Vet TimesThe website for the veterinary professionhttpswwwvettimescouk

Chronic fatigue syndrome in horses

Author TIM WATSON

Categories Vets

Date March 2 2009

TIM WATSON describes the features of chronic fatigue and explains how aloe vera can be the keyto bringing affl icted horses back to full functionality

EQUINE chronic fatigue syndrome is an anecdotally common and much talked aboutcondition ndash a Google (www googlecom) search returns more than 100000 results ndash which ischaracterised by lethargy and poor performance which lasts for up to two years

It is however poorly understood and this is borne out by the fact that a PubMed (wwwncbinlmnihgovpubmed) search of scientific literature on equine chronic fatigue identifies onlytwo directly relevant papers The majority of the Google returns are in fact comments made byhorse owners in blogs and discussion forums They often report that a diagnosis of chronic fatiguesyndrome has been ascribed by their veterinarian indicating that ndash despite the paucity of publishedpapers ndash the condition is recognised by many working in equine practice

So what do we know about equine chronic fatigue syndrome other than the fact that it can be asequally debilitating and as frustrating to treat as its identically named human counterpart What isits cause(s) how can it be diagnosed and is there any treatment other than prolonged rest that iseffective

Scientific reports

Looking at the two reports of chronic fatigue in horses in the scientific literature the first which wasa letter published in The Veterinary Record in 1992 reported on a number of horses with persistentand marked lethargy (Ricketts et al 1992) The second paper describes the diagnosis and

1 15

treatment of four horses with chronic weakness and fatigue in Italy (Tarello 2001)

Over a two-year period Ricketts et al (based in Newmarket) investigated 32 horses aged betweentwo to 24 years and of both sexes with clinical signs lasting between four weeks and two yearsHaematological examinations showed leucopaenia ndash with white cell counts as low as three times109litre in some cases ndash andor a reversed neutrophillymphocyte ratio These findings whichsuggested the existence of a persistent viral challenge were present in 28 of the 32 horses (88 percent)

While the results of serum biochemistry and screening for conventional equine viruses wereunremarkable there was evidence of enterovirus infection (in the form of detectable enterovirusvirus protein-1) ndash in 22 of the 28 horses (79 per cent) with haematological abnormalities One ofthe four affected horses that did not have haematological changes was also positive forenterovirus In contrast enterovirus virus protein-1 was not detected in serum samples from 11clinically and haematologically healthy horses

The enterovirus genus includes the polio and Coxsackie viruses and further testing using primersto Coxsackie B virus showed that the enterovirus found in the blood of these horses wasindistinguishable from human enteroviruses Infection with Coxsackie virus has been linked to anumber of diseases in humans including chronic fatigue syndrome ndash with which equine chronicfatigue syndrome shares some similarities ndash although this finding is variable

On this basis the authors suggested that infection of horses with enteroviruses may be associatedwith persistent lethargy and exercise intolerance and as such represent a clinically definedsyndrome which they called equine fatigue syndrome

The four horses with equine fatigue syndrome reported in Italy (Tarello 2001) would appear tohave been affected by a more severe and probably different condition to that described inNewmarket

Fatigue was accompanied in some cases by inappetence and marked weight loss as well as lowcarriage of the head and neck with drooping of the lips and drooling of saliva constipation and dryfaeces pyrexia muscle tremors and a dull and easily shed hair coat Intercurrent bacterialinfections of the skin and conjunctiva were also noted in one horse

The likelihood that the four Italian horses were affected by a separate condition is supported by thefinding of Micrococci-like bacteria adherent to the surface of erythrocytes in peripheral bloodsmears The fact that all horses recovered following treatment with sodium thiacetarsamidesuggests that a Haemobartonella- like parasitic bacteria might have been responsible for thehorsesrsquo condition The findings of this study have however attracted some controversy with oneinternet blogger going as far as to suggest that the haematological abnormalities might have beenstaining artefacts (thehorsedoctor 2008)

2 15

Causes

Aside from the preliminary observations of Ricketts et al (1992) there have been no furtherscientific studies of the pathogenesis of chronic fatigue syndrome in horses It is howevertempting to assume equine chronic fatigue syndrome does indeed represent a post-viral diseasecomplex This is because clinical experiences often suggest a history of an initial illness typicallyascribed to a ldquovirusrdquo which is accompanied by one or more of pyrexia mild respiratory signsandor leucopaenia

