Haemonchus contortus-Sheep relationship: A review.

Relación Haemonchus contortus-Ovino: Una Revisión.

Francisco J. Angulo-Cubillán ^1,2, Leticia García-Coiradas ¹, Montserrat Cuquerella ¹, Concepción de la Fuente ¹ y José M. Alunda ¹

¹ Dpto. Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid. 28040, Madrid. España. E-mail: jmalunda@vet.ucm.es.

² Cátedra Enf. Parasitarias, Facultad de Cs. Veterinarias, Universidad del Zulia. 15252, Maracaibo. Venezuela. E-mail: fangulo@luz.edu.ve

ABSTRACT

Haemonchosis, caused by the abomasal nematode Haemonchus contortus, is among the most relevant parasitic diseases of small ruminants all over the world. The infections are responsible for anemic and bad digestion/absorption syndromes causing the death of severely infected animals in acute cases and the reduction of production scores in the chronic forms of the disease. The keys for the appearance of the disease include the biological behavior of the helminth and mechanisms of pathogenesis, besides the host’s response. The updated knowledge of these aspects would result in a higher efficiency of diagnostic and control methods, thus reducing the risks of appearance of the disease. In the present review, several aspects of the sheep - H. contortus relationship are analyzed with the aim of reducing the impact of this parasitosis on livestock health and productivity.

Key words: Haemonchosis, Haemonchus contortus, pathophysiology, immune response, sheep.

RESUMEN

Palabras clave: Hemoncosis, Haemonchus contortus, fisiopatología, respuesta inmunitaria, ovinos.

Recibido: 22 / 01 / 2006. Aceptado: 30 / 03 / 2007.

INTRODUCTION

Sheep are an important source of high quality food products for humans (meat, milk). Gastrointestinal nematodoses are among the most destructive pathologies affecting ovine production, given the high prevalence in flocks and the serious consequences of infection. In lambs, the acute form of gastrointestinal nematode infection causes death; the more frequent, chronic form leads to notable reductions in productivity.

Sheep haemonchosis is a parasitic disease caused by Haemonchus contortus, a nematode species that during its adult stage lives in the host’s abomasa. H. contortus is widely distributed in all geographic areas where small ruminants are bred. Clinical signs of the infection include anemia, digestion-absorption syndromes and, in many cases, the death of animals. The severity of the disease depends on a variety of factors, including the number of helminths infecting an animal (intensity of the infection), isolated-related parasite virulence, host age, animal breed, and the nutritional and immunological status of the infected sheep. All these factors can be aggravated by local environmental conditions. Therefore, in order to ascertain the factors favoring the appearance and severity of the disease in small ruminants, it is necessary to gain an insight into the relationship between sheep and H. contortus, covering biological aspects of the parasite helminth as well as the importance of the physiological and immune responses of infected animals.

Haemonchus contortus (Rudolphi, 1803) Cobb, 1898

The taxonomic position of the nematode is as follows:

Kingdom: Animalia; Phylum: Nemathelmintes; Class: Secernentea; Order: Strongylida; Suborder: Trichostrongylina; Superfamily: Trichostrongyloidea; Family: Haemonchidae; Subfamily: Haemonchinae; Genus: Haemonchus; Species: H.contortus [32, 47, 60, 123].

The genus Haemonchus apparently originated in Africa, with an initial diversification in antelopes and subsequent colonization and development in other wild ruminants. There were independent colonizations in domestic ruminants. Later, human migrations enabled the spread of Haemonchus to wild and domestic ruminants on other continents and H.contortus in sheep [2, 50, 70]. In addition, eleven more species have been described in the genus: H. similis (Travassos, 1914); H. longistipes (Railliet y Henry, 1909); H. placei (Place, 1893) Ransom 1911; H. bedfordi (LeRoux, 1929); H. mitchelli (LeRoux, 1929); H. vegliali (LeRoux, 1929); H. lawrencei (Sandground, 1933); H. okapiae (van den Berghe, 1937); H. krugeri (Ortlepp, 1964); H. horaki [71]; H. dinnik [50, 55, 70]. Moreover, hybrids of H. contortus and H. placei have arisen [69].

H.contortus has a direct life cycle, part of which occurs in the external environment, where the infective larvae (L3) develop. Under optimal humidity and temperature conditions, development from egg to L3 in the environment takes place in 6-7 days. The sheep acquire the infection by ingesting L3 in the grass. Ingested larvae unsheathe and penetrate the glands of the gastric mucosa where they molt to fourth stage larvae (L4) [28, 86, 110]. At this point, due to a variety of factors (adverse macro- and micro-environmental conditions, immune response of the host, parasite genetic constitution, among others), a phenomenon called “hypobiosis” occurs, in which L4 diminishes its metabolism, halts its development and remains inside the gastric gland. Hypobiosis, as a rule, takes place in winter in temperate areas and during the dry season in arid areas of the world [19, 41]. Once development resumes, L4 leaves the mucosa and, in the gastric lumen, molts to young adult, which copulates when it reaches maturity. The prepatent period varies between 15 and 18 days in normal conditions [61, 91, 110].

Pathogenesis

Several factors are involved in the pathogenesis of haemonchosis. In terms of the development of disease, the most important factors are parasite virulence and host-response. The main pathogenic mechanisms of H. contortus are a direct lesion on the gastric mucosa and hematophagy. The effects of pathogenic mechanisms during intra-host parasite development and the subsequent response of infected ruminants provoke morpho-functional changes, particularly in the abomasum. Also, variations appear in some blood parameters, resulting in the appearance of both anemic and impaired digestion-absorption syndromes.

H.contortus adult parasites can ingest 0.05 ml of blood/ helminth/day [95], causing notable blood loss [130] with a reduction of packed cell volume (PCV). This parameter has, in fact, been used as a marker of parasite virulence [33, 113] and indirect estimation of parasite burden in haemonchosis [34, 129].

The fall in PCV, a common finding in sheep haemonchosis [3, 38, 46, 84, 87, 111, 127, 128], is visible from day 4 post infection (PI), coinciding with the L4 exit from the mucosa. The decline accelerates with the beginning of the patent period (3 weeks PI), due to the combined effect of young and adult parasites’ increased blood demand, the efficiency of now well-developed lancet in the worms’ oral cavity, and blood loss to the gastrointestinal tract caused by infection-related hemorrhagic gastritis [52, 95, 111]. Minimum values are reached in the 7th week PI [63].

The fall in PCV values coincides (3 weeks PI) with a fall in hemoglobin concentration (5.3 -7.7 mg/dL) [63]. This is related to the hematophagy of the worms, as well as to blood loss through the intestine [95] and erythrocyte lysis caused by hemolytic factors excreted by the parasite [36, 37].

A reduction of plasma protein concentrations has been found in haemonchosis [4, 45, 128, 131] due to blood loss [130] and hemorrhagic gastritis. In addition, leakage of proteins to the gastric lumen occurs as a result of the disruption of intercellular unions and increased permeability [8, 39, 95], epithelial cells loss, tissue reparation, increase in mucus production, and increased requirements for protein synthesis by the immune system [106].

Moreover, many factors prevent such protein losses from being replaced through feeding. Infected animals have lower food intake [126], due to anemia [100, 111, 129]; gastrin reduces food passage through the gastrointestinal tract [39, 106]; bad digestion syndrome, caused by the increase of abomasal pH value, which prevents pepsin synthesis [49, 81, 103, 106], reduces aminoacid and small peptides absorption [105, 106].

This pH increase in the abomasum comes from a decrease in the production and excretion of hydrochloric acid (HCl) by the parietal cells of the gastric mucosa, generated by their loss and/or a decrease in their number. Lowered numbers of parietal cells is due to tissue lesion, cellular infiltration caused by the presence of the parasitic stages or their secretion-excretion products released into the medium, and cellular replacement by immature nonfunctional cells [49, 81, 102, 103, 106].

