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PubMed1996

Response of Dorper and red Maasai lambs to trickle Haemonchus contortus infections.

Six-month-old red Maasai lambs were more resistant than Dorper lambs to repeated infections at one to two week intervals with 1000 Haemonchus contortus infective larvae. Resistance after infection was assessed by means of faecal egg counts, packed cell volumes, eosinophil counts, total serum protein concentrations and mortality rates. The weight gains of the infected animals were only marginally lower than those of their uninfected controls, most probably because of their significantly higher feed consumption, and evidently the infected lambs were not utilising all of the extra feed for growth. This absence of anorexia in spite of the infection was probably due to the palatability of the high protein diet fed to the lambs.

Animals↗
PubMed2000

Cellular profiles in the abomasal mucosa and lymph node during primary infection with Haemonchus contortus in sheep.

Cellular changes in the abomasal tissue and draining abomasal lymph nodes were examined after primary infection of lambs with Haemonchus contortus for 3, 5 or 27-36 days. Infection with H. contortus larvae resulted in a rapid and selective increase in the percentage of CD4(+) T-cells in the abomasal lymph node at 3 days post-infection (PI). By 5 days PI, the lymph node weight had increased two-fold; however, the percentage of lymphocyte populations in the abomasal lymph node resembled that seen in uninfected sheep. Lymph node weights remained at increased levels in the adult nematode infected sheep and down-regulation of B-cell surface markers (sIg and MHC Class II) was apparent in this group. Significant increases in the percentage of CD4(+) T-cells co-expressing MHC Class II, but not CD25, were observed in the larval infected groups except in adult nematode infected sheep. Increased numbers of eosinophils, CD4(+), gamma delta(+) T-cells and B-cells were found in the abomasal tissue by 5 days PI, but no further increases in these cell populations were observed in the adult nematode infected group. In contrast, the level of both lamina propria and intraepithelial mast cells observed in the abomasal mucosa was highest in the sheep carrying an adult nematode burden. These findings indicate that sheep are able to generate an early immune response to infection with H. contortus larvae, characterised by the activation of CD4 T-cells and B-cells in the draining lymph nodes and recruitment of eosinophils, CD4(+) and gamma delta-TCR,WC1(+) T-cells and B-cells in larval infected tissues. However, these changes do not seem to be maintained during infection with the adult parasite where increases in mast cell numbers dominate the local response, indicating that different parasite stages may induce distinct and possibly counteractive immune responses.

Abomasum↗
PubMed1997

Resistance of four sheep breeds to natural and subsequent artificial Haemonchus contortus infection.

The response of Red Maasai sheep to natural and artificial Haemonchus contortus infections was compared with sheep of Blackheaded Somali, Dorper and Romney Marsh breeds. Significant breed differences in egg count, packed cell volume (PCV), and mortality rates showed that the Red Maasai sheep were more resistant to natural H. contortus infection than sheep from the other three breeds. Of the initial groups of 15 wethers of each breed, two animals from each of the Dorper and Blackheaded Somali groups and nine from the Romney Marsh group died with haemonchosis during a 12 month field study. Following artificial infection of the Red Maasai, Dorpers and Blackheaded Somalis, with 10000 H. contortus L3, the Red Maasai sheep maintained a lower egg output and a higher PCV than animals of the other two breeds. The results clearly showed that breed substitution with the Red Maasai is a control option in areas where sheep are kept for meat and H. contortus is endemic.

Animals↗
PubMed1997

Response to artificial and subsequent natural infection with Haemonchus contortus in red Maasai and Dorper ewes.

Maiden Red Maasai and Dorper ewes were kept indoors and artificially infected with a single oral dose of 5000 infective larvae of Haemonchus contortus. Their faecal egg counts (FEC) and packed red cell volumes (PCV) were monitored for 9 weeks. They were then treated with an anthelmintic and turned out to graze together on a pasture contaminated with H. contortus. They grazed this pasture for 14 months and were allowed to mate and lamb. While at pasture the ewes were monitored for FEC, PCV and peripheral eosinophilia. Red Maasai ewes had significantly lower FEC, and for certain periods, significantly higher PCV and peripheral eosinophilia. During the periparturient period, FEC were about twice as high in the Dorper breed as the Red Maasai. These results confirm and extend previous reports on the superiority of the Red Maasai breed in East Africa.

