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Intestinal nematode infection ameliorates experimental colitis in mice.

Epidemiological studies suggest that inflammatory bowel disease (IBD) is common in developed countries and rare in countries where intestinal nematode infections are common. T cells are critical in many immune responses, including those associated with IBD and nematode infection. Among the distinct T helper (Th) cell subsets, Th1-type immune response is predominantly associated with Crohn's disease, while many nematode infections generate a strong Th2 response. The reciprocal cross regulation between Th1 and Th2 cells suggests that generation of a Th2 response by nematodes could prevent or reduce the effects of Th1-mediated diseases. In the present study, we investigated the effect of polarizing the immune response toward the Th2 type, using intestinal nematode infection, on subsequent experimental colitis. Mice were infected with the intestinal nematode Trichinella spiralis and allowed to recover before colitis was induced with dinitrobenzene sulfonic acid. The mice were sacrificed postcolitis to assess colonic damage macroscopically, histologically, and by myeloperoxidase (MPO) activity and Th cytokines. Prior nematode infection reduced the severity of colitis both macroscopically and histologically together with a decreased mortality and was correlated with a down-regulation of MPO activity, Th1-type cytokine expression in colonic tissue, and emergence of a Th2-type immune response. These results indicate a protective role of nematode infection in Th1 cell-driven inflammation and prompt consideration of a novel therapeutic strategy in IBD based on immunological distraction.

Animals↗

Immunological control of gastrointestinal nematode infections.

Control of nematode parasitism by an active manipulation of the host immune response has been a goal of veterinary and medical parasitologists for decades. The reality of achieving this goal has been questioned vigorously and demonstrations of the feasibility of using immunological control under field conditions are minimal. Nevertheless, with the rapid growth of modern biotechnology and the identification of novel parasite molecules as vaccine targets, the potential for success in this area has recently generated considerable excitement. The induction and regulation of the ruminant immune response against nematode parasites can be controlled either by management programs which include anthelmintic treatment or by vaccination. Both approaches will be discussed in this session.

Animals↗

Anthelminthic effect of oxantel and oxantel-pyrantel in intestinal nematode infections.

704 patients with intestinal nematode infestation were treated with oxantel and oxantel-pyrantel in either liquid or tablet form, at doses from 10 to 25mg/kg. All were given the drug or drugs as a single dose. In 699 patients with trichuriasis cure rates between 64 and 93% were obtained and there were egg reduction rates of between 90 and 100%. The best results were obtained using oxantel, either alone or in combination with pyrantel, at 15 to 20mg/kg. Only 2 of 152 patients with ascariasis were not cured after a single dose of pyrantel (given as oxantel-pyrantel) of 10, 15 or 20mg/kg, and both these patients were from the group given the lowest dose. Only mild side-effects were noted. The combination, oxantel-pyrantel is a safe and effective treatment for multiple intestinal nematode infection.

Adolescent↗

[Comparative immunofluorescent-histological investigations on 7 nematode species in respect to its antigenic properties for differential diagnosis of nematode infections (author's transl)].

Five nematode species of the Onchocercidae family and one from the Strongylidae and Trichuridae family were tested as antigen in the immunofluorescence test (IIFT) against reference sera from six nematode infections. The localisation of the cytosomal antigen antibody-reaction in the IIFT which was described on D. Viteae, was found to be the same for B. malayi, B. pahangi, L. carinii, O. volvulus and A. caninum. This test, just as egg membrane crude preparations of 5 nematodes from the Onchocercidae family, could not differentiate between W. bancrofti, onchocerciasis, loiasis and D. perstans sera. The cuticular fluorescence of five Onchocercidae species, which was observed only in frozen sections, appeared only with W. bancrofti-filariasis and onchocerciasis sera. T. spiralis larvae antigen exhibited only cuticular fluorescence in the frozen section, but in the case, however, against all reference sera. Trichinellosis patients' serum reacted on the other hand only with T. spiralis antigen. Uterine microfilaria from B. malayi, L. carinii, O. volvulus and D. viteae could differenciate species specifically between reference sera.

Adult↗

[Prevention and control of intestinal nematode infection in Shanghai].

