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PubMed2004

Resistance to benzimidazole and macrocyclic lactone anthelmintics in cattle nematodes in Argentina.

In April 2003, persistent scouring and ill-thrift that was reported in calves form an intensive beef rearing operation in central Argentina despite treatments with benzimidazole and ivermectin. In order to conduct a controlled faecal egg count reduction test on this herd, 40 calves 5-8-months-old were selected on the basis that they had a nematode eggs per gram (epg) of faeces count greater than 150. Animals were divided into four groups (1-4) of 10 calves. Calves of groups 1-3 were treated, respectively, with subcutaneous injection of ivermectin (200 mcg/kg), ricobendazole (4 mg/kg) and levamisole (7.5 mg/kg), while calves of group 4 remained as untreated controls. The egg count reductions carried out 10 days later were lower than 15% in calves treated with ivermectin and ricobendazole, but 100% in animals receiving levamisole. Pooled post-treatment faecal cultures showed larval percentages of 92 and 95 for Haemonchus and 8 and 5 for Cooperia in the faeces of calves treated with ivermectin and ricobendazole, respectively. This is the first reported case of Haemonchus parasiting cattle showing simultaneous resistance to avermectins and benzimidazole type anthelmintics.

Albendazole↗
PubMed2005

Multiple anthelmintic resistance in Haemonchus contortus isolated from South African Boer goats in Switzerland.

A suspected case of multiple anthelmintic resistance on a farm in the canton of Zurich, Switzerland, into which South African Boer goats had previously been imported, was confirmed in a controlled test. Twenty sheep were allocated into one control group and three treatment groups to determine the efficacy of mebendazole, ivermectin and moxidectin applying the faecal egg count reduction test (FECRT). The sheep were slaughtered 1 week later and post-mortem worm counts were performed. Benzimidazole and ivermectin resistance were found in Haemonchus contortus with an efficacy of 55 and 61%, respectively. Moxidectin appeared to be effective when the data was analysed according to the recommended analytical techniques with an efficacy of 96%. This is the first description of resistance of gastrointestinal nematodes to one of the macrocyclic lactones in small ruminants in Switzerland. The results are discussed in relation to the importance of controlling livestock before importation.

Abomasum↗
PubMed2005

Is anthelmintic resistance a concern for heartworm control? What can we learn from the human filariasis control programs?

Heartworm prophylaxis is currently largely dependent on the ability of avermectins and milbemycins to arrest the development of third and fourth stages of Dirofilaria immitis for prolonged periods, without producing adulticidal effects. Major control programs, dependent on the activity of ivermectin, are being implemented for human onchocerciasis and lymphatic filariasis. The avermectins and milbemycins act on glutamate-gated and gamma-aminobutyrate-gated chloride channel subunit proteins in nematodes. Ivermectin resistance has been widely described in trichostrongylid nematodes of ruminants. There is evidence that when ivermectin resistance occurs in nematodes, there may be selection on some, but not all of the genes that code for ligand-gated chloride channel subunit proteins as well as on some ABC-transporter genes, whose products may be involved in regulating macrocyclic lactone drug concentrations at receptors, and on some structural protein genes of amphidial neurones. Although ivermectin resistance has not been reported in filarial nematodes, there have recently been reports of suboptimal responses to ivermectin in Onchocerca volvulus. Evidence has been found of ivermectin selection on at least ABC-transporter genes and some neuronal structural protein genes in O. volvulus. To date, there is no evidence of avermectin/milbemycin resistance in D. immitis, also a filarial nematode. Chemotherapy against trichostrongylids of animals, human filariae, and D. immitis, relies on avermectins or milbemycins. However, control involves targeting different stages or processes in the nematode life cycles, different control strategies, different proportions of the nematode population in refugia, and different drug dosage rates. Consideration of the proportion of the D. immitis population normally in refugia, the life cycle stage targeted, and the anthelmintic dosages used suggest that it is unlikely that significant avermectin/milbemycin resistance will be selected in D. immitis with current treatment strategies.

