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Comparative study of the quality and efficacy of originator and generic albendazole for mass treatment of soil-transmitted nematode infections in Nepal.

The quality and efficacy of two locally manufactured generic albendazole (ABZ) products (Curex and Royal Drug) used for deworming children in Nepal since 1999 were tested against the originator product (GlaxoSmithKline (GSK)). The study included disintegration and dissolution testing according to the Indian Pharmacopoeia (IP) and the United States Pharmacopeia (USP), respectively, as well as a randomised controlled clinical trial comparing cure rates (CR) and egg reduction rates (ERR) for Ascaris lumbricoides, Trichuris trichiura and hookworm infections. Stool samples from 1277 children were examined before and 21 days after treatment. For A. lumbricoides, GSK (97.0%) and Royal Drug (95.0%) ABZ achieved significantly higher CRs than Curex ABZ (82.6%); however, all products achieved ERRs >90%. For T. trichiura, Curex ABZ showed significantly lower ERRs (63.2%). For hookworms, GSK ABZ performed significantly better (CR 74.3%, ERR 87.1%) than Royal Drug ABZ (CR 53.3%, ERR 80.8%) and Curex ABZ (CR 50.7%, ERR 73.1%). Only the GSK product passed both disintegration and dissolution tests according to the IP and USP. Both generic products failed the dissolution tests. Curex ABZ showed poor disintegration. Despite its lower efficacy, the cheaper Curex product achieved good results in controlling morbidity due to soil-transmitted helminth infections. This study shows that the cost effectiveness of drugs used in mass deworming campaigns should not be inferred on the basis of a single quality testing parameter.

Adolescent↗

The anthelmintic efficacy of fenbendazole against a mixed nematode infection in sheep.

Fenbendazole (methyl-5-(phenylthio)-2-benzimidazole carbamate) at dose rates of 5 mg/kg and above was 100 per cent effective in eliminating a naturally acquired Dictyocaulus filaria infection in sheep. The drug was 100 per cent effective in eliminating concurrent infections of adult Trichostrongylus axei, Haemonchus contortus, Haemonchus placei, Ostertagia circumcincta, Ostertagia ostertagii, Cooperia oncophora, Cooperia mcmasterii, Nematodirus spathiger, Neumatodirus filcollis, Oesophagostomum venulosum and Chabertia ovina. Fenbendazole was 93 per cent and 97 per cent effective at doses of 5 and 10 mg/kg respectively in removing infection with adult T colubriformis, and post-treatment worm-egg production was completely suppressed in surviving female worms. No adverse side-effects were observed in treated sheep at either of the two dose rates used.

Animals↗

Efficacy of moxidectin 2% equine gel against natural nematode infections in ponies.

The efficacy of moxidectin 2% oral gel (Equest, Fort-Dodge) against European worm strains was studied through post-mortem worm counts and feacal egg counts (FECs) in 12 young ponies naturally infected. The animals were allocated in two groups of six ponies each: the first one was treated at 0.4 mg/kg b.w. and the second one received a placebo and served as control. All the ponies were necropsied 14 days post-treatment. The efficacy of moxidectin in reducing strongyle FECs ranged from 99.8% to 100% from 3 to 14 days after treatment. Moxidectin efficacy was 100% against Trichostrongylus axei and Triodontophorus spp., > 99.9% against Cyathostomes adults and L5, 92% against S. edentatus L5, 100% against O. equi L5, 99% against O. equi L4, and 92% against G. intestinalis. No animal treated with moxidectin was harbouring P. equorum, Habronema spp., G. pecorum nor G. nasalis, while the control group was slightly infected with these parasites. This experiment confirms the post-mortem worm count results obtained in the United States and the FECs results reported in Europe. Moxidectin showed to be safe in young ponies.

Animals↗

Segregation of natural and experimental gastrointestinal nematode infection in F2 progeny of susceptible Suffolk and resistant Gulf Coast Native sheep and its usefulness in assessment of genetic variation.

