Chapter 9

Chapter 9. Helminth diseases of sheep

Introduction | Ecology of sheep helminths | Host immune responses | Hypobiosis | Epidemiology | Pathogenesis of helminth infestation | Clinical signs | Effects on production | Mortality | Diagnosis | Treatment | Anthelmintic resistance | Control programs | Recommended reading Return to Sheep Health & Production Index

Introduction The major parasites of sheep in Australia, against which control programs have been developed and which account for the greatest share of the losses of production caused by helminth infestation, are Ostertagia circumcincta, intestinal Trichostrongylus spp, Haemonchus contortus and Fasciola hepatica.There are a number of other parasites which can occasionally produce significant effects on the health of sheep and these are listed below. Helminth parasites are one of the most serious causes of economic losses to Australian sheep producers in the medium and high rainfall areas of the country.Great advances have occurred in our ability to limit these losses since the introduction of the first of the highly effective anthelmintics, thiabendazole, in 1962. The euphoria which greeted the successes of new anthelmintics has been generally short lived as a consequence of the development of populations of parasites resistant to each chemical, growing concerns about chemical residues in animal products and the effects of anthelmintics on non-target species. Since the Australian release in 1987 of the latest anthelmintic group, represented by ivermectin, much emphasis has been placed on the use of an epidemiological approach to the control of the parasites in an effort to remove the dependence on chemicals for helminth control. Research efforts have also focused recently on immunological and genetic protection from the effects of parasitism with the development of vaccination against Trichostrongylus colubriformis and the estimation of genetic parameters for resistance against parasites in Merino sheep. Research into biological control of the free-living stages of parasites, particularly with nematode trapping fungi and endoparasitic fungi, is at an early stage but may produce positive results in the next decade[1]. It is likely that the control of helminths in the future will involve a combination of these techniques and approaches. In response, we can also expect genetic change in parasites themselves towards populations which are favoured by the new environment imposed on them by our new technologies. The battle to control worm parasites in sheep is likely to continue for many years to come.

Ecology of sheep helminths The major nematodes of sheep, with the exception of Trichuris spp, belong to the order Rhabditida and all of these except for Strongyloides papillosus, are members of the sub-order

Strongylata (Figure 9.1).Consequently there are many features of the life cycle and ecology common to most sheep nematodes[2]. Life cycles are direct except for the protostrongylidae. They are generally very prolific egg producers. Development within the egg occurs from the original egg cell to a morula, then a 'tadpole' then a larva. The larva goes through 4 moults or ecdyses before adulthood and at each moult the cuticle is shed and replaced. These larval stages are referred to as L1 to L5. >With the exception of Nematodirus spp and Trichuris spp hatching occurs at the L1 stage. Between moults, the free-living L1 and L2 have an active phase, during which they feed, mainly on bacteria, and an inactive phase preceding the next moult. The larvae are infective to sheep only at the L3 stage and, if these are free-living, the cuticle of the L2 is retained as a protective sheath, except for Strongyloides papillosus. For Nematodirus spp, hatching occurs at the L3 stage; for Muellerius capillaris and Protostrongylus rufescens, the infective stage occurs in the intermediate host snail.

Figure 9.1 All major nematodes of sheep are in the order Rhabditida except Trichuris

Sub-order Rhabditata Strongyloides spp have two adult forms, one parasitic and one free-living. The parasitic forms are parthenogenetic and eggs give rise to either (i) infective larvae or (ii) males and females of a free-living generation which, in turn, gives rise to a parasitic generation. Infective larvae enter the host by ingestion or, more commonly, by skin penetration following which they travel via the bloodstream to the lungs then via the trachea and pharynx to the gut. The pre-patent

period is 5 to 7 days. When passed in the faeces eggs contain fully developed embryos or may even have hatched.

Sub-order Strongylata The gastrointestinal strongylate parasites of sheep have many features in common. All have a very similar egg shape and size, except Nematodirus spp which have much larger eggs than the others. The eggs are passed in faeces and embryonation commences immediately provided there is moisture, oxygen and a favourable temperature. At 26ºC, for example, an L1 forms and hatches within 24 hours. Low temperatures (below 9°C generally but this depends on the species) and lack of moisture slow or inhibit development. For many of the trichostrongylidae, development from the egg to the L3 can occur in 4 to 6 days at 27°C provided sufficient oxygen and moisture are available. The ensheathed L3 does not feed but exists on food reserves. When these are exhausted the larva dies. Infective larvae of all species gain access to the host per os; of the strongyles of sheep only Bunostomum trigonocephalum can enter the host percutaneously. The activity of infective larvae serves to increase the probability of being ingested by sheep. They are capable of migrating (also called 'translating') onto herbage provided there is a thin film of water in which to crawl. Excessive moisture hinders migratory movements. The larvae are negatively geotropic, positively phototropic to mild light but negatively phototropic to strong light. There is also an element of randomness in the migration of larvae which limits the number of larvae which move up on herbage on any one day to a low percentage of those present. Most of those larvae that do climb remain near the base of plant stems and tillers. Approximately 60% of those that do climb remain in the lowest 2.5 cm[3]. The strongylate lungworms have some features different from the gastrointestinal parasites. Eggs of Dictyocaulus filaria hatch in the gastrointestinal tract or, less commonly, in the lungs. L1 are passed in the faeces and all free-living stages remain ensheathed in the cuticle of the previous stage - consequently none of the free-living stages feeds. Infection of sheep is by ingestion. Both Protostrongylus rufescens and Muellerius capillaris have snails as intermediate hosts; infection of the final host occurs when the snail is eaten by the sheep. The pre-patent periods of the sheep strongyles are 19 to 21 days for the trichostrongylidae, 48 to 54 days for Chabertia spp, 41 days for Oesophagostomum spp and 30 to 56 days for Bunostomum spp.

Order Trichocephalida, sub-order Trichurata Trichuris spp differ from the strongyles in being much slower to develop to L3 and these larvae remain in the egg until ingested by sheep. The eggs can remain viable for extended periods. The pre-patent period is 1 to 3 months.

Survival of free-living stages The ability of the eggs and larvae to survive environmental conditions depends on the species of parasite and the developmental stage of the parasite when adverse conditions occur.

Dessication is generally lethal to eggs which have not developed to the pre-hatch stage and to free-living L1 and L2. The sheath of free-living L3 is protective and assists resistance to dessication. The infective L3 of Strongyloides papillosus has no protective sheath and does not readily survive desiccation. L3 of Haemonchus spp are less resistant to adverse conditions than other strongyles and are particularly sensitive to dessication and high temperatures. Nematodirus spp, the L3 of which remain in the egg, are particularly resistant to prolonged hot and dry conditions. Survival of free-living L3 is enhanced by a micro-climate at soil level or lower which is likely to be cooler and moister than on the herbage. Conditions which are favourable for migration (warmth, moisture, fluctuations in light) lead to rapid utilization of food reserves and death[4]. As a general rule, larvae can survive for 12 months if conditions are favourable; few in fact survive more than 6 months in winter or 3 months in summer. The particular conditions which lead to prolonged survival of nematode eggs and larvae are relevant to the epidemiology of helminthosis and will be discussed under that heading.

Common helminths of sheep in Australia Location Abomasum

Small intestine

Parasite Specific name Common name Nematodes Barber's pole Haemonchus contortusSmall brown Ostertagia circumcinctaStomach hair worm Trichostrongylus axei

worm stomach

T colubriformisBlack scour worm T vitrinus T rugatus Nematodirus spathigerThin-necked intestinal worm N abnormalis N filicollis Strongyloides papillosusThreadworm Cooperia curticeiSmall intestinal worm Bunostomum trigonocephalum Hookworm Large intestine Trichuris ovisWhipworm T skrjabini[5]Whipworm Oesophagostomum Nodule worm columbianum Large bowel worm Oes venulosumLarge-mouthed bowel worm Chabertia ovina Lungs Dictyocaulus filariaLarge lungworm Muellerius capillarisSmall lungworm Protostrongylus rufescens Liver Trematodes Fasciola hepatica Liver fluke Rumen and reticulum Calicophoron calicophoronStomach fluke Orthocoelium streptocoelium Small intestine Cestodes Moniezia expansaTapeworm M benedini Thysaniezia giardi Lungs, liver and other organs Echinococcus granulosus Hydatid Muscle Cysticercus ovis Sheep measles Abdominal cavity Cys tenuicollis Bladder worm

Other, less common species of nematodes of sheep in Australia Location

Parasite Specific name Comment Oesophagus Gongylonema pulchrum Abomasum Haemonchus placeiPresence associated with cattle Ostertagia trifurcata O ostertagiPresence associated with cattle Teladorsagia davtiana Camelostrongylus Originally a parasite of camels mentulatus Small intestine Trichostrongylus probolorusPresence associated with cattle Infests sheep Nematodirus helvetianusand cattle Cooperia oncophoraPreviously C mcmasteri C surnabada*Presence associated with cattle C pectinataPresence associated with cattle C punctata *morph types of a single species

Fasciola hepatica The host snails for F hepatica in Australia are Lymnaea tomentosa and L columella. The currently known ranges of fascioliasis in Australia are largely associated with the normal range of L tomentosa.L columella is a recent introduction into Australia[6] and it could increase the range of infection with F hepatica as it has in New Zealand[7]. Under ideal conditions of warmth and moisture (26º C), eggs of F hepatica hatch in 10 to 12 days.Low temperatures (below 10ºC) prevent development but eggs can remain viable for months.Typically, in Australia, hatching occurs in 21 days in summer and 90 days in winter.The miracidia can survive only in moisture. They actively invade the aquatic snail which serves as the intermediate host. Development and multiplication of the sporocyst within the snail requires temperatures over 10ºC. Depending on temperature, cercariae emerge 5 to 7 weeks after infecting the snail and encyst on herbage. These metacercariae are ingested by the definitive host. Within the sheep, the immature flukes migrate in the liver for approximately 5 weeks before taking up residence in the bile ducts. Infections are patent 8 weeks after infection although some flukes may take several more weeks before arriving in the bile ducts and commencing egg production.

Host immune responses Sheep are not born with any significant innate resistance to gastrointestinal parasites. Exposure to parasites, however, does lead to the development of an acquired resistance against infection which, although far from total, enables the satisfactory co-existence of host and parasite. For successful sheep management, it is necessary to take extra protection against parasites for young animals while an acquired resistance develops and for ewes when the immune response is temporarily depressed during lactation. Adult, non-reproducing sheep, however, have a highly efficient immune response to parasites which is, in fact,

essential for sheep production in most environments in Australia. Without it, even with effective anthelmintics, profitable sheep farming would be impossible. Immune competence develops with age and with experience of infection. It is slow to develop and may not be expressed to a practically useful degree for Trichostrongylus spp and Ostertagia spp until sheep are 8 to 15 months of age and have had a period of exposure to the parasite of at least 4 months. For H contortus, immunity may develop at younger ages[8].

