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Protective immune response to Plasmodium chabaudi, developed by mice after drug controlled infection or vaccination with parasite extracts: analysis of stage specific antigens from the asexual blood cycle.

The protective immune response to asexual blood infection by Plasmodium chabaudi was studied in mice immunized either by drug controlled infection or by vaccination with preparations of merozoïtes or free parasites at different stages of development. Animals immunized by the first method developed a sterile immunity. The passive transfer of their serum protected naïve recipients from the lethal development of the infection, but affected only moderately the initial course of the parasitaemia. Animals immunized with either ring, schizont or merozoïte preparations exhibited a limited but significant resistance to infection: when challenged with 10(6) parasites of the homologous strain they exhibited a reduced parasitaemia as compared to control mice, and in addition, 50% of them recovered from the infection. Immunochemical analysis of parasite antigens showed that a family of high molecular weight proteins synthesized essentially at the schizont stage and conserved in the merozoites are important immunogens. Quantitative rather than qualitative differences were observed in the pattern of parasite proteins immunoprecipitated by serum of animals exhibiting sterile immunity or moderate protective immunity. A schizont specific polypeptide of mol. wt 82 Kd which is found in the surface of the merozoite is preferentially immunoprecipited by serum from animals exhibiting sterile immunity.

Animals↗

Circulating immune complex-associated parasite antigens in human onchocerciasis.

This study identified and characterized parasite antigens in sera from humans infected with Onchocerca volvulus. Immune complexes were precipitated from human sera with polyethylene glycol and analyzed by immunoblot with rabbit antibodies to O. volvulus. A 23-kDa parasite antigen was detected in sera from 17 of 23 Nigerian onchocerciasis patients and 5 of 10 endemic controls. Other parasite antigens with apparent molecular masses of 62, 66, and 70 kDa were less consistently observed. These antigens were not present in Nigerian or US nonendemic control sera, in sera from patients with various other parasitic infections, or in sera from US patients with autoimmune diseases. Biochemical studies indicated that these antigens are nonglycosylated acidic proteins that do not contain phosphorylcholine. These antigens may be useful as targets for improved diagnostic tests for onchocerciasis based on parasite antigen detection.

Adult↗

Potential chemotherapeutic targets in the purine metabolism of parasites.

Parasites are responsible for a wide variety of infectious diseases in human as well as in domestic and wild animals, causing an enormous health and economical blight. Current containment strategies are not entirely successful and parasitic infections are on the rise. In the absence of availability of antiparasitic vaccines, chemotherapy remains the mainstay for the treatment of most parasitic diseases. However, there is an urgent need for new drugs to prevent or combat some major parasitic infections because of lack of a single effective approach for controlling the parasites (e.g., trypanosomiasis) or because some serious parasitic infections developed resistance to presently available drugs (e.g., malaria). The rational design of a drug is usually based on biochemical and physiological differences between pathogens and host. Some of the most striking differences between parasites and their mammalian host are found in purine metabolism. Purine nucleotides can be synthesized by the de novo and/or the so-called "salvage" pathways. Unlike their mammalian host, most parasites studied lack the pathways for de novo purine biosynthesis and rely on the salvage pathways to meet their purine demands. Moreover, because of the great phylogenic separation between the host and the parasite, there are in some cases sufficient distinctions between corresponding enzymes of the purine salvage from the host and the parasite that can be exploited to design specific inhibitors or "subversive substrates" for the parasitic enzymes. Furthermore, the specificities of purine transport, the first step in purine salvage, diverge significantly between parasites and their mammalian host. This review highlights the unique transporters and enzymes responsible for the salvage of purines in parasites that could constitute excellent potential targets for the design of safe and effective antiparasitic drugs.

Animals↗

Characterization of the microbial community colonizing the anal and vulvar pores of helminths from the hindgut of zebras.

Scanning and transmission electron microscopy were used to examine the adherence and in situ morphology of the microbial community colonizing the anal and vulvar pores of the subfamily Cyathostominae (Nematoda: Strongylidae) from the colon of Burchell's zebra (Equus burchelli antiquorum). Two different morphological types of asporogenous rod were prominent in the microbial community. One was a thin, septate, filamentous organism (0.4 to 0.5 micron by 2 to 3 microns) with blunt ends, which was more prominent at the site of attachment. The other was a larger (1.8 to 2.4 microns by 5 to 10 microns) multicellular rod with round ends in the form of a trichome. Spiral- and vibrio-shaped bacteria were also present in the thin sections. The septate filaments were shown to contain a cell spacer similar to those described in Methanospirillum hungatei. Attachment to the cuticle was by means of an amorphous electron-dense material with fibrillar appearance and not by specialized holdfast segments. Ten isolates were obtained from a habitat-simulating medium on which a homogenate from the posterior region was plated. Antibodies were raised to whole cells of five rod-shaped isolates in rabbits and fluorescein isothiocyanate labeled. Positive bright-yellow fluorescence was obtained with one of the clostridial isolates. The results are discussed with reference to other bacteria with similar morphology, the nature of this unique interrelationship between the microbial community and its parasitic host inside the equine hindgut, and the possibility of biological control of parasitic helminths.