OBJECTIVE: To evaluate the current status of intestinal nematode infection in Shanghai and make recommendations for further control activities. METHODS: Retrospective review of the control program was made based on the change of nematode prevalence in Shanghai area since the 1950s, and challenges under the current situation were analysed. RESULTS: The intervention measures included chemotherapy, health education, sanitary disposal of human excreta and safe water supply. With the control strategy, socio-economical development and the change of farming patterns, the prevalence of intestinal nematode infection in population was reduced by 88.5%, from 62.6% in 1955 to 8.2% in 2000. Among them, ascaris infection decreased by 89.0%, from 52.1% to 6.3%, hookworm infection decreased by 99.0%, from 12.9% to 0.1%, but pinworm infection was still as high as 18.9% in 1999. CONCLUSION: Prevalence of nematode infection in Shanghai was considerably reduced. To match it with the current socio-economical development in the Municipality, however, more needs to be done. Sustainable control activities and surveillance are recommended.

China↗

The prevalence and control of soil-transmitted nematode infections among children and women in the plantations in Sri Lanka.

OBJECTIVE: To determine the prevalence of soil-transmitted nematode infections among children and to assess the magnitude of nematode infections among women in the reproductive age group. DESIGN: Cross-sectional study. SETTING: 14 government owned plantations in the up-country and low-country regions of Sri Lanka. SUBJECTS: 1614 children 3 to 12 years of age and 246 women 18 to 44 years selected using a multi-stage random sampling technique. MEASUREMENTS: Egg count from stool samples collected from subjects using the quantitative Kato-Katz technique; percentage of children and women infected. RESULTS: 89.7% of the children and 86.2% of the women had at least one type of soil-transmitted nematode infection. Ascaris lumbricoides was the most common infection (77.0% of the children and 69.5% of the women). 69.4% of the children and 56.5% of the women had Trichuris trichiura infection and 23.2% of the children and 41.4% of the women had hookworm infection. Hookworm infection was much more common in the low country plantations. CONCLUSION: The high prevalence rates reflect widespread faecal contamination of the environment in the plantations due to poor and congested housing conditions and insufficient sanitary facilities. As the physical environment is not likely to change in the short term, the strategy for control of soil-transmitted nematode infections should focus on regular deworming of children and health education. A control program based on these principles was initiated in the estate sector after this study was completed.

Adolescent↗

Resilience of second year grazing cattle to parasitic gastroenteritis following negligible to moderate exposure to gastrointestinal nematode infections in their first year.

The influence of gastrointestinal nematode infections on performance of four groups of female Holstein Friesian calves was monitored until the end of the second grazing season (SGS). In the first year three groups were grazed and one group (G4) was permanently housed. General and grazing management during the first grazing season (FGS) was arranged such that G1 acquired moderate infections, G2 low infections and G3 very low infections with gastrointestinal nematodes. These infections were monitored through faecal egg counts, differentiation of faecal larval cultures, pasture larval counts, serum pepsinogen values, ELISA with a recombinant Cooperia oncophora protein, weight gain, tracer worm counts and sentinel worm counts. In 1998 all four groups were grazed together as one herd from 23 April to 26 October and infections were monitored with the same techniques with the exception of sentinel calves. In the FGS weight gain was higher in G4 than in the other groups and higher in G3 (28. 6kg) than in G1. Weight gain of G2 was intermediate to G1 and G3 but did not significantly differ from either group. In the SGS weight gain in G4 was far less than in any other group and the mean weight at the end of the experiment was 41.9, 38.6 and 50.9kg lower than G3, G1 and G2, respectively. Though no significant differences were observed between G1, G2 and G3 at the end of the experiment it was obvious that the weight gain advantage of G3 over G1 at the end of the FGS had disappeared. Parasitological and serological findings in the SGS indicated that G3 and G4 had build up less immunity during the FGS compared to G1 and G2. The conclusion of the experiment is that resilience to parasitic gastroenteritis in the SGS depends on the level of exposure to nematodes in the FGS. However, problems with poor weight gain only will be expected when exposure is very low in the FGS and high in the SGS.

Animal Feed↗

The effect of repeated moves to clean pasture on the build up of gastrointestinal nematode infections in calves.

