Role of a peptide tagging system in degradation of proteins synthesized from damaged messenger RNA.

Variants of lambda repressor and cytochrome b562 translated from messenger RNAs without stop codons were modified by carboxyl terminal addition of an ssrA-encoded peptide tag and subsequently degraded by carboxyl terminal-specific proteases present in both the cytoplasm and periplasm of Escherichia coli. The tag appears to be added to the carboxyl terminus of the nascent polypeptide chain by cotranslational switching of the ribosome from the damaged messenger RNA to ssrA RNA.

The potential to control Haemonchus contortus in indigenous South African goats with copper oxide wire particles.

The high prevalence of resistance of Haemonchus contortus to all major anthelmintic groups has prompted investigations into alternative control methods in South Africa, including the use of copper oxide wire particle (COWP) boluses. To assess the efficacy of COWP against H. contortus in indigenous South African goats, 18 male faecal egg-count-negative goats were each given ca.1200 infective larvae of H. contortus three times per week during weeks 1 and 2 of the experiment. These animals made up an "established" infection group (ESTGRP). At the start of week 7, six goats were each given a 2-g COWP bolus orally; six goats received a 4-g COWP bolus each and six animals were not treated. A further 20 goats constituted a "developing" infection group (DEVGRP). At the beginning of week 1, seven of the DEVGRP goats were given a 2-g COWP bolus each; seven goats were treated with a 4-g COWP bolus each and no bolus was given to a further six animals. During weeks 1-6, each of these DEVGRP goats was given ca. 400 H. contortus larvae three times per week. All 38 goats were euthanized for worm recovery from the abomasa and small intestines in week 11. In the ESTGRP, the 2-g and 4-g COWP boluses reduced the worm burdens by 95% and 93%, respectively compared to controls (mean burden+/-standard deviation, SD: 23+/-33, 30+/-56 and 442+/-518 worms, P=0.02). However, in the DEVGRP goats, both the 2-g and 4-g COWP treatments were ineffective in reducing the worm burdens relative to the controls (mean burdens+/-SD: 1102+/-841, 649+/-855, 1051+/-661 worms, P=0.16). Mean liver copper levels did not differ between the ESTGRP goats treated with 2-g COWP, 4-g COWP or no COWP (mean+/-standard error of the mean, SEM, in ppm: 93.7+/-8.3; 101.5+/-8.3; 71.8+/-8.3, P=0.07) nor did they differ between the DEVGRP goats (mean+/-SEM, in ppm: 74.1+/-9.1; 75.4+/-9.1; 74.9+/-10.0, P>0.99). The copper values were considered adequate, but not high, for goats. The COWP boluses have the potential to be used in the place of conventional anthelmintics for the control of established H. contortus infections in indigenous South African goats, but their use as part of an integrated approach to control H. contortus in the field must be fully investigated.

Non-coding RNAs - A primer for the laboratory scientist.

Advances in molecular genetics have identified several species of RNA that fail to translate - hence the non-coding RNAs. The two major groups within this class of nucleic acids are microRNAs (miRNA) and long non-coding RNAs (lncRNA). There is growing body of evidence supporting the view that these molecules have regulatory effect on both DNA and RNA. The objective of this brief review is to explain the molecular genetic of these molecules, to summarize their potential as mediators of disease, and to highlight their value as diagnostic markers and as tools in disease management.

A 3-year field evaluation of pasture rotation and supplementary feeding to control parasite infection in first-season grazing cattle: dynamics of pasture infectivity.