Gastrointestinal nematode parasitism is a concern to small ruminants worldwide. Productivity has been compromised because such nematodes, particularly Haemonchus contortus, have developed resistance to available anthelmintics. Some sheep breeds and lines within breeds are relatively resistant to infection, a trait that may be useful for developing control strategies. Suffolk sheep, which are susceptible to infection, were crossed with Gulf Coast Native sheep, which are more resistant to infection, to produce F1 progeny. F1 rams were bred to F1 ewes which produced 227 F2 offspring. These F2 offspring were evaluated for variability in infection levels, based on fecal egg count (FEC) and blood packed cell volume (PCV), under two natural infection conditions (one at weaning and another after a summer grazing period) and one experimental infection. The range of both FEC and PCV was large for all three infection periods with annual variation. Overall, the range for the three infection periods, respectively, were 167-149,933, 0-31,400 and 17-114,667 eggs per gram (EPG) of feces and 8.7-37.0%, 7.3-33.0% and 8.3-36.0%. This segregation of infection is what would be expected of F(2) progeny from susceptible and resistant parent breeds. Heritabilities of FEC and PCV for the three infection periods, respectively, were 0.15, 0.29 and 0.12, and 0.11, 0.22 and 0.12. Based on segregation of infection, larger heritabilities and maternal environment effects that declined after weaning, the summer natural infection was probably the best model for assessing genetic variation.

Animals↗

Injection tube differentiation in gun cells of a haptoglossa species which infects nematodes

The gun cells which develop from germinating cysts in Haptoglossa produce a specialized infection apparatus, the injection tube. Upon eversion this tube fires a missile-like projectile which penetrates the host cuticle and then forms an infective sporidium within the body cavity of the nematode host. The temporal assembly of this complex cell organelle has been determined by serial-section reconstructions of maturing gun cells in a previously undescribed Haptoglossa species. The differentiation of the partially walled inverted injection tube is an unusual example of internal tube growth, in which membrane and wall assembly are temporally separated. There is no evidence that the shape of this inverted tube, which coils around the nucleus until it doubles back on itself, is dictated by the disposition of cytoplasmic microtubules. However, actin-like material was associated with the delimiting membrane of the differentiating tube, particularly in the regions of extension. From these studies it seems likely that the "head and buttress" structures previously depicted as the barbed tip of the "harpoon-like" penetration missile are part of a separate, structurally complex system which we suggest locks the "missile" into position in the invaginated injection tube. From this detailed account of cell architecture, models for the likely mechanism of infection cell firing are discussed, and unresolved questions relating to the cell biology and biochemistry of these complex organelles are highlighted. Copyright 1998 Academic Press.

Journal Article↗

Efficacy of ivermectin against induced gastrointestinal nematode infections in goats.

The efficacy of ivermectin (0.08 per cent w/v oral solution) at different dose levels was evaluated against induced infections of adult Haemonchus contortus (21 days old) and Trichostrongylus colubriformis (21 days old) and fourth stage larvae of Oesophagostomum columbianum (17 days old), Ostertagia circumcincta (five days old) and Strongyloides papillosus (five days old). Twenty-five Boergoats (mutton goats) were randomly allocated by bodyweight within each sex to an untreated control group and four ivermectin treatment groups; ivermectin was administered at either 25, 50, 100 or 200 micrograms/kg orally, once. The goats were killed and processed for worm recovery 25 to 27 days after treatment. At 25 micrograms/kg the efficacy of ivermectin varied from 43 per cent for adult T colubriformis to more than 99 per cent for fourth larval stage O columbianum. Ivermectin at 50 micrograms/kg or higher was 99 per cent or more effective against all induced parasite infections with the exception of ivermectin at 50 micrograms/kg against S papillosus (97 per cent). For all parasites there was a statistically significant (P less than 0.05) difference between the control group and the pooled treated groups. No adverse reactions to ivermectin treatment were observed in the goats.

Animals↗

Quantitative analysis of a bacteria-derived antibiotic in nematode-infected insects using HPLC-UV and TLC-UV methods.

3,5-Dihydroxy-4-isopropylstilbene (ST), an antibiotic produced by the bacterial symbiont Photorhabdus luminescens of the nematodes of the genus Heterorhabditis was determined quantitatively in nematode bacterium-infected insects using HPLC or TLC for separation and UV for quantification. Comparable and reproducible results were obtained with both HPLC-UV and TLC-UV methods. Several factors, including solvents for extraction of the antibiotic from the infected insects, eluents for TLC development and programs for HPLC operation, were investigated. Of the four solvents used, namely acetone, methanol, ethyl acetate and diethyl ether, acetone had the highest extraction efficacy, and the ST recovery rate was about 95%. ST can be easily separated from all other bacterial metabolites on a TLC plate using a mixture of chloroform-methanol (98.5:1.5) or by HPLC using acetonitrile and water as the mobile phase.

