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PubMed2002

Anthelmintic efficacy of Flemingia vestita: genistein-induced effect on the activity of nitric oxide synthase and nitric oxide in the trematode parasite, Fasciolopsis buski.

The root-tuber peel of Flemingia vestita, an indigenous leguminous plant of Meghalaya (Northeast India), has usage in local traditional medicine as curative against worm infections. The peel and its active component, genistein, have been shown to cause flaccid paralysis, deformity of tegumental architecture and alterations in the activity of several enzymes in platyhelminth parasites. To investigate further the mode of action and anthelmintic efficacy of the plant-derived components, the crude peel extract of F. vestita and genistein were tested, hitherto for the first time, in respect of the unique neuronal messenger nitric oxide (NO) and the enzyme nitric oxide synthase (NOS) in Fasciolopsis buski, the large intestinal fluke of swine and human host. NADPH-diaphorase histochemical staining (a selective marker for NOS in neuronal tissues), which was demonstrable in the neuronal cell bodies in the cerebral ganglia, the brain commissure, the main nerve cords and in the innervation of the pharynx, ventral sucker, terminal genitalia and genital parenchyma of the parasite, showed a stronger activity in the treated worms. In biochemical analysis also, the NOS activity showed a significant increase in the parasites treated with the test materials and reference drug, compared to the untreated controls. The increase in NOS activity in the treated parasites can be attributed to an inducing effect of the plant-derived components.

Animals↗
PubMed2003

Anthelmintic efficacy of Flemingia vestita (Fabaceae): Effect of genistein on glycogen metabolism in the cestode, Raillietina echinobothrida.

The edible root-tuber peel of Flemingia vestita and its major active component, genistein, have been earlier shown to have a vermifugal/vermicidal effect on cestodes in vitro by causing a flaccid paralysis and alterations in the tegumental architecture and activity of several enzymes associated with the tegumental interface of the parasite. Pursuing further investigation on the mode of action of this putative anthelmintic, the crude peel extract and pure genistein were further tested in respect of glycogen metabolism in the fowl tapeworm, Raillietina echinobothrida. On exposure to the plant root peel crude extract (5 mg/ml) and genistein (0.2 mg/ml), the glycogen concentration was found to decrease by 15-44%, accompanied by an increase of activity of the active form of glycogen phosphorylase (GPase a) by 29-39% and decrease of activity of the active form of glycogen synthase (GSase a) by 36-59% in treated parasites as compared to untreated controls, but without affecting the total activity (a+b) of both the enzymes. Praziquantel (1 microg/ml), the reference drug, also caused quantitative reduction in glycogen level and alterations in enzyme activities somewhat at par with the genistein treatment. These results suggest that this plant-derived component may influence the glycogen metabolism of the parasite by directing it towards utilization of glycogen.

Animals↗
PubMed1988

An investigation of hookworm infection and reinfection following mass anthelmintic treatment in the south Indian fishing community of Vairavankuppam.

Hookworm infections, as assessed by counting worms expelled following anthelmintic treatment and by egg output, were found to be of low prevalence and intensity in a South Indian fishing community. The initial overall prevalence of infection in the community was 43%, and the average burden was estimated at 2.2 hookworms per person. The age profiles of prevalence and intensity differed between males and females, with the latter harbouring significantly higher levels of infection. Children of both sexes under 10 years of age rarely harboured hookworms. Treatment with pyrantel pamoate was estimated to be 91% effective in clearing hookworm infections. Egg counts made on stools collected during an 11-month period of reinfection indicated that female patients became reinfected soon after treatment, while little hookworm egg excretion was observed in males during the observation period following treatment. Females acquired a significantly higher number of worms during the reinfection period compared with males, although the average burden in females reached only 28% of the initial, pre-treatment level. The hookworm population consisted of predominantly Necator americanus, and less than 10% of Ancylostoma duodenale. The parasites were highly aggregated within the host population with 10% of the community harbouring over 65% of the total hookworms. Low values of the negative binomial aggregation parameter, k, (indicating extreme over-dispersion) were recorded in groups stratified by age and sex. Highly significant positive correlations were observed between the initial (pre-treatment) and reinfection worm burdens of female (but not of male) patients. It is suggested that occupational practices related to walking through areas contaminated with hookworm larvae play an important role in generating the observed patterns of infection within this community.

