W.A.A.V.P. and Pfizer award for excellence in research in veterinary parasitology. Veterinary helminthology 1954–1993: a personal view of four decades of research

veterinary parasitology ELSEVIER

Veterinary Parasitology 54 (1994) 11-22

W.A.A.V.P. and Pfizer award for excellence in research in veterinary parasitology. Veterinary helminthology 1954-1993: a personal view of four decades of research J. A r m o u r University of Glasgow, UK

I have been involved with veterinary parasitology and in particular veterinary helminthology for close on four decades. At the request of the President of the World Association for the Advancement of Veterinary Parasitology, Dr Owen Slocombe, I have been asked to reflect on seminal research achievements during that period with emphasis where appropriate to my own work. By way of a preamble I will start by describing how I came into veterinary parasitology. As a young veterinarian I had joined the British Colonial Service in 1953 and was posted to the Veterinary Research Station at Vom, Nigeria. Although my remit was to work in the general area of animal production I soon recognised that apart from major scourges such as rinderpest, the biggest problems affecting animal production were parasitic infections and nutrition and the interaction between these. A vacancy occurred in the Parasitology Division of the Department of Animal Production and I joined the team led by Professor Rob Lee and Dr John Ross, both of whom are distinguished veterinary helminthologists; they were my mentors and my friends. Our laboratory concentrated on helminthology while another on the same station dealt with entomology and blood protozoa. I now propose to provide a personal view of research in veterinary helminthology over the past four decades, i.e. 1954-1993.

1954-1963 Following on the famous self-cure paper by Stewart (1955) working at the McMaster laboratory in Sydney and a series of stimulating reviews by Soulsby, 0304-4017/94/$07.00 © 1994 Elsevier Science B.V. All rights reserved SSD10304-4017 (94) 03074-7

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interest in helminth immunology increased dramatically during this decade and research into the mechanisms of host immunity was initiated in laboratories worldwide. Working in Nigeria, my own interest was stimulated by our inability to prevent haemonchosis in lambs, kids or calves on Government research farms or grazing under natural conditions. The cry was for either a good vaccine or anthelmintic; neither was available. Then in 1957 the publication by my colleagues at Glasgow, led by George Urquhart, of a paper reporting the successful development of a vaccine against the cattle lungworm, Dictyocaulus viviparus, using X-irradiated infective larvae (Jarrett et al., 1957), changed the scientific direction of several research groups. Attempts were made to vaccinate against a wide range of pulmonary and gastrointestinal helminths using the same approach as that used so successfully for D. viviparus. Although there were some subsequent successes, for example the Dictyocaulusfilaria work in Kashmir (Tewari et al., 1973) and those with the dog hookworm Ancylostoma caninum at Glasgow (Miller, 1971 ) other attempts to develop X-irradiated larval vaccines achieved only partial success. For example, our own group in Nigeria used X-irradiated Haemonchus placei infective larvae to immunise calves successfully against experimental challenge but the vaccine was unable to confer worthwhile resistance when the vaccinated calves were subjected to a natural field challenge. This result and others which gave equally disappointing data, particularly with gastro-intestinal helminths, probably delayed alternative immunological approaches to the control of helminthiasis until a very much later date. Incidentally, the successful D. viviparus immunisation studies rather overshadowed what were a series of excellent studies on the pathogenesis of lungworm disease in cattle by Jarrett, Urquhart and their colleagues at Glasgow. These experiments were to be the forerunner in terms of experimental design of others which I will describe later. The control of helminths remained largely dependent on the use of anthelmintics despite the commercial success of the cattle lungworm vaccine and the early promise of other experimental X-irradiated larval vaccines. The epidemiology papers which came from Roberts in Queensland (Roberts et al., 1952 ) and from Hugh Gordon's laboratory in Sydney, summarised in Gordon ( 1973 ), heralded the first control programmes based on strategic anthelmintic use. In the early part of the decade the main restraint on the development of successful strategic programmes was the efficacy of the anthelmintics available, which were only effective against adult parasitic stages. A breakthrough came in the early 1960s with the appearance of a new anthelmintic, thiabendazole, which had a broad spectrum of activity against both adult and larval stages of gastro-intestinal nematodes. So the era of strategic anthelmintic medication was upon us. Meanwhile, a paper by Martin et al. (1957) and colleagues at Glasgow on atypical clinical parasitic gastritis in cattle housed for the winter stimulated interest in the role of parasitic larvae, inhibited in their development, usually at the fourth stage, on both the epidemiology of gastro-intestinal nematodes and the delayed onset of clinical nematodosis. Various groups, including our own in Vom, Nigeria, had been studying how

