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Directing differentiation in Theileria annulata: old methods and new possibilities for control of apicomplexan parasites.

Apicomplexan parasites are major pathogens of humans and domesticated animals. The ability of these organisms to evade the host immune response and the emergence of drug-resistant parasites indicates a need for the identification of novel control strategies. Ideally, selected targets should be shared by a range of apicomplexans and fundamental to parasite biology. One process of apicomplexan biology which may provide this type of target is the molecular regulation of stage differentiation. This paper has reviewed studies carried out on differentiation of Theileria annulata and has highlighted general similarities with other apicomplexan differentiation steps. Similarities include asynchrony of differentiation, the loss (attenuation) of differentiation potential and an association between reduced proliferation and differentiation. In addition, novel data are presented assessing a possible role for a signal transduction mechanism or a direct involvement of classical heat-shock polypeptides in regulating differentiation of T. annulata in vitro. These studies, and previously published data, have led to the postulation that progression to the next stage of the life-cycle can be predetermined and involves the attainment of a quantitative threshold by regulators of gene expression. A modification of this model takes into account that for certain in-vitro systems, or differentiation steps in vivo, the process has to be initiated by alteration of the extracellular environment. Work which has shown that the time taken to achieve differentiation can be increased or decreased is also outlined. The ability to change the timing of differentiation suggests that the associated regulatory mechanism could be manipulated directly to significantly influence the outcome of an apicomplexan infection. The observation that a number of existing drugs and control strategies may exert their protective effect by altering differentiation potential supports this possibility.

Animals↗

Rhizosphere Interactions and the Exploitation of Microbial Agents for the Biological Control of Plant-Parasitic Nematodes.

A range of specialist and generalist microorganisms in the rhizosphere attacks plant-parasitic nematodes. Plants have a profound effect on the impact of this microflora on the regulation of nematode populations by influencing both the dynamics of the nematode host and the structure and dynamics of the community of antagonists and parasites in the rhizosphere. In general, those organisms that have a saprophytic phase in their life cycle are most affected by environmental conditions in the rhizosphere, but effects on obligate parasites have also been recorded. Although nematodes influence the colonization of roots by pathogenic and beneficial microorganisms, little is known of such interactions with the natural enemies of nematodes in the rhizosphere. As nematodes influence the quantity and quality of root exudates, they are likely to affect the physiology of those microorganisms in the rhizosphere; such changes may be used as signals for nematode antagonists and parasites. Successful biological control strategies will depend on a thorough understanding of these interactions at the population, organismal, and molecular scale.

cyst nematodes↗

Biological control of gastrointestinal parasitic nematodes using Duddingtonia flagrans in sheep under natural conditions in Mexico.

This investigation was aimed to evaluate the use of an oral bio-preparation containing Duddingtonia flagrans chlamydospores for the control of sheep gastrointestinal parasitic nematodes under the Mexican cold high plateau conditions. Two groups of gastrointestinal parasitic nematode naturally infected sheep, were randomly selected and located into two free-gastrointestinal nematode larvae paddocks. Group 1 received once a week a supplement containing D. flagrans chlamydospores mixed with oats and molasses. Group 2 received a similar supplement without any fungal material. After 5 months grazing animals were discarded from the experiment and two groups of free-nematode "tracer" sheep were located into the same paddocks to collect larvae from the contaminated pastures. Animals were slaughtered and necropsied and the nematodes were obtained and counted. A screening of the number of gastrointestinal nematode larvae present on the grass was performed and compared between the two grazing areas. The results showed 56% reduction in the Ostertagia (Teladorsagia) circumcincta and 94% reduction in the Nematodirus sp. population of the "tracer" sheep who grazed on the D. flagrans-treated sheep area, compared to the nematode population in animals grazed on the non-treated area. The results of the number of larvae on the grazing pastures showed a 51.1% reduction for H. contortus, and 100% for Cooperia sp. in the area with fungi. In the case of Trichostrongylus sp. no reduction was observed, when compared to the control group.

Animal Feed↗

Density dependence and the control of helminth parasites.

1. The transient dynamics and stability of a population are determined by the interplay between species density, its spatial distribution and the positive and negative density-dependent processes regulating population growth. 2. Using the human-helminth parasite system as an example, we propose that the life-stage upon which negative density dependence operates will influence the rate of host reinfection following anthelmintic chemotherapy, and the likely success of control programmes. 3. Simple deterministic models are developed which highlight how a parasite species whose population size is down-regulated by density-dependent establishment will reinfect a host population at a faster rate than a species with density-dependent parasite fecundity. 4. Different forms of density dependence can produce the same equilibrium behaviour but different transient dynamics. Under-representing the nature and magnitude of density-dependent mechanisms, and in particular those operating upon establishing life-stages, may cause the resilience of the parasite population to a control perturbation to be underestimated.

Animals↗

Toll-like receptor 4 contributes to efficient control of infection with the protozoan parasite Leishmania major.