Animals↗

Use of hydroethidine and flow cytometry to assess the effects of leukocytes on the malarial parasite Plasmodium falciparum.

Flow cytometry was evaluated as a method of assessing in vitro the effects of leukocytes on blood-stage Plasmodium falciparum. Hydroethidine is converted by metabolizing cells to ethidium, a nucleic acid fluorochrome. After incubation with hydroethidine, viable and dead leukocytes and parasitized and uninfected erthrocytes could all be identified on the basis of fluorescence intensity and size. Leukocytes can therefore be eliminated from further analysis; this allows assessment, at any parasite developmental stage, of the level of parasitemia within erythrocytes in the presence of any of several types of leukocytes. Whether leukocytes actually kill intraerythrocytic parasites can therefore be determined and the level of cytotoxicity can be assessed. The ability of leukocytes to prevent merozoites from invading new erythrocytes, i.e., inhibition of parasite invasion, can also be assessed by this method. When erythrocytes containing schizont-stage parasites were cocultured with different leukocyte populations and the level of parasitemia was determined after merozoite release and invasion, only cultures containing gamma delta T cells inhibited parasite invasion. The different blood-stage forms of the parasite vary in nucleic acid content, which allows each of the developmental stages to be distinguished by flow cytometry; this permits assessment of changes in parasite development in the presence of leukocytes. Monocyte-derived macrophages (MDMs) appeared to have an effect on parasite development. In this instance, when erythrocytes containing ring-form parasites were cocultured with MDMs and harvested 24 h later, the parasites in cultures containing MDMs were at the late schizont stage, whereas parasites in control cultures were early trophozoites; this finding suggests that MDMs accelerate parasite development. Together, these results indicate that flow cytometry is potentially useful for measuring the following effects mediated by leukocytes: (i) level of cytotoxicity, (ii) changes in parasite development, and (iii) inhibition of parasite invasion.

Animals↗

Human factors facilitating the spread of a parasitic honey bee in South Africa.

Workers of the honey bee subspecies Apis mellifera capensis (Eschscholtz) produce female offspring by thelytokous parthenogenesis and can parasitize colonies of other subspecies. In 1990, translocation of 400 colonies of A. m. capensis into the distribution area of A. m. scutellata by a commercial beekeeper triggered a dramatic parasitic phenomenon. Parasitized colonies died within a few months of infestation, and this resulted in the loss of tens of thousands of colonies by commercial beekeepers in the A. m. scutellata range in South Africa. To deal with the problem and to identify methods that would limit the impact of the social parasite, we investigated the link between beekeeping management and severity of parasitic infestations in terms of colony mortality and productivity. We demonstrate that colonies from apiaries subjected to migrations are very susceptible to infestation and consequently show dramatic mortality. Their productivity is also inferior to sedentary colonies and those in isolated apiaries in terms of honey yield and brood quantity. Furthermore, by concentrating hives in small areas and often in the vicinity of other beekeepers, cross-infestations can easily occur. This can undermine previously parasite-free beekeeping businesses. As a result of our surveys, we propose beekeeping practices based on locally trapped bees, reduced migration, and better control of parasite spread, thus promoting the conservation of these pollinators. If followed by all the South African beekeepers, these measures should limit the spread of the parasite until it is eliminated within a few years, after which full migratory beekeeping practices could resume.

Animal Husbandry↗

Implications of fungicidal effects of benzimidazole compounds on Duddingtonia flagrans in integrated nematode parasite management in livestock.

