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Item Pathophysiology and immunomodulation associated with Haemonchus contortus infection : a dissertation presented in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Massey University, Palmerston North, New Zealand(Massey University, 2015) Zia-ur-RehmanThe aim of this project was to investigate host-parasite interactions, which might lead to alternate strategies to control the sheep abomasal nematode Haemonchus contortus. The project focused on two aspects of host parasite interactions: the initiation of host pathology and suppression of host immune responses associated with the onset of infection. Adult H. contortus ES products increased the permeability of Caco-2 cell monolayers and this increase could be blocked by single chain antibodies against ES products displayed on phage. Recombinant H. contortus enolase may be one of the active components of ES as it mimicked the action of ES products on Caco-2 cells. This is the first study of immunomodulation by adult H. contortus ES products of the phenotypic and functional properties of human monocyte-derived dendritic cells (mdDCs). Incubation with ES products resulted in semi-maturation of mdDCs, with weak up-regulation of the co-stimulatory molecules CD40 and CD80 and increased surface expression of the tolerogenic markers CD32, CD305 and galectin-1. The highly variable responses of mdDCs of individual donors biased the group data, particularly in response to co-stimulation with ES products and LPS. This highlights genetic diversity in the immune system and possible difficulties in developing worm-based therapies. The blastogenic activities of cells from lymph nodes collected from two groups of infected and vaccinated sheep were measured by 3H-thymidine uptake after exposure to ConA or ES products. The Stimulation Index (SI) with ConA was 1 0-fold higher in cells from the older animals. Cells only from younger infected sheep had a reduced response to ConA and vaccinated groups with reduced parasite burdens had the highest Sl. There was little response to ES products in older sheep, but in younger animals there was a trend for lymphocyte Sl to be greater with 10% ES in sheep with the fewest parasites. These experiments show that H. contortus ES products may facilitate the initiation of host pathology and the potential to modulate responses of dendritic and lymph node cells during parasitism. Further identification of the specific ES components responsible may allow disruption of their actions, resulting in resilient and immune sheep.Item Studies on Bunostomum trigoncephalum [i.e. trigonocephalum] the hookworm of sheep : a thesis submitted in partial fulfilment of the requirements for the degree of Master of Veterinary Science at Massey University(Massey University, 1969) Graham, J. M.This thesis records a series of experimental observations on Bunostomum trigonocephalum. The studies were made under the following broad headings: a) pre-parasitic development b) comparison of routes of infection and studies of the mechanism of infection including exsheathment of the infective larvae c) the pathogenesis and patnogenicity of the parasite for the sheep host. The morphology and development of the first 1 second and third larval stages was examined, The moult of the first to the second stage was observed and the first stage cuticle appeared to disintegrate rather than be cast as an intact sheath. This moult occurred after about 5 days incubation at 21°c. Little larval growth occurred after the first moult and the second moult followed comparatively quickly, 80% of the larvae were in the infective stage after 7 days incubation. 0 0 Survival of infective larvae was compared at temperatures of 0 C, 10 c, 0 0 0 0 20 C, 27 C and 37 C. Larvae survived longest at 10 C. Infective larvae were administered to sheep intravenously, subcutaneously, intraruminally, orally and percutaneously. The largest infections were established after percutaneous administration. Infective larvae applied to the skin of sheep exsheathed rapidly and penetrated the keratinised layers of the skin. They were also found to exsheath on and penetrate into the skin of calves, gtli.nea pigs and rabbits. There was evidence that larvae migrated to the lungs in the guinea pigs and patent infections were established in some calves, During exsheathment the anterior portion of the sheath appeared to disintegrate allowing the larvae to emerge, This is unlike the processes which have been described in other strongylate nematodes. A variable proportion of the infective larvae were found to exsheath "spontaneously" in faecal cultures, Attempts were made to find what stimulates the infective larvae to exsheath, The results were inconclusive. The highest rate of exsheathment was obtained by·exposing larvae to buffer of pH 2. The addition of co2 enhanced the exsheathment rate but only at pH 2. Even so, the results were variable and difficult to reconcile with conditions on the skin surface. After infection of sheep the prepatent period was found to range from 54 to 60 days. The 24 hour egg-output