Epidemiology, pathogenesis, and control of major swine helminth parasites.
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Animals↗
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Invasion, control and persistence of Leishmania parasites.
Significant advances in research on the immunopathogenesis of leishmaniasis include the discovery of novel putative evasion and survival strategies of Leishmania parasites, a more detailed understanding of the function and regulation of interleukin-12, definition of molecules involved in cognate interaction between macrophages and T cells and new ideas concerning the mechanisms of host resistance and susceptibility. The use of transgenic mice for (re)probing certain immunological aspects of leishmaniasis has yielded not only predictable and confirmatory but also unexpected and pioneering results which require critical appreciation.
Animals↗
The IL-27R (WSX-1) is required to suppress T cell hyperactivity during infection.
Although recent studies have described IL-27 and its receptor, WSX-1, as promoters of Th1 differentiation in naive CD4+ T cells, the data presented here indicate that signaling through this receptor is involved in limiting the intensity and duration of T cell activity. When WSX-1-deficient mice are infected with the intracellular pathogen Toxoplasma gondii, they establish protective T cell responses, characterized by production of inflammatory cytokines and control of parasite replication. However, infected WSX-1-/- mice are unable to downregulate these protective responses, and develop a lethal, T cell-mediated inflammatory disease. This pathology was characterized by the excessive production of IFN-gamma, persistence of highly activated T cells, and enhanced T cell proliferation in vivo. Together, these findings demonstrate that WSX-1 is not required for the generation of IFN-gamma-mediated immunity to this parasitic infection and identify a novel function for this receptor as a potent antagonist of T cell-mediated, immune hyperactivity.
Animals↗
Identification of HLA-A*0201-restricted cytotoxic T-cell epitopes of Trypanosoma cruzi TcP2beta protein in HLA-transgenic mice and patients.
Trypanosoma cruzi-specific cytotoxic T-lymphocyte (CTL) responses are critical in the control of parasite growth and will play an important part in therapeutic and prophylactic T. cruzi vaccines. The identification of parasite-specific epitopes that are efficiently recognized by CTLs is the first step in the development of future vaccines. HLA-A2 transgenic mice (HHD) were shown to provide a powerful model for studying the induction of HLA-A*0201-restricted immune responses in vivo, since these mice are endowed with a CTL repertoire representative of HLA-A2.1 individuals. Here, we describe the immunological characterization of T-cell epitopes of the T. cruzi ribosomal P2 protein (TcP2beta) that are recognized by HLA-A*0201-restricted CTLs in HLA-transgenic mice and humans. Epitopes identified in the present study do not share sequence homology with the homologous human or murine counterparts and so they should not induce any autoreactive response. Moreover, HHD mice vaccinated with these peptide epitopes have reduced parasitemia after challenge with a lethal T. cruzi infection. Hence, these epitopes represent potential subunit components of multi-protein vaccines to prevent Chagas' disease.
Amino Acid Sequence↗
Genomics, pathogenesis and control of infection with protozoan parasites.
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Animals↗
Immunodiagnostic and molecular approaches for the detection of taeniid cestode infections.
This article summarizes the most recent advances in techniques and applications for the detection of taeniid cestode-infected persons or animals. In addition, the use of molecular approaches for strain identification and control of parasite transmission is discussed.
Animals↗
Mosquito avoidance and bed net use in the Greater Accra Region, Ghana.
Qualitative research and cross-sectional survey methods were used in a study conducted in rural and urban areas of the Greater Accra Region, Ghana, to explore people's understanding of the cause of malaria and patterns of mosquito avoidance, in particular bed net ownership and use. The study indicated far higher bed net ownership and use in rural than urban areas, which was related partly to perceived affordability and partly to the different contexts of and reasons for avoiding mosquitoes. Knowledge of an association between mosquitoes and malaria, the most common cause of illness in both areas, was related to residence but not to literacy or formal education, and this knowledge did not predict bed net use. The paper points to the complexity of social and personal factors implicated in behavioural interventions for malaria control, and questions behavioural models that assume a linear relationship between knowledge and practice.
Adult↗
Experimental Schistosoma bovis infection in goats. Circulating antigen and antibody responses to egg and adult worm antigens during infection and following treatment with praziquantel.
