Introduction

Gastrointestinal nematodes (GINs) pose a major threat to the productivity of small ruminants, and the economic impact inflicted by these parasites is quite substantial throughout the world (Barger and Cox 1984; Larsen et al. 1995; Campos et al. 2009). For example, losses due to GINs are over AUD 400 million annually only in Australia (Sacket et al. 2006). A number of GINs (e.g. Haemonchus spp., Trichostrongylus spp. Teladorsagia spp., Cooperia spp. Nematodirus spp. and Oesophagostomum spp.) are known to cause significant morbidity as well as mortality in small ruminants. Among these GINs, Haemonchus (H.) contortus is prevalent in tropical, subtropical and temperate regions, especially under warm and wet conditions (Jabbar et al. 2008; Paraud et al. 2010; Khan et al. 2010). It is a highly fecund and voracious blood-sucking parasite of the sheep/goat abomasum and causes significant production losses, especially in growing lambs due to haemorrhages, anorexia, depression, severe chronic anaemia, loss of condition and eventually death of the affected animals (Allonby 1975; van Wyk and Malan 1988; Overend et al. 1994; Miller et al. 1998; Amarante et al. 1999a; Gauly et al. 2002; Notter et al. 2003).

Over the years, anthelmintics have played an integral role in the control of GINs; however, the increasing resistance of H. contortus as well as other GINs to anthelmintic treatments (Saddiqi et al. 2006; Saeed et al. 2010; Cezar et al. 2010; Sargison et al. 2010; Kamaraj et al. 2011), concerns over possible chemical residues from anthelmintics (Lumaret et al. 1984), and the cost of treatment threaten the sustainability of using anthelmintics to control GINs. Therefore, alternative control strategies are being sought, which will lessen the dependence on anthelmintics and reduce the cost of parasite control. One of the options to control GINs is to evaluate or breed sheep that are tolerant to these parasites (Miller et al. 1998; Kemper et al. 2009). A plethora of information is available for the variation (within and between breeds) in sheep/goat resistance to GINs. The selection of these animals for the resistance against GINs is known to be effective only in some livestock rich countries, such as Australia, USA, New Zealand, etc. (Barger 1989; Bisset and Morris 1996; Woolaston and Baker 1996; Miller et al. 1998). In the light of existing literature, this paper reviews the diversity in resistance of various small ruminant breeds against GINs particulary with reference to H. contortus.

Tribulations associated with the conventional control methods for GINs

Anthelmintics have played a pivotal role in the control of highly fecund parasites such as H. contortus (Woolaston and Baker 1996); however, there are a number of problems associated with the use of anthelmintics against GINs, viz., the development of resistance in GINs against almost all groups of anthelmintics (Waller 1994; Jabbar et al. 2006; Cezar et al. 2010), anthelmintic cost, non-availability in remote areas of the developing countries and the limited scope in many communal pastoral systems (Haile et al. 2002). Among all these issues, anthelmintic resistance is the single most important problem throughout the world (Miller et al. 2006; Saddiqi 2005, 2006; Jabbar et al. 2006, 2008; Königová et al. 2008; Cezar et al. 2010). This particular problem mandates that the future control of GINs should be an integrated and multi-faceted approach.

In addition to chemotherapeutics, other GIN control methods have not proved to be reliable as well as reproducible. For example, methods relying on rotational grazing (Barger 1999) are inadequate in communal grazing systems. Similarly, development and maintenance of resilience/tolerance through nutritional management (Burke et al. 2009a) on a large scale in many parts of the world is not possible, whereas the use of copper oxide wire particles to control GINs is still under investigation (Vatta et al. 2009). Ethnoveterinary medicines have shown some potential as anthelmintics (Iqbal et al. 2005, 2007), but they cannot be marketed until appropriate dosage, toxicity are active ingredients with mode (s) of action are known, which would require a reasonable period of time and resources.

