maltophilia. A broader-spectrum empiric antibiotic regimen is usually recommended in patients with a history of prior bloodstream infection caused by a MDR GNB, in those colonized by a MDR GNB, and if MDR GNBs are frequently isolated in the initial blood cultures. In any situation, de-escalation to standard empiric regimen is advised if infection with MDR GNB is not documented.

  1. Unprecedented Silver Resistance in Clinically Isolated Enterobacteriaceae: Major Implications for Burn and Wound Management

    PubMed Central

    Norton, Rhy; Austin, Cindy; Mitchell, Amber; Zank, Sara; Durham, Paul

    2015-01-01

    Increased utilization of inorganic silver as an adjunctive to many medical devices has raised concerns of emergent silver resistance in clinical bacteria. Although the molecular basis for silver resistance has been previously characterized, to date, significant phenotypic expression of these genes in clinical settings is yet to be observed. Here, we identified the first strains of clinical bacteria expressing silver resistance at a level that could significantly impact wound care and the use of silver-based dressings. Screening of 859 clinical isolates confirmed 31 harbored at least 1 silver resistance gene. Despite the presence of these genes, MIC testing revealed most of the bacteria displayed little or no increase in resistance to ionic silver (200 to 300 μM Ag+). However, 2 isolates (Klebsiella pneumonia and Enterobacter cloacae) were capable of robust growth at exceedingly high silver concentrations, with MIC values reaching 5,500 μM Ag+. DNA sequencing of these two strains revealed the presence of genes homologous to known genetic determinants of heavy metal resistance. Darkening of the bacteria's pigment was observed after exposure to high silver concentrations. Scanning electron microscopy images showed the presence of silver nanoparticles embedded in the extracellular polymeric substance of both isolates. This finding suggested that the isolates may neutralize ionic silver via reduction to elemental silver. Antimicrobial testing revealed both organisms to be completely resistant to many commercially available silver-impregnated burn and wound dressings. Taken together, these findings provide the first evidence of clinical bacteria capable of expressing silver resistance at levels that could significantly impact wound management. PMID:26014954

  2. Unprecedented Silver Resistance in Clinically Isolated Enterobacteriaceae: Major Implications for Burn and Wound Management.

    PubMed

    Finley, Phillip J; Norton, Rhy; Austin, Cindy; Mitchell, Amber; Zank, Sara; Durham, Paul

    2015-08-01

    Increased utilization of inorganic silver as an adjunctive to many medical devices has raised concerns of emergent silver resistance in clinical bacteria. Although the molecular basis for silver resistance has been previously characterized, to date, significant phenotypic expression of these genes in clinical settings is yet to be observed. Here, we identified the first strains of clinical bacteria expressing silver resistance at a level that could significantly impact wound care and the use of silver-based dressings. Screening of 859 clinical isolates confirmed 31 harbored at least 1 silver resistance gene. Despite the presence of these genes, MIC testing revealed most of the bacteria displayed little or no increase in resistance to ionic silver (200 to 300 μM Ag(+)). However, 2 isolates (Klebsiella pneumonia and Enterobacter cloacae) were capable of robust growth at exceedingly high silver concentrations, with MIC values reaching 5,500 μM Ag(+). DNA sequencing of these two strains revealed the presence of genes homologous to known genetic determinants of heavy metal resistance. Darkening of the bacteria's pigment was observed after exposure to high silver concentrations. Scanning electron microscopy images showed the presence of silver nanoparticles embedded in the extracellular polymeric substance of both isolates. This finding suggested that the isolates may neutralize ionic silver via reduction to elemental silver. Antimicrobial testing revealed both organisms to be completely resistant to many commercially available silver-impregnated burn and wound dressings. Taken together, these findings provide the first evidence of clinical bacteria capable of expressing silver resistance at levels that could significantly impact wound management.

  3. Defenders of a lost cause: terror management and violent resistance to the disengagement plan.

    PubMed

    Hirschberger, Gilad; Ein-Dor, Tsachi

    2006-06-01

    Two studies, conducted 3 months before the Israeli pullout from the Gaza Strip and the Northern West Bank, examined whether reminders of death would lead right-wing Israelis to endorse violent resistance against the disengagement plan. More specifically, we hypothesized that this reaction would be particularly strong among participants high in denial--those who were unable to come to terms with the Israeli withdrawal. In Study 1 (N = 63), right-wing Israeli undergraduates were primed with death and asked to indicate whether they view violent resistance as legitimate and whether they would be willing to partake in such violence. In Study 2 (N = 42), Israeli settlers in the Gaza Strip completed a similar procedure as in Study 1. In both studies, primes of death led to greater support of violent resistance, but only among participants high in denial. The discussion examines the applicability of terror management theory to understanding real-life political crises.

  4. 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.

  5. 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...

  6. Anthelmintic potential of chicory forage is influenced by sesquiterpene lactone composition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  7. Determination of anthelmintic drug residues in milk using UPLC-MS/MS with rapid polarity switching

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  8. 21 CFR 500.25 - Anthelmintic drugs for use in animals.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 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 Decisions... that, in order to assure that anthelmintic drugs, including animal feeds bearing or containing...

  9. 21 CFR 500.25 - Anthelmintic drugs for use in animals.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 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 Decisions... that, in order to assure that anthelmintic drugs, including animal feeds bearing or containing...

  10. 21 CFR 500.25 - Anthelmintic drugs for use in animals.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 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 Decisions... that, in order to assure that anthelmintic drugs, including animal feeds bearing or containing...

  11. New Method for Analysis of Multiple Anthelmintic Residues in Animal Tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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. Acute toxicity of praziquantel (an anthelmintic) to grass carp and golden shiners

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Praziquantel is an anthelmintic that can be applied to the water to kill tapeworm and trematode parasites in fish. Effective praziquantel treatment rates have been determined but there is little information on the toxicity of this chemical to fish hosts of the parasites. Acute praziquantel toxicit...

  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. Enhancing Integrated Pest Management in GM Cotton Systems Using Host Plant Resistance

    PubMed Central

    Trapero, Carlos; Wilson, Iain W.; Stiller, Warwick N.; Wilson, Lewis J.

    2016-01-01

    Cotton has lost many ancestral defensive traits against key invertebrate pests. This is suggested by the levels of resistance to some pests found in wild cotton genotypes as well as in cultivated landraces and is a result of domestication and a long history of targeted breeding for yield and fiber quality, along with the capacity to control pests with pesticides. Genetic modification (GM) allowed integration of toxins from a bacteria into cotton to control key Lepidopteran pests. Since the mid-1990s, use of GM cotton cultivars has greatly reduced the amount of pesticides used in many cotton systems. However, pests not controlled by the GM traits have usually emerged as problems, especially the sucking bug complex. Control of this complex with pesticides often causes a reduction in beneficial invertebrate populations, allowing other secondary pests to increase rapidly and require control. Control of both sucking bug complex and secondary pests is problematic due to the cost of pesticides and/or high risk of selecting for pesticide resistance. Deployment of host plant resistance (HPR) provides an opportunity to manage these issues in GM cotton systems. Cotton cultivars resistant to the sucking bug complex and/or secondary pests would require fewer pesticide applications, reducing costs and risks to beneficial invertebrate populations and pesticide resistance. Incorporation of HPR traits into elite cotton cultivars with high yield and fiber quality offers the potential to further reduce pesticide use and increase the durability of pest management in GM cotton systems. We review the challenges that the identification and use of HPR against invertebrate pests brings to cotton breeding. We explore sources of resistance to the sucking bug complex and secondary pests, the mechanisms that control them and the approaches to incorporate these defense traits to commercial cultivars. PMID:27148323

  15. Enhancing Integrated Pest Management in GM Cotton Systems Using Host Plant Resistance.

    PubMed

    Trapero, Carlos; Wilson, Iain W; Stiller, Warwick N; Wilson, Lewis J

    2016-01-01

    Cotton has lost many ancestral defensive traits against key invertebrate pests. This is suggested by the levels of resistance to some pests found in wild cotton genotypes as well as in cultivated landraces and is a result of domestication and a long history of targeted breeding for yield and fiber quality, along with the capacity to control pests with pesticides. Genetic modification (GM) allowed integration of toxins from a bacteria into cotton to control key Lepidopteran pests. Since the mid-1990s, use of GM cotton cultivars has greatly reduced the amount of pesticides used in many cotton systems. However, pests not controlled by the GM traits have usually emerged as problems, especially the sucking bug complex. Control of this complex with pesticides often causes a reduction in beneficial invertebrate populations, allowing other secondary pests to increase rapidly and require control. Control of both sucking bug complex and secondary pests is problematic due to the cost of pesticides and/or high risk of selecting for pesticide resistance. Deployment of host plant resistance (HPR) provides an opportunity to manage these issues in GM cotton systems. Cotton cultivars resistant to the sucking bug complex and/or secondary pests would require fewer pesticide applications, reducing costs and risks to beneficial invertebrate populations and pesticide resistance. Incorporation of HPR traits into elite cotton cultivars with high yield and fiber quality offers the potential to further reduce pesticide use and increase the durability of pest management in GM cotton systems. We review the challenges that the identification and use of HPR against invertebrate pests brings to cotton breeding. We explore sources of resistance to the sucking bug complex and secondary pests, the mechanisms that control them and the approaches to incorporate these defense traits to commercial cultivars. PMID:27148323

  16. Taxanes in the management of metastatic castration-resistant prostate cancer: efficacy and management of toxicity.

    PubMed

    Schutz, Fabio A; Buzaid, Antonio C; Sartor, Oliver

    2014-09-01

    Androgen deprivation is the therapy of choice in the majority of patients with metastatic prostate cancer. However, a state of castration resistance ultimately occurs after hormone therapy, thus defining metastatic castration-resistant prostate cancer (mCRPC). mCRPC has historically been considered a relatively chemoresistant tumor. However, due to its ability to improve survival and the quality of life in comparison with mitoxantrone, docetaxel has been established as the standard chemotherapeutic agent for first-line therapy since 2004. Moreover, recent results have shown that the novel taxane cabazitaxel is able to prolong the overall survival of patients with mCRPC previously treated with docetaxel. Even though these taxanes display a favorable toxicity profile, their routine use in clinical practice requires knowledge about the most frequent and distinct adverse events that may result from their administration.

  17. [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

  18. 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

  19. A novel role for raloxifene nanomicelles in management of castrate resistant prostate cancer.

    PubMed

    Taurin, Sebastien; Nehoff, Hayley; van Aswegen, Thalita; Rosengren, Rhonda J; Greish, Khaled

    2014-01-01

    Of patients with castrate resistant prostate cancer (CRPC), less than 25-33% survive more than five years. Recent studies have implicated estrogen, acting either alone or synergistically with androgens in the development of castrate resistant prostate cancer. Several in vitro and in vivo studies, as well as a limited number of clinical trials, have highlighted the potential of selective estrogen receptor modulators, such as raloxifene (Ral) for the treatment of castrate resistant prostate cancer. However, the poor oral bioavailability and metabolism of selective estrogen receptor modulators limit their efficiency in clinical application. To overcome these limitations, we have used styrene co-maleic acid (SMA) micelle to encapsulate raloxifene. Compared to free drug, SMA-Ral micelles had 132 and 140% higher cytotoxicity against PC3 and DU 145 prostate cell lines, respectively. SMA-Ral effectively inhibits cell cycle progression, increases apoptosis, and alters the integrity of tumor spheroid models. In addition, the micellar system induced changes in expression and localization of estrogen receptors, epidermal growth factor receptor (EGFR), and downstream effectors associated with cell proliferation and survival. Finally, SMA-Ral treatment decreased migration and invasion of castrate resistant prostate cancer cell lines. In conclusion, SMA-Ral micelles can potentially benefit new strategies for clinical management of castrate resistant prostate cancer. PMID:24689036

  20. Beverton-Holt discrete pest management models with pulsed chemical control and evolution of pesticide resistance

    NASA Astrophysics Data System (ADS)

    Liang, Juhua; Tang, Sanyi; Cheke, Robert A.

    2016-07-01

    Pest resistance to pesticides is usually managed by switching between different types of pesticides. The optimal switching time, which depends on the dynamics of the pest population and on the evolution of the pesticide resistance, is critical. Here we address how the dynamic complexity of the pest population, the development of resistance and the spraying frequency of pulsed chemical control affect optimal switching strategies given different control aims. To do this, we developed novel discrete pest population growth models with both impulsive chemical control and the evolution of pesticide resistance. Strong and weak threshold conditions which guarantee the extinction of the pest population, based on the threshold values of the analytical formula for the optimal switching time, were derived. Further, we addressed switching strategies in the light of chosen economic injury levels. Moreover, the effects of the complex dynamical behaviour of the pest population on the pesticide switching times were also studied. The pesticide application period, the evolution of pesticide resistance and the dynamic complexity of the pest population may result in complex outbreak patterns, with consequent effects on the pesticide switching strategies.

  1. Anthelmintic and in vitro antioxidant evaluation of fractions of methanol extract of Leea asiatica leaves

    PubMed Central

    Sen, Saikat; De, Biplab; Devanna, N.; Chakraborty, Raja

    2012-01-01

    Leea asiatica, a folk medicinal plant of India, is used in the treatment of worm infection and other oxidative stress-related disorders, traditionally. In the present study, the in vitro anthelmintic and in vitro antioxidant activity of different fractions of the methanol extract from the Leea asiatica leaves were evaluated. The fraction displayed significant anthelmintic activity against Indian adult earthworms (Pheretima posthuma). The ethyl acetate fraction showed a better paralysis activity (13.99 ± 0.59), while the methanol fraction showed a better death time (63.76 ± 0.73 minutes), when compared with other fractions, at a dose of 50 mg/ml concentration. The anthelmintic activity of methanol and the ethyl acetate fraction were almost similar and comparable to the standard drug, piperazine citrate. The petroleum ether fraction did not produce a potent anthelmintic effect compared to the standard. The in vitro antioxidant activity was evaluated by using the diphenyl-picrylhydrazyl (DPPH) radical scavenging assay, nitric oxide radical scavenging assay, lipid peroxidation assay, and the ferric thiocyanate method. The ethyl acetate fraction showed better antioxidant activity in all tested methods. The IC50 value of the ethyl acetate fraction in the DPPH radical, nitric oxide radical scavenging assay, and lipid peroxidation assay were 9.5, 13.0, and 57.0 μg/ml, respectively. The fractions significantly (P < 0.05) inhibited the peroxidation of linoleic acid. The results confirmed the folk use of Leea asiatica in warm infection and the plant could be viewed as a potential source of natural anthelmintic and antioxidant compound. PMID:23284215

  2. Emergency slaughter of casualty cattle increases the prevalence of anthelmintic drug residues in muscle.

    PubMed

    Cooper, K M; Whyte, M; Danaher, M; Kennedy, D G

    2012-08-01

    The ProSafeBeef project studied the prevalence of residues of anthelmintic drugs used to control parasitic worms and fluke in beef cattle in Ireland. Injured (casualty) cattle may enter the human food chain under certain conditions, verified by an attending veterinarian and the livestock keeper. An analytical survey was conducted to determine if muscle from casualty cattle contained a higher prevalence of anthelmintic drug residues than healthy (full slaughter weight) cattle as a result of possible non-observance of complete drug withdrawal periods. A validated analytical method based on matrix solid-phase dispersive extraction (QuEChERS) and ultra-performance liquid chromatography-tandem mass spectrometry was used to quantify 37 anthelmintic drugs and metabolites in muscle (assay decision limits, CCα, 0.15-10.2 µg kg⁻¹). Of 199 control samples of beef purchased in Irish shops, 7% contained detectable anthelmintic drug residues but all were compliant with European Union Maximum Residue Limits (MRL). Of 305 muscle samples from injured cattle submitted to abattoirs in Northern Ireland, 17% contained detectable residues and 2% were non-compliant (containing either residues at concentrations above the MRL or residues of a compound unlicensed for use in cattle). Closantel and ivermectin were the most common residues, but a wider range of drugs was detected in muscle of casualty cattle than in retail beef. These data suggest that specific targeting of casualty cattle for testing for anthelmintic residues may be warranted in a manner similar to the targeted testing for antimicrobial compounds often applied in European National Residues Surveillance Schemes. PMID:22632575

  3. Anthelmintic effect of a methanol extract of leaves of Dregea volubilis on Paramphistomum explanatum.

    PubMed

    Hossain, Emdad; Chandra, Goutam; Nandy, Anadi P; Mandal, Subhash C; Gupta, Jayanta Kumar

    2012-02-01

    Dregea volubilis (family Asclepediaceae) is widely used as anthelmintic in traditional system of medicine in eastern and southern part of India. The aim of this study was to evaluate the anthelmintic activity of the methanol extract of D. volubilis leaves (MEDV) and to observe its effect through SEM study. Live parasites (trematode Paramphistomum explanatum) were collected from buffalo in 0.9% phosphate-buffered saline (PBS). It was incubated at 37 ± 1°C in media containing either no extract (control), the test drug, MEDV at four dose levels (10, 25, 50, and 100 mg/ml) or the standard drug, albendazole, at a dose of 10 mg/ml. The effectiveness of the extract was judged on the basis of the loss of spontaneous movement and/or complete destruction or death of the trematodes. After being removed from the experimental medium, trematodes were dipped in PBS at 37 ± 1°C and on gentle stimulation, the paralyzed parasite showed immobility. Death was confirmed when it completely lost its motility even when vigorously shaken or dipped in warm water (50°C). The trematodes, both drug treated and others, were further processed for SEM study using standard method. The anthelmintic activity was found with all the doses through paralysis and death of the organisms (p < 0.001). Maximum anthelmintic activity was found with a dose of 100 mg/ml. Minor damage was observed with both suckers, but severe distortion was found with tegumental surface of the treated trematodes. The present SEM-based study established the anthelmintic activity of MEDV.

  4. Benzimidazole resistance in equine cyathostomes in Slovakia.

    PubMed

    Várady, M; Königová, A; Corba, J

    2000-12-20

    The present study included 19 stud farms, including 243 horses, that were investigated for the occurrence of anthelmintic resistant cyathostomes. The number of horses on the farms varied from nine to more than 100, and horses of all ages were included. A minimum of seven horses were used for faecal egg count reduction (FECR) tests. The anthelmintics included were: fenbendazole (paste formulation), ivermectin (paste formulation) and pyrantel (powder). Resistance to benzimidazoles was detected on 14 farms, with FECR values ranging from 65.1 to 86.3%. Larval cultures after fenbendazole treatment revealed exclusively cyathostome larvae. Ivermectin was tested on eight farms and proved to be effective on all. Pyrantel was tested on two farms and FECR test indicated high efficacy (92-97%). Egg hatch assay (EHA) results showed that mean concentrations of thiabendazole that inhibited hatching in 50% of the eggs (ED(50)) in resistant populations were over 0.1 microg ml(-1). The results of our study suggest widespread resistance to fenbendazole in equine cyathostomes in Slovakia, and possible strategies to delay anthelmintic resistance are discussed briefly.

  5. Resource burden associated with contact precautions for methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus: the patient access managers' perspective.

    PubMed

    Shenoy, Erica S; Walensky, Rochelle P; Lee, Hang; Orcutt, Benjamin; Hooper, David C

    2012-08-01

    We surveyed patient access managers on the impact of contact precautions (CP) for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE) on time to bed assignment, and we investigated the factors influencing infection control policies allowing for discontinuation of CP. The majority of respondents reported an increase in time to bed assignment for patients with a history of MRSA and/or VRE infection or colonization. PMID:22759555

  6. Resilience and resistance of sagebrush ecosystems: implications for state and transition models and management treatments

    USGS Publications Warehouse

    Chambers, Jeanne C.; Miller, Richard F.; Board, David I.; Pyke, David A.; Roundy, Bruce A.; Grace, James B.; Schupp, Eugene W.; Tausch, Robin J.

    2014-01-01

    In sagebrush ecosystems invasion of annual exotics and expansion of piñon (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 by reducing woody fuels and increasing native perennial herbaceous species. We used Sagebrush Steppe Treatment Evaluation Project data to test predictions on effects of fire vs. mechanical treatments on resilience and resistance for three site types exhibiting cheatgrass (Bromus tectorum L.) invasion and/or piñon and juniper expansion: 1) warm and dry Wyoming big sagebrush (WY shrub); 2) warm and moist Wyoming big sagebrush (WY PJ); and 3) cool and moist mountain big sagebrush (Mtn PJ). Warm and dry (mesic/aridic) WY shrub sites had lower resilience to fire (less shrub recruitment and native perennial herbaceous response) than cooler and moister (frigid/xeric) WY PJ and Mtn PJ sites. Warm (mesic) WY Shrub and WY PJ sites had lower resistance to annual exotics than cool (frigid to cool frigid) Mtn PJ sites. In WY shrub, fire and sagebrush mowing had similar effects on shrub cover and, thus, on perennial native herbaceous and exotic cover. In WY PJ and Mtn PJ, effects were greater for fire than cut-and-leave treatments and with high tree cover in general because most woody vegetation was removed increasing resources for other functional groups. In WY shrub, about 20% pretreatment perennial native herb cover was necessary to prevent increases in exotics after treatment. Cooler and moister WY PJ and especially Mtn PJ were more resistant to annual exotics, but perennial native herb cover was still required for site recovery. We use our results to develop state and transition models that illustrate how resilience and resistance influence vegetation dynamics and management options.

  7. Partial Hepatectomy for the Resistant Fasciola Hepatica Infection in a Child.

    PubMed

    Belgin, Gülhan; S, Kanık Yüksek; H, Tezer; A, Özkaya Parlakay; B, Dalgıç; A, Dalgıç; G, Yilmaz

    2015-01-01

    Fascioliasis is an emerging and important chronic parasitic disease caused by two trematode liver fluke species: Fasciola hepatica (F. hepatica) and Fasciola gigantica (F. gigantica) infecting several herbivorous mammals including cattle, goats, sheep, and humans. We report a 9-year-old girl who suffered from F. hepatica infection and underwent right hepatectomy because of increasing abdominal pain resistant to anthelmintic chemotherapy. When anthelmintic drug treatment is not effective and abdominal pain persists, surgical resection including hepatectomy should be kept in mind for resistant F. hepatica infection.

  8. Resistance Management Techniques of Milton H. Erickson, M.D.: An Application to Nonhypnotic Mental Health Counseling.

    ERIC Educational Resources Information Center

    Otani, Akira

    1989-01-01

    Delineates five selected hypnotically based techniques of client resistance management pioneered by Milton H. Erickson: acceptance; paradoxical encouragement; reframing; displacement; dissociation. Explains how techniques can be applied to nonhypnotic mental health counseling. Discusses relevant clinical, theoretical, and empirical issues related…

  9. Anthelmintic effect of plant extracts containing condensed and hydrolyzable tannins on Caenorhabditis elegans and their antioxidant capacity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although tannin-rich forages are known to increase protein uptake and to reduce gastrointestinal nematode infections in grazing ruminants, most published research involves forages with condensed tannins (CT), while published literature lacks information on the anthelmintic capacity, nutritional bene...

  10. In vitro screening of compounds against laboratory and field isolates of human hookworm reveals quantitative differences in anthelmintic susceptibility.

    PubMed

    Treger, Rebecca S; Otchere, Joseph; Keil, Martin F; Quagraine, Josephine E; Rai, Ganesha; Mott, Bryan T; Humphries, Debbie L; Wilson, Michael; Cappello, Michael; Vermeire, Jon J

    2014-01-01

    A panel of 80 compounds was screened for anthelmintic activity against a laboratory strain of Ancylostoma ceylanicum and field isolates of hookworm obtained from school children in the Kintampo North District of the Brong Ahafo Region of Ghana. Although the laboratory strain of A. ceylanicum was more susceptible to the compounds tested than the field isolates of hookworm, a twofold increase in compound concentration resulted in comparable egg hatch percent inhibition for select compounds. These data provide evidence that the efficacy of anthelmintic compounds may be species-dependent and that field and laboratory strains of hookworm differ in their sensitivities to the anthelmintics tested. These data also suggest that both compound concentration and hookworm species must be considered when screening to identify novel anthelmintic compounds.

  11. In vitro Screening of Compounds against Laboratory and Field Isolates of Human Hookworm Reveals Quantitative Differences in Anthelmintic Susceptibility

    PubMed Central

    Treger, Rebecca S.; Otchere, Joseph; Keil, Martin F.; Quagraine, Josephine E.; Rai, Ganesha; Mott, Bryan T.; Humphries, Debbie L.; Wilson, Michael; Cappello, Michael; Vermeire, Jon J.

    2014-01-01

    A panel of 80 compounds was screened for anthelmintic activity against a laboratory strain of Ancylostoma ceylanicum and field isolates of hookworm obtained from school children in the Kintampo North District of the Brong Ahafo Region of Ghana. Although the laboratory strain of A. ceylanicum was more susceptible to the compounds tested than the field isolates of hookworm, a twofold increase in compound concentration resulted in comparable egg hatch percent inhibition for select compounds. These data provide evidence that the efficacy of anthelmintic compounds may be species-dependent and that field and laboratory strains of hookworm differ in their sensitivities to the anthelmintics tested. These data also suggest that both compound concentration and hookworm species must be considered when screening to identify novel anthelmintic compounds. PMID:24297811

  12. Clinical implications of antibiotic resistance for management of acute otitis media.

    PubMed

    Klein, J O

    1998-11-01

    Antibiotic resistance to available antimicrobial agents has been constant since the introduction of the sulfonamides in the 1930s. Multidrug-resistant Streptococcus pneumoniae and beta-lactamase-producing Haemophilus influenzae are a concern now because of the importance of these pathogens in infections of the respiratory tract in infants and children. Amoxicillin remains the drug of choice for initial episodes of acute otitis media (AOM) although increase of the dosage schedule to 80 mg/kg/day has been recommended by some investigators. There are 15 additional antimicrobial agents approved by the Food and Drug Administration for the indication of AOM. All approved drugs are clinically effective but some have been suggested to have priority for patients who fail amoxicillin: amoxicillin-clavulanate; an oral cephalosporin such as cefuroxime axetil; and intramuscular ceftriaxone. Management of the child with severe and recurrent disease should include antibiotic prophylaxis but the increased incidence of resistance requires selective use. Prevention of infection may be achieved by innovative techniques for interference with attachment of bacteria to the nasal mucosa such as administration of oligosaccharides in a nasal spray. The currently available polysaccharide pneumococcal vaccines have limited immunogenicity in infants, but the vaccine is useful in children 2 years of age and older who still have recurrent AOM. Children with frequent AOM during the prior respiratory season are candidates also for influenza virus vaccine. If medical management fails to prevent new episodes of AOM in children with severe and recurrent disease, placement of tympanostomy tubes and possible adenoidectomy should be considered.

