bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Wellcome Trust Lecture: Infection and disease in lymphatic filariasis: an immunological perspective
Authors: OtteSen E. A. 
Published: June 2009

SUMMARYThe basic tenet of the immunological perspective of fuiarial disease is that differential immune responsiveness among individuals exposed to infection results in the different clinical manifestations that develop. The mechanisms involved in this differential responsiveness appear to reflect different T-cell cytokine response patterns. Asymptomatic patients with the clinically silent presentation of ‘asymptomatic microfilaraemia’, who have been previously described as being ‘immunosuppressed’ with respect to their generating pro-inflammatory (Th1-type) immune responses to parasite antigen, are now recognized to be fully responsive to parasite antigen but to produce cytokines and mediators that have primarily anti-inflammatory (Th2-like) effects. Studies with immunodeficient mice have indicated the existence of two alternative pathways to the development of lymphatic pathology: one dependent on the induction of inflammatory reactions by the host immune response, the other entirely independent of the immune system and reflecting the direct actions of the parasite or its products on the lymphatics. As histopathology of affected human lymphatics is consistent with this hypothesis, it may be that the lymphatic pathology seen normally in the amicrofilaraemic, highly immunoresponsive infected patients derives from inflammation induced by immune responses to parasite antigen, whereas the lymphatic pathology sometimes seen coexisting with the ‘immunosuppressed’ state of asymptomatic microfilaraemia actually reflects lymphatic damage that is not immunologically mediated. Though little information exists about the ‘natural history’ of lymphatic filariasis, there is no evidence for an inevitable progression from one clinical form to another. Instead, there appears to be a definite plasticity in the response that depends on prior (? pre-natal) and current exposure to the parasite as well as on the immunomodulatory effects it induces. This plasticity does not appear to be complete, however, as there is no evidence that a chronically infected host who has developed strong pro-inflammatory immune responses can subsequently become sufficiently ‘down-regulated’ to support an asymptomatic microfilaraemia type of infection. Another possible constraint to the plasticity of the clinical and immunological responses may be the genetic determination of certain unusual syndromes, such as tropical pulmonary eosinophilia or TPE, though this hypothesis remains to be proven.
Immuno-epidemiology of human geohelminthiasis: ecological and immunological determinants of worm burden
Authors: Bundy D. A. P. , Medley G. F. 
Published: June 2009

SUMMARYThe morbidity and transmission dynamics of geohelminthiases are determined by the patterns of infection intensity in the community. Understanding the determinants of these patterns requires a combination of field, laboratory and theoretical study. Studies of age-specific reinfection, and of the phenomenon of predisposition, indicate that the major determinant of convex age-intensity profiles and of heterogeneity in infection intensity is the rate of establishment of infection, rather than the rate of adult worm mortality. The rate of establishment is, in turn, determined by exposure to, and protection from, infection. The evidence indicates that exposure, at least to the orally-transmitted geohelminths, varies with age and is highly heterogeneous between hosts. The immune response in geohelminthiasis is vigorous, parasite-specific, hetero geneous between hosts, and both age and infection dose dependent, but has yet to be convincingly shown to be protective. Since the immune response is itself a function of exposure, unravelling the interaction between ecology and immunology as determinants of geohelminth worm burden will require simultaneous assessment of both processes via immuno epidemiological study.
Food-borne bacterial infections
Authors: Lacey R. W. 
Published: June 2009

SUMMARYThe number of episodes of diseases caused by bacterial contamination of food has shown a real increase by about threefold in the last decade in the U.K. The numbers for 1992 are estimated to be 2 million. The causes are multifactorial and complex, and 4 representative pathogens are reviewed. The main increase in diseases due to salmonella has been caused bySalmonella enteritidis, especially from eggs. The commonest bacterial food pathogen is Campylobacter, which causes an illness with specific season peaks in May and June. This may be related to the activities of birds and mammals. Both these bacteria cause common diseases that are rarely fatal. In contrast, Listeria andE. coliare ubiquitous but rarely produce disease; however, the consequences of any such illness are often dire. Procedures and techniques are available for the control of most of these diseases, but society does not seem determined to implement them.
Filariasis: nutritional interactions in human and animal hosts
Authors: Storey D. M. 
Published: June 2009

