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Anthelmintic activity of Artemisia brevifolia in sheep.

This paper describes the in vitro and in vivo anthelmintic activity of Artemisia brevifolia in comparison with levamisole. In vitro studies revealed anthelmintic effects of crude aqueous (CAE) and methanol extracts (CME) of Artemisia brevifolia (whole plant) on live Haemonchus contortus as evident from their paralysis and/or mortality at 6 h post exposure. For in vivo studies, the whole plant of Artemisia brevifolia was administered as crude powder (CP), CAE and CME at graded doses (1, 2 and 3 g kg(-1) body weight (b.w.) to sheep naturally infected with mixed species of gastrointestinal nematodes. Maximum reduction (67.2%) in eggs per gram (EPG) of faeces was recorded on day 14 post treatment in sheep treated with Artemisia brevifolia CAE at 3 g kg(-1) b.w. It was found that, although, Artemisia brevifolia whole plant possesses anthelmintic activity against nematodes, it is not comparable with levamisole (99.2% reduction in EPG) at any of the doses tried in this study. However, increase in EPG reduction was noted with an increase in the dose of Artemisia brevifolia administered as CP, CAE and CME. The graded dose response suggested further studies on a larger number of animals on higher doses than those used in the current study.

Administration, Oral↗

Anthelmintic activity of Calotropis procera (Ait.) Ait. F. flowers in sheep.

The anthelmintic activity of Calotropis (C.) procera flowers in comparison with levamisole was evaluated through in vitro and in vivo studies. In vitro studies revealed anthelmintic effects (P<0.05) of crude aqueous (CAE) and crude methanolic extracts (CME) of Calotropis procera flowers on live Haemonchus (H.) contortus as evident from their mortality or temporary paralysis. For in vivo studies, Calotropis procera flowers were administered as crude powder (CP), CAE and CME to sheep naturally infected with mixed species of gastrointestinal nematodes. Egg count percent reduction (ECR) was recorded as 88.4 and 77.8% in sheep treated with CAE and CP at 3gkg(-1) body weight on day 7 and 10 post-treatment (PT), respectively. CME was least effective resulting in 20.9% reduction in ECR on day 7 PT. It was found that Calotropis procera flowers possess good anthelmintic activity against nematodes, yet it was lower than that exhibited by levamisole (97.8-100%). It is suggested that further research on large scale be carried out involving a large number of animals, doses higher than those used in the current study, identification of active principles, and standardization of dose and toxicity studies for drug development.

Animals↗

Evaluation of some plants used in Turkish folk medicine against parasitic infections for their in vivo anthelmintic activity.

Ethanolic and aqueous extracts obtained from nine plant species from seven families selected depending on their use in Turkish folk medicine, including Citrillus lanatus (Thunb.) Matsum. (seed), Jasminum fruticans L. (branches), Juniperus drupacea Labill. (fruits), Juniperus nana L. (fruit and leaves), Juniperus oxcycedrus L (fruit and leaves), Mentha longifolia L. (herba), Pinus nigra ssp. pallasiana (Lamb.) Richt. (fruits), Plantago lanceolata L. (leaves), and Zea mays L. (seed) were evaluated for their in vivo anthelmintic activity. Among the plant extracts studied, both ethanolic and aqueous extracts of Jasminum fruticans, Mentha longifolia and Pinus nigra ssp. pallasiana, the aqueous extracts of Zea mays, the ethanolic extracts of Citrillus lanatus, Juniperus drupacea (fruit), Juniperus oxcycedrus and Plantago lanceolata displayed significant anthelmintic activity against pinworms, Syphacia obvelata and Aspiculuris tetraptera, in mice. Rest of the extracts from plants did not show any remarkable anthelmintic activity. The results were considered significant at p<0.05.

Animals↗

Anthelmintic resistance: the state of play revisited.