Circulating antigen levels and antibody responses in Schistosoma bovis-infected West African Dwarf goats were evaluated during infection and following treatment with praziquantel (60 mg/kg) 13 weeks post-infection. One day, 1 week and 4 weeks post-treatment, subgroups of goats were sacrificed and perfused for worm recovery. For comparison, parasite-free control animals were included. Blood and faecal samples were collected biweekly. Two gut-associated schistosome antigens, circulating cathodic and circulating anodic antigen (CCA and CAA) and 3 specific antibody responses (total Ig, IgG and IgM) were measured. For specific antibody detection, crude S. bovis adult worm and egg homogenates were used. The level of CCA in the infected groups was significantly elevated from the time of onset of egg excretion onwards. However, following treatment, the CCA titres dropped to control levels within 1 week post-treatment. Strong positive correlations were found between CCA levels and worm counts and faecal egg counts during peak egg excretion. The correlations of CAA and specific antibody titres to egg and worm counts were poor. The antibody responses were all significantly elevated in the infected goats during patency, but only marginally affected by the treatment. Hence, CCA proved to be superior by correlating strongly to the level of infection and by being a sensitive indicator of the effect of treatment.
Animals↗
Hymenolepis diminuta: an investigation of juvenile hormone titre, degradation and supplementation in the intermediate host, Tenebrio molitor.
Metacestodes of Hymenolepis diminuta cause a perturbance of vitellogenesis in the intermediate host Tenebrio molitor. The reduction in host reproductive output associated with infection may be due to this pathophysiology. Many of these events are regulated by host juvenile hormone (JH). A comparison of the titre of JH and its rate of degradation in female control and parasitized 15-day-old insects has been made. Haemolymph from female beetles contained 1.27 pMol JH equivalents/100 microliters. No significant difference was associated with infection. Likewise, the activity of JH esterase in female haemolymph was not affected by infection. However, topical application of a JH analogue, methoprene, at the time of infection or 8 days post-infection reduced the significant accumulation of vitellogenin usually found in the haemolymph of females 12 days or more post-infection. These findings indicate that parasite-induced alteration of host vitellogenesis is not mediated via alteration in JH titres, although observations made after hormone supplementation suggest some form of interaction between the parasite and the host endocrine system.
Animals↗
Crystal structure of Tritrichomonas foetus inosine-5'-monophosphate dehydrogenase and the enzyme-product complex.
Inosine-5'-monophosphate dehydrogenase (IMPDH) is an attractive drug target for the control of parasitic infections. The enzyme catalyzes the oxidation of inosine monophosphate (IMP) to xanthosine monophosphate (XMP), the committed step in de novo guanosine monophosphate (GMP) biosynthesis. We have determined the crystal structures of IMPDH from the protozoan parasite Tritrichomonas foetus in the apo form at 2.3 A resolution and the enzyme-XMP complex at 2.6 A resolution. Each monomer of this tetrameric enzyme is comprised of two domains, the largest of which includes an eight-stranded parallel beta/alpha-barrel that contains the enzyme active site at the C termini of the barrel beta-strands. A second domain, comprised of residues 102-220, is disordered in the crystal. IMPDH is expected to be active as a tetramer, since the active site cavity is formed by strands from adjacent subunits. An intrasubunit disulfide bond, seen in the crystal structure, may stabilize the protein in a less active form, as high concentrations of reducing agent have been shown to increase enzyme activity. Disorder at the active site suggests that a high degree of flexibility may be inherent in the catalytic function of IMPDH. Unlike IMPDH from other species, the T. foetus enzyme has a single arginine that is largely responsible for coordinating the substrate phosphate in the active site. This structural uniqueness may facilitate structure-based identification and design of compounds that specifically inhibit the parasite enzyme.
Amino Acid Sequence↗
Prolonged persistence of fecally excreted ivermectin from reindeer in a sub-arctic environment.
In December 2001 and 2002, feces from reindeer calves treated with ivermectin were distributed on plots established on two types of forested reindeer pasture in northern Finland. The ungrazed plots were on an enclosure that had been fenced to prevent reindeer access for the last 6 years. The grazed plots were on an area that had been heavily stocked by reindeer during the last 5 years. After enclosures had been established, reindeer and large wildlife were prevented from entering by a fence. Topsoil samples (feces, vegetation, and soil) were collected monthly during the summers of the following 2 years, over a period of from 25 to 95 weeks after deposition. The samples were analyzed for ivermectin using HPLC. Although ivermectin degradation rapidly took place during the first spring, considerable residual ivermectin could be measured throughout the sampling time, showing that ivermectin in feces on pasture may not be photodegraded as rapidly as previously believed. The results support the need for further environmental evaluation studies on the use of ivermectin to control reindeer parasites.