A 3-year grazing trial (2002-2004) was conducted on a commercial beef cattle farm in south-central Sweden to assess different methods of parasite control. This paper focuses on the dynamics of the free-living larval stages, whereas data on performance and within-host parasitological variables are presented in a complementary paper. Each year in May, 4 groups of 10 first-season grazing (FSG) steers were turned out on to separate 2ha paddocks and subjected to the following strategies: (1) spring turn-out on to pasture which had been grazed the previous year by second-season grazing (SSG) steers (paddock RT), followed by a move to aftermath (paddock AM) after 10 weeks (mid-July), (2) supplementary feeding with concentrate and hay for 4 weeks following turn-out (paddock FD), set stocked, (3) untreated control (paddock UT), set stocked and (4) anthelmintic treated control (paddock DO), set stocked. All paddocks were assigned a new set of FSG cattle each year whereas the treatments remained the same. Pasture infectivity were monitored partly by two tracer calves that grazed each paddock along with the FSG calves for 3 weeks after turn-out and prior to housing, partly by analysis of herbage samples for infective larvae (L3) that were collected from each paddock at monthly intervals between April and October. The predominant genera found were Cooperia and Ostertagia. Tracers grazing paddock RT overall harboured less worms, and in particular less Ostertagia spp., and tracers grazing paddock AM in mid-July harboured insignificant numbers of nematodes compared to tracers on the FD and UT paddocks. Although total worm counts varied between groups, smaller numbers were generally observed early in the grazing-season (May), compared to close to housing (September) when inhibited early L4 larvae were almost exclusively found. Results observed from herbage samples showed high numbers of L3 in spring before the time of turn-out, compared to around housing. In conclusion, the rotation control strategy showed promising results and provided a turn-out pasture that was 'nematode safe' to FSG cattle the following spring, whereas the feeding strategy failed as applied in this experiment.

A field study on the effect of some anthelmintics on cyathostomins of horses in sweden.

The objective of the study was to investigate different aspects on the efficacy of three anthelmintics on cyathostomin nematodes of Swedish horses. A faecal egg count reduction (FECR) test was performed on 26 farms. Horses were treated orally with recommended doses of ivermectin, pyrantel pamoate or fenbendazole. Faecal samples were collected on the day of deworming and 7, 14 and 21 days later. No resistance was shown against ivermectin; the FECR was constantly >99%. The effect of pyrantel was assessed as equivocal in 6 farms 14 days after treatment; the mean FECR was 99%. As many as 72% of the fenbendazole-treated groups met the criteria for resistance; the mean FECR was 86%, ranging from 56% to 100%. A re-investigation of two farms where pyrantel resistance had been suspected clearly revealed unsatisfactory efficacy of pyrantel on one of these farms; the FECR varied from 72% to 89%. Twenty-six of the horses previously dosed with pyrantel or fenbendazole, and which still excreted >/=150 eggs per gram of faeces 14 days after treatment, were dewormed with ivermectin and fenbendazole or pyrantel in order to eliminate the remaining cyathostomins. A total of 13 cyathostomin species were identified from horses that initially received fenbendazole and seven species were identified from pyrantel-treated individuals. The egg reappearance period (ERP) following treatment with ivermectin and pyrantel was investigated on two farms. The shortest ERP after ivermectin treatment was 8 weeks and after pyrantel was 5 weeks. We conclude that no substantial reversion to benzimidazole susceptibility had taken place, although these drugs have scarcely been used (<5%) in horses for the last 10 years. Pyrantel-resistant populations of cyathostomins are present on Swedish horse farms, but the overall efficacy of pyrantel is still acceptable.

Governance and oversight of researcher access to electronic health data: the role of the Independent Scientific Advisory Committee for MHRA database research, 2006-2015.

In order to promote understanding of UK governance and assurance relating to electronic health records research, we present and discuss the role of the Independent Scientific Advisory Committee (ISAC) for MHRA database research in evaluating protocols proposing the use of the Clinical Practice Research Datalink. We describe the development of the Committee's activities between 2006 and 2015, alongside growth in data linkage and wider national electronic health records programmes, including the application and assessment processes, and our approach to undertaking this work. Our model can provide independence, challenge and support to data providers such as the Clinical Practice Research Datalink database which has been used for well over 1,000 medical research projects. ISAC's role in scientific oversight ensures feasible and scientifically acceptable plans are in place, while having both lay and professional membership addresses governance issues in order to protect the integrity of the database and ensure that public confidence is maintained.

From discovery to development: current industry perspectives for the development of novel methods of helminth control in livestock.