SUMMARYVector-borne nematodes of the Order Filarioidea produce chronic, debilitating human infections which are usually non-fatal but are associated with a high degree of severe morbidity. Weight loss often accompanies infection and is probably a consequence of the increased energy cost associated with filarial fever, lymphangitis and lymphadenitis. In onchocerciasis, weight loss is associated with heavy worm loads as assessed by abundant nodules and large numbers of skin microfilariae. Experimental infections using rodent filariae have confirmed these observations and have also shown that low protein diets render hosts more susceptible to infection; nevertheless, parasite growth and embryogenesis is retarded in stunted female worms from protein deficient animals. In the absence of appropriate evidence, studies of experimental filariasis suggest that human protein-energy malnutrition may delay the development of stage-specific acquired immunity with a corresponding prolongation of patency. Epidemiological and experimental evidence shows that filarial nematodes acquire certain nutrients directly from their hosts. Of major importance in this respect is vitamin A which is taken up preferentially by human and rodent filariae; in humans, symptoms of hypovitaminosis A often accompany infection and could be an aggravating factor in onchocerciasis. Filariae also appear to require other specific nutrients such as iodine, thiamine and pyridoxine; dietary levels of these nutrients affect the host-parasite relationships in filariasis and pyridoxine seems to be of particular importance in this respect. Filarial parasites obviously compete with their hosts for available nutrients and, in the real world, human filariasis is often associated with a deterioration in the plane of nutrition of infected individuals.
Nutritional and physiological consequences of tumour glycolysis
Authors: Dills W. L. 
Published: June 2009

SUMMARYA frequent characteristic of many malignant tumours is an increase in anaerobic glycolysis, that is the conversion of glucose to lactate, when compared to normal tissues. The causes of this intensification involve changes in enzyme and glucose transporter levels, shifts of the isoenzyme patterns in the cancer cells to those similar to foetal tissues and a breakdown in the normal control mechanisms, most notably the Pasteur effect. The host must adapt, with a corresponding increase in gluconeogenesis. This change, along with other adaptations made by the host, eventually results in the syndrome known as cancer cachexia, which is characterized by anorexia and depletion and redistribution of the host energy stores. In some ways many malignant tumours behave much like parasites, drawing upon the host for nutrients such as glucose and returning waste products such as lactate to the host for recycling or disposal. This cycling of glucose and lactate between host and tumour has been the target for a number of proposed and tested treatments, with regard to the possible inhibition of tumour growth and/or possible prevention of some or all of the cachectic effects. Some of these suggested treatments have reached the point of clinical testing and show promise for continued research.
Characterization of phosphoglycan-containing secretory products ofLeishmania
Authors: Ilg T. , Stierhof Y.-D. , Wiese M. , McConville M. J. , Overath P. 
Published: June 2009

SUMMARYThis article presents an overview on phosphoglycan-containing components secreted by the insect and mammalian stages of several species ofLeishmania, the causative agents of leishmaniasis in the Old and New World. Firstly, promastigotes of all three species considered,L. mexicana, L. donovaniandL. major, shed lipophosphoglycan (LPG) into the culture medium possibly by release of micelles from the cell surface. Like the cell-associated LPG, culture supernatant LPG is arhphiphilic and composed of a lysoalkylphosphatidylinositol-phosphosaccharide core connected to species-specific phosphosaccharide repeats and oligosaccharide caps. Secondly, all three species release hydrophilic phosphoglycan. Thirdly, all three species appear to secrete proteins covalently modified by phosphosaccharide repeats and oligosaccharide caps. In the case of promastigotes ofL. mexicana, these components are organized as two filamentous polymers released from the flagellar pocket: the secreted acid phosphatase (sAP) composed of a 100 kDa phosphoglycoprotein and a protein- containing high-molecular-weight-phosphoglycan (proteo-HMWPG) and fibrous networks likewise composed of phosphoglycan possibly linked to protein. Structural analyses and gene cloning suggest that the parasites can covalently modify protein regions rich in serine and threonine residues by the attachment of phosphosaccharide repeats capped by oligosaccharides. We propose that the networks formedin vitrocorrespond to fibrous material previously demonstrated in the digestive tract of infected sandflies. In the case ofL. donovani, the sAP is also modified by phosphoglycans but contains neither proteo-HMWPG nor does it aggregate to filaments. Finally,L. mexicanaamastigotes release proteo-HMWPG via the flagellar pocket into the parasitophorous vacuole of infected macrophages. This material appears to be released into the tissue of the infected mammal upon rupture of infected macrophages during lesion development. This secretory product may contribute to the pathology of lesion development.
Inhibitory action of the anti-malarial compound atovaquone (566C80) against Plasmodium berghei ANKA in the mosquito, Anopheles stephensi
Authors: Fowler R. E. , Billingsley P. F. , Pudney M. , Sinden R. E. 
Published: June 2009

