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PubMed2003

Immunity to Trichuris muris in the laboratory mouse.

Of all the laboratory models of intestinal nematode infection, Trichuris muris in the mouse is arguably the most powerful. This is largely due to the fact that the ability to expel this parasite is strain dependent. Thus, most mouse strains readily expel T. muris. However certain mouse strains, and indeed some individuals within particular mouse strains, are unable to mount a protective immune response and harbour long term chronic infections. This unique model thus presents an opportunity to examine the immune events underlying both resistance to infection and persistent infection within the same host species, and in some cases, the same host strain.

Animals↗
PubMed2003

Animal self-medication and ethno-medicine: exploration and exploitation of the medicinal properties of plants.

Early in the co-evolution of plant-animal relationships, some arthropod species began to utilize the chemical defences of plants to protect themselves from their own predators and parasites. It is likely, therefore, that the origins of herbal medicine have their roots deep within the animal kingdom. From prehistoric times man has looked to wild and domestic animals for sources of herbal remedies. Both folklore and living examples provide accounts of how medicinal plants were obtained by observing the behaviour of animals. Animals too learn about the details of self-medication by watching each other. To date, perhaps the most striking scientific studies of animal self-medication have been made on the African great apes. The great ape diet is often rich in plants containing secondary compounds of non-nutritional, sometimes toxic, value that suggest medicinal benefit from their ingestion. Chimpanzees (Pan troglodytes), bonobos (Pan paniscus) and gorillas (Gorilla gorilla) are known to swallow whole and defecate intact leaves. The habit has been shown to be a physical means of purging intestinal parasites. Chimpanzees and man co-existing in sub-Saharan Africa are also known to ingest the bitter pith of Vernonia amygdalina for the control of intestinal nematode infections. Phytochemical studies have demonstrated a wide array of biologically-active properties in this medicinal plant species. In light of the growing resistance of parasites and pathogens to synthetic drugs, the study of animal self-medication and ethno-medicine offers a novel line of investigation to provide ecologically-sound methods for the treatment of parasites using plant-based medicines in populations and their livestock living in the tropics.

Animals↗
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↗
PubMed2001

Consequences of anthelmintic resistance on liveweight gain of lambs on commercial sheep farms.

AIM: To assess the consequences of anthelmintic resistance on commercial sheep farms on liveweight (LW) gains and susceptibility to diarrhoea of growing lambs. METHODS: Five farms with a history of resistance to benzimidazole drenches were selected. On each farm, 150 ewe lambs were randomly allocated to 1 of 3 treatment groups (n=50). Group 1 was treated 5 times at 28-day intervals with oxfendazole (to which nematode resistance had been demonstrated); Group 2 was treated 5 times at 28-day intervals with levamisole or levamisole + oxfendazole (to which nematode resistance had not been demonstrated) and; Group 3 was treated with a combination of slow-release albendazole capsules and oral moxidectin (intended to totally suppress nematode infection). Differentiated faecal egg counts (FECs), FEC reduction tests (FECRT), LW gain and degree of faecal soiling around the breech (dag scores) were determined and compared between groups. RESULTS: Pre-treatment FECs in Group 1 were similar to or slightly lower than those of Group 2. Efficacy of oxfendazole in Group 1 varied between farms and over time within farms, the reduction in FECs after treatment varying from 0% to 95%. The genera identified as resistant on each farm also varied over time. Lambs from Group 3 had lower FECs, lower dag scores and higher growth rates than lambs from Group 2, which in turn had higher LW gains than lambs from Group 1. The overall LW gains during the 5 months of the study were 7.03+/-0.27 kg for Group 1, 8.33+/-0.27 kg for Group 2, and 9.91+/-0.31 kg for Group 3 (mean+/-SEM; means differed significantly from each other, p<0.01). CONCLUSIONS: The decrease in growth rates associated with the continued use of an incompletely effective anthelmintic were surprisingly small in situations where all lambs grazed together.

Journal Article↗
PubMed2001

Interactions between nutrition and gastrointestinal parasitism in sheep.

