Examining the stable door after the horse has bolted: Why is EIA such a challenge?
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htimely reminder that a casual approach to a dangerous disease can
ing indifference and complacency in disease control. This isunacceptable. There is a clear need for a better understanding ofthe way the EIA virus evades the immune system so effectively;seroconversion is efcient and forms the basis of serological diag-nosis, but the virus survives in spite of it. If the particular mecha-nisms of immune evasion could be understood the chances ofdeveloping genuine preventative measures would improve signi-cantly. It is therefore satisfying that this issue of The Veterinary
in many disease conditions are a direct result of intracellular oxi-
of peroxides and free radicals that damage all components of thecell, including proteins, lipids, and DNA. The recognised responsesthat arise from oxidative stress form the basis of the pathogenesisif many disease conditions. These include programmed cell death(apoptosis) and even necrosis in the most severe circumstances(Lennon et al., 1991) The natural defences against oxidative stressinclude the physical barriers that restrict free radicals to their sitesof production within cells, enzymes that neutralize dangerous
The Veterinary Journal 192 (2012) 253254
w.elead to considerable loss.Where a disease has no known treatment and where the prog-
nosis is extremely poor, there is a marked tendency to forget ordisregard it; the fact that many countries have supposedly elimi-nated EIA whilst others accept its endemicity, has led to an appall-
dative stress representing an imbalance between the productionand manifestation of reactive oxygen species in the cell and a bio-logical systems ability to overcome the resulting cellular damagewithout causing harm to the body. Disturbances in the normal re-dox state of tissues can cause toxic effects through the productionGuest Editorial
Examining the stable door after the horse
It is an unfortunate fact that research into a disease is only trig-gered when outbreaks that have a signicant nancial impact oc-cur and, as a result, the responses are often frantic and illthought out. Only then are some of the fundamental issues of thecondition brought into public and scientic scrutiny and, all toofrequently, we simply close the stable door after the horse hasbolted or, more particularly, we examine the door to see why thehorse has bolted and then close it (Brangan et al., 2008). Such ret-rospective approaches do little to encourage prospective diseaseresearch and surveillance since there is usually panic, and hasty,irrational, wrong or unjustied decisions are frequently made. Itis unwise simply to accept the dogma that is included in textbookssince that is often based on dubious science from ages past. Withwidespread movement of animals for sport, breeding, leisure orslaughter, it has become increasingly critical that more effort ismade to encourage prospective research.
Equine infectious anaemia (EIA) has been recognised and fearedin Europe since the middle of the 19th century. The disease iswidely distributed worldwide and it remains endemic in someparts of Europe where its geographic proximity to areas wherethe disease is supposedly not present carries a signicant threat.It has very high morbidity and mortality yet remarkably little isknown about it. The most important problem with EIA is that novaccine has proved effective, and even the natural immune pro-cesses seem unable to counter its devastating pathological effects.Although in many endemic regions some affected horses seem ableto survive for years, the majority succumb. A recent outbreak inIreland caused severe damage to the equine industry at a timewhen economic circumstances were already becoming more dif-cult. The events associated with this outbreak opened the debateabout the published facts on the disease (More et al., 2008). Theoutbreak probably arose as a result of infection via a plasma trans-fusion (More et al., 2008) and highlighted the need for proper scru-tiny of the use of biological products. The outbreak was however a
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journal homepage: ww1090-0233/$ - see front matter 2011 Elsevier Ltd. All rights reserved.doi:10.1016/j.tvjl.2011.09.029as bolted: Why is EIA such a challenge?
Journal carries a genuine scientic study that seeks to answer atleast some of the unknown questions on the pathophysiology ofthe disease (Bolfa et al., 2012).
The immune systemmakes use of the lethal effects of oxidants toovercome pathogens by forcing the production of both reactive oxy-gen species and reactive nitrogen oxidizing species (Nathan and Shi-loh, 2000). Most of these oxygen-derived species are produced at alow level by normal aerobicmetabolism and the damage they causeto cells is constantly repaired. However, under the severe levels ofoxidative stress that cause necrosis, the damage causes ATP deple-tion, preventing controlled apoptotic death and causing the cell tobreak down (Lelli et al., 1998). The system is highly efcient butsome lentiviruses in particular seem more than able to overcomethe hosts immune processes and can induce serious disease evenin the face of an active immune system and response; EIA, HIV andMaedi-visna viruses are good examples of this.
In the case of EIA virus, the almost unique way in which thevirus evades the immune systems best efforts to overcome it, indi-cates that it must in some way prevent or impede the naturaldestructive and protective mechanisms. The pathological effectsof the virus however continue without any effective immune re-sponses. It is almost as though the virus is always one step aheadof the hosts ability to overcome it and this ultimately results inthe demise of the host. Bolfa et al. (2012) have identied possiblysignicant imbalances between oxidants and antioxidants in EIAvirus infected horses. It is interesting that EIA in horses is acceptedas a model of lentivirus activity in HIV in humans and the role ofoxidative stress in the immune evasion may be a signicant aspectof the unique pathogenesis of these conditions. Whether the oxida-tive imbalances that have been identied provide any immediatelyuseful contribution to the possible treatment of the disease isdoubtful but measures that address these may support manage-ment methods that could possibly prolong the life of the patient.
It is generally accepted that the pathological processes involved
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reactive oxygen species, natural dietary quenchers of free radicalsthat donate electrons and so restrict the chain reactions early intheir course, intracellular mechanisms that repair oxidative dam-age to DNA, proteins and membranes, and complex stress re-sponses that may culminate in apoptosis if the damage is too great.
Pathology arises when the balance between oxidants and anti-oxidants is biased towards cell damage and it is this imbalance thatBolfa et al. (2012) have explored. The clinical events associatedwith EIA have been well described but if solutions are to be foundthen more fundamental research has to be carried out.
Derek C. KnottenbeltPhilip Leverhulme Equine Hospital,
University of Liverpool,Leahurst, Neston, Wirral CH64 7TE, UK
E-mail address: [email protected]
Bolfa, P.F., Leroux, C., Pintea, A., Andrei, S., Catoi, C., Taulescu, M., Tabaran, F., Spinu,M., 2012. Oxidantantioxidant imbalances in horses infected with equineinfectious anaemia virus. The Veterinary Journal 192, 449454.
Brangan, P., Bailey, D.C., Larkin, J.F., Myers, T., More, S.J., 2008. Management of thenational programme to eradicate equine infectious anaemia from Irelandduring 2006: A review. Equine Veterinary Journal 40, 702704.
Lelli, J.L., Becks, L.L., Dabrowska, M.I., Hinshaw, D.B., 1998. ATP converts necrosis toapoptosis in oxidant-injured endothelial cells. Free Radical Biological Medicine25, 694702.
Lennon, S.V., Martin, S.J., Cotter, T.G., 1991. Dose-dependent induction of apoptosisin human tumour cell lines by widely diverging stimuli. Cell Proliferation 24,203214.
More, S.J., Aznar, I., Myers, T., Leadon, D.P., Clegg, A., 2008. An outbreak of equineinfectious anaemia in Ireland during 2006: The modes of transmission andspread in the Kildare cluster. Equine Veterinary Journal 40, 709711.
Nathan, C., Shiloh, M.U., 2000. Reactive oxygen and nitrogen intermediates in therelationship between mammalian hosts and microbial pathogens. Proceedingsof the National Academy of Sciences, USA 97, 88418848.
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Examining the stable door after the horse has bolted: Why is EIA such a challenge?References