Genetic resistance to haemonchosis in sheep

ParasitologyToday,voL 3, no. 8, 1987

Focus

253

Genetic Resistance to Haemonchosis in Sheep G,D. Gray

Parasitic nematodes cause huge economic losses to the domestic livestock industry. Control requires skilled farm management and heavy use of anthelmintics, but breeding for resistant animals has long been held a possibility. For about 20 years after World War II, the genetics of association between sheep breeds and Haemonchus contortus - the main parasite of importance in sheep - w a s studied in the USA and Europe. Since the early 1970s, however, such studies have received greater emphasis in Australia, where anthelmintic resistance has become widespread, In this article, Douglas Gray discusses the background to breeding progrommes for resistance to hoemonchosis - paying homage to the 'Golden Ram', o Merino believed to have carried a single major gene for immunological resistance to Haemonchus and Trichostrongylus. To most of Australia's 150 million sheep (I 984 figure), Haemonchus contortus and other internal parasites are a major threat. H. contortus (Fig. I) is a blood sucking parasite of the abomasum, causing haemorrhages and severe chronic anaemia in affected animals. Control depends heavily on anthelmintics but resistance to these drugs s now widespread ~. In 1984, the estimated cost of controlling sheep nematodes was A$50m, with lost wool production still reaching A$400m (Ref. 2). In the same year the total value of Australian wool exports was A$2400m (Ref. 3). In other words, one in seven bales of wool were being embezzled by worms at the point of production. If organized crime was involved in a similar racket, hundreds of millions of dollars

would be spent on law enforcement. Investment in research on the genetics of parasitism has been modest by comparison but has been sufficient to assessthe prospects of breeding sheep with high levels of resistance. In Australia, infection with Haemonchus alone occurs rarely; Tnchostrongylus and Ostertagia infections are often concurrent and contribute significantly to lost production of wool and meat. Plansto breed animals resistant to infection must therefore consider all three types of nematode, but in experimental work the emphasis is on Haemonchus because of the highly predictable egg output which follows single artificial infection (usually expressed as eggs per gram of faeces or EPG) and its high correlation with anaemia caused by the blood-

Fig. I. Head ofHaemonchus contortus, the main parasite of sheep (courtesyof Dr C.J. Nicholls and ProfessorD.L Lee, University of Leeds). ~)1987, ElsevierPublications,Cambridge0169~7581871502.00

sucking activity of the nematode in the abomasum. This anaemia is usually measured by a decline in blood packed cell vo!ume (PCV).

Genetic Control of Haemonchosis Resistance

Resistance of infection with Haemonthus has been expressed using one of, or a combination of, three traits: numbers of adult worms of slaughtered sheep; egg output (EPG); and anaemia (PCV decline). Evidence for genetic control of these traits comes from the comparison of different sheep breeds and statistical estimates of the heritability* of resistance from studies within breeds. Breed differences can be substantial. For example, Red Masai sheep achieve higher levels of IgA and inhibit establishment of larval H. contortus to a greater extent than Merinos 4,s. Similarly, Rambouillet/British breed crosses show higher resistance than Florida Native or St Croix 6. Thus, substantial gains in resistance could be obtained simply by replacing a susceptible breed with a resistant breed. But in the examples given, the immediate improvement in resistance would be associated with highly undesirable changes in meat and wool characteristics and would be unrealistic in many production systems. Certainly in Australia, where these breeds are not available, their introduction to Merino flocks would necessitate an expensive and long term programme of interbreeding to remove undesirable traits 7,8. Studies within a breed indicate that resistance of haemonchosis is 'moderately' heritable and the best evidence for this comes from studies carried out in Armidale. By single sire mating of 157 Merino rams with randomly selected ewes from the same flocks, resistance (reduction in EPG) and PCV were measured in 1583 offspring. The heritability of EPG reduction after artificial infection in 18month-old male offspring was 0.27 ___O. 13 (Ref. 9), and 0.34 4- O. I0 (Ref. I0) in 5-8month-old lambs of mixed sex. Similar heritabilities were found for PCV decline. The term 'moderate' here is possibly misleading as similar heritabilities are found for fleece weight and weaning weight for *For a primer on the statistics of heritability, see 139 (May, 1987),

Parasitol%oyToday3, p.

254

Parasitology Today, vol. 3, no. 8, 1987

Fig. 2. The Golden Ram, a Merino that may have carried a single major gene for immunological resistance to Haemonchus and Trichostrongylus.

which selection has been highly successful. By inference, these experiments indicate that selection for parasite resistance could be effective and a prediction of the rate of improvement can be made 8. With a heritability of 0.3, a variation in resistance within a flock (coefficient of variation) of 40% and a selection intensity of 5% in males and 30% in females, flock resistance levels would increase by 6% of the flock mean per year. In terms of egg output, EPG levels following artificial infection would be halved after approximately three generations of selection.