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free-living larval stages of nematodes persisted through adverse conditions such as the prolonged dry season. The results of these studies were overtaken when one of our group, John Hart, reported that in Northern Nigeria inhibited fourth stage Haemonchus spp. larvae accumulated in cattle at the end of the wet season and persisted through the long dry season, suggesting that these larvae played the major role in the persistence of nematode infections from one dry season to the next (Hart, 1964). Most research groups assumed that inhibited larvae accumulated as a result of the immunity acquired through exposure during either a wet season in tropical areas or a summer grazing season in the Northern Hemisphere when conditions were optimal for free-living larval development. In the end this decade will be remembered for the first helminth vaccine, the development of thiabendazole and a burgeoning interest in the role of inhibited larvae in epidemiology and disease. It also saw the birth of W.A.A.V.P. at Hannover in 1963, the full benefits of which became evident in subsequent decades.

1964-1973

This could easily be named the Ostertagia decade in which the pathogenesis, epidemiology and control of infections caused by nematodes of the genus Ostertagia were prominent in publications on veterinary helminthology. Many of these reports came from the veterinary parasitology group at Glasgow University which I was privileged to join in 1963 following a short spell in the pharmaceutical industry at the Cooper Technical Bureau, following my Nigerian sojourn. At Glasgow we were fortunate in being well-funded by the Agricultural Research Council for our work on ostertagiosis, and this encouraged us to design experiments which would largely fulfil Koch's postulates in terms of reproducing the clinical disease experimentally and determining the serial biochemical and histopathological changes which occurred after experimental infection. Perhaps the most rewarding of the experiments was that which monitored changes in the abomasum of Ostertagia ostertagi infected calves fitted with an abomasal cannula (Jennings et al., 1966 ). This provided the basis for many subsequent pathophysiological experiments. A significant feature of our studies on the pathogenesis and pathophysiology of Ostertagia infections was the manner in which different scientific disciplines co-operated. It would have been impossible for veterinary helminthologists to complete these studies without the co-operation of our colleagues in physiology, biochemistry, pathology and clinical medicine. Apart from our studies using experimental infections of O. ostertagi in cattle and Ostertagia circumcincta in sheep, we followed in detail the sequential development of ostertagiosis in ruminants under natural grazing conditions (Anderson et al., 1969). Using batches of parasite-naive tracer calves or lambs grazed for successive periods of 14 days to monitor the levels of infective larvae on the pastures grazed by groups of permanent calves or lambs, the epidemiology of ostertagiosis in the Northern Hemisphere was unravelled. Thus, the pasture contamination with Ostertagia spp. eggs which resulted from