Effects of gastrointestinal nematode infection on metabolism and nutrient utilisation in sheep are reviewed. Infection induces protein deficiency by increasing the demand for amino acids in the alimentary tract while reducing supply through depression of appetite. Mechanisms through which improved protein nutrition could improve the performance of the host are then discussed. Opportunities for capitalising on such effects are limited by our rudimentary understanding of the cell-mediated immune response in gastrointestinal epithelial tissue. Both resistance of the animal to larval establishment and performance in the face of larval challenge can be enhanced by improved protein nutrition. However, enhanced immune responses may not necessarily be synonymous with improved productivity except at luxurious levels of protein intake, because of apparently competing demands for protein. Such levels of protein nutrition are difficult to achieve in pasture-based systems, because of the protein limiting role of the rumen. Work with proteinprotecting tannins to overcome this limitation is discussed. The much more limited evidence for effect of mineral nutrition, particularly copper (Cu), molybdenum (Mo), cobalt (Co) and phosphorus (P), on outcome of larval challenge is also reviewed.

Journal Article↗
PubMed2003

Probable multigeneric resistance to macrocyclic lactone anthelmintics in cattle in New Zealand.

AIM: To establish the efficacy of topical formulations of eprinomectin and abamectin against naturally acquired abomasal and small intestinal nematode infections in cattle purchased from a North Island bull-beef property. METHODS: A controlled slaughter trial, involving eighteen 6-8-month-old mixed breed calves, was conducted in May 2002.The animals were randomly allocated on the basis of faecal egg count to one of three equal-sized groups (n=6), consisting of an untreated control group and two treatment groups. One of the treatment groups was treated with a topical formulation of eprinomectin, the other with abamectin. Both anthelmintics were administered as a single topical treatment on an individual liveweight basis, at the manufacturer's recommended dose rates of 0.5 mg/kg. All calves were housed in separate groups with no access to pasture throughout the entire trial and were slaughtered 7-10 days after treatment. RESULTS: Both anthelmintic treatments were highly effective(worm count reduction >98%) against Ostertagia ostertagi, Trichostrongylus axei and Cooperia punctata, but were not effective at reducing worm counts significantly of either Cooperia oncophora or Trichostrongylus longispicularis. Against these latter two parasites, worm count reductions of only 72% and 79%, and 81% and 76%, respectively, were recorded following treatment with eprinomectin or abamectin, respectively (all p>0.05). CONCLUSIONS: These results demonstrate evidence of resistance to macrocyclic lactone anthelmintics by C. oncophora and probably T. longispicularis also. CLINICAL RELEVANCE: As well as perhaps providing the first record of resistance to any anthelmintic by T. longispicularis, the present findings may also represent the first case of resistance to macrocyclic lactone anthelmintics exhibited by more than one parasite species at a time in cattle in New Zealand.

Journal Article↗
PubMed1984

Gut mucosal mast cells. Origin, traffic, and differentiation.

Gut mucosal mast cells (MMC), which are nearly absent in normal mice are abundant during nematode infection. In normal mice, study of MMC precursors (MMC-P: cells giving rise to MMC colonies in the presence of IL-3) show that: (a) their frequency, judged by limiting dilution is very high in bone marrow (BM) and gut, and very low in most lymphoid organs and thoracic duct lymph (TDL); (b) gut MMC-P are Thy-1- Lyt-1-2- and are not rapidly replicating; (c) they are the progeny of less differentiated BM MMC-P which are attracted from the blood to the gut mucosa by local factor(s), other than antigen and T cell factors (since normal amounts of gut MMC-P are found in germ-free, nude, and newborn mice). In mice bearing the Wehi 3 tumor (which releases enough IL-3 to produce detectable blood levels) spleen and mesenteric lymph nodes (LN) show increased MMC-P frequency, the greatest increase being in the gut and BM, where numerous differentiated MMC are found. In Nippostrongylus brasiliensis (Nb)-infested mice (known to develop a large, T cell-dependent, gut MMC infiltration), gut MMC-P proliferation is induced by IL-3 released from gut mucosal Thy-1+ Lyt-2- cells, whose in vitro IL-3 release capability is much higher than that of similar cells from normal mice. Both Nb-stimulated T blasts and proliferating MMC-P undergo cyclic traffic, migrating into the TDL and then seeding the whole length of the gut (a process which allows a widespread immune defense after a local antigenic stimulus). Experiments using 2-d interruption of this traffic and fetal gut grafts, suggest that the continuous homing of T blasts back to the gut which leads to permanent Nb-stimulated IL-3 release, is essential for the full maturation of MMC. Transfer experiments in the rat show that TDL circulating MMC-P rapidly mature into MMC when they home back to the Nb-infested gut. It is proposed that gut MMC arise after several stages of progressive differentiation of MMC-P, influenced both by IL-3 and unidentified gut factor(s).

Animals↗
PubMed1995

Impaired mucosal immune responses in interleukin 4-targeted mice.