The build up of gastrointestinal nematode infections was followed in two grazing experiments. Both experiments included four groups of six calves, a permanently housed non-infected control group and three groups which were grazed from May to October. One of these was moved to aftermath in the beginning of July, the second in the beginning of July and August and the third in the beginning of July, August and September. The build up of gastrointestinal nematode infections was followed by performing faecal egg counts, differentiation of faecal larval cultures, pasture larval counts, serum pepsinogen values, serum antibodies against Cooperia oncophora, weight gain and worm counts. In the second experiment four of the principal trial animals of each group were treated with oxfendazole and subsequently challenged with 100,000 larvae of Ostertagia ostertagi to examine development of immunity against O. ostertagi. The faecal egg counts and the worm counts of the sentinels necropsied in July indicated low initial infections in both experiments. Infection levels in experiment 1 remained low in each group until the beginning of September. However, during the last month, moderate to high infections were acquired by the groups which were moved once or twice. In contrast, low to moderate infections were maintained in the group moved three times. In the second experiment moderate C. oncophora burdens were already observed in the sentinels grazed until the beginning of August. Tracers grazing in August-September with the group moved once acquired high O. ostertagi and C. oncophora infections, whereas those grazed with both other groups acquired moderate infections. In October high infections with both species occurred in the groups moved once and twice, whereas low to moderate infections were observed in the group moved three times. The challenge infection demonstrated a reduction of establishment of O. ostertagi of approximately 70% in all three groups on pasture. The results demonstrate that moving calves at monthly intervals to clean pasture can be an effective method for the control of parasitic gastroenteritis. In addition, the data indicate that it is essential that the last move does not occur more than 1 month before the end of the grazing season.

Age Factors↗

Value of present diagnostic methods for gastrointestinal nematode infections in ruminants.

In this paper the different options for the diagnosis of gastrointestinal nematode infections are discussed. Diagnostic tests have a role in confirming the clinical diagnosis of parasitic gastroenteritis, but are more important for herd health monitoring of nematode infections, in particular for cattle. Therefore, emphasis is placed on discussing the available diagnostic parameters on their usefulness for that purpose. For clinical diagnosis the clinical signs, combined with the history of the animals is usually sufficient and a laboratory confirmation is not required. Faecal egg counts are, with two exceptions, not suitable for confirmation of the clinical diagnosis, because correlation between faecal egg counts and infection levels is usually low. These exceptions are the diagnosis of haemonchosis in small ruminants and the detection of anthelmintic resistance. This also limits the value of DNA-based tests of faecal material; even quantitative tests of nematode species specific DNA will have little value for diagnosis and monitoring. Pasture larval counts and worm counts are useful parameters for basic epidemiological studies on nematode infections. However, they are too laborious to be used for either routine diagnosis or monitoring. Blood parameters, such as gastrin and pepsinogen and serology are valuable tools for diagnosis. Pepsinogen and ELISAs based on recombinant proteins show most promise as parameters for herd health monitoring. However, extensive epidemiological studies are still needed before these parameters can be implemented in routine herd health monitoring schemes for parasitic gastroenteritis.

Animals↗

IL-12 gene transfer alters gut physiology and host immunity in nematode-infected mice.

Immune responses elicited by nematode parasite infections are characterized by T helper 2 (Th2) cell induction. The immunologic basis for changes in intestinal physiology accompanying nematode infection is poorly understood. This study examined whether worm expulsion and associated goblet cell hyperplasia and muscle contractility share a similar immune basis by shifting the response from Th2 to Th1 using interleukin-12 (IL-12) overexpression. We used a single administration of recombinant adenovirus vector expressing IL-12 (Ad5IL-12) in Trichinella spiralis-infected mice. Ad5IL-12 administered 1 day after infection prolonged worm survival and inhibited infection-induced muscle hypercontractility and goblet cell hyperplasia. This was correlated with upregulated interferon-gamma (IFN-gamma) expression and downregulated IL-13 expression in the muscularis externa layer. We also observed increased IFN-gamma production and decreased IL-4 and IL-13 production from in vitro stimulated spleen and mesenteric lymph node cells of infected Ad5IL-12-treated mice. These results indicate that transfer and overexpression of the IL-12 gene during Th2-based nematode infection shifts the immune response toward Th1 and delays worm expulsion. Moreover, the immune response shift abrogated the physiological responses to infection, attenuating both muscle hypercontractility and goblet cell hyperplasia. These findings strongly indicate that worm expulsion, muscle hypercontractility, and goblet cell hyperplasia share a common immunologic basis and may be causally linked.

Adenoviridae↗

Reduced protective efficacy of a blood-stage malaria vaccine by concurrent nematode infection.