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infections acquired in spring by the ingestion of the low numbers of infective larvae which had survived the winter, produced a marked increase in the levels of infective larvae on pasture during the late summer and autumn; this resulted in clinical ostertagiosis, the severity depending on various factors such as stocking rate, the previous grazing history of the pasture, age of the grazing animals and the weather pattern. These outbreaks of clinical disease in the summer or autumn, characterised by severe diarrhoea and weight loss, were designated Type 1 disease to differentiate them from outbreaks seen in housed yearling cattle, or less commonly lambs, during the subsequent late winter and spring and designated Type 2 disease. From a veterinary helminthology standpoint the most interesting finding of our field studies was that an accumulation of inhibited fourth stage larvae of Ostertagia spp. occurred at precisely the same time, namely in the late autumn, in both the parasite-naive tracers grazed for 14 days and the permanent calves which had grazed throughout the spring, summer and autumn. Previously it had quite reasonably been assumed that the accumulation of inhibited larvae in a host occurred as a consequence of an immunity acquired following prolonged exposure. The results from our tracer calf and lamb work suggested that factors other than host immunity were involved. The suggestion that this was an adaptation mechanism to ensure survival of the parasitic population at a time when late autumn and winter conditions were unfavourable for free-living larval development or survival was well accepted. It was also recognised from our field studies that when large numbers of inhibited larvae resumed development in the late winter or spring, clinical ostertagiosis, designated Type 2, could occur. The trigger to inhibit in the autumn or to develop subsequently in the spring remains unknown although we were able to induce arrestment of O. ostertagi following exposure to declining or low temperatures. The term hypobiosis was coined by Hugh Gordon to describe larvae inhibited in development as a result of such seasonal influence. While I am a strong protagonist of co-operation between different disciplines in research, the value of inter-institutional competition as a stimulus to progress should never be underestimated. While we were undertaking our epidemiological studies on ostertagiosis in the West of Scotland, contemporaneous work in the U K by Gibson and Michel at Weybridge, Thomas at Newcastle, Connan at Cambridge, and by our former colleague Norman Anderson working in Australia, and the resulting competition between our laboratories, undoubtedly contributed to the progress during this decade. Michel's paper on the control of bovine osteragiosis by moving calves to alternative and ungrazed pastures before the annual mid-summer increase in numbers of infective larvae on pasture remains a landmark, as does Thomas's work on the role of the ewe in the epidemiology of ovine ostertagiosis (see review by Michel, 1976 ). Although I regard this as the Ostertagia era, it would be churlish to suggest that other helminths were ignored. Certainly, in Europe there was considerable interest in the pathophysiology and epidemiology of fasciolosis with major programmes of research in the Netherlands, Northern Ireland and in my own laboratory. New interest was displayed in horse parasites and the work of Drudge and

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Lyons (1966), my colleague Jim Duncan at Glasgow (Duncan and Pirie, 1972 ) and Owen Slocombe's group in Canada (Slocombe et al., 1977 ) provided milestones in equine parasitology. Relatively slow progress was made during this decade on the immunological control of helminths, although there was outstanding basic research on the mechanism of the self-cure reaction using the Nippostrongylus brasiliensis model in rats (Barth et al., 1966). So control of helminths continued to be based on strategic anthelmintic medication mainly using thiabendazole and another new broadspectrum drug, levamisole, which was also effective against lungworms. Unfortunately these anthelmintics were not effective against inhibited fourth stage O. ostertagi larvae in cattle or many of the inhibited stages of important equine nematodes. The need for better anthelmintics against nematodes and cestodes was partially met with the synthesis of diamphenethide which proved to be highly effective against hepatic stages of Fasciola hepatica in sheep but not cattle. 1974-1983

If the previous decade was the golden era for my own research in ostertagiosis and fasciolosis, the ten years between 1973 and 1983 saw the blossoming of applied veterinary helminthology in many parts of the world. The reasons for this are not absolutely clear but the gatherings of those interested in Veterinary Parasitology in Hannover (1963), Philadelphia (1964), Lyon (1967), and subsequent meetings under the auspices of W.A.A.V.P., undoubtedly had a positive effect on research in the next decade. A European conference held at Glasgow 1973, where key speakers reviewed the major helminth problems in European livestock and representatives from many European countries, both East and West, outlined problems pertinent to their own states, had a considerable influence on the resurgence of applied veterinary parasitology in Europe (Urquhart and Armour, 1974). The bond between European workers was later strengthened through a series of workshops held in the Netherlands and in Denmark. However, perhaps the best stimulus of all was provided by the memorable W.A.A.V.P. conference held at Sydney in 1977. Many veterinary parasitologists, still inspired by the early work of Clunies Ross, Stewart, Gordon and Roberts, made the pilgrimage to Australia and they were not disappointed. The range and quality of the presentations from different parts of the globe made this, for myself and many others, an enriching experience. The sheer variety of work undertaken during the decade makes it difficult to identify the highlights. Let me start by looking at anthelmintic developments since they had a high profile during the decade. In the mid 1970s a range ofbenzimidazoles which were less soluble than thiabendazole and therefore more persistent, were generated. These drugs were highly active against inhibited/hypobiotic larval stages, thus making the strategic use of anthelmintics based on known epidemiology more effective. Technological advances in the administration ofanthelmintics also made rapid progress, highlighted by the development of a sustained release rumen bolus