Helminthosis is one of the major constraints in the successful wool and mutton industry throughout the world. Anthelmintic Resistance (AR) is said to have been established when previously effective drug ceases to kill exposed parasitic population at the therapeutically recommended dosages. Anthelmintic resistance is almost cosmopolitan in distribution and it has been reported in almost all species of domestic animals and even in some parasites of human beings. Some of the most important species of parasites of small ruminants in which AR has been reported include: Haemonchus spp., Trichostrongylus spp. Teladorsagia spp., Cooperia spp. Nematodirus spp., and Oesophagostomum spp. All the major groups of anthelmintics have been reported for development of variable degrees of resistance in different species of gastrointestinal nematodes. This paper describes the global scenario of prevalence and methods used for detection of AR in small ruminants. Different mechanisms and contributory factors for the development of AR are discussed. Various options and alternate strategies for the control and/or delay in the onset of AR are suggested in the light of available information.

Animals↗

New anthelmintics for livestock: the time is right.

The viability of small-ruminant enterprises is under threat in some locations because anthelmintic resistance continues to increase in prevalence and severity. Despite this, no new anthelmintic group has been developed for many years, and animal health companies seem unconvinced of the commercial justification for new compounds for the ruminant market. It is now argued, however, that market conditions are becoming favourable because of increases in multiple-drug resistance in nematodes of ruminants and other hosts and because few non-chemical options exist. A new anthelmintic is urgently needed and will find ready acceptance in an increasing market, and with better knowledge of resistance management, greater product longevity can be achieved.

Animal Husbandry↗

Evaluation of the anthelmintic activity of Khaya senegalensis extract against gastrointestinal nematodes of sheep: in vitro and in vivo studies.

The anthelmintic effect of Khaya senegalensis is described. In vitro and in vivo studies were conducted to determine possible direct anthelmintic effects of ethanolic and aqueous extracts of K. senegalensis towards different ovine gastrointestinal nematode. A larval development assay was used to investigate in vitro, the effect of aqueous and ethanolic extracts towards larvae of strongyles. The LC50 values of the effects of both the aqueous and ethanolic extracts were calculated. Another study was conducted in vivo to evaluate the therapeutic efficacy of the extracts administered orally at a dose rate of 125, 250 and 500 mg/kg of sheep harbouring naturally acquired infection of gastrointestinal nematodes. The presence of K. senegalensis extracts in the cultures decreased the viability of larvae. The LC50 of the aqueous extract (0.69 mg/ml) is not significantly different (P >0.05, t-test) from the ethanolic extract (0.51 mg/ml). The activity of the extract is concentration dependent in vivo. Sheep drenched with 500 mg/kg K. senegalensis ethanolic extract had a mean faecal egg count (FEC) reduction of 88.82%. The extract of K. senegalensis could find application in anthelmintic therapy in veterinary practice.

Animals↗

Anthelmintic activity of Azadirachta indica A. Juss against sheep gastrointestinal nematodes.

Gastrointestinal nematode control has been performed through use of anthelmintics. However, the development of resistant populations has required research into new alternatives. There are popular reports about anti-parasitic activity of Azadirachta indica in animals and plants. The aim of this study was to evaluate the anthelmintic activity of A. indica after feeding sheep with the dried leaves. In this experiment, 40 sheep were allotted into four treatment groups. Group I received a treatment of A. indica dry leaves mixed in a concentrate at a rate of 0.1 g/kg dose for 3 months. Group II was treated with double the dose of Group I. Group III was treated with closantel (Diantel) at the manufacturer-recommended dose once at the beginning of the study and Group IV was not treated. To compare treatment effects, the following parameters were evaluated: egg count per gram of feces (EPG), worm burden, weight gain and haematocrit. EPG and worm burden results were statistically evaluated using the Kruskal-Wallis test. Haematocrit and live weight gain were submitted to analysis of variance (ANOVA) and the means evaluated by Tukey's test with 95% probability. None of the evaluated parameters of the treatment groups were statistically different when compared to the control group, demonstrating that, with the protocol used, A. indica has no anthelmintic effect.

Analysis of Variance↗

Control of gastrointestinal nematodes in goats on pastures in South Africa using nematophagous fungi Duddingtonia flagrans and selective anthelmintic treatments.