Up to 80 per cent of humans that develop chronic fatigue syndrome report initial rsquofl u-likesymptoms and a number of organisms have been implicated These include BrucellaToxoplasma Coxiella burnetii and Chlamydia pneumoniae as well as herpesvirus type-6 humanTcell lymphotropic virus Epstein- Barr virus Cytomegalovirus parvovirus B19 and the group BCoxsackie viruses

Although no single aetiological agent is consistently found in human sufferers of chronic fatiguesyndrome it is widely held that an infectious organism ndash most likely a virus ndash is not only the triggerfor the condition but also initiates and subsequently perpetuates damage to the immune systemwhich allows the agent to persist This smouldering viral infection of several sites in the body isthen associated with chronic inflammation in these tissues and accounts for the diverse range ofsymptoms reported by patients

Several other factors also play important roles in this process notably genetic predispositionneurological hormonal and immune system abnormalities and psychiatic or emotional conditions

The potential role of enteroviruses in equine chronic fatigue syndrome is intriguing given that thereis increasing experimental and clinical evidence that supports the role of these viruses in humandisease (Chia 2005) Enteroviruses are well-known causes of acute respiratory andgastrointestinal infections in a range of species and can be persistent in the central nervoussystem skeletal muscle and heart

Very little is known about enteroviruses in horses An early study examined the biological andphysical properties of an equine respiratory virus with the characteristics of an enterovirus but didnot describe any associated clinical disease (Plummer 1963)

Horses were used in the initial production of reference antisera to human enteroviruses includingpolio virus and Coxsackie viruses A9 and B3 but again there is no mention of any clinical sequelae(Hampil et al 1965 1968) Naturally occurring immunoglobulins that react with poliovirus havebeen found in equine sera (Urasawa et al 1987) as well as neutralising antibodies to humanenterovirus type-70 (Sasagawa et al 1982)

The involvement of other viruses in equine chronic fatigue syndrome cannot be discounted

3 15

Infection with equine herpesviruses should be considered especially when there is biochemicalevidence of myositis

It is also probable that other factors particularly those that impair immune function contribute tothe condition I and others (Celia Marr personal communication) have identified low serum copperconcentrations in horses with chronic fatigue The owner of two affected horses in my practicereported a dramatic improvement with dietary copper supplementation and the affected horsesmade a successful return to competition even though their serum copper levels did not increasesubstantially

Diagnosis

It is clear from the two published reports that while the clinical presentation of equine chronicfatigue syndrome can vary with respect to both the clinical signs and their severity it is thepersistence of signs over a long period of time that is characteristic of the condition As is the casewith the human disease no specific tests are available for chronic fatigue syndrome in horses anddiagnosis is symptom based

Haematological abnormalities are present in the majority of horses and principally includeleucopaenia with a reduction in lymphocyte numbers or a reversal in the ratio of lymphocytes toneutrophils Many cases are also anaemic with lower than normal values for red blood cellnumbers haematocrit and haemoglobin concentrations On the basis of the Italian report (Tarello2001) the blood smear should be carefully examined for any cellular abnormalities

Diagnostic efforts are then usually directed at identifying possible aetiologies of chroniclymphopaenia (Table 1) as well as eliminating other more com- mon causes of lethargy and poorperformance

A full lameness evaluation including the back and sacroiliac region is warranted to identify anypossible contribution from musculoskeletal pain Blood samples taken before and after exerciseshould detect the presence of low-grade or subclinical exertional myopathies

Endoscopic examination of the respiratory tract along with cytological examination of trachealwash or bronchoalveolar fl uids is indicated with recurrent airway obstruction infl ammatory airwaydisease and exerciseinduced pulmonary haemorrhage in mind

Diagnostic attention should also be turned to the cardiovascular system looking for evidence ofmurmurs arrhythmias or myocardial disease as well as examining for the presence of gastriculceration

Serological analysis of paired blood samples may identify the involvement of equine herpes rhinitisor infl uenza viruses Finally the presence of recurrent skin infections which respond to antibiotic

4 15

treatment but simply recur once this has finished is suggestive of the immune suppression that ischaracterised by chronic fatigue in some horses

Treatment

Treatment for equine chronic fatigue syndrome is largely empirical and typically comprises aprolonged period of rest Dietary supplementation with vitamins and minerals is often suggested tocorrect any anaemia as well as in an effort to support immune function NSAIDs may be used torelieve any musculoskeletal pain

