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The role of polymorphonuclear leukocytes in the resistance to cutaneous Leishmaniasis.

The massive infiltration by polymorphonuclear leukocytes (PMN) soon after skin infection with Leishmania major suggests that PMN could participate in reducing parasite load and controlling the spreading of leishmanial infection. Yet, direct evidence for the participation of PMN in host defense against L. major was lacking. We investigated L. major infection in susceptible and resistant mice treated with the monoclonal (mAb) antibody RB6-8C5 that depletes the population of mature neutrophils and eosinophils. Both BALB/c and C57BL/6 mice depleted of PMN show accelerated parasite spreading and more severe footpad swelling than similarly infected untreated mice. In addition, significant higher parasite numbers were found in the lesion draining lymph nodes from PMN-depleted C57BL/6 mice. Histopathological analysis of the paw confirmed neutrophils containing ingested parasites as the dominant cell type in the infiltrate of the first days after infection and the nearly absolute neutrophil depletion in mAb-treated mice. Our data show the importance of PMN in early control of parasite load and parasitism spreading in cutaneous leishmaniasis.

Animals↗

Husbandry management, worm control practices and gastro-intestinal parasite infections of sows in pig-breeding farms in Münsterland, Germany.

A cross-sectional survey was performed on 144 farms randomly selected from 3 breeding organisations in Münsterland, Germany, to obtain representative data on husbandry management, worm control practices and their possible associations with gastro-intestinal parasite infections in sows. Straw bedding was provided in the majority of gestation units; lactating sows were frequently kept strawless. Pasturing of gilts and non-lactating sows were performed in 37% of the farms. Sows were treated with anthelmintics (mainly benzimidazoles, ivermectin or levamisole) in 98% of the farms. The proportions of farmers performing the 'targeted' (mainly prefarrowing) or 'non-targeted' treatment strategy (treatment of all animals several times per year) were similar. Piglets were anthelmintically dosed in only 19% of the farms. Patent infections of sows with Oesophagostomum spp., Ascaris suum, Trichuris suis and Eimeria spp. were detected in 79%, 7%, 8% and 29% of all the farms, respectively. Hyostrongylus rubidus infections were only found in farms with pasturing. The within-farm prevalences of both the strongylid and Eimeria infections were negatively correlated with the herd size but positively with the weaning age. Risk factors for strongylid infections were straw bedding in pens and pasturing. Pasturing was a risk factor for Eimeria infections too. There was a positive association between the time interval to last deworming of sows and strongylid egg counts. However, neither the treatment strategy nor the anthelmintic class used was associated with nematode infections. No relations were found between different cleaning methods in stables and endoparasite infections.

Animal Husbandry↗

Larval Apis mellifera L. (Hymenoptera: Apidae) mortality after topical application of antibiotics and dusts.

Beekeepers apply various dusts to honey bee, Apis mellifera L., colonies to dislodge parasitic mites and control bacterial brood diseases. Anecdotal reports by beekeepers indicate that the antibiotic oxytetracycline (OTC) can be toxic when applied in powdered sugar to cells containing immature bee brood, but it was not known whether the purported toxicity is caused by the antibiotic or the sugar carrier. Additionally, the toxicity of various dusts, proposed for parasitic mite control, is poorly known. In the current studies, we tested OTC and two other antibiotics (tylosin and lincomycin, candidate compounds for use in honey bee colonies) in a powdered sugar carrier for larval toxicity. We also tested for larval toxicity, several dusts that have been proposed for mite control. OTC caused significant brood mortality of approximately 80% at the concentrations used in the hive (200 mg in 20 g sugar). In contrast, tylosin and lincomycin at the 200 mg dose were both similar to untreated controls, and only five times that concentration (1000 mg) caused significant brood mortality of approximately 65%. The addition of dusts, wheat flour, talc, and a commercially available protein supplement, BeePro, resulted in mortality levels between 65 and 80%, similar to that seen with OTC. The common antibiotic carrier, powered confectioners sugar, was nontoxic. The use of 100 unsealed brood cells was demonstrated to be a reliable means of assessing potential adverse affects of dry compounds on larval honey bees. Two new candidate antibiotics for use in honey bee colonies were less toxic to larval bees than the currently labeled antibiotic, OTC.

Animals↗

Seasonal transmission of equine cyathostomes in warm climates.