per female worm was estimated in 5 infected sheep and was found to range from 2579 to 10480 eggs. Most of the Bunostomum were found in the intestine between 5 and 35 feet posterior to the gastric pylorus. Numbers of Bunostomum in excess of 2-300 caused a significant and progressive decline in haemoglobin, packed cell volume and total serum protein levels over observation periods of up to 16 weeks after infection, The serum protein decline was primarily due to a fall in albumin concentration. The animals so affected also showed evidence of anorexia, retarded growth rate and loss of weight, Diarrhoea occurred sporadically.Item Epidemiological studies of parasitism in sheep and reproduction in horses : a thesis presented in partial fulfilment of the requirements for the degree of Master of Veterinary Studies (Epidemiology) at Massey University(Massey University, 1997) Macchi, ChiaraAnthelmintic resistance is a well-recognised problem for control of nemotodes in sheep in most countries of the world. The climatic conditions in New Zealand are particularly favourable to the survival and development of gastrointestinal nemo=atodes. As a consequence, gastrointestinal parasitism is a major impediment to profitable sheep raising in New Zealand. A random postal survey of 300 sheep farmers in the southern North Island region of Manawatu was conducted with the purpose of examining current farming and drenching practices and investigating possible risk factors in the development of anthelmintic resistance. The results of this study, reported in Chapter 2, revealed a high degree of awareness and concern about the problem of resistance, but also a lack of understanding on how grazing management strategies should be combined in order to achieve integrated control over gastrointestinal nematodes while minimising the use of anthelmintic drugs. Only 31% of respondents had performed at least one drench test on their property. Amond testing farms, prevalence of resistance approached 70% and involved benzimidazole products in all but one case. Subsequently, a trial was undertaken to investigate the economic consequences of anthelmintic resistance in growing lambs on commercial farms (Chapters 3 and 4). Five farms with a history of resistance to benzimidazole drenches were selected. The effects of three treatment strategis on nematode egg counts, bodyweight gains and susceptibility to diarrhoea were compared between groups of ewe lambs. Suppressively treated lambs performed significantly better than effectively treated lambs, which in turn performed better than ineffectively treated lambs. However, a partial budgeting analysis carried out by means of a stochastic simulation model (Chapter 4) indicated that effective treatment yielded the highest net returns. The model also showed that the range of possible outcomes oscillated substantially around the mean, reflecting the degree of uncertainty about the outcome on any single farm due to variation between farms. Chapter 5 describes a study which was carried out with the objective of evaluating two management strategies for breeding mares after foaling. Mares were examined on day 7-9 postpartum by palpation and ultrasound. Pregnancy rates, pregnancy loss rates and time from foaling to conception in two groups were compared. The statistical power of the study as determined by power analysis, was insufficient for the observed differences to reach statistical significance.Item Parasitism and production in fleeceweight-selected and control sheep : a thesis presented in partial fulfilment of the requirements for the degree of Master of Agricultural Science at Massey University(Massey University, 1994) Williamson, John FInternal parasitism in sheep selected for increased wool production for 37 years (FW) and in unselected controls (C) was studied. FW sheep were shown to consistently develop higher FECs than C sheep when grazing naturally infected pasture. Resistance to establishment of infective larvae of Haemonchus contortus and Ostertagia circumcincta, but not Trichostrongylus colubriformis, was lower in artificially infected adult FW sheep. Several parasitological and immunological parameters were compared between lines. Antiparasite antibody levels in grazing lambs and artificially infected adult sheep did not differ between lines. There was a typical strong inverse relationship between numbers of mucosal mast cells and numbers of parasites in FW sheep, whereas no relationship was evident in C sheep. Packed cell volume was lower in FW sheep than C sheep and thymus weights were heavier in FW sheep. Blood gastrin levels tended to rise more in C sheep than FW sheep when infected. Production loss associated with infection in each line was examined. Albendazole controlled release capsules (CRC) were used to prevent infection in some sheep from each line while the remainder were allowed to become subclinically infected. Despite FW sheep developing a larger burden than C sheep there was little evidence that this resulted in greater production loss in FW sheep. Production loss was not found to be associated with decreased