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PubMed1982

Studies on haemonchus contortus. VII. The effect of treatment of Trichostrongylus axei prior to challenge with H. contortus.

Four-month-old worm-free Merino lambs were dosed with 20 000 infective larvae of Trichostrongylus axei on Day 0 and again on Day +14. On Day +83 they were treated with mebendazole at 15 mg/kg. All lambs in this group and a further group of 11 worm-free Merino control lambs were challenged with 50 000 infective larvae of Haemonchus contortus dosed from Day +90-Day +92. At necropsy 27 and 28 days later there was no significant difference between the worm burdens of the 2 groups. T. axei must be present in the abomasum to protect sheep from challenge with H. contortus.

Animals↗
PubMed1982

Quantitative studies of ovine haemonchosis. 2. Relationship between total worm counts of Haemonchus contortus, haemoglobin values and bodyweight.

The relationships between Haemonchus contortus burdens, haemoglobin levels and bodyweight, were examined in 50 commercial Merino sheep, 9-18 months of age, in south-east Queensland where haemonchosis was endemic. Worm counts and haemoglobin levels were predictable (P less than 0.001, r = 0.68) from the equations log worm count = B.wt. X 0.06942 + log worm count X (-2.18896) + 12.51557. Bodyweight was not predictable from either worm counts or haemoglobin levels. Although bodyweight was represented in both equations, it was only a small and insignificant contributor. When haemoglobin levels became moderately depressed (less than 10.5 g%) or severely depressed (less than 8.0 g%), then the number of worms associated with these haemoglobin levels varied with the bodyweight of the sheep. For sheep up to 20 kg, 10.5 g% Hb was associated with 112 worms and 8 g% with 355 worms. However, 355 worms caused only moderate depression of Hb levels in sheep over 50 kg, and 1259 worms were required to cause severe depression (less than 8.0 g%) in sheep over 50 kg. Three sheep were found to be severely anaemic in the presence of less than 100 worms. It was postulated that additional factors of time and nutrition may have affected these sheep. The sheep were of low bodyweight, in poor condition (low fat score) and were subject to high stocking rates on long grass pastures and high rainfall in autumn. Other internal parasite species present were Nematodirus spp. and Trichostrongylus spp. However, their numbers were low (57 and 218 worms, respectively) and did not contribute to anaemia. The correlation between H. contortus and Nematodirus spp. was found to be negative but non-significant (r = -0.26, P less than 0.01), while the correlation between H. contortus and Trichostrongylus spp. was positive and significant (r = 0.38, P less than 0.01).

Abomasum↗
PubMed1981

Five generations of selection with benzimidazole and non-benzimidazole anthelmintics against benzimidazole resistant strains of Haemonchus and Ostertagia spp in sheep.

Benzimidazole resistant strains of Haemonchus contortus and Ostertagia spp were subjected to selection pressure over five laboratory generations with the recommended dose rates of either cambendazole, oxfendazole or morantel. A change in response, with larger residual worm burdens remaining after treatment at the fifth generation, was shown for both cambendazole and oxfendazole against both species of nematode. No change in response against either species are shown for morantel. The results are discussed in terms of the problem associated with inefficient removal of the adult parasites after treatment.

Animals↗
PubMed1978

Haemonchus contortus infections in Targhee and Targhee-Barbados Black-Belly cross lambs.

Targhee and Targhee-Barbados Black-Belly cross lambs that were raised helminth-free were experimentally infected with 10,000 or 25,000 infective larvae of Haemonchus contortus. There were no significant (P = less than 0.05) differences in results of weight gain, packed cell volumes, numbers of eggs per gram of feces, or numbers of helminths between the 2 groups of lambs.

Animals↗
PubMed1981

Studies on Haemonchus contortus. V. Chemoprophylaxis and its effect on worm egg counts and the haematocrit.

A group of 12 10-month-old, worm-free Merino lambs were given a single injection of disophenol at 10 mg/kg. This group and another group of 12 worm-free lambs were infested with infective larvae of Haemonchus contortus 1-3 times a week with a maximum dose of 4000/week from 0-91 days. From 95-168 days the dose was increased to a maximum of 6000/week. Every 7 days faeces were examined for worm eggs and blood samples for haematocrit (Ht). Worm egg counts in the controls rose from 21-56 days, fluctuated, and rose to another peak at 84 days, while the Ht fell from 28 days to rise again after 105 days. In the group treated with disophenol egg counts were negative until 161 days and Ht remained at normal values throughout.

Animals↗
PubMed1980

Efficacy of albendazole and levamisole in sheep against Thysanosoma actinioides and Haemonchus contortus from the Edwards Plateau, Texas.