Few studies investigating the seasonal transmission of equine cyathostomes have been done in warm climates. Two Australian studies used experimentally-infected plots to determine hatching, development and survival of free living stages of equine cyathostomes. Four studies in the southern United States used pasture larval counts, and in some instances tracer animals, to determine seasonal availability of infective cyathostome larvae on naturally-infected pastures. With the exception of the dry Australian tropics, a general pattern of peak transmission of cyathostomes during the cooler seasons of the year and minimal transmission during the warmest seasons was observed. Infective larvae and developing stages survived poorly in hot weather, although the rate of development was most rapid during that time. In contrast, infective larvae and developing stages survived well in cool weather, although the rate of development was slower. Adequate moisture was crucial to cyathostome transmission in warm climates, thus hot, dry weather effectively sterilized a pasture, whereas cool, moist weather was optimum for transmission. These data suggest that suppression of cyathostome egg output in feces of horses beginning shortly before the onset of cooler and/or more moist weather, and continued through the favorable period for development and survival of larvae on pasture - usually the autumn and winter should provide adequate control of these parasites. However, the efficacy of such seasonal control programs has yet to be adequately tested against that of traditional year round treatments.

Animals↗

Parasites that cause problems in Malaysia: soil-transmitted helminths and malaria parasites.

Malaysia is a developing country with a range of parasitic infections. Indeed, soil-transmitted helminths and malaria parasites continue to have a significant impact on public health in Malaysia. In this article, the prevalence and distribution of these parasites, the problems associated with parasitic infections, the control measures taken to deal with these parasites and implications for the future will be discussed.

Helminthiasis↗

Infectivity of Trichinella isolates in mice is determined by host immune responsiveness.

A comparison was made of the development, survival and reproduction of 5 isolates of Trichinella spiralis in inbred mice. Low responder C57BL/10 mice allowed worms of all isolates to survive longer and reproduce more successfully than did high responder NIH mice, suggesting that host immunity exerted a dominant influence upon infectivity. One isolate (Is-5 (W) -an arctic isolate) had a markedly lower infectivity than all other isolates, and was selected for more detailed study, together with isolate Is-1 (S) (a temperate isolate) which showed high infectivity. The lower infectivity of Is-5 (W) reflected a more rapid onset of immunity in mice infected with this parasite, immunity reducing the reproductive potential of female worms and causing an early expulsion from the intestine. No evidence of a dose-dependent suppression of immunity was found to explain the higher infectivity of Is-1 (S). Is-5 (W) provided a very rapid mucosal mastocytosis Is-1 (S) elicited higher levels of circulating parasite-specific antibodies than did Is-5 (W). These results are discussed in relation to the interplay of parasite immunogenicity and host immune responsiveness in determining infectivity, and point to the importance of identifying those immunodominant parasite molecules which control the balance of the host-parasite relationship.

Animals↗

Control of iron and other micronutrient deficiencies in the English-speaking Caribbean.

Most micronutrient deficiencies affect relatively few people in the Caribbean; however, many Caribbean residents are affected by anemia that appears due primarily to a lack of dietary iron. While generally substantial, the prevalences of such anemia have differed a good deal from place to place and study to study, observed rates ranging from 27% to 75% in pregnant women, 19% to 55% in lactating women, and 15% to 80% in young children. Severe anemia, defined by a blood hemoglobin concentration below 8 g/dl, has been found in approximately 6% of the pregnant women and 11% of the preschool children in some Caribbean countries. The principal ways of controlling iron deficiency anemia are through food fortification, control of intestinal parasites, direct oral supplementation, and dietary modification. Progress has been made in iron fortification of wheat flour and wheat products (the principal foodstuffs consumed by the general public in most of the English-speaking Caribbean). Data on control of relevant parasites in the Caribbean (primarily hookworm and to a lesser extent whipworm) are limited. Health services throughout the English-speaking Caribbean have been providing direct iron supplementation for pregnant women, but high levels of anemia during pregnancy still exist because of coverage, monitoring, and compliance problems. All the Caribbean countries also have education programs, which mainly advise pregnant women about iron-rich foods and iron absorption inhibitors and enhancers.

Anemia, Iron-Deficiency↗

Chelation of iron within the erythrocytic Plasmodium falciparum parasite by iron chelators.