Adult↗
PubMed1988

The importance of host age and sex to patterns of reinfection with Ascaris lumbricoides following mass anthelmintic treatment in a South Indian fishing community.

Analysis of egg and worm counts of Ascaris recorded at various intervals following a mass anthelmintic treatment programme in a South Indian fishing community is presented. Three indices of infection in the community are compared, namely the prevalence and intensity of egg output (at 2, 6 and 11 months following treatment) and the number of worms expelled following an 11 month period of reinfection. Detailed examination of these measurements revealed significant associations with patient sex and age. The age-prevalence profile of Ascaris infection changed little over time (except immediately following treatment) with the peak prevalence found in the 5-9 year age group. Although 85% of both males and females harboured Ascaris initially, the prevalence following 11 months reinfection was decreased, due to a significantly lower proportion of males being reinfected. By the 11th month of reinfection, the age-intensity profiles of egg output were similar to those observed at initial treatment in the older age groups (10 years and above) and in male children (less than 10 years). However, a dramatic increase in the egg output of female children, greatly exceeding the initial mean, was observed within a 6 month period of reinfection. The intensity of egg output did not accurately reflect the abundance of Ascaris recovered via drug-induced expulsion following an 11 month period of reinfection. Although the egg output attained preintervention levels, the average worm intensity reached only half the initial value. The trends in the sex- and age-intensity profiles were consistent at the two sampling dates and showed similar patterns to the egg output curves. The relevance of the results to helminth control and the monitoring of reinfection is discussed.

Adolescent↗
PubMed2006

The early drug selection of nematodes to anthelmintics: stochastic transmission and population in refuge.

We have developed an individual-based model to reflect the complexity of the early phase of drug resistance selection in a nematode/sheep model. The infection process consists of the stochastic ingestion of infective larvae spatially aggregated in clumps. Each clump corresponds to infective larvae, which are the offspring of the mature nematodes from a given sheep. We studied the dynamics of the parasitic population and the frequency of the recessive resistance alleles during selection by anthelmintic treatments. The interaction between genetic and demographic processes illustrated the trade-off between the control of the infection and the delay of resistance selection. We confirmed the importance of the number of treatments and their timing. The same treatment frequency may result in different outcomes on resistance selection in relation to the size of the refuge (infective larvae on pasture). Treatment applied during the summer (when the mortality of infective larvae on pasture was high), may lead to a rapid selection of drug resistance and a lack of control of sheep and pasture contamination. We showed that higher stocking rates were also a force in promoting the resistance allele selection.

Animals↗
PubMed2006

Anthelmintic action of plant cysteine proteinases against the rodent stomach nematode, Protospirura muricola, in vitro and in vivo.

Cysteine proteinases from the fruit and latex of plants, including papaya, pineapple and fig, were previously shown to have a rapid detrimental effect, in vitro, against the rodent gastrointestinal nematodes, Heligmosomoides polygyrus (which is found in the anterior small intestine) and Trichuris muris (which resides in the caecum). Proteinases in the crude latex of papaya also showed anthelmintic efficacy against both nematodes in vivo. In this paper, we describe the in vitro and in vivo effects of these plant extracts against the rodent nematode, Protospirura muricola, which is found in the stomach. As in earlier work, all the plant cysteine proteinases examined, with the exception of actinidain from the juice of kiwi fruit, caused rapid loss of motility and digestion of the cuticle, leading to death of the nematode in vitro. In vivo, in contrast to the efficacy against H. polygyrus and T. muris, papaya latex only showed efficacy against P. muricola adult female worms when the stomach acidity had been neutralized prior to administration of papaya latex. Therefore, collectively, our studies have demonstrated that, with the appropriate formulation, plant cysteine proteinases have efficacy against nematodes residing throughout the rodent gastrointestinal tract.

Animals↗
PubMed1998

Neurophysiology of glutamatergic signalling and anthelmintic action in Ascaris suum: pharmacological evidence for a kainate receptor.

