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Evaluation of the efficacy of pyrantel-oxantel for the treatment of soil-transmitted nematode infections.

A randomized controlled trial comparing the efficacy of pyrantel-oxantel (10 mg/kg) with mebendazole (500 mg) was performed on 1329 schoolchildren aged 6-9 years on Pemba Island in September-October 2000 to evaluate alternative single-dose drugs for regular treatment of intestinal nematode infections. Both mebendazole and pyrantel-oxantel were very effective in eliminating Ascaris lumbricoides infection, inducing cure rates of more than 96% and reducing the mean egg counts by more than 95%. Both drugs had a moderate efficacy against Trichuris trichiura infection, but pyrantel-oxantel had a higher cure rate (31.5% vs. 23.3%, P < 0.01), though the reductions in egg counts did not differ significantly and were more than 80%. Pyrantel-oxantel and mebendazole had a similar, poor efficacy in curing hookworm infections and had a moderate effect in reducing the egg counts by 67% and 68%, respectively. Pyrantel-oxantel (10 mg/kg) offers a valuable alternative to mebendazole as a single-dose treatment for the control of intestinal nematode infections in children in endemic areas of sub-Saharan Africa, due to its comparable efficacy, its low cost and its suitability for use in young children.

Antinematodal Agents↗

Essential role for TLR4 and MyD88 in the development of chronic intestinal nematode infection.

Expulsion of the gastrointestinal nematode Trichuris muris is mediated by a T helper 2 type response involving IL-4 and IL-13. Here we show that Th1 response-associated susceptibility is dependent on activation signals mediated by MyD88 and Toll-like receptor 4 (TLR4). TLR4- and MyD88-deficient mice are highly resistant to chronic T. muris infection and develop strong antigen-specific Th2 responses in mucosa-associated lymphoid tissues. Hence, TLR4 and MyD88 are involved not only in the development of pro-inflammatory responses against bacterial pathogens but are also crucially involved in responses against multicellular organisms such as helminths. These results provide the first demonstration of the critical role of TLR4 and MyD88 in bridging the innate and acquired immune response during gastrointestinal nematode infection.

Adaptor Proteins, Signal Transducing↗

Stat6 dependent goblet cell hyperplasia during intestinal nematode infection.

To identify the role of signal transducer and activator of transcription factor 6 (Stat6) in the development of intestinal goblet cell hyperplasia during nematode infection, we compared the number of goblet cells in Stat6 deficient (Stat6 -/-) mice with that generated in wild-type (Stat6 +/+) mice in Trichinella spiralis infection. The number of goblet cells significantly increased with infection in wild-type mice. However, Stat6 -/- failed to generate infection-induced goblet cell hyperplasia and a significantly lower number of goblet cells was observed in Stat6 -/- mice on days 14 and 21 postinfection compared to Stat6 +/+ mice. In addition to suppressed goblet cell numbers, Stat6 -/- mice exhibited severe impairment in their ability to produce IL-4 and IL-13 and to expel the parasites from the gut. Our study clearly shows an essential role of Stat6 in intestinal goblet cell hyperplasia which accompanies this infection. We postulate that Th2 cytokines regulate the development of goblet cell hyperplasia in gut during nematode infection via Stat6 activation and that the increased number of goblet cells plays an important role in host protective immunity against the infection.

Animals↗

The influence of stocking rate on gastrointestinal nematode infections of sheep over a 2-year grazing period.

