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.     

Global perspectives on nematode parasite control in ruminant livestock: the need to adopt alternatives to chemotherapy,with emphasis on biological control

Effective, sustainable control of nematode parasites of grazing livestock is becoming evermore challenging and difficult. This is largely due to two contrasting issues. One is the rapid escalation of resistance to anthelmintic drugs, which is arguably the greatest problem now facing the small ruminant industries worldwide. Secondly, there is the increasing trend towards organic farming, in which there is prohibition of the prophylactic use of all chemical compounds. Livestock producers urgently need non-chemotherapeutic alternatives in parasite control. Researchers have responded to this challenge and a variety of quite different approaches have been the subject of intense investigation in many countries for several decades now. These vary in relation to their stage of development for on-farm use, their utility, and their applicability across the spectrum of grazing livestock enterprises throughout the world. One relatively recent innovation is the biological control approach to nematode parasites. This has now reached the stage of commercialization. This review focuses on these issues and provides an overview of the possible ways in which the biological control of nematode parasites could be employed in grazing ruminant livestock systems worldwide.     

Knowledge and attitudes of Australian livestock producers concerning biosecurity practices

Biosecurity risks are a major threat to the profitability of the industry as well as impacting human and animal health. Livestock producers play a crucial role in biosecurity as the first to notice changes in the health or productivity of their stock and are generally responsible for implementing protective measures. However, uptake of biosecurity measures by producers is variable. We critically appraised the current literature regarding biosecurity practices in Australian livestock industries and highlight aspects that are well understood as well as those where further research or information is needed. Findings from 12 cross-sectional studies suggest that Australian producers' knowledge of biosecurity methods and importance might have a positive influence on their willingness to implement or incorporate biosecurity practices. There is moderate evidence supportive of biosecurity being well understood by livestock producers across Australia. Barriers to producers using biosecurity practices included lack of information or communication from agricultural, veterinary or government organisations. It was found that larger stock numbers were positively correlated with biosecurity implementation and that producers used veterinarians, government and industry agencies as resources for trusted information.     

Developing vaccines to control protozoan parasites in ruminants: dead or alive?

Protozoan parasites are among some of the most successful organisms worldwide, being able to live and multiply within a very wide range of hosts. The diseases caused by these parasites cause significant production losses in the livestock sector involving reproductive failure, impaired weight gain, contaminated meat, reduced milk yields and in severe cases, loss of the animal. In addition, some protozoan parasites affecting livestock such as Toxoplasma gondii and Cryptosporidium parvum may also be transmitted to humans where they can cause serious disease. Data derived from experimental models of infection in ruminant species enables the study of the interactions between parasite and host. How the parasite initiates infection, becomes established and multiplies within the host and the critical pathways that may lead to a disease outcome are all important to enable the rational design of appropriate intervention strategies. Once the parasites invade the hosts they induce both innate and adaptive immune responses and the induction and function of these immune responses are critical in determining the outcome of the infection. Vaccines offer green solutions to control disease as they are sustainable, reducing reliance on pharmacological drugs and pesticides. The use of vaccines has multiple benefits such as improving animal health and welfare by controlling animal infections and infestations; improving public health by controlling zoonoses and food borne pathogens in animals; solving problems associated with resistance to acaricides, antibiotics and anthelmintics; keeping animals and the environment free of chemical residues and maintaining biodiversity. All of these attributes should lead to improved sustainability of animal production and economic benefit. Using different protozoan parasitic diseases as examples this paper will discuss various approaches used to develop vaccines to protect against disease in livestock and discuss the relative merits of using live versus killed vaccine preparations. A range of different vaccination targets and strategies will be discussed to help protect against: acute disease, congenital infection and abortion, persistence of zoonotic pathogens in tissues of food animals and passive transfer of immunity to neonates.     

Identifying animal welfare impacts of livestock air transport

Air transport of livestock occurs frequently from most Australian major cities. The total journey time starts with road transport from the farm or pre-export facility to the departing airport where livestock are crated, and ends with the unloading of animals at the premises or farm in the importing country. We reviewed the literature regarding airfreight and conclude that there was minimal information on current practices within this industry, particularly for procedures after arrival at the Australian airport, and during the on-board phase.     

Ethnoveterinary plant preparations as livestock dewormers: practices, popular beliefs, pitfalls and prospects for the future

Ethnomedicine is an integral part of traditional medical practices in many countries of the developing world. A large proportion of the population uses this form of treatment for primary health care and for the treatment of ailments in their livestock. Livestock is a major asset for resource-poor smallholder farmers and pastoralists throughout the world and internal parasites are recognized by these communities as having an impact on livestock health. Parasitic infections are among those infections that traditional healers confidently treat and against which an enormous variety of remedies exist. Many of these are based on the use of plant preparations. Although various methods have been used for the validation of traditional phytomedical preparations, there is a lack of standardization of these procedures. The present study is aimed at providing an overview of ethnoveterinary deworming preparations, the various methods that have been used in their validation and the future prospects for their use against helminth parasites of ruminant livestock in developing countries, with an emphasis on nematode parasites. Recommendations are made on the procedures that should be followed to conduct in vivo and in vitro assays. Fostering better interaction between traditional healers and scientists is advocated to prevent harmful overexploitation, both of local knowledge and of plant species that may have effects against nematode parasites.     

