Detection of anthelmintic resistance in sheep and goat against fenbendazole by faecal egg count reduction test.

PubMed

Singh, Ramandeep; Bal, M S; Singla, L D; Kaur, Paramjit

2017-06-01

Anthelmintic resistance against commonly used anthelmintic fenbendazole was evaluated by employing faecal egg count reduction test (FECRT) in naturally occurring gastrointestinal (GI) nematodes in the semi organized sheep and goat farms of Ludhiana and Amritsar districts. A total of 80 animals (20 each for sheep and goat in both districts) were randomly selected and their faecal samples were examined by qualitative and quantitative parasitological techniques. Results indicate presence of high level of resistance against fenbendazole in both sheep and goat population of Ludhiana and Amritsar districts. More resistance was observed in the GI nematodes from animals reared in Amritsar district as compared to Ludhiana district. The level of anthelmintic resistance observed was apparently more in sheep than goats.

Computer modelling of anthelmintic resistance and worm control outcomes for refugia-based nematode control strategies in Merino ewes in Western Australia.

PubMed

Cornelius, M P; Jacobson, C; Dobson, R; Besier, R B

2016-04-15

This study utilised computer simulation modelling (Risk Management Model for Nematodes) to investigate the impact of different parasite refugia scenarios on the development of anthelmintic resistance and worm control effectiveness. The simulations were conducted for adult ewe flocks in a Mediterranean climatic region over a 20 year time period. Factors explored in the simulation exercise were environment (different weather conditions), drug efficacy, the percentage of the flock left untreated, the timing of anthelmintic treatments, the initial worm egg count, and the number of drenches per annum. The model was run with variable proportions of the flock untreated (0, 10, 20, 30, 40 and 50%), with ewes selected at random so that reductions in the mean worm burden or egg count were proportional to the treated section of the flock. Treatments to ewes were given either in summer (December; low refugia potential, hence highly selective) or autumn (March; less selective due to a greater refugia potential), and the use of different anthelmintics was simulated to indicate the difference between active ingredients of different efficacy. Each model scenario was run for two environments, specifically a lower rainfall area (more selective) and a higher rainfall area (less selective) within a Mediterranean climatic zone, characterised by hot, dry summers and cool, wet winters. Univariate general linear models with least square difference post-hoc tests were used to examine differences between means of factors. The results confirmed that leaving a proportion of sheep in a flock untreated was effective in delaying the development of anthelmintic resistance, with as low as 10% of a flock untreated sufficient to significantly delay resistance, although this strategy was associated with a small reduction in worm control. Administering anthelmintics in autumn rather than summer was also effective in delaying the development of anthelmintic resistance in the lower rainfall

Genomic introgression mapping of field-derived multiple-anthelmintic resistance in Teladorsagia circumcincta

PubMed Central

Hallsworth-Pepin, Kymberlie; Martin, John; Mitreva, Makedonka

2017-01-01

Preventive chemotherapy has long been practiced against nematode parasites of livestock, leading to widespread drug resistance, and is increasingly being adopted for eradication of human parasitic nematodes even though it is similarly likely to lead to drug resistance. Given that the genetic architecture of resistance is poorly understood for any nematode, we have analyzed multidrug resistant Teladorsagia circumcincta, a major parasite of sheep, as a model for analysis of resistance selection. We introgressed a field-derived multiresistant genotype into a partially inbred susceptible genetic background (through repeated backcrossing and drug selection) and performed genome-wide scans in the backcross progeny and drug-selected F2 populations to identify the major genes responsible for the multidrug resistance. We identified variation linking candidate resistance genes to each drug class. Putative mechanisms included target site polymorphism, changes in likely regulatory regions and copy number variation in efflux transporters. This work elucidates the genetic architecture of multiple anthelmintic resistance in a parasitic nematode for the first time and establishes a framework for future studies of anthelmintic resistance in nematode parasites of humans. PMID:28644839

Anthelmintic resistance of nematodes in communally grazed goats in a semi-arid area of South Africa.

PubMed

Bakunzi, F R

2003-09-01

A survey was conducted on the occurrence of anthelmintic resistance of nematodes in communally grazed goats in a semi-arid area in South Africa. In herds belonging to 10 small-holder goat farmers, the efficacies of fenbendazole, levamisole and rafoxanide were tested by faecal egg count reduction (FECR) tests. Efficacies of 80% were considered a threshold for anthelmintic resistance. The FECR tests showed that all drugs tested more than 80% effective in most instances, but there were notable exceptions. In 1 case, rafoxanide was only 31% effective and in another case fenbendazole was only 47% effective. The occurrence of anthelmintic resistance in this farming sector is of concern. Steps should be taken to prevent its further spread and to avoid the development of a situation as on numerous commercial sheep farms in South Africa where resistance is very common.

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

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.

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

A multi-species model to assess the effect of refugia on worm control and anthelmintic resistance in sheep grazing systems.

PubMed

Dobson, R J; Barnes, E H; Tyrrell, K L; Hosking, B C; Larsen, J W A; Besier, R B; Love, S; Rolfe, P F; Bailey, J N

2011-06-01

Develop a computer simulation model that uses daily meteorological data and farm management practices to predict populations of Trichostrongylus colubriformis, Haemonchus contortus and Teladorsagia (Ostertagia) circumcincta and the evolution of anthelmintic resistance within a sheep flock. Use the model to explore if increased refugia, provided by leaving some adult sheep untreated, would delay development of anthelmintic resistance without compromising nematode control. Compare model predictions with field observations from a breeding flock in Armidale, NSW. Simulate the impact of leaving 1-10% of adult sheep untreated in diverse sheep-grazing systems. Predicted populations of Tr. colubriformis and T. circumcincta were less than those observed in the field, attributed to nutritional stress experienced by the sheep during drought and not accounted for by the model. Observed variation in faecal egg counts explained by the model (R(2) ) for these species was 40-50%. The H. contortus populations and R(2) were both low. Leaving some sheep untreated worked best in situations where animals were already grazing or were moved onto pastures with low populations of infective larvae. In those cases, anthelmintic resistance was delayed and nematode control was maintained when 1-4% of adult stock remained untreated. In general, the model predicted that leaving more than 4% of adults untreated did not sufficiently delay the development of anthelmintic resistance to justify the increased production risk from such a strategy. The choice of a drug rotation strategy had an equal or larger effect on nematode control, and selection for resistance, than leaving 1-10% of adults untreated. © 2011 The Authors. Australian Veterinary Journal © 2011 Australian Veterinary Association.

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

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

Blueprint for an automated specific decision support system for countering anthelmintic resistance in Haemonchus spp. at farm level.

PubMed

van Wyk, J A; Reynecke, D P

2011-05-11

This article is the first of a series aimed at developing specific decision support software for on-farm optimisation of sustainable integrated management of haemonchosis. It contains a concept framework for such a system for use by farmers and/or their advisors but, as reported in the series, only the first steps have been taken on the road to achieve this goal. Anthelmintic resistance has reached such levels of prevalence and intensity that recently it evoked the comment that for small ruminants the final phase of resistance was being entered, without effective chemotherapeutic agents on some farms with which to control worms at a level commensurate with profitable animal production. In addition, in the case of cattle, a recent survey in New Zealand showed 92% of worm populations to be resistant to at least one anthelmintic group. Ironically, new technology, such as the FAMACHA(©) system which was devised for sustainable management of haemonchosis, is at present being adopted relatively slowly by the majority of farmers and it is suggested that an important reason for this is the complexity of integration of new methods with epidemiological factors. The alternatives to the simple drenching programmes of the past are not only more difficult to manage, but are also more labour-intensive. The problem is further complicated by a progressive global shortage of persons with the necessary experience to train farmers in the new methods. The opinion is advanced that only computerised, automated decision support software can optimise the integration of the range of factors (such as rainfall, temperature, host age and reproductive status, pasture type, history of host and pasture infection, and anthelmintic formulation) for more sustainable worm management than is obtainable with present methods. Other than the conventional method (in which prospective analysis of laboratory and other data is mainly used to suggest when strategic prophylactic drenching of all animals for

A field study on the anthelmintic resistance of Parascaris spp. in Arab foals in the Riyadh region, Saudi Arabia.

PubMed

Alanazi, Abdullah D; Mukbel, Rami M; Alyousif, Mohamed S; AlShehri, Zafer S; Alanazi, Ibrahim O; Al-Mohammed, Hamdan I

2017-12-01

In the last decade, Parascaris spp. resistance to anthelmintics has been recorded in many countries. In Saudi Arabia, there are limited data available on Parascaris spp. resistance to anthelmintics. To determine the current status of ivermectin, abamectin and praziquantel combined, and fenbendazole resistance to Parascaris spp. in horses in Saudi Arabia. Three hundred and forty-one foals from eleven different farms were examined by faecal egg count (FEC). The foals were all Arab horses aged 17.2 ± 4.5 (SD) months. Ivermectin (n = 46 foals), abamectin and praziquantel combined (n = 46), and fenbendazole (n = 46) were administered on day 0 and faeces were collected on day 14. The study comprised 41 untreated foals as controls. Animals that have FEC of ≥100 eggs per gram (EPG) were used to measure anthelmintic efficacy. Parascaris spp. populations were considered susceptible when faecal egg count reduction (FECR) was ≥95% associated with a lower 95% confidence limit (LCL) >90%, suspected resistant when FECR ≤90% or LCL <90% and resistant when FECR <90% and LCL <90%. Prevalence of Parascaris spp. infection was 53% (179/341 horses). Anthelmintic resistance to Parascaris spp. were highest following fenbendazole (55% of farms and 65% of foals) and to a lower extent following ivermectin or the combination of abamectin and praziquantel which comprised 27% of farms (and 46% of foals) and 18% of farms (and 10% of foals), respectively. These data indicate that anthelmintics-resistant Parascaris spp. populations are present on horse farms in Saudi Arabia.

Prevalence of anthelmintic resistance on Lithuanian sheep farms assessed by in vitro methods.

PubMed

Kupčinskas, Tomas; Stadalienė, Inga; Šarkūnas, Mindaugas; Riškevičienė, Vita; Várady, Marian; Höglund, Johan; Petkevičius, Saulius

2015-12-16

This study examines the prevalence of drug resistance in gastrointestinal nematodes to macrocyclic lactones (ML) and benzimidazoles (BZ) in Lithuanian sheep using sensitive and precise in vitro methods. The survey was conducted from August 2013 to November 2014. Thirty-three farms with sheep previously treated with BZ and ivermectin (IVM) were included in the study. On 12 farms where only BZ were used, egg hatch discrimination dose testing (EHDDT) was conducted to detect anthelmintic resistance (AR) to BZ. On eight farms where only ML were used, micro agar larval development testing (MALDT) was conducted to detect AR to ivermectin (IVM). On the remaining 13 farms, where both classes of drugs were used, EHDDT and MALDT were both applied to detect multidrug resistance to BZ and IVM. BZ-resistant gastrointestinal nematodes were found on all 25 farms with a previous history of BZ use. High levels of resistance (>40 % of hatching) were recorded on 36 % of these farms, and low levels (<20 % of hatching) on 40 % of farms. IVM-resistant populations were found on 13 out of 21 sheep farms using this drug. Of these 13 farms with AR to IVM, low levels of resistance (<30 % development) were recorded on 84.6 % of farms and high levels (>30 % development) on 15.4 % of farms. No resistance to IVM was recorded on 38.1 % of farms. Multi-drug resistance was detected on five farms out of 13 (38.5 %) using both classes of drugs. The present study demonstrates the existence of AR to BZ and ML on Lithuanian sheep farms thus confirming results in a previous in vivo study. Cases of multi-drug resistance were recorded in the present study and require further consideration. An appropriate strategy for anthelmintic treatment, measures to prevent gastrointestinal nematode infection and a better understanding of the management practices associated with resistance may slow down further development of AR.

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

PubMed

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

2017-03-01

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

Assessment of gastrointestinal nematode infection, anthelmintic usage and husbandry practices on two small-scale goat farms in Malaysia.

PubMed

Wong, Flora; Sargison, Neil

2018-03-01

Haemonchosis is a common problem on goat farms in tropical countries such as Malaysia. Prevention of production losses generally depends on the use of anthelmintic drugs, but is threatened by the emergence of anthelmintic resistance. This study investigates anthelmintic efficacy on small-scale Malaysian goat farms and describes putative risk factors. Adult goats had moderate to high pre-treatment faecal trichostrongyle egg counts, despite being housed on slatted floors and fed on cut-and-carry forage, raising questions about the source of nematode infection. Our results show multiple resistance to benzimidazole and macrocyclic lactone anthelmintic drugs and allow us to discuss the genetic origins of resistance with reference to farm husbandry and management. We conclude that improvement in Malaysian goat production efficiency will require the development of sustainable helminth control strategies, underpinned by a better understanding of the origins and population genetics of anthelmintic resistance.

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

PubMed

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

2016-10-15

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

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.

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. Copyright © 2015 Elsevier B.V. All rights reserved.

Repurposing Salicylanilide Anthelmintic Drugs to Combat Drug Resistant Staphylococcus aureus

PubMed Central

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

2015-01-01

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

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

PubMed

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

2013-09-23

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

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

PubMed

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

2014-04-07

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

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

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

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 (%). Copyright © 2011 Elsevier B.V. All rights reserved.

A nationwide survey of anthelmintic treatment failure on sheep farms in Ireland.

PubMed

Keegan, Jason D; Keane, Orla M; Good, Barbara; De Waal, Theo; Denny, Marian; Hanrahan, James P; Fitzgerald, William; Sheehan, Maresa

2017-01-01

Between 2013 and 2015 the Department of Agriculture, Food and the Marine (DAFM) administered a sheep technology adoption programme (STAP), with the aim of increasing profitability on Irish sheep farms by encouraging the adoption of best management practices. One of the options available to STAP participants was to test the efficacy of the anthelmintic treatment (benzimadazole, levamisole or macrocyclic lactone) used in their flocks by means of a drench test, which is a modification of the faecal egg count reduction test; individual faecal samples were collected from the same group of lambs before and after anthelmintic treatment, the number of eggs present pre and post treatment was subsequently determined from a pooled sample. In total, 4211 drench tests were undertaken by farmers during the 3 years of the programme. Information on the anthelmintic product used was available for 3771 of these tests; anthelmintics from the classes benzimidazole (BZ), levamisole (LV) and macrocyclic lactone (ML) (avermectins (AVM) plus moxidectin (MOX)) were used in 42.0%, 23.4% and 32.5% of tests, respectively. The remaining 2.1% of tests involved an inappropriate product. The efficacy of treatment against 'other trichostrongyles' (excluding Nematodirus spp and Strongyloides papillosus .) could be established for 1446 tests, and 51% of these tests were considered effective (i.e. a reduction of faecal egg count (FEC) ≥ 95%). There was a significant difference among the drug groups in efficacy; 31.5%, 51.9%, 62.5% and 84% of treatments were considered effective for BZ, LV, AVM, MOX, respectively. The efficacy of treatment against Nematodirus spp. could be established for 338 tests and the overall efficacy was 96%. Due to the significant difference among the anthelmintic classes for efficacy against 'other trichostrongyles' along with the high level of efficacy against Nematodirus spp., a genus for which anthelmintic resistance is rarely reported, it is concluded that anthelmintic

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

PubMed

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

2017-04-18

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

Influence of sustained deworming pressure on the anthelmintic resistance status in strongyles of sheep under field conditions.

PubMed

Vijayasarathi, M K; Sreekumar, C; Venkataramanan, R; Raman, M

2016-10-01

Anthelmintic resistance (AR) status in Madras Red sheep from selected field flocks of a government funded scheme, covered by regular, sustained anthelmintic treatment for more than 10 years was determined. Parameters such as fecal egg count reduction test (FECRT), larval paralysis assay (LPA), and allele-specific-PCR (AS-PCR) were used to test the efficacy of fenbendazole, tetramisole, and ivermectin at recommended doses, in two seasons. Sheep belonging to non-beneficiary farmers were used as controls. Mean FECRT values of beneficiary group during winter and summer seasons were 77.77 and 76.04, 93.65 and 92.12, and 95.37 and 98.06 %, respectively, for fenbendazole, tetramisole, and ivermectin. In the non-beneficiary groups, the corresponding values were 74.82 and 81.09 %, 96.05 and 97.40 %, and 97.26 and 98.23 %, respectively. The results revealed resistance to fenbendazole, suspect resistance to tetramisole and susceptibility to ivermectin in beneficiary flock. In non-beneficiary flock, while resistance was noticed against fenbendazole, both tetramisole and ivermectin were effective. FECR values were found to be significantly different between beneficiary and non-beneficiary groups against tetramisole. The results of LPA confirmed this finding, as 50 % of the Haemonchus contortus larvae were paralyzed at the concentration of 0.0156 μg/ml in the beneficiary group, while those of non-beneficiary groups required lower concentrations of 0.0078 μg/ml. AS-PCR revealed the predominance of heterozygous susceptible population of H. contortus in the beneficiary group. In this study, resistance to fenbendazole was confirmed in both the beneficiary and non-beneficiary groups and this could be attributed to frequent use of benzimidazoles as seen from the deworming records. Emergence of tetramisole resistance was detected in the beneficiary group, where the drug was used continuously for 4 years. Ivermectin was found to be effective in all the flocks. It is

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

PubMed

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

2011-09-27

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

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

PubMed

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

2009-12-23

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

A survey of the trichostrongylid nematode species present on UK sheep farms and associated anthelmintic control practices.

PubMed

Burgess, Charlotte G S; Bartley, Yvonne; Redman, Elizabeth; Skuce, Philip J; Nath, Mintu; Whitelaw, Fiona; Tait, Andrew; Gilleard, John S; Jackson, Frank

2012-10-26

A survey of sheep farms from across the UK was conducted to establish information on farming practices, the trichostrongylid nematode species present and anthelmintic usage. Questionnaires and faecal samples were returned from 118 farms. First stage larvae (L(1)) were cultured from faecal samples and used for PCR analysis to determine the presence/absence of selected trichostrongylid species. Teladorsagia circumcincta was the only species present on 100% of farms. Haemonchus contortus was found on ∼50% of farms and was widespread throughout the UK. The most common Trichostrongylus spp. was T. vitrinus, found on 95% of farms. Determining the anthelmintic dose rate based on the weight of the heaviest animal in the flock to avoid under dosing was carried out on 58% of farms and was associated with a significantly lower mean epg (p<0.001) in lambs. However, the weight of animals was only estimated (as opposed to animals weighed) on 32% of farms. Macrocyclic lactones (ML) were the most commonly used anthelmintic class for ewes, whilst benzimidazoles (BZ) were the most widely used in lambs. Twenty-two of the surveyed farms had confirmed anthelmintic resistance, of these, 18 had BZ resistance, one had levamisole (LEV) resistance and 3 had resistance to both BZ and LEV. No farms in this survey reported resistance to ML. Location had a significant effect on the incidence of anthelmintic resistance on the farms in this survey (p=0.002). There was evidence of a lower risk of anthelmintic resistance occurring on farms from Scotland compared to those in England (p(f)=0.047) and Wales (p(f)=0.012). Farm type, flock type and open or closed status did not have any significant effect on the incidence of anthelmintic resistance when all other factors were taken into consideration. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Comparative anthelmintic activity investigation of selected ethno-medicinal weeds

NASA Astrophysics Data System (ADS)

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

2017-01-01

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

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

Evaluation of Anthelmintic Resistance and Exhaust Air Dust PCR as a Diagnostic Tool in Mice Enzootically Infected with Aspiculuris tetraptera

PubMed Central

Kapoor, Pratibha; Hayes, Yumiko O; Jarrell, Leslie T; Bellinger, Dwight A; Thomas, Rhiannon D; Lawson, Gregory W; Arkema, Jaclyn D; Fletcher, Craig A; Nielsen, Judith N

2017-01-01

The entry of infectious agents in rodent colonies occurs despite robust sentinel monitoring programs, strict quarantine measures, and stringent biosecurity practices. In light of several outbreaks with Aspiculuris tetraptera in our facilities, we investigated the presence of anthelmintic resistance and the use of exhaust air dust (EAD) PCR for early detection of A. tetraptera infection. To determine anthelmintic resistance, C57BL/6, DBA/2, and NCr nude mice were experimentally inoculated with embryonated A. tetraptera ova harvested from enzootically infected mice, followed by treatment with 150 ppm fenbendazole in feed, 150 ppm fenbendazole plus 5 ppm piperazine in feed, or 2.1 mg/mL piperazine in water for 4 or 8 wk. Regardless of the mouse strain or treatment, no A. tetraptera were recovered at necropsy, indicating the lack of resistance in the worms to anthelmintic treatment. In addition, 10 of 12 DBA/2 positive-control mice cleared the A. tetraptera infection without treatment. To evaluate the feasibility of EAD PCR for A. tetraptera, 69 cages of breeder mice enzootically infected with A. tetraptera were housed on a Tecniplast IVC rack as a field study. On day 0, 56% to 58% of the cages on this rack tested positive for A. tetraptera by PCR and fecal centrifugation flotation (FCF). PCR from EAD swabs became positive for A. tetraptera DNA within 1 wk of placing the above cages on the rack. When these mice were treated with 150 ppm fenbendazole in feed, EAD PCR reverted to pinworm-negative after 1 mo of treatment and remained negative for an additional 8 wk. The ability of EAD PCR to detect few A. tetraptera positive mice was investigated by housing only 6 infected mice on another IVC rack as a field study. The EAD PCR from this rack was positive for A. tetraptera DNA within 1 wk of placing the positive mice on it. These findings demonstrate that fenbendazole is still an effective anthelmintic and that EAD PCR is a rapid, noninvasive assay that may be a useful

Comparison of biotransformation and efficacy of aminoacetonitrile anthelmintics in vitro.

PubMed

Stuchlíková, Lucie; Lecová, Lenka; Jirásko, Robert; Lamka, Jiří; Vokřál, Ivan; Szotáková, Barbora; Holčapek, Michal; Skálová, Lenka

2016-02-01

The present in vitro study was designed to test and compare anthelmintic activity, hepatotoxicity, and biotransformation of four selected aminoacetonitrile derivatives (AADs): monepantel (MOP, anthelmintic approved for the treatment), AAD-970, AAD-1154, and AAD-1336. Micro-agar larval development test, MTT test of cytotoxicity, and biotransformation study coupled with Ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technique were used for this purpose. Larvae of two Haemonchus contortus strains (drug susceptible and multi-drug resistant) and primary cultures of rat and ovine hepatocytes served as model systems. All AADs (including MOP) exhibited significant larvicidal effect in H. contortus susceptible as well as multi-resistant strains, much higher than those of reference anthelmintics thiabendazole and flubendazole. AAD-1154 provides the best results for most tested parameters among all AADs in this study. The cytotoxicity test showed that all AADs can be considered as nontoxic for hepatocytes. In the biotransformation study, Phase I and Phase II metabolites of AADs were identified and schemes of possible metabolic pathways in ovine hepatocytes were proposed. Biotransformation of MOP was much more extensive than biotransformation of other AADs. Based on obtained results, AAD-1154 and AAD-1336 can be considered as promising candidates for further in vivo testing. Copyright © 2015 John Wiley & Sons, Ltd.

Helminthiasis characterization and anthelmintic efficacy for ewes and lambs raised in tropical semiarid region.

PubMed

Bastos, Gabriela Almeida; Fonseca, Leydiana Duarte; de Paiva Ferreira, Adriano Vinícius; Costa, Marco Aurélio Morais Soares; Silva, Maria Luiza França; de Oliveira Vasconcelos, Viviane; de Sousa, Rogério Marcos; Duarte, Eduardo Robson

2017-06-01

In this study the helminthiasis and anthelmintic effectiveness in ewes and lambs were evaluated in a semiarid region of Brazil. Twelve sheep farms were investigated using semi-structured questionnaires and fecal egg count (FEC) reduction test was employed to analyze the profile of anthelmintic resistance. Groups of at least 10 animals with FEC ≥ 300 were selected. After 12 h of fasting, homogeneous groups of lambs or ewes were treated with albendazole, levamisole moxidectin, or oxfendazole and control groups were not treated. Feces were collected before treatments and 14 days after, and larvae genera were identified after cuprocultures in both periods. Extensive grazing was the predominant creation system, using hybrid Santa Ines animals. The separation by age was promoted in 75% of herds; however, maternity pickets there were only in three farms. The strategic treatments were performed only in 8.4% of sheep farms and 16.6% used the anthelmintic efficacy test and alternated anthelmintic classes after 1 year. The initial FEC means for lambs were significantly higher than ewe FEC averages. For lamb tests, moxidectin and levamisole showed higher efficacy (p ≤ 0.05) than benzimidazoles. For ewe tests, moxidectin and levamisole showed efficiencies >75%. Haemonchus spp. and Trichostrongylus spp. were the most frequent nematodes before treatments and the genus Haemonchus was the most prevalent after anthelmintic treatments (p < 0.05). Variations of anthelmintic susceptibility were observed for categories and herds evaluated, which emphasizes the importance of the effectiveness tests for the choice of anthelmintics for ewes and lambs.

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 is...

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 is...

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 is...

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 is...

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 is...

Field evaluation of the efficacy of common anthelmintics used in the control of gastrointestinal nematodes of sheep in Dabat district, Northwest Ethiopia.

PubMed

Seyoum, Zewdu; Demessie, Yitayew; Bogale, Basazinew; Melaku, Achenef

2017-01-01

Gastrointestinal nematode (GIN) infections are the main impediments that restrict the welfare and productivity of small ruminant in the world. Effective management of GINs in grazing sheep relies heavily on the use of highly efficacious anthelmintic drugs. However, anthelmintic resistance is becoming a significant concern in the world, and this phenomenon severely threatens the potential utilisation of this control strategy. Therefore, this study was conducted 1) to evaluate the efficacy of commonly used anthelmintic on GINs in naturally infected sheep and 2) to assess the farmers' perception on anthelmintics utilisation practices in Dabat district, Northwest Ethiopia. One hundred twenty nematode infected sheep were used in this study. Sheep were selected based on the egg count (≥150 eggs per gram of faeces). The animals were allocated randomly into four groups (30 animals per group). Group-I, II and III were treated with Albendazole, Tetramisole, and Ivermectin, respectively. The 4th group was left untreated (as control). Faecal samples were collected on day 0 (before treatment), on day 3, 7, 10 and 14 (post-treatment). The modified McMaster technique was used for quantifying the eggs. Faecal egg count reduction test (FECRT) was applied to determine the efficacy of anthelmintic at day 14 (post-treatment). In addition, a questionnaire survey was conducted on 100 randomly selected sheep owners. All anthelmintics tested revealed significant ( P  < 0.05) reduction in nematode egg excretion in the sheep post-treatment. Faecal egg count reduction (FECR) levels for Albendazole, Tetramisole, and Ivermectin were 97.2, 98.9 and 97.7%, respectively. Post-treatment egg counts and percentage reduction of egg counts were not significantly different ( P  > 0.05) among the treatment groups. The nematode genera identified before treatment were Haemonchus , Trichostrongylus , Cooperia , Trichuris , Teladorsagia , Bunostomum, and Strongyloides. Haemonchus and

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

PubMed

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

2016-10-26

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

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

PubMed

Lifschitz, A; Lanusse, C; Alvarez, L

2017-07-01

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

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

Targeted and Untargeted Metabolic Profiling of Wild Grassland Plants identifies Antibiotic and Anthelmintic Compounds Targeting Pathogen Physiology, Metabolism and Reproduction.

PubMed

French, Katherine E; Harvey, Joe; McCullagh, James S O

2018-01-26

Plants traditionally used by farmers to manage livestock ailments could reduce reliance on synthetic antibiotics and anthelmintics but in many cases their chemical composition is unknown. As a case study, we analyzed the metabolite profiles of 17 plant species and 45 biomass samples from agricultural grasslands in England using targeted and untargeted metabolite profiling by liquid-chromatography mass spectrometry. We identified a range of plant secondary metabolites, including 32 compounds with known antimicrobial/anthelmintic properties which varied considerably across the different plant samples. These compounds have been shown previously to target multiple aspects of pathogen physiology and metabolism in vitro and in vivo, including inhibition of quorum sensing in bacteria and egg viability in nematodes. The most abundant bioactive compounds were benzoic acid, myricetin, p-coumaric acid, rhamnetin, and rosmarinic acid. Four wild plants (Filipendula ulmaria (L.) Maxim., Prunella vulgaris L., Centuarea nigra L., and Rhinanthus minor L.) and two forage legumes (Medicago sativa L., Trifolium hybridium L.) contained high levels of these compounds. Forage samples from native high-diversity grasslands had a greater abundance of medicinal compounds than samples from agriculturally improved grasslands. Incorporating plants with antibiotic/anthelmintic compounds into livestock feeds may reduce global drug-resistance and preserve the efficacy of last-resort drugs.

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

PubMed

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

2014-01-24

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

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

PubMed Central

2014-01-01

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

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

PubMed Central

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

2011-01-01

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

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.

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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

PubMed

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

2017-07-01

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

Using a health-rating system to evaluate the usefulness of Caenorhabditis elegans as a model for anthelmintic study

PubMed Central

Weaver, Kathryn J.; May, Cassandra J.

2017-01-01

Soil-transmitted helminths (STHs) are intestinal parasitic nematodes that infect humans, and are transmitted through contaminated soil. These nematodes include the large roundworm (Ascaris lumbricoides), whipworm (Trichuris trichiura), and hookworm (Ancylostoma ceylanicum, Ancylostoma duodenale, and Necator americanus). Nearly 1.5 billion people (~24% of the population) worldwide are infected with at least one species of these parasites, burdening the poor, in particular, children and pregnant women. To combat these diseases, the WHO only recognizes four anthelmintic drugs, including the preferred drug, albendazole, for mass drug administration (MDA). These four drugs have a total of two different mechanisms of action, and, as expected, resistance has been observed. This problem calls for new drugs with different mechanisms of action. Although there is precedence for the use of Caenorhabditis elegans (C. elegans), a free-living nematode, as a model for drug screening and anthelmintic testing, their usefulness for such anthelmintic study is not clear as past research has shown that C. elegans did not show a strong response to albendazole, the MDA drug of choice, in comparison with various STHs under similar treatment. To further examine if C. elegans has the potential to be a good model organism for anthelmintic drug study, we employed a health rating scale in order to tease out potential effects of albendazole, and other anthelmintics, that may have been missed using a binary, dead/alive scale. Using the health-rating scale we found that although the worms may have not been dying, they were sick, showing dose responses to anthelmintic drugs, including albendazole, reinforcing C. elegans as a useful model for anthelmintic study. PMID:28632749

[Current situation and developmental trend of anthelmintics by bibliometrics].

PubMed

Zheng, Qi; Chen, Ying; Tian, Li-Guang; Zhou, Xiao-Nong

2009-08-01

To understand the current situation and developmental trend of anthelmintics in English journals through a bibliometric analysis. The literature was searched in Pubmed Database (1997-2007) using the following key words: "drug therapy", "anthelmintics", "humans", "pharmacology", and "parasitology". Access Database was constructed by relative literature through proper data admission method. The relative articles in the database were sorted by different categories, such as "research categories", "publishing year" and "research drug". Data were analyzed by using SPSS software. The annual number of anthelmintics articles increased steadily from year 1997 to 2007. The average number of annual increase was about 6. The major research category was applied research. The major diseases were schistosomiasis, filariasis, ascariasis, echinococcosis and hookworm disease. The number of articles on schistosomiasis was higher than that of other four diseases (P<0.05). The major drugs involved were albendazole, praziquantel, mebendazole, ivermectin and diethylcarbamazine. Articles on the anthelmintics were published mostly in medical journals. From the total database, articles published at the top five journals occupied 5.52%, 4.39%, 3.76%, 3.26%, and 3.26%, respectively. Increasingly importance has been attached to anthelmintics in the last decade. Meanwhile, the researchers focused on a few anthelmintics, and it is inevitable to develop new drugs.

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.

Ethyl 3-oxo-2-(2,5-dioxopyrrolidin-3-yl)butanoate derivatives: Anthelmintic and cytotoxic potentials, antimicrobial and docking studies

NASA Astrophysics Data System (ADS)

Mahmood, Fawad; Jan, Muhammad S.; Ahmad, Sajjad; Rashid, Umer; Ayaz, Muhammad; Ullah, Farhat; Hussain, Fida; Ahmad, Ashfaq; Khan, Arif-ullah; Aasim, Muhammad; Sadiq, Abdul

2017-12-01

The development of novel and more effective drugs is slow asthe resistance produced by pathogens.From the current scenario it can be imagine that this field of research will enter into the pre-antibiotic era. This work aims to study and evaluate the preliminary antibacterial, anthelmintic and cytotoxic potentials of ethyl 3-oxo-2-(2,5-dioxopyrrolidin-3-yl)butanoates.Among all of the four compounds, compound 2 has displayed remarkable potency with MIC values of 0.125, 0.083, 0.073 and 0.109 mg/ml against E. sakazakii, E. coli. S. aureus and K. pneumonia respectively. Compared to etoposide (LC50 9.8 µg/ml), the compounds demonstrated LC50 values from 280 to 765 µg/ml. For anthelmintic assay, three concentrations of each compound and standard drug were studied in determination of time of death of the two species. Excellent anthelmintic activity was observed by all four compounds against P. posthuma and A. gallibetter than standard albendazole. High GOLD fitness score data from docking analysis towards the targets represent better protein–ligand binding affinity and thus indicate a high propensity for all the active compounds to bind to the active site.Thepromisingin-vitro antimicrobial, anthelmintic activity and cytotoxicity data conclusively revealed that these compounds may serve as viable lead compounds for the treatment of bacterial and parasitic infections, and therefore, could help the medicinal chemists to design future chemotherapeutic agents to avoid rapid drug resistance.

Capacity building in anthelmintic drug discovery.

PubMed

Kron, Michael; Yousif, Fouad; Ramirez, Bernadette

2007-10-01

International collaboration in anthelmintic drug discovery holds special challenges compared with local or national discovery projects, and at the same time presents the opportunity to build capacity, forge long lasting inter-institutional relationships and strengthen infrastructure in multinational priority areas. This chapter discusses important issues that should be considered in the context of anthelmintic screening centre development and will give examples (Philippines and Egypt) of the productivity of developing country based screening centres. The positive outcomes of infrastructure building is realised in greater capacities for anthelmintic screening at institutions in the countries where the parasitic diseases are endemic and allows for optimum use of specialised resources for public health priority diseases that may be different from those in Western countries. Support for developing country based screening centres also can help countries optimise product development procedures and policies and can facilitate diffusion of desirable technology in corresponding global regions around the world.

Essential oils of Citrus aurantifolia, Anthemis nobile and Lavandula officinalis: in vitro anthelmintic activities against Haemonchus contortus.

PubMed

Ferreira, Luis Eduardo; Benincasa, Bruno Iglesias; Fachin, Ana Lúcia; Contini, Silvia Helena Taleb; França, Suzelei Castro; Chagas, Ana Carolina Souza; Beleboni, Rene Oliveira

2018-04-25

Infections of sheep with gastrointestinal parasites, especially Haemonchus contortus, have caused serious losses in livestock production, particularly after the emergence of resistance to conventional anthelmintics. The search for new anthelmintic agents, especially those of botanical origin, has grown substantially due to the perspective of less contamination of meat and milk, as well as other advantages related to their cost and accessibility in less developed countries. The aim of this study was to evaluate the in vitro anthelmintic activity of essential oils of the plant species Citrus aurantifolia, Anthemis nobile and Lavandula officinalis against the main developmental stages of the parasite H. contortus. Plant species were selected based on substantial ethnopharmacological information. Analysis of the composition of each oil by gas chromatography coupled to mass spectrometry (GC-MS) demonstrated the presence of limonene (56.37%), isobutyl angelate (29.26%) and linalool acetate (35.97%) as the major constituents in C. aurantifolia, A. nobile and L. officinalis, respectively. Different concentrations of each oil were tested in vitro for their capacity to inhibit egg hatching (EHT), larval development (LDT) and adult worm motility (AWMT) using a multidrug-resistant strain of H. contortus (Embrapa 2010). The IC 50 values obtained for the oils of C. aurantifolia, A. nobile and L. officinalis were 0.694, 0.842 and 0.316 mg/ml in the EHT and 0.044, 0.117 and 0.280 mg/ml in the LDT, respectively. The three oils were able to inhibit adult worm motility completely within the first 8-12 h of observation in the AWMT. The present results demonstrate significant anthelmintic activity of the three oils against the different developmental stages of H. contortus. Furthermore, this study is of ethnopharmacological importance by validating the anthelmintic activity of the oils studied. Although new experiments are necessary, these data contribute to the development of

Single vs. double dose of copper oxide wire particles (COWP) for treatment of anthelmintic resistant Haemonchus contortus in weanling lambs.

PubMed

Schweizer, Nikki M; Foster, Derek M; Knox, William B; Sylvester, Hannah J; Anderson, Kevin L

2016-10-15

Haemonchus contortus parasitism is a major disease of sheep, with these parasites frequently demonstrating multi-drug class anthelmintic resistance. Copper oxide wire particles (COWP) have shown potential as adjuncts or alternatives to anthelmintics in resistant flocks. The purpose of this study was to compare the efficacy of two different COWP treatment regimens or placebo in the control of H. contortus in weaned lambs within a flock historically shown to have multi-drug resistant H. contortus using the DrenchRite ® assay. Data from 43 lambs within 3 treatment groups in a double blind study were included in the experiment. Treatments were administered as a total of 2 boluses, each given on separate occasions (day 0 and day 42), so that each lamb received either 2 placebos, a single dose of 2g COWP followed by placebo, or two doses of 1g COWP. Strongyle-type fecal egg counts (FEC) were performed at initial treatment (day 0), on day 10, at second treatment (day 42), on day 52, and at study end (day 84). At the start of the trial, mean±standard deviation FEC were 1634.4±825.2, 2241.7±1496.8, and 2013.3±1194.2epg for the 2g, 1g×2, and control groups, respectively. At the end of the trial, FEC were 757.1±825.3, 483.4±557.2, and 1660.0±1345.3epg for the 2g, 1g×2, and control groups, respectively. Lambs given a 2g single dose of COWP or a 1g dose of COWP twice had reductions in strongyle-type FEC (p≤0.01) from trial start to trial end, whereas lambs given placebo did not. Average daily gains did not differ significantly among groups. Although copper is potentially toxic to sheep, no signs of toxicity were observed during this trial, which was consistent with similar studies at this treatment dose. The study indicated that administering COWP to lambs at weaning reduced FEC. Copyright © 2016 Elsevier B.V. All rights reserved.

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

USDA-ARS?s Scientific Manuscript database

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

The efficacy of a combined oral formulation of derquantel-abamectin against anthelmintic resistant gastro-intestinal nematodes of sheep in the UK.

PubMed

Geurden, Thomas; Hodge, Andrew; Noé, Laura; Winstanley, Dana; Bartley, David J; Taylor, Mike; Morgan, Colin; Fraser, Sarah J; Maeder, Steven; Bartram, David

2012-10-26

The objective of the present studies was to evaluate the efficacy of a combined formulation (Startect(®) Dual Active Oral Solution for Sheep, Pfizer Animal Health) of derquantel (DQL) and abamectin (ABA) for the treatment of: (1) sheep experimentally infected with a moxidectin (MOX)-resistant isolate of Teladorsagia circumcincta, and (2) multi-drug resistant gastrointestinal nematode parasites under UK field conditions. In the first study, a total of 40 animals were allocated into 4 treatment groups, and were either left untreated or treated with DQL+ABA, MOX or ABA. Faecal samples were collected on days 1-5 and on day 7 after treatment to examine the reduction in faecal egg excretion and to evaluate the egg viability. On day 14 post treatment all animals were euthanised for abomasal worm counts. There was a 100% reduction in geometric mean worm counts for the DQL+ABA treated animals compared to the untreated control animals (P<0.0001), whereas the percentage reduction in worm counts for the MOX- (P>0.05) and ABA-treated (P=0.0004) animals was 12.4% and 71.8%, respectively. The data from the egg hatch assay (EHA) indicated that in the MOX-treated and the ABA-treated animals, the majority of the eggs hatched after treatment. In the field study, performed on four farms, animals were allocated into 6 groups of 11-15 animals each in order to conduct a faecal egg count reduction test (FECRT), based on arithmetic mean egg counts. One group of animals remained untreated, whereas the other animals were treated with DQL+ABA, MOX, fenbendazole (FBZ), levamisole (LV) or ivermectin (IVM). On each of the farms the reduction in egg excretion after treatment with FBZ, LV or IVM was below 95.0%, indicating anthelmintic resistance. The efficacy of DQL+ABA ranged from 99.1 to 100%, yielding significantly lower egg counts compared to the untreated control group (P ≤ 0.003). For MOX the egg counts were significantly (P ≤ 0.003) lower compared to the untreated group at each farm

Drug Resistance in Human Helminths: Current Situation and Lessons from Livestock

PubMed Central

Geerts, S.; Gryseels, B.

2000-01-01

In this review the available reports on drug resistance in human helminths, particularly hookworms and schistosomes, are critically analyzed. The experiences with helminths of livestock are then reviewed, in particular the factors contributing to the development of anthelmintic resistance, the mechanisms and genetics of resistance to various anthelmintic classes, and the methods available for detection. These experiences appear to be worryingly similar and relevant to the potential development of drug resistance in human helminths. Recommendations to reduce its risks are suggested. PMID:10755998

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

Anthelmintic, Antibacterial and Cytotoxicity Activity of Imidazole Alkaloids from Pilocarpus microphyllus Leaves.

PubMed

Rocha, Jefferson A; Andrade, Ivanilza M; Véras, Leiz M C; Quelemes, Patrick V; Lima, David F; Soares, Maria J S; Pinto, Pedro L S; Mayo, Simon J; Ivanova, Galya; Rangel, Maria; Correia, Manuela; Mafud, Ana Carolina; Mascarenhas, Yvonne P; Delerue-Matos, Cristina; de Moraes, Josué; Eaton, Peter; Leite, José R S A

2017-04-01

Pilocarpus microphyllus Stapf ex Wardlew (Rutaceae), popularly known as jaborandi, is a plant native to the northern and northeastern macroregions of Brazil. Several alkaloids from this species have been isolated. There are few reports of antibacterial and anthelmintic activities for these compounds. In this work, we report the antibacterial and anthelmintic activity of five alkaloids found in P. microphyllus leaves, namely, pilosine, epiisopilosine, isopilosine, epiisopiloturine and macaubine. Of these, only anthelmintic activity of one of the compounds has been previously reported. Nuclear magnetic resonance, HPLC and mass spectrometry were combined and used to identify and confirm the structure of the five compounds. As regards the anthelmintic activity, the alkaloids were studied using in vitro assays to evaluate survival time and damaged teguments for Schistosoma mansoni adult worms. We found epiisopilosine to have anthelmintic activity at very low concentrations (3.125 μg mL -1 ); at this concentration, it prevented mating, oviposition, reducing motor activity and altered the tegument of these worms. In contrast, none of the alkaloids showed antibacterial activity. Additionally, alkaloids displayed no cytotoxic effect on vero cells. The potent anthelmintic activity of epiisopilosine indicates the potential of this natural compound as an antiparasitic agent. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Anthelmintic Potential of Thymoquinone and Curcumin on Fasciola gigantica

PubMed Central

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

2017-01-01

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

Anthelmintic Potential of Thymoquinone and Curcumin on Fasciola gigantica.

PubMed

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

2017-01-01

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

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. © S.N. Chiejina et al., published by EDP Sciences, 2015.

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

Resistance delaying strategies on UK sheep farms: A cost benefit analysis.

PubMed

Learmount, Jane; Glover, Mike J; Taylor, Mike A

2018-04-30

UK guidelines for the sustainable control of parasites in sheep (SCOPS) were formulated with the primary aim of delaying development of anthelmintic resistance (AR) on UK sheep farms. Promoting their use requires the engagement and commitment of stakeholders. An important driver for behavioural change in sheep farmers is evidence of economic benefits. A recent evaluation of SCOPS guidance in practice demonstrated a significant reduction in anthelmintic use, suggesting economic benefits through a direct reduction in product and labour costs. However, in order to maintain production, a range of alternative control strategies are advised, resulting in additional costs to farmers and so a full cost benefit analysis of best practice management was undertaken. We allocated financial values to the management recommendations described in the SCOPS technical manual. Benefits were calculated using data for production variables and anthelmintic use measured during studies to evaluate the effect of SCOPS recommendations on 16 UK sheep farms and from other published work. As SCOPS control is not prescriptive and a range of different diagnostics are available, best and worst case scenarios were presented, comparing the cheapest methods (e.g. egg counts without larval culture) and management situations (e.g closed flocks not requiring quarantine treatments) with the most laborious and expensive. Simulations were run for farms with a small, medium or large flock (300; 1000; 1900 ewes) as well as comparing scenarios with and without potential production benefits from using effective wormers. Analysis demonstrated a moderate cost for all farms under both scenarios when production benefits were not included. A cost benefit was demonstrated for medium and large farms when production benefits were included and the benefit could be perceived as significant in the case of the large farms for the best case scenario (>£5000 per annum). Despite a significant potential reduction in

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

PubMed

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

2006-06-01

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

Anthelmintic activity of Croton zehntneri and Lippia sidoides essential oils.

PubMed

Camurça-Vasconcelos, A L F; Bevilaqua, C M L; Morais, S M; Maciel, M V; Costa, C T C; Macedo, I T F; Oliveira, L M B; Braga, R R; Silva, R A; Vieira, L S

2007-09-30

Because of the development of anthelmintic resistant populations, the search for new drugs is essential to maintain the productivity of small ruminants. The aim of this study was to evaluate the anthelmintic activity of Croton zehntneri and Lippia sidoides essential oils and their major constituents, anethole and thymol. The effects of these oils and their constituents were determined by in vitro assays with the eggs and larvae of the sheep gastrointestinal nematode Haemonchus contortus. The two essential oils were evaluated on intestinal nematodes of mice at 800 mg kg(-1) dose. In the last experiment, the mice were treated with larger doses of L. sidoides, 1200 and 1600 mg kg(-1). The essential oils and their constituents prevented more than 98% of the H. contortus eggs from hatching at a concentration of 1.25 mg ml(-1) and inhibited more than 90% of H. contortus larval development at a concentration of 10 mg ml(-1). At a concentration of 800 mg kg(-1), the two essential oils were 46.3% and 11.64% effective against Syphacia obvelata and Aspiculuris tetraptera. At 1200 and 1600 mg kg(-1), L. sidoides essential oil's efficacy on the mouse worm burden was 57.6% and 68.9%, respectively. The fact that L. sidoides essential oil was almost 70% effective against mouse intestinal nematodes indicates it should be evaluated against gastrointestinal nematodes of sheep and goats.

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

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

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.

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

USDA-ARS?s Scientific Manuscript database

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

The Anthelmintic Ingredient Moxidectin Negatively Affects Seed Germination of Three Temperate Grassland Species

PubMed Central

Eichberg, Carsten; Wohde, Manuel; Müller, Kerstin; Rausch, Anja; Scherrmann, Christina; Scheuren, Theresa; Düring, Rolf-Alexander; Donath, Tobias W.

2016-01-01

In animal farming, anthelmintics are regularly applied to control gastrointestinal nematodes. There is plenty of evidence that also non-target organisms, such as dung beetles, are negatively affected by residues of anthelmintics in faeces of domestic ungulates. By contrast, knowledge about possible effects on wild plants is scarce. To bridge this gap of knowledge, we tested for effects of the common anthelmintic formulation Cydectin and its active ingredient moxidectin on seed germination. We conducted a feeding experiment with sheep and germination experiments in a climate chamber. Three wide-spread plant species of temperate grasslands (Centaurea jacea, Galium verum, Plantago lanceolata) were studied. We found significant influences of both, Cydectin and moxidectin, on germination of the tested species. Across species, both formulation and active ingredient solely led to a decrease in germination percentage and synchrony of germination and an increase in mean germination time with the formulation showing a more pronounced response pattern. Our study shows for the first time that anthelmintics have the potential to negatively affect plant regeneration. This has practical implications for nature conservation since our results suggest that treatments of livestock with anthelmintics should be carefully timed to not impede endozoochorous seed exchange between plant populations. PMID:27846249

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

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

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

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

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

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

PubMed

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

2009-01-22

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

Ethnobotanical survey of medicinal plants used as anthelmintic remedies in Gabon.

PubMed

Bajin Ba Ndob, Idensi; Mengome, Line Edwige; Bourobou Bourobou, Henri-Paul; Lossangoye Banfora, Yvon; Bivigou, Francis

2016-09-15

In this article, we report on an ethnobotanical survey realized at the Peyrie market in Libreville on Gabonese medicinal plants used to treat helminthiasis. While several alerts about cases of resistance to conventional anthelmintic treatments are causing to fear a public and animal health issue, the search for new sources of active compounds becomes an urgent issue. In Gabon like in many developing countries, people regularly turn to traditional medicine in case of physical ailments and/or spiritual healing therapies. To determine which medicinal plants are traditionally used by the populations of Libreville to fight against nematodes, medicinal plant traders were interviewed with standardized questionnaires. The surveys were conducted in the main market of Libreville. Ethnobotanical data such as frequency and percentage of families, species, administrations pathways, modes of preparations and parts of plants used were analyzed and summarized. Thirty-four (34) traders were interviewed belonging to five (5) different ethnic groups. Twenty-four 24 plants used to treat intestinal, cutaneous and ocular helminthiasis were listed. The healers mainly turned towards to ligneous species. The parts of the plant used are mostly leaves and trunk bark. Most of the traditional remedies are prepared directly in water and four (4) principal routes were used for administration namely, oral, rectal, ocular and dermal. This study allowed us to list anthelmintic species which will be subjected to a series of chemical and pharmacological assays. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Anthelmintic activity of Chenopodium album (L) and Caesalpinia crista (L) against trichostrongylid nematodes of sheep.