Despite the extraordinary success in the development of anthelmintics in the latter part of the last century, helminth parasites of domestic ruminants continue to pose the greatest infectious disease problem in grazing livestock systems worldwide. Newly emerged threats to continuing successful livestock production, particularly with small ruminants, are the failure of this chemotherapeutic arsenal due to the widespread development of anthelmintic resistance at a time when the likelihood of new products becoming commercially available seems more remote. Changing public attitudes with regards to animal welfare, food preferences and safety will also significantly impact on the ways in which livestock are managed and their parasites are controlled. Superimposed on this are changes in livestock demographics internationally, in response to evolving trade policies and demands for livestock products. In addition, is the apparently ever-diminishing numbers of veterinary parasitology researchers in both the public and private sectors. Industries, whether being the livestock industries, the public research industries, or the pharmaceutical industries that provide animal health products, must adapt to these changes. In the context of helminth control in ruminant livestock, the mind-set of 'suppression' needs to be replaced by 'management' of parasites to maintain long-term profitable livestock production. Existing effective chemical groups need to be carefully husbanded and non-chemotherapeutic methods of parasite control need to be further researched and adopted, if and when, they become commercially available. This will require veterinary parasitology researchers from both the public and private sectors to work in close co-operation to ensure 'sustainability' - not only of the livestock industries that they service - but also for their very own activities and enterprises.

Towards the eradication of Haemonchus contortus from sheep flocks in Sweden.

Previous studies have shown that between-year transmission of Haemonchus contortus in Swedish sheep flocks is almost entirely as over-wintered populations within housed animals, and not on pasture. This suggests that eradication of this parasite is a realistic possibility. Thus, two sheep farms with a history of H. contortus infection on the Swedish island of Oland were selected for study. During the winter housing period of 2003/2004 all ruminants (sheep and cattle) on both farms were treated with ivermectin. Monitoring by faecal egg counts and infective larval differentials of ewes and lambs for the subsequent two grazing seasons, together with total abomasal worm counts of 10 lambs from each farm at the end of the first grazing year, showed that this objective was achieved.

Population dynamics of nematode parasites of reindeer in the sub-arctic.

Nematode parasite infections of semi-domestic reindeer grazing in their natural habitat in northern Finland were monitored for approximately 2 years. This was achieved by monthly faecal egg counts of male and female calves and adult females from an experimental reindeer herd, in addition to estimating the acquisition of nematode infection from pasture using tracer reindeer calves. The most abundant parasite was Ostertagia gruehneri in the worm counts of tracer animals and in faecal egg counts of adult female reindeer. Capillaria sp. eggs were detected in calves and adults, but Nematodirinae eggs were only recovered from calves. Faecal egg counts showed variations between months for each nematode species, with male and female calves shedding similar numbers of eggs. During each year, calves shed more Capillaria sp. eggs than adult female reindeer, but similar numbers of O. gruehneri eggs. Egg counts of O. gruehneri were more abundant in late summer-autumn (July-September), whereas Capillaria sp. and the Nematodirinae dominated the winter months (November-February). The seasonal trends of adult worm burdens of O. gruehneri in the tracers paralleled the egg count patterns. Capillaria sp. was not detected in tracer worm counts. Tracer worm burdens showed that the proportion of inhibited larvae of O. gruehneri and Nematodirinae steadily increased from spring to early winter, followed by a decline and a commensurate increase in the number of adult parasites in the second summer. This investigation showed that parasite transmission occurs continuously throughout the year for nematode parasites of reindeer in northern Finland.

Reindeer as hosts for nematode parasites of sheep and cattle.