  13. In vivo anthelmintic activity of an aqueous extract from sisal waste (Agave sisalana Perr.) against gastrointestinal nematodes in goats.

    PubMed

    Botura, M B; Silva, G D; Lima, H G; Oliveira, J V A; Souza, T S; Santos, J D G; Branco, A; Moreira, E L T; Almeida, M A O; Batatinha, M J M

    2011-04-19

    The resistance of gastrointestinal nematodes (GINs) of small ruminants to anthelmintics has required the investigation of new alternatives. The aim of the present study was to evaluate the in vivo anthelmintic activity of an aqueous extract from sisal waste (Agave sisalana) (AESW) against GINs in goats and to observe the animals for toxic effects. Thirty animals that were naturally infected with GINs were distributed into three groups: group I, was treated with daily doses of AESW (1.7 g/kg) for eight days; Group II, the positive control, was treated with a single dose of levamisole phosphate (6.3mg/kg); and group III, the negative control, was left untreated. Faecal eggs counts (FECs), coprocultures and post-mortem worm counts were performed to assess the efficacy of the treatments. Clinical and laboratory analyses were performed to evaluate any toxic effects associated with the treatment. In the goats in groups I and II, a significant reduction (p<0.05) of the number of eggs and infective larvae (L(3)) was observed. The maximum reductions of the FECs were 50.3% and 93.6% for groups I and II, respectively, whereas the percent reductions of the total number of L(3) larvae were 80% (group I) and 85.6% (group II). There was no difference between groups I and III with respect to worm burden, and the percent reductions were 28.8% and 63.4% for Oesophagostomum columbianum and Trichostrongylus colubriformis, respectively. No reduction was detected for the Haemonchus contortus. The positive control group demonstrated a 74% reduction of the parasites that were recovered from the digestive tract. There were no changes in clinical and haematological parameters. The levels of serum urea and creatinine were higher in group I, but remained within the normal range. At necropsy, pale mucous membranes, abomasitis and enteritis were associated with parasitism. In addition, a histological analysis of the liver and kidney did not reveal any changes suggestive of toxicity. A chemical

  14. Evaluation of Anthelmintic Activity and Composition of Pumpkin (Cucurbita pepo L.) Seed Extracts—In Vitro and in Vivo Studies

    PubMed Central

    Grzybek, Maciej; Kukula-Koch, Wirginia; Strachecka, Aneta; Jaworska, Aleksandra; Phiri, Andrew M.; Paleolog, Jerzy; Tomczuk, Krzysztof

    2016-01-01

    A significant number of studies report growing resistance in nematodes thriving in both humans and livestock. This study was conducted to evaluate the in vitro and in vivo anthelmintic efficiency of Curcubita pepo (C. pepo) L. hot water extract (HWE), cold water extract (CWE) or ethanol extract (ETE) on two model nematodes: Caenorhabditis elegans (C. elegans) and Heligmosoides bakeri (H. bakeri). Methods: Raman, IR and LC-MS spectroscopy analyses were performed on the studied plant material to deliver qualitative and quantitative data on the composition of the obtained extracts: ETE, HWE and CWE. The in vitro activity evaluation showed an impact of C. pepo extracts on C. elegans and different developmental stages of H. bakeri. The following in vivo experiments on mice infected with H. bakeri confirmed inhibitory properties of the most active pumpkin extract selected by the in vitro study. All of the extracts were found to contain cucurbitine, aminoacids, fatty acids, and-for the first time-berberine and palmatine were identified. All C. pepo seed extracts exhibited a nematidicidal potential in vitro, affecting the survival of L1 and L2 H. bakeri larvae. The ETE was the strongest and demonstrated a positive effect on H. bakeri eggs hatching and marked inhibitory properties against worm motility, compared to a PBS control. No significant effects of pumpkin seed extracts on C. elegans integrity or motility were found. The EtOH extract in the in vivo studies showed anthelmintic properties against both H. bakeri fecal egg counts and adult worm burdens. The highest egg counts reduction was observed for the 8 g/kg dose (IC50 against H. bakeri = 2.43; 95% Cl = 2.01–2.94). A decrease in faecal egg counts (FEC) was accompanied by a significant reduction in worm burden of the treated mice compared to the control group. Conclusions: Pumpkin seed extracts may be used to control of Gastrointestinal (G.I.) nematode infections. This relatively inexpensive alternative to the

  15. Assessment of the Anthelmintic Efficacy of Albendazole in School Children in Seven Countries Where Soil-Transmitted Helminths Are Endemic

    PubMed Central

    Vercruysse, Jozef; Behnke, Jerzy M.; Albonico, Marco; Ame, Shaali Makame; Angebault, Cécile; Bethony, Jeffrey M.; Engels, Dirk; Guillard, Bertrand; Hoa, Nguyen Thi Viet; Kang, Gagandeep; Kattula, Deepthi; Kotze, Andrew C.; McCarthy, James S.; Mekonnen, Zeleke; Montresor, Antonio; Periago, Maria Victoria; Sumo, Laurentine; Tchuem Tchuenté, Louis-Albert; Thach, Dang Thi Cam; Zeynudin, Ahmed; Levecke, Bruno

    2011-01-01

    Background The three major soil-transmitted helminths (STH) Ascaris lumbricoides, Trichuris trichiura and Necator americanus/Ancylostoma duodenale are among the most widespread parasites worldwide. Despite the global expansion of preventive anthelmintic treatment, standard operating procedures to monitor anthelmintic drug efficacy are lacking. The objective of this study, therefore, was to define the efficacy of a single 400 milligram dose of albendazole (ALB) against these three STH using a standardized protocol. Methodology/Principal Findings Seven trials were undertaken among school children in Brazil, Cameroon, Cambodia, Ethiopia, India, Tanzania and Vietnam. Efficacy was assessed by the Cure Rate (CR) and the Fecal Egg Count Reduction (FECR) using the McMaster egg counting technique to determine fecal egg counts (FEC). Overall, the highest CRs were observed for A. lumbricoides (98.2%) followed by hookworms (87.8%) and T. trichiura (46.6%). There was considerable variation in the CR for the three parasites across trials (country), by age or the pre-intervention FEC (pre-treatment). The latter is probably the most important as it had a considerable effect on the CR of all three STH. Therapeutic efficacies, as reflected by the FECRs, were very high for A. lumbricoides (99.5%) and hookworms (94.8%) but significantly lower for T. trichiura (50.8%), and were affected to different extents among the 3 species by the pre-intervention FEC counts and trial (country), but not by sex or age. Conclusions/Significance Our findings suggest that a FECR (based on arithmetic means) of >95% for A. lumbricoides and >90% for hookworms should be the expected minimum in all future surveys, and that therapeutic efficacy below this level following a single dose of ALB should be viewed with concern in light of potential drug resistance. A standard threshold for efficacy against T. trichiura has yet to be established, as a single-dose of ALB is unlikely to be satisfactory for this

  16. Cyclotide Structure–Activity Relationships: Qualitative and Quantitative Approaches Linking Cytotoxic and Anthelmintic Activity to the Clustering of Physicochemical Forces

    PubMed Central

    Park, Sungkyu; Strömstedt, Adam A.; Göransson, Ulf

    2014-01-01

    Cyclotides are a family of plant-derived proteins that are characterized by a cyclic backbone and a knotted disulfide topology. Their cyclic cystine knot (CCK) motif makes them exceptionally resistant to thermal, chemical, and enzymatic degradation. Cyclotides exert much of their biological activity via interactions with cell membranes. In this work, we qualitatively and quantitatively analyze the cytotoxic and anthelmintic membrane activities of cyclotides. The qualitative and quantitative models describe the potency of cyclotides using four simple physicochemical terms relevant to membrane contact. Specifically, surface areas of the cyclotides representing lipophilic and hydrogen bond donating properties were quantified and their distribution across the molecular surface was determined. The resulting quantitative structure-activity relation (QSAR) models suggest that the activity of the cyclotides is proportional to their lipophilic and positively charged surface areas, provided that the distribution of these surfaces is asymmetric. In addition, we qualitatively analyzed the physicochemical differences between the various cyclotide subfamilies and their effects on the cyclotides' orientation on the membrane and membrane activity. PMID:24682019

  17. Anthelmintic activity of chicory (Cichorium intybus): in vitro effects on swine nematodes and relationship to sesquiterpene lactone composition.

    PubMed

    Williams, Andrew R; Peña-Espinoza, Miguel A; Boas, Ulrik; Simonsen, Henrik T; Enemark, Heidi L; Thamsborg, Stig M

    2016-05-01

    Chicory is a perennial crop that has been investigated as a forage source for outdoor-reared ruminants and pigs, and has been reported to have anthelmintic properties. Here, we investigated in vitro anthelmintic effects of forage chicory-extracts against the highly prevalent swine parasites Ascaris suum and Oesophagostomum dentatum. Methanol extracts were prepared and purified from two different cultivars of chicory (Spadona and Puna II). Marked differences were observed between the anthelmintic activity of extracts from the two cultivars. Spadona extracts had potent activity against A. suum third (L3) and fourth (L4) - stage larvae, as well as O. dentatum L4 and adults, whereas Puna II extracts had less activity against A. suum and no activity towards O. dentatum L4. Transmission-electron microscopy of A. suum L4 exposed to Spadona extracts revealed only subtle changes, perhaps indicative of a specific anthelmintic effect rather than generalized toxicity. Ultra-high liquid chromatography-mass spectrometry analysis revealed that the purified extracts were rich in sesquiterpene lactones (SL), and that the SL profile differed significantly between cultivars. This is the first report of anthelmintic activity of forage chicory towards swine nematodes. Our results indicate a significant anthelmintic effect, which may possibly be related to SL composition. PMID:26935644

  18. Acute toxicity, brine shrimp cytotoxicity, anthelmintic and relaxant potentials of fruits of Rubus fruticosus Agg

    PubMed Central

    2013-01-01

    Background Rubus fruticosus is used in tribal medicine as anthelmintic and an antispasmodic. In the current work, we investigated the anthelmintic and antispasmodic activities of crude methanol extract of fruits of R. fruticosus on scientific grounds. Acute toxicity and brine shrimp cytotoxicity activity of the extract were also performed. Methods Acute toxicity study of crude methanol extract of R. fruticosus was performed on mice. In vitro Brine shrimp cytotoxicity assay was performed on shrimps of Artemia salina. In vitro Anthelmintic activity was tested against Raillietina spiralis and Ascaridia galli. Relaxant activities were tested on spontaneous rabbits’ jejunal preparations. Calcium chloride curves were constructed to elucidate possible mode of action of the extract. Results LD 50 of the extract for acute toxicity studies was 887.75 ± 9.22 mg/ml. While CC 50 of the extract for Brine shrimps cytotoxicity assay was 13.28 ± 2.47 μg/ml. Test samples of crude methanolic extract of R. fruticosus (Rf.Cr) at concentration 20 mg/ml showed excellent anthelmintic activity against Raillietina spiralis. Anthelmintic activity was 1.37 times of albendazole against the Raillietina spiralis at concentration 40 mg/ml. At higher concentration (40 mg/ml), Rf.Cr has 89. 83% parasiticidal activity. The mean EC50 relaxation activity for spontaneous and KCl-induced contractions was 7.96 ± 0.1 and 6.45 ± 0.29 mg/ml, respectively. EC 50 (Log[Ca++]M) for control calcium chloride curves was −1.75 ± 0.01 vs. EC 50 −1.78 ± 0.06 in the presence of 3.0 mg/ml of Rf.Cr. Similarly, EC 50(Log[Ca++]M) in the absence and presence of verapamil (0.1 μM) were −2.46 ± 0.01 and −1.72 ± 0.02, respectively. Conclusions The anthelmintic and relaxant activities explained traditional uses of R. fruticosus on scientific grounds. Relaxant activity follows the inhibition of voltage gated channels. Although the plant extract has cytotoxic effects, yet it is

  19. microRNAs: a role in drug resistance in parasitic nematodes?

    PubMed

    Devaney, Eileen; Winter, Alan D; Britton, Collette

    2010-09-01

    Drug resistance in parasitic nematodes is an increasing problem worldwide, with resistance reported to all three commonly used classes of anthelmintics. Most studies to date have sought to correlate the resistant phenotype with genotypic changes in putative target molecules. Although this approach has identified mutations in several relevant genes, resistance might result from a complex interaction of different factors. Here we propose an alternative mechanism underlying the development of drug resistance based on functional differences in microRNA activity in resistant parasites. microRNAs play an important role in resistance to chemotherapeutic agents in many tumour cells and here we discuss whether they might also be involved in anthelmintic resistance in parasitic nematodes.

  20. A Prescription for Resistance: Management of Staphylococcal Skin Abscesses by General Practitioners in Australia

    PubMed Central

    Parrott, Christine; Wood, Gillian; Bogatyreva, Ekaterina; Coombs, Geoffrey W.; Johnson, Paul D. R.; Bennett, Catherine M.

    2016-01-01

    Objectives: We investigated the management of staphylococcal abscesses (boils) by general practitioners (GPs) in the context of rising antibiotic resistance in community strains of Staphylococcus aureus. Design, Setting, Participants: We analyzed patient-reported management of 66 cases of uncomplicated skin abscesses from the frequency matched methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) Community-Onset Staphylococcus aureus Household Cohort (COSAHC) study (Melbourne, Australia, 2008–2012). Susceptibilities in all cases were known: 50/66 abscesses were caused by MRSA. In order to investigate GP-reported management of staphylococcal abscesses, we surveyed a random subset of GPs, from the COSAHC study (41), and of GPs (39) who used the same community-based pathology service (December 2011–May 2012). Main outcome measures: Patient outcomes, antibiotics prescribed, antibiotic resistance profiles of infecting strains, rates of incision and drainage (I&D), and attitudes to ordering microbiological cultures. Results: MRSA was three times more likely to be cultured from an abscess than MSSA. Patient-reported management revealed 100% were prescribed antibiotics and only 60.6% had I&D. Of those 85% who remembered their prescription(s), 81% of MRSA cases and 23% of MSSA cases initially received inactive antibiotics. Repeat GP visits where antibiotics were changed occurred in 45 MRSA and 7 MSSA cases, although at least 33% of subsequent prescriptions were inactive for the MRSA infections. Patients treated with I&D and antibiotics did no better than those treated with only I&D, regardless of the antibiotic activity. In the GP surveys, 89% reported I&D, with or without antibiotics, to be their preferred management. Only 29.9% of GPs would routinely swab abscesses. Conclusion: The recommended management of uncomplicated Staphylococcus abscesses is I&D without antibiotics to reduce exposure to unnecessary antibiotics. In our study, I&D was

  1. Use of anthelmintics in herbivores and evaluation of risks for the non target fauna of pastures.

    PubMed

    Lumaret, Jean-Pierre; Errouissi, Faiek

    2002-01-01

    The overall purpose ofthis paperwas to review the major and most recent literature relating the effects of anthelmintics on dung breeding invertebrates and dung degradation. Faecal residues or metabolites of drugs belonging to the benzimidazole and levamisole/morantel groups are relatively harmless to dung fauna, on the contrary to other anthelmintics such as coumaphos, dichlorvos, phenothiazine, piperazine, synthetic pyrethroids, and most macrocyclic lactones which have been shown to be highly toxic for dung beetles (abamectin, ivermectin, eprinomectin, doramectin), among which moxidectin was the less toxic for dung beetles. To date, the detrimental impact upon non-target organisms has been considered acceptable in eradicating the parasites because of their economic importance to commercial livestock production. The consequences of routine treatments are discussed with consideration of the long-term consequences for cow pat fauna and sustainable pastureland ecology.

  2. Anthelmintic efficacy of extracts of Spigelia anthelmia Linn on experimental Nippostrongylus braziliensis in rats.

    PubMed

    Jegede, Olorunfemi Cornelius; Ajanusi, Joseph Ologunja; Adaudi, Ambrose O; Agbede, Rowland I S

    2006-09-01

    Spigelia anthelmia Linn is used as a herb and is a common annual weed of cultivation in open re-growths, on unused land in towns as well as on road sides. The plant can grow to approximately 30 cm in height. The aim of this study was to screen extracts of Spigelia anthelmia for their anthelmintic activity against an experimental Nippostrongylus braziliensis infection in rats. Acute oral toxicity occurred at a dose of 1,140 mg/kg, while anthelmintic trials against Nippostrongylus braziliensis in rats using the aqueous fraction showed a progressive decrease in worm count with increasing dose (10, 13, 16, 20 and 25 mg per kg body weight) (p < 0.05). At 25 mg per kg body weight, the worm count was significantly lower than that at 10 mg per kg body weight (p < 0.05).

  3. Anthelmintics residues in raw milk. Assessing intake by a children population.

    PubMed

    Tsiboukis, D; Sazakli, E; Jelastopulu, E; Leotsinidis, M

    2013-01-01

    Anthelmintics, such as benzimidazoles and probenzimidazoles, are veterinary drugs used against endoparasites in food producing animals. A number of these drugs are considered responsible for embryotoxicity and teratogenicity. The residue levels of Albendazole, Febantel, Fenbendazole, Mebendazole and some of their metabolites (Albendazole sulphoxide, Albendazole sulphone, Fenbendazole sulfone) were assessed in 123 (42 goat, 69 sheep, 12 bovine) raw milk samples collected from all farms throughout Southern Greece. Sample analysis was performed by HPLC with Diode Array Detector. A high percentage (27.6%) of the samples examined was found to be positive for the investigated compounds. In 14 samples (11.4%), the residues' concentration exceeded the established Maximum Residue Limits. Estimated Daily Intakes were calculated for a population of 723 children aged 10-12 years. Data on milk consumption were obtained by personal interview through a 7-day food frequency questionnaire. The maximum Estimated Daily Intakes for the anthelmintic residues, concerning raw milk, did not exceed the current Acceptable Daily Intake.

  4. Management of bone metastases in patients with castration-resistant prostate cancer.

    PubMed

    Cathomas, Richard; Bajory, Zoltan; Bouzid, Mounira; El Ghoneimy, Ahmed; Gillessen, Silke; Goncalves, Frederico; Kacso, Gabriel; Kramer, Gero; Milecki, Piotr; Pacik, Dalibor; Tantawy, Wahid; Lesniewski-Kmak, Krzystof

    2014-01-01

    Bone metastases are a very common problem in prostate cancer. They are associated with considerable morbidity, adversely affect quality of life and frequently lead to advanced bone events (so-called skeletal-related events, SREs); SREs include fractures, spinal cord compression and the requirement for bone surgery or bone radiation. The aim of this paper was to evaluate currently available treatment options in the prevention and management of SREs and bone metastases in men with castration-resistant prostate cancer and to outline the importance of interdisciplinary management strategies. It also discusses the diagnostic workup of osseous metastases and practical considerations for the utilization of bone-targeted therapies in accordance with current guidelines to provide a consensus for special and/or difficult clinical situations.

  5. Effect of selected anthelmintics on three common helminths in the brown pelican (Pelecanus occidentalis).

    PubMed

    Grimes, J; Suto, B; Greve, J H; Albers, H F

    1989-01-01

    The effect of selected anthelmintics (albendazole, fenbendazole, piperazine dihydrochloride and clorsulon) against three major helminths (Contracaecum multipapillatum, Mesostephanus appendiculatoides, and Phagicola longus) were studied in 29 brown pelicans (Pelecanus occidentalis). Albendazole and fenbendazole were highly effective against all three parasites. Clorsulon had moderate effect against M. appendiculatoides and poor effect against C. multipapillatum and P. longus. Piperazine dihydrochloride had no effect against these helminths. PMID:2915399

  6. An extensive comparison of the effect of anthelmintic classes on diverse nematodes.

    PubMed

    Hu, Yan; Ellis, Brian L; Yiu, Ying Y; Miller, Melanie M; Urban, Joseph F; Shi, Linda Z; Aroian, Raffi V

    2013-01-01

    Soil-transmitted helminths are parasitic nematodes that inhabit the human intestine. These parasites, which include two hookworm species, Ancylostomaduodenale and Necator americanus, the whipworm Trichuristrichiura, and the large roundworm Ascarislumbricoides, infect upwards of two billion people and are a major cause of disease burden in children and pregnant women. The challenge with treating these diseases is that poverty, safety, and inefficient public health policy have marginalized drug development and distribution to control infection in humans. Anthelmintics (anti-worm drugs) have historically been developed and tested for treatment of non-human parasitic nematodes that infect livestock and companion animals. Here we systematically compare the in vitro efficacy of all major anthelmintic classes currently used in human therapy (benzimidazoles, nicotinic acetylcholine receptor agonists, macrocyclic lactones, nitazoxanide) against species closely related to human parasitic nematodes-Ancylostoma ceylanicum, Trichurismuris, and Ascarissuum--- as well as a rodent parasitic nematode used in veterinary drug discovery, Heligmosomoidesbakeri, and the free-living nematode Caenorhabditis elegans. Extensive in vitro data is complemented with single-dose in vivo data in three rodent models of parasitic diseases. We find that the effects of the drugs in vitro and in vivo can vary greatly among these nematode species, e.g., the efficacy of albendazole is strong on A. ceylanicum but weak on H. bakeri. Nonetheless, certain commonalities of the in vitro effects of the drugs can be seen, e.g., nitazoxanide consistently shows an all-or-nothing response. Our in vitro data suggest that further optimization of the clinical efficacy of some of these anthelmintics could be achieved by altering the treatment routine and/or dosing. Most importantly, our in vitro and in vivo data indicate that the hookworm A. ceylanicum is a particularly sensitive and useful model for anthelmintic

  7. Evaluation of enhanced virgin coconut oil and senduduk (Melastoma malabathricum) as anthelmintics against caprine strongyle nematodes.

    PubMed

    Basripuzi, H B; Sani, R A; Ariff, O M; Chandrawathani, P

    2013-09-01

    A study was conducted to evaluate the anthelmintic properties of enhanced virgin coconut oil (EVCO) and senduduk (Melastoma malabathricum) plant against strongyle nematodes in goats. Two preparations of 10% EVCO dissolved in 90% virgin coconut oil and 10% EVCO dissolved in 90% palm oil, were given orally to two groups of mixed breeds goats. The efficacy test indicated that EVCO was insufficiently active as an anthelmintic. Four concentrations of senduduk solution (1.25, 2.5, 5.0 and 10 mg ml(-1)) were compared with a control and albendazole in an in vitro test for larvicidal effect. There was no significant larval mortality using senduduk solution. An in vivo test of senduduk was conducted by comparing three groups of goats, namely control, levamisole and treatment groups that were given a daily oral dose of senduduk crude extract with 1g kg(-1) from Day 0 to Day 12 and 2 g kg(-1) from Day 13 to Day 30. This efficacy test with senduduk also gave negative results. The findings obtained indicated that EVCO and senduduk were ineffective as anthelmintics against caprinestrongyle nematodes at the concentrations used.

  8. Determination of anthelmintic efficacy against Toxocara canis in dogs by use of capsule endoscopy.

    PubMed

    Lee, Alice C Y; Epe, Christian; Bowman, Dwight D

    2015-09-15

    Industry guidelines for anthelmintic testing call for postmortem inspection of animals to verify treatment efficacy. A previous study showed that capsule endoscopy (CE) can be performed on dogs in vivo to quantify hookworms in the small intestine. Adoption of a minimally invasive procedure such as this could reduce the need for necropsy in efficacy trials. The present study employed CE to enumerate Toxocara canis in dogs, with two main goals: to determine if multiple capsule examinations improves the accuracy of worm counts compared to a single examination, and to establish if the efficacy of an anthelmintic compound is the same whether calculated using CE or necropsy data. To avoid needless animal sacrifice, the study was carried out on beagle dogs already in a product development trial with a planned terminal endpoint. Dogs were infected by oral inoculation with T. canis eggs. Untreated control dogs (n=8) were evaluated by CE three times while dogs treated with test compounds (3 groups of 4) were examined only once. Utilizing either the average count or just the last complete capsule examination, a robust correlation was found between CE and postmortem numbers (r=0.94, p<0.001). Calculated anthelmintic efficacy was essentially identical for the two enumeration methods, ranging from 94% to 100% for the three research compounds. CE may therefore be a viable alternative to necropsy for T. canis parasiticide trials. PMID:26321133

  9. Evaluation of enhanced virgin coconut oil and senduduk (Melastoma malabathricum) as anthelmintics against caprine strongyle nematodes.

    PubMed

    Basripuzi, H B; Sani, R A; Ariff, O M; Chandrawathani, P

    2013-09-01

    A study was conducted to evaluate the anthelmintic properties of enhanced virgin coconut oil (EVCO) and senduduk (Melastoma malabathricum) plant against strongyle nematodes in goats. Two preparations of 10% EVCO dissolved in 90% virgin coconut oil and 10% EVCO dissolved in 90% palm oil, were given orally to two groups of mixed breeds goats. The efficacy test indicated that EVCO was insufficiently active as an anthelmintic. Four concentrations of senduduk solution (1.25, 2.5, 5.0 and 10 mg ml(-1)) were compared with a control and albendazole in an in vitro test for larvicidal effect. There was no significant larval mortality using senduduk solution. An in vivo test of senduduk was conducted by comparing three groups of goats, namely control, levamisole and treatment groups that were given a daily oral dose of senduduk crude extract with 1g kg(-1) from Day 0 to Day 12 and 2 g kg(-1) from Day 13 to Day 30. This efficacy test with senduduk also gave negative results. The findings obtained indicated that EVCO and senduduk were ineffective as anthelmintics against caprinestrongyle nematodes at the concentrations used. PMID:24189681

  10. The efficacy of anthelmintic drugs against nematodes infecting free-ranging eastern grey kangaroos, Macropus giganteus.