Lambs naturally infected with Thysanosoma actinioides and naturally and experimentally infected with Haemonchus contortus were used in a controlled experiment to determine the anthelmintic activity of albendazole as compared with levamisole. The lambs were given 10,000 H contortus larvae 25 to 35 days before treatment, were slaughtered 7 to 9 days after treatment, and were housed on concrete from the time of treatment until slaughter. In lambs given doses of 7.5 mg or 3.8 mg of albendazole/kg or 7.5 mg of levamisole/kg, reductions in numbers of H contortus were 99%, 85%, and 98%, respectively. Reductions in numbers of T actinioides were 98%, 45%, and 0% respectively, as compared with untreated controls.

Albendazole↗
PubMed1993

[The behavior of hematological parameters (hemoglobin, hematocrit, leukocyte count) and clinicochemical values in plasma (glucose, total proteins, alpha-amino-N, urea, pepsinogen, ascorbic acid, Fe, Cu, Zn) and the content of ascorbic acid in liver, spleen and adrenal glands in healthy lambs and lambs infected with Haemonchus contortus and Trichostrongylus colubriformis].

In 8 healthy, noninfected lambs with an initial body weight (b. w.) of 24.79 +/- 1.16 kg as well as in 3 groups of lambs (n = 8 per group) of a similar body weight after an inoculation with 3rd stage larvae of Haemonchus contortus (2500) and Trichostrongylus colubriformis (10,000) analyses of the blood plasma were performed for 45 days thereafter. On the 37th day after infection ivermectin (0.2 mg/kg b. w.) was administered per os respectively subcutaneously to the lambs of 2 groups. After 7 and 8 days the content of ascorbic acid in the liver, the spleen and the adrenals as well as that of vitamin A in the liver was analysed. The behaviour of the values influenced by a moderate infection with trichostrongylid nematodes is discussed.

Animals↗
PubMed1993

Controlled tests of activity of several antiparasitic compounds against natural infections of Haemonchus contortus and other helminths in lambs from a flock established in 1962.

Antiparasitic activity of several compounds was evaluated over a long period (about 25 years) in the same flock of sheep. Haemonchus contortus was of special interest, including its relation to drug resistance, especially to thiabendazole and other benzimidazoles, in addition to phenothiazine. Eleven compounds were evaluated in 15 controlled tests, done between 1966 and 1989 in naturally infected lambs (n = 145) born and raised on the same pasture. Sheep were first placed on the pasture in 1962, and a few more were added thereafter. Internal parasites in these sheep were classified in 3 general categories: indeterminate exposure to parasiticides; H contortus, resistant to thiabendazole; and H contortus, resistant to phenothiazine. The parasitic infections probably became more homogeneous after several years because of few introductions of outside sheep after initial establishment of the flock. Activity against naturally acquired internal helminths was evaluated for cambendazole (CBZ: dosage, 20 mg/kg of body weight), fenbendazole (FBZ: 5 or 7.5 mg/kg), mebendazole (MBZ: 10 mg/kg); oxfendazole (OFZ: 3.5 or 10 mg/kg), oxibendazole (OBZ: 10 mg/kg); parbendazole (PBZ: 15 mg/kg), phenothiazine (PTZ: 550 mg/kg); pyrantel pamoate (PRT: 25 mg base/kg), tetramizole (TET: 15 mg/kg); thiabendazole (TBZ: 30 or 44 mg/kg), and trichlorfon (TCF: 100 mg/kg). Thiabendazole was used more often (9 tests) than the other compounds. Thiabendazole was more active against mature H contortus in later years than when first used in 1966, although it was never 100% effective. Efficacy against immature H contortus for TBZ did not exceed 86%. Activity against immature and mature stages of this parasite was good overall for the other benzimidazoles.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1980

Use of disophenol for the control of Haemonchus contortus in sheep in West Java, Indonesia.

The result of a field trial investigating the anthelmintic effect of disophenol against H. contortus in sheep raised under Asian small farming practice is reported. it was clearly shown that a single injection of disophenol suppressed the numbers of H. contortus to very low levels for periods up to 3 months despite the presence of large populations of H. contortus infective larvae available on pasture and herbage grasses.

Animals↗
PubMed2004

Purifying selection and demographic expansion affect sequence diversity of the ligand-binding domain of a glutamate-gated chloride channel gene of Haemonchus placei.