The development of parasites and their secretion-excretion products stimulate the liberation of substances such as acetylcholine, histamine, epithelial growth factor and gastrin, which in turn stimulate the principal cells to produce and release more pepsinogen [40, 77]. In experiments in sheep and goats, it has been demonstrated that the levels of serum pepsinogen in infections with H. contortus show a significant increase from days 4 to 14 PI, with average values of 741 mUTyr, later diminishing to pre-infection values by 40 PI [31, 38, 39, 103].

While these pathogenic actions directly affect the health of the animals, they also indirectly affect ovine yield, although this loss may be unnoticed if the parasitism presents a sub clinical course. Thus, the nematode infection of the abomasum has a notable effect on live weight [18, 84, 111, 125]. This has also been observed in weight and carcass conversion [127, 128]. This indirect effect is mainly due to a decrease in nutrient use [127] resulting from many factors, such as a lack of appetite and a decrease in the voluntary feed intake observed in the parasitized animal [40, 92, 117, 125], irreversible loss of proteins in the gastric lumen by hematophagy, hemorrhagic gastritis and loss of plasma proteins through greater mucosa permeability [39, 95, 100] and lowered digestibility [22, 23, 24, 39, 105, 106].

The symptoms of haemonchosis include lack of appetite [65, 124], lethargy, loss of weight [18], reduction in milk and wool production [21, 85], presence of pale mucosa, edemas, diminution of PCV [12, 63, 91], hemoglobin, plasma proteins [45] and increase in the number of circulating eosinophils in peripheral blood [3, 7] and serum pepsinogen and gastrin [40, 102, 103, 105, 106]. The final stages of the disease may be accompanied by emaciation, and death may result [123].

In the necropsy, the macroscopic lesions observed are: emaciation, pale mucosa, edemas in body cavities [91], degradation of the fat deposits [123], hypertrophy of local lymph nodes [30, 88], edema of the abomasal mucosa with petechial hemorrhages, presence of nodules and the observation of adult parasites [110]. In the microscopic evaluation, cellular infiltration, dilatation of the gastric glands, ulcers, edema, hemorrhage and an increase in the number of mastocytes and eosinophils [4, 5, 11, 14, 17, 54, 89] are observed.

Host immune response

Host immune response to haemonchosis is complex and shows cellular, humoral, and inflammatory mechanisms [75, 78] that can vary depending on the parasitic phases present [11]. The parasitic antigens interact with innate immune system cells (macrophages, dendritic cells, natural killer (NK), basophils, among others), which release cytokines, mainly IL-4, that provide instructions to T and B cells of the acquired immune system to generate a specific response [35, 51, 72, 75].

Infection with helminths induces the liberation of cytokines associated with T helper 2 (Th2) response, accompanied by eosinophilia, mastocytosis and the production of IgE. The cells that recognize parasitic antigens send molecular signals that induce T helper (Th) cells to secrete interleukins (4, 5, 10, 12). Interleukins stimulate B cells to produce and secrete antibodies (IgE, IgG, IgA); these antibodies bind to antigens. The complex formed is recognized by mastocytes, eosinophils and neutrophils, which release the content of their granules (histamine, leukotrienes, prostaglandins and other mediators). This induces an inflammatory process, increases mucus production, and provokes the contraction of smooth musculature, causing the expulsion of the parasite or its death. [5, 64, 72, 78, 81, 132].

The increase of complement receptors on the eosinophils’ surface and the complement protein deposits on the helminth surface cause cell degranulation and a direct effect on the parasite as well as an indirect effect through the complement classic pathway [79].

Many studies on natural or experimental infections with H. contortus have reported cellular infiltrations in the mucosa and regional lymph nodes , increases in T CD4+, T CD8+, T gamma delta (gd) and B lymphocytes, eosinophils and mastocytes [5, 11, 17, 75]. Also, a rise in immunoglobulins has been observed during infections with increases in IgE, IgG, IgA [3, 5, 15, 25, 26, 27, 29, 30, 44, 45, 46, 132].

There is no evidence that CD4+ cells directly limit parasitic establishment, survival and fecundity. It is more probable that they contribute with the production of cytokines which extend and regulate the differentiation, proliferation and recruitment of effector cells and antibody producers [43].

This role for CD4+ cells is supported by research with lambs resistant to gastrointestinal nematodes. The lambs were given successive doses of monoclonal anti-CD4+ antibodies, a treatment that severely affected resistance to infection. This group showed significantly greater amounts of eggs per grams (EPG) in faeces and parasitic burdens [59]. Furthermore, there was a significant reduction in mastocyte and eosinophil numbers in mucosa and lower levels of specific anti-H. contortus antibodies [43]. Also, an increase in the regional lymph nodes weight was observed in infected animals [11, 30].

CD8+ lymphocytes are considered effector and regulatory cells of the immune system, carrying out suppressing and cytotoxic functions [104]. In H. contortus infections their role is less important, as observed by the lack of effect of CD8+ reduction on HPG, parasitic burdens in lambs, and cell infiltration in abomasal mucosa during the infection [43].

The gd lymphocytes express on their surface a TcR receiver (T lymphocytes specific) made up of gd heterodimers, and CD3. They do not express CD4, CD8, or surface immunoglobulins and were previously called non B non T lymphocytes. These gd lymphocytes are found in much larger proportions in the peripheral blood of ruminants than in other species such as humans or mice [22, 107, 121]. The location of the gd lymphocytes in the epithelia, intestines, and the reproductive and respiratory tracts indicate their importance as a forward line of defense against pathogens [121]. The increases in these cells in the abomasal mucosa after the H. contortus infection suggest that they may play some role in the immune response to this nematode [11].

B lymphocytes mediate the humoral immune response and are in charge of antibody production, expressing on their surface when they are mature: CD19, PAN B antigens (CD21, CD24) and surface immunoglobulins, in addition to major complex antigens of type II histocompatibility and complement receptors [1]. Balic et al. [11] did not detect effects of the infection on the B lymphocyte population occurring in lymph nodes. However, these authors did observe a reduction in the values of fluorescence intensity in the surface immunoglobulins, which is probably attributable either to the reduction of surface molecules in activated B cells in the final differentiation to plasma cells, or to an increase in immature cells [75].

T lymphocytes are mediators of cellular immunity and can be used to measure cellular specific immune reactions [15]. This quantification can be made by determining the proliferation of mononuclear cells exposed to parasitic antigens in vitro. Several authors have reported proliferation of lymphocytes from peripheral blood or lymph nodes in infected animals, induced by larval and adult stages of nematode antigens [42, 98, 119, 120].

Alunda et al. [3] observed an elevation of the cellular response in the infected lambs, with maximum values of stimulation indices (S.I.) of 11, against mononuclear cells of the experimental H. contortus antigen-infected animals, although this increase was observed in late patency of the infection. Other authors have shown increases in S.I. of lymphocytes with values of 2.5 [100] and 10 [76]. The use of isolated lymphocytes from regional lymph nodes has served to measure local cellular response, obtaining from low or non-differentiable [30, 56] to significant values, as shown by McClure et al. [76] of 8 S.I.

Mastocytes are markers of helminth infection [35]. They are generated in the bone marrow from a haematopoyetic precursory cell that expresses CD34 on its surface, similar to eosinophils and basophils, and must mature in the target organ [35]. Mastocytes play an effector role in resistance against gastrointestinal nematodes [42], and their proliferation, recruitment and differentiation are regulated by cytokines released by lymphocytes CD4+ [43].