feed intake. Decreased resistance to internal parasites (of some species) following selection for increased wool production has been clearly demonstrated. This suggests that resistance traits and wool production are unfavourably genetically correlated, which will slow selection responses when all traits need to be simultaneously improved. Despite the effectiveness of CRC treatment in preventing establishment of an adult parasite burden, production in treated sheep, particularly rams, was lower than in subclinicaily infected sheep at some stages of the trial. The cause of this effect is unknown. The effect of CRC treatment of young sheep (aged 6 months) was examined 10 months later when sheep were artificially infected. Resistance to establishment of T. colubriformis larvae was lower in previously treated sheep, as were thymus weights. It appears that CRC treatment of sheep may have a detrimental long term effect on resistance to parasites. In an unrelated study the effect of kiwifruit vinegar (8.2g/100ml) on parasitological and production parameters in lambs and fertility in two-tooth ewes was investigated. There was a tendency (not significant) for FECs in vinegar treated lambs to be lower than in untreated lambs. Treatment had no effect on liveweight gain, wool growth, or wool colour, but caused a small reduction in wool yield. Pre-mating liveweight of two-tooth ewes and reproductive status 38 days after removal of the ram was not affected by vinegar treatment.Item Anti-parasitic activity of bovine milk : a thesis presented in partial fulfilment of the requirements for the degree of Master in Nutritional Science at Massey University(Massey University, 2000) Zeng, Shu'erPrevious studies have shown that milk-fed ruminants were less susceptible to gastro-intestinal parasites compared with young animals that were given solid feed in the diet. The present studies were carried out to gain a better understanding of how milk feeding reduces worm establishment in newborn lambs. Two approaches have been taken: an in vivo study in which lambs were infected from three weeks of age with third-stage larval Ostertagia circumcincta and an in vitro examination of direct effects of bovine milk and some of its crude fractions on the motility of O. circumcincta larvae. The in vivo experiment was designed to compare parasite establishment in lambs either fed entirely on milk from birth, weaned on to solid feed by three weeks of age, or provided with solid feed from two weeks of age and given a milk feed once a day. To examine whether lack of rumen development was a crucial factor, each diet group consisted of lambs given normal ensheathed third-stage larvae and an equal number of lambs given exshcathed larvae. A total of 24 lambs were included in the study, in six groups each of four lambs. All lambs were infected by tube (into the oesophagus) twice a week with either 1000 exsheathed or ensheathed third-stage O. circumcincta larvae. Infection began after the week taken to establish the lambs on their new diet, so that starting on week lour of life, the lambs were trickle infected for six weeks. There were highly significantly lower worm burdens at necropsy in the two milk-fed groups of lambs than in both the other groups, but no difference between the burdens in those completely fed solid food and in lambs receiving a 600 ml milk feed once a day along with solids. Irrespective of the diet, female worms made up half the total number of worms in each lamb, with males and immature stages equally making up the other half. Faecal egg counts in the Milk groups were also very low, three of the eight lambs never providing a faecal sample in which eggs were found. Also consistent with the lower worm burdens were the thinner abomasal mucosa and lower abomasal pH, although these may also have been affected by the diet. Nodules were visible in the abomasa of all lambs in all groups. All groups had increased serum gastrin and pepsinogen levels, with considerable variation between animals within all groups. An important observation was that there was no significant difference between lambs receiving exsheathed or ensheathed larvae for any parameter measured. The immaturity of the reticulo-rumen and omasum does not appear to prevent ensheathed larvae from exsheathing and establishing in the abomasum of lambs with an underdeveloped rumen. The similar worm burdens in the milk-fed lambs given ensheathed and exsheathed larvae therefore does not support the conclusions from an earlier study in calves that lack of rumen function was the reason for lower worm burdens in non-ruminating calves. Instead, it would appear that the milk itself is reducing parasite establishment. In vitro exposure to fresh bovine milk, commercial bovine milk with either 3.3% or 0.2% fat, the milk powder fed to the lambs, whey protein, casein or ultra low heat skim milk powder all reduced the motility of exsheathed third-stage O. circumcincta larvae. The effect on motility was concentration and time dependent for all milks. The active component appears to be associated with proteins and not with the