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(Paratect) containing the anthelmintic, morantel tartrate. In the Northern Hemisphere the oral administration of this rumen bolus, prior to turning out young cattle to graze in the spring, so limited pasture contamination following the ingestion of overwintered larvae that the burdens of gastrointestinal nematodes subsequently acquired were reduced to insignificant levels with clear production benefits. Towards the end of the decade a new class of anthelmintic, the avermectins, was developed and one of these, ivermectin, was marketed. Apart from the broad spectrum effect on nematodes, ivermectin was very effective against a range of ectoparasites earning it the title of endectocide. Ivermectin was effective at very low dosage levels yet persisted in the body of the animal to the extent that it continued to have an effect on ingested larvae for up to 3 weeks; this proved to be of great benefit in the design of strategic medication programmes. The advent of triclabendazole with its efficacy against all the hepatic stages ofF. hepatica in all ruminants was another key development. The emergence of the avermectins was timely as, during the 1970s and into the 1980s, anthelmintic resistance particularly to the benzimidazoles became a real problem in major sheep rearing areas of the world, such as Australia, New Zealand, South America and South Africa. The studies of Australian scientists, notably Donald, Prichard and Waller at Sydney and the pioneering experimental work of Le Jambre and colleagues at Armadale, New South Wales, have provided an insight into the development of resistance by different trichostrongyle species, cross resistance between related drugs, the regression to susceptibility following no exposure to the resistant drug and the rapid reappearance of resistance once the drug was re-introduced and the genetics of drug resistance. Much of this work was with Haemonchus contortus, although other trichostrongyles were also involved, and is reviewed by Waller (1987) and Prichard (1990). The identification ofanthelmintic resistance as a major and escalating problem intensified the search for other methods of helminth control such as rotational grazing with different host species or different age groups within one species which did not rely solely on anthelmintics. In Australia, other solutions to worm control were pursued vigorously, based on the identification of individual resistant sheep. These were selected as responding in a positive immunological way by limiting the establishment of challenge infections, compared with more susceptible members of the flock--the so-called responders and non-responders. This work initiated in the late 1970s has now produced lines of Merino sheep which portray significant resistance to H. contortus and the productivity of these sheep is currently under investigation. It is interesting to reflect that nearly 50 years ago work in New York State by Whitlock had identified rams whose progeny were different in their susceptibility to H. contortus. In Kenya, a slightly different approach was adopted by Allonby, Preston and Dargie from Glasgow (Preston and Allonby, 1979). They found that a local breed of sheep, the Red Masai was highly resistant to H. contortus and thrived on grazing where the more productive Merinos re-