Animals↗
Identification and characterization of a putative sevenless homologue in the malaria vector Anopheles gambiae.
Tyrosine kinase sequences were identified and characterized in Anopheles gambiae, the major vector of malaria in subsaharan Africa. One of these sequences has the characteristics expected for a homologue of the Drosophila sevenless gene, which is necessary for R7 photoreceptor cell fate determination in the developing compound eye. The putative Anopheles sevenless gene homologue is located in a telomeric region of the X chromosome and is expressed in the head of late larval and pupal stage mosquitoes. Identification of the Anopheles homologue of the sevenless gene is a first step towards the development of a dominant phenotypic marker that could be used for detecting transformed Anopheles mosquitoes in a wide variety of genetic backgrounds and, as such, could be used in the development of transgenic mosquitoes for the control of parasite transmission. Preliminary evidence for sevenless sequences were also found in DNA from blackfly, Mediterranean fruit fly and the honeybee.
Amino Acid Sequence↗
Redox balance mechanisms in Schistosoma mansoni rely on peroxiredoxins and albumin and implicate peroxiredoxins as novel drug targets.
Schistosoma mansoni, a causative agent of schistosomiasis, resides in the hepatic portal circulation of their human host up to 30 years without being eliminated by the host immune attack. Production of an antioxidant "firewall," which would neutralize the oxidative assault generated by host immune defenses, is one proposed survival mechanism of the parasite. Schistosomes lack catalase, the main H2O2-neutralizing enzyme of many organisms, and their glutathione peroxidases are in the phospholipid class with poor reactivity toward H2O2. Evidence implicates peroxiredoxins (Prx) as providing the main enzymatic activity to reduce H2O2 in the parasite. Quantitative monitoring of Prx mRNAs during parasite life cycle indicated that Prx proteins are differentially expressed, with highest expression occurring in adult stages (oxidative resistant stages). Incubation of schistosomula with Prx1 double-stranded RNA knocked down total Prx enzymatic activity and resulted in lowered survival of cultured parasites compared with controls demonstrating that Prx are essential parasite proteins. These results represent the first report of lethal gene silencing in Schistosoma. Investigation of downstream effects of Prx silencing revealed an abrupt increase of lipid peroxides and the generation of several oxidized proteins. Using mass spectrometry, parasite albumin and actin were identified as the main oxidized proteins. Gene expression analysis showed that schistosome albumin was induced by oxidative stress. This study highlights Prx proteins as essential parasite proteins and potential new targets for anti-schistosome drug development and albumin as a novel, sacrificial oxidant scavenging protein in parasite redox regulation.
Albumins↗
Gender-planned health services.
Gender-planned health services are planned on the basis that women and men play different roles in society and have different medical needs. The feminist movement has provided a broad charter of rights for women, reflecting women's needs, but these have yet to be translated into operational programmes. National programmes for women would allow co-ordination of broad-based programmes to improve women's health and social position. To change social norms discriminating against women will require changing male attitudes. Health programmes for males have received little attention, except from family planning organizations, although in most countries, males have a high rate of accidents, infections and parasitic disease. Controlled studies are required to evaluate the benefits of gender-planned health services.
Developing Countries↗
Estimating the economic effects of cystic echinococcosis: Uruguay, a developing country with upper-middle income.
Cost-benefit analyses, run before the commencement of a programme to control a parasitic disease, should include estimates of the economic losses attributable to the disease. Uruguay, a middle-income, developing country, has a recent history of persistent problems with cystic echinococcosis, in both its human population and livestock. The economic effects in Uruguay of this disease, caused by the larval stage of the canine tapeworm Echinococcus granulosus, have now been evaluated. Data on the incidence of the disease, in humans and livestock, were used to construct cost estimates. The estimated minimum cost (U.S.$2.9 million/year) was based on the condemnation costs of infected offal together with the actual costs of the hospital treatment of the human cases. The estimate of the maximum cost (U.S.$22.1 million/year) also included the production losses resulting from lower livestock efficiency and the reduced income of individuals with morbidity attributable to the disease.
Animals↗
Novel forages for growth and health in farmed deer.