The hyperplasia of mastocytes in the abomasum mucosa is associated mainly with the presence of adult parasites and is greater in re-infections [10, 42], requiring a continuous stimulation on the part of parasitic antigens [4, 10]. The increase in its number suggests a local inflammatory response, implied in the protective response against re-infection [115] and is influenced by animals’ age, being more evident in adults [96, 126]. Mastocytes release, during infection, granules content, composed of proteoglycans, basic proteins and monoamines [53] which are found in host mucous secretions [14] after their degranulation and are associated with larvae expulsion [10]. The degranulated mastocytes present in the mucosa are called globule leukocytes [53, 74].

Eosinophils are antiparasitic effector cells [20, 114], whose main function is as a defense against non-phagocytable organisms, particularly helminths [13]. For this reason, they are considered markers of nematode infections [35, 81]. The IL-4 and IL-5 release by CD4+ and gd lymphocytes triggers eosinophils activation and an increase in their production by the bone marrow [79]. Eosinophils migrate to the target organs through the bloodstream [10, 54, 79, 132], which causes eosinophilia, a characteristic of helminth infections [64, 81].

During nematode infection, eosinophils present a direct cytotoxic effect, in particular due to the granule protein release and the superoxide anion production, killing larval stages [10] and damaging the host tissue [64, 81]. The increased expression of complement receptors on the cells surface, along with the abundant protein deposits of the same on the surface of the parasite, would cause degranulation and death [79]. A greater amount of eosinophils in the tissue suggests that they might be involved in larvae development prevention or in the rapid expulsion phenomenon [17].

In experimental infections, eosinophilia appears from the 5th PI day, reaching a peak between the second and third PI week, and soon declines between the fourth and fifth PI week [4, 7, 10, 42, 115]. This demonstrates an active modulation which generally happens when the infection becomes patent [64]. Cell quantifications in the infected abomasum mucosa have shown significantly increases in eosinophils in the infected animals in comparison to control groups [11, 42, 99, 126].

In several studies, negative correlations have been observed between the eosinophil number in abomasal mucosa and both EPG [5] and parasitic burden [43], although in other cases this has not been observed [4, 42]. In the case of the circulating eosinophils, significant associations have not been reported [4, 114].

With regard to humoral immune response, it has been shown in different papers that H. contortus infection causes an increase in specific immunoglobulins, slightly in primary infections and strongly in re-infections [25, 26, 44, 45, 46].

These immunoglobulin increases are associated with the immediate hypersensitivity response, by means of the binding of the IgE to parasitic antigens with the subsequent degranulation of the effector cells. The result is the expulsion or death, thus regulating the parasitic burden [5]. The specific local response of IgA and IgG is consistently associated with reduction of the helminth size and parasitic fecundity [5, 112], by metabolic enzyme neutralization, interfering with the feeding [100] and metabolism of H. contortus [116], although participation of the immediate hypersensitivity should not be ruled out [42].

In primary infections, lambs infected with H. contortus did not show any serum- IgG specific response with values of optical density (O.D.) in basal levels similar to those of the non infected group [15, 25, 26, 29, 30, 42, 45, 68, 98]. Alunda et al. [3], observed a slight increase in the values of IgG after the primary infection of 0.46 O.D. Other authors have observed increases in the serum levels of IgG in primary infections with O.D. values of 0.353 [87], 0.55 [101] and 0.6 [126].

In the case of IgA levels, basal levels similar to pre-infection values have been reported [45], although in other cases a slight increase in O.D. values of 0.68 [116] and 1.0 [128] has been observed. In re-infections, significant increases in IgA in serum [46] have been observed. For the IgE, the O.D. of the primarily infected group remains near 0.2 [68, 126]. It seems that humoral responses regulate parasite size and fecundity, while hypersensitivity reactions regulate parasite burden [5].

The immunoprofilaxis of haemonchosis has evolved from the use of vaccines with irradiated larvae [122] to the characterization of parasite antigens, recognized or not by the infected animal. For the last twenty years, vaccines have been tried, using proteins isolated from the microvilli of the digestive tract of H.contortus (Contortin) [83], cuticle [16], membranes (H11) [6, 66, 84, 109], infecting larvae cuticle [57], glycoprotein complexes containing galactose [H-gal-GP] [58, 108], helminth soluble extracts (p26/23) [3, 29, 30] and secretory-excretory (E/S) products [9, 99, 126]. These antigens, according to their exposure to the host immune system have been classified as natural and hidden [82, 93, 94]. Studies carried out by the aforementioned authors have reported marked reductions (40 to 80.14%) in the parasitic burdens of vaccinated animals.

H. contortus immune evasion

Parasites are exposed to host immune system attack, which is why they must develop efficient immune evasion strategies [48]. Among the mechanisms used by H. contortus to diminish the host’s local response efficacy are: location in the abomasum lumen and parasite mobility. In addition, the helminths produce a number of inhibitors of proteases as well as immunomodulator components that block host effector mechanisms [81, 130].

Thus, cystatins of H. contortus are inhibitors of proteases involved in the process of antigen presentation, reducing the T lymphocytes response. Moreover, they modulate cytokine response, by reducing the co-stimulator molecule expression on macrophage surface, thus contributing to an anti-inflammatory microenvironment induction with a strong diminution of cellular proliferation [48]. Type C lectin, identified in H. contortus and other nematodes, inhibits leukocyte adhesion to endothelial cells by competing with selectin and their subsequent migration to infected tissue, reducing the inflammation [73]. It has been determined that another E/S protein of adult H. contortus called calreticulin, in addition to inhibiting blood clothing and facilitating haematophagy, binds with and inhibits complement C1q component, which facilitates helminth survival [118].

CONCLUSIONS

In the Haemonchus contortus – ovine livestock relationship, there are numerous elements that may or may not favor the appearance of haemonchosis, whose the clinical manifestation is not only caused by parasite pathogenesis, but also by different host responses to infection. This complex situation requires the planning of different control strategies in order to reduce parasite action and stimulate host resistance, and thus increase the productivity of ovine flocks.

ACKNOWLEDGEMENTS

The work was partially funded by the research project AGL2000-81 from the Spanish Ministry of Science and Technology.

BIBLIOGRAPHIC REFERENCES

1. ABBAS, A.K.; LICHTMAN, A.H. Maduración, activación y regulación de los linfocitos. Immunología celular y molecular. Elsevier España S.A. Madrid, España. 149-153 pp. 2004.         [ Links ]

2. ACHI, Y.L.; ZINSSTAG, J.; YAO, K.; YEO, N.; DORCHIES, P.; JACQUIET, P. Host specificity of Haemonchus spp. for domestic rumminants in the savanna in northern Ivory Coast. Vet. Parasitol. 116: 151-158. 2003.         [ Links ]

3. ALUNDA, J.M.; ANGULO-CUBILLÁN, F.; CUQUERELLA, M. Immunization against ovine haemonchosis with three low molecular weight somatic antigens of adult Haemonchus contortus. J. Vet. Med. S. B. 50(2): 70-74. 2003.         [ Links ]

4. AMARANTE, A.F.T.; CRAIG, T.M.; RAMSEY, W.S.; DAVIS, S.K.; BAZER, F.W. Nematode burdens and cellular responses in the abomasal mucosa and blood of Florida native, Rambouillet and crossbreed lambs. Vet. Parasitol. 80: 311-324. 1999.         [ Links ]

5. AMARANTE, A.F.T.; BRICARELLO, P.A.; HUNTLEY, J.F.; MAZZOLIN, L.P.; GOMES, J.C. Relationship of abomasal histology and parasite-specific immunoglobulin A with the resistance to Haemonchus contortus infection in three breeds of sheep. Vet. Parasitol. 128: 99-107. 2005.         [ Links ]

6. ANDREWS, S.J.; ROLPH, T.P.; MUNN, E.A.; TAYLOR, M.A. Duration of protective immunity against ovine haemonchosis following vaccination with the nematode gut membrane antigen H11. Res. Vet. Sci. 62: 223-227. 1997.         [ Links ]