Animals↗
PubMed2005

The effectiveness of copper oxide wire particles as an anthelmintic in pregnant ewes and safety to offspring.

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 (<or=4 g) have been used in lambs without clinical signs of copper toxicity. Use in pregnant ewes has not been examined. Mature Katahdin ewes were administered 0 (n=14), 2 (n=15), or 4 (n=15)g of COWP 33+/-1.6 days before lambing in late March 2004. Fecal egg counts (FEC) and blood packed cell volume (PCV) were determined between Days 0 (day of COWP administration) and 35. Lambs were weighed within 24h after birth, at 30 and 60 days of age, and in mid-September ( approximately 120 days of age). Blood was collected from lambs within 24h after birth and at 30 days of age for determination of the activity of the liver enzyme, aspartate aminotransferase (AST) in plasma. Within 7 days after COWP administration, FEC decreased by 1308 and 511 eggs/g (epg) in the 2 and 4 g groups, respectively, compared with an increase of 996 epg in the control group (P<0.02). PCV was similar among groups between Days 0 and 35. Lamb plasma AST activity at birth increased with increasing dose of COWP in dams (P<0.001). Plasma AST activity at 30 days of age was similar for lambs from ewes treated with 0 and 2g COWP, but was slightly greater in lambs from ewes treated with 4 g COWP (P<0.02). Birth weights decreased with increasing COWP (P<0.003). By 30 (COWPxbirth type, P<0.02) and 60 (COWPxbirth type, P<0.02) days of age, weight of multiple-born lambs decreased with increasing COWP, while weight of single-born lambs was similar among treatments. In mid-September ( approximately 120 days of age) weights of multiple-born lambs from ewes treated with 4 g COWP tended to be lightest compared with lambs from ewes treated with 0 or 2g COWP or single-born lambs (P<0.09). Lamb survival to 30, 60, or 120 days of age was not affected by COWP treatment to ewes. Administration of 4 g COWP to late pregnant ewes may negatively impact multiple-born offspring, but the 2g appears to be safe for production.

Animals↗
PubMed2005

Contractile activity and motility responses of the dog heartworm Dirofilaria immitis to classical anthelmintics and other compounds.

A variety of compounds including classical anthelmintics and avermectin analogs were screened for their effects on movements of adult heartworms (HW) (Dirofilaria immitis). Contractile activity was measured by tension recording of spontaneous movements of intact HW coil preparations (6 min compound exposure) and motility was evaluated by observation of spontaneous, free movements in culture (3 and 7 days compound exposure). Results for female HW indicated that some compounds caused spastic paralysis of contractile activity and inhibition of motility in culture (bephenium, DL-tetramisole, and pyrantel); some caused only spastic paralysis of contractile activity (methyridine and disophenol); and some caused only inhibition of motility in culture (chlorpromazine, dithiazanine, 1-ethoxycarbonylmethyl-1-methylpyrrolidinium, and 4-methyltropolone). Effects on motility in culture appeared to be lethal. The following compounds lacked effects: amprolium, 2-amino-2-thiazoline, bithionol, bitoscanate, bitriben, hexachlorophene, ivermectin, and 10 H-phenothiazine. A group of avermectin analogs was screened for effects only on motility in culture of both adult female and male HW. Several of the analogs affected motility, but the effects appeared to be non-lethal. Microfilaria release into the culture media was suppressed by two of the analogs (an aglycone and avermectin B2). The HW maintenance system used in the present study facilitated screening of compounds for effects on this parasite.

Animals↗
PubMed2006

Molecular diagnosis of anthelmintic resistance.

Conventional and real time polymerase chain reaction-based tests have been developed for the diagnosis of anthelmintic resistance (AR) in populations of several small and large ruminant as well as horse gastro-intestinal nematode species. To date, molecular markers that correlate well with AR are available only for the detection of benzimidazole resistance. Recently, however, a single nucleotide polymorphism was found in vitro to be of functional relevance for reduced drug efficacy to macrocylic lactones. The focus of the present review, therefore, is the molecular mechanism of action of these two drug classes and potential applications of this knowledge to the diagnosis of AR. It is argued that a prerequisite for future molecular diagnosis will be tests providing reliable and exact quantification of resistance related alleles in DNA extracted from representative pools of parasites.