Helminth infections, which are prevalent in areas where malaria is endemic, have been shown to modulate immune responses to unrelated pathogens and have been implicated in poor efficacy of malaria vaccines in humans. We established a murine coinfection model involving blood-stage Plasmodium chabaudi AS malaria and a gastrointestinal nematode, Heligmosomoides polygyrus, to investigate the impact of nematode infection on the protective efficacy of a malaria vaccine. C57BL/6 mice immunized with crude blood-stage P. chabaudi AS antigen in TiterMax adjuvant developed strong protection against malaria challenge. The same immunization protocol failed to induce strong protection in H. polygyrus-infected mice. Immunized nematode-infected mice produced significantly lower levels of malaria-specific antibody than nematode-free mice produced. In response to nematode and malarial antigens, spleen cells from immunized nematode-infected mice produced significantly lower levels of gamma interferon but more interleukin-4 (IL-4), IL-13, and IL-10 in vitro than spleen cells from immunized nematode-free mice produced. Furthermore, H. polygyrus infection also induced a strong transforming growth factor beta1 response in vivo and in vitro. Deworming treatment of H. polygyrus-infected mice before antimalarial immunization, but not deworming treatment after antimalarial immunization, restored the protective immunity to malaria challenge. These results demonstrate that concurrent nematode infection strongly modulates immune responses induced by an experimental malaria vaccine and consequently suppresses the protective efficacy of the vaccine against malaria challenge.

Adjuvants, Immunologic↗

Impairment of protective immunity to blood-stage malaria by concurrent nematode infection.

Helminthiases, which are highly prevalent in areas where malaria is endemic, have been shown to modulate or suppress the immune response to unrelated antigens or pathogens. In this study, we established a murine model of coinfection with a gastrointestinal nematode parasite, Heligmosomoides polygyrus, and the blood-stage malaria parasite Plasmodium chabaudi AS in order to investigate the modulation of antimalarial immunity by concurrent nematode infection. Chronic infection with the nematode for 2, 3, or 5 weeks before P. chabaudi AS infection severely impaired the ability of C57BL/6 mice to control malaria, as demonstrated by severe mortality and significantly increased malaria peak parasitemia levels. Coinfected mice produced significantly lower levels of gamma interferon (IFN-gamma) during P. chabaudi AS infection than mice infected with malaria alone. Concurrent nematode infection also suppressed production of type 1-associated, malaria-specific immunoglobulin G2a. Mice either infected with the nematode alone or coinfected with the nematode and malaria had high transforming growth factor beta1 (TGF-beta1) levels, and concurrent nematode and malaria infections resulted in high levels of interleukin-10 in vivo. Splenic CD11c(+) dendritic cells (DC) from mice infected with malaria alone and coinfected mice showed similarly increased expression of CD40, CD80, and CD86, but DC from coinfected mice were unable to induce CD4(+) T-cell proliferation and optimal IFN-gamma production in response to the malaria antigen in vitro. Importantly, treatment of nematode-infected mice with an anthelmintic drug prior to malaria infection fully restored protective antimalarial immunity and reduced TGF-beta1 levels. These results demonstrate that concurrent nematode infection strongly modulates multiple aspects of immunity to blood-stage malaria and consequently impairs the development of protective antimalarial immunity.

Animals↗

Effects of the initial level of milk production and of the dietary protein intake on the course of natural nematode infection in dairy goats.

The level of dietary protein is known to alter the establishment and the pathophysiology of gastrointestinal nematodes in sheep. On the other hand, high-producing dairy goats are less resistant and/or resilient than low-producing ones to experimental nematode infection. During a 2-year study, we have investigated the course of a natural nematode infection (mainly T. colubriformis) in a high-producing dairy goat flock. In year 1, 50 grazing goats divided in high (HP) or low producer (LP) were compared from April to October for parasitological and milk parameters. In year 2, the 25 HP goats were only considered and were allocated to two levels of dietary protein, high level (HPr) with a protein coverage of 125% or normal level (NPr) with a protein coverage of 106%. They were monitored as above. In year 1, HP goats showed a greater nematode egg output (1856 vs. 1000epg) associated with higher values in T. colubriformis IgG in autumn than LP ones whereas the decrease in serum phosphate concentration was similar in both groups. In year 2, HPr goats exhibited lower egg output in autumn (2219 vs. 2817) vs. NPr ones. Moreover, milk yield and fat content were significantly higher in HPr vs. NPr in the 2nd part of the study. HP goats are less resistant to nematode infection in natural conditions. Resistance and resilience of HP goats may partially be improved by a protein supplementation in the diet.