An in vitro trial with carbendazim fungicide on the growth profile of the predatory fungus Duddingtonia flagrans was undertaken and in vivo trials in sheep and buffaloes, fed on chlamydospores of D. flagrans and administered albendazole anthelmintic, were conducted. Although no growth inhibition was detected at a carbendazim concentration of 0.05 ppm, growth inhibition was recorded of 50% and above at concentrations of 0.25 and 1.00 ppm (p < 0.001) and of around 90% at concentrations of 2.00 to 5.00 ppm (p <0.0001). Scanty recovery of the fungus was made from faecal culture 48 h following a single dose of albendazole both in sheep and buffaloes. However, profuse fungal recovery was made from 96 h post dosing onwards. When the drug was used as an intraruminal slow-release capsule, no faecal fungal recovery could be made from day 3 after administration of the capsule, when the albendazole sulphoxide concentration was around 1.0 microg/ml. However, profuse and scanty fungal recovery could be made on days 1 and 2, respectively, after administration of the capsule, when the plasma albendazole sulphoxide concentration was around 0.4 and 0.9 microg/ml, respectively. The implications for use of a combination of anthelmintics and biological control in sustainable parasite control programmes are discussed.

Animals↗

[Myocardial cell response to Trypanosoma cruzi infection].

The aim of this study is to establish the response of cardiac myocytes to the infection with Trypanosoma cruzi. The role of myocardial cell proliferation on heart remodelation and the ability of these cells to produce nitric oxide and control intracellular parasite growth during T. cruzi infection were evaluated. The presence of proliferating cell nuclear antigen (PCNA) was determined in myocardial cells of Wistar rats infected with T. cruzi, resulting in a significant increase of PCNA+ labelling in all stages of disease. The ability of myocardial cells to control growth of intracellular parasites and the production of nitric oxide were evaluated in cultures of cardiac myocytes obtained from neonatal rats. Different combinations of cytokines were added to culture media. The number of cardiac cells displaying intracellular amastigotes was lower in cultures supplemented with IL-1b, TNF-a and IFN-g than with other cytokine combinations and controls. The addition of cytokines resulted also in an increase of nitric oxide production in both infected and non-infected controls. These results demonstrate that myocardial cells participate actively in the response of the heart to the infection with T. cruzi.

Acute Disease↗

Top dressing of feed with desiccated chlamydospores of Duddingtonia flagrans for biological control of the pre-parasitic stages of ovine Haemonchus contortus.

Feeding trials were conducted with stall-fed sheep parasitized with Haemonchus contortus. For 10 days they were offered 250 g of a concentrate feed that had been top-dressed with desiccated chlamydospores of Duddingtonia flagrans at 1 x 10(5), 5 x 10(5), 1 x 10(6) or 2 x 10(6) chlamydospores/kg body weight. Pooled faeces from each group on day 7 of spore feeding were spread on different pasture plots. On day 28 after the start of spore feeding, further pooled faeces from each group were spread on the same plots. The larval burdens on the plots were monitored for 2 months and the larval harvest from in vitro faecal cultures were monitored regularly. The application of 1 x 10(6) or more spores/kg body weight virtually eliminated larvae from both the pasture and the faecal cultures. The application of as few as 1 x 10(5) spores/kg body weight had a profound impact on larval recovery. The effect persisted while the spores were being fed but not for more than 4 days following discontinuation of spore feeding. Top dressing supplementary feed with dried chlamydospores offers a potential way of using D. flagrans for biological control of the pre-parasitic stages of H. contortus.

Acetyltransferases↗

Parasite-mediated selection in experimental Daphnia magna populations.

It has been suggested that parasites are a strong selecting force for their hosts and therefore may alter the outcome of competition among host genotypes. We tested the extent to which parasite-mediated selection by different parasite species influenced competition among clones of the cyclic parthenogen Daphnia magna. We monitored clone frequency changes in laboratory microcosm populations consisting of 21 D. magna clones. Parasite treatments (two microsporidians, Glugoides intestinalis and Ordospora colligata) and a parasite-free control treatment were followed over a nine-month period. A further treatment with the bacterium Pasteuria ramosa failed. We found significant differences in clonal success among the treatments: the two parasite treatments differed from the control treatment and from each other. Additionally, we measured the clone-specific population carrying capacity, competitive ability against tester clones, and reproductive success of infected and uninfected females to test whether they correlate with clonal success in the microcosms. The clone-specific competitive ability was a good predictor of clonal success in the microcosms, but clonal carrying capacity and host reproductive success were not. Our study shows that parasite-mediated selection can strongly alter the outcome of clonal competition. The results suggest that parasites may influence microevolution in Daphnia populations during periods of asexual reproduction.

Animals↗

Antigens and immunity in Theileria annulata.

About 200 million cattle are believed to be at risk from the debilitating and often fatal effects of tropical theileriosis, caused by Theileria annulata. Currently, there is no very cheap effective drug for treatment of T. annulata infections, although the hydroxynophthoquinones parvaquone and buparvaquone are reported to give good results(1-4). Control of the parasite principally involves vector control against the ixodid tick vectors - mainly by cattle dipping and spraying with acaricides - and vaccination using attenuated macroschizont-infected leucocytes (1-17) (see Box I). In this article, Roger Hall discusses the nature of immunity that can be achieved against T. annulata, and progress in identifying the main antigens involved in this immunity.