No ldquomagicrdquo therapies are available for humans with chronic fatigue syndrome and a range oftreatments are employed to manage an individualrsquos symptoms These include a well-balanceddiet graded exercise and pacing programmes and cognitive behavioural therapy (Baker andShaw 2007)

Complementary treatments such as relaxation therapy acupuncture homoeopathy special dietsor mineral supplements are also often recommended even though there is no scientific evidencethat they are effective Although the efficacy of antiviral therapies is also debatable there is someevidence of benefit from a combination of interferon- and- in patients with detectable enterovirusRNA in their lymphocytes (Chia 2005)

There may be benefits from stimulating immune function in horses with chronic fatigue syndromeespecially because of the likely role of viral infection Immunostimulants used in horses range fromrelatively crude bacterial extracts to the endogenous immunomodulators interferon- andgranulocytecolony stimulating factor as well as the anthelmintic levamisole and several plantextracts (Lunn and Rush 2004)

Extracts of Propionibacterium acnes and mycobacterial cell walls are sold in other veterinarymarkets (EqStim and Equimune IV respectively) and are licensed for the treatment of acute andchronic respiratory conditions caused by viruses and bacteria Immunostimulation has beendemonstrated in controlled clinical studies of both products In addition to respiratory diseasessuccess in the treatment of endometritis osteomyelitis papillomatosis abdominal abscessationfistulous withers and by intralesional injection sarcoid tumours has been reported (Rush andLunn 2004)

There are some anecdotal reports of EqStim being used in horses with chronic fatigue syndromeon the internet but these are owner rather than veterinarian described

Oral administration of interferon- has been shown to reduce pulmonary inflammation in horseswith chronic inflammatory airway disease (Rush Moore et al 1996) High parenteral doses ofinterferon-aacute have been used to treat horses with West Nile virus and direct antiviral activity hasbeen documented in vitro (Rush and Lunn 2004) I have used oral interferon at a once-daily dose

5 15

of 22 IUkg bodyweight in horses with both acute respiratory viruses and chronic fatigue syndromewith variable results

Granulocyte-colony stimulating factor has been used in horses for the treatment of neutropeniaresulting from sepsis (Zinkl et al 1994) endotoxaemia (Sullivan et al 1993) and drug-inducedmyeloid hypoplasia (Toribio et al 1998) There is no evidence of any effect on the lymphocyte orcell-mediated immunity or reports of its use in viral conditions

Levamisole has been shown to repair immune defences in humans and a number of animalspecies (Sajid et al 2006) Although controlled studies of the immunostimulatory potential oflevamisole have not been reported it is widely used as an immune stimulant by horse trainers inNorth America and it is seen as an important element of therapy for equine protozoal myelitis

The internet is awash with so-called natural immune stimulants for horses ndash with a Google searchreturning 171000 results ndash but there is practically no scientific support for their use Productsinclude essentials oils curcumin ginger garlic Ginkgo biloba ginseng Capsicum Boswellia andgrape seed There is however some evidence for the efficacy of acemannan and extracts of Echinacea

Acemannan is extracted from the pulp of the ldquomeatyrdquo leaves of aloe vera plants and is a potentanti-viral agent that also has the ability to enhance the immune system particularly the function oflymphocytes It is used for the treatment of certain viral diseases and cancers of dogs and catsand has a US licence for the treatment of fibrosarcomas

A number of anecdotal reports exist over the use of acemannan in horses either by intravenousinjection or oral administration of aloe vera gels and drinks

Clinical efficacy in the treatment of equine respiratory disease has been reported as has successin treating sarcoids when the acemannan is injected directly into the tumour (Rush and Flaminio2000) An experience with aloe vera in the treatment of equine chronic fatigue syndrome ishighlighted in the accompanying case history

Extracts of the plant Echinacea angustifolia are widely reported to be immune stimulants and thereis some scientific support for an immunostimulatory effect in horses In a controlled study Echinacea was found to boost peripheral lymphocyte counts increase the phagocytic ability ofisolated neutrophils and stimulate neutrophil migration from peripheral circulation into the tissues(OrsquoNeill et al 1992) Supplementation also increased the size and concentration of peripheral redblood cells the concentration of haemoglobin and packed cell volume

Case history

Vinnie was a 12-year-old gelding eventing at intermediate level that went off his food developed a