Six groups of four ewes with twin lambs grazed six paddocks during two consecutive seasons from May to September in a two-factorial study on stocking rate (9, 13 and 17 ewes ha-1) and infected (designated I-low, I-medium and I-high) versus clean pasture (C-low, C-medium and C-high). All animals were treated with anthelmintic at turn-out and the C-groups were further treated fortnightly. The two sets of paddocks received 0, 80 and 160 kg N fertilizer ha-1 annually with increasing stocking rate. Ewes were withdrawn at the end of July, and all lambs were slaughtered at the end of the grazing season for total worm counts. Nematode infections were subclinical during the first year. The second year, diarrhoea and soiled hindquarters were present from early August onwards in all I-groups with highest incidence at high stocking rate. The faecal egg counts of I-ewes were similar the first year but were substantially higher in I-medium and I-high compared with I-low in the second year. The lambs had differences in faecal egg counts related to stocking rate both years (P < 0.05) and group I-high had faecal egg counts ten-fold higher than I-medium and I-low at the end of the second year. A significant effect of the interaction of stocking rate times +/- infection was found in serum-pepsinogen levels in lambs (P < 0.05). Worm burdens (predominantly Trichostrongylus vitrinus, Ostertagia circumcincta and Nematodirus filicollis) were not related to stocking rate in lambs at the end of the first year whereas there was a significant effect of stocking rate on T. vitrinus burdens the second year. Pasture larval counts and results of tracer lambs indicated a positive relationship between stocking rate and pasture infectivity. It is concluded that the level of ovine nematode infections, especially Trichostrongylus spp., in weaned lambs increased with increasing stocking rate even though pasture production was enhanced by increased rates of fertilizer application.

Animal Feed↗

Differences in susceptibility to gastrointestinal nematode infection between Angus and Brangus cattle in south Louisiana.

Breed susceptibility to nematode infection was evaluated in Angus (Bos taurus) and Brangus (B. indicus crossbreed) cattle. A cow-calf herd and a yearling replacement heifer herd were monitored during one grazing season. Calves were born in March and were weaned in October. Individual rectal fecal samples were collected monthly from the two herds and processed for fecal egg counts (FEC) and coprocultures. Cow and calf FEC increased from April, reaching maximum values during the summer. Angus cows and calves had significantly (p<0.05) greater FEC than Brangus cows and calves, and Haemonchus and Cooperia were the predominant genera. Replacement heifer FEC showed a similar pattern with maximum levels during late summer/fall, and Haemonchus was the predominant genus. No significant differences were seen between breeds, however, infection levels were consistently lower in Brangus heifers. Ostertagia was present in cows and heifers only in fall/winter, which is consistent with summer inhibition. The data suggested that cows were an important source of pasture contamination for their susceptible calves and that the Brangus breed was relatively more resistant to infection. The use of B. indicus crossbreeds may help in alleviating reliance on chemical control by reducing the rate of pasture contamination and subsequent infection losses.

Animals↗

The dynamics of nematode infections of farmed ruminants.

In this paper the dynamics and control of nematode parasites of farmed ruminants are discussed via a qualitative analysis of a differential equation model. To achieve this a quantity, 'the basic reproduction quotient' (Q0), whose definition coincides with previous definitions of R0 for macroparasites, but extends to models with periodic time-varying transition rates between parasite stages or management interventions, is introduced. This quantity has the usual threshold property: if Q0 is less than one the parasite population cannot maintain itself in the host population, and in the long term becomes extinct; but if Q0 is greater than one the parasite can invade the host population. An alternative quantity, R(E), that is often easier to calculate is also introduced, and shown to have the same threshold property. The use of these two quantities in analysing models for the dynamics of nematodes in complex situations is then demonstrated, with reference to the dynamics of mixed parasite species in one host; the effects of breeding host animals for resistance to parasitism; and the development of parasite strains that are resistant to chemotherapy. Five examples are discussed using parameters for the dynamics of nematode infections in sheep, and some statements on control policies are derived.

Animals↗

Epidemiology of nematode infections of Soay sheep (Ovis aries L.) on St Kilda.

The epidemiology of nematode infections of Soay sheep on the island of St Kilda over a period of 2 years (August 1988-August 1990) spanning a host population crash is described. Infective larvae (L3) levels on pasture were high (2422 +/- 365 L3/kg D.M. grass in midsummer 1988) when host population density was high, decreasing after the sheep population declined by 70% in early 1989 (601 +/- 14 L3/kg D.M. in midsummer 1989). The availability of infective larvae to sheep increased during the winter of 1988-1989, probably as a result of concentration of existing larvae on grass as vegetation was destroyed by bad weather and overgrazing. Increased availability of pre-parasitic stages was accompanied by a marked increased in faecal egg counts from sheep of all ages and both sexes. Prevalence and intensity of infection (faecal egg counts) were higher in males than females throughout the 2-year study (chi 2 = 208.3, P < 0.005 and F1, 2000 = 304, P < 0.001 respectively), except during the lambing periods, and decreased with age in both sexes. Changes in prevalence and intensity of strongyle infections were associated with changes in host population density. Prevalence and intensity of Dictyocaulus filaria larvae in faeces increased during the host population crash. Infection intensity decreased with age (F1, 203 = 44.02, P < 0.001) and was higher in males than females (F1, 203 = 13.45, P < 0.001).