The effectiveness of selective anthelmintic treatments and use of nematophagous fungi Duddingtonia flagrans in reducing levels of gastrointestinal nematodes in goats was investigated at Onderstepoort, South Africa. Nineteen (19) naturally infected indigenous male goats, aged 10 months, were separated into four groups and grazed in separate previously ungrazed paddocks for two worm seasons (February 2002-March 2003). Two groups of goats were fed D. flagrans chlamydospores daily and two groups did not receive fungi. The FAMACHA system was used to determine which goats required anthelmintic treatments. Twice as many goats in the no-fungi fed group required treatments as compared with the fungi fed group. Mean FAMACHA scores in the no-fungi fed group were higher during most of the sampling occasions compared to the group fed fungi, but the difference was not significant. The group-mean faecal egg counts and PCV% were comparable between the two treatment groups throughout the study. Haemonchus was the predominant parasite genus in composite group faecal cultures. Group-mean body weights and body condition scores were higher for the no-fungi fed group from May 2002 up to the end of the study, though statistical differences were not significant. Mean worm burdens indicated that the most abundant species infecting animals were Haemonchus contortus and Trichostrongylus spp. and were higher in the fungi fed group. More animals required individual anthelmintic treatments in the no-fungi fed group. The requirement for extra treatments in the no-fungi fed group must, however, be considered against the financial cost of the fungi, the requirement of daily feeding of the fungi, the lower performance and higher worm burdens in the fungi fed group.

Animals↗

World association for the advancement of veterinary parasitology (WAAVP): second edition of guidelines for evaluating the efficacy of anthelmintics in swine.

Guidelines are provided for evaluating the efficacy of anthelmintics in swine which, in conjunction with other sets of guidance such as those of the International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products (VICH GL7 and VICH GL16), should encourage the adoption of uniform registration requirements globally. Testing of efficacy should be carried out according to the principles of "Good Clinical Practice" (VICH GL9, 2000). Data obtained according to these guidelines should be internationally acceptable for the registration of anthelmintics for swine. Further, the use of the guidelines should expedite development, government review, and approval of anthelmintics for swine, as well as contribute towards reducing costs and the number of experimental animals used for drug testing.

Animals↗

Direct and indirect anthelmintic effects of condensed tannins in sheep.

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

Animal Feed↗

Anthelmintic resistance--the state of play.

There is evidence that the incidence of anthelmintic resistance is increasing in livestock in countries throughout the world including the United Kingdom. Early detection of emerging drug resistance is important since reversion to susceptibility appears not to occur in highly selected homozygous strains. Because the current in vivo and in vitro assays, which generally determine the degree of disruption of normal physiological function of different parasite stages, are relatively insensitive, effort is being made to develop more direct genetic and biochemical diagnostic assays. Studies on the selection and genetics of resistance suggest that resistance is normally polygenic and arises from within the normal phenotypic range and that there are three phases in the selection process. An initial susceptible phase is followed by an intermediate one in which heterozygous resistant individuals are common within the population and finally homozygous resistant individuals predominate within the population. For these reasons low efficacy treatments, which enable the survival of heterozygous resistant individuals, and suppressive regimes, which only allow homozygous resistant individuals to survive, increase the rate of development of drug resistance. Strategies to delay the onset of resistance and control resistant strains usually incorporate minimal chemoprophylaxis, seek to maximize drug efficacy, and if possible include a 'slow' drug rotation and seek to limit host parasite contact by manipulation of the grazing environment. Although multi-species mathematical models of anthelmintic resistance appear to offer a means of assessing the long term impact of these and other control strategies, current models are limited by a lack of detailed biological knowledge. In particular, more information on the status and numbers of alleles associated with resistance to specific drugs, their frequencies within populations of different species and the fitness of resistant and susceptible populations is required. Anthelmintic resistance provides an example of the adaptability of metazoan parasites under intensive selection and suggests that sustainable control strategies will require an integrated approach in which both chemotherapy and immunotherapy, together with environmental management are used to control nematodoses.

Animal Diseases↗

Transtegumental diffusion of benzimidazole anthelmintics into Moniezia benedeni: correlation with their octanol-water partition coefficients.