Manifestations of immunity Immunity to helminth parasites is manifest in various combinations of : •

failure of infective (L3) larvae to establish in the gut

•

failure of arrested L4 to develop to adults

•

reduction in fecundity of adult female parasites

•

expulsion of adult parasites (also occurs without an immune response)

•

discrimination against the female worm by arresting development and expulsion

Regulation of helminth burdens Adult dry sheep have sufficiently strong immunity against most helminths to prevent clinical disease in the face of continued larval intake provided they do not suffer nutritional stress. They maintain generally stable low worm burdens and produce fewer worm eggs than younger sheep or reproducing ewes. Sheep do not, however, develop a significant immunity against infection with Fasciola hepatica[9]. The immune response is generally strong for Nematodirus spp and Trichostrongylus spp but more labile in the case of Ostertagia spp and H contortus[10]. The effect of immunity is to prevent the continuing accumulation of worm burdens as a simple consequence of ingesting larvae. In the case of Ostertagia spp, the population is maintained by 'turnover', in which established adult worms are expelled and replaced by adults newly developed from ingested larvae. With H contortus the process of regulation is different. Once immunity develops, a certain number of adult worms reside in the gut and further ingested larvae are either rejected or their development arrested. Trichostrongylus spp burdens are regulated in a similar way to H contortus but the development of immunity often leads to the expulsion of adult worms and the establishment of a new but low worm burden typical of adult resistant animals. The rate of development of immunity against Trichostrongylus spp appears to be dose dependen[11]. For immunity to develop in young sheep, exposure to parasites is necessary. This sensitising exposure must be considered when planning the administration of anthelmintics to control worm burdens in sheep grazing infective pastures. In non-immune animals, treatment will be followed by re-establishment, the rate depending on the infectivity of the pasture, and the development of immunity will be delayed.If the animals are not treated, however, expensive losses may occur. For some parasites, particularly Trichostrongylus spp and Haemonchus spp, timing the treatment with anthelmintics to coincide with the development of immunity may be followed by the re-establishment of a significantly smaller burden. Treatment of lambs

which have only partially developed immunity and are infected with relatively stable burdens of H contortus may dramatically increase their susceptibility and expose them to a higher risk of haemonchosis than would occur without treatment, unless they are moved to clean pasture or treated with prolonged acting anthelmintics[12][13].

Genetic variation in immune response The variation in parasite burdens and FEC between sheep within a mob is, at least in part, a reflection of an underlying genetic variation in resistance to infection. The genetic differences exist most noticeably at the level of acquired resistance to infection, rather than innate resistance. It is necessary, therefore for sheep to be exposed to parasites before acquired resistance is manifest and genetically resistant sheep differ from normal sheep in the rapidity or ease with which they are able to mount an effective response to infection[14][15]. Experiments show that animals bred in flocks selected for resistance to H contortus and T colubriformis do not display superior resistance to infection, as measured by worm count or FEC, when first exposed to the parasite either naturally or artificially. When challenged subsequent to an initial artificial challenge, or after a period of natural exposure or, in the case of T colubriformis, vaccination with irradiated infective larvae, lambs bred in the resistant flocks develop lower infestations with lower FECs than lambs bred in randomly selected flocks[16][17]. The genetically influenced acquired resistance is expressed through prevention of establishment of ingested larvae (immune exclusion), through depression of the size and fecundity of adult worms that do establish and, possibly, through increased rates of expulsion of L4 and adult worms. There appears to be substantial cross resistance to T rugatus, T axei and O circumcincta and some resistance to H contortus[18] in sheep selected for resistance to T colubriformis , and to T colubriformis for sheep selected for resistance to H contortus[19][20]. The genetic differences in resistance between individual sheep in a flock at a young age appear to be continued into adult life. Woolaston et al[21] recorded significant differences in the PPR in FEC of ewes from the H contortus resistance selection lines, supporting the role of the immunological response in the development of a PPR and demonstrating one of the important benefits which may arise from the breeding of more resistant Merino sheep. Estimates of the heritability of resistance to internal parasites range from 0.2, for H contortus, based on one FEC[22] following artificial challenge to 0.44 for T colubriformis. These moderate heritabilities make genetic progress for parasite resistance a realistic goal for stud sheep breeders. Progress can be made by using artificial challenge and subsequent FEC of young rams as a selection criterion in addition to the normal production related criteria or by selecting on productivity in the presence of natural infection[23]. Continuing to select on productivity traits only (fleece weight in particular) in environments where worm parasites are not prevalent or are controlled by anthelmintics will not lead to any improvement in host resistance; in fact, host resistance may even decline with growing dependence on anthelmintic control of parasites.

Worm populations in lambing ewes

The 'peri-parturient rise' in faecal egg output often occurs in ewe flocks. The underlying cause appears to be a relaxation in immunity, which allows increases in the fecundity of the parasites and, pasture and season permitting, increased rate of establishment of ingested larvae[24]. If hypobiotic larvae of Ostertagia spp or H contortus are present, the relaxation in immunity or the endocrine changes associated with parturition and lactation may stimulate the resumption of their development and allow their uninterrupted development to patency. The peri-parturient reactivation of dormant larvae is an important epidemiological feature of haemonchosis in ewes and their lambs in summer rainfall regions. The timing of the rise in FEC with respect to lambing is variable. Characteristically, it commences approximately 4 weeks before lambing, peaking 4 to 9 weeks post lambing, lasting up to 14 weeks or more, in individual ewes[25]. Considering that mobs of ewes lamb over periods of 5 weeks or more, the period of raised FEC from a mob may be considerably more prolonged. A similar pattern has been observed in New Zealand in spring lambing ewes. Work in that country has also made clear that the size of the rise is very variable between individual sheep[26] and between flocks[27]. The cessation of lactation, even if soon after lambing, results in a sudden drop of FEC, expulsion of adult parasites and a return to levels of immune response typical of nonreproductive adult sheep.

Hypobiosis Ostertagia spp, H contortus and T axei can arrest their development at the early L4 stage. This phenomenon is probably not primarily a host immune response but a survival technique developed by the parasite.Inhibition is not a characteristic of intestinal trichostrongylosis. Ingested larvae are more likely to be inhibited at some particular times of the year. For H contortus, some ingested larvae are immediately rejected, depending on the immune status of the host. Of those that are not, the proportion which becomes inhibited instead of developing directly to adults increases from near zero in January to an overwhelming majority in winter in summer rainfall zones. This seasonal inhibition occurs independently of the immune response of the animal and appears to be a result of an environmental effect on the larvae during the free-living stage.Infective larvae ingested in spring and summer have the ability to develop directly to adults, if not rejected by the host. The inhibition of larvae ingested in autumn and winter appears to be an evolutionary adaptation which favours the parasite by delaying the egg laying phase of the life cycle until after winter when a higher proportion of eggs will be able to develop and complete their life cycles. Hypobiosis is not a feature of H contortus populations in southern Australia. Maximum inhibition of Ostertagia spp and T axei occurs for larvae ingested in late winter and early spring. Without treatment effective against inhibited larvae, it is assumed that development of these parasites resumes in autumn, leading to contamination of pastures in autumn and winter, when eggs have a higher biotic potential than in spring. Firm proof of the normal fate of inhibited Ostertagia spp and T axei is lacking. Inhibited larvae of any genus do not cause any pathogenic effects while they remain inhibited[28].

Epidemiology For nematode parasites, survival outside the host, development to infective stages and the ability to move onto the herbage are all determined by climatic conditions. Broadly speaking, the free-living stages cannot survive for extended periods in high temperatures, they cannot develop in low temperatures and they cannot move onto the herbage without moisture. Variations between genera and between species in their ability to function within these broad ranges ensures that sheep anywhere in Australia will be exposed to some gastrointestinal parasite, albeit to varying intensities and with differing results.

Contamination and infectivity of pastures The availability of infective larvae on pasture determines the infectivity of that pasture. Pastures can be contaminated with worm eggs and infective larvae without being infective. Provided conditions are not adverse for the survival of free-living stages or they are protected in a suitable and stable micro-climate, pastures can remain contaminated for long periods. Contaminated pastures become infective when climatic conditions suitable for the development and migration of the particular parasite prevail.

Winter rainfall zones T vitrinus and O circumcincta predominate numerically and as pathogens in the winter rainfall zones. C ovina and Nematodirus spp also occur, usually in lower numbers.T rugatus is more prevalent than T vitrinus in drier winter rainfall zones. T colubriformis occurs but is generally less common than at least one of the other two species. T vitrinus differs from T colubriformis in its ability to develop at low temperatures and its inability to survive and develop at high temperatures. The optimum soil temperature and relative humidity for development of T vitrinus are higher than for O circumcincta; T axei is intermediate in its optimum requirements. All three nematodes have basically similar ecology and, consequently, similar epidemiology[29][30]. T axei is usually present in sheep in low numbers but can occasionally be sufficiently numerous to become a significant pathogen.H contortus does occur in winter rainfall areas but numbers are usually only significant in southern coastal areas or areas with some summer rainfall. Dash comments that haemonchosis in summer rainfall zones is an orderly and predictable disease causing outbreaks in weaner lambs and occasionally lactating ewes, but not in other sheep over 15 months of age. In some winter rainfall zones, haemonchosis behaves more like the disease described by Gordon in the late 1940s[31][32], in that resistance to infection is erratic and transient and severe outbreaks occur in adult sheep as well as young lambs and ewes.

Larval availability On pastures continuously grazed by sheep, the availability of O circumcincta and Trichostrongylus spp larvae increases after opening rains in late autumn or early winter and

falls as ambient temperatures rise in spring.H contortus may have periods of high availability following summer rains and in autumn and early winter if temperatures do not fall too low. In experiments conducted in western Victoria[33][34] and South Australia[35][36] on pastures contaminated by sheep with naturally acquired trichostrongylid infections, infective larvae were abundantly available on pasture from June to October but much less available at other times and virtually absent from herbage in the hot, dry summer months. The pattern of availability has been demonstrated by the use of immunologically naive 'tracer' sheep to serially graze pastures for two week periods after which they are killed (Figure 9.2). The rise in temperature (above a mean maximum of 15.5ºC) and decrease in relative humidity (mean 3:00 pm humidity below 60%) in September and October dramatically reduces the availability of larvae on pasture. There are large differences between years in the numbers of larvae available but in most years the pattern of larval intake is similar. There are also differences between years and between areas of different mean annual rainfall in the proportion of each genus and species of parasite which are present on pasture. O circumcincta makes up a higher proportion of larval intake in years when autumn or early winter is drier. In the experiment responsible for the data illustrated in 9.2, the low number of available larvae throughout the summer, despite the continued deposition of eggs, shows that hot, dry weather is unsuitable for the translation of eggs to available L3. There remains the possibility that eggs and larvae may survive in significant numbers in faeces and soil to become available at a later time.