The reindeer husbandry range of Scandinavia overlaps with sheep, goat, and cattle pastures. The aim of this study was to determine whether reindeer are suitable hosts for ovine or bovine nematode parasites, and thus may spread these parasites into the reindeer husbandry regions. To render worm-free, twelve 4-month-old male reindeer calves, six lambs, and six bovine calves were given ivermectin at 200 microg/kg body weight. Five weeks post-treatment, six reindeer calves were each artificially dosed with 10,000 third-stage larvae (L3) of gastrointestinal nematodes derived from sheep, and an additional six reindeer with L3 derived from cattle. Lambs and bovine calves received the same dose of ovine and bovine larvae as reindeer, from the same larval source, respectively. Faecal samples collected on five occasions after the larval dosing revealed that by the fourth week, all reindeer calves, lambs, and bovine calves were infected. Animals were slaughtered on days 40 (reindeer) or 47 (lambs and bovine calves) after the larval dosing. Reindeer calves were most susceptible to L3 derived from sheep. The overall mean intensity of Haemochus contortus, Trichostrongylus axei, and Teladorsagia circumcincta, did not differ between reindeer and sheep; however, early fourth-stage larvae of H. contortus were more abundant in reindeer (p = 0.002). The establishment of bovine-derived Ostertagia ostertagi was similar in reindeer (62%) and bovine calves (57%), but larval inhibition was much higher in reindeer (91%, p < 0.001) than in cattle (31%). Very poor establishment of bovine derived Cooperia oncophora was recorded in reindeer calves (2%) compared with bovine calves (59%). These results show that young reindeer are susceptible hosts to the important gastrointestinal parasites of sheep (T. circumcincta, H. contortus) and cattle (O. ostertagi), as well as being a suitable host for T. axei.

A 3-year field evaluation of pasture rotation and supplementary feeding to control parasite infection in first-season grazing cattle--effects on animal performance.

To evaluate non-chemical strategies to control pasture-borne parasites in first-season grazing (FSG) cattle, a 3-year grazing trial was conducted during 2002-2004 on naturally infected pastures on a commercial beef cattle farm in Sweden. A uniform pasture was divided in 4 equal 2 ha paddocks onto each of which 10, 5-9 months old dairy breed steer calves were allocated at turn-out in May each year. Two strategies were evaluated: (1) turn-out onto pasture which had been grazed the previous year by second-season grazing (SSG) steers, followed by a move to aftermath in mid-July (RT) and (2) supplementation with concentrate and roughage for 4 weeks from turn-out (FD). Comparisons were made with an untreated (UT), and an anthelmintic treated control group (DO). Animal parasitology and performance were monitored monthly throughout the 20 weeks grazing period. Additional sampling occasions were performed on day 9 (for coccidia) and 10 weeks after turn-out (mid-July). Due to clinical parasitic gastro-enteritis (PGE), salvage treatments were performed on all animals in group FD approximately 7 weeks after turn-out in 2003 and of three animals in group UT 5 weeks after turn-out in 2004. In 2003, the geometric mean oocyst excretion 9 days after turn-out was approximately 150,000 opg of mainly Eimeria alabamensis in group FD, and in 2004 approximately 180,000 opg in group UT. Apart from the DO group, geometric mean faecal egg counts (FEC) were between 80 and 400 epg 4 weeks after turn-out. Mean serum pepsinogen concentrations (SPC) of approximately 3.6 U tyrosine were recorded in the FD and UT groups from late August 2002. In 2003 and 2004, mean concentrations in these groups were between 4.1 and 7.2 U tyrosine 8 weeks after turn-out. By the end of the three grazing seasons the average weight gain difference compared to the DO group was for FD -29, -38 and -5 kg and for RT -4, -21 and +14 kg, and compared to the UT group -18, +2 and +22 for FD and +7, +19 and +41 kg for group RT. In conclusion, the rotation control strategy showed promising results, whereas the strategic feeding was poor from a parasite control standpoint.

Biological control of sheep parasites using Duddingtonia flagrans: trials on commercial farms in Sweden.

Trials were conducted on 3 commercial sheep farms in Sweden to assess the effect of administering spores of the nematode trapping fungus, Duddingtonia flagrans, together with supplementary feed to lactating ewes for the first 6 weeks from turn-out on pastures in spring. Also control groups of ewes, receiving only feed supplement, were established on all 3 farms. Groups were monitored by intensive parasitological investigation. The ewes and their lambs were moved in late June to saved pastures for summer grazing, the lambs receiving an anthelmintic treatment at this time. After approximately 6 weeks on summer pasture the lambs were weaned, treated a second time with anthelmintic, and returned to their original lambing pastures for finishing. Decisions as to when lambs were to be marketed were entirely at the discretion of the farmer co-operators. No difference in lamb performance was found between the two treatments on all three farms. This was attributed to the high levels of nutrition initially of the ewes limiting their post-partum rise in nematode faecal egg counts in spring, which in turn resulted in low levels of nematode infection on pastures throughout the autumn period. Additionally, pastures were of good quality for the lambs during the finishing period, so they grew at optimal rates as far as the farmers were concerned.

