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PubMed2003

Severe anemia affects both splenectomized and non-splenectomized Plasmodium falciparum-infected Aotus infulatus monkeys.

Severe anemia is the earliest and a frequently fatal complication of Plasmodium falciparum infection. Here we describe Aotus infulatus as a primate model suitable to study this malaria complication. Both non-splenectomized and splenectomized monkeys receiving different inocula of P. falciparum FVO strain presented large (> 50%) decreases in hematocrit values during infection. Non-splenectomized animals were able to control parasite growth (parasitemia did not exceed 4%), but they had to be treated because of severe anemia. Three of 4 splenectomized monkeys did not control parasitemia and were treated, but developed severe anemia after treatment when presenting a negative blood film. Destruction of parasitized red blood cells alone cannot account for the degree of anemia. Non-splenectomized monkeys repeatedly infected with homologous parasites became rapidly and progressively resistant to reinfection and to the development of severe anemia. The data presented here point to A. infulatus as a suitable model for studying the pathogenesis of severe malarial infection.

Anemia↗
PubMed2002

Anthelmintic resistance detection methods.

The development of species and populations of parasitic helminths with resistance to one or more anthelmintics is an increasing problem world-wide. The majority of currently available anthelmintics used to control parasitic nematodes of cattle and sheep belong to only three main groups, the benzimidazoles, imidazothiazoles and the avermectins/milbemycins. The successful implementation of helminth control programmes designed to limit the development of resistance in nematode populations depends to some degree on the availability of effective and sensitive methods for its detection and monitoring. A variety of in vivo and in vitro tests have been developed for the detection of nematode populations resistant to the main anthelmintic groups, but each suffers to some degree from reliability, reproducibility, sensitivity and ease of interpretation. This review covers those tests that have been reported and described and highlights some of their strengths and weaknesses.

Animals↗
PubMed2002

Influence of nematophagous fungi, earthworms and dung burial on development of the free-living stages of Ostertagia (Teladorsagia) circumcincta in New Zealand.

Biological options for nematode parasite control are being sought, as the long-term efficacy of conventional anthelmintics comes increasingly under threat from drug-resistant parasites. Three biological methods with the potential to reduce pasture contamination by parasitic nematode larvae were examined: (a) killing of larvae developing in dung by nematophagous fungi; (b) removal of dung through earthworm ingestion; (c) burial of dung in soil as might occur through the action of dung beetles. Field trials with the test bio-control agents were carried out in autumn and spring by adding dung from sheep infected with Ostertagia (Teladorsagia) circumcincta to pots of ryegrass/white clover. The factorial treatment structure included five fungal treatments (individual applications of Duddingtonia flagrans, Monacrosporium gephyropagum and Harposporium helicoides, a combination of all the three fungi together and an untreated control), two dung burial treatments (dung buried or deposited on the soil surface) and two earthworm treatments (earthworms present or absent). D. flagrans and H. helicoides, individually or in combination, reduced recovery of infective stage larvae in experiment 1, while only H. helicoides reduced recovery in experiment 2. In both the experiments, dung burial increased the total number of larvae recovered, while the number of infective larvae were reduced by the action of earthworms. Increased recovery following burial, along with the fact that larvae moved rapidly from soil onto herbage, suggests that soil may provide a protective reservoir for infective larvae infesting herbage.

Animals↗
PubMed2003

Biological control of nematode parasites of small ruminants in Malaysia using the nematophagous fungus Duddingtonia flagrans.

Control of nematode parasites of small ruminants in a wet, tropical environment using the nematophagous fungus, Duddingtonia flagrans, was assessed in this study. Two methods of fungal delivery were tested, namely as a daily feed supplement, or incorporated into feed blocks. Initially, pen trials were conducted with individually penned groups of sheep and goats at dose rates of 125,000 spores and 250,000 spores/kg live weight per day. At the lower dose rate this reduction was between 80 and 90% compared with the pre-treatment levels. At the higher dose rate, there was virtually complete suppression (>99% reduction) of larval recovery. Trials using the fungal feed blocks, showed that when animals were individually penned, they consumed only small amounts of the block (particularly goats), hence little effect on larval recovery in faecal cultures was observed. Grouping animals according to species and dose rate induced satisfactory block consumption and subsequent high levels of larval reduction in faecal cultures. These larval reductions were mirrored by the presence of fungus in faecal cultures. This work was followed by a small paddock trial, whereby three groups of sheep were fed either a feed supplement without fungal spores, supplement with spores, or offered fungal blocks. The dose rate of spores in the latter two groups was 500,000 spores/kg live weight per day. Egg counts were significantly reduced in the two fungal groups, compared with the control group and the latter required two salvage anthelmintic treatments to prevent mortality due to haemonchosis. Pasture larval numbers on the two fungal group plots were also much lower than on the control plot.