To examine the site of action of antimalarial iron chelators, iron ligands were added to control erythrocytes and to erythrocytes parasitized with Plasmodium falciparum, and the concentration of intracellular labile iron was monitored with the fluorescent probe, calcein. The fluorescence of calcein quenches upon binding iron and increases upon releasing iron. The chelators included desferrioxamine B, 2',2'-bipyridyl, and aminophenol II, a compound that is being newly reported as having anti-plasmodial properties. Calcein-loaded parasitized cells displayed fluorescence predominantly within the cytosol of both rings and trophozoites. The addition of chelators to both control and parasitized erythrocytes led to significant increases of fluorescence (P < 0.001). Fluorescence was observed to increase within the parasite itself after addition of iron chelators, indicating that these agents bound labile iron within the plasmodium. The relative increases of fluorescence after addition of chelators were greater in control than parasitized erythrocytes (P < 0.05) as were the estimated labile iron concentrations (P < or = 0.001). These results suggest that (i) the anti-malarial action of iron chelators might result from the ability to reach the infected cell's parasite compartment and bind iron within the parasite cytosol, and (ii) the labile iron pool of the host red cell may be either utilized or stored during plasmodial growth.

2,2'-Dipyridyl↗

Endogenous CD4(+) CD25(+) regulatory T cells have a limited role in the control of Trypanosoma cruzi infection in mice.

Infection with the protozoan parasite Trypanosoma cruzi results in a robust and multifaceted immune response that controls parasite load but is unable to completely clear infection, resulting in parasite persistence and a chronic illness known as Chagas' disease in humans. The severity of Chagas' disease is correlated with persistent parasitism of muscle, neuronal, and gut tissues. The natural immunomodulatory function of endogenous CD4(+) CD25(+) regulatory T cells (Treg cells) to limit hyperactive immune responses may be exploited by microbes to persist despite host responses. In this study, we show that Treg cells are not necessary for T. cruzi evasion of immune responses during acute or chronic infection. In vivo anti-CD25 monoclonal antibody-mediated depletion of Treg cells from mice prior to challenge with a lethal strain or prior to and during acute infection with a nonlethal strain of parasite neither improved nor worsened the outcome of immune responses: differences in parasitemia, kinetics of antigen-specific CD8(+) T-cell expansion, and CD8(+) T-cell effector function (both in vivo and ex vivo) were of similar magnitudes for both depleted and control groups. Furthermore, depletion of CD25(+) cells from chronically infected mice did not enhance immune responses of muscle-derived CD8(+) T cells, nor could FoxP3 mRNA/scurfin-expressing leukocytes be isolated from muscle tissue. Based on the results of this study, it is concluded that Treg cells do not appear to play a major role in regulating CD8(+) T-cell effector responses during the acute phase of infection or in the muscles of mice during chronic T. cruzi infection.

Animals↗

Progresses in the field of drug design to combat tropical protozoan parasitic diseases.

The progresses made in the field of drug design to combat tropical protozoan parasitic diseases, such as Chagas' disease, leishmaniasis, and sleeping sickness are discussed. This article is focused on different approaches based on unique aspects of parasites biochemistry and physiology, selecting the more promising molecular targets for drug design. In spite of the enormous amount of work on the above features, the chemotherapy for all of these diseases remains unsolved. It is based on old and fairly not specific drugs associated, in several cases, with long-term treatments and severe side effects. Drug resistance and different strains susceptibility are further drawbacks of the existing chemotherapy. In this review article, a thorough analysis of selected molecular targets, mainly those that are significantly different compared with the mammalian host or, even, are not present in mammals would be described in terms of their potencial usefulness for drug design. Therefore, this article covers rational approaches to the chemotherapeutic control of these parasitic infections, such as the progresses in the search for novel metabolic pathways in parasites that may be essential for parasites survival but with no counterpart in the host. Ergosterol biosynthesis is a very interesting example. There are many enzymes involved in this biosynthetic pathway such us squalene synthase, farnesylpyrophosphate synthase, and other enzymes that are able to deplete endogenous sterols will be treated in this article. The enzymes involved in trypanothione biosynthesis, glutathionyl spermidine synthetase and trypanothione synthetase do not have an equivalent in mammals, and therefore it can be predicted low toxicity for compounds that are able to produce highly selective inhibition. Trypanothione reductase (TR), glyceraldehyde-3-phosphate dehydrogenase, dihydrofolate reductase, prenyltransferases, ornithine decarboxylase, etc, will be thoroughly analyzed. The design of specific inhibitors of such metabolic activities as possible means of controlling the parasites without damaging the hosts will be presented. The recent advances in the biochemistry of pathogenic parasites including the discovery of novel organelles will be discussed.