Analysis of Variance↗

Susceptibility of Suffolk and Gulf Coast Native suckling lambs to naturally acquired strongylate nematode infection.

Three trials compared responses to naturally-acquired strongylate nematode infection between suckling Suffolk and Gulf Coast Native (Native) lambs which grazed together. In Trial 1 (1992), infection in 14 lambs of each breed was monitored from birth to 12 weeks of age using fecal egg count (FEC) and blood packed cell volume (PCV). In Trial 2 (1993), two age-matched lambs of each breed were sacrificed at seven and ten weeks of age to estimate nematode burdens. In Trial 3 (1994), infection in 18 lambs of each breed was monitored (FEC, PCV, white blood cell count, differential leukocyte count, and anti-Haemonchus contortus immunoglobulin level) from birth to 8 weeks of age, at which time six age-matched lambs of each breed were sacrificed to estimate nematode burdens. The remaining 24 lambs were monitored until 12 weeks of age. In both Trials 1 and 3, infection in Native lambs peaked and then declined between 6-10 weeks of age. Infection in Suffolk lambs continued to increase as evidenced by increasing FEC with concomitant reduction in PCV, higher morbidity and mortality (Trial 1), and number of anthelmintic treatments required (Trial 3). In Trials 2 and 3, the principal nematode found at necropsy was H. contortus, and infection level was consistently lower (> 64%) in Native compared with Suffolk lambs. In Trial 3, there was no difference between breeds for WBC, any leukocyte type, or anti-H. contortus immunoglobulin level. These results demonstrated that suckling Native lambs developed resistance to H. contortus infection during their first exposure to infection at an age when they are considered immune incompetent and colostrally transferred anti-H. contortus immunoglobulin did not appear to be involved in the resistance.

Age Factors↗

Comparison of two techniques used for the recovery of nematode infective larvae from pasture.

The recovery of gastrointestinal nematode infective larvae from herbage collected manually was compared with the recovery from herbage ingested by sheep with oesophageal fistulae, on five occasions during the grazing season. At least three times more larvae were recovered from the oesophageal fistulates than by manual collection. There was no significant variation between the numbers of larvae collected at 09.00, 12.00 and 15.00, nor was there any difference in the distribution of genera recovered by the two methods. The worm burdens of tracer lambs and the larval counts from the fistulated sheep were used to estimate the rate of larval establishment.

Animals↗

Efficacy of moxidectin against naturally acquired nematode infections in cattle.

The efficacy of moxidectin, a new endectocide against natural nematode infections, was evaluated. Twenty-five calves were divided into two groups of eight calves each and a third group of nine calves. Moxidectin was administered s.c. to two groups (I, 0.2 mg kg-1 body weight (BW); II, 0.3 mg kg-1 BW) and the third group (III) received the vehicle (placebo) s.c. Two pre-treatment and one post-treatment faecal nematode egg count determinations were made from all calves, and they were necropsied 2 weeks after treatment for the identification and enumeration of nematode parasites. Group III calves, which received the drug-free vehicle, harboured eight species of nematodes (Ostertagia ostertagi, Trichostrongylus axei, Cooperia oncophora, Cooperia punctata, Nematodirus helvetianus, Trichuris discolor, Oesophagostomum radiatum and Dictyocaulus viviparus). The mean total worm burden for this group was 8935. There was a significant reduction in the numbers of many species of nematodes (Ostertagia, Trichostrongylus, Cooperia and Nematodirus) in both treated groups. Cooperia oncophora was reduced by 94% in Group I and by 96% in Group II, while all other nematode species were reduced by 99%. Immature stages of Ostertagia and Nematodirus were significantly reduced in the two treated groups. Two weeks after treatment, the mean faecal egg counts of both treated groups were reduced by more than 98%. There was no significant difference in mean total worm burdens or egg counts between the two treated groups.