Figure 9.2 Larval availability, as measured by tracer worm counts, to continuously grazing sheep in the winter rainfall zone (western Victoria), 1966/67

Source of larvae Nematode eggs are deposited on the pasture in faecal pellets and pass through developmental stages in that faecal matter.L3 move out of the faeces and onto herbage. The development from egg to L3, the survival of all stages to that point, the translation of L3 onto herbage and the duration of survival of L3 determine the infectivity of pastures. All of the factors are themselves dependent on climatic conditions. The rate of mortality of eggs and pre-infective larvae broadly parallel the rate of loss of moisture from faecal pellets. In hot, dry summer weather the moisture content of faecal pellets can fall from 60% to 9% in 2 days.Despite this, some L3 are able to survive over summer, particularly those that remain in faecal pellets. The contribution of eggs deposited in spring to infectivity in the following winter is generally much less than that of autumn contamination and the relative importance of spring contamination varies between years. Cool temperatures favour over-summer survival, probably by allowing retention of moisture in faecal pellets. There is a significant difference between years in the proportion of spring deposited eggs which survive and translate to L3 on pasture. Summer rainfall rehydrates faecal pellets and encourages the migration of L3 onto soil and herbage. It also may lead to large daily fluctuations of temperature and rapid changes in relative humidity - events likely to increase the mortality of L3. Following such summer conditions spring deposited eggs are likely to make less of a contribution to pasture infectivity in the following winter. In summer conditions which are consistently hot and dry it seems likely that more larvae remain in faecal pellets where they are protected from desiccation and are relatively inactive[37]. Generally, larvae derived from eggs deposited early in summer are available on pasture in greatest numbers during autumn months, whereas larvae on pasture in winter are mainly derived from eggs deposited in late summer and early autumn[38]. Larvae derived from autumn deposition have much more favourable conditions for survival during their free-living stages and generally show prolonged survival through winter. Nematodirus larval availability fluctuates much less between years than that of Ostertagia spp or Trichostrongylus spp - indicating greater resistance to the adverse weather conditions in summer.

Variation in faecal egg output Faecal egg counts vary with the size of the worm burden, the fecundity of the parasite and the faecal output of the sheep, which is related to feed intake. The fecundity of the parasite is also affected by the immune status of the sheep. Figure 9.3 illustrates the variation in FEC from weaner and adult sheep which were grazing naturally contaminated pastures without anthelmintic treatment in Anderson's experiments in western Victoria. Faecal egg counts rose in summer and remained high until the autumn rains although worm burdens changed little in that time. The rise in egg count occurred partly as a result of lower faecal output and partly as a result of increased egg output from each female worm. Pullman et al, in South Australia , observed the same increase in egg count over summer but related it to increasing worm burdens.

The higher FEC in the winter of 1967 compared to 1966 (Figure 9.3) was associated with much lower levels of larval availability and lower worm burdens.This evidence suggests a negative feedback relationship between larval intake and worm egg output. The mediating influence is presumably the immune response of the sheep, which is heightened under more severe challenge. Weaners are not always able to resist high levels of larval challenge in this way. Under different circumstances, weaners may accumulate large and fatal burdens of adult parasites over winter. The outcome of challenging young weaners in winter possibly depends on their prior exposure to parasites, the pattern and severity of exposure to parasites in their first year, the genus and species of parasite and the genetic ability of the sheep to resist infection. The use of faecal egg count data for diagnosis of gastro-enteric helminthosis will be discussed shortly but, clearly, from these observations they must be considered unreliable indicators of the size of an adult worm burden and the severity of pasture infectivity. Even limiting their use to young sheep may be hazardous unless local experience has shown that particular interpretations can be made. The counts do, however, give a reliable indication of the level of pasture contamination which is occurring at the time of testing. Strategic worm control programs, based on reducing contamination of pastures at particular times of the year, can thus be modified in the light of information about faecal egg counts.

Figure 9.3 Faecal egg output of continuously grazing sheep in the winter rainfall zone (western Victoria), 1966/67

Summer rainfall zones T colubriformis, H contortus and O circumcincta predominate in the summer rainfall zones, the main sheep raising area of which is the Northern Tablelands of NSW. (Oes columbianum occurs but is much less common now than it was before the 1970s.

Larval availability Larval availability generally rises from early spring, peaking in late summer and autumn, declining as temperatures fall. For H contortus, temperatures are usually favourable for the development of eggs and larvae from November to March, the major factor which influences larval availability is the occurrence of rainfall. Pasture infectivity is lowest from late autumn to early spring[39]. T colubriformis has two peaks of availability - one in autumn, again dependent on rainfall, and a second peak in late winter and spring. O circumcincta also shows two peaks of availability. The development of Ostertagia spp is favoured by cooler conditions and, consequently, availability of larvae is highest in late winter and spring. In contrast to the winter rainfall zones where larval development of Ostertagia spp virtually ceases over summer, a few larvae will develop at that time in the Northern Tablelands. The availability of infective larvae declines in late spring and early summer, presumably in response to rising temperatures and dry pasture conditions.

Source of larvae Without anthelmintic control, the principal source of H contortus larvae in late summer and autumn are eggs deposited in spring and summer. Summer contamination is rapidly translated to larvae on pasture. With falling temperatures in autumn, development of eggs and larvae is greatly slowed but a small proportion survive over winter on pasture. Eggs dropped on pasture during winter largely fail to develop and make little contribution to spring pasture infectivity[40]. Infective larvae derived from autumn deposited eggs and still surviving over winter may die off more rapidly as temperatures rise in spring but make a contribution to early spring worm burdens and, indirectly therefore, to summer contamination. This early spring contamination, derived from overwintered larvae, is augmented by the resumed development of hypobiotic larvae in late winter and early spring, particularly in lambing ewes. Although early spring contamination does not lead to high availability of larvae, or large worm burdens, it does lead to persisting pasture contamination which can give rise to massive larval availability following summer rains. The principal source of infective Ostertagia spp larvae is contamination of pasture in autumn and early winter, much as occurs in southern Australia. T colubriformis shows some features in common with both. Spring contamination appears to be an ineffective source of later infectivity. Eggs deposited in summer develop rapidly to infective larvae, eggs deposited in

autumn develop slowly with a spring peak of availability. Unlike H contortus, pre-infective stages can survive in significant numbers in winter and continue to slowly develop.

Hypobiotic H contortus as a source of pasture contamination Seasonal inhibition of ingested larvae and later resumption of development appears to be a feature of the natural history of haemonchosis in sheep on the Northern Tablelands of NSW. Development of dormant L4 resumes in late winter. In non-lactating sheep, most of the developing larvae are rejected before they reach the adult stage[41]. In lactating ewes, however, many larvae develop to adults. The PPR of spring lambing ewes in summer rainfall zones may be largely derived from the development to patency of previously inhibited H contortus larvae.

PPR in ewes as a source of contamination and pasture infectivity> The peri-parturient rise (PPR) in faecal egg output from the ewe would appear to be an important source of infection for the lambs, particularly if climatic conditions encourage the rapid development of eggs and translation of larvae onto pasture. In developing programs to limit the exposure of the susceptible lambs to highly infective pastures, it is necessary to know how effective the PPR is in leading to pasture infectivity for lambs. Is it, for example, as important as the residual level of contamination which has accumulated in the months of grazing before lambing - when egg counts may have been lower but the period of contamination longer? Salisbury and Arundel showed in 1970 that the PPR in Corriedale ewes lambing in August in Victoria led to worm burdens of Ostertagia spp in lambs several times higher than the burdens of lambs exposed only to residual contamination, caused by untreated weaners. An important point to note from this experiment is that lambs were exposed to the pastures contaminated by the PPR until 18 weeks post-lambing. The only production effect measured in this experiment was lamb liveweight. There was a 2 kg difference in favour of the lambs not exposed to the PPR but all of the difference in liveweight emerged in the last 6 weeks of that 18 week period. Donald and Waller[42] in the warmer environment of Badgery's Creek, also compared the relative contribution of autumn and early winter contamination and the PPR in FEC of August lambing ewes to pasture infectivity for lambs. Larvae derived from eggs deposited in the PPR did not appear on pasture until 8 weeks after the beginning of lambing but were present in increasing numbers for the subsequent 7 weeks, when lambs were weaned.Lamb egg output (self-augmentation) did not contribute to pasture infectivity before weaning. Lambs up to weaning at 15 weeks of age had similar FECs and similar liveweight gains whether the pastures were contaminated by dry sheep before lambing, by a normal PPR in lambing ewes, both or prior contamination and a PPR delayed by pre-lambing treatment. Lambs were then weaned into the same paddocks, untreated, and clinical signs of parasitism developed after weaning. Clinical signs occurred despite the prior treatment of ewes and the sources of infectivity included over-wintered larvae and the contamination caused by the lambs themselves in the few weeks pre-weaning. The PPR in ewes, where it occurred, contributed

to pasture infectivity after weaning but was not essential to the development of clinical parasitism in the weaned lambs.

Epidemiology of Fasciola hepatica Fasciola hepatica is endemic over a large portion of eastern New South Wales, the Murray basin, central and eastern Victoria and north-eastern Tasmania. It occurs to a limited extent in South Australia and not at all in Western Australia. The main habitats of the snails are temporary or permanent springs which expand in wet years and provide refuge in long, dry spells. Big creeks, rivers and large lakes are not preferred habitats but adjacent backwaters and swamps provide more suitable conditions[43].

Seasonal availability of metacercariae Development of larval stages in snails is slow in winter. There is a significant mortality of snails over winter and fluke infested snails have higher mortality rates than non-infected snails.Consequently, eggs which survive on pasture over winter form a more important source of spring metacercarial availability than those which hatch in autumn and provide miracidia for over-wintering snails. These latter do, however, contribute to an early spring availability of metacercariae. Metacercariae themselves can survive for prolonged periods over winter and remain available and infective to grazing animals for 10 weeks or more. Their survival in summer is of the order of one week[44]. As a consequence of the somewhat synchronous hatching of over-wintered eggs and improved environmental conditions for development within snails in early spring, availability increases from late spring and builds up until April in cold areas and until May in warmer areas. Outbreaks of fascioliasis occur in the summer-autumn period in the southern winter rainfall regions and in winter in the northern summer rainfall regions. In the warmer irrigation areas, where entire paddocks may be suitable habitats for snails after irrigation, outbreaks of fascioliasis may occur at any time from spring to late autumn. This seasonal pattern, and the occasional outbreaks of unexpectedly severe fluke disease which occur, are probably largely determined by the timing of the grazing of sheep on swampy areas which they would normally choose to avoid when paddock feed is green.

Pathogenesis of helminth infestation Haemonchosis H contortus is a blood sucking parasite and the development of clinical signs are related to the loss of whole blood. In acute infections, where large numbers of larvae are ingested over a period of days, anaemia can cause death before any effective erythropoiesis can commence.In chronic infections, where the rate of infection has been slower, both anaemia and hypoalbuminaemia result from the loss of whole blood and the exhaustion of erythropoietic reserves.

Ostertagosis, trichostrongylosis Damage to the abomasal and small intestinal mucosae lead to a reduction in feed intake which is sufficient to account for much of the lost productivity associated with these parasites. With O circumcincta infection there is a loss of plasma protein into the abomasum. Much of this loss could be recovered in the small intestine except that the usually concurrent infection with intestinal trichostrongyles interferes with absorption there. Malabsorption caused by the parasites is a much less important contributor to the parasitic effects on productivity.