Crashes and violations among drivers with Alzheimer disease.

BACKGROUND: Several small studies have found a high automobile crash rate for drivers with Alzheimer disease (AD) compared with unaffected elderly drivers, prompting the suggestion that the diagnosis of AD mandate cessation of driving. OBJECTIVES: To compare automobile crash and violation rates of a large number of patients with AD with appropriately matched elderly subjects. To determine if neuropsychological test scores predict these adverse driving events. To determine if intervention by physicians or family members influences driving cessation. DESIGN: Review of crashes and violations from 1986 to 1993 in police-filed Michigan State driving records of 143 licensed patients with AD and 715 licensed comparison subjects matched 5 to 1 in age (+/- 6 years), sex, and county of residence. We correlated crashes and violations with neuropsychological test scores. A questionnaire-based inquiry on the influence of physician, family, and state interventions on driving cessation was administered. RESULTS: The crash and violation rates of patients with AD were not significantly different from those of comparison subjects. However, patients with AD probably drove fewer kilometers than did comparison subjects. Neuropsychological test scores did not predict future crashes or violations. CONCLUSIONS: This study, the largest to our knowledge involving state driving records of patients with AD, does not confirm the previously reported excessive crash rate among drivers with AD relative to an appropriate comparison population. Reduced driving exposure of patients with AD probably kept their crash adverse equal to that of comparison subjects. Intervention by physicians and family members was major factor in reducing driving exposure. These findings affirm that the mere diagnosis of AD does not justify license revocation.

Comparison of enalapril and atenolol in mild to moderate hypertension.

PURPOSE: Short-term therapy with angiotensin converting enzyme (ACE) inhibitors for hypertension is effective and well tolerated, and compared with beta blockers, may cause fewer adverse reactions. Furthermore, enalapril has been observed to have a greater effect on systolic blood pressure than beta blockers. We therefore decided to compare the ACE inhibitor enalapril and the beta blocker atenolol as monotherapy in a double-blind study of patients with mild to moderate hypertension. PATIENTS AND METHODS: After a four-week placebo run-in period, 162 patients were allocated randomly to receive atenolol (50 to 100 mg daily) or enalapril (20 to 40 mg daily) for 12 weeks. To assess the influence of these drugs on quality of life, a series of psychologic tests was performed, and a subset of patients also underwent treadmill exercise and pulmonary function tests. RESULTS: In 147 patients who completed the study, enalapril reduced supine blood pressure by 19/12 mm Hg, compared with 9/7 mm Hg for atenolol (p less than 0.001/p less than 0.005). The modest blood pressure response to atenolol was not due to poor compliance. A target blood pressure of 140/90 mm Hg or less was achieved by 35 percent of enalapril-treated atenolol (p less than 0.01). The frequency and severity of adverse effects with the two drugs were similar, and few important differences emerged from the quality-of-life assessments. CONCLUSION: At the doses used, enalapril induced a greater short-term blood pressure response than atenolol; long-term studies of its safety and efficacy are required.

The use of cranial CT scans in the triage of pediatric patients with mild head injury.

OBJECTIVE: Recent evidence suggests that patients with a normal cranial CT scan after head injury can be safely discharged home from the emergency department. However, supporting data from previous studies has relied on incomplete patient follow-up. We utilized a statewide comprehensive hospital abstract reporting system (CHARS) to assess whether children with normal CT scans after head injury subsequently developed intracranial sequelae in the month following their initial injury. DESIGN: Retrospective case-series study, with comprehensive statewide follow-up for 1 month. SETTING: The emergency department of a Level 1 Trauma Center in Seattle, Washington. PARTICIPANTS: All children (n = 400) with head injury, Glasgow Coma Score of 13 to 15, and initial normal CT scan seen over a 4.5-year time period. All were matched against CHARS to evaluate admissions within 30 days after emergency department disposition. For readmissions, International Classification of Diseases (9th revision) discharge and procedure information was collected. All children were also matched against the state death files. RESULTS: Four children were readmitted for neurologic reasons within 1 month following injury. One child on coumadin for heart disease developed a symptomatic subdural hematoma 5 days after head injury, requiring neurosurgical drainage. One child developed a symptomatic hemorrhagic contusion 3 days after injury, requiring observation only. Two children were readmitted 1 day after injury for concussive symptoms; both were discharged home after observation only. There were no deaths among the study population. CONCLUSIONS: Among children with a normal cranial CT scan after mild head injury, delayed intracranial sequelae requiring intervention are extremely uncommon. In otherwise stable patients, a normal cranial CT scan can identify patients to be safely discharged from the emergency department, and would be more cost-effective than 1 to 2 days of hospital observation.