Animals↗

Nematode infection triggers the de novo formation of unloading phloem that allows macromolecular trafficking of green fluorescent protein into syncytia.

Syncytial feeding complexes induced by the cyst nematode Heterodera schachtii represent strong metabolic sinks for photoassimilates. These newly formed structures were described to be symplastically isolated from the surrounding root tissue and their mechanism of carbohydrate import has repeatedly been under investigation. Here, we present analyses of the symplastic connectivity between the root phloem and these syncytia in nematode-infected Arabidopsis (Arabidopsis thaliana) plants expressing the gene of the green fluorescent protein (GFP) or of different GFP fusions under the control of the companion cell (CC)-specific AtSUC2 promoter. In the same plants, phloem differentiation during syncytium formation was monitored using cell-specific antibodies for CCs or sieve elements (SEs). Our results demonstrate that free, CC-derived GFP moved freely from the phloem into the syncytial domain. No or only marginal cell-to-cell passage of GFP was observed into other root cells adjacent to these syncytia. In contrast, membrane-anchored GFP variants as well as soluble GFP fusions with increased molecular masses were restricted to the SE-CC complex. The presented data also show that nematode infection triggers the de novo formation of phloem containing an approximately 3-fold excess of SEs over CCs. This newly formed phloem exhibits typical properties of unloading phloem previously described in other sink tissues. Our results reveal the existence of a symplastic pathway between phloem CCs and nematode-induced syncytia. The plasmodesmata responsible for this symplastic connectivity allow the cell-to-cell movement of macromolecules up to 30 kD and are likely to represent the major or exclusive path for the supply of assimilates from the phloem into the syncytial complex.

Animals↗

A model for predicting parasitic gastroenteritis in lambs subject to mixed nematode infections.

A model previously developed for the prediction of parasitic gastroenteritis in lambs arising from infection by the nematode parasite Ostertagia circumcincta has been adapted to consider mixed infection and retested. The importance of the lambs as a contributing source to the summer wave of infective larvae is highlighted as are certain apparent deficiencies in the use of grass sampling techniques as a means of assessing pasture larval contamination.

Animals↗

The mutual influence of nematode infection and allergy.

Several studies have now shown that the prevalence of helminth infections is negatively correlated with the prevalence and/or severity of allergic diseases. Here, we describe studies in rodents infected with Strongyloides venezuelensis examining the mutual influence of nematode infection and allergy. S. venezuelensis has a lung cycle, much akin to the human hookworm and Strongyloidiasis, and induces airway eosinophilia, local IgE and mucus production, and airway hyperreactivity. Both the Th2 and functional responses are relevant for the ability of rodents to deal with S. venezuelensis infection. Nevertheless, the parasite elicits the release of cytokines, such as IL-10, which are capable of regulating immune and functional manifestations. In infected animals, allergic inflammation prevents parasite migration and establishment. Nevertheless, the parasite is capable of regulating the allergic response, preventing part of the tissue damage and functional changes induced by allergy. Understanding the mechanisms by which helminths regulate inflammation may potentially lead to the development of strategies aimed at controlling unwanted inflammation in allergic and autoimmune diseases.

Animals↗

The prevalence of concurrent trypanosome and gastrointestinal nematode infections in west African dwarf sheep and goats in Nsukka area of eastern Nigeria.

The prevalence of concurrent nematode-trypanosome infections in traditionally reared West African Dwarf sheep and goats in eastern Nigeria was monitored over a 12-month period during 1987-1988. The most prevalent nematodes were Haemonchus contortus and Trichostrongylus colubriformis, which usually occurred together in all nematode infected animals. Their combined prevalence rates ranged from 90 to 100% throughout the year and they accounted for 66 to 98% of the total monthly worm burdens. Of the 107 animals examined 13.6% were infected with trypanosome species comprising Trypanosoma brucei (50%), Trypanosoma congolense (43%) and Trypanosoma vivax (36%). No clear seasonal pattern was observed in the prevalence of concurrent nematode-trypanosome infection but owing to the widespread prevalence of gastrointestinal nematode infections, all trypanosome infected animals were invariably infected with H. contortus and Trichostrongylus colubriformis.