Fasciola hepatica infestation Acute hepatic fascioliasis occurs 5 to 6 weeks after the ingestion of large numbers of metacercariae and is due to the sudden invasion of the liver by masses of young flukes. The lesions in the liver parenchyma are basically traumatic but there is an element of coagulation necrosis associated with the tracts which is possibly related to toxic excretions of the flukes. If unusually large numbers of flukes invade the liver over a short period, the damage may be sufficiently severe to cause acute hepatitis[45]. Sub-acute fascioliasis, developing from a lower rate of ingestion of metacercariae, causes similar but less severe hepatic damage and results in a syndrome reflecting the reduced activity of the liver, including reduced synthesis of albumin. The migration of immature flukes also predisposes the animal to the development of infectious necrotic hepatitis (black disease) by providing a suitable environment for the sporulation and multiplication of Clostridium novyi spores. When small numbers of metacercariae are ingested over longer periods, acute and sub-acute syndromes are not evident. Adult flukes in the bile ducts cause cholangitis, biliary obstruction, fibrosis and anaemia. The adults are tissue feeders which possibly suck blood leading to losses of plasma protein into the gut. The anaemia may result from the combined effects of mechanical blood loss, decreased erythrocyte production and increased erythrocyte destruction.

Clinical signs Sudden death Sudden death due to anaemia can follow acute infections with H contortus and F hepatica. The latter parasite can also cause sudden death consequent on uncomplicated liver damage and or by precipitating black disease.

Inanition, weight loss, diarrhoea and death In infections with Ostertagia spp, Trichostrongylus spp, Nematodirus spp and possibly with other, less well understood, parasites, these are the predominant clinical signs. Within one mob, some animals may appear unaffected, others show only signs attributable to reduced feed intake while others develop severe diarrhoea with dark green or black faeces. Some

animals can die quickly while others linger for days or weeks and become progressively weaker.

Sub-mandibular oedema Dependent oedema occurs in chronic infections with H contortus, F hepatica and paramphistomes. The sub-mandibular oedema is frequently called 'bottle jaw' and is recognised by producers as a sign of haemonchosis or liver fluke infection, although it is occasionally a misdiagnosis of sub-mandibular abscesses or mandibular swellings.

Pallor, lack of stamina and collapse Anaemic sheep, particularly those with sub-acute and chronic haemonchosis or fascioliasis, have pale mucosal surfaces and collapse readily when driven. The conjunctivae are good mucosal surfaces to examine for pallor; examination of the skin can be frequently misleading.

Coughing Coughing is the principal clinical sign in heavy infections with Dictyocaulus filaria. It is not a sign of infection with Muellerius capillaris.

Effects on production[*] Mortality Mortality rates can be high in weaners, hoggets and lactating ewes.Non-lactating (dry) adult sheep suffer low mortality rates.Generally, producers will intervene before too many mortalities occur but 2% to 10% can die within a few days of an outbreak of helminthosis before preventive action is taken.Deaths in lambs from malnutrition following parasitism in lactating ewes can also be important.

Wool production and liveweight gain Reductions in productivity of animals with mild helminth infections are often similar in magnitude to those seen in survivors of severe infections. The grazing of highly infective pastures by ewes between lambing and weaning can lead to losses of wool production over that 4 month period of the order of 40% compared to ewes grazing pastures of low infectivity[46]. Mild infections can result in losses of 10% to 30% of wool weight and 15% to 55% in liveweight gain. Adult dry sheep which have been previously exposed to helminths also suffer production loss, although the effect seems to be most on depression of wool production rather than liveweight. Losses of 20% in wool growth rate have been recorded in untreated mature wethers continously grazing pastures compared to suppressively treated wethers[47]. The

losses presumably are due to the intake of infective larvae by resistant sheep rather than established burdens of adult parasites and the phenomenon is known as larval challenge[48].

Dags Diarrhoea caused by some intestinal parasites can lead to the collection of faecal 'dags' on the wool of the breech. The moisture associated with the dags creates an attractive environment for flystrike. Economic losses can occur from the losses associated with flystrike, and the need to take preventive action - jetting or crutching. The presence of dags can necessitate extra labour at shearing. Daggy wool, dirty crutchings and short wool removed at crutching have lower value than full length clean wool.

Ewe fertility Parasitic infection can have an effect on ewe fertility and fecundity via an effect on liveweight at joining and by reductions in effective nutritional status during pregnancy. The improvement in pregnacy rates of ewes treated with flukicides before joining has been recorded in Britain[49].

Diagnosis History To investigate a case of suspected parasitic disease it is essential to collect information on:•

age and reproductive status of the sheep

•

breed

•

state of nutrition

•

paddock grazing history

•

treatment history

This information,considered with the time of the year in which the investigation is occurring and possibly with treatment history, should always be collected as background information. With experience, this information will also suggest which parasite is involved.

Clinical signs The presence of clinical signs characteristic of the particular genus of parasite involved are generally well recognised by experienced producers and veterinarians. Nematodiasis may be over-diagnosed as a cause of diarrhoea on some occasions and other causes of diarrhoea (campylobacteriosis, yersiniosis, coccidiosis in weaners, lush feed in sheep of all ages) should be considered. The absence of a significant faecal egg count cannot always be relied upon to distinguish nematodiasis from gut infections but the relatively good condition and appetite of sheep scouring on lush feed assists in eliminating nematodiasis in those cases.

Nematodiasis may also be under-diagnosed as a cause of diarrhoea, particularly following the failure of anthelmintics to effect control. If other signs and diagnostic aids suggest nematode infections, the failure of the anthelmintic due to chemical resistance, rapid reinfection on highly infective pastures or diarrhoea due to larval challenge in the absence of a patent infection should be considered. In sheep of any age, weight loss and poor appetite is the most consistent clinical finding in cases of gastrointestinal infections with O circumcincta, Trichostrongylus spp and Nematodirus spp. When these signs are present and the history and absence of other signs suggests nematodiasis, necropsy of at least three animals for a total worm count should be undertaken, even if diarrhoea is not prevalent in the mob. Signs referable to anaemia (low exercise tolerance and pallor of mucosae) are caused by haemonchosis and fascioliasis. Chronic manifestations of the two can be readily differentiated by faecal egg count. Eperythrozoon ovis infection is a cause of anaemia in lambs and weaners but can be differentiated on the basis of clinical pathology. Necropsy of a sample of weaners readily confirms the helminthoses. Coughing and respiratory difficulties occur with both D filaria infection and enzootic pneumonia and the pneumonic conditions are difficult to distinguish clinically; indeed, both may be present simultaneously. Sudden death occurs with acute haemonchosis, acute fascioliasis and black disease. Necropsy will allow differentiation of the first from the latter two which can be difficult to differentiate without histology.

Faecal examinations Faecal egg counts (FECs) are useful for the diagnosis of worm parasite diseases in sheep. In conjunction with clinical signs and history a confident diagnosis is usually possible. If, however, FECs are used to anticipate an outbreak of clinical disease or to diagnose a subclinical disease which may be reducing productivity, a number of potential problems arise:•

It is not possible to differentiate between Ostertagia spp, Trichostrongylus spp, Haemonchus spp, Chabertia ovina and Oesophagostomum spp on egg morphology.

•

With some genera (eg Nematodirus) egg production is not strongly related to the size of the worm burden. The fecundity of adult female Ostertagia of sheep is inversely density dependent; egg production per worm is higher when the number of worms in the gut is lower. FECs are better correlated with worm burdens of H contortus and with burdens of Trichostrongylus spp in young animals.

•

Nematode genera and species within genera differ in their fecundity and their pathogenicity.H contortus, for example, is highly fecund and relatively pathogenic.

•

As sheep grow older and develop immunity, an egg count becomes a less reliable indicator of the size of a worm burden.

•

Faecal egg count per worm present varies with the time of year, particularly in sheep with immunity.Generally, egg production is highest when larval intake is lowest.

•

In outbreaks of acute helminthosis, egg counts may be low because the parasites have not yet become patent.

FECs are also used for the diagnosis of fascioliasis of sheep. (F hepatica egg counts are generally higher in sheep than cattle which makes FEC a more useful test in sheep than cattle.) F hepatica infestations are not patent for 8 to 10 weeks in sheep and considerable damage can occur before FECs are positive. Fluke egg counts attain their maximum level around 17 weeks after infection. Daily egg production per fluke averages 21,000 to 24,000 (about 20 epg per fluke present) but the egg production per fluke varies with the density of the burden[50]. Trematode eggs have higher specific gravities than nematode eggs so a sedimentation, rather than flotation, technique is necessary for quantitative testing. This testing is laborious, so laboratories often charge more for 'fluke tests' and adopt time-saving procedures, such as bulking samples before testing. Bulking samples lowers the sensitivity of tests but also lowers the cost. D filaria is diagnosed by the presence of larvae in the faeces. Interpretation of FECs FECs are used for two diagnostic purposes; first, to estimate the size of the worm burden and, hence, the current degree of production loss or the probability of imminent mortalities. This purpose is made difficult by the limitations listed above. Second, egg counts are a direct measure of the degree of pasture contamination and the need for strategic treatment. Egg counts are more accurate for this purpose than for the first. To estimate the mean FEC of a mob of sheep, at least 10 animals should be sampled. The accuracy of the estimate is not strongly affected by the size of the mob but is affected by the number of samples. The distribution of FECs within a mob of sheep is not normal; a large proportion of sheep have low egg counts, the majority of the eggs are produced by a minority of the sheep. This distribution is said to be overdispersed. When interpreting mean egg counts of groups of sheep it is important to consider the variation in egg count and the probability of individual sheep having highly pathogenic burdens even when half the sheep have relatively low burdens (Table 9.3). Table 9.3 indicates critical values at which tactical treatments could be performed; note that strategic treatments could often be justified at lower mean counts. Table 9.1 : Approximate relationship between egg count and fluke numbers (from Happich and Boray 1969 Expected disease condition

Typical count Sub-clinical chronic fascioliasis 75 Chronic clinical fascioliasis 150 Serious chronic clinical300 fascioliasis

flukeExpected egg countepg per (eggs per gram) present 2500 33 3000 20 4000 12

fluke

Table 9.2 : Guide to the interpretation of FEC in individual sheep (Note; this is intended as an approximate guide only.There is very large variation between individual sheep in the nature of these relationships.) Parasite

Egg productionepg per adultSignificant Significant per femalepresent burden* (ifegg count

parasite Haemonchus contortus Trichostrongylus spp Ostertagia sp Nematodirus spp Chabertia ovina

5000 - 10,000 &100 - 200

5 0.1

monospecific (epg) infection) 1000 5000 10,000 1000

50 3000 - 5000

0.05 3

10,000 200

500 600

*significant burdens are those at which readily measurable and practically significant losses of production are expected to occur Table 9.3 : Guide to the interpretation of FEC in flocks of sheep (mean of 10 or more samples) Type of burden Mixed (Haemonchus absent) Predominantly Haemonchus Fasciola hepatica

Light burden < 200 < 1000 < 200

Moderate burden 200 - 500 1000 - 2500 200 - 500

Heavy burden > 500 > 2500 > 500

Note 1. Decisions to treat a flock are often made when mean egg counts are at the low end of the 'moderate' range; sometimes even lower if the treatment is at least partly strategic 2. If mean egg counts are in the 'moderate' range (Table 9.3), some individuals will have egg counts in the 'significant' range (Table 9.2)

3. Mixed infections including Haemonchus require careful interpretation in the 200 to 1000 range 4. Critical values shown above are a guide only and should be modified with local experience.