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quired treatment with anthelmintics every 3 weeks to survive the ravages of haemonchosis. Differing breed susceptibility to H. contortus was also reported from other parts of the world including Florida and South Africa. Gray (1987) has provided an excellent up-to-date review on genetic resistance to haemonchosis. Studies on ostertagiosis were also prominent during this decade particularly in Australia, New Zealand, South America and the USA, where there was a resurgence of interest in applied veterinary parasitology, with strong groups developing in Louisiana and Ohio. The similarities and contrasts to the situation described by our own and other European studies were highlighted. In my own laboratory, studies on ostertagiosis continued. Although we had observed clinical Type 2 disease in young cattle housed for some months following their first grazing season and, by serial post mortem examination of the parasite populations, deduced that the re-emergence of previously inhibited larvae was responsible for the Type 2 clinical condition, we had not been able to reproduce this form of the disease experimentally. However, following daily inoculation of parasite-naive calves over a period of 10 days with 100 000 O. ostertagi infective larvae, subjected to chilling at 4 °C for the previous 8 weeks, we succeeded in establishing significant burdens of inhibited fourth stage larvae. The calves were then monitored for the next 4 months and, at 16 weeks after the last infection, two of the calves developed clinical signs of ostertagiosis which was confirmed at post-mortem; so with the reproduction of Type 2, Dr. Koch was satisfied (Armour and Bruce, 1974). Studies also continued on the role of the adult animal in the epidemiology of ostertagiosis. We found that most adult cows in our area have very low burdens of O. ostertagi which are insufficient to cause a production effect and, with only a few patent infections developing, their impact on the epidemiology of ostertagiosis was minimal. How then could one account for the loss of milk production which for some time has been associated with parasitism in the milking cow or indeed in ewes or goats? In co-operation with my colleagues in physiology and pharmacology we were able to demonstrate that, in immune adult ruminants under challenge from Ostertagia spp. infective larvae, few of which became established, there was an increased permeability of the gut epithelium, presumably at the site of the immune reaction and so a loss of essential plasma proteins occurred via the gut which contributed to the loss in production (Yakoob et al., 1983). Fox and his colleagues in London have confirmed and extended these observations. Using similar radioisotope techniques, several laboratories including our own carried out further experiments to study the effects of a range of trichostrongyles in the host metabolism and carcass composition. Although scientifically interesting, perhaps the greatest impact of these studies was to convince the doubters that even moderate loads of helminths severely affected production and health and therefore required treatment. These studies are well reviewed by Parkins and Holmes ( 1989 ). A most significant immunological advance was made when Rickard and Adolph (1976) in Melbourne successfully vaccinated cattle against the intermediate larval stages of the human tapeworm Taenia saginata using extracts of sonicated oncospheres from the tapeworm. Using similar techniques experimental vaccines

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were later developed against the intermediate stages of a range of tapeworms including Taenia ovis, Taenia hydatigena and Taenia multiceps in sheep; Taenia soliurn in pigs and Echinococcus granulosus in sheep. In order to overcome the problems of antigen supply Rickard and his colleagues used recombinant DNA methods to produce the protective oncosphere antigens and this has led to the development of a vaccine against ovine cysticercosis which is in the final stages of commercial development (Rickard, 1989). This work with the Taenia spp. was the most inspiring and practically useful piece of research in parasite immunology, since the lungworm vaccine studies in the 1950s. However, it would be wrong to suggest that no other advances were made in the intervening period. The series of studies on Nippostrongylus in the rat and the self-cure reaction by Ellen Jarrett at Glasgow, Hugh Miller at Moredun, Edinburgh (Jarrett and Miller, 1982 ), Bridget Ogilvie and colleagues at Mill Hill and Luffau in France, established that these infections produced a state of gut hypersensitivity associated with an increase in mucosal mast cells in the lamina propria and the production of worm specific IgE, much bound to mast cell surfaces. The interaction between worm antigen and these sensitised mast cells released vasoactive amines which cause an increase in capillary and epithelial permeability and hyperproduction of mucus. The precise role of other immunoglobulins and T lymphocytes is still being investigated but it is clear that their passage through the gut wall and contact with helminths located on the surface is likely to be increased by the increased permeability. The Nippostrongylus studies, although admirable, were primarily centred on the mechanism of worm expulsion and perhaps more attention and funding should have been directed as to why most attempts to immunise gastro-intestinal helminths had proved unsatisfactory. The classical work on immunological unresponsiveness to Haemonchus infection in young lambs, particularly those of the Merino breed, the respective roles of tolerance, age and lactation and the immunosuppressive effect of some nematode infections are examples of areas which were studied by laboratories in several countries and are reviewed by Lloyd ( 1983 ) and Soulsby ( 1988 ). This period also heralded the involvement of mathematical models for the prediction of parasitic disease in grazing animals and also the onset of anthelmintic resistance under various control programmes (Gettinby, 1989). Based on the biology of different parasites, fitting such data to known epidemiological facts and then applying various mathematical formula, these models have produced remarkably accurate predictions of disease incidence in susceptible stock. Subsequent models will hopefully take into account the influence of host immunity. It is important that the modellers work in close harmony with the veterinary parasitologists so that all the relevant factors such as host immunity are taken into account. In my own case I was fortunate in the liaison formed with George Gettinby of the University of Strathclyde.

