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PubMed1991

Development of a mechanism of action-based screen for anthelmintic microbial metabolites with avermectinlike activity and isolation of milbemycin-producing Streptomyces strains.

A high-volume screen for anthelmintic microbial metabolites with an avermectinlike mode of action was developed. The primary screen used the free-living nematode Caenorhabditis elegans in a whole-organism assay. The specificity for avermectinlike compounds resides in the secondary screen, which takes advantage of the chloride channel-opening properties of the avermectins. By using standard microelectrode techniques, membrane conductance changes following exposure to extracts of microbial cultures were measured in the walking leg stretcher muscle fibers of the lined shore crab Pachygrapsus crassipes. The avermectins and related milbemycins give a characteristic response of rapid loss of membrane resistance coupled with a slight hyperpolarization of the membrane. This is partially (near 50%) reversible with the chloride channel blocker picrotoxinin. Four morphologically similar cultures that produced avermectinlike activities were identified by this screen. Isolation of the active components from one of these cultures (strain UC 8984) followed by nuclear magnetic resonance spectroscopy resulted in the identification of milbemycins alpha 1 and alpha 3. These metabolites are members of a large family of milbemycins produced by Streptomyces hygroscopicus subsp. aureolacrimosus NRRL 5739. Systematic studies revealed that strain UC 8984 is also a S. hygroscopicus strain, but which is taxonomically distinct from NRRL 5739.

Animals↗
PubMed1977

Controlled trials of the anthelmintic oxfendazole in ewes and lambs naturally infected with gastrointestinal nematodes.

Oxfendazole doses at a rate of 5 mg per kg, before or after lambing, reduced nematode egg output to insignificant levels in ewes, most of which were not exposed to re-infection. Ewes treated with oxfendazole had a significantly lower egg output than those treated with levamisole, although the latter anthelmintic was also highly effective. In lambs, oxfendazole at a dose rate of 5 mg per kg, showed 100 per cent efficacy for Ostertagia circumcincta, O trifurcata, Teledorsagia davtiani, Trichostrongylus axei, T vitrinus, T colubriformis, Nematodirus battus, N filicollis, immature Nematodirus, Chabertia ovina, and 93 per cent efficacy for Trichuris spp. Levamisole showed similar efficacies but did not remove Trichuris.

Animals↗
PubMed1980

Anthelmintic efficiency of ivermectin against naturally acquired bovine gastrointestinal nematodes.

Ivermectin, one of the new avermectin group of anthelmintics, was more than 99 per cent effective in removing all stages of Ostertagia ostertagi including inhibited larvae, and adult Trichostrongylus axei when administered to cattle orally at 100 microgram/kg body-weight or subcutaneously at 100 and 200 microgram/kg body-weight. High efficacy (> 98.6 per cent) was also obtained against adults and inhibited larvae of Cooperia oncophora at 100 microgram/kg orally or 200 microgram/kg by subcutaneous injection. The latter treatment caused an 82.3 per cent reduction of adult Nematodirus helvetianus.

Administration, Oral↗
PubMed1991

Effectiveness of strategic anthelmintic dosing in controlling Haemonchus contortus infections in sheep in the United Kingdom.

The strategic use of anthelmintics in the control of infections of Haemonchus contortus in ewes and lambs, was investigated in a series of paddock trials. The levels of infection and clinical signs associated with the presence of either benzimidazole-resistant or benzimidazole-susceptible strains of H contortus in lambs were controlled by regular drenching with levamisole or mebendazole, respectively, or by the strategic use of closantel in combination with mebendazole. In the latter case, control was achieved by dosing either the ewes in the early part of the grazing season, or the lambs from June onwards. It was concluded that worm control strategies based on closantel could provide effective control of both benzimidazole-susceptible and benzimidazole-resistant strains of H contortus on farms in the United Kingdom.

Animals↗
PubMed1992

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

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

Animals↗
PubMed1994

Detection of anthelmintic resistant nematodes in sheep in southern England by a faecal egg count reduction test.