Faecal culture for larval differentiation Faecal culture allows the accurate differentiation between nematode genera but the proportion of each genera hatched may not be in the same proportion as they are represented in the FEC. Different species and different genera have different optimum hatching temperatures so small departures from an 'average optimum' temperature can markedly influence the proportion of each species hatching.

ELISA test for F hepatica An ELISA test for antibodies to F hepatica has been developed. The test is highly specific (for trematodes) and sensitive but remains positive for 5 months after treatment with or without the presence of flukes. The test can be particularly useful for the early detection of F hepatica infection.

Necropsy findings

In acute fascioliasis, there may be peritonitis, particularly on the visceral surface of the hepatic capsule. The migrations of the flukes in the liver leave dark haemorrhagic streaks and foci. The liver is swollen, friable and has capsular perforations marked by haemorrhagic tags. Older tunnels appear as slight yellow streaks. Chronic fascioliasis is characterised by enlarged and thickenned bile ducts. These stand out as whitish, firm branching cords which fluctuate over extended segments or in localized areas of ectasia. The lesions of cholangitis are often most obvious in the ventral lobe. In long standing lesions there is fibrosis of the hepatic parenchyma[51]. Anaemia, oedema and emaciation are also present. Mature flukes are readily detectable in the larger bile ducts.

Total worm counts A definitive diagnosis of the parasite status of one animal can be made by a TWC. To extend that diagnosis to a whole mob requires that a representative number of animals are necropsied.Commonly, 3 animals are chosen for reasons of cost and practicality but information from so few animals should only be considered supporting information of a diagnosis in conjunction with history, symptoms and FEC. The number of parasites that constitute a pathogenic infection varies with the species of parasite, the age and the condition of the animal. For H contortus, 2,000 to 10,000 parasites constitute a heavy infection.For Ostertagia spp and Trichostrongylus spp, 20,000 to 50,000 is a heavy burden, often fatal. For Fasciola hepatica, 200 adult flukes will produce symptoms of chronic disease. In natural outbreaks of disease, 1000 flukes of mixed ages are commonly present in adult sheep.

Treatment The modern anthelmintics used for the chemical treatment of helminthosis in sheep fall under 5 major headings. These, and their spectrums of activity, are summarised in Table 9.4. The benzimadazoles (BZ), colloquially known as white drenches, are extremely safe and, with one exception, broad spectrum drugs[**]. The evamisole/morantel group (LEV) (or clear drenches) are also broad spectrum.Ivermectin and moxidectin are in a third group of broad spectrum anthelmintics, the avermectins or macrocyclic lactones. The substituted phenols (nitroxynil) and salicylanilides (bromsalans, closantel, oxyclozanide) characteristically bind to plasma protein in the host which provide a portal of entry for the blood feeding parasites - specifically Haemonchus spp and F hepatica[52]. Closantel is unique among the anthelmintics of sheep for its sustained activity. Given at the recommended dose it maintains a sufficiently high plasma concentration to kill susceptible H contortus for 4 weeks at a very high efficacy; and with a declining but significant efficacy for a further 1 to 2 weeks. The most effective chemicals against liver fluke have high efficiency against adult and immature stages.These treatments are effective for chronic and sub-acute fascioliasis and have the important added benefit of preventing pasture contamination for extended periods.Triclabendazole ('Fasinex', Ciba Australia) at the recommended dose rate kills 95% of

1 week old fluke and 99% of all older stages.Closantel is effective against adult fluke and immatures over 6 weeks of age. Nitroxynil must be given by injection to avoid bacterial degradation in the rumen. It stains wool and is less effective than closantel and triclabendazole so is rarely used in sheep. Control release capsules (CRCs) containing albendazole were released in 1989. These intraruminal devices release low doses of anthelmintic (approximately one eighth of the therapeutic bolus dose) for a period of approximately 100 to 110 days. These devices are effective on many farms which have moderate or lower levels of BZ resistance[53], presumably because some populations of BZ resistant parasites are able to survive short periods of contact with active BZ metabolites but not prolonged exposure. A growing number of reports of failures on properties which were thought to have moderate BZ resistance suggests that considerable care should be taken before depending on the efficacy of the capsules without post-treatment FEC monitoring. The capsules are effective against BZ susceptible strains of H contortus, Trichostrongylus spp and O circumcincta, the latter being the dose-limiting species.They are not effective against F hepatica[54]. Table 9.4 : Anthelmintic preparations for sheep Compound

Trade name

Spectrum Ost H F Comments of Activity Trich contortus hepatica Nem Coop Chab Oes

Benzimadazoles Broad Act by inhibiting tubulin activity in intestinal cells of nematodes or cuticle cells of cestodes, thus preventing uptake of glucose. Albendazole Valbazen + + + > 10 w Fenbendazole Panacur + + Febantel Rintal + + Mebendazole Telmin + + Oxfendazole Systamex + + Triclabendazole Fasinex Narrow +> Levamisole, morantel Broad These act on the nerve ganglion of the parasite, each chemical in a different way, but with the result of causing paralysis of the helminth. Levamisole Nilverm et al + + Morantel Exhelm-E + + Organophosphates Narrow These act by antagonising acetylcholinesterase, resulting in stimulation of the nerve ending or muscle and subsequent paralysis. Naphthalophos Rametin some + !! niclosamide or OP dips etc. Substituted phenols andNarrow salicylanilides Act by uncoupling oxidative phosphorylation at the mitochondrial level, reducing the availability of ATP, NADH, NADPH. The host binds them to plasma protein, increasing the duration of activity against blood suckers. Only effective against cestodes, trematodes and blood sucking nematodes. Closantel Seponver + (4 w) + > 6 w 28 d withdrawal Nitroxynil Trodax dose + + > 8 w Injection only. !! wool staining. Oxyclozanide Nilzan LV +>9w

(+levamisole) Avermectins Broad These act by binding GABA in nerve endings, blocking nerve transmission, causing paralysis of the parasite. Ivermectin Ivomec + + Mite activity Moxidectin Cydectin + + Mite activity

Anthelmintic resistance Resistance of H contortus and T colubriformis to thiabendazole (TBZ) was first observed in Australia in the summer of 1966-67, 4 years after its introduction[55][56] and was subsequently reported in O circumcincta[57]. When first used in sheep flocks the newer benzimadazoles (BZs) are initially more effective than TBZ, because of their longer persistence in the sheep, but resistance to them develops quickly amongst populations of TBZ-resistant nematodes. Resistance to levamisole (LEV) and morantel tartrate (MT) was first reported in 1976. There is side-resistance[***] between LEV and MT, presumably because they are both cholinergic agonists.There is no cross-resistance between BZ and LEV or BZ and MT. Multiple resistance occurs when all members of a population of nematodes are resistant to both BZ and LEV (biresistance). Nematode populations can, however, consist of two distinct populations - one resistant to BZ, one to LEV (mono-resistant populations). The implications for treatment options in flocks with mono-resistant populations and flocks with bi-resistant populations are quite different. Resistance to salicylanilide drugs (rafoxanide, closantel) in F hepatica[58] and to closantel in H contortus[59] has also been reported.

Factors associated with the development of resistance Frequency of drenching Repeated frequent drenching, particularly when the frequency approaches the pre-patent period of the parasite, is the most effective way to select for anthelmintic resistance. Low frequency of treatment reduces the number of parasites exposed to the anthelmintic and allows the continued survival and reproduction of susceptible parasites.

Dose rates High dose rates are likely to retard the development of resistance when anthelmintics are used a few times a year for therapy or preventive treatment but not necessarily if they are used for suppressive treatment. Low dose rates in a largely susceptible population encourage the development of resistance by allowing the survival of heterozygotes or, in the case of polygenic resistance, worms with relatively few genes for resistance[60]. If resistance is apparent and resistant genes are not rare, high dose rates will hasten their increase in frequency, but at that stage nothing is to be gained by reducing dose rates.

Alternating treatments Alternation of anthelmintics which do not share cross-resistance has been proposed as a method which will delay the development of resistance when the frequency of resistant genes is low. The recommended frequency for alternation is once annually. More frequent alternation applies selection for two chemicals on the one generation of parasites, which may encourage the selection of bi-resistance[61]. Theoretically, reversion to susceptibility may occur if the resistant parasites have not had sufficient generations of selection to co-adapt for survival with the resistant genes. Field experiments to support this theory do not exist but the recommendations have been widely accepted.

Using combinations of chemicals Combinations of 2 anthelmintics (usually BZ and LEV) with 2 different modes of action have been recommended as a way to delay the development of resistance in a susceptible population. Theoretically, if resistant genes to each anthelmintic are initially rare, dual resistant parasites will be extremely rare[62]. The rate of development of resistance in a population of parasitic nematodes is initially slow when genes are rare and most rapid when the gene frequency is approximately 50%[63][****]. If combinations are used in an effort to delay resistance it is important that full doses of each chemical be administered. Heterozygous worms, or those with an incomplete set of resistance genes, are more likely to be removed if the dose rate of the anthelmintic is high. The issue is not that resistance will not develop to the combination but that both chemicals will remain effective longer if used simultaneously than if used alternately. The end result of using them is bi-resistant parasites; the use of combinations takes longer to reach the biresistant stage but it is more expensive to use two anthelmintics rather than one. Once again, evidence to support the use of combinations to delay the initial development of resistance does not come from field studies but is the conclusion of a number of simulation studies[64]. BZ-LEV combinations are also recommended on farms where the combination is more effective than either chemical alone - where the resistant genes are largely concentrated in mono-resistant genotypes. The consequent creation of a clinically effective anthelmintic (the combination) from two ineffective compounds provides the ability to obtain helminth control while using ivermectin only in alternate years. BZ-LEV combinations can also be considered in flocks where either one, but not both, of the chemicals is effective. While there is little evidence to support the view that the development of further resistance will be delayed, it is unlikely to develop any faster than would follow the use of the effective chemical alone. If any part of the helminth population on the farm remains in a susceptible state (genera or species other than those in which resistance was measured) there is some hope that the combination may delay resistance development in them.

Detecting resistance In the field, the most common method of detecting resistance is to conduct a faecal egg count reduction trial. This is a field trial which uses, by necessity, young sheep which have grazed

on the property under test for several weeks. 10 to 15 sheep are allocated to each of 4 to 7 treatment groups (total of 40 to 105 sheep) and each group treated with a different anthelmintic. Faecal samples are collected 10 to 14 days later and the efficacy of each treatment group is compared to an untreated control group. The details of the conduct of a FECRT are important and will be examined closely in a practical class. The purpose of conducting FECRTs is to be able to make recommendations for the use of a particular anthelmintic on the property on which the trial is performed for at least the following year. Under normal circumstances, FECRT's should be repeated on commercial sheep properties every year, every second year or every third year, depending on the number of effective compounds available to the producer.