lipid fraction and may be nonspecific, as both whey and casein were effective. Different components may be responsible for inhibition of larvae by whey and casein proteins. The activity of whey protein increased as the pH increased; the whey was most active at pH 4.5 and above, when it would be in the anion form. In contrast, there was no difference in activity at pH 5.5 and 6.5 for casein. The effect of time of incubation also differed for whey and casein. A possible explanation for the in vitro and in vivo effects of milk are the attachment of the proteins to the larvae. The lack of effect when milk and solid feed are ingested together may result from the protein attaching to the food particles in preference to the larvae or, alternatively, the milk may have left the abomasum before the larvae were administered. This suggests that practical applications for milk proteins as anti-parasite agents may be limited in ruminants consuming solid feed.Item A survey of anthelmintic resistance and parasite management practices on sheep farms in New Zealand : a dissertation presented in partial fulfilment of the requirements for the degree of Master of Veterinary Studies (Veterinary Parasitology) at Massey University(Massey University, 2004) Sharma, Shyam SundarThe occurrence of anthelmintic resistance in sheep nematodes in New Zealand was conducted by using DrenchRite and Inhouse larval development assays (LDA) on 25 randomly selected farms. Samples from 6 farms were put onto both DrenchRite and Inhouse LDA plates and were available for comparison. Both showed a similar LC50 and LC50 well for benzimidazoles but not for levamisole. Including results from both assay systems it is concluded that anthelmintic resistance in Trichostrongylus (either suspected or high level) was demonstrated in 60% of the farms (9/15) to benzimidazole (BZ), resistance to levamisole (LEV) in 66% of farms (10/15), combination drench (BZ+LEV) on 43% of farms (3/7) and avermectin on 1 of 8 farms. For those farms where Trichostrongylus was the predominant genus there was resistance to at least one anthelmintic on all tested farms (n=12). A survey of parasite control procedures over 2002/2003 was conducted on 38 farms. The principle findings were: about 58% farmers (n=37) performed quarantine drenching of brought-in sheep for which a majority of farmers (52%) used macrocyclic lactones alone or in combination with other anthelmintics; about 78% (n=37) of farmers followed a 5-6 drench programme to lambs/hoggets; the annual frequency of anthelmintic treatments (n=38) were 6.1 drenches to lambs/hoggets; 1.4 to two-tooths and 1.8 to mature ewes; about 71% farmers used macrocyclic lactones for lambs/hoggets on at least one occasion either alone or in combination with other anthelmintics; a majority (61%) of farmers followed a planned annual drench family rotation; about 76.5% (29/38) farmers had never carried out a test for drench resistance and about 57%(4/7) of those farmers who had tested did identify resistance on their farms to either the benzimidazole or combination (benzimidazole + levamisole) drench. Worms were considered "very important" by 55% farmers (n=38) for the cause of economic losses in their farm, whereas 42% farmer considered it "important". Drench resistance was considered as a "serious problem" today for the industry by 47% farmers (n=38), whereas, 34% farmers believe it as a problem but "not serious one today" for the industry.Item Some investigations into the larval development assay and trichostrongylid nematodes of sheep : a thesis presented in partial fulfillment of the requirements for the degree of Master of Veterinary Science at Massey University(Massey University, 1998) Hoza, Shaaban BakariTwo experiments were conducted to investigate the change over time in LD50 values in an in vitro larval development assay. In each experiment, six field-reared Romney lambs were effectively treated with an anthelmintic and housed. In experiment I, six three month old lambs were given a single infection of 35000 infective larvae of T. colubriformis. From ten days post infection (DPI) three lambs (Group 1.1) were treated twice weekly with 0.5mg/kg of dexamethasone trimethylacetate whilst the other three (Group 1.2) served as controls and remained untreated. In experiment II, three lambs (Group 2.2), six month old were infected with a single dose of 22000 infective larvae of T. colubriformis whilst the other three (Group 2.1) of the same age were trickle-infected with 2000 infective larvae once weekly for 14 weeks. Larval development assays were conducted weekly for 14 weeks with ivermectin in Experiment I and ivermectin, avermectinB2 and levamisole in Experiment II. In Experiment I and II for ivermectin, the LD50 values rose to a 4x increase between 50-70 DPIand fell again. The general pattern seen following a single infection with all anthelmintics was for the LD50 values to be relatively constant from 21-35 DPI, then rose 2.5-7x increase to peak 49-56 DPI and declined at the same rate again to original starting values by 84 DPI where they remained until the end of the