Electrophysiological and pharmacological techniques were used to study glutamatergic signalling in the parasitic nematode, Ascaris suum. Glutamate or kainate injections into whole worms produced a paralysed quasi-static posture similar to the waveform in behaving worms. The DE2 motorneuron class is a primary target. Several glutamatergic substances produced pronounced conductance increases and depolarization in DE2; domoate and kainate were the most potent agonists tested. Glutamate responses and spontaneous excitatory post-synaptic potentials in DE2 were reversibly blocked in sodium-free saline. DE2 sensitivity to exogenous glutamate was sustained during block of synaptic transmission suggesting that glutamatergic receptors are located on DE2 neurons. The glutamate-induced response was localized to the DE2 dendrite, coincident with the synapses responsible for spontaneous potentials in DE2. Steady-state potentials reached during glutamate superfusion were similar to the reversal potentials for both the spontaneous post-synaptic potentials and glutamate, also suggesting that these potentials may be glutamatergic. Non-N-methyl-D-aspartate receptor antagonists partially blocked spontaneous DE2 excitatory potentials and responses elicited by exogenous glutamate and kainate. This glutamatergic pathway may play a role in nematode locomotory behaviour and account for the paralysing anthelmintic action of excitatory amino acid analogues like kainate and domoate.

Animals↗
PubMed1985

Synthesis and anthelmintic activity of 5(6)-(benzimidazol-2-ylcarbamoyl) and (4-substituted piperazin-1-yl)benzimidazoles.

The synthesis of alkyl 5(6)-(benzimidazol-2-ylcarbamoyl)benzimidazole-2-carbamates (6, 7), and alkyl 5(6)-(4-substituted piperazin-1-yl)benzimidazole-2-carbamates (31-40) has been carried out. When the compounds were tested for their anthelmintic activity against Ancylostoma ceylanicum in hamsters, Hymenolepis nana in rats, Litomosoides carinii in cotton rats, and Dipetalonema viteae in Mastomys natalensis, methyl 5(6)-(4-benzoylpiperazin-1-yl)benzimidazole-2-carbamate (31), methyl 5(6)-[4-(2-furoyl)piperazin-1-yl]benzimidazole-2-carbamate and methyl 5(6)-[4-[(diethylamino)carbonyl]piperazin-1-yl]benzimidazole- -2-carbamate (36) showed 100% elimination of tapeworms H. nana at three oral doses of 100-250 mg/kg. Compounds 34 and 36 also killed the microfilariae and adult worms of L. carinii in cotton rats at an intraperitoneal dose of 30 mg/kg given for 5 days.

Ancylostomiasis↗
PubMed2003

Effect of simultaneous and/or consecutive administration of the broad spectrum anthelmintic flubendazole together with praziquantel in experimental Schistosoma mansoni infection.

This study is a trial to demonstrate the effect of the broad spectrum anthelmintic drug flubendazole (methyl 5-(p-fluoro-benzoyl)-2-benzimidazolecarbamate, CAS 31430-15-6), a mebendazole derivative, together with praziquantel (CAS 55268-74-1, EMBAY 8440, Biltricide) in murine schistosomiasis mansoni. Moreover, the relationship between the posttreatment worm burden, oogram pattern, tissue egg load and hepatic granuloma volume was also investigated. Three main groups of Swiss albino mice infected with Schistosoma mansoni cercariae were used in the experiment. Group I included infected untreated control mice. Group II: Subgroup II (a): Animals received 1/3 the dose of praziquantel 25 days post infection. Subgroup II (b): Mice were given 1/3 dose of flubendazole 25 days post infection. Subgroup II (c): Animals received the combination (1/3 dose of flubendazole + 1/3 the dose of praziquantel 25 days post infection. Group III: Subgroup III (a): Mice were given 1/3 the dose of praziquantel 7 weeks post infection. Subgroup III (b): Mice received 1/3 dose of flubendazole 25 days post infection. 24 days later, 1/3 the dose of praziquantel was given. Mice given the consecutive drug regimen (flubendazole 1/3 single oral dose 25 days post infection, then praziquantel 1/3 oral dose for two successive days 24 days later, revealed a significant reduction in the recovery of adult schistosomes after portal perfusion (95.9%), absence of immature stages of ova development, a higher level of dead ova in the oogram and the smallest granuloma mean diameter. These data were less conspicuous in mice given the simultaneous drug regimen.