6 15

serous nasal discharge and dry cough and had a fever in January 2007

Blood samples showed a markedly reduced white blood cell count an almost total depletion oflymphocytes and low haematocrit (Table 2) Initial treatment with trimethoprim- sulphonamideantibiotics and a clenbuterol-based syrup improved Vinniersquos respiratory condition Subsequentendoscopic examination with a tracheal wash revealed no significant abnormalities White bloodcell and lymphocyte counts increased with a fourweek period of rest so Vinnie returned to work

Three months later the owner became concerned that Vinnie was not able to cope with hiscompetition programme and was tiring easily He performed badly in the cross-country phases ofseveral events with an unusual number of jumping penalties and a couple of retirements

Further blood tests at the end of May revealed a lowering of the white blood cell and lymphocytecounts although he was now no longer anaemic These parameters remained low despitetreatment with a dietary copper supplement levamisole and interferon- over the ensuing twomonths Vinnie was then turned away to grass for three months with no ridden exercise

Prolonged rest did not improve the blood picture with the white blood cell count in particularremaining low and this did not improve with further rest over the winter months In spring 2008 theowner came across an article on the usefulness of acemannan in post-viral lethargy syndromesand Vinnie was started on a six-week treatment with aloe vera gel

The owner noticed a significant improvement in Vinniersquos demeanour and general condition andblood samples taken towards the end of the treatment period in June 2008 showed substantialimprovements in white blood cell and lymphocyte counts ndash which had more than doubled during thecourse of treatment ndash and haematocrit This was accompanied by a marked transformation in hiswork with him being much more responsive not tiring and making fewer jumping errors Vinniereturned to competitive activities soon after

Conclusion

Vinniersquos story is typical of many horses with equine chronic fatigue syndrome and serves toillustrate the frustration that it can cause owners particularly of competition horses

Symptoms can persist for a long period of time ndash in Vinniersquos instance considerably longer than 12months ndash and treatment including prolonged rest and potential immunostimulants can beineffective However the six-week course of aloe vera gel cost pound180 and was backed by a 60-daymoney-back guarantee from the local distributor which promised a full refund if there was noimprovement

References

7 15

Baker R and Shaw E J (2007) Diagnosis and management of chronic fatigue syndrome ormyalgic encephalomyelitis (or encephalopathy) summary of NICE guidance BMJ 335446-448Chia J K (2005) The role of enterovirus in chronic fatigue syndrome J Clin Pathol Nov 58(11) 1126-1132 Hampil B et al (1965) Preparation of antiserum to enteroviruses inlarge animals J Immunol 95 895-908Hampil B and Melnick J L (1968) WHO collaborative studies on enterovirus referenceantisera second report Bull World Health Organ 38 577-593Lunn D P and Rush B R (2004) Immunomodulation in horses principles and mechanismsIn Proceedings of 50th Annual Convention of the American Association of EquinePractitioners Denver P14811204OrsquoNeill W McKee S and Clarke A F (2002) Immunological and haematinic consequencesof feeding a standardized Echinacea (Echinacea angustifolia) extract to healthy horses Equine Vet J 34 222-227Plummer G (1963) An equine respiratory enterovirus some biological and physicalproperties Archives of Virology 12(5) 694-700Ricketts SW et al (1992) Equine fatigue syndrome The Veterinary Record 131 58-59Rush B R and Flaminio M J (2000) Immunomodulation in horses Vet Clin North Am Pract 16 183-197Rush B R and Lunn D P (2004) Immunomodulation in horses indications and preparationsProceedings of 50th Annual Convention of the American Association of EquinePractitioners Denver P14811204Rush Moore B R et al (1996) Changes in airway inflammatory cell populations instandardbred racehorses after interferon-alpha administration Vet Immunol Immunopathol 49 347-358Sajid M S et al (2006) Immunomodulatory effect of various anti-parasitics a review Parasitology 132 301-313Sasagawa A Miyamura K and Kono R (1982) Enterovirus type-70 neutralising IgM inanimal sera Jpn J Med Sci Biol 35 63-73Sullivan K E et al (1993) Effects of perioperative G-CSF on horses with ascending colonicischaemia Vet Surg 22 343-350Tarello W (2001) Chronic fatigue syndrome in horses diagnosis and treatment of fourcases Comparative Immunology Microbiology and Infectious Diseases 24 57-70Toribio R E et al (1998) Congenital defects in newborn foals of mares treated for equineprotozoal myeloencephalitis during pregnancy J Am Vet Med Assoc 212 697-701Urasawa S et al (1987) Comparison of naturally occurring poliovirusreactiveimmunoglobulins in bovine and equine sera Jpn J Med Sci Biol 40(2) 61-74thehorsedoctor (2008) www thehorsedoctorblogspotcom200808chronic-fatiguesyndrome- in-horseshtmlZinkl J G et al (1994) Haematological bone marrow and clinical chemical changes inneonatal foals given canine recombinant granulocytecolony stimulating factor Equine Vet J 26 313-318