PubMed

Jabbar, Abdul; Zaman, Muhammad Arfan; Iqbal, Zafar; Yaseen, Muhammad; Shamim, Asim

2007-10-08

The present study was carried out to determine the anthelmintic activity of Caesalpinia crista (L.) (Fabaceae) seed kernel and Chenopodium album (L.) (Chenopodiaceae) whole plant in order to justify their traditional use in veterinary medicine. In vitro anthelmintic activity of crude aqueous methanolic extract (AME) of both the plants was determined using mature Haemonchus contortus and their eggs in adult motility assay and egg hatch test, respectively. In vivo anthelmintic activity was evaluated in sheep naturally infected with mixed species of gastrointestinal nematodes by administering crude powder (CP) and AME in increasing doses (1.0-3.0 g/kg). Both plants exhibited dose- and time-dependent anthelmintic effects by causing mortality of worms and inhibition of egg hatching. Caesalpinia crista (LC50=0.134 mg/mL) was found to be more potent than Chenopodium album (LC50=0.449 mg/mL) in egg hatch test. In vivo, maximum reduction in eggs per gram (EPG) of faeces was recorded as 93.9 and 82.2% with Caesalpinia crista and Chenopodium album AME at 3.0 g/kg on day 13 and 5 post-treatment, respectively. Levamisole (7.5 mg/kg), a standard anthelmintic agent, showed 95.1-95.6% reduction in EPG. These data show that both Caesalpinia crista and Chenopodium album possess anthelmintic activity in vitro and in vivo, thus, justifying their use in the traditional medicine system of Pakistan.

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

PubMed

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

2017-01-01

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

Nippostronglylus brasiliensis infection in the rat: effect of iron and protein deficiency and dexamethasone on the efficacy of benzimidazole anthelmintics.

PubMed Central

Duncombe, V M; Bolin, T D; Davis, A E; Kelly, J D

1977-01-01

Malnutrition, anaemia, and gut parasites are commonly interrelated. Using the Nippostrongylus brasiliensis-rat model, the effect of iron and protein deficiency on the efficacy of benzimidazole anthelmintics was studied. It was demonstrated that the anthelmintics mebendazole and fenbendazole were significantly less effective in eradicating parasites when animals were deficient in iron and protein. This decreased efficacy of anthelmintics in iron and protein deficiency could not be overcome by intraperitoneal administration of the drug. Since nutritional deficiencies may act via impairment of the immune response, anthelmintic efficacy was determined in adequately nourished rats treated with the immunosuppressive drug dexamethasone. A similar decrease in efficacy of mebendazole was shown when these animals were treated with dexamethasone. Thus it is possible that lowered anthelmintic efficacy in iron and protein deficient animals is mediated by immune deficiency. These findings may be relevant to anthelmintic programmes in malnourished communities. PMID:590849

A field evaluation of anthelmintics for control of cyathostomes of horses in Brazil.

PubMed

Pereira, M C; Kohek Júnior, I; Campos, R; Lima, S B; Foz, R P

1991-03-01

The anthelmintic efficacy of ivermectin (IVM), piperazine citrate (PPZ) and fenbendazole (FBZ) alone, and combinations of FBZ with varying dosages of PPZ, was evaluated for the control of strongyles of Mangalarga equids. In all cases of positive strongly egg counts per gram of faeces (EPG) before and after treatment, pure populations of cyathostome larvae with eight gut cells were consistently observed in faecal cultures. The faecal egg count reductions (FECR) were evaluated between Day 7 and Day 56 post-treatment. Significant differences (P less than or equal to 0.05) were found between Day 7 and Day 49 when comparing the mean EPG values of IVM with those of the other anthelmintics. PPZ alone and the combination of FBZ (7.5 mg kg-1) and PPZ (55 mg base kg-1) did not show significant differences during the trial; both groups exhibiting an FECR of greater than 90% between Day 7 and Day 30. Horses treated with the combinations of FBZ (7.5 mg kg-1) and PPZ at either 40 or 25 mg base kg-1, and with FBZ alone at either 7.5 or 15 mg kg-1, showed an FECR of less than 90% 2 weeks after treatment. The emergence of a degree of resistance of strongyles to FBZ and PPZ in a segment of the cyathostomes in this population is suggested.

[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

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. Copyright © 2016 Elsevier B.V. All rights reserved.

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

USDA-ARS?s Scientific Manuscript database

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

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

PubMed Central

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

2017-01-01

Background: Helminths is a endoparasites that cause the major losses for profitable sheep production in Brazil. The increased development of resistant strains of endoparasites have enforced the search for sustainable alternatives. The aim of this paper was to provide information about endoparasites control with banana leaves in infected sheep as alternative control strategies and see its viability. Materials and Methods: In this study, we performed two trials to investigate the anthelmintic properties of banana leaves on endoparasites in sheep. In Trial 1, twelve sheep were artificially infected with Trichostrongylus colubriformis; in Trial 2, eleven sheep were artificially infected with Haemonchus contortus. Clinical examinations, packed cell volume, total protein, faecal egg counts (FECs) and egg hatchability tests (EHTs) were performed. At the end of the trials, the sheep were humanely slaughtered, and total worm counts were performed. Results: In Trial 1 and 2, no significant FEC decreases were note but significant diference in EHTs were observed. Total worm counts, clinical and haematological parameters did not reveal significant changes between the treatment and control groups. These results suggest that feeding dried ground banana plant leaves to sheep may reduce the viability of Trichostrongylus colubriformis eggs, and this anthelmintic activity is potentially exploitable as part of an integrated parasite management programme. Conclusion: However, further investigation is needed to establish the optimal dosage, develop a convenient delivery form and confirm the economic feasibility of using banana plantation byproducts as feed for ruminant species. Abbreviations: Coproculture test (CT)., Faecal egg count (FEC)., Egg hatchability test (EHT) PMID:28480391

Anthelmintic activity of Trianthema portulacastrum L. and Musa paradisiaca L. against gastrointestinal nematodes of sheep.

PubMed

Hussain, Altaf; Khan, Muhammad Nisar; Iqbal, Zafar; Sajid, Muhammad Sohail; Khan, Muhammad Kasib

2011-06-30

Evaluation of anthelmintic effects of Trianthema (T.) portulacastrum L. (Aizoaceae) whole plant and Musa (M.) paradisiaca L. (Musaceae) leaves against prevalent gastrointestinal worms of sheep was done that may justify their traditional use in veterinary clinical medicine. In vitro anthelmintic activity of the crude aqueous methanolic extract (CAME) of both the plants was determined using mature female Haemonchus (H.) contortus and their eggs in adult motility assay (AMA) and egg hatch test (EHT), respectively. In vivo anthelmintic activity of crude powder (CP) and CAME in increasing doses (1.0-8.0 g kg(-1)) was determined in sheep naturally infected with mixed species of nematodes using fecal egg count reduction test (FECRT) and larval counts. The study design also included untreated as well as treated controls. Fecal egg count reduction and larval counts from coprocultures were performed pre- and post-treatments to assess the anthelmintic activity of the plants. CAME of T. portulacastrum and M. paradisiaca showed a strong in vitro anthelmintic activity and pronounced inhibitory effects on H. contortus egg hatching as observed through AMA and EHT, respectively. Both plants exhibited dose and time dependent anthelmintic effects on live worms as well as egg hatching. M. paradisiaca (LC(50)=2.13 μg mL(-1)) was found to be more potent than T. portulacastrum (LC(50)=2.41 μg mL(-1)) in EHT. However, in vivo, maximum reduction in eggs per gram (EPG) of faeces was recorded as 85.6% and 80.7% with CAME of T. portulacastrum and M. paradisiaca at 8.0 g kg(-1) on 15th day post-treatment, respectively as compared to that of Levamisole (7.5 mg kg(-1)) that caused 97.0% reduction in EPG. All the species of gastrointestinal nematodes (GINs), i.e. Haemonchus contortus, Trichostronglyus spp., Oesophagostomum columbianum and Trichuris ovis which were prevalent, found susceptible (P<0.01) to the different doses of CP and CAME of both plants. The data showed that both T

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 ...

Evaluation of anthelmintic activity of Iris hookeriana against gastrointestinal nematodes of sheep.

PubMed

Tariq, K A; Chishti, M Z; Ahmad, F; Shawl, A S; Tantray, M A

2008-06-01

The objective of this study was to evaluate the anthelmintic efficacy of Iris hookeriana Linn. rhizome against gastrointestinal nematodes of sheep. A worm motility inhibition assay was used for in vitro study and a faecal egg count reduction assay was used for an in vivo study. The in vitro study revealed anthelmintic effects of crude aqueous extracts and crude ethanolic extracts on live Trichuris ovis worms (P < or = 0.05) as evident from their paralysis and/or death at 8 h after exposure. The aqueous extracts of I. hookeriana resulted in a mean worm motility inhibition of 54.0%, while ethanolic extracts resulted in a mean worm motility inhibition of 84.6%. The mean mortality index of aqueous extracts was 0.55, while for ethanolic extracts it was 0.85. The lethal concentration 50 for aqueous extracts was 0.45 mg ml- 1 and for ethanolic extracts it was 0.15 mg ml- 1. The in vivo anthelmintic activity of aqueous and ethanolic extracts of I. hookeriana in sheep naturally infected with mixed species of gastrointestinal nematodes demonstrated a maximum (45.62%) egg count reduction in sheep treated with ethanolic extracts at 2 g kg- 1 body weight on day 10 after treatment, closely followed by ethanolic extracts at 1 g kg- 1 body weight on day 10 after treatment (43.54% egg count reduction). The aqueous extracts resulted in a maximum of 31.53% reduction in faecal egg counts on day 10 after treatment with 1 g kg- 1 body weight. Thus ethanolic extracts exhibited greater anthelmintic activity under both in vitro and in vivo conditions; this could be due to the presence of alcohol-soluble active ingredients in I. hookeriana. From the present study it can be suggested that I. hookeriana rhizome exhibited significant anthelmintic activity against gastrointestinal nematodes of sheep and has the potential to contribute to the control of gastrointestinal nematode parasites of small ruminants.

A cost-benefit analysis of pre- and post-lambing anthelmintic treatments to twin-bearing ewes on commercial farms in the southern North Island of New Zealand.

PubMed

Garland, C B; Leathwick, D M

2015-07-01

lower net benefit than a CRC containing albendazole administered pre-lambing (p<0.05). A positive financial return resulting from the anthelmintic treatment of adult ewes around lambing is neither consistent nor predictable, and is often not achieved. Given that the additional costs of accelerating the development of anthelmintic resistance were not included in these calculations, farmers need to consider carefully the merits of administering anthelmintics to ewes around lambing.

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

USDA-ARS?s Scientific Manuscript database

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

The Emergence of Resistance to the Benzimidazole Anthlemintics in Parasitic Nematodes of Livestock Is Characterised by Multiple Independent Hard and Soft Selective Sweeps

PubMed Central

Redman, Elizabeth; Whitelaw, Fiona; Tait, Andrew; Burgess, Charlotte; Bartley, Yvonne; Skuce, Philip John; Jackson, Frank; Gilleard, John Stuart

2015-01-01

Anthelmintic resistance is a major problem for the control of parasitic nematodes of livestock and of growing concern for human parasite control. However, there is little understanding of how resistance arises and spreads or of the “genetic signature” of selection for this group of important pathogens. We have investigated these questions in the system for which anthelmintic resistance is most advanced; benzimidazole resistance in the sheep parasites Haemonchus contortus and Teladorsagia circumcincta. Population genetic analysis with neutral microsatellite markers reveals that T. circumcincta has higher genetic diversity but lower genetic differentiation between farms than H. contortus in the UK. We propose that this is due to epidemiological differences between the two parasites resulting in greater seasonal bottlenecking of H. contortus. There is a remarkably high level of resistance haplotype diversity in both parasites compared with drug resistance studies in other eukaryotic systems. Our analysis suggests a minimum of four independent origins of resistance mutations on just seven farms for H. contortus, and even more for T. circumincta. Both hard and soft selective sweeps have occurred with striking differences between individual farms. The sweeps are generally softer for T. circumcincta than H. contortus, consistent with its higher level of genetic diversity and consequent greater availability of new mutations. We propose a model in which multiple independent resistance mutations recurrently arise and spread by migration to explain the widespread occurrence of resistance in these parasites. Finally, in spite of the complex haplotypic diversity, we show that selection can be detected at the target locus using simple measures of genetic diversity and departures from neutrality. This work has important implications for the application of genome-wide approaches to identify new anthelmintic resistance loci and the likelihood of anthelmintic resistance emerging

Anthelmintic Therapy Modifies the Systemic and Mycobacterial Antigen-Stimulated Cytokine Profile in Helminth-Latent Mycobacterium tuberculosis Coinfection.

PubMed

Anuradha, Rajamanickam; Munisankar, Saravanan; Bhootra, Yukthi; Dolla, Chandrakumar; Kumaran, Paul; Nutman, Thomas B; Babu, Subash

2017-04-01

Helminth infections are known to modulate cytokine responses in latent tuberculosis (LTB). However, very few studies have examined whether this modulation is reversible upon anthelmintic therapy. We measured the systemic and mycobacterial (TB) antigen-stimulated levels of type 1, type 2, type 17, and regulatory cytokines in individuals with LTB and with or without coexistent Strongyloides stercoralis infection before and after anthelmintic therapy. Our data reveal that individuals with LTB and coexistent S. stercoralis infection have significantly lower levels of systemic and TB antigen-stimulated type 1 (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-2 [IL-2]) and type 17 (IL-17A and/or IL-17F) cytokines and significantly higher levels of systemic but not TB antigen-stimulated type 2 (IL-4 and IL-5) and regulatory (transforming growth factor beta [TGF-β]) cytokines. Anthelmintic therapy resulted in significantly increased systemic levels of type 1 and/or type 17 cytokines and in significantly decreased systemic levels of type 2 and regulatory (IL-10 and TGF-β) cytokines. In addition, anthelmintic therapy resulted in significantly increased TB antigen-stimulated levels of type 1 cytokines only. Our data therefore confirm that the modulation of systemic and TB antigen-stimulated cytokine responses in S. stercoralis -LTB coinfection is reversible (for the most part) by anthelmintic treatment. Copyright © 2017 American Society for Microbiology.

Synthesis and in vitro anthelmintic properties of some new dithiaarsanes.

PubMed

Loiseau, P M; Lubert, P; Wolf, J G

1999-11-01

Fifteen new trivalent organoarsenicals were synthesized and evaluated for anthelmintic properties on three in vitro models, infective larvae of the filaria Molinema dessetae, infective larvae of an intestinal nematode, Nippostrongylus brasiliensis and adults and larvae of Rhabditis pseudoelongata a free living nematode. On the M. dessetae model, the most active compound after a 24 h incubation period had an EC50 of 0.02 mumol/l (compound 3a). Twelve compounds had an EC50 lower than 1 mumol/l whereas potassium melarsonyl exhibited an EC50 of 45.6 mumol/l. After 7 days incubation time, compound 1d had an EC50 of 2 nmol/l. On the N. brasiliensis model, compound 1d was also the most efficient after a 4 day incubation period (EC50 of 1 mumol/l). This compound was 100 times more active than potassium melarsonyl used as a reference compound. Nevertheless, no compound had an EC50 less than 100 mumol/l on Rhabditis pseudoelongata. Concerning the effect of dithiol ligands on the anthelmintic activity of these trivalent organoarsenicals on M. dessetae and N. brasiliensis, 2,2'-dimercaptodiethyloxide was more efficient as dithiol ligand than 1,3-dimercaptopropane which was more efficient than 1,2-dimercaptoethane. Moreover, the para-amino haptophore was more efficient than the melaminyl haptophore. These results showed that the use of new dithiol ligands for trivalent arsenicals enhanced greatly the anthelmintic activity compared with potassium melarsonyl.

Pooling sheep faecal samples for the assessment of anthelmintic drug efficacy using McMaster and Mini-FLOTAC in gastrointestinal strongyle and Nematodirus infection.

PubMed

Kenyon, Fiona; Rinaldi, Laura; McBean, Dave; Pepe, Paola; Bosco, Antonio; Melville, Lynsey; Devin, Leigh; Mitchell, Gillian; Ianniello, Davide; Charlier, Johannes; Vercruysse, Jozef; Cringoli, Giuseppe; Levecke, Bruno

2016-07-30

In small ruminants, faecal egg counts (FECs) and reduction in FECs (FECR) are the most common methods for the assessment of intensity of gastrointestinal (GI) nematodes infections and anthelmintic drug efficacy, respectively. The main limitation of these methods is the time and cost to conduct FECs on a representative number of individual animals. A cost-saving alternative would be to examine pooled faecal samples, however little is known regarding whether pooling can give representative results. In the present study, we compared the FECR results obtained by both an individual and a pooled examination strategy across different pool sizes and analytical sensitivity of the FEC techniques. A survey was conducted on 5 sheep farms in Scotland, where anthelmintic resistance is known to be widespread. Lambs were treated with fenbendazole (4 groups), levamisole (3 groups), ivermectin (3 groups) or moxidectin (1 group). For each group, individual faecal samples were collected from 20 animals, at baseline (D0) and 14 days after (D14) anthelmintic administration. Faecal samples were analyzed as pools of 3-5, 6-10, and 14-20 individual samples. Both individual and pooled samples were screened for GI strongyle and Nematodirus eggs using two FEC techniques with three different levels of analytical sensitivity, including Mini-FLOTAC (analytical sensitivity of 10 eggs per gram of faeces (EPG)) and McMaster (analytical sensitivity of 15 or 50 EPG).For both Mini-FLOTAC and McMaster (analytical sensitivity of 15 EPG), there was a perfect agreement in classifying the efficacy of the anthelmintic as 'normal', 'doubtful' or 'reduced' regardless of pool size. When using the McMaster method (analytical sensitivity of 50 EPG) anthelmintic efficacy was often falsely classified as 'normal' or assessment was not possible due to zero FECs at D0, and this became more pronounced when the pool size increased. In conclusion, pooling ovine faecal samples holds promise as a cost-saving and efficient

Dry selection and wet evaluation for the rational discovery of new anthelmintics

NASA Astrophysics Data System (ADS)

Marrero-Ponce, Yovani; Castañeda, Yeniel González; Vivas-Reyes, Ricardo; Vergara, Fredy Máximo; Arán, Vicente J.; Castillo-Garit, Juan A.; Pérez-Giménez, Facundo; Torrens, Francisco; Le-Thi-Thu, Huong; Pham-The, Hai; Montenegro, Yolanda Vera; Ibarra-Velarde, Froylán

2017-09-01

Helminths infections remain a major problem in medical and public health. In this report, atom-based 2D bilinear indices, a TOMOCOMD-CARDD (QuBiLs-MAS module) molecular descriptor family and linear discriminant analysis (LDA) were used to find models that differentiate among anthelmintic and non-anthelmintic compounds. Two classification models obtained by using non-stochastic and stochastic 2D bilinear indices, classified correctly 86.64% and 84.66%, respectively, in the training set. Equation 1(2) correctly classified 141(135) out of 165 [85.45%(81.82%)] compounds in external validation set. Another LDA models were performed in order to get the most likely mechanism of action of anthelmintics. The model shows an accuracy of 86.84% in the training set and 94.44% in the external prediction set. Finally, we carry out an experiment to predict the biological profile of our 'in-house' collections of indole, indazole, quinoxaline and cinnoline derivatives (∼200 compounds). Subsequently, we selected a group of nine of the theoretically most active structures. Then, these chemicals were tested in an in vitro assay and one good candidate (VA5-5c) as fasciolicide compound (100% of reduction at concentrations of 50 and 10 mg/L) was discovered.

Screening of plant extracts for anthelmintic activity against Dactylogyrus intermedius (Monogenea) in goldfish (Carassius auratus).

PubMed

Huang, Ai-Guo; Yi, Yang-Lei; Ling, Fei; Lu, Lin; Zhang, Qi-Zhong; Wang, Gao-Xue

2013-12-01

With the aim of finding natural anthelmintic agents against Dactylogyrus intermedius (Monogenea) in goldfish (Carassius auratus), 26 plants were screened for antiparasitic properties using in vivo anthelmintic efficacy assay. The results showed that Caesalpinia sappan, Lysima chiachristinae, Cuscuta chinensis, Artemisia argyi, and Eupatorium fortunei were found to have 100% anthelmintic efficacy at 125, 150, 225, 300, and 500 mg L(-1) after 48 h of exposure. Crude extract of the five plants were further partitioned with petroleum ether, chloroform, ethyl acetate, methanol, and water to obtain anthelmintically active fractions with various polarity. Among these fractions tested, the ethyl acetate extract of L. chiachristinae was found to be the most effective with a 50% effective concentration (EC50) value of 5.1 mg/L after 48 h of exposure. This was followed by ethyl acetate extract of C. chinensis (48 h-EC50 = 8.5 mg L(-1)), chloroform extracts of C. sappan (48 h-EC50 = 15.6 mg L(-1)), methanol extract of C. chinensis (48 h-EC50 = 15.9 mg L(-1)), and chloroform and petroleum ether extract of L. chiachristinae (EC50 values of 17.2 and 21.1 mg/L, respectively), suggesting that these plants, as well as the active fractions, provide potential sources of botanic drugs for the control of D. intermedius in aquaculture.

An Update Review on the Anthelmintic Activity of Bitter Gourd, Momordica charantia.

PubMed

Poolperm, Sutthaya; Jiraungkoorskul, Wannee

2017-01-01

Momordica charantia (Family: Cucurbitales ), as known as bitter melon or gourd, is a daily consumption as food and traditional medicinal plant in Southeast Asia and Indo-China. It has been shown to possess anticancer, antidepressant, antidiabetic, anti-inflammatory, antimicrobial, antiobesity, antioxidant, and antiulcer properties. Its common phytochemical components include alkaloids, charantin, flavonoids, glycosides, phenolics, tannins, and terpenoids. This plant is rich in various saponins including momordicin, momordin, momordicoside, karavilagenin, karaviloside, and kuguacin, all of which have been reported to contribute to its remedial properties including antibacterial, antifungal, antiviral, and antiparasitic infections. Based on established literature on the anthelmintic activity of M. charantia and possible mode of action, this review article has attempted to compile M. charantia could be further explored for the development of potential anthelmintic drug.

Phenolics and Terpenoids; the Promising New Search for Anthelmintics: A Critical Review.

PubMed

Mukherjee, Niladri; Mukherjee, Suprabhat; Saini, Prasanta; Roy, Priya; Sinha Babu, Santi P

2015-02-26

Ailments caused by helminth parasites are global causing different types of clinical complications with permanent and long term morbidity in humans. Although huge advances have been made in medical sciences the effectiveness of available anthelmintics are still quite limited. Starting from the 50's, most importance was given to synthetic compounds for developing remedies from them, however, the traditional knowledge of medicine of different countries continued to provide us clues against this widespread health problem. Natural products or structural analogs with diverse structures are always been the major sources for discovering new therapeutics and in recent past different active compounds have also been identified form these plant sources having anthelmintic properties. Although compounds of diverse chemical nature and classes were identified most active ones belong to either phenol or terpene in broad chemical nature. The mechanism of action of these phytotherapeutics is usually multi-targeted and can act against the helminth parasites through diverse spectrum of activities. In this reviewwe summarized the effective anthelmintics belong to either phenolics or terpenoids and highlighted the major way of their effectiveness. This also highlights the recent development of new therapeutic strategies against helminth parasites in the light of recent advances of knowledge. In addition, developing efficient strategies to promote apoptosis and disturbing redox status in them by natural products can provide us a clue in antifilarial drug developmental research and crucial unmet medical need.

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

PubMed

Jamkhande, Prasad G; Barde, Sonal R

2014-01-01

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. 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. 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). 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.

An Update Review on the Anthelmintic Activity of Bitter Gourd, Momordica charantia

PubMed Central

Poolperm, Sutthaya; Jiraungkoorskul, Wannee

2017-01-01

Momordica charantia (Family: Cucurbitales), as known as bitter melon or gourd, is a daily consumption as food and traditional medicinal plant in Southeast Asia and Indo-China. It has been shown to possess anticancer, antidepressant, antidiabetic, anti-inflammatory, antimicrobial, antiobesity, antioxidant, and antiulcer properties. Its common phytochemical components include alkaloids, charantin, flavonoids, glycosides, phenolics, tannins, and terpenoids. This plant is rich in various saponins including momordicin, momordin, momordicoside, karavilagenin, karaviloside, and kuguacin, all of which have been reported to contribute to its remedial properties including antibacterial, antifungal, antiviral, and antiparasitic infections. Based on established literature on the anthelmintic activity of M. charantia and possible mode of action, this review article has attempted to compile M. charantia could be further explored for the development of potential anthelmintic drug. PMID:28503051

The anthelmintic efficacy of natural plant cysteine proteinases against the equine tapeworm, Anoplocephala perfoliata in vitro.

PubMed

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

2016-09-01

Papaya latex has been demonstrated to be an efficacious anthelmintic against murine, porcine, ovine and canine nematode parasites, and even those infecting poultry, and it has some efficacy against rodent cestodes. The active ingredients of papaya latex are known to be cysteine proteinases (CPs). The experiments described in this paper indicate that CPs in papaya latex, and also those in pineapples, are highly efficacious against the equine cestode Anoplocephala perfoliata in vitro, by causing a significant reduction in motility leading to death of the worms. The susceptibility of A. perfoliata to damage by CPs was considerably greater than that of the rodent cestodes Hymenolepis diminuta and H. microstoma. Our results are the first to report anthelmintic efficacy of CPs against an economically important equine helminth. Moreover, they provide further evidence that the spectrum of activity of CPs is not restricted to nematodes and support the idea that these plant-derived enzymes can be developed into useful broad-spectrum anthelmintics.

Concurrent treatment with a macrocyclic lactone and benzimidazole provides season long performance advantages in grazing cattle harboring macrocyclic lactone resistant nematodes.

PubMed

Edmonds, M D; Vatta, A F; Marchiondo, A A; Vanimisetti, H B; Edmonds, J D

2018-03-15

In 2013, a 118-day study was initiated to investigate the efficacy of concurrent treatment at pasture turnout with an injectable macrocyclic lactone with activity up to 28 days and an oral benzimidazole, referred to as "conventional" anthelmintics, when compared to treatment with conventional macrocyclic lactone alone or an injectable macrocyclic lactone with extended activity of 100 days or longer. A group of 210 steers were obtained from a ranch in California and transported to Idaho, USA. A total of 176 steers with the highest fecal egg counts were blocked by pre-treatment body weights and pasture location. A total of 44 pasture paddocks were assigned with 4 steers per paddock with 12 paddocks per therapeutic treatment group and 8 paddocks per controls. The four treatments were injectable doramectin (Dectomax ® , Zoetis Inc., 0.2 mg kg -1 BW, SC), injectable doramectin concurrently with oral albendazole (Valbazen ® , Zoetis Inc., 10 mg kg -1 BW, PO), extended release injectable eprinomectin (LongRange™, Merial Limited, 1 mg kg -1 BW, SC) or saline. Cattle were individually weighed and sampled for fecal egg count on Days 0, 31/32, 61, 88, and 117/118 with an additional fecal sample on Day 14. At conclusion, one steer per paddock was euthanized for nematode recovery. The results from the first 32 days found evidence of macrocyclic lactone resistance against injectable doramectin and extended release eprinomectin. During this period the concurrent therapy provided nearly 100% efficacy based on fecal egg count reduction and a 19.98% improvement in total weight gain compared to controls (P = 0.039). At the conclusion of the 118-day study and past the approved efficacy for the conventional anthelmintics, the concurrent therapy with conventional anthelmintics provided a 22.98% improvement in total weight gain compared to controls (P = 0.004). The 118-day improvement in weight gain for the extended release eprinomectin group (29.06% compared to

Three-year evaluation of best practice guidelines for nematode control on commercial sheep farms in the UK.

PubMed

Learmount, Jane; Stephens, Nathalie; Boughtflower, Valerie; Barrecheguren, Alba; Rickell, Kayleigh; Massei, Giovanna; Taylor, Mike

2016-08-15

Anthelmintics are commonly used on the majority of UK commercial sheep farms to reduce major economic losses associated with parasitic diseases. With increasing anthelmintic resistance worldwide, several countries have produced evidence-based, best practice guidelines with an example being the UK's Sustainable Control of Parasites in Sheep (SCOPS) initiative. In 2012, a pilot study demonstrated that SCOPS-managed farms used fewer anthelmintic treatments than traditionally managed farms, with no impact on lamb productivity and worm burden. Building on these results, we collected data for three consecutive years (2012-2014) with the following aims: (1) To compare the effects of traditional and SCOPS-based parasite management on lamb productivity and worm burden; (2) To evaluate the effect of region and farm type on lamb productivity and worm burden; (3) To compare the frequency and patterns of use of anthelmintic treatment on traditional and SCOPS-managed farms. The study was carried out on 16 farms located in the North east and the South west of England and Wales. Lamb productivity was assessed by quantifying birth, mid-season and finish weights and calculating daily live-weight gains and time to finish in a cohort of 40-50 lambs on each farm. Five annual faecal egg counts were carried out on each farm to assess worm burden. No differences in lamb productivity and worm burdens were found between farms that adopted SCOPS guidelines and traditional farms across the three years. However, mean infection levels increased for both the SCOPS and the traditional groups. Lamb production was not significantly different for farm type and region but the effect of region on infection was significant. For both ewes and lambs, SCOPS farms carried out significantly fewer anthelmintic treatments per year, and used fewer anthelmintic doses/animal than traditional farms. The data suggest a trend to increasing use of anthelmintics in ewes on traditional but not on the SCOPS farms and a

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

PubMed Central

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

2013-01-01

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

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

Non-invasive indicators associated with the milk yield response after anthelmintic treatment at calving in dairy cows.

PubMed

Verschave, Sien H; Vercruysse, Jozef; Forbes, Andrew; Opsomer, Geert; Hostens, Miel; Duchateau, Luc; Charlier, Johannes

2014-11-14

Gastrointestinal nematodes are an important cause of reduced performance in cattle. Previous studies in Europe showed that after anthelmintic treatment an average gain in milk production of around 1 kg per day/cow can be expected. However, (1) these studies have mainly evaluated group-based anthelmintic treatments during the grazing season or at housing and (2) little is known about parameters affecting variations in the treatment response amongst cows. A better knowledge of such parameters could help to select animals that benefit most from treatment and thus lead to a more rational use of anthelmintics. Therefore, a randomized, non-blinded, controlled clinical trial was performed on 11 commercial dairy farms (477 animals) in Belgium, aiming (1) to study the effect of eprinomectin treatment at calving on milk production and (2) to investigate whether the milk yield response was related to non-invasive animal parameters such that these could be used to inform targeted selective treatment decisions. Analyses show that eprinomectin treatment around calving resulted in an average (± standard error) increase of 0.97 (±0.41) kg in daily milk yield that was followed up over 274 days on average. Milk yield responses were higher in multiparous compared to primiparous cows and in cows with a high (4(th) quartile) anti-O. ostertagi antibody level in a milk sample from the previous lactation. Nonetheless, high responses were also seen in animals with a low (1(st) quartile) anti-O. ostertagi antibody level. In addition, positive treatment responses were associated with higher faecal egg counts and a moderate body condition score at calving (2(nd) quartile). In conclusion, this study provides novel insights into the production response after anthelmintic treatment at calving and factors which influence this. The data could be used to support the development of evidence-based targeted selective anthelmintic treatment strategies in dairy cattle.

Phenolics and Terpenoids; the Promising New Search for Anthelmintics: A Critical Review.

PubMed

Mukherjee, Niladri; Mukherjee, Suprabhat; Saini, Prasanta; Roy, Priya; Babu, Santi P Sinha

2016-01-01

Ailments caused by helminth parasites are global causing different types of clinical complications with permanent and long term morbidity in humans. Although huge advances have been made in medical sciences the effectiveness of available anthelmintics are still quite limited. Starting from the 50's, most importance was given to synthetic compounds for developing remedies from them, however, the traditional knowledge of medicine of different countries continued to provide us clues against this widespread health problem. Natural products or structural analogs with diverse structures are always been the major sources for discovering new therapeutics and in recent past different active compounds have also been identified form these plant sources having anthelmintic properties. Although compounds of diverse chemical nature and classes were identified, most active ones belong to either phenol or terpene in broad chemical nature. The mechanism of action of these phytotherapeutics is usually multi-targeted and can act against the helminth parasites through diverse spectrum of activities. In this review we summarized the effective anthelmintics belong to either phenolics or terpenoids and highlighted the major way of their effectiveness. This also highlights the recent development of new therapeutic strategies against helminth parasites in the light of recent advances of knowledge. In addition, developing efficient strategies to promote apoptosis and disturbing redox status in them by natural products can provide us a clue in antifilarial drug developmental research and crucial unmet medical need.

New solid state forms of antineoplastic 5-fluorouracil with anthelmintic piperazine

NASA Astrophysics Data System (ADS)

Moisescu-Goia, C.; Muresan-Pop, M.; Simon, V.

2017-12-01

The aim of the present study was to asses the formation of solid forms between the 5-fluorouracil chemotherapy drug and the anthelmintic piperazine. Two new solid forms of antineoplastic agent 5-fluorouracil with anthelmintic piperazine were obtained by liquid assisted ball milling and slurry crystallization methods. The Nsbnd H hydrogen bonding donors and C = O hydrogen bonding acceptors of 5-fluorouracil allow to form co-crystals with other drugs delivering improved properties for medical applications, as proved for other compounds of pharmaceutical interest. Both new solid forms were investigated using X-ray powder diffraction (XRD), differential thermal analysis (DTA) and Fourier transform infrared (FTIR) spectroscopy. The XRD results show that by both methods were successfully synthesized new solid forms of 5-fluorouracil with piperazine. According to FTIR results the form prepared by lichid assisted grinding process was obtained as co-crystal and the other one, prepared by slurry method, resulted as a salt.

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.

In vivo and in vitro studies of Cry5B and nicotinic acetylcholine receptor agonist anthelmintics reveal a powerful and unique combination therapy against intestinal nematode parasites.

PubMed

Hu, Yan; Miller, Melanie; Zhang, Bo; Nguyen, Thanh-Thanh; Nielsen, Martin K; Aroian, Raffi V

2018-05-01

The soil-transmitted nematodes (STNs) or helminths (hookworms, whipworms, large roundworms) infect the intestines of ~1.5 billion of the poorest peoples and are leading causes of morbidity worldwide. Only one class of anthelmintic or anti-nematode drugs, the benzimidazoles, is currently used in mass drug administrations, which is a dangerous situation. New anti-nematode drugs are urgently needed. Bacillus thuringiensis crystal protein Cry5B is a powerful, promising new candidate. Drug combinations, when properly made, are ideal for treating infectious diseases. Although there are some clinical trials using drug combinations against STNs, little quantitative and systemic work has been performed to define the characteristics of these combinations in vivo. Working with the hookworm Ancylostoma ceylanicum-hamster infection system, we establish a laboratory paradigm for studying anti-nematode combinations in vivo using Cry5B and the nicotinic acetylcholine receptor (nAChR) agonists tribendimidine and pyrantel pamoate. We demonstrate that Cry5B strongly synergizes in vivo with both tribendimidine and pyrantel at specific dose ratios against hookworm infections. For example, whereas 1 mg/kg Cry5B and 1 mg/kg tribendimidine individually resulted in only a 0%-6% reduction in hookworm burdens, the combination of the two resulted in a 41% reduction (P = 0.020). Furthermore, when mixed at synergistic ratios, these combinations eradicate hookworm infections at doses where the individual doses do not. Using cyathostomin nematode parasites of horses, we find based on inhibitory concentration 50% values that a strongylid parasite population doubly resistant to nAChR agonists and benzimidazoles is more susceptible or "hypersusceptible" to Cry5B than a cyathostomin population not resistant to nAChR agonists, consistent with previous Caenhorhabditis elegans results. Our study provides a powerful means by which anthelmintic combination therapies can be examined in vivo in the

New Method for Analysis of Multiple Anthelmintic Residues in Animal Tissue

USDA-ARS?s Scientific Manuscript database

For the first time, 39 of the major anthelmintics can be detected in one rapid and sensitive LC-MS/MS method, including the flukicides, which have been generally overlooked in surveillance programs. Utilizing the QuEChERS approach, residues were extracted from liver and milk using acetonitrile, sod...

In vitro and in vivo anthelmintic effects of Caesalpinia bonducella (L.) Roxb. leaf extract on Hymenolepis diminuta (Cestoda) and Syphacia obvelata (Nematoda)

PubMed Central

Gogoi, Shyamalima; Yadav, Arun K.

2016-01-01

Background: Leaves of Caesalpinia bonducella (L.) Roxb. have been traditionally used as an herbal remedy to treat the intestinal helminthic infections in traditional medicine of India. Aim: This study was undertaken to evaluate the potential in vitro and in vivo anthelmintic effects of C. bonducella leaf extract against Syphacia obvelata (Nematoda) and Hymenolepis diminuta (Cestoda). Materials and Methods: The in vitro anthelmintic activity of the extract was investigated on adult worms of S. obvelata (Nematoda) and H. diminuta (Cestoda) in terms of physical motility and mortality of parasites. The in vivo study was performed in H. diminuta-rat model and S. obvelata-mice model, by monitoring the egg per gram of feces count and worm count of animals following the treatment with different doses of plant extract. Results: The study recorded significant and dose-dependent anthelmintic effects of the extract on both the parasites. In the in vitro study, 30 mg/ml concentration of extract caused mortality of H. diminuta in 2.5 ± 0.2 h and S. obvelata in 3.57 ± 0.16 h. In the in vivo study, the extract showed a comparatively better efficacy on S. obvelata, where its 800 mg/kg dose revealed 93% reduction of worm load in mice, as compared to 85% worm load reduction of H. diminuta in rats. Conclusions: The findings suggest that leaf extract of C. bonducella possesses significant anthelmintic effects and supports its use as an anthelmintic in traditional medicine. This appears to be the first report of in vivo anthelmintic activity of C. bonducella against these parasites. PMID:27757275

Evaluation of pharmaceuticals and personal care products with emphasis on anthelmintics in human sanitary waste, sewage, hospital wastewater, livestock wastewater and receiving water.

PubMed

Sim, Won-Jin; Kim, Hee-Young; Choi, Sung-Deuk; Kwon, Jung-Hwan; Oh, Jeong-Eun

2013-03-15

We investigated 33 pharmaceuticals and personal care products (PPCPs) with emphasis on anthelmintics and their metabolites in human sanitary waste treatment plants (HTPs), sewage treatment plants (STPs), hospital wastewater treatment plants (HWTPs), livestock wastewater treatment plants (LWTPs), river water and seawater. PPCPs showed the characteristic specific occurrence patterns according to wastewater sources. The LWTPs and HTPs showed higher levels (maximum 3000 times in influents) of anthelmintics than other wastewater treatment plants, indicating that livestock wastewater and human sanitary waste are one of principal sources of anthelmintics. Among anthelmintics, fenbendazole and its metabolites are relatively high in the LWTPs, while human anthelmintics such as albendazole and flubendazole are most dominant in the HTPs, STPs and HWTPs. The occurrence pattern of fenbendazole's metabolites in water was different from pharmacokinetics studies, showing the possibility of transformation mechanism other than the metabolism in animal bodies by some processes unknown to us. The river water and seawater are generally affected by the point sources, but the distribution patterns in some receiving water are slightly different from the effluent, indicating the influence of non-point sources. Copyright © 2013 Elsevier B.V. All rights reserved.

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

Regulation of the resistance to nematode parasites of single- and twin-bearing Merino ewes through nutrition and genetic selection.

PubMed

Kahn, L P; Knox, M R; Walkden-Brown, S W; Lea, J M

2003-05-15

Periparturient Merino ewes obtained from lines of sheep that had been selected either for increased resistance to Haemonchus contortus (R) or at random (C) were supplemented, while grazing at pasture, with either nil or 250 g/day cottonseed meal (CSM) for the 6 weeks prior to or the 6 weeks after the start of parturition. Ewes from both supplement groups had lower (mean 66% reduction) faecal egg counts (FECs) during the postpartum period and this coincided with a period of maternal body weight loss. Factors which increased the rate of maternal body weight loss, such as pregnancy and lactation status, also increased FEC. Evidence is presented that the magnitude of the periparturient rise (PPR) in FEC in grazing ewes will be greatest during periods of maternal weight loss and at these times supplementation to increase metabolisable protein (MP) supply will be most effective in increasing resistance to nematode parasites. The resistance of R ewes to nematode parasites was greater than that of C ewes throughout the experiment and was sufficiently low such that anthelmintic treatment in a commercial environment may not have been required. Irrespective of actual FEC, ewes from all treatment combinations exhibited a PPR in FEC. Reduced FEC of R ewes resulted in reduced apparent pasture larval contamination after 18 weeks of continuous grazing but supplementation was ineffective in this regard. It is suggested that integrated parasite management (IPM) programs for periparturient ewes should make use of both protein supplementation and genetic selection to increase worm resistance and reduce dependency on anthelmintics for worm control.

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

PubMed

Wilson, John W; Tsukayama, Dean T

2016-04-01

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

Little anthelmintic drenching required for lambs finished over winter and spring on annually re-established irrigated pasture on the Highveld of Gauteng Province, South Africa.

PubMed

van Wyk, J A; Meyer, J; van Rensburg, L J

2003-03-01

As part of a trial to test the profitability of finishing weaner lambs over winter and spring on the Highveld of Gauteng province, an investigation was carried out over 4 consecutive years as to whether or not worm control was necessary while the lambs were on irrigated, improved pastures. Pastures that had not been grazed by sheep or other livestock for at least 5 years were planted to annual ryegrass (Lolium multiflora) that was ploughed under and replanted annually. Weaner lambs were randomly divided into either 2 (A and B) or 3 (A, B and C) groups and finished from April/May to November/December on a separate pasture per group. While Group A lambs were dewormed before being placed on pasture, those in Groups B and C were not. Faecal egg counts were performed at irregular intervals, and when the lambs were sold at the conclusion of each year's trial, the gastrointestinal tracts of 4-5 lambs per trial group were processed for worm recovery. Haemonchus contortus was the dominant worm species, while Trichostrongylus colubriformis, Ostertagia circumcincta and Trichuris spp. were encountered sporadically. From the results obtained it seems unlikely that there is appreciable 'carry-over' of the various worm species from year to year on pastures that are ploughed and replanted annually; thus it is improbable that there will be a build-up of anthelmintic-resistant worms. While on pasture, no drenching was required for the Group A lambs (dewormed before placing on the pasture), nor in 2 of the 4 years in Groups B or B+C that were not drenched and were lightly infected at the start. In the remaining 2 years Groups B or B+C were drenched once only during the course of each trial. Thus, under the conditions as in this study, little worm control is necessary, provided faecal worm egg counts are done to gauge the levels of infection before the lambs are placed on pasture, and to guard against the possibility of an increase in worm burdens thereafter in some years. Also

Managing the evolution of herbicide resistance.

PubMed

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

2016-01-01

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

Alternative approaches for the control of gastrointestinal nematodes in sheep farming: a review.

PubMed

Šimpraga, Miljenko; Ljubičić, Iva; Hlede, Jadranka Pejaković; Vugrovečki, Ana Shek; Marinculić, Albert; Tkalčić, Suzana

2015-01-01

Gastrointestinal nematodes (GIN) are a serious health problem and represent the most significant constraint in sheep grazing operations. Problems tend to be worse in organic sheep farming systems, as a consequence of a less restricted access of animals to outdoor environment with a higher exposure to infective larvae. In domestic animals, GIN are effectively controlled by an aggressive prophylactic administration of commercially available anthelmintics. As a consequence to a common overdose and misuse of readily available antiparasitic treatments, there is an inevitable development of populations of GIN resistant to all major classes of anthelmintics. Also, the control of GIN that is based entirely on the anthelmintic use, threatens sustainability of the sheep farming worldwide. The combination of the optimized use of anthelmintic drugs and alternative approaches seem to be a reasonable choice in sustainable parasitic control programs that offer a substantial reduction of anthelmintic treatments and conservation of anthelmintic efficacy. In that aspect, a "targeted selective treatment (TST)" directed towards animals clinically diagnosed with GIN, seems to be an effective approach to leave some parasite populations unexposed to anthelmintics (refugia) and to reduce development of anthelmintic resistance. Also, many current research efforts aim to find and validate sustainable non-chemotherapeutic approaches to GIN control, including changes in grazing management, optimized nutrition, dietary supplementation, consumption of plants with anthelmintic properties, biological control by nematophagous fungi, copper oxide wire particles (COWP), and homeopathic treatments. This manuscript outlines (outlines) and discusses relevant alternative approaches for GIN control in modern sheep farming systems.

Immunogenomics of gastrointestinal nematode infection in ruminants - breeding for resistance to produce food sustainably and safely.

PubMed

Sweeney, T; Hanrahan, J P; Ryan, M T; Good, B

2016-09-01

Gastrointestinal nematode (GIN) infection of ruminants represents a major health and welfare challenge for livestock producers worldwide. The emergence of anthelmintic resistance in important GIN species and the associated animal welfare concerns have stimulated interest in the development of alternative and more sustainable strategies aimed at the effective management of the impact of GINs. These integrative strategies include selective breeding using genetic/genomic tools, grazing management, biological control, nutritional supplementation, vaccination and targeted selective treatment. In this review, the logic of selecting for "resistance" to GIN infection as opposed to "resilience" or "tolerance" is discussed. This is followed by a review of the potential application of immunogenomics to genetic selection for animals that have the capacity to withstand the impact of GIN infection. Advances in relevant genomic technologies are highlighted together with how these tools can be advanced to support the integration of immunogenomic information into ruminant breeding programmes. © 2016 John Wiley & Sons Ltd.

Effects of diet on plasma concentrations of oral anthelmintics for cattle and sheep.

PubMed

Taylor, S M; Mallon, T R; Blanchflower, W J; Kennedy, D G; Green, W P

1992-03-28

Groups of parasite-free lambs and calves which were either housed and fed hay and concentrates or were grazing on pasture were dosed separately with the oral anthelmintics fenbendazole and ivermectin (lambs only). The plasma concentrations of the drugs and their major metabolites were monitored during the period of their metabolism and excretion. The peak plasma concentrations and the availability of the drugs, as estimated by the areas under the plasma concentration-time curves, were significantly less in the grazing animals. When similar groups of lambs were dosed orally with the inert marker chromium EDTA, which has a particle size similar to the anthelmintics, it was observed that a higher percentage of chromium was excreted by the grazing lambs during the first 40 hours after dosing, suggesting that the extent of absorption in the grazing animals was less than in the housed animals.

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

PubMed

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

2017-11-15

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

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.

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

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.

Progressive alveolar echinococcosis after discontinuation of anthelmintic therapy

PubMed Central

2013-01-01

We report a case of a female patient with alveolar echinococcosis (AE) who presented with progressive pulmonary and hepatic lesions and had a fatal outcome. AE affecting the liver, the lungs and the brain had been diagnosed 20 years ago and treated successfully with albendazole and stereotactic gamma knife therapy. Due to severe hair loss albendazole was stopped 14 years before presentation. Lesions had remained stable in imaging studies for at least 11 years, but then had started to progress. Lifelong anthelmintic maintenance therapy and regular follow-up may therefore be crucial in order to prevent such a dramatic clinical course. PMID:24289745

Resistant nematodes in cattle: Pharmaco-therapeutic assessment of the ivermectin- ricobendazole combination.

PubMed

Canton, Candela; Ceballos, Laura; Fiel, César; Moreno, Laura; Domingo Yagüez, Pablo; Bernat, Gisele; Lanusse, Carlos; Alvarez, Luis

2017-01-30

Nematodicidal combinations have been proposed as a valid strategy to achieve effective nematode control in the presence of drug resistance. The goals of this study were: (1) to compare the clinical efficacy (therapeutic response) of ivermectin (IVM) and ricobendazole (RBZ) given subcutaneously either by separate or combined administration to calves naturally infected with gastrointestinal nematodes resistant to IVM, and (2) to evaluate the potential pharmacokinetic (PK) and/or pharmacodynamic (PD) interactions occurring after the co-administration of both anthelmintics. Sixty male calves naturally infected with gastrointestinal nematodes resistant to IVM were randomly allocated into four groups (n=15). Untreated control: animals not receiving anthelmintic treatment; IVM alone: animals treated with IVM by subcutaneous (SC) injection (0.2mg/kg); RBZ alone: animals received RBZ by the SC route (3.75mg/kg); IVM+RBZ: animals treated with IVM and RBZ (0.2 and 3.75mg/kg, respectively), by SC injection in two separates sites. Eight animals of each treated group were randomly selected to perform the PK study. Plasma samples were taken from those animals up to 28days post-treatment. IVM and RBZ plasma concentrations were quantified by HPLC. The therapeutic response was determined by faecal egg count reduction test (FECRT). The proportions of third-stage larvae (L3) recovered from coprocultures were used to calculate the efficacy against the main parasite genera. The daily total egg deposition for each experimental group was estimated. Similar pharmacokinetic trends were obtained for both IVM and RBZ allying the single-drug and the combined treatments, which indicates the absence of PK interactions between both anthelmintics. The observed overall clinical drug efficacies were 48% (IVM alone), 94% (RBZ alone) and 98% (IVM+RBZ). Haemonchus spp. and Cooperia spp. were recovered in the coproculture after IVM treatment, suggesting that resistance to IVM includes both genera. In

A dual anthelmintic treatment strategic scheme for the control of fasciolosis in dairy sheep farms.

PubMed

Cringoli, Giuseppe; Rinaldi, Laura; Veneziano, Vincenzo; Genchi, Claudio

2006-11-01

A clinical longitudinal field trial was conducted on a dairy sheep farm in southern Italy to assess the effectiveness of a novel anthelmintic treatment strategic scheme against Fasciola hepatica. The scheme utilizes a dual anthelmintic treatment (DAT), i.e., the use of either one of two different anthelmintics on the flock, albendazole sulphoxide (SO) at 1-month intervals and rafoxanide at 2-month intervals, administered to the lactating and non-lactating animals, respectively. The DAT strategic scheme lasted 3 years. In Year 1 and Year 2, shotgun monthly DATs for 5 consecutive months (July, August, September, October, and November) were performed on the flock. In Year 3 there was only one monthly DAT, in July. Overall, the DAT scheme reduced the prevalence of F. hepatica infection by 94.4% (from an average prevalence of 71.1% during the pre-DAT period to an average prevalence of 4.0% during Year 3), and the eggs/gram of faeces (EPG) from 29.3 to 1.3. In conclusion, the DAT strategic scheme reported in the present study successfully reduced both the prevalence and EPGs of F. hepatica to a level at which there were no longer any clinical symptoms of the disease. This scheme did not influence the albendazole SO efficacy against GI nematodes and might be used for the treatment of fasciolosis in dairy sheep farms.