Animals↗
PubMed1998

Hypobiosis of Haemonchus contortus in natural infections of sheep and goats in a semi-arid area of Kenya.

A total of 42 lambs, 42 kids, 21 ewes and 21 does were necropsied during an investigation of the epidemiology of Haemonchus contortus infection of sheep (Red Maasai) and goats (Small East African Goat) in a semi-arid area of Kenya. Availability and establishment of the infective stages were monitored by the necropsy of 21 tracer lambs and 21 tracer kids. Prevalence of H. contortus was over 90% in both sheep and goats and this species contributed to about 80% of the total worm burden. Only about 10% of the hypobiotic larvae were recovered from the mucosal digest whereas about 90% were recovered from the abomasal contents and washings, thereby suggesting that hypobiotic larvae may be loosely attached to the abomasal mucosa from which they may be dislodged during the processing of the abomasa for examination. Throughout the study, both adult worms and hypobiotic larvae were found in proportions that varied with seasons. Statistically, a higher proportion of hypobiotic larvae was found during the dry months than during the wet months, an indication that hypobiosis was an important feature in the survival of H. contortus during the dry months. Negligible worm burdens were acquired by the tracers during the short rains, suggesting that few H. contortus larvae survived on pasture in this season. The effectiveness of strategic control using ivermectin varied according to the timing in relation to the wet season. Treatment did not influence the seasonal pattern of hypobiosis but the treatment administered before the onset of the rains significantly reduced the numbers of both hypobiotic larvae and the adult worms. Treatment during the rains conferred a temporary relief of adult worm burden but had no impact on hypobiotic larvae.

Animals↗
PubMed1982

Gastro-duodenal motor and transit disturbances associated with Haemonchus contortus infection in sheep.

Abomasal and duodenal motility was investigated by electromyography in 4 lambs fitted with permanent abomasal and duodenal cannulae and infected twice with 25,000 Haemonchus contortus larvae at an interval of 39 days. In addition, abomasal and duodenal pH, flow rate of digesta of the duodenum, and faecal water content were determined. The 80-90 min cycles of antral contractions were shortened for at least 3 weeks after infection. This was accompanied by a 26% increase in the number of duodenal migrating myoelectric complexes/day during the intraparietal development of the larvae (10-12 days). Concomitantly, the duodenal flow of digesta increased from 215 +/- 22 ml/h to 318 +/- 15 ml/h 4 days after infection and was associated with a higher water content of the faeces. The frequency of the migrating myoelectric complexes, but not the duration of antral motor cycles (or the duodenal flow rate), was correlated with both gastric (P less than 0.01) and duodenal (P less than 0.05) pH after the first and second infections. The duodenal flow rate was correlated with the Cl- concentrations of the abomasal contents (P less than 0.01) and with the duodenal pH (P less than 0.05). It is concluded that, (i) the duodenal motor disturbances associated with experimental H. contortus infection are related to the alterations in abomasal gastric acid secretion which occurs during the histotrophic phase of larval development and (ii) the increased duodenal flow is a consequence of ionic permeability changes of the gastro-intestinal mucosae.

Abomasum↗
PubMed1978

Genetic resistance to helminths. The influence of breed and haemoglobin type on the response of sheep to re-infection with Haemonchus contortus.

The influence of genetic factors on acquired resistance to Haemonchus contortus infections in sheep was investigated. Animals whose primary infections were terminated with an anthelmintic failed to develop any immunity against subsequent challenge as judged by worm numbers. Nevertheless, all were better able to retard the development and reduce the fecundity and haematophagic activities of their parasite populations than animals undergoing primary infections. High levels of resistance, as judged by all these parameters, were observed in most animals when the challenge larvae were superimposed on existing worm populations. The patterns of worm establishment and disease indicated that genetic factors operated in determining resistance, since fewer worms became established and less severe clinical and pathophysiological changes were observed in Scottish Blackface than in Finn Dorset sheep with the same haemoglobin type. Similar advantages were displayed by animals with haemoglobin AA and to a lesser extent those with haemoglobin AB over haemoglobin BB types. The importance of breed was further indicated by the occurrence of 'self-cure' in the majority of the Scottish Blackfaces but in only one Finn Dorset. There was no evidence that this reaction was associated with haemoglobin type.

