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Modified plasma and abomasal disposition of albendazole in nematode-infected sheep.

The influence of gastrointestinal nematode infection on the kinetics of albendazole (ABZ) and its metabolites, albendazole sulphoxide (ABZSO) and sulphone (ABZSO2) in plasma and abomasal fluid was investigated in sheep. A micronised suspension of ABZ was administered intraruminally at 7.5 mg kg-1 to the following groups of sheep: (a) non-parasitised (control); (b) artificially infected with Haemonchus contortus; (c) naturally infected with Haemonchus contortus and other species of gastrointestinal nematodes. Plasma and abomasal fluid samples were obtained serially over 72 h post-treatment and they were analysed by HPLC for ABZ and its metabolites. The ABZ parent drug was not detected in plasma at any time post-treatment, however the metabolites ABZSO and ABZSO2 were recovered in the bloodstream. The active metabolite ABZSO was recovered in plasma between 0.5 and 48 (uninfected), 60 (H. contortus infected) or 72 h (naturally infected sheep) post-administration. The area under the plasma concentration vs time curve (AUC) values for ABZSO were higher in both artificially infected (64.0 micrograms h ml-1) and naturally infected (79.3 micrograms h ml-1) sheep as compared with non-infected animals (41.8 micrograms h ml-1). Peak plasma concentrations for ABZSO and ABZSO2 were higher in both artificially and naturally infected sheep than in non-parasitised animals. No changes in the half-lives and mean residence times for these metabolites were observed in infected sheep. ABZ and its metabolites were found in the abomasum between 0.5 and 48 (infected animals) or 72 h (uninfected) post-treatment. The availability (total AUCs) of ABZ and its metabolites in abomasal fluid were lower in H. contortus infected sheep than in the uninfected control animals. The increased abomasal pH induced by the presence of the H. contortus infection may reduce the plasma/abomasum pH gradient, which results in a decreased ionic-trapping of ABZ and its metabolites in the abomasum. Such a phenomenon correlates with: (a) the higher total AUC values obtained for ABZ metabolites in the bloodstream of the infected compared to the control sheep, (b) the lower concentration profiles of the ABZ parent drug and its metabolites found in the abomasal fluid of the infected animals.

Abomasum↗

Nematode infection induces Th2 cell-associated immune responses in LEC mutant rats with helper T cell immunodeficiency.

Long-Evans Cinnamon (LEC) rats have maturational arrest of CD4+8- T cells from CD4+8+ cells in the thymus. Despite this, CD4+8- T cells are always present in peripheral lymphoid organs of LEC rats, suggesting that these CD4+8- T cells are generated by an uncommon pathway. We investigated the role of LEC rat peripheral CD4+8- T cells in Th2-associated responses to infection with the nematode Nippostrongylus brasiliensis. After infection, the numbers of CD4+8- TCR alpha beta + T cells significantly increased in mesenteric lymph nodes (MLN) and the spleen, while those in the thymus were still negligible. Infection also induced significant up-regulation of IL-4 gene expression in LEC rat MLN cells. Total serum IgE levels in LEC rats were markedly increased two weeks after infection. Mucosal mast cell responses in the gut and lungs of LEC rats were induced as prominently as in control Long-Evans Agouti (LEA) rats. Faecal egg count data indicated that LEC rats rejected nematodes faster than LEA rats. These results suggested that Th2-associated responses can be induced by nematode infection in LEC rats probably through the extrathymic recruitment and proliferation of CD4+8- TCR alpha beta + T cells.

Animals↗

Interleukin-9 is involved in host protective immunity to intestinal nematode infection.