Interleukin 4-targeted (IL-4-/-) mice are defective in T helper (Th)2 cytokine production as determined after nematode infection. As Th2 cells appear to be selectively induced by oral immunization we investigated the ability of IL-4-/- mice to respond to perorally administered antigen. We found that IL-4-/- mice failed to respond to soluble protein antigens given perorally together with cholera toxin (CT) as a mucosal adjuvant. In contrast to wild-type mice no or poor anti-keyhole limpet hemocyanin (KLH) or anti-ovalbumin (OVA) B cell responses were observed in gut lamina propria, spleen, or serum of IL-4-/- mice after oral immunization. In addition, mucosal immunization failed to stimulate antigen-specific T cell responses in these mice. The lack of responsiveness was specific for mucosal administration of antigen and was not seen after intravenous injections with antigen and CT-adjuvant. The systemic adjuvant effect of CT was not impaired in IL-4-/- mice as evidenced by the strong enhancement of anti-KLH responses after intravenous immunization with KLH plus CT as opposed to KLH alone. However, CT as an immunogen, in contrast to KLH or OVA, stimulated significant mucosal and systemic immune responses in IL-4-/- mice after oral immunization. Both serum and intestinal IgA anti-CT antibodies were demonstrable in IL-4-/- mice as well as in wild-type mice. Total IgA levels in gut lavage and in serum of immunized IL-4-/- mice were of similar magnitude as in wild-type mice, suggesting that the ability of naive B cells to undergo isotype switch-differentiation from IgM to IgA in IL-4-/- mice did not appear to be impaired. Immunohistochemical analysis of Peyer's patches demonstrated a complete inability to form germinal centers in IL-4-/- mice in contrast to wild-type mice. Our data suggest that IL-4-/- mice are unable to respond to oral/mucosal immunization due to a failure to stimulate antigen-specific cells required to induce germinal center reactions in the Peyer's patches. Our findings demonstrate that IL-4 and probably functional Th2 cells are required for induction of gut mucosal antibody responses.

Adjuvants, Immunologic↗
PubMed2000

Delayed expulsion of the nematode Trichinella spiralis in mice lacking the mucosal mast cell-specific granule chymase, mouse mast cell protease-1.

Expulsion of gastrointestinal nematodes is associated with pronounced mucosal mast cell (MMC) hyperplasia, differentiation, and activation, accompanied by the systemic release of MMC granule chymases (chymotrypsin-like serine proteases). The beta-chymase mouse mast cell protease-1 (mMCP-1) is expressed predominantly by intraepithelial MMCs, and levels in the bloodstream and intestinal lumen are maximal at the time of worm expulsion in parasitized mice. To address the in vivo functions of MMC-specific beta-chymases, we have generated transgenic mice that lack the mMCP-1 gene. They were backcrossed onto a congenic BALB/c background to investigate the response to nematode infection. The deletion of the mMCP-1 gene is associated with significantly delayed expulsion of Trichinella spiralis and increased deposition of muscle larvae in BALB/c mice despite the presence of normal and sometimes increased numbers of MMCs. Neither worm fecundity nor worm burdens were altered in Nippostrongylus-infected mMCP-1(-/)- BALB/c mice. These data demonstrate, for the first time, that the ablation of an MMC-derived effector molecule compromises the expulsion process.

Animals↗
PubMed1977

Trichinosis in an immunosuppressed human host.

The clinical presentation and autopsy findings in the case of a patient with acute myelomonocytic leukemia and trichinosis are described. Cellular immunity is an important host defense against nematode infections such as strongyloidiasis. It is therefore probable that the severe trichinosis seen in this immunosuppressed patient was more than coincidental. Due to concomitant failure of humoral immunity, serodiagnosis of trichinosis would have been impossible. The only means of making the diagnosis antemortem would have been muscle biopsy.

Female↗
PubMed2025

The ecology, evolution, and physiology of Cardinium: a widespread heritable endosymbiont of invertebrates.