The emergence of genetically mediated resistance to anthelmintics in GINs (Overend et al. 1994) and increasing environmental concerns (organic farming) have compelled the researchers to search for those nematode control strategies, which are less dependent on chemotherapeutics (Besier and Love 2003). One of such strategies may be the selection of animals that are naturally superior in resistance to GINs.

Resistance and resilience

The term resistance encompasses both passive and active mechanisms that prevent successful parasitism. Passive resistance includes physical or chemical barriers (e.g. cuticle or integument) that deny parasite entry into the body of the host or that provide a physiologically inadequate environment, e.g. pH for the parasite development. Active resistance entails innate and/or adaptive immune responses produced in response to infection (Coustau et al. 2000). Resistance (referred herein) is the ability to suppress the establishment and/or subsequent development of infection (Albers et al. 1987), whereas resilience (or tolerance) is the ability of the host to survive and be productive in the face of parasite challenge (Clunies-Ross 1932; Woolaston and Baker 1996). McClure (2000) described host resistance as the ability of an animal to eliminate a parasitic infection and to prevent reinfection by utilising both innate (non-specific) and acquired (learned and parasite-specific) immune responses. Resistance and resilience are not necessarily manifested at the same time, and the start may vary depending not only on the breed, but also on the location and possibly the level of challenge infection.

Types of immune response against GINs

The immune mechanisms responsible for resistance are not fully understood (Meeusen 1999; Kemper et al. 2009; Andronicos et al. 2010); however, it is generally agreed that the immune system plays a key role in the manifestation of inherited resistance (Wakelin 1985) and is polygenic in nature (Kemper et al. 2009). It is believed that GINs induce a Th type 2 (Th2) antibody-dependent responses (Svetic et al. 1993; Andronicos et al. 2010), whereas intracellular parasites induce a Th type 1 response. Th2 responses involve the influx of inflammatory cells into the local mucosa and generation of immunoglobulin (Ig) E antibody (Harrison et al. 1999; Huntley et al. 2001). Locally, there is an increase in the number of mast cells, eosinophils, specific antibodies, mucus production and inhibitory substances (Huntley et al. 1992; Pfeffer et al. 1996; Harrison et al. 1999; Bricarello et al. 2004). Initially, Th2 cytokines, including a number of interleukins (IL) (IL-4, IL-5, IL-9, IL-10 and IL-13), appear in the mesenteric lymph nodes and Peyer’s patches and then go to spleen following the systemic circulation. Functional immunity to GINs does require expression of IL-4 (Urban et al. 1992; Loukas and Prociv 2001) as demonstrated in studies where anti-IL-4 and receptor antibodies and deficiencies in IL-4 signal transducer and transcriptional activator blocked immunological control leading to increased worm burdens (Urban et al. 1991). IL-10 is an important immunomodulatory cytokine, and it has its own importance in the maintenance of pro-inflammatory responses under control at the sites of infection (Li et al. 2006) and is usually higher in resistant animals. IL-10 has been considered a powerful anti-inflammatory cytokine with the ability to inhibit the synthesis of pro-inflammatory cytokines, such as tumor necrosis factor alpha, to suppress the effect on Th1 lymphocytes/T-cell activation and to decrease antigenic appearance. In addition to the above mentioned immune mediators, progenitor B cells, mucosal mast cells and eosinophils infiltrate the gut by chemotaxis where they proliferate and mature in response to the stimulatory signals from the Th2 cytokines and parasite antigens. It is well known that GINs have high genetic variability (Gilleard and Beech 2007), which is necessary for rapid adaptation. Mouse models have indicated that host immune function can select sub-populations of GINs (Su and Dobson 1997). The prospect of adapting GINs to resistant sheep cannot easily be dismissed (Kemper et al. 2009).