Journal Article↗

Impact of dengue virus infection and its control.

Dengue virus infection has been counted among emerging and re-emerging diseases because of (1) the increasing number of patients, (2) the expansion of epidemic areas, and (3) the appearance of severe clinical manifestation of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS), which is often fatal if not properly treated. In the meantime, there are no effective dengue control measures: a dengue vaccine is still under development and vector control does not provide a long-lasting effect. In order to obtain direct evidence for the virulent virus theory concerning the pathogenesis of DHF/DSS, type 2 dengue virus strains isolated from patients with different clinical severities in the same epidemic area in northeast Thailand, during the same season, were comparatively sequenced. The result revealed a DF strain specific amino acid substitution from I to R in the PrM, and a DSS strain specific amino acid substitution from D to G in the NS1 gene regions, which could significantly alter the nature of these proteins. Moreover, DF strain specific nucleotide substitutions in the 3' noncoding region were predicted to alter its secondary structure. These amino acid and nucleotide substitutions in other strains isolated in different epidemic areas during other seasons, together with their biological significance, remain to be confirmed. In order to innovate dengue vector control, field tests were carried out in dengue epidemic areas in Vietnam to examine the efficacy of Olyset Net screen, which is a wide-mesh net made of polyethylene thread impregnated with permethrin. The results show that Olyset Net (1) reduced the number of principal dengue vector species, Aedes aegypti, (2) interrupted the silent transmission of dengue viruses and (3) was highly appreciated by the local people as a convenient and comfortable vector control method. This encouraging evaluation of the Olyset Net screen should be confirmed further by other tests under different settings.

Aedes↗

Visceral Leishmania donovani infection in interleukin-13-/- mice.

Leishmania donovani-infected interleukin-13-/- BALB/c mice showed impaired initial gamma interferon secretion and incomplete granuloma assembly at parasitized liver foci. Nonetheless, control of early parasite replication, resolution of liver infection, and responsiveness to antileishmanial chemotherapy were intact. By itself, interleukin-13 does not appear to materially influence acquired resistance in this intracellular infection.

Animals↗

[Endoparasites in swine in different age groups and management systems].

In different age groups endoparasites are of varying importance. Sows are predominantly infected with gastrointestinal strongyles (mainly Oesophagostomum spp.), Ascaris suum and Eimeriae, to a lesset extent with Trichuris suis, Hyostrongylus rubidus, Strongyloides ransomi or Isospora suis, while in suckling piglets I. suis and occasionally S. ransomi frequently occur. Weaners and fatteners are infected with coccidia and gastrointestinal strongyles, later with A. suum. Whipworms are also found occasionally. I suis causes diarrhoea in suckling piglets, while in older animals the infection is not correlated with disease. Damage induced by helminths is mainly due to reduced performance, in the case of ascarosis to reduced carcass value. Therefore planned antiparasitic measures should be taken at all stages of pig keeping. Hygienic measures can reduce infection pressure; however parasite elimination is difficult to obtain under conventional management conditions. Consequently the control of parasitic infection at the early stage of piglet production is desirable.

Age Factors↗

Life history and population biology of adult Acanthocephalus lucii (Acanthocephala: Echinorhynchidae).

The life history and population biology of adult A. lucii in perch, Perca fluviatilis L., from the Forth and Clyde canal, Scotland, was investigated during May 1979-September 1981. There was an annual cycle in the size of the parasite population; prevalence and abundance (+/- SE) were highest during late spring and summer (70-90% and 14 +/- 4.3 to 16 +/- 5.6 worms/fish, respectively) but declined during late autumn and reached a minimum during winter (50-60% and 2.1 +/- 0.9 to 3.2 +/- 0.6 worms/fish). Parasite maturation was associated with higher water temperatures during spring and summer and most shelled acanthors were probably produced during summer and fall. There was only 1 generation of A. lucii per year, although generations tended to overlap and individuals within each generation did not develop synchronously. The sex ratio of adults was initially near unity but favoured females in the later stages of the infection. The distribution of A. lucii among perch was highly aggregated and stomach content analysis suggested that this was partly due to heterogeneity in perch feeding behaviour. The negative binomial and Poisson lognormal models fitted the data on worm distribution. Seasonal changes in the degree of parasite aggregation were detected, but no conclusive evidence of density-dependent controls on parasite population growth was obtained.

Acanthocephala↗