Candidatus Cardinium hertigii (Cardinium) are maternally transmitted obligate intracellular bacteria found in a wide range of invertebrate hosts, including arthropods and nematodes. Infection with Cardinium has substantial consequences for host biology, with many strains manipulating host reproduction to favor symbiont transmission by (i) feminizing male hosts, (ii) altering host sex allocation, (iii) inducing parthenogenesis, or (iv) causing cytoplasmic incompatibility. Other Cardinium strains can confer benefits to their host or alter host behavior. Cardinium-modified host phenotypes can result in selective sweeps of cytological elements through host populations and potentially reinforce host speciation. Cardinium has potential for applications in controlling arthropod pest species and arthropod-vectored disease transmission, although much remains to be explored regarding Cardinium physiology and host interactions. In this review, we provide an overview of Cardinium evolution and host distribution. We describe the various host phenotypes associated with Cardinium and how biological and environmental factors influence these symbioses. We also provide an overview of Cardinium metabolism, physiology, and potential mechanisms for interactions with hosts based on recent studies using genomics and transcriptomics. Finally, we discuss new methodologies and directions for Cardinium research, including improving our understanding of Cardinium physiology, response to environmental stress, and potential for controlling arthropod pest populations.

Symbiosis↗
PubMed1990

IgG4 subclass antibody serology for onchocerciasis.

Antibodies to phosphorylcholine and carbohydrate determinants responsible for much of the cross-reactivity among nematodes are subclass restricted in humans and absent in the IgG4 subclass. Total IgG and IgG4 antibody responses to Onchocerca volvulus were examined by enzyme immunoassay and by immunoblot. Significant background IgG reactivity was detected in both assays in US control sera and sera from patients with intestinal nematode infections, but background reactivity was negligible in the IgG4 assays. IgG4 antibodies were detected by enzyme immunoassay in 17 of 18 Nigerian onchocerciasis serum samples and in 2 of 9 endemic control serum samples. Cross-reactive IgG4 antibodies were present in serum pools from patients infected with other filariae. IgG4 antibodies recognized a restricted subset of O. volvulus antigens in immunoblots relative to IgG. These results confirm the previously reported enhanced specificity of IgG4 antibody assays for filariasis and extend the observation to include onchocerciasis. Whereas IgG4 subclass antibody serology is more specific than measurement of total IgG antibodies for onchocerciasis, cross-reactivity among filariae limits the utility of this approach.

Animals↗
PubMed1996

A critical role for stem cell factor and c-kit in host protective immunity to an intestinal helminth.

In common with many intestinal nematode infections, Trichinella spiralis infections in mice are associated with a pronounced intestinal mast cell hyperplasia. The expulsion of the parasite from the gut is temporally associated with intestinal mastocytosis and mast cell function reflected by the secretion of mast cell protease into tissue and serum. In vivo, mucosal mast cell production is highly dependent upon T cell-derived cytokines including IL-3 and IL-4. We present data here to show that intestinal mast cell hyperplasia induced by helminth infection is also dependent upon the production of stem cell factor (SCF). Neutralization of SCF by anti-SCF or anti-SCF receptor mAb completely abrogated the mast cell hyperplasia generated by T. spiralis infection. Moreover, worm expulsion was dramatically delayed in treated mice and a reduced intestinal eosinophilia was observed. These effects did not appear to be mediated through alteration of Th cell responses and the parasite-specific serum antibody response was not affected. The reduction in the mast cell response and worm expulsion observed after SCF neutralization were reversible following cessation of monoclonal treatment. The data presented here clearly demonstrate a major role for SCF in the generation of intestinal mastocytosis and the host protective immune response following parasitic infection.

Animals↗
PubMed1997

Evaluation of methods of insecticide application for control of smokybrown cockroaches (Dictyoptera: Blattidae).

The insecticide components of a previously developed integrated pest management system for smokybrown cockroaches, Periplaneta fuliginosa (Serville), were tested individually and at reduced application rates in 4 separate trials over 2 yr. A 2-bait combination (pellet and gel baits) did not significantly reduce cockroach abundance more than a single constituent bait alone. A targeted spray of trelamethrin was significantly less effective than a 2-bait combination. Residual activity of insecticides was determined with American cockroaches, P. americana (L.), in a laboratory bioassay. Chlorpyrifos wettable powder remained active < 12 d in the field, after which time its activity was not different from an experimental control (no insecticide residues), whereas chlorpyrifos pellet and hydramethylnon paste baits retained initial activity for > 27 d. Nematodes [Steinernema carpocapsae (Weiser)] applied as a spray solution did not effect the abundance of smokybrown cockroaches, and no cockroaches were recovered that exhibited nematode infection. Time needed to apply various insecticide treatments did not differ substantially (15-25 min per house), even for lower application rates.

Animals↗
PubMed2000

Both induction and morphogenesis of cyst nematode feeding cells are mediated by auxin.