7. AUMONT, G.; GRUNER, L.; HOSTACHE, G. Comparison of the resistence to sympatric and allopatric isolates of Haemonchus contortus of Black Belly sheep in Guadalupe (FWI) and INRA 401 sheep in France. Vet. Parasitol. 116: 139-150. 2003.         [ Links ]

8. BAKER, R.L.; NAGDA, S.; RODRIGUEZ-ZAS, S.L.; SOUTHEY, B.R.; AUDHO, J.O.; ADUDA, E.O.; THORPE, W. Resistance and resilience to gastro-intestinal nematode parasites and relationships with productivity of Red Massai, Dorper and Red Massai X Dorper crossbred lambs in the sub-humid tropics. Anim. Sci. 76: 119-136. 2003.         [ Links ]

9. BAKKER, N.; VERVELDE, L.; KANOBANA, K.; KNOX, D.P.; CORNELISSEN, A.W.C.A.; DE VRIES, E.; YATSUDA, A.P. Vaccination against the nematodo Haemonchus contortus with a tilo-binding fraction from the excretory/secretory products (ES). Vacc. 22: 618-628. 2004.         [ Links ]

10. BALIC, A.; BOWLES, V.M.; MEEUSEN, E.N.T. The immunobiology of gastrointestinal nematode infections in ruminants. Adv. Parasitol. 45: 181-241. 2000a.         [ Links ]

11. BALIC, A.; BOWLES, V.M.; MEEUSEN, E.N.T. Cellular profiles in the abomasal mucosa and lymph node during primary infection with Haemonchus contortus in sheep. Vet. Immunol. Immunopathol. 75: 109-120. 2000b.         [ Links ]

12. BARGER, I.A.; DASH, K.M. Repeatibility of ovine faecal egg counts and blood packed cell volumes in Haemonchus contortus infections. Int. J. Parasitol. 17(4): 977-980. 1987.         [ Links ]

13. BEHM, C.A.; OVINGTON, K.S. The role of eosinophils in parasitic helminth infections: Insights from genetically modified mice. Parasitol. Today. 16(5): 202-209. 2000.         [ Links ]

14. BENDIXSEN, T.; EMERY, D.L.; JONES, W.O. The sensitization of mucosal mast cells during infections with Trichostrongylus colubriformis or Haemonchus contortus in sheep. Int. J. Parasitol. 25(6): 741-748. 1995.         [ Links ]

15. BEREZHKO, V.K.; AKULIN, N.A.; BUZMAKOVA, R.A.; KUROCHKINA, K.G. Immunoallergic reactions and a phenomenon of self-cure in experimental haemonchosis (Haemonchus contortus) of sheep depending on host’s age. Helminthol. 24: 119-131. 1987.         [ Links ]

16. BOISVENUE, R.J.; STIFF, M.I.; TONKINSON, L.V.; COX, G.N. Protective studies in sheep immunised with cuticular collagen proteins and peptides of Haemonchus contortus. Par. Immunol. 13: 227-240. 1991.         [ Links ]

17. BRICARELLO, P.A.; GENNARI, S.M.; OLIVEIRA-SEQUEIRA, T.C.G.; VAZ, C.M.S.L.; GONCALVES DE G., I.; ECHEVARRIA, F.A.M. Worm burden and immunological responses in Corriedale and Crioula Lanada sheep following natural infection with Haemonchus contortus. S. Rum. Res. 51: 75-83. 2004.         [ Links ]

18. BURKE, J.M.; MILLER, J.E. Relative resistance of Dorper crossbred ewes to gastrointestinal nematode infection compared with St. Croix and Katahdin ewes in the southeastern United States. Vet. Parasitol. 109: 265-275. 2002.         [ Links ]

19. CAPITINI, L.A.; MCCLURE, K.E.; HERD, R.P. Effect of environmental stimuli on pre-infective and infective stages of Haemonchus contortus in the Northern United States for the induction of hypobiosis. Vet. Parasitol. 35: 281-293. 1990.         [ Links ]

20. CLAEREBOUT, E.; VERCRUYSSE, J. The immune response and the evaluation of acquired immunity against gastrointestinal nematodes in cattle: a review. Parasitol. 120: S25-S42. 2000.         [ Links ]

21. COBON, D.H.; O’SULLIVAN, B.M. Effect of Haemonchus contortus on productivity of ewes, lambs and weaners in a semi-arid environment. J. Agr. Sci. 118: 245-248. 1992.         [ Links ]

22. COLLINS, R.A.; SOPP, P.; PARSONS, K.R.; MORRISON, W.I.; HOWARD, C.J. What are the cells and molecules involved in stimulating bovine g/d T cells? Vet. Immunol. Immunopathol. 54: 93. 1996.         [ Links ]

23. COOP, R.L.; KYRIAZAKIS, L. Nutrition-parasite interaction. Vet. Parasitol. 84(3-4): 187-204. 1999.         [ Links ]

24. COOP, R.L.; KYRIAZAKIS, L. Influence of host nutrition on the development and consequences of nematode parasitism in ruminants. Trends Parasitol. 17: 325-330. 2001.         [ Links ]

25. CUQUERELLA, M.; GÓMEZ-MUÑOZ, M.T.; ALUNDA, J.M. Serum IgG response of Manchego lambs to infections with Haemonchus contortus and preliminary characterization of adult antigens. Vet. Parasitol. 38: 131-143. 1991.         [ Links ]

26. CUQUERELLA, M.; GÓMEZ-MUÑOZ, M.T.; MÉNDEZ, S.; ALUNDA, J.M. Partial protection of Manchego sheep against Haemonchus contortus after a 6-month postpriming period. Preliminary note. J. Vet. Med. B. 41: 399-406. 1994a.         [ Links ]

27. CUQUERELLA, M.; GÓMEZ-MUÑOZ, M.T.; CARRERA, L.; DE LA FUENTE, C.; ALUNDA, J.M. Croos antigenicity among ovine trichosntrongyloidea. Preliminary Report. Vet. Parasitol. 53: 243-251. 1994b.         [ Links ]

28. DASH, K.M. Distribution of trichostrongylid nematodes in the abomasum of sheep. Int. J. Parasitol. 15: 505-510. 1985.         [ Links ]

29. DOMÍNGUEZ-TORAÑO, I.A.; CUQUERELLA, M.; GOMEZ-MUÑOZ, M.T.; MÉNDEZ, S.; ALUNDA, J.M. Vaccination of Manchego lambs against Haemonchus contortus with a somatic fraction (p26/23) of adult parasites. Parasitol. Immunol. 22: 131-138. 2000.         [ Links ]

30. DOMÍNGUEZ-TORAÑO, I.A.; FERNÁNDEZ-PÉREZ, F.J.; GOMEZ-MUÑOZ, M.T.; ALUNDA, J.M.; CUQUERELLA, M. Humoral and cellular response in lambs vaccinated against Haemonchus contortus with p26/23. S. Rum. Res. 50: 29-37. 2003.         [ Links ]

31. DORNY, P.; VERCRUYSSE, J. Evaluation of a micro method for the routine determination of serum pepsinogen in cattle. Res. Vet. Sci. 65: 259-262. 1998.         [ Links ]

32. DURETTE-DESSET, M.C.; HUGOT, J.P.; DARLU, P.; CHABAUD, A.G. A cladistic analysis of the Trichostrongyloidea (Nematoda). Int. J. Parasitol. 29: 1065-1086. 1999.         [ Links ]

33. EYSKER, M.; PLOEGER, H.W. Value of present diagnostic methods for gastrointestinal nematode infections in ruminants. Parasitol. 120: S109-S119. 2000.         [ Links ]