8 15

Causes

Aside from the preliminary observations of Ricketts et al (1992) there have been no furtherscientific studies of the pathogenesis of chronic fatigue syndrome in horses It is howevertempting to assume equine chronic fatigue syndrome does indeed represent a post-viral diseasecomplex This is because clinical experiences often suggest a history of an initial illness typicallyascribed to a ldquovirusrdquo which is accompanied by one or more of pyrexia mild respiratory signsandor leucopaenia

Up to 80 per cent of humans that develop chronic fatigue syndrome report initial rsquofl u-likesymptoms and a number of organisms have been implicated These include BrucellaToxoplasma Coxiella burnetii and Chlamydia pneumoniae as well as herpesvirus type-6 humanTcell lymphotropic virus Epstein- Barr virus Cytomegalovirus parvovirus B19 and the group BCoxsackie viruses

Although no single aetiological agent is consistently found in human sufferers of chronic fatiguesyndrome it is widely held that an infectious organism ndash most likely a virus ndash is not only the triggerfor the condition but also initiates and subsequently perpetuates damage to the immune systemwhich allows the agent to persist This smouldering viral infection of several sites in the body isthen associated with chronic inflammation in these tissues and accounts for the diverse range ofsymptoms reported by patients

Several other factors also play important roles in this process notably genetic predispositionneurological hormonal and immune system abnormalities and psychiatic or emotional conditions

The potential role of enteroviruses in equine chronic fatigue syndrome is intriguing given that thereis increasing experimental and clinical evidence that supports the role of these viruses in humandisease (Chia 2005) Enteroviruses are well-known causes of acute respiratory andgastrointestinal infections in a range of species and can be persistent in the central nervoussystem skeletal muscle and heart

Very little is known about enteroviruses in horses An early study examined the biological andphysical properties of an equine respiratory virus with the characteristics of an enterovirus but didnot describe any associated clinical disease (Plummer 1963)

Horses were used in the initial production of reference antisera to human enteroviruses includingpolio virus and Coxsackie viruses A9 and B3 but again there is no mention of any clinical sequelae(Hampil et al 1965 1968) Naturally occurring immunoglobulins that react with poliovirus havebeen found in equine sera (Urasawa et al 1987) as well as neutralising antibodies to humanenterovirus type-70 (Sasagawa et al 1982)

The involvement of other viruses in equine chronic fatigue syndrome cannot be discounted

3 15

Infection with equine herpesviruses should be considered especially when there is biochemicalevidence of myositis

It is also probable that other factors particularly those that impair immune function contribute tothe condition I and others (Celia Marr personal communication) have identified low serum copperconcentrations in horses with chronic fatigue The owner of two affected horses in my practicereported a dramatic improvement with dietary copper supplementation and the affected horsesmade a successful return to competition even though their serum copper levels did not increasesubstantially

Diagnosis

It is clear from the two published reports that while the clinical presentation of equine chronicfatigue syndrome can vary with respect to both the clinical signs and their severity it is thepersistence of signs over a long period of time that is characteristic of the condition As is the casewith the human disease no specific tests are available for chronic fatigue syndrome in horses anddiagnosis is symptom based

Haematological abnormalities are present in the majority of horses and principally includeleucopaenia with a reduction in lymphocyte numbers or a reversal in the ratio of lymphocytes toneutrophils Many cases are also anaemic with lower than normal values for red blood cellnumbers haematocrit and haemoglobin concentrations On the basis of the Italian report (Tarello2001) the blood smear should be carefully examined for any cellular abnormalities

Diagnostic efforts are then usually directed at identifying possible aetiologies of chroniclymphopaenia (Table 1) as well as eliminating other more com- mon causes of lethargy and poorperformance

A full lameness evaluation including the back and sacroiliac region is warranted to identify anypossible contribution from musculoskeletal pain Blood samples taken before and after exerciseshould detect the presence of low-grade or subclinical exertional myopathies