Murine studies have demonstrated that, as with other nematodes, infection with the intestinal nematode Trichinella spiralis is associated with a pronounced intestinal mastocytosis, eosinophilia and an elevation in serum levels of total IgE. Both interleukin (IL)-4 and IL-5 are clearly important in the generation of IgE responses and eosinophilia, respectively, but the control of mucosal mastocytosis in vivo is not as well defined. Mucosal mast cells appear to be particularly important with regard to T. spiralis infections as there is good evidence to suggest their involvement in expulsion of the parasite from the host. In this study we examined the effect of the overproduction of the Th2 cytokine IL-9 on infection with this nematode. We demonstrate that naive IL-9-transgenic mice have an intense intestinal mastocytosis and high serum levels of mouse mast cell protease-1. Moreover, upon infection high titers of parasite-specific IgG1 were observed with a heightened mast cell response, which was associated with the rapid expulsion of T. spiralis from the gut. Furthermore, as depression of this mast cell response, using anti-c-kit antibodies, resulted in the inability of these mice to expel the parasite, this study clearly demonstrates an activity of IL-9 on mucosal mastocytosis and the host protective immune response in vivo.

Animals↗

Schistosoma mansoni, nematode infections, and progression to active tuberculosis among HIV-1-infected Ugandans.

Rates of tuberculosis (TB) in Africa are highest among people infected with HIV. Searching for additional risk factors in a cohort of HIV-infected Ugandan adults, we previously found that a type 2 cytokine bias and eosinophilia were associated with progression to active TB. A possible role for helminth infection was assessed in this study. We analyzed TB incidence in 462 members of this cohort who were screened for filarial infections, gastrointestinal nematodes, and schistosomiasis. Progression to TB was not associated with gastrointestinal nematodes (rate ratio [RR], 1.18; confidence intervals [CIs], 0.66-2.10) or Mansonella perstans (RR, 0.42; CI, 0.13-1.34). A weak association between Schistosoma mansoni infection and TB was found (RR, 1.42; CI, 0.86-2.34); after adjusting for potential explanatory variables and using more stringent diagnostic criteria, the association was strengthened (RR, 2.31; 1.00-5.33). This analysis suggests an effect of S. mansoni infection on progression to active TB among HIV-1-infected Ugandans.

Adolescent↗

The epidemiology of gastrointestinal nematode infections in communal cattle and commercial beef cattle on the highveld of Zimbabwe.

An epidemiological study of gastrointestinal nematode infections of cattle was conducted on the highveld of Zimbabwe from June 1993 to May 1995. The study was carried out in two communal areas, two conventional beef farms and two commercial beef farms with irrigated pastures. On all farms/areas, faecal egg counts were low (< 500 eggs per g faeces) during the dry season. During the rainy season faecal egg counts were highest in communal areas and lowest in conventional beef farms. Those of irrigated farms had intermediate values. During the dry season pasture larval counts were low in irrigated pastures and conventional beef farms and virtually zero in communal areas. They increased and peaked during the rainy season, coinciding with the egg count peaks. Worm burdens of necropsied cattle indicated that 100% of the animals were infected with nematodes. The important species were Cooperia pectinata, C. punctata, Haemonchus placei, Trichostrongylus axei and Oesophagostomum radiatum in all farms/areas and Ostertagia ostertagi in a beef farm with irrigated pastures. Haemonchus survived the dry season as inhibited early fourth stage larvae whereas Cooperia and Trichostrongylus survived as adults.

Abomasum↗

A modified technique for the estimation of the number of infective nematode larvae present on pasture, and its application in the field under South Australian conditions.

A modified technique for the recovery of larvae from pasture is described involving two centrifugations of pasture washings in a solution of potassium iodide. On average, the technique recovered 96% of larvae and was simple to perform. At three sites in South Australia (rainfall 550-330 mm year-1), the numbers of larvae present on pasture each month using this technique was compared with results obtained using one or four tracer sheep. The general pattern of larval availability was similar using the two methods, but discrepancies were noted. In some instances, particularly when numbers of larvae were low, pasture sampling underestimated the numbers of larvae available to sheep; in other situations, when the numbers of larvae were high, tracer sheep probably underestimated the number being ingested. Increasing the numbers of tracer sheep from one to four did not appreciably increase the correspondence between the two methods.

Animals↗

The efficacy of Michel's dose and move system on gastrointestinal nematode infections in diary calves.