34. FAKAE, B.B.; CHIEJINA, S.N.; BEHNKE, J.M.; EZEOKONKWO, R.C.; NNADI, P.A.; ONYENWE, W.I.; GILBERT, F.S.; WAKELIN, D. The response of Nigerian West African Dwarf goats to experimental infections with Haemonchus contortus. Res. Vet. Sci. 66: 147-158. 1999.         [ Links ]

35. FALCONE, F.H.; PRITCHARD, D.I.; GIBBS, B.F. Do basophils play a role in immunity against parasites?. Trends Parasitol. 17(3): 126-129. 2001.         [ Links ]

36. FETTERER, R.H.; RHOADS, M.L. Characterization of haemolytic activity from adult Haemonchus contortus. Int. J. Parasitol. 27(9): 1037-1040. 1997.         [ Links ]

37. FETTERER, R.H.; RHOADS, M.L. A haemolytic factor from Haemonchus contortus alters erythrocyte morphology. Vet. Parasitol. 80: 37-45. 1998.         [ Links ]

38. FOX, M.T.; PITT, S.R.; GERRELLI, D.; JACOBS, D.E.; ADHIKARI, D.R.; GODDARD, P.J. Use of blood gastrin assay in the diagnosis of ovine haemonchiasis. Vet. Rec. 122: 136-137. 1988.         [ Links ]

39. FOX, M.T.; JACOBS, D.E. Blood gastrin and pepsinogen responses of native village goats in Malaysia to infection with Haemonchus contortus. Ann. Trop. Med. Parasitol. 85: 263-267. 1991.         [ Links ]

40. FOX, M.T. Pathophysiology of infection with gastrointestinal nematodes in domestic ruminants: recent developments. Vet. Parasitol. 72: 285-308. 1997.         [ Links ]

41. GATONGI, P.M.; PRICHARD, R.K.; RANJAN, S.; GATHUMA, J.M.; MUNYUA, W.K.; CHERUIYOT, H.; SCOTT, M.E. Hypobiosis of Haemonchus contortus in natural infections of sheep ang goats in a semi-arid area of Kenya. Vet. Parasitol. 77: 49-61. 1998.         [ Links ]

42. GILL, H.S. Genetic control of acquired resistance to haemonchosis in Merino lambs. Parasitol. Immunol. 13: 617-628. 1991.         [ Links ]

43. GILL, H.S.; WATSON, D.L.; BRANDON, M.R. Monoclonal antibody to CD4+ T cells abrogates genetic resistance to Haemonchus contortus in sheep. Immunol. 78: 43-49. 1993.         [ Links ]

44. GÓMEZ-MUÑOZ, M.T.; CUQUERELLA, M.; DE LA FUENTE, C.; GÓMEZ-IGLESIAS, L.A.; ALUNDA, J.M. Infection-induced protection against Haemonchus contortus in Merino and Manchego sheep. Relationship to serum antibody response. J. Vet. Med. B. 45: 449-459. 1998.         [ Links ]

45. GÓMEZ-MUÑOZ, M.T.; CUQUERELLA, M.; GÓMEZ-IGLESIAS, L.A.; MÉNDEZ, S.; FERNÁNDEZ-PÉREZ, F.J.; DE LA FUENTE, C.; ALUNDA, J.M. Serum antibody response of Castellana sheep to Haemonchus contortus infection and challenge: relationship to abomasal worm burdens. Vet. Parasitol. 81: 281-293. 1999.         [ Links ]

46. GÓMEZ-MUÑOZ, M.T.; GÓMEZ-IGLESIAS, L.A.; FERNÁNDEZ-PÉREZ, F.J.; MÉNDEZ, S.; DOMÍNGUEZ, I.A.; DE LA FUENTE, C.; ALUNDA, J.M.; CUQUERELLA, M. Experimental Haemonchus contortus infection and challenge in the Churra sheep breed: immunological and pathophysiological parameters. Rev. Ibér. Parasitol. 61: 83-89. 2001.         [ Links ]

47. GOUŸ DE B., J.; FERTE, H.; DEPAQUIT, J.; JUSTINE, J.L.; TILLIER, A.; DURETTE-DESSET, M.C. Phylogeny of the Trichostrongylina (Nematoda) inferred from 28s rDNA sequences. Mol. Phylogenet. Evolut. 19(3): 430-442. 2001.         [ Links ]

48. HARTMANN, S.; LUCIUS, R. Modulation af host immune responses by nematode cystatins. Int. J. Parasitol. 33: 1291-1302. 2003.         [ Links ]

49. HERTZBERG, H.; GUCETTI, F.; LISCHER, C.; KOHLER, L.; NEIGER, R.; ECKERT, J. Evidence for a parasite-mediated inhibition of abomasal acid secretion in sheep infected with Ostertagia leptospicularis. Vet. J. 159:238-251. 2000.         [ Links ]

50. HOBER, E.; LICHTENFELS, J.; GIBBONS, L. Phylogeny for species of the genus Haemonchus (Nematoda: Trichostrongyloidea): Considerations of their evolutionary history and global biogeography among Camelidae and Pecora (Artiodactyla). J. Parasitol. 90(6): 1378-1386. 2004.         [ Links ]

51. HOWARD, C.J.; BROOKE, G.P.; WERLING, D.; SOPP, P.; HOPE, J.C.; PARSONS, K.R.; COLLINS, R.A. Dendritic cells in cattle: phenotype and function. Vet. Immunol. Immunopathol. 72: 119-124. 1999.         [ Links ]

52. HUNTER, A.R.; MACKENZIE, G. The pathogenesis of a single challenge dose of Haemonchus contortus in lambs under six months of age. J. Helminthol. 56: 135-144. 1982.         [ Links ]

53. HUNTLEY, J.F.; NEWLANDS, G.; MILLER, H.R.P. The isolation and characterization of globule leucocytes: their derivation from mucosal mast cells in parasitized sheep. Parasitol. Immunol. 6: 371-390. 1984.         [ Links ]

54. HUNTLEY, J.F.; JACKSON, F.; COOP, R.L.; MACALDOWIE, C.; HOUDIJK, J.G.M.; FAMILTON, A.S.; XIEH, H.L.; STANKIEWICZ, M.; SYKES, A.R. The sequential analysis of local inflammatory cells during abomasal nematode infection in periparturient sheep. Vet. Immunol. Immunopathol. 97: 163-176. 2004.         [ Links ]

55. JACQUIET, PH.; CABARET, J.; CHEIKH, D.; THIAM, E. Identification of Haemonchus species in domestic ruminants based on morphometrics of spicules. Parasitol. Res. 83: 82-86. 1997.         [ Links ]

56. JACOBS, H.J.; ASHMAN, K.; MEEUSEN, E. Humoral and cellular responses following local immunization with a surface antigen of the gastrointestinal parasite Haemonchus contortus. Vet. Immunol. Immunopathol. 48: 323- 332. 1995.         [ Links ]

57. JACOBS, H.J.; WILTSHIRE, C.; ASHMAN, K.; MEEUSEN, E.N.T. Vaccination against the gastrointestinal nematode, Haemonchus contortus, using a purified larval surface antigen. Vacc. 17: 362-368. 1999.         [ Links ]

58. KABAGAMBE, E.K.; BARRAS, S.R.; LI, Y.; PEÑA, M.T.; SMITH, W.D.; MILLER, J.E. Attempts to control haemonchosis in grazing ewes by vaccination with gut membrane proteins of the parasite. Vet. Parasitol. 92: 15-23. 2000.         [ Links ]

59. KARANU, F.N.; MCGUIRE, T.C.; DAVIS, W.C.; BESSER, T.E.; JASMER, D.P. CD4+ T lymphocytes contribute to protective immunity induced in sheep and goats by Haemonchus contortus gut antigens. Parasitol. Immunol. 19: 435-445. 1997.         [ Links ]