Animals↗
PubMed2000

Effect of the broad spectrum anthelmintic drug flubendazole upon Schistosoma mansoni experimentally infected mice.

The effect of the broad spectrum anthelmintic drug flubendazole (methyl 5-(p-fluorobenzoyl)-2-benzimidazolecarbamate, CAS 31430-15-6), a mebendazole derivative with a molecular weight of 313.29, on Schistosoma mansoni infection in mice was evaluated. Moreover, the relationship between the posttreatment worm burden, hepatic granuloma volume, and serum immunoglobulin profile (immunoglobulin G and immunoglobulin M, IgG and IgM), was also investigated. Two main groups of Swiss albino mice infected with Schistosoma mansoni cercariae were used in the experiment. Group I consisted of infected untreated control mice. The mice of group II were submitted to treatment with flubendazole 100 mg/kg body weight as single oral dose at different time intervals: Group IIa received treatment 24 h before infection. Group IIb received treatment 4 h after infection. Group IIc received treatment 25 days after infection. Mice treated 25 days after infection, compared to those treated in other time intervals, revealed a significant reduction in the recovery of adult schistosomes after portal perfusion (79.5%), a lower immunoglobulin level (IgG and IgM), and the smallest granuloma mean diameter (220.0 +/- 10.3 microns). These data were less salient in mice treated 4 h after, and 24 h before infection.

Animals↗
PubMed1983

Survey of internal parasitism and anthelmintic use in farmed deer.

Faecal samples and questionnaires from 115 and 130 farms respectively were used to survey the internal parasite status of the national deer herd and examine current drenching practices. The survey included farms with red deer and wapiti-red deer crosses (Cervus elaphus), and fallow deer (Dama dama). Gastrointestinal nematode eggs were recorded from 84% of all farms, Dictyocaulus viviparus larvae from 85% of all farms, and Elaphostrongylus cervi larvae from 35% of the farms with C. elaphus. Faecal egg and larval counts were generally low. There was a significant relationship between the presence of Elaphostrongylus and the introduction of deer from Southland/Fiordland. Fenbendazole, oxfendazole and albendazole were the most frequently used anthelmintics of the 14 reported. Drenching programmes were extremely varied.

Journal Article↗
PubMed1989

Utilisation of the persistent anthelmintic activity of ivermectin in a preventive drenching programme for dairy calves.

A study was undertaken to assess whether the persistent anthelmintic effect of ivermectin in cattle would allow an extension of the drenching interval in the currently recommended preventive drenching programme for the control of gastrointestinal nematode infection in dairy calves. A comparison was made of the parasitological and production responses of treatment groups of calves, grazing replicated plots, receiving either six drenches of oxfendazole at four-weekly intervals or four subcutaneous treatments with ivermectin at six-weekly intervals. Compared with the levels of infective larvae on pasture grazed by untreated control calves, mean larval numbers on pasture grazed by ivermectin and oxfendazole treated calves were 94.3% and 98.3% lower, respectively, during the period of maximum larval availability (March-May). Mean liveweight gains (December-August) of the treated groups (101.4kg and 110.2kg respectively) were not significantly different, but both were highly significantly different from that of the untreated controls (57.4kg). Mean plasma pepsinogen levels for the ivermectin, oxfendazole and control groups over the period of maximum values (June-August) were 1.92 i.u., 1.72 i.u. and 5.53 i.u., respectively. The difference between the treated groups was not statistically significant but both were highly significant different from the control group. The present results indicate that four treatments with ivermectin (subcutaneously) at six-weekly intervals achieved a similar level of prophylactic control to that effected by six treatments with oxfendazole at four-weekly intervals.

Journal Article↗
PubMed1989

Multigeneric resistance to benzimidazole anthelmintics in sheep.