experiment. In experiments I, the steroid treated group started with similar values but had a 5x fall by 42 DPI which was not seen in the single infection group. The trickle infection group in Experiment II generally resulted in a small increase of 1-1.5x from 42-77 DPI and then declined again to starting values until the remainder of the experiment. The study demonstrates that there is a similar change in the LD50 values with time for T. colubriformis with all three anthelmintics tested and that the change was prevented in steroid treated animals and was less apparent in trickle-infected animals.Item Risk factor epidemiological studies of ivermectin resistant Ostertagia circumcinta on Western Australian sheep farms : a thesis presented in partial fulfilment of the requirements for the degree of Master of Veterinary Studies in Epidemiology at Massey University, Palmerston North, New Zealand(Massey University, 2004) Suter, Robert JohnThis study was designed to investigate the farm level epidemiology of ivermectin resistant Ostertagia circumcincta on Western Australian sheep farms. The study involved a postal survey and the results of that survey were used to develop statistical models to identify risk factors associated with ivermectin resistance. The survey was mailed to farmers in July 2001 who had conducted faecal egg count reduction tests on their properties in 1999 and 2000. The questionnaire contained questions about farm management practices, particularly those pertaining to worm control. Some mail and telephone follow-up was conducted. The response rate to the survey was 54%. The period prevalence for ivermectin resistance in Western Australia 1999 – 2000 as defined in this study was 38% (95% CI 29%, 46%) and for the period 1999 – 2001 was 44% (95% CI 39%, 58%) as some farms were diagnosed with ivermectin resistance in 2001. Two main effects models of anthelmintic resistance at the farm level were developed: a logistic regression model for risk factors for a farm having been diagnosed with ivermectin resistant Ostertagia circumcincta by 2000, and a Weibull parametric survival model studying the effective life defined as time to onset of resistance, for those farms using ivermectin. The logistic regression model contained three main effects variables: selling 10% more sheep in 2000 than is the usual policy (OR = 4.00), farm purchased since 1975 (OR = 2.34), and number of winter flock anthelmintic treatments in the previous 5 years (OR = 1.04). A secondary logistic-regression model assessed risk factors for farms selling 10% more sheep than usual in 2000; these farmers appeared less committed to their sheep enterprises than other farmers. The survival analysis model contained four main effects variables: winter drenching frequency, 0-2 vs. 3+ flock treatments in 5 years (RH 0.52); availability of alternative effective anthelmintic classes on the farm (RH 0.30); always using safe pastures (RH 0.23); and veterinarians as the primary source of worm control advice (RH 0.58). A major outcome of the study has been to identify that the farmer’s management of worm control in the sheep flock has an important influence on whether or not the farm develops anthelmintic (ivermectin) resistance.Item Studies on Cooperia curticei (Ransom 1907) a nematode parasite of sheep : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy(Massey University, 1970) Ahluwalia, Jagjit SinghThis thesis records in part I studies on the ecology of the free living stages of Cooperia curticei , both under controlled and natural conditions. At constant temperatures free living stages developed throughout the temperature range of 10-37c. At all temperatures each larval stage occupied the same proportion of the total developmental time to reach the infective stage. The relationship between the rate of development in log days and temperature was found to be linear. Under natural conditions the rate of development was most strongly correlated with mean maximum air temperature and was not significantly different to that observed under controlled conditions. When faecal cultures were kept at 10°C, 27°C and 37°C a higher proportion of eggs completed development to the infective stage at 27°C than at the other temperatures. Under natural conditions the percentage recovery was influenced by weather conditions particularly rainfall. Submergence of the free living stages in water inhibited their further development. First and second stage larvae survived longest at temperatures between 5°C and 15°C but for a much-shorter time than infective larvae. Between the extremes of -6 and 52°C, the longest survival of infective larvae was 312 days at 10°C. Techniques are described for the recovery of Cooperia curticei larvae from sample units of pasture, soil and faecal pellets. Under natural conditions the maximum survival of larvae from monthly experiments ranged from 9 - 26 weeks. Maximum survival was particularly influenced by temperature. Infective larvae survived through the winter. There was an exponential relationship between the percentage survival and percentage of larvae recovered