60. KASSAI, T. Clasificación de helmintos parásitos. Helmintología Veterinaria. Ed. Acribia S.A. Zaragoza, España. XXIII-XXVIII pp. 2002.         [ Links ]

61. KAUFMANN, J. Parasites of sheep and goats. Parasitic infections of domestic animals. A diagnostic manual. Berlin: Birkhäuser. 37-39 pp. 1996.         [ Links ]

62. KERBOEUF, D. ; KOCH, C.; LE DREAN ET, E.; LACOURT, A. Méthode simplifiée de mesure de la concentration en pepsinogéne dans le sérum. Rev. Méd. Vét. 153 : 707-712. 2002.         [ Links ]

63. KHAN, M.Q.; HAYAT, S.; HUSSAIN, M.I.M.; IQBAL, Z. Effect of haemonchosis on body weigth gain and values in sheep. Pak. Vet. J. 8(2): 62-67. 1988.         [ Links ]

64. KLION, A.D.; NUTMAN, T.B. The role of eosinophils in host defense against helminth parasites. J. Allerg. Clinic. Immunol. 113(1): 30-37. 2004.         [ Links ]

65. KNOX, M.R.; STEEL, J.W. The effects of urea supplementation on production and parasitological responses of sheep infected with Haemonchus contortus and Trichostrongylus colubriformis. Vet. Parasitol. 83: 123-135. 1999.         [ Links ]

66. KNOX, D.P.; SMITH, S.K.; SMITH, W.D. Immunization with an affinity purified protein extract from the adult parasite protects lambs against infection with Haemonchus contortus. Parasitol. Immunol. 21: 201-210. 1999.         [ Links ]

67. KNOX, D.P.; SMITH, W.D. Vaccination against gastrointestinal nematode parasites of ruminants using gut-expressed antigens. Vet. Parasitol. 100: 21-32. 2001.         [ Links ]

68. KOOYMAN, F.N.J.; SCHALLIG, H.D.F.H.; VAN LEEUWEN, M.A.W.; MACKELLAR, A.; HUNTLEY, J.F.; CORNELISSEN, A.W.C.A.; VERVELDE, L. Protection in lambs vaccinated with Haemonchus contortus antigens is age related, and correlates with IgE rather than IgG1 antibody. Parasitol. Immunol. 22: 13-20. 2000.         [ Links ]

69. LE JAMBRE, L.F. Relationship of blood loss to worm numbers, biomass and egg production in Haemonchus infected sheep. Int. J. Parasitol. 25: 269-273. 1995.         [ Links ]

70. LICHTENFELS, J.R.; PILITT, P.A.; HOBERG, E.P. New morphological characters for identifying individual specimens of Haemonchus spp. (Nematoda: Trichostrongyloidea) and key to species in ruminants of north America. J. Parasitol. 80: 107-119. 1994.         [ Links ]

71. LICHTENFELS, J.R.; PILITT, P.A.; GIBBONS, L.M.; BOOMKER, J.D. Haemonchus horaki n. Sp. (Nematoda: Trichostrongyloidea) from the grey rhebuck Pelea capreolus in South Africa. J. Parasitol. 87(5): 1095-1103. 2001.         [ Links ]

72. LONDON, C.A.; ABBAS, A.K.; KELSO, A. Helper T cell subsets: Heterogeinity, functions and development. Vet. Immunol. Immunopathol. 63: 37-44. 1998.         [ Links ]

73. LOUKAS, A.; MAIZELS, R.M. Helminth C-type lectins and host-parasite interactions. Parasitol. Today. 16(8): 333-339. 2000.         [ Links ]

74. MACALDOWIE, C.; JACKSON, F.; HUNTLEY, J.; MACKELLAR, A.; JACKSON, E. A comparison of larval development and mucosal mast cell responses in worm-naïve goat yearling, kids and lambs undergoing primary and secondary challenge with Teladorsagia circumcincta. Vet. Parasitol. 114: 1-13. 2003.         [ Links ]

75. McCLURE, S.J.; DAVEY, R.L.; EMERY, D.L.; COLDITZ, I.G.; LLOYD, J.B. In vivo depletion of T-cells and cytokines during primary exposure of sheep to parasites. Vet. Immunol. Immunopathol. 54: 83-90. 1996.         [ Links ]

76. McCLURE, S.J.; EMERY, D.L.; BENDIXSEN, T.; DAVEY, R.J. Attempts to generate immunity against Trichostrongylus colubriformis and Haemonchus contortus in young lambs by vaccination with viable parasites. Int. J. Parasitol. 28: 739-746. 1998.         [ Links ]

77. McKELLAR, Q.A. Interactions of Ostertagia species with their bovine and ovine host. Int. J. Parasitol. 23: 451-462. 1993.         [ Links ]

78. MEEUSEN, E.N.T. Immunology of helminth infections, with special reference to immunopathology. Vet. Parasitol. 84: 259-273. 1999.         [ Links ]

79. MEEUSEN, E.N.T.; BALIC, A. Do eosinophils have a role in the killing of helminth parasites?. Parasitol. Today. 16(3): 95-101. 2000.         [ Links ]

80. MERKELBACH, P.; SCOTT, I.; KHALAF, S.; SIMPSON, H.V. Excretory/Secretory products of Haemonchus contortus inhibit aminopyrine accumulation by rabbit gastric glands in vitro. Vet. Parasitol. 104: 217-228. 2002.         [ Links ]

81. MULCAHY, G.; O’NEILL, S.; DONNELLY, S.; DALTON, J.P. Helminths at mucosal barriers-interaction with the immune system. Adv. Drug Deliv. Rev. 56: 853-868. 2004.         [ Links ]

82. MUNN, E.A. Rational design of nematode vaccine: hidden antigens. Int. J. Parasitol. 27(4): 359-366. 1987.         [ Links ]

83. MUNN, E.A.; GREENWOOD, C.A.; COADWELL, W.J. Vaccination of young lambs by means of a protein fraction extracted from adult Haemonchus contortus. Parasitol. 385-397. 1987.         [ Links ]

84. NEWTON, S.E.; MORRISH, L.E.; MARTIN, P.J.; MONTAGUE, P.E.; ROLPH, T.P. Protection against multiply drug-resistant and geographically distant strains of Haemonchus contortus by vaccination with H11, a gut membrane-derived protective antigen. Int. J. Parasitol. 25(4): 511-521. 1995.         [ Links ]

85. NOTTER, D.R.; ANDREW, S.A.; ZAJAC, A.M. Res- ponses of hair and wool sheep to a single fixed dose of infective larvae of Haemonchus contortus. S. Rum. Res. 47: 221-225. 2003.         [ Links ]

86. ONYIAH, L.C.; ARSLAN, O. Simulating the development period of a parasite of sheep on pasture under varying temperature conditions. J. Thermal Biol. 30: 203-211. 2005.         [ Links ]

87. PEÑA, M.T.; MILLER, J.E.; HOROHOV, D.W. Effect of dexamethasone treatment on the immune response of Gulf Cosat Native lambs to Haemonchus contortus infection. Vet. Parasitol. 119(2-3): 223-235. 2004.         [ Links ]

88. PÉREZ, J.; GARCÍA, P.M.; HERNÁNDEZ, S.; MARTÍNEZ-MORENO, A.; DE LAS MULAS, J.M.; CÁMARA, S. Pathological and immunohistochemical study of the abomasum and abomasal lymph nodes in goats experimentally infected with Haemonchus contortus. Vet. Res. 32: 463-473. 2001.         [ Links ]

89. PÉREZ, J.; GARCÍA, P.M.; HERNÁNDEZ, S.; MOZOS, E.; CÁMARA, S.; MARTÍNEZ-MORENO, A. Experimental haemonchosis in goats: effects of single and multiple infections in the host response. Vet. Parasitol. 111: 333-342. 2003.        [ Links ]