The essential role of Toll-like receptors (TLR) in innate immune responses to bacterial pathogens is increasingly recognized, but very little is known about the role of TLRs in host defense against infections with eukaryotic pathogens. For the present study, we investigated whether TLRs contribute to the innate and acquired immune response to infection with the intracellular protozoan parasite Leishmania major. Our results show that TLR4 contributes to the control of parasite growth in both phases of the immune response. We also addressed the mechanism that results in killing or growth of the intracellular parasites. Control of parasite replication correlates with the early induction of inducible nitric oxide synthase in TLR4-competent mice, whereas increased parasite survival in host cells from TLR4-deficient mice correlates with a higher activity of arginase, an enzyme known to promote parasite growth. This is the first study showing that TLR4 contributes to the effective control of Leishmania infection in vivo.

Animals↗

The effect of birdsfoot trefoil (Lotus corniculatus) and chicory (Cichorium intybus) on parasite intensities and performance of lambs naturally infected with helminth parasites.

Conventionally, farmers rely upon the routine use of anthelmintics to control helminth parasites and their use has proved highly cost-effective. However, several factors, including the emergence of helminths resistant to pharmaceutical anthelmintics, are forcing farmers to seek alternative approaches to parasite control. Studies in New Zealand have shown that some alternative forages may reduce parasitic infestation in sheep. In the current study, it was found that under UK environmental conditions lambs with naturally acquired helminth infections grazing chicory (Cichorium intybus) and birdsfoot trefoil (Lotus corniculatus) had fewer helminth parasites than sheep grazing ryegrass/white clover (Lolium perenne/Trifolium repens). Twelve pure-bred Lleyn male lambs grazed replicated 0.5ha plots of birdsfoot trefoil, chicory or ryegrass/white clover for 5 weeks. Liveweight and faecal egg counts (FECs) were determined weekly and eight lambs per forage were slaughtered at the end of the trial to determine total helminth intensities. Lambs grazing birdsfoot trefoil had a lower FEC on day 7 (P<0.05) and fewer total adult helminths than those grazing the other forages on day 35 (P<0.01). Lambs grazing chicory did not have significantly lower FEC than lambs grazing other forages but these lambs were found to have fewer total adult abomasal helminths than lambs grazing ryegrass/white clover (P<0.001). As the performance of grazing lambs is inversely correlated with the intensity of helminth parasites, these alternative forages could be used to improve the liveweight gain of lambs produced in the UK. Overall, the results support the contention that alternative forages could have a positive role in the control of helminth parasites in sheep, subject to successful agronomic development and integration of these forages into whole farm systems.

Abomasum↗

Screening for Indian isolates of predacious fungi for use in biological control against nematode parasites of ruminants.

Four isolates of predacious fungi, two each of Arthrobotrys oligospora isolated from a sheep and a male crossbred calf and of Duddingtonia flagrans isolated from a sheep and a female buffalo in western India, were studied for their suitability as biocontrol agents against parasitic nematodes of ruminants, using growth assay, predatory activity, germination potential and ability to survive passing through the ruminants gut as criteria. The study showed that isolates of D. flagrans grew well in artificial media, had encouraging predatory activity, produced profuse chlamydospores that germinated easily at 25 degrees C and could survive passage through the ruminant gut. The ovine isolate of D. flagrans was superior in all respects to the isolate from buffalo and was the most promising candidate for biological control of nematode parasites of ruminants.

Animals↗

Cross-sectional serological survey on gastrointestinal and lung nematode infections in first and second-year replacement stock in the netherlands: relation with management practices and use of anthelmintics.

A cross-sectional survey was carried out on 86 farms randomly distributed in The Netherlands. After housing following the first and the second grazing season (FGS and SGS) serum samples were collected to determine IgG levels against Cooperia oncophora and Dictyocaulus viviparus, and the pepsinogen content. A questionnaire was used to inquire on grazing management practices and the use of anthelmintic drugs. On 80.7 and 60.2% of the farms FGS and SGS animals, respectively, were treated at least once with an anthelmintic drug. The percentage for the SGS animals indicates that the use of anthelmintic drugs in those animals has increased enormously over the last 10-15 years. Generally, parasitic nematode control in the FGS is good on most farms, but it can be characterised as being overprotective. There is a tendency that if anthelmintic drugs are used in the FGS they also are used more often in the SGS. On 12 farms (14%), no anthelmintic drugs were given in the FGS and the SGS. These farms did not differ from the others with respect to management practices in any obvious way. The serological results were in general very low, indicating low levels of exposure to gastrointestinal nematode infection in both FGS and SGS animals. This was not surprising in view of the good to high level of nematode control practices reported by the farmers. Although not statistically significant, a consistent result was that serological results for the SGS animals were more often positive or on average higher on those farms where FGS parasite control tended to be excessive. For D. viviparus, a prevalence rate of 41% positive farms was found. Following comparison with previous data, it is speculated that lungworm (sero-)prevalence in replacement stock may be declining as a result of continuing high levels of parasite control in replacement stock. It is concluded that the results confirm previous surveys, lending support to the conclusion that parasitic nematode control on Dutch dairy farms, certainly in FGS calves, is good but tends to be overprotective.

Animal Husbandry↗

The avian tail reduces body parasite drag by controlling flow separation and vortex shedding.

The aerodynamic effect of the furled avian tail on the parasite drag of a bird's body was investigated on mounted, frozen European starling Sturnus vulgaris in a wind tunnel at flight speeds between 6 and 14 m s(-1). Removal of tail rectrices and dorsal and ventral covert feathers at the base of the tail increased the total parasite drag of the body and tail by between 25 and 55%. Flow visualization and measurements of dynamic pressure in the tail boundary layer showed that in the intact bird a separation bubble forms on the ventral side of the body, and reattaches to the ventral side of the tail. This bubble is a consequence of the morphology of the body, with a rapid contraction posterior to the pelvis and hind legs. The tail and the covert feathers at its base act as a combined splitter plate and wedge to control vortex shedding and body wake development, and thereby are important to minimize drag. This hitherto unsuspected mechanism is central to understanding the morphology of the avian body, and may have had a significant influence on the evolution of avian tail morphology by pre-adapting the tail for radiation and specialization as an aerodynamic lifting structure and as an organ of communication in sexual selection.

Animals↗

Evaluation of exclusive use of ivermectin vs alternation of antiparasitic compounds for control of internal parasites of horses.

A study for about a 30-month period was done to compare strongyle control programs, using per os treatments of ivermectin (IVE) paste exclusively or alternation of 4 antiparasitic paste compounds: IVE, oxfendazole (OFZ), oxibendazole (OBZ), or pyrantel pamoate (PRT). Every 8 weeks, 1 group of horses (barn C; n = 14 to 16) was given IVE paste exclusively, and a second group (barn E; n = 16) was given the 4 antiparasitic pastes on an alternating schedule. Worm eggs and larvae per gram of feces (epg and lpg, respectively) values were determined every 2 weeks during the investigation. This study in grazing horses (mares and fillies), naturally infected with internal parasites, was conducted during the period between Oct 22, 1987 and Feb 8, 1990, with an additional observation on Mar 28, 1990. For barn-C horses, treated exclusively with IVE (200 micrograms/kg of body weight) 14 times, 2-week posttreatment mean strongyle epg and lpg (small strongyle) values were reduced 99 to 100%. Mean strongyle epg and lpg (small strongyle) values for each 2-week sample period remained low (less than 20) throughout the study period, except for 1 moderate transient increase in July 1988. For the entire study period, the aggregate mean strongyle epg value was 12 and the lpg value was 6. Two-week posttreatment mean strongyle epg and lpg (small strongyle) values for barn-E horses, treated alternately with therapeutic (approx) dosage of IVE (200 micrograms/kg; 4 times), OFZ (10 mg/kg; 5 times), OBZ (10 mg/kg; 4 times), or PRT (6.6 mg base/kg; 2 times), varied within and between compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

A 4-year study on the effectiveness of alternate grazing of cattle and sheep in the control of bovine parasitic gastro-enteritis.

In many farming enterprises, animal management systems which could provide a practical and effective alternative to chemotherapy for the control of bovine helminthosis would be readily accepted. One system which has been proposed and shown to be effective in the short or medium term involves grazing different host species on a rotational basis. The study described here examined the effect of alternating cattle and sheep annually over an extended period of 4 years. Up to the second grazing season the system appeared to be successful, with a marked reduction in the cattle worm burdens. However, by the end of the study period the parasite burdens in calves grazed on the alternated pasture were equal to, or greater than, those of set-stocked control animals. It was thus clear that the alternate grazing strategy had failed. Data obtained from other parameters measured, i.e. faecal egg counts, pasture larval numbers and plasma pepsinogen levels, confirmed this observation.

Animal Feed↗

Resistance as a tool for discovering and understanding targets in parasite neuromusculature.

The problem of anthelmintic resistance prevents efficient control of parasites of livestock and may soon compromise human parasite control. Research into the mechanisms of resistance and the quest for diagnostic tools to aid control has required research that focuses on field resistance. On the other hand, resistant worms, including those kept in the laboratory, provide useful tools for studying drug action, especially at neuromuscular targets in worms. While the needs and directions of these research aims overlap, this review concentrates on research on drug targets. In this context, resistance is a useful tool for site of action confirmation. For example, correlations between molecular expression studies and resistance assays conducted on whole worms can strengthen claims for sites of anthelmintic action. Model systems such as Caenorhabditis elegans have been very useful in understanding targets but give a limited picture as it is now clear that resistance mechanisms in this worm are different from those in parasites. Accordingly, research on parasites themselves must also be performed. Resistant isolates of the sheep nematode parasite Haemonchus contortus are the most widely used for this purpose as in vivo, in vitro, physiological and molecular studies can be performed with this species. Neuromuscular target sites for the anthelmintics levamisole and ivermectin are the best studied and have benefited most from the use of resistant worm isolates. Resistance to praziquantel and the newer chemical groups should provide new tools to explore targets in the future.

Animals↗