The experiments described here report on the correlation between the ex vivo diffusion of different benzimidazole (BZD) anthelmintics into the cestode parasite Moniezia benedeni, and their octanol-water partition coefficients (P.C.). The characterisation of the drug diffusion process into target parasites is relevant to understand the mechanism of drug penetration and the pharmacological activity of anthelmintic drugs. Specimens of the tapeworm M. benedeni, used as a helminth parasite model, were obtained from untreated cattle killed at the local abattoir. The collected parasites were incubated (5-210 min) with either fenbendazole (FBZ), albendazole (ABZ), ricobendazole (RBZ), oxfendazole (OFZ), mebendazole (MBZ), oxibendazole (OBZ), or thiabendazole (TBZ), in a Kreb's Ringer Tris buffer medium at a final concentration of 5 nmol/ml. After the incubation time elapsed, samples of parasite material were chemically extracted and prepared for high performance liquid chromatography (HPLC) analysis to measure drug/metabolite concentrations. Additionally, the octanol-water P.C. for each molecule was estimated as an indicator of drug lipophilicity, using reversed phase HPLC analysis. All the incubated drugs were recovered from the tapeworms as early as 5 min post incubation. There was a high correlation (r=0.87) between drug lipophilicity, expressed as octanol-water P.C. (Log P), and drug availability within the parasite. The most lipophilic BZD compounds (FBZ, ABZ, and MBZ), with P.C. values higher than 3.7, were measured at significative higher concentrations within the tapeworm compared to those drugs with the lowest P.C. values. Considering the results from the current and previous studies, it is clear that passive diffusion is a major mechanism of BZD penetration into cestode parasites, where lipid solubility is a determinant factor influencing the diffusion of these anthelmintic molecules through the parasite tegument.

Animals↗

Selection of different genotype larvae and adult worms for anthelmintic resistance by persistent and short-acting avermectin/milbemycins.

To understand the factors that influence selection for anthelmintic resistance, it is necessary to examine the impact of drug treatment, particularly persistent drugs, on all phases of the worm life cycle. The efficacy of various avermectin/milbemycin anthelmintics was determined against resident worms, incoming larvae (L3) and development of eggs in faecal culture. Homozygote-resistant and maternal and paternal F1-heterozygote genotypes of Haemonchus contortus were used to infect sheep before or after treatment with ivermectin (IVM) oral, IVM capsule, moxidectin (MOX) oral or MOX injectable. Total worm count and quantitative larval culture were used to determine efficacy against parasitic and free-living stages, respectively. Selection for resistance by IVM capsules occurred at the adult and L3 stages because of poor efficacy against these stages for all resistant genotypes. However, the selective advantage of these surviving worms was reduced due to the low development of their eggs to L3 in faecal culture. For MOX, selection for resistance predominantly occurred after treatment because of high efficacy against resident adult worms of all resistant genotypes but poor efficacy against resistant L3 ingested after drug administration. The results indicated no evidence of sex-linked inheritance for IVM resistance. Mean IVM efficacies against homozygous and heterozygous resistant adult worms were not different, and IVM capsule efficacy against incoming L3 was approximately 70% for all resistant genotypes, consistent with a dominant trait. MOX was highly effective against adults of all resistant genotypes and approximately 76% effective against incoming L3 regardless of resistance genotype, also consistent with a dominant trait. These results will enable the impact of persistent drugs on worm control and anthelmintic resistance to be estimated. The results indicate that IVM capsules should not be used in populations where avermectin/milbemycin resistance is present.

Administration, Oral↗

Anthelmintic resistance: past, present and future.

Anthelmintic resistance continues to increase in geographic range, in the number of species affected and the range of drugs involved. Several aspects of resistance have emerged as important issues. They include lack of genetic reversion, presence of side resistance and lack of universality. Furthermore, resistant isolates recovered from the field may have different characteristics to those selected in pen passage. Research into anthelmintic resistance has not progressed far beyond the stage of descriptive research. Some progress has been made in developing control strategies and in diagnosing resistance, especially in the development and adoption of in-vitro tests. However, these still need improvements in their ability to detect resistance to closantel and avermectin/milbemycin anthelmintics. Less progress into understanding the basis of resistance has occurred. Research priorities include improvement of diagnostic tests and the development of molecular tests, particularly for resistance to levamisole and the avermectin/milbemycins. Resistance itself, as a selectable marker for genetic transfection in parasites, is a potential tool for investigating parasite biology.