The first line of defense is gut-associated lymphoid tissue, which is the largest extrathymic site for lymphocytes. This lymphoid tissue responds by processing the antigens released by GINs and by initiating a cascade of specialised immune responses. Although close evolutionary relationships exist in the family Trichostrongylidae, different species face variable immune responses. In addition, different responses have been observed against the adult and larval stages of the same parasite (Balic et al. 2000). Immunity against adult stages of GINs is manifested as expulsion of adult worms. Rapid expulsion may involve the activity of several cell types, including mucosal mast cells, globule leukocytes (Huntley et al. 1987) and goblet mucosal cells (Khan et al. 2001), although the relative involvement of these cell populations and magnitude of their responses has often made the interpretation difficult. Other mechanisms involving adult worms are changes in the morphology and reduction in the fecundity of the female worms. In the case of H. contortus, expulsion of worm is facilitated through IgE/mast cell mediation in which IgE-sensitised mast cells release histamine and eosinophils are the basis for delayed rejection (Balic et al. 2002). Developmental arrest and failure of infective larvae to establish infection are common during the larval invasion (Balic et al. 2000). Wakelin (1978) proposed that genetically determined resistance to H. contortus consisted of both immunological and non-immunological components and a strong immunological component acted at the level of parasite establishment. It is believed that the abomasal lymph nodes also have their own significance in immunised kids (Perez et al. 2003) infected with single or multiple doses of H. contortus. Larvae of H. contortus apparently fail to reach their predilection site in the gastric pits of immune sheep, and over 90% are expelled within 48 h of infection (Miller et al. 1983).

Removal of GINs

The mechanisms by which nematodes are eliminated are unclear. Despite the significant efforts over the last three decades, it is still not possible to define exactly the immune response(s) remove parasites from the host owing to the high degree of complexity and redundancy among various immunological responses. Worms might be damaged directly by the effector cells and molecules of the immune system (Viney 2002). Alternatively, they might be damaged by the physiological stress of their efforts to resist attack. Thus, the interaction between worms and the host immune response can be considered as the interaction of opposing forces in that nematodes actively attempt to persist in the face of attack by the host immune response. At extremes, the outcome is either that the infection persists obviously or that the worms are killed or expelled (Amarante and Amarante 2003). An intermediate outcome is that infection persists, but features of nematode survival and fecundity are reduced below some maximum (Viney 2002). Therefore, an alternative view of nematode infections is that the reduction in the fecundity and survival of infections in immune hosts is, at least in part, a result of the energy expended by a parasite to protect itself against immune attack (Viney 2002). It has been observed that the role of IL-4 may be replaced by IL-13 in some GINs (Finkelman et al. 1999). Others have shown that anti-IL-5 and anti-IL-5 receptor mAB ablate IL-5 and the accompanying peripheral blood and tissue eosinophilia in some hosts (Korenaga et al. 1991) but not others (Urban et al. 1991, 1992). In case of Trichostrongylus colubriformis, an increase in the number of crypt goblet cells in the jejunum was also reported (Angus and Coop 1984) in relation to the expulsion of the worm.

The role of reactive oxygen and nitric oxide to kill nematode has also been reported in vitro (Kotze and McClure 2001), and its importance in in vivo expulsion has been incidental but has not been defined in other studies (Smith and Bryant 1989; Bensmith et al. 2002). Nitric oxide has also been reported as being cytotoxic to a range of parasites (Cloasanti et al. 2002), but according to Lawrence et al. (2000) and Ganley et al. (2001), it has a little impact on the course of nematode elimination. Nitric oxide and reactive oxygen mediate many functions including pro-inflammatory effects (Guzik et al. 2003) and modification of mucus composition/production (Shao and Nadel 2005). Genetically, transcripts of inducible NOS2A that function in the production of reactive oxygen as well as reactive nitrogen have been observed (Ingham et al. 2008).

Immune response versus host-associated physiological factors

Resistance of animals to nematode parasites is influenced by a number of factors, which are detailed given below.

Age

It is believed that lambs are less resistant to infection than adult sheep. In some studies, it was noticed that age has no major impact on resistance of some (exotic) breeds where immune competence appeared at an early age (Courtney et al. 1985; Bahirathan et al. 1996). On the other hand, domestic lambs were better able to resist challenge after puberty. Schallig (2000) demonstrated that lambs under 6 months of age were more susceptible to infection than older sheep. It was also noted that peripheral blood eosinophils and mast cells in the abomasum of older compared with younger lambs were high. Kosi and Scott (2001) reported that the younger animals were deficient in Th2 immune response.