Antiprotozoal Agents↗

Movement and biological activity of drip-applied 1,3-dichloropropene and chloropicrin in raised mulched beds in the southeastern USA.

Movement and biological activity of 1,3-dichloropropene (1,3-D) and chloropicrin applied through drip irrigation in raised beds was investigated at three locations in the southeastern USA. Tests were conducted in fields with dense populations of nutsedge (Cyperus spp), with one location also having a high level of soil nematodes, both of which served as biological indicators of the distribution of effective concentrations of 1,3-D and chloropicrin. Objectives were (1) to gain a better understanding of 1,3-D and chloropicrin movement and the extent of biological activity outside of the wetted bed area, and (2) to examine the effect of application rate, application concentration and subsequent irrigation events on movement and activity of 1,3-D and chloropicrin. InLine, an emulsifiable concentrate containing 60.8% w/w 1,3-D and 33.3% w/w chloropicrin, was injected into polyethylene mulched beds through the drip tubes and water movement in the beds was visualized by adding a blue dye to the injection system. Gas concentrations of 1,3-D and chloropicrin in soil were measured using Gastec detection tubes at different positions relative to the drip tube at 1-4 days after InLine application. After one week, mulch was removed and nutsedge survival evaluated at different positions in the bed. High concentrations of 1,3-D and chloropicrin were measured at the bed center and midway between the bed center and the shoulder, but concentrations were low at the bed shoulder. Width of nutsedge control was significantly greater than width of water movement. Plant-parasitic nematodes were controlled over the entire bed width, but nutsedge re-emerged at the bed shoulders regardless of treatment. Higher application rates and concentrations of 1,3-D + chloropicrin resulted in higher fumigant concentrations in soil air. Irrigations subsequent to application reduced soil air concentrations of 1,3-D and chloropicrin and increased water movement, as did the use of two drip tubes instead of one. The data show that the pesticidal activity of 1,3-D + chloropicrin extends beyond the waterfront and indicate a significant degree of fumigant activity of emulsifiable 1,3-D + chloropicrin. However, unlike plant-parasitic nematodes, nutsedge could not be controlled over the entire bed width, regardless of rate, concentration and volume of water applied.

Agriculture↗

Biosynthesis of isoprenoid compounds in cattle filarial parasite Setaria digitata.

The biological significance of isoprenoid compounds such as ubiquinones, prenols and sterols have been well established. The presence and biological function of the two quinones Q6 and Q8 in the cattle filarial parasite Setaria digitata have already been reported. Inhibition of the function of quinone was already shown to be an effective means of controlling the filarial parasite. Detailed investigations of the non-saponifiable lipids from S. digitata using column, thin layer, reverse phase and high performance liquid chromatography showed the presence and formation of isoprenoid compounds such as prenols and sterols, in addition to the two quinones. Blocking of the biosynthesis of these useful compounds may prove to be an additional means of control of filarial parasites.

Animals↗

Evaluation of a nematode (Capillaria hepatica Bancroft, 1893) as a control agent for populations of house mice (Mus musculus domesticus Schwartz and Schwartz, 1943).

Sudden, large-scale infestations of house mice (Mus musculus domesticus) occur irregularly in the cereal-growing regions of Australia, resulting in substantial economic losses. Mathematical modelling has been used to evaluate the use of the liver nematode Capillaria hepatica as a potential agent for the biological control of mouse populations. The models suggest that C. hepatica is unlikely to be successful as a single-release control agent: instead, the parasite would need to be released when it becomes apparent that an outbreak is likely. Stage-structured models, including time delays and seasonal mouse demographic parameters, suggest that the parasite may be successful as a control agent, provided it can be introduced into the mouse population at least one year before an outbreak occurs. The optimum time for introduction is in summer or autumn. Some generalisations of this work are discussed. A parasite which affects fecundity alone is unlikely to be a good control agent, because it will destabilize the host population. Macroparasites may be unable to spread sufficiently rapidly to control sudden rises in vertebrate populations.