Control programs[*****] General principles Worm control programs have been developed with the aim of achieving a number of objectives. •

Maintaining productivity at high levels for the lowest possible cost

•

Reducing the rate of development of anthelmintic resistance so that the high productivity and low costs are maintained into the future

•

Permitting sufficient exposure of sheep to gastrointestinal parasites to develop an effective immunity against infection

At times, the achievement of the second and third objectives requires some compromise of the first. The principles involved in realising these objectives in a practical way are based on the previously discussed epidemiological and ecological factors of helminthosis : •

Anthelmintics have their most sustained and, therefore, most cost-effective effect on pasture contamination if given at the beginning of a period when reinfection of sheep occurs at low rates. Anthelmintics given such that they have a sustained benefit are termed strategic treatments. 'Strategic' means that there is an effect on levels of exposure to parasites later in the season instead of, or in addition to, an immediate benefit. The timing of strategic treatments can be related to either seasonal or management events. Using seasonal conditions to help prevent reinfection The timing can be based on the probability of particular seasonal conditions occurring - usually hot, dry conditions or very cold conditions - which are unsuitable for development or translation of the free-living stages.

Using low pasture contamination to help prevent reinfection Anthelmintics will also have a sustained effect if given when sheep are moved to pastures of low infectivity. The recognition of the low worm egg output of non-lactating adult sheep or cattle compared to the worm egg output of young sheep or lactating ewes has led to the use of grazing management as an additional tool to extend the effectiveness of anthelmintics and to reduce the frequency of their use. •

Using each anthelmintic as infrequently as possible, given the need to maintain health and production, will extend its effective life in the flock and will reduce treatment costs. Use of narrow spectrum anthelmintics, where appropriate, spares the use of a broad-spectrum drug.

Strategic anthelmintic treatments Winter rainfall zones Worm control with the strategic application of anthelmintics in the winter rainfall zones revolves around the effective control of trichostrongylosis and ostertagiosis. The keystones of such programmes are the two summer drenches - treatments given to all sheep on the property in late spring/early summer and again in late summer/early autumn. The objective of these treatments is to reduce the contamination of pastures in summer and, particularly, autumn; contamination which gives rise to infective pastures in winter, as described on page 203. These treatments fit the first of the conditions described above for strategic treatments that is, they are given at a time when reinfection will occur at a low rate because the pastures are generally hot and dry. In areas where H contortus occurs, treatment with closantel in early summer is highly effective in preventing the persistence of H contortus over summer[65]. Treatment of ewes pre-lambing with closantel may be necessary when summer treatments have been omitted or are unsuccessful because of particularly suitable conditions for survival of H contortus larvae over summer. Strategic treatment for Trichostrongylus spp and Ostertagia spp at other times related to grazing management rather than climatic conditions will be discussed below.

Summer rainfall zones In the summer rainfall zones, the opportunities to treat sheep prior to hot, dry weather is limited because of the frequency of rain in the hot months of summer. As discussed on page 206 et seq, the major sources of pasture infectivity for H contortus are spring and summer deposition. Strategic treatment is aimed at preventing contamination over this period by using 2 or 3 consecutive treatments of closantel 8 to 9 weeks apart. Dash[66] showed that 3 treatments at 12 week intervals with closantel, the first in August given to ewes pre-lambing, prevented haemonchosis in ewes and their lambs. Subsequent experience has indicated that early treatment is relatively ineffective and better control is obtained by treating first in

September or October. Additionally, it is now clear that, after adequate control is obtained on a farm, the first treatment may be omitted and only two treatments given, preferably 8 to 10 weeks apart, commencing in November or December. Strategic treatments also need to prevent trichostrongylosis in lambing and lactating ewes and, more particularly, their lambs before and after weaning. This period coincides with the months of September to April on most farms in the summer rainfall areas of NSW. Treatment of lambs with broad-spectrum anthelmintic in early November and early February is effective in preventing trichostrongylosis of lambs but ineffective in preventing haemonchosis. The timing of these treatments is often modified to coincide better with husbandry procedues determined by actual lambing time.

The use of grazing management in worm control Despite strategic treatments, sheep pastures become progressively more contaminated as the season proceeds, particularly if grazed by young sheep or lambing ewes. They often become so highly infective that adult sheep suffer serious losses of production and there are clinical signs of helminthosis in susceptible sheep.Because anthelmintics are ineffective against the losses caused by larval challenge, and because frequent tactical treatments are both expensive and likely to encourage anthelmintic resistance, it is desirable to move sheep after treatment to pastures which have been specifically prepared to be low in infectivity. Such pastures are not required until other pastures have become contaminated, and contamination usually occurs by lactating ewes, their lambs and one year old sheep (hoggets). Low contamination pastures late in the season are at a premium on most sheep farms.Consequently, a heirarchy of need for such pastures has to established. The classes of sheep most deserving of low contamination pastures are those which would otherwise suffer the greatest losses, usually weaners, hoggets, lambing ewes and dry adult sheep in that order. Weaners, therefore, are usually given first preference, then hoggets, then ewes, either just before lambing or at the time of lamb marking.To gain the most benefit from the low infectivity of such pastures, sheep should be treated before being moved onto them. This treatment qualifies as strategic as described on page >220.

Preparation of low contamination pastures Pastures can be prepared as low contamination in a number of ways. •

ungrazed entirely

•

grazed by animals of another species with few or no parasites in common with sheep, usually cattle, but not goats

•

grazed by suppressively treated sheep, or sheep treated with CRCs grazed by adult dry sheep which have

•

strongly developed immune response and therefore low FEC

In all cases, the period for which the paddocks must be maintained in this way is related to the rate at which infectivity develops and persists on the pasture. In winter rainfall zones,

specifically prepared low contamination pastures are required in July, August or later, for lambs at weaning, hoggets after contaminating their early winter paddock, or ewes at marking time. Many Trichostrongylus spp and Ostertagia spp larvae present on pasture in July arise from February/March contamination[67] (see also page 202). Low contamination pastures, therefore, must be managed to minimize worm egg deposition for 6 months before they are required. Similarly, in summer rainfall regions, low contamination pastures are required for lambs at weaning in mid-summer and subsequently at 2 monthly intervals for the same sheep. At that time of the year, eggs hatch and larvae develop to infective stages rapidly.Pastures should be prepared for at least 3 months before they are required[68]. The benefits to worm control and animal production from grazing pastures with cattle for 6 months from July to January, when lambs were weaned, have been clearly demonstrated in the summer rainfall zones[69].

Tactical treatments Anthelmintics also are given at times to have a curative effect. Despite the implementation of measures which reduce contamination of pastures, helminth burdens can still develop to levels at which production is severely impaired and some sheep may die. Treatments given primarily to remove a clinically significant burden of adult worms are termed tactical treatments. In some environments, strategic treatment and carefully planned grazing management will obviate the need for tactical treatments.In high rainfall zones and, in some seasons in most sheep raising areas other than the pastoral zones, some sheep will require tactical treatment. For hoggets or ewes at lamb-marking, tactical treatment may coincide with the development or return of a useful immunity and there may be no need for repeated treatments.In other cases, tactical treatments may give only short term respite from clinical signs unless treatment is followed by a move to a low contamination pasture, as described above.

Control programs for lambing ewes Experiments reported in a previous section demonstrated that the PPR in FEC of lambing and lactating ewes, if it occurs, contributes significantly to the parasite burdens of lambs from about 14 weeks post-lambing[70], but not before. There is also evidence that pre-lambing anthelmintic treatment of ewes delays or reduces the PPR but does not affect the performance of lambs up to 12 or 15 weeks post-lambing. A number of other experiments have shown that treatment of ewes prior to lambing or shortly after lambing has no effect on lamb performance to 12 weeks of age when Ostertagia spp and Trichostrongylus spp are the main parasites present and when pastures available to the lambing ewes have been at least moderately contaminated before lambing, as usually happens in commercial flocks[71][72]. Consequently, in Merino flocks where the production of lambs for sale as meat animals at 4 to 5 months of age is not usually a goal, lamb production systems are often optimised by weaning lambs to low contamination pastures 12 to 14 weeks after lambing starts and treating them at that time. If this system is adopted, treatment of ewes before or after lambing is irrelevant to lamb performance. When lambs are not removed

from the lambing paddocks at 12 to 14 weeks of age, as commonly occurs in prime lamb production systems, there may be benefits in drenching ewes pre-lambing, post-lambing or both[73]. This may still not necessarily be the optimal system. Drenching ewes at or about the time of lambing may have beneficial effects on the productivity of the ewes through the lactation period if the contamination of the pastures is low, such as that produced by grazing with cattle with low FECs. If cattle are used to prepare safe pastures, it is important that they are treated before they graze the pastures because they can cause significant pasture infectivity with T axei[74] or even Ostertagia ostertagi. Steps to prepare low contamination pastures for lambing plus a pre-lambing drench for ewes may have additional benefits in reducing faecal soiling (dags) in ewes and lambs. Reduction of dags in ewes appears to be a significant advantage favouring drenching ewes at marking (6 to 8 weeks post-lambing) under most commercial conditions. Treatment 6 weeks pre- and 8 week post-lambing markedly reduced dags caused by T colubriformis in September lambing ewes in a 2 year experiment at Armidale[75] and similar observations are often made by sheep producers in winter rainfall zones.

Regional worm control programmes Without an understanding of the epidemiology of helminth disease, worm control programs could become basically a series of tactical treatments.Consequently, regional worm control programs have been developed in most states of Australia to persuade producers to use more strategic treatments in their programs. These programs have generally been developed by state Departments of Agriculture but in NSW the programs have been the result of cooperation between CSIRO, NSW Agriculture and Rural Lands Protection Boards. Programs differ between the winter rainfall and summer rainfall zones of Australia. DRENCHPLAN (NSW), WORMBUSTER (Qld), WORMPLAN (Vic), WORMCHECK (SA) and CRACK (WA) have been designed for the winter rainfall zones. DRENCHPLAN is largely based on the effective control of trichostrongylosis and ostertagiosis demonstrated by Anderson in the western district of Victoria(Two summer treatments dramatically reduced the infectivity of pastures to grazing sheep in the following winter. Tactical treatments are suggested for hoggets in autumn and early winter, repeated if necessary.Lambs are treated and moved to a low contamination pasture at weaning, which may coincide with the first summer drench for spring born lambs. WORMKILL has been designed for the summer rainfall zone of NSW where H contortus is a serious problem. The use of closantel allowed the reduction in frequency of use of broadspectrum anthelmintics, which are no longer necessary to control H contortus. Experience of early versions of WORMKILL has led to the development of the program shown on the following page. The design of the programs has been based on the most likely behaviour of the worm parasites in each particular area and for the most common flock management systems. Largely, the programs have been extremely successful, to the extent that H contortus may have been eradicated from some farms using WORMKILL in northern NSW[76]. Nevertheless, it is possible in some flocks for producers to improve the results obtained from using the programs by either altering the timing of treatments to give better results, based on

local knowledge, or by withholding treatments from particular groups of sheep which do not need treatment or will not respond to treatment. This 'interference' with the structured programs will usually require the services of an experienced adviser to assist the producer in interpreting faecal egg counts in relation to the management of individual mobs of sheep on the property.