In vitro anthelmintic effects of Spigelia anthelmia protein fractions against Haemonchus contortus.

PubMed

Araújo, Sandra Alves; Soares, Alexandra Martins Dos Santos; Silva, Carolina Rocha; Almeida Júnior, Eduardo Bezerra; Rocha, Cláudia Quintino; Ferreira, André Teixeira da Silva; Perales, Jonas; Costa-Júnior, Livio M

2017-01-01

Gastrointestinal nematodes are a significant concern for animal health and well-being, and anthelmintic treatment is mainly performed through the use of chemical products. However, bioactive compounds produced by plants have shown promise for development as novel anthelmintics. The aim of this study is to assess the anthelmintic activity of protein fractions from Spigelia anthelmia on the gastrointestinal nematode Haemonchus contortus. Plant parts were separated into leaves, stems and roots, washed with distilled water, freeze-dried and ground into a fine powder. Protein extraction was performed with sodium phosphate buffer (75 mM, pH 7.0). The extract was fractionated using ammonium sulfate (0-90%) and extensively dialyzed. The resulting fractions were named LPF (leaf protein fraction), SPF (stem protein fraction) and RPF (root protein fraction), and the protein contents and activities of the fractions were analyzed. H. contortus egg hatching (EHA), larval exsheathment inhibition (LEIA) and larval migration inhibition (LMIA) assays were performed. Proteomic analysis was conducted, and high-performance liquid chromatography (HPLC) chromatographic profiles of the fractions were established to identify proteins and possible secondary metabolites. S. anthelmia fractions inhibited H. contortus egg hatching, with LPF having the most potent effects (EC50 0.17 mg mL-1). During LEIA, SPF presented greater efficiency than the other fractions (EC50 0.25 mg mL-1). According to LMIA, the fractions from roots, stems and leaves also reduced the number of larvae, with EC50 values of 0.11, 0.14 and 0.21 mg mL-1, respectively. Protein analysis indicated the presence of plant defense proteins in the S. anthelmia fractions, including protease, protease inhibitor, chitinase and others. Conversely, secondary metabolites were absent in the S. anthemia fractions. These results suggest that S. anthelmia proteins are promising for the control of the gastrointestinal nematode H. contortus.

Findings from an ovine parasitological monitoring service provided by a rural veterinary practice in New South Wales, Australia.

PubMed

Kozaruk, M K; Churchill, R; Windsor, P A

2015-04-01

To describe an ovine parasitological monitoring service delivered by a rural veterinary practice and determine associations between flock, anthelmintic and monitoring factors and worm control. Retrospective study of records from a rural veterinary practice in south-eastern Australia over an 8.75-year period. Records of sheep producers using veterinary services for gastrointestinal parasite management from 1 August 2003 to 30 April 2012 were analysed. Results from pre- (FECt1 ) and post-treatment faecal egg counts (FECt2 ) were used to identify factors influencing anthelmintic effectiveness, calculated as faecal egg count reduction percentage (FECR%) by linear mixed model analyses. The trends in anthelmintic merchandising and uptake of veterinary services for parasite management were determined by logistic regression analyses. FECR% varied according to the treatment group used (P < 0.001), with an apparent decreasing effectiveness of the macrocylic lactone group over the duration of the study (P = 0.008). Wether and ram flocks displayed lower FECR% than ewe flocks (P < 0.05). Time between FECt1 and treatment (P = 0.031), as well as time between treatment and FECt2 (P < 0.001), had a significant negative association with FECR%. The proportion of properties purchasing 4-way combination anthelmintics increased significantly over the study period (P < 0.001), with declines observed in other anthelmintics (P < 0.05). The proportion of properties performing FECR% monitoring to those that purchased anthelmintics increased significantly over the study period (P = 0.001). Anthelmintic treatment type, sex of the flock and time between drenching and testing had the greatest influence on drench effectiveness (FECR%). An increasing reliance on 4-way combination drenches to manage gastrointestinal parasitism was demonstrated. Benefits of parasitological monitoring include: appropriate advice on parasitological management; observations on trends in regional anthelmintic usage

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

PubMed

Katiki, Luciana M; Ferreira, Jorge F S; Gonzalez, Javier M; Zajac, Anne M; Lindsay, David S; Chagas, Ana Carolina S; Amarante, Alessandro F T

2013-02-18

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 benefits, and antioxidant capacity of alternative forages containing hydrolyzable tannins (HT). We evaluated the anthelmintic activity and the antioxidant capacity of plant extracts containing either mostly CT, mostly HT, or both CT and HT. Extracts were prepared with 70% acetone, lyophilized, redissolved to doses ranging from 1.0mg/mL to 25mg/mL, and tested against adult Caenorhabditis elegans as a test model. The extract concentrations that killed 50% (LC(50)) or 90% (LC(90)) of the nematodes in 24h were determined and compared to the veterinary anthelmintic levamisole (8 mg/mL). Extracts were quantified for CT by the acid butanol assay, for HT (based on gallic acid and ellagic acid) by high-performance liquid chromatography (HPLC) and total phenolics, and for their antioxidant activity by the oxygen radical absorbance capacity (ORAC) assay. Extracts with mostly CT were Lespedeza cuneata, Salix X sepulcralis, and Robinia pseudoacacia. Extracts rich in HT were Acer rubrum, Rosa multiflora, and Quercus alba, while Rhus typhina had both HT and CT. The extracts with the lowest LC(50) and LC(90) concentrations, respectively, in the C. elegans assay were Q. alba (0.75 and 1.06 mg/mL), R. typhina collected in 2007 (0.65 and 2.74 mg/mL), A. rubrum (1.03 and 5.54 mg/mL), and R. multiflora (2.14 and 8.70 mg/mL). At the doses of 20 and 25mg/mL, HT-rich, or both CT- and HT-rich, extracts were significantly more lethal to adult C. elegans than extracts containing only CT. All extracts were high in antioxidant capacity, with ORAC values ranging from 1800 μmoles to 4651 μmoles of trolox equivalents/g, but ORAC did not correlate with anthelmintic activity. The total phenolics test had a

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

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. Copyright

Lack of efficacy of monepantel against trichostrongyle nematodes in a UK sheep flock.

PubMed

Hamer, Kim; Bartley, Dave; Jennings, Amy; Morrison, Alison; Sargison, Neil

2018-06-15

Monepantel resistance was diagnosed during routine monitoring of the effectiveness of a farm's roundworm control strategy. Weaned lambs had become ill thrifty and developed diarrhoea, despite the routine use of monepantel. This clinical presentation was caused by trichostrongylosis. The faecal egg count reduction was 76.7% (95% CI: 55.1-82.2%) following treatment with 2.5 mg/kg monepantel. Predominantly Trichostrongylus vitrinus along with small proportions of Oesophagostomum venulosum and Trichostrongylus vitrinus were identified by deep amplicon sequencing of pools of larvae recovered from pre and post monepantel treatment coprocultures and on postmortem examinations. The undifferentiated FECRT showed resistance to monepantel, but not to levamisole, ivermectin, or moxidectin. Examination of farm anthelmintic treatment and animal movement records suggested that treatments before movement onto silage aftermaths, putatively with low numbers of susceptible nematodes in refugia, may have placed a high selection pressure on monepantel resistance. Effective control of parasitic gastroenteritis using anthelmintic drugs is a prerequisite for sustainable sheep production. This case reiterates the need for care when combining anthelmintic treatments with movements to safe grazing, and the value of monitoring of anthelmintic efficacy as part of iterative planned animal health management. Copyright © 2018 Elsevier B.V. All rights reserved.

Compounds Derived from the Bhutanese Daisy, Ajania nubigena, Demonstrate Dual Anthelmintic Activity against Schistosoma mansoni and Trichuris muris.

PubMed

Wangchuk, Phurpa; Pearson, Mark S; Giacomin, Paul R; Becker, Luke; Sotillo, Javier; Pickering, Darren; Smout, Michael J; Loukas, Alex

2016-08-01

Whipworms and blood flukes combined infect almost one billion people in developing countries. Only a handful of anthelmintic drugs are currently available to treat these infections effectively; there is therefore an urgent need for new generations of anthelmintic compounds. Medicinal plants have presented as a viable source of new parasiticides. Ajania nubigena, the Bhutanese daisy, has been used in Bhutanese traditional medicine for treating various diseases and our previous studies revealed that small molecules from this plant have antimalarial properties. Encouraged by these findings, we screened four major compounds isolated from A. nubigena for their anthelmintic properties. Here we studied four major compounds derived from A. nubigena for their anthelmintic properties against the nematode whipworm Trichuris muris and the platyhelminth blood fluke Schistosoma mansoni using the xWORM assay technique. Of four compounds tested, two compounds-luteolin (3) and (3R,6R)-linalool oxide acetate (1)-showed dual anthelmintic activity against S. mansoni (IC50 range = 5.8-36.9 μg/mL) and T. muris (IC50 range = 9.7-20.4 μg/mL). Using scanning electron microscopy, we determined luteolin as the most efficacious compound against both parasites and additionally was found effective against the schistosomula, the infective stage of S. mansoni (IC50 = 13.3 μg/mL). Luteolin induced tegumental damage to S. mansoni and affected the cuticle, bacillary bands and bacillary glands of T. muris. Our in vivo assessment of luteolin (3) against T. muris infection at a single oral dosing of 100 mg/kg, despite being significantly (27.6%) better than the untreated control group, was markedly weaker than mebendazole (93.1%) in reducing the worm burden in mice. Among the four compounds tested, luteolin demonstrated the best broad-spectrum activity against two different helminths-T. muris and S. mansoni-and was effective against juvenile schistosomes, the stage that is refractory to the current

Compounds Derived from the Bhutanese Daisy, Ajania nubigena, Demonstrate Dual Anthelmintic Activity against Schistosoma mansoni and Trichuris muris

PubMed Central

Pearson, Mark S.; Giacomin, Paul R.; Becker, Luke; Sotillo, Javier; Pickering, Darren

2016-01-01

Background Whipworms and blood flukes combined infect almost one billion people in developing countries. Only a handful of anthelmintic drugs are currently available to treat these infections effectively; there is therefore an urgent need for new generations of anthelmintic compounds. Medicinal plants have presented as a viable source of new parasiticides. Ajania nubigena, the Bhutanese daisy, has been used in Bhutanese traditional medicine for treating various diseases and our previous studies revealed that small molecules from this plant have antimalarial properties. Encouraged by these findings, we screened four major compounds isolated from A. nubigena for their anthelmintic properties. Methodology/Principal Findings Here we studied four major compounds derived from A. nubigena for their anthelmintic properties against the nematode whipworm Trichuris muris and the platyhelminth blood fluke Schistosoma mansoni using the xWORM assay technique. Of four compounds tested, two compounds—luteolin (3) and (3R,6R)-linalool oxide acetate (1)—showed dual anthelmintic activity against S. mansoni (IC50 range = 5.8–36.9 μg/mL) and T. muris (IC50 range = 9.7–20.4 μg/mL). Using scanning electron microscopy, we determined luteolin as the most efficacious compound against both parasites and additionally was found effective against the schistosomula, the infective stage of S. mansoni (IC50 = 13.3 μg/mL). Luteolin induced tegumental damage to S. mansoni and affected the cuticle, bacillary bands and bacillary glands of T. muris. Our in vivo assessment of luteolin (3) against T. muris infection at a single oral dosing of 100 mg/kg, despite being significantly (27.6%) better than the untreated control group, was markedly weaker than mebendazole (93.1%) in reducing the worm burden in mice. Conclusions/Significance Among the four compounds tested, luteolin demonstrated the best broad-spectrum activity against two different helminths—T. muris and S. mansoni—and was

Persistent challenge with Trichostrongylus colubriformis and Haemonchus contortus larvae does not affect growth of meat-breed lambs suppressively treated with anthelmintics when grazing.

PubMed

Dever, M L; Kahn, L P; Doyle, E K

2015-04-15

This experiment tested the hypothesis that persistent challenge with anthelmintic susceptible Trichostrongylus colubriformis and Haemonchus contortus larvae would not affect growth of grazing, meat-breed lambs when suppressively treated with anthelmintics. The experiment was a 2×2 factorial design using 6-7 months old White Suffolk X Border Leicester/Merino (meat-breed) lambs which were either infected with 2000 T. colubriformis and 300 H. contortus L3/week (IF) or remained uninfected (UIF) for 9 weeks and were either treated (TX) with a combination of short and long-acting anthelmintics or remained untreated (UTX). Lambs grazed as one flock and were rotated between paddocks to avoid autoinfection from pasture. Lambs were humanely euthanised on day 63 and the abomasum and small intestine collected to determine total worm burdens and tissue antibody response specific to T. colubriformis. As expected, worm egg count (WEC) and worm burden were significantly higher in IF UTX lambs (p<0.001). WEC was dominated by H. contortus and peaked at 2,325 epg on day 63 but remained at zero for the other treatment groups for the duration of the experiment. Tissue antibody responses were evident in IF lambs (titres; 9982 vs 2767, p=0.012) but treatment had no effect (titres; 5912 vs 5349, p=0.829). Lambs grew an average of 2.6 kg during the experiment with no difference between IF TX and UIF TX groups (p=0.432). Elevated tissue antibody responses were not associated with differences in growth. Results from this experiment support the hypothesis that persistent larval challenge with anthelmintic susceptible H. contortus and T. colubriformis will not affect growth of grazing, meat-breed lambs when suppressively treated with effective anthelmintics. Therefore the use of sheep suppressively treated with effective anthelmintics appears to be a valid substitute for gastrointestinal nematode-free lambs in field experiments. Copyright © 2015 Elsevier B.V. All rights reserved.

Exploration of interaction zones of β-tubulin colchicine binding domain of helminths and binding mechanism of anthelmintics.

PubMed

Ranjan, Prabodh; Kumar, Sivakumar Prasanth; Kari, Vijayakrishna; Jha, Prakash Chandra

2017-06-01

Numerous studies postulated the possible modes of anthelmintic activity by targeting alternate or extended regions of colchicine binding domain of helminth β-tubulin. We present three interaction zones (zones vide -1 to -3) in the colchicine binding domain of Haemonchus contortus (a helminth) β-tubulin homology model and developed zone-wise structure-based pharmacophore models coupled with molecular docking technique to unveil the binding hypotheses. The resulted ten structure-based hypotheses were then refined to essential three point pharmacophore features that captured recurring and crucial non-covalent receptor contacts and proposed three characteristics necessary for optimal zone-2 binding: a conserved pair of H bond acceptor (HBA to form H bond with Asn226 residue) and an aliphatic moiety of molecule separated by 3.75±0.44Å. Further, an aliphatic or a heterocyclic group distant (11.75±1.14Å) to the conserved aliphatic site formed the third feature component in the zone-2 specific anthelmintic pharmacophore model. Alternatively, an additional HBA can be substituted as a third component to establish H bonding with Asn204. We discern that selective zone-2 anthelmintics can be designed effectively by closely adapting the pharmacophore feature patterns and its geometrical constraints. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2016-01-01

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. 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. 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 IC 50 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. The study therefore suggests the importance of tested plants as a natural source of free radical scavenger and plausible veterinary uses.

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

The anthelmintic effect of aqueous methanol extract of Combretum molle (R. Br. x. G. Don) (Combretaceae) in lambs experimentally infected with Haemonchus contortus.

PubMed

Simon, M K; Ajanusi, O J; Abubakar, M S; Idris, A L; Suleiman, M M

2012-06-08

The aqueous methanol extract from the stem-bark of Combretum molle was evaluated for anthelmintic activity in lambs infected with Haemonchus contortus using faecal egg count (FEC) reduction assay. The extract showed a dose-dependent reduction in FEC in infected animals. At doses of 500, 1000 and 2000 mg kg(-1), the extract caused FEC reduction of 63%, 69.25% and 96.23%, respectively. Similarly, the standard anthelmintic (albendazole) at a dose of 200 mg kg(-1) produced FEC reduction of 99.24%. FEC reduction produced by the extract at doses of 500 and 1000 mg kg(-1) is below the minimum standard of 90% FEC recommended by the World Association for the Advancement of Veterinary Parasitology (WAAVP). However, there was no significant (P>0.05) difference between the means of groups treated with 1000 mg kg(-1) and 2000 mg kg(-1) compared to that of albendazole. In this study, C. molle has shown a promising anthelmintic activity against experimental haemonchosis. Nonetheless, further studies to evaluate its detailed toxicity are required for the plant extract to be developed into a useful anthelmintic drug. There is also the need to evaluate other parts of the plant (root, leaves, fruits, etc.) for the same effect. Copyright © 2012 Elsevier B.V. All rights reserved.

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

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

USDA-ARS?s Scientific Manuscript database

A new UPLC-MS/MS (ultra-performance liquid chromatography coupled to tandem mass spectrometry) method was developed and validated to detect 38 anthelmintic drug residues, consisting of benzimidazoles, avermectins and flukicides. A modified QuEChERS-type extraction method was developed with an added...

Anthelmintic activity of silver-extract nanoparticles synthesized from the combination of silver nanoparticles and M. charantia fruit extract.

PubMed

Rashid, Md Mamun Or; Ferdous, Jannatul; Banik, Sujan; Islam, Md Rabiul; Uddin, A H M Mazbah; Robel, Fataha Nur

2016-07-26

Present study has been conducted to know the anthelmintic activity of polyaniline coated silver nanoparticles (AgNPs) synthesized from Momordica charantia fruit extract. By reduction of AgNO3 in presence of NaBH4, silver nanoparticles were prepared. After mixing silver nanoparticles and extracts, coating was given on nanoparticles using polyaniline. Prepared nanoparticles were characterized by Visual, UV, FTIR spectroscopy, SEM techniques, and TEM analysis. The FTIR results implied that AgNPs were successfully synthesized and capped with bio-compounds present in the extract. The result showed that death times of worm were 35.12 ± 0.5 and 59.3 ± 0.3 minutes for M. charantia extract and Ag-nanoparticles individually. But when these two combined together, paralysis and death time fall drastically which were only 6.16 ± 0.6 and 9.1 ± 0.4 minutes respectively. Albendazole tablet was used as standard, which made worms death in 3.66 ± 0.1 minutes. Ag-Extract NPs showed strong anthelmintic activity against worm. This study has paved the way for further research to design new anthelmintic drug from the combination of M. charantia and AgNPs.

A field study on the effect of some anthelmintics on cyathostomins of horses in sweden.

PubMed

Lind, E Osterman; Kuzmina, T; Uggla, A; Waller, P J; Höglund, J

2007-01-01

The objective of the study was to investigate different aspects on the efficacy of three anthelmintics on cyathostomin nematodes of Swedish horses. A faecal egg count reduction (FECR) test was performed on 26 farms. Horses were treated orally with recommended doses of ivermectin, pyrantel pamoate or fenbendazole. Faecal samples were collected on the day of deworming and 7, 14 and 21 days later. No resistance was shown against ivermectin; the FECR was constantly >99%. The effect of pyrantel was assessed as equivocal in 6 farms 14 days after treatment; the mean FECR was 99%. As many as 72% of the fenbendazole-treated groups met the criteria for resistance; the mean FECR was 86%, ranging from 56% to 100%. A re-investigation of two farms where pyrantel resistance had been suspected clearly revealed unsatisfactory efficacy of pyrantel on one of these farms; the FECR varied from 72% to 89%. Twenty-six of the horses previously dosed with pyrantel or fenbendazole, and which still excreted >/=150 eggs per gram of faeces 14 days after treatment, were dewormed with ivermectin and fenbendazole or pyrantel in order to eliminate the remaining cyathostomins. A total of 13 cyathostomin species were identified from horses that initially received fenbendazole and seven species were identified from pyrantel-treated individuals. The egg reappearance period (ERP) following treatment with ivermectin and pyrantel was investigated on two farms. The shortest ERP after ivermectin treatment was 8 weeks and after pyrantel was 5 weeks. We conclude that no substantial reversion to benzimidazole susceptibility had taken place, although these drugs have scarcely been used (<5%) in horses for the last 10 years. Pyrantel-resistant populations of cyathostomins are present on Swedish horse farms, but the overall efficacy of pyrantel is still acceptable.

A weed resistance management game: a teaching tool.

PubMed

Frisvold, George B

2018-04-15

This article provides instructions and materials to moderate an interactive resistance management game. The game is designed to generate discussion about the challenges and possibilities of coordinating resistance management activities among groups of farmers. The game has been successfully applied in classroom settings, extension workshops, and at professional weed science meetings. Research has found farmers often perceive the success of their own resistance management may be thwarted if their neighbors are not adequately managing resistance as well. This can lead to negative 'tragedy of the commons' outcomes. In past applications of the game exercise, participants have often responded in ways consistent with similar studies in experimental and behavioral economics. This includes dividing benefits evenly (even though this is not a requirement of the game) or treating one-time transactions as potentially repeated exchanges. Player behavior may also be greatly influenced by their attitudes toward monetary risks. The game allows participants to explore ways to overcome the tragedy of the commons and illustrates the roles of information sharing and economic incentives in finding solutions. It also allows participants to experiment with bottom-up voluntary approaches toward resistance management as an alternative to top-down regulatory approaches. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Synthesis and anthelmintic activity of arctigenin derivatives against Dactylogyrus intermedius in goldfish.

PubMed

Hu, Yang; Liu, Lei; Liu, Guang-Lu; Tu, Xiao; Wang, Gao-Xue; Ling, Fei

2017-08-01

To control the parasitic disease of Dactylogyrus intermedius, a series of new arctigenin derivatives were designed, synthesized and tested in our study. The anthelmintic activity of most of the derivatives ranged from 1 to 10mg/L. Compared to traditional drug praziquantel (EC 50 =2.69mg/L), ether derivatives 2g and 2h exhibited slightly higher anti-parasitic activity, with the EC 50 values of 2.48 and 1.52mg/L, respectively. Furthermore, the arctigenin-imidazole hybrids 4a and 4b also removed D. intermedius effectively, with the EC 50 values of 2.13 and 2.07mg/L, respectively. The structure-activity relationship analysis indicated that four carbon atoms length of linker and imidazole substitute group could significantly increase the anthelmintic activity, and reduced the toxicity. Through the scanning electron microscope observation, compounds 4a and 4b caused the D. intermedius tegumental damage such as intensive wrinkles, holes and nodular structures. Overall, the structural optimization analysis of arctigenin suggested that 4a and 4b can be used for preventing and controlling Dactylogyrus infections and considered as promising lead compounds for the development of commercial drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Questionnaire study on parasite control practices on Thoroughbred and Standardbred breeding farms in New Zealand.

PubMed

Bolwell, Charlotte F; Rosanowski, Sarah M; Scott, Ian; Sells, Patrick D; Rogers, Chris W

2015-04-15

Against a global background of increasing anthelmintic resistance in parasites, little is known about the current parasite control strategies adopted within the equine industry in New Zealand. The aim of the study was to describe and compare the current parasite management and control practices used on Thoroughbred and Standardbred stud farms in New Zealand. An online questionnaire was used to collect data on the demographics of respondents, parasite control methods, grazing management, and use of faecal egg counts. Questions regarding parasite control strategy, how often horses were dewormed, number of treatments per year and stocking density were stratified by horse type: young stock (foals/weanlings/yearlings), wet mares (nursing a foal) or dry mares, and industry (Thoroughbred and Standardbred). Questions on grazing management were stratified by horse type and the breeding and non-breeding season. In total, 136 respondents completed the survey, of which most (66%; 90/136) were involved in the Thoroughbred breeding industry. Most (98%; 134/136) respondents used anthelmintic products to treat the horses on their property, and regardless of industry type most respondents were using interval drenching for young stock (86/129; 53%), dry mares (51/124; 41%) or wet mares (50/126; 40%). Of those respondents treating on regular interval, 55% (68/123), 42% (50/119) and 38% (46/122) were treating young stock, wet mares and dry mares every 6-8 weeks. The median number of treatments per year for young stock, dry mares and wet mares was 6 (IQR 4-8), 4 (IQR 3-6) and 4 (IQR 3-6), respectively; there was no difference in frequency of treatments by industry type. In the last 12 months respondents used a median of 2 (IQR 2-4) and 3 (IQR 2-4) different anthelmintic products to treat horses on Thoroughbred and Standardbred breeding farms, respectively. Of the respondents reporting the anthelmintic products used in the last 12 months, 95% used at least one product containing

Grazing sericea lespedeza for control of gastrointestinal nematodes in lambs

USDA-ARS?s Scientific Manuscript database

Alternatives to chemical dewormers are needed to counter anthelmintic resistance and improve organic management systems. The objective was to examine the effectiveness of grazing sericea lespedeza (SL) compared with grass pastures for control of gastrointestinal nematodes (GIN) in lambs. In Experi...

Anthelmintic efficacies of a tablet formula of ivermectin-praziquantel on horses experimentally infected with three Strongylus species.

PubMed

Bonneau, Stephane; Maynard, Laurence; Tomczuk, Krzysztof; Kok, Dawid; Eun, Hyone-Myong

2009-09-01

In this blinded randomized and controlled study, the anthelmintic efficacy of a tablet formula of ivermectin-praziquantel was evaluated in horses experimentally infected with three species of Strongylus larvae. Eighteen previously dewormed horses were inoculated on study day 0 with third-stage larvae of Strongylus vulgaris, Strongylus equinus, and Strongylus edentatus. The horses were randomly allocated to three groups (n = 6): test-drug (tablet formula), positive-control (reference gel), and negative-control (placebo tablet). On day 56, the horses were treated once with the respective drugs. On day 95, the horses were sacrificed, and necropsy examinations were performed to assess the status of the parasite burden (L4 and immature L5) and pathological lesions on selected organs and tissues. By the criteria of worm counts, the test-drug and positive-control showed, respectively, 100% and 97.3% anthelmintic efficacies on S. vulgaris, 100% and 81.4% on S. equinus, and equally 100% on S. edentatus. However, the efficacies on S. equinus and S. edentatus should be taken only as face values considering their respective low worm counts in the placebo group. The S. vulgaris-induced arterial lesions were also reduced in the test-drug and positive-control groups with efficacies of 73.9% and 62.9%, respectively. No adverse reactions were observed with either of the drugs. Our data demonstrate that the Equimax tablet formula was as safe and efficacious as the gel formula anthelmintic on large strongyles in horses.

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

USDA-ARS?s Scientific Manuscript database

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...

Correlation of polyphenolic content with radical-scavenging capacity and anthelmintic effects of Rubus ulmifolius (Rosaceae) against Haemonchus contortus.

PubMed

Akkari, Hafidh; Hajaji, Soumaya; B'chir, Fatma; Rekik, Mourad; Gharbi, Mohamed

2016-05-15

Phenolic content, antioxidant and anthelmintic activities of herbal extracts are of particular interest to drug industry; plant extracts with significant anthelmintic activity have the potential to be used as alternatives to conventional chemical drugs. In the present study, Rubus ulmifolius fruit extracts obtained using solvents of increasing polarity (water, methanol, chloroform and hexane) were examined for their antioxidant and anthelmintic activities in correlation with their polyphenolic content. In vitro antioxidant activity of all extracts was carried out using free radical-scavenging activity by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethilenebenzotiazolin)-6-sulfonic acid (ABTS) radical cation. In vitro anthelmintic activities were investigated on the egg and adult worms of Haemonchus contortus from sheep in comparison to albendazole. Total polyphenol content of R. ulmifolius was higher in more polar extract, ranging from 64.5 in aqueous extract to 1.57 mg gallic acid equivalents per gram of dry weight (GAE/g DW) in hexanic extract. Likewise, highest amounts of flavonoids and condensed tannins were found in aqueous extract (28.06 mg QE/g and 7.42 mg CE/g DW, respectively) compared to hexanic extract (0.71 mg QE/g and 0.29 mg CE/g DW, respectively) (p<0.05). Both DPPH and ABTS antioxidant assays showed that all tested extracts possess free radical scavenging activity, while the inhibitory concentration 50% (IC50) range values were similar for both assays (2.13-45.54 μg/mL and 1.2-43.82 μg/mL, respectively). All plant extracts showed ovicidal activity at all tested concentrations. Fruit methanolic (IC50=2.76mg/mL) and aqueous (IC50=2.08 mg/mL) extracts showed higher inhibitory effects than chloroformic (IC50=7.62 mg/mL) and hexanic (IC50=12.93 mg/mL) extracts on egg hatching (p<0.05). There was a significant correlation of total polyphenol, flavonoids and tannins content with scavenging of either DPPH (r=0.722, 0.764 and 0.752, p<0

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.

Dihydrobenz[e][1,4]oxazepin-2(3H)-ones, a new anthelmintic chemotype immobilising whipworm and reducing infectivity in vivo

PubMed Central

Bataille, Carole J. R.; Forman, Ruth; Heyer-Chauhan, Narinder; Marinič, Bruno; Sowood, Daniel J. C.; Wynne, Graham M.; Else, Kathryn J.; Russell, Angela J.

2017-01-01

Trichuris trichiura is a human parasitic whipworm infecting around 500 million people globally, damaging the physical growth and educational performance of those infected. Current drug treatment options are limited and lack efficacy against the worm, preventing an eradication programme. It is therefore important to develop new treatments for trichuriasis. Using Trichuris muris, an established model for T. trichiura, we screened a library of 480 novel drug-like small molecules for compounds causing paralysis of the ex vivo adult parasite. We identified a class of dihydrobenz[e][1,4]oxazepin-2(3H)-one compounds with anthelmintic activity against T. muris. Further screening of structurally related compounds and resynthesis of the most potent molecules led to the identification of 20 active dihydrobenzoxazepinones, a class of molecule not previously implicated in nematode control. The most active immobilise adult T. muris with EC50 values around 25–50μM, comparable to the existing anthelmintic levamisole. The best compounds from this chemotype show low cytotoxicity against murine gut epithelial cells, demonstrating selectivity for the parasite. Developing a novel oral pharmaceutical treatment for a neglected disease and deploying it via mass drug administration is challenging. Interestingly, the dihydrobenzoxazepinone OX02983 reduces the ability of embryonated T. muris eggs to establish infection in the mouse host in vivo. Complementing the potential development of dihydrobenzoxazepinones as an oral anthelmintic, this supports an alternative strategy of developing a therapeutic that acts in the environment, perhaps via a spray, to interrupt the parasite lifecycle. Together these results show that the dihydrobenzoxazepinones are a new class of anthelmintic, active against both egg and adult stages of Trichuris parasites. They demonstrate encouraging selectivity for the parasite, and importantly show considerable scope for further optimisation to improve potency and

Dihydrobenz[e][1,4]oxazepin-2(3H)-ones, a new anthelmintic chemotype immobilising whipworm and reducing infectivity in vivo.

PubMed

Partridge, Frederick A; Murphy, Emma A; Willis, Nicky J; Bataille, Carole J R; Forman, Ruth; Heyer-Chauhan, Narinder; Marinič, Bruno; Sowood, Daniel J C; Wynne, Graham M; Else, Kathryn J; Russell, Angela J; Sattelle, David B

2017-02-01

Trichuris trichiura is a human parasitic whipworm infecting around 500 million people globally, damaging the physical growth and educational performance of those infected. Current drug treatment options are limited and lack efficacy against the worm, preventing an eradication programme. It is therefore important to develop new treatments for trichuriasis. Using Trichuris muris, an established model for T. trichiura, we screened a library of 480 novel drug-like small molecules for compounds causing paralysis of the ex vivo adult parasite. We identified a class of dihydrobenz[e][1,4]oxazepin-2(3H)-one compounds with anthelmintic activity against T. muris. Further screening of structurally related compounds and resynthesis of the most potent molecules led to the identification of 20 active dihydrobenzoxazepinones, a class of molecule not previously implicated in nematode control. The most active immobilise adult T. muris with EC50 values around 25-50μM, comparable to the existing anthelmintic levamisole. The best compounds from this chemotype show low cytotoxicity against murine gut epithelial cells, demonstrating selectivity for the parasite. Developing a novel oral pharmaceutical treatment for a neglected disease and deploying it via mass drug administration is challenging. Interestingly, the dihydrobenzoxazepinone OX02983 reduces the ability of embryonated T. muris eggs to establish infection in the mouse host in vivo. Complementing the potential development of dihydrobenzoxazepinones as an oral anthelmintic, this supports an alternative strategy of developing a therapeutic that acts in the environment, perhaps via a spray, to interrupt the parasite lifecycle. Together these results show that the dihydrobenzoxazepinones are a new class of anthelmintic, active against both egg and adult stages of Trichuris parasites. They demonstrate encouraging selectivity for the parasite, and importantly show considerable scope for further optimisation to improve potency and

Bio-important antipyrine derived Schiff bases and their transition metal complexes: Synthesis, spectroscopic characterization, antimicrobial, anthelmintic and DNA cleavage investigation

NASA Astrophysics Data System (ADS)

Manjunath, M.; Kulkarni, Ajaykumar D.; Bagihalli, Gangadhar B.; Malladi, Shridhar; Patil, Sangamesh A.

2017-01-01

Spectroscopic (IR, NMR, UV-vis, ESR, ESI-mass), magnetic and TGA studies suggests octahedral geometry for all the CoII, NiII and CuII complexes of the Schiff bases, derived from 4-aminoantipyrine and 8-formyl-7-Hydroxy-4-methylcoumarin/5-formyl-6-hydroxycoumarin, coordinated through ONO donor sites. Antibacterial (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi), antifungal (Aspergillus niger, Aspergillus flavus and Cladosporium) and DNA cleavage properties of the metal complexes are investigated. The results suggested that some of the synthesized compounds are potential antimicrobials. The synthesized compounds tested for their anthelmintic activities and it was found that CoII and NiII complexes exhibited good anthelmintic properties.

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

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.

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

Multidrug-resistant tuberculosis/rifampicin-resistant tuberculosis: Principles of management

PubMed Central

Prasad, Rajendra; Gupta, Nikhil; Banka, Amitabh

2018-01-01

Multidrug-resistant tuberculosis (MDR-TB)/rifampicin-resistant TB (RR-TB) is human-made problem and emerging due to poor management of TB and is a threat to control of TB. Early suspicion and diagnosis are important. Culture and drug susceptibility testing are gold standards, but newer molecular methods help in rapid diagnosis. Once diagnosed, prompt treatment should be started, preferably under direct observation. Treatment can be standardized or individualized. Conventional regimen takes up to 24 months but recently shorter regimen of up to 12 months was introduced in specific subset of MDR-TB/RR-TB patients. Management of MDR-TB/RR-TB is complicated, costlier, and challenging and is a concern for human health worldwide. It must be emphasized that optimal treatment of MDR-TB/RR-TB alone is not sufficient. Efforts must be made to ensure effective use of first- and second-line anti-TB drugs. PMID:29319042

Multidrug-resistant tuberculosis/rifampicin-resistant tuberculosis: Principles of management.

PubMed

Prasad, Rajendra; Gupta, Nikhil; Banka, Amitabh

2018-01-01

Multidrug-resistant tuberculosis (MDR-TB)/rifampicin-resistant TB (RR-TB) is human-made problem and emerging due to poor management of TB and is a threat to control of TB. Early suspicion and diagnosis are important. Culture and drug susceptibility testing are gold standards, but newer molecular methods help in rapid diagnosis. Once diagnosed, prompt treatment should be started, preferably under direct observation. Treatment can be standardized or individualized. Conventional regimen takes up to 24 months but recently shorter regimen of up to 12 months was introduced in specific subset of MDR-TB/RR-TB patients. Management of MDR-TB/RR-TB is complicated, costlier, and challenging and is a concern for human health worldwide. It must be emphasized that optimal treatment of MDR-TB/RR-TB alone is not sufficient. Efforts must be made to ensure effective use of first- and second-line anti-TB drugs.

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

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.

Evaluation of anthelmintic potential of the Ethiopian medicinal plant Embelia schimperi Vatke in vivo and in vitro against some intestinal parasites.

PubMed

Debebe, Yared; Tefera, Mesfin; Mekonnen, Walelign; Abebe, Dawit; Woldekidan, Samuel; Abebe, Abiy; Belete, Yehualashet; Menberu, Temesgen; Belayneh, Bethelhem; Tesfaye, Berhanu; Nasir, Ibrahim; Yirsaw, Kidist; Basha, Hirut; Dawit, Asrat; Debella, Asfaw

2015-06-18

Embelia schimperi has been used for the treatment of intestinal parasites especially tapeworm infestations for centuries in Ethiopia. However, there is lack of scientific based evidences regarding the efficacy, safety and phytochemical analysis of this plant despite its frequent use as an anthelmintic. This study has therefore evaluated the efficacy and acute toxicity of E. schimperi thereby generating relevant preclinical information. The anthelmintic activities of the crude hydroalcoholic extract of E. schimperi and the isolated compound, embelin, were conducted using in vivo and in vitro models against the dwarf tapeworm, Hymenolepis nana, and the hookworm, Necator americanus, respectively. LD50 of the crude hydroalcoholic extract was determined using Swiss albino mice following the OECD guidelines. Chemical characterization of the isolated embelin was conducted using UV-spectroscopy, HPLC and NMR. In the acute toxicity study no prominent signs of toxicity and mortality were recorded among the experimental animals at the highest administered dose. Hence the LD50 of the plant was found to be higher than 5000 mg/kg. In vivo cestocidal activity of the crude hydroalcoholic extract of E. schimperi showed 100% parasite clearance at 1000 mg/kg, while the diammonium salt of embelin showed 85.3% parasite clearance at 750 mg/kg. The in vitro anthelminthic activity study revealed that the LC50 value of the crude extract and albendazole were 228.7 and 51.33 μg/mL, respectively. The results clearly indicated that the hydroalcoholic extract of E. schimperi and the diammonium salt of the isolated compound embelin had anthelmintic activity against hookworm larva in vitro and H. nana in vivo. Hence the findings of this study showed Embelia schimperi appears to possess some anthelmintic activity that may support the usage of these plants by local traditional healers to treat helminthic infestations.

Impact of gastrointestinal parasitic nematodes of sheep, and the role of advanced molecular tools for exploring epidemiology and drug resistance - an Australian perspective

PubMed Central

2013-01-01

Parasitic nematodes (roundworms) of small ruminants and other livestock have major economic impacts worldwide. Despite the impact of the diseases caused by these nematodes and the discovery of new therapeutic agents (anthelmintics), there has been relatively limited progress in the development of practical molecular tools to study the epidemiology of these nematodes. Specific diagnosis underpins parasite control, and the detection and monitoring of anthelmintic resistance in livestock parasites, presently a major concern around the world. The purpose of the present article is to provide a concise account of the biology and knowledge of the epidemiology of the gastrointestinal nematodes (order Strongylida), from an Australian perspective, and to emphasize the importance of utilizing advanced molecular tools for the specific diagnosis of nematode infections for refined investigations of parasite epidemiology and drug resistance detection in combination with conventional methods. It also gives a perspective on the possibility of harnessing genetic, genomic and bioinformatic technologies to better understand parasites and control parasitic diseases. PMID:23711194

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

USDA-ARS?s Scientific Manuscript database

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...

Schistosoma comparative genomics: integrating genome structure, parasite biology and anthelmintic discovery

PubMed Central

Swain, Martin T.; Larkin, Denis M.; Caffrey, Conor R.; Davies, Stephen J.; Loukas, Alex; Skelly, Patrick J.; Hoffmann, Karl F.

2011-01-01

Schistosoma genomes provide a comprehensive resource for identifying the molecular processes that shape parasite evolution and for discovering novel chemotherapeutic or immunoprophylactic targets. Here, we demonstrate how intra- and intergenus comparative genomics can be used to drive these investigations forward, illustrate the advantages and limitations of these approaches and review how post genomic technologies offer complementary strategies for genome characterisation. While sequencing and functional characterisation of other schistosome/platyhelminth genomes continues to expedite anthelmintic discovery, we contend that future priorities should equally focus on improving assembly quality, and chromosomal assignment, of existing schistosome/platyhelminth genomes. PMID:22024648

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

Anthelmintic activity of a standardized extract from the rhizomes of Acorus calamus Linn. (Acoraceae) against experimentally induced cestodiasis in rats

PubMed Central

Nath, Purobi; Yadav, Arun K

2016-01-01

Background: The rhizomes of a herb Acorus calamus Linn. (Acoraceae) have been widely used as a traditional medicine to cure intestinal-helminthic infections in India and South Africa. Aim: This study was undertaken to investigate the in vivo anthelmintic activity of a standardized methanolic extract obtained from the rhizomes A. calamus in a rodent model. Materials and Methods: A methanolic extract obtained from rhizomes of A. calamus was characterized for active principle using nuclear magnetic resonance 1H NMR, 13C NMR, mass and infrared spectroscopy. The amount of active principle in rhizome isolated active fraction of plant was assayed using high-performance liquid chromatography (HPLC). Later, the standardized rhizome extract of plant and its active principle were tested for in vivo anthelmintic efficacy against experimentally induced Hymenolepis diminuta, a zoonotic cestode, infections in rats. Results: The study revealed that b-asarone is the active principle of plant. The HPLC analysis of local variety of A. calamus revealed that active fraction contains 83.54% (w/w) of b-asarone. The in vivo study revealed that treatment of H. diminuta infected rats by a single 800 mg/kg dose of rhizome extract for 5 days results into 62.30% reduction in eggs per gram of feces counts and 83.25% reduction in worm counts of animals. These findings compared well with the efficacy of a reference drug, praziquantel. The active principle b-asarone showed slightly better anthelmintic effects than crude extract. In acute toxicity assay, a single oral 2000 mg/kg dose of extract did not reveal any signs of toxicity or mortality in mice, and the LD50 of the extract was noted to be >2000 mg/kg. Conclusion: Taken together, the results of this study indicate that rhizomes of A. calamus bear significant dose-dependent effects against intestinal helminths. Further, the Indian variety of A. calamus contains high b-asarone content. Therefore, there exists a great potential to develop some

Unique structure and regulation of the nematode detoxification gene regulator SKN-1: implications to understanding and controlling drug resistance

PubMed Central

Choe, Keith P.; Leung, Chi K.; Miyamoto, Michael M.

2012-01-01

Nematodes parasitize an alarming number of people and agricultural animals globally and cause debilitating morbidity and mortality. Anthelmintics have been the primary tools used to control parasitic nematodes for the past several decades, but drug resistance is becoming a major obstacle. Xenobiotic detoxification pathways defend against drugs and other foreign chemicals in diverse organisms, and evidence is accumulating that they play a role in mediating resistance to anthelmintics in nematodes. Related anti-oxidation pathways may also provide filarial parasites protection against host free radical-mediated immune responses. Upstream regulatory pathways have received almost no attention in nematode parasites despite their potential to co-regulate multiple detoxification and anti-oxidation genes. The NRF2 transcription factor mediates inducible detoxification and anti-oxidation defenses in mammals and recent studies have demonstrated that it promotes multidrug resistance in some human tumors. Recent studies in the free-living model nematode Caenorhabditis elegans have defined the homologous transcription factor SKN-1 as a master regulator of detoxification and anti-oxidation genes. Despite similar functions, SKN-1 and NRF2 have important differences in structure and regulatory pathways. Protein alignment and phylogenetic analyses indicate that these differences are shared among many nematodes making SKN-1 a candidate for specifically targeting nematode detoxification and anti-oxidation. PMID:22656429

Use of a mixed sericea lespedeza and grass pasture system for control of gastrointestinal nematodes in lambs and kids

USDA-ARS?s Scientific Manuscript database

Because of a high prevalence of anthelmintic resistance and consumer demand for chemical free meat products, management tools to minimize the need for deworming are needed. The objective was to examine the effectiveness of grazing sericea lespedeza (SL) in a mixed grass or a pure forage system for ...

Comparison of two long acting pre-lambing anthelmintic treatments on the productivity of ewes in low body condition.

PubMed

Bingham, C; Hodge, A; Mariadass, B

2017-05-01

To determine if there was a benefit from treating ewes with a low body condition score (BCS) with long acting anthelmintic products pre-lambing and to compare the effects of two commonly used treatment options. The study was conducted on a single commercial hill country sheep and beef property in the central North Island of New Zealand. Mixed age twin-bearing ewes were preselected by the farmer as being in poor condition 4 weeks before the planned start of lambing, and were sequentially drafted into three equal groups identified with coloured ear tags. The negative control group (n=199) received no anthelmintic treatment; the other two groups received either a controlled release capsule (CRC) containing abamectin, albendazole, Se and Co (n=200) or a long-acting injection of moxidectin (n=200). All ewes were body condition scored (1-5 scale) and weighed at pre-lambing, docking (65 days after treatment) and at weaning (127 days after treatment). Faecal nematode egg counts (FEC) were carried out on 10 ewes from each group at these three times. Most lambs were matched to the ewe treatment groups at weaning, and weighed. At weaning the mean body weight of ewes treated with moxidectin was 3.2 (95% CI=2.3-4.3) kg heavier than controls, and of ewes treated with CRC was 3.6 (95% CI=2.5-4.5) kg heavier than control ewes (p<0.001). At the start of the trial only 61/599 (10.2%) ewes had a BCS≥3. At weaning, more ewes treated with CRC (140/194; 72%) or moxidectin (122/187; 65%) had a BCS≥3 than control ewes (55/179 (31%); p<0.001). In lambs that were matched with ewes from the treatment groups, the mean weight at weaning of lambs from ewes treated with moxidectin was 2.6 (95% CI=1.9-3.3) kg heavier, and from ewes treated with CRC was 2.6 (95% CI=1.9-3.4) kg heavier than lambs from control ewes (p<0.001). Treating twin-bearing ewes with low BCS pre-lambing with long acting anthelmintic treatments (moxidectin long acting injection or CRC) resulted in an increase in mean body

The diterpenoid 7-keto-sempervirol, derived from Lycium chinense, displays anthelmintic activity against both Schistosoma mansoni and Fasciola hepatica.

PubMed

Edwards, Jennifer; Brown, Martha; Peak, Emily; Bartholomew, Barbara; Nash, Robert J; Hoffmann, Karl F

2015-03-01

Two platyhelminths of biomedical and commercial significance are Schistosoma mansoni (blood fluke) and Fasciola hepatica (liver fluke). These related trematodes are responsible for the chronic neglected tropical diseases schistosomiasis and fascioliasis, respectively. As no vaccine is currently available for anti-flukicidal immunoprophylaxis, current treatment is mediated by mono-chemical chemotherapy in the form of mass drug administration (MDA) (praziquantel for schistosomiasis) or drenching (triclabendazole for fascioliasis) programmes. This overreliance on single chemotherapeutic classes has dramatically limited the number of novel chemical entities entering anthelmintic drug discovery pipelines, raising significant concerns for the future of sustainable blood and liver fluke control. Here we demonstrate that 7-keto-sempervirol, a diterpenoid isolated from Lycium chinense, has dual anthelmintic activity against related S. mansoni and F. hepatica trematodes. Using a microtiter plate-based helminth fluorescent bioassay (HFB), this activity is specific (Therapeutic index = 4.2, when compared to HepG2 cell lines) and moderately potent (LD50 = 19.1 μM) against S. mansoni schistosomula cultured in vitro. This anti-schistosomula effect translates into activity against both adult male and female schistosomes cultured in vitro where 7-keto-sempervirol negatively affects motility/behaviour, surface architecture (inducing tegumental holes, tubercle swelling and spine loss/shortening), oviposition rates and egg morphology. As assessed by the HFB and microscopic phenotypic scoring matrices, 7-keto-sempervirol also effectively kills in vitro cultured F. hepatica newly excysted juveniles (NEJs, LD50 = 17.7 μM). Scanning electron microscopy (SEM) evaluation of adult F. hepatica liver flukes co-cultured in vitro with 7-keto-sempervirol additionally demonstrates phenotypic abnormalities including breaches in tegumental integrity and spine loss. 7-keto-sempervirol negatively

Deciphering the molecular determinants of cholinergic anthelmintic sensitivity in nematodes: When novel functional validation approaches highlight major differences between the model Caenorhabditis elegans and parasitic species

PubMed Central

Blanchard, Alexandra; Charvet, Claude L.; Sauvé, Christine; Duguet, Thomas; O’Connor, Vincent; Castagnone-Sereno, Philippe; Wolstenholme, Adrian J.; Beech, Robin N.; Holden-Dye, Lindy

2018-01-01

Cholinergic agonists such as levamisole and pyrantel are widely used as anthelmintics to treat parasitic nematode infestations. These drugs elicit spastic paralysis by activating acetylcholine receptors (AChRs) expressed in nematode body wall muscles. In the model nematode Caenorhabditis elegans, genetic screens led to the identification of five genes encoding levamisole-sensitive-AChR (L-AChR) subunits: unc-38, unc-63, unc-29, lev-1 and lev-8. These subunits form a functional L-AChR when heterologously expressed in Xenopus laevis oocytes. Here we show that the majority of parasitic species that are sensitive to levamisole lack a gene orthologous to C. elegans lev-8. This raises important questions concerning the properties of the native receptor that constitutes the target for cholinergic anthelmintics. We demonstrate that the closely related ACR-8 subunit from phylogenetically distant animal and plant parasitic nematode species functionally substitutes for LEV-8 in the C. elegans L-AChR when expressed in Xenopus oocytes. The importance of ACR-8 in parasitic nematode sensitivity to cholinergic anthelmintics is reinforced by a ‘model hopping’ approach in which we demonstrate the ability of ACR-8 from the hematophagous parasitic nematode Haemonchus contortus to fully restore levamisole sensitivity, and to confer high sensitivity to pyrantel, when expressed in the body wall muscle of C. elegans lev-8 null mutants. The critical role of acr-8 to in vivo drug sensitivity is substantiated by the successful demonstration of RNAi gene silencing for Hco-acr-8 which reduced the sensitivity of H. contortus larvae to levamisole. Intriguingly, the pyrantel sensitivity remained unchanged thus providing new evidence for distinct modes of action of these important anthelmintics in parasitic species versus C. elegans. More broadly, this highlights the limits of C. elegans as a predictive model to decipher cholinergic agonist targets from parasitic nematode species and provides

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

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

PubMed

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

2016-09-01

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). 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. Pumpkin seed extracts may be used to control of Gastrointestinal (G.I.) nematode infections. This relatively inexpensive alternative to the currently available

Assessment of the anthelmintic efficacy of albendazole in school children in seven countries where soil-transmitted helminths are endemic.