Consequencesof Selective Breeding for Resistance Sheep are never exposed to single large doses of infective larvae as used to initiate artificial infections. Thus it is essential that selection on the basis of artificial infection will lead to a corresponding increase in resistance to naturally acquired infections. This has been demonstrated in a selection experiment started in 1978 in which rams and ewes were selected for resistance or susceptibility to artificial infection. The re-

(a) 12

Q.

4 weeksm

9 6

~

sponse to selection was then assessed on the basis of infections acquired while grazing. These selection lines have now diverged sufficiently to indicate that there are common genes which regulate the response to both artificial and natural infections 9. Of equal importance is the effect of selective breeding on primary traits such as meat and wool production. The single breed studies in Armidale enabled genetic correlations between resistance and production traits to be calculated: I In uninfected sheep, there is no genetic correlation between resistance and production traits (measured as liveweight gain, wool growth and fibre diameter). This is important because it predicts that when sheep are bred for resistance, their productivity does not decline. 2 In infected sheep, genetic correlations between resistance and production traits are positive: sheep bred for resistance will produce more meat and wool than non-resistant sheep in a parasitized environment. These predicted benefits of selective breeding have yet to be demonstrated in a selection programme, but as the genetic correlation between productivity while infected and resistance is 30:-60% it may be possible to improve flock resistance by selecting individuals with high productivity while the flock is exposed to infection I°. Progress would be slower than by selecting for resistance alone, but no parasitolo~cal measurements would be required and only two liveweights would need measurement, at the beginning and end of the parasite season. This approach would be akin to natural selection in an endemic environment, which is believed to explain the superior resistance of some indigenous sheep breeds - such as Red

o (D 3

(b) 2OO

L/3 0 12 n

9

Z

6

E

100

& --80 --70 --60 --50 --40 --30 --20 --10

0

Xv//eggs/grom

10

20

30

of faeces

40

50

60

o; V~eks offer Infection

Fig. 3. (a) Frequency distribution of the mean egg output (square root transformed EPG) of groups of lambs from 60 fine-medium wool Merino rams which were each mated with 25 randomly selected ewes. Egg output at four and five weeksafter artificial infection was estimated. The progeny from the "Golden Ram', which is postulated to have had a single major resistance gene, is indicated by the shaded bar. (From Ref. 10, reproduced with the permission of Pergamon Press.) (b) Pattern of egg output in the progeny of the Golden Ram (e ) compared to progeny from three susceptibe rams (o) after artificial infection with H. This low egg counts shown in (a) in the resistant progeny at four and five are result of a delay in egg production. The progeny of the Golden Ram have recently been shown to be resistantto Trichostrongylus infections (Gray and Berger, unpublished).

contortus.

showsthatthe

weeks notthe

Parasitology Today, vol. 3, no. 8, 1987 Masai - to Haemonchus infe~on 4. An associated effect would be the development of animals which are more productive in the absence of infection.

Resistance Genes In the course of the studies in Armidale, Albers et al. io postulated that one ram, the Golden Ram (Fig. 2), carried a major single resistance gene. The effect: of this gene was to decrease EPG by an amount equivalent to two standard deviations (Fig. 3). The presence of this gene has not yet been confirmed by the necessary segregation studies but use of such resistant stock would have an immediate effect on levels of flock resistance I i. The Golden Ram died, aged 15, in the course of conjugation, but sufficient progeny exist for studies to continue. The nature of this putative gene is unknown but preliminary results indicate that its expression is abolished by immunosuppressive therapy (B. Presson and G.D. Gray, unpublished). Haemoglobin type has been postulated as a marker for resistance to Haernonchus 12, with sheep homozygous for haemoglobin A showing fewer effects of parasitic infection compared to those homozygous for haemoglobin B. However, evidence for this is equivocal s,13,14, and studies in Armidale (Albers and Burgess, unpublished) have revealed no significant association. The relationship between genes of the ovine major histocompatibility complex (MHC) and resistance to Haemanchus are under study. There are indications of an association between lymphocyte surface antigens and resistance to Trichostrongylus

colubriformis I5.

Prospects of Selective Breeding for Resistance Any breeding scheme designed to increase resistance to parasites must be subjected to a cost-bene.fit analysis II. This is particularly important where alternative methods of control are available, such as anthelmintics in the case of nematode control. If anthelmintics fail because of genetic adaptation by the parasite then breeding for resistance becomes a more favoured solution. Other alternatives involve radical changes in management such as cattle/sheep/crop rotations. No effective vaccine for gastrointestinal nematodes of ruminants has yet been developed. But is there sufficient evidence to justify expensive breeding programmes for