Animals↗
PubMed1997

Production of a monoclonal antibody specific for ovine immunoglobulin E and its application to monitor serum IgE responses to Haemonchus contortus infection.

Part of the C epsilon 3-C epsilon 4 region of the ovine immunoglobulin E (IgE) gene (nucleotides 1111-1575) was amplified by PCR. The recombinant protein (recIgE1-2) was expressed in E. coli and both monoclonal and polyclonal antibodies were produced. These antibodies recognized recIgE1-2 and native IgE on Western blots and in ELISA. The polyclonal serum showed cross-reactivity with other sheep immunoglobulin classes. The monoclonal antibody was specific for ovine IgE and goat IgE. Infection of sheep with the abomasal nematode Haemonchus contortus resulted in elevated IgE levels in serum 2-4 weeks after infection, as measured by sandwich ELISA using the rabbit polyclonal as capture antibody and the monoclonal antibody against ovine IgE as second antibody. A negative correlation between worm counts and total serum IgE levels at the end of the experiment was found in repeatedly infected sheep. Significant increased levels of excretory-secretory antigens specific IgE levels were found after H. contortus infection. In contrast, no significant changes in 3rd-stage larvae (L3) antigen-specific IgE titre in sera could be detected after infection.

Animals↗
PubMed1983

Investigation with dexamethasone of the processes which moderate immunity against the nematode, Haemonchus contortus, in sheep.

Treatment of sheep with the corticosteroid, dexamethasone, was used to investigate some properties of the immunoregulatory process which dampens the expression of protective responses against the abomasal nematode, Haemonchus contortus, and which may occur as an adaptation for evasion of host immunity by this parasite. The protective responses released by giving dexamethasone early in infection operated during a series of superimposed infections. Accordingly, they may also operate during field exposure to the parasite. Dexamethasone-released protective responses acted earlier than 7 days after infection. Accordingly, there is no reason to suggest that they are distinct from the responses which usually produce refractoriness to infection. Results from two consecutive but not superimposed infections show that activity of the immunoregulatory process identified by dexamethasone treatment can persist for a month. This implies that there is memory for immunoregulation in infection by H. contortus.

Animals↗
PubMed1997

Vaccination against Haemonchus contortus with denatured forms of the protective antigen H11.

As part of a systematic examination of the protective epitopes on H11, groups of sheep were vaccinated with preparations of purified H11 used untreated (group A), or progressively denatured (linearized) by incubation with sodium dodecyl sulphate (SDS) (group B) or by boiling with SDS in the presence of dithiothreitol (group C). All the sheep developed antibodies which bound to the untreated H11. When challenged with 10,000 infective larvae of Haemonchus contortus the mean levels of protection relative to the mean values for adjuvant controls were 99.8%, 85% and 79% for faecal egg counts and 95%, 79% and 54% for worm burden at post-mortem for groups A, B and C respectively. The H11-specific antibodies inhibited the microsomal aminopeptidase activity of H11 in vitro up to 80%. The levels of inhibition by sera from individual animals correlated with levels of protection with r2, of 0.69-0.87.

Aminopeptidases↗
PubMed2000

Protection in lambs vaccinated with Haemonchus contortus antigens is age related, and correlates with IgE rather than IgG1 antibody.

Protection by vaccination with excretory-secretory products (ES) from Haemonchus contortus, containing predominantly proteins of 15 and 24 kDa, against an experimental challenge infection depends on the age of the sheep. Vaccinated sheep 9, 6 or 3 months of age were protected for 83%, 77% and -34%, respectively. There was a significant difference in ES-specific serum IgE response but not in IgG1 response, after the last vaccination between the different age groups. In the protected 9-month-old animals, there was an increase up to 18 times the prevaccination levels, while the increase in the unprotected 3-month-old animals was at most 1.4 times. The 6-month-old animals showed an intermediate increase of approximately six times the prevaccination level. There was no correlation within the 9-month-old sheep between ES-specific IgE levels and protection, measured as worm burden. However, when the different age groups were combined, there was a positive correlation (r = 0.38) between protection and ES-specific IgE levels 1 week after the vaccination. At the end of the experiment, peripheral blood eosinophils and mast cell counts in abomasal tissue were also significantly higher in the vaccinated and challenged 9-month-old sheep than in the vaccinated and challenged 3-month-old or than in the 9-month-old sheep with challenge, but without vaccination. Increased serum IgE levels, eosinophilia and mucosal mast cell hyperplasia are the hallmarks of a Th2 response and were all demonstrated in protected, older sheep, but not in unprotected, younger sheep.