PubMed

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

2011-03-29

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. 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. 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 parasite. ClinicalTrials.gov NCT01087099.

Plasma disposition, concentration in the hair, and anthelmintic efficacy of eprinomectin after topical administration in donkeys.

PubMed

Gokbulut, Cengiz; Di Loria, Antonio; Gunay, Necati; Masucci, Roberto; Veneziano, Vincenzo

2011-12-01

To investigate plasma disposition, concentration in the hair, and anthelmintic efficacy of eprinomectin after topical administration in donkeys. 12 donkeys naturally infected with strongyle nematodes. The pour-on formulation of eprinomectin approved for use in cattle was administered topically to donkeys at a dosage of 0.5 mg/kg. Heparinized blood samples and hair samples were collected at various times between 1 hour and 40 days after administration. Samples were analyzed via high-performance liquid chromatography with fluorescence detection. Fecal strongyle egg counts were performed by use of a modified McMaster technique before and at weekly intervals for 8 weeks after treatment. Plasma concentration and systemic availability of eprinomectin were relatively higher in donkeys, compared with values reported for other animal species. Concerning the anthelmintic efficacy against strongyle nematodes, eprinomectin was completely effective (100%) on days 7 and 14 and highly effective (> 99%) until the end of the study at 56 days after treatment. No abnormal clinical signs or adverse reactions were observed for any donkeys after treatment. Eprinomectin had excellent safety. The relatively high plasma concentration after topical administration could result in use of eprinomectin for the control and treatment of parasitic diseases in donkeys.

Underpinning Sustainable Vector Control through Informed Insecticide Resistance Management

PubMed Central

Hemmings, Kay; Hughes, Angela J.; Chanda, Emmanuel; Musapa, Mulenga; Kamuliwo, Mulakwa; Phiri, Faustina N.; Muzia, Lucy; Chanda, Javan; Kandyata, Alister; Chirwa, Brian; Poer, Kathleen; Hemingway, Janet; Wondji, Charles S.; Ranson, Hilary; Coleman, Michael

2014-01-01

Background There has been rapid scale-up of malaria vector control in the last ten years. Both of the primary control strategies, long-lasting pyrethroid treated nets and indoor residual spraying, rely on the use of a limited number of insecticides. Insecticide resistance, as measured by bioassay, has rapidly increased in prevalence and has come to the forefront as an issue that needs to be addressed to maintain the sustainability of malaria control and the drive to elimination. Zambia's programme reported high levels of resistance to the insecticides it used in 2010, and, as a result, increased its investment in resistance monitoring to support informed resistance management decisions. Methodology/Principal Findings A country-wide survey on insecticide resistance in Zambian malaria vectors was performed using WHO bioassays to detect resistant phenotypes. Molecular techniques were used to detect target-site mutations and microarray to detect metabolic resistance mechanisms. Anopheles gambiae s.s. was resistant to pyrethroids, DDT and carbamates, with potential organophosphate resistance in one population. The resistant phenotypes were conferred by both target-site and metabolic mechanisms. Anopheles funestus s.s. was largely resistant to pyrethroids and carbamates, with potential resistance to DDT in two locations. The resistant phenotypes were conferred by elevated levels of cytochrome p450s. Conclusions/Significance Currently, the Zambia National Malaria Control Centre is using these results to inform their vector control strategy. The methods employed here can serve as a template to all malaria-endemic countries striving to create a sustainable insecticide resistance management plan. PMID:24932861

Insights from agriculture for the management of insecticide resistance in disease vectors.

PubMed

Sternberg, Eleanore D; Thomas, Matthew B

2018-04-01

Key to contemporary management of diseases such as malaria, dengue, and filariasis is control of the insect vectors responsible for transmission. Insecticide-based interventions have contributed to declines in disease burdens in many areas, but this progress could be threatened by the emergence of insecticide resistance in vector populations. Insecticide resistance is likewise a major concern in agriculture, where insect pests can cause substantial yield losses. Here, we explore overlaps between understanding and managing insecticide resistance in agriculture and in public health. We have used the Global Plan for Insecticide Resistance Management in malaria vectors, developed under the auspices of the World Health Organization Global Malaria Program, as a framework for this exploration because it serves as one of the few cohesive documents for managing a global insecticide resistance crisis. Generally, this comparison highlights some fundamental differences between insect control in agriculture and in public health. Moreover, we emphasize that the success of insecticide resistance management strategies is strongly dependent on the biological specifics of each system. We suggest that the biological, operational, and regulatory differences between agriculture and public health limit the wholesale transfer of knowledge and practices from one system to the other. Nonetheless, there are some valuable insights from agriculture that could assist in advancing the existing Global Plan for Insecticide Resistance Management framework.

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

PubMed

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

2016-06-01

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

Insecticide resistance management strategies against the western flower thrips, Frankliniella occidentalis.

PubMed

Bielza, Pablo

2008-11-01

Western flower thrips (WFT), Frankliniella occidentalis (Pergande), is an economically important pest of a wide range of crops grown throughout the world. Insecticide resistance has been documented in many populations of WFT. Biological and behavioural characteristics and pest management practices that promote insecticide resistance are discussed. In addition, an overview is provided of the development of insecticide resistance in F. occidentalis populations and the resistance mechanisms involved. Owing to widespread resistance to most conventional insecticides, a new approach to insecticide resistance management (IRM) of F. occidentalis is needed. The IRM strategy proposed consists of two parts. Firstly, a general strategy to minimise the use of insecticides in order to reduce selection pressure. Secondly, a strategy designed to avoid selection of resistance mechanisms, considering cross-resistance patterns and resistance mechanisms. Copyright (c) 2008 Society of Chemical Industry.

New Method for the Analysis of Flukicide and Other Anthelmintic Residues in Bovine Milk and Liver using LC-MS/MS

USDA-ARS?s Scientific Manuscript database

A liquid chromatographic-tandem mass spectrometric (LC-MS/MS) multi-residue method for the simultaneous quantification and identification of 38 residues of the most widely used anthelmintic veterinary drugs (including benzimidazoles, macrocyclic lactones, and flukicides) in milk and liver has been d...

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

Framing the issues of resistance management in soybean

USDA-ARS?s Scientific Manuscript database

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

In vivo anthelmintic efficacy of Aloe ferox, Agave sisalana, and Gunnera perpensa in village chickens naturally infected with Heterakis gallinarum.

PubMed

Mwale, Marizvikuru; Masika, Patrick Julius

2015-01-01

The study was conducted to determine the anthelmintic efficacy of Aloe ferox, Agave sisalana, and Gunnera perpensa against Heterakis gallinarum in village chickens. The chickens naturally infected with H. gallinarum were randomly divided into 14 groups of eight chickens and orally administered distilled water (negative control), mebendazole (positive control), and graded levels (50-, 100-, 200-, and 400-mg/kg doses) of the three plant extracts. At days 0, 7, and 14, the floatation technique was used to determine fecal egg counts and H. gallinarum worms from chicken ceca were counted at days 0 and 14. Egg count reduction percentage (ECR%) was high at day 7 for all the test materials except for A. sisalana (100 mg/kg) that had 33%. At day 14, ECR% was high for all the other test materials save for A. ferox (200 mg/kg), mebendazole, and distilled water which was 50, 32, and 50%, respectively. A. ferox (200 mg/kg), G. perpensa (200 and 400 mg/kg), and A. sisalana (50 and 100 mg/kg) had the highest (85, 78, 74, 86, and 73%, respectively) worm count reduction percentage. The plants had anthelmintic properties. Advocacy and utilization of these plants in improving the health of village chickens could lead to increased productivity, boosting profits for the poultry industry thereby enabling it to meet the supply of animal protein and enhance livelihoods. It is imperative to determine compounds in the crude extracts of these medicinal plants which are responsible for the anthelmintic activities and their mechanism of action.

Field trial assessment of ivermectin pharmacokinetics and efficacy against susceptible and resistant nematode populations in cattle.

PubMed

Canton, Candela; Canton, Lucila; Domínguez, María Paula; Moreno, Laura; Lanusse, Carlos; Alvarez, Luis; Ceballos, Laura

2018-05-30

The study compared the pharmacokinetic (PK) behaviour and anthelmintic efficacy against susceptible and resistant nematodes following subcutaneous (SC) and oral administration of ivermectin (IVM) to cattle. Six commercial farms were involved: Farms 1 and 2 (IVM-susceptible nematode population) and Farms 3, 4, 5 and 6 (IVM-resistant nematode population). On each farm, forty-five calves naturally infected with gastrointestinal (GI) nematodes were randomly allocated into three groups (n = 15): untreated control, IVM SC administration, and IVM oral administration (both at 0.2 mg/kg). PK assessment (plasma and faeces) was performed on Farm 1. Efficacy was determined by Faecal Egg Count Reduction Test. IVM systemic availability upon SC administration (421 ± 70.3 ng·d/mL) was higher (P < 0.05) compared to the oral treatment (132 ± 31.3 ng·d/mL). However, higher (P < 0.05) faecal IVM concentrations were observed following oral treatment (9896 ± 1931 ng·d/mL) compared to SC administration (4760 ± 924 ng·d/mL). Similar (91-93%) IVM efficacy was observed on Farms 1 and 2 by both routes. Efficacy against resistant nematodes was slightly higher on Farms 3 and 4 after the oral (63 and 82%, respectively) compared to the SC (36 and 68%, respectively) treatment. However, there was complete therapeutic failure (0% efficacy) on Farm 5 and a very low response on Farm 6 (40 and 41% for SC and oral administration, respectively). Although larger faecal concentrations following IVM oral administration may increase drug exposure of GI adult worms, this does not always improve efficacy against resistant nematodes. The potential therapeutic advantages of oral treatments should be cautiously assessed, especially in presence of anthelmintic resistance. Copyright © 2018 Elsevier B.V. All rights reserved.

Direct anthelmintic effects of Cereus jamacaru (Cactaceae) on trichostrongylid nematodes of sheep: in vivo studies.

PubMed

Vatta, A F; Kandu-Lelo, C; Ademola, I O; Eloff, J N

2011-08-25

Following claims of anthelmintic activity of Cereus jamacaru DC (Cactaceae) by a commercial farmer, in vivo studies were conducted to determine the possible direct anthelmintic effects of the plant on ovine gastrointestinal nematodes. Eighteen sheep were infected with 4000 Haemonchus contortus and 6000 Trichostrongylus colubriformis larvae given in three divided doses over a period of three days. Once the infections were patent, the sheep were allocated to three groups and were drenched once a week for six weeks with fresh blended C. jamacaru plant material at a single (32.3g/sheep) or double dose (64.6g/sheep) or they remained as undrenched controls. Faeces were collected from individual animals on the day of treatment and three days thereafter on a weekly basis for seven weeks for faecal egg count. While there were no statistically significant differences in the egg counts between the groups, a double dose of C. jamacaru was effective in reducing the egg counts in the sheep by 18-65% over the 49 days of the experiment. Given that all animals remained in good health throughout the course of the experiment, with no adverse events occurring during the study, further experiments using higher doses or administering the plant material for a longer period of time than in the present study would be warranted. Copyright © 2011 Elsevier B.V. All rights reserved.

Effects of feeding on the plasma disposition kinetics of the anthelmintic albendazole in laying hens.

PubMed

Bistoletti, M; Alvarez, L; Lanusse, C; Moreno, L

2014-01-01

1. To optimise the use of albendazole (ABZ) as an anthelmintic in hens, the effects of fasting and type of diet on the plasma kinetics of ABZ and its metabolites were evaluated. 2. Twenty-four hens were distributed into 4 groups: In experiment I the Fed group were fed ad libitum, while the Fasted group was fasted over a 12-h period. In experiment II the Pelleted group was fed with pelleted commercial food, while the Grain group was fed with cereal grains. All the groups were treated with ABZ by oral route. Blood samples were taken and plasma analysed by HPLC. 3. ABZ and its metabolites albendazole-sulphoxide (ABZSO) and albendazole-sulphone (ABZSO2) were recovered in plasma in all the groups. The 12-h fasting period did not modify the disposition kinetics of ABZ in hens. The type of feed affected ABZ kinetics. ABZSO concentration profile was higher and detected for longer in the Grain group compared to the Pelleted group. Statistical differences were not found for AUC0-∞ values, whereas the T1/2for and T1/2el were different between groups. 4. Factors affecting ABZ kinetic behaviour should be taken into account to optimise its use to ensure the sustainability of the limited available anthelmintic therapeutic tools in avian parasite control.

The anthelmintic efficacy of fenbendazole in the control of Moniezia expansa and Trichuris ovis in sheep.

PubMed

Townsend, R B; Kelly, J D; James, R; Weston, I

1977-11-01

The anthelmintic efficacy of fenbendazole (methyl 5-(phenyl-thio)-2-benzimidazole-carbamate) against Moniezia expansa and Trichuris ovis was tested. At dose rates of 5 mg per kg and above, efficacies were found to be greater than 91 percent against M expansa and greater than 92 per cent against T ovis. At these dose rates efficacy on egg suppression was 100 per cent for Moniezia and greater than 97 per cent for Trichuris.

Grassland Resistance and Resilience after Drought Depends on Management Intensity and Species Richness

PubMed Central

Vogel, Anja; Scherer-Lorenzen, Michael; Weigelt, Alexandra

2012-01-01

The degree to which biodiversity may promote the stability of grasslands in the light of climatic variability, such as prolonged summer drought, has attracted considerable interest. Studies so far yielded inconsistent results and in addition, the effect of different grassland management practices on their response to drought remains an open question. We experimentally combined the manipulation of prolonged summer drought (sheltered vs. unsheltered sites), plant species loss (6 levels of 60 down to 1 species) and management intensity (4 levels varying in mowing frequency and amount of fertilizer application). Stability was measured as resistance and resilience of aboveground biomass production in grasslands against decreased summer precipitation, where resistance is the difference between drought treatments directly after drought induction and resilience is the difference between drought treatments in spring of the following year. We hypothesized that (i) management intensification amplifies biomass decrease under drought, (ii) resistance decreases with increasing species richness and with management intensification and (iii) resilience increases with increasing species richness and with management intensification. We found that resistance and resilience of grasslands to summer drought are highly dependent on management intensity and partly on species richness. Frequent mowing reduced the resistance of grasslands against drought and increasing species richness decreased resistance in one of our two study years. Resilience was positively related to species richness only under the highest management treatment. We conclude that low mowing frequency is more important for high resistance against drought than species richness. Nevertheless, species richness increased aboveground productivity in all management treatments both under drought and ambient conditions and should therefore be maintained under future climates. PMID:22615865

Genetic basis of benzimidazole resistance in Teladorsagia circumcincta in Ireland.

PubMed

Keegan, Jason D; Good, Barbara; de Waal, Theo; Fanning, June; Keane, Orla M

2017-01-01

Resistance to benzimidazole (BZ) anthelmintics is common in ovine nematodes of economic importance. Single nucleotide polymorphisms (SNP) at three positions in the isotype 1 β- tubulin gene have been associated with BZ resistance and molecular tests for the detection of BZ resistance have been developed. In order to determine if such tests are practicable in Ireland the polymorphisms associated with BZ resistance must be identified. To this end, BZ-resistant nematodes were recovered from four farms in Ireland. Resistant Teladorsagia circumcincta , Cooperia curticei and Trichostrongylus colubriformis were recovered, with resistant T. circumcincta the most common and the only species studied further. Sequencing of the isotype 1 β-tubulin gene from resistant T. circumcincta identified a T - A transition, resulting in an F200Y substitution known to be responsible for BZ-resistance, on three of the farms. However, on the fourth farm the frequency of the resistant A allele was only 0.33 indicating another BZ resistance mechanism may be present on this farm. An additional polymorphism resulting in a substitution of glutamate for leucine (E198L) was also found on this farm at low frequency (0.17). No polymorphisms at position 167 were identified on any farm. Therefore, molecular tests to detect BZ resistance in T. circumcincta in Ireland could prove useful; however, they may result in some instances of resistance remaining undetected.

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. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Common errors in multidrug-resistant tuberculosis management.

PubMed

Monedero, Ignacio; Caminero, Jose A

2014-02-01

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

The effects of stage-specific selection on the development of benzimidazole resistance in Haemonchus contortus in sheep.

PubMed

Taylor, M A; Hunt, K R; Goodyear, K L

2002-10-16

Resistance to the benzimidazole (BDZ) class of anthelmintics in nematodes of sheep has become a common and global phenomenon. The rate at which the selection process and development of resistance occurs is influenced by a number of factors. Of these, the effects of stage-specific exposures to anthelmintic were investigated with a BDZ-resistant strain of Haemonchus contortus (HCR) over five parasite generations. Sheep were infected at each generation with the HCR strain and were treated with thiabendazole (TBZ), either 5 days post-infection (p.i.) (larval line), 21 days p.i. (adult line), or left untreated (no selection line). Additionally eggs from each generation were exposed to TBZ (egg line). Geometric worm burdens were calculated from post-mortem worm counts, both at the start of the study, and after the final selection studies for each of the selection lines. Egg hatch assays (EHAs) were also conducted throughout the study. All data relating to worm burdens and EHAs for each generation were analysed by linear regression to produce dose titration curves and lethal dose(50) (LD(50)) values for each of the selection lines. Over the five generations, LD(50) values on dose-response were increased and worm survival occurred at higher dose rates of TBZ irrespective of the parasite stage exposed to treatment. A similar picture was seen with ED(50) values, which showed a fluctuating but generally upward trend for each of the three selection lines. In contrast, LD(50) and ED(50) values were decreased in the no selection line, indicating some degree of reversion albeit to levels still considered to be BDZ-resistant.

Worm control practice against gastro-intestinal parasites in Norwegian sheep and goat flocks

PubMed Central

2011-01-01

Background Anthelmintic treatment is the most common way of controlling nematode infections in ruminants. However, several countries have reported anthelmintic resistance (AR), representing a limitation for sustainable small ruminant production. The knowledge regarding worm control management represents a baseline to develop a guideline for preventing AR. The aim of the present study was therefore to improve our knowledge about the worm control practices in small ruminant flocks in Norway. Methods A questionnaire survey regarding worm control practices was performed in small ruminant flocks in Norway. Flocks were selected from the three main areas of small ruminant farming, i.e. the coastal, inland and northern areas. A total of 825 questionnaires, comprising 587 sheep flocks (return rate of 51.3%) and 238 goat flocks (52.6%) were included. Results The results indicated that visual appraisal of individual weight was the most common means of estimating the anthelmintic dose used in sheep (78.6%) and goat (85.1%) flocks. The mean yearly drenching rate in lambs and ewes were 2.5 ± 1.7 and 1.9 ± 1.1, respectively, whereas it was 1.0 (once a year) in goats. However, these figures were higher in sheep in the coastal area with a rate of 3.4 and 2.2 in lambs and ewes, respectively. Benzimidazoles were the predominant anthelmintic class used in sheep flocks (64.9% in 2007), whereas benzimidazoles and macrocyclic lactones were both equally used in dairy goat flocks. In the period of 2005-2007, 46.3% of the sheep flocks never changed the anthelmintic class. The dose and move strategy was practiced in 33.2% of the sheep flocks. Conclusions The present study showed that inaccurate weight calculation gives a risk of under-dosing in over 90% of the sheep and goat flocks in Norway. Taken together with a high treatment frequency in lambs, a lack of anthelmintic class rotation and the common use of a dose-and-move strategy, a real danger for development of anthelmintic resistance

Benzimidazole resistance in Nematodirus spathiger and N. filicollis in New Zealand.

PubMed

Oliver, Amb; Pomroy, W E; Leathwick, D M

2016-07-01

in N. spathiger than N. filicollis. While resistance to benzimidazole anthelmintics has been reported previously in New Zealand, this is the first report of N. filicollis being resistant to benzimidazole anthelmintics.

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.

Associations between fasciolosis and milk production, and the impact of anthelmintic treatment in dairy herds.

PubMed

Köstenberger, Kerstin; Tichy, Alexander; Bauer, Karl; Pless, Peter; Wittek, Thomas

2017-07-01

Liver fluke is a ubiquitous parasite that causes extensive production losses in cattle and is a zoonosis. The aims of this study were to determine the prevalence of fasciolosis in 178 dairy cattle herds in Styria (federal state of Austria) and its influence on production, to detect the risk factors for infection, and to explore effective strategies in management and control. A questionnaire on farm management, prophylaxis, and therapy was developed and applied. Furthermore, production parameters (milk yield, milk protein content, butter fat content, non-return rate 90, calving to conception interval, service period) were recorded for 2014 and 2015, and a commercial ELISA for detection of Fasciola hepatica antibodies was applied in bulk tank milk in March 2014 and March 2015. Analysis of bulk tank milk samples showed a prevalence of 61.3% in 2014 and 45.5% in 2015. No associations could be found between F. hepatica exposure and farm structure or pasture management. Farms with highly positive (optical density ratio (ODR) ≥ 0.6 and lying above the upper interquartile range) antibody levels had a significantly lower annual milk yield of 438 kg per cow per year (p = 0.045), butterfat content of 0.091% (p = 0.004), and milk protein content of 0.046% (p = 0.024). However, fertility parameters were not significantly associated with liver fluke exposure. Anthelmintic treatment led to significantly lower antibody levels in the subsequent year (p = 0.042) and had a significant influence on protein content in milk (p = 0.003). This study highlighted the importance of fasciolosis in Austria and its influence on milk production and the need for veterinary advice regarding prophylactic measures to reduce economic losses.

Influence of the cyclooctadepsipeptides PF1022A and PF1022E as natural products on the design of semi-synthetic anthelmintics such as emodepside.

PubMed

Jeschke, R; Iinuma, K; Harder, A; Schindler, M; Murakami, T

2005-10-01

The 24-membered cyclooctadepsipeptide (CODP) PF1022A, the active metabolite of the fungus imperfectus Mycelia sterilia (Rosellinia sp.) isolated from the plant Camellia japonica in Japan, is described as a powerful broad-spectrum anthelmintic natural product with low toxicity in animals. Further CODPs such as PF1022B, C, D and E have been isolated from the same culture and their structures have been established. Both PF1022A and PF1022E serve as valuable starting materials for the synthesis of semi-synthetic CODP derivatives with improved intrinsic anthelmintic potency and broad-spectrum activity. It was found that in most cases the di-substituted PF1022A derivatives showed a greater (or equal) activity by oral application against the gastrointestinal nematode Haemonchus contortus compared to the corresponding mono-substituted PF1022A analogues as exemplified by emodepside. In order to get additional information on the bioactive conformation, emodepside was transformed into its mono- and tetra-thionated derivatives by isosteric replacement. In the light of the increased efficacy of these derivatives against H. contortus or Trichostrongylus colubriformis, it has been suggested that the asymmetric conformation clearly influences the anthelmintic activity of CODPs. Although useful synthetic pathways are available today for the preparation of the semi-synthetic CODP emodepside, the fermentative production of its bis-para-nitro and bis-para-amino precursors could be the process used for its industrial-scale production in the future.

Discovery of genomic intervals that underlie nematode responses to benzimidazoles.

PubMed

Zamanian, Mostafa; Cook, Daniel E; Zdraljevic, Stefan; Brady, Shannon C; Lee, Daehan; Lee, Junho; Andersen, Erik C

2018-03-01

Parasitic nematodes impose a debilitating health and economic burden across much of the world. Nematode resistance to anthelmintic drugs threatens parasite control efforts in both human and veterinary medicine. Despite this threat, the genetic landscape of potential resistance mechanisms to these critical drugs remains largely unexplored. Here, we exploit natural variation in the model nematodes Caenorhabditis elegans and Caenorhabditis briggsae to discover quantitative trait loci (QTL) that control sensitivity to benzimidazoles widely used in human and animal medicine. High-throughput phenotyping of albendazole, fenbendazole, mebendazole, and thiabendazole responses in panels of recombinant lines led to the discovery of over 15 QTL in C. elegans and four QTL in C. briggsae associated with divergent responses to these anthelmintics. Many of these QTL are conserved across benzimidazole derivatives, but others show drug and dose specificity. We used near-isogenic lines to recapitulate and narrow the C. elegans albendazole QTL of largest effect and identified candidate variants correlated with the resistance phenotype. These QTL do not overlap with known benzimidazole target resistance genes from parasitic nematodes and present specific new leads for the discovery of novel mechanisms of nematode benzimidazole resistance. Analyses of orthologous genes reveal conservation of candidate benzimidazole resistance genes in medically important parasitic nematodes. These data provide a basis for extending these approaches to other anthelmintic drug classes and a pathway towards validating new markers for anthelmintic resistance that can be deployed to improve parasite disease control.

Blended Refuge and Insect Resistance Management for Insecticidal Corn

PubMed Central

Crespo, Andre L B; Pan, Zaiqi; Crain, Philip R; Thompson, Stephen D; Pilcher, Clinton D; Sethi, Amit

2018-01-01

Abstract In this review, we evaluate the intentional mixing or blending of insecticidal seed with refuge seed for managing resistance by insects to insecticidal corn (Zea mays). We first describe the pest biology and farming practices that will contribute to weighing trade-offs between using block refuges and blended refuges. Case studies are presented to demonstrate how the trade-offs will differ in different systems. We compare biological aspects of several abstract models to guide the reader through the history of modeling, which has played a key role in the promotion or denigration of blending in various scientific debates about insect resistance management for insecticidal crops. We conclude that the use of blended refuge should be considered on a case-by-case basis after evaluation of insect biology, environment, and farmer behavior. For Diabrotica virgifera virgifera, Ostrinia nubilalis, and Helicoverpa zea in the United States, blended refuge provides similar, if not longer, delays in the evolution of resistance compared to separate block refuges. PMID:29220481

United States Department of Agriculture-Agricultural Research Service research on managing insect resistance to insecticides.

PubMed

Elzen, Gary W; Hardee, Dick D

2003-01-01

Insecticide resistance has developed within many classes of pesticide, and over 500 species of insects and mites are resistant to one or more insecticides. Insecticide resistance and the consequent losses of food and fiber caused by failure to control insect and mite pests causes economic losses of several billion dollars worldwide each year. It is the goal of insect resistance management (IRM) to preserve useful pesticides by slowing, preventing or reversing development of resistance in pests. Important aspects of this goal are understanding the development of resistance and monitoring to determine ways to prevent its development. We describe programs specific to missions of the US Department of Agriculture, Agricultural Research Service, which are designed to characterize insecticide resistance in insects and mites with the goal of managing pests in an ecologically acceptable manner. Resistance management of cotton, potatoes, vegetables, melons, ornamentals, greenhouse crops, corn, stored grains, livestock, honeybees and mites, as well as management of transgenic crops are evaluated. We conclude that IRM is a vital part of stewardship of any pest management product and must be a combined effort of manufacturers, growers, consultants, extension services and grower organizations, working closely with regulators, to achieve logistically and economically feasible systems that prolong the effectiveness of all pest-control products.

Examination of commercially available copper oxide wire particles in combination with albendazole for control of gastrointestinal nematodes in lambs

USDA-ARS?s Scientific Manuscript database

Alternatives to synthetic anthelmintics remain critical due to the prevalence of anthelmintic resistance. The objective of the experiment was to determine the efficacy of copper oxide wire particles (COWP) from three commercial sources to control Haemonchus contortus in lambs. Naturally infected Ka...

Factors affecting fecal egg counts in peri-parturient Katahdin ewes and their lambs

USDA-ARS?s Scientific Manuscript database

Selection for low fecal egg counts (FEC) can be used to genetically enhance resistance to gastrointestinal nematode parasites in growing lambs, thereby reducing the frequency of use of anthelmintics, facilitating marketing of organic lamb, and reducing the risk of development of anthelmintic resista...

In vitro anthelmintic activity of Combretum molle (R. Br. ex G. Don) (Combretaceae) against Haemonchus contortus ova and larvae.

PubMed

Ademola, I O; Eloff, J N

2010-04-19

Parasitic nematodes, especially Haemonchus contortus (Rudolphi), are among the most common and economically important causes of disease in sheep and goats owned by pastoralists and small holder farmers in Africa. The control of these infections relies mainly on the use of anthelmintic drugs. However, herbal preparations are widely used by pastoralists and small holder farmers for the treatment of their livestock against helminth parasites. The anthelmintic effect of acetone leaf extract and fractions of Combretum molle was investigated to determine the relative efficacy of the components against gastrointestinal sheep nematodes. The fractions were obtained by solvent:solvent extraction from the acetone extract. These were evaluated for nematocidal activity by means of an egg hatch (EHA) and larval a development and viability assay (LDVA) in vitro. The effect of the test extracts on the hatchability of eggs and development of first to third stage larvae and the survival rate of the third stage larvae. H. contortus, were used to determine the relative bioactivities. Best-fit LC(50) values were computed using global model of nonlinear regression curve-fitting. The extracts inhibited egg hatching and development of the larvae of H. contortus in a concentration-dependent manner. Best-fit LC(50) values for the egg hatch test were 0.866, 0.333, 0.833, 0.747, and 0.065mg/mL for acetone extract, n-butanol, hexane, chloroform, and 35% water in methanol fractions, respectively. The best-fit LC(50) values for the LDVA were 0.604, 0.362, 1.077, 0.131 and 0.318mg/mL for the acetone extract, butanol, hexane, chloroform, and 35% water in methanol fractions, respectively. In the EHA the 35% water in methanol fraction was significantly more active than all the other fractions (p<0.05); however the activity was not significantly different with the LDVA. C. molle leaf could find application in anthelmintic therapy in veterinary practice.

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

PubMed Central

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

Abstract 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

Western flower thrips resistance to insecticides: detection, mechanisms, and management strategies

USDA-ARS?s Scientific Manuscript database

Insecticide resistance continues to be one of the most important issues facing agricultural production. The challenges in insecticide resistance and its management are exemplified by the situation with the western flower thrips Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae). This ...

Antimicrobial, Anthelmintic, and Antiviral Activity of Plants Traditionally Used for Treating Infectious Disease in the Similipal Biosphere Reserve, Odisha, India

PubMed Central

Panda, Sujogya K.; Padhi, Laxmipriya; Leyssen, Pieter; Liu, Maoxuan; Neyts, Johan; Luyten, Walter

2017-01-01

In the present study, we tested in vitro different parts of 35 plants used by tribals of the Similipal Biosphere Reserve (SBR, Mayurbhanj district, India) for the management of infections. From each plant, three extracts were prepared with different solvents (water, ethanol, and acetone) and tested for antimicrobial (E. coli, S. aureus, C. albicans); anthelmintic (C. elegans); and antiviral (enterovirus 71) bioactivity. In total, 35 plant species belonging to 21 families were recorded from tribes of the SBR and periphery. Of the 35 plants, eight plants (23%) showed broad-spectrum in vitro antimicrobial activity (inhibiting all three test strains), while 12 (34%) exhibited narrow spectrum activity against individual pathogens (seven as anti-staphylococcal and five as anti-candidal). Plants such as Alangium salviifolium, Antidesma bunius, Bauhinia racemosa, Careya arborea, Caseria graveolens, Cleistanthus patulus, Colebrookea oppositifolia, Crotalaria pallida, Croton roxburghii, Holarrhena pubescens, Hypericum gaitii, Macaranga peltata, Protium serratum, Rubus ellipticus, and Suregada multiflora showed strong antibacterial effects, whilst Alstonia scholaris, Butea monosperma, C. arborea, C. pallida, Diospyros malbarica, Gmelina arborea, H. pubescens, M. peltata, P. serratum, Pterospermum acerifolium, R. ellipticus, and S. multiflora demonstrated strong antifungal activity. Plants such as A. salviifolium, A. bunius, Aporosa octandra, Barringtonia acutangula, C. graveolens, C. pallida, C. patulus, G. arborea, H. pubescens, H. gaitii, Lannea coromandelica, M. peltata, Melastoma malabathricum, Millettia extensa, Nyctanthes arbor-tristis, P. serratum, P. acerifolium, R. ellipticus, S. multiflora, Symplocos cochinchinensis, Ventilago maderaspatana, and Wrightia arborea inhibit survival of C. elegans and could be a potential source for anthelmintic activity. Additionally, plants such as A. bunius, C. graveolens, C. patulus, C. oppositifolia, H. gaitii, M. extensa, P

Antimicrobial, Anthelmintic, and Antiviral Activity of Plants Traditionally Used for Treating Infectious Disease in the Similipal Biosphere Reserve, Odisha, India.

PubMed

Panda, Sujogya K; Padhi, Laxmipriya; Leyssen, Pieter; Liu, Maoxuan; Neyts, Johan; Luyten, Walter

2017-01-01

In the present study, we tested in vitro different parts of 35 plants used by tribals of the Similipal Biosphere Reserve (SBR, Mayurbhanj district, India) for the management of infections. From each plant, three extracts were prepared with different solvents (water, ethanol, and acetone) and tested for antimicrobial ( E. coli, S. aureus, C. albicans ); anthelmintic ( C. elegans ); and antiviral ( enterovirus 71 ) bioactivity. In total, 35 plant species belonging to 21 families were recorded from tribes of the SBR and periphery. Of the 35 plants, eight plants (23%) showed broad-spectrum in vitro antimicrobial activity (inhibiting all three test strains), while 12 (34%) exhibited narrow spectrum activity against individual pathogens (seven as anti-staphylococcal and five as anti-candidal). Plants such as Alangium salviifolium, Antidesma bunius, Bauhinia racemosa, Careya arborea, Caseria graveolens, Cleistanthus patulus, Colebrookea oppositifolia, Crotalaria pallida, Croton roxburghii, Holarrhena pubescens, Hypericum gaitii, Macaranga peltata, Protium serratum, Rubus ellipticus , and Suregada multiflora showed strong antibacterial effects, whilst Alstonia scholaris, Butea monosperma, C. arborea, C. pallida, Diospyros malbarica, Gmelina arborea, H. pubescens, M. peltata, P. serratum, Pterospermum acerifolium, R. ellipticus , and S. multiflora demonstrated strong antifungal activity. Plants such as A. salviifolium, A. bunius, Aporosa octandra, Barringtonia acutangula, C. graveolens, C. pallida, C. patulus, G. arborea, H. pubescens, H. gaitii, Lannea coromandelica, M. peltata, Melastoma malabathricum, Millettia extensa, Nyctanthes arbor-tristis, P. serratum, P. acerifolium, R. ellipticus, S. multiflora, Symplocos cochinchinensis, Ventilago maderaspatana , and Wrightia arborea inhibit survival of C. elegans and could be a potential source for anthelmintic activity. Additionally, plants such as A. bunius, C. graveolens, C. patulus, C. oppositifolia, H. gaitii, M. extensa

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

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

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

PubMed

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

2014-04-01

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

Current management of advanced and castration resistant prostate cancer.

PubMed

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

2014-04-01

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

Opioids Resistance in Chronic Pain Management

PubMed Central

Morrone, Luigi A.; Scuteri, Damiana; Rombolà, Laura; Mizoguchi, Hirokazu; Bagetta, Giacinto

2017-01-01

Abstract: Chronic pain management represents a serious healthcare problem worldwide. Chronic pain affects approximately 20% of the adult European population and is more frequent in women and older people. Unfortunately, its management in the community remains generally unsatisfactory and rarely under the control of currently available analgesics. Opioids have been used as analgesics for a long history and are among the most used drugs; however, while there is no debate over their short term use for pain management, limited evidence supports their efficacy of long-term treatment for chronic non-cancer pain. Therapy with opioids is hampered by inter-individual variability and serious side effects and some opioids often result ineffective in the treatment of chronic pain and their use is controversial. Accordingly, for a better control of chronic pain a deeper knowledge of the molecular mechanisms underlying resistance to opiates is mandatory. PMID:28503117

Benchmark study on glyphosate-resistant crop systems in the United States. Economics of herbicide resistance management practices in a 5 year field-scale study.

PubMed

Edwards, C Blake; Jordan, David L; Owen, Michael Dk; Dixon, Philip M; Young, Bryan G; Wilson, Robert G; Weller, Steven C; Shaw, David R

2014-12-01

Since the introduction of glyphosate-resistant (GR) crops, growers have often relied on glyphosate-only weed control programs. As a result, multiple weeds have evolved resistance to glyphosate. A 5 year study including 156 growers from Illinois, Iowa, Indiana, Nebraska, North Carolina and Mississippi in the United States was conducted to compare crop yields and net returns between grower standard weed management programs (SPs) and programs containing best management practices (BMPs) recommended by university weed scientists. The BMPs were designed to prevent or mitigate/manage evolved herbicide resistance. Weed management costs were greater for the BMP approach in most situations, but crop yields often increased sufficiently for net returns similar to those of the less expensive SPs. This response was similar across all years, geographical regions, states, crops and tillage systems. Herbicide use strategies that include a diversity of herbicide mechanisms of action will increase the long-term sustainability of glyphosate-based weed management strategies. Growers can adopt herbicide resistance BMPs with confidence that net returns will not be negatively affected in the short term and contribute to resistance management in the long term. © 2014 Society of Chemical Industry.

Motility in the L3 stage is a poor phenotype for detecting and measuring resistance to avermectin/milbemycin drugs in gastrointestinal nematodes of livestock.

PubMed

George, Melissa M; Lopez-Soberal, Lorraine; Storey, Bob E; Howell, Sue B; Kaplan, Ray M

2018-04-01

Motility is a commonly used in vitro phenotype for assessing anthelmintic activity of candidate compounds, and for detecting anthelmintic resistance in nematodes. Third-stage larvae (L3) of parasitic nematodes are commonly used in motility-based assays because L3 are simple to obtain and can remain viable in storage for extended periods. To improve the measurement of motility of microscopic stages of nematodes, our laboratory developed the Worminator, which quantitatively measures motility of parasites. Using the Worminator, we compared the dose-response characteristics of several avermectin/milbemycin (AM) compounds using L3 from both AM-susceptible and AM-resistant Cooperia spp. (abamectin, doramectin, eprinomectin, ivermectin, moxidectin) and Haemonchus contortus (eprinomectin, ivermectin, moxidectin). Concentrations tested with the Worminator ranged from 0.156 to 40 μM. Differences in EC 50 between AM-susceptible and AM-resistant isolates of Cooperia spp. and Haemonchus contortus were small, with resistance ratios ranging from 1.00 to 1.34 for Cooperia spp., 0.99 to 1.65 for Haemonchus contortus. Larval migration inhibition assays were conducted using the same isolates and were equally ineffective for detection of resistance with resistance ratios less than 2.0. These results contrast with those of the Larval Development Assay where we obtained a resistance ratio of 16.48 using the same isolates of Haemonchus contortus. Moreover, even at the highest concentration tested (40 μM), 100% inhibition of motility was never achieved and EC 50 for Worminator assays were more than 100× higher than peak plasma levels achieved in vivo following treatment. These data demonstrate that dose-response characteristics for inhibition of motility in L3 of gastrointestinal nematodes of livestock do not significantly differ for AM-susceptible and AM-resistant isolates. These data challenge the suitability of motility as a phenotype for detecting and measuring resistance to AM

In vivo anthelmintic activity of Anogeissus leiocarpus Guill & Perr (Combretaceae) against nematodes in naturally infected sheep.

PubMed

Soro, Dramane; Koné, Witabouna Mamidou; Bonfoh, Bassirou; Dro, Bernadin; Toily, Kassédo Bénédicte; Kamanzi, Kagoyire

2013-07-01

The identification of new anthelmintic drugs becomes a priority because of the availability of a handful of drugs, cost of treatments, and recent emergence of drug resistance. Medicinal plants are a good source of bioactive compounds for development of drugs. In this study, in vivo efficacy of Anogeissus leiocarpus was assessed in sheep naturally infected with gastrointestinal nematodes. Fecal examination, serological analyses, and necropsy were carried out to determine the egg and worm-burden reduction. The administration of ethanolic extract (single oral dose of 80 mg/kg) of A. leiocarpus induced a moderate fecal egg reduction (81 %) and adult worm-burden reduction (87 %) against Haemonchus contortus and Trichostrongylus colubriformis (82 %). The plant exhibited high efficacy against adult Strongyloïdes papillosus (100 %), Gaigeria pachyscelis (90 %), Cooperia curticei (100 %), and Oesophagostomum columbianum (95 %) but low efficacy against Trichostrongylus axei (67 %) and Trichuris globulosa (79 %). All these helminthes were sensitive to fenbendazole, except O. columbianum which showed a decrease susceptibility (17 %). The plant extract also improved certain biological parameters by increasing bodyweight from 0.7 ± 2.9 to 3.3 ± 1.9 % and improving hematocrit of 6.9 ± 1.6 % 3-week posttreatment. It emerges from the results that the plant possesses significant effectiveness on diarrhea; all treated animals gave normal feces. This study has shown that A. leiocarpus could find an application in the control of multiparasitism in small ruminants.

Positive and normative modeling for Palmer amaranth control and herbicide resistance management.

PubMed

Frisvold, George B; Bagavathiannan, Muthukumar V; Norsworthy, Jason K

2017-06-01

Dynamic optimization models are normative; they solve for what growers 'ought to do' to maximize some objective, such as long-run profits. While valuable for research, such models are difficult to solve computationally, limiting their applicability to grower resistance management education. While discussing properties of normative models in general, this study presents results of a specific positive model of herbicide resistance management, applied to Palmer amaranth control on a representative cotton farm. This positive model compares a proactive resistance management strategy to a reactive strategy with lower short-run costs, but greater risk of herbicide resistance developing. The proactive strategy can pay for itself within 1-4 years, with a yield advantage of 4% or less if the yield advantage begins within 1-2 years of adoption. Whether the proactive strategy is preferable is sensitive to resistance onset and yield losses, but less sensitive to cotton prices or baseline yields. Industry rebates to encourage residual herbicide use (to delay resistance to post-emergence treatments) may be too small to alter grower behavior or they may be paid to growers who would have used residuals anyway. Rebates change grower behavior over a relatively narrow range of model parameters. The size of rebates needed to induce a grower to adopt the proactive strategy declines significantly if growers extend their planning horizon from 1 year to 3-4 years. Whether proactive resistance management is more profitable than a reactive strategy is more sensitive to biological parameters than economic ones. Simulation results suggest growers with longer time horizons (perhaps younger ones) would be more responsive to rebate programs. More empirical work is needed to determine how much rebates increase residual use above what would occur without them. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Resistance Exercise to Prevent and Manage Sarcopenia and Dynapenia

PubMed Central

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

2016-01-01

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

Resistance Exercise to Prevent and Manage Sarcopenia and Dynapenia.

PubMed

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

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

Organizational risk management of resistance to care episodes in health facilities.

PubMed

Kable, Ashley; Guest, Maya; McLeod, Mary

2012-09-01

This article reports a study of organizational risk management approaches to resistance to care episodes in specific clinical areas: prevention measures, provision of subsequent support and follow-up by management and resultant organizational change. Resistance to care describes a patient's unwillingness to be assisted by healthcare staff and is manifested in defensive behaviours ranging from minor non-compliance/dissent to aggression. It has previously been studied in aged care settings and focused on patient behaviours and appropriate responses. This was a cross-sectional survey of a representative sample of nurses (n = 5044) who were members of the New South Wales Nurses' Association in Australia, in 2008-2009. Of 1132 participants, 80% reported being involved in resistance to care episodes during the previous month and this was higher in some settings. Episodes were not routinely reported internally, and often did not lead to organizational change. Nurses reported that talking with other staff was the most effective action in dealing with the consequences of these episodes. Half of the respondents considered that they were provided with sufficient support and follow-up after a resistance to care episode. Prevention measures and follow-up strategies adopted by employers varied across clinical settings. Resistance to care is not confined to aged care settings, and risk management of resistance to care can increase safety in the workplace. Preventive strategies such as increased staff, training and security should be focused on high risk clinical areas; and appropriate support, follow-up and organizational change instituted in response to these episodes. © 2011 Blackwell Publishing Ltd.

Discovery of quantitative trait loci for resistance to parasitic nematode infection in sheep: I. Analysis of outcross pedigrees

PubMed Central

Crawford, Allan M; Paterson, Korena A; Dodds, Ken G; Diez Tascon, Cristina; Williamson, Penny A; Roberts Thomson, Meredith; Bisset, Stewart A; Beattie, Anne E; Greer, Gordon J; Green, Richard S; Wheeler, Roger; Shaw, Richard J; Knowler, Kevin; McEwan, John C

2006-01-01

Background Currently most pastoral farmers rely on anthelmintic drenches to control gastrointestinal parasitic nematodes in sheep. Resistance to anthelmintics is rapidly increasing in nematode populations such that on some farms none of the drench families are now completely effective. It is well established that host resistance to nematode infection is a moderately heritable trait. This study was undertaken to identify regions of the genome, quantitative trait loci (QTL) that contain genes affecting resistance to parasitic nematodes. Results Rams obtained from crossing nematode parasite resistant and susceptible selection lines were used to derive five large half-sib families comprising between 348 and 101 offspring per sire. Total offspring comprised 940 lambs. Extensive measurements for a range of parasite burden and immune function traits in all offspring allowed each lamb in each pedigree to be ranked for relative resistance to nematode parasites. Initially the 22 most resistant and 22 most susceptible progeny from each pedigree were used in a genome scan that used 203 microsatellite markers spread across all sheep autosomes. This study identified 9 chromosomes with regions showing sufficient linkage to warrant the genotyping of all offspring. After genotyping all offspring with markers covering Chromosomes 1, 3, 4, 5, 8, 12, 13, 22 and 23, the telomeric end of chromosome 8 was identified as having a significant QTL for parasite resistance as measured by the number of Trichostrongylus spp. adults in the abomasum and small intestine at the end of the second parasite challenge. Two further QTL for associated immune function traits of total serum IgE and T. colubiformis specific serum IgG, at the end of the second parasite challenge, were identified on chromosome 23. Conclusion Despite parasite resistance being a moderately heritable trait, this large study was able to identify only a single significant QTL associated with it. The QTL concerned adult parasite

Discovery of quantitative trait loci for resistance to parasitic nematode infection in sheep: I. Analysis of outcross pedigrees.

PubMed

Crawford, Allan M; Paterson, Korena A; Dodds, Ken G; Diez Tascon, Cristina; Williamson, Penny A; Roberts Thomson, Meredith; Bisset, Stewart A; Beattie, Anne E; Greer, Gordon J; Green, Richard S; Wheeler, Roger; Shaw, Richard J; Knowler, Kevin; McEwan, John C

2006-07-18

Currently most pastoral farmers rely on anthelmintic drenches to control gastrointestinal parasitic nematodes in sheep. Resistance to anthelmintics is rapidly increasing in nematode populations such that on some farms none of the drench families are now completely effective. It is well established that host resistance to nematode infection is a moderately heritable trait. This study was undertaken to identify regions of the genome, quantitative trait loci (QTL) that contain genes affecting resistance to parasitic nematodes. Rams obtained from crossing nematode parasite resistant and susceptible selection lines were used to derive five large half-sib families comprising between 348 and 101 offspring per sire. Total offspring comprised 940 lambs. Extensive measurements for a range of parasite burden and immune function traits in all offspring allowed each lamb in each pedigree to be ranked for relative resistance to nematode parasites. Initially the 22 most resistant and 22 most susceptible progeny from each pedigree were used in a genome scan that used 203 microsatellite markers spread across all sheep autosomes. This study identified 9 chromosomes with regions showing sufficient linkage to warrant the genotyping of all offspring. After genotyping all offspring with markers covering Chromosomes 1, 3, 4, 5, 8, 12, 13, 22 and 23, the telomeric end of chromosome 8 was identified as having a significant QTL for parasite resistance as measured by the number of Trichostrongylus spp. adults in the abomasum and small intestine at the end of the second parasite challenge. Two further QTL for associated immune function traits of total serum IgE and T. colubiformis specific serum IgG, at the end of the second parasite challenge, were identified on chromosome 23. Despite parasite resistance being a moderately heritable trait, this large study was able to identify only a single significant QTL associated with it. The QTL concerned adult parasite burdens at the end of the second

Management of methicillin-resistant Staphylococcus aureus bacteremia.

PubMed

Cosgrove, Sara E; Fowler, Vance G

2008-06-01

Staphylococcus aureus bacteremia and endocarditis are serious infections that demand prompt clinical attention to ensure good outcomes. Of foremost importance is identifying and managing the source of infection and any associated complications. Evaluation for the presence of cardiac involvement is essential because inadequately managed S. aureus endocarditis is life threatening. Thus, physicians must aggressively negotiate treatment paths, considering whether the S. aureus bacteremia is complicated, whether foreign sources of infection should be removed or replaced, and whether surgical intervention is necessary. Selection of an antibiotic treatment is also an essential factor for optimal management. The increasing prevalence of methicillin-resistant S. aureus (MRSA) infections has created a tremendous demand for effective and safe antimicrobial agents other than the historic anti-MRSA agent vancomycin.

The in vitro anthelmintic effects of plumbagin on newly excysted and 4-weeks-old juvenile parasites of Fasciola gigantica.