    PubMed

    Cripps, Jemma; Beveridge, Ian; Coulson, Graeme

    2013-07-01

    Effective anthelmintics are valuable tools for biologists conducting manipulative field experiments to examine effects of parasites on wildlife. However, before such experiments are carried out the efficacy of these drugs must be determined. We conducted three field experiments (May 2010-September 2011) on free-ranging eastern grey kangaroos (Macropus giganteus) at a golf course in Victoria, Australia, treating animals with the anthelmintic drugs moxidectin (subcutaneous, 1 mg/kg, 2 mg/kg), ivermectin (subcutaneous, 200 μg/kg), and albendazole (oral, 3.8 mg/kg). After treatment we monitored strongylid fecal egg counts (FECs) over time and assessed anthelmintic efficacy using fecal egg count reduction tests (FECRTs). We also performed a larval development assay (LDA) to evaluate directly the efficacy in the nematode population. Unexpectedly, moxidectin and ivermectin had low efficacy with maximum FEC reductions of 82% and 28%, respectively. However, treatment with albendazole reduced FECs by 100% in all kangaroos and egg counts remained low for up to 3 mo. The results from the LDA supported the FECRTs, with low macrocyclic lactone efficacy and high albendazole efficacy. Macrocyclic lactones, at recommended dose rates, were much less effective against strongylid nematodes in kangaroos than has been reported for domestic herbivores. This may be partly due to pharmacokinetics in the host and partly due to low susceptibility in some of the nematodes infecting eastern grey kangaroos.

  11. The efficacy of four anthelmintics against Calicophoron daubneyi in naturally infected dairy cattle.

    PubMed

    Arias, M S; Sanchís, J; Francisco, I; Francisco, R; Piñeiro, P; Cazapal-Monteiro, C; Cortiñas, F J; Suárez, J L; Sánchez-Andrade, R; Paz-Silva, A

    2013-10-18

    The paramphistomicidal activity of four anthelmintics in dairy cattle naturally infected by Calicophoron (Paramphistomum) daubneyi was evaluated. Seventy Friesian adult cows were treated at drying-off (19 albendazole; 23 netobimin; 13 closantel and 15 oxyclozanide), and 21 remained untreated as controls. The anthelmintic efficacy was determined by estimating the faecal egg count reduction (FECR) values for each of the anthelmintics. The reduction in the number of cows shedding eggs in the faeces was also estimated. The C. daubneyi egg-output was not fully suppressed following the administration of any of the parasiticides. The FECR values ranged from 0% to 26% in the cows receiving albendazole or netobimin, with 11-39% of cattle becoming negative after therapy. Better results were achieved with closantel and oxyclozanide, with FECR values of 97-99% and CPCR (cattle positive by coprology reduction) percentages of 85-93%. The observation of a similar efficacy with closantel and oxyclozanide against C. daubneyi led us to recommend the administration of closantel in those countries where oxyclozanide is not available.

  12. Managing and resisting stigma: a qualitative study among people living with HIV in South Africa

    PubMed Central

    Abrahams, Naeemah; Jewkes, Rachel

    2012-01-01

    Background Living with HIV is of daily concern for many South Africans and poses challenges including adapting to a chronic illness and continuing to achieve and meet social expectations. This study explored experiences of being HIV-positive and how people manage stigma in their daily social interactions. Methods Using qualitative methods we did repeat interviewed with 42 HIV-positive men and women in Cape Town and Mthatha resulting in 71 interviews. Results HIV was ubiquitous in our informants’ lives, and almost all participants reported fear of stigma (perceived stigma), but this fear did not disrupt them completely. The most common stigma experiences were gossips and insults where HIV status was used as a tool, but these were often resisted. Many feared the possibility of stigma, but very few had experiences that resulted in discrimination or loss of social status. Stigma experiences were intertwined with other daily conflicts and together created tensions, particularly in gender relations, which interfered with attempts to regain normality. Evidence of support and resistance to stigma was common, and most encouraging was the evidence of how structural interventions such as de-stigmatizing policies impacted on experiences and transference into active resistance. Conclusions The study showed the complex and shifting nature of stigma experiences. These differences must be considered when we intensify stigma reduction with context- and gender-specific strategies focussing on those not yet on ARV programmes. PMID:22905361

  13. Effect of insecticide management history on emergence phenology and neonicotinoid resistance in Leptinotarsa decemlineata (Coleoptera: Chrysomelidae).

    PubMed

    Huseth, A S; Groves, R L

    2013-12-01

    Emergence phenology and fitness attributes of several Colorado potato beetle, Leptinotarsa decemlineata (Say), populations were measured under field and greenhouse conditions. Anecdotal observations by producers and pest managers in many locations of the upper Midwest increasingly suggested that select populations of Colorado potato beetle were emerging over a longer period in the spring and were less sensitive to systemic neonicotinoids in cultivated potato. These changes in emergence phenology may be related to changes in systemic insecticide concentration over time. Specifically, a prolonged period of adult emergence in the spring increases the potential of low-dose chronic exposure to systemic neonicotinoid insecticides in potato. In 2010 and 2011, our objectives were twofold: 1) establish a common garden experiment to compare the emergence phenology of Colorado potato beetle populations uniquely managed with variable insecticide inputs, and 2) measure postdormancy fitness of emerged adult beetles from among these selected populations. Cumulative adult emergence was modeled with logistic regression. Results from this study found no clear evidence for direct relationships between phenology and management history or resistance. Differences in reproductive capacity, sex ratio, and body size were apparent in some instances. However, these results did not uniformly correspond to one specific form of potato pest management tested here. In this study, long-term reliance on systemic insecticides for Colorado potato beetle control did not serve as a strong predictor for variable life history for selected populations in Wisconsin. PMID:24498751

  14. [Support for and resistance to homeopathy among managers of the Unified National Health System].

    PubMed

    Salles, Sandra Abrahão Chaim; Schraiber, Lilia Blima

    2009-01-01

    This article presents partial findings from a study on trends towards greater or lesser proximity between homeopathic and allopathic physicians, from the perspective of the latter. Forty-eight health professionals were interviewed (faculty, managers, and physicians working in the public health system). This specific article focused only on the interviews with health system managers. The following concepts were used as references: social and scientific field (Bourdieu); medical rationalities (Madel Luz); technological arrangements in health work (Mendes-Gonçalves); and physician's professional identity (Donnangelo & Schraiber). According to the findings, support by managers for the presence of Homeopathy in the Unified National Health System is related to their perception of social demand, defense of patients' right to choose, and the observation that it is a medical practice that reclaims the humanist dimension of medicine, thus contributing to user satisfaction. The difficulties and resistances identified by managers highlight that the lack of information on homeopathic procedures limits the possibilities for use of Homeopathy because it leads to insecurity towards this area of medicine. PMID:19180302

  15. Effect of insecticide management history on emergence phenology and neonicotinoid resistance in Leptinotarsa decemlineata (Coleoptera: Chrysomelidae).

    PubMed

    Huseth, A S; Groves, R L

    2013-12-01

    Emergence phenology and fitness attributes of several Colorado potato beetle, Leptinotarsa decemlineata (Say), populations were measured under field and greenhouse conditions. Anecdotal observations by producers and pest managers in many locations of the upper Midwest increasingly suggested that select populations of Colorado potato beetle were emerging over a longer period in the spring and were less sensitive to systemic neonicotinoids in cultivated potato. These changes in emergence phenology may be related to changes in systemic insecticide concentration over time. Specifically, a prolonged period of adult emergence in the spring increases the potential of low-dose chronic exposure to systemic neonicotinoid insecticides in potato. In 2010 and 2011, our objectives were twofold: 1) establish a common garden experiment to compare the emergence phenology of Colorado potato beetle populations uniquely managed with variable insecticide inputs, and 2) measure postdormancy fitness of emerged adult beetles from among these selected populations. Cumulative adult emergence was modeled with logistic regression. Results from this study found no clear evidence for direct relationships between phenology and management history or resistance. Differences in reproductive capacity, sex ratio, and body size were apparent in some instances. However, these results did not uniformly correspond to one specific form of potato pest management tested here. In this study, long-term reliance on systemic insecticides for Colorado potato beetle control did not serve as a strong predictor for variable life history for selected populations in Wisconsin.

  16. Insect resistance management for stored product pests: a case study of cowpea weevil (Coleoptera: Bruchidae).

    PubMed

    Kang, Jung Koo; Pittendrigh, Barry R; Onstad, David W

    2013-12-01

    The cowpea weevil, Callosobruchus maculatus F. (Coleoptera: Bruchidae), can cause up to 100% yield loss of stored cowpea seeds in a few months in West Africa. Genes expressing toxins delaying insect maturation (MDTs) are available for genetic engineering. A simulation model was used to investigate the possible use of MDTs for managing C. maculatus. Specifically, we studied the effect of transgenic cowpea expressing an MDT, an insecticide, or both, on the evolution of resistance by C. maculatus at constant temperature. Transgenic cowpea expressing only a nonlethal MDT causing 50-100% maturation delay did not control C. maculatus well. Mortality caused by a maturation delay improved the efficacy of transgenic cowpea expressing only a lethal MDT, but significantly reduced the durability of transgenic cowpea Transgenic cowpea expressing only a lethal MDT causing 50% maturation delay and 90% mortality controlled C. maculatus better than one expressing only a nonlethal MDT, but its durability was only 2 yr. We concluded that transgenic cowpea expressing only an MDT has little value for managing C. maculatus. The resistance by C. maculatus to transgenic cowpea expressing only an insecticide rapidly evolved. Stacking a gene expressing a nonlethal MDT and a gene expressing an insecticide in transgenic cowpea did not significantly improve the durability of an insecticide, but stacking a gene expressing a lethal MDT and a gene expressing an insecticide in transgenic cowpea significantly improved the durability of an insecticide and an MDT. We also discussed this approach within the idea of using transgenic RNAi in pest control strategies. PMID:24498750

  17. Insect resistance management for stored product pests: a case study of cowpea weevil (Coleoptera: Bruchidae).

    PubMed

    Kang, Jung Koo; Pittendrigh, Barry R; Onstad, David W

    2013-12-01

    The cowpea weevil, Callosobruchus maculatus F. (Coleoptera: Bruchidae), can cause up to 100% yield loss of stored cowpea seeds in a few months in West Africa. Genes expressing toxins delaying insect maturation (MDTs) are available for genetic engineering. A simulation model was used to investigate the possible use of MDTs for managing C. maculatus. Specifically, we studied the effect of transgenic cowpea expressing an MDT, an insecticide, or both, on the evolution of resistance by C. maculatus at constant temperature. Transgenic cowpea expressing only a nonlethal MDT causing 50-100% maturation delay did not control C. maculatus well. Mortality caused by a maturation delay improved the efficacy of transgenic cowpea expressing only a lethal MDT, but significantly reduced the durability of transgenic cowpea Transgenic cowpea expressing only a lethal MDT causing 50% maturation delay and 90% mortality controlled C. maculatus better than one expressing only a nonlethal MDT, but its durability was only 2 yr. We concluded that transgenic cowpea expressing only an MDT has little value for managing C. maculatus. The resistance by C. maculatus to transgenic cowpea expressing only an insecticide rapidly evolved. Stacking a gene expressing a nonlethal MDT and a gene expressing an insecticide in transgenic cowpea did not significantly improve the durability of an insecticide, but stacking a gene expressing a lethal MDT and a gene expressing an insecticide in transgenic cowpea significantly improved the durability of an insecticide and an MDT. We also discussed this approach within the idea of using transgenic RNAi in pest control strategies.

  18. Performance and cross-crop resistance of Cry1F-maize selected Spodoptera frugiperda on transgenic Bt cotton: implications for resistance management.

    PubMed

    Yang, Fei; Kerns, David L; Brown, Sebe; Kurtz, Ryan; Dennehy, Tim; Braxton, Bo; Head, Graham; Huang, Fangneng

    2016-01-01

    Transgenic crops producing Bacillus thuringiensis (Bt) proteins have become a primary tool in pest management. Due to the intensive use of Bt crops, resistance of the fall armyworm, Spodoptera frugiperda, to Cry1F maize has occurred in Puerto Rico, Brazil, and some areas of the southeastern U.S. The sustainability of Bt crops faces a great challenge because the Cry1F-maize resistant S. frugiperda may also infest other Bt crops in multiple cropping ecosystems. Here we examined the survival and plant injury of a S. frugiperda population selected with Cry1F maize on three single-gene and five pyramided Bt cotton products. Larvae of Cry1F-susceptible (SS), -heterozygous (RS), and -resistant (RR) genotypes of S. frugiperda were all susceptible to the pyramided cotton containing Cry1Ac/Cry2Ab, Cry1Ac/Cry1F/Vip3A, Cry1Ab/Cry2Ae, or Cry1Ab/Cry2Ae/Vip3A, and the single-gene Cry2Ae cotton. Pyramided cotton containing Cry1Ac/Cry1F was effective against SS and RS, but not for RR. These findings show that the Cry1F-maize selected S. frugiperda can cause cross-crop resistance to other Bt crops expressing similar insecticidal proteins. Resistance management and pest management programs that utilize diversify mortality factors must be implemented to ensure the sustainability of Bt crops. This is especially important in areas where resistance to single-gene Bt crops is already widespread. PMID:27301612

  19. Performance and cross-crop resistance of Cry1F-maize selected Spodoptera frugiperda on transgenic Bt cotton: implications for resistance management

    PubMed Central

    Yang, Fei; Kerns, David L.; Brown, Sebe; Kurtz, Ryan; Dennehy, Tim; Braxton, Bo; Head, Graham; Huang, Fangneng

    2016-01-01

    Transgenic crops producing Bacillus thuringiensis (Bt) proteins have become a primary tool in pest management. Due to the intensive use of Bt crops, resistance of the fall armyworm, Spodoptera frugiperda, to Cry1F maize has occurred in Puerto Rico, Brazil, and some areas of the southeastern U.S. The sustainability of Bt crops faces a great challenge because the Cry1F-maize resistant S. frugiperda may also infest other Bt crops in multiple cropping ecosystems. Here we examined the survival and plant injury of a S. frugiperda population selected with Cry1F maize on three single-gene and five pyramided Bt cotton products. Larvae of Cry1F-susceptible (SS), -heterozygous (RS), and -resistant (RR) genotypes of S. frugiperda were all susceptible to the pyramided cotton containing Cry1Ac/Cry2Ab, Cry1Ac/Cry1F/Vip3A, Cry1Ab/Cry2Ae, or Cry1Ab/Cry2Ae/Vip3A, and the single-gene Cry2Ae cotton. Pyramided cotton containing Cry1Ac/Cry1F was effective against SS and RS, but not for RR. These findings show that the Cry1F-maize selected S. frugiperda can cause cross-crop resistance to other Bt crops expressing similar insecticidal proteins. Resistance management and pest management programs that utilize diversify mortality factors must be implemented to ensure the sustainability of Bt crops. This is especially important in areas where resistance to single-gene Bt crops is already widespread. PMID:27301612

  20. Measurement of phenotypic resilience to gastro-intestinal nematodes in Merino sheep and association with resistance and production variables.

    PubMed

    Kelly, Gareth A; Kahn, Lewis P; Walkden-Brown, Stephen W

    2013-03-31

    A cross-over experiment was conducted to compare six different phenotypic measures of resilience to gastro-intestinal nematodes (predominantly Haemonchus contortus) in Merino sheep and their association with resistance and production levels. On each of six farms, 120 ewes born in 2006 and 120 older mixed age ewes were selected at shearing in 2007. Of these, 60 in each mob were serially treated with long-acting anthelmintics to suppress worm populations. The other 60 ewes were managed according to management practices employed on the farm (infected, INF). At shearing in 2008, the experimental sheep had their anthelmintic treatments switched. The experiment concluded at shearing in 2009. Measures of resilience were greasy fleece weight (GFW), live weight gain (LWG) and haematocrit (HCT) when infected and the difference in these variables between infected and suppressed. Resistance was determined from multiple faecal worm egg counts (WEC) when infected. Measures of resilience based on GFW, LWG and HCT were moderately correlated with each other (r=0.25-0.50) suggesting that they represent different traits. Correlations between a measure in infected animals, and the difference in the same measurement between infected and uninfected animals were higher (r=-0.37 to -0.82), indicating that measurement during infection is an adequate measure of resilience. WEC was negatively correlated with LWG and HCT during infection but not GFW. Correlations with resilience measures based on difference between infected and uninfected were positive. Surviving infected sheep were found to have higher haematocrit (HCT), and lower WEC in summer and autumn than sheep that died following the measurement. These results show that measurement of performance traits while infected is a reasonable approximation of measurement of resilience based on the difference in performance between infected and non-infected. They also show that resilience to worm infection is not a single trait, but rather a

  1. Anthelmintic Effect of Biocompatible Zinc Oxide Nanoparticles (ZnO NPs) on Gigantocotyle explanatum, a Neglected Parasite of Indian Water Buffalo

    PubMed Central

    Khan, Yasir Akhtar; Singh, Braj Raj; Ullah, Rizwan; Shoeb, Mohd; Naqvi, Alim H.; Abidi, Syed M. A.

    2015-01-01

    Helminth parasites of veterinary importance cause huge revenue losses to agrarian economy worldwide. With the emergence of drug resistance against the current formulations, there is a need to focus on the alternative approaches in order to control this menace. In the present study, biocompatible zinc oxide nanoparticles (ZnO NPs) were used to see their in vitro effect on the biliary amphistomes, Gigantocotyle explanatum, infecting Bubalus bubalis because these nanoparticles are involved in generation of free radicals that induce oxidative stress, resulting in disruption of cellular machinery. The ZnO NPs were synthesized by using egg albumin as a biotemplate and subsequently characterized by Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), X-ray Diffraction and Spectrophotometrical, which showed that ZnO NPs were highly purified wurtzite type polycrystals, with a mean size of 16.7 nm. When the parasites were treated with lower concentrations (0.004% and 0.008%) of the ZnO NPs, the worms mounted a protective response by stimulating the antioxidant system but the treatment of G. explanatum with 0.012% ZnO NPs produced significant inhibition of the antioxidant enzymes like superoxide dismutase (SOD) (p< 0.05) and glutathione S- transferase (GST) (p<0.01), while the level of malondialdehyde (MDA), a lipid peroxidation marker, was significantly (p< 0.01) elevated. SEM and histopathology revealed pronounced tegumental damage showing the disruption of surface papillae and the annulations, particularly in the posterior region near acetabulum. The under expression of a number of polypeptides, loss of worm motility in a time dependent manner, further reflect strong anthelmintic potential of ZnO NPs. It can be concluded that the anthelmintic effect might be due to the production of reactive oxygen species that target a variety of macromolecules such as nucleic acid, protein and lipids which are involved in different cellular processes. PMID:26177503

  2. Anthelmintic Effect of Biocompatible Zinc Oxide Nanoparticles (ZnO NPs) on Gigantocotyle explanatum, a Neglected Parasite of Indian Water Buffalo.

    PubMed

    Khan, Yasir Akhtar; Singh, Braj Raj; Ullah, Rizwan; Shoeb, Mohd; Naqvi, Alim H; Abidi, Syed M A

    2015-01-01

    Helminth parasites of veterinary importance cause huge revenue losses to agrarian economy worldwide. With the emergence of drug resistance against the current formulations, there is a need to focus on the alternative approaches in order to control this menace. In the present study, biocompatible zinc oxide nanoparticles (ZnO NPs) were used to see their in vitro effect on the biliary amphistomes, Gigantocotyle explanatum, infecting Bubalus bubalis because these nanoparticles are involved in generation of free radicals that induce oxidative stress, resulting in disruption of cellular machinery. The ZnO NPs were synthesized by using egg albumin as a biotemplate and subsequently characterized by Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), X-ray Diffraction and Spectrophotometrical, which showed that ZnO NPs were highly purified wurtzite type polycrystals, with a mean size of 16.7 nm. When the parasites were treated with lower concentrations (0.004% and 0.008%) of the ZnO NPs, the worms mounted a protective response by stimulating the antioxidant system but the treatment of G. explanatum with 0.012% ZnO NPs produced significant inhibition of the antioxidant enzymes like superoxide dismutase (SOD) (p< 0.05) and glutathione S- transferase (GST) (p<0.01), while the level of malondialdehyde (MDA), a lipid peroxidation marker, was significantly (p< 0.01) elevated. SEM and histopathology revealed pronounced tegumental damage showing the disruption of surface papillae and the annulations, particularly in the posterior region near acetabulum. The under expression of a number of polypeptides, loss of worm motility in a time dependent manner, further reflect strong anthelmintic potential of ZnO NPs. It can be concluded that the anthelmintic effect might be due to the production of reactive oxygen species that target a variety of macromolecules such as nucleic acid, protein and lipids which are involved in different cellular processes.

  3. Infection Management and Multidrug-Resistant Organisms in Nursing Home Residents With Advanced Dementia

    PubMed Central

    Mitchell, Susan L.; Shaffer, Michele L.; Loeb, Mark B.; Givens, Jane L.; Habtemariam, Daniel; Kiely, Dan K.; D’Agata, Erika

    2014-01-01

    IMPORTANCE Infection management in advanced dementia has important implications for (1) providing high-quality care to patients near the end of life and (2) minimizing the public health threat posed by the emergence of multidrug-resistant organisms (MDROs). DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of 362 residents with advanced dementia and their health care proxies in 35 Boston area nursing homes for up to 12 months. MAINOUTCOMESAND MEASURES Data were collected to characterize suspected infections, use of antimicrobial agents (antimicrobials), clinician counseling of proxies about antimicrobials, proxy preference for the goals of care, and colonization with MDROs (methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and multidrug-resistant gram-negative bacteria). Main outcomes were (1) proportion of suspected infections treated with antimicrobials that met minimum clinical criteria to initiate antimicrobial treatment based on consensus guidelines and (2) cumulative incidence of MDRO acquisition among noncolonized residents at baseline. RESULTS The cohort experienced 496 suspected infections; 72.4% were treated with antimicrobials, most commonly quinolones (39.8%) and third- or fourth-generation cephalosporins (20.6%). At baseline, 94.8% of proxies stated that comfort was the primary goal of care, and 37.8% received counseling from clinicians about antimicrobial use. Minimum clinical criteria supporting antimicrobial treatment initiation were present for 44.0% of treated episodes and were more likely when proxies were counseled about antimicrobial use (adjusted odds ratio, 1.42; 95% CI, 1.08–1.86) and when the infection source was not the urinary tract (referent). Among noncolonized residents at baseline, the cumulative incidence of MDRO acquisition at 1 year was 48%. Acquisition was associated with exposure (>1 day) to quinolones (adjusted hazard ratio [AHR], 1.89; 95% CI, 1.28–2.81) and third- or fourth

  4. A Prospective Study of Tuberculosis Drug Susceptibility in Sabah, Malaysia, and an Algorithm for Management of Isoniazid Resistance

    PubMed Central

    Rashid Ali, Muhammad Redzwan S.; Parameswaran, Uma; William, Timothy; Bird, Elspeth; Wilkes, Christopher S.; Lee, Wai Khew; Yeo, Tsin Wen; Anstey, Nicholas M.; Ralph, Anna P.

    2015-01-01

    Introduction. The burden of tuberculosis is high in eastern Malaysia, and rates of Mycobacterium tuberculosis drug resistance are poorly defined. Our objectives were to determine M. tuberculosis susceptibility and document management after receipt of susceptibility results. Methods. Prospective study of adult outpatients with smear-positive pulmonary tuberculosis (PTB) in Sabah, Malaysia. Additionally, hospital clinicians accessed the reference laboratory for clinical purposes during the study. Results. 176 outpatients were enrolled; 173 provided sputum samples. Mycobacterial culture yielded M. tuberculosis in 159 (91.9%) and nontuberculous Mycobacterium (NTM) in three (1.7%). Among outpatients there were no instances of multidrug resistant M. tuberculosis (MDR-TB). Seven people (4.5%) had isoniazid resistance (INH-R); all were switched to an appropriate second-line regimen for varying durations (4.5–9 months). Median delay to commencement of the second-line regimen was 13 weeks. Among 15 inpatients with suspected TB, 2 had multidrug resistant TB (one extensively drug resistant), 2 had INH-R, and 4 had NTM. Conclusions. Current community rates of MDR-TB in Sabah are low. However, INH-resistance poses challenges, and NTM is an important differential diagnosis in this setting, where smear microscopy is the usual diagnostic modality. To address INH-R management issues in our setting, we propose an algorithm for the treatment of isoniazid-resistant PTB. PMID:25838829

  5. Red Maasai x Dorper resistance to gastrointestestinal parasite infections associated to a panel of SNPs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gastrointestinal (GI) parasitic infection is a main health constraint that affects small ruminant production. Anthelmintic drugs are used to control parasites, however long-term use led to selection pressure, resulting in parasite resistance against all current chemical interventions available in th...

  6. Cytotoxic chemotherapy in the contemporary management of metastatic castration-resistant prostate cancer (mCRPC).

    PubMed

    Sonpavde, Guru; Wang, Christopher G; Galsky, Matthew D; Oh, William K; Armstrong, Andrew J

    2015-07-01

    For several years, docetaxel was the only treatment shown to improve survival of patients with metastatic castration-resistant prostate cancer (mCRPC). There are now several novel agents available, although chemotherapy with docetaxel and cabazitaxel continues to play an important role. However, the increasing number of available agents will inevitably affect the timing of chemotherapy and therefore it may be important to offer this approach before declining performance status renders patients ineligible for chemotherapy. Patient selection is also important to optimise treatment benefit. The role of predictive biomarkers has assumed greater importance due to the development of multiple agents and resistance to available agents. In addition, the optimal sequence of treatments remains undefined and requires further study in order to maximize long-term outcomes. We provide an overview of the clinical data supporting the role of chemotherapy in the treatment of mCRPC and the emerging role in metastatic castration-sensitive prostate cancer. We review the key issues in the management of patients including selection of patients for chemotherapy, when to start chemotherapy, and how best to sequence treatments to maximise outcomes. In addition, we briefly summarise the promising new chemotherapeutic agents in development in the context of emerging therapies.