Animals↗

Effect of naturally occurring nematode infections on growth performance of first-season grazing calves.

Liveweight of calves on 89 dairy farms was measured at the end of the grazing season and related per herd to the level of exposure to nematode infection during the grazing season. There were significant between-herd variations in antibody titres against Ostertagia spp., Cooperia spp. and Dictyocaulus viviparus as well as in pepsinogen values. All but six herds (93.1%) had gastrointestinal nematode infections, as measured by faecal egg counts in September. Faecal samples of 17 herds (19.3%) contained lungworm larvae in September. Liveweight of calves per herd deviated from -68.1 kg to +84.1 kg from the age-adjusted population mean after their first grazing season. Growth performance up to the time of liveweight measurements was significantly correlated negatively with several serological and parasitological parameters. Data could be fitted by means of both linear and segmented curvilinear regression. Antibody titre against Cooperia spp. and gastrointestinal nematode egg output measured in September accounted for 3.1% (P less than 0.10) and 6.7% (P less than 0.05), respectively, of the variation in growth performance among herds. Certain infection parameters, when combined, accounted for 9.2% of this variation; these were antibody titre against Cooperia spp. and larval counts for both gastrointestinal nematodes and lungworm. Adding certain management factors to these infection parameters resulted in a model explaining 27.6% of the observed variation in growth performance among herds. These factors were supplementary feeding, lungworm vaccination, anthelmintic treatment at housing, date of housing and herd age.

Age Factors↗

Elemental analysis of cetacean skull lesions associated with nematode infections.

The elemental composition of both healthy and eroded cetacean skulls associated with nematode infections was evaluated. A total of 27 samples of eroded and non-eroded prepared museum cetacean skulls were characterised by elemental (CHN), X-ray fluorescence, and X-ray diffraction methods. The inorganic composition and crystal line structure (hydroxylapatite-like minerals) were similar for both types of skull samples, but the CHN values clearly differed. The results suggest that the carbon-rich fraction is lost in eroded areas, probably as a result of glycosaminoglycan-degrading Crassicauda enzymes.

Animals↗

Chemoprophylactic action of a substituted methyl benzimidazole carbamate against experimental nematode infections.

The prophylactic action of a substituted methylbenzimidazole carbamate was investigated against experimental nematode infections. The compound at the dose of 100 mg/kg x 1, i.m., protected hamsters against Ancylostoma ceylanicum for about 45 days and at 500 mg/kg x 1 protected rats against Nippostrongylus brasiliensis for 28 days. The uteri of female worms recovered from treated animals were devoid of ova so long the compound had considerable phophylactic action. In case of A. ceylanicum the compound exerted lethal action on L4 stage and in N. brasiliensis, mild action was noticed on L4 which became more pronounced on L5. The reference drugs, mebendazole and thiabendazole, had weaker prophylactic action.

Ancylostoma↗

Systemic autoimmune disease and concurrent nematode infection in a dog.

Systemic lupus erythematosus was diagnosed in a dog with concurrent nematode infection. The clinical signs of disease were unusually severe and included multiple neurologic deficits, polyarthritis, and weight loss. The dog was thrombocytopenic, and serotest results included positive lupus erythematosus test, positive rheumatoid factor test, positive antinuclear antibody test, hypergammaglobulinemia, and high platelet-associated IgG concentration. After treatment of hookworm, whipworm, and heartworm infections concurrently with corticosteroid and empiric treatment, the dog's condition improved. However, 10 days later, cyclophosphamide administration was necessary for continued immunosuppression. The dog was euthanatized because of progressive deterioration and development of canine coronavirus diarrhea. Serotest data generated from the dog's serum obtained at the time of referral suggested that autoantibodies and circulating immune complexes may have included IgE isotypes.

Ancylostomiasis↗