On five farms identified by in vitro tests to have benzimidazole resistance, and on one farm with apparent anthelmintic failure, faecal egg count reduction tests were performed using benzimidazoles, levamisole and ivermectin. With benzimidazoles efficacy was less than 70 per cent on all farms, confirming the validity of the in vitro tests to detect benzimidazole resistance. On two farms levamisole had an efficacy of less than 90 per cent but laboratory tests failed to demonstrate levamisole resistance. Ivermectin reduced egg counts by 100 per cent on all farms.

Animals↗
PubMed1994

Anthelmintic suppression of Fasciola hepatica infections in sheep.

In an experiment to examine the use of anthelmintics to suppress the faecal egg output of Fasciola hepatica from sheep and reduce the prevalence of infection on a sheep farm with a history of chronic fasciolosis, triclabendazole was administered four times annually for three years. During the first year, treatments in April, June, August and October failed to reduce the prevalence. In the subsequent two years the first annual treatment was brought forward to January and February, and the prevalence was reduced by 74.6 and 69.7 per cent, respectively. The mean plasma gamma-glutamyl transpeptidase concentration of the flock was significantly reduced from 55.9 units/litre before the experiment to 40.9 and 38.3 units/litre. In the second and third years the packed cell volume increased from 0.29 litre/litre to 0.36 litre/litre and the percentage of infected Lymnaea truncatula decreased to zero.

Animals↗
PubMed1996

Occurrence of anthelmintic resistant nematodes on sheep farms in England and goat farms in England and Wales.

A survey in 1992 showed that 44 per cent of the sheep farms tested in the south west and 15 per cent of those in the north east of England had parasitic nematode worm burdens which were resistant to benzimidazole anthelmintics, and that 65 per cent of the non-dairy goat farms tested in England and Wales had resistant worms. Ostertagia circumcincta was the main species in sheep and Haemonchus contortus in goats. The resistance to benzimidazoles was diagnosed by a combination of an egg hatch assay and a larval development test. A simplified faecal egg count reduction test was used to investigate sheep and goat farms for signs of ivermectin resistance but no positive cases were detected. The initial identification of levamisole resistance on one farm, both from a faecal egg count reduction test and a positive larval development test, was confirmed by a 'dose and slaughter' trial.

Animals↗
PubMed1997

Oesophageal injury associated with the administration of an anthelmintic bolus to calves.

Six of 18 calves from a suckler herd which were dosed with a sustained-release anthelmintic bolus, using appropriate equipment, developed clinical signs related to oesophageal perforation. Two died as a direct result of the injuries sustained, one required surgical removal of the paraoesophageal bolus and the remaining three were managed medically. The calves were in the approximate weight range advised by the manufacturers as suitable for dosing, but some were younger than the minimum recommended age. These animals were of a fractious nature having been relatively little handed.

Animals↗
PubMed1998

Pharmaceutical quality of anthelmintics sold in Kenya.

Nine anthelmintic products in pharmacies and from agricultural merchants in Kenya were tested for pharmaceutical quality. The concentration of active drug was compared with the claim on the label, and the variability of several products was tested between batches and between bottles within the same batch. All the products purchased claimed to contain levamisole but its mean (sd) concentration varied from 0 to 118.0 (13.3) per cent of the claimed. The concentration of levamisole in different batches of the same product ranged from 0 to 85.4 per cent of that claimed. One product consisting in part of mebendazole was found to contain 73.2 (9.4) per cent of the claimed concentration of this active component and two products consisting in part of oxyclozanide were found to contain 106.0 (14.4) and 120.6 (6.1) per cent of the expected concentration of oxyclozanide.

Animals↗
PubMed1998

Nephrotic syndrome in strongyloidiasis: remission after eradication with anthelmintic agents.