Animal Feed↗
PubMed2005

Protein kinases as targets for antimalarial intervention: Kinomics, structure-based design, transmission-blockade, and targeting host cell enzymes.

The surge of interest in protein kinases as targets for chemotherapeutic intervention in a number of diseases such as cancer and neurodegenerative disorders has stimulated research aimed at determining whether enzymes of this class might also be considered as targets in the context of diseases caused by parasitic protists. Here, we present an overview of recent developments in this field, concentrating (i) on the benefits gained from the availability of genomic databases for a number of parasitic protozoa, (ii) on the emerging field of structure-aided design of inhibitors targeting protein kinases of parasitic protists, (iii) on the concept known as transmission-blockade, whereby kinases implicated in the development of the parasite in their arthropod vector might be targeted to interfere with disease transmission, and (iv) on the possibility of controlling parasitic diseases through the inhibition of host cell protein kinases that are required for the establishment of infection by the parasites.

Animals↗
PubMed2001

The effect of parasite dose on disease severity in the rodent malaria Plasmodium chabaudi.

Experiments were designed to look at the relationship between infective dose and disease severity using 2 clones of Plasmodium chabaudi that differ in virulence. We asked whether there were dose-severity relationships, whether clone differences in virulence were maintained over a range of doses, and whether disease severity could be accounted for by parasite dynamics. Groups of mice were infected with parasite doses differing by an order of magnitude, ranging from 100 to 1 x 10(8) parasites. Infective dose affected the probability of death, but only with the more virulent clone. Dose also affected morbidity. For both clones, higher doses induced greater anaemia. Larger doses caused greater weight loss, but only for infections with the more virulent clone. Here, for a given dose, mice lost a fixed amount of weight, irrespective of their initial weight. Larger doses induced earlier mortality and morbidity than did lower dose treatments. Finally, dose affected parasite dynamics, with earlier and higher peak parasite densities in larger dose infections. All these effects were small relative to clone differences in disease severity, which were apparent across the range of doses. Dose effects were manifested through the timing and/or magnitude of peak parasite densities, broadly supporting the idea that dose affects disease severity by altering the time the host has to control parasite densities and ameliorate the effects of parasites. We discuss the possible efficacy of intervention strategies aimed at reducing human disease severity by reducing infective parasite dose.

Animals↗
PubMed2004

Leishmania braziliensis: partial control of experimental infection by interleukin-12 p40 deficient mice.

Resistance to infection by Leishmania major has been associated with the development of a Th1 type response that is dependent on the presence of interleukin 12 (IL-12). In this work the involvement of this cytokine in the response to infection by L. braziliensis, a less virulent species in the mouse model, was evaluated. Our results show that while interferon (IFN-gamma) deficient (-/-) mice inoculated L. braziliensis develop severe uncontrolled lesions, chronic lesions that remained under control up to 12 weeks of infection were observed in IL-12p40 -/- mice. IL 12p40 -/- mice had fewer parasites in their lesions than IFN-gamma (-/-) mice. Lymph node cells from IL-12p40 -/- were capable of producing low but consistent levels of IFN-gamma suggestive of its involvement in parasite control. Furthermore, as opposed to previous reports on L. major-infected animals, no switch to a Th2 response was observed in IL-12p40 -/- infected with L. braziliensis.

Animals↗
PubMed2002

Prevalence of parasitic infections in a rural area of Karachi, Pakistan.