Reproductive status

Around parturition, ewes are more susceptible to infection due to the relaxation of immunity, which normally affects the existing adult worm population and/or the mechanism of expulsion (Sykes 1994), a phenomenon called peri-parturient rise (PPR). PPR is responsible for contamination of pasture and new-borne lambs are exposed to this infection. Huntley et al. (2004) reported that there were changes in the population of inflammatory cells during the PPR. It has also been found that ewes with twins show a higher PPR than ewes with singles (Bishop and Stear 2001). The role of PPR in the resistant breeds of sheep is still not clear (Courtney et al. 1984; Zajac et al. 1988; Miller et al. 1998).

Sex

Male sheep are known to be more susceptible to GINs than female sheep as a result of both natural and experimental infections (Barger 1993). However, this difference was not present before puberty (Courtney et al. 1985). Thorson (1970) proposed that in the female, natural resistance increases dramatically after puberty, whereas in the male, it develops gradually from birth to adulthood. Windon and Dineen (1981) found greater responses in female than in male lambs that were vaccinated with irradiated larvae of T. colubriformis before puberty. Greater resistance in ewe lambs than ram lambs after a secondary challenge infection was reported by Yazwinski et al. (1981) and Diaz-Rivera et al. (2000). Klein (2000a) also found that male Rhön lambs had higher faecal egg count (FEC) compared with those of female lambs. The susceptibility of male animals to infections may be due to sex steroids (androgens), which modulate several aspects of host immunity (Klein 2000a,b), and hence, these are often more susceptible to infection and carry higher parasite burdens in the field. It is becoming increasingly more apparent that, in addition to affecting host immunity, sex steroid hormones alter genes and behaviours that influence susceptibility and resistance to infection (Klein 2000a).

Nutrition

Nutrition is a vital factor in the development of immunity against GINs in sheep. The host immune response is under genetic control and is greatly influenced by the quality of nutrition. Sheep kept in good nutritional condition with a high metabolisable protein supply are known to show greater resistance to infection (Wallace et al. 1996; Coop and Kyriazakis 2001). Use of supplements is often considered to be compulsory in animals grazing poorer quality forages or when forage growth is inadequate (Burke et al. 2009b). Torres-Acosta et al. (2004) found that in tropical Mexico, supplementary feeding improved resilience and possibly resistance of browsing Criollo kids against natural infection during the wet season. Vanimisetti et al. (2004) demonstrated that differences among breeds (Dorset and Dorper sheep) to cope with infection were decreased when animals were maintained on a higher plane of nutrition, and such differences were less apparent especially when infection levels were low. Better nutrition is known to have a powerful modulatory influence on the host responsiveness, and such effect has been demonstrated for H. contortus where an increased level of IgA production was associated with impaired parasite growth and fecundity (Amarante et al. 2005). Contrarily, relaxation of resistance can occur as a consequence of dietary changes that may lead to an increase in infection and FEC and, consequently, higher pasture contamination (Peña et al. 2000).

Mineral supplementation a significant role in the natural resistance against GINs as deficiencies of iron, molybdenum, copper and zinc have been associated with higher worm burdens (Koski and Scott 2003), which indicates that there may be an optimum trace element level in the diet above and/or below which the parasite has an advantage (Koski and Scott 2003). It has also been seen that each trace element behaves differently with regards to its impact on each type of GINs (Koski and Scott 2003). Nevertheless, these concepts need further investigations for the confirmation of the role of trace elements in the resistance against GINs.