Journal Article↗
PubMed2006

Haemonchus contortus (Nematoda: Trichostrongylidae) infection in lambs elicits an unequivocal Th2 immune response.

Selection of resistant animals and host immunization have been proposed as alternative methods for the control of gastrointestinal nematode parasites. However, a better knowledge of the mechanisms involved in protective immunity against these parasites is required for the development of optimal strategies. In this study, 3 month old INRA 401 lambs (n = 81) were allocated into three groups: uninfected control, challenged either once (primary-infected animals) or twice (previously-infected animals) with 10,000 Haemonchus contortus L3. Uninfected control and challenged animals were sequentially sacrificed at 3, 7, 15 and 28 days post challenge. In both challenged groups, a clear Th2-oriented immune response was observed in the abomasal lymph node and mucosa. IL-4 and IL-13 mRNA over-expression, recruitment of eosinophils, mast cells and globule leukocytes and production of specific systemic IgG and mucosal IgA were observed earlier in previously-infected animals than in primary-infected ones. At 28 days post infection, no differences between intensities of these responses were observed between the challenged groups. Worm establishment rates were similar in previously-infected and primary-infected lambs. However, reductions of worm development, female fecundity and fecal egg output were observed in previously-infected sheep. We conclude that H. contortus infection in young INRA 401 lambs induced an unequivocal Th2 immune response resulting in the regulation of worm egg production without affecting their establishment.

Abomasum↗
PubMed1987

Removal of Haemonchus contortus, Ostertagia circumcincta and Trichostrongylus spp. from goats, by morantel citrate, levamisole hydrochloride, fenbendazole, and oxfendazole.

Young feral goats harbouring 3, 7 and 36 day old experimental infections of strains of gastrointestinal nematodes, known to be susceptible to anthelmintics in sheep, were dosed orally with commercially available anthelmintics at the manufacturers' recommended rates for sheep. The drugs and overall removals of Ostertagia circumcincta and Trichostrongylus spp. (T. colubriformis and T. vitrinus) respectively were: morantel citrate 69% and 68%; levamisole hydrochloride 55% and >99%; fenbendazole 98.5% and >99%; oxfendazole >99% and >99%. Results for Haemonchus contortus, while not inconsistent with high efficacy for all four drugs, must be interpreted with caution, in view of the erratic establishment of this worm in the controls.

Journal Article↗
PubMed1989

Failure of young goats to acquire resistance to Haemonchus contortus.

Two experiments were carried out to investigate the acquisition by goats of resistance to Haemonchus contortus. In Experiment 1, five Saanen wethers reared worm-free and averaging 5 1/2 months of age at the start of the experiment, were dosed with 200 H. contortus infective larvae three times per week for 10 weeks (approximately 23 infective larvae/kg mean initial liveweight/week) and then given anthelmintic treatment. Each goat and an equal number of worm-free controls were then challenged with 10,000 infective larvae. Post mortem worm counts were carried out 30 days later. In Experiment 2, eight worm-free Saanen wethers, 14 months old at the start of the experiment, were dosed with 825 infective larvae per week for 14 weeks (approximately 23 infective larvae/kg mean initial liveweight/week) except for one week when only 300 larvae were given and one week when no larvae were given. After anthelmintic treatment, each received, together with seven worm-free control animals, a challenge dose of 15,000 infective larvae. Post-mortem worm counts were carried out 28 days later. There were no significant differences in post-mortem worm counts between previously infected and uninfected groups in either experiment. In both experiments, serum pepsinogen values rose significantly as a result of infection but there was no significant (p>0.5) correlation between worm counts and pepsinogen values on the day of slaughter.

Journal Article↗
PubMed2001

Resistance to macrocyclic lactone anthelmintics by Haemonchus contortus and Ostertagia circumcincta in sheep in New Zealand.