  7. Colonization with Multi-Drug Resistant Organisms in Nursing Homes: Scope, Importance, and Management

    PubMed Central

    Cassone, Marco; Mody, Lona

    2015-01-01

    Bacterial infections are among the most common causes of morbidity and mortality in Nursing Homes (NH) and other long term care facilities. Multi-drug resistant organisms (MDROs) represent an ever-increasing share of causative agents of infection, and their prevalence in NHs is now just as high as in acute-care facilities, or even higher. Indeed, NHs are now considered a major reservoir of MDROs for the community at large. Asymptomatic colonization is usually a prerequisite to development of symptomatic infection. While progress has been made in defining epidemiology of MDROs in NHs, few studies have evaluated the role of changing healthcare delivery in introducing and further transmitting MDROs in this setting. Furthermore, the factors influencing the spread of colonization and the key prognostic indicators leading to symptomatic infections in the burgeoning short stay population need to be explored further. The difficulty of this task lies in the heterogeneity of NHs in terms of focus of care, organization and resources, and on the diversity among the many MDRO species encountered, which harbor different resistance genes and with a different prevalence depending on the geographic location, local antimicrobial pressure and residents risk factors such as use of indwelling devices, functional disability, wounds and other comorbidities. We present literature findings on the scope and importance of colonization as a pathway to infection with MDROs in NHs, underline important open questions that need further research, and discuss the strength of the evidence for current and proposed screening, prevention, and management interventions. PMID:25664233

  8. Programmatic Management of Drug-Resistant Tuberculosis: An Updated Research Agenda

    PubMed Central

    Mitnick, Carole D.; Hatton, Marita L.; Brigden, Grania; Cobelens, Frank; Grobusch, Martin P.; Horsburgh, Robert; Lange, Christoph; Lienhardt, Christian; Oren, Eyal; Podewils, Laura J.; Seaworth, Barbara; van den Hof, Susan; Daley, Charles L.; Gebhard, Agnes C.; Wares, Fraser

    2016-01-01

    Introduction There are numerous challenges in delivering appropriate treatment for multidrug-resistant tuberculosis (MDR-TB) and the evidence base to guide those practices remains limited. We present the third updated Research Agenda for the programmatic management of drug-resistant TB (PMDT), assembled through a literature review and survey. Methods Publications citing the 2008 research agenda and normative documents were reviewed for evidence gaps. Gaps were formulated into questions and grouped as in the 2008 research agenda: Laboratory Support, Treatment Strategy, Programmatically Relevant Research, Epidemiology, and Management of Contacts. A survey was distributed through snowball sampling to identify research priorities. Respondent priority rankings were scored and summarized by mean. Sensitivity analyses explored weighting and handling of missing rankings. Results Thirty normative documents and publications were reviewed for stated research needs; these were collapsed into 56 research questions across 5 categories. Of more than 500 survey recipients, 133 ranked priorities within at least one category. Priorities within categories included new diagnostics and their effect on improving treatment outcomes, improved diagnosis of paucibacillary and extra pulmonary TB, and development of shorter, effective regimens. Interruption of nosocomial transmission and treatment for latent TB infection in contacts of known MDR−TB patients were also top priorities in their respective categories. Results were internally consistent and robust. Discussion Priorities retained from the 2008 research agenda include shorter MDR-TB regimens and averting transmission. Limitations of recent advances were implied in the continued quest for: shorter regimens containing new drugs, rapid diagnostics that improve treatment outcomes, and improved methods of estimating burden without representative data. Conclusion There is continuity around the priorities for research in PMDT. Coordinated

  9. The anthelmintic efficacy of natural plant cysteine proteinases against two rodent cestodes Hymenolepis diminuta and Hymenolepis microstoma in vitro.

    PubMed

    Mansur, F; Luoga, W; Buttle, D J; Duce, I R; Lowe, Ann; Behnke, J M

    2014-03-17

    Little is known about the efficacy of cysteine proteinases (CP) as anthelmintics for cestode infections. We examined the effects of CPs on two rodent cestodes, Hymenolepis diminuta and H. microstoma in vitro. Our data showed that naturally occurring mixtures of CPs, such as those found in papaya latex, and relatively pure preparations of fruit bromelain, papain and stem bromelain, were active in vitro against both juvenile, artificially excysted scoleces, as well as against adult worms of both rodent cestodes. Significant dose-dependent reduction in motility, ultimately leading to death of the worms, was observed with both species, and against both freshly excysted scoleces and 14-day old pre-adult worms. The most effective was fruit bromelain (after 30 min of incubation of juvenile H. diminuta and H. microstoma IC50=63 and 74 μM, respectively, and for pre-adult worms=199 and 260 μM, respectively). The least effective was stem bromelain (after 30 min of incubation of juvenile H. diminuta and H. microstoma IC50=2855 and 2772 μM, respectively, and for pre-adult worms=1374 and 1332 μM, respectively) and the efficacies of papaya latex supernatant and papain were between these extremes. In all cases these values are higher than those reported previously for efficacy of CPs against intestinal nematodes, and in contrast to nematodes, all CPs were effective against cestodes in the absence of exogenous cysteine in incubation media. The CPs appeared to attack the tegument resulting in generalised erosion mainly on the strobila. The scolex was more resistant to CP attack but nevertheless some damage to the tegument on the scolex was detected. PMID:24462509

  10. ReTrust: attack-resistant and lightweight trust management for medical sensor networks.

    PubMed

    He, Daojing; Chen, Chun; Chan, Sammy; Bu, Jiajun; Vasilakos, Athanasios V

    2012-07-01

    Wireless medical sensor networks (MSNs) enable ubiquitous health monitoring of users during their everyday lives, at health sites, without restricting their freedom. Establishing trust among distributed network entities has been recognized as a powerful tool to improve the security and performance of distributed networks such as mobile ad hoc networks and sensor networks. However, most existing trust systems are not well suited for MSNs due to the unique operational and security requirements of MSNs. Moreover, similar to most security schemes, trust management methods themselves can be vulnerable to attacks. Unfortunately, this issue is often ignored in existing trust systems. In this paper, we identify the security and performance challenges facing a sensor network for wireless medical monitoring and suggest it should follow a two-tier architecture. Based on such an architecture, we develop an attack-resistant and lightweight trust management scheme named ReTrust. This paper also reports the experimental results of the Collection Tree Protocol using our proposed system in a network of TelosB motes, which show that ReTrust not only can efficiently detect malicious/faulty behaviors, but can also significantly improve the network performance in practice.

  11. The Cyclooctadepsipeptide Anthelmintic Emodepside Differentially Modulates Nematode, Insect and Human Calcium-Activated Potassium (SLO) Channel Alpha Subunits

    PubMed Central

    Schoenhense, Eva; Harder, Achim; Raming, Klaus; O’Kelly, Ita; Ndukwe, Kelechi; O’Connor, Vincent; Walker, Robert J.; Holden-Dye, Lindy

    2015-01-01

    The anthelmintic emodepside paralyses adult filarial worms, via a mode of action distinct from previous anthelmintics and has recently garnered interest as a new treatment for onchocerciasis. Whole organism data suggest its anthelmintic action is underpinned by a selective activation of the nematode isoform of an evolutionary conserved Ca2+-activated K+ channel, SLO-1. To test this at the molecular level we compared the actions of emodepside at heterologously expressed SLO-1 alpha subunit orthologues from nematode (Caenorhabditis elegans), Drosophila melanogaster and human using whole cell voltage clamp. Intriguingly we found that emodepside modulated nematode (Ce slo-1), insect (Drosophila, Dm slo) and human (hum kcnma1)SLO channels but that there are discrete differences in the features of the modulation that are consistent with its anthelmintic efficacy. Nematode SLO-1 currents required 100 μM intracellular Ca2+ and were strongly facilitated by emodepside (100 nM; +73.0 ± 17.4%; n = 9; p<0.001). Drosophila Slo currents on the other hand were activated by emodepside (10 μM) in the presence of 52 nM Ca2+ but were inhibited in the presence of 290 nM Ca2+ and exhibited a characteristic loss of rectification. Human Slo required 300nM Ca2+ and emodepside transiently facilitated currents (100nM; +33.5 ± 9%; n = 8; p<0.05) followed by a sustained inhibition (-52.6 ± 9.8%; n = 8; p<0.001). This first cross phyla comparison of the actions of emodepside at nematode, insect and human channels provides new mechanistic insight into the compound’s complex modulation of SLO channels. Consistent with whole organism behavioural studies on C. elegans, it indicates its anthelmintic action derives from a strong activation of SLO current, not observed in the human channel. These data provide an important benchmark for the wider deployment of emodepside as an anthelmintic treatment. PMID:26437177

  12. Anthelmintic effects of Salix babylonica L. and Leucaena leucocephala Lam. extracts in growing lambs.

    PubMed

    Hernandez, Pablo Mejia; Salem, Abdelfattah Z M; Elghandour, Mona M M Y; Cipriano-Salazar, Moisés; Cruz-Lagunas, Blas; Camacho, Luis Miguel

    2014-01-01

    Twenty Katahdin × Pelibuey crossbreed male lambs, 3 to 4 months of age and 24 ± 0.3 kg of body weight, were used to study the anthelmintic effects of administering extracts of Salix babylonica L. (SB) and Leucaena leucocephala Lam. (LL). Lambs had not been treated with anthelmintics previously and were randomly allocated into four groups of five lambs each in a completely randomized design. Treatments were as follows: control (lambs fed on total mixed ration without extracts), SB (as control plus S. babylonica L. extract at 30 ml/day), LL (as control plus L. leucocephala Lam. extract at 30 ml/day), and SBLL (as control plus 30 ml/day of S. babylonica L. and L. leucocephala Lam. extracts in a 1:1 (v/v) mixture) for 63 days. Extracts were orally administered before the 8:00 a.m. feeding to each lamb. Rectal fecal samples were collected from each lamb at day 22 (P1), day 43 (P2), and day 63 (P3) of the experiment. Adult worm and egg counts were determined in each fecal sample immediately after collection. Plant secondary metabolites of total phenolics, saponins, and the aqueous fraction were 50 % lower in the SB versus LL extracts. Overall, the oral administration of extracts has improved the egg and worm count reductions in lamb feces by 54, 47, and 40 % for LL, SB, and SBLL, respectively, versus the control lambs. Reductions of worm egg counts in lamb feces were higher (P < 0.05) in P2 and P3 versus P1. Extracts of SB and LL or possibly isolated bioactive compounds could be a promising alternative to conventional anthelmintics to treat gastrointestinal parasites of small ruminants. Such treatments could be used in control strategies against gastrointestinal nematodes in organic and conventional production systems. PMID:24077919

  13. Phytochemicals, antioxidant, and anthelmintic activity of selected traditional wild edible plants of lower Assam

    PubMed Central

    Swargiary, Ananta; Daimari, Abhijita; Daimari, Manita; Basumatary, Noymi; Narzary, Ezekiel

    2016-01-01

    Objective: Clerodendrum viscosum, Eryngium foetidum, Lippia javanica, and Murraya koenigii are one among the common wild edible plants in Northeast India which are also used as antidiabetic, stomach-ache relieving drugs, etc., The present study was aimed to reveal the phytochemical, antioxidant, and anthelmintic activity of the plants. Materials and Methods: The antioxidant capacity of methanolic extract of plants was studied by 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant power, TBARS, and total antioxidant activity (TAA). Total phenolics, flavonoids, Vitamin C, carbohydrate, and protein are also estimated following standard protocols. Anthelmintic activity of the extracts has also been studied in vitro against trematode parasites. Results: The result showed that the methanolic extracts of plants possess a substantial quantity of alkaloids, phenolics, flavonoids, proteins, carbohydrates, and Vitamin C. Phenolics, flavonoids, and Vitamin C contents were found higher in C. viscosum followed by M. koenigii, L. javanica, and E. foetidum. The in vitro antioxidant assays revealed substantial free radical scavenging property in all the plants. TAA increased in the order C. viscosum > M. koenigii > L. javanica > E. foetidum. Similarly, C. viscosum displayed a better antioxidant capacity with IC50 values 29.74 ± 3.63 μg and 148.77 ± 18.38 μg for DPPH and thiobarbituric acid reactive species, respectively. In addition, the plant extracts also showed good anthelmintic activity against Paramphistomum sp. Time taken for paralysis and death were 0:56 ± 0:09 h and 1:35 ± 0:07 h for L. javanica at 50 mg/mL concentration. Conclusion: The study therefore suggests the importance of tested plants as a natural source of free radical scavenger and plausible veterinary uses. PMID:27756954

  14. Anthelmintic effects of Salix babylonica L. and Leucaena leucocephala Lam. extracts in growing lambs.

    PubMed

    Hernandez, Pablo Mejia; Salem, Abdelfattah Z M; Elghandour, Mona M M Y; Cipriano-Salazar, Moisés; Cruz-Lagunas, Blas; Camacho, Luis Miguel

    2014-01-01

    Twenty Katahdin × Pelibuey crossbreed male lambs, 3 to 4 months of age and 24 ± 0.3 kg of body weight, were used to study the anthelmintic effects of administering extracts of Salix babylonica L. (SB) and Leucaena leucocephala Lam. (LL). Lambs had not been treated with anthelmintics previously and were randomly allocated into four groups of five lambs each in a completely randomized design. Treatments were as follows: control (lambs fed on total mixed ration without extracts), SB (as control plus S. babylonica L. extract at 30 ml/day), LL (as control plus L. leucocephala Lam. extract at 30 ml/day), and SBLL (as control plus 30 ml/day of S. babylonica L. and L. leucocephala Lam. extracts in a 1:1 (v/v) mixture) for 63 days. Extracts were orally administered before the 8:00 a.m. feeding to each lamb. Rectal fecal samples were collected from each lamb at day 22 (P1), day 43 (P2), and day 63 (P3) of the experiment. Adult worm and egg counts were determined in each fecal sample immediately after collection. Plant secondary metabolites of total phenolics, saponins, and the aqueous fraction were 50 % lower in the SB versus LL extracts. Overall, the oral administration of extracts has improved the egg and worm count reductions in lamb feces by 54, 47, and 40 % for LL, SB, and SBLL, respectively, versus the control lambs. Reductions of worm egg counts in lamb feces were higher (P < 0.05) in P2 and P3 versus P1. Extracts of SB and LL or possibly isolated bioactive compounds could be a promising alternative to conventional anthelmintics to treat gastrointestinal parasites of small ruminants. Such treatments could be used in control strategies against gastrointestinal nematodes in organic and conventional production systems.

  15. Anthelmintic effect of a methanol extract of Bombax malabaricum leaves on Paramphistomum explanatum.

    PubMed

    Hossain, Emdad; Chandra, Goutam; Nandy, Anadi P; Mandal, Subhash C; Gupta, Jayanta Kumar

    2012-03-01

    Bombax malabaricum (family Bombacaceae) is used as anthelmintic in traditional system of medicine in Southern Punjab of Pakistan. The objective of this study was to evaluate the anthelmintic activity of the methanol extract of B. malabaricum leaves (MEBM). Live parasites (trematode: Paramphistomum explanatum) were collected from buffalo in 0.9% phosphate-buffered saline. It was incubated in Petri dishes at 37 ± 1°C in media containing either no extract (control) or MEBM, the test drug at 10, 25, 50, and 100 mg/ml dose level or albendazole, the standard drug at 10 mg/ml. The efficacy of the extract or albendazole was measured on the basis of the loss of spontaneous movement and/or death of the trematodes. Paralysis was considered when there is no movement unless shaken vigorously. Death was confirmed when the trematodes completely lost their motility, even when vigorously shaken or dipped in warm water (50°C), followed by fading away of their body color. The trematodes, both drug treated and others, were further processed for SEM study using the standard method. All trematodes died with all the above-mentioned doses of MEBM within a short period of time (less than 45 min) which was statistically highly significant (p < 0.001). MEBM at 100 mg/ml showed maximum efficacy. It paralyzed and killed trematodes in 18.50 ± 0.62 and 22.17 ± 0.48 min, respectively. SEM study showed that MEBM-treated trematodes were stretched. The study established the anthelmintic activity of MEBM.

  16. Response of antibiotics and resistance genes to high-intensity and low-intensity manure management.

    PubMed

    Storteboom, Heather N; Kim, Sung-Chul; Doesken, Kathy C; Carlson, Kenneth H; Davis, Jessica G; Pruden, Amy

    2007-01-01

    The purpose of this study was to determine the response of antibiotics and antibiotic resistance genes (ARG) to manure management. A pilot field study was conducted using horse manure containing no antibiotics, into which chlortetracycline (CTC), tylosin (TYL), and monensin (MON) were spiked and compared to unspiked controls. Subsequently, a large-scale field study was conducted comparing manure from a dairy with minimal use of antibiotics and a feedlot with regular subtherapeutic use of antibiotics. The manures were subjected to high-intensity management (HIM) (amending, watering, and turning) and low-intensity management (LIM) (no amending, watering, or turning) and were monitored for antibiotic concentrations and levels of tetracycline ARG [tet(W) and tet(O)] using quantitative real-time polymerase chain reaction. All three antibiotics in the pilot study dissipated more rapidly in HIM manure, with half-lives ranging from 4 to 15 d, compared to LIM manure, with half-lives ranging from 8 to 30 d. Levels of tet(W) were significantly higher after 141 d of treatment, but levels of tet(O) were significantly lower in all treatments. In the large-scale study, the feedlot manure had higher initial concentrations than the dairy manure of tetracycline (TC), oxytetracycline (OTC), and CTC as well as tet(W) and tet(O). Tetracycline and OTC dissipated more rapidly in HIM manure, with half-lives ranging from 6 to 15 d, compared to LIM manure, with half-lives ranging from 7 to 31 d. After 6 mo of treatment, tet(W) and tet(O) decreased significantly in feedlot manure, whereas dairy manure required only 4 mo of treatment for similar results.

  17. Potential anthelmintic: D-psicose inhibits motility, growth and reproductive maturity of L1 larvae of Caenorhabditis elegans.

    PubMed

    Sato, Masashi; Kurose, Hiroyuki; Yamasaki, Toru; Izumori, Ken

    2008-04-01

    No anthelmintic sugars have yet been identified. Eight ketohexose stereoisomers (D- and L-forms of psicose, fructose, tagatose and sorbose), along with D-galactose and D-glucose, were examined for potency against L1 stage Caenorhabditis elegans fed Escherichia coli. Of the sugars, D-psicose specifically inhibited the motility, growth and reproductive maturity of the L1 stage. D-Psicose probably interferes with the nematode nutrition. The present results suggest that D-psicose, one of the rare sugars, is a potential anthelmintic.

  18. Evaluation of antibacterial and anthelmintic activities with total phenolic contents of Piper betel leaves

    PubMed Central

    Akter, Kazi Nahid; Karmakar, Palash; Das, Abhijit; Anonna, Shamima Nasrin; Shoma, Sharmin Akter; Sattar, Mohammad Mafruhi

    2014-01-01

    Objective: The study was conducted to investigate the antibacterial and anthelmintic activities and to determine total phenolic contents of methanolic extract of Piper betel leaves. Materials and Methods: The extract was subjected to assay for antibacterial activity using both gram positive and gram negative bacterial strains through disc diffusion method; anthelmintic activity with the determination of paralysis and death time using earthworm (Pheritima posthuma) at five different concentrations and the determination of total phenolic contents using the Folin-ciocalteau method. Results: The extract showed significant (p<0.01) zone of inhibitions against gram positive Staphylococcus aureus [(6.77±0.25) mm] and Gram negative Escherichia coli [(8.53±0.25) mm], Salmonella typhi [(5.20±0.26) mm], Shigella dysenteriae [(11.20±0.26) mm] compared to positive control Azithromycin (ranging from 20.10±0.17 to 25.20±0.35 mm) while no zone inhibitory activity was found for both the extract and the standard drug against Gram positive Bacillus cereus. The extract also showed potent anthelmintic activity requiring less time for paralysis and death compared to the standard drug albendazole (10 mg/ml). At concentrations 10, 20, 40, 60 and 80 mg/ml, leaves extract showed paralysis at mean time of 9.83±0.60, 8.50±0.29, 6.60±0.17, 6.20±0.44 and 4.16±0.60; death at 11.33±0.88, 9.67±0.33, 7.83±0.17, 7.16±0.60 and 5.16±0.72 minutes, respectively. Whereas the standard drug showed paralysis and death at 19.33±0.71 and 51.00±0.23 minutes respectively. The extract confirmed the higher concentration of phenolic contents (124.42±0.14 mg of GAE /g of extract) when screened for total phenolic compounds. Conclusion: As results confirmed potential antibacterial and anthelmintic activities of Piper betel leaves extract, therefore it may be processed for further drug research. PMID:25386394

  19. Screening of indigenous plants for anthelmintic action against human Ascaris lumbricoides: Part--II.

    PubMed

    Raj, R K

    1975-01-01

    Alcoholic extracts of the rhizomes of Alpinia galanga, Andrographis paniculata, bark of Cinnamomum zeylanicum, rind of Citrus decumana, Desmodium triflorum, seeds of Hydnocarpus wightiana, rhizomes of Kaempfaria galanga, Lippia nodiflora, tender leaves of Morinda citrifolia, rhizomes of Pollia serzogonian, Tephrosia purpuria and rhizomes of Zingiber zerumbeth showed good in vitro anthelmintic activity against human Ascaris lumbricoides. While, the alcoholic extracts of the bark of Alibzzia lebbek, the bulb of Allium sativum, rhizomes of Alpinia calcaratta, rind of Citrus acida, rind of Citrus aromatium, rind of Citrus medica, rhizomes of Curcuma aromatica and rind of Punica granatum showed moderate invitro activity.

  20. Comparative pharmacology of flatworm and roundworm glutamate-gated chloride channels: Implications for potential anthelmintics

    PubMed Central

    Lynagh, Timothy; Cromer, Brett A.; Dufour, Vanessa; Laube, Bodo

    2014-01-01

    Pharmacological targeting of glutamate-gated chloride channels (GluCls) is a potent anthelmintic strategy, evidenced by macrocyclic lactones that eliminate numerous roundworm infections by activating roundworm GluCls. Given the recent identification of flatworm GluCls and the urgent need for drugs against schistosomiasis, flatworm GluCls should be evaluated as potential anthelmintic targets. This study sought to identify agonists or modulators of one such GluCl, SmGluCl-2 from the parasitic flatworm Schistosoma mansoni. The effects of nine glutamate-like compounds and three monoterpenoid ion channel modulators were measured by electrophysiology at SmGluCl-2 recombinantly expressed in Xenopus laevis oocytes. For comparison with an established anthelmintic target, experiments were also performed on the AVR-14B GluCl from the parasitic roundworm Haemonchus contortus. l-Glutamate was the most potent agonist at both GluCls, but l-2-aminoadipate, d-glutamate and d-2-aminoadipate activated SmGluCl-2 (EC50 1.0 ± 0.1 mM, 2.4 ± 0.4 mM, 3.6 ± 0.7 mM, respectively) more potently than AVR-14B. Quisqualate activated only SmGluCl-2 whereas l-aspartate activated only AVR-14B GluCls. Regarding the monoterpenoids, both GluCls were inhibited by propofol, thymol and menthol, SmGluCl-2 most potently by thymol (IC50 484 ± 85 μM) and least potently by menthol (IC50 > 3 mM). Computational docking suggested that agonist and inhibitor potency is attributable to particular interactions with extracellular or membrane-spanning amino acid residues. These results reveal that flatworm GluCls are pharmacologically susceptible to numerous agonists and modulators and indicate that changes to the glutamate γ-carboxyl or to the propofol 6-isopropyl group can alter the differential pharmacology at flatworm and roundworm GluCls. This should inform the development of more potent compounds and in turn lead to novel anthelmintics. PMID:25516835

  1. Anti-coccidial, anthelmintic and antioxidant activities of pomegranate (Punica granatum) peel extract.

    PubMed

    Dkhil, Mohammed A

    2013-07-01

    Coccidiosis and helminthosis in poultry are responsible for worldwide economic losses. The methanolic extract of Punica granatum (pomegranate) peel was used in vivo for its pharmacological, antioxidant and anti-coccidial properties and in vitro for its anthelmintic activity. For the in vivo study, four groups of mice were investigated. The first group was inoculated only with sterile saline and served as the control group. The second group was treated by oral gavage with pomegranate extract (300 mg/kg) daily for 5 days. The third and fourth groups were infected with 10(3) sporulated oocysts of Eimeria papillata. The fourth group was also treated once daily with pomegranate peel extract for 5 days. For the in vitro study, the anthelmintic effect of pomegranate peel extract was observed on live adult Allolobophora caliginosa. Paraffin sections from jejunum as well as jejunal homogenate were prepared for the histopathological and biochemical investigations, respectively. The data showed that mice infected with E. papillata revealed an output of approximately 2.9 × 10(5) oocysts per gram faeces on day 5 p.i. This output is significantly decreased to 50 % in pomegranate-treated mice. Infection with E. papillata induced marked histopathological alterations in jejunum in the form of inflammation, vacuolation of the epithelium and destruction of some villi. In addition, pomegranate extract caused a great diminish in body weight loss of infected mice. Moreover, the number of goblet cells stained with Alcian blue within the infected villi was significantly increased by about 26 % after pomegranate treatment. In addition, Pomegranate significantly lowered the increased number of apoptotic cells due to E. papillata infection by about 36 %. The results showed that E. papillata enhanced hydrogen peroxide, lipid peroxidation and nitric oxide production with concomitant reduction in glutathione. Pomegranate induced marked improvements in all of the studied parameters as well as

  2. Clinical trials of broad spectrum anthelmintics against soil-transmitted helminthiasis.

    PubMed

    Cabrera, B D; Valdez, E V; Go, T G

    1980-12-01

    Clinical trials on the three broad spectrum anthelmintics against trichuriasis, ascariasis and hookworm infection were carried out in a rural community in Irosin, Sorsogon. Flubendazole (Fluvermal) appears to be a promising drug against trichuriasis particularly when periodic mass treatment of a community is carried out. Mebendazole (Antiox) also appears to be promising given as single dose during mass treatment of soil-transmitted helminthiasis. As shown in previous studies, oxantel-pyrantel (Quantrel) should be given at 15 mg/kg body weight at 12-hour intervals or 20 mg/kg body weight single dose rather than 10 mg/kg body weight in a single dose when treating trichuriasis.

  3. Comparative pharmacology of flatworm and roundworm glutamate-gated chloride channels: Implications for potential anthelmintics.