Breed

The ability of sheep to acquire immunity and express resistance varies substantially among and within breeds and is controlled through the genetics of animals. Some breeds of sheep such as Florida Native (Courtney et al. 1985; Amarante et al. 1999a,b), St. Croix (Zajac et al. 1990; Gamble and Zajac 1992), Red Maasai (Mugambi et al. 1996, 1997; Wanyangu et al. 1997) and Gulf Coast Native (Bahirathan et al. 1996; Miller et al. 1998) are considered to be resistant to GINs. It is believed that the breed differences in FEC and worm burden are under genetic control, and these are also heritable (Whitlock 1955; Good et al. 2006). This greater resistance is the result of a complex reaction involving a more favourable response in terms of haematological, biochemical, parasitological and immunological parameters. Watson et al. (1994) attributed a similar immune unresponsiveness in Merino sheep to lower numbers of CD4+ and CD8+ cells and lower levels of specific antibodies. Similarly, in resistant flock of Creole kids, levels of B lymphocyte were lower in susceptible animals, but levels of circulating sub-population cells (LTCD4+ and LTCD8+) were relatively higher in susceptible animals after fifth week of infection that may be due to localisation of activated cells in abomasal mucosa of resistant animals in case of haemonchosis (Bambou et al. 2009).

History of resistant sheep and goats breeds

Breeding or evaluation of genetically resistant livestock is a potentially alternative means of controlling GINs. Since mid-1930s, there have been many reports of substantial variations among sheep breeds in resistance, particularly to H. contortus, Teladorsagia circumcincta and T. colubriformis. Gray (1991) and Baker et al. (1992) comprehensively reviewed the breed resistance efforts. For about 20 years after World War II, the genetic association between sheep breeds and H. contortus was studied in USA and Europe. Since the early 1970s, these studies have received greater emphasis in Australia, where anthelmintic resistance has become a widespread problem. A number of reports have demonstrated variation among different breeds of sheep, and such differences have also been reported in different individuals of the same breed (Gregory et al. 1940; Whitlock 1955; Jilek and Bradley 1969; Gamble and Zajac 1992; Bishop et al. 1996; Miller et al. 1998; Baker et al. 1999; Woolaston and Windon 2001). Most of the studies for examining resistance to GINs have largely focused on H. contortus, which is the primary GIN in tropical or warmer climates, and much less on Teladorsagia and Trichostrongylus (Ross 1970; Gruner et al. 2002), which predominate in temperate environments. Various breeds of small ruminants have been evaluated for their genetic potential to resist the GINs infection (Tables 1 and 2). A number of studies have been carried out to study the genetic variation in resistance to GINs as well as its utilisation for selective breeding (Woolaston et al. 1991; Baker et al. 2001; Mirkena et al. 2010). These reports involved primarily sheep; however, very few reports are also available for goats. Within and between breed genetic variations in resistance to GINs, however, is also a reality in goat breeds. For instance, Small East African goat of Kenya was found more resistant than Borana (Baker and Gray 2004).

Table 1 Selected references of comparative studies of resistant and susceptible sheep breeds for their genetic potential to GINs
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Table 2 Selected references of comparative studies of resistant and susceptible goat breeds for their genetic potential to GINs
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Breeding of resistant and susceptible breeds

The process of choosing superior animals and using them for breeding is the basis of genetic-based stock improvement and is often called ‘selective breeding’ or ‘selection’. A number of studies have been carried out to select and breed resistant animals in order to have animals having superior genetic potential to resist GINs; however, these efforts resulted in variable outcomes. For example, F1 offspring of resistant and susceptible breed crosses have shown an intermediate response to infection in most of the cases (Amarante et al. 1999a; Li et al. 2001; Amarante et al. 2009). Amarante et al. (1999a) observed that the cross between F1 (1/2 Florida Native × 1/2 Rambouillet) and Rambouillet lambs resulted in animals, which were more susceptible to H. contortus challenge than Florida Native lambs. Barras (1997) and Li et al. (2001) showed that an F1 line (Suffolk and Gulf Coast Native) had intermediate infection levels. Gruner et al. (1992) reported that F1 offspring from Romanov (resistant) and Dorper crossbreeding appeared to be susceptible to parasite infection. Mugambi et al. (2005) demonstrated that backcross lambs differed in their levels of resistance as well as resilience with the 75% Red Maasai superior [(lower FEC and higher packed cell volume (PCV)] to the 75% Dorper.