Animal Feed↗

Cytokine regulation of resistance and susceptibility to intestinal nematode infection - from host to parasite.

Intestinal nematode infection is one of the most common forms of parasite infection worldwide. Both man and domestic stock suffer considerable morbidity from these infectious agents. The majority of our current understanding of the host parasite relationship to gut dwelling nematodes comes from well-defined laboratory models. One of the most informative over recent years has been study of whipworm infection in the mouse, Trichuris muris (T. muris). Infection in inbred strains of mouse shows a spectrum of response phenotypes reflecting the variation observed under natural conditions in the wild. Resistance and worm expulsion is mediated by CD4+ T helper two cells with a dominant role for interleukin (IL)-13. The effector mechanisms responsible for worm expulsion remain undefined but new evidence suggests a role for tumour necrosis factor alpha (TNF-alpha). Susceptibility to chronic infection is mediated through a T helper 1 (Th1) response characterised through the secretion of interferon gamma (IFN-gamma). A major new role for IL-18 has been defined in induction of a Th1 response through a novel down-regulation of IL-13. Moreover, progression to chronic infection may involve the parasite itself. T. muris secretes a protein that shares epitopes with host IFN-gamma, which may interfere with host protective cytokine, mediated protection and thus, promotes its own survival.

Animals↗

[Economical consequences of intestinal nematodes infection in pigs].

The studies wers carried out in ZZD Kolbacz on 14 sows. The experimental groups control and treated consisted of 7 sows each. The sows were treated with Dectomax - 1 ml/33 kg of body weight. The efficacy of sows treatment's was verified with the Wllis-Schlaaf and McMaster method. The studies indicate, that subclinical infection of intestinal nematodes could influence the swine production. The piglets from treated with Dectomax sows were infected in 8% only; when all piglets from non treated sows were infected with nematodes. From treated sows 0.8 more piglet were obtained and the weight gain of litter was after 6 weeks 24.4 kg higher comparing with the control group.

Animals↗

Forecasting the peak of gastrointestinal nematode infection in lambs.

The pattern of sheep nematode infective larvae on pasture shows a marked midsummer peak arising largely from the ewe peri-parturient egg output. Records of larval pattern over a nine-year period were examined in relation to meteorological data, and a correlation was demonstrated between the time of the summer peak and cumulative rainfall. A "wet score" was allocated to 12-hourly rainfall figures, and a "critical index" of 440 units of wetness was shown to be necessary before the larval peak was reached. A "warning index" of 350 to 380 wetness units is suggested which would allow a prediction to be made of the onset of major infection in lambs.

Animals↗

Implications of nutrition for the ability of ruminants to withstand gastrointestinal nematode infections.

Resistance and resilience of the ruminant host to gastrointestinal (GI) parasitic nematode infections are influenced by many factors, including nutrition. This review examines the effects of host nutrition on the ability of ruminants to withstand GI nematode infections. Firstly the effects of infection on host metabolism are summarised briefly. An important factor in the pathogenesis is a reduction in feed intake by the host. Gut nematodes also increase endogenous protein losses, which result in net loss of amino acids to the parasitised host, though energy and mineral metabolism are also perturbed. The indications are that the major nutritional change is in protein metabolism. Resilience (the ability of an animal to withstand the effects of infection) can be enhanced markedly by increasing metabolisable protein supply and to a lesser extent metabolisable energy supply. Resistance to GI nematodes (ability of host to prevent establishment and/or development of infection) is also influenced by diet, particularly metabolisable protein supply. While there do not appear to be any effects of host nutrition on establishment of infective larvae, the rate of rejection of adult worms can be enhanced by improved nutrition. The exact nutritional requirements or the mechanisms involved are not known. It appears that the effects of improving nutritional status on host resilience are more clearly defined than effects on host resistance. The implication of changes in host resistance with nutritional state for host productivity need to be better described. Understanding the role of nutrition in improving both resistance and resilience of the host to GI parasites will be important if producers are to make better use of host acquired immunity and reduce dependence on pesticides for prophylaxis.

Animal Nutritional Physiological Phenomena↗