AIM: To establish the efficacy of oral formulations of ivermectin and moxidectin against naturally acquired abomasal nematode infections on a North Island sheep farm. METHODS: Two controlled slaughter trials were undertaken. In the first, 30 sheep on pasture were randomly allocated on the basis of faecal egg count to 1 of 3 groups, comprising an untreated control group and 2 treatment groups. One treatment group was given a single oral dose of ivermectin and the other a single oral dose of moxidectin, both at the manufacturer's recommended dose rates of 0.2 mg/kg liveweight. Six days after treatment, all animals were slaughtered and their abomasa recovered for worm counting. The second trial, which involved 47 animals, was essentially the same as the first except that, as well as involving the slaughter of 30 sheep from all 3 groups, 6 days after treatment, it also included a further 8 untreated control animals and 9 moxidectin treated animals which were slaughtered 27 days after treatment. RESULTS: At 6 days after treatment, moxidectin was highly effective against all 3 of the abomasal nematodes present. While ivermectin was similarly effective against Trichostrongylus axei 6 days after treatment, it was not effective against either Ostertagia circumcinta or Haemonchus contortus, against which average efficacies of only 63.6% and 61.6%, respectively, were recorded. At 27 days after treatment, moxidectin, was also highly effective against T. axei (97.3% reduction) but not against either H. contortus (71.4% reduction) or O. circumcinta (61.0% reduction). CONCLUSIONS: These results provide the first record of macrocyclic lactone resistance in H. contortus in sheep or in any other host in New Zealand, and the first case where such resistance has been exhibited in more than one parasite species at a time. Although the therapeutic efficacy of moxidectin was high against these resistant H. contortus and O. circumcincta strains, resistance to moxidectin was indicated by its diminished prophylactic activity against them. It is suggested that this reduction in the prophylactic activity of moxidectin is also likely to reduce its apparent current high therapeutic efficacy. CLINICAL RELEVANCE: As well as providing further evidence that it can no longer be automatically assumed that macrocylic lactone anthelmintics will be effective on sheep farms in this country, these findings also present a warning that increasingly complex parasite control options may have to be faced in the future.

Journal Article↗
PubMed1993

A search for associations between major histocompatibility complex restriction fragment length polymorphism bands and resistance to Haemonchus contortus infection in sheep.

Polymorphic bands were detected within the DQB and DRB regions of the ovine major histocompatibility complex by probing TaqI digested DNA from three large sheep half-sib families derived from a highly resistant ram. All animals were phenotypically assessed for Haemonchus contortus resistance by faecal egg counts and associations with RFLP bands and haplotypes were estimated using mixed model, best linear unbiased prediction statistical methods. Although the highly resistant sire was homozygous at the MHC, no significant associations were found between any band or haplotype and faecal egg count.

Animals↗
PubMed1988

Lymphocyte phenotypes in the abomasal mucosa of sheep infected with Haemonchus contortus.

Lymphocyte subpopulations in the abomasal mucosa of worm-free and parasitized sheep were assessed in situ. A preponderance of T-lymphocytes, with approximately equal numbers of cells expressing CD5, CD4 and CD8 antigens, was found. Most of the lymphocytes expressing CD8 lacked CD5. Using a panel of 15 monoclonal antibodies to ovine leucocyte antigens, abomasal lymphoid follicles in the mucosa were shown to resemble lymph node follicles phenotypically. Abomasal epithelial cells contained major histocompatibility complex (MHC) class II antigen. Infection or hyperimmunization of pasture-reared sheep with the gastric nematode Haemonchus contortus increased the numbers of mucosal mast cells and eosinophils but did not alter the phenotypic composition or number of mucosal lymphocytes or the pattern of expression of MHC class II antigens.

Abomasum↗
PubMed1988

The effect of immunosuppression with dexamethasone on Haemonchus contortus infections in genetically resistant merino sheep.

The effect of immunosuppression with the glucocorticosteroid, dexamethasone, on the susceptibility to Haemonchus contortus infection of a highly resistant Merino genotype was investigated. Higher faecal egg counts, larger worm burdens and heavier worms were recorded in immunosuppressed wethers. The characteristic globule leucocyte infiltrate in the abomasum of resistant wethers (12-month-old castrated males) was absent in immunosuppressed animals. Treatment with dexamethasone abolished differences between resistant and susceptible genotypes in faecal egg counts, worm weights, thymus weights and globule leucocyte responses to infection with H. contortus. These results suggest that an immunological basis underlies the high level of resistance to infection in the resistant genotype.

Animals↗