AIMS: This paper reviews recent research on the use of new forages in deer farming that may be useful for increasing growth in weaner deer for venison production, increasing the trace element status of deer, and for developing systems less reliant on chemical inputs, notably of anthelmintics used to control internal parasites. GROWTH: Grazing on pure swards of red clover (Trifolium pratense) or chicory (Chicorium intybus) increased weaner growth during autumn by 26-47% and during spring by 10-14%, relative to red deer (Cervus elaphus) grazed on perennial ryegrass (Lolium perenne) /white clover (Trifolium repens) pasture (0.8/0.2). Pre-weaning growth during lactation was increased by approximately 20%. These increases were due to increased rate of degradation of feed particles in the rumen, leading to higher digestibility and higher voluntary feed intakes (VFI). Red clover and chicory produce a greater proportion of their total dry matter (DM) during late summer and autumn than perennial ryegrass/white clover pastures, and are therefore better aligned with the seasonal feed requirements of deer. Grazing on the legume, sulla (Hedysarum coronarium), in autumn and spring increased the growth of weaner deer by 33% and 10%, respectively, relative to pasture-fed animals. PARASITES: Plants containing substantial concentrations of secondary compounds such as condensed tannins (CT) show promise for reducing problems caused by internal parasites. CT present in some legumes and the presence of low concentrations of both CT and sesquiterpene lactones in chicory are reviewed. Feeding sulla containing 35g CT /kg DM reduced abomasal nematode establishment and tended to reduce lungworm (Dictyocaulis eckerti) larval counts in faeces. Relative to weaner deer grazing pasture, weaner deer grazing chicory during autumn required fewer anthelmintic treatments without depressing growth rates. CT extracted from a range of legumes, and CT and sesquiterpene lactones extracted from chicory reduced the in vitro motility of both lungworm and gastrointestinal nematode larvae. The beneficial effects of CT-containing forages on the ability of young deer to manage internal parasite infections could be due to: indirect effects of CT resulting in increased amino-acid absorption, better meeting demands of the immune system; direct inhibitory effects of CT on parasite larvae and; taller plant morphology, reducing the ingestion of infective larvae. The effects of CT depend upon both their structure and CT Condensed tannins DM Dry matter L1 First-stage larvae L3 Infective third-stage larvae LWG Liveweight gain ME Metabolisable energy OM Organic matter OMD Organic matter digestibility VFIVoluntary food intake concentration in the plant, which vary between growing conditions, plant varieties and species. TRACE ELEMENTS: Chicory contained higher concentrations of copper and cobalt than perennial ryegrass/white clover pasture grown on the same farm, and deer grazing chicory had higher liver concentrations of both copper and vitamin B12. These forages may contribute to maintaining adequate trace element status in deer. CONCLUSIONS: Grazing systems that include legumes and herbs such as sulla, red clover and chicory can be used to substantially increase the growth of weaner deer for venison production whilst maintaining deer health and reducing requirements for chemical inputs. For maximum plant persistence and animal responses, these plants should be grown and managed as special-purpose forages and not used in seed mixtures with perennial grasses.
Journal Article↗
Natural killer T cell ligand alpha-galactosylceramide enhances protective immunity induced by malaria vaccines.
The important role played by CD8(+) T lymphocytes in the control of parasitic and viral infections, as well as tumor development, has raised the need for the development of adjuvants capable of enhancing cell-mediated immunity. It is well established that protective immunity against liver stages of malaria parasites is primarily mediated by CD8(+) T cells in mice. Activation of natural killer T (NKT) cells by the glycolipid ligand, alpha-galactosylceramide (alpha-GalCer), causes bystander activation of NK, B, CD4(+), and CD8(+) T cells. Our study shows that coadministration of alpha-GalCer with suboptimal doses of irradiated sporozoites or recombinant viruses expressing a malaria antigen greatly enhances the level of protective anti-malaria immunity in mice. We also show that coadministration of alpha-GalCer with various different immunogens strongly enhances antigen-specific CD8(+) T cell responses, and to a lesser degree, Th1-type responses. The adjuvant effects of alpha-GalCer require CD1d molecules, Valpha14 NKT cells, and interferon gamma. As alpha-GalCer stimulates both human and murine NKT cells, these findings should contribute to the design of more effective vaccines against malaria and other intracellular pathogens, as well as tumors.
Adjuvants, Immunologic↗