Characterization of transgenic livestock production

The objective of transgenic livestock improvement projects is to develop and bring to market superior breeding stock, as well as germplasm for the artificial insemination and embryo transfer industries. Livestock animal biotechnology programs hold the promise of achieving, in a single generation, improvements in commercially important livestock species previously possible only through long-term traditional selective breeding practices or by chance mutation. Transgenic farm animals harboring growth hormone or metabolically related structural genes have been created. Studies of these animals demonstrate the effects of inadequate regulation of transgene expression. Research continues to explore the intricacies of developmental regulation of such genes and phenotypic consequences of mammalian gene transfer. Ultimately, genetically engineered livestock will provide producers with the benefit of increased production efficiencies while the consumer will have healthier animal food products. Conceivably, products will be produced with lower levels of fat, cholesterol, feed additives and pharmaceutical residues from animals with altered carcass composition that will result in greater nutritional benefit for the consumer.     

Ectoparasites of livestock in Europe and the Mediterranean region

Arthropod ectoparasites can have a major impact on the productivity and welfare of livestock. In recent years, many parts of Europe have seen important changes in the nature of animal husbandry and parasite control, which have increased the need for a precise understanding of the current distribution and prevalence of livestock ectoparasites. In some cases, these changes have been associated with moves towards increased productivity, such as higher-stocking densities, large-scale rearing units, indoor confinement, reduced genetic diversity and large-scale movement of animals and, in others, with a move towards organic farming. There have also been changes in parasite control, associated with the development of new parasiticides, such as the macrocyclic lactones, and concern over the continued use of some of the older neurotoxic compounds. These changes have been exacerbated by outbreaks of endemic disease, the threats of exotic disease introduction and fears of potential changes in arthropod distribution associated with climate change. This paper therefore, reviews the current status of livestock ectoparasites in Europe and the Mediterranean region.     

Anthelmintic resistance and the future for roundworm control

Anthelmintic resistance has emerged as the most important problem confronting the successful control of nematode parasites of grazing animals. Although the significance of the problem varies between, and within, countries and farming enterprises, there is little likelihood that it will disappear of its own accord. On the contrary, it is reasonable to assume that it will increase if there is no change in traditional methods of parasite control. Although progress is being made in non-chemotherapeutic methods of control, these are unlikely to provide any practical alternatives in the short-term future. Nor can the pharmaceutical industry be expected to solve the problem because of the long period and the exceedingly high costs involved in bringing a completely new class of drug on to the market. The answer must lie in carefully husbanding the currently available anthelmintics, by providing farmers with programs which give good levels of parasite control and maintain high productivity in animals with fewer anthelmintic treatments. To be enthusiastically adopted by farmers, the programs require a commitment by both research and advisory workers. Such success can be achieved, as exemplified by the "Drenchplan" and "Wormkill" programs in Australia. It behoves workers in all countries which have a significant grazing livestock industry, not only those with an existing resistance problem, to consider how such schemes could be implemented.     

Control strategies for ostertagiasis

There are currently four major options for control of ostertagiasis and other ruminant gastrointestinal parasites. These are the traditional, suppressive, integrated and strategic approaches. Strategic dosing is the most realistic and beneficial approach for most regions of the world, including the U.S.A. It is effective, practical, labor-saving and can yield big economic returns. Today this approach is even more appropriate because of important advances in the technology of controlled release and pulse-release devices. Top priority in worm control programs should be given to dairy replacement heifers in their first year at pasture and to beef calves in the immediate post-weaning period. This is preferable to recommendations for blanket treatment of all beef and dairy cattle, regardless of age, immune status or pasture infectivity. An anthelmintic overkill is both wasteful and potentially harmful in that it increases the selection pressure for drug resistance. It is suggested that better dissemination of information is needed to make producers aware of the benefits of strategic dosing programs. This would eliminate much of the confusion about parasite control and focus attention on simple and effective programs that could significantly reduce current losses to the livestock industries.     