PubMed

Lorsuwannarat, Natcha; Piedrafita, David; Chantree, Pathanin; Sansri, Veerawat; Songkoomkrong, Sineenart; Bantuchai, Sirasate; Sangpairot, Kant; Kueakhai, Pornanan; Changklungmoa, Narin; Chaichanasak, Pannigan; Chansela, Piyachat; Sobhon, Prasert

2014-01-01

The effect of plumbagin (PB, 5-hydroxy-2-methyl-1,4-naphthoquinone) against newly excysted juveniles (NEJs) and 4-weeks-old immature parasites of Fasciola gigantica were compared with triclabendazole (TCZ). The anthelmintic efficacy of 1, 10 and 100μg/ml of PB or TCZ following incubation in vitro for 1-24h was compared using a combination of relative motility (RM), survival index (SI) and larval migration inhibition (LMI) assays for parasite viability. The RM and SI values of the PB-treated group decreased at a more rapid rate than the TCZ-treated group. For NEJs, the decreased RM values were first observed at 1h incubation with 1μg/ml PB, and 90% of flukes were killed at 24h. In contrast, in TCZ-treated groups a 10-fold higher concentration of TCZ (10μg/ml) resulted in only 9% dead parasites after 24h incubation. In 4-weeks-old juvenile parasites, PB reduced the RM value at 10μg/ml with 100% of flukes dead after 3h, while TCZ decreased RM values at the concentration of 100μg/ml but with only 5% of flukes killed at 24h. NEJs treated with PB exhibited 88%, 99% and 100% of LMIs at the concentrations of 1, 10 and 100μg/ml, respectively. NEJs incubated with TCZ have an LMI of only 32% at the highest concentration of 100μg/ml. Similarly PB had a significantly greater killing of immature 4weeks juvenile stages than TCZ at all concentrations; however, 4-weeks-old juvenile parasites were more resistant to killing by PB or TCZ at all concentrations when compared to NEJs. Further studies were carried out to investigate the alterations of the parasite tegument by scanning electron microscope (SEM). PB caused similar tegumental alterations in 4-weeks-old juveniles as those observed in TCZ treatment but with greater damage at comparative time points, comprising of swelling, blebbing and rupture of the tegument, loss of spines, and eventual erosion, lesion and desquamation of the total tegument. These data indicate that PB had a greater fasciolicidal effect against

Country-level operational implementation of the Global Plan for Insecticide Resistance Management

PubMed Central

Hemingway, Janet; Vontas, John; Poupardin, Rodolphe; Raman, Jaishree; Lines, Jo; Schwabe, Chris; Matias, Abrahan; Kleinschmidt, Immo

2013-01-01

Malaria control is reliant on the use of long-lasting pyrethroid-impregnated nets and/or indoor residual spraying (IRS) of insecticide. The rapid selection and spread of operationally significant pyrethroid resistance in African malaria vectors threatens our ability to sustain malaria control. Establishing whether resistance is operationally significant is technically challenging. Routine monitoring by bioassay is inadequate, and there are limited data linking resistance selection with changes in disease transmission. The default is to switch insecticides when resistance is detected, but limited insecticide options and resistance to multiple insecticides in numerous locations make this approach unsustainable. Detailed analysis of the resistance situation in Anopheles gambiae on Bioko Island after pyrethroid resistance was detected in this species in 2004, and the IRS program switched to carbamate bendiocarb, has now been undertaken. The pyrethroid resistance selected is a target-site knock-down resistance kdr-form, on a background of generally elevated metabolic activity, compared with insecticide-susceptible A. gambiae, but the major cytochrome P450-based metabolic pyrethroid resistance mechanisms are not present. The available evidence from bioassays and infection data suggests that the pyrethroid resistance mechanisms in Bioko malaria vectors are not operationally significant, and on this basis, a different, long-lasting pyrethroid formulation is now being reintroduced for IRS in a rotational insecticide resistance management program. This will allow control efforts to be sustained in a cost-effective manner while reducing the selection pressure for resistance to nonpyrethroid insecticides. The methods used provide a template for evidence-based insecticide resistance management by malaria control programs. PMID:23696658

Country-level operational implementation of the Global Plan for Insecticide Resistance Management.

PubMed

Hemingway, Janet; Vontas, John; Poupardin, Rodolphe; Raman, Jaishree; Lines, Jo; Schwabe, Chris; Matias, Abrahan; Kleinschmidt, Immo

2013-06-04

Malaria control is reliant on the use of long-lasting pyrethroid-impregnated nets and/or indoor residual spraying (IRS) of insecticide. The rapid selection and spread of operationally significant pyrethroid resistance in African malaria vectors threatens our ability to sustain malaria control. Establishing whether resistance is operationally significant is technically challenging. Routine monitoring by bioassay is inadequate, and there are limited data linking resistance selection with changes in disease transmission. The default is to switch insecticides when resistance is detected, but limited insecticide options and resistance to multiple insecticides in numerous locations make this approach unsustainable. Detailed analysis of the resistance situation in Anopheles gambiae on Bioko Island after pyrethroid resistance was detected in this species in 2004, and the IRS program switched to carbamate bendiocarb, has now been undertaken. The pyrethroid resistance selected is a target-site knock-down resistance kdr-form, on a background of generally elevated metabolic activity, compared with insecticide-susceptible A. gambiae, but the major cytochrome P450-based metabolic pyrethroid resistance mechanisms are not present. The available evidence from bioassays and infection data suggests that the pyrethroid resistance mechanisms in Bioko malaria vectors are not operationally significant, and on this basis, a different, long-lasting pyrethroid formulation is now being reintroduced for IRS in a rotational insecticide resistance management program. This will allow control efforts to be sustained in a cost-effective manner while reducing the selection pressure for resistance to nonpyrethroid insecticides. The methods used provide a template for evidence-based insecticide resistance management by malaria control programs.

Antimicrobial resistance and management of invasive Salmonella disease.

PubMed

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

2015-06-19

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

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

Parasite control in the age of drug resistance and changing agricultural practices.

PubMed

Molento, Marcelo Beltrão

2009-08-07

The benefits of using antiparasitic drugs in farm animals are unquestionable. However, despite anthelmintic use as the predominant control strategy, extreme parasite infection cases are appearing in sheep and goat production; these impact productivity and have show mortality rates reaching pre-drug use levels. This was a predictable situation resulting from the loss of efficacy by all available products, particularly when some products were used as the sole intervention. The concepts of agroecology and holistic agriculture, which advocate the use of integrated management strategies, such as target selected treatment, herbal medicine, and the application of other parasite control alternatives, are not completely new, but are undergoing a resurgence because of their more sustainable appeal. The objective of this review article is to examine the problem of parasite control in the face of parasite drug resistance and to outline some strategies that may be used in parasite control programmes. Before they are accepted and recommended by the WAAVP, agroecological methods such as those listed above and described in detail herein should be validated based on scientific evidence of their efficacy for parasite control and should be tested for both host and environmental safety.

Evaluation of efficacy of school-based anthelmintic treatments against anaemia in children in the United Republic of Tanzania.

PubMed Central

Guyatt, H. L.; Brooker, S.; Kihamia, C. M.; Hall, A.; Bundy, D. A.

2001-01-01

OBJECTIVE: To determine the impact of deworming on anaemia as part of a large-scale school-based anthelmintic treatment programme in the Tanga Region of the United Republic of Tanzania. METHODS: Both the reduction in the prevalence of anaemia and the cost per case prevented were taken into consideration. Cross-sectional studies involved parasitological examination and anaemia evaluation before and at 10 months and 15 months after schoolchildren were dewormed. FINDINGS: Baseline studies indicated that the prevalence of anaemia (haemoglobin < 110 g/l) was high (54%) among schoolchildren, particularly those with high intensities of hookworm and schistosomiasis. Attributable fraction analysis suggested that hookworm and schistosomiasis were responsible for 6% and 15% of anaemia cases, respectively. Fifteen months after deworming with albendazole and praziquantel the prevalence of anaemia was reduced by a quarter and that of moderate-to-severe anaemia (haemoglobin <90 g/l) was reduced by nearly a half. The delivery of these anthelmintics through the school system was achieved at the relatively low cost of US$ 1 per treated child. The cost per anaemia case prevented by deworming schoolchildren was in the range US$ 6-8, depending on the haemoglobin threshold used. CONCLUSIONS: The results suggested that deworming programmes should be included in public health strategies for the control of anaemia in schoolchildren where there are high prevalences of hookworm and schistosomiasis. PMID:11545325

Integrated palmer amaranth management in glufosinate-resistant cotton

USDA-ARS?s Scientific Manuscript database

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

Lessons from the History of Ivermectin and Other Antiparasitic Agents.

PubMed

Campbell, William C

2016-01-01

The twentieth century's arsenal of chemical anthelmintics brought manifold improvement in human health and, more abundantly, in animal health. The benefits were not only in health per se but also in agricultural economics, livestock management, and the overall production of food and fiber to support expanding human populations. Nevertheless, there remains (due in large part to drug resistance and paucity of available vaccines) a great need for new means of controlling disease caused by parasitic worms. Prudence should persuade us to look to our past for lessons that might help in our quest for new drugs. The lessons suggested here derive from the history of ivermectin and other anthelmintics. They deal with the means of finding substances with useful antiparasitic activity and with alternative approaches to drug discovery.

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

A review of pharmacokinetic drug-drug interactions with the anthelmintic medications albendazole and mebendazole.

PubMed

Pawluk, Shane Ashley; Roels, Craig Allan; Wilby, Kyle John; Ensom, Mary H H

2015-04-01

Medications indicated for helminthes and other parasitic infections are frequently being used in mass populations in endemic areas. Currently, there is a lack of guidance for clinicians on how to appropriately manage drug interactions when faced with patients requiring short-term anthelmintic therapy with albendazole or mebendazole while concurrently taking other agents. The objective of this review was to systematically summarize and evaluate published literature on the pharmacokinetics of albendazole or mebendazole when taken with other interacting medications. A search of MEDLINE (1946 to October 2014), EMBASE (1974 to October 2014), International Pharmaceutical Abstracts (1970 to October 2014), Google, and Google Scholar was conducted for articles describing the pharmacokinetics of albendazole or mebendazole when given with other medications (and supplemented by a bibliographic review of all relevant articles). Altogether, 17 articles were included in the review. Studies reported data on pharmacokinetic parameters for albendazole or mebendazole when taken with cimetidine, dexamethasone, ritonavir, phenytoin, carbamazepine, phenobarbital, ivermectin, praziquantel, diethylcarbamazine, azithromycin, and levamisole. Cimetidine increased the elimination half-life of albendazole and maximum concentration (Cmax) of mebendazole; dexamethasone increased the area under the plasma concentration-time curve (AUC) of albendazole; levamisole decreased the Cmax of albendazole; anticonvulsants (phenytoin, phenobarbital, carbamazepine) decreased the AUC of albendazole; praziquantel increased the AUC of albendazole; and ritonavir decreased the AUC of both albendazole and mebendazole. No major interactions were found with ivermectin, azithromycin, or diethylcarbamazine. Future research is required to clarify the clinical relevance of the interactions observed.

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

PubMed

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

2017-01-01

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

Drug resistance in influenza A virus: the epidemiology and management

PubMed Central

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

2017-01-01

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

Production benefits from pre- and post-lambing anthelmintic treatment of ewes on commercial farms in the southern North Island of New Zealand.

PubMed

Miller, C M; Ganesh, S; Garland, C B; Leathwick, D M

2015-07-01

To measure the magnitude and variability in production responses to anthelmintic treatments administered to adult ewes around lambing. Ewes carrying twin lambs, from sheep and beef farms (eight in Year 1 and six in Year 2) in the Wairarapa region of New Zealand, were enrolled in 14 trials (part of an experiment carried out on one farm in one year). Experiment 1 compared ewes treated 2-4 weeks pre-lambing with a controlled release capsule (CRC) containing abamectin, albendazole, Se and Co, to ewes injected pre-lambing with a long-acting Se plus vitamin B12 product, and to untreated ewes. Experiment 2 included these treatments, plus a CRC administered at pregnancy scanning. Experiment 3 included the same treatments as Experiment 1, plus administration of a CRC containing albendazole, Se and Co, injectable moxidectin or oral derquantel plus abamectin, all administered pre-lambing, or oral derquantel plus abamectin administered 4-6 weeks after lambing. Variables compared were ewe liveweight at weaning and pre-mating, lamb liveweight at weaning, total weight of lamb weaned per ewe and ewe dag score at weaning. Ewes treated with a CRC pre-lambing were heavier than untreated ewes (mean 3.2 kg) at weaning in 12/14 trials, and pre-mating (mean 2.8 kg) in 9/14 trials (p<0.001). Compared with mineral-treated ewes the mean difference was 2.8 kg pre-lambing (9/14 trials) and 1.7 kg pre-weaning (6/14 trials). Lambs reared by treated ewes were heavier (mean 1.55 kg) at weaning in 6/14 trials (p<0.001), but there was no effect of CRC treatment on total weight of lambs weaned per ewe (p=0.507). Variation in weight of lamb weaned per ewe was largely explained by differences in lamb survival from birth to weaning (p<0.001), with no effect of CRC treatment (p>0.65). Treatment of ewes with a CRC at pregnancy scanning was neither better nor worse than a pre-lambing treatment (p=0.065). There was no difference in the response from treatment with either of the two CRC or moxidectin

Data driven weed management: Tracking herbicide resistance at the landscape scale

USDA-ARS?s Scientific Manuscript database

Limiting the prevalence of herbicide resistant (HR) weeds requires consistent management implementation across space and time. Although weed population dynamics operate at scales above farm-level, the emergent effect of neighboring management decisions on in-field weed densities and the spread of re...

The impact of anthelmintic treatment intervention on malaria infection and anaemia in school and preschool children in Magu district, Tanzania: an open label randomised intervention trial.

PubMed

Kinung'hi, Safari M; Magnussen, Pascal; Kishamawe, Coleman; Todd, Jim; Vennervald, Birgitte J

2015-03-20

Some studies have suggested that helminth infections increase the risk of malaria infection and are associated with increased number of malaria attacks and anaemia. Thus interventions to control helminth infections may have an impact on incidence of clinical malaria and anaemia. The current study assessed the impact of two anthelmintic treatment approaches on malaria infection and on anaemia in school and pre-school children in Magu district, Tanzania. A total of 765 children were enrolled into a prospective randomized anthelmintic intervention trial following a baseline study of 1546 children. Enrolled children were randomized to receive either repeated treatment with praziquantel and albendazole four times a year (intervention group, 394 children) or single dose treatment with praziquantel and albendazole once a year (control group, 371 children). Follow up examinations were conducted at 12 and 24 months after baseline to assess the impact of the intervention. Stool and urine samples were collected and examined for schistosome and soil transmitted helminth infections. Blood samples were also collected and examined for malaria parasites and haemoglobin concentrations. Monitoring of clinical malaria attacks was performed at each school during the two years of the intervention. Out of 1546 children screened for P. falciparum, S. mansoni, S. haematobium, hookworm and T. Trichiura at baseline, 1079 (69.8%) were infected with at least one of the four parasites. There was no significant difference in malaria infection (prevalence, parasite density and frequency of malaria attacks) and in the prevalence of anaemia between the repeated and single dose anthelmintic treatment groups at 12 and 24 months follow up (p>0.05). However, overall, there was significant improvement in mean haemoglobin concentrations (p<0.001) from baseline levels of 122.0 g/L and 123.0 g/L to 136.0 g/L and 136.8 g/L for the repeated and single dose treatment groups, respectively, at 24 months follow

Determination of anthelmintic drug residues in milk using ultra high performance liquid chromatography-tandem mass spectrometry with rapid polarity switching.

PubMed

Whelan, Michelle; Kinsella, Brian; Furey, Ambrose; Moloney, Mary; Cantwell, Helen; Lehotay, Steven J; Danaher, Martin

2010-07-02

A new UHPLC-MS/MS (ultra high 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 concentration step to detect most of the analytes at <1 microg kg(-1) levels in milk. Anthelmintic residues were extracted into acetonitrile using magnesium sulphate and sodium chloride to induce liquid-liquid partitioning followed by dispersive solid phase extraction for cleanup. The extract was concentrated into dimethyl sulphoxide, which was used as a keeper to ensure analytes remain in solution. Using rapid polarity switching in electrospray ionisation, a single injection was capable of detecting both positively and negatively charged ions in a 13 min run time. The method was validated at two levels: the unapproved use level and at the maximum residue level (MRL) according to Commission Decision (CD) 2002/657/EC criteria. The decision limit (CCalpha) of the method was in the range of 0.14-1.9 and 11-123 microg kg(-1) for drugs validated at unapproved and MRL levels, respectively. The performance of the method was successfully verified for benzimidazoles and levamisole by participating in a proficiency study.

Aspects of the pharmacology of a new anthelmintic

PubMed Central

Aubry, M. L.; Cowell, Pauline; Davey, M. J.; Shevde, S.

1970-01-01

1. The pharmacological properties of an anthelmintic, pyrantel, and some of its analogues have been described and compared with piperazine in a variety of vertebrate and helminth preparations. 2. Pyrantel and its analogues in common with nicotine and decamethonium cause spastic paralysis in chicks and contracture of the chick semispinalis and toad rectus abdominis muscles. 3. In the soleus and anterior tibialis muscles of the cat, pyrantel in large amounts caused a short-lived neuromuscular block that was preceded by initial depolarization. 4. In preparations from cat and rat, pyrantel showed properties common to both competitive and depolarizing neuromuscular blocking drugs. 5. Pyrantel blocked the contracture evoked by transmural stimulation and caused a marked contracture of the worm. Piperazine caused a gradually developing reduction in the responses to transmural stimulation and no contracture. 6. Pyrantel and its analogues caused a slowly developing contracture of strip preparations of Ascaris, being more than 100 times more active than acetylcholine in this respect. Piperazine caused a relaxation of Ascaris strip preparations and in common with (+)-tubocurarine blocked the responses to acetylcholine and pyrantel analogues on this preparation. 7. Pyrantel caused depolarization and increased spike discharge frequency in single muscle cells of Ascaris, these changes being accompanied by increase in tension. Piperazine, on the other hand, caused hyperpolarization and reduction in spike discharge frequency and relaxation, and antagonized the effects of pyrantel. PMID:5417856

In Vitro Anthelmintic Activity of Crude Extracts of Aerial Parts of Cissus quadrangularis L. and Leaves of Schinus molle L. against Haemonchus contortus.

PubMed

Zenebe, Selamawit; Feyera, Teka; Assefa, Solomon

2017-01-01

Haemonchus contortus, the causative agent of Haemonchosis, is the most economically important parasite in small ruminant production. Control with chemotherapy has not been successful due to rapid emergence of drug-resistant strains. There is a continuous search for alternative leads particularly from plants. The study aimed to evaluate the anthelmintic activity of crude methanolic extracts of leaves of Schinus molle and aerial parts of Cissus quadrangularis against H. contortus. Methods . Adult motility test and egg hatching inhibition assay were employed to investigate the in vitro adulticidal and egg hatching inhibitory effects of the extracts. Higher concentrations of the extracts (10 and 5 mg/ml) had a significantly superior adulticidal activity ( p < 0.05) compared to the negative control and lower concentration levels, which was comparable to albendazole. Similarly, the relative egg hatch inhibition efficacy of S. molle and C. quadrangularis extracts indicated a maximum of 96% and 88% egg hatch inhibition, respectively, within the 48 hrs of exposure at 1 mg/ml. The current study evidenced that the crude methanolic extracts of the plants have promising adulticidal and egg hatching inhibitory effects against H. contortus .

In Vitro Anthelmintic Activity of Crude Extracts of Aerial Parts of Cissus quadrangularis L. and Leaves of Schinus molle L. against Haemonchus contortus

PubMed Central

Zenebe, Selamawit; Feyera, Teka

2017-01-01

Background Haemonchus contortus, the causative agent of Haemonchosis, is the most economically important parasite in small ruminant production. Control with chemotherapy has not been successful due to rapid emergence of drug-resistant strains. There is a continuous search for alternative leads particularly from plants. The study aimed to evaluate the anthelmintic activity of crude methanolic extracts of leaves of Schinus molle and aerial parts of Cissus quadrangularis against H. contortus. Methods. Adult motility test and egg hatching inhibition assay were employed to investigate the in vitro adulticidal and egg hatching inhibitory effects of the extracts. Results Higher concentrations of the extracts (10 and 5 mg/ml) had a significantly superior adulticidal activity (p < 0.05) compared to the negative control and lower concentration levels, which was comparable to albendazole. Similarly, the relative egg hatch inhibition efficacy of S. molle and C. quadrangularis extracts indicated a maximum of 96% and 88% egg hatch inhibition, respectively, within the 48 hrs of exposure at 1 mg/ml. Conclusion The current study evidenced that the crude methanolic extracts of the plants have promising adulticidal and egg hatching inhibitory effects against H. contortus. PMID:29410960

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

USDA-ARS?s Scientific Manuscript database

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

Insecticide Resistance Management

DTIC Science & Technology

2013-01-01

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

Successes and challenges of managing resistance in Helicoverpa armigera to Bt cotton in Australia.

PubMed

Downes, Sharon; Mahon, Rod

2012-01-01

Bt cotton has been gradually released and adopted by Australian growers since 1996. It was initially deployed in Australia primarily to control the polyphagous pest Helicoverpa armigera (Hübner), which in the 1990s became increasingly difficult to control due to widespread resistance to synthetic chemical insecticides. Bt-cotton has become a key tool in a program of integrated pest management for the production system that reduces pesticide dependence and the problems associated with its use. Herein we overview the deployment of Bt cotton in Australia including its performance and the approaches used to prolong the evolution of resistance to it by H. armigera. An integral component of this approach is monitoring resistance in this pest. We outline resistance screening methods, as well as the characteristics of resistant strains of H. armigera that have been isolated from field populations, or selected in the laboratory. We then highlight the successes and challenges for Bt cotton in Australia by way of discussing adaptive resistance management in light of potential changes in resistance.

The genetic basis for the selection of dairy goats with enhanced resistance to gastrointestinal nematodes

PubMed Central

Heckendorn, Felix; Bieber, Anna; Werne, Steffen; Saratsis, Anastasios; Maurer, Veronika; Stricker, Chris

2017-01-01

Gastrointestinal nematodes (GIN) severely affect small ruminant production worldwide. Increasing problems of anthelmintic resistance have given strong impetus to the search for alternative strategies to control GIN. Selection of animals with an enhanced resistance to GIN has been shown to be successful in sheep. In goats, the corresponding information is comparatively poor. Therefore, the present study was designed to provide reliable data on heritabilities of and genetic correlations between phenotypic traits linked to GIN and milk yield in two major dairy goat breeds (Alpine and Saanen). In all, 20 herds totalling 1303 goats were enrolled in the study. All herds had (i) a history of gastrointestinal nematode infection, (ii) uniform GIN exposure on pasture and (iii) regular milk recordings. For all goats, individual recordings of faecal egg counts (FEC), FAMACHA© eye score, packed cell volume (PCV) and milk yield were performed twice a year with an anthelmintic treatment in between. The collected phenotypic data were multivariately modelled using animal as a random effect with its covariance structure inferred from the pedigree, enabling estimation of the heritabilities of the respective traits and the genetic correlation between them. The heritabilities of FEC, FAMACHA© and PCV were 0.07, 0.22 and 0.22, respectively. The genetic correlation between FEC and FAMACHA© was close to zero and −0.41 between FEC and PCV. The phenotypic correlation between FEC and milk yield was close to zero, whereas the genetic correlation was 0.49. Our data suggest low heritability of FEC in Saanen and Alpine goats and an unfavourable genetic correlation of FEC with milk yield. PMID:28792887

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

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

2016-06-15

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.

Pest control and resistance management through release of insects carrying a male-selecting transgene.

PubMed

Harvey-Samuel, Tim; Morrison, Neil I; Walker, Adam S; Marubbi, Thea; Yao, Ju; Collins, Hilda L; Gorman, Kevin; Davies, T G Emyr; Alphey, Nina; Warner, Simon; Shelton, Anthony M; Alphey, Luke

2015-07-16

Development and evaluation of new insect pest management tools is critical for overcoming over-reliance upon, and growing resistance to, synthetic, biological and plant-expressed insecticides. For transgenic crops expressing insecticidal proteins from the bacterium Bacillus thuringiensis ('Bt crops') emergence of resistance is slowed by maintaining a proportion of the crop as non-Bt varieties, which produce pest insects unselected for resistance. While this strategy has been largely successful, multiple cases of Bt resistance have now been reported. One new approach to pest management is the use of genetically engineered insects to suppress populations of their own species. Models suggest that released insects carrying male-selecting (MS) transgenes would be effective agents of direct, species-specific pest management by preventing survival of female progeny, and simultaneously provide an alternative insecticide resistance management strategy by introgression of susceptibility alleles into target populations. We developed a MS strain of the diamondback moth, Plutella xylostella, a serious global pest of crucifers. MS-strain larvae are reared as normal with dietary tetracycline, but, when reared without tetracycline or on host plants, only males will survive to adulthood. We used this strain in glasshouse-cages to study the effect of MS male P. xylostella releases on target pest population size and spread of Bt resistance in these populations. Introductions of MS-engineered P. xylostella males into wild-type populations led to rapid pest population decline, and then elimination. In separate experiments on broccoli plants, relatively low-level releases of MS males in combination with broccoli expressing Cry1Ac (Bt broccoli) suppressed population growth and delayed the spread of Bt resistance. Higher rates of MS male releases in the absence of Bt broccoli were also able to suppress P. xylostella populations, whereas either low-level MS male releases or Bt broccoli

Efficacy of the amino-acetonitrile derivative, monepantel, against experimental and natural adult stage gastro-intestinal nematode infections in sheep.

PubMed

Sager, Heinz; Hosking, Barry; Bapst, Béatrice; Stein, Philip; Vanhoff, Kathleen; Kaminsky, Ronald

2009-01-22

Multiple drug resistance by nematodes, against anthelmintics has become an important economic problem in sheep farming worldwide. Here we describe the efficacy of monepantel, a developmental molecule from the recently discovered anthelmintic class, the amino-acetonitrile derivatives (AADs). Efficacy was tested against adult stage gastro-intestinal nematodes (GINs) in experimentally and naturally infected sheep at a dose of 2.5mg/kg body weight when administered as an oral solution. Some of the isolates used in experimental infection studies were known to be resistant to the benzimidazoles or levamisole anthelmintics; strains resistant to the macrocyclic lactones were not available for these tests. Worm count-based efficacies of >98% were determined in these studies. As an exception, Oesophagostomum venulosum was only reduced by 88% in one study, albeit with a low worm burden in the untreated controls (geometric mean 15.4 worms). Similar efficacies for monepantel were also confirmed in naturally infected sheep. While the efficacy against most species was >99%, the least susceptible species was identified as Nematodirus spathiger, and although efficacy was 92.4% in one study it was generally >99%. Several animals were infected with Trichuris ovis, which was not eliminated after the treatment. Monepantel demonstrated high activity against a broad range of the important GINs of sheep, which makes this molecule an interesting candidate for use in this species, particularly in regions with problems of anthelmintic resistance. Monepantel was well tolerated by the treated sheep, with no treatment related adverse events documented.

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

PubMed

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

2007-08-01

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

The anthelmintic efficacy of plant-derived cysteine proteinases against the rodent gastrointestinal nematode, Heligmosomoides polygyrus, in vivo.

PubMed

Stepek, G; Lowe, A E; Buttle, D J; Duce, I R; Behnke, J M

2007-09-01

Gastrointestinal (GI) nematodes are important disease-causing organisms, controlled primarily through treatment with synthetic drugs, but the efficacy of these drugs has declined due to widespread resistance, and hence new drugs, with different modes of action, are required. Some medicinal plants, used traditionally for the treatment of worm infections, contain cysteine proteinases known to damage worms irreversibly in vitro. Here we (i) confirm that papaya latex has marked efficacy in vivo against the rodent gastrointestinal nematode, Heligmosomoides polygyrus, (ii) demonstrate the dose-dependent nature of the activity (>90% reduction in egg output and 80% reduction in worm burden at the highest active enzyme concentration of 133 nmol), (iii) establish unequivocally that it is the cysteine proteinases that are the active principles in vivo (complete inhibition of enzyme activity when pre-incubated with the cysteine proteinase-specific inhibitor, E-64) and (iv) show that activity is confined to worms that are in the intestinal lumen. The mechanism of action was distinct from all current synthetic anthelmintics, and was the same as that in vitro, with the enzymes attacking and digesting the protective cuticle. Treatment had no detectable side-effects on immune cell numbers in the mucosa (there was no difference in the numbers of mast cells and goblet cells between the treated groups) and mucosal architecture (length of intestinal villi). Only the infected and untreated mice had much shorter villi than the other 3 groups, which was a consequence of infection and not treatment. Plant-derived cysteine proteinases are therefore prime candidates for development as novel drugs for the treatment of GI nematode infections.

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.

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

2007-04-04

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).

A quantitative analysis of attitudes and behaviours concerning sustainable parasite control practices from Scottish sheep farmers.

PubMed

Jack, Corin; Hotchkiss, Emily; Sargison, Neil D; Toma, Luiza; Milne, Catherine; Bartley, David J

2017-04-01

Nematode control in sheep, by strategic use of anthelmintics, is threatened by the emergence of roundworms populations that are resistant to one or more of the currently available drugs. In response to growing concerns of Anthelmintic Resistance (AR) development in UK sheep flocks, the Sustainable Control of Parasites in Sheep (SCOPS) initiative was set up in 2003 in order to promote practical guidelines for producers and advisors. To facilitate the uptake of 'best practice' approaches to nematode management, a comprehensive understanding of the various factors influencing sheep farmers' adoption of the SCOPS principles is required. A telephone survey of 400 Scottish sheep farmers was conducted to elicit attitudes regarding roundworm control, AR and 'best practice' recommendations. A quantitative statistical analysis approach using structural equation modelling was chosen to test the relationships between both observed and latent variables relating to general roundworm control beliefs. A model framework was developed to test the influence of socio-psychological factors on the uptake of sustainable (SCOPS) and known unsustainable (AR selective) roundworm control practices. The analysis identified eleven factors with significant influences on the adoption of SCOPS recommended practices and AR selective practices. Two models established a good fit with the observed data with each model explaining 54% and 47% of the variance in SCOPS and AR selective behaviours, respectively. The key influences toward the adoption of best practice parasite management, as well as demonstrating negative influences on employing AR selective practices were farmer's base line understanding about roundworm control and confirmation about lack of anthelmintic efficacy in a flock. The findings suggest that improving farmers' acceptance and uptake of diagnostic testing and improving underlying knowledge and awareness about nematode control may influence adoption of best practice behaviour

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.

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.

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

The unique resistance and resilience of the Nigerian West African Dwarf goat to gastrointestinal nematode infections

PubMed Central

2011-01-01

Background West African Dwarf (WAD) goats serve an important role in the rural village economy of West Africa, especially among small-holder livestock owners. They have been shown to be trypanotolerant and to resist infections with Haemonchus contortus more effectively than any other known breed of goat. Methods In this paper we review what is known about the origins of this goat breed, explain its economic importance in rural West Africa and review the current status of our knowledge about its ability to resist parasitic infections. Conclusions We suggest that its unique capacity to show both trypanotolerance and resistance to gastrointestinal (GI) nematode infections is immunologically based and genetically endowed, and that knowledge of the underlying genes could be exploited to improve the capacity of more productive wool and milk producing, but GI nematode susceptible, breeds of goats to resist infection, without recourse to anthelmintics. Either conventional breeding allowing introgression of resistance alleles into susceptible breeds, or transgenesis could be exploited for this purpose. Appropriate legal protection of the resistance alleles of WAD goats might provide a much needed source of revenue for the countries in West Africa where the WAD goats exist and where currently living standards among rural populations are among the lowest in the world. PMID:21291550

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

Using Epidemiological Principles to Explain Fungicide Resistance Management Tactics: Why do Mixtures Outperform Alternations?

PubMed

Elderfield, James A D; Lopez-Ruiz, Francisco J; van den Bosch, Frank; Cunniffe, Nik J

2018-07-01

Whether fungicide resistance management is optimized by spraying chemicals with different modes of action as a mixture (i.e., simultaneously) or in alternation (i.e., sequentially) has been studied by experimenters and modelers for decades. However, results have been inconclusive. We use previously parameterized and validated mathematical models of wheat Septoria leaf blotch and grapevine powdery mildew to test which tactic provides better resistance management, using the total yield before resistance causes disease control to become economically ineffective ("lifetime yield") to measure effectiveness. We focus on tactics involving the combination of a low-risk and a high-risk fungicide, and the case in which resistance to the high-risk chemical is complete (i.e., in which there is no partial resistance). Lifetime yield is then optimized by spraying as much low-risk fungicide as is permitted, combined with slightly more high-risk fungicide than needed for acceptable initial disease control, applying these fungicides as a mixture. That mixture rather than alternation gives better performance is invariant to model parameterization and structure, as well as the pathosystem in question. However, if comparison focuses on other metrics, e.g., lifetime yield at full label dose, either mixture or alternation can be optimal. Our work shows how epidemiological principles can explain the evolution of fungicide resistance, and also highlights a theoretical framework to address the question of whether mixture or alternation provides better resistance management. It also demonstrates that precisely how spray tactics are compared must be given careful consideration. [Formula: see text] Copyright © 2018 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .

Evaluation of Antioxidant Properties, Phenolic Compounds, Anthelmintic, and Cytotoxic Activities of Various Extracts Isolated from Nepeta cadmea: An Endemic Plant for Turkey.

PubMed

Kaska, Arzu; Deniz, Nahide; Çiçek, Mehmet; Mammadov, Ramazan

2018-05-10

Nepeta cadmea Boiss. is a species endemic to Turkey that belongs to the Nepeta genus. Several species of this genus are used in folk medicine. This study was designed to investigate the phenolic compounds, antioxidant, anthelmintic, and cytotoxic activities of various extracts (ethanol, methanol, acetone, and water) of N. cadmea. The antioxidant activities of these extracts were analyzed using scavenging methods (DPPH, ABTS, and H 2 O 2 scavenging activity), the β-carotene/linoleic acid test system, the phosphomolybdenum method, and metal chelating activity. Among the 4 different extracts of N. cadmea that were evaluated, the water extract showed the highest amount of radical scavenging (DPPH, 25.54 μg/mL and ABTS, 14.51 μg/mL) and antioxidant activities (β-carotene, 86.91%). In the metal chelating and H 2 O 2 scavenging activities, the acetone extract was statistically different from the other extracts. For the phosphomolybdenum method, the antioxidant capacity of the extracts was in the range of 8.15 to 80.40 μg/mg. The phenolic content of the ethanol extract was examined using HPLC and determined some phenolics: epicatechin, chlorogenic, and caffeic acids. With regard to the anthelmintic properties, dose-dependent activity was observed in each of the extracts of N. cadmea. All the extracts exhibited high cytotoxic activities. The results will provide additional information for further studies on the biological activities of N. cadmea, while also helping us to understand the importance of this species. Furthermore, based on the results obtained, N. cadmea may be considered as a potentially useful supplement for the human diet, as well as a natural antioxidant for medicinal applications. The plants of the Nepeta genus have been extensively used as traditional herbal medicines. Nepeta cadmea Boiss., one of the species belonging to the Nepeta genus, is a species endemic to Turkey. In our study, we demonstrated the antioxidant capacities, total phenolic

Evaluation of In vitro Anthelmintic Activity, Total Phenolic Content and Cytotoxic Activity of Crinum latifolium L. (Family: Amaryllidaceae).

PubMed

Aziz, Abdul; Sarwar Raju, Golam; Das, Abhijit; Ahmed, Jamiuddin; Moghal, Md Mizanur Rahman

2014-01-01

Crinum latifolium is a widely used plant in Asian folk and traditional medicine.In the present study, we have tried to find out the anthelmintic activity, total phenolic contents and cytotoxicity of the methanolic extract of the target plant. Anthelmintic activity was assessed applying five different concentrations of the plant extract and recording the time of paralysis and death. Total phenolic contents were determined using Folin-Ciocaltu method, using Gallic acid as standard; while brine shrimp lethality test (BSLT) method was used to evaluate the cytotoxicity of the plant extract, where vincristine sulphate and DMSO was used as positive and negative control respectively. The lowest time for paralysis and death of worms, for test sample at highest concentration (50mg/ml), were found 24±0.45 and 46.4±0.60 min respectively, which gradually increased with the decrease of concentration. On the other hand, albendazole, which was used as standard, caused paralysis and death of worms at 56.2±0.20 min and 77.4±0.24 min respectively; whereas no mortality of the worms was observed, when distilled water was used as control. The crude methanolic extract exhibited lower amount of total phenolic content (17.50±2.64 mg/ml). In case of cytotoxicity measurement, the crude methanolic extract showed positive result (with LC50 15.652 µg/ml) compared to standard Vincristine sulphate (0.839 µg/ml); which indicated that the leaves of Crinum latifolium possess mild cytotoxic principles. Therefore, further studies are suggested to evaluate the possible mechanism of action and the active compounds responsible for the biological activities of the plant extract.

A randomized triple blind trial to assess the effect of an anthelmintic programme for working equids in Morocco

PubMed Central

2011-01-01

Background Gastro-intestinal parasitism has been identified as a significant cause of disease in working equids in many countries. This randomized triple-blind trial was designed to assess the impact of an anthelmintic treatment programme (using oral ivermectin and fenbendazole) comparing treated and placebo control populations of working donkeys, mules and horses in field conditions in Morocco. In particular, we assessed animal body weight and condition score, together with a questionnaire-based owner evaluation of number of subjective animal health parameters. Faecal worm egg count was also measured. Results 239 animals completed the full study, 130 in the treatment group and 109 in the control group. Although the average animal weight increased during the study, this change was not significantly different between the two groups. Animals in the treatment group had a significantly lower strongyle worm egg count and increased in body condition score compared to animals in the control group at each examination during the study period. Owners of animals in the treatment group reported improvement in health and work ability and a beneficial effect on pruritus during the early period of the study. These differences in owner perception between treatment groups had disappeared in the latter stages of the study. Conclusion This study demonstrated that a routine anthelmintic treatment programme of three treatments annually can have a significant effect on faecal worm egg count. There may be beneficial consequences for the animal health and productivity. Further research on other populations of working equids in different environments would facilitate the objective planning of effective parasite control strategies for specific situations and provide better understanding of the likely clinical benefits of such programmes. PMID:21208398

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

PubMed Central

2013-01-01

Although much advancement has been achieved in the treatment of chronic hepatitis B, antiviral resistance is still a challenging issue. Previous generation antiviral agents have already developed resistance in a number of patients, and it is still being used especially in resource limited countries. Once antiviral resistance occurs, it predisposes to subsequent resistance, resulting in multidrug resistance. Therefore, prevention of initial antiviral resistance is the most important strategy, and appropriate choice and modification of therapy would be the cornerstone in avoiding treatment failures. Until now, management of antiviral resistance has been evolving from sequential therapy to combination therapy. In the era of tenofovir, the paradigm shifts again, and we have to decide when to switch and when to combine on the basis of newly emerging clinical data. We expect future eradication of chronic hepatitis B virus infection by proper prevention and optimal management of antiviral resistance. PMID:24133659

Anthelmintic drug ivermectin inhibits angiogenesis, growth and survival of glioblastoma through inducing mitochondrial dysfunction and oxidative stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Yingying; Fang, Shanshan; Sun, Qiushi

Glioblastoma is one of the most vascular brain tumour and highly resistant to current therapy. Targeting both glioblastoma cells and angiogenesis may present an effective therapeutic strategy for glioblastoma. In our work, we show that an anthelmintic drug, ivermectin, is active against glioblastoma cells in vitro and in vivo, and also targets angiogenesis. Ivermectin significantly inhibits growth and anchorage-independent colony formation in U87 and T98G glioblastoma cells. It induces apoptosis in these cells through a caspase-dependent manner. Ivermectin significantly suppresses the growth of two independent glioblastoma xenograft mouse models. In addition, ivermectin effectively targets angiogenesis through inhibiting capillary network formation, proliferation andmore » survival in human brain microvascular endothelial cell (HBMEC). Mechanistically, ivermectin decreases mitochondrial respiration, membrane potential, ATP levels and increases mitochondrial superoxide in U87, T98G and HBMEC cells exposed to ivermectin. The inhibitory effects of ivermectin are significantly reversed in mitochondria-deficient cells or cells treated with antioxidants, further confirming that ivermectin acts through mitochondrial respiration inhibition and induction of oxidative stress. Importantly, we show that ivermectin suppresses phosphorylation of Akt, mTOR and ribosomal S6 in glioblastoma and HBMEC cells, suggesting its inhibitory role in deactivating Akt/mTOR pathway. Altogether, our work demonstrates that ivermectin is a useful addition to the treatment armamentarium for glioblastoma. Our work also highlights the therapeutic value of targeting mitochondrial metabolism in glioblastoma. - Highlights: • Ivermectin is effective in glioblastoma cells in vitro and in vivo. • Ivermectin inhibits angiogenesis. • Ivermectin induces mitochondrial dysfunction and oxidative stress. • Ivermectin deactivates Akt/mTOR signaling pathway.« less

Antioxidant, anti-adipocyte differentiation, antitumor activity and anthelmintic activities against Anisakis simplex and Hymenolepis nana of yakuchinone A from Alpinia oxyphylla

PubMed Central

2013-01-01

Background Alpinia oxyphylla is a common remedy in traditional Chinese medicine. Yakuchinone A is a major constituent of A. oxyphylla and exhibits anti-inflammatory, antitumor, antibacterial, and gastric protective activities. Methods Antioxidant and antitumor characteristics of yakuchinone A in skin cancer cells as well as novel mechanisms for the inhibition of adipocyte differentiation, cestocidal activities against Hymenolepis nana adults, and nematocidal activities against Anisakis simplex larvae are investigated. Results Yakuchinone A presents the ability of the removal of DPPH·and ABTS+ free radicals and inhibition of lipid peroxidation. Yakuchinone A suppresses intracellular lipid accumulation during adipocyte differentiation in 3 T3-L1 cells and the expressions of leptin and peroxisome proliferator-activated receptor γ (PPARγ). Yakuchinone A induces apoptosis and inhibits cell proliferation in skin cancer cells. The inhibition of cell growth by yakuchinone A is more significant for non-melanoma skin cancer (NMSC) cells than for melanoma (A375 and B16) and noncancerous (HaCaT and BNLCL2) cells. Treatment BCC cells with yakuchinone A shows down-regulation of Bcl-2, up-regulation of Bax, and an increase in cleavage poly (ADP-ribose) polymerase (PARP). This suggests that yakuchinone A induces BCC cells apoptosis through the Bcl-2-mediated signaling pathway. The anthelmintic activities of yakuchinone A for A. simplex are better than for H. nana. Conclusions In this work, yakuchinone A exhibits antioxidative properties, anti-adipocyte differentiation, antitumor activity, and anthelmintic activities against A. simplex and H. nana. PMID:24070160

Management of herbicide resistance in wheat cropping systems: learning from the Australian experience.

PubMed

Walsh, Michael J; Powles, Stephen B

2014-09-01

Herbicide resistance continues to escalate in weed populations infesting global wheat (Triticum aestivum L.) crops, threatening grain production and thereby food supply. Conservation wheat production systems are reliant on the use of efficient herbicides providing low-cost, selective weed control in intensive cropping systems. The resistance-driven loss of herbicide resources combined with limited potential for new herbicide molecules means greater emphasis must be placed on preserving existing herbicides. For more than two decades, since the initial recognition of the dramatic consequences of herbicide resistance, the challenge of introducing additional weed control strategies into herbicide-based weed management programmes has been formidable. Throughout this period, herbicide resistance has expanded unabated across the world's wheat production regions. However, in Australia, where herbicide resources have become desperately depleted, the adoption of harvest weed seed control is evidence, at last, of a successful approach to sustainable weed management in wheat production systems. Growers routinely including strategies to target weed seeds during crop harvest, as part of herbicide-based weed management programmes, are now realising significant weed control and crop production benefits. When combined with an attitude of zero weed tolerance, there is evidence of a sustainable weed control future for wheat production systems. The hard-learned lessons of Australian growers can now be viewed by global wheat producers as an example of how to stop the continual loss of herbicide resources in productive cropping systems. © 2013 Society of Chemical Industry.

Determination of benzimidazole anthelmintics in milk and honey by monolithic fiber-based solid-phase microextraction combined with high-performance liquid chromatography-diode array detection.

PubMed

Zhang, Yong; Huang, Xiaojia; Yuan, Dongxing

2015-01-01

A porous poly(methacrylic acid-co-ethylene dimethacrylate) monolithic fiber (MEMF) for solid-phase microextraction (SPME) of five benzimidazole anthelmintics was prepared by in-situ polymerization. The effect of polymerization conditions on SPME of the target analytes was studied thoroughly. The physicochemical properties of the monolith were characterized by infrared spectroscopy, elemental analysis, scanning electron microscopy, and mercury intrusion porosimetry. Several conditions affecting the extraction efficiency were investigated and, under the optimized conditions, a simple and sensitive method for the determination of trace benzimidazoles residues in milk and honey was established by coupling MEMF-SPME with high-performance liquid chromatography-diode array detection (MEMF-SPME-HPLC-DAD). Under the optimum experimental conditions, the limits of detection (S/N = 3) of the method were 0.11-0.30 μg L(-1) for milk and 0.086-0.28 μg L(-1) for honey. Evaluation of intra-day and inter-day precision showed reproducibility was satisfactory-relative standard deviations (RSD) for both were <10 %. Finally, the method was successfully used for determination of benzimidazole residues in milk and honey. Recoveries obtained for determination of benzimidazole anthelmintics in spiked samples ranged from 72.3 to 121 %, with RSD always <11 %.

Characterisation of ALS genes in the polyploid species Schoenoplectus mucronatus and implications for resistance management.

PubMed

Scarabel, Laura; Locascio, Antonella; Furini, Antonella; Sattin, Maurizio; Varotto, Serena

2010-03-01

The polyploid weed Schoenoplectus mucronatus (L.) Palla has evolved target-site resistance to ALS-inhibiting herbicides in Italian rice crops. Molecular and genetic characterisation of the resistance mechanism is relevant to the evolution and management of herbicide resistance. The authors aimed (a) to study the organisation of the target-site loci in two field-selected S. mucronatus populations with different cross-resistance patterns, (b) to identify the mutations endowing resistance to ALS inhibitors and determine the role of these mutations by using transgenesis and (c) to analyse the implications for the management of the S. mucronatus populations. Two complete ALS genes (ALS1 and ALS2) having an intron and a third partial intronless ALS gene (ALS3) were identified. The presence of multiple ALS genes was confirmed by Southern blot analyses, and ALS loci were characterised by examining cytosine methylation. In S. mucronatus leaves, the transcripts of ALS1, ALS2 and ALS3 were detected. Two mutations endowing resistance (Pro(197) to His and Trp(574) to Leu) were found in both resistant populations, but at different frequencies. Tobacco plants transformed with the two resistant alleles indicated that the Pro(197)-to-His substitution conferred resistance to SU and TP herbicides, while the allele with the Trp(574)-to-Leu substitution conferred cross-resistance to SU, TP, IMI and PTB herbicides. Schoenoplectus mucronatus has multiple ALS genes characterised by methylated sites that can influence the expression profile. The two mutated alleles proved to be responsible for ALS resistance. At population level, the resistance pattern depends on the frequency of various resistant genotypes, and this influences the efficacy of various ALS-inhibiting herbicides.

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...

Gastrointestinal helminths of free-ranging Florida panthers (Puma concolor coryi) and the efficacy of the current anthelmintic treatment protocol.

PubMed

Foster, Garry W; Cunningham, Mark W; Kinsella, John M; McLaughlin, Grace; Forrester, Donald J

2006-04-01

Thirty-five Florida panthers (Puma concolor coryi [Bangs, 1899]) collected from six counties in southern Florida between 1978 and 2003 were examined at necropsy for gastrointestinal helminths. The panthers were placed into two groups: 1) treated with anthelmintics (n = 17), and 2) untreated (n = 18). Nine species of helminths (one trematode, six nematodes, and two cestodes) were identified in the untreated panthers. The most prevalent helminths were Alaria marcianae (LaRue, 1917) (100%), Spirometra mansonoides (Mueller, 1935) (91%), and Ancylostoma pluridentatum (Alessandrini, 1905) (89%). Ancylostoma caninum (Ercolani, 1859) is reported from the Florida panther for the first time. The intensities of helminths with prevalences >10% did not differ between untreated panthers collected in 1978-1983 and 1996-2003. Treated panthers had helminth faunas similar to those of untreated panthers. The current anthelmintic treatment being used reduced the intensity of both A. marcianae and A. pluridentatum in panthers < or =6 mo posttreatment (PT); however, treated panthers between 6 and 9 mo PT, and >9 mo PT were similar to untreated panthers. Treatment was less effective on S. mansonoides and Taenia omissa Lühe, 1910. Treated panthers had slightly lower intensities of S. mansonoides at < or =6 mo PT; however, between 6 and 9 mo PT and >9 mo PT they had significantly higher intensities than untreated panthers. At all periods PT, the intensity of T. omissa for the treated panthers was similar to that of untreated panthers. We suggest that Mesocestoides sp. may not be present in the Florida panther population as reported earlier by Forrester et al. (1985), due to parasite misidentification by those authors.

Anthelmintic activity of extracts of Spondias mombin against gastrointestinal nematodes of sheep: studies in vitro and in vivo.

PubMed

Ademola, I O; Fagbemi, B O; Idowu, S O

2005-04-01

This study was carried out to validate the efficacy of Spondias mombin, used locally as an anthelmintic, and to standardize the effective dose of the plant extract required for worm control in livestock. In vitro and in vivo studies were conducted to determine the direct anthelmintic effect of ethanolic and aqueous extracts of S. mombin towards different ovine gastrointestinal nematodes. A larval development assay (LDA) was used to investigate the in vitro effect of extracts on strongyle larvae. Another study 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 gastrointestinal nematodes. Twenty sheep were selected on the basis of positive faecal egg counts (750 epg). The sheep were allocated randomly to a non-medicated control group (A) or to groups given 125 mg/kg (B), 250 mg/kg (C) or 500 mg/kg (D) of extract, respectively. Sheep in groups B-D were given extracts orally on two days. Individual faecal egg counts were performed on days 0, 3, 6, 9 and 12. The presence of S. mombin extracts in in vitro cultures of larvae decreased the survival of L3 larvae. The LC50 of the aqueous extract of S. mombin was 0.907 mg/ml, while the LC50 of the ethanolic extract was 0.456 mg/ml. This difference in LC50 was statistically significant (p > 0.05). The mean percentage faecal egg reduction of sheep drenched with 500 mg/kg S. mombin extracts was 15.0%, 27.5%, 65.0%, 65.0%, 100.0% against Haenmonchus spp., Trichostrongylus spp., Oesophagostomunm spp., Strongyloides spp. and Trichuris spp. respectively, on day 12. Extracts of S. mombin could find application in the control of helminths in livestock.