90. PEERSON-WALLER, K.; COLDITZ, I.G. Expression of surface antigen on blood and mammary leukocytes in lactating and dry ewes. Vet. Immunol. Immunopathol. 62: 273-278. 1998.         [ Links ]

91. QUIROZ, R.H. Estrongilosis gastroentéricas. Parasitología y enfermedades parasitarias de los animales domésticos. 2º Ed. Ed. Limusa, S.A., México. 430-458 pp. 1999.         [ Links ]

92. RAHMAN, W.A.; COLLINS, G.H. The establishment and development of Haemonchus contortus in goats. Vet. Parasitol. 35: 189-193. 1990.         [ Links ]

93. REDMOND, D.L.; GELDHOF, P.; KNOX, D.P. Evaluation of Caenorhabditis elegans glycoproteins as protective immunogens against Haemonchus contortus challenge in sheep. Int. J. Parasitol. 34: 1347-1353. 2004.         [ Links ]

94. REDMOND, D.L.; KNOX, D.P. Protection studies in sheep using affinity-purified and recombinant cysteine proteinases of adult Haemonchus contortus. Vacc. 22: 4252-4261. 2004.         [ Links ]

95. ROWE, J.B.; NOLAN, J.V.; DE CHANEET, G.; TELENI, E. The effect of haemonchosis and blood loss into the abomasum on digestion in sheep. Brit. J. Nut. 59: 125-139. 1988.         [ Links ]

96. SALMAN, S.K.; DUNCAN, J.L. The abomasal histology of worm free sheep given primary and challenge infections of Haemonchus contortus. Vet. Parasitol. 16: 43-54. 1984.         [ Links ]

97. SANGSTER, N.C. Introduction to Symposium on Recent Research on Haemonchus contortus. Int. J. Parasitol. 25: 1271-1272. 1995.         [ Links ]

98. SCHALLIG, H.D.F.H.; LEEUWEN, M.A.W.; HENDRIKX, W.M.L. Immune response of Texel sheep to excretory/secretory products of adult Haemonchus contortus. Parasitol. 108: 351-357. 1994.         [ Links ]

99. SCHALLIG, H.D.F.H.; VAN LEEUWEN, M.A.W.; CORNELISSEN, W.C.A. Protective immunity induced by vaccination with two Haemonchus contortus excretory secretory proteins in sheep. Parasitol. Immunol. 19: 447-453. 1997.         [ Links ]

100. SCHALLIG, H.D.F.H. Immunological responses of sheep to Haemonchus contortus. Parasitol. 120: S63-S72. 2000.         [ Links ]

101. SCHALLIG, H.D.F.H.; VAN DER AAR, W.M.; BOERSEMA, J.H.; CORNELISSEN, A.W.C.A. The effect of oxfendazole terminated infections with Haemonchus contortus on the development of immunity in sheep. Vet. Parasitol. 88: 61-72. 2000.         [ Links ]

102. SCOTT, I.; DICK, A.; IRVINE, J.; STEAR, M.J.; McKELLAR, Q.A. The distribution of pepsinogen within the abomasa of cattle and sheep infected with Ostertagia spp. and sheep infected with Haemonchus contortus. Vet. Parasitol. 82: 145-159. 1999.         [ Links ]

103. SCOTT, I.; KHALAF, S.; SIMCOCK, D.C.; KNIGHT, C.G.; REYNOLDS, G.W.; POMROY, W.E.; SIMPSON, H.V. A sequential study of the pathology associated with the infection of sheep with adult and larval Ostertagia circumcincta. Vet. Parasitol. 89: 79-94. 2000.         [ Links ]

104. SHER, A. Regulation of immunity to parasites by T cells and T cell-derived cytokines. Ann. Rev. Immunol. 10: 385-409. 1992.         [ Links ]

105. SIMCOCK, D.C.; JOBLIN, K.N.; SCOTT, I.; BURGESS, D.M.; ROGERS, C.W.; POMROY, W.E.; SIMPSON, H.V. Hypergastrinaemia, abomasal bacterial population densities and pH in sheep infected with Ostertagia circumcincta. Int. J. Parasitol. 29: 1053-1063. 1999.         [ Links ]

106. SIMPSON, H.V. Pathophysiology of parasitism abomasal: is the host or parasite responsible?. Vet. J. 160: 177-191. 2000.         [ Links ]

107. SMITH, H.E.; JACOBS, R.M.; SMITH, C. Flow cytometric analysis of ovine peripheral blood lymphocytes. Can. J. Vet. Res. 58: 152-155. 1994.         [ Links ]

108. SMITH, S.K.; SMITH, W.D. Immunisation of sheep with a integral membrane glycoprotein complex of Haemonchus contortus and with its major polypeptide components. Res. Vet. Sci. 60: 1-6. 1996.         [ Links ]

109. SMITH, W.D. Protection in lambs immunised with Haemonchus contortus gut membrane proteins. Res. Vet. Sci. 54: 94-101. 1993.         [ Links ]

110. SOULSBY, E.J.L. Género: Haemonchus Cobb, 1898. Parasitología y enfermedades parasitarias en los animales domésticos. 7º Ed. Interamericana S.A. México. 232-238 pp. 1987.         [ Links ]

111. STEAR, M.J.; BAIRDEN, K.; DUNCAN, J.L.; MURRAY, M. A comparison of the responses to repeated experimental infections with Haemonchus contortus among Scottish Blackface lambs. Vet. Parasitol. 60: 69-81. 1995.         [ Links ]

112. STEAR, M.J.; STRAIN, S.; BISHOP, S.C. Mechanisms underlying resistence to nematode infection. Int. J. Parasitol. 29: 51-56. 1999a.         [ Links ]

113. STEAR, M.; BAIRDEN, K.; McKELLAR, Q.A.; SCOTT, I.; STRAIN, S.; BISHOP, S. The relationship between the number and size of nematodes in the abomasums and the concentration of pepsinogen in ovine plasma. Res. Vet. Sci. 67: 89-92. 1999b.         [ Links ]

114. STEAR, M.J.; HENDERSON, N.G.; KERR, A.; McKELLAR, Q.A.; MITCHELL, S.; SEELEY, C.; BISHOP, S.C. Eosinophilia as a marker of resistence to Teladorsagia circumcincta in Scottish Blackface lambs. Parasitol. 124: 553-560. 2002.         [ Links ]

115. STEVENSON, L.M.; HUNTLEY, J.F.; SMITH, W.D.; JONES, D.G. Local eosinophil and mast cell related responses in abomasal nematode infections of lambs. Immunol. Med. Microbiol. 8: 167-174. 1994.         [ Links ]

116. STRAIN, S.A.; STEAR, M.J. The influence of protein supplementation on the immune response to Haemonchus contortus. Parasitol. Immunol. 23: 527-531. 2001.         [ Links ]

117. SUAREZ, V.H.; LORENZO, R.M.; BUSETTI, M.R.; SANTUCHO, G.M. Physiological and parasitological responses to nematode infections of fattening cattle in the Western Pampas of Argentina. Vet. Parasitol. 81: 137-148. 1999.         [ Links ]

118. SUCHITRA, S.; JOSHI, P. Characterizations of Haemonchus contortus calreticulin suggests its role in feeding and immune evasion by the parasite. Bioch. Bioph. Acta. 1722: 293-303. 2005.         [ Links ]

119. TORGERSON, P.R.; LLOYD, S. The B cell dependence of Haemonchus contortus antigen induced lymphocyte proliferation. Int. J. Parasitol. 23(7): 925-930. 1993a.         [ Links ]

120. TORGERSON, P.R.; LLOYD, S. The same fractions of Haemonchus contortus soluble antigen induce lymphocyte responses in naive lambs and immune sheep. Res. Vet. Sci. 54: 244-246. 1993b.         [ Links ]