By increasing the proportion of resistant genes, efficiency of breed resistance against GINs can be improved. For example, Baker et al. (2003) reported that by increasing the proportion of Dorper gene in Dorper (susceptible) × Red Maasai (resistant) cross, the lambs exhibited reduced resistance (i.e. increased FEC) and resilience (i.e. decreased PCV). Notter et al. (2003) reported that 4 month old St. Croix × Barbados Black Belly lambs had lower FEC and had higher PCV than lambs of 50% Dorset, 25% Rambouilett and 25% Finn sheep breeding in response to an artificial infection. The Barbados Black Belly lambs were much more resistant to H. contortus infections than the INRA 401 lambs, their crosses giving a similar response after the challenge dose. This resistance was extended to T. colubriformis and at a lesser extent to Teladorsagia circumcincta (Gruner et al. 2003). F1 animals produced by crossing Suffolk or Ile de France (susceptible breeds) with resistant Santa Ines resulted in cross with a superior resistance potential to GINs infections similar to that of the parental-resistant breed (Amarante et al. 2009). They also harboured a higher proportion of worms at the L4 stage and had shorter female worms. The drawback of resistant breeds is low productivity as compared to those selected for other traits (higher weight gain and better meat quality). However, cross-breeding of resistant and susceptible can solve this problem of farming community as cross bred animals show heterosis in performance (Amarante et al. 2009). Comparison of crosses of resistant and susceptible with pure bred breeds is summed up in the Table 3.

Table 3 Crosses of sheep breeds evaluated for genetic potential to GINs
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The magnitude of the differences between sires can be the same as the largest differences between breeds (Gray et al. 1987). Many of the breed differences reported could reflect a single sire effect and hence should be interpreted cautiously. Resistant breeds and their ancestral populations in Western Africa (Bradford and Fitzhugh 1983) are a particularly significant genetic resource for the development of parasite-resistant lines of sheep. The Katahdin is a hair-type sheep developed in the USA from West African hair sheep and wooled British sheep (Parker et al. 1991). The Dorper was developed in South Africa from the Dorset Horn and Blackheaded Persian for use in arid regions under both extensive and intensive management (De Waal and Combrinck 2000). Both breeds have good production capabilities and do not require shearing, but Dorpers in Kenya were more susceptible to parasitism than Red Maasai (Baker et al. 1999).

Markers/parameters of genetic resistance

Successful selection of animals for genetic resistance is related to the markers, which are used and depends on the correlation with the trait, heritabilities and cost of testing. A number of phenotypic traits such as FEC, worm burden, serum antibodies, peripheral eosinophilia, pepsinogen, fructosamine and plasma albumin concentration have been used to identify animals with increased resistance to infection (Beh and Maddox 1996; Dominik 2005). Of these traits, the principal and most practicable measurement used to evaluate resistance in small ruminants undergoing similar parasite challenge is FEC. FEC has been proposed as the only proven way of selecting sheep for parasite resistance in many breeds (Woolaston 1992; Bisset and Morris 1996). In case of Haemonchus and other related blood feeding parasites, haematocrit may be a useful marker (Taylor et al. 1990). Both FEC and PCV are traits of value, as FEC is an indirect measure of resistance and PCV is an indicator of resilience, i.e. the ability of the animal to withstand the effects of infection. In ideal circumstances, it would be desirable to select for both decreased FEC and increased PCV. Evidence for genetic control of these traits comes from the comparison of different sheep/goat breeds and statistical estimates of the heritability of resistance from studies within breeds. IgA, IgE and IgG concentrations, mast cells, eosinophils, globule leucocytes and concentration of histamine can also be used as markers to evaluate genetic potential of small ruminant breeds against GINs (Urban et al. 1992; Woolaston and Baker 1996; Burke and Miller 2004).

The reliability of individual trials is often questioned, but useful information can be obtained from combining data from large numbers of trials (Woolaston and Baker 1996). Miller et al. (2006) proposed that in the absence of infection, quantitative trait loci (QTL) may enable the selection to be performed, but the trait selected for would be dependent upon the results that are found.