The DRENCHPLAN worm control program Month

December February April July September

ALL sheepSpring-drop (including lambs) Broad Broad Closantel spectrum spectrum * (+) * * *

Autumn-drop Broad spectrum

* *

(+)Closantel is used in addition to the broad-spectrum drench on farms where Barber's Pole Worm may be a problem. DRENCHPLAN is designed for sheep properties in the Central and Southern Tablelands and Slopes of NSW WORMKILL: Integrated Worm Control Program for Sheep on the New England Tablelands Adult Sheep &Lambs/Weaners Added Hoggets Fluke Control Date* Monitoring GrazingClosantel Effective Closantel Effective (all sheep) Management Broads Broad pectrum spectrum late August PRELAMBING Ö M WORMTEST (Ewes) ** Prepare 1st LOW-WORM (weaner) pasture*** 14th LAMBING September October MARKING ¤ ¤ November Spell 1st LOW-WORM (weaner) pasture Prepare 2nd LOW-WORM (weaner) pasture 22nd WEANING ¤ Ö ¤ Ö December Drench and move weaners to 1st LOW-WORM pasture 22nd Drench and move weaners to ¤ ¤ Ö February 2nd LOW-WORM pasture late WORMTEST to monitor March/April program (all classes of sheep eg ewes, wethers, weaners) April/May Drench and move weaners Ö M again if possible

June/July WORMTEST (weaners) * -If these dates don't fit with your management speak to your Veterinary Advisor ** See over for pasture preparation hints. *** Most adult sheep (esp. wethers) will not require drenching at this time. WORMTEST results should be used to determine the necessity.

WORMKILL Developed by CSIRO Rural Lands Protection Board NSW Agriculture Veterinary Consultants Bruce Chick and Betty Hall The Wormkill program has been developed for a September 14 lambing. Where this does not apply the program can be readily adjusted for other lambing times with the help of your veterinary advisor.

Prelambing Monitoring your sheep using a Wormtest may well save you the effort and expense of a drench before lambing. If required, this drench is most effective when administered within 2 weeks of the due lambing date.Broadspectrum drenches are used mainly to control Black Scour and Brown Stomach Worms. Weaners require broadspectrum drenches regularly until their immunity has developed. Healthy, dry adult sheep rarely require broadspectrum drenches.

Marking Drench all sheep with closantel at marking. Closantel drenches are essential to control Barber's Pole Worm.It is important that closantel drenches are administered not more than 10 weeks apart. In some cases the marking drench may be left out; but only on veterinary advice.

Weaning Weaning is best done at 14 weeks from the start of lambing (assuming a 6 week joining period). By then milk is a very small part of the lamb's diet and the lambs are competing directly with the ewes for pasture.Weaning at 14 weeks allows the lambs to obtain the best from the feed available. When drenched and moved to the first low-worm pasture, the lambs no longer continue to pick up worms off the lambing pasture. The ewes rapidly recover their immunity and can then prepare the second low-worm pasture and recover bodyweight prior to joining. If you do not normally wean at 14 weeks then it is important that lambs receive their first broadspectrum drench at this time and a further drench at weaning.

Preparing LOW-WORM pastures Do not put weaners back onto the lambing paddock unless it has been grazed by cattle or healthy, dry adult sheep for at least three months. After each Wormkill drench the maximum benefit will be achieved if sheep, especially weaners are moved to low-worm pastures. Use cattle or healthy, dry adult sheep (older than 24 months) to prepare low-worm pastures for weaners or lambing ewes. To allow regrowth, some short periods of spelling may be required.

Monitoring with Wormtests Monitor your sheep with a Wormtest before drenching. No program can anticipate how changes in weather will affect nutrition and worm control.Wormtests allow you to assess the performance of the program on your property and may eventually allow you to drench less often.

Good nutrition Good nutrition is crucial to worm control. Sheep in good condition can tolerate heavier worm burdens and can develop immunity to worms at an earlier age than sheep in poor condition. In the long term, well fed sheep require less drenching. Broadspectrum Drenches The selection of an effective broadspectrum drench on your property should be made after a drench trial has been performed. An effective broadspectrum drench group should then be used from August to the following July. There are currently three broadspectrum groups: BENZIMIDAZOLES ("BZ's" or "Whites") LEVAMISOLES ("Clear") IVERMECTINS Combinations can be used; preferably on the recommendation of your veterinary advisor and usually after a drench trial. Similarly, the Controlled Release Capsule is best used on the recommendation of your veterinary advisor.

Closantel Drenches Closantel is effective against Barber's Pole Worm, late immature and mature Liver Fluke and Nasal Bot. After following the program for two years if you have not had a Barber's Pole outbreak then only two closantel drenches are necessary. The selection of which closantel drench to drop should be made with your veterinary advisor.

Fluke Drenches Where fluke is a problem, drench in spring and autumn. Fasinex (Ciba Geigy) is the only fluke drench effective against all stages of fluke.

Make Every Drench Count Weigh your sheep before drenching and drench to the heaviest in the mob. Select an effective drench, check the dose rate and regularly check that your drench gun is giving the correct dose.

Introduced Sheep Drench all introduced sheep with Ivomec before putting them out into the paddock.If from a fluke affected property, then also give them Fasinex.

Control programs against F hepatica Control of F hepatica is based on two strategies. Firstly, treatment in late winter or early spring will remove all adult fluke and prevent pasture contamination for 4 to 12 weeks, depending on the flukicide used.Retreatment in late spring or early summer may be necessary to remove fluke arising from overwintering metacercariae and sporocysts in snails. Treatment in summer will remove fluke arising principally from overwintering eggs and early spring contamination. Treatment in autumn will remove any remaining adult flukes and prevent the deposition of eggs over winter, greatly reducing the infectivity of spring pastures. With persistent treatment and more effective flukicides the infectivity of pastures will decline and some of these treatments can be omitted. Secondly, on properties where paddocks containing the lymnaeid snails are identified and where snail free paddocks also exist, a system of rotational grazing can be used.Sheep graze the fluke-infected paddocks for a maximum of 9 weeks during which time they ingest metacercariae but deposit no eggs on pasture. They are then removed to a snail-free pasture where they may deposit fluke eggs which have no chance of completing their life-cycle. After a period of 2 to 12 weeks, depending on the efficacy of the treatment against immature flukes, the sheep can be treated and returned to the snail-infested pasture for 9 weeks. The rotation continues, gradually reducing the infectivity of the snail-infested pasture[77][78]. The practice is observed most rigorously in the period of the year when metacercariae are most available. Control or elimination of the intermediate host snails has been attempted in the past but success has often been elusive. The snails are capable of rapid multiplication and incomplete removal of the snail population achieves only a temporary reduction in their numbers. Of more practicality is the drainage or fencing out of snail infested swampy areas but such schemes are only likely to be affordable on a small scale. Measures which reduce the impact of snails without eliminating them are both practical and successful. Removing the herbage from the banks of streams often removes a large portion of the available metacercariae because of the habit of snails of sheltering under foliage beside the water. Molluscicides have also been used to reduce snail populations.

Recommended reading

Arundel JH (1989) Diseases Caused by Helminth Parasites In Veterinary Medicine 7th Ed (by Blood DC and Radostits OM) p 1016 Dash KM (1988) Helminth Control Strategies In Sheep Health and Production, University of Sydney Post-graduate Committee in Veterinary Science, Proceedings No 110, p 295 Donald AD (1983) Anthelmintic Resistance in Parasites of Sheep In Sheep Production and Preventive Medicine, University of Sydney Post-graduate Committee in Veterinary Science, Proceedings No 67, p 493 Donald AD (1983) Internal parasites In Sheep Production and Preventive Medicine, University of Sydney Post-graduate Committee in Veterinary Science, Proceedings No 67, p 533 Martin PJ (1988) Anthelmintic Resistance In Sheep Health and Production, University of Sydney Post-graduate Committee in Veterinary Science, Proceedings No 110, p 347 [1] Waller PJ (1992) Prospects for biological control of nematode parasites of ruminants NZ vet J 40 p 1 [2] Soulsby EJL (1968) Helminths, Arthropods and Protozoa of DomesticatedAnimals publ Baillere, Tindall and Cassell, London [3] Silangwa SM and Todd AC (1964) Vertical migration of Trichostrongylid Larvae on Grasses J Parasit 50 p 278 [4] Dash KM (1988) Helminth control strategies and anthelmintics In Sheep Health and Production, University of Sydney Post-graduate Committee in Veterinary Science, Proceedings No 110, p 295 [5] Beveridge I and Green PE (1981) Species of Trichuris in domestic ruminants in Australia Aust Vet J 57 p 141 [6] Boray JC, Fraser GC, Williams JD and Wilson JM (1985) The occurrence of the snail Lymnaea columella on grazing areas in New South Wales and studies on its susceptibility to Fasciola hepatica Aust Vet J 62 p 4 [7] Harris RE and Charleston WAG (1980) Vet Parasitol 7 p 39 [8] Barger IA (1988) Resistance of young lambs to Haemonchus contortus infection, and its loss following anthelmintic treatment Int J Parasit 18 1107 [9] Meek AH and Morris RS (1979) The effect of prior infection with Fasciola hepatica on the resistance of sheep to the same parasite Aust Vet J 55 p 61 [10] Anderson N, Dash KM, Donald AD, Southcott WH and Waller PJ (1978) The Epidemiology and Control of Gastrointestinal Parasites of Sheep in Australia, edited by Donald AD, Southcott WH and Dineen JK, CSIRO, Melbourne [11] Barger IA (1987) Population regulation in trichostrongylids of ruminants Int J Parasit 17 531 [12] Davidson S (1990) Resistant lambs turn against worms Rural Research (CSIRO) 146 8 [13] Donald AD, Dineen JK and Adams DB (1969) The dynamics of the host-parasite relationship-VII. The effect of discontinuity of infection on resistance to Haemonchus contortus in sheep Parasitology 59 497 [14] Barger IA and Southerst RW (1991) Population biology of host and parasite In Breeding for resistance in sheep ed GD Gray and RR Woolaston publ Wool Research and Development Corporation, Melb p 51