121. TUO, W.; BAZER, F.W.; DAVIS, W.C.; ZHU, D.; BROWN, W.C. Differential effects to type I IFNs on the growth of WC1- CD8+ gd T cells and WC1+ CD8 - gd T cells in vitro. J. Immunol. 162: 245-253. 1999.         [ Links ]

122. URQUHART, G.M.; JARRETT, W.F.H.; JENNINGS, F.W.; McINTYRE, W.I.M.; MULLIGAN, W. Immunity to Haemonchus contortus infection: Relationship between age and successful vaccination with irradiated larvae. Am. J. Vet. Res. 27(121): 1645-1648. 1966.         [ Links ]

123. URQUHART, G.M.; ARMOUR, J.; DUNCAN, J.L.; DUNN, A.M.; JENINGS, F.W. Veterinary Helminthology. Veterinary Parasitology. 2º Ed. Blackwell Science Ltd. London. UK. 19-22 pp. 2001.         [ Links ]

124. VALDERRÁBANO, J.; DELFA, R.; URIARTE, J. Effect of level of feed intake on the development of gastrointestinal parasitism in growing lambs. Vet. Parasitol. 104: 327-338. 2002.         [ Links ]

125. VALDERRÁBANO, J.; URIARTE, J. Effect of nutrition in early pregnancy on the periparturient relaxation of immunity to gastro-intestinal parasitism in prolific ewes. Anim. Sci. 76: 481-489. 2003.         [ Links ]

126. VERVELDE, L.; KOOYMAN, F.N.J.; VAN LEEUWEN, M.A.W.; SCHALLIG, H.D.F.H.; McKELLAR, A.; HUNTLEY, J.F.; CORNELISSEN, A.W.C.A. Age related protective immunity after vaccination with Haemonchus contortus excretory/secretory proteins. Parasitol. Immunol. 23:419-426. 2001.         [ Links ]

127. WALLACE, D.S.; BAIRDEN, K.; DUNCAN, J.L.; FISHWICK, G.; GILL, M.; HOLMES, P.H.; McKELLAR, Q.A.; MURRAY, M.; PARKINS, J.J.; STEAR, M. Influence of supplementation with dietary soyabean meal on the resistance to haemonchosis in Hampshire down lambs. Res. Vet. Sci. 58: 232-237. 1995.         [ Links ]

128. WALLACE, D.S.; BAIRDEN, K.; DUNCAN, J.L.; FISHWICK, G.; GILL, M.; HOLMES, P.H.; McKELLAR, Q.A.; MURRAY, M.; PARKINS, J.J.; STEAR, M. Influence of soyabean meal supplementation on the resistance of Scottish Blackface lambs to haemonchosis. Res. Vet. Sci. 60: 138-143. 1996.         [ Links ]

129. WALLER, P.J. International approaches to the concept of integral control of nematode parasites of livestock. Int. J. Parasitol. 29: 155-164. 1999.         [ Links ]

130. WILLIAMSON, A.L.; BRINDLEY, P.J.; KNOX, D.P.; HOTEZ, P.J.; LOUKAS, A. Digestive proteases of blood-feeding nematodes. Trends Parasitol. 19(9): 417-423. 2003.         [ Links ]

131. YACOOB, A.; HOLMES, P.H.; ARMOUR, J. Pathophisiology of gastrointestinal trichostrongyles in sheep: plasma losses and changes in plasma pepsinogen levels associated with parasitic challenge of immune animals. Res. Vet. Sci. 34: 305-309. 1983.         [ Links ]

132. YONG, W.K.; EDWARDS, L.D.; HUCKER, D.A. Peripheral blood white cell responses during concurrent copper deficiency and gastro-intestinal nematodiasis in sheep. Exp. Biol. Med. Sci. 63: 273-281. 1985.        [ Links ] ]]> 1 2004 149-153 2 2003 116 151-158 3 2003 50 2 2 70-74 4 1999 80 311-324 5 2005 128 99-107 6 1997 62 223-227 7 2003 116 139-150 8 2003 76 119-136 9 2004 22 618-628 10 2000 a 45 181-241 11 2000 b 75 109-120 12 1987 17 4 4 977-980 13 2000 16 5 5 202-209 14 1995 25 6 6 741-748 15 1987 24 119-131 16 1991 13 227-240 17 2004 51 75-83 18 2002 109 265-275 19 1990 35 281-293 20 2000 120 S25-S42 21 1992 118 245-248 22 1996 54 93 23 1999 84 3-4 3-4 187-204 24 2001 17 325-330 25 1991 38 131-143 26 1994 a 41 399-406 27 1994 b 53 243-251 28 1985 15 505-510 29 2000 22 131-138 30 2003 50 29-37 31 1998 65 259-262 32 1999 29 1065-1086 33 2000 120 S109-S119 34 1999 66 147-158 35 2001 17 3 3 126-129 36 1997 27 9 9 1037-1040 37 1998 80 37-45 38 1988 122 136-137 39 1991 85 263-267 40 1997 72 285-308 41 1998 77 49-61 42 1991 13 617-628 43 1993 78 43-49 44 1998 45 449-459 45 1999 81 281-293 46 2001 61 83-89 47 2001 19 3 3 430-442 48 2003 33 1291-1302 49 2000 159 238-251 50 2004 90 6 6 1378-1386 51 1999 72 119-124 52 1982 56 135-144 53 1984 6 371-390 54 2004 97 163-176 55 1997 83 82-86 56 1995 48 323- 332 57 1999 17 362-368 58 2000 92 15-23 59 1997 19 435-445 60 2002 XXIII-XXVIII 61 1996 37-39 62 2002 153 707-712 63 1988 8 2 2 62-67 64 2004 113 1 1 30-37 65 1999 83 123-135 66 1999 21 201-210 67 2001 100 21-32 68 2000 22 13-20 69 1995 25 269-273 70 1994 80 107-119 71 2001 87 5 5 1095-1103 72 1998 63 37-44 73 2000 16 8 8 333-339 74 2003 114 1-13 75 1996 54 83-90 76 1998 28 739-746 77 1993 23 451-462 78 1999 84 259-273 79 2000 16 3 3 95-101 80 2002 104 217-228 81 2004 56 853-868 82 1987 27 4 4 359-366 83 1987 385-397 84 1995 25 4 4 511-521 85 2003 47 221-225 86 2005 30 203-211 87 2004 119 2-3 2-3 223-235 88 2001 32 463-473 89 2003 111 333-342 90 1998 62 273-278 91 1999 2º 430-458 92 1990 35 189-193 93 2004 34 1347-1353 94 2004 22 4252-4261 95 1988 59 125-139 96 1984 16 43-54 97 1995 25 1271-1272 98 1994 108 351-357 99 1997 19 447-453 100 2000 120 S63-S72 101 2000 88 61-72 102 1999 82 145-159 103 2000 89 79-94 104 1992 10 385-409 105 1999 29 1053-1063 106 2000 160 177-191 107 1994 58 152-155 108 1996 60 1-6 109 1993 54 94-101 110 1987 7º 232-238 111 1995 60 69-81 112 1999 a 29 51-56 113 1999 b 67 89-92 114 2002 124 553-560 115 1994 8 167-174 116 2001 23 527-531 117 1999 81 137-148 118 2005 1722 293-303 119 1993 a 23 7 7 925-930 120 1993 b 54 244-246 121 1999 162 245-253 122 1966 27 121 121 1645-1648 123 2001 2º 19-22 124 2002 104 327-338 125 2003 76 481-489 126 2001 23 419-426 127 1995 58 232-237 128 1996 60 138-143 129 1999 29 155-164 130 2003 19 9 9 417-423 131 1983 34 305-309 132 1985 63 273-281