Strongyloides stercoralis infection is known to be important because of its potential for life-threatening disseminated infection in immunosuppressed hosts. Apart from direct invasion into nearly every organ in systemic infection, evidence suggests that immunological reaction also plays a role in the pathogenesis of the disease, including both uncomplicated and disseminated infections. However, Strongyloides-related glomerulonephritis has not been well documented. We present a case of steroid- and cyclophosphamide-resistant nephrotic syndrome complicated by disseminated strongyloidiasis which responded to anthelmintic agents. The remission of nephrotic syndrome after treatment of Strongyloides infection strongly suggests the possibility of Strongyloides-associated glomerulonephritis. Nephrotic patients in endemic areas of Strongyloides infection should have the differential white cell count checked. Strongyloides infection should be ruled out in patients with eosinophilia before immunosuppressants are initiated to prevent the complication of disseminated strongyloidiasis.

Adult↗
PubMed2003

Anthelmintic treatment improves the hemoglobin and serum ferritin concentrations of Tanzanian schoolchildren.

To investigate the relationships between helminth infections and iron status among school-aged children, 1,115 Tanzanian children in grades 2 through 5 were randomly assigned to treatment or control groups. The children in the treatment group were screened for infection with Schistosoma haematobium and hookworm at baseline, 3 months, and 15 months; infected children were given albendazole against hookworm and praziquantel against schistosomiasis. The control group received a placebo and did not undergo parasitological screening until 15 months after the baseline. Hematological variables were compared between the treatment and control groups. The main results were, first, that the hemoglobin concentration significantly improved after treatment for hookworm (p < .001) by 9.3 g/L in children treated for hookworm only and by 8.8 g/L in children treated for hookworm and schistosomiasis. The ferritin concentration also improved in children treated for schistosomiasis (p = .001) or hookworm (p = .019). Second, a longitudinal analysis of the data from the children in the control group showed that hookworm and schistosomiasis loads were negatively associated with hemoglobin and ferritin concentrations. Moreover, ferritin concentrations increased as C-reactive protein levels increased. Overall, the results showed that anthelmintic treatment is a useful tool for reducing anemia in areas with high hookworm and schistosomiasis endemicity. The empirical relationship between ferritin and C-reactive protein indicated that simple procedures for adjusting cutoff points for the use of ferritin as an indicator of low iron stores were unlikely to be useful in this population.

Albendazole↗
PubMed2006

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

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

Anthelmintics↗
PubMed1991

Anthelmintic efficacy of milbemycin D against Toxocara cati and Ancylostoma tubaeforme in domestic cats.

Anthelmintic efficacy of milbemycin D was evaluated against Toxocara cati and Ancylostoma tubaeforme in domestic cats. Twelve cats naturally infected with each nematode species were allocated among 2 groups of 6 animals each, and milbemycin D was orally administered to the 2 groups of cats in doses of 0.05 mg/kg and 0.1 mg/kg body weight, respectively. In all the cats infected with T. cati, fecal egg counts decreased followed by their disappearance from the feces and 2-35 worms were excreted into the feces after the medication in both doses of 0.05 mg/kg and 0.1 mg/kg. At postmortem of these medicated groups, no worms were detected from 4 cats of each group, but 1 and 2 immature worms were recovered from the other 2 cats respectively. In the cats infected with A. tubaeforme, fecal egg counts decreased followed by the disappearance from the feces and 2-62 worms were excreted into the feces in all the cats of the 2 groups, no nematodes remaining at postmortem. These results indicate that milbemycin D is fully effective against T. cati and A. tubaeforme in cats in a dose of 0.05-0.1 mg/kg.

Ancylostomiasis↗
PubMed1993

Purification and identification of a serum protein increased by anthelmintic drugs for Dirofilaria immitis in dogs.

Polyacrylamide gel electrophoretic analysis of canine serum protein has revealed that the administration of anthelmintics elicits an increase in a certain serum protein. This protein, named PT60, was partially purified by ammonium sulfate fractionation and preparative electrophoresis. The purified PT60 gave a single band with the molecular size of 53 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under non-reducing conditions. After reduction with 2-mercaptoethanol, two bands appeared at 35 kDa and 17 kDa, indicating that PT60 consists of two subunits which are linked with each other by disulfide bonds. PT60 had the capacity to bind to hemoglobin. In an immunodiffusion test, an antiserum against PT60 cross-reacted with canine haptoglobin (Hp). N-terminal amino acid sequences of two PT60 subunits were identical to those of alpha and beta subunits of canine Hp, respectively. Thus, PT60 was identified as Hp.