[15] Eady SJ and Woolaston RR (1992) A guide to selection of Merino sheep for worm resistance Proc Aust Assoc Anim Breed Genet 10 139 [16] Gill HS, Gray GD and Watson DL (1991) Mechanisms underlying genetic resistance to Haemonchus contortus in sheep In Breeding for resistance in sheep ed GD Gray and RR Woolaston publ Wool Research and Development Corporation, Melb p 67 [17] Windon RG (1991) Resistance mechanisms in the Trichostrongylus selection flock In Breeding for resistance in sheep ed GD Gray and RR Woolaston publ Wool Research and Development Corporation, Melb p 77 [18] Windon RG, Dineen JK and Wagland BM (1987) Genetic control of immunological responsiveness against the intestinal nematode Trichostrongylus colubriformis in lambs In Merino Improvement Programs in Australia ed BJ McGuirk, publ Australian Wool Corporation, Melb p 371 [19] Woolaston RR (1990) Genetic improvement of resistance to internal parasites in sheep Wool Technol Sheep Breed 38 1 [20] Woolaston RR, Barger IA and Piper LR (1990) Response to helminth infection of sheep selected for resistance to Haemonchus contortus Int J Parasit 20 1015 [21] Woolaston RR, Windon RG and Gray GD (1991) Genetic variation in resistance to internal parasites in Armidale experimental flocks In Breeding for resistance in sheep ed GD Gray and RR Woolaston publ Wool Research and Development Corporation, Melb p 1 [22] Cummins LJ, Thompson RL, Yong WK, Riffkin GG, Goddard ME, Callinan APL and Saunders MJ (1991) Genetics of Ostertagia selection lines In Breeding for disease resistance in sheep ed GD Gray and RR Woolaston publ Wool Research and Development Corporation, Melb p 11 [23] Albers GAA, Gray GD, Piper LR, Barker JSF, LeJambre LF and Barger IA (1987) The genetics of resistance and resilience to Haemonchus contortus infection in young Merino sheep Int J Parasit 17 p 1355 [24] O'Sullivan BM and Donald AD (1970) A field study of nematode parasite populations in the lactating ewe Parasitology 61 301 [25] Salisbury JR and Arundel JH (1970) Peri-parturient deposition of nematode eggs by ewes and residual pasture contamination as sources of infection for lambs Aust Vet J 46 p 523 [26] Brunsdon RV (1964) The seasonal variations in the nematode egg counts of sheep: a comparison of the spring rise phenomenon in breeding and unmated ewes NZ Vet J 12 75 [27] Brunsdon RV (1966) Importance of the ewe as a source of trichostrongyle infection for lambs: control of the spring-rise phenomenon by a single post-lambing anthelmintic treatment NZ vet J 14 118 [28] Dash KM (1973) Haemonchosis in sheep University of Sydney Post-graduate Committee in Veterinary Science, Proceedings No 19, p 285 [29] Callinan APL (1979) The Ecology of the free-living stages of Trichostrongylus vitrinus Int J Parasit 9 p 133 [30] Callinan APL (1978) The Ecology of the free-living stages of Ostertagia circumcincta Int J Parasit 8 p 233 [31] Gorgon HMcL (1948) The epidemiology of parasitic diseases, with special reference to studies with nematode parasites of sheep Aust Vet J 24 17 [32] Gordon HMcL (1950) Some aspects of parasitic gastro-enteritis of sheep Aust Vet J 26 14

[33] Anderson N (1972) Trichostrongylid infections of sheep in a winter rainfall region; I. Epizootiological Studies in the Western District of Victoria Aust J Agric Res 23 p 1113 [34] Anderson N (1973) Trichostrongylid infections of sheep in a winter rainfall region; II. Epizootiological Studies in the Western District of Victoria Aust J Agric Res 24 p 599 [35] Pullman AL, Beveridge I and Martin RR (1988) Epidemiology of Nematode Infections of Weaner Sheep in the Cereal Zone of South Australia Aust J Agric Res 39 p 691 [36] Beveridge I, Brown TH, Fitzsimons, Ford GE, Judson GJ, Martin RR and Miller DW (1985) Mortality in Weaner Sheep in South Australia under Different Regimes of Anthelmintic Treatment Aust J Agric Res 36 p 857 [37] Young RR (1983) Populations of Free-Living Stages of Ostertagia ostertagi and O. circumcincta in a Winter Rainfall Region Aust J Agric Res 34 p 569 [38] Anderson N (1983) The Availability of Trichostrongylid Larvae to Grazing Sheep after seasonal Contamination of Pastures Aust J Agric Res 34 p 583 [39] Southcott WH, Major GW and Barger IA (1976) Seasonal pasture contamination and availability of nematodes for grazing sheep Aust J Agric Res 27 277 [40] Donald AD (1968) Ecology of the free-living stages of nematode parasites of sheep Aust Vet J 44 139 [41] Dash KM and Southcott WH (1973) CSIRO Division of Animal Health Annual Report p 55 [42] Donald AD and Waller PJ (1973) Gastro-intestinal nematode parasite populations in ewes and lambs and the origin and time course of infective larval availability in pastures Int J Parasit 3 219 [43] Barger IA, Dash KM and Southcott WH Epidemiology and control of liver fluke in sheep In The Epidemiology and Control of Gastrointestinal Parasites of Sheep in Australia, edited by Donald AD, Southcott WH and Dineen JK, CSIRO, Melbourne, p 65 [44] Meek AH and Morris RS (1979) The longevity of Fasciola hepatica metacercariae encysted on herbage Aust Vet J 55 p 58 [45] Jubb KVF and Kennedy PC (1970) Pathology of Domestic Animals Vol 2 2nd ed, Academic Press, New York & London p 241 [*] For a more detailed review of experimental results on this subject, see the review of IA Barger (1982) Helminth parasites and animal production In Biology and control of endoparasites Academic Press, Australia p 133 [46] Waller PJ, Axelson A, Donald AD, Morley FHW, Dobson RJ and Donnelly JR (1987) Effects of helminth infection on the pre-weaning production of ewes and lambs: comparison between safe and contminated pasture Aust Vet J 64 p 357 [47] Johnstone IL (1978) The comparative effect of parasites on liveweight and wool production in maturing Merino wethers, in two environments Proc Aust Soc Anim Prod 12 p 273 [48] Barger IA and Southcott WH (1975) Trichostrongylosis and wool growth. 3. The wool growth response of resistant grazing sheep to larval challenge Aust J Exp Agric Anim Husb 15 p 167 [49] Hope Cawdrey MJ (1976) The effects of fascioliasis on ewe fertility Br vet J 132 p 568 [50] Happich FA and Boray JC (1969) Quantitative diagnosis of chronic fascioliasis 2. The estimation of daily total egg production of Fasciola hepatica and the number of adult flukes in sheep by faecal egg counts Aust Vet J 45 p 329

[51] Arundel JH (1989) Diseases Caused by Helminth Parasites In Veterinary Medicine 7th Ed (by Blood DC and Radostits OM) p 1016 [**] The term broad spectrum is used with respect to helminth parasites to imply that more than one genus of trichostrongylid parasites is totally or near totally susceptible to the chemical when administered at the recommended dose. Thus, benzimadazoles are 'broad spectrum' because they are effective against all important genera of the trichostrongylidae. They generally have no action against F hepatica. Closantel is 'narrow spectrum' because it is only effective against Haemonchus spp, despite the fact that it is effective against F hepatica. [52] Arundel JH (1985) Veterinary Anthelmintics University of Sydney Post-graduate Committee in Veterinary Science (Veterinary Review No. 26) [53] Barger IA, Steel JW and Rodden BR (1993) Effects of a controlled-release albendazole capsule on parasitism and production from grazing Merino ewes and lambs Aust Vet J 70 41 [54] Anderson N, Barton NJ, Hennessy DR, Page SW and Steel JW (1988) The anthelmintic efficacy of controlled release albendazole in sheep Australian Advances in Veterinary Science 1988 p 60 [55] Smeal MG, Gough PA Jackson and Hotson IK (1968) The occurrence of strains of Haemonchus contortus resistance to thiabendazole Aust Vet J 44 p 108 [56] Hotson IK, Campbell NJ and Smeal MG (1970) Anthelmintic resistance in Trichostrongylus colubriformis Aust Vet J 46 p 356 [57] Le Jambre LF, Southcott WH and Dash KM (1977) Resistance of selected lines of Ostertagia circumcincta to thiabendazole, morantel tartrate and levamisole Int J Parasit 7 p 473 [***] Cross-resistance refers to resistance between two compounds with different modes of action, side-resistance between compounds with similar modes of action [58] Boray JC and De Bono D (1989) Drug resistance in Fasciola hepatica Aust Adv in Vet Science p 166 [59] Rolfe PF, Boray JC, Fitzgibbon C, Parsons G, Kemsley P and Sangster N (1990) Closantel resistance in Haemonchus contortus from sheep Aust Vet J 67 p 29 [60] Martin PJ (1990) Ecological genetics of anthelmintic resistance In Resistance of parasites to antiparasitic drugs The proceedings of a round table conference held at the VIIth International Congress of Parasitology, Paris, August 1990, eds JC Boray, PJ Martin and Roush RT, publ MSD Agvet, Rahway, New Jersey [61] Prichard RK, Hall CA, Kelly JD, Martin ICA and Donald AD (1980) The problem of anthelmintic resistance in nematodes Aust Vet J 56 p 239 [62] Donald AD (1983) Anthelmintic Resistance in Parasites of Sheep In Sheep Production and Preventive Medicine, University of Sydney Post-graduate Committee in Veterinary Science, Proceedings No 67, p 493 [63] Falconer DS (1981) Introduction to Quantitative Genetics 2nd ed p 30 [****] This apparent high selection pressure is not the same as that which we see in breeding programs for farm animals. In domestic animals, all non-selected males are prevented from siring progeny; in the nematode breeding program, resistance-gene carrying parents must compete with an unselected population of worms - those in refugia in the free-living stages at the time the anthelmintic is administered. This unselected population becomes a relatively

larger proportion of the parents of the next generation if the anthelmintic removes more of the nematodes existing in the parasitic state. [64] McKenna PB (1990) The use of benzimadazole-levamisole mixtures for the control and prevention of anthelmintic resistance in sheep nematodes: an assessment of their likely effect NZ vet J 38 p 45 [*****] See the review of FHW Morley and AD Donald (1980) (Farm management and systems of helminth control Vet Parasit 6 105) for a general discussion of helminth control and its integration into the management of cattle and sheep. The comments on the application of grazing management are particularly useful. [65] Besier B (1987) Barber's Pole worm: a new solution Journal of Agriculture, Western Australia Department of Agriculture, 4 114 [66] Dash KM (1986) Control of helminthosis in lambs by strategic treatment with closantel and broad-spectrum anthelmintics Aust Vet J 63 4 [67] Donald AD, Morley FHW, Waller PJ, Axelson A and Donnelly JR (1978) Aust J Agric Res 29 [68] Barger IA and Southcott WH (1975) Control of nematode parasites by grazing management II. Decontamination of sheep and cattle pastures by varying periods of grazing with the alternate host 5 45 [69] Barger IA and Southcott WH (1978) Parasitism and production in weaner sheep grazing alternately with cattle Aust J Exp Agric Anim Husb 18 340 [70] Arundel JH and Ford GE (1969) The use of a single anthelmintic treatment to control the post-parturient rise in faecal worm egg count of sheep Aust Vet J 45 89 [71] Donnelly JR, McKinney GT and Morley FHW (1972) Lamb growth and ewe production following anthelmintic drenching before and after lambing Proc Aust Soc Anim Prod 9 392 [72] Waller PJ, Donnelly JR, Dobson RJ, Donald AD, Axelson A and Morley FHW (1987) Effects of helminth infection on the pre-weaning production of ewes and lambs: evaluation of pre- and post-lambing drenching and provision of safe lambing pasture Aust Vet J 64 339 [73] Johnstone IL, Coote BG and Smart KE (1979) Effects of parasite control in the periparturient period on lamb birth weight and liveweight gain Aust J Exp Agric Anim Husb 19 414 [74] Abbott KA and McFarland IJ (1991) Trichostrongylus axei infection as a cause of deaths and loss of weight in sheep Aust Vet J 68 368 [75] Watts JE, Dash KM and Lisle KA (1978) The effect of anthelmintic treatment and other management factors on the incidence of breech strike in Merino sheep Aust Vet J 54 352 [76] Barger IA, Hall E and Dash KM (1991) Local eradication of Haemonchus contortus using closantel Aust Vet J 38 p 347 [77] Osborne HG (1967) Control of fascioliasis in sheep in the New England District of New South Wales Aust Vet J 43 p 116 [78] Boray JC (1981) Fasciolosis in sheep In Sheep Health, University of Sydney Postgraduate Committee in Veterinary Science, Proceedings No 58, p 508