The efficacy of a move to aftermath in July combined with moxidectin or fenbendazole treatment for the control of parasitic gastroenteritis (PGE) in calves was evaluated in three field experiments in the Netherlands. In all five treated groups high gastrointestinal nematode infections and PGE were prevented by a dose and move in July. Cooperia infections increased to moderate levels in two groups treated with moxidectin and one group treated with fenbendazole. In both other groups and also for Ostertagia in these three groups, low to extremely low infections were acquired. In the first experiment high primary infections, resulting in high faecal egg counts and a moderate increase of blood pepsinogen values occurred before the dose and move. Nevertheless, these primary infections were not high enough to result in PGE. In both other experiments primary infection levels were low and faecal egg counts increased to 100-650 eggs/g faeces at the end of the grazing season. The blood pepsinogen values of non-treated control groups demonstrated that it took more than a month after their move to aftermath before substantial reinfection occurred on the new pasture. In the first and the last experiment only, high Ostertagia and Cooperia infections developed in the control group at the end of the grazing season, though it did not result in clinical PGE. The experiments demonstrate all theoretical risks of the dose and move system: (1) PGE early in the grazing season as a result of high overwintered pasture infectivity. (2) PGE just before the move as a result of an early midsummer increase in pasture infectivity. (3) PGE around housing as a result of insufficient suppression of pasture infectivity late in the grazing season. (4) Underexposure to nematode infections due to a high suppression of nematode infections. Nevertheless, it can be concluded that under normal conditions the dose and move system remains to be a valuable and easily applicable system for the control of PGE.

Animal Husbandry↗

The effect of nematode infection upon intestinal smooth muscle function.

Nematode infections are useful in studying both host defence and inflammation induced changes in intestinal physiology, including increased contraction by intestinal muscle. Our initial studies of the heightened muscle function found during T. spiralis infection led to investigations of the role of immune and inflammatory cells and mediators in the immunodulation of intestinal muscle function. By infecting various immunodeficient mouse strains, as well as gene transfer to the intestine, T lymphocytes, and in particular the CD4+ve subset were found to be responsible for altering smooth muscle function. However, eosinophils as well as the cytokine interleukin-4 may also be involved. Investigations also indicate a potential role for increased muscle function and propulsive activity in expelling nematode parasites. Mutant mice which suffer aberrant intestinal propulsion, or based upon an immunodeficiency, undergo reduced changes in muscle function during infection, undergo prolonged infections. While increased muscle function may be an adaptive host response, the changes in muscle function may persist long after the resolution of the infection. Thus understanding the mechanisms behind the immunomodulation of intestinal muscle function may also impact upon clinical gastroenterology, since motility disturbances in man often occur following enteric infections, or other inflammatory conditions of the bowel.

Animals↗

Gnathostomiasis: a rare nematode infection.

Gnathostoma, primarily an animal nematode, can infect human by the third stage larva by consumption of undercooked or raw fish, poultry, or pork. In Bangladesh gnathostomiasis is a very rare condition. The first case, an ocular infection by gnathostoma was reported in 2001 from Rangpur, a northern district. This is the second case report of gnathostomiasis which also is an ocular infection, occurred in an area of greater district of Rangpur. A female patient of 32 year of age of the northern district, Nilphamari has got infected with a species of Gnathostoma, manifested by the appearance of a live larva near the right lateral margin of anterior surface of iris of her right eye. The larva was removed surgically from her eye and the patient was cured from symptoms.

Adult↗

Molecular and immunodiagnosis of human filarial nematode infections.

The filarial nematodes Wuchereria bancrofti, Brugia malayi and Onchocerca volvulus represent major public health problems in the Tropics. Effective diagnosis of infection with these parasites is required both for administration of drugs to infected individuals and for monitoring of control programs. However parasitological diagnosis is associated with a number of problems including frequently inadequate sensitivity, long pre-patency of infection and inconvenience for patients. For these reasons there has been considerable effort expended in developing other forms of diagnosis, in particular immunoassays for measuring antibody and circulating parasite antigen as well as molecular-biology-based assays for detecting parasite DNA. This article reviews the progress and achievements obtained to date. The latter include the development of ELISAs employing recombinant antigen for detection of antibody to O. volvulus which have both high sensitivity and specificity, the commercial availability of immunoassays to measure circulating antigen in W. bancrofti infection and the generation of specific DNA-based detection systems for all three parasites.