OBJECTIVE: To find the prevalence of human intestinal pathogenic parasites. SETTING: The study was conducted in Konkor, Gadap, District East, Karachi. METHODS: After taking the verbal consent, all the villagers, selected by area sampling technique were interviewed by a structured questionnaire and then each person in the house was provided with a clean, plastic container to collect the stool samples. Samples were examined using normal saline, iodine preparation and zinc floatation technique where appropriate. RESULTS: Out of 263 residents 185 tested for intestinal parasites and 88 (47.5%) had pathogenic parasites. The distributions of parasites were Giardia lamblia 50% and Entamoeba histolytica 48.86%. Statistically none of the socio-demographic variables were associated except education and age group. CONCLUSION: In the light of the study result it is concluded that there is a high prevalence of parasitic infection in the community and an intervention strategy including health education program should be designed and implemented to control parasitic infections.

Adolescent↗
PubMed1995

[Studies on the enzyme cytochemistry of Toxoplasma gondii and the influence of artemether].

Male mice of Kunming strain were infected with 10,000 tachyzoites intraperitoneally. 2 hours after infection the mice were divided into 2 groups and administered 5% of amylum and 200 mg/kg of artemether by gavage for 8 consecutive days. The ultrastructural enzyme cytochemical studies on cytidine monophosphatase (CMP-ase) and glucose-6-phosphatase (G-6-P-ase) of the parasites were carried out. CMP-ase was found scattered in the lysosomes of the parasites as well as in the macrophages. No differences were observed in the localization and intensity of CMP-ase activity between the nontreated and treated with drug parasites. G-6-P-ase was found surrounding the parasite membrane and scattered in the parasitophorous vacuole in the nontreated parasites. After treatment with artemether, the intensity of G-6-P-ase activity was decreased compared with nontreated control parasites. It is suggested that artemether may exert some action on the G-6-P-ase of T. gondii and thus influence the energy metabolis of the parasite.

Animals↗
PubMed1982

Control of bovine parasitic gastroenteritis and parasitic bronchitis in a rotational grazing system using the morantel sustained release bolus.

Sixty cattle (12 first season and 48 second season grazing animals) were allocated to three groups according to age and bodyweight. Each group was divided into "control" and "treated" subgroups. Before turnout, a morantel sustained release bolus (MSRB) was administered to each animal in the "treated" category. The groups were moved from field to field according to the farmer's normal rotational grazing policy. Each field was, however, divided into two equal halves, one of which was reserved for the MSRB treated cattle, while the other was used exclusively for the controls. Severe parasitic gastroenteritis occurred in the first season controls during early September, while milder disease affected the untreated animals in the smaller of the second season groups. No gastrointestinal disease was apparent in the corresponding MSRB treated cattle. A mild outbreak of parasitic bronchitis occurred in the first year controls during October; there was evidence of less sever lungworm infection in the matching MSRB treated animals. The larger second season group showed no signs of parasitic disease.

Animal Husbandry↗
PubMed1996

Nematode sperm.

Parasitic nematode infections remain a major public health problem in many parts of the world. Because most of the current strategies aimed at controlling parasitic nematode infections have met with only limited success, it may be time to consider alternative approaches. An aspect of nematode biology that has drawn little attention as a target for control is the reproductive process. Although there are numerous facets of the overall reproductive biology of nematodes that hold potential as targets for intervention, Alan Scott here focuses on the male reproductive system, and outlines some of the known unique processes and characteristics of sperm formation and sperm function that could be exploited to block fertilization.

Journal Article↗
PubMed1996

Control of intestinal parasitic infections in Seychelles: a comprehensive and sustainable approach.

Intestinal parasitic infections have been perceived as a public health problem in Seychelles for decades. A comprehensive strategy to reduce morbidity and, in the long term, transmission of intestinal parasites has been implemented successfully since 1993. Management of the programme is integrated into the well established primary health care system, with control activities being undertaken through existing health facilities. The strategy is based on periodic chemotherapy of schoolchildren, intense health education and improvement of sanitation and safe water supply. The initial objectives of the control programme were met after 2 years of activities, with an overall reduction in prevalence of intestinal parasitic infections of 44%. The intensity of infection with Trichuris trichiura, the commonest parasite, was halved (from 780 to 370 eggs per g of faeces). The programme's integrated approach, in concert with political commitment and limited operational costs, is a warranty for the future sustainability of control activities. The programme can be seen as a model for other developing countries, even where health and socioeconomic conditions are different and the control of parasitic infections will need a much longer-term commitment.