    PubMed

    Lynagh, Timothy; Cromer, Brett A; Dufour, Vanessa; Laube, Bodo

    2014-12-01

    Pharmacological targeting of glutamate-gated chloride channels (GluCls) is a potent anthelmintic strategy, evidenced by macrocyclic lactones that eliminate numerous roundworm infections by activating roundworm GluCls. Given the recent identification of flatworm GluCls and the urgent need for drugs against schistosomiasis, flatworm GluCls should be evaluated as potential anthelmintic targets. This study sought to identify agonists or modulators of one such GluCl, SmGluCl-2 from the parasitic flatworm Schistosoma mansoni. The effects of nine glutamate-like compounds and three monoterpenoid ion channel modulators were measured by electrophysiology at SmGluCl-2 recombinantly expressed in Xenopus laevis oocytes. For comparison with an established anthelmintic target, experiments were also performed on the AVR-14B GluCl from the parasitic roundworm Haemonchus contortus. l-Glutamate was the most potent agonist at both GluCls, but l-2-aminoadipate, d-glutamate and d-2-aminoadipate activated SmGluCl-2 (EC50 1.0 ± 0.1 mM, 2.4 ± 0.4 mM, 3.6 ± 0.7 mM, respectively) more potently than AVR-14B. Quisqualate activated only SmGluCl-2 whereas l-aspartate activated only AVR-14B GluCls. Regarding the monoterpenoids, both GluCls were inhibited by propofol, thymol and menthol, SmGluCl-2 most potently by thymol (IC50 484 ± 85 μM) and least potently by menthol (IC50 > 3 mM). Computational docking suggested that agonist and inhibitor potency is attributable to particular interactions with extracellular or membrane-spanning amino acid residues. These results reveal that flatworm GluCls are pharmacologically susceptible to numerous agonists and modulators and indicate that changes to the glutamate γ-carboxyl or to the propofol 6-isopropyl group can alter the differential pharmacology at flatworm and roundworm GluCls. This should inform the development of more potent compounds and in turn lead to novel anthelmintics.

  4. Kdr mutations in Triatoma infestans from the Gran Chaco are distributed in two differentiated foci: Implications for pyrethroid resistance management.

    PubMed

    Sierra, Ivana; Capriotti, Natalia; Fronza, Georgina; Mougabure-Cueto, Gastón; Ons, Sheila

    2016-06-01

    Point mutations in the voltage-gated sodium channel, the primary target of pyrethroid insecticides, have been associated with the resistance in Triatoma infestans, an important vector of Chagas' disease. Hence, the sustainability of vector control programs requires the implementation of resistance management strategies. We determined the sensitivity of the molecular assays previously designed for early resistance detection to be used in pooled samples from a wide area of the endemic region, and validated them for their routine use in control campaigns for the monitoring of insecticide resistance in T. infestans. Consequently, we used these methods to examine the distribution of resistance-associated mutations in the sodium channel gene in populations of T. infestans from the Argentinean and Bolivian Gran Chaco. The PASA and REA assays tested proved sensitive enough to detect kdr SNPs in pooled samples, indicating these assays are suitable for routine screening in insecticide resistance surveillance. Two geographically differentiated foci were detected in T. infestans populations from the Argentinean and Bolivian Gran Chaco, with populations on the Bolivian-Argentinean border carrying L1014F mutation, and those from the Argentinean Chaco carrying L925I mutation. In all highly resistant populations analyzed, one of both kdr mutations was present, and toxicological assays determined that all pyrethroid resistant populations analyzed herein were sensitive to fenitrothion. The principal cause of pyrethroid resistance in T. infestans from the Gran Chaco ecoregion is kdr mutations in the sodium channel. Different levels of resistance occur in different populations carrying identical mutation, suggesting the existence of contributory mechanisms. PMID:26992297

  5. Evidence of Fasciola spp. resistance to albendazole, triclabendazole and bromofenofos in water buffaloes (Bubalus bubalis).

    PubMed

    Venturina, Virginia M; Alejandro, Ma Antonette F; Baltazar, Cyril P; Abes, Nancy S; Mingala, Claro N

    2015-01-01

    Fasciolosis caused by Fasciola spp. is considered the most important helminth infection of ruminants in tropical countries. Anthelmintic resistance has become a global concern. This study compared the efficacy of the commonly used anthelmintics, determined the toxicity level and any indication of resistance. Thirty two water buffaloes naturally-infected with Fasciola spp. were used to determine the efficacy of triclabendazole (TBZ), albendazole (ABZ), and bromofenofos (BRO) using Fecal Egg Count Reduction Test (FECRT). To test the toxicity of the drugs given, serum glutamic-pyruvic transaminase (SGPT) was evaluated before and within one week after treatment. One dose administration of ABZ registered an efficacy of 79.17%, 73.33% for TBZ and 70.83% for BRO. Efficacy in two dose- treatment group was 83.33% for both BRO and ABZ, and 90.00% for TBZ. Two dose-treatment was effective for TBZ (90%), ineffective for BRO and ABZ. SGPT levels were not significantly different between pre-treatment and post- treatment across all treatments. Giving one or two doses of anthelmintics, at one month interval, does not increase the efficacy of the three drugs tested. The study also implies that anthelmintic resistance may have developed in the animals.

  6. Evidence of Fasciola spp. resistance to albendazole, triclabendazole and bromofenofos in water buffaloes (Bubalus bubalis).

    PubMed

    Venturina, Virginia M; Alejandro, Ma Antonette F; Baltazar, Cyril P; Abes, Nancy S; Mingala, Claro N

    2015-01-01

    Fasciolosis caused by Fasciola spp. is considered the most important helminth infection of ruminants in tropical countries. Anthelmintic resistance has become a global concern. This study compared the efficacy of the commonly used anthelmintics, determined the toxicity level and any indication of resistance. Thirty two water buffaloes naturally-infected with Fasciola spp. were used to determine the efficacy of triclabendazole (TBZ), albendazole (ABZ), and bromofenofos (BRO) using Fecal Egg Count Reduction Test (FECRT). To test the toxicity of the drugs given, serum glutamic-pyruvic transaminase (SGPT) was evaluated before and within one week after treatment. One dose administration of ABZ registered an efficacy of 79.17%, 73.33% for TBZ and 70.83% for BRO. Efficacy in two dose- treatment group was 83.33% for both BRO and ABZ, and 90.00% for TBZ. Two dose-treatment was effective for TBZ (90%), ineffective for BRO and ABZ. SGPT levels were not significantly different between pre-treatment and post- treatment across all treatments. Giving one or two doses of anthelmintics, at one month interval, does not increase the efficacy of the three drugs tested. The study also implies that anthelmintic resistance may have developed in the animals. PMID:26878627

  7. Weight loss resistance: a further consideration for the nutritional management of obese Equidae.

    PubMed

    Argo, Caroline McG; Curtis, Gemma C; Grove-White, Dai; Dugdale, Alexandra H A; Barfoot, Clare F; Harris, Patricia A

    2012-11-01

    Evidence-based, weight loss management advice is required to address equine obesity. Changes in body mass (BM), body condition score (BCS), heart (HG) and belly circumference (BG), direct (ultrasonographic) and indirect (D(2)O dilution, bioelectrical impedance analysis [BIA]) measures of body fat as well as indices of insulin resistance (IR) were monitored in 12 overweight (BCS ≥ 7/9) horses and ponies of mixed breed and gender for 16 weeks. Animals were randomly assigned to two groups (Group 1, n=6, BCS 7.6/9 ± 0.6, 489 ± 184.6 kg; Group 2, n=6, BCS 8.1/9 ± 0.6, 479 ± 191.5 kg). Daily dry matter intake (DMI) was restricted to 1.25% BM as one of two, near-isocaloric (DE ∼0.115 MJ/kg BM/day), forage-based diets (Group 1, 0.8% BM chaff-based feed: 0.45% BM hay; Group 2, 1.15% BM hay: 0.1% BM nutrient-balancer). Statistical modelling revealed considerable between-animal heterogeneity in proportional weight losses (0.16-0.55% of Week 1 BM weekly). The magnitude of weight loss resistance (WLR) or sensitivity to dietary restriction was independent of diet or any measured outset variable and was largely (65%) attributed to animal identity. Predicted rates of weight loss decreased over time. BCS and BIA were poor estimates of D(2)O-derived body fat%. Reciprocal changes in depths of retroperitoneal and subcutaneous adipose tissues were evident. Changes in BG were associated with losses in retroperitoneal fat and BM (r(2), 0.67 and 0.79). Indices of IR improved for 9/12 animals by Week 16. For obese animals, weight loss should be initiated by restricting forage DMI to 1.25% BM. Subsequent restriction to 1% BM may be warranted for WLR animals.

  8. Captures of MFO-resistant Cydia pomonella adults as affected by lure, crop management system and flight.

    PubMed

    Bosch, D; Rodríguez, M A; Avilla, J

    2016-02-01

    The main resistance mechanism of codling moth (Cydia pomonella) in the tree fruit area of Lleida (NE Spain) is multifunction oxidases (MFO). We studied the frequency of MFO-resistant adults captured by different lures, with and without pear ester, and flights in orchards under different crop management systems. The factor year affected codling moth MFO-resistance level, particularly in the untreated orchards, highlighting the great influence of codling moth migration on the spread of resistance in field populations. Chemical treatments and adult flight were also very important but mating disruption technique showed no influence. The second adult flight showed the highest frequency, followed by the first flight and the third flight. In untreated orchards, there were no significant differences in the frequency of MFO-resistant individuals attracted by Combo and BioLure. Red septa lures baited with pear ester (DA) captured sufficient insects only in the first generation of 2010, obtaining a significantly lower proportion of MFO-resistant adults than Combo and BioLure. In the chemically treated orchards, in 2009 BioLure caught a significantly lower proportion of MFO-resistant adults than Combo during the first and third flight, and also than DA during the first flight. No significant differences were found between the lures or flights in 2010. These results cannot support the idea of a higher attractiveness of the pear ester for MFO-resistant adults in the field but do suggest a high influence of the response to the attractant depending on the management of the orchard, particularly with regard to the use of chemical insecticides.

  9. Susceptibility of Bonagota salubricola (Lepidoptera: Tortricidae) to Insecticides in Brazilian Apple Orchards: Implications for Resistance Management.

    PubMed

    Bernardi, Daniel; Botton, Marcos; Andreazza, Felipe; Arnaldo Batista Neto E Silva, Oscar; João Arioli, Cristiano; Omoto, Celso

    2016-08-01

    The Bonagota salubricola (Meyrick) is a major pest in apple orchards in Brazil, and chemical control has been the primary tool for insect management. To support the development of an insect resistance management (IRM) program, baseline studies of the susceptibility of a reference (laboratory) B. salubricola population were conducted; seven wild B. salubricola populations were monitored for susceptibility to insecticide; and the toxicity of some new chemicals to third-instar larvae and adults was evaluated by a leaf dip and ingestion bioassay, respectively. Neonates from the susceptible (laboratory) population exposed to insecticide showed an LC50 ranging from 0.34 (spinetoram) to 30.19 (novaluron) µg of a.i. ml(-1) (88.8-fold variation), so the diagnostic concentrations for an IRM program in Brazil based on the LC99 were as follows: 19.0 µg of a.i./ml chlorantraniliprole, 510.0 novaluron, 72.0 phosmet, 4.1 spinetoram, 12.8 spinosad, and 110.0 tebufenozide. Based on the LC99, significant differences were not observed in the susceptibility of the field and laboratory populations to chlorantraniliprole, phosmet, spinetoram, spinosad, and tebufenozide insecticides, but there were significant differences in the survival rates of the two populations to novaluron insecticide (3.3%). All insecticides at the diagnostic concentrations showed high toxicity to third-instar larvae (mortality rates between 73 to 97%). Phosmet, spinetoram, and spinosad insecticides were toxic to B. salubricola adults (mortality >85%), while chlorantraniliprole, novaluron, and tebufenozide insecticides caused mortality below 5%. The evaluated insecticides showed high toxicity to different developmental stages of B. salubricola, so the diagnostic concentrations may be used in IRM programs in Brazil. PMID:27341888

  10. Development of partial ontogenic resistance to powdery mildew in hop cones and its management implications.

    PubMed

    Twomey, Megan C; Wolfenbarger, Sierra N; Woods, Joanna L; Gent, David H

    2015-01-01

    Knowledge of processes leading to crop damage is central to devising rational approaches to disease management. Multiple experiments established that infection of hop cones by Podosphaera macularis was most severe if inoculation occurred within 15 to 21 days after bloom. This period of infection was associated with the most pronounced reductions in alpha acids, cone color, and accelerated maturation of cones. Susceptibility of cones to powdery mildew decreased progressively after the transition from bloom to cone development, although complete immunity to the disease failed to develop. Maturation of cone tissues was associated with multiple significant affects on the pathogen manifested as reduced germination of conidia, diminished frequency of penetration of bracts, lengthening of the latent period, and decreased sporulation. Cones challenged with P. macularis in juvenile developmental stages also led to greater frequency of colonization by a complex of saprophytic, secondary fungi. Since no developmental stage of cones was immune to powdery mildew, the incidence of powdery mildew continued to increase over time and exceeded 86% by late summer. In field experiments with a moderately susceptible cultivar, the incidence of cones with powdery mildew was statistically similar when fungicide applications were made season-long or targeted only to the juvenile stages of cone development. These studies establish that partial ontogenic resistance develops in hop cones and may influence multiple phases of the infection process and pathogen reproduction. The results further reinforce the concept that the efficacy of a fungicide program may depend largely on timing of a small number of sprays during a relatively brief period of cone development. However in practice, targeting fungicide and other management tactics to periods of enhanced juvenile susceptibility may be complicated by a high degree of asynchrony in cone development and other factors that are situation-dependent.

  11. Development of Partial Ontogenic Resistance to Powdery Mildew in Hop Cones and Its Management Implications

    PubMed Central

    Twomey, Megan C.; Wolfenbarger, Sierra N.; Woods, Joanna L.; Gent, David H.

    2015-01-01

    Knowledge of processes leading to crop damage is central to devising rational approaches to disease management. Multiple experiments established that infection of hop cones by Podosphaera macularis was most severe if inoculation occurred within 15 to 21 days after bloom. This period of infection was associated with the most pronounced reductions in alpha acids, cone color, and accelerated maturation of cones. Susceptibility of cones to powdery mildew decreased progressively after the transition from bloom to cone development, although complete immunity to the disease failed to develop. Maturation of cone tissues was associated with multiple significant affects on the pathogen manifested as reduced germination of conidia, diminished frequency of penetration of bracts, lengthening of the latent period, and decreased sporulation. Cones challenged with P. macularis in juvenile developmental stages also led to greater frequency of colonization by a complex of saprophytic, secondary fungi. Since no developmental stage of cones was immune to powdery mildew, the incidence of powdery mildew continued to increase over time and exceeded 86% by late summer. In field experiments with a moderately susceptible cultivar, the incidence of cones with powdery mildew was statistically similar when fungicide applications were made season-long or targeted only to the juvenile stages of cone development. These studies establish that partial ontogenic resistance develops in hop cones and may influence multiple phases of the infection process and pathogen reproduction. The results further reinforce the concept that the efficacy of a fungicide program may depend largely on timing of a small number of sprays during a relatively brief period of cone development. However in practice, targeting fungicide and other management tactics to periods of enhanced juvenile susceptibility may be complicated by a high degree of asynchrony in cone development and other factors that are situation

  12. The Evolving Role of Antimicrobial Stewardship in Management of Multidrug Resistant Infections.

    PubMed

    Goff, Debra A; File, Thomas M

    2016-06-01

    This article summarizes the current literature describing how antimicrobial stewardship interventions impact antimicrobial resistance. Discussion includes why we need stewardship, how to collaborate with team members, and the evidence of stewardship's impact on resistance.

  13. Anthelmintic efficacy of crude neem (Azadirachta indica) leaf powder against bovine strongylosis.

    PubMed

    Jamra, Nirmala; Das, Giridhari; Singh, Priyanka; Haque, Manjurul

    2015-12-01

    The present study was conducted to evaluate the anthelmintic efficacy of crude neem (Azadirachta indica) leaf powder against strongyle infections in cattle. Based on copro-examination, 30 cattle positive for strongyle infection with at least 250 [eggs per gram (EPG) of faeces] were selected and grouped as A, B and C (10 animals/group). Group A and B were treated respectively with fendendazole and neem leaf powder @ 5 and 500 mg/kg body weight, whereas Group C served as infected untreated control. Faecal sample from each animal of these groups was examined on day 0, 7, 14 and 28 post treatments and EPG was determined. The result showed significant decrease (p < 0.05) in EPG in Group A and B after day 7 post treatment but there was no significant variation in terms of EPG in control group. Thus it can be concluded that crude neem leaf powder has anthelmintic property and it can further be studied to isolate the active component to produce herbal anthelminthics.

  14. Oral dosing with papaya latex is an effective anthelmintic treatment for sheep infected with Haemonchus contortus

    PubMed Central

    2011-01-01

    Background The cysteine proteinases in papaya latex have been shown to have potent anthelmintic properties in monogastric hosts such as rodents, pigs and humans, but this has not been demonstrated in ruminants. Methods In two experiments, sheep were infected concurrently with 5,000 infective larvae of Haemonchus contortus and 10,000 infective larvae of Trichostrongylus colubriformis and were then treated with the supernatant from a suspension of papaya latex from day 28 to day 32 post-infection. Faecal egg counts were monitored from a week before treatment until the end of the experiment and worm burdens were assessed on day 35 post-infection. Results We found that the soluble fraction of papaya latex had a potent in vivo effect on the abomasal nematode H. contortus, but not on the small intestinal nematode T. colubriformis. This effect was dose-dependent and at tolerated levels of gavage with papaya latex (117 μmol of active papaya latex supernatant for 4 days), the H. contortus worm burdens were reduced by 98%. Repeated treatment, daily for 4 days, was more effective than a single dose, but efficacy was not enhanced by concurrent treatment with the antacid cimetidine. Conclusions Our results provide support for the idea that cysteine proteinases derived from papaya latex may be developed into novel anthelmintics for the treatment of lumenal stages of gastro-intestinal nematode infections in sheep, particularly those parasitizing the abomasum. PMID:21406090

  15. Anthelmintic and cytotoxic activities of extracts of Markhamia obtusifolia Sprague (Bignoniaceae).

    PubMed

    Nchu, F; Githiori, J B; McGaw, L J; Eloff, J N

    2011-12-29

    The anthelmintic activity of Markhamia obtusifolia Sprague (Bignoniaceae) leaf extracts was evaluated against the ruminant gastrointestinal nematode parasite Trichostrongylus colubriformis (Nematoda: Strongylida) using the in vitro egg hatch test. Also, the cytotoxic activity of aqueous extracts of M. obtusifolia was evaluated in cell line cytotoxicity assays. The results indicated that the effective concentration (EC(50)) for the water extract of M. obtusifolia leaves (0.46 mg/mL; Confidence Interval [CI] 0.3-0.5mg/mL) was significantly lower than the EC(50) for the acetone extract of M. obtusifolia (0.8 mg/mL; CI 0.7-1mg/mL). Aqueous extracts were twice as potent as the acetone extracts. The EC(90) (0.2mg/mL; CI 0.1-0.02) for thiabendazole (positive control) was significantly lower than the EC(90) for the water extract of M. obtusifolia (10.7 mg/mL; CI 8.3-13.7 mg/mL). In the cytotoxicity bioassay, the lethal concentration (LC(50)) for the aqueous extract of M. obtusifolia was 0.476 mg/mL, which was relatively high (low toxicity) in comparison to the highly toxic berberine (LC(50)=9.80 μg/mL). The current study showed that M. obtusifolia plant extracts possess anthelmintic activity and are relatively non-cytotoxic, thus providing support for their use in traditional veterinary practices.

  16. In vitro anthelmintic effect of Vicia pannonica var. purpurascens on trichostrongylosis in sheep.

    PubMed

    Kozan, Esma; Anul, Serap Arabaci; Tatli, I Irem

    2013-07-01

    Vicia species are used for the treatment of malaria, diarrhea, hemorrhoids, kidney problems and infertility in Turkish traditional medicine. The present study was carried out to evaluate the in vitro anthelmintic effects of Vicia pannonica Crantz. var. purpurascens (DC). Ser. extracts. Larval motility test was used to determine anthelmintic activity of this plant. Motility of the larvae is measured by observation. The methanol, n-hexane, chloroform, acetone, and aqueous extracts of the aerial parts of the plant including the leaves and flowers were applied to developing trichostrongylus larvae at 1, 0.8, 0.6, 0.4, 0.2 and 0.1 mg/ml doses. Thiabendazole and distilled water with 5% DMSO was used as positive and negative control. All of the extracts were 100% effective. Two flavone and flavonol glycosides; luteolin-7-β-O-glucopyranoside (1) and quercetin-3-O-β-glucopyranoside (2) were isolated from the acetone extract and their structures were elucidated by spectral techniques. The solutions prepared from two flavonoid fractions at several doses were performed in vitro to larvae in the same way. Both of them were 100% effective at 1 and 0.8 mg/ml doses. Results of the present study support the utilization of these plant species employed in Turkish folk medicine.

  17. Acetylcholinesterase secretion--a parameter for the interpretation of in vitro anthelmintic screens.

    PubMed

    Rapson, E B; Chilwan, A S; Jenkins, D C

    1986-04-01

    Interpretation of anthelmintic activity using in vitro screens has, until now, relied on the detection of drug-induced effects on nematode development, viability and motility. A novel biochemical parameter dependent upon the spectrophotometric assay of acetylcholinesterase (AChE), an enzyme secreted in large quantities by certain trichostrongylid nematodes, has been developed to replace these often subjective indices of activity. Using Nippostrongylus brasiliensis, a worm frequently employed for primary screening, the secretion of this enzyme in the presence or absence of a large number of drugs in vitro was determined. During a 4-day incubation period in a complex undefined medium without serum. AChE was secreted by normal 4th larval and immature adult stages of the worm in a linear fashion. All modern broad-spectrum veterinary anthelmintics, regardless of their mode of action, dramatically reduced the amount of enzyme secreted. Correlation between the biochemical and observational parameters was excellent and the selectivity of the assay when based solely on enzyme secretion was not lost. Other advantages were that the time required for the activity of certain slow-acting compounds to be detected was reduced from 7 to 4 days and that close microscopical examination of the worms was not necessary.

  18. Factors affecting the anthelmintic efficacy of papaya latex in vivo: host sex and intensity of infection.

    PubMed

    Luoga, Wenceslaus; Mansur, Fadlul; Lowe, Ann; Duce, Ian R; Buttle, David J; Behnke, Jerzy M

    2015-07-01

    The development of plant-derived cysteine proteinases, such as those in papaya latex, as novel anthelmintics requires that the variables affecting efficacy be fully evaluated. Here, we conducted two experiments, the first to test for any effect of host sex and the second to determine whether the intensity of the worm burden carried by mice would influence efficacy. In both experiments, we used the standard C3H mouse reference strain in which papaya latex supernatant (PLS) consistently shows >80 % reduction in Heligmosomoides bakeri worm burdens, but to broaden the perspective, we also included for comparison mice of other strains that are known to respond more poorly to treatment with papaya latex. Our results confirmed that there is a strong genetic influence affecting efficacy of PLS in removing adult worm burdens. However, there was no effect of host sex on efficacy (C3H and NIH) and no effect of infection intensity (C3H and BALB/c). These results offer optimism that plant-derived cysteine proteinases (CPs), such as these from papaya latex, can function as effective anthelmintics, with neither host sex nor infection intensity presenting further hurdles to impede their development for future medicinal and veterinary usage.

  19. The relative anthelmintic efficacy of plant-derived cysteine proteinases on intestinal nematodes.

    PubMed

    Luoga, W; Mansur, F; Buttle, D J; Duce, I R; Garnett, M C; Lowe, A; Behnke, J M

    2015-03-01

    We examined the in vitro and in vivo efficacy of plant cysteine proteinases (CPs) derived from pineapple (Ananas comosus) and kiwi fruit (Actinidia deliciosa), and compared their efficacy as anthelmintics to the known effects of CPs from the latex of papaya (Carica papaya) against the rodent intestinal nematode, Heligmosomoides bakeri. Both fruit bromelain and stem bromelain had significant in vitro detrimental effects on H. bakeri but in comparison, actinidain from kiwi fruit had very little effect. However, in vivo trials indicated far less efficacy of stem bromelain and fruit bromelain than that expected from the in vitro experiments (24.5% and 22.4% reduction in worm burdens, respectively) against H. bakeri. Scanning electron microscopy revealed signs of cuticular damage on worms incubated in fruit bromelain, stem bromelain and actinidain, but this was far less extensive than on those incubated in papaya latex supernatant. We conclude that, on the basis of presently available data, CPs derived from pineapples and kiwi fruits are not suitable for development as novel anthelmintics for intestinal nematode infections.

  20. Host genetic influences on the anthelmintic efficacy of papaya-derived cysteine proteinases in mice.

    PubMed

    Luoga, Wenceslaus; Mansur, Fadlul; Stepek, Gillian; Lowe, Ann; Duce, Ian R; Buttle, David J; Behnke, Jerzy M

    2015-06-01

    Eight strains of mice, of contrasting genotypes, infected with Heligmosomoides bakeri were studied to determine whether the anthelmintic efficacy of papaya latex varied between inbred mouse strains and therefore whether there is an underlying genetic influence on the effectiveness of removing the intestinal nematode. Infected mice were treated with 330 nmol of crude papaya latex or with 240 nmol of papaya latex supernatant (PLS). Wide variation of response between different mouse strains was detected. Treatment was most effective in C3H (90·5-99·3% reduction in worm counts) and least effective in CD1 and BALB/c strains (36·0 and 40·5%, respectively). Cimetidine treatment did not improve anthelmintic efficacy of PLS in a poor drug responder mouse strain. Trypsin activity, pH and PLS activity did not differ significantly along the length of the gastro-intestinal (GI) tract between poor (BALB/c) and high (C3H) drug responder mouse strains. Our data indicate that there is a genetic component explaining between-mouse variation in the efficacy of a standard dose of PLS in removing worms, and therefore warrant some caution in developing this therapy for wider scale use in the livestock industry, and even in human medicine.

  1. Antiproliferative effect of benzimidazole anthelmintics albendazole, ricobendazole, and flubendazole in intestinal cancer cell lines.