The critical importance of planned small ruminant livestock health and production in addressing global challenges surrounding food production and poverty alleviation

ABSTRACT

Small ruminants are particularly well suited to meet United Nations Sustainable Development Goals surrounding food security, human wellbeing and poverty alleviation in different environmental and climatic settings. However the current efficiency of food production from small ruminants in both developed agricultural regions and in lower and middle income countries is woefully inadequate to meet predicted global needs over the forthcoming decades. Most global research to address this challenge is focussed on the genetics of animal growth, conformation and disease tolerance or resistance traits, albeit the practical consequences of such selection and strategies to use genetically improved animals in the field are uncertain. Any long-term benefits derived from small ruminant genetic selection will only be impactful if steps are first taken to keep animals alive, healthy and productive through iterative planned health management. Parasites are the foremost global infectious disease constraints to efficient small ruminant production. Their genetic adaptability to exploit opportunities afforded by effects of climatic or management changes on free-living stages, or exposure of parasitic stages to drugs, presents specific challenges to their sustainable control. Hence, parasite control provides a relevant means of engagement with livestock keepers and farmers on the topic of planned animal health management. The value of parasitology in this regard is enhanced by the availability of simple to use and accessible diagnostic tools.     

Worms in smallholder livestock systems: technologies and practices that make a difference

Australian scientists, in partnership with Asian, African and Pacific nations have longstanding interests in applied research on helminth parasite control. Many technologies and practices have been successfully developed to control the parasite problems of smallholder and emerging farmers. This wide range extends from simple herbal remedies to complex, integrated use of chemicals, feeding and breeding. In many cases widespread adoption has been limited by lack of technical support, poor access to input markets and lack of incentives for poorer farmers to seek out and pay for innovations. A further new approach may be required that encompasses the wider production and market environment. The biological, social and economic context of each 'emerging farming system' is different and the matching of technologies to each system requires sound understanding of farmer needs and requirements. Thus, it is essential that farmers, extension workers, and scientists jointly decide what technologies to try, what results mean and, if successful, how to sustain their use. In one Asian example a range of technologies were considered for pig, large ruminant and goat production and parasite control through a participatory process which was also used to agree on what determines sustainability beyond testing. The criteria use to screen technologies and practices were (a) continued availability of inputs including dewormers, (b) dependence on related innovations (e.g. weaning or fencing) and (c) degree of community organisation required (e.g. control of breeding or communal grazing). On this basis deworming with chemicals, especially for Toxacara infection in cattle and buffalo calves following on from supplementary feeding with forages were the most feasible entry points. Further interventions were dependent on changes to the production system, including the introduction of weaning and controlled breeding. Further, the incentives for these production changes could not exist without improved market access and market signals for improved weight and condition. Examples such as this point to the need for stronger multidisciplinary and participatory approaches to parasite control.     

Genetics of fear in ruminant livestock

We provide first an overview of studies on ruminant livestock that emphasises an inter-individual variability and a relative intra-individual consistency in fear responsiveness. Then, we provide evidence that genetic factors underlie fear responsiveness. We discuss problems that may hinder the genetic evaluation and the application of fearfulness traits for genetic selection in livestock. These problems include the absence of validation in experimental designs, the complexity of fear-related responses, and the interaction between genetic factors and environmental influences that limit the consistency in fear-related responses. Some possible welfare consequences of current selection programs are also considered. Finally, we discuss the possibility for including fear criteria in current selection programs and consider how such approaches may have considerable promise in ruminant livestock. More particularly, we outline current knowledge about how genes control fearfulness. Even if fear-related responses in ruminant livestock are complex, the capacity to select on fear-related criteria or even perhaps on genes that confer fearfulness traits has the potential to significantly enhance our ability to optimise livestock for their production environment and reduce the potential for compromise to their welfare.     

Nematophagous fungi as a biological control agent for nematode parasites of small ruminants in Malaysia: a special emphasis on Duddingtonia flagrans

Approximately 2,800 fresh dung samples from animals, mainly ruminant livestock, were screened for the presence of nematophagous fungi in Malaysia. Arthrobotrys spp. was noted on numerous occasions, but only one isolate of Duddingtonia flagrans was made. For the purposes of producing sufficient quantities of this fungus for feeding trials in sheep, various, commonly available, cheap plant materials were tested as possible growth substrates. This showed that cereal grains (wheat, millet and rice) were the best media for fungal growth. Pen feeding trials were carried out using sheep, both naturally and experimentally infected with nematode parasites (predominantely Haemonchus contortus), to test the efficiency of D. flagrans when administered either in a grain supplement, or incorporated into a feed block. These showed that the fungus survived gut passage in sheep and that dose rates of approximately 1 x 10(6) D. flagrans spores / animal / day, reduced the percentage of infective larvae developing in faecal cultures by more than 90%. These results indicate that using D. flagrans as a biological control agent of nematode parasites, is a promising alternative to nematode parasite control of small ruminants in Malaysia, where anthelmintic resistance is now a major problem.     