Resistant genes

Elucidation of mechanisms that underlie genetic variation in resistance to GINs is critical for the identification of genetically resistant breeding livestock (Gill et al. 2000). Determination of specific genes associated with resistance to GIN infections is important for a better understanding of genetic resistance, biological pathways as well as the biology of the host response to GINs especially against H. contortus and T. colubriformis (Beh and Maddox 1996; Andronicos et al. 2010). A successful search for resistance/susceptibility genes is dependent upon having a number of resources available. These resources include an animal population with a carefully defined pedigree, an accurate measure of the trait of importance and the tools and reagents to map the trait on the genome. When the genes for resistance and their functions are identified, this will provide valuable insights into the molecular basis of the host resistance to GINs. Microarray studies have been very helpful to detect genetic variability between resistant and susceptible animals (Diez-Tascon et al. 2005). Following infection, gene expression differs between resistant and susceptible breeds or between infected and noninfected animals (Mackinnon et al. 2009). Susceptible animals appear to be generating a hypersensitive immune response to non-nematode challenges. The gastrointestinal tract of susceptible animals is under stress even in the absence of GINs (Keane et al. 2006).

Albers et al. (1987) postulated that one ram ‘the Golden Ram’ carried a major single resistance gene having a function to decrease FEC by an amount equivalent to two standard deviations. The relationship between genes of the ovine major histocompatibility complex and resistance to H. contortus remained under study, and it has been shown that this is the densest region in the genome that is having significant links with disease (Siva Subramaniam et al. 2010). The interferon gamma (IFN-γ) gene has received much attention because of its proposed association with nematode resistance. Outteridge et al. (1986) reported an association between lymphocyte surface antigens and resistance to T. colubriformis. It was speculated that QTL for resistance to Heligomosoides polygyrus in mice has homologs for resistance to Trichostrongyle infections in domestic livestock (Iraqi et al. 2003). Using microsatellite, Coltman et al. (2001) reported a significant association within the IFN-γ gene in feral sheep. Using the same approach, other authors also found various associations in or near the MHC (Schwaiger et al. 1995). A number of studies have been undertaken to identify QTL for resistance to GINs in sheep (Beh and Maddox 1996; Crawford 2001), which are summarised in the Table 4.

Table 4 Possible reported genes relating to resistance in different animals
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Currently, putative genes responsible for host response to infections are mapped using dense single nucleotide polymorphism markers, and then, these are studied for their functional significance. The results from such experiments suggest that genes can be detected which are differentially expressed between ‘resistant’ and ‘susceptible’ sheep (Diez-Tascon et al. 2005). Furthermore, it is anticipated that the sequencing of whole genomes of the resistant and susceptible breeds of animals using next-generation sequencing (Bennett et al. 2005; Margulies et al. 2005; Ondov et al. 2008) would be able to identify the genes and hence the genetic markers for the rapid identification of animals resistant to GINs.

Artificial vs. natural infections

Resistant status of sheep and goats can be evaluated by both artificial and natural infections, and both approaches have advantages as well as disadvantages. Natural infection is better than artificial infection as the heritability of infection (based on FEC and PCV) was greater with natural infection (Miller et al. 2006). Sayers (2004) showed that breed differences in susceptibility were evident when a similar infection challenge was administered to lambs of different breeds; however, artificial infection may under- or over-estimate the true difference between breeds and individuals due to grazing behaviour, which may influence total worm burden. The advantage of measuring immune parameters after artificial infection also circumvents the variability from environmental and management factors. The disadvantage of giving all sheep the same number of larvae is that it would not reflect differences in larval intake during natural infection (Barger and Dash 1987). According to Amarante et al. (2009), selection of animals having superior genetic potential to resist GINs could be more feasible during natural pasture trials as Mugambi et al. (2005) noted that the Red Maasai showed better response to natural infection compared with artificial challenge with H. contortus. A number of recent reports suggest that both natural and artificial GIN infections for the evaluation of small ruminant breeds for their resistance have been used and both types of experimental infections have given reliable results depending upon the objectives of the experiment (Saddiqi et al. 2010a,b).