Acetone↗

Energy restriction and zinc deficiency impair the functions of murine T cells and antigen-presenting cells during gastrointestinal nematode infection.

This study examined whether the impaired immune responses in zinc deficient- and/or energy-restricted mice exposed to a challenge infection of Heligmosomoides polygyrus might be associated with reduced numbers of spleen cells, altered proportions of spleen cell subpopulations and/or altered function of the T cells or antigen-presenting cells (APC). Female BALB/c mice were given free access to either a zinc-sufficient (60 mg zinc/kg diet, Zn+) or a zinc-deficient diet (0.75 mg zinc/kg diet, Zn-) or were pair-fed (PF) the zinc-sufficient diet. Significant differences in parasite burdens were observed. Worm numbers were lowest in Zn+ mice, intermediate in the PF mice and highest in the Zn- mice, showing that both zinc deficiency and energy restriction reduced protective immunity against the gastrointestinal nematode H. polygyrus. Although the absolute numbers of spleen cells were reduced in both Zn- and energy-restricted (PF) mice, neither deficiency altered the phenotypic distribution of the subpopulations of positive marker cells in the spleen. In vitro functional assays using a 1:1 ratio of APC:T cells showed that T-cell proliferation in response to parasite antigen (Ag) was impaired by a dietary effect of zinc deficiency on T cells and of energy restriction and zinc deficiency on APC function. Consequences of the nutritional deficiencies on cytokine production in response to parasite antigen were more complex: zinc deficiency reduced T-cell function [interleukin-4 and interleukin-5 (IL-4 and IL-5) production], and both nutritional deficits depressed APC functions [IL-4, IL-5, and interferon-gamma (IFN-gamma) production] and T-cell function (IFN-gamma production). Thus, this study showed that zinc deficiency and energy restriction played identifiably distinct roles in regulating host immune responses against the gastrointestinal nematode H. polygyrus.

Animals↗

[The initial experience with embovin treatment in a a focus of intestinal nematode infections in the Socialist Republic of Vietnam].

Comparative trials of pirantel analogs--combatrin (Pfizer, Philippines) and embovin (Russia) were carried out in a hyperendemic focus of intestinal nematodoses in Vietnam. The drugs were prescribed in a single dose of 10 mg/kg. No significant differences in the efficacies of the drugs were revealed: combatrin and embovin efficacies in ascariasis were 94.3 and 98.0%, respectively (p > 0.05), in ankylostomiasis 76.3 and 58.3%, respectively (p > 0.05).

Adolescent↗

[Embovin efficacy and tolerance in the treatment of patients with intestinal nematode infections].

The efficacy and tolerance of embovin, a new anthelminthic manufactured in Russia, was studied in 60 patients with nematodiases. The results evidence its high efficacy in ankylostomiasis (100%), enterobiasis (100%), and ascariasis (90 +/- 6.4%). The drug was well tolerated in all the cases. No adverse effects on the liver, pancreas, kidneys, as well as on the peripheral blood and urine composition were detected. This recommends embovin for wide use in medical practice.

Adolescent↗

Predicting effects of naturally acquired abomasal nematode infections on growth rate and food intake in reindeer using serum pepsinogen levels.

An experiment was performed on semiwild reindeer with naturally acquired parasite infections to assess whether measures of serum pepsinogen concentration and fecal egg counts can be used to predict effects of abomasal nematodes on reindeer weight gain and food intake. Food intake and weight gains were lower in infected calves compared with calves where parasites had been removed by anthelmintic treatment. Among the infected animals, concentration of pepsinogen in serum was correlated with food intake and weight gains. Concentration of abomasal nematode eggs in feces was not. Our results suggest that measures of pepsinogen levels in serum, but not fecal egg counts, may be used to predict the effects of abomasal nematodes on food intake and weight gain of reindeer.