Animals↗
PubMed1999

The cost of large-scale school health programmes which deliver anthelmintics to children in Ghana and Tanzania. The Partnership for Child Development.

It has been argued that the delivery of anthelmintics to school-children through existing education infrastructure can be one of the most cost-effective approaches to controlling parasitic worm infection. This paper examines the actual costs of a combination of mass and selective treatment for schistosomiasis using praziquantel and mass treatment for intestinal nematodes using albendazole, as an integral part of school health programmes reaching 80442 pupils in 577 schools in Volta Region, Ghana, and reaching 109099 pupils in 350 schools in Tanga Region, Tanzania. The analysis shows that financial delivery costs per child treated using praziquantel, which involved a dose related to body mass and a prior screening at the school level, were US$ 0.67 in Ghana and US$ 0.21 in Tanzania, while the delivery costs for albendazole, which was given as a fixed dose to all children, were US$ 0.04 in Ghana and US$ 0.03 in Tanzania. The higher unit costs in Ghana reflect the epidemiology of infection; overall, fixed costs were similar in both countries, but fewer children required treatment in Ghana. Analysis of economic costs-which includes the cost of unpaid days of labour--indicates that the financial costs are increased in Ghana by 78% and in Tanzania by 44%. It is these additional costs which are avoided by integration into an existing infrastructure. It is concluded that: the base cost of delivering a universal, standard, school-based health intervention can be as low as US$ 0.03 per child treated; that even a slight increase in the complexity of delivery can have a significant impact on the cost of intervention; and that the use of the education infrastructure does indeed offer significant savings in delivery costs.

Albendazole↗
PubMed2002

A glutamate-gated chloride channel subunit from Haemonchus contortus: expression in a mammalian cell line, ligand binding, and modulation of anthelmintic binding by glutamate.

Glutamate-gated chloride channels (GluCls) are inhibitory ion channels that are sensitive to the antiparasitic drugs ivermectin (IVM) and moxidectin (MOX). We have transiently transfected COS-7 cells with a subunit of a GluCl (HcGluCla) from the parasitic nematode Haemonchus contortus. This subunit bound [3H]-IVM and [3H]-MOX with K(d) values of 0.11+/-0.021 and 0.18+/-0.02nM, respectively. Displacement analysis revealed that IVM and MOX bind to the same site on HcGluCla and that this site is likely distinct from the glutamate binding site. Glutamate was found to be an allosteric modulator of [3H]-MOX and [3H]-IVM binding and increased the affinity of [3H]-MOX for HcGluCla by more than 50% and that of [3H]-IVM by more than 7-fold. These results point to both similarities and differences in the interactions of IVM and MOX with the GluCl. Aspartate, which is structurally similar to glutamate, had little or no effect on [3H]-IVM and [3H]-MOX binding, suggesting that this ligand does not induce the conformational change necessary to potentiate macrocyclic lactone binding. These results also indicate that it may be possible to enhance the efficacy of macrocyclic lactone anthelmintics by administering these compounds with ligands acting allosterically to enhance their binding.

Animals↗
PubMed2001

Filaricidal efficacy of anthelmintically active cyclodepsipeptides.