Ninety-five genomic sequences of the ligand-binding domain of glutamate-gated chloride channel genes of three populations of the parasitic nematode H. placei were evaluated for patterns of diversity, demography, and selection. These genes code for subunits of ion channels, which are involved in the mode of action of the most commonly used antiparasitic drugs, the macrocyclic lactones. An extremely high frequency of unique segregating sites in exons and introns was observed, with significantly negative neutrality tests in each population for noncoding, synonymous, and nonsynonymous sites. Several tests indicated that support for balancing selection, positive selection, and hitchhiking was lacking. McDonald-Kreitman tests using H. contortus or C. elegans as an outgroup revealed an extreme excess of replacement polymorphism, consistent with weak purifying selection. Although these tests agree that negative selection may explain the excess of replacement changes, an alternative interpretation is required for the significantly negative Fu and Li's D statistics based on silent and noncoding sites. These include homogeneous forces such as background selection and demographic expansion. The lack of population subdivision and the negative values of Tajima's D for this outbreeding parasitic nematode render background selection less likely than demographic expansion. Comparison of D statistics based on different site types using neutral coalescent simulations supported this interpretation. Although this statistic was more negative for nonsynonymous sites than for synonymous sites, most comparisons of the D statistic were not significantly different between mutation classes. A few significant site comparisons were also consistent with demographic expansion, because the observed test statistic ( D(neutral) - D(selected)) were low relative to the neutral expectations. Finally, previous mitochondrial studies also identified a demographic expansion of this parasitic nematode species, which lends further support to a scenario involving both demographic and purifying forces in the ligand-binding domain of H. placei.

Amino Acid Sequence↗
PubMed2002

Analysis and partial reversal of multidrug resistance to anthelmintics due to P-glycoprotein in Haemonchus contortus eggs using Lens culinaris lectin.

Our previous work has shown that drug efflux pumps close to MDR1 P-glycoprotein (Pgp) can regulate anthelmintic efflux in nematodes in a way similar to that of the mutidrug resistance system (MDR) in vertebrate cancer cells. In the present study, the role of the glycosylation of Pgp was studied using a lectin specific for the alpha-mannosyl residues ( Lens culinaris agglutinin, LCA). Highly significant reversion (up to 50%) in the resistance to thiabendazole of eggs pre-treated with the lectin was obtained. Flow cytometric examinations were performed using FITC-labelled lectin. The results demonstrated that: (1) the number of Pgp sites was higher in resistant H aemonchus contortus, (2) resistance can also be associated with a decreased affinity of LCA for these sites, (3) eggs stained with LCA were also stained with specific MDR1 monoclonal antibodies. The implication of the glycosylation of Pgp in the activity and/or degradation of these pumps in eukaryotic cells is discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Detection of P-glycoprotein-mediated multidrug resistance against anthelmintics in Haemonchus contortus using anti-human mdr1 monoclonal antibodies.

The "multidrug resistance" (MDR) system involves the action of transmembrane P-glycoproteins (Pgp) which may be responsible for failure of chemotherapy in both invertebrates and vertebrates. We previously obtained partial reversion of anthelmintic resistance in nematodes subjected to both anthelmintics and inhibitors of this system. The results presented here are able to describe more accurately the presence of Pgp in nematodes because of the use of C219 and UIC2 monoclonal antibodies, which are used for the detection of human and mouse mdr1 gene products. These antibodies demonstrated the presence of Pgp in eggshells. Their role in these structures, which are considered to be passive barriers, remains to be determined. Flow cytometry analyses of the UIC2 staining allowed determination of the resistance of individuals, which varied within the parasite population. UIC2 demonstrated both the presence and activity of Pgp in nematodes as has previously been shown in tumour cells. Resistance seems to be due to an increase in both the number of Pgp sites and parasites with high levels of Pgp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Cyclohexadepsipeptides (CHDPs) with improved anthelmintical efficacy against the gastrointestinal nematode (Haemonchus contortus) in sheep.

Besides 24-membered cyclooctadepsipeptides (CODPs) with the most prominent member of this class emodepside, the structurally related 18-membered cyclohexadepsipeptides (CHDPs) were of interest with regard to their efficacy against the nematode H. contortus in sheep.The CHDPs prepared by a simple total synthesis represent enniatin derivatives with strong in vivo activity against H. contortus in sheep. The correlation between the nature of the CHDP major conformers and their anthelmintic activities was studied in detail. All CHDPs with strong in vivo activity exists in deuterochloroform solution as conformers with restricted flexibility which was found by 2D-NMR spectroscopic analysis. This reduced flexibility of the major conformer can be exemplified by CHDPs containing e.g.: (i) an unsymmetrically folded conformation with no cis-amide bound, (ii) an internal hydrogen bond or (iii) one cis-amide bond, respectively.The strong in vivo anthelmintic activity against H. contortus in sheep indicates that the stereochemistry in 2-position of CHDPs is less important for their high inding affinity. It may be assumed that the identified inflexible region of the major conformers might mimic the active conformation of these CHDPs, which could be helpful for rational design of anthelmintics with less complicated structures.

Animals↗