Abomasum↗

Genetic and environmental factors associated with nematode infection of dairy goats in northwestern France.

The helminth parasitism (strongyles and Muellerius) of dairy goats was investigated in commercial farms of northwestern France. The study was undertaken in spring (n = 263 goats) and autumn (n = 165); the breed, age, polledness, absence or presence of wattles, and reproductive status were recorded for each goat. The faecal output of strongyle eggs was significantly related to breed, polledness, presence of wattles and age. The faecal output of first stage larvae of Muellerius was correlated with breed, age and pregnancy.

Age Factors↗

Intestinal mucosal mast cells in normal and nematode-infected rat intestines are in intimate contact with peptidergic nerves.

Inflammatory or allergic conditions, as well as situations where healing and repair processes occur, are characterized by the presence of increased numbers of mast cells. Previous work on the effect of neuropeptides on mast cell mediator release showed that only substance P caused such release from intestinal mucosal mast cells [Shanahan, F., Denburg, J. A., Fox, J., Bienenstock, J. & Befus, A. D. (1985) J. Immunol. 135, 1331-1337]. Accordingly, we investigated the microanatomical relationship between mast cells and enteric nerves in normal rat intestine and parasite-infected rat intestine, in which mucosal mast cell hyperplasia occurs. Combined immunohistochemistry for neuron-specific enolase and staining with alcian blue at pH 0.5 was employed on paraffin-embedded sections of normal and Nippostrongylus brasiliensis-infected rat jejunum. Sixty-seven percent of intestinal mucosal mast cells were touching subepithelial nerves, and an additional 20% were within 2 micron of nerves. Assessment of the proportion of the lamina propria occupied by mast cells (12.5%), the average mast cell area (121 +/- 28 microns 2), and the density of enteric nerves (one per 788 +/- 151 microns 2) suggested that the association was 5 times greater than would be expected by chance alone (P less than 0.0001). In consecutive sections, the nerves in contact with mast cells were also shown to contain substance P and/or calcitonin-gene-related peptide. Electron microscopy confirmed this association: 8% of the mast cells in infected rats exhibited membrane-membrane contact with unmyelinated axons containing 70- to 170-nm dense-core vesicles, and an additional 31% were situated less than 250 nm from nerves. Other mast cells appeared to embrace nerve bundles through the projection of lamellopodia. These data provide systematic quantitative evidence that a structural foundation for communication between the immune and nervous systems exists in the rat gastrointestinal tract.

Animals↗

[Study of the therapeutic efficacy of Nilsan preparation against Paramphistomatidae and nematode infections in sheep].

Experiments were carried out with the preparation Nilsan (oxiclozanide + levamizal) in the treatment of sheep with Fasciola, Dictyocaulus, and Trichostrongylus infection. The trials involved a total of 2782 sheep on two sheep-breeding farms, constituting 15 flocks. The liveweight of the adult animals ranged from 40 to 60 kg, and that of the year-old female ones--from 40 to 45 kg. The daily ration on the two farms did not differ essentially from that offered to the animals in the past 2-3 years. It was found that at the rate of 22 to 28 cm3 per head Nilsan produced 76.67 to 96.67 percent effect against Paramphistomum infection, 100 percent effect against Dictyocaulus infection, 73.37 to 90.00 percent effect against Trichostrongylus infection, and 23.34 to 83.34 percent effect against Dicrocelium infection. The application of an ex tempore combination of oxiclozanide and levamizal to sheep at the rate of 24 cm3 per head produced 86.67 to 100 percent effect against Paramphistomum, 96.67 to 100 percent effect against Dictyocaulus, 86.67 to 96.67 percent effect against Trichostrongylus, and 46.67 to 86.67 percent effect against Dicrocelium. The experimental sheep produced 16.41 to 37.40 per cent more wool, 0.85 to 35.09 per cent more milk, and 8 to 12 per cent more weight gain.

Animals↗

Efficacy of doramectin in the prevention of gastrointestinal nematode infections in grazing cattle.