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

PubMed

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

2014-12-01

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

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

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.

Anthelmintic drug niclosamide enhances the sensitivity of chronic myeloid leukemia cells to dasatinib through inhibiting Erk/Mnk1/eIF4E pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Zhong; Li, Yong; Lv, Cao

Chronic myeloid leukemia (CML) responds well to BCR-ABL tyrosine kinase inhibitors (TKI), but becomes resistant to TKIs after it progresses to blast phase (BP). Here we show that niclosamide, a FDA-approved anthelmintic drug, enhances the sensitivity of BP-CML cells to dasatinib (2nd generation of BCR-ABL TKI) through inhibiting Erk/Mnk1/eIF4E signaling pathway. Niclosamide dose-dependently inhibits proliferation and induces apoptosis in a panel of CML cell lines. It also selectively targets BP-CML CD34 stem/progenitor cells through inducing apoptosis, inhibiting colony formation and self-renewal capacity while sparing normal bone marrow (NBM) counterparts. In addition, combination of niclosamide and dasatinib is synergistic in CMLmore » cell lines and BP-CML CD34 cells. Importantly, niclosamide inhibits phosphorylation of Erk, Mnk1 and eIF4E in CML cells. Overexpression of phosphomimetic but not nonphosphorylatable form of eIF4E reverses the inhibitory effects of niclosamide, suggesting that eIF4E inhibition is required for the action of niclosamide in CML. Compared to NBM, the increased levels of eIF4E and its activity in CML CD34 cells might explain the selective toxicity of niclosamide in CML versus NBM. We further show that dasatinib time-dependently induces eIF4E phosphorylation. The combination of eIF4E depletion and dasatinib results in similar effects as the combination of niclosamide and dasatinib, suggesting that niclosamide enhances dasatinib through targeting eIF4E. Our work is the first to demonstrate that niclosamide is a potential drug to overcome resistance to BCR-ABL TKI treatment in BP-CML. Our findings also suggest the therapeutic value of Erk/Mnk/eIF4E in CML treatment.« less

UV/Visible Spectroscopic Quantification of Veterinary Anthelmintic Drug Oxfendazole in Pharmaceuticals

NASA Astrophysics Data System (ADS)

Rajendraprasad, N.; Basavaiah, K.

2016-07-01

Oxfendazole (OFA) is a broad spectrum benzimidazole anthelmintic medication used to treat veterinary diseases. Two new, simple, rapid, precise and accurate, and sensitive spectrophotometric methods have been developed and validated for the assay of OFA in its pure form and in its boluses. The first method (method A) is based on the measurement of green colored manganate obtained due to oxidation of OFA by permanganate in an alkaline medium at 610 nm. In the second method (Method B), the chromophoric activity of OFA is measured at 290 nm in the acetic acid-water (1:1) solvent system. OFA has been quantified over the linear ranges of 1.25-12.5 and 1.25-10 μg/mL in method A and method B, respectively, with apparent molar absorptivity values of 2.54 × 104 and 2.13 × 104 L·mol-1·cm-1. The limit of detection (LOD), limit of quantification (LOQ), and Sandell sensitivity values are 0.15 u 0.18 μg/mL, 0.46 and 0.56 μg/mL, and 0.0124 and 0.0148 μg/cm2. The developed methods were successfully applied to determine OFA in the bolus. No interference from adjuvants was observed.

Temporo-spatial distribution of insecticide-resistance in Indian malaria vectors in the last quarter-century: Need for regular resistance monitoring and management.

PubMed

Raghavendra, Kamaraju; Velamuri, Poonam Sharma; Verma, Vaishali; Elamathi, Natarajan; Barik, Tapan Kumar; Bhatt, Rajendra Mohan; Dash, Aditya Prasad

2017-01-01

The Indian vector control programme similar to other programmes in the world is still reliant on chemical insecticides. Anopheles culicifacies is the major vector out of six primary malaria vectors in India and alone contributes about 2/3 malaria cases annually; and per se its control is actually control of malaria in India. For effective management of vectors, current information on their susceptibility status to different insecticides is essential. In this review, an attempt was made to compile and present the available data on the susceptibility status of different malaria vector species in India from the last 2.5 decades. Literature search was conducted by different means mainly web and library search; susceptibility data was collated from 62 sources for the nine malaria vector species from 145 districts in 21 states and two union territories between 1991 and 2016. Interpretation of the susceptibility/resistance status was made on basis of the recent WHO criteria. Comprehensive analysis of the data indicated that An. culicifacies, a major vector species was resistant to at least one insecticide in 70% (101/145) of the districts. It was reported mostly resistant to DDT and malathion whereas, its resistant status against deltamethrin varied across the districts. The major threat for the malaria control programmes is multiple-insecticide-resistance in An. culicifacies which needs immediate attention for resistance management in order to sustain the gains achieved so far, as the programmes have targeted malaria elimination by 2030.

Comparing the refuge strategy for managing the evolution of insect resistance under different reproductive strategies.

PubMed

Crowder, David W; Carrière, Yves

2009-12-07

Genetically modified (GM) crops are used extensively worldwide to control diploid agricultural insect pests that reproduce sexually. However, future GM crops will likely soon target haplodiploid and parthenogenetic insects. As rapid pest adaptation could compromise these novel crops, strategies to manage resistance in haplodiploid and parthenogenetic pests are urgently needed. Here, we developed models to characterize factors that could delay or prevent the evolution of resistance to GM crops in diploid, haplodiploid, and parthenogenetic insect pests. The standard strategy for managing resistance in diploid pests relies on refuges of non-GM host plants and GM crops that produce high toxin concentrations. Although the tenets of the standard refuge strategy apply to all pests, this strategy does not greatly delay the evolution of resistance in haplodiploid or parthenogenetic pests. Two additional factors are needed to effectively delay or prevent the evolution of resistance in such pests, large recessive or smaller non-recessive fitness costs must reduce the fitness of resistance individuals in refuges (and ideally also on GM crops), and resistant individuals must have lower fitness on GM compared to non-GM crops (incomplete resistance). Recent research indicates that the magnitude and dominance of fitness costs could be increased by using specific host-plants, natural enemies, or pathogens. Furthermore, incomplete resistance could be enhanced by engineering desirable traits into novel GM crops. Thus, the sustainability of GM crops that target haplodiploid or parthenogenetic pests will require careful consideration of the effects of reproductive mode, fitness costs, and incomplete resistance.

Renal denervation in the management of resistant hypertension: current evidence and perspectives.

PubMed

Jin, Yu; Persu, Alexandre; Staessen, Jan A

2013-09-01

Catheter-based renal denervation has emerged as a novel treatment modality for resistant hypertension. This review summarizes the current evidence on this procedure in treatment of resistant hypertension, limitations of available evidence and questions to be answered. The SYMPLICITY studies showed that renal denervation is feasible in treating resistant hypertension, but failed to provide conclusive evidence on the size and durability of the antihypertensive, renal and sympatholytic effects, as well as the long-term safety. The definition of resistant hypertension was loose in the SYMPLICITY studies and the management of resistant hypertension was suboptimal. Future studies should have a randomized design and enroll truly resistant hypertension patients by excluding secondary hypertension, white-coat hypertension and nonadherent patients. Questions to be addressed by the ongoing and future trials include the long-term efficacy and safety of this procedure, identification of responders and uncovering of the underlying mechanisms. Only well-designed, randomized clinical trials addressing the limitations of the SYMPLICITY studies will be able to demonstrate whether renal denervation is an efficacious treatment modality in resistant hypertension and in which patients. For now, renal denervation remains an experimental procedure and should only be offered to truly resistant hypertensive patients in a research context after careful selection.

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

Seeds of change: corn seed mixtures for resistance management and IPM

USDA-ARS?s Scientific Manuscript database

The use of mixtures of insecticidal seed and non-toxic seed to provide an in-field refuge for susceptible insects in an insect-resistance-management (IRM) plan has been considered for at least two decades, but the US Environmental Protection Agency has only recently authorized their use in commercia...

CHEMICAL AND BIOLOGICAL STABILITY OF ARTEMISININ IN COW RUMEN FLUID AND ITS KINETICS IN GOATS (CAPRA HIRCUS)

USDA-ARS?s Scientific Manuscript database

There is a pressing need to develop alternative, natural anthelmintics to control widespread drug-resistant gastrointestinal nematodes in ruminants, such as Haemonchus contortus. Artemisinin and its semi-synthetic derivatives are widely used against drug-resistant Plasmodium falciparum, but their r...

Synergistic interaction of ten essential oils against Haemonchus contortus in vitro

USDA-ARS?s Scientific Manuscript database

Anthelmintic resistance in sheep gastrointestinal nematodes is a worldwide problem. Multi-drug resistant haemonchosis is the most serious impediment for small ruminant systems, and there are no new drug candidates currently under development. Molecules from natural sources have demonstrated anthelmi...

The efficacy of ivermectin, pyrantel and fenbendazole against Parascaris equorum infection in foals on farms in Australia.

PubMed

Armstrong, S K; Woodgate, R G; Gough, S; Heller, J; Sangster, N C; Hughes, K J

2014-10-15

This study was performed to estimate the prevalence of patent Parascaris equorum infections and determine the efficacy of ivermectin, pyrantel and fenbendazole against P. equorum infection in foals on farms in southern Australia. Foals aged >3 months on five farms in the south-western slopes region of New South Wales were used. Faeces were collected from each foal and foals with a P. equorum faecal egg count (FEC) of >100 eggs per gram (EPG) were used to measure anthelmintic efficacy using the FEC reduction (FECR) test, after random allocation to a control group or an ivermectin, pyrantel embonate or fenbendazole treatment group. Treatment was administered on day 0 and faeces were collected on day 14 and a FEC was performed. For determination of anthelmintic efficacy, FECRs and lower 95% confidence intervals (LCL) were calculated using previously described methods, based on individual or group FECRs. P. equorum populations were considered susceptible when FECR was >90% and LCL >90%, suspected resistant when FECR was FECR was 80-90% and LCL <90% and resistant when FECR was <80% and LCL <90%. A Poisson distribution quality control method was applied to the data to remove suspected erroneous FECR results. Prevalence of patent P. equorum infection was 58.3% (147/252 foals) and 89 foals on 5 farms were included in the FECR study. Resistance of P. equorum to ≥ 1 anthelmintic was present on all five farms prior to and on four farms after application of the quality control method. Two farms had evidence of multiple drug resistance. Ivermectin was effective and ineffective on two and three farms, respectively. Fenbendazole was effective on two farms, equivocal on one farm and ineffective on one farm. Pyrantel embonate was effective on three farms and ineffective on one farm. These data indicate that anthelmintic-resistant P. equorum populations are present on farms in Australia and multiple drug resistance may occur on individual farms. Copyright © 2014 Elsevier B.V. All

Familiarity with and uptake of alternative methods to control sheep gastro-intestinal parasites on farms in England.

PubMed

Moore, Hope; Pandolfi, Fanny; Kyriazakis, Ilias

2016-05-15

A questionnaire was distributed electronically amongst sheep farmers in England; it aimed to provide a quantification of current anthelmintic practices, farmer awareness of the issue of anthelmintic resistance (AR) and the uptake, awareness and opinions surrounding conventional and alternative methods of nematode control. The majority of farmers relied on several anthelmintics and used faecal egg counts to identify worm problems. Although farmers were aware of the issue of AR amongst helminth parasites in the UK, there was a disconnection between such awareness and on farm problems and practice of nematode control. Grazing management was used by 52% of responders, while breeding for resistance and bioactive forages by 22 and 18% respectively. Farms with more than 500 ewes, and farmers who felt nematodes were a problem, had a higher probability of using selective breeding. Farmers who considered their wormer effective, had a qualification in agriculture and whose staff did not include any family members, were more likely to use bioactive forages; the opposite was the case if farmers dosed their lambs frequently. Amongst the alternatives, highest preference was for selective breeding and vaccination, if the latter was to become commercially available, with more respondents having a preference for breeding than actually using it. Several barriers to the uptake of an alternative were identified, the most influential factor being the cost to set it up and the length of time for which it would remain effective. The disconnection between awareness of AR and practice of nematode control on farm reinforces the need for emphasising the links between the causes of AR and the consequences of strategies to address its challenge. Copyright © 2016 Elsevier B.V. All rights reserved.

Multidrug-resistant bacteria infection and nursing quality management application in the department of physical examination.

PubMed

Xu, Li; Luo, Qiang; Chen, Liangzhen; Jiao, Lingmei

2017-09-01

The main problem of clinical prevention and control of multi drug resistant bacteria infection is to strengthen the monitoring of pathogenic bacteria spectrum, this study research on the multi drug-resistant bacteria infection and nursing quality management application in the department of physical examination. The results of this study showed that the number of patients with multiple drug resistant infections showed an increasing trend. Therefore, once the patients with multiple drug-resistant bacteria infection are found, the prevention and control of the patients with multiple drug-resistant bacteria should be strictly followed, and the patient's medication care should be highly valued. Also, the nurses need to be classified based on the knowledge and skill characteristics of the nurses in the department of physical examination, and compare the nursing effect before and after classification and grouping. The physicians and individuals receiving physical examinations in the department of physical examination had a higher degree of satisfaction for nursing effect after classification compared with those before classification. Classification and grouping management helps improve the nursing quality and overall quality of the nurses in the department of physical examination.

Phenotypic and genotypic analysis of benzimidazole resistance in the ovine parasite Nematodirus battus.

PubMed

Morrison, Alison A; Mitchell, Sian; Mearns, Rebecca; Richards, Iain; Matthews, Jacqui B; Bartley, David J

2014-12-09

Benzimidazole resistance is common amongst many ovine trichostrongylid nematodes species globally. Although anthelmintics have been used for over half a century in some areas of the world for the control of Nematodirus battus, resistance has never been detected. Veterinary investigations conducted in 2010 demonstrated reduced efficacy in a flock that had been treated previously with fenbendazole (FBZ), suggesting probable resistance in N. battus. Infective larvae (L3; designated MNba2) were generated from the original material to conduct a controlled efficacy test (CET). Faecal egg counts showed an average of 37% reduction in the FBZ treated group 7 days post treatment compared to the untreated lambs. Average worm burden results showed no reduction after FBZ treatment compared to the untreated group (3850 and 3850 worms respectively). A molecular assay to assess the frequency of the commonly associated single nucleotide polymorphisms (SNP) in the β-tubulin isotype 1 gene, F200Y and E198A, was developed. Larval genotypes were predominantly homozygous resistant at codon 200 SNP, ranging from 56%-83% and remained stable at 70% for adult worm populations taken from treated and control lambs in the CET. Only susceptible genotypes were found at codon 198. The allele frequency for F200Y ranged between 80-83% in adult worms taken from the CET from treated and control lambs. The results confirmed initial findings and demonstrated the first report of FBZ resistance in N. battus whilst providing evidence that the P200 point mutation in the β-tubulin isotype 1 gene is a potential mechanism of resistance in the species.

Synergistic interaction of ten essential oils against Haemonchus contortus in vitro.

PubMed

Katiki, L M; Barbieri, A M E; Araujo, R C; Veríssimo, C J; Louvandini, H; Ferreira, J F S

2017-08-30

Anthelmintic resistance in sheep gastrointestinal nematodes is a worldwide problem. Multi-drug resistant haemonchosis is the most serious impediment for small ruminant systems, and there are no new drug candidates currently under development. Molecules from natural sources have demonstrated anthelmintic activity against parasites. In this work, the monoterpenoids carvacrol, carvone, cineole, linalool, limonene, and thymol and the phenylpropanoids cinnamaldehyde, anethole, vanillin, and eugenol were assessed individually or in mixtures of ten binary, three ternary, and three quaternary combinations using the in vitro egg hatch assay with eggs of a multi-drug resistant strain of Haemonchus contortus. The main objective of this study was to identify the most effective interaction among essential oils with the greatest individual anthelmintic efficacy and to determine the most powerful combinations. The essential oils were ranked by their 50% lethal concentration (LC 50 ) as follows (mg/mL): cinamaldehyde (0.018), anethole (0.070), carvone (0.085), carvacrol (0.11), thymol (0.13), linalool (0.29), vanillin (0.57), eugenol (0.57), cineole (4.74), and limonene (207.5). Quantification of synergism, additive effect, and antagonism were calculated for binary, ternary, and quaternary combinations. The best anthelmintic effect resulting from synergistic activity among 16 different combinations was for cinnamaldehyde:carvacrol (CL 50 0.012mg/mL) and anethole:carvone (CL 50 0.013mg/mL). These results indicate that these binary combinations would be promising to be tested in sheep infected with H. contortus. Copyright © 2017 Elsevier B.V. All rights reserved.

Species differences in hepatic biotransformation of the anthelmintic drug flubendazole.

PubMed

Maté, M L; Geary, T; Mackenzie, C; Lanusse, C; Virkel, G

2017-10-01

Flubendazole (FLBZ) is a broad-spectrum benzimidazole anthelmintic used in pigs, poultry, and humans. It has been proposed as a candidate for development for use in elimination programmes for lymphatic filariasis and onchocerciasis in humans. Moreover, FLBZ has shown promise in cancer chemotherapy, particularly for neuroblastoma. This work investigated the hepatic carbonyl-reducing pathway of FLBZ in different species, including humans. Microsomal and cytosolic fractions were obtained from sheep, cattle, pig, hen, rat, and human liver. Both subcellular fractions of each species converted FLBZ into a reduced metabolite (red-FLBZ). The rate of microsomal red-FLBZ production was highest in sheep (1.92 ± 0.13 nmol/min.mg) and lowest in pigs (0.04 ± 0.02 nmol/min.mg); cytosolic red-FLBZ production ranged from 0.02 ± 0.01 (pig) to 1.86 ± 0.61 nmol/min.mg (sheep). Only subcellular fractions from sheep liver oxidized red-FLBZ to FLBZ in a NADP + -dependent oxidative reaction. Liver microsomes from both pigs and humans transformed FLBZ to red-FLBZ and a hydrolyzed metabolite. Very significant differences in the pattern of FLBZ metabolism were observed among the tested species and humans. These results reinforce the need for caution in extrapolating data on metabolism, efficacy, and safety of drugs derived from studies performed in different species. © 2017 John Wiley & Sons Ltd.

Essential oil of Siparuna guianensis as an alternative tool for improved lepidopteran control and resistance management practices.

PubMed

Lourenço, Adriano M; Haddi, Khalid; Ribeiro, Bergman M; Corrêia, Roberto F T; Tomé, Hudson V V; Santos-Amaya, Oscar; Pereira, Eliseu J G; Guedes, Raul N C; Santos, Gil R; Oliveira, Eugênio E; Aguiar, Raimundo W S

2018-05-08

Although the cultivation of transgenic plants expressing toxins of Bacillus thuringiensis (Bt) represents a successful pest management strategy, the rapid evolution of resistance to Bt plants in several lepidopteran pests has threatened the sustainability of this practice. By exhibiting a favorable safety profile and allowing integration with pest management initiatives, plant essential oils have become relevant pest control alternatives. Here, we assessed the potential of essential oils extracted from a Neotropical plant, Siparuna guianensis Aublet, for improving the control and resistance management of key lepidopteran pests (i.e., Spodoptera frugiperda and Anticarsia gemmatalis). The essential oil exhibited high toxicity against both lepidopteran pest species (including an S. frugiperda strain resistant to Cry1A.105 and Cry2Ab Bt toxins). This high insecticidal activity was associated with necrotic and apoptotic effects revealed by in vitro assays with lepidopteran (but not human) cell lines. Furthermore, deficits in reproduction (e.g., egg-laying deterrence and decreased egg viability), larval development (e.g., feeding inhibition) and locomotion (e.g., individual and grouped larvae walking activities) were recorded for lepidopterans sublethally exposed to the essential oil. Thus, by similarly and efficiently controlling lepidopteran strains susceptible and resistant to Bt toxins, the S. guianensis essential oil represents a promising management tool against key lepidopteran pests.

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

EPA Pesticide Factsheets

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

An evaluation of an oral formulation of moxidectin against selected anthelmintic-resistant and -susceptible strains of nematodes in lambs.

PubMed

Bisset, S A; Vlassoff, A; McMurtry, L W; Elliott, D C; Cobb, R M; Kieran, P J; Wood, I B

1992-09-01

The efficacy of an oral formulation of the newly developed parasiticide, moxidectin, was tested against benzimidazole-resistant Haemonchus contortus, Trichostrongylus colubriformis, and Nematodirus spathiger, levamisole-resistant Ostertagia circumcincta, and susceptible Cooperia curticei infections in weaned lambs. Thirty-two lambs were experimentally infected with mixed doses of the above strains of nematodes. They were allocated into four treatment groups by stratified randomisation using liveweights and faecal egg counts 28 days later. One group received moxidectin at 0.2 mg/kg liveweight, one group oxfendazole at 4.5 mg/kg liveweight, one group levamisole at 7.5 mg/kg liveweight and the last group remained untreated as the control. Worm burdens in the lambs at slaughter 10 days after oral treatment confirmed the resistance status of the nematode strains used, and showed that moxidectin had a greater than 99.9% efficacy (p<0.01) against all of them. No adverse effects due to treatment with moxidectin were observed in any of the animals.

Urinary Tract Infection in Children: Management in the Era of Antibiotic Resistance-A Pediatric Urologist's View.

PubMed

Kutasy, Balazs; Coyle, David; Fossum, Magdalena

2017-04-01

Antibiotic resistance to uropathogens has grown significantly worldwide. Today, pediatric urologist experience a situation that needs appropriate action because urinary tract infections are one of the most common bacterial infections in children. In this overview we aimed at presenting the clinical aspects of antibiotic usage in pediatric urology. Our intention was to take part of the important debate regarding future management of bacterial resistance against antibiotics. We searched PubMed for the terms: [UTI in children], [Recurrent UTI in children], and [Antibiotic resistance in UTI]. When using these terms, we found a numerous amount (3875) of published clinical articles related to the topic. By means of an overview, we chose not to focus on a specific condition but to an overall understanding of the problems related to pediatric urology in general. We found that usage of antibiotics has had an unquestionable benefit to reduce the morbidity and mortality related to urinary tract infections in childhood. However, recent studies suggest that early exposure to antibiotics in childhood might have negative systemic effects related to neurocognitive function, body metabolism, and fat distribution. In addition to increased resistance to common antimicrobial agents, it has resulted in increased costs and inadequate effect in severe infections. This calls for changes in the clinical management of urinary pathogens in pediatric urology. As the prevalence of antibiotic resistance grows, pediatric urologists have a key role in managing its consequences and its prevention. In this overview we looked at the consequences of antibiotic usage treating urinary tract infections in childhood. We found that the prevalence of antibiotic resistance has grown. We concluded that decision-makers must know about the short- and long-term effects of antibiotic usage in children. When we understand the development of antibiotic resistance better, we can build up prevention strategies

Current status for gastrointestinal nematode diagnosis in small ruminants: where are we and where are we going?

PubMed

Preston, Sarah Jane Margaret; Sandeman, Mark; Gonzalez, Jorge; Piedrafita, David

2014-01-01

Gastrointestinal nematode (GIN) parasites pose a significant economic burden particularly in small ruminant production systems. Anthelmintic resistance is a serious concern to the effective control of GIN parasites and has fuelled the focus to design and promote sustainable control of practices of parasite control. Many facets of sustainable GIN parasite control programs rely on the ability to diagnose infection both qualitatively and quantitatively. Diagnostics are required to determine anthelmintic efficacies, for targeted treatment programs and selection of animals for parasite resistant breeding. This review describes much of the research investigated to date to improve the current diagnostic for the above practices which is based on counting the number of parasite eggs in faeces.

Effectiveness of Ivermectin and Albendazole against Haemonchus contortus in Sheep in West Java, Indonesia.

PubMed

Puspitasari, Silvia; Farajallah, Achmad; Sulistiawati, Erni; Muladno

2016-02-01

Administering a half dose of an anthelmintic is a simple method for detecting resistance in parasites infesting small ruminants. When a single anthelmintic fails in native sheep from Indonesia, a combination of anthelmintics from different chemical classes with different modes of action are administered as an alternative parasite-control strategy. This study compared the anthelmintic efficacy of ivermectin (IVM) and albendazole (ABZ) given either separately as a single dose or half dose or co-administered to sheep naturally infected with Haemonchus contortus. Twelve sheep from Bogor, West Java, Indonesia were divided into the following six treatment groups: half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, combined IVM + ABZ, and control. The treatment efficacy was determined using the faecal egg count reduction test (FECRT) at day 0 (pre-treatment) and post-treatment at days 7, 14, 21, 28, 35, and 42. The efficacies of half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, and the combination treatment ranged from -1900% to 100%, 99% to 100%, -167% to 100%, -467% to 89%, and -200% to 100%, respectively. The FECRT for the half-dose IVM, half-dose ABZ, full-dose ABZ showed that H. contortus is resistant to half-dose IVM and ABZ. Full-dose IVM was effective against H. contortus. The combined treatment was more effective against H. contortus than ABZ alone.

Diagnosis before treatment: Identifying dairy farmers' determinants for the adoption of sustainable practices in gastrointestinal nematode control.

PubMed

Vande Velde, F; Claerebout, E; Cauberghe, V; Hudders, L; Van Loo, H; Vercruysse, J; Charlier, J

2015-09-15

Anthelmintic resistance is emerging in dairy cattle and this can result in a lack of effective control and production losses. Therefore, sustainable control strategies, such as targeted treatments (TT) and targeted selected treatments (TST), should be adopted by the industry. TT and TST approaches require the use of diagnostic methods to take informed treatment decisions. To understand the factors affecting the farmers' intention to adopt diagnostic methods before implementing anthelmintic drugs ('adoption intention'), a cross-sectional survey was carried out in dairy farms in Belgium (Flanders). A framework was constructed to predict adoption intentions based on two fundamental theories in the field of behavioural psychology and health psychology: the Theory of Planned Behaviour and the Health Belief Model. In the tested model, adoption intentions were predicted based on attitudes towards anthelminthics, attitudes towards diagnostic methods, subjective norms, behavioural control and perceived risk. Structural equation modelling was used for analyses. The model fitted the data well and explained 46% of the variance in adoption intention of diagnostics. The factors 'attitude towards diagnostic methods' and 'subjective norm'; i.e. the influence of significant others, had the strongest, positive influence on adoption intention of diagnostic methods. 'Perceived behavioural control' had a weak, positive effect on intention. Further, 'attitude towards the use of anthelmintic drugs' had a negative effect on adoption intention of the diagnostic methods. This implicates an effect of current behaviour on future adoption, which should be considered in future research. Factors measuring risk perception of anthelmintic resistance; perceived severity and perceived susceptibility, had no effect on the adoption intention of diagnostic methods. The threat of anthelmintic resistance is perceived to be low for dairy herds. The study further did not find any differences in the effects

Insecticide resistance and resistance mechanisms in bed bugs, Cimex spp. (Hemiptera: Cimicidae).

PubMed

Dang, Kai; Doggett, Stephen L; Veera Singham, G; Lee, Chow-Yang

2017-06-29

The worldwide resurgence of bed bugs [both Cimex lectularius L. and Cimex hemipterus (F.)] over the past two decades is believed in large part to be due to the development of insecticide resistance. The transcriptomic and genomic studies since 2010, as well as morphological, biochemical and behavioral studies, have helped insecticide resistance research on bed bugs. Multiple resistance mechanisms, including penetration resistance through thickening or remodelling of the cuticle, metabolic resistance by increased activities of detoxification enzymes (e.g. cytochrome P450 monooxygenases and esterases), and knockdown resistance by kdr mutations, have been experimentally identified as conferring insecticide resistance in bed bugs. Other candidate resistance mechanisms, including behavioral resistance, some types of physiological resistance (e.g. increasing activities of esterases by point mutations, glutathione S-transferase, target site insensitivity including altered AChEs, GABA receptor insensitivity and altered nAChRs), symbiont-mediated resistance and other potential, yet undiscovered mechanisms may exist. This article reviews recent studies of resistance mechanisms and the genes governing insecticide resistance, potential candidate resistance mechanisms, and methods of monitoring insecticide resistance in bed bugs. This article provides an insight into the knowledge essential for the development of both insecticide resistance management (IRM) and integrated pest management (IPM) strategies for successful bed bug management.

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...

Dominance of P-glycoprotein 12 in phenotypic resistance conversion against ivermectin in Caenorhabditis elegans

PubMed Central

Figueiredo, Luiza Almeida; Rebouças, Thais Fuscaldi; Ferreira, Sebastião Rodrigo; Rodrigues-Luiz, Gabriela Flavia; Miranda, Rodrigo Cambraia; Araujo, Ricardo Nascimento

2018-01-01

While diseases caused by nematodes remains a considerable drawback for the livestock, agriculture and public health, anthelmintics drug resistance has been observed over the past years and is a major concern for parasite control. Ivermectin, initially considered as a highly potent drug, currently presents a reduced anti-helminthic efficacy, which is influenced by expression of several ATP-binding cassette transporters (ABC), among them the P-glycoproteins (Pgps). Here we present some evidences of Pgps dominance during Ivermectin resistance/susceptibility using Pgps double silencing in C. elegans and the phylogenetic relationship of Pgps among nematodes, which strengthen the use of this model for study of drug resistance in nematodes. Firstly, we evaluated the quantitative gene expression of 12 out the 15 known Pgps from resistant and WT strains of C. elegans, we demonstrated the upregulation of Pgps 12 and 13 and downregulation of all remaining Pgps in ivermectin resistant strain. By using an RNAi loss-of-function approach we observed that Pgp 12 gene silencing reverts the resistance phenotype to ivermectin, while Pgp 4 gene silencing does not alter the resistance phenotype but induces a resistance in wild type strain. Interestingly, the dual silencing of Pgp 12 and Pgp 4 expression demonstrates the dominance of phenotype promoted by Pgp 12 silencing. Finally, in silico analysis reveals a close relationship between Pgps from C. elegans and several nematodes parasites. Taken together, our results indicate that Pgp 12 is crucial for the resistance to ivermectin and thus a good candidate for further studies aiming to develop specific inhibitors to this transporter, allowing the continuous use of ivermectin to control the burden on animal and human health inflicted by nematode parasites globally. PMID:29474375

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...

Report: EPA Can Strengthen Its Oversight of Herbicide Resistance With Better Management Controls

EPA Pesticide Factsheets

Report #17-P-0278, June 21, 2017. Billions of dollars in U.S. crop value are at risk due to the threat of herbicide-resistant weeds. With private and public partners, the EPA can establish better controls to manage and minimize the threat.

Exploring the host transcriptome for mechanisms underlying protective immunity and resistance to nematode infections in ruminants.

PubMed

Li, Robert W; Choudhary, Ratan K; Capuco, Anthony V; Urban, Joseph F

2012-11-23

Nematode infections in ruminants are a major impediment to the profitable production of meat and dairy products, especially for small farms. Gastrointestinal parasitism not only negatively impacts weight gain and milk yield, but is also a major cause of mortality in small ruminants. The current parasite control strategy involves heavy use of anthelmintics that has resulted in the emergence of drug-resistant parasite strains. This, in addition to increasing consumer demand for animal products that are free of drug residues has stimulated development of alternative strategies, including selective breeding of parasite resistant ruminants. The development of protective immunity and manifestations of resistance to nematode infections relies upon the precise expression of the host genome that is often confounded by mechanisms simultaneously required to control multiple nematode species as well as ecto- and protozoan parasites, and microbial and viral pathogens. Understanding the molecular mechanisms underlying these processes represents a key step toward development of effective new parasite control strategies. Recent progress in characterizing the transcriptome of both hosts and parasites, utilizing high-throughput microarrays and RNA-seq technology, has led to the recognition of unique interactions and the identification of genes and biological pathways involved in the response to parasitism. Innovative use of the knowledge gained by these technologies should provide a basis for enhancing innate immunity while limiting the polarization of acquired immunity can negatively affect optimal responses to co-infection. Strategies for parasite control that use diet and vaccine/adjuvant combination could be evaluated by monitoring the host transcriptome for induction of appropriate mechanisms for imparting parasite resistance. Knowledge of different mechanisms of host immunity and the critical regulation of parasite development, physiology, and virulence can also selectively

Efficacy of closantel against ivermectin- and fenbendazole-resistant Haemonchus sp. in sheep in Ontario, Canada.

PubMed

Westers, T; Jones-Bitton, A; Menzies, P; Van Leeuwen, J; Poljak, Z; Peregrine, A S

2016-09-15

In Ontario, Canada, widespread resistance to ivermectin and fenbendazole, the only readily available ovine anthelmintics, has been documented, primarily in Haemonchus sp. In other parts of the world, closantel has been used to control such infections; however, the drug was not currently licensed for use in Canada and the USA. A randomized controlled trial was conducted on six client-owned farms in Ontario in 2013 and 2014 to determine the efficacy of closantel (Flukiver ® 5% Oral Suspension, Elanco Animal Health, 10mg/kg bodyweight) against ivermectin- and fenbendazole-resistant Haemonchus sp. infections in periparturient ewes and grazing lambs. Three farms were randomly assigned to treat all ewes, and three farms were randomly assigned to selectively treat individual ewes at lambing, using predetermined criteria. Fecal samples were collected from a minimum of 15 randomly selected ewes and 13 lambs per group on each farm at the time of treatment and approximately 14days later. Trichostrongyle-type fecal egg counts (FEC) were performed using a modified McMaster technique with a lower detection limit of 8.3 eggs per gram of feces (epg). Haemonchus-specific FECs were determined by multiplying FECs by the proportion of Haemonchus sp. identified from coproculture for each farm; Haemonchus-specific FEC reductions were calculated for each farm. Twenty grazing lambs had FECs conducted monthly, and when mean monthly FECs surpassed 200 epg, all lambs were randomly allocated to either closantel, positive control (ivermectin, fenbendazole, or levamisole) or negative control groups. Pre-treatment Haemonchus-specific mean FECs ranged from 27 to 3359 epg in ewes and 0-5698 epg in lambs. Efficacy of closantel against Haemonchus sp. ranged from 99% (95% CI: 97%-99%) to 100% in recently lambed ewes on all farms in both years (total n=274 ewes), and from 99% (95% CI: 98%-99%) to 100% in grazing lambs in both years on all but one farm (total n=171 lambs). On the latter farm, a whole

In vitro nematicidal effect of Chenopodium ambrosioides and Castela tortuosa n-hexane extracts against Haemonchus contortus (Nematoda) and their anthelmintic effect in gerbils.

PubMed

Zamilpa, A; García-Alanís, C; López-Arellano, M E; Hernández-Velázquez, V M; Valladares-Cisneros, M G; Salinas-Sánchez, D O; Mendoza-de Gives, P

2018-05-06

The in vitro nematicidal effect of Chenopodium ambrosioides and Castela tortuosa n-hexane extracts (E-Cham and E-Cato, respectively) on Haemonchus contortus infective larvae (L3) and the anthelmintic effect of these extracts against the pre-adult stage of the parasite in gerbils were evaluated using both individual and combined extracts. The in vitro confrontation between larvae and extracts was performed in 24-well micro-titration plates. The results were considered 24 and 72 h post confrontation. The in vivo nematicidal effect was examined using gerbils as a study model. The extracts from the two assessed plants were obtained through maceration using n-hexane as an organic agent. Gerbils artificially infected with H. contortus L3 were treated intraperitoneally with the corresponding extract either individually or in combination. The results showed that the highest individual lethal in vitro effect (96.3%) was obtained with the E-Cham extract at 72 h post confrontation at 40 mg/ml, followed by E-Cato (78.9%) at 20 mg/ml after 72 h. The highest combined effect (98.7%) was obtained after 72 h at 40 mg/ml. The in vivo assay showed that the individual administration of the E-Cato and E-Cham extracts reduced the parasitic burden in gerbils by 27.1% and 45.8%, respectively. Furthermore, the anthelmintic efficacy increased to 57.3% when both extracts were administered in combination. The results of the present study show an important combined nematicidal effect of the two plant extracts assessed against L3 in gerbils.

Resistance evolution to the first generation of genetically modified Diabrotica-active Bt-maize events by western corn rootworm: management and monitoring considerations.

PubMed

Devos, Yann; Meihls, Lisa N; Kiss, József; Hibbard, Bruce E

2013-04-01

Western corn rootworm (Diabrotica virgifera virgifera; WCR) is a major coleopteran maize pest in North America and the EU, and has traditionally been managed through crop rotation and broad-spectrum soil insecticides. Genetically modified Bt-maize offers an additional management tool for WCR and has been valuable in reducing insecticide use and increasing farm income. A concern is that the widespread, repeated, and exclusive deployment of the same Bt-maize transformation event will result in the rapid evolution of resistance in WCR. This publication explores the potential of WCR to evolve resistance to plant-produced Bt-toxins from the first generation of Diabrotica-active Bt-maize events (MON 863 and MON 88017, DAS-59122-7 and MIR604), and whether currently implemented risk management strategies to delay and monitor resistance evolution are appropriate. In twelve of the twelve artificial selection experiments reported, resistant WCR populations were yielded rapidly. Field-selected resistance of WCR to Cry3Bb1 is documented in some US maize growing areas, where an increasing number of cases of unexpected damage of WCR larvae to Bt-maize MON 88017 has been reported. Currently implemented insect resistance management measures for Bt-crops usually rely on the high dose/refuge (HDR) strategy. Evidence (including laboratory, greenhouse and field data) indicates that several conditions contributing to the success of the HDR strategy may not be met for the first generation of Bt-maize events and WCR: (1) the Bt-toxins are expressed heterogeneously at a low-to-moderate dose in roots; (2) resistance alleles may be present at a higher frequency than initially assumed; (3) WCR may mate in a non-random manner; (4) resistance traits could have non-recessive inheritance; and (5) fitness costs may not necessarily be associated with resistance evolution. However, caution must be exercised when extrapolating laboratory and greenhouse results to field conditions. Model predictions

Horse infection with intestinal helminths in relation to age, sex, access to grass and farm system.

PubMed

Kornaś, S; Cabaret, J; Skalska, M; Nowosad, B

2010-12-15

A 11-year survey on helminth intestinal infection of horses was done in seven provinces of southern Poland. 21,641 faecal samples were collected from horses of different age, sex, breed and management system originating from 84 farms. Age was the major factor influencing the cyathostome egg excretion, the maximum being observed in yearlings and second year horses. Parascaris was found mostly in foals and yearlings. The main factor for Anoplocephala was the access to pasture. The level of cyathostome egg shedding (EPG) could be related to sex (geldings had higher values of EPG), breed (Thoroughbred had higher EPG than other breeds), and type of farm (large farms had higher EPG than others). The change during the survey of anthelmintic treatment (from benzimidazole or pyrantel embonate to avermectins) was associated with lower cyathostome EPG, and this was probably due to partial resistance to benzimidazole. The seasonality of egg shedding (lowest from November to January included) was due to management (leaving the pasture to stable, anthelmintic treatment in October). The influence of climate on EPG was significant but small, annual rainfalls and average temperature being associated negatively and positively, respectively, with high cyathostome EPG. Copyright © 2010 Elsevier B.V. All rights reserved.

Evaluation of targeted drenching using Famacha method in Creole goat: reduction of anthelmintic use, and effects on kid production and pasture contamination.

PubMed

Mahieu, Maurice; Arquet, Rémy; Kandassamy, Tony; Mandonnet, Nathalie; Hoste, Hervé

2007-05-15

Haemonchus infection was monitored for 2 years (six kidding periods) in a Creole goat flock grazing under oceanic-tropical climate. Two hundred and thirty individual does were involved from late pregnancy to weaning. Anaemia diagnoses using Famacha method and packed cell volume (PCV) were compared. The best agreement (Kappa=0.33) was found if anaemia was declared when PCV values fell to 16 or below and Famacha score was 4 or 5. Drenching policy according to Famacha method was compared to systematic drenching policy. Using the Famacha method allowed a dramatic decrease in anthelmintic use during the periparturient period (0.57 individual dose instead of three doses for the control). The proportion of the nematode population on the pasture not derived from previously-treated goats (in refugia) was estimated to about 79% (65-90%) of the pasture contamination derived from the Famacha group. On the average, goats which needed to be drenched produced less than the control or undrenched goats (kid average daily gain was decreased by about 15%). The repeatability of the need for drenching individual does was estimated to 0.41. The older goats or the goats in poorer body condition at kidding needed more drenching than the younger animals and the animals in good body condition. Consequently the Famacha method may be used as an additional tool for the culling management.

Antimicrobial resistance in Neisseria gonorrhoeae in the UK: surveillance and management.

PubMed

Ison, Catherine A; Alexander, Sarah

2011-10-01

Successful antimicrobial therapy is fundamental to the public health control of gonorrhea, in the absence of a protective immune response. Neisseria gonorrhoeae, the causative agent, has presented a constant challenge for the provision of such therapy as it has demonstrated the ability to become resistant to successive highly active agents chosen for first-line treatment. Acquisition of plasmids from other bacteria and long-term use of a single agent has selected both single step high-level and low-level resistance due to multiple mutations. While therapeutic failure of the current recommended agents cefixime and ceftriaxone begins to emerge, choice of alternative therapies is limited. Guidelines for therapy will be dependent on surveillance programs but individual patient management will require a viable organism to detect emerging resistance. Advances in molecular detection, while advantageous for the diagnosis of gonorrhea, fail to provide a viable organism, posing even greater challenges for the definition of treatment failure, and appropriate end points for test of cure. Innovative and collaborative approaches will be essential to maintain gonorrhea as a treatable infection.

Influence of protein supplementation on the resistance and resilience on young hair sheep naturally infected with gastrointestinal nematodes during rainy and dry seasons.

PubMed

Louvandini, H; Veloso, C F M; Paludo, G R; Dell'Porto, A; Gennari, S M; McManus, C M

2006-04-15

Thirty, 4-month-old entire Santa Ines lambs were grazed on an Andropogon gayanus pasture, during a 34-week period (rainy season weeks 0-20 and dry season weeks 21-34) and allocated in two treatment groups (n = 15) each with different protein supplementation: high protein (HP-19% CP) and low protein (LP-11% CP). These were subdivided into those receiving anthelmintic treatment (c) (n = 7) and without anthelmintic treatment (i) (n = 8). The objective was to evaluate the effects of supplementation with protein on resistance and resilience to natural helminth infection of hair breed lambs. Lamb weight, blood collection and faecal egg counts (FEC) were carried out monthly. The lambs were slaughtered after 34 weeks, when worm burdens, worm length and eosinophil cell counts were taken. The sheep on treatments HPc and HPi were heavier in live weight than those from LPi and LPc (P < 0.05) at the end of the rainy period. The HPc group finished heavier (P < 0.05) than the other groups in the dry season, which had no significant differences between them. The predominant species of nematode found was T. colubriformis followed by H. contortus, Trichuris globulosa and Moniezia expansa. Animals on HPi had lower FEC than LPi (P < 0.05). The number of worms was lower for both HP groups (P < 0.05) with worm length shorter in the HPc group (P < 0.05) compared with all other groups. The number of eosinophils was higher in animals in the LPi group, which also showed anaemia and lower plasma urea at the end of the dry season. Diet supplementation with high protein was able to improve resilience and resistance to natural infection by endoparasites during the rainy season. In the dry season there was a decrease in both of these traits, which were intimately linked to the quality of available forage under tropical conditions.

Peptaibols from Two Unidentified Fungi of the Order Hypocreales with Cytotoxic, Antibiotic, and Anthelmintic Activities

PubMed Central

Ayers, Sloan; Ehrmann, Brandie M.; Adcock, Audrey F.; Kroll, David J.; Carcache de Blanco, Esperanza J.; Shen, Qi; Swanson, Steven M.; Falkinham, Joseph O.; Wani, Mansukh C.; Mitchell, Sheila M.; Pearce, Cedric J.; Oberlies, Nicholas H.

2012-01-01

As part of an ongoing investigation of filamentous fungi for anticancer leads, an active culture was identified from the Mycosynthetix library (MSX 70741, of the order Hypocreales, Ascomycota). The fungal extract exhibited cytotoxic activity against the H460 (human non-small cell lung carcinoma) cell line, and bioactivity-directed fractionation yielded peptaibols 1–12 and harzianums A (13) and B (14). Structure elucidation of 1–12 was facilitated by high-resolution MS/MS obtained on a Thermo LTQ Orbitrap XL using Higher-Energy Collisional Dissociation (HCD) and by high field NMR (950 MHz). The absolute configuration was determined by Marfey’s analysis of the individual amino acids; the time required for such analysis was decreased via the development of a 10 min UPLC method. The isolated peptaibols (1–12), along with three other peptaibols isolated and elucidated from a different fungus (MSX 57715) of the same Order (15–17), were examined for activity in a suite of biological assays, including those for cytotoxic, antibacterial, and anthelmintic activities. PMID:22744757

HIV-1 Drug Resistance and Resistance Testing

PubMed Central

Clutter, Dana S; Jordan, Michael R; Bertagnolio, Silvia; Shafer, Robert W

2016-01-01

The global scale-up of antiretroviral (ARV) therapy (ART) has led to dramatic reductions in HIV-1 mortality and incidence. However, HIV drug resistance (HIVDR) poses a potential threat to the long-term success of ART and is emerging as a threat to the elimination of AIDS as a public health problem by 2030. In this review we describe the genetic mechanisms, epidemiology, and management of HIVDR at both individual and population levels across diverse economic and geographic settings. To describe the genetic mechanisms of HIVDR, we review the genetic barriers to resistance for the most commonly used ARVs and describe the extent of cross-resistance between them. To describe the epidemiology of HIVDR, we summarize the prevalence and patterns of transmitted drug resistance (TDR) and acquired drug resistance (ADR) in both high-income and low- and middle-income countries (LMICs). We also review to two categories of HIVDR with important public health relevance: (i) pre-treatment drug resistance (PDR), a World Health Organization-recommended HIVDR surveillance metric and (ii) and pre-exposure prophylaxis (PrEP)-related drug resistance, a type of ADR that can impact clinical outcomes if present at the time of treatment initiation. To summarize the implications of HIVDR for patient management, we review the role of genotypic resistance testing and treatment practices in both high-income and LMIC settings. In high-income countries where drug resistance testing is part of routine care, such an understanding can help clinicians prevent virological failure and accumulation of further HIVDR on an individual level by selecting the most efficacious regimens for their patients. Although there is reduced access to diagnostic testing and to many ARVs in LMIC, understanding the scientific basis and clinical implications of HIVDR is useful in all regions in order to shape appropriate surveillance, inform treatment algorithms, and manage difficult cases. PMID:27587334

Multidrug resistance: prospects for clinical management.

PubMed

Mansouri, A; Henle, K J; Nagle, W A

1992-01-01

Clinical success in the treatment of tumors with chemotherapy has significantly improved over the past several years. However, treatment failures due to drug resistance of cancer cells has remained a major problem. The classical form of multiple drug resistance is perhaps also the most common type of drug resistance, and represents the overexpression of a transmembrane glycoprotein pump (P-170) that mediates the efflux of a spectrum of structurally and functionally unrelated drugs. Here, we discuss recent evidence that support the concept that the total phenomenon of multiple drug resistance (MDR) involves several other mechanisms in addition to that underlying "classical" MDR. These include the action of other energy-dependent membrane efflux pumps, elevated levels of GSH for drug conjugation and detoxification to facilitate export, enhanced DNA repair facility, gene amplification and oncogene activation. The combination of mechanisms used by any particular cell line is variable and suggests that many of these mechanisms are independent. Successful reversal of drug resistance appears to require the identification of relevant operative resistance mechanisms. An example is the competitive inhibition of P-170 with verapamil, quinine and tamoxifen. A broadly successful strategy for killing drug-resistant cancer cells, however, could be based on either selective energy depletion of cancer cells or the permeabilization of tumor cells with an effective bypass of efflux pumps, since many mechanisms of drug resistance entail the energy-dependent export of toxins. The latter approach may be achieved via membrane lipid modifications or the introduction of membrane pores by biological or physical (electroporation) means.

An antagonist of the retinoid X receptor reduces the viability of Trichuris muris in vitro.

PubMed

Hurst, Rebecca J M; Hopwood, Thomas; Gallagher, Amanda L; Partridge, Frederick A; Burgis, Timothy; Sattelle, David B; Else, Kathryn J

2014-09-27

Trichuriasis is a parasitic disease caused by the human whipworm, Trichuris trichiura. It affects millions worldwide, particularly in the tropics. This nematode parasite burrows into the colonic epithelium resulting in inflammation and morbidity, especially in children. Current treatment relies mainly on general anthelmintics such as mebendazole but resistance to these drugs is increasingly problematic. Therefore, new treatments are urgently required. The prospect of using the retinoid X receptor (RXR) antagonist HX531 as a novel anthelmintic was investigated by carrying out multiple viability assays with the mouse whipworm Trichuris muris. HX531 reduced both the motility and viability of T. muris at its L3, L4 and adult stages. Further, bioinformatic analyses show that the T. muris genome possesses an RXR-like receptor, a possible target for HX531. The study suggested that Trichuris-specific RXR antagonists may be a source of much-needed novel anthelmintic candidates for the treatment of trichuriasis. The identification of an RXR-like sequence in the T. muris genome also paves the way for further research based on this new anthelmintic lead compound.

Effectiveness of Ivermectin and Albendazole against Haemonchus contortus in Sheep in West Java, Indonesia

PubMed Central

Puspitasari, Silvia; Farajallah, Achmad; Sulistiawati, Erni; Muladno

2016-01-01

Administering a half dose of an anthelmintic is a simple method for detecting resistance in parasites infesting small ruminants. When a single anthelmintic fails in native sheep from Indonesia, a combination of anthelmintics from different chemical classes with different modes of action are administered as an alternative parasite-control strategy. This study compared the anthelmintic efficacy of ivermectin (IVM) and albendazole (ABZ) given either separately as a single dose or half dose or co-administered to sheep naturally infected with Haemonchus contortus. Twelve sheep from Bogor, West Java, Indonesia were divided into the following six treatment groups: half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, combined IVM + ABZ, and control. The treatment efficacy was determined using the faecal egg count reduction test (FECRT) at day 0 (pre-treatment) and post-treatment at days 7, 14, 21, 28, 35, and 42. The efficacies of half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, and the combination treatment ranged from −1900% to 100%, 99% to 100%, −167% to 100%, −467% to 89%, and −200% to 100%, respectively. The FECRT for the half-dose IVM, half-dose ABZ, full-dose ABZ showed that H. contortus is resistant to half-dose IVM and ABZ. Full-dose IVM was effective against H. contortus. The combined treatment was more effective against H. contortus than ABZ alone. PMID:27019686

Serum Strongylus vulgaris-specific antibody responses to anthelmintic treatment in naturally infected horses.