Primary vs. secondary infection

Evaluation of animals for their resistance to GINs can be judged by giving primary and secondary infections. In secondary infection, animals show relatively better response to nematode infection (Gruner et al. 2003; Saddiqi et al. 2010b), which may be attributed to the development of immunity with growing age (Good et al. 2006) and due to priming during primary infections. It was reported that infecting the lambs, when they were 7- instead of 3.5 months old, significantly lowered egg excretion of nematodes in the F1 (Black Belly × INRA 401). Gulf Coast Native lambs have also been reported to develop resistance to H. contortus during their first exposure to infection (Bahirathan et al. 1996). Acquired immune animals regulate the worm length, whereas adult ewes regulate both fecundity and worm burdens as reported by Stear et al. (1999) in Scottish Blackface with Teladorsagia circumcincta infection. Previously infected animals have been reported to have activated Th2 cells (Finkelman et al. 1991) in secondary infection.

Possible consequences genetic resistance and its influence on epidemiology

The use of genetically resistant animals influences the epidemiology of GINs, which can lead to reduction in the seasonal peaks in parasite burden, pasture contamination and re-infection rate (Barger 1989; Bisset et al. 1997). Such reduction in reinfection rates would result in the improvement of both animal health and productivity (Bishop and Stear 1999). This selection is based on the fact that nematode distributions are overdispersed where most hosts carry few parasites, while a few heavily infected hosts harbor a large proportion of the total parasite population (Amarante et al. 1998; Stear et al. 1998). This pattern of distribution occurs because the immune response is not uniform among the animals of a particular flock. It has also been shown that sheep selected for resistance to H. contortus also showed resistance to T. colubriformis infections with both artificial (Woolaston et al. 1990) and natural challenges (Gray et al. 1992), which indicate that sheep resistant to one species may genetically be resistant to the other (Gruner et al. 2004b). These findings suggest that by selecting sheep for high responsiveness to a certain species of nematodes, one can also achieve a substantial improvement of resistance against other species (Sréter et al. 1994).

Prospects of developing genetically resistant breeds

Small ruminants that are resistant to infection should be considered for breeding programs in many regions where pathogenic nematodes, like H. contortus, can develop on pasture and infect animals throughout the year. A large number of countries are yet far behind in the evaluation of genetic potential of small ruminants against GINs, and this trait is mostly ignored in breeding program. Selection of resistant animals within breed and/or incorporation of resistant sires into breeding programs are the available options (Woolaston and Baker 1996; Bisset and Morris 1996). Breeding/evaluation of genetically resistant stock between and within breed is a sustainable strategy, which has been used successfully to establish flocks of sheep with high level of resistance in some small ruminant’s rearing countries like Australia and New Zealand (Albers et al. 1987; Baker et al. 1991; Woolaston and Baker 1996). The incorporation of the resistant animals into production schemes in other livestock rich countries would be a valuable adjunct in order to control GINs like H. contortus. Crossbreeding of resistant sheep with any of the susceptible breeds could be helpful to increase production and degree of infection resistance particularly against H. contortus and T. colubriformis (Amarante et al. 2009); however, any breeding scheme designed to increase resistance/tolerance against parasites must be subjected to a cost benefit analysis (Albers and Gray 1986). If anthelmintics fail because of genetic adaptation by the parasite, then breeding for resistance becomes a more favoured solution as in current situation.

Genetic selection could extend the useful life of effective anthelmintics slowing development of drug resistance. In short, genetic selection will be helpful in (1) the management of anthelmintic resistance, (2) in areas of subsistence farming where anthelmintics are either unavailable or costly, (3) breeding sheep for low worm burden is imperative for small ruminant production system as it regulates the worm life cycle and lessens pasture contamination and (4) for the vaccine development. Breeding sheep for low FEC/worm burden should therefore be an integral part of sustainable worm management on farm for small ruminants. The ultimate objective is to increase production and improve the meat industry.