Various lines of evidence show that local changes in the auxin concentration are involved in the initiation and directional expansion of syncytia induced by cyst nematodes. Analysis of nematode infections on auxin-insensitive tomato and Arabidopsis mutants revealed various phenotypes ranging from complete inhibition of syncytium development to a decrease in hypertrophy and lateral root formation at the infection site. Specific activation of an auxin-responsive promoter confirmed the role of auxin and pointed at a local accumulation of auxin in developing syncytia Disturbance of auxin gradients by inhibiting polar auxin transport with N-(1-naphthyl)phtalamic acid (NPA) resulted in abnormal feeding cells, which were characterized by extreme galling, massive disordered cell divisions in the cortex, and absence of radial expansion of the syncytium initial toward the vascular bundle. The role of auxin gradients in guiding feeding cell morphogenesis and the cross-talk between auxin and ethylene resulting in a local activation of cell wall degrading enzymes are discussed.

Animals↗
PubMed1997

Regulatory sequences of Arabidopsis drive reporter gene expression in nematode feeding structures.

In the quest for plant regulatory sequences capable of driving nematode-triggered effector gene expression in feeding structures, we show that promoter tagging is a valuable tool. A large collection of transgenic Arabidopsis plants was generated. They were transformed with a beta-glucuronidase gene functioning as a promoter tag. Three T-DNA constructs, pGV1047, p delta gusBin19, and pMOG553, were used. Early responses to nematode invasion were of primary interest. Six lines exhibiting beta-glucuronidase activity in syncytia induced by the beet cyst nematode were studied. Reporter gene activation was also identified in galls induced by root knot and ectoparasitic nematodes. Time-course studies revealed that all six tags were differentially activated during the development of the feeding structure. T-DNA-flanking regions responsible for the observed responses after nematode infection were isolated and characterized for promoter activity.

Animals↗
PubMed2006

Interdigital lesions and frequency of acute dermatolymphangioadenitis in lymphoedema in a filariasis-endemic area.

BACKGROUND: Lymphatic filariasis (LF) is a mosquito-borne nematode infection that causes permanent lymphatic dysfunction in virtually all infected individuals and clinical disease in a subset of these. One major sequel of infection is lymphoedema of the limbs. Lymphoedema of the leg affects an estimated 15 million persons in LF-endemic areas worldwide. Acute dermatolymphangioadenitis (ADLA) in people with filarial lymphoedema causes acute morbidity and increasingly severe lymphoedema. Episodes of ADLA are believed to be caused by bacteria, and it has been shown that entry lesions in the skin play a causative role. Clinical observations suggest that interdigital skin lesions of the feet, often assumed to be fungal, may be of particular importance. OBJECTIVES: To investigate the epidemiology and aetiology of interdigital lesions (IDL) of the feet in filarial lymphoedema. METHODS: The frequency and mycological aetiology of IDL in 73 patients with filarial lymphoedema were compared with 74 individuals without lymphoedema in a region of Guyana highly endemic for Wuchereria bancrofti. RESULTS: More than 50% of patients with lymphoedema had one or more IDL (odds ratio 2.69; 95% confidence interval 1.31-5.66; P<0.005 compared with controls). The number of lesions was the strongest predictor of frequency of ADLA. Only 18% of the lesions had positive microscopy or culture for fungi (dermatophytes and Scytalidium). CONCLUSIONS: These findings highlight the importance of interdigital entry lesions as risk factors for episodes of ADLA and have implications for the control of morbidity from filarial lymphoedema.

Acute Disease↗
PubMed1992

Effect of inflammation of enteric nerves. Cytokine-induced changes in neurotransmitter content and release.

The results of our previously published work provide evidence of inflammation-induced functional disturbances in the enteric nervous system. Data presented in this paper describe our preliminary results indicating that the altered function in enteric nerves in the nematode-infected rat model of intestinal inflammation is mediated by interleukin-1. This is based on the ability of the exogenous cytokine to mimic changes observed in the model, and on the ability of a specific IL-1 antagonist to attenuate these changes. In addition, we have identified mechanisms underlying the actions of IL-1 in the myenteric plexus. Our data are consistent with a direct interaction between the cytokine and neural membranes. In addition, the delayed effect of IL-1 beta on neurotransmitter release appears to be due to the release of endogenous IL-1, most likely from macrophage-like cells in the myenteric plexus (Fig. 3). If such cells possess receptors for neuropeptides, as has been found with macrophages elsewhere in the gut, a neuroimmune axis would exist in the myenteric plexus. Thus, the finding of a source of IL-1 in the plexus of the noninflamed intestine invites speculation on a neuromodulatory role of the cytokine within the enteric nervous system.

Animals↗