PubMed

Nielsen, Martin K; Vidyashankar, Anand N; Bellaw, Jennifer; Gravatte, Holli S; Cao, Xin; Rubinson, Emily F; Reinemeyer, Craig R

2015-02-01

Strongylus vulgaris is the most pathogenic helminth parasite of horses, causing verminous endarteritis with thromboembolism and infarction. A serum enzyme-linked immunosorbent assay (ELISA) has been validated for detection of antibodies to an antigen produced by migrating larvae of this parasite. The aim was to evaluate ELISA responses to anthelmintic treatment in cohorts of naturally infected horses. Fifteen healthy horses harboring patent S. vulgaris infections were turned out for communal grazing in May 2013 (day 0). On day 55, horses were ranked according to ELISA titers and randomly allocated to the following three groups: no treatment followed by placebo pellets daily; ivermectin on day 60 followed by placebo pellets daily; or ivermectin on day 60 followed by daily pyrantel tartrate. Fecal and serum samples were collected at ∼28-day intervals until study termination on day 231. Increased ELISA values were observed for the first 53 days following ivermectin treatment. Titers were significantly reduced 80 days after ivermectin treatment. Horses receiving daily pyrantel tartrate maintained lower ELISA values from 137 days post ivermectin treatment until trial termination. These results illustrate that a positive ELISA result is indicative of either current or prior exposure to larval S. vulgaris infection within the previous 5 months.

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

Insecticide resistance in disease vectors from Mayotte: an opportunity for integrated vector management.

PubMed

Pocquet, Nicolas; Darriet, Frédéric; Zumbo, Betty; Milesi, Pascal; Thiria, Julien; Bernard, Vincent; Toty, Céline; Labbé, Pierrick; Chandre, Fabrice

2014-07-01

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. 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. 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. The low resistance observed in Mayotte's main disease vectors is particularly interesting, because it leaves a range of tools useable by vector control

Anthelmintic efficacy of Clerodendrum viscosum on fowl tapeworm Raillietina tetragona.

PubMed

Nandi, Suranjana; Ukil, Bidisha; Roy, Saptarshi; Kundu, Suman; Lyndem, Larisha Mawkhlieng

2017-12-01

Clerodendrum viscosum Vent. (Verbenaceae) is a shrub, widely used amongst the natives of India against various diseases. Crude extract of the plant was tested in vitro on a tapeworm Raillietina tetragona Molin (Davaineidae) to evaluate its potential anthelmintic efficacy and ultrastructural changes in the parasite. Parasites were exposed to different concentrations of ethanolic leaf extract (10-80 mg/mL) and praziquantel (0.0005-0.005 mg/mL) and incubated in phosphate-buffered saline (PBS). The pH was 7.4 at 37 °C, while one set of worms was incubated only with PBS as a control. Permanent immobilization of worms was determined visually when no motility occurred on physically disturbing them. The parasites exposed to high concentrations of leaf extract and praziquantel treatments were processed for histological and electron microscopic studies, as these concentrations took the least time for paralysis and death to occur. With an increase in the concentration of the leaf extract from 10 to 80 mg/mL and praziquantel from 0.0005 to 0.005 mg/mL, the time for the onset of paralysis and death was shortened. The treated parasites lost their spontaneous movement rapidly followed by death. Electron microscopic observations revealed disruptions in the tegument and parenchymal layer, accompanied by deformities in cell organelles. Extensive structural alterations in the tegument indicate that the plant-derived components cause permeability changes in the parasite leading to paralysis and subsequent death. These observations suggest that phytochemicals present in C. viscosum have vermifugal or vermicidal activity, and thus may be exploited as alternative chemotherapeutic agents.

In vitro and in vivo characterization of p-amino-phenethyl-m-trifluoromethylphenyl piperazine (PAPP), a novel serotonergic agonist with anthelmintic activity against Haemonchus contortus, Teladorsagia circumcincta and Trichostrongylus colubriformis.

PubMed

White, W Hunter; Gutierrez, Jesus A; Naylor, Sharon A; Cook, Carolyn A; Gonzalez, Isabel C; Wisehart, Mark A; Smith, Charles K; Thompson, William A

2007-05-15

The neurotransmitter serotonin (5-hydroxy tryptamine or 5HT) regulates key physiological processes in nematodes such as locomotion and feeding. PAPP (p-amino-phenethyl-m-trifluoromethylphenyl piperazine) is a known agonist of the 5-HT(1Hc) receptor of the barber pole worm, Haemonchus contortus. In this study, PAPP was highly active against L3-stage larvae of H. contortus and Trichostrongylus colubriformis in an in vitro larval migration assay, with EC50 values of 9.36 and 11.8 microM, respectively, that were comparable to levamisole (10.2 microM) and superior to pyrantel (55.39 microM). When administered orally or subcutaneously to nematode infected gerbils, PAPP provided >99% efficacy against H. contortus and >98% efficacy against Teladorsagia circumcincta at 100 mg/kg, comparable to levamisole at 10 mg/kg. Drug titration revealed significant activity down to 50 mg/kg against these two species. Spectrum was limited, however, with somewhat lower efficacy (83%) in T. colubriformis infected gerbils at 100 mg/kg. Oral delivery of hydrochloride, acetate and phosphate salts of PAPP to nematode infected gerbils did not result in an increase in either potency or spectrum. The finding that PAPP exhibits significant anthelmintic activity suggests that the nematode-specific serotonergic system is a viable target for future anthelmintic discovery.

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

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

EPA Pesticide Factsheets

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

Ontogenic resistance and plant disease management: a case study of grape powdery mildew.

PubMed

Ficke, Andrea; Gadoury, David M; Seem, Robert C

2002-06-01

ABSTRACT A fundamental principle of integrated pest management is that actions taken to manage disease should be commensurate with the risk of infection and loss. One of the less-studied factors that determines this risk is ontogenic, or age-related resistance of the host. Ontogenic resistance may operate at the whole plant level or in specific organs or tissues. Until recently, grape berries were thought to remain susceptible to powdery mildew (Uncinula necator) until late in their development. However, the development of ontogenic resistance is actually quite rapid in berries, and fruit become nearly immune to infection within 4 weeks after fruit set. Our objective was to determine how and at what stage the pathogen was halted in the infection process on ontogenically resistant berries. Adhesion of conidia, germination, and appressorium formation were not impeded on older berries. However, once berries were approximately 3 weeks old and older, few germlings were able to form secondary hyphae. Ontogenically resistant berries responded rapidly to infection by synthesis of a germin-like protein that had been previously shown to play a role in host defense against barley powdery mildew. On susceptible berries, cell discoloration around penetration sites indicated the oxidation of phenolic compounds; a process that was followed by localized cell death. However, the pathogen was still able to infect such cells prior to their death, continue secondary growth, and thereby colonize young berries. Formation of papillae was not involved in the differential resistance mechanism of older berries. In susceptible berries, papillae formed frequently at infection sites but did not always contain the pathogen, whereas in resistant berries, the pathogen was always halted prior to the formation of papillae. The host defense, which conditions ontogenic resistance, operates in the earliest stages of the infection process, in the absence of gross anatomical barriers, prior to the

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

A prospective study of tuberculosis drug susceptibility in sabah, malaysia, and an algorithm for management of isoniazid resistance.

PubMed

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.

Resistance Management for Asian Citrus Psyllid, Diaphorina citri Kuwayama, in Florida.

PubMed

Chen, Xue Dong; Stelinski, Lukasz L

2017-09-20

The Asian citrus psyllid, Diaphorina citri Kuwayma, is one of the most important pests in citrus production. The objective of this study was to evaluate D. citri resistance management with three insecticide rotations and compare them with no rotation and an untreated check. The different insecticides (modes of action) tested were: dimethoate, imidacloprid, diflubenzuron, abamectin 3% + thiamethoxam 13.9%, and fenpropathrin. Eggs, nymph, and adult psyllids were counted weekly. Five insecticide applications were made in 2016. Insecticide susceptibility was determined by direct comparison with a laboratory susceptible population and field populations before and after all treatments were applied. Rankings of eggs, nymphs, and adults counted in treated plots were significantly lower than in the untreated control plots after each application. Initially, the resistance ratio (RR 50 ) for each rotation model, as compared with laboratory susceptible strain and the field population before application, was less than 5.76 and 4.31, respectively. However, after five applications with dimethoate, the RR 50 using the laboratory and pre-treatment field populations was 42.34 and 34.74, respectively. Our results indicate that effectively rotating modes of action can delay and/or prevent development of insecticide resistance in populations of D. citri .

Disruption of the blood–brain barrier in pigs naturally infected with Taenia solium, untreated and after anthelmintic treatment

PubMed Central

Guerra-Giraldez, Cristina; Marzal, Miguel; Cangalaya, Carla; Balboa, Diana; Orrego, Miguel Ángel; Paredes, Adriana; Gonzales-Gustavson, Eloy; Arroyo, Gianfranco; García, Hector H.; González, Armando E.; Mahanty, Siddhartha; Nash, Theodore E.

2014-01-01

Neurocysticercosis is a widely prevalent disease in the tropics that causes seizures and a variety of neurological symptoms in most of the world. Experimental models are limited and do not allow assessment of the degree of inflammation around brain cysts. The vital dye Evans Blue (EB) was injected into 11 pigs naturally infected with Taenia solium cysts to visually identify the extent of disruption of the blood brain barrier. A total of 369 cysts were recovered from the 11 brains and classified according to the staining of their capsules as blue or unstained. The proportion of cysts with blue capsules was significantly higher in brains from pigs that had received anthelmintic treatment 48 and 120 h before the EB infusion, indicating a greater compromise of the blood brain barrier due to treatment. The model could be useful for understanding the pathology of treatment-induced inflammation in neurocysticercosis. PMID:23684909

Longitudinal study for anthelmintic efficacy against intestinal helminths in naturally exposed Lithuanian village dogs: critical analysis of feasibility and limitations.

PubMed

Vienažindienė, Ž; Joekel, D E; Schaper, R; Deplazes, P; Šarkūnas, M

2018-05-01

The efficacy of anthelmintic treatment at 1, 3, and 6 month intervals was evaluated in a prospective controlled field study with naturally exposed Lithuanian village dogs by monthly coproscopy during 1 year. A placebo-treated control group (C) (n = 202) and groups treated with two broad-spectrum anthelmintics, febantel/pyrantel-embonate/praziquantel (Drontal® Plus, Bayer) (D1, D3, D6; n = 113-117) and emodepside/praziquantel (Profender®, Bayer) (P1, P3, P6; n = 114-119), were included. At the beginning of the study, eggs of Toxocara canis (4.02%) and T. cati (0.44%) identified morphometrically and/or molecularly and eggs of taeniid- (0.78%) and Capillaria-like eggs (5.03%) were present in the feces without significant differences in prevalence between groups. Significant decreases in excretion of T. canis eggs was found 1 month after the treatment with Drontal® Plus in February (D1) and with Profender® in October (P1), November (P1), December (P3), February (P1), and March (P1, P3), as compared to controls in the same months. The incidence of egg excretion per dog at least once a year was significantly lower in group P1 for T. canis (4.24%; p < 0.01) and in groups D1, P1 for taeniid eggs (0%; p < 0.01 and p < 0.001), when compared to controls (16.96 and 6.70%, respectively). A critical analyses of factors possibly responsible for intestinal passage of canine helminth eggs revealed that chained dogs excreted T. canis eggs more frequently 1 month after treatment compared to dogs in pens, particularly from November to March (p = 0.01). The incidence of single detection of T. cati eggs was significantly increased in chained dogs (12.46%) as compared to fenced dogs (1.08%; p = 0.0001).

HIV-1 drug resistance and resistance testing.

PubMed

Clutter, Dana S; Jordan, Michael R; Bertagnolio, Silvia; Shafer, Robert W

2016-12-01

The global scale-up of antiretroviral (ARV) therapy (ART) has led to dramatic reductions in HIV-1 mortality and incidence. However, HIV drug resistance (HIVDR) poses a potential threat to the long-term success of ART and is emerging as a threat to the elimination of AIDS as a public health problem by 2030. In this review we describe the genetic mechanisms, epidemiology, and management of HIVDR at both individual and population levels across diverse economic and geographic settings. To describe the genetic mechanisms of HIVDR, we review the genetic barriers to resistance for the most commonly used ARVs and describe the extent of cross-resistance between them. To describe the epidemiology of HIVDR, we summarize the prevalence and patterns of transmitted drug resistance (TDR) and acquired drug resistance (ADR) in both high-income and low- and middle-income countries (LMICs). We also review to two categories of HIVDR with important public health relevance: (i) pre-treatment drug resistance (PDR), a World Health Organization-recommended HIVDR surveillance metric and (ii) and pre-exposure prophylaxis (PrEP)-related drug resistance, a type of ADR that can impact clinical outcomes if present at the time of treatment initiation. To summarize the implications of HIVDR for patient management, we review the role of genotypic resistance testing and treatment practices in both high-income and LMIC settings. In high-income countries where drug resistance testing is part of routine care, such an understanding can help clinicians prevent virological failure and accumulation of further HIVDR on an individual level by selecting the most efficacious regimens for their patients. Although there is reduced access to diagnostic testing and to many ARVs in LMIC, understanding the scientific basis and clinical implications of HIVDR is useful in all regions in order to shape appropriate surveillance, inform treatment algorithms, and manage difficult cases. Copyright © 2016 Elsevier B

Piper aduncum against Haemonchus contortus isolates: cross resistance and the research of natural bioactive compounds.

PubMed

Gaínza, Yousmel Alemán; Fantatto, Rafaela Regina; Chaves, Francisco Celio Maia; Bizzo, Humberto Ribeiro; Esteves, Sérgio Novita; Chagas, Ana Carolina de Souza

2016-01-01

The anthelminthic activity of the essential oil (EO) of Piper aduncum L. was tested in vitro on eggs and larvae of resistant (Embrapa2010) and susceptible (McMaster) isolates of Haemonchus contortus. The EO was obtained by steam distillation and its components identified by chromatography. EO concentrations of 12.5 to 0.02 mg/mL were used in the egg hatch test (EHT) and concentrations of 3.12 to 0.01 mg/mL in the larval development test (LDT). Inhibition concentrations (IC) were determined by the SAS Probit procedure, and significant differences assessed by ANOVA followed by Tukey's test. In the EHT, the IC50 for the susceptible isolate was 5.72 mg/mL. In the LDT, the IC50 and IC90 were, respectively, 0.10 mg/mL and 0.34 mg/mL for the susceptible isolate, and 0.22 mg/mL and 0.51 mg/mL for the resistant isolate. The EO (dillapiole 76.2%) was highly efficacious on phase L1. Due to the higher ICs obtained for the resistant isolate, it was raised the hypothesis that dillapiole may have a mechanism of action that resembles those of other anthelmintic compounds. We further review and discuss studies, especially those conducted in Brazil, that quantified the major constituents of P. aduncum-derived EO.

Perceptions and actions of Dutch sheep farmers concerning worm infections.

PubMed

Ploeger, H W; Antonis, A F G; Verkaik, J C; Vellema, P; Bokma-Bakker, M H

2016-10-15

efficacy of the treatment. Slightly over 40% of the respondents said they did not experience bottlenecks in parasite control. Yet, over half of these said having problems with worm infections, over half did see clinical signs related to worm infections and over three quarters used anthelmintics. Within the group of farmers experiencing difficulties in parasite control, the most often mentioned bottleneck concerned pasture management (75.8%). When asking farmers for solutions, 90% of all respondents indicated they are willing to adjust their pasture management. Farmers are also interested in other methods to reduce the risk of worm infections, such as possibilities to enhance the immune system of sheep in general (71%), to increase specific genetic resistance to worms and to apply anti-parasite forages, both about 40%. Results of this study gave the following potential foci of attention: (1) making complex scientific knowledge more accessible to farmers through simple tools and applicable in the daily farming process; (2) changing the mindset of farmers about their current worm control practices, i.e. breaking long-standing habits such as treating ewes and lambs at fixed moments rather than based on actual worm infection monitoring data; (3) demonstrating effective pasture rotation schemes on specific farms and using these in extension work; (4) making farmers more aware that checking anthelmintic efficacy is important; (5) improving quarantine procedures; (6) creating a wider array of applicable alternative control measures from which individual farmers can choose what fits them most; and finally, (7) improving mutual understanding among farmers, veterinary practitioners and parasitologists alike. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

Flower morphology and development in Artemisia annua, a medicinal plant used as a treatment against malaria

USDA-ARS?s Scientific Manuscript database

Artemisia annua produces a wide spectrum of bioactive phytochemicals that possess pharmacological properties including antimalarial, antitumor, anti-inflammatory, and anthelmintic activities. The main active ingredient, artemisinin, is extremely effective against multi-drug resistant Plasmodium fal...

Assessment of Anthelmintic Efficacy of Mebendazole in School Children in Six Countries Where Soil-Transmitted Helminths Are Endemic

PubMed Central

Levecke, Bruno; Montresor, Antonio; Albonico, Marco; Ame, Shaali M.; Behnke, Jerzy M.; Bethony, Jeffrey M.; Noumedem, Calvine D.; Engels, Dirk; Guillard, Bertrand; Kotze, Andrew C.; Krolewiecki, Alejandro J.; McCarthy, James S.; Mekonnen, Zeleke; Periago, Maria V.; Sopheak, Hem; Tchuem-Tchuenté, Louis-Albert; Duong, Tran Thanh; Huong, Nguyen Thu; Zeynudin, Ahmed; Vercruysse, Jozef

2014-01-01

Background Robust reference values for fecal egg count reduction (FECR) rates of the most widely used anthelmintic drugs in preventive chemotherapy (PC) programs for controlling soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura, and hookworm) are still lacking. However, they are urgently needed to ensure detection of reduced efficacies that are predicted to occur due to growing drug pressure. Here, using a standardized methodology, we assessed the FECR rate of a single oral dose of mebendazole (MEB; 500 mg) against STHs in six trials in school children in different locations around the world. Our results are compared with those previously obtained for similarly conducted trials of a single oral dose of albendazole (ALB; 400 mg). Methodology The efficacy of MEB, as assessed by FECR, was determined in six trials involving 5,830 school children in Brazil, Cambodia, Cameroon, Ethiopia, United Republic of Tanzania, and Vietnam. The efficacy of MEB was compared to that of ALB as previously assessed in 8,841 school children in India and all the above-mentioned study sites, using identical methodologies. Principal Findings The estimated FECR rate [95% confidence interval] of MEB was highest for A. lumbricoides (97.6% [95.8; 99.5]), followed by hookworm (79.6% [71.0; 88.3]). For T. trichiura, the estimated FECR rate was 63.1% [51.6; 74.6]. Compared to MEB, ALB was significantly more efficacious against hookworm (96.2% [91.1; 100], p<0.001) and only marginally, although significantly, better against A. lumbricoides infections (99.9% [99.0; 100], p = 0.012), but equally efficacious for T. trichiura infections (64.5% [44.4; 84.7], p = 0.906). Conclusions/Significance A minimum FECR rate of 95% for A. lumbricoides, 70% for hookworm, and 50% for T. trichiura is expected in MEB-dependent PC programs. Lower FECR results may indicate the development of potential drug resistance. PMID:25299391

Choosing the best cropping systems to target pleiotropic effects when managing single-gene herbicide resistance in grass weeds. A blackgrass simulation study.

PubMed

Colbach, Nathalie; Chauvel, Bruno; Darmency, Henri; Délye, Christophe; Le Corre, Valérie

2016-10-01

Managing herbicide-resistant weeds is becoming increasingly difficult. Here we adapted the weed dynamics model AlomySys to account for experimentally measured fitness costs linked to mutants of target-site resistance to acetyl-coenzyme A carboxylase (ACCase)-inhibiting herbicides in Alopecurus myosuroides. We ran simulations to test how effectively cultural practices manage resistance. Simulations of an oilseed rape/winter wheat/winter barley rotation showed that, when replacing one of the seven applied herbicides with an ACCase-inhibiting one, resistant mutants exceeded 1 plant m(-2) , with a probability of 40%, after an average of 18 years. This threshold was always exceeded when three or four ACCase-inhibiting herbicides were used, after an average of 8 and 6 years respectively. With reduced herbicide rates or suboptimal spraying conditions, resistance occurred 1-3 years earlier in 50% of simulations. Adding spring pea to the rotation or yearly mouldboard ploughing delayed resistance indefinitely in 90 and 60% of simulations respectively. Ploughing also modified the genetic composition of the resistant population by selecting a previously rare mutant that presented improved pre-emergent growth. The prevalence of the mutations was influenced more by their associated fitness cost or benefit than by the number of ACCase-inhibiting herbicides to which they conferred resistance. Simulations allowed us to rank weed management practices and suggest that pleiotropic effects are extremely important for understanding the frequency of herbicide resistance in the population. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

The benefits of herbicide-resistant crops.

PubMed

Green, Jerry M

2012-10-01

Since 1996, genetically modified herbicide-resistant crops, primarily glyphosate-resistant soybean, corn, cotton and canola, have helped to revolutionize weed management and have become an important tool in crop production practices. Glyphosate-resistant crops have enabled the implementation of weed management practices that have improved yield and profitability while better protecting the environment. Growers have recognized their benefits and have made glyphosate-resistant crops the most rapidly adopted technology in the history of agriculture. Weed management systems with glyphosate-resistant crops have often relied on glyphosate alone, have been easy to use and have been effective, economical and more environmentally friendly than the systems they have replaced. Glyphosate has worked extremely well in controlling weeds in glyphosate-resistant crops for more than a decade, but some key weeds have evolved resistance, and using glyphosate alone has proved unsustainable. Now, growers need to renew their weed management practices and use glyphosate with other cultural, mechanical and herbicide options in integrated systems. New multiple-herbicide-resistant crops with resistance to glyphosate and other herbicides will expand the utility of existing herbicide technologies and will be an important component of future weed management systems that help to sustain the current benefits of high-efficiency and high-production agriculture. Copyright © 2012 Society of Chemical Industry.

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

USDA-ARS?s Scientific Manuscript database

A three-year field experiment was conducted to evaluate the role of inversion tillage, cover crops and spring tillage methods for Palmer amaranth between-row (BR) and within-row (WR) management in glufosinate-resistant cotton. Main plots were two inversion tillage systems: fall inversion tillage (IT...

[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. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

A comparison of two integrated approaches of controlling nematode parasites in small ruminants.

PubMed

Miller, J E; Burke, J M; Terrill, T H; Kearney, M T

2011-06-10

Control of gastrointestinal nematodes (GIN) in small ruminants in regions of the world where anthelmintic resistance is prevalent must rely on more than just chemical deworming strategies. The objective of this experiment was to compare two integrated treatment protocols for control of GIN (primarily Haemonchus contortus in this region) using anthelmintics, copper oxide wire particles (COWP) and FAMACHA(©), compared to traditional anthelmintic use only. Three separate trials were conducted on mature ewes, weaned goats, and weaned lambs in which three deworming management strategies were applied: 1) all animals were dewormed with levamisole at four week intervals (LEV), 2) individual animals were dewormed with moxidectin when scored≥4 (ewes) or ≥3 (kids and lambs) using FAMACHA(©) (FAM/MOX), 3) all animals were dewormed with moxidectin initially and again with COWP (2g) when group mean FEC exceeded 500 (ewes), 3000 (kids), or 1000 (lambs) eggs/g (MOX/COWP). In this final group, during periods between group treatments, individual animals were dewormed with albendazole and levamisole according to FAMACHA(©) score. Fecal egg counts (FEC) and blood packed cell volume (PCV) were determined every 7 days and body weight every 28 days for 30, 20, or 16 weeks in ewes, goats, and lambs, respectively. Efficacy of levamisole was 83.4-86.4%, efficacy of moxidectin was 93.5-100%, and efficacy of COWP was 10.8-98.1% among the three trials. The mean number of deworming treatments per animal that occurred for the LEV, FAM/MOX, and MOX/COWP groups, respectively, was 7.9, 0.6, and 2.5±0.4 (P<0.001) for ewes, 5.2, 1.6, and 3.4±0.3 (P<0.001) for goats, and 4.0, 1.7, and 3.6±0.2 (P<0.001) for lambs. Production (body weight of lambs weaned from ewes or final body weight of kids and lambs) was similar among management strategy groups for ewes and kids, but FAM/MOX lambs were lighter by the end of the trial (P<0.003). While more time and labor was required to use the FAMACHA

Confirmation of resistance to herbicides and evaluation of resistance levels

USDA-ARS?s Scientific Manuscript database

As cases of resistance to herbicides escalate worldwide, there is increasing demand from growers to test for weed resistance and how to manage it. Scientists have developed resistance testing protocols for numerous herbicides and weed species. Growers need immediate answers and scientists are faced ...

Nutritional Management of Insulin Resistance in Nonalcoholic Fatty Liver Disease (NAFLD)

PubMed Central

Conlon, Beth A.; Beasley, Jeannette M.; Aebersold, Karin; Jhangiani, Sunil S.; Wylie-Rosett, Judith

2013-01-01

Nonalcoholic fatty liver disease (NAFLD) is an emerging global health concern. It is the most common form of chronic liver disease in Western countries, affecting both adults and children. NAFLD encompasses a broad spectrum of fatty liver disease, ranging from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH), and is strongly associated with obesity, insulin resistance, and dyslipidemia. First-line therapy for NAFLD includes weight loss achieved through diet and physical activity. However, there is a lack of evidenced-based dietary recommendations. The American Diabetes Association’s (ADA) recommendations that aim to reduce the risk of diabetes and cardiovascular disease may also be applicable to the NAFLD population. The objectives of this review are to: (1) provide an overview of NAFLD in the context of insulin resistance, and (2) provide a rationale for applying relevant aspects of the ADA recommendations to the nutritional management of NAFLD. PMID:24152749

Effect of molecular weight and concentration of legume condensed tannins on in vitro larval migration inhibition of Haemonchus contortus.

PubMed

Naumann, H D; Armstrong, S A; Lambert, B D; Muir, J P; Tedeschi, L O; Kothmann, M M

2014-01-17

The effect of molecular weight of condensed tannins (CT) from a variety of warm-season perennial legumes commonly consumed by sheep and goats on anthelmintic activity has not been previously explored. The objectives of this study were to determine if molecular weight of CT from warm-season perennial legumes could predict the biological activity of CT relative to anthelmintic activity against ivermectin resistant L3 stage Haemonchus contortus (HC) using a larval migration inhibition (LMI) assay. A second objective was to determine if CT from warm-season perennial legumes possess anthelmintic properties against L3 stage (HC). Lespedeza stuevei had the greatest concentration of total condensed tannin (TCT; 11.7%), whereas, with the exception of Arachis glabrata, a CT-free negative control, Leucaena retusa had the least TCT (3.3%). Weight-average molecular weight of CT ranged from 552 Da for L. stuevei to 1483 Da for Lespedeza cuneata. The treatments demonstrating the greatest percent LMI were L. retusa, L. stuevei and Acacia angustissima var. hirta (65.4%, 63.1% and 42.2%, respectively). The ivermectin treatment had the smallest percent LMI (12.5%) against ivermectin resistant L3 HC. There was a weak correlation (R(2)=0.34; P=0.05) between CT MW and percent LMI, suggesting that molecular weight of CT is a weak contributing factor to CT biological activity as it relates to LMI of L3 stage HC. L. stuevei, L. retusa and A. angustissima var. hirta STP5 warrant further evaluation of anthelmintic properties in vivo. Copyright © 2013 Elsevier B.V. All rights reserved.

In vitro effects of anthelmintics on the histochemistry of Haemonchus contortus and Trichuris globulosa.

PubMed

Kaur, M; Sood, M L

1996-12-01

In vitro incubation of Haemonchus contortus (RUD., 1803) and Trichuris globulosa (v. LINSTOW, 1901) were proformed for 10-12 h in Tyrode's solution and 10 and 50 micrograms/ml concentrations each of albendazole (ABZ), fenbendazole (FBZ), thiophenate (TP), dl-tetramisole and oxyclozanide (TO), dl-tetramisole HCI (TMS) and levamisole HCI (LMS) to study morphological and histochemical alterations. The major structural changes observed after treatment with all the drugs were vacuolation in the intestine of H. contortus except with TP treatment and disruption of the epithelium in T. globulosa except with TMS treatment. The other major alteration in T. globulosa was the loss of muscle striations after TP, TO, TMS and LMS treatments. All the six anthelmintics reduced the quantity of neutral mucopolysaccharides in the intestine of H. contortus and T. globulosa except with TMS and LMS treatments in the latter. Acidic mucopolysaccharides detected in the microvilli of the intestine of H. contortus were lost after TO and ABZ treatments. The loss of lipids from the intestine was evident after TO, ABZ, FBZ and TP treatments in H. contortus and by all the drugs in T. globulosa. LMS treatment caused accumulation of very large lipid droplets in the intestine of H. contortus.

Benchmark study on glyphosate-resistant cropping systems in the United States. Part 6: Timeliness of economic decision-making in implementing weed resistance management strategies.

PubMed

Weirich, Jason W; Shaw, David R; Coble, Keith H; Owen, Micheal D K; Dixon, Philip M; Weller, Stephen C; Young, Bryan G; Wilson, Robert G; Jordan, David L

2011-07-01

The introduction of glyphosate-resistant (GR) crops in the late 1990s made weed control in maize, cotton and soybean simple. With the rapid adoption of GR crops, many growers began to rely solely on glyphosate for weed control. This eventually led to the evolution of GR weeds. Growers are often reluctant to adopt a weed resistance best management practice (BMP) because of the added cost of additional herbicides to weed control programs which would reduce short-term revenue. This study was designed to evaluate when a grower that is risk neutral (profit maximizing) or risk averse should adopt a weed resistance BMP. Whether a grower is risk neutral or risk averse, the optimal decision would be to adopt a weed resistance BMP when the expected loss in revenue is greater than 30% and the probability of resistance evolution is 0.1 or greater. However, if the probability of developing resistance increases to 0.3, then the best decision would be to adopt a weed resistance BMP when the expected loss is 10% or greater. Given the scenarios analyzed, risk-neutral or risk-averse growers should implement a weed resistance BMP with confidence that they have made the right decision economically and avoided the risk of lost revenue from resistance. If the grower wants to continue to see the same level of return, adoption of BMP is required. Copyright © 2011 Society of Chemical Industry.

Managing a case of extensively drug-resistant (XDR) pulmonary tuberculosis in Singapore.

PubMed

Phua, Chee Kiang; Chee, Cynthia B E; Chua, Angeline P G; Gan, Suay Hong; Ahmed, Aneez D B; Wang, Yee Tang

2011-03-01

Extensively drug-resistant tuberculosis (XDR-TB) is an emerging global health risk. We present the first case report of XDR-TB in Singapore. A 41-year-old Indonesian lady with previously treated pulmonary tuberculosis presented with chronic cough. Her sputum was strongly acid-fast bacilli positive and grew Mycobacterium tuberculosis complex resistant to first and second-line TB medications. She received 5 months of intensive multidrug treatment without sputum smear conversion. She then underwent resection of the diseased lung. The total cost incurred amounted to over S$100,000. She achieved sputum smear/culture conversion post-surgery, but will require further medical therapy for at least 18 months. XDRTB is poorly responsive to therapy and extremely expensive to manage. Its prevention by strict compliance to therapy is paramount.

Preparation of stir cake sorptive extraction based on polymeric ionic liquid for the enrichment of benzimidazole anthelmintics in water, honey and milk samples.

PubMed

Wang, Yulei; Zhang, Jie; Huang, Xiaojia; Yuan, Dongxing

2014-08-20

In this work, a new stir cake sorptive extraction (SCSE) using polymeric ionic liquid monolith as sorbent was prepared. The sorbent was obtained by in situ copolymerization of an ionic liquid, 1-allyl-3-methylimidazolium bis[(trifluoro methyl)sulfonyl]imide (AMII) and divinylbenzene (DB) in the presence of N,N-dimethylformamide. The influence of the content of ionic liquid and the porogen in the polymerization mixture on extraction performance was studied thoroughly. The physicochemical properties of the polymeric ionic liquid were characterized by infrared spectroscopy, elemental analysis, scanning electron microscopy and mercury intrusion porosimetry. The usefulness of SCSE-AMIIDB was demonstrated by the enrichment of trace benzimidazole anthelmintics. Several parameters affecting the extraction efficiency were investigated, and under the optimized conditions, a simple and effective method for the determination of trace benzimidazoles residues in water, milk and honey samples was established by coupling SCSE-AMIIDB with high performance liquid chromatography/diode array detection (SCSE-AMIIDB-HPLC/DAD). Results indicated that the limits of detection (S/N=3) for target compounds were 0.020-0.072 μg L(-1), 0.035-0.10 μg L(-1) and 0.026-0.076 μg L(-1) in water, milk and honey samples, respectively. In addition, an acceptable reproducibility was achieved by evaluating the repeatability and intermediate precision with relative standard deviations (RSD) of less than 9% and 11%, respectively. Finally, the established AMII-SCSE-HPLC/DAD method was successfully applied for the determination of benzimidazoles residues in milk, honey and environmental water samples. Recoveries obtained for the determination of benzimidazole anthelmintics in spiking samples ranged from 70.2% to 117.6%, with RSD below 12% in all cases. Copyright © 2014 Elsevier B.V. All rights reserved.

Fasciola hepatica: a comparative survey of adult fluke resistance to triclabendazole, nitroxynil and closantel on selected upland and lowland sheep farms in Northern Ireland using faecal egg counting, coproantigen ELISA testing and fluke histology.

PubMed

Hanna, R E B; McMahon, C; Ellison, S; Edgar, H W; Kajugu, P-E; Gordon, A; Irwin, D; Barley, J P; Malone, F E; Brennan, G P; Fairweather, I

2015-01-15

testing. The study highlights the high level of penetration of TCBZ resistance throughout F. hepatica populations in areas of intensively managed sheep production with a high level of fluke challenge. Further, it emphasises the importance of pre-emptive chemotherapeutic action against chronic fasciolosis, using flukicides effective against the egg-producing adult flukes to minimise pasture contamination for the next season's lamb crop. This study also exemplifies the use of several complementary methods (FECRT; CRT; fluke histology; comparative anthelmintic efficacy testing) for confirmation of a diagnosis of fluke drug resistance. Copyright © 2014 Elsevier B.V. All rights reserved.

Managing aquatic parasites for reduced drug resistance: lessons from the land.

PubMed

McEwan, Gregor F; Groner, Maya L; Burnett, Danielle L; Fast, Mark D; Revie, Crawford W

2016-12-01

Atlantic salmon farming is one of the largest aquaculture industries in the world. A major problem in salmon farms is the sea louse ectoparasite Lepeophtheirus salmonis, which can cause stress, secondary infection and sometimes mortality in the salmon host. Sea lice have substantial impacts on farm economics and potentially nearby wild salmonid populations. The most common method of controlling sea louse infestations is application of chemicals. However, most farming regions worldwide have observed resistance to the small set of treatment chemicals that are available. Despite this, there has been little investigation of treatment strategies for managing resistance in aquaculture. In this article, we compare four archetypical treatment strategies inspired by agriculture, where the topic has a rich history of study, and add a fifth strategy common in aquaculture. We use an agent-based model (ABM) to simulate these strategies and their varying applications of chemicals over time and space. We analyse the ABM output to compare how the strategies perform in controlling louse abundance, number of treatments required and levels of resistance in the sea louse population. Our results indicated that among the approaches considered applying chemicals in combination was the most effective over the long term. © 2016 The Author(s).

Resistance Management for Asian Citrus Psyllid, Diaphorina citri Kuwayama, in Florida

PubMed Central

Chen, Xue Dong; Stelinski, Lukasz L.

2017-01-01

The Asian citrus psyllid, Diaphorina citri Kuwayma, is one of the most important pests in citrus production. The objective of this study was to evaluate D. citri resistance management with three insecticide rotations and compare them with no rotation and an untreated check. The different insecticides (modes of action) tested were: dimethoate, imidacloprid, diflubenzuron, abamectin 3% + thiamethoxam 13.9%, and fenpropathrin. Eggs, nymph, and adult psyllids were counted weekly. Five insecticide applications were made in 2016. Insecticide susceptibility was determined by direct comparison with a laboratory susceptible population and field populations before and after all treatments were applied. Rankings of eggs, nymphs, and adults counted in treated plots were significantly lower than in the untreated control plots after each application. Initially, the resistance ratio (RR50) for each rotation model, as compared with laboratory susceptible strain and the field population before application, was less than 5.76 and 4.31, respectively. However, after five applications with dimethoate, the RR50 using the laboratory and pre-treatment field populations was 42.34 and 34.74, respectively. Our results indicate that effectively rotating modes of action can delay and/or prevent development of insecticide resistance in populations of D. citri. PMID:28930170

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

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.

Anthelmintic activity of Spigelia anthelmia extract against gastrointestinal nematodes of sheep.

PubMed

Ademola, I O; Fagbemi, B O; Idowu, S O

2007-06-01

In vitro (larval development assay) and in vivo studies were conducted to determine possible direct anthelmintic effect of ethanolic and aqueous extracts of Spigelia anthelmia towards different ovine gastrointestinal nematodes. The effect of extracts on development and survival of infective larvae stage (L(3)) was assessed. Best-fit LC(50) values were computed by global model of non-linear regression curve fitting (95% confidence interval). Therapeutic efficacy of the ethanolic extracts administered orally at a dose rate of 125, 250, and 500 mg/kg, relative to a non-medicated control group of sheep harbouring naturally acquired infection of gastrointestinal nematodes, was evaluated in vivo.The presence of S. anthelmia extracts in the cultures decreased the survival of L(3) larvae. The LC(50) of aqueous extract (0.714 mg/ml) differ significantly from the LC(50) of the ethanolic extract (0.628 mg/ml) against the strongyles (p < 0.05, paired t-test). Faecal egg counts on day 12 after treatment showed that the extract is effective, relative to control (one-way analysis of variance [ANOVA], Dunnett's multiple comparison test) at 500 mg/kg against Strongyloides spp. (p < 0.01), 250 mg/kg against Oesophagostomum spp., Trichuris spp. (p < 0.05), and 125 mg/kg against Haemonchus spp. and Trichostrongylus spp. (p < 0.01). The effect of the doses is significant in all cases, the day after treatment is also extremely significant in most cases, whereas interaction between dose and day after treatment is significant (two-way ANOVA). S. anthelmia extract could, therefore, find application in the control of helminth in livestock, by the ethnoveterinary medicine approach.

Herbicide Resistant Weed Management

USDA-ARS?s Scientific Manuscript database

Metribuzin and rimsulfuron are the only two herbicides registered for postemergence broadleaf weed control in potatoes, and represent the two classes of herbicides, triazines and ALS inhibitors, with the most reported cases of resistant weeds world wide. Other postemergence grass herbicides belongin...

Resistance to gastrointestinal nematodes in dairy sheep: Genetic variability and relevance of artificial infection of nucleus rams to select for resistant ewes on farms.

PubMed

Aguerre, S; Jacquiet, P; Brodier, H; Bournazel, J P; Grisez, C; Prévot, F; Michot, L; Fidelle, F; Astruc, J M; Moreno, C R

2018-05-30

Breeding sheep for enhanced resistance to gastrointestinal parasites is a promising strategy to limit the use of anthelmintics due to the now widespread resistance of parasites to these molecules. This paper reports the genetic parameters estimated for parasite resistance and resilience traits in the Blond-faced Manech dairy sheep breed and the putative impacts of the selection for resistance to gastrointestinal nematodes (GIN) on farms. Two datasets were used. First, the rams of the selection scheme were artificially infected twice with L3 Haemonchus contortus larvae. Faecal egg counts (FEC) and packed cell volume (PCV) loss were measured 30 days after each infection. Secondly, the FEC, PCV and body condition score (BCS) (1-6 measures per ewe) of naturally infected ewes on farms were measured in the spring, summer and autumn over a two-year period. Genetic parameters were estimated for each dataset independently but also globally based on the pedigree connections between the two datasets. For the experimentally infected sires, the FEC following the second infection was moderately heritable (heritability: 0.35) and strongly correlated with FEC after the first infection (genetic correlation: 0.92). For the naturally infected ewes, FEC was also heritable (0.18). Using the two datasets together, a genetic correlation of 0.56-0.71 was estimated between the FEC values of the experimentally infected rams and naturally infected ewes. Consequently, the genetic variability of parasite resistance is similar whatever the physiological status (males or milking/pregnant ewes) and the infection conditions (experimental infection with one parasite or natural infection with several parasites). In practice, when the sire population is divided into two groups based on their genetic value, the FEC of the ewes born to the 50% most resistant sires is half that of the ewes born to the 50% most susceptible sires. Our study shows the feasibility and efficiency of genetic selection for

New Generation of Resistant Sugar Beet Varieties for Advanced Integrated Management of Cercospora Leaf Spot in Central Europe.

PubMed

Vogel, Johannes; Kenter, Christine; Holst, Carsten; Märländer, Bernward

2018-01-01

Cercospora leaf spot (CLS) epidemics in sugar beet have been increasing in recent years causing higher use of fungicides. Concomitantly, the availability of effective fungicides is at risk because of resistance development in the fungus, the lack of new active ingredients as well as restrictive approval practices. A key option for an integrated management of CLS is cultivation of resistant varieties. Because of the yield penalty in resistant varieties, acceptance in commercial practice so far has been low. The aim of our study was to characterize recent sugar beet varieties registered in Germany in terms of resistance and tolerance to CLS and their value for integrated pest management. The genetic basis of CLS resistance in varieties is protected by intellectual property rights even after variety registration and not open to the public due to economic competition. To gain reliable data for cultivation, varieties have to be tested for their resistance traits under field conditions at varying levels of infection with Cercospora beticola . In collaboration with variety related stakeholders, 15 sugar beet varieties were tested in 49 field trials in Germany from 2014 to 2016 for their yield response to CLS. The trials were set up in a split-plot design with and without infection (i.e., with and without fungicide). The classification of varietal reaction to CLS is based on symptomatic leaf area (susceptibility) and the resulting relative yield loss (tolerance). Since the relation between both parameters varied among varieties, it was used as an additional parameter to describe tolerance. On this basis, three groups of varieties were identified. They can be characterized as a susceptible, a resistant and a presumably tolerant cluster. A comparison of the data with an older dataset originating from 2009 to 2011 revealed that yield performance of recent varieties with resistance to C. beticola caught up with susceptible varieties due to breeding progress. They showed no

New Generation of Resistant Sugar Beet Varieties for Advanced Integrated Management of Cercospora Leaf Spot in Central Europe

PubMed Central

Vogel, Johannes; Kenter, Christine; Holst, Carsten; Märländer, Bernward

2018-01-01

Cercospora leaf spot (CLS) epidemics in sugar beet have been increasing in recent years causing higher use of fungicides. Concomitantly, the availability of effective fungicides is at risk because of resistance development in the fungus, the lack of new active ingredients as well as restrictive approval practices. A key option for an integrated management of CLS is cultivation of resistant varieties. Because of the yield penalty in resistant varieties, acceptance in commercial practice so far has been low. The aim of our study was to characterize recent sugar beet varieties registered in Germany in terms of resistance and tolerance to CLS and their value for integrated pest management. The genetic basis of CLS resistance in varieties is protected by intellectual property rights even after variety registration and not open to the public due to economic competition. To gain reliable data for cultivation, varieties have to be tested for their resistance traits under field conditions at varying levels of infection with Cercospora beticola. In collaboration with variety related stakeholders, 15 sugar beet varieties were tested in 49 field trials in Germany from 2014 to 2016 for their yield response to CLS. The trials were set up in a split-plot design with and without infection (i.e., with and without fungicide). The classification of varietal reaction to CLS is based on symptomatic leaf area (susceptibility) and the resulting relative yield loss (tolerance). Since the relation between both parameters varied among varieties, it was used as an additional parameter to describe tolerance. On this basis, three groups of varieties were identified. They can be characterized as a susceptible, a resistant and a presumably tolerant cluster. A comparison of the data with an older dataset originating from 2009 to 2011 revealed that yield performance of recent varieties with resistance to C. beticola caught up with susceptible varieties due to breeding progress. They showed no

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

USDA-ARS?s Scientific Manuscript database

Cercospora leaf spot (CLS, Cercospora beticola) is the most serious foliar disease of sugarbeet in Michigan and Ontario.Management of CLS depends on timely fungicide applications, disease forecasting prediction models and the use of CLS resistant sugar beet varieties. Fungicides have a dominant role...

Moxidectin: a review of chemistry, pharmacokinetics and use in horses

PubMed Central

Cobb, Rami; Boeckh, Albert

2009-01-01

This article reviews the current knowledge of the use of moxidectin (MOX) in horses, including its mode of action, pharmacokinetic and pharmacodynamic properties, efficacy, safety and resistance profile. Moxidectin is a second generation macrocyclic lactone (ML) with potent endectocide activity. It is used for parasite control in horses in an oral gel formulation. The principal mode of action of MOX and of other MLs is binding to gamma-aminobutyric (GABA) and glutamate-gated chloride channels. Moxidectin is different from other MLs in that it is a poor substrate for P-glycoproteins (P-gps) and therefore less susceptible to elimination from parasite cells through this mechanism. Due to its unique physicochemical and pharmacokinetic characteristics, MOX provides broad distribution into tissues, long half-life, significant residual antiparasitic activity, and high efficacy against encysted cyathostomin larvae. These characteristics allow for high efficacy and longer treatment interval against all important nematodes, when compared to other equine anthelmintics. A combination of MOX with praziquantel provides expanded spectrum of activity by adding activity against cestodes. Appropriate use of MOX allows for the development of strategic anthelmintic programmes that are different from those with conventional anthelmintics. Fewer treatments are required over a period of time, and therefore impose less frequent selection pressure for resistance. PMID:19778466

Effective drug combination for Caenorhabditis elegans nematodes discovered by output-driven feedback system control technique

PubMed Central

Ding, Xianting; Njus, Zach; Kong, Taejoon; Su, Wenqiong; Ho, Chih-Ming; Pandey, Santosh

2017-01-01

Infections from parasitic nematodes (or roundworms) contribute to a significant disease burden and productivity losses for humans and livestock. The limited number of anthelmintics (or antinematode drugs) available today to treat these infections are rapidly losing their efficacy as multidrug resistance in parasites becomes a global health challenge. We propose an engineering approach to discover an anthelmintic drug combination that is more potent at killing wild-type Caenorhabditis elegans worms than four individual drugs. In the experiment, freely swimming single worms are enclosed in microfluidic drug environments to assess the centroid velocity and track curvature of worm movements. After analyzing the behavioral data in every iteration, the feedback system control (FSC) scheme is used to predict new drug combinations to test. Through a differential evolutionary search, the winning drug combination is reached that produces minimal centroid velocity and high track curvature, while requiring each drug in less than their EC50 concentrations. The FSC approach is model-less and does not need any information on the drug pharmacology, signaling pathways, or animal biology. Toward combating multidrug resistance, the method presented here is applicable to the discovery of new potent combinations of available anthelmintics on C. elegans, parasitic nematodes, and other small model organisms. PMID:28983514

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...

Using resilience and resistance concepts to manage persistent threats to sagebrush ecosystems and greater sage-grouse

USGS Publications Warehouse

Chambers, Jeanne C.; Maestas, Jeremy D.; Pyke, David A.; Boyd, Chad S.; Pellant, Mike; Wuenschel, Amarina

2017-01-01

Conservation of imperiled species often demands addressing a complex suite of threats that undermine species viability. Regulatory approaches, such as the US Endangered Species Act (1973), tend to focus on anthropogenic threats through adoption of policies and regulatory mechanisms. However, persistent ecosystem-based threats, such as invasive species and altered disturbance regimes, remain critical issues for most at-risk species considered to be conservation-reliant. We describe an approach for addressing persistent ecosystem threats to at-risk species based on ecological resilience and resistance concepts that is currently being used to conserve greater sage-grouse (Centrocercus urophasianus)and sagebrush ecosystems. The approach links biophysical indicators of ecosystem resilience and resistance with species-specific population and habitat requisites in a risk-based framework to identify priority areas for management and guide allocation of resources to manage persistent ecosystem-based threats. US federal land management and natural resource agencies have adopted this framework as a foundation for prioritizing sage-grouse conservation resources and determining effective restoration and management strategies. Because threats and strategies to address them cross-cut program areas, an integrated approach that includes wildland fire operations, postfire rehabilitation, fuels management, and habitat restoration is being used. We believe this approach is applicable to species conservation in other largely intact ecosystems with persistent, ecosystem-based threats.

Resistance gene management: concepts and practice

Treesearch

Christopher C. Mundt

2012-01-01

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

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.

Proactive udder health management in South Africa and monitoring of antibiotic resistance of Staphylococcus aureus; in dairy herds from 2001 to 2010.

PubMed

Karzis, Joanne; Petzer, Inge-Marie; Donkin, Edward F; Naidoo, Vinny

2018-05-07

Antibiotic resistance of strains of Staphylococcus aureus isolated from bovine milk is of concern internationally. The objective of this study was to investigate trends of resistance of S. aureus to antibiotics administered to dairy cows in 19 South African and one Zambian dairy herds (participating in the South African proactive udder health management programme) and to identify possible contributing factors. The resistance of S. aureus strains to eight commonly used antibiotics in South Africa from 2001 to 2010 was evaluated. Staphylococcus aureus isolates (n = 2532) were selected from cows with subclinical mastitis in 20 herds routinely sampled as part of the proactive udder health management programme. The isolates were selected from milk samples that had somatic cell counts more than 400 000 cells/mL and were tested for antibiotic resistance using a standard Kirby-Bauer test with published clinical breakpoints. The prevalence of antibiotic resistance was evaluated as a percentage of S. aureus isolates susceptible out of the total numbers for each antibiotic selected per year. Staphylococcus aureus showed a significant increase in percentage of susceptible isolates over time for all antibiotics tested except for ampicillin. The overall prevalence of mastitis did not change during the study period. However, the prevalence of mastitis caused by S. aureus (mostly subclinical cases) in the selected herds decreased numerically but not significantly. Reduction in the incidence of antibiotic resistance shown by S. aureus was presumed to be a result of the application of the proactive udder health management programme. The fact that the overall prevalence of mastitis was kept stable was possibly because of the influence of the management programme in conjunction with the return of infections caused by non-resistant strains.