from the herbage. Vertical migration of larvae appeared to be primarily affected by rainfall and evaporation. It is concluded that infective larvae of Cooperia curticei are available to grazing sheep throughout the year. Theoretically the nematode can complete from 9 - 11 generations in each year. Part II of this thesis records experiments on the relationship between Cooperia curticei and the host sheep. Experiments carried out in vivo and in vitro demonstrated that infective larvae of C. curticei exsheath under conditions provided by the rumen. The process of exsheathment was similar to that described for H. contortus. A series of experimental observations were made on the effect of Cooperia curticei infection in sheep using animals of differing ages, on different diets and with various sizes of infection. The prepatent period of infection was 14- 16 days. Peak egg counts were recorded 5 - 7 days after infection became patent . There after they declined gradually in sheep given 10,000 larvae but in sheep given 50,000 to 100,000 larvae the decline was more abrupt. The egg output per female worm was found to range up to 1,958 eggs per day. No clinical sign of infection was observed from any experimental animal. Body weights, wool growth and blood analyses showed no significant changes and no gross lesions or significant histopathological changes were observed. The results indicate a well balanced relationship between C. curticei and the sheep. The distribution of the C. curticei in the small intestine was skewed, and most of the worms were recovered from 5- 10 feet from the gastric pylorus. A predominance of female worms was observed at all levels of the small intestine. Maximum percentage recovery of C. curticei was observed in sheep given 10,000 larvae. Experimental animals with higher doses besides giving a lower rate of recovery showed inhibition of development and stunted growth of worms. Serum and intestinal mucus samples from infected animals were tested for precipitating antibodies by gel diffusion against five antigens. Antigens were prepared from first stage, second stage, ensheathed third stage, exsheathed third stage larvae and exsheathing fluid. Variable numbers of precipitin lines were obtained with serum and mucus from infected sheep more than 6-7 months old. Sheep 2-3 months old showed no such response but did show evidence of an acquired resistance to infection.Item Nitrogen metabolism in Haemonchus contortus and Teladorsagia circumcincta : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy at Massey University, Palmerston North, New Zealand(Massey University, 2012) Umair, SallahThis is the first study to characterise proline, arginine and lysine metabolism in homogenates of L3 and adult Haemonchus contortus and Teladorsagia circumcincta. The properties of glutamate dehydrogenase (GDH), glutamate synthase and the GABA shunt were also compared in the two species. The kinetic properties of 26 enzymes were determined. The gene encoding T. circumcincta GDH was sequenced and recombinant TcGDH expressed and biochemically characterised. The ornithine-glutamate-proline pathway was fully functional. The mammalian α-AAA (saccharopine) and pipecolate pathways of lysine catabolism, but not the bacterial enzymes lysine dehydrogenase and decarboxylase, were present in adult worms. The pipecolate pathway was incomplete in L3 of both species, as Pip2CR activity was undetectable. Unusually, lysine ketoglutarate reductase and saccharopine dehydrogenase, Δ1-pyrroline-5-carboxylate synthase and reductase were able to use both cofactors. The glutamine synthetase-glutamate synthase pathway of ammonia incorporation into glutamate was present, except in L3 H. contortus. T. circumcincta GDH was cloned, purified and characterised and the predicted protein sequence was very similar to H. contortus GDH. T. circumcincta recombinant and H. contortus homogenate GDH were both dual co-factor specific, although the latter had 50% greater activity with NAD+/H as cofactor. GDH activity was inhibited by GTP and stimulated by ADP whereas ATP either inhibited or stimulated depending on the concentration and direction of the reaction. The GABA shunt enzymes glutamate decarboxylase and succinic semialdehyde dehydrogenase was not detected in homogenates of whole L3 or adult H. contortus or T. circumcincta. Neither parasite had a full functional ornithine urea cycle, nor appeared to use bacterial pathways to covert arginine to ornithine. NOS were demonstrated histochemically in nerves of adult H. contortus, but was undetectable in homogenates of both species. There was species variation in polyamine metabolism: T. circumcincta used arginase to form ornithine, followed by decarboxylation by ODC, while in H. contortus there was the additional pathway of first decarboxylation by ADC to form agmatine, then hydrolysis by agmatinase to putrescine. The present study helped in the better understanding of nitrogen metabolism and these enzymes can be useful targets if they differ antigenically from the host, provided the enzyme is accessible to blockage by immune effectors.