Amino Acid Sequence↗
PubMedDate not supplied

Studies in enteric anthelmintics: activity profile of prodrug of a bisbenzimidazole [1].

The comparative anthelmintic activity of a possible prodrug, 2,2'-dicarbomethoxyamino-5,5'-dibenzimidazolyl methanol (2) with its parent compound 2,2'-dicarbomethoxyamino-5,5'-dibenzimidazolyl ketone (1) and the reference drug mebendazole (3a) is reported. At a dose of 25 mg/kg, compound 2 was 100% effective against Ancylostoma ceylanicum in hamsters. Compound 2 also exhibited a similar order of activity against Syphacia obvelata, Hymenolepis nana and H. diminuta at a dose of 100 mg/kg. The drug exhibited lethal effects against metamorphic forms of A. ceylanicum at a dose of 100 mg/kg. However the trichostrongylids, Nippostrongylus brasiliensis remained unaffected up to a dose of 250 mg/kg of 2. Both 1 and 3a exhibited inferior activity than 2 except against adult A. ceylanicum. The activity of 1 and 2 has been explained on the basis of their ability to resist systemic hydrolysis resulting in higher concentration of the active drug in biophase.

Animals↗
PubMed1986

Anthelmintics. Current concepts in the treatment of helminthic infections.

This article discusses the anthelmintics now in common use and describes their mode of action and toxic side effects. The drugs reviewed include: pyrantel pamoate, mebendazole, piperazine, thiabendazole, niclosamide, praziquantel, niridazole, oxamniquine and diethylcarbamazine. Most of the common roundworm intestinal infections respond to treatment with pyrantel pamoate, which has the advantage of single-dose therapy. Trichuriasis requires therapy with mebendazole, while the filariases are treated with diethylcarbamazine. There is no specific therapy for trichinellosis, but its symptoms can be alleviated. Intestinal cestode infections respond to treatment with niclosamide and cerebral cysticercosis to praziquantel, but echinococcal hydatid disease still requires surgical intervention in certain cases, although prolonged treatment with mebendazole shows promise. The greatest recent advance in the therapy of helminthiases is the development of praziquantel which effectively treats the most severe of these infections.

Anthelmintics↗
PubMed2001

Optimising the benefits of anthelmintic treatment in children.

Optimal use of anthelmintics in children is of major public health importance because the parasites involved probably infect over 2 billion persons, and most are especially common and debilitating in children. Well targeted drug delivery, particularly via community chemotherapy, can substantially decrease aggregate morbidity and mortality and also improve growth rates, physical fitness and activity, cognitive and school performance, and social well-being. The drugs discussed here include the benzimidazoles (albendazole, levamisole and mebendazole), pyrantel, praziquantel, oxamniquine, ivermectin, diethylcarbamazine and some traditional medicines. The parasitic infections discussed are hookworm, ascariasis, trichuriasis, strongyloidiasis, schistosomiasis and lymphatic filariasis; onchocerciasis and loiasis are also mentioned briefly. Dosage regimens and effectiveness, including combination treatment, are discussed. Mechanisms by which parasites may cause or aggravate malnutrition and retard development are shown, along with examples of nutritional and functional improvement at various ages due to antiparasitic treatment. Improvement in appetite is likely to be the single most important mechanism through which a variety of physiological improvements occur. We recommend community treatment of girls and women of childbearing age in areas with widespread hookworm and anaemia, because effective treatment can reduce the incidence of low birthweight, mortality in infancy and pregnancy, and stunted growth and morbidity in children and adults. Treatment of moderate-to-severe anaemia improves appetite, growth and cognitive and school performance in children, and also improves work and social capacity and productivity in children and adults. Since treatment for helminth infections may also decrease both the probability of contracting HIV infection and the rate of viral replication in those infected with both types of organisms, large-scale treatment and control of helminths and treatment of individual cases when diagnosed are now truly urgent.

Anthelmintics↗