    PubMed

    Králová, Věra; Hanušová, Veronika; Staňková, Petra; Knoppová, Kateřina; Čáňová, Kristýna; Skálová, Lenka

    2013-10-01

    This study aimed to test the antiproliferative effect of three benzimidazole anthelmintics in intestinal cancer cells and to investigate whether these drugs, which inhibit tubulin polymerization, can potentiate the efficacy of the microtubule-stabilizing drug paclitaxel (PTX). Four intestinal cancer cell lines, SW480, SW620, HCT8, and Caco2, with different origins and growth characteristics were used. The antiproliferative effect of albendazole (ABZ), ricobendazole (RBZ), flubendazole (FLU), and their combinations with PTX was tested using three different end-point viability assays, cell cycle distribution analysis, and the x-CELLigence System for real-time cell analysis. ABZ and FLU inhibited cell proliferation significantly in a concentration-dependent and time-dependent manner through cell arrest in the G2/M phase. RBZ was not effective at any concentration tested. The cell lines differed in sensitivity to FLU and ABZ, with HCT8 being the most sensitive, showing IC₅₀ values for ABZ and FLU that reached 0.3 and 0.9 μmol/l, respectively. Combinations of PTX+ABZ and PTX+FLU decreased cell viability more effectively when compared with treatment with individual drugs alone. The anthelmintic benzimidazole drugs ABZ and FLU show a significant cytostatic effect and potentiate the efficacy of PTX in intestinal cancer cells.

  2. Anthelmintic Activities of Aporphine from Nelumbo nucifera Gaertn. cv. Rosa-plena against Hymenolepis nana

    PubMed Central

    Lin, Rong-Jyh; Wu, Mei-Hsuan; Ma, Yi-Hsuan; Chung, Li-Yu; Chen, Chung-Yi; Yen, Chuan-Min

    2014-01-01

    Nelumbo nucifera Gaertn. cv. Rosa-plena (Nelumbonaceae), commonly known as lotus, is a perennial aquatic plant grown and consumed throughout Asia. All parts of N. nucifera have been used for various medicinal purposes in oriental medicine. From the leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena (an aquatic plant), liriodenine (1), lysicamine (2), (−)-anonaine (3), (-)-asimilobine (4), (-)-caaverine (5), (-)-N-methylasimilobine (6), (-)-nuciferine (7), (-)-nornuciferine (8), (-)-roemerine (9), 7-hydroxydehydronuciferine (10) and cepharadione B (11) were isolated and identification and anthelmintic activities of aporphine was evaluated against Anisakis simplex and Hymenolepis nana. This study found that the above constituents killed H. nana or reduced their spontaneous movements (oscillation/peristalsis). However, the above constituents at various concentrations demonstrated no larvicidal effect or ability to halt spontaneous parasite movement for 72 h against A. simplex, respectively. In addition, according to an assay of cestocidal activity against H. nana and nematocidal activity against A. simplex, we found that the above compounds showed greater lethal efficacy on H. nana than against A. simplex. Further investigation showed that these above constituents have effects against peroxyl radicals under cestocidal effect. Together, these findings suggest that these constituents of Nelumbo nucifera Gaertn. cv. Rosa-plena might be used as anthelmintic agents against H. nana. PMID:24583851

  3. In vitro anthelmintic effect of Vicia pannonica var. purpurascens on trichostrongylosis in sheep.

    PubMed

    Kozan, Esma; Anul, Serap Arabaci; Tatli, I Irem

    2013-07-01

    Vicia species are used for the treatment of malaria, diarrhea, hemorrhoids, kidney problems and infertility in Turkish traditional medicine. The present study was carried out to evaluate the in vitro anthelmintic effects of Vicia pannonica Crantz. var. purpurascens (DC). Ser. extracts. Larval motility test was used to determine anthelmintic activity of this plant. Motility of the larvae is measured by observation. The methanol, n-hexane, chloroform, acetone, and aqueous extracts of the aerial parts of the plant including the leaves and flowers were applied to developing trichostrongylus larvae at 1, 0.8, 0.6, 0.4, 0.2 and 0.1 mg/ml doses. Thiabendazole and distilled water with 5% DMSO was used as positive and negative control. All of the extracts were 100% effective. Two flavone and flavonol glycosides; luteolin-7-β-O-glucopyranoside (1) and quercetin-3-O-β-glucopyranoside (2) were isolated from the acetone extract and their structures were elucidated by spectral techniques. The solutions prepared from two flavonoid fractions at several doses were performed in vitro to larvae in the same way. Both of them were 100% effective at 1 and 0.8 mg/ml doses. Results of the present study support the utilization of these plant species employed in Turkish folk medicine. PMID:23562885

  4. Potential anthelmintics: polyphenols from the tea plant Camellia sinensis L. are lethally toxic to Caenorhabditis elegans.

    PubMed

    Mukai, Daisuke; Matsuda, Noriko; Yoshioka, Yu; Sato, Masashi; Yamasaki, Toru

    2008-04-01

    A novel gallate of tannin, (-)-epigallocatechin-(2 beta-->O-->7',4 beta-->8')-epicatechin-3'-O-gallate (8), together with (-)-epicatechin-3-O-gallate (4), (-)-epigallocatechin (5), (-)-epigallocatechin-3-O-gallate (6), and (+)-gallocatechin-(4 alpha-->8')-epigallocatechin (7), were isolated from the tea plant Camellia sinensis (L.) O. Kuntze var. sinensis (cv., Yabukita). The structure of 8, including stereochemistry, was elucidated by spectroscopic methods and hydrolysis. The compounds, along with commercially available pyrogallol (1), (+)-catechin (2), and (-)-epicatechin (3), were examined for toxicity towards egg-bearing adults of Caenorhabditis elegans. The anthelmintic mebendazole (9) was used as a positive control. Neither 2 nor 3 were toxic but the other compounds were toxic in the descending order 8, 7 approximately 6, 9, 4, 5, 1. The LC(50) (96 h) values of 8 and 9 were evaluated as 49 and 334 micromol L(-1), respectively. These data show that many green tea polyphenols may be potential anthelmintics. PMID:18404315

  5. Microbial ecology, bacterial pathogens, and antibiotic resistant genes in swine manure wastewater as influenced by three swine management systems.

    PubMed

    Brooks, John P; Adeli, Ardeshir; McLaughlin, Michael R

    2014-06-15

    The environmental influence of farm management in concentrated animal feeding operations (CAFO) can yield vast changes to the microbial biota and ecological structure of both the pig and waste manure lagoon wastewater. While some of these changes may not be negative, it is possible that CAFOs can enrich antibiotic resistant bacteria or pathogens based on farm type, thereby influencing the impact imparted by the land application of its respective wastewater. The purpose of this study was to measure the microbial constituents of swine-sow, -nursery, and -finisher farm manure lagoon wastewater and determine the changes induced by farm management. A total of 37 farms were visited in the Mid-South USA and analyzed for the genes 16S rRNA, spaQ (Salmonella spp.), Camp-16S (Campylobacter spp.), tetA, tetB, ermF, ermA, mecA, and intI using quantitative PCR. Additionally, 16S rRNA sequence libraries were created. Overall, it appeared that finisher farms were significantly different from nursery and sow farms in nearly all genes measured and in 16S rRNA clone libraries. Nearly all antibiotic resistance genes were detected in all farms. Interestingly, the mecA resistance gene (e.g. methicillin resistant Staphylococcus aureus) was below detection limits on most farms, and decreased as the pigs aged. Finisher farms generally had fewer antibiotic resistance genes, which corroborated previous phenotypic data; additionally, finisher farms produced a less diverse 16S rRNA sequence library. Comparisons of Camp-16S and spaQ GU (genomic unit) values to previous culture data demonstrated ratios from 10 to 10,000:1 depending on farm type, indicating viable but not cultivatable bacteria were dominant. The current study indicated that swine farm management schemes positively and negatively affect microbial and antibiotic resistant populations in CAFO wastewater which has future "downstream" implications from both an environmental and public health perspective.

  6. Microbial ecology, bacterial pathogens, and antibiotic resistant genes in swine manure wastewater as influenced by three swine management systems.

    PubMed

    Brooks, John P; Adeli, Ardeshir; McLaughlin, Michael R

    2014-06-15

    The environmental influence of farm management in concentrated animal feeding operations (CAFO) can yield vast changes to the microbial biota and ecological structure of both the pig and waste manure lagoon wastewater. While some of these changes may not be negative, it is possible that CAFOs can enrich antibiotic resistant bacteria or pathogens based on farm type, thereby influencing the impact imparted by the land application of its respective wastewater. The purpose of this study was to measure the microbial constituents of swine-sow, -nursery, and -finisher farm manure lagoon wastewater and determine the changes induced by farm management. A total of 37 farms were visited in the Mid-South USA and analyzed for the genes 16S rRNA, spaQ (Salmonella spp.), Camp-16S (Campylobacter spp.), tetA, tetB, ermF, ermA, mecA, and intI using quantitative PCR. Additionally, 16S rRNA sequence libraries were created. Overall, it appeared that finisher farms were significantly different from nursery and sow farms in nearly all genes measured and in 16S rRNA clone libraries. Nearly all antibiotic resistance genes were detected in all farms. Interestingly, the mecA resistance gene (e.g. methicillin resistant Staphylococcus aureus) was below detection limits on most farms, and decreased as the pigs aged. Finisher farms generally had fewer antibiotic resistance genes, which corroborated previous phenotypic data; additionally, finisher farms produced a less diverse 16S rRNA sequence library. Comparisons of Camp-16S and spaQ GU (genomic unit) values to previous culture data demonstrated ratios from 10 to 10,000:1 depending on farm type, indicating viable but not cultivatable bacteria were dominant. The current study indicated that swine farm management schemes positively and negatively affect microbial and antibiotic resistant populations in CAFO wastewater which has future "downstream" implications from both an environmental and public health perspective. PMID:24704907

  7. Effects of environmental factors and management practices on microclimate, winter physiology, and frost resistance in trees.

    PubMed

    Charrier, Guillaume; Ngao, Jérôme; Saudreau, Marc; Améglio, Thierry

    2015-01-01

    Freezing stress is one of the most important limiting factors determining the ecological distribution and production of tree species. Assessment of frost risk is, therefore, critical for forestry, fruit production, and horticulture. Frost risk is substantial when hazard (i.e., exposure to damaging freezing temperatures) intersects with vulnerability (i.e., frost sensitivity). Based on a large number of studies on frost resistance and frost occurrence, we highlight the complex interactive roles of environmental conditions, carbohydrates, and water status in frost risk development. To supersede the classical empirical relations used to model frost hardiness, we propose an integrated ecophysiologically-based framework of frost risk assessment. This framework details the individual or interactive roles of these factors, and how they are distributed in time and space at the individual-tree level (within-crown and across organs). Based on this general framework, we are able to highlight factors by which different environmental conditions (e.g., temperature, light, flood, and drought), and management practices (pruning, thinning, girdling, sheltering, water aspersion, irrigation, and fertilization) influence frost sensitivity and frost exposure of trees. PMID:25972877

  8. Effects of environmental factors and management practices on microclimate, winter physiology, and frost resistance in trees.

    PubMed

    Charrier, Guillaume; Ngao, Jérôme; Saudreau, Marc; Améglio, Thierry

    2015-01-01

    Freezing stress is one of the most important limiting factors determining the ecological distribution and production of tree species. Assessment of frost risk is, therefore, critical for forestry, fruit production, and horticulture. Frost risk is substantial when hazard (i.e., exposure to damaging freezing temperatures) intersects with vulnerability (i.e., frost sensitivity). Based on a large number of studies on frost resistance and frost occurrence, we highlight the complex interactive roles of environmental conditions, carbohydrates, and water status in frost risk development. To supersede the classical empirical relations used to model frost hardiness, we propose an integrated ecophysiologically-based framework of frost risk assessment. This framework details the individual or interactive roles of these factors, and how they are distributed in time and space at the individual-tree level (within-crown and across organs). Based on this general framework, we are able to highlight factors by which different environmental conditions (e.g., temperature, light, flood, and drought), and management practices (pruning, thinning, girdling, sheltering, water aspersion, irrigation, and fertilization) influence frost sensitivity and frost exposure of trees.

  9. Effects of environmental factors and management practices on microclimate, winter physiology, and frost resistance in trees

    PubMed Central

    Charrier, Guillaume; Ngao, Jérôme; Saudreau, Marc; Améglio, Thierry

    2015-01-01

    Freezing stress is one of the most important limiting factors determining the ecological distribution and production of tree species. Assessment of frost risk is, therefore, critical for forestry, fruit production, and horticulture. Frost risk is substantial when hazard (i.e., exposure to damaging freezing temperatures) intersects with vulnerability (i.e., frost sensitivity). Based on a large number of studies on frost resistance and frost occurrence, we highlight the complex interactive roles of environmental conditions, carbohydrates, and water status in frost risk development. To supersede the classical empirical relations used to model frost hardiness, we propose an integrated ecophysiologically-based framework of frost risk assessment. This framework details the individual or interactive roles of these factors, and how they are distributed in time and space at the individual-tree level (within-crown and across organs). Based on this general framework, we are able to highlight factors by which different environmental conditions (e.g., temperature, light, flood, and drought), and management practices (pruning, thinning, girdling, sheltering, water aspersion, irrigation, and fertilization) influence frost sensitivity and frost exposure of trees. PMID:25972877

  10. Identification of single nucleotide polymorphisms (SNPs)associated to Red Maasai x Dorper resistance to gastrointestinal parasite infections

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gastrointestinal (GI) parasitic infection is a main health constraint that affects small ruminant production. Anthelmintic drugs are used to control parasites, however long-term use led to selection pressure, resulting in parasite resistance against all current chemical interventions available in th...

  11. Resistance and resilience of N and P cycling microbes in differently managed agricultural systems after heat perturbation

    NASA Astrophysics Data System (ADS)

    Singh, Priyashiela; Scow, Kate

    2013-04-01

    Agricultural management and resistance and resilience of microbial communities is key to long-term agricultural sustainability. Agricultural management practices impact soil through physical disturbance, inputs of fertilizers and pesticides, and cultivation of monoculture or low-diversity plant systems. Resistance and resilience of soil microbial communities to disturbance events is a topic of growing importance with predicted rising temperatures and large unpredictability in rainfall patterns associated with global climate change. Diverse microbial communities are essential for the sustainability of agriculture. Previous research has focused on the resistance of soil systems in relation to total microbial biomass but has ignored relationships with specific functional groups of microbes. Denitrifiers are key organisms in N cycling and these organisms control the pools of plant-available N in soil, while alkaline phosphatase is a key microbially produced enzyme involved in the regulation of pools of available phosphate. In this soil incubation experiment abundance of total bacteria and archaea were quantified along with denitrifying and alkaline phosphatase genes after subjecting differently managed agricultural soils to severe temperature perturbation (60 oC for 15 minutes). The organic treatment showed the lowest resistance and resilience in terms of total bacterial and archaeal abundance but was resilient in terms of respiration activity. The high input systems show lower resistance for key functional groups of N and P cycling organisms compared to low input systems. However, all of the differently managed soils have similar resilience and show higher levels of N cycling organisms and lower levels of P cycling organisms after 30 days compared to starting levels.

  12. Characterization of phytoconstituents and evaluation of total phenolic content, anthelmintic, and antimicrobial activities of Solanum violaceum Ortega

    PubMed Central

    Raju, Golam Sarwar; Moghal, Mizanur Rahman; Dewan, Syed Masudur Rahman; Amin, Mohammad Nurul; Billah, Mustahsan

    2013-01-01

    Objective: The present study was conducted to detect possible chemicals (phytoconstituents), prove ethno-medicinal value of the plant, and investigate antimicrobial, anthelmintic, and total phenolic content of crude methanolic extract of the Solanum violaceum plant. Materials and Methods: Phytochemical screening was carried out using different chemical group test methods. In anthelmintic activity test (using Pheretima posthuma model), five concentrations (10, 20, 30, 40, 50, and 80 mg/ml in distilled water) of extracts and albendazole as standard were used which involved the vermifuge and vermicidal activity on the worms. For the evaluation of in vitro antimicrobial activity, disc diffusion method, and to determine the total phenolic content, Folin-Ceocalteu method (gallic acid as standard) were used. Results: The phytoconstituent analysis revealed presence of alkaloids, carbohydrate, glycoside, flavonoid, saponin, gum, diterpenes, phenol, protein, and tannin. The crude extract exhibited significant anthelmintic property comparing with the standard. The methanolic extract revealed broad-spectrum antimicrobial activity at the concentration of 400 µg/disc. The results were compared with that of the standard ciprofloxacin. The extract exhibited moderate amount of total phenolic compound (54.67±1.18 mg/gm of gallic acid equivalent). Conclusion: Since S. violaceum have shown antimicrobial, antioxidant, and anthelmintic activities, more studies such as anti-inflammatory, analgesic, antipyretic, and other pharmacological activities should be carried out to justify its traditional use, as the plant is available and used broadly in the rural areas for folkloric remedies. PMID:25050288

  13. Caenorhabditis elegans as a model to screen plant extracts and compounds as natural anthelmintics for veterinary use

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The most challenging obstacles to testing plant products for their anthelmintic activity are: 1) establishing a suitable nematode in vitro assay from which results can be indicative of potential use against a parasitic nematode of interest, and 2) preparing the extracts in a way that, once lyophiliz...

  14. Monoaminergic signaling as a target for anthelmintic drug discovery: receptor conservation among the free-living and parasitic nematodes.

    PubMed

    Komuniecki, Richard; Law, Wen Jing; Jex, Aaron; Geldhof, Peter; Gray, John; Bamber, Bruce; Gasser, Robin B

    2012-05-01

    This review is designed to summarize the information on monoamine-dependent paralysis as a target for anthelmintic development, examine the conservation of monoamine receptors in the genomes of both free-living and parasitic nematodes, and highlight the utility of the Caenorhabditis elegans model system for dissecting the monoaminergic modulation of locomotory decision-making. PMID:22343182

  15. Monoaminergic signaling as a target for anthelmintic drug discovery: receptor conservation among the free-living and parasitic nematodes.

    PubMed

    Komuniecki, Richard; Law, Wen Jing; Jex, Aaron; Geldhof, Peter; Gray, John; Bamber, Bruce; Gasser, Robin B

    2012-05-01

    This review is designed to summarize the information on monoamine-dependent paralysis as a target for anthelmintic development, examine the conservation of monoamine receptors in the genomes of both free-living and parasitic nematodes, and highlight the utility of the Caenorhabditis elegans model system for dissecting the monoaminergic modulation of locomotory decision-making.

  16. Effectiveness of current anthelmintic treatment programs on reducing fecal egg counts in US cow-calf operation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    During the USDA National Animal Health Monitoring System’s (NAHMS) Beef 2007-08 study producers from 24 states collected fecal samples from weaned calves for evaluation of internal parasite burdens and response to treatment with an anthelmintic product. Participating producers were provided instruc...

  17. The activity of drug-metabolizing enzymes and the biotransformation of selected anthelmintics in the model tapeworm Hymenolepis diminuta.

    PubMed

    Bártíková, Hana; Vokřál, Ivan; Skálová, Lenka; Kubíček, Vladimír; Firbasová, Jana; Briestenský, David; Lamka, Jiří; Szotáková, Barbora

    2012-05-01

    The drug-metabolizing enzymes of some helminths can deactivate anthelmintics and therefore partially protect helminths against these drugs' toxic effect. The aim of our study was to assess the activity of the main drug-metabolizing enzymes and evaluate the metabolism of selected anthelmintics (albendazole, flubendazole, mebendazole) in the rat tapeworm Hymenolepis diminuta, a species often used as a model tapeworm. In vitro and ex vivo experiments were performed. Metabolites of the anthelmintics were detected and identified by HPLC with spectrofluorometric or mass-spectrometric detection. The enzymes of H. diminuta are able to reduce the carbonyl group of flubendazole, mebendazole and several other xenobiotics. Although the activity of a number of oxidation enzymes was determined, no oxidative metabolites of albendazole were detected. Regarding conjugation enzymes, a high activity of glutathione S-transferase was observed. A methyl derivative of reduced flubendazole was the only conjugation metabolite identified in ex vivo incubations of H. diminuta with anthelmintics. The results revealed that H. diminuta metabolized flubendazole and mebendazole, but not albendazole. The biotransformation pathways found in H. diminuta differ from those described in Moniezia expanza and suggest the interspecies differences in drug metabolism not only among classes of helminths, but even among tapeworms.

  18. In vitro and In vivo anthelmintic activity of Nicotiana tabacum L. leaves against gastrointestinal nematodes of sheep.

    PubMed

    Iqbal, Zafar; Lateef, Muhammad; Jabbar, Abdul; Ghayur, Muhammad Nabeel; Gilani, Anwarul Hassan

    2006-01-01

    The in vitro and in vivo anthelmintic activity of Nicotiana tabacum L. leaves was studied to rationalize its traditional use. Live Haemonchus contortus were used to assess the in vitro anthelmintic effect of a crude aqueous extract (CAE) and a methanol extract (CME) of N. tabacum. The in vitro inhibitory effect of both the extracts was evident from the paralysis and/or mortality of worms noted at 6 h post-exposure. For the in vivo studies, CAE and CME were administered in increasing doses (1.0-3.0 g/kg) to sheep naturally infected with mixed species of gastrointestinal nematodes. A maximum reduction of 73.6% in eggs per gram (EPG) of faeces was recorded on day 5 post-treatment with CME (3.0 g/kg) while the same dose of CAE showed a 49.4% reduction. Levamisole (7.5 mg/kg), a standard anthelmintic agent, showed a 99.6% reduction in EPG. These data show that the aqueous and methanol extracts of Nicotiana tabacum exhibit dose-dependent anthelmintic activity both in vitro and in vivo, thus justifying its use in the traditional medicine system of Pakistan.

  19. Long-Term Monitoring of Infiltration at a Managed Aquifer Recharge Site Using Electrical Resistivity Probes

    NASA Astrophysics Data System (ADS)

    Cockett, R.; Pidlisecky, A.; Knight, R. J.

    2010-12-01

    As part of an effort to understand the hydrogeologic parameters that influence the performance of a managed aquifer recharge project, four Electrical Resistivity Imaging (ERI) probes were installed beneath an artificial recharge pond to monitor changes in bulk electrical resistivity as a function of time. The probes were three meters long and installed to a depth of two meters below the pond bottom, with a one-meter section of the probe extending into the water. Resistance measurements were obtained through a group of 21 electrodes below the pond bottom, and a group of 4 electrodes in the water column. Spacing between electrodes in each group was 10 cm, while spacing between the subsurface and water column electrodes was 75 cm. While one probe failed immediately, the remaining three have been in operation for two years beneath the pond. A total of 96 measurements were made on each probe, every 18 minutes for two operational seasons (January - August). These seemingly simple measurements have provided tremendous insight into the subsurface flow at the base of the pond, and the challenges associated with using these data in a quantitative manner. Inversion of these data using an axially symmetric cylindrical inversion approach with both a L-1 and L-2 norm demonstrates that, despite the use of direct-push methods for probe emplacement, there is a significant disturbed zone adjacent to the probes. This disturbed zone adjacent to the probe leads to a violation of a one-dimensional assumption, and therefore complicates interpretation of the data. We note that, had we only used a traditional sampling array along the probe (e.g. a fixed a-spacing Wenner array), we would not see this disturbed zone and our calculated resistivity estimates would be influenced by the disturbed zone. In addition to being able to detect, and subsequently account for, the disturbed zone, the high temporal sampling rate of these measurements gives us the ability to generate robust error estimates

  20. The novel ABC transporter ABCH1 is a potential target for RNAi-based insect pest control and resistance management

    PubMed Central

    Guo, Zhaojiang; Kang, Shi; Zhu, Xun; Xia, Jixing; Wu, Qingjun; Wang, Shaoli; Xie, Wen; Zhang, Youjun

    2015-01-01

    Insect pests cause serious crop damage and develop high-level resistance to chemical insecticides and Bacillus thuringiensis (Bt) insecticidal Cry toxins. A new promising approach for controlling them and overcoming this resistance is RNA interference (RNAi). The RNAi-based insect control strategy depends on the selection of suitable target genes. In this study, we cloned and characterized a novel ABC transporter gene PxABCH1 in diamondback moth, Plutella xylostella (L.). Phylogenetic analysis showed that PxABCH1 is closely related to ABCA and ABCG subfamily members. Spatial-temporal expression detection revealed that PxABCH1 was expressed in all tissues and developmental stages, and highest expressed in head and male adult. Midgut sequence variation and expression analyses of PxABCH1 in all the susceptible and Bt-resistant P. xylostella strains and the functional analysis by sublethal RNAi demonstrated that Cry1Ac resistance was independent of this gene. Silencing of PxABCH1 by a relatively high dose of dsRNA dramatically reduced its expression and resulted in larval and pupal lethal phenotypes in both susceptible and Cry1Ac-resistant P. xylostella strains. To our knowledge, this study provides the first insight into ABCH1 in lepidopterans and reveals it as an excellent target for RNAi-based insect pest control and resistance management. PMID:26333918

  1. The novel ABC transporter ABCH1 is a potential target for RNAi-based insect pest control and resistance management.

    PubMed

    Guo, Zhaojiang; Kang, Shi; Zhu, Xun; Xia, Jixing; Wu, Qingjun; Wang, Shaoli; Xie, Wen; Zhang, Youjun

    2015-01-01

    Insect pests cause serious crop damage and develop high-level resistance to chemical insecticides and Bacillus thuringiensis (Bt) insecticidal Cry toxins. A new promising approach for controlling them and overcoming this resistance is RNA interference (RNAi). The RNAi-based insect control strategy depends on the selection of suitable target genes. In this study, we cloned and characterized a novel ABC transporter gene PxABCH1 in diamondback moth, Plutella xylostella (L.). Phylogenetic analysis showed that PxABCH1 is closely related to ABCA and ABCG subfamily members. Spatial-temporal expression detection revealed that PxABCH1 was expressed in all tissues and developmental stages, and highest expressed in head and male adult. Midgut sequence variation and expression analyses of PxABCH1 in all the susceptible and Bt-resistant P. xylostella strains and the functional analysis by sublethal RNAi demonstrated that Cry1Ac resistance was independent of this gene. Silencing of PxABCH1 by a relatively high dose of dsRNA dramatically reduced its expression and resulted in larval and pupal lethal phenotypes in both susceptible and Cry1Ac-resistant P. xylostella strains. To our knowledge, this study provides the first insight into ABCH1 in lepidopterans and reveals it as an excellent target for RNAi-based insect pest control and resistance management. PMID:26333918

  2. A risk analysis framework for the long-term management of antibiotic resistance in food-producing animals.

    PubMed

    Salisbury, Janet G; Nicholls, Terence J; Lammerding, Anna M; Turnidge, John; Nunn, Michael J

    2002-09-01

    In recent years, there has been increasing concern that the use of antibiotics in food-producing animals, particularly their long-term use for growth promotion, contributes to the emergence of antibiotic-resistant bacteria in animals. These resistant bacteria may spread from animals to humans via the food chain. They may also transfer their antibiotic-resistance genes into human pathogenic bacteria, leading to failure of antibiotic treatment for some, possibly life-threatening, human conditions. To assist regulatory decision making, the actual risk to human health from antibiotic use in animals needs to be determined (risk assessment) and the requirements for risk minimisation (risk management and risk communication) determined. We propose a novel method of risk analysis involving risk assessment for three interrelated hazards: the antibiotic (chemical agent), the antibiotic-resistant bacterium (microbiological agent) and the antibiotic-resistance gene (genetic agent). Risk minimisation may then include control of antibiotic use and/or the reduction of the spread of bacterial infection and/or prevention of transfer of resistance determinants between bacterial populations.