SUMMARYThe activity of atovaquone against Plasmodium berghei ANKA during sporogonic development has been examined. Anopheles stephensi mosquitoes were fed on gametocyte infected mice which had been treated 8 h previously with atovaquone or diluent alone. Mosquito midguts were examined for oocysts, and salivary gland infections were estimated using an ELISA for the circumsporozoite protein (CSP). The number of oocysts per midgut fell by at least 97% when mosquitoes were fed on mice dosed with 0·1–10 mg atovaquone/kg body weight. This was paralleled by a decrease in the prevalence of oocyst-infected mosquitoes from 70–90% in controls to 40% or 10% respectively. No oocysts were observed at a dose of 100 mg/kg. CSP ELISA results indicated that mosquitoes fed on atovaquone failed to produce sporozoites. Mosquitoes which fed on gametocytaemic, atovaquone-treated mice (0·1–100 mg/kg) did not transmit malaria to naive mice. These results demonstrate that atovaquone has a highly potent inhibitory activity against the mosquito stages of P. berghei.
Schistosoma mansoni: immunolocalization of two different fucose-containing carbohydrate epitopes
Authors: Köster B. , Strand M. 
Published: June 2009

SUMMARYWe have used two monoclonal antibodies, 128C3/3 and 504B1, to immunolocalize their carbohydrate epitopes in different developmental stages ofSchistosoma mansoni. Both epitopes contain fucose: mAb 128C3/3, as we have shown previously, recognizes fucose in a novel, possibly internal linkage (Leveryet al.1992) while mAb 504B1, as we show here, bound to the Lexepitope, which contains fucose α1 → 3 linked toN-acetyl-glucosamine. The tissue expression of these epitopes was strikingly different and both elicit an immune response in infected hosts. The mAb 128C3/3-defined epitope was exposed on the surface of all larval stages but not on adult worms; however, it was found in the excretory system of adult worms of both sexes. In contrast, surface expression of the Lexepitope was initiated after the transformation of cercariae to schistosomula and was maintained throughout the adult life in both sexes.
Immunological relationships during primary infection withHeligmosomoides polygyrus: Th2 cytokines and primary response phenotype
Authors: Wahid F. N. , Behnke J. M. , Grencis R. K. , Else K. J. , Ben-Smith A. W. 
Published: June 2009

SUMMARYThe primary immune response to infection withHeligmosomoides polygyruswas studied in mice differing in response phenotype (fast-SWR, intermediate-NIH, slow-CBA). Marked IgGl and IgE but not IgG2a antibody responses were detected in infected mice and the former were more intense in fast compared with slow responder strains. Mastocytosis, MMCP-1, and the secretion of cytokines by mesenteric lymph node cells, following stimulationin vitroby Con A, were also more intense initially in SWR mice. Secretion of IL-4 declined in all strains by the 4th week of infection, irrespective of response phenotype. IL-10 was only produced briefly by SWR mice. However, the temporal patterns of secretion of IL-3 and IL-9 clearly distinguished fast from slow responder phenotypes. Following initial intense secretion of IL-3, production declined in all strains but in the 5–6th weeks enhanced secretion was evident in SWR and NIH mice and was sustained until week 10 p.i. In contrast, CBA mice never recovered from the initial down-regulation in weeks 3–4 and secretion declined to background levels by week 6 p.i. despite the continued presence of adult worms. Temporal changes in the secretion of IL-9 were very similar: secretion declined in CBA mice by week 6 p.i., whilst SWR and NIH mice continued to secrete high amounts. We suggest that fast and slow responder mice differ not only in their initial responsiveness to parasite antigens but also in their ability to sustain a Th2 response to the parasite and we propose that the latter is in part determined by their different susceptibilities to parasite-mediated immunomodulation. Only the fast responder strains can sustain a Th2 response of sufficient intensity to facilitate expulsion of adult worms.
The detection of AKH/HrTH-like peptides inAscaridia galliandAscaris suumusing an insect hyperglycaemic bioassay
Authors: Davenport T. R. B. , Eaves L. A. , Hayes T. K. , Lee D. L. , Isaac R. E. 
Published: June 2009