PF 1022A, a novel anthelmintically active cyclodepsipeptide, and Bay 44-4400, a semisynthetic derivative of PF 1022A were tested for filaricidal efficacy in Mastomys coucha infected with Litomosoides sigmodontis, Acanthocheilonema viteae and Brugia malayi. The parent compound PF 1022A showed limited anti-filarial efficacy in L. sigmodontis and B. malayi infected animals. Oral doses of 5 x 100 mg/kg on consecutive days caused only a temporary decrease of microfilariaemia levels. By contrast, Bay 44-4400 was highly effective against microfilariae of all three species in single oral, subcutaneous and cutaneously applied (spot on) doses. Minimum effective doses (MED, reducing parasitaemia density by > or =95%) determined 3 and 7 days after treatment were 3.125-6.25 and 6.25-12.5mg/kg, respectively. Using the spot on formulation, doses of 6.25mg/kg (L. sigmodontis), 12.5mg/kg (A. viteae) and 25mg/kg (B. malayi) were required to cause reductions of microfilaraemia levels by > or =95% until day 56. Adulticidal effects, determined as minimum curative doses (MCD, eliminating adult parasites within 56 days by >95%) after single dose treatment were limited to A. viteae (MCD, 100mg/kg independent of the route of administration). Repeated oral treatment (100mg/kg on 5 consecutive days) killed all adult L. sigmodontis but did not affect B. malayi. However, single doses of 6.25 and 25mg/kg resulted in severe pathological alterations of intrauterine stages of L. sigmodontis and B. malayi, respectively. These alterations may be responsible for long-lasting reductions of microfilaraemia even when curative effects could not be achieved.

Administration, Oral↗
PubMed1997

The death rate of Ostertagia circumcincta and Trichostrongylus colubriformis in lactating ewes: implications for anthelmintic resistance.

Lactating adult Romney ewes were infected, 4 weeks post-lambing, with benzimidazole (bz) resistant strains of Ostertagia circumcincta and Trichostrongylus colubriformis. Commencing 4 weeks after the initial infection the ewes were subjected to challenge 3 times weekly with 5000 L3 of bz-susceptible strains of both parasite species. At weekly intervals over the following 6 weeks, groups of ewes were drenched with a bz anthelmintic (oxfendazole) to remove bz-susceptible parasites and slaughtered to determine adult worm burdens of the bz-resistant parasites. The O. circumcincta infection declined exponentially with a mean daily death rate of 10.6% day-1 and no worms were recovered after 4 weeks or more of challenge. The T. colubriformis infection did not decline significantly over the 6 weeks of continuous challenge, indicating that the death rate could not be distinguished from zero. The upper 95% confidence limit for the death rate of T. colubriformis was 4.9%. The implications of these death rates on selection for drug resistance following ewe drenching during the post-partum period are discussed with selection pressure likely to be greater for T. colubriformis than for O. circumcincta.

Animals↗
PubMed1990

Determination of benzimidazole anthelmintics in meat samples.

A procedure for the detection of eight benzimidazole anthelmintics in meat samples using high-performance liquid chromatography is described. The limits of detection are in the range 20-50 micrograms/kg with a recovery of 66-87%. Chromatography is performed on an octadecylsilane column using mobile phases of acetonitrile-water with an ion-pair reagent, with UV detection. For verification of positive results, the drug substances are derivatized to methyl or pentafluorobenzyl derivatives suitable for detection by gas chromatography-mass spectrometry in the electron-impact or positive or negative chemical-ionization mode.

Animals↗
PubMed2003

The effects of benzimidazole anthelmintics on P4501A in rat hepatocytes and HepG2 cells.

Benzimidazole anthelmintics including albendazole, fenbendazole, and mebendazole are widely used in veterinary medicine. The effects of these benzimidazoles on cytochrome P4501A were investigated in primary cultures of rat hepatocytes and in the HepG2 cell line. After incubation of rat hepatocytes and HepG2 for 24-, 48-, and 72-h cells with drugs at various concentrations (0.1-50 microM), the enzyme activities associated with P4501A1/2 (7-ethoxyresorufin O-deethylation and 7-methoxyresorufin O-demethylation) were measured. The P4501A1/2 protein levels in both model systems were determined by Western blotting. Although all benzimidazoles provoked a significant increase of P4501A1/2 protein levels and P4501A activities, large differences in the induction response were found which was dependent on drug structure, concentration, and model system used. Based on the results, relationships between induction potency and structure of drug were demonstrated, as well as differences between the in vitro systems used. Therefore, pharmacological and toxicological consequences of cytochrome P4501A induction by benzimidazole drugs should be taken into account in veterinary therapy.