Animals↗

Novel anthelmintic compounds and molluscicides from medicinal plants.

This review assesses the role that can be played by allelochemicals (bioactive secondary compounds) from medicinal and other plants in the control of human helminthic diseases. In the search for new anthelmintics among plant allelochemicals, 3 practical issues have considerable significance. They are the range and capacity of anthelmintic bioassays utilised in preclinical studies in vitro on plant extracts, the phenomenon of coexistent allelochemicals with overlapping activity spectra within single plants, and the problem of non-specific cytotoxins among plant allelochemicals. These topics are discussed in the context of the present absence of any clinically useful plant anthelmintics. In the search for new plant molluscicides for schistosomiasis control, the characteristics of a range of molluscicidal plants are measured against those of the synthetic molluscicide of choice, niclosamide, and against the postulated attributes of practically useful plant molluscicides.

Animals↗

Antenatal anthelmintic treatment, birthweight, and infant survival in rural Nepal.

Anthelmintic treatment, which is recommended during pregnancy in areas where there is a high rate of anaemia, needs further investigation. We examined prospectively the association between anthelmintic treatment and maternal anaemia, birthweight, and infant mortality in a study of prenatal supplements, in which women received albendazole twice during pregnancy. Women given albendazole in the second trimester of pregnancy had a lower rate of severe anaemia during the third trimester. Birthweight of infants of women who had received two doses of albendazole rose by 59 g (95% CI 19-98), and infant mortality at 6 months fell by 41% (RR 0.59; 95% CI 0.43-0.82). Antenatal anthelmintics could be effective in reducing maternal anaemia and improving birthweight and infant survival in hookworm-endemic regions.

Albendazole↗

Control of anthelmintic resistant endoparasites in a commercial sheep flock through parasite community replacement.

An effort was undertaken to replace a community of sheep endoparasites that had been classified as resistant to levamisole and albendazole with a community of more susceptible parasites using a dilution approach that could be integrated into the management of a commercial flock. For this study, pastures on this sheep farm were divided into two areas: north and south. Strategically timed anthelmintic treatments combined with pasture management reduced to nondetectable levels the endemic community of anthelmintic resistant parasites in this flock and on these pastures by early summer. A group of 102 ewes, lambs, and rams were experimentally infected with third stage larvae from the more susceptible community of parasites. These sheep then seeded the south pastures with the new parasite community, while sheep on the north pastures maintained the endemic resistant community. Despite its insensitivity as a technique for detecting anthelmintic resistance, fecal egg count reduction tests at the end of the grazing season indicated that the more susceptible parasites were present on the south pastures while resistant parasites were present on the north. The following grazing season, similar protocols were used to introduce the more susceptible parasites onto the north pastures. At the end of the grazing season, fecal egg count reduction tests indicated that the new community of parasites had become established on both groups of pastures of the farm.

Albendazole↗

Drought and flock isolation may enhance the development of anthelmintic resistance in nematodes.

A survey of anthelmintic resistant nematodes was conducted in sheep and goat flocks in Greece using in vivo and in vitro tests. Faecal egg count reduction tests in Macedonia were all greater than 99% indicating very high sensitivity of the nematodes to anthelmintics. In vitro tests showed benzimidazole resistant Teladorsagia circumcincta in 17 out of 106 flocks on small islands. On the mainland there were only three cases of benzimidazole resistance out of 310 flocks and animals had recently been introduced to the flocks. Flocks on the islands are isolated and there are higher temperatures than on the more mountainous mainland, where flocks tend to intermingle. It is concluded that drought and isolation are likely to be the major factors accounting for the development of anthelmintic resistance in nematodes in the island flocks.

Animal Husbandry↗