Endoscopic examination of the respiratory tract along with cytological examination of trachealwash or bronchoalveolar fl uids is indicated with recurrent airway obstruction infl ammatory airwaydisease and exerciseinduced pulmonary haemorrhage in mind

Diagnostic attention should also be turned to the cardiovascular system looking for evidence ofmurmurs arrhythmias or myocardial disease as well as examining for the presence of gastriculceration

Serological analysis of paired blood samples may identify the involvement of equine herpes rhinitisor infl uenza viruses Finally the presence of recurrent skin infections which respond to antibiotic

4 15

treatment but simply recur once this has finished is suggestive of the immune suppression that ischaracterised by chronic fatigue in some horses

Treatment

Treatment for equine chronic fatigue syndrome is largely empirical and typically comprises aprolonged period of rest Dietary supplementation with vitamins and minerals is often suggested tocorrect any anaemia as well as in an effort to support immune function NSAIDs may be used torelieve any musculoskeletal pain

No ldquomagicrdquo therapies are available for humans with chronic fatigue syndrome and a range oftreatments are employed to manage an individualrsquos symptoms These include a well-balanceddiet graded exercise and pacing programmes and cognitive behavioural therapy (Baker andShaw 2007)

Complementary treatments such as relaxation therapy acupuncture homoeopathy special dietsor mineral supplements are also often recommended even though there is no scientific evidencethat they are effective Although the efficacy of antiviral therapies is also debatable there is someevidence of benefit from a combination of interferon- and- in patients with detectable enterovirusRNA in their lymphocytes (Chia 2005)

There may be benefits from stimulating immune function in horses with chronic fatigue syndromeespecially because of the likely role of viral infection Immunostimulants used in horses range fromrelatively crude bacterial extracts to the endogenous immunomodulators interferon- andgranulocytecolony stimulating factor as well as the anthelmintic levamisole and several plantextracts (Lunn and Rush 2004)

Extracts of Propionibacterium acnes and mycobacterial cell walls are sold in other veterinarymarkets (EqStim and Equimune IV respectively) and are licensed for the treatment of acute andchronic respiratory conditions caused by viruses and bacteria Immunostimulation has beendemonstrated in controlled clinical studies of both products In addition to respiratory diseasessuccess in the treatment of endometritis osteomyelitis papillomatosis abdominal abscessationfistulous withers and by intralesional injection sarcoid tumours has been reported (Rush andLunn 2004)

There are some anecdotal reports of EqStim being used in horses with chronic fatigue syndromeon the internet but these are owner rather than veterinarian described

Oral administration of interferon- has been shown to reduce pulmonary inflammation in horseswith chronic inflammatory airway disease (Rush Moore et al 1996) High parenteral doses ofinterferon-aacute have been used to treat horses with West Nile virus and direct antiviral activity hasbeen documented in vitro (Rush and Lunn 2004) I have used oral interferon at a once-daily dose

5 15

of 22 IUkg bodyweight in horses with both acute respiratory viruses and chronic fatigue syndromewith variable results

Granulocyte-colony stimulating factor has been used in horses for the treatment of neutropeniaresulting from sepsis (Zinkl et al 1994) endotoxaemia (Sullivan et al 1993) and drug-inducedmyeloid hypoplasia (Toribio et al 1998) There is no evidence of any effect on the lymphocyte orcell-mediated immunity or reports of its use in viral conditions

Levamisole has been shown to repair immune defences in humans and a number of animalspecies (Sajid et al 2006) Although controlled studies of the immunostimulatory potential oflevamisole have not been reported it is widely used as an immune stimulant by horse trainers inNorth America and it is seen as an important element of therapy for equine protozoal myelitis

The internet is awash with so-called natural immune stimulants for horses ndash with a Google searchreturning 171000 results ndash but there is practically no scientific support for their use Productsinclude essentials oils curcumin ginger garlic Ginkgo biloba ginseng Capsicum Boswellia andgrape seed There is however some evidence for the efficacy of acemannan and extracts of Echinacea

Acemannan is extracted from the pulp of the ldquomeatyrdquo leaves of aloe vera plants and is a potentanti-viral agent that also has the ability to enhance the immune system particularly the function oflymphocytes It is used for the treatment of certain viral diseases and cancers of dogs and catsand has a US licence for the treatment of fibrosarcomas