Adolescent↗
PubMed2000

The effect of birdsfoot trefoil (Lotus corniculatus) and white clover (Trifolium repens) in mixed pasture swards on incoming and established nematode infections in young lambs.

Lotus corniculatus L., a leguminous plant containing condensed tannins, is now being evaluated in Sweden as a component of mixed pastures. This is because of its high nutritive value, palatability, modest requirement for water, calcium and phosphorous and particularly because it has the ability to survive harsh weather conditions that typify northern Scandinavia. This trial was undertaken to assess the possible parasitological benefits of using L. corniculatus when fed as a minor component in a mixed pasture sward to young sheep. This was compared with similar sheep that were fed pasture with a comparable legume content consisting of Trifolium repens L. Separate groups of lambs, maintained in pens and provided with fresh pasture cuts containing either L. corniculatus or T. repens each day, were trickle-dosed with infective larvae of mixed parasite species. For each pasture type, groups of 6 lambs had either established worm burdens only, received incoming infections only, or had the combination of both adult and incoming infections. Worm burdens were monitored by serial faecal egg counts and at the termination of the study, all animals were slaughtered for worm recovery, identification and enumeration. The results showed that there were no differential effects between L. corniculatus and T. repens on the different stages of development for a range of nematode parasite species recovered from these lambs. Several reasons may account for this: such as the low level of condensed tannins in the L. corniculatus variety tested, the minor proportion of this plant in the diet and/or the variety of L. corniculatus used in this trial which do not provide any benefits to controlling parasites of sheep.

Animals↗
PubMed2005

CXCR3-/- mice mount an efficient Th1 response but fail to control Leishmania major infection.

Chemokines play a critical role in recruitment of leukocytes to the site of infection, which is essential for host defense. We analyzed the role of CXC chemokine receptor 3 (CXCR3) in the control of cutaneous leishmaniasis using CXCR3-/- C57BL/6 mice. We found that Leishmania major-infected CXCR3-/- mice mount an efficient Th1 response as evident by markedly increased serum levels of Th1-associated IgG2a and significant production of IFN-gamma and IL-12 by the draining lymph node cells, restrict systemic spread of infection, but fail to control parasite replication at the site of infection and develop chronic non-healing lesions. Furthermore, the inability of CXCR3-/- mice to control cutaneous L. major growth was associated with fewer CD4+ and CD8+ T cells and significantly lower levels of IFN-gamma in their lesions as compared to CXCR3+/+ mice. These results demonstrate that CXCR3 plays a critical role in the host defense against cutaneous leishmaniasis caused by L. major. Furthermore, they also suggest that the susceptibility of CXCR3-/- mice to L. major is due to impaired CD4+ and CD8+ T cell trafficking and decreased production of IFN-gamma at the site of infection rather than to their inability to mount a parasite-specific Th1 response.

Animals↗
PubMed2004

Evaluation of biological control of sheep parasites using Duddingtonia flagrans under commercial farming conditions on the island of Gotland, Sweden.

Field trials, conducted over 3 consecutive years, were aimed at assessing farmer opinions of the practicality and effectiveness of using Duddingtonia flagrans to control nematode parasites in their flocks on the Swedish island of Gotland. These trials were also monitored by intensive parasitological investigation. On Gotland, lambing occurs in spring, and around mid-summer (late June), ewes and lambs are moved to saved pastures due to pasture deterioration caused by dry conditions. Weaned lambs are then returned to original lambing pastures in early autumn for finishing. One farm (B) was used for 2001-2003 and a second farm (N) was also used in 2002 and 2003. On each farm, two flocks (each of 20 ewes + twin lambs) were managed separately, namely: fungus group which received a daily supplement + fungal spores from lambing until the summer move (6 weeks) and: control group which received supplement only. For Farm B, the numbers of lambs that were marketed prior to the end of the grazing season, were 13, 18, 19 for the fungus treatment whereas corresponding numbers for the control treatment were 8, 16 and 11 for years 2001, 2002 and 2003, respectively. Final weights of the remaining lambs at the end of each year were also consistently heavier, and the numbers of lambs retained for finishing during winter were less, on the fungus treatment compared with the control treatment. On Farm N, similar results were recorded, with more lambs marketed earlier in the fungus group (25 and 19) compared with the control (19 and 15) in 2002 and 2003, respectively. The weights of the remaining lambs at the end of the trial in 2003 showed a 4.5 kg weight gain advantage of the fungus group compared to the controls. Tracer tests during autumn 2001 on Farm B, showed that Teladorsagia circumcincta plus Trichostrongylus spp. levels were significantly less on the fungus treatment (P=0.018). The summer/autumn of 2002 was one of the driest on record for Gotland. This resulted in very low levels of infective larval availability. But on both farms, T. circumcincta numbers were less on the fungus than on the control paddocks (P=0.048 on Farm B). In 2003 very low numbers of infective larvae were recorded in the autumn tracers for both treatments on both farms. Both farmer co-operators were encouraged with these results and consider that biological control of nematode parasites in their flocks, using D. flagrans, is of practical value.