Nematode parasite control of livestock in the tropics/subtropics: the need for novel approaches.

Because parasites are more abundant, small ruminants in the tropical/subtropical regions of the world experience much greater ravages from internal parasitic disease than those in the temperate regions. In the tropics/subtropics, the limiting ecological factor influencing the severity of parasitism is rainfall, as temperatures almost always favour hatching and development of the free-living stages. Attempts to expand sheep and goat production by replacing traditional village production systems, which rarely involve anthelmintic treatment, with large-scale intensive commercial enterprises invariably induce complete reliance on anthelmintics to control nematode parasites. This has led to the widespread development of high level, multiple anthelmintic resistance throughout the tropics/subtropics, and in certain regions this has reached the ultimate disastrous scenario of total chemotherapeutic failure. Immediate concerted efforts are needed to resolve this crisis. Significant benefits are likely to emerge from research into non-chemotherapeutic approaches to nematode parasite control, such as grazing management, worm vaccines, breed selection and biological control. However, it is likely that none, in isolation or collectively, will completely replace the need for effective anthelmintics. What is needed is the integration of all methods of parasite control as they come to hand, with the underlying aim of reducing the use and thus preserving the effectiveness of anthelmintics. Although cheap and simple procedures, based on sound epidemiological principles, can achieve dramatic benefits in worm control, they have been poorly adopted by livestock owners. Clearly then, the greatest need is for technology transfer and education programmes, but these activities are generally found to be chronically under-resourced.

International approaches to the concept of integrated control of nematode parasites of livestock.

Livestock production systems throughout the world are under severe and sustained pressures. These are diverse and multi-factorial, ranging from the need to redress the oversupply of livestock commodities from the protected industries of the industrialised world, meeting animal welfare expectations, attempts to ease animal-induced land degradation and pollution, and competition with alternative products. As a consequence, funding for research to the ruminant livestock industries has been contracting universally. This applies particularly to research on those diseases of grazing livestock that are not zoonotic, threats to trade, or major "killer" diseases. Gastrointestinal helminths fall outside these priorities. The last decade has witnessed a major contraction throughout the world in the number of research centres and staff involved in applied veterinary parasitology research. This coincides with a time when these livestock industries need the most help. Resistance to anthelmintic drugs amongst the major nematode parasites of sheep and goats has now reached alarming proportions throughout the world and threatens the future viability of continued small ruminant production in many countries. Anthelmintic resistance is also increasing in the important nematode parasites of cattle. Also, this time coincides with the apparent reduction in the discovery and development of entirely new anthelmintic products by the pharmaceutical industry. As a consequence, those remaining researchers and extension personnel who have the responsibility of providing support to the ruminant livestock industry, are showing innovation and lateral thinking in ways to combat the perennial problem of internal parasites in grazing livestock. There are a number of excellent examples of parasite-control schemes, which do not rely entirely on anthelmintic treatment. These are now being supplemented with some exciting novel approaches to dealing with particularly pressing parasite problems. Also there is a move towards the development of true integrated approaches in the control of nematode parasites of livestock, which employ several of these methods when appropriate. This proves that as far as worm control in livestock is concerned, the old adage "necessity is the mother of invention", holds true.

The role of nematophagous fungi in the biological control of nematode parasites of livestock.