SUMMARYEvidence for the presence of adipokinetic hormone/hypertrehalosaemic hormone (AKH/HrTH)-like peptides in the parasitic nematodesAscaridia galliandAscaris suumhas been obtained using insect bioassays which measure hyperglycaemic responses to peptides belonging to the AKH/HrTH family of insect hormones. A peptide fraction extracted from heads and tails ofAscaridia gallievoked a dose-dependent hyperglycaemic response when injected into the cockroach,Periplaneta americana. Maximal bioactivity was obtained with material that was equivalent to 38 mg (wet weight) of nematode. Bioactivity appeared to be highest in extracts from heads and tails of both male and female worms and could be fractionated into at least three peaks of hyperglycaemic activity by reversed-phase high-performance liquid chromatography. An extract from heads and tails ofA. suumalso evoked a hyperglycaemic response when injected into the cockroach,Blaberus discoidalis. The bioactivity was inactivated on incubation with pure endopeptidase 24.11, confirming the peptidic nature of the bioactive material. These results provide evidence for the existence of peptides related to the insect AKH/HrTH family of peptides in parasitic nematodes.
Cytoadherence-related neoantigens onPlasmodium falciparum(human malaria)-infected human erythrocytes result from the exposure of normally cryptic regions of the band 3 protein
Authors: Crandall I. , Sherman I. W. 
Published: June 2009

SUMMARYMurine monoclonal antibodies (Mabs) were produced by vaccination of Balb/c mice with livePlasmodium falciparuminfected red cells (iRBC). The iRBC Mabs recognized altered forms of the human erythrocyte membrane protein band 3; however, these Mabs did not recognize the band 3 molecule in uninfected or ring-infected red cells. The location of epitopes was determined by studying the binding of the iRBC Mabs after selective proteolysis of band 3 as well as by the reactivity of these Mabs to synthetic peptides that corresponded to putative exofacial regions of band 3. Treatment of uninfected red cell membranes with trypsin under low ionic strength conditions resulted in exposure of cryptic epitopes of band 3 which were recognized by the iRBC Mabs. Several of the anti-iRBC Mabs (two of which were described previously) inhibited thein vitroadherence of infected erythrocytes to C32 amelanotic melanoma cells. A mouse polyclonal serum against a synthetic peptide based on an amino acid sequence motif of band 3 reacted (by immunostaining) only with the surface of iRBC and blocked adhesion. Thus, it appears that cryptic residues of the band 3 protein become exposed upon parasitization, and their presence contributes to the increased adhesiveness of theP. falciparum-infected red cell.
Analysis of the high molecular weight rhoptry complex ofPlasmodium falciparumusing monoclonal antibodies
Authors: Doury J.-C. , Bonnefoy S. , Roger N. , Dubremetz J.-F. , Mercereau-Puijalon O. 
Published: June 2009

SUMMARYTwenty-one monoclonal antibodies, obtained after immunization of mice with erythrocytic stages ofPlasmodium falciparum, produced a double dot image in IFA. Immunoelectronmicroscopy indicated that the mAbs reacted with the rhoptries. Rhoptries are pear-shaped apical organelles, believed to be involved in invasion of the host cell by the parasite. The mAbs all immunoprecipitated the high molecular weight antigen complex. Some mAbs recognized on immunoblots only 1 protein of this complex, whereas others reacted with RhopH1 and RhopH3, or RhopH2 and RhopH3 or with the 3 proteins. An additional antigen of 52 kDa was also recognized by some of the mAbs. The epitopes defined by the mAbs were present in most of the 40P. falciparumstrains or isolates studied by IFA. Interestingly, the mAbs also reacted with high titres onP. vivaxandP. ovale, but produced images that did not indicate an apical location. The mAbs failed to react on the non-human malaria parasites studied,P. cynomolgiandP. inui. OnP. bergheiorP. chabaudiparasites, only 5 mAbs gave a positive reaction, labelling a large network outside the parasite. Finally, the mAbs did not react withP. falciparumsporozoites, indicating that the rhoptries of merozoites and sporozoites, the two invasive stages of the malaria life-cycle are equipped with distinct sets of proteins.
Coproantigen detection in rats experimentally infected with Strongyloides ratti
Authors: Nageswaran C. , Craig P. S. , Devaney E. 
Published: June 2009