Anthelmintic utilisation practices and prevalence of gastrointestinal helminth infections in sheep kept in the urban and peri-urban areas of Bishoftu Town.

PubMed

Datiko, Jallale; Terefe, Getachew; Bekele, Jemere

2013-02-01

Assessment of the anthelmintic (AH) utilisation practices and estimation of the prevalence of gastrointestinal helminth infections in sheep were carried out from November 2010 to April 2011 in urban and peri-urban areas of Bishoftu Town, central Ethiopia. A structured questionnaire was employed to assess the AH utilisation practices in sheep of 310 owners/households, while floatation and sedimentation techniques were used to study the prevalence of helminth infections. Faecal examinations revealed that 53.9 % of sheep harboured gastrointestinal helminth infections with a high frequency due to strongyles (77.3 %). The questionnaire survey revealed that sources of AH for sheep were government and private veterinary clinics for 98.5 % of urban and 65.4 % peri-urban respondents. In peri-urban areas, AH were also purchased from open markets and illegal dealers. Albendazole was the most common (75.5 %) drug used in sheep followed by ivermectin (18.7 %) and tetramisole (5.8 %). The criteria for selecting AH were: prescription by veterinarians (51.6 %), efficacy (31.9 %), price (12.3 %) and arbitrary reasons (4.2 %). Treatment frequency was minimal with 51.3, 32.3 and 15.8 % of the owners treating their sheep once, twice and less than once per year, respectively. Treatments mainly depended on manifestations of general (45.8 %) and digestive (23.3 %) symptoms. Irrespective of the body weight of the sheep, albendazole was the only drug reported to be given at half bolus/sheep (14.1 %). Owing to this practice, albendazole faces the risk of reduced efficacy or AH resistance due to its wide spread utilisation, handling by untrained personnel and suspected underdosage, which altogether support the perception of sheep owners on its lower effect on the performance of treated sheep.

Analysis of the protective immune response following intramuscular vaccination of calves against the intestinal parasite Cooperia oncophora

USDA-ARS?s Scientific Manuscript database

Anthelmintic resistance in the bovine parasite Cooperia oncophora is developing and spreading rapidly worldwide. Vaccination is therefore often put forward as a cost-effective alternative for chemical drugs. Recently we reported the successful evaluation of a double domain activation-associated secr...

Evaluation of Cymbopogon schoenanthus essential oil in lambs experimentally infected with Haemonchus contortus

USDA-ARS?s Scientific Manuscript database

Hematophagous gastrointestinal parasites cause significant economic losses in small ruminant grazing systems. The growing reports of multi-drug resistant parasites call for intensive research on alternative treatments for anthelmintics to help small ruminants cope with these parasites. Two-month-o...

Effect of fall-grazed sericea lespedeza (Lespedeza cuneata) on gastrointestinal nematode infections of growing goats

USDA-ARS?s Scientific Manuscript database

Infection with gastrointestinal nematodes (GIN), particularly Haemonchus contortus, a highly pathogenic blood-feeder, has a major effect on profitability of goat production world-wide. High prevalence of anthelmintic-resistant GIN in goats has increased pressure to find effective, alternative non-sy...

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

USDA-ARS?s Scientific Manuscript database

Giant ragweed has been increasing as a major weed of row crops in North America. We conducted a web-based survey of Certified Crop Advisors in the Corn Belt to determine the current distribution of giant ragweed, the distribution of herbicide resistant populations, and management and ecological fact...

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…

Praziquantel for Schistosomiasis: Single-Drug Metabolism Revisited, Mode of Action, and Resistance.

PubMed

Vale, Nuno; Gouveia, Maria João; Rinaldi, Gabriel; Brindley, Paul J; Gärtner, Fátima; Correia da Costa, José M

2017-05-01

Schistosomiasis, a major neglected tropical disease, affects more than 250 million people worldwide. Treatment of schistosomiasis has relied on the anthelmintic drug praziquantel (PZQ) for more than a generation. PZQ is the drug of choice for the treatment of schistosomiasis; it is effective against all major forms of schistosomiasis, although it is less active against juvenile than mature parasites. A pyrazino-isoquinoline derivative, PZQ is not considered to be toxic and generally causes few or transient, mild side effects. Increasingly, mass drug administration targeting populations in sub-Saharan Africa where schistosomiasis is endemic has led to the appearance of reduced efficacy of PZQ, which portends the selection of drug-resistant forms of these pathogens. The synthesis of improved derivatives of PZQ is attracting attention, e.g., in the (i) synthesis of drug analogues, (ii) rational design of pharmacophores, and (iii) discovery of new compounds from large-scale screening programs. This article reviews reports from the 1970s to the present on the metabolism and mechanism of action of PZQ and its derivatives against schistosomes. Copyright © 2017 American Society for Microbiology.

Anthelmintic efficacy of five tropical native Australian plants against Haemonchus contortus and Trichostrongylus colubriformis in experimentally infected goats (Capra hircus).

PubMed

Moreno, F C; Gordon, I J; Knox, M R; Summer, P M; Skerrat, L F; Benvenutti, M A; Saumell, C A

2012-06-08

The study of the anthelmintic properties of plants rich in plant secondary metabolites can provide ecologically sound methods for the treatment of parasites on grazing animals. The purpose of the present study was to evaluate the anthelmintic effect of five tropical native Australian plant species rich in plant secondary metabolites on adult Haemonchus contortus and Trichostrongylus colubriformis in experimentally infected goats. Thirty young, nematode-free goats were infected with 2500 H. contortus and 5000 T. colubriformis infective larvae thrice weekly for a week (day 1-7 of the experiment). On day 27 after first infection, the goats were allocated into six groups of five animals per group. From day 28 to day 35, fresh leaves from Acacia salicina, Acacia nilotica, Eucalyptus corymbia, Casuarina cunninghamiana and Eucalyptus drepanophylla were included in the goats diet. Five groups were offered leaves from one of these plant species and one group, the untreated control, received only the basal diet formulated with 20% Medicago sativa and 80% Avena sativa. Following plant material administration, the goats were monitored daily until day 40 and then slaughtered on day 41. Total faecal worm egg output, total production of larvae recovered from faecal cultures, total post-mortem worm burdens and the per capita fecundity of female worms were estimated. The toxicity of the plant species for the goats was measured by histopathological analyses of liver and kidney samples. Results showed that goats feeding on the plant material rich in plant secondary metabolites had significantly lower egg output compared to the control goats (P<0.05). A similar response was found for larval production in both H. contortus and T. colubriformis supporting that egg output was affected in both species. Although the total worm burdens were not affected by the plant material (P>0.05), the per capita fecundity was significantly reduced by E. corymbia, A. nilotica and A. salicina (P<0.05). No

Altered levels of memory T cell subsets and common γc cytokines in Strongyloides stercoralis infection and partial reversal following anthelmintic treatment.

PubMed

Rajamanickam, Anuradha; Munisankar, Saravanan; Bhootra, Yukti; Dolla, Chandra Kumar; Thiruvengadam, Kannan; Nutman, Thomas B; Babu, Subash

2018-05-01

CD4+ and CD8+ T cells are central players in immunity to helminth infections. However, the role of T cell subsets in human helminth infections is not well understood. In addition, the common γc cytokines, IL-2, IL-4, IL-7, IL-9 and IL-15 play an important role in the maintenance of these CD4+ and CD8+ T cell subsets. To examine the major T cell subsets and their association with the common γc cytokines, the absolute numbers of CD4+ and CD8+ naïve, central memory, effector memory and effector cells and the plasma levels of IL-2, IL-4, IL-7, IL-9 and IL-15 were measured in Strongyloides stercoralis (Ss) infected (INF, n = 60), helminth-uninfected (UN, n = 58) and in post treatment INF individuals. Ss infection is characterized by significantly increased absolute numbers of naïve and decreased absolute numbers of central and effector memory CD4+ T cells in comparison to UN individuals. No significant difference in the numbers of CD8+ T cell subsets was observed between the groups. The numbers of naïve cells and central memory CD4+ T cells were significantly reversed after anthelmintic treatment. Circulating levels of IL-2, IL-7 and IL-15 were significantly diminished, whereas the levels of IL-4 and IL-9 were significantly increased in INF compared to UN individuals. Following anthelminthic treatment, IL-2, IL-7 and IL-15 levels were significantly increased, while IL-4 and IL-9 levels were significantly decreased. Our data also showed a significant positive correlation between the levels of IL-7 and the numbers of central and effector memory CD4+ T cells. Ss infection is characterized by alterations in the absolute numbers of CD4+ T cell subsets and altered levels of common γc cytokines IL-2, IL-4, IL-7, IL-9 and IL-15; alterations which are partially reversed after anthelmintic treatment.

Benchmark study on glyphosate-resistant cropping systems in the United States. Part 3: Grower awareness, information sources, experiences and management practices regarding glyphosate-resistant weeds.

PubMed

Givens, Wade A; Shaw, David R; Newman, Michael E; Weller, Stephen C; Young, Bryan G; Wilson, Robert G; Owen, Micheal D K; Jordan, David L

2011-07-01

A survey was conducted with nearly 1200 growers in US states (Illinois, Indiana, Iowa, Mississippi, Nebraska and North Carolina) in 2005 with the objective in part of determining the awareness of the potential for development of glyphosate resistance, the experience with glyphosate-resistant (GR) weeds and the sources of information that growers had utilized for information on glyphosate resistance. Growers were asked a series of questions to determine the level of glyphosate resistance awareness and to list the sources of information used to learn about glyphosate resistance issues. The majority of the growers (88%) were aware of a weed's potential to evolve resistance to herbicide, while 44% were aware of state-specific documented cases of GR weeds, and 15% reported having had personal experience with GR weeds. Among sources of information concerning glyphosate resistance issues, farm publications, dealers/retailers and university/extension were the most frequent responses (41, 17 and 14% respectively). Based on a 1-10 effectiveness scale, growers ranked tillage the least effective practice (5.5) and using the correct label rates of herbicides at the proper timing for the size and type of weeds present the most effective practice (8.6) with respect to how effectively the practices mitigated the evolution of GR weeds. Results from this survey can be used by researchers, extension specialists and crop advisors further to bridge the information gap between growers and themselves and better to disseminate information concerning glyphosate resistance and glyphosate resistance management practices through more targeted information and information delivery methods. Copyright © 2011 Society of Chemical Industry.

Resilience and resistance of sagebrush ecosystems: Implications for state and transition models and management treatments

Treesearch

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

2014-01-01

In sagebrush ecosystems invasion of annual exotics and expansion of pinon (Pinus monophylla Torr. and Frem.) and juniper (Juniperus occidentalis Hook., J. osteosperma [Torr.] Little) are altering fire regimes and resulting in large-scale ecosystem transformations. Management treatments aim to increase resilience to disturbance and enhance resistance to invasive species...

Effects of artemisinin and Artemisia annua extracts on Haemonchus contortus in gerbils (Meriones unguiculatus)

USDA-ARS?s Scientific Manuscript database

Haemonchus contortus is a blood-sucking abomasal parasite of small ruminants that is responsible for major losses to producers worldwide. Resistance of this nematode to commercial anthelmintics has produced a demand for alternative control methods. Artemisia annua is the sole commercial source of ...

Effect of ram semen extenders and supplements on computer assisted sperm analysis parameters

USDA-ARS?s Scientific Manuscript database

Gastrointestinal nematode (GIN) infection of lambs is a major health issue that can cause anemia, reduced weight gains, poor performance, mortality and discouragement to farmers. Anthelmintic resistance limits the control of GIN by available dewormers, and most alternatives to dewormers have some dr...

Cross-disciplinary approaches for measuring parasitic helminth viability and phenotype.

PubMed

Peak, Emily; Hoffmann, Karl F

2011-06-01

Parasitic worms (helminths) within the Phyla Nematoda and Platyhelminthes are responsible for some of the most debilitating and chronic infectious diseases of human and animal populations across the globe. As no subunit vaccine for any parasitic helminth is close to being developed, the frontline strategy for intervention is administration of therapeutic, anthelmintic drugs. Worryingly, and unsurprising due to co-evolutionary mechanisms, many of these worms are developing resistance to the limited compound classes currently being used. This unfortunate reality has led to a renaissance in next generation anthelmintic discovery within both academic and industrial sectors. However, a major bottleneck in this process is the lack of quantitative methods for screening large numbers of small molecules for their effects on the whole organism. Development of methodologies that can objectively and rapidly distinguish helminth viability or phenotype would be an invaluable tool in the anthelmintic discovery pipeline. Towards this end, we describe how several basic techniques currently used to assess single cell eukaryote viability have been successfully applied to parasitic helminths. We additionally demonstrate how some of these methodologies have been adopted for high-throughput use and further modified for assessing worm phenotype. Continued development in this area is aimed at increasing the rate by which novel anthelmintics are identified and subsequently translated into everyday, practical applications.

Sorption of benzimidazole anthelmintics to dissolved organic matter surrogates and sewage sludge.

PubMed

Kim, Hyo-Jung; Lee, Dong Soo; Kwon, Jung-Hwan

2010-06-01

The sorption coefficients of four rarely studied zwitterionic pharmaceuticals (benzimidazoles: fenbendazole, albendazole, thiabendazole and flubendazole) and four metabolites of fenbendazole to various dissolved organic matter surrogates (humic acid, sodium dodecyl sulfate micelle, hydroxypropyl-beta-cyclodextrin and liposomes made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and sewage sludge) were measured to extend the available sorption coefficients and eventually to evaluate their environmental fate in soil and water environment. For the entire range of dissolved organic matters, the more hydrophobic fenbendazole and albendazole had higher sorption coefficients than thiabendazole and flubendazole, indicating that the traditional hypothesis of hydrophobic interaction holds for zwitterionic benzimidazole anthelmintics. However, the sorption coefficients of a given benzimidazole to selected dissolved organic matters (DOMs) varied within an order of magnitude. The measured K(oc) values decreased in the order of fenbendazole, albendazole, thiabendazole and flubendazole for sewage sludge and hydroxypropyl-beta-cyclodextrin whereas the orders were different for the other DOM surrogates, implying the hydrophilic nature of sewage sludge. This was also supported by the (N+O)/C elemental ratio of the sewage sludge sample used in this study. The correlations between log K(oc) and log K(ow) were weak (r(2)=0.28-0.64) and the magnitude of the sorption coefficients to the hydrophilic organic matters (hydroxypropyl-beta-cyclodextrin and sewage sludge) were similar to or slightly smaller than those for the hydrophobic organic matters (humic acids and liposome). This suggests that specific hydrophilic interactions also play a significant role in the sorption of moderately hydrophobic benzimidazoles to organic matters. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

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

Analysis of Heavy-Chain Antibody Responses and Resistance to Parelaphostrongylus tenuis in Experimentally Infected Alpacas

PubMed Central

Purdy, S. R.; Gagliardo, L. F.; Lefman, S.; Hamel, P. J. S.; Ku, S.; Mainini, T.; Hoyt, G.; Justus, K.; Daley-Bauer, L. P.; Duffy, M. S.

2012-01-01

The parasitic nematode Parelaphostrongylus tenuis is an important cause of neurologic disease of camelids in central and eastern North America. The aim of this study was to determine whether alpacas develop resistance to disease caused by P. tenuis in response to a previous infection or a combination of controlled infection and immunization. Alpacas were immunized with a homogenate of third-stage larvae (L3) and simultaneously implanted subcutaneously with diffusion chambers containing 20 live L3. Sham-treated animals received adjuvant alone and empty chambers. The protocol was not effective in inducing resistance to oral challenge with 10 L3, and disease developed between 60 and 71 days following infection. Immediately following the onset of neurologic disease, affected animals were treated with a regimen of anthelmintic and anti-inflammatory drugs, and all recovered. One year later, a subset of alpacas from this experiment was challenged with 20 L3 and the results showed that prior infection induced resistance to disease. Primary and secondary infections induced production of conventional and heavy-chain IgGs that reacted with soluble antigens in L3 homogenates but did not consistently recognize a recombinant form of a parasite-derived aspartyl protease inhibitor. Thus, the latter antigen may not be a good candidate for serology-based diagnostic tests. Antibody responses to parasite antigens occurred in the absence of overt disease, demonstrating that P. tenuis infection can be subclinical in a host that has been considered to be highly susceptible to disease. The potential for immunoprophylaxis to be effective in preventing disease caused by P. tenuis was supported by evidence of resistance to reinfection. PMID:22593238

Insulin resistance syndrome in children : pathophysiology and potential management strategies.

PubMed

Decsi, Tamás; Molnár, Dénes

2003-01-01

The simultaneous presence of various cardiovascular risk factors in the same individual is not rare, even in the pediatric age group. The clustering of risk factors can be termed insulin resistance syndrome (IRS) because of the putative central role of tissue insulin insensitivity in the background of the inter-related metabolic disturbances. Fasting hyperinsulinemia, impaired glucose tolerance, dyslipidemia, and hypertension are considered to represent the basic abnormalities of IRS. The most prevalent related disturbances are increased plasma levels of plasminogen activator inhibitor-1, fibrinogen, uric acid, homocysteine, and C-reactive protein, as well as visceral adiposity, microalbuminuria, disturbed essential fatty acid metabolism, low availability of lipid-soluble antioxidant vitamins, and enhanced expression of tumor necrosis factor-alpha in adipose tissues. Certain genetic abnormalities have been associated with IRS, but explain only a small part of the variability in insulin resistance. The exact prevalence of IRS in children remains to be defined; it was found to be 9% in one survey among children with obesity seeking medical attention. Modification of lifestyle, i.e. reduction of energy intake and enhancement of physical activity, are unquestionable prerequisites for long-term success in the management of IRS. In at least two randomized controlled studies, metformin proved to be clinically effective in increasing insulin sensitivity in hyperinsulinemic, nondiabetic adolescents. Thiazolidinediones have been successfully tested for the treatment of insulin resistance in adults, but not in children as yet. Prevention of the development of IRS in children is obviously of great significance for the health status of the community. However, the efficacy of various preventive approaches should be investigated further in carefully designed controlled trials.

Effectiveness of the High Dose/Refuge Strategy for Managing Pest Resistance to Bacillus thuringiensis (Bt) Plants Expressing One or Two Toxins

PubMed Central

Gryspeirt, Aiko; Grégoire, Jean-Claude

2012-01-01

To delay resistance development to Bacillus thuringiensis (Bt) plants expressing their own insecticide, the application of the Insect Resistance Management strategy called “High Dose/Refuge Strategy” (HD/R) is recommended by the US Environmental Protection Agency (US EPA). This strategy was developed for Bt plants expressing one toxin. Presently, however, new Bt plants that simultaneously express two toxins are on the market. We used a mathematical model to evaluate the efficiency of the HD/R strategy for both these Bt toxins. As the current two-toxin Bt plants do not express two new Cry toxins but reuse one toxin already in use with a one-toxin plant, we estimated the spread of resistance when the resistance alleles are not rare. This study assesses: (i) whether the two toxins have to be present in high concentration, and (ii) the impact of the relative size of the refuge zone on the evolution of resistance and population density. We concluded that for Bt plants expressing one toxin, a high concentration is an essential condition for resistance management. For the pyramided Bt plants, one toxin could be expressed at a low titer if the two toxins are used for the first time, and a small refuge zone is acceptable. PMID:23162699

Effectiveness of the high dose/refuge strategy for managing pest resistance to Bacillus thuringiensis (Bt) plants expressing one or two toxins.

PubMed

Gryspeirt, Aiko; Grégoire, Jean-Claude

2012-10-01

To delay resistance development to Bacillus thuringiensis (Bt) plants expressing their own insecticide, the application of the Insect Resistance Management strategy called "High Dose/Refuge Strategy" (HD/R) is recommended by the US Environmental Protection Agency (US EPA). This strategy was developed for Bt plants expressing one toxin. Presently, however, new Bt plants that simultaneously express two toxins are on the market. We used a mathematical model to evaluate the efficiency of the HD/R strategy for both these Bt toxins. As the current two-toxin Bt plants do not express two new Cry toxins but reuse one toxin already in use with a one-toxin plant, we estimated the spread of resistance when the resistance alleles are not rare. This study assesses: (i) whether the two toxins have to be present in high concentration, and (ii) the impact of the relative size of the refuge zone on the evolution of resistance and population density. We concluded that for Bt plants expressing one toxin, a high concentration is an essential condition for resistance management. For the pyramided Bt plants, one toxin could be expressed at a low titer if the two toxins are used for the first time, and a small refuge zone is acceptable.

Efficacy of sericea lespedeza hay as a natural dewormer in goats: Dose titration study

USDA-ARS?s Scientific Manuscript database

Gastrointestinal nematode (GIN) parasitism is the greatest threat to economic sheep and goat production in the southern USA, and there is widespread prevalence of GIN resistance to broad-spectrum anthelmintics in this region. A natural alternative for controlling GIN in small ruminants is feeding h...

Using copper oxide wire particles or sericea lespedeza to prevent a peri-parturient rise of gastrointestinal nematodes in sheep and goats

USDA-ARS?s Scientific Manuscript database

Gastrointestinal nematodes (GIN) continue to plague the small ruminant industry, especially parts of the world with warm, humid climates. Alternatives to chemicals are needed for GIN control because of anthelmintic resistance of GIN and a desire to reduce chemical residues in meat products. A stud...

Efficacy of compound X (Bedoukian Research) on reducing fecal egg count in lambs

USDA-ARS?s Scientific Manuscript database

Gastrointestinal nematode (GIN) parasites are a major constraint to profitable sheep production. Due to long-term use of anthelmintics, GIN populations have developed resistance to those available. The objective of this study was to determine the efficacy of a proprietary compound developed by Bedou...

Palatability of tannin-rich sericea lespedeza fed to broilers.

USDA-ARS?s Scientific Manuscript database

As parasites become resistant to available anthelmintics, new methods of control are needed. New drugs take a long time to develop in addition to being expensive; therefore, there is increasing interest in finding and using natural alternatives. Additionally, natural remedies are needed for the or...

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. Published by Elsevier Ltd.

Putting resilience and resistance concepts into practice

Treesearch

Jeanne C. Chambers; Jeremy D. Maestas; Mike Pellant

2015-01-01

Land managers are increasingly interested in improving resilience to disturbances, such as wildfire, and resistance to invasive species, such as cheatgrass and medusahead. This factsheet is designed to assist land managers in using resilience and resistance concepts to assess risks, prioritize management activities, and select appropriate treatments.

acr-23 Encodes a Monepantel-Sensitive Channel in Caenorhabditis elegans

PubMed Central

Rufener, Lucien; Bedoni, Nicola; Baur, Roland; Rey, Samantha; Glauser, Dominique A.; Bouvier, Jacques; Beech, Robin; Sigel, Erwin; Puoti, Alessandro

2013-01-01

Monepantel is a member of the recently identified class of anthelmintics known as the amino-acetonitrile derivatives (AADs). Monepantel controls all major gastro-intestinal nematodes in sheep including those that are resistant to the classical anthelmintics. Previous studies have shown that the Caenorhabditis elegans acr-23 and the Haemonchus contortus Hco-mptl-1 genes may be prominent targets of monepantel. With this discovery it became possible to investigate the mode of action of monepantel in nematodes at the molecular level. In the present study, we show that a C. elegans mutant acr-23 strain is fully rescued by expressing the wild-type acr-23 gene. Moreover, we present a new mutant allele, and characterize acr-23 alleles genetically. We also show that acr-23 is expressed in body wall muscle cells, and provide therefore a possible explanation for the paralysis caused by monepantel. Furthermore, genetic evidence suggests that the chaperone RIC-3 is required for expression of full monepantel resistance. Finally, we present reconstitution of the C. elegans ACR-23 receptor in Xenopus laevis oocytes and provide direct evidence of its modulation by monepantel. Conversely, co-injection of the chaperone RIC-3 had no impact for channel reconstitution in X. laevis oocytes. These results reinforce the involvement of the ACR-23 family in the mode of action of monepantel and advance our understanding of this new class of anthelmintics. PMID:23950710

Albendazole in environment: faecal concentrations in lambs and impact on lower development stages of helminths and seed germination.

PubMed

Prchal, Lukáš; Podlipná, Radka; Lamka, Jiří; Dědková, Tereza; Skálová, Lenka; Vokřál, Ivan; Lecová, Lenka; Vaněk, Tomáš; Szotáková, Barbora

2016-07-01

Albendazole (ABZ), widely used benzimidazole anthelmintic, administered to animals enters via excrements into environment and may impact non-target organisms. Moreover, exposure of lower development stages of helminths to anthelmintics may also encourage the development of drug-resistant strains of helminths. In present project, the kinetics of ABZ (10 mg kg(-1) p.o.) and its metabolite (ABZ.SO, ABZSO2) elimination in faeces from treated Texel lambs were studied using UHPLC/MS/MS with the aim to find out their concentrations achievable in the environment. Consequently, the effect of these compounds on lower development stages of Barber's pole worm (Haemonchus contortus) and on germination of white mustard (Sinapis alba) seeds was evaluated. The results showed that ABZ concentrations in faeces excreted in 4-60 h after treatment were above the concentrations lethal for H. contortus eggs. Moreover, pre-incubation with sub-lethal doses of ABZ and ABZ.SO did not increase the resistance of H. contortus eggs and larvae to anthelmintics. On the other hand, concentrations of ABZ and ABZ.SO in faeces are so high that might have negative influence on non-target soil invertebrates. As neither ABZ nor its metabolites affect the germination of mustard seeds, phytoremediation could be considered as potential tool for detoxification of ABZ in the environment.

Herbicide resistance and biodiversity: agronomic and environmental aspects of genetically modified herbicide-resistant plants.

PubMed

Schütte, Gesine; Eckerstorfer, Michael; Rastelli, Valentina; Reichenbecher, Wolfram; Restrepo-Vassalli, Sara; Ruohonen-Lehto, Marja; Saucy, Anne-Gabrielle Wuest; Mertens, Martha

2017-01-01

Farmland biodiversity is an important characteristic when assessing sustainability of agricultural practices and is of major international concern. Scientific data indicate that agricultural intensification and pesticide use are among the main drivers of biodiversity loss. The analysed data and experiences do not support statements that herbicide-resistant crops provide consistently better yields than conventional crops or reduce herbicide amounts. They rather show that the adoption of herbicide-resistant crops impacts agronomy, agricultural practice, and weed management and contributes to biodiversity loss in several ways: (i) many studies show that glyphosate-based herbicides, which were commonly regarded as less harmful, are toxic to a range of aquatic organisms and adversely affect the soil and intestinal microflora and plant disease resistance; the increased use of 2,4-D or dicamba, linked to new herbicide-resistant crops, causes special concerns. (ii) The adoption of herbicide-resistant crops has reduced crop rotation and favoured weed management that is solely based on the use of herbicides. (iii) Continuous herbicide resistance cropping and the intensive use of glyphosate over the last 20 years have led to the appearance of at least 34 glyphosate-resistant weed species worldwide. Although recommended for many years, farmers did not counter resistance development in weeds by integrated weed management, but continued to rely on herbicides as sole measure. Despite occurrence of widespread resistance in weeds to other herbicides, industry rather develops transgenic crops with additional herbicide resistance genes. (iv) Agricultural management based on broad-spectrum herbicides as in herbicide-resistant crops further decreases diversity and abundance of wild plants and impacts arthropod fauna and other farmland animals. Taken together, adverse impacts of herbicide-resistant crops on biodiversity, when widely adopted, should be expected and are indeed very hard

Kinetics and degradation pathways of photolytic and photocatalytic oxidation of the anthelmintic drug praziquantel.

PubMed

Čizmić, Mirta; Ljubas, Davor; Ćurković, Lidija; Škorić, Irena; Babić, Sandra

2017-02-05

In this study, an anthelmintic drug, praziquantel(PZQ), was degraded using the direct photolysis, photocatalysis, and oxidation processes including UV radiation, TiO 2 film, and hydrogen peroxide. The photolytic degradation with predominant wavelengths of 185/254nm (UV-C) proved to be more efficient with a half-life of 3.13min compared to the radiation of 365nm (UV-A) where the degradation did not occur. In order to enhance the rate of PZQ photolytic degradation, H 2 O 2 was added, which resulted in two to three times higher degradation rates. In the photocatalytic degradation, TiO 2 film was used as catalyst. The degradation was ten times faster in the photocatalytic experiments where UV-C light (k=0.2390min -1 ) was used than in those with UV-A (k=0.0201min -1 ). Comparing the results from all performed experiments it can be concluded that the UV-C/TiO 2 /H 2 O 2 process yielded the highest degradation rate and complete degradation of PZQ was obtained in less than 7min. The degradation of PZQ followed the first order kinetics in all the experiments. The photo degradation was inhibited in the presence of methanol. The degradation pathways and the structural formulae of five degradation products (m/z 273, 269, 189, 147, 132) were proposed based on the liquid chromatography tandem mass spectrometry analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Anthelmintic activity of trans-cinnamaldehyde and A- and B-type proanthocyanidins derived from cinnamon (Cinnamomum verum)

PubMed Central

Williams, Andrew R.; Ramsay, Aina; Hansen, Tina V. A.; Ropiak, Honorata M.; Mejer, Helena; Nejsum, Peter; Mueller-Harvey, Irene; Thamsborg, Stig M.

2015-01-01

Cinnamon (Cinnamomum verum) has been shown to have anti-inflammatory and antimicrobial properties, but effects on parasitic worms of the intestine have not been investigated. Here, extracts of cinnamon bark were shown to have potent in vitro anthelmintic properties against the swine nematode Ascaris suum. Analysis of the extract revealed high concentrations of proanthocyanidins (PAC) and trans-cinnamaldehyde (CA). The PAC were subjected to thiolysis and HPLC-MS analysis which demonstrated that they were exclusively procyanidins, had a mean degree of polymerization of 5.2 and 21% of their inter-flavan-3-ol links were A-type linkages. Purification of the PAC revealed that whilst they had activity against A. suum, most of the potency of the extract derived from CA. Trichuris suis and Oesophagostomum dentatum larvae were similarly susceptible to CA. To test whether CA could reduce A. suum infection in pigs in vivo, CA was administered daily in the diet or as a targeted, encapsulated dose. However, infection was not significantly reduced. It is proposed that the rapid absorption or metabolism of CA in vivo may prevent it from being present in sufficient concentrations in situ to exert efficacy. Therefore, further work should focus on whether formulation of CA can enhance its activity against internal parasites. PMID:26420588

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…

Myths, models and mitigation of resistance to pesticides.

PubMed Central

Hoy, M A

1998-01-01

Resistance to pesticides in arthropod pests is a significant economic, ecological and public health problem. Although extensive research has been conducted on diverse aspects of pesticide resistance and we have learned a great deal during the past 50 years, to some degree the discussion about 'resistance management' has been based on 'myths'. One myth involves the belief that we can manage resistance. I will maintain that we can only attempt to mitigate resistance because resistance is a natural evolutionary response to environmental stresses. As such, resistance will remain an ongoing dilemma in pest management and we can only delay the onset of resistance to pesticides. 'Resistance management' models and tactics have been much discussed but have been tested and deployed in practical pest management programmes with only limited success. Yet the myth persists that better models will provide a 'solution' to the problem. The reality is that success in using mitigation models is limited because these models are applied to inappropriate situations in which the critical genetic, ecological, biological or logistic assumptions cannot be met. It is difficult to predict in advance which model is appropriate to a particular situation; if the model assumptions cannot be met, applying the model sometimes can increase the rate of resistance development rather than slow it down. Are there any solutions? I believe we already have one. Unfortunately, it is not a simple or easy one to deploy. It involves employing effective agronomic practices to develop and maintain a healthy crop, monitoring pest densities, evaluating economic injury levels so that pesticides are applied only when necessary, deploying and conserving biological control agents, using host-plant resistance, cultural controls of the pest, biorational pest controls, and genetic control methods. As a part of a truly multi-tactic strategy, it is crucial to evaluate the effect of pesticides on natural enemies in order to

Anthelmintic effects of the essential oil of fennel (Foeniculum vulgare Mill., Apiaceae) against Schistosoma mansoni.

PubMed

Wakabayashi, Kamila A L; de Melo, Nathalya I; Aguiar, Daniela P; de Oliveira, Pollyanna F; Groppo, Milton; da Silva Filho, Ademar A; Rodrigues, Vanderlei; Cunha, Wilson R; Tavares, Denise C; Magalhães, Lizandra G; Crotti, Antônio E M

2015-07-01

Foeniculum vulgare Mill. (Apiaceae), known as fennel, is a widespread aromatic herbaceous plant, and its essential oil is used as additive in the food, pharmaceutical, cosmetic, and perfume industries. The in vitro antischistosomal activity and cytotoxic effects against V79 cells of the essential oil of F. vulgare cultivated in southeastern Brazil (FV-EO) was investigated. The FV-EO was obtained by hydrodistillation and characterized by GC-FID and GC/MS analyses. (E)-Anethole (69.8%) and limonene (22.5%) were identified as the major constituents. Its anthelmintic activity against Schistosoma mansoni was evaluated at concentrations of 10, 50, and 100 μg/ml, and it was found to be active against adult S. mansoni worms, although it was less effective than the positive control praziquantel (PZQ) in terms of separation of the coupled pairs, mortality, and decreased motor activity. However, FV-EO elicited an interesting dose-dependent reduction in the number of S. mansoni eggs. On their own, (E)-anethole and the limonene enantiomers were much less effective than FV-EO and PZQ. An XTT-cytotoxicity-based assay evidenced no FV-EO cytotoxicity against V79 cells. In summary, FV-EO displayed moderate in vitro schistosomicidal activity against adult S. mansoni worms, exerted remarkable inhibitory effects on the egg development, and was of low toxicity. Copyright © 2015 Verlag Helvetica Chimica Acta AG, Zürich.

How well will stacked transgenic pest/herbicide resistances delay pests from evolving resistance?

PubMed

Gressel, Jonathan; Gassmann, Aaron J; Owen, Micheal Dk

2017-01-01

Resistance has evolved to single transgenic traits engineered into crops for arthropod and herbicide resistances, and can be expected to evolve to the more recently introduced pathogen resistances. Combining transgenes against the same target pest is being promoted as the solution to the problem. This solution will work if used pre-emptively, but where resistance has evolved to one member of a stack, resistance should easily evolve for the second gene in most cases. We propose and elaborate criteria that could be used to evaluate the value of stacked traits for pest resistance management. Stacked partners must: target the same pest species; be in a tandem construct to preclude segregation; be synchronously expressed in the same tissues; have similar tissue persistence; target pest species that are still susceptible to at least two stacked partners. Additionally, transgene products must not be degraded in the same manner, and there should be a lack of cross-resistance to stacked transgenes or to their products. With stacked herbicide resistance transgenes, both herbicides must be used and have the same persistence. If these criteria are followed, and integrated with other pest management practices, resistance may be considerably delayed. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Physico-Chemical-Managed Killing of Penicillin-Resistant Static and Growing Gram-Positive and Gram-Negative Vegetative Bacteria

NASA Technical Reports Server (NTRS)

Schramm, Jr., Harry F. (Inventor); Farris, III, Alex F. (Inventor); Defalco, Francis G. (Inventor); Richmond, Robert Chaffee (Inventor)

2012-01-01

Systems and methods for the use of compounds from the Hofmeister series coupled with specific pH and temperature to provide rapid physico-chemical-managed killing of penicillin-resistant static and growing Gram-positive and Gram-negative vegetative bacteria. The systems and methods represent the more general physico-chemical enhancement of susceptibility for a wide range of pathological macromolecular targets to clinical management by establishing the reactivity of those targets to topically applied drugs or anti-toxins.

Management of Field-Evolved Resistance to Bt Maize in Argentina: A Multi-Institutional Approach.

PubMed

Signorini, Ana M; Abratti, Gustavo; Grimi, Damián; Machado, Marcos; Bunge, Florencia F; Parody, Betiana; Ramos, Laura; Cortese, Pablo; Vesprini, Facundo; Whelan, Agustina; Araujo, Mónica P; Podworny, Mariano; Cadile, Alejandro; Malacarne, María F

2018-01-01

Evolution of resistance to control measures in insect populations is a natural process, and management practices are intended to delay or mitigate resistance when it occurs. During the 2012/13 season the first reports of unexpected damage by Diatraea saccharalis on some Bt maize hybrids occurred in the northeast of San Luis province, Argentina. The affected Bt technologies were Herculex I® (HX-TC1507) and VT3PRO® (MON 89034 × MON 88017 * ). Event TC1507 expresses Cry1F and event MON 89034 expresses Cry1A.105 and Cry2Ab2, whichr are all Bt proteins with activity against the lepidopterans D. saccharalis and Spodoptera frugiperda (MON 88017 expresses the protein Cry3Bb1 for control of coleopteran insects and the enzyme CP4EPSPS for glyphosate tolerance). The affected area is an isolated region surrounded by sierra systems to the northeast and west, with a hot semi-arid climate, long frost-free period, warm winters, hot dry summers, and woody shrubs as native flora. To manage and mitigate the development of resistance, joint actions were taken by the industry, growers and Governmental Agencies. Hybrids expressing Vip3A protein (event MIR162) and/or Cry1Ab protein (events MON 810 and Bt11) as single or stacked events are used in early plantings to control the first generations of D. saccharalis , and in later plantings date's technologies with good control of S. frugiperda . A commitment was made to plant the refuge, and pest damage is monitored. As a result, maize production in the area is sustainable and profitable with yields above the average.

Management of Field-Evolved Resistance to Bt Maize in Argentina: A Multi-Institutional Approach

PubMed Central

Signorini, Ana M.; Abratti, Gustavo; Grimi, Damián; Machado, Marcos; Bunge, Florencia F.; Parody, Betiana; Ramos, Laura; Cortese, Pablo; Vesprini, Facundo; Whelan, Agustina; Araujo, Mónica P.; Podworny, Mariano; Cadile, Alejandro; Malacarne, María F.

2018-01-01

Evolution of resistance to control measures in insect populations is a natural process, and management practices are intended to delay or mitigate resistance when it occurs. During the 2012/13 season the first reports of unexpected damage by Diatraea saccharalis on some Bt maize hybrids occurred in the northeast of San Luis province, Argentina. The affected Bt technologies were Herculex I® (HX-TC1507) and VT3PRO® (MON 89034 × MON 88017*). Event TC1507 expresses Cry1F and event MON 89034 expresses Cry1A.105 and Cry2Ab2, whichr are all Bt proteins with activity against the lepidopterans D. saccharalis and Spodoptera frugiperda (MON 88017 expresses the protein Cry3Bb1 for control of coleopteran insects and the enzyme CP4EPSPS for glyphosate tolerance). The affected area is an isolated region surrounded by sierra systems to the northeast and west, with a hot semi-arid climate, long frost-free period, warm winters, hot dry summers, and woody shrubs as native flora. To manage and mitigate the development of resistance, joint actions were taken by the industry, growers and Governmental Agencies. Hybrids expressing Vip3A protein (event MIR162) and/or Cry1Ab protein (events MON 810 and Bt11) as single or stacked events are used in early plantings to control the first generations of D. saccharalis, and in later plantings date's technologies with good control of S. frugiperda. A commitment was made to plant the refuge, and pest damage is monitored. As a result, maize production in the area is sustainable and profitable with yields above the average. PMID:29888224

Antibiotic Resistance in Plant-Pathogenic Bacteria.

PubMed

Sundin, George W; Wang, Nian

2018-06-01

Antibiotics have been used for the management of relatively few bacterial plant diseases and are largely restricted to high-value fruit crops because of the expense involved. Antibiotic resistance in plant-pathogenic bacteria has become a problem in pathosystems where these antibiotics have been used for many years. Where the genetic basis for resistance has been examined, antibiotic resistance in plant pathogens has most often evolved through the acquisition of a resistance determinant via horizontal gene transfer. For example, the strAB streptomycin-resistance genes occur in Erwinia amylovora, Pseudomonas syringae, and Xanthomonas campestris, and these genes have presumably been acquired from nonpathogenic epiphytic bacteria colocated on plant hosts under antibiotic selection. We currently lack knowledge of the effect of the microbiome of commensal organisms on the potential of plant pathogens to evolve antibiotic resistance. Such knowledge is critical to the development of robust resistance management strategies to ensure the safe and effective continued use of antibiotics in the management of critically important diseases. Expected final online publication date for the Annual Review of Phytopathology Volume 56 is August 25, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The effectiveness of copper oxide wire particles as an anthelmintic in pregnant ewes and safety to offspring.

PubMed

Burke, J M; Miller, J E; Brauer, D K

2005-08-10

The objective of the experiment was to determine the effectiveness of copper oxide wire particles (COWP) in pregnant ewes and safety to lambs. COWP have been used recently as an anthelmintic in small ruminants to overcome problems associated with nematode resistance to chemical dewormers. Doses of COWP (

Evaluation and management of the patient with difficult-to-control or resistant hypertension.

PubMed

Viera, Anthony J; Hinderliter, Alan L

2009-05-15

High blood pressure is often difficult to control. Resistant hypertension is blood pressure above goal despite adherence to a combination of at least three antihypertensive medications of different classes, optimally dosed and usually including a diuretic. The approach to blood pressure that is apparently difficult to control begins with an assessment of the patient's adherence to the management plan, including lifestyle modifications and medications. White-coat hypertension may need to be ruled out. Suboptimal therapy is the most common reason for failure to reach the blood pressure goal. Once-daily fixed-dose combination pills may improve control through the synergism of antihypertensive agents from different classes and improved adherence. Truly drug-resistant hypertension is commonly caused by chronic kidney disease, obstructive sleep apnea, or hyperaldosteronism, all of which can lead to fluid retention. Higher doses of diuretics (or a change to a loop diuretic) are usually needed. Other strategies include adding an alpha blocker, alpha-beta blocker, clonidine, or an aldosterone antagonist (e.g., spironolactone). Particularly in patients with diabetes or renal disease, combining a long-acting nondihydropyridine with a dihydropyridine calcium channel . blocker can also be considered. Obesity, heavy alcohol intake, high levels of dietary sodium, and interfering substances (especially nonsteroidal anti-inflammatory drugs) contribute to hypertension that is resistant or difficult to control.

Association between FAMACHA© Scores and Fecal Egg Counts in Katahdin Lambs

USDA-ARS?s Scientific Manuscript database

The FAMACHA system was introduced to the U.S. just over 10 yr ago in order to allow selective deworming of lambs with anemia associated with Haemonchus contortus and retard the development of anthelmintic resistance. The FAMACHA system was initially developed as a predictor of packed cell volume (PC...

Helminth infections and type 2 diabetes: a cluster-randomized placebo controlled SUGARSPIN trial in Nangapanda, Flores, Indonesia.

PubMed

Tahapary, Dicky L; de Ruiter, Karin; Martin, Ivonne; van Lieshout, Lisette; Guigas, Bruno; Soewondo, Pradana; Djuardi, Yenny; Wiria, Aprilianto E; Mayboroda, Oleg A; Houwing-Duistermaat, Jeanine J; Tasman, Hengki; Sartono, Erliyani; Yazdanbakhsh, Maria; Smit, Johannes W A; Supali, Taniawati

2015-03-18

Insulin resistance is a strong predictor of the development of type 2 diabetes mellitus. Chronic helminth infections might protect against insulin resistance via a caloric restriction state and indirectly via T-helper-2 polarization of the immune system. Therefore the elimination of helminths might remove this beneficial effect on insulin resistance. To determine whether soil-transmitted helminth infections are associated with a better whole-body insulin sensitivity and whether this protection is reversible by anthelmintic treatment, a household-based cluster-randomized, double blind, placebo-controlled trial was conducted in the area of Nangapanda on Flores Island, Indonesia, an area endemic for soil-transmitted helminth infections. The trial incorporates three monthly treatment with albendazole or matching placebo for one year, whereby each treatment round consists of three consecutive days of supervised drug intake. The presence of soil-transmitted helminths will be evaluated in faeces using microscopy and/or PCR. The primary outcome of the study will be changes in insulin resistance as assessed by HOMA-IR, while the secondary outcomes will be changes in body mass index, waist circumference, fasting blood glucose, 2 h-glucose levels after oral glucose tolerance test, HbA1c, serum lipid levels, immunological parameters, and efficacy of anthelmintic treatment. The study will provide data on the effect of helminth infections on insulin resistance. It will assess the relationship between helminth infection status and immune responses as well as metabolic parameters, allowing the establishment of a link between inflammation and whole-body metabolic homeostasis. In addition, it will give information on anthelmintic treatment efficacy and effectiveness. This study has been approved by the ethical committee of Faculty of Medicine Universitas Indonesia (ref: 549/H2.F1/ETIK/2013), and has been filed by the ethics committee of Leiden University Medical Center, clinical

Targeted flock/herd and individual ruminant treatment approaches.

PubMed

Kenyon, F; Jackson, F

2012-05-04

In Europe, most nematodoses are subclinical involving morbid rather than mortal effects and control is largely achieved using anthelmintics. In cattle, the genera most associated with sub-optimal performance are Ostertagia and Cooperia whereas in sheep and goats, subclinical losses are most often caused by Teladorsagia and Trichostrongylus. In some regions, at certain times, other species such as Nematodirus and Haemonchus also cause disease in sheep and goats. Unfortunately, anthelmintic resistance has now become an issue for European small ruminant producers. One of the key aims of the EU-funded PARASOL project was to identify low input and sustainable approaches to control nematode parasites in ruminants using refugia-based strategies. Two approaches to optimise anthelmintic treatments in sheep and cattle were studied; targeted treatments (TT) - whole-group treatments optimised on the basis of a marker of infection e.g. faecal egg count (FEC), and targeted selected treatment (TST) - treatments given to identified individuals to provide epidemiological and/or production benefits. A number of indicators for TT and TST were assessed to define parasitological and production-system specific indicators for treatment that best suited the regions where the PARASOL studies were conducted. These included liveweight gain, production efficiency, FEC, body condition score and diarrhoea score in small ruminants, and pepsinogen levels and Ostertagia bulk milk tank ELISA in cattle. The PARASOL studies confirmed the value of monitoring FEC as a means of targeting whole-flock treatments in small ruminants. In cattle, bulk milk tank ELISA and serum pepsinogen assays could be used retrospectively to determine the levels of exposure and hence, in the next season to optimise anthelmintic usage. TST approaches in sheep and goats examined production efficiency and liveweight gain as indicators for treatment and confirmed the value of this approach in maintaining performance and

Ovicidal and larvicidal activity of crude extracts of Maesa lanceolata and Plectranthus punctatus against Haemonchus contortus.

PubMed

Tadesse, Dereje; Eguale, Tadesse; Giday, Mirutse; Mussa, Abiy

2009-03-18

The widespread development of anthelmintic resistance and high cost of the conventional anthelmintic drugs, has limited the control of gastrointestinal nematode parasites of sheep and goats and hence led to evaluation of medicinal plants as an alternative source of anthelmintics. In the current study, in vitro ovicidal and larvicidal activity of the leaves and fruits of the aqueous and hydro-alcoholic extracts of Maesa lanceolata and aerial parts of Plectranthus punctatus were evaluated on the egg and larvae of Haemonchus contortus using egg hatch assay and larval development test. All extracts of plants tested have shown complete inhibition of egg hatching at or below 1 mg/ml. ED50 for egg hatch inhibition ranged from 0.11 to 0.29 mg/ml, for both the aqueous and hydro-alcoholic extracts of Plectranthus punctatus and Maesa lanceolata. All extracts have shown dose dependent inhibition of larval development with variable results. The complete inhibition (100%) at the maximum concentration tested (50 mg/ml) was obtained only for hydro-alcoholic extract of the fruits of Maesa lanceolata and the lowest inhibition (50.33%) was recorded for the hydro-alcoholic extract of the leaves of the same plant. The overall findings of the present study has shown that Plectranthus punctatus and Maesa lanceolata contain possible anthelmintic compounds and further evaluation of different extracts and fractions of these plants should be carried out.

High residue cover crops alone or with strategic tillage to manage glyphosate-resistant palmer amaranth (amaranthus palmeri) in Southeastern cotton (gossypium hirsutum)

USDA-ARS?s Scientific Manuscript database

Glyphosate-resistant (GR) Palmer amaranth (Amaranthus palmeri S. Wats) is redefining row crop weed management in the Southeast due to its widespread distribution, high competitive ability, copious seed production, and resilience to standard weed management programs. Herbicides alone are failing to p...

Managing effects in CD control from PED and PEB in advanced DUV photomask manufacturing using FEP-171 resist

NASA Astrophysics Data System (ADS)

Paulsson, Adisa; Xing, Kezhao; Fosshaug, Hans; Lundvall, Axel; Bjoernberg, Charles; Karlsson, Johan

2005-05-01

A continuing improvement in resist process is a necessity for high-end photomask fabrication. In advanced chemically amplified resist systems the lithographic performance is strongly influenced by diffusion of acid and acid quencher (i.e. bases). Beside the resist properties, e.g. size and volatility of the photoacid, the process conditions play important roles for the diffusion control. Understanding and managing these properties influences lithographic characteristics on the photomask such as CD uniformity, CD and pitch linearity, resolution, substrate contamination, clear-dark bias and iso-dense bias. In this paper we have investigated effects on the lithographic characteristics with respect to post exposure bake conditions, when using the chemically amplified resist FEP-171. We used commercially available mask blanks from the Hoya Mask Blank Division with NTAR7 chrome and an optimized resist thickness for the 248 nm laser tool at 3200Å. The photomasks were exposed on the optical DUV (248nm) Sigma7300 pattern generator. Additionally, we investigated the image stability between exposure and post exposure bake. Unlike in wafer fabrication, photomask writing requires several hours, making the resist susceptible to image blur and acid latent image degradation.