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1984-1993

With one notable exception this decade provided 'more of the same' and identified some constraints on the future of applied veterinary helminthology. In the area of anthelmintics, several new avermectins or closely allied drugs were identified while the technology of sustained or pulsatile release boli spawned several new devices suitable for most of the broad spectrum anthelmintics. Those marketed so far for cattle or sheep provide alternatives to the trendsetting bolus containing morantel tartrate and in some cases also offered control of lungworm infections as well as those nematodes found in the gastro-intestinal tract. My own laboratory and those of colleagues in the Netherlands, Belgium and the UK, including Northern Ireland, played a significant role in assessing the control achieved by these boli and, while proving their ability to offer season long control, at least in the Northern Hemisphere, possible problems in delaying the onset of immunity have been identified (reviewed by Armour, 1989). Basically, the better the control in the first grazing season, the more risk there is of animals remaining susceptible or partly susceptible to infections in their second year. Time alone will tell if nematode helminth infections which are currently common in young ruminants will become more prevalent in older livestock. Another problem surrounding the modern anthelmintics apart from resistance, is the more stringent requirements of licensing authorities. At the beginning of the decade it was residues in food animals that created headlines but now we are faced with increasingly rigorous assessment of the ecotoxicological effects of anthelmintics, particularly relating to the avermectins. It is important that a balanced view of the environmental risk is taken in conjunction with the recognition that the welfare of our animals exposed to helminth challenge could be severely compromised if availability of the best anthelmintics were to be curtailed. It was unfortunate that during this decade there was a reluctance of funding bodies to support veterinary parasitology research which involved studies in diseases judged to be under control; the attitude was very much one of "it's all been done and good control methods are available". Drug resistance was seen to be the problem of the pharmaceutical companies and studies on improved production systems through helminth control programmes were considered to be too applied in nature for the funding panels to consider. It was easier to get funds to look at parasite problems in livestock in the developing countries and many of the major research groups from Europe, Australasia and the USA became involved in Africa, South America and South East Asia. I was personally gratified that W.A.A.V.P. held the 1986 Congress in Brazil where the results of the epidemiology studies, with which I was involved in Argentina, Brazil and Paraguay, were presented by the enthusiastic and innovative young veterinary helminthologists in that sub-continent. As access to major funding for farm animal parasitology, particularly involving ruminants, became difficult, more emphasis has been placed on studying the helminths of companion animals particularly with parasites involved in zoonoses. An exception to this was the well-funded studies by Danish workers on the epi-

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demiology and control of pig helminths and the production losses caused by these parasites. The expanding market for anthelmintics in companion animals has led to good support for studies in a range of helminths including ascarids in dogs and cats at London and Cambridge Universities and heartworms in dogs, primarily in Georgia and the Southern States of the USA. By the end of the decade excellent control programmes were available for most of the major helminths in companion animals and considerable progress has been made in the control of those associated with zoonoses by Eckert's group in Switzerland and Gemmell and colleagues in New Zealand. Progress on immunological control continued in a mechanistic fashion during the first half of the decade. Apart from studies on different cell types and inflammation mediators there has been a steady stream of publications on the isolation, cloning and expression of theoretically protective antigens and possible vaccine delivery systems. Most of the attempts to vaccinate ruminants against pathogenic nematodes centred on the use of exsheathing fluids or excretory-secretory antigens from infective larvae, and provided very mixed and generally disappointing protection with the exception of the Strongylus vulgaris vaccination studies of Klei et al. (1989). Following promising results published by Munn et al. ( 1987 ) and Jasper and McGuire ( 1991 ) the big breakthrough finally came in 1993 with the publication by Munn (Munn et al., 1993 ) and his colleagues at Babraham, Cambridge, and Smith ( 1993 ) at Moredun, Edinburgh, of experiments describing the successful immunisation of young Merino lambs (previously considered immunologically unresponsive) against H. contortus using membrane associated proteins from the intestinal microviUi of adult H. contortus. Protection of approximately 90% against experimental challenge was obtained with two injections into lambs at 14 day intervals with extracts of adult Haemonchus enriched with H 11, an integral membrane glycoprotein from the parasites intestinal microvilli. This approach is more likely to be successful with blood-sucking nematodes since sheep are not normally exposed to covert antigens such as the worm's gut protein. Obviously, for commercial vaccination it will be necessary to purify the protective antigens and to reproduce these in a large scale by recombinant DNA methods. So the wheel has returned to where I started in that the quest for the golden bullet to control haemonchosis seems to be closer to success. We now have excellent drugs and the possibility of a vaccine. Whether the same principles can be applied to produce 'cost effective' vaccines against other main helminth scourges such as Ostertagia and Fasciola remains to be seen.