SUMMARYThe possibility of coproantigen detection in the diagnosis of strongyloidiasis was investigated in rats experimentally infected with Strongyloides ratti. A capture ELISA was developed using affinity-purified polyclonal antibodies raised in rabbits against adult and filariform larval somatic antigens. The first detection of coproantigen coincided with patency and the coproantigen level remained elevated even when the parasite count was low. Following challenge infection, when examination of stool for larvae or ova was negative, coproantigen was detected by anti-adult somatic capture ELISA. Despite the use of antisera raised against crude worm extracts, the test was specific showing only low cross-reactivity with Necator americanus and Syphacia muris.
Naturally acquired infections with Leishmania enriettii Muniz and Medina 1948 in guinea-pigs from São Paulo, Brazil
Authors: Machado M. I. , Milder R. V. , Pacheco R. S. , Silva M. , Braga R. R. , Lainson R. 
Published: June 2009

SUMMARYTwo domestic guinea-pigs (Cavia porcellus), bought in Pinheiros, São Paulo State, Brazil, were taken by their owners a farm in the rural district of Capão Bonito, close to the Atlantic Forest, São Paulo, where they both developed tumour-like and ulcerating lesions on the ears. The causative agent was identified as Leishmania (L.) enriettii, based on biological characters and isoenzyme profiles. Sources of the parasite in wild mammals, and the possible sandfly vector species discussed.
Neoglycosylated liposomes as efficient ligands for the evaluation of specific sugar receptors on macrophages in health and in experimental leishmaniasis
Authors: Dutta M. , Bandyopadhyay R. , Basu M. K. 
Published: June 2009

SUMMARYReceptors interacting with terminal sugars as ligands are involved in the binding ofLeishmania donovanipromastigotes to the macrophage surface and their subsequent internalization. Mannose and glucose are specifically involved in the binding process. Decreased binding occurs to macrophages already infected withL. donovanieitherin vivoorin vitro. When mannose- or glucose-bearing liposomes are used as ligands the binding shows similar trends and the percentage inhibition of binding with mannose-bearing liposomes increases when compared to that for the glucose-bearing ones. The decreased binding of the ligand seems to be due to a decrease in the number of receptors after infection. The affinity of the ligands for the binding sites either on the normal macrophages or on the infected macrophages apparently remains the same. The results based on the incorporation of [3H]phenyl alanine and supported by the binding of glycosylated liposomes to both infected and non-infected macrophages suggest that protein synthesis, in general, is suppressed inL. donovaniinfected macrophages thus affecting also mannose/glucose receptor protein synthesis, resulting in fewer receptors on the macrophage surface.
The potential of vervet monkeys (Cercopithecus aethiops) and baboons (Papio anubis) as models for the study of the immunology of Echinococcus granulosus infections
Authors: Rogan M. T. , Marshall I. , Reid G. D. F. , Macpherson C. N. L. , Craig P. S. 
Published: June 2009

SUMMARYNine vervet monkeys and nine baboons were infected with eggs of Echinococcus granulosus per as. Six of the vervets and one of the baboons possessed hydatid cysts at autopsy, 15–28 months post-infection. The sequential IgG response to hydatid fluid and protoscolex antigens showed considerable inter-animal variation. Infected vervets and baboons became seropositive after an average of 8 months post-infection. Considerable fluctuation in the IgG response was observed, particularly to the hydatid fluid antigen which, in humans, may contribute to the existence of a significant proportion of seronegative individuals. Vervets, in particular, may be useful to study immunological events associated with exposure, development and resolution of hydatid disease in outbred human populations.