Benzimidazole resistance involving several gastrointestinal nematode genera on a single sheep farm in New Zealand is reported for the first time. A controlled slaughter trial showed that at the recommended dose rate of 12.5 mg/kg, mebendazole had efficacies of 0, 60, 66, 90, 54 and 38% against Haemonchus contortus, Ostertagia spp., Nematodirus spp., intestinal Trichostrongylus spp., Strongyloides spp. and Oesophagostomum venulosum, respectively. The relevance of such multigeneric resistance to possible future options for controlling anthelmintic resistant sheep trichostrongylids is briefly discussed.

Journal Article↗
PubMed1989

Multigeneric resistance to benzimidazole anthelmintics in four sheep flocks.

Clinical parasitism associated with multigeneric resistance to benzimidazole anthelmintics was investigated in four sheep flocks during February and March 1989. The genera considered resistant were Haemonchus and Nematodirus spp. on all four farms and Trichostrongylus and Ostertagia spp. on three of the four farms. It is suggested that when investigating cases of suspected drench resistance, post-drenching worm counts are useful to help identify the resistant worm species present.

Journal Article↗
PubMed1989

A survey of anthelmintic resistance on ten goat farms in the Manawatu region in 1988.

A survey of anthelmintic resistance on ten goat farms was carried out. The criterion for resistance was a faecal egg count reduction (FECR) of <90 percent based on arithmetic means of 11 to 19 goats per group. It was found that nine of the ten farms harboured nematodes resistant to oxfendazole when used at 5mg/kg although on two of these, the FECR's were 89.2 percent and 89.8 percent. Post treatment larval cultures indicated Haemonchus, Ostertagia and Trichostrongylus were the resistant genera involved. On none of the ten farms was resistance to oral ivermectin at 0.2mg/kg detected.

Journal Article↗
PubMed1990

The use of benzimidazole-levamisole mixtures for the control and prevention of anthelmintic resistance in sheep nematodes: an assessment of their likely effects.

Literature relevant to the use of benzimidazole-levamisole combinations for the control and prevention of anthelmintic resistance in gastrointestinal nematodes in sheep is reviewed and the likely consequences of such a strategy are considered. It is suggested that while a system of multiple attack involving the simultaneous administration of both compounds, each given at their full recommended individual dose rates, may have limited scope in combatting resistance once it has arisen, as a means of delaying or preventing its emergence in the first place it may be more appropriate. In these latter circumstances, it seems unlikely that the use of a benzimidazole-levamisole mixture would result in a faster build-up of resistance then would the sequential application of either drug on its own, and indeed may greatly delay it.

Journal Article↗
PubMed1990

Simultaneous resistance to two or more broad-spectrum anthelmintics by gastrointestinal nematode parasites of sheep and goats.

The detection, by means of faecal egg count reduction tests and larval cultures, of two cases of multiple anthelmintic resistance in goats and two in sheep, is reported. The former cases appeared to involve resistance to all three broad-spectrum drench groups (benzimidazole, levamisole, ivermectin) by mainly Ostertagia spp., the latter resistance to two of them (benzimidazole, levamisole) by Trichostrongylus spp.

Journal Article↗
PubMed1990

Anthelmintic usage on goat farms in New Zealand: results of a postal survey.

A nationwide postal survey in New Zealand of about 3850 goat farmers was conducted in 1988 to determine gastrointestinal nematode control practices. The analysis of 848 replies revealed that at least 16.9%, 20.0% and 34.4% were drenching their adults, yearlings and kids respectively 10 or more times per year. During 1987-88, 42.0% used only ivermectin, 9.0% only a benzimidazole and 1.9% only levamisole or morantel; 42.7% used anthelmintics from two different action families and 3.5% used all three action families. In total, 85.8% had used ivermectin at some stage during the preceding 12 months. Ivermectin was used by 46.5% during the 1987-88 season and also for the 3 preceding years. Sixty percent estimated the weight of their goats only by eye. Twenty-seven percent set the dose volume of the drench gun for the average weight of the goats in the mob, not the heaviest. Drenching frequency was positively correlated with the ratio of goat stock units to total stock units and also with the actual stocking rate of kids and yearlings.

Journal Article↗