Managing anthelmintic resistance in small ruminant livestock of resource-poor farmers in South Africa

Gastrointestinal parasitism is one of the most important disease complexes of sheep and goats impacting on the resource-poor livestock farmer. Of the responsible nematodes, Haemonchus contortus, a blood-sucking worm of the abomasum, poses possibly the greatest threat. Over the past several decades, the worm has been controlled through the use of anthelmintics, but the emergence of anthelmintic resistance has threatened this chemotherapeutic approach. In Africa, the overall prevalence of anthelmintic resistance has not been extensively investigated, particularly within the resource-poor farming sector, but resistance has been reported from at least 14 countries with most of the reports emanating from Kenya and South Africa and the majority concerning H. contortus. While levels of resistance under commercial sheep farming systems in South Africa is considered to be amongst the worst in the world, resistance has also been reported from the resource-poor farming sector. Increases in productivity and reproduction of livestock and the development of markets for sale of animals are seen by international funding bodies as a way out of poverty for communities that keep livestock. This must lead to the greater need for parasite control. At such times, the risk of levels of anthelmintic resistance escalating is much greater and there is therefore a need to look at alternatives to their use. Proposed strategies include the appropriate, but judicious use of anthelmintics by application of the FAMACHA system and the use of alternatives to anthelmintics such as strategic nutrient supplementation. It is also very clear that there is a strong demand for knowledge about animal diseases, including helminthosis, and their effective management in the resource-poor livestock farming communities. This is an important challenge to meet.     

Genetic aspects of sheep parasitic diseases

There is evidence of genetically determined host resistance mechanisms for most of the sheep parasites evaluated. The mechanisms vary; from no or reduced establishment, early expulsion, to suppression of parasites resulting in reduced size and fecundity. There is a need to integrate breeding for parasite resistance with the genetic improvement of production traits in farm animals, aiming for optimum solutions for potentially conflicting responses. Sustainable parasite control must be based on Integrated Parasite Management utilising an interdisciplinary approach.     

Diagnostic methods for parasitic infections in livestock.

Parasitic infections are a primary cause of lost productivity in livestock world-wide. Accurate detection of parasites depends on many factors, including collection, storage, and transport of the sample, as well as the method of laboratory evaluation. However, the presence of a particular parasite does not always indicate the presence of parasitic disease. For many parasites, there exists a level at which the effect on production characteristics is balanced by the effect on the development of immunity. Interpretation of test results, therefore, should also consider such factors as the age of the animal or animals, clinical history, nutrition, local epidemiology of the parasites prevalent in the area, and any treatments that have been implemented.     

Fluoroacetate in plants-a review of its distribution,toxicity to livestock and microbial detoxification

Fluoroacetate producing plants grow worldwide and it is believed they produce this toxic compound as a defence mechanism against grazing by herbivores. Ingestion by livestock often results in fatal poisonings, which causes significant economic problems to commercial farmers in many countries such as Australia, Brazil and South Africa.Several approaches have been adopted to protect livestock from the toxicity with limited success including fencing,toxic plant eradication and agents that bind the toxin. Genetically modified bacteria capable of degrading fluoroacetate have been able to protect ruminants from fluoroacetate toxicity under experimental conditions but concerns over the release of these microbes into the environment have prevented the application of this technology.Recently, a native bacterium from an Australian bovine rumen was isolated which can degrade fluoroacetate. This bacterium, strain MFA1, which belongs to the Synergistetes phylum degrades fluoroacetate to fluoride ions and acetate. The discovery and isolation of this bacterium provides a new opportunity to detoxify fluoroacetate in the rumen. This review focuses on fluoroacetate toxicity in ruminant livestock, the mechanism of fluoroacetate toxicity,tolerance of some animals to fluoroaceate, previous attempts to mitigate toxicity, aerobic and anaerobic microbial degradation of fluoroacetate, and future directions to overcome fluoroacetate toxicity.     

Enantiomeric behaviour of albendazole and fenbendazole sulfoxides in domestic animals: Pharmacological implications

Albendazole and fenbendazole are methylcarbamate benzimidazole anthelmintics extensively used to control gastrointestinal parasites in domestic animals. These parent compounds are metabolised to albendazole sulfoxide and fenbendazole sulfoxide (oxfendazole), respectively. Both sulfoxide derivatives are anthelmintically active and are manufactured for use in animals. They metabolites have an asymmetric centre on their chemical structures and two enantiomeric forms of each sulfoxide have been identified in plasma, tissues of parasite location and within target helminths. Both the flavin-monooxygenase and cytochrome P450 systems are involved in the enantioselective biotransformation of these anthelmintic compounds in ruminant species. A relevant progress on the understanding of the relationship among enantioselective metabolism and systemic availability of each enantiomeric form has been achieved. This article reviews the current knowledge on the pharmacological implications of the enantiomeric behaviour of albendazole sulfoxide and oxfendazole in domestic animals.     

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