255 resistance to haemonchosis, or for resistance to be included in existing breeding objectives? More data are required but available evidence seems to justify experimental breeding programmes based on egg counts following artificial infection, natural egg counts, liveweight change during the infection period, or an index combining parasitism and production. Inclusion of unselected lines of sheep would be necessary to enable progress in resistance to be measured against a reference population, and other traits of importance should be monitored, such as fleece weight, fibre diameter, weaning weight, hogget weight, reproductive capacity and resistance to other diseases such as blowfly strike. Selection techniques need improvement, and major genes for resistance should be identified: but for animal breeders, resistance to parasitism, including haemonchosis, is a worthy objective. References

I Waller, P,J.(1986)Agric. Zool. Rev. I, 333-373 2 Beck, T., Moir, B, and Meppem, T. (1985) Q, Rev. Rural Econ. 7,336-343 3 Anon (1985) Q. Rev. Rural Econ. 7, 7 4 Preston, J,M. and AIIonby, E,W. (1978) Vet. Rec. 103, 509-512 5 Preston, JM. and AIIonby, E.W. (1979) Res. Vet. Sci. 26, 134-139 6 Courtney, C,H,, Parker, C.F,, McClure, KE

and Herd, R.P, (1985) Int. J. Parasitol. 15, I 0 I 109 7 Le Jambre, LF. (1978) Host genetic factors in helminth control, in The Epidemiology and Control of Gastrointestinal Parasites of Sheep in Australia (Donald, A D , Southcot~, W.H, and Dineen, J.K., eds), pp. 137-141, CSIRO Divi-

sion of Animal Health, Melbourne, Australia 8 Gray, G.D. et al. (1987) Comparison of within and between breed variation in resistance to haemonchosis in sheep, in Merino Improvement Programs in Australia (McGuirk, B.J., ed,), 528 pp, Australian Wool Corporation, Sydney, Australia 9 Piper, L,R, (1987) Genetic Vanation in Resistance to Internal Parasites, in Merino Improvement Programs in Australia (McGuirk, B.J., ed), 528 pp, Australian Wool Corporation, Sydney, Australia 10 Albers, G.A.A. et aL Int.j. Parasitot, (in press) I I Albers, G.A.A. and Gray, G.D. (1986) Breeding for worm resistance: a perspective, in Parasitology - Q u o Vadit? (Howell, M.J., ed.), pp. 559566, Australian Academy of Science, Canberra, Australia 12 Altaif, K.I. and Dargie, i.D. (1978) Parasitology 77, 161-187 13 Evans, J.V. , Blunt, M.H.Y. and Southcott, W.H, (I 963)Aust.J. Agric. Res. 14, 549-558 14 Riffkin, G.G. and Dobson, C. (1979) Vet. Parasitol. 5, 365-378 15 Outteridge, P.M,, Windon, R.G,, Dineen, J.K. and Smith, E.F. (I 986) Int.j. Parasitof. 16, 369374

Douglas Gray is at the Department of Animal Science, University of New England, Armidale, NSW, Australia.

Guide for Authors Subscriptions Most a~des in Parasitology Today are com- [ ] Personal Subscriptions (I 987, missioned, but unsolicited manuscriptsare welcome, preferably after consultation with the editor from whom detailed instructions to authors are available. I ~ v i o w articles should offer a synthesisof current knowledge in fields of active research; the text should not exceed 3000 words with up to 50 references. Focus articles are short, specializedreviews, commentaries or hypotheses - sometimes based on recent meetings or specialist workshops. The text should not exceed 1500 words with up to 20 references. All articles should be well illustrated,and are subjectto external review. Lette~ to the Editor can offer comment on articles published in Parasitology Today, or other matters of interest. They should be signed by all authors and should state clearly if they are intended for publication. Long and boring letters will be rigorously edited.

12 monthly issues) UK £26.00; USA/Canada US$45.00; Europe 120.00 Dutch Guilders; Rest of World 135.00 Dutch Guilders.

[ ] Library

Subscriptions

(I 987,

12

monthly issuesplus hardcover bound compendium with index) UK, USA, Canada, Europe 435.00 Dutch Guilders; Rest of World 450.00 Dutch Guilders.

[ ] Student

Subscriptions

(1987,

12

monthly issues) UK £18.50; USA/Canada US$31.50; Europe 95.00 Dutch Guilders; Rest of World I I 0.00 Dutch Guilders.(Student Subscriptions must be accompanied by valid proof of student status.) All prices include postage (air delivery outside UK). All subscriptions can be paid by cheque, bank draft or UNESCO coupons. Personaland Library subscripl]onscan also be paid by credit card - Access/Mastercard, Eurocard, Visa or American Express.Subscription orders should be sent to one of the addressesbelow.

ElsevierPublicationsCambridge Elsevier SciencePublishingCo. ElsevierSciencePublishers ElsevierTokyoBranch, 68 Hills Road, JournallnformationCenter, PO Box 548, 28-1, Yushirna3-chome, Cambridge,CB2 ILA, UK 52 VanderbiltAvenue, 1000 AM Amsterdam, Bunkyo-ku,Tokyo l l 3, Japan New York, NY 10017, USA The Netherlands