  3. Environmental influences on mosquito foraging and integrated vector management can delay the evolution of behavioral resistance.

    PubMed

    Stone, Chris; Chitnis, Nakul; Gross, Kevin

    2016-03-01

    Along with the scaled-up distribution of long-lasting insecticidal nets for malaria control has become concern about insecticide resistance. A related concern regards the evolution of host-seeking periodicity from the nocturnal to the crepuscular periods of the day. Why we observe such shifts in some areas but not others and which methods could prove useful in managing such behavioral resistance remain open questions. We developed a foraging model to explore whether environmental conditions affect the evolution of behavioral resistance. We looked at the role of the abundance of blood hosts and nectar sources and investigated the potential of attractive toxic sugar baits for integrated control. Higher encounter rates with hosts and nectar sources allowed behaviorally resistant populations to persist at higher levels of bed net coverage. Whereas higher encounter rates with nectar increased the threshold where resistance emerged, higher encounter rates of hosts lowered this threshold. Adding sugar baits lowered the coverage level of bed nets required to eliminate the vector population. In certain environments, using lower bed net coverage levels together with toxic sugar baits may delay or prevent the evolution of behavioral resistance. Designing sustainable control strategies will depend on an understanding of vector behavior expressed in local environmental conditions. PMID:26989441

  4. Human Management of a Wild Plant Modulates the Evolutionary Dynamics of a Gene Determining Recessive Resistance to Virus Infection

    PubMed Central

    Poulicard, Nils; Pacios, Luis Fernández; Gallois, Jean-Luc; Piñero, Daniel; García-Arenal, Fernando

    2016-01-01

    This work analyses the genetic variation and evolutionary patterns of recessive resistance loci involved in matching-allele (MA) host-pathogen interactions, focusing on the pvr2 resistance gene to potyviruses of the wild pepper Capsicum annuum glabriusculum (chiltepin). Chiltepin grows in a variety of wild habitats in Mexico, and its cultivation in home gardens started about 25 years ago. Potyvirus infection of Capsicum plants requires the physical interaction of the viral VPg with the pvr2 product, the translation initiation factor eIF4E1. Mutations impairing this interaction result in resistance, according to the MA model. The diversity of pvr2/eIF4E1 in wild and cultivated chiltepin populations from six biogeographical provinces in Mexico was analysed in 109 full-length coding sequences from 97 plants. Eleven alleles were found, and their interaction with potyvirus VPg in yeast-two-hybrid assays, plus infection assays of plants, identified six resistance alleles. Mapping resistance mutations on a pvr2/eIF4E1 model structure showed that most were around the cap-binding pocket and strongly altered its surface electrostatic potential, suggesting resistance-associated costs due to functional constraints. The pvr2/eIF4E1 phylogeny established that susceptibility was ancestral and resistance was derived. The spatial structure of pvr2/eIF4E1 diversity differed from that of neutral markers, but no evidence of selection for resistance was found in wild populations. In contrast, the resistance alleles were much more frequent, and positive selection stronger, in cultivated chiltepin populations, where diversification of pvr2/eIF4E1 was higher. This analysis of the genetic variation of a recessive resistance gene involved in MA host-pathogen interactions in populations of a wild plant show that evolutionary patterns differ according to the plant habitat, wild or cultivated. It also demonstrates that human management of the plant population has profound effects on the

  5. Human Management of a Wild Plant Modulates the Evolutionary Dynamics of a Gene Determining Recessive Resistance to Virus Infection.

    PubMed

    Poulicard, Nils; Pacios, Luis Fernández; Gallois, Jean-Luc; Piñero, Daniel; García-Arenal, Fernando

    2016-08-01

    This work analyses the genetic variation and evolutionary patterns of recessive resistance loci involved in matching-allele (MA) host-pathogen interactions, focusing on the pvr2 resistance gene to potyviruses of the wild pepper Capsicum annuum glabriusculum (chiltepin). Chiltepin grows in a variety of wild habitats in Mexico, and its cultivation in home gardens started about 25 years ago. Potyvirus infection of Capsicum plants requires the physical interaction of the viral VPg with the pvr2 product, the translation initiation factor eIF4E1. Mutations impairing this interaction result in resistance, according to the MA model. The diversity of pvr2/eIF4E1 in wild and cultivated chiltepin populations from six biogeographical provinces in Mexico was analysed in 109 full-length coding sequences from 97 plants. Eleven alleles were found, and their interaction with potyvirus VPg in yeast-two-hybrid assays, plus infection assays of plants, identified six resistance alleles. Mapping resistance mutations on a pvr2/eIF4E1 model structure showed that most were around the cap-binding pocket and strongly altered its surface electrostatic potential, suggesting resistance-associated costs due to functional constraints. The pvr2/eIF4E1 phylogeny established that susceptibility was ancestral and resistance was derived. The spatial structure of pvr2/eIF4E1 diversity differed from that of neutral markers, but no evidence of selection for resistance was found in wild populations. In contrast, the resistance alleles were much more frequent, and positive selection stronger, in cultivated chiltepin populations, where diversification of pvr2/eIF4E1 was higher. This analysis of the genetic variation of a recessive resistance gene involved in MA host-pathogen interactions in populations of a wild plant show that evolutionary patterns differ according to the plant habitat, wild or cultivated. It also demonstrates that human management of the plant population has profound effects on the

  6. Emerging Rapid Resistance Testing Methods for Clinical Microbiology Laboratories and Their Potential Impact on Patient Management

    PubMed Central

    Frickmann, Hagen; Zautner, Andreas E.

    2014-01-01

    Atypical and multidrug resistance, especially ESBL and carbapenemase expressing Enterobacteriaceae, is globally spreading. Therefore, it becomes increasingly difficult to achieve therapeutic success by calculated antibiotic therapy. Consequently, rapid antibiotic resistance testing is essential. Various molecular and mass spectrometry-based approaches have been introduced in diagnostic microbiology to speed up the providing of reliable resistance data. PCR- and sequencing-based approaches are the most expensive but the most frequently applied modes of testing, suitable for the detection of resistance genes even from primary material. Next generation sequencing, based either on assessment of allelic single nucleotide polymorphisms or on the detection of nonubiquitous resistance mechanisms might allow for sequence-based bacterial resistance testing comparable to viral resistance testing on the long term. Fluorescence in situ hybridization (FISH), based on specific binding of fluorescence-labeled oligonucleotide probes, provides a less expensive molecular bridging technique. It is particularly useful for detection of resistance mechanisms based on mutations in ribosomal RNA. Approaches based on MALDI-TOF-MS, alone or in combination with molecular techniques, like PCR/electrospray ionization MS or minisequencing provide the fastest resistance results from pure colonies or even primary samples with a growing number of protocols. This review details the various approaches of rapid resistance testing, their pros and cons, and their potential use for the diagnostic laboratory. PMID:25343142

  7. Emerging rapid resistance testing methods for clinical microbiology laboratories and their potential impact on patient management.

    PubMed

    Frickmann, Hagen; Masanta, Wycliffe Omurwa; Zautner, Andreas E

    2014-01-01

    Atypical and multidrug resistance, especially ESBL and carbapenemase expressing Enterobacteriaceae, is globally spreading. Therefore, it becomes increasingly difficult to achieve therapeutic success by calculated antibiotic therapy. Consequently, rapid antibiotic resistance testing is essential. Various molecular and mass spectrometry-based approaches have been introduced in diagnostic microbiology to speed up the providing of reliable resistance data. PCR- and sequencing-based approaches are the most expensive but the most frequently applied modes of testing, suitable for the detection of resistance genes even from primary material. Next generation sequencing, based either on assessment of allelic single nucleotide polymorphisms or on the detection of nonubiquitous resistance mechanisms might allow for sequence-based bacterial resistance testing comparable to viral resistance testing on the long term. Fluorescence in situ hybridization (FISH), based on specific binding of fluorescence-labeled oligonucleotide probes, provides a less expensive molecular bridging technique. It is particularly useful for detection of resistance mechanisms based on mutations in ribosomal RNA. Approaches based on MALDI-TOF-MS, alone or in combination with molecular techniques, like PCR/electrospray ionization MS or minisequencing provide the fastest resistance results from pure colonies or even primary samples with a growing number of protocols. This review details the various approaches of rapid resistance testing, their pros and cons, and their potential use for the diagnostic laboratory.

  8. Grassland management affects belowground carbon allocation in mountain grasslands and its resistance and resilience to drought

    NASA Astrophysics Data System (ADS)

    Karlowsky, Stefan; Augusti, Angela; Ingrisch, Johannes; Hasibeder, Roland; Bahn, Michael; Gleixner, Gerd

    2015-04-01

    Future climate scenarios do not only forecast increased extreme events during summer, but also more frequent drought events in the early season. In mountain grasslands, different land uses may contribute to the response of the ecosystem to climate changes, like drought in May and June. In this study, we examined the drought response of two differently managed grasslands, 1) a more intensive used meadow and 2) a less intensive used abandoned area. Our aim was to highlight differences in both resistance and resilience of ecosystem functioning, based on carbon (C) belowground allocation as a key function in the plant-rhizosphere continuum. Therefore, we used an isotopic approach and in particular, we used 13C pulse labelling to track the fate of newly assimilated C from leaves, to roots and to soil, up to different microbial communities. We performed two 13C pulse labellings, the first during the acute phase of drought, when the water status of soil was drastically decreased compared to the control; and the second during the recovery phase, when the soil water status was restored to control level. We followed the kinetics of 13C incorporation in above- and below-ground bulk material as well as non-structural sugars, in general soil microbial biomass, in different soil microbial communities and in CO2 respired from roots, up to 5 days from each labelling. Preliminary results from the 13C analyses of bulk phytomass material and soil microbial biomass indicate, as expected, different kinetics of aboveground 13C incorporation and its belowground allocation. During the acute phase of drought, 13C incorporation shows a decrease compared to the control for both land uses, with generally higher reductions in meadow treatments. Root 13C tracer dynamics follow the leaf 13C enrichment with a delay. High label amounts are found in leaves directly after labelling, whereas in roots high 13C incorporation is found first after 24 hours, accompanied by a fast decrease of 13C label in

  9. Implementation of the global plan for insecticide resistance management in malaria vectors: progress, challenges and the way forward.

    PubMed

    Mnzava, Abraham P; Knox, Tessa B; Temu, Emmanuel A; Trett, Anna; Fornadel, Christen; Hemingway, Janet; Renshaw, Melanie

    2015-01-01

    In recent years, there has been an increase in resistance of malaria vectors to insecticides, particularly to pyrethroids which are widely used in insecticide-treated nets. The Global Plan for Insecticide Resistance Management in malaria vectors (GPIRM), released in May 2012, is a collective strategy for the malaria community to tackle this challenge. This review outlines progress made to date and the challenges experienced in the implementation of GPIRM, and outlines focus areas requiring urgent attention. Whilst there has been some advancement, uptake of GPIRM at the national level has generally been poor for various reasons, including limited availability of vector control tools with new mechanisms of action as well as critical financial, human and infrastructural resource deficiencies. There is an urgent need for a global response plan to address these deficits and ensure the correct and efficient use of available tools in order to maintain the effectiveness of current vector control efforts whilst novel vector control tools are under development. Emphasis must be placed on enhancing national capacities (such as human and infrastructural resources) to enable efficient monitoring and management of insecticide resistance, and to support availability and accessibility of appropriate new vector control products. Lack of action by the global community to address the threat of insecticide resistance is unacceptable and deprives affected communities of their basic right of universal access to effective malaria prevention. Aligning efforts and assigning the needed resources will ensure the optimal implementation of GPIRM with the ultimate goal of maintaining effective malaria vector control. PMID:25899397

  10. EPA RESISTANCE MONITORING RESEARCH (NCR)

    EPA Science Inventory

    The 2006 resistance management research program was organized around three components: development of resistance monitoring program for Bt corn using remote sensing, standardization of resistance assays, and testing of resistance management models. Each area of research has shown...

  11. Hepatic biotransformation pathways and ruminal metabolic stability of the novel anthelmintic monepantel in sheep and cattle.

    PubMed

    Ballent, M; Virkel, G; Maté, L; Viviani, P; Lanusse, C; Lifschitz, A

    2016-10-01

    Monepantel (MNP) is a new amino-acetonitrile derivative anthelmintic drug used for the treatment of gastrointestinal (GI) nematodes in sheep. The present work investigated the main enzymatic pathways involved in the hepatic biotransformation of MNP in sheep and cattle. The metabolic stability in ruminal fluid of both the parent drug and its main metabolite (monepantel sulphone, MNPSO2 ) was characterized as well. Additionally, the relative distribution of both anthelmintic molecules between the fluid and particulate phases of the ruminal content was studied. Liver microsomal fractions from six (6) rams and five (5) steers were incubated with a 40 μm of MNP. Heat pretreatment (50 °C for 2 min) of liver microsomes was performed for inactivation of the flavin-monooxygenase (FMO) system. Additionally, MNP was incubated in the presence of 4, 40, and 80 μm of methimazole (MTZ), a FMO inhibitor, or equimolar concentrations of piperonyl butoxide (PBx), a well-known general cytochrome P450 (CYP) inhibitor. In both ruminant species, MNPSO2 was the main metabolite detected after MNP incubation with liver microsomes. The conversion rate of MNP into MNPSO2 was fivefold higher (P < 0.05) in sheep (0.15 ± 0.08 nmol/min·mg) compared to cattle. In sheep, the relative involvement of both FMO and CYP systems (FMO/CYP) was 36/64. Virtually, only the CYP system appeared to be involved in the production of MNPSO2 in cattle liver. Methimazole significantly reduced (41 to 79%) the rate of MNPSO2 production in sheep liver microsomes whereas it did not inhibit MNP oxidation in cattle liver microsomes. On the other hand, PBx inhibited the production of MNPSO2 in liver microsomes of both sheep (58 to 98%, in a dose-dependent manner) and cattle (almost 100%, independently of the PBx concentration added). The incubation of MNP and MNPSO2 with ruminal contents of both species showed a high chemical stability without evident metabolism and/or degradation as well as an extensive

  12. Liquid chromatography-tandem mass spectrometry method for the determination of anthelmintics in alfalfa plants.

    PubMed

    Islam, M Dabalus; Haberhauer, G; Gerzabek, M; Cannavan, A

    2012-01-01

    A simple and inexpensive liquid chromatography-tandem mass spectrometric method for the determination of anthelmintics in alfalfa plants (Medicago sativa L.) was developed and validated. Anthelmintics in plant leaves and stems (green chops) were extracted with methanol/acetonitrile (7:3, v/v) followed by a concentration and clean-up step using solid-phase extraction (Strata-X, 500 mg, 6 ml cartridge). After drying with nitrogen gas, the adsorbed analytes were eluted with methanol/acetonitrile (50:50, v/v) mixture followed by 100% acetonitrile. Chromatographic separation was achieved on an Atlantis T-3 (2.1 × 100 mm × 3 µm) analytical column with a Phenomenex guard cartridge (C8, 4 × 3 mm) attached to a Waters triple quadrupole mass spectrometer operated in positive electrospray ionisation mode with selected reaction monitoring. Samples were analysed using gradient elution at a flow rate of 0.35 ml min⁻¹. The mobile phase consisted of a 10 mM ammonium formate solution in (A) water/acetonitrile (90:10, v/v) and (B) methanol/acetonitrile (50:50, v/v). The method was validated for levamisole, fenbendazole, fenbendazole sulphoxide and fenbendazole sulphone at 10, 20 and 40 µg kg⁻¹ and for eprinomectin at 20, 40 and 80 µg kg⁻¹. Limits of quantification (LOQ) were 10 µg kg⁻¹ for all analytes except eprinomectin, which had an LOQ of 20 µg kg⁻¹. The overall mean recovery in green plants was between 74.2% and 81.4% with repeatabilities ranging from 2.2% to 19.1% and reproducibilities in the range 3.8-8.7%. The validated method was applied to plant samples in a study on the behaviour of anthelmintic drugs in a soil, plant and water system.

  13. Hepatic biotransformation pathways and ruminal metabolic stability of the novel anthelmintic monepantel in sheep and cattle.

    PubMed

    Ballent, M; Virkel, G; Maté, L; Viviani, P; Lanusse, C; Lifschitz, A

    2016-10-01

    Monepantel (MNP) is a new amino-acetonitrile derivative anthelmintic drug used for the treatment of gastrointestinal (GI) nematodes in sheep. The present work investigated the main enzymatic pathways involved in the hepatic biotransformation of MNP in sheep and cattle. The metabolic stability in ruminal fluid of both the parent drug and its main metabolite (monepantel sulphone, MNPSO2 ) was characterized as well. Additionally, the relative distribution of both anthelmintic molecules between the fluid and particulate phases of the ruminal content was studied. Liver microsomal fractions from six (6) rams and five (5) steers were incubated with a 40 μm of MNP. Heat pretreatment (50 °C for 2 min) of liver microsomes was performed for inactivation of the flavin-monooxygenase (FMO) system. Additionally, MNP was incubated in the presence of 4, 40, and 80 μm of methimazole (MTZ), a FMO inhibitor, or equimolar concentrations of piperonyl butoxide (PBx), a well-known general cytochrome P450 (CYP) inhibitor. In both ruminant species, MNPSO2 was the main metabolite detected after MNP incubation with liver microsomes. The conversion rate of MNP into MNPSO2 was fivefold higher (P < 0.05) in sheep (0.15 ± 0.08 nmol/min·mg) compared to cattle. In sheep, the relative involvement of both FMO and CYP systems (FMO/CYP) was 36/64. Virtually, only the CYP system appeared to be involved in the production of MNPSO2 in cattle liver. Methimazole significantly reduced (41 to 79%) the rate of MNPSO2 production in sheep liver microsomes whereas it did not inhibit MNP oxidation in cattle liver microsomes. On the other hand, PBx inhibited the production of MNPSO2 in liver microsomes of both sheep (58 to 98%, in a dose-dependent manner) and cattle (almost 100%, independently of the PBx concentration added). The incubation of MNP and MNPSO2 with ruminal contents of both species showed a high chemical stability without evident metabolism and/or degradation as well as an extensive

  14. In vitro analysis of the anthelmintic activity of forage chicory (Cichorium intybus L.) sesquiterpene lactones against a predominatly Haemonchus contortus egg population

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The anthelmintic activity of chicory (Cichorium intybus L.) herbage has been attributed to sesquiterpene lactones. Chicory leaves contain significant amounts of lactucin (LAC), 8-deoxylactucin (DOL), and lactucopicrin (LPIC), but the proportions of these three sesquiterpene lactones vary among fora...

  15. Practical management of patients with chronic myeloid leukemia who develop tyrosine kinase inhibitor-resistant BCR-ABL1 mutations

    PubMed Central

    Ai, Jing

    2014-01-01

    Five BCR-ABL1 tyrosine kinase inhibitors (TKIs), imatinib, nilotinib, dasatinib, bosutinib, and ponatinib, are currently approved for the treatment of chronic myeloid leukemia (CML). Standard treatment of CML with TKIs is highly effective in reducing disease burden, delaying disease progression, and prolonging overall survival of patients; however, resistance to TKI treatment has become an increasingly important cause of treatment failure. The emergence of mutations in the BCR-ABL1 kinase domain is a common mechanism of TKI resistance, and laboratory testing to detect these mutations is currently available for clinical use. Patients who do not respond or have lost their response to TKI therapy should be considered for mutational testing. Despite clinical practice guidelines that recommend testing for BCR-ABL1 mutations in patients with clinical signs of TKI resistance, many oncologists and hematologists managing patients with CML do not perform such testing. This review addresses outstanding questions related to when testing should be conducted, what type of testing should be done, and how testing results should be applied to subsequent therapeutic decisions. It describes how BCR-ABL1 kinase domain mutations confer resistance, outlines the prevalence of mutations in patients with resistance to TKIs, summarizes the common and investigational methods used in mutational testing, and presents an algorithm reflecting a clinical perspective on how and when to conduct mutational testing, and what to do with test results. PMID:25360237

  16. Epidemiological and evolutionary management of plant resistance: optimizing the deployment of cultivar mixtures in time and space in agricultural landscapes

    PubMed Central

    Fabre, Frédéric; Rousseau, Elsa; Mailleret, Ludovic; Moury, Benoît

    2015-01-01

    The management of genes conferring resistance to plant–pathogens should make it possible to control epidemics (epidemiological perspective) and preserve resistance durability (evolutionary perspective). Resistant and susceptible cultivars must be strategically associated according to the principles of cultivar mixture (within a season) and rotation (between seasons). We explored these questions by modeling the evolutionary and epidemiological processes shaping the dynamics of a pathogen population in a landscape composed of a seasonal cultivated compartment and a reservoir compartment hosting pathogen year-round. Optimal deployment strategies depended mostly on the molecular basis of plant–pathogen interactions and on the agro-ecological context before resistance deployment, particularly epidemic intensity and landscape connectivity. Mixtures were much more efficient in landscapes in which between-field infections and infections originating from the reservoir were more prevalent than within-field infections. Resistance genes requiring two mutations of the pathogen avirulence gene to be broken down, rather than one, were particularly useful when infections from the reservoir predominated. Combining mixture and rotation principles were better than the use of the same mixture each season as (i) they controlled epidemics more effectively in situations in which within-field infections or infections from the reservoir were frequent and (ii) they fulfilled the epidemiological and evolutionary perspectives. PMID:26640518

  17. Detection and management of drug-resistant tuberculosis in HIV-infected patients from lower income countries

    PubMed Central

    Ballif, Marie; Nhandu, Venerandah; Wood, Robin; Dusingize, Jean Claude; Carter, E. Jane; Cortes, Claudia P.; McGowan, Catherine C.; Diero, Lameck; Graber, Claire; Renner, Lorna; Hawerlander, Denise; Kiertiburanakul, Sasisopin; Du, Quy Tuan; Sterling, Timothy R.; Egger, Matthias; Fenner, Lukas

    2015-01-01

    Setting Drug resistance threatens tuberculosis (TB) control, particularly among HIV-infected persons. Objective We surveyed antiretroviral therapy (ART) programs from lower-income countries on prevention and management of drug-resistant TB. Design We used online questionnaires to collect program-level data in 47 ART programs in Southern Africa (14), East Africa (8), West Africa (7), Central Africa (5), Latin America (7) and Asia-Pacific (6 programs) in 2012. Patient-level data were collected on 1,002 adult TB patients seen at 40 of the participating ART programs. Results Phenotypic drug susceptibility testing was available at 36 (77%) ART programs, but only used for 22% of all TB patients. Molecular drug resistance testing was available at 33 (70%) programs and used for 23% of all TB patients. Twenty ART programs (43%) provided directly observed therapy (DOT) during the whole treatment, 16 (34%) during intensive phase only and 11 (23%) did not follow DOT. Fourteen (30%) ART programs reported no access to second-line TB regimens; 18 (38%) reported TB drug shortages. Conclusions Capacity to diagnose and treat drug-resistant TB was limited across ART programs in lower income countries. DOT was not always implemented and drug supply was regularly interrupted, which may contribute to the global emergence of drug resistance. PMID:25299866

  18. Infections Caused by Resistant Gram-Negative Bacteria: Epidemiology and Management.

    PubMed

    Kaye, Keith S; Pogue, Jason M

    2015-10-01

    Infections caused by resistant gram-negative bacteria are becoming increasingly prevalent and now constitute a serious threat to public health worldwide because they are difficult to treat and are associated with high morbidity and mortality rates. In the United States, there has been a steady increase since 2000 in rates of extended-spectrum β-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and multidrug-resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii, particularly among hospitalized patients with intraabdominal infections, urinary tract infections, ventilator-associated pneumonia, and bacteremia. Colonization with resistant gram-negative bacteria is common among residents in long-term care facilities (particularly those residents with an indwelling device), and these facilities are considered important originating sources of such strains for hospitals. Antibiotic resistance is associated with a substantial clinical and economic burden, including increased mortality, greater hospital and antibiotic costs, and longer stays in hospitals and intensive care units. Control of resistant gram-negative infections requires a comprehensive approach, including strategies for risk factor identification, detection and identification of resistant organisms, and implementation of infection-control and prevention strategies. In treating resistant gram-negative infections, a review of surveillance data and hospital-specific antibiograms, including resistance patterns within local institutions, and consideration of patient characteristics are helpful in guiding the choice of empiric therapy. Although only a few agents are available with activity against resistant gram-negative organisms, two recently released β-lactam/β-lactamase inhibitor combinations - ceftolozane/tazobactam and ceftazidime/avibactam - have promising activity against these organisms. In this article, we review the epidemiology, risk factors, and

  19. Selection and characterisation of monepantel resistance in Teladorsagia circumcincta isolates

    PubMed Central

    Bartley, D.J.; Devin, L.; Nath, M.; Morrison, A.A.