Animals↗
PubMedDate not supplied

Is the exclusion of children under 24 months from anthelmintic treatment justifiable?

There are no reports documenting toxicity or adverse effects after treatment of children aged < 24 months with benzimidazole derivatives and there is an urgent need to clarify this point in light of the potential detrimental effect that soil-transmitted helminthiasis has on this age-group. A total of 653 treatments (317 mebendazole 500 mg; 336 placebo) were administered in 1996/97 to 212 children aged < 24 months as part of a 1-year anthelmintic drug study conducted among preschool-age children in Tanzania. Data on fever, cough, diarrhoea, dysentery and acute respiratory illness were collected 1 week following the treatment. No differences between the occurrence of adverse effects in the 2 groups were observed. In light of the potential nutritional benefit achieved by regular deworming in this young age-group, the policy that excludes children aged < 24 months from treatment should be re-considered.

Anthelmintics↗
PubMed2003

Effects of the antibacterial agents tiamulin, olanquindox and metronidazole and the anthelmintic ivermectin on the soil invertebrate species Folsomia fimetaria (Collembola) and Enchytraeus crypticus (Enchytraeidae).

Veterinary pharmaceutical products such as antibacterial agents and antiparasitics are widely used to control diseases and promote production in the agricultural sector. Exposure of non-target organisms are a likely result of using manure from treated live stocks or from dung dropped on the field by grazing animals. The aim of this study was to determine the toxic threshold levels of three antibacterial agents (tiamulin, olanquindox and metronidazole) and one anthelmintic (ivermectin) to two species of soil dwelling organisms (springtails and enchytraeids), that are often found in bio-solids such as manure or dung. The antibacterial agents were not toxic to adults and effects on reproduction occurred generally above concentrations normally found in soil or dung. The threshold values for toxicity (10% reduced reproduction or EC10 values) were in the range of 61-111 mg kg(-1) dry soil for springtails and 83-722 mg kg(-1) dry soil for enchytraeids. Ivermectin was significantly more toxic with EC10 values of 0.26 mg kg(-1) dry soil for the springtails and 14 mg kg(-1) dry soil for the enchytraeids. A comparison of these results with rough estimates of likely and worse case environmental concentrations indicates a potential risk of ivermectin to non-target species such as springtails and enchytraeids, whereas direct toxic effect of antibacterial agents is very unlikely to occur at environmental realistic concentrations. However, indirect effects of antibacterial agents driven through changes in the food web cannot be abolished at this stage.

Animals↗
PubMed1997

Returns from strategic anthelmintic treatments in village cattle in the Gambia.

A large-scale study was undertaken to investigate the effects of two systematic anthelmintic treatments on village cattle productivity in the Gambia. Treated animals had significantly higher performance in terms of live weights and age at first calving, but the mortality rate of 0- to 1-yr-old cattle appeared to be negatively affected. These results and financial data on treatment costs were used in a herd simulation model to assess the profitability of the intervention. Treatment was profitable on average, but the risks of losing money were large and average returns were sensitive to various hypotheses examined. The treatment regimen studied can only be recommended in certain herds and further research is needed to identify the factors determining the negative response in other herds.

Aging↗
PubMed2001

Effects of previous suppressive anthelmintic treatments on subsequent nematode infection in fattening cattle in Argentina.