The future

After what I regard, perhaps wrongly, as a relatively fallow period in veterinary helminthology, the Haemonchus vaccine story has given the subject a real shot in the arm. The problems of anthelmintic resistance and of the environmental pressures against the prophylactic use of drugs to control helminth problems in farm

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livestock will intensify. These environmental pressures are in many cases an overreaction and disguise the tremendous benefits brought to animal welfare and production via the anthelmintic developments of the past 30 years which began with thiabendazole. It remains to be seen whether the cost of developing and marketing the new breed of vaccines and the impractical nature of many grazing control systems will prolong the use of anthelmintics used as prophylactics and therapeutics, but the stimulus has been provided to look again in depth at the potential role of vaccines in the control of helminthoses. It will require teamwork involving molecular biologists, immunologists and veterinary parasitologists if real progress is to be made. In the course of these studies we might even find out the real cause of hypobiosis in parasitic nematodes. The exciting work on gene sequencing with the free living nematode Caenorhabditis elegans is proceeding apace and we will soon know the complete DNA sequence of its genome and be in a much better position to understand how information is interpreted during development and in the adult worm; hopefully this in turn will provide vital clues about the biology of the parasite and the mechanism of drug resistance. In conclusion it has clearly been a profitable 40 years for veterinary helminthology in which I feel privileged to have played a part and which I have enjoyed. I hope that the funding bodies will recognise the exciting new era for veterinary parasitology and sustain their support over a sufficient time to generate worthwhile results. Apart from good funding future progress will depend on teamwork involving different disciplines and a healthy cadre of post-graduate students.

References Anderson, N., Armour, J., Jennings, F.W., Ritchie, J.S.D. and Urquhart, G.M., 1969. The sequential development of naturally occurring ostertagiasis in calves. Res. Vet. Sci., 10:18-28. Armour, J., 1989. The influence of host immunity on the epidemiology of trichostrongyle infections in cattle. Vet. Parasitol., 32: 5-19. Armour, J. and Bruce, R.G., 1974. The inhibition of development ofOstertagia ostertagi--a diapause phenomenon in a nematode. Parasitology, 69:161-174. Barth, E.E.E., Jarrett, W.F.H. and Urquhart, G.M., 1966. Studies on the mechanism of the self-cure reaction in rats infected with Nippostrongylus brasiliensis. Immunology, 10: 459-464. Drudge, J.H. and Lyons, E.T., 1966. Control of internal parasites of the horse. J. Am. Vet. Med. Assoc., 148: 378-383. Duncan, J.L. and Pirie, H.M., 1972. The life cycle ofStrongylus vulgaris in the horse. Res. Vet. Sci., 13: 374-379. Gettinby, G., 1989. Computational veterinary parasitology with an application to chemical resistance. Vet. Parasitol., 32: 57-72. Gordon, H., 1973. Epidemiology and control of gastrointestinal nematodes of ruminants. Adv. Vet. Sci., 17: 395-437. Gray, G.D., 1987. Genetic resistance to haemonchosis in sheep. Parasitol. Today, 3: 253-255. Hart, J.A., 1964. Observations on the dry season strongyle infections of Zebu cattle in North Nigeria. Br. Vet. J., 120: 87-95. Jarrett, E.E.E. and Miller, H.R.P., 1982. Production and activities oflgE in helminth infection. Prog. Allergy, 31: 178-233.

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