    2015-01-01

    Monepantel (MPTL) is one of two new anthelmintic compounds introduced onto the sheep market to control gastro-intestinal nematodes. Resistance to this compound is rare but has been reported. In order to preserve the efficacy of this and other anthelmintics, it is essential to understand both (a) the mechanisms involved in the selection of resistance and (b) how the parasites evolve to deal with these compounds. To address these questions three MPTL-resistant Teladorsagia circumcincta isolates (MTci2-11, MTci5-13 and MTci7-12) have been artificially selected in vivo from phenotypically characterised parent isolates (MTci2, MTci5, MTci7 respectively). The selection process involved collecting and culturing eggs from surviving worms from sheep administered sub-optimal dosages of MPTL (Zolvix®) to provide infective larvae to infect further sheep until resistant isolates were generated (between 9 and 13 rounds of selection). A controlled efficacy test was conducted using the original parental isolates and the newly generated MPTL resistant isolates (n = 5 per group). Selected isolates were assessed both under anthelmintic stress (Zolvix®, 2.5 mg/kg bodyweight; MTci-MPTL) and at rest (untreated, MTci-CON). A number of life-history traits were assessed, namely, worm establishment rates, time to patency, faecal egg output, body length of adults and eggs in utero. The estimated resistance status of the selected isolates was confirmed with 48%, 28% and 9% reductions in worm burden at 7-days post Zolvix® administration for MTci2-11-MPTL, MTci5-13-MPTL and MTci7-12-MPTL, respectively, compared with untreated controls. One of the selected isolates MTci7-12-CON showed significantly greater total worm burden (p = 0.025), greater establishment rate (p = 0.033), decreased time to patency (p = 0.048), higher cumulative egg outputs (p = 0.002) compared with its parental derivative MTci7. The trial results suggest that anthelmintic selection in T

  20. Selection and characterisation of monepantel resistance in Teladorsagia circumcincta isolates.

    PubMed

    Bartley, D J; Devin, L; Nath, M; Morrison, A A

    2015-08-01

    Monepantel (MPTL) is one of two new anthelmintic compounds introduced onto the sheep market to control gastro-intestinal nematodes. Resistance to this compound is rare but has been reported. In order to preserve the efficacy of this and other anthelmintics, it is essential to understand both (a) the mechanisms involved in the selection of resistance and (b) how the parasites evolve to deal with these compounds. To address these questions three MPTL-resistant Teladorsagia circumcincta isolates (MTci2-11, MTci5-13 and MTci7-12) have been artificially selected in vivo from phenotypically characterised parent isolates (MTci2, MTci5, MTci7 respectively). The selection process involved collecting and culturing eggs from surviving worms from sheep administered sub-optimal dosages of MPTL (Zolvix®) to provide infective larvae to infect further sheep until resistant isolates were generated (between 9 and 13 rounds of selection). A controlled efficacy test was conducted using the original parental isolates and the newly generated MPTL resistant isolates (n = 5 per group). Selected isolates were assessed both under anthelmintic stress (Zolvix®, 2.5 mg/kg bodyweight; MTci-MPTL) and at rest (untreated, MTci-CON). A number of life-history traits were assessed, namely, worm establishment rates, time to patency, faecal egg output, body length of adults and eggs in utero. The estimated resistance status of the selected isolates was confirmed with 48%, 28% and 9% reductions in worm burden at 7-days post Zolvix® administration for MTci2-11-MPTL, MTci5-13-MPTL and MTci7-12-MPTL, respectively, compared with untreated controls. One of the selected isolates MTci7-12-CON showed significantly greater total worm burden (p = 0.025), greater establishment rate (p = 0.033), decreased time to patency (p = 0.048), higher cumulative egg outputs (p = 0.002) compared with its parental derivative MTci7. The trial results suggest that anthelmintic selection in T

  1. Comparison of ivermectin, oxfendazole and levamisole for use as anthelmintics during the periparturient period in sheep.

    PubMed

    McKellar, Q; Marriner, S; Bogan, J

    1988-06-01

    Ewes synchronised with progestin impregnated sponges to reduce the spread of lambing were treated during the periparturient period with anthelmintic. The suppression of nematode egg output in faeces was measured in ewes given ivermectin either by subcutaneous injection or orally, or oxfendazole or levamisole orally. Ivermectin and oxfendazole reduced the output of eggs in the faeces of the ewes significantly (P less than 0.05) and the period of suppressed egg output was extended when ivermectin was given by subcutaneous injection. Plasma pepsinogen activity was estimated as a measure of abomasal damage. Pepsinogen values were significantly (P less than 0.001) lower in those animals treated with ivermectin by subcutaneous injection than in control animals. Levamisole showed a poorer response in terms of the output of eggs in faeces than either ivermectin or oxfendazole.

  2. Anthelmintic treatment alters the parasite community in a wild mouse host

    PubMed Central

    Pedersen, Amy B.; Antonovics, Janis

    2013-01-01

    Individuals are often co-infected with several parasite species, yet the consequences of drug treatment on the dynamics of parasite communities in wild populations have rarely been measured. Here, we experimentally reduced nematode infection in a wild mouse population and measured the effects on other non-target parasites. A single oral dose of the anthelmintic, ivermectin, significantly reduced nematode infection, but resulted in a reciprocal increase in other gastrointestinal parasites, specifically coccidial protozoans and cestodes. These results highlight the possibility that drug therapy may have unintended consequences for non-target parasites and that host–parasite dynamics cannot always be fully understood in the framework of single host–parasite interactions. PMID:23658004

  3. Avermectins, New Family of Potent Anthelmintic Agents: Producing Organism and Fermentation

    PubMed Central

    Burg, Richard W.; Miller, Brinton M.; Baker, Edward E.; Birnbaum, Jerome; Currie, Sara A.; Hartman, Robert; Kong, Yu-Lin; Monaghan, Richard L.; Olson, George; Putter, Irving; Tunac, Josefino B.; Wallick, Hyman; Stapley, Edward O.; Oiwa, Ruiko; Ōmura, Satoshi

    1979-01-01

    The avermectins are a complex of chemically related agents which exhibit extraordinarily potent anthelmintic activity. They are produced by a novel species of actinomycete, NRRL 8165, which we have named Streptomyces avermitilis. The morphological and cultural characteristics which differentiate the producing organism from other species are described. The avermectins have been identified as a series of macrocyclic lactone derivatives which, in contrast to the macrolide or polyene antibiotics, lack significant antibacterial or antifungal activity. The avermectin complex is fully active against the gastrointestinal nematode Nematospiroides dubius when fed to infected mice for 6 days at 0.0002% of the diet. Fermentation development, including medium modification and strain selection, resulted in increasing the broth yields from 9 to 500 μg/ml. Images PMID:464561

  4. The anthelmintic effects of the leaf extract of Ocimum gratissimum (L.).

    PubMed

    Njoku, C J; Asuzu, I U

    1998-12-01

    The leaf extract (F005) of Ocimum gratissimum was isolated by a bioassay-guided chromatographic separation technique using the brine shrimp lethality test assay. The effects of various concentrations (0.5, 1.0, 2.0, 4.0, and 8.0 mg/ml) of F005 were tested in vitro on infective larvae (L(3)) of Haemonchus contortus and Heligmosomoides polygyrus. Cockerels experimentally infected with Ascaridia galli infective eggs were also treated with various doses (500, 1000, and 1500 mg/kg) of F005 in vivo. F005 produced 15% and 16.6% paralysis of H. contortus and H. polygyrus larvae, respectively, at 8 mg/ml. It induced significant anthelmintic effect in chicks infected with A. galli in a dose-dependent manner with 1,500 mg/kg producing the highest effect (55.8%). PMID:23196034

  5. Anthelmintic treatment alters the parasite community in a wild mouse host.

    PubMed

    Pedersen, Amy B; Antonovics, Janis

    2013-08-23

    Individuals are often co-infected with several parasite species, yet the consequences of drug treatment on the dynamics of parasite communities in wild populations have rarely been measured. Here, we experimentally reduced nematode infection in a wild mouse population and measured the effects on other non-target parasites. A single oral dose of the anthelmintic, ivermectin, significantly reduced nematode infection, but resulted in a reciprocal increase in other gastrointestinal parasites, specifically coccidial protozoans and cestodes. These results highlight the possibility that drug therapy may have unintended consequences for non-target parasites and that host-parasite dynamics cannot always be fully understood in the framework of single host-parasite interactions.

  6. Anthelmintic Efficacy of Gold Nanoparticles Derived from a Phytopathogenic Fungus, Nigrospora oryzae

    PubMed Central

    Kar, Pradip Kumar; Murmu, Sanatan; Saha, Saswati; Tandon, Veena; Acharya, Krishnendu

    2014-01-01

    Exploring a green chemistry approach, this study brings to the fore, the anthelmintic efficacy of gold nanoparticles, highlighting the plausible usage of myconanotechnology. Gold nanoparticles of ∼6 to ∼18 nm diameter were synthesized by treating the mycelia-free culture filtrate of the phytopathogenic fungus with gold chloride. Their size and morphology were confirmed by UV-Vis spectroscopy, DLS data, AFM and TEM images. The XRD studies reveal a crystalline nature of the nanoparticles, which are in cubic phase. The FTIR spectroscopic studies before and after the formation of nanoparticles show the presence of possible functional groups responsible for the bio-reduction and capping of the synthesized gold nanoparticles. The latter were tested as vermifugal agents against a model cestode Raillietina sp., an intestinal parasite of domestic fowl. Further, ultrastructural and biochemical parameters were used to corroborate the efficacy study. PMID:24465424

  7. WIPO Re:Search: Accelerating anthelmintic development through cross-sector partnerships

    PubMed Central

    Ramamoorthi, Roopa; Graef, Katy M.; Dent, Jennifer

    2014-01-01

    Neglected tropical diseases (NTDs), malaria, and tuberculosis have a devastating effect on an estimated 1.6 billion people worldwide. The World Intellectual Property Organization (WIPO) Re:Search consortium accelerates the development of new drugs, vaccines, and diagnostics for these diseases by connecting the assets and resources of pharmaceutical companies, such as compound libraries and expertise, to academic or nonprofit researchers with novel product discovery or development ideas. As the WIPO Re:Search Partnership Hub Administrator, BIO Ventures for Global Health (BVGH) fields requests from researchers, identifies Member organizations able to fulfill these requests, and helps forge mutually beneficial collaborations. Since its inception in October 2011, WIPO Re:Search membership has expanded to more than 90 institutions, including leading pharmaceutical companies, universities, nonprofit research institutions, and product development partnerships from around the world. To date, WIPO Re:Search has facilitated over 70 research agreements between Consortium Members, including 11 collaborations focused on anthelmintic drug discovery. PMID:25516832

  8. Is the exclusion of children under 24 months from anthelmintic treatment justifiable?

    PubMed

    Montresor, Antonio; Stoltzfus, Rebecca J; Albonico, Marco; Tielsch, James M; Rice, Amy L; Chwaya, Hababu M; Savioli, Lorenzo

    2002-01-01

    There are no reports documenting toxicity or adverse effects after treatment of children aged < 24 months with benzimidazole derivatives and there is an urgent need to clarify this point in light of the potential detrimental effect that soil-transmitted helminthiasis has on this age-group. A total of 653 treatments (317 mebendazole 500 mg; 336 placebo) were administered in 1996/97 to 212 children aged < 24 months as part of a 1-year anthelmintic drug study conducted among preschool-age children in Tanzania. Data on fever, cough, diarrhoea, dysentery and acute respiratory illness were collected 1 week following the treatment. No differences between the occurrence of adverse effects in the 2 groups were observed. In light of the potential nutritional benefit achieved by regular deworming in this young age-group, the policy that excludes children aged < 24 months from treatment should be re-considered.

  9. Photo- and thermal-stability studies on benzimidazole anthelmintics by HPLC and GC-MS.

    PubMed

    Ragno, Gaetano; Risoli, Antonella; Ioele, Giuseppina; De Luca, Michele

    2006-06-01

    Photo- and thermal-stability of the anthelmintics Albendazole, Mebendazole and Fenbendazole as in solid as in solution form has been investigated, by using a Xenon arc lamp as a radiation source, according to the ICH guideline for the drug stability tests. The degradation process was monitored by a HPLC method. All drugs showed high photosensitivity in solution but a reliable stability in solid form and when exposed to a temperature up to 50 degrees C. Two main degradation products from hydrolysis of the carbamic groups were identified by GC-MS. Validation studies demonstrated high accuracy (recovery 94 to 106%) and precision (RSD under 4.6%) of the HPLC method. The analytical procedure was successfully applied to the control of the drugs in the respective pharmaceutical formulations. PMID:16755047

  10. The prevention and management of infections due to multidrug resistant organisms in haematology patients

    PubMed Central

    Trubiano, Jason A; Worth, Leon J; Thursky, Karin A; Slavin, Monica A

    2015-01-01

    Infections due to resistant and multidrug resistant (MDR) organisms in haematology patients and haematopoietic stem cell transplant recipients are an increasingly complex problem of global concern. We outline the burden of illness and epidemiology of resistant organisms such as gram-negative pathogens, vancomycin-resistant Enterococcus faecium (VRE), and Clostridium difficile in haematology cohorts. Intervention strategies aimed at reducing the impact of these organisms are reviewed: infection prevention programmes, screening and fluoroquinolone prophylaxis. The role of newer therapies (e.g. linezolid, daptomycin and tigecycline) for treatment of resistant and MDR organisms in haematology populations is evaluated, in addition to the mobilization of older agents (e.g. colistin, pristinamycin and fosfomycin) and the potential benefit of combination regimens. PMID:24341410

  11. Comparison between anthelmintic treatment strategies against Ascaridia galli in commercial laying hens.

    PubMed

    Tarbiat, B; Jansson, D S; Tydén, E; Höglund, J

    2016-08-15

    The efficacy of a sustainable deworming strategy based on targeted treatments (TT) against Ascaridia galli was investigated for the first time in laying hen flocks on a Swedish commercial farm. Three experimental protocols with different levels of treatment, e.g. targeted treatment (TT), conventional treatment (CT) and untreated (UT), were tested in randomly allocated flocks of two different bird hybrids. Every second week faecal egg counts (FECs) were determined from pooled faecal materials collected on trays (20×27cm) placed for a maximum of 12h on the litter belts. In the TT, anthelmintic administration (fenbendazole, 1mg/kg body weight for 5days) started at 22 weeks post placement (wpp) and was repeated twice when the pooled FECs surpassed the assigned threshold of 200 egg per gram faeces (EPG). The CT flocks were treated once at 27wpp using the same anthelmintic. Hens in the UT were not dewormed and served as controls. Additionally, FECs on cloacal contents, worm fecundity and worm burdens were determined at 19, 35 and 45wpp. None of the flocks became infected until after 16wpp. The cumulative pooled FECs at the end of the study were significantly (p<0.01) lower in the TT compared to both CT and UT. Although repeated treatment in the TT protocol did not affect the fecundity, a worm density-dependent increase in fecundity was observed. Cloacal FECs and the number of adult A. galli in TT at 35 and 45wpp were significantly lower compared to other flocks. This study provides evidence that the TT strategy is better in terms of lower worm burden and decreased cumulative environmental parasite egg numbers compared to CT strategy. The TT strategy should be considered as an alternative to the CT strategy with regard to A. galli control in commercial laying hens. PMID:27514895

  12. Studies on the traditional herbal anthelmintic Chenopodium ambrosioides L.: ethnopharmacological evaluation and clinical field trials.

    PubMed

    Kliks, M M

    1985-01-01

    Infusions and decoctions of the leaves, roots and inflorescences of the herbaceous shrub Chenopodium ambrosioides (American wormseed, goosefoot, epazote, paico) and related species indigenous to the New World have been used for centuries as dietary condiments and as traditional anthelmintics by native peoples for the treatment of intestinal worms. Commercial preparations of oil of chenopodium and its active constituent, ascaridol, obtained by steam distillation, have been and continue to be, used with considerable success in mass treatment campaigns. Ethnopharmacological studies in a community of Mayan subsistence farmers in Chiapas, Mexico, confirmed that decoctions containing up to 300 mg of dry plant material per kg body weight (MGKGW) were widely used and traditionally highly regarded in the treatment of ascariasis. However, therapeutic doses of up to 6000 MGKGW of powdered, dried plant had no significant anthelmintic effect on the adults of Necator, Trichuris of Ascaris. Gas-liquid chromatographic analyses of plant samples used consistently demonstrated the presence of ascaridol in the expected amounts. Possible origins of subjective belief in the efficacy of C. ambrosioides as used, may be related to the positive association of spontaneous, or peristalsis-induced passage of senescent worms immediately following a therapeutic episode. It is also possible that in the past varieties of the plant containing much more ascaridol were used. The results of these controlled field studies did not sustain widely held traditional beliefs, nor the value of therapeutic practices regarding this plant. It is, therefore, essential that all indigenous ethnomedical practices be objectively evaluated for efficacy and safety using appropriate protocols before being considered for adoptation or promotion in health care programs.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Multi-class determination of anthelmintics in soil and water by LC-MS/MS.

    PubMed

    Islam, Marivil D; Haberhauer, Georg; Kist, Alla; Rathor, M Nasir; Gerzabek, Martin; Cannavan, Andrew

    2013-01-01

    The translocation of antiparasitic drugs from animal excrement through soil and water to crops and forages and their recycling to food-producing animals is a potential concern with respect to the contamination of the food chain. To facilitate the investigation of this problem, an LC-MS/MS method for selected anthelmintics in soil and water was developed. The soil sample preparation involved a simple solvent extraction and dispersive clean-up technique. The method was validated at 10, 20 and 40 µg kg(-1) for levamisole, fenbendazole, fenbendazole sulphoxide and fenbendazole sulphone and at 20, 40 and 80 µg kg(-1) for eprinomectin. LOQs were 10 µg kg(-1) for the first four compounds and 20 µg kg(-1) for eprinomectin. The overall mean recoveries ranged from 76.1% to 89% for loamy soils and from 79.9% to 96.9% for sandy soils. Analysis of water samples was performed by extraction/concentration on an Oasis-HLB (Aschaffenburg, Germany) cartridge. Validation was performed at 0.25, 0.5 and 1.0 µg l(-1). The LOQ for all compounds was 0.25 µg l(-1). Method recovery (and RSD) varied between 35.4% (28) for eprinomectin and 125.1% (16) for fenbendazole sulphone. The validated methods were applied to soil and water samples in a study on the behaviour of anthelmintic drugs in a soil-plant-water system (manuscript on "transport investigation of antiparasitic drugs based on a lysimeter experiment" in preparation).

  14. In vitro and in vivo anthelmintic activity of crude extracts of Coriandrum sativum against Haemonchus contortus.

    PubMed

    Eguale, T; Tilahun, G; Debella, A; Feleke, A; Makonnen, E

    2007-04-01

    In vitro anthelmintic activities of crude aqueous and hydro-alcoholic extracts of the seeds of Coriandrum sativum (Apiaceae) were investigated on the egg and adult nematode parasite Haemonchus contortus. The aqueous extract of Coriandrum sativum was also investigated for in vivo anthelmintic activity in sheep infected with Haemonchus contortus. Both extract types of Coriandrum sativum inhibited hatching of eggs completely at a concentration less than 0.5 mg/ml. ED(50) of aqueous extract of Coriandrum sativum was 0.12 mg/ml while that of hydro-alcoholic extract was 0.18 mg/ml. There was no statistically significant difference between aqueous and hydro-alcoholic extracts (p>0.05). The hydro-alcoholic extract showed better in vitro activity against adult parasites than the aqueous one. For the in vivo study, 24 sheep artificially infected with Haemonchus contortus were randomly divided into four groups of six animals each. The first two groups were treated with crude aqueous extract of Coriandrum sativum at 0.45 and 0.9 g/kg dose levels, the third group with albendazole at 3.8 mg/kg and the last group was left untreated. Efficacy was tested by faecal egg count reduction (FECR) and total worm count reduction (TWCR). On day 2 post treatment, significant FECR was detected in groups treated with higher dose of Coriandrum sativum (p<0.05) and albendazole (p<0.001). On days 7 and 14 post treatment, significant FECR was not detected for both doses of Coriandrum sativum (p>0.05). Significant (p<0.05) TWCR was detected only for higher dose of Coriandrum sativum compared to the untreated group. Reduction in male worms was higher than female worms. Treatment with both doses of Coriandrum sativum did not help the animals improve or maintain their PCV while those treated with albendazole showed significant increase in PCV (p<0.05).

  15. Effect of the ionophore antibiotic monensin on the ruminal biotransformation of benzimidazole anthelmintics.

    PubMed

    Virkel, G; Lifschitz, A; Sallovitz, J; Inza, G; Lanusse, C

    2004-05-01

    The benzimidazole (BZD) anthelmintics, netobimin (NTB) pro-drug and albendazole sulphoxide (ABZSO) are reduced to albendazole (ABZ) by ruminal microflora. The aim of the current work was to evaluate the influence of the ionophore monensin (MON) on the in vitro biotransformation of NTB and ABZSO by sheep ruminal fluid. Ruminal fluid, collected from Corriedale sheep, was preincubated (24 h) either without (control) or with known MON concentrations (0.5, 1.5 and 3.0 microg/mL) at 38 degrees C under a CO2 atmosphere. Afterwards, aliquots from both MON-pretreated and control ruminal fluid samples were incubated (30 and 60 min) with 2 microg/mL of either NTB or ABZSO. Incubated samples were chemically extracted and analysed by High Performance Liquid Chromatography to quantify the metabolites formed. The rate of ABZ production after 30 min of NTB incubation with control ruminal fluid was 0.023 microg/min. Conversely, the rates of ABZ formation were significantly (P<0.05) lower (0.009, 0.011 and 0.013 microg/min) when NTB was incubated with ruminal fluid pretreated with MON (at 0.5, 1.5 and 3.0 microg/mL, respectively). After both incubation periods, the reduction of ABZSO to ABZ was 22 to 70% lower when the ruminal fluid was preincubated with the different MON concentrations. The lower ABZ production observed in the presence of MON may result in a modified availability of this molecule in the gastrointestinal (GI) tract and hence, on its anthelmintic efficacy against GI nematodes.

  16. Anthelmintic effect of Mentha spp. essential oils on Echinococcus granulosus protoscoleces and metacestodes.

    PubMed

    Maggiore, Marina A; Albanese, Adriana A; Gende, Liesel B; Eguaras, Martín J; Denegri, Guillermo M; Elissondo, María Celina

    2012-03-01

    The aim of the present work was to determine the in vitro effect of Mentha piperita and Mentha pulegium essential oils against Echinococcus granulosus and to compare the effectiveness of both oils according to the exposure time and concentration. Although both treatments had a protoscolicidal effect, M. pulegium had a considerably stronger effect than M. piperita. Essential oil of M. pulegium produced dose- and time-dependent effects. Maximal protoscolicidal effect was observed after 12 days of incubation and reached 0% after 18 days. This lack of viability was proved during the determination of infectivity into mice. Essential oil of M. piperita produced only a time-dependent effect. At 24 days p.i., the viability of protoscoleces decreased to approximately 50%. Scanning and transmission electron microscopy (SEM and TEM) demonstrated the drug-induced ultrastructural damage. On the other hand, a loss of turgidity was detected in all M. pulegium-treated cysts respective of the drug concentration. There was a correlation between the intensity of damage and the concentration of the essential oil assayed. Studies by SEM revealed that the germinal layer of treated cysts lost the feature multicellular structure. M. pulegium essential oil showed piperitone oxide as main compound in their composition, and we suggest that this component could be responsible of the markedly anthelmintic effect detected. Our data suggest that essential oils of Mentha spp. can be a promising source of potential protoscolicidal agents. The isolation of active anthelmintic constituents is in progress and may lead to the discovery of compounds with improved therapeutic value.

  17. Protection and Delivery of Anthelmintic Protein Cry5B to Nematodes Using Mesoporous Silicon Particles.

    PubMed

    Wu, Chia-Chen; Hu, Yan; Miller, Melanie; Aroian, Raffi V; Sailor, Michael J

    2015-06-23

    The ability of nano- and microparticles of partially oxidized mesoporous silicon (pSi) to sequester, protect, and deliver the anthelmintic pore-forming protein Cry5B to nematodes is assessed in vitro and in vivo. Thermally oxidized pSi particles are stable under gastric conditions and show relatively low toxicity to nematodes. Fluorescence images of rhodamine-labeled pSi particles within the nematodes Caenorhabditis elegans and Ancylostoma ceylanicum show that ingestion is dependent on particle size: particles of a 0.4 ± 0.2 μm size are noticeably ingested by both species within 2 h of introduction in vitro, whereas 5 ± 2 μm particles are excluded from C. elegans but enter the pharynx region of A. ceylanicum after 24 h. The anthelmintic protein Cry5B, a pore-forming crystal (Cry) protein derived from Bacillus thuringiensis, is incorporated into the pSi particles by aqueous infiltration. Feeding of Cry5B-loaded pSi particles to C. elegans leads to significant intoxication of the nematode. Protein-loaded particles of size 0.4 μm display the highest level of in vitro toxicity toward C. elegans on a drug-mass basis. The porous nanostructure protects Cry5B from hydrolytic and enzymatic (pepsin) degradation in simulated gastric fluid (pH 1.2) for time periods up to 2 h. In vivo experiments with hookworm-infected hamsters show no significant reduction in worm burden with the Cry5B-loaded particles, which is attributed to slow release of the protein from the particles and/or short residence time of the particles in the duodenum of the animal.

  18. Studies on the traditional herbal anthelmintic Chenopodium ambrosioides L.: ethnopharmacological evaluation and clinical field trials.

    PubMed

    Kliks, M M

    1985-01-01

    Infusions and decoctions of the leaves, roots and inflorescences of the herbaceous shrub Chenopodium ambrosioides (American wormseed, goosefoot, epazote, paico) and related species indigenous to the New World have been used for centuries as dietary condiments and as traditional anthelmintics by native peoples for the treatment of intestinal worms. Commercial preparations of oil of chenopodium and its active constituent, ascaridol, obtained by steam distillation, have been and continue to be, used with considerable success in mass treatment campaigns. Ethnopharmacological studies in a community of Mayan subsistence farmers in Chiapas, Mexico, confirmed that decoctions containing up to 300 mg of dry plant material per kg body weight (MGKGW) were widely used and traditionally highly regarded in the treatment of ascariasis. However, therapeutic doses of up to 6000 MGKGW of powdered, dried plant had no significant anthelmintic effect on the adults of Necator, Trichuris of Ascaris. Gas-liquid chromatographic analyses of plant samples used consistently demonstrated the presence of ascaridol in the expected amounts. Possible origins of subjective belief in the efficacy of C. ambrosioides as used, may be related to the positive association of spontaneous, or peristalsis-induced passage of senescent worms immediately following a therapeutic episode. It is also possible that in the past varieties of the plant containing much more ascaridol were used. The results of these controlled field studies did not sustain widely held traditional beliefs, nor the value of therapeuti