Animals↗

Comparison of nematode infections of the gastrointestinal tract in Angora and dairy goats in a rangeland environment: relations with the feeding behaviour.

A study was conducted in order to examine the possible influence of feeding behaviour on differences in the diversity and the intensity of nematode infections of the gastrointestinal tract between two breeds of goats placed in the same rangeland environment. Within the same flock bred on rangeland conditions, 10 Saanen dairy goats and 14 Angora goats were surveyed for 5 months (from May to September) and parasitological and behavioural parameters were measured. The level of nematode infection was estimated by monthly measurements of faecal egg counts whereas the feeding behaviour was assessed every fortnight. During the whole survey, nematode egg excretion was repeatedly higher in the Angora goats compared to the Saanen ones and significant differences were observed in May and September. This difference in egg excretion was related to major difference in feeding behaviour between the two breeds. In contrast with the Saanen does, Angora goats did not show any browsing and resting activities at any date of observation. Hence, Angora goats can be considered mainly as grazers whereas Saanen goats exhibit feeding activities close to browsers. The relative influence of feeding behaviour and host immune response on the susceptibility to gastrointestinal nematode infection in goats is discussed.

Animal Husbandry↗

Amines of the mucosal mast cell of the gut in normal and nematode infected rats.

Infection with the nematode N. brasiliensis is accompanied by a marked increase of the number of mucosal mast cells (MMC) and the mucosal content of histamine and 5-hydroxytryptamine (5-HT). We compared amine levels, determined by ion exchange and high performance liquid chromatography (HPLC) with numbers of MMC and enterochromaffin cells (ECC). Furthermore, we measured 5-HT cytofluorometrically in individual MMC and ECC. The cellular distribution of 5-HT was studied immunohistochemically. Our results corroborate previous findings that histamine is stored in MMC. Quotients between histamine content and numbers of MMC decreased throughout the period of worm expulsion, followed by a recovery, suggesting a histamine release during this defense reaction. The HPLC analysis gave no evidence for a storage of dopamine in MMC. ECC and MMC of normal and infected rats showed a formaldehyde induced fluorescence and 5-HT immunoreactivity. The formaldehyde induced fluorescence of MMC from normal rats was about 10% that of ECC, but MMC exceeded ECC three times by numbers. These findings suggest that a considerable proportion of the intestinal 5-HT in the normal rat is stored in MMC. ECC numbers did not change during the infection and their content of 5-HT was unchanged, as judged by cytofluorometry. The cytofluorometric measurements showed that the intensity of the monoamine fluorescence from the MMC of infected animals was about three times as high as that of controls. It was concluded that the increased tissue levels of 5-HT was due to both an increase in MMC numbers and an increase in the 5-HT content of individual MMC. The results suggest a different role for histamine and 5-HT in the defense reaction towards the nematode infection.

Animals↗

Efficacy of moxidectin pour-on against nematode infections in cattle.

Three groups of eight calves, naturally infected with gastrointestinal nematodes and artificially infected with Dictyocaulus viviparus were used to evaluate the efficacy of moxidectin pour-on at dose rates of 0.35 mg/kg and 0.5 mg/kg bodyweight. With both doses the efficacy was 100 per cent against adult D viviparus, Trichostrongylus axei, Ostertagia species and Nematodirus helvetianus. It was more than 99 per cent against Ostertagia and Nematodirus species fourth stage larvae. A small number of Cooperia species were found after treatment, and for this parasite, the efficacy of moxidectin ranged from 97.6 per cent against the larval stages to 98.8 per cent against the adults. No adverse reactions to the moxidectin treatment were observed.

Abomasum↗

Chitinase and Fizz family members are a generalized feature of nematode infection with selective upregulation of Ym1 and Fizz1 by antigen-presenting cells.