Two studies were performed to investigate the efficacy of doramectin in the prevention of infection with Ostertagia ostertagi and Cooperia oncophora in grazing calves. In each study, 24 parasite-naive calves were randomly allotted to two equal groups and treated with either doramectin at 200 micrograms kg-1 or saline prior to mid-season turnout (Day 0) onto contaminated pasture. Faecal egg counts were carried out twice weekly from 15 to 64 days after turnout and the cumulative faecal egg count was calculated for each group of calves. In the doramectin-treated animals, eggs first appeared in the faeces 19 days and 22 days later than in controls for Studies 1 and 2, respectively. Mean cumulative faecal egg counts over the 64 days were reduced in the doramectin-treated groups by 71% and 87% for Studies 1 and 2, respectively (P < 0.01). The potential utility of injectable doramectin in the seasonal control of gastrointestinal nematode infestations in relation to these findings is discussed.

Analysis of Variance↗

The response of histamine degrading enzymes to nematode infection.

The response of intestinal mucosal enzymes which metabolize histamine i.e. diamine oxidase (DAO), histamine N-methyltransferase (HMT), and monoamine oxidase (MAO), to infection with Nippostrongylus brasiliensis has been examined in mice and compared to the changes evoked by in vivo administration of compound 48/80. Infection with the parasite resulted in a significant decrease in the concentration of both amine oxidases, followed by recovery of MAO and an overshoot in DAO activity. HMT activity was enhanced at the beginning of infection, then decreased markedly by days 11 to 15, and sharply increased thereafter. Histamine levels were on average only 20% higher than the basal levels over the entire period studied, except on day 4 when they were slightly reduced. Histamine is alleged to be a potential inducing factor for degrading enzymes. Consistently, the histamine releaser 48/80 significantly elevated intestinal mucosal DAO and in some of the mice also increased HMT activity.

Amine Oxidase (Copper-Containing)↗

Production of dairy replacement stock in relation to level of exposure to gastrointestinal nematode infection in the first grazing season: second-year calves and heifers.

In two experiments, groups of calves which had been exposed to different levels and patterns of infection with Ostertagia and Cooperia spp. in a simulated first grazing season (FGS), were followed throughout a natural second grazing season (SGS). Milk yields in the subsequent first lactation period were also recorded. The results suggest that although there had been differences in immune status among groups, which had been infected in the FGS, prior to the SGS, weight gain among these groups was not significantly different during the SGS. Apparently, resistance to the pathogenic effects of reinfection had developed more strongly and at lower levels of exposure to infection than resistance against establishment of larvae as shown after an experimental challenge. The groups of calves not infected during the FGS did gain less than all other groups during the SGS. Further, infection-induced differences in weight gain among the infected groups in the FGS appeared to be permanent, at least up to the end of the SGS. Finally, first lactation yield was positively correlated with body weight at calving. On average, approximately 10 kg less milk was produced for each kg of lower body weight at calving. With respect to the implications for preventive control strategies in the FGS, it is suggested that parasite control should not be applied beyond a level at which weight gain reduction is prevented.

Animal Feed↗

The effectiveness of doramectin pour-on in the control of gastrointestinal nematode infections in cow-calf herds.

Two field studies were conducted in the USA to determine the efficacy of a single strategically-timed dose of doramectin pour-on in the control of gastrointestinal nematodosis in beef cow-calf herds and the resultant effects on calf productivity. One study was carried out between May and October 1996 in a spring-calving herd at a site located in Idaho (ID) and the other between January and July 1997 in a fall-calving herd at a site located in Mississippi (MS). In each study, cow-calf pairs were randomly allotted by sex of calf to pastures and one of two treatment groups (doramectin pour-on at the recommended dose rate of 500 microg/kg body weight or untreated control). There were four pasture replicates per treatment at each site. Each pasture contained 12 cow-calf pairs at the ID site and 15 cow-calf pairs at the MS site. Treatment was administered to cows and calves on 21 May 1996 (ID) or 23 January 1997 (MS). Following treatment, cow-calf pairs were assigned to their designated pastures where they remained until the calves were weaned 140 (ID) or 168 (MS) days later. Cow and calf fecal egg counts and calf body weights were recorded on treatment day and then at monthly intervals until study termination. Doramectin treatment reduced nematode egg output in cows and calves over the entire grazing season compared to untreated controls and resulted in calf weight gain improvements of 9.8kg (p=0.295) at the ID site and 17.4kg (p=0.0002) at the MS site.

Animals↗