Animals↗
PubMed2001

Modulation of chagasic cardiomyopathy by interleukin-4: dissociation between inflammation and tissue parasitism.

Chronic chagasic cardiomyopathy (CChC) is characterized by an inflammatory reaction which may eventually lead to heart enlargement, arrythmia, and death. As described herein, interleukin-4-deficient mice mount increased specific T helper (Th) 1 immune responses when infected with Trypanosoma cruzi, as compared to wild-type mice. Interestingly, these mice had reduced parasitism and mortality and exacerbated inflammation in their hearts, demonstrating a clear dissociation between inflammation and parasite load. The modulation of these phenomena so as to maximize host and parasite survivals may depend on a fine balance between Th responses, in which a Th1 response will, on one hand, control parasitism and, on the other hand, enhance heart inflammation throughout the course of the infection.

Animals↗
PubMed2001

Role of peroxynitrite in macrophage microbicidal mechanisms in vivo revealed by protein nitration and hydroxylation.

The cytotoxins produced by phagocytic cells lacking peroxidases such as macrophages remain elusive. To elucidate macrophage microbicidal mechanisms in vivo, we compared the lesion tissue responses of resistant (C57Bl/6) and susceptible (BALB/c) mice to Leishmania amazonensis infection. This comparison demonstrated that parasite control relied on lesion macrophage activation with inducible nitric oxide synthase expression (iNOS), nitric oxide synthesis, and extensive nitration of parasites inside macrophage phagolysosomes at an early infection stage. Nitration and iNOS expression were monitored by confocal microscopy; nitric oxide synthesis was monitored by EPR. The main macrophage nitrating agent was shown to be peroxynitrite derived because parasite nitration occurred in the virtual absence of polymorphonuclear cells (monitored as peroxidase activity) and was accompanied by protein hydroxylation (monitored as 3-hydroxytyrosine levels). In vitro studies confirmed that peroxynitrite is cytotoxic to parasites whereas nitric oxide is cytostatic. The results indicate that peroxynitrite is likely to be produced close to the parasites and most of it reacts with carbon dioxide to produce carbonate radical anion and nitrogen dioxide whose concerted action leads to parasite nitration. In parallel, some peroxynitrite decomposition to the hydroxyl radical should occur due to the detection of hydroxylated proteins in the healing tissues. Consequently, peroxynitrite and derived radicals are likely to be important macrophage-derived cytotoxins.

Animals↗
PubMed2006

The effect of an indirect anthelmintic treatment on parasites and breeding success of free-living pheasants Phasianus colchicus.

In Great Britain free-living common pheasants Phasianus colchicus are often managed at high densities owing to their popularity as a quarry species. They are prone to infection by a range of parasite species including Heterakis gallinarum, Capillaria spp. and Syngamus trachea. In 1995 the efficacy of an indirect anthelmintic technique for controlling parasitic worm burdens of pheasants was determined in a pilot study on a shooting estate in the south of England. Between 2000 and 2003 a large-scale field experiment was conducted on nine estates in eastern England to determine the effect of the technique on parasite burden and pheasant breeding success. In the absence of anthelmintic treatment worm burdens increased rapidly through March and April, whereas birds given anthelmintic-treated grain had lower worm burdens during the same period. The breeding success of pheasants was significantly higher on plots provided with anthelmintic treatment, although no long-term increases in population densities were observed. The burdens of the most common parasite H. gallinarum were significantly lower in pheasants from treatment plots six weeks after the anthelmintic treatment had ceased, but spring treatment did not influence parasite burden in the following winter.

Animal Feed↗