A number of anecdotal reports exist over the use of acemannan in horses either by intravenousinjection or oral administration of aloe vera gels and drinks

Clinical efficacy in the treatment of equine respiratory disease has been reported as has successin treating sarcoids when the acemannan is injected directly into the tumour (Rush and Flaminio2000) An experience with aloe vera in the treatment of equine chronic fatigue syndrome ishighlighted in the accompanying case history

Extracts of the plant Echinacea angustifolia are widely reported to be immune stimulants and thereis some scientific support for an immunostimulatory effect in horses In a controlled study Echinacea was found to boost peripheral lymphocyte counts increase the phagocytic ability ofisolated neutrophils and stimulate neutrophil migration from peripheral circulation into the tissues(OrsquoNeill et al 1992) Supplementation also increased the size and concentration of peripheral redblood cells the concentration of haemoglobin and packed cell volume

Case history

Vinnie was a 12-year-old gelding eventing at intermediate level that went off his food developed a

6 15

serous nasal discharge and dry cough and had a fever in January 2007

Blood samples showed a markedly reduced white blood cell count an almost total depletion oflymphocytes and low haematocrit (Table 2) Initial treatment with trimethoprim- sulphonamideantibiotics and a clenbuterol-based syrup improved Vinniersquos respiratory condition Subsequentendoscopic examination with a tracheal wash revealed no significant abnormalities White bloodcell and lymphocyte counts increased with a fourweek period of rest so Vinnie returned to work

Three months later the owner became concerned that Vinnie was not able to cope with hiscompetition programme and was tiring easily He performed badly in the cross-country phases ofseveral events with an unusual number of jumping penalties and a couple of retirements

Further blood tests at the end of May revealed a lowering of the white blood cell and lymphocytecounts although he was now no longer anaemic These parameters remained low despitetreatment with a dietary copper supplement levamisole and interferon- over the ensuing twomonths Vinnie was then turned away to grass for three months with no ridden exercise

Prolonged rest did not improve the blood picture with the white blood cell count in particularremaining low and this did not improve with further rest over the winter months In spring 2008 theowner came across an article on the usefulness of acemannan in post-viral lethargy syndromesand Vinnie was started on a six-week treatment with aloe vera gel

The owner noticed a significant improvement in Vinniersquos demeanour and general condition andblood samples taken towards the end of the treatment period in June 2008 showed substantialimprovements in white blood cell and lymphocyte counts ndash which had more than doubled during thecourse of treatment ndash and haematocrit This was accompanied by a marked transformation in hiswork with him being much more responsive not tiring and making fewer jumping errors Vinniereturned to competitive activities soon after

Conclusion

Vinniersquos story is typical of many horses with equine chronic fatigue syndrome and serves toillustrate the frustration that it can cause owners particularly of competition horses

Symptoms can persist for a long period of time ndash in Vinniersquos instance considerably longer than 12months ndash and treatment including prolonged rest and potential immunostimulants can beineffective However the six-week course of aloe vera gel cost pound180 and was backed by a 60-daymoney-back guarantee from the local distributor which promised a full refund if there was noimprovement