Ym1 and Fizz1 are secreted proteins that have been identified in a variety of Th2-mediated inflammatory settings. We originally found Ym1 and Fizz1 as highly expressed macrophage genes in a Brugia malayi infection model. Here, we show that their expression is a generalized feature of nematode infection and that they are induced at the site of infection with both the tissue nematode Litomosoides sigmodontis and the gastrointestinal nematode Nippostrongylus brasiliensis. At the sites of infection with N. brasiliensis, we also observed induction of other chitinase and Fizz family members (ChaFFs): acidic mammalian chitinase (AMCase) and Fizz2. The high expression of both Ym1 and AMCase in the lungs of infected mice suggests that abundant chitinase production is an important feature of Th2 immune responses in the lung. In addition to expression of ChaFFs in the tissues, Ym1 and Fizz1 expression was observed in the lymph nodes. Expression both in vitro and in vivo was restricted to antigen-presenting cells, with the highest expression in B cells and macrophages. ChaFFs may therefore be important effector or wound-repair molecules at the site of nematode infection, with potential regulatory roles for Ym1 and Fizz1 in the draining lymph nodes.

Amino Acid Sequence↗

Resistance of Santa Inês and Ile de France suckling lambs to gastrointestinal nematode infections.

A trial was carried out to determine the resistance to natural infection by gastrointestinal nematodes in 12 Santa Inês and nine Ile de France lambs before weaning. Faecal samples were obtained for faecal nematode egg counts (FEC). Blood samples were collected to determine packed cell volume (PCV), total plasma protein levels and peripheral eosinophil counts. Most Ile de France lambs (77.8%) were treated with an anthelmintic at 43 days of age, while 50% off Santa Inês lambs were treated at weaning, 57 days of age. The mean PCV values were normal in Santa Inês lambs, while in Ile de France lambs showed lower values reaching 22.3% at 43 days of age. The lowest mean plasma protein values were observed in Ile de France lambs (4.13 g/dl) at 43 days of age and in Santa Inês lambs (5.0 g/dl) at 57 days of age. Before weaning, Santa Inês lambs were susceptible to natural infections by gastrointestinal nematodes but with a greater capacity to stand the adverse effects of parasitism compared to Ile de France lambs.

Animals↗

Epidemiologic findings on canine and feline intestinal nematode infections from records of the Iowa state University Veterinary Clinic.

A wealth of data was available on intestinal nematode infections of dogs and cats in the Ames, Iowa, practice area served by the Iowa State University Veterinary Clinic. From July 1966 through June 1974, 8.5% of 33,594 dogs and 4.5% of 11,995 cats hospitalized for 1 or more days were recorded as infected with at least 1 type of intestinal nematode. For both dogs and cats, infection rates were generally higher in males than in females and in those that were sexually intact, compared with those that were neutered. The highest prevalence of hookworm infections in both dogs and cats was recorded in June and July, and the highest prevalence of ascarid infections in cats, but not in dogs, was in December. Seasonal patterns were not demonstrated for other nematode infections. Ascarid infections in dogs and cats and hookworms infections in dogs were most prevalent in 2-week-old to 2-month-old animals. Whipworm infections in dogs and hookworm infections in cats generally appeared at greater ages, reaching their highest prevalence in hosts 1 to 2 years old.

Animals↗

T cell and cytokine basis of host variability in response to intestinal nematode infections.

Infection by a variety of species of intestinal nematode infection gives rise to a wide variation in parasite load within a host population. There has been much investigation into the basis of this variation and is thought to involve several factors. Studies of infections of gut dwelling nematodes in laboratory rodents has clearly demonstrated that this variation may be due to the production of cytokines produced as part of the host immune response to infection. More specifically, activation of distinct T helper cell subsets leads to the generation of effective or ineffective responses resulting in clearance of the parasite load or maintenance of chronic infection. The induction of differential responses remains to be determined but is likely to be influenced at a number of levels including involvement of accessory cells and activation of co-stimulatory molecules on antigen presenting cells. Moreover, it appears that these parasites may actively interfere with the host cytokine response to promote their own survival. This review concentrates on recent findings of cytokine mediated control of intestinal nematodes highlighting a central role for the immune system in regulating both acute and chronic infection by these parasites.

Animals↗