Animals↗

Progress in the control of schistosomiasis in Zimbabwe since 1984.

Schistosomiasis remains the second most important parasitic disease in Zimbabwe. In terms of its combined morbidity and prevalence, schistosomiasis is thought to be the most important helminth infection of man. Since 1984, a number of control programmes have commenced around the country and a national control programme aimed at reducing morbidity is being implemented. The strategy adopted in Zimbabwe is a community based approach integrated in the primary health care system.

Child↗

The potential of nematophagous fungi to control the free-living stages of nematode parasites of sheep: survey for the presence of fungi in fresh faeces of grazing livestock in Australia.

In the course of 12 months, 1742 fresh faecal samples from grazing livestock, principally ruminants, from various States of Australia were examined for the presence of nematophagous fungi. In total, 48 separate isolations were made representing various species from the genus Arthrobotrys and also 16 isolates of the single Duddingtonia species, Duddingtonia flagrans. These isolates will be used in continuing studies to select the most suitable species, on the basis of nematophagous capability and ruminant gut survival capacity, for development of a biological means of controlling nematode parasites of livestock.

Animal Husbandry↗

The development of protective immunity against gastrointestinal nematode and lungworm infections after use of an ivermectin bolus in first-year grazing calves.

Interactions between treatment with an ivermectin bolus at turnout and immunity to bovine parasitic gastroenteritis and bronchitis were examined. Immunity related parameters, i.e. development of clinical disease, parasite development and stimulation of parasite specific antibodies were examined for two grazing seasons and compared with untreated second season cattle (immune control) and untreated parasite naive cattle (nonimmune control). With respect to gastrointestinal nematodes, clinical condition, body weight development, faecal egg counts and pepsinogen concentrations of the bolus treated animals were not significantly different from the respective values of untreated immune cattle, showing a considerable degree of resistance in both groups compared to the parasite naive cattle. With respect to lungworms, untreated immune cattle were protected against clinical disease, but two of eight animals shed larvae again. Bolus treated animals transiently showed mild clinical symptoms and six of seven animals shed low numbers of larvae again, whereas all parasite naive cattle shed high numbers of lungworm larvae and showed signs of disease during the whole grazing season. In spite of the effective treatment with an ivermectin bolus during the first year a considerable resistance to gastrointestinal nematode and lungworm infection was present in the second grazing season.

Animals↗

Transmission dynamics of helminth parasites of pigs on continuous pasture: Ascaris suum and Trichuris suis.

In Denmark, alternative outdoor production systems for pigs are becoming more frequent, and information on the transmission of Ascaris suum and Trichuris suis under continuously grazed pasture conditions is needed. A group of pigs was turned out on a pasture in May 1993 (Year 1 of the study), inoculated with 200 eggs of A. suum and 1000 eggs of T. suis, and followed parasitologically. A non-experimentally infected group of pigs was similarly turned out on the same pasture the following year (Year 2) and again followed parasitologically. Pasture infectivity was measured using helminth-naïve tracer pigs. During the summer of Year 1, A. suum eggs became infective within 4-6 weeks on the pasture. However, transmission was moderate until August of Year 2, when a pronounced increase in transmission occurred. After 2 months on the pasture, the continuously exposed pigs in summer seasons of both Years 1 and 2 harboured small overdispersed populations of adult A. suum, moderate numbers of liver white spots, and high specific IgG responses. These parasitological measures on chronically exposed pigs did not, however, correlate well with pasture infectivity or with each other. In contrast, the liver inflammation and specific IgG responses (but not the intestinal A. suum burdens) of the tracer pigs were highly correlated (P = 0.0001) and appeared to better reflect pasture infectivity. The inoculated pigs excreted T. suis eggs by the late summer of Year 1, but no transmission took place before August of Year 2. Thus, the T. suis population of infective eggs built up very slowly. The results indicate that T. suis eggs may survive for a considerable time, however. The study results reveal that A. suum and T. suis eggs are much more resistant to environmental factors than free-living infective larvae of pig parasites such as Oesophagostomum dentatum and Hyostrongylus rubidus. Control of these parasites in outdoor systems will present more difficult challenges than that for parasites transmitted by free-living larvae.

Animal Husbandry↗