The effect of previous suppressive anthelmintic treatments after weaning on parasitological parameters and weight gain of cattle was studied in the Pampeana region of Argentina. The study was carried out at two grazing fattening periods: April 1995/July 1996 and April 1997/July 1998. During both periods, 60 weaned calves that grazed contaminated pastures, were divided into three groups during the first part of the periods: GY1 group was treated every 2 weeks with doramectin while GY2 and GY3 groups remained untreated. During the second part of the periods, from October onwards GY1 and GY2 remained untreated and GY3 was treated every 2 weeks. In this second period two new groups of 20 weaning young calves were added: TG (treated every 2 weeks) and UG (untreated). Egg counts (EPG), larval cultures, pasture larval counts, serum pepsinogen (Pep) and live weight gain (LWG) were recorded monthly. Ostertagia, Cooperia, Trichostrongylus and Haemonchus were the predominant genera. Despite low levels of previous infection during the first part of the period, slight differences of EPG between GY1 (P<0.09) or UG (P<0.05) and GY2 were detected in the second part of the fattening period in 1995/1996. In 1997/1998 moderate infection levels during the first part of the period were observed. During the second part of this period, GY1 and UG showed higher (P<0.001) EPG than GY2, and only GY3 and TG had (P<0.05) lower Pep levels. Also, during the second part of 1997/1998, LWG responses of GY3 were higher (P<0.001) than those of GY1 and GY2. Live weight gain of GY2 exceeded GY1 by 10.7kg (P<0.006). Higher EPG and lower LWG of GY1 suggest that suppressive treatments negatively affected the level of resistance to infection of yearlings, but these effects were influenced by previous levels of nematode infection. The lack of differences between yearling (GY1) and calves (UG) groups suggest that, under the conditions of this study, there was no evidence that resistance to infection and the related parameters are influenced by the age.

Age Factors↗
PubMed2001

Direct anthelmintic effects of condensed tannins towards different gastrointestinal nematodes of sheep: in vitro and in vivo studies.

In vitro and in vivo studies were conducted to determine possible direct anthelmintic effects of condensed tannins towards different ovine gastrointestinal nematodes. A larval development/viability assay was used to investigate the effect of a condensed tannin extract (Quebracho) towards larvae of Haemonchus contortus, Teladorsagia circumcincta and Trichostrongylus vitrinus. The development to infective larvae and their viability was assessed in all three species and LD 50 values were calculated. The presence of Quebracho extract in the cultures decreased the viability of L3 in all species; the LD 50 were not significantly different for the different species. Forty-eight sheep were allocated to one of eight groups and were infected with a single dose of either 4000 L3 H. contortus (groups 1 and 2) or 5000 L3 T. colubriformis and 5000 L3 Nematodirus battus simultaneously (groups 3-6) or 10,000 L3 of T. circumcincta (groups 7 and 8). From day 28 until day 31 of the experiment, sheep infected with the intestinal species were drenched with Quebracho extract at 4, 8 or 16% w/w of food intake, or remained as undrenched controls; sheep infected with the abomasal species were either drenched with Quebracho extract at 8% w/w of food intake or remained as undrenched controls. All sheep were slaughtered 4 days after the end of the drenching period. Sheep infected with the intestinal species and drenched with 16% w/w Quebracho had lower FEC compared to sheep drenched with 8% w/w (P<0.05), which in turn were lower than in sheep either drenched with 4% Quebracho or which remained undrenched (P<0.05). The lowest intestinal worm burden was recovered from sheep drenched with 8% w/w Quebracho extract (P<0.05). The administration of Quebracho extract at 8% of food intake for 3 days did not affect FEC or worm burdens in sheep infected with the abomasal species compared to controls.

Animal Feed↗
PubMed2002

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

These guidelines have been designed to assist in the planning, operation and interpretation of studies which would serve to assess the efficacy of drugs against internal parasites of horses. Although the term anthelmintic is used in the title and text, these guidelines include studies on drug efficacy against larvae of horse bot flies, Gasterophilus spp., which are non-helminth parasites commonly occurring in the stomach of horses. The advantages, disadvantages and application of critical and controlled tests are presented. Information is also provided on selection of animals, housing, feed, dose titration, confirmatory and clinical trials, record keeping and necropsy procedures. These guidelines should assist both investigators and registration authorities in the evaluation of compounds using comparable and standard procedures with the minimum number of animals.

Animals↗