References

7 15

Baker R and Shaw E J (2007) Diagnosis and management of chronic fatigue syndrome ormyalgic encephalomyelitis (or encephalopathy) summary of NICE guidance BMJ 335446-448Chia J K (2005) The role of enterovirus in chronic fatigue syndrome J Clin Pathol Nov 58(11) 1126-1132 Hampil B et al (1965) Preparation of antiserum to enteroviruses inlarge animals J Immunol 95 895-908Hampil B and Melnick J L (1968) WHO collaborative studies on enterovirus referenceantisera second report Bull World Health Organ 38 577-593Lunn D P and Rush B R (2004) Immunomodulation in horses principles and mechanismsIn Proceedings of 50th Annual Convention of the American Association of EquinePractitioners Denver P14811204OrsquoNeill W McKee S and Clarke A F (2002) Immunological and haematinic consequencesof feeding a standardized Echinacea (Echinacea angustifolia) extract to healthy horses Equine Vet J 34 222-227Plummer G (1963) An equine respiratory enterovirus some biological and physicalproperties Archives of Virology 12(5) 694-700Ricketts SW et al (1992) Equine fatigue syndrome The Veterinary Record 131 58-59Rush B R and Flaminio M J (2000) Immunomodulation in horses Vet Clin North Am Pract 16 183-197Rush B R and Lunn D P (2004) Immunomodulation in horses indications and preparationsProceedings of 50th Annual Convention of the American Association of EquinePractitioners Denver P14811204Rush Moore B R et al (1996) Changes in airway inflammatory cell populations instandardbred racehorses after interferon-alpha administration Vet Immunol Immunopathol 49 347-358Sajid M S et al (2006) Immunomodulatory effect of various anti-parasitics a review Parasitology 132 301-313Sasagawa A Miyamura K and Kono R (1982) Enterovirus type-70 neutralising IgM inanimal sera Jpn J Med Sci Biol 35 63-73Sullivan K E et al (1993) Effects of perioperative G-CSF on horses with ascending colonicischaemia Vet Surg 22 343-350Tarello W (2001) Chronic fatigue syndrome in horses diagnosis and treatment of fourcases Comparative Immunology Microbiology and Infectious Diseases 24 57-70Toribio R E et al (1998) Congenital defects in newborn foals of mares treated for equineprotozoal myeloencephalitis during pregnancy J Am Vet Med Assoc 212 697-701Urasawa S et al (1987) Comparison of naturally occurring poliovirusreactiveimmunoglobulins in bovine and equine sera Jpn J Med Sci Biol 40(2) 61-74thehorsedoctor (2008) www thehorsedoctorblogspotcom200808chronic-fatiguesyndrome- in-horseshtmlZinkl J G et al (1994) Haematological bone marrow and clinical chemical changes inneonatal foals given canine recombinant granulocytecolony stimulating factor Equine Vet J 26 313-318

8 15

Infection with equine herpesviruses should be considered especially when there is biochemicalevidence of myositis

It is also probable that other factors particularly those that impair immune function contribute tothe condition I and others (Celia Marr personal communication) have identified low serum copperconcentrations in horses with chronic fatigue The owner of two affected horses in my practicereported a dramatic improvement with dietary copper supplementation and the affected horsesmade a successful return to competition even though their serum copper levels did not increasesubstantially

Diagnosis

It is clear from the two published reports that while the clinical presentation of equine chronicfatigue syndrome can vary with respect to both the clinical signs and their severity it is thepersistence of signs over a long period of time that is characteristic of the condition As is the casewith the human disease no specific tests are available for chronic fatigue syndrome in horses anddiagnosis is symptom based

Haematological abnormalities are present in the majority of horses and principally includeleucopaenia with a reduction in lymphocyte numbers or a reversal in the ratio of lymphocytes toneutrophils Many cases are also anaemic with lower than normal values for red blood cellnumbers haematocrit and haemoglobin concentrations On the basis of the Italian report (Tarello2001) the blood smear should be carefully examined for any cellular abnormalities

Diagnostic efforts are then usually directed at identifying possible aetiologies of chroniclymphopaenia (Table 1) as well as eliminating other more com- mon causes of lethargy and poorperformance

A full lameness evaluation including the back and sacroiliac region is warranted to identify anypossible contribution from musculoskeletal pain Blood samples taken before and after exerciseshould detect the presence of low-grade or subclinical exertional myopathies

Endoscopic examination of the respiratory tract along with cytological examination of trachealwash or bronchoalveolar fl uids is indicated with recurrent airway obstruction infl ammatory airwaydisease and exerciseinduced pulmonary haemorrhage in mind

Diagnostic attention should also be turned to the cardiovascular system looking for evidence ofmurmurs arrhythmias or myocardial disease as well as examining for the presence of gastriculceration

Serological analysis of paired blood samples may identify the involvement of equine herpes rhinitisor infl uenza viruses Finally the presence of recurrent skin infections which respond to antibiotic

4 15

treatment but simply recur once this has finished is suggestive of the immune suppression that ischaracterised by chronic fatigue in some horses

Treatment

Treatment for equine chronic fatigue syndrome is largely empirical and typically comprises aprolonged period of rest Dietary supplementation with vitamins and minerals is often suggested tocorrect any anaemia as well as in an effort to support immune function NSAIDs may be used torelieve any musculoskeletal pain

No ldquomagicrdquo therapies are available for humans with chronic fatigue syndrome and a range oftreatments are employed to manage an individualrsquos symptoms These include a well-balanceddiet graded exercise and pacing programmes and cognitive behavioural therapy (Baker andShaw 2007)

Complementary treatments such as relaxation therapy acupuncture homoeopathy special dietsor mineral supplements are also often recommended even though