The control of nematode parasites of livestock is presently based entirely on anthelmintic treatment and grazing management. On their own, these methods are not sustainable because parasites invariably develop resistance to anthelmintics and because of increasing public concern about chemical residues in livestock products and the environment. Although alternative, non-chemotherapeutic control strategies, such as vaccines and genetic selection for resistance are the focus of considerable research activity worldwide, biological control of nematode parasites has been virtually ignored. The little work that has been done is restricted largely to western Europe and involves virtually just one fungal species, namely Arthrobotrys oligospora. More recent studies indicate other known nematophagous fungal species are more efficient predators of infective larvae in sheep faeces than A. oligospora, and others have a greater capacity to survive passage through the gastrointestinal tract of ruminants. These findings plus the relatively sparse numbers of microbial competitors in the fresh faecal environment, compared with the plant rhizosphere where biological control of plant parasites is proving a particularly intractable problem, engenders optimism that the biological control of animal parasitic nematodes may become a practical reality. Such control will never be a substitute for chemotherapy, where the primary purpose is worm removal from the host, but should be incorporated together with other options into integrated pest management systems to provide sustainable nematode control of livestock into the twenty-first century.

The prospects for biological control of the free-living stages of nematode parasites of livestock.

Control of nematode parasites of livestock is focused almost entirely on the parasitic stages within the host. Current methods rely on anthelmintic drugs, but these are under increasing threat with the development of resistance covering the whole spectrum of anthelmintics amongst the important nematode species of a range of livestock. However, invariably the greatest proportion of the parasite biomass resides not within the animal hosts, but in the external environment-commonly on pasture. It is in this environment that the free-living stages are vulnerable to a range of abiotic factors (extremes in temperature and desiccation) and biotic factors (macro- and micro-organisms) that may decimate their numbers. Of the latter, there are organisms, which exert their effects either indirectly by rendering faecal deposits inimical for the development of nematode eggs through to infective larvae, or directly by acting as pathogens or by exploiting the free-living stages as a food source. Within this vast assemblage of organisms, which include microarthropods, protozoa, viruses, bacteria and fungi, could well emerge a variety of biological control agents of nematode parasites. At present, greatest interest lies with the nematode-destroying fungi. Work has progressed from Petri dishes, to plots, to paddocks with several species of the genus Arthrobotrys and Duddingtonia flagrans. These studies indicate that the voracious nematophagous capabilities of these fungi, clearly demonstrated in vitro, translate to reductions in the number of infective larvae on pasture and indicate that levels of control, comparable to conventional schemes using anthelmintics, can be achieved. The challenge now lies in developing methods of administration of fungi to animals which can be applied under practical farm conditions. However, the pursuit of candidates for biological control of nematode parasites of livestock should not involve just a few species of nematophagous fungi. More than 100 species of fungi have been identified as possessing nematode destroying capabilities. These need to be more specifically investigated for their effects on free-living stages of nematode parasites of livestock, together with other classes of organisms, particularly bacteria, which have proved successful as biological control agents of arthropods.

Population dynamics of Trichostrongylus colubriformis in sheep: the effect of infection rate on the establishment of infective larvae and parasite fecundity.

The establishment of Trichostrongylus colubriformis was estimated in helminthologically naive 20-week-old Merino sheep given third stage infective larvae (L3) at rates of 2000, 632 or 200 L3 per day, 5 days per week. After varying periods of continuous L3 intake, a levamisole-susceptible strain of T. colubriformis was replaced with a highly resistant strain for 1 week. The animals were then treated with levamisole to remove the susceptible population, and establishment of the cohort of resistant worms was estimated. In previously uninfected sheep, approximately 65% of the L3 given in the first week became established as adults. This fell to low levels (less than 5%) after 7, 10 and 14 weeks of continuous L3 intake for the high, medium and low infection rates, respectively. At the low infection rate, establishment remained at maximum levels for the first 4 weeks, but then fell at a rate similar to that observed for the higher infection rates. This implied that a threshold of worm exposure was required before resistance to establishment developed. Parasite egg production, expressed as eggs per gram of faeces, was proportional to infection rate and is explained by higher worm burdens occurring at high infection rates. However, estimates of fecundity in eggs per female per day showed the opposite relationship with rate of infection. Fecundity stayed high (approximately 600) for 5 weeks at the low infection rate but only maintained this level for 3 weeks and 1 week at the medium and high rates, respectively. This suggests that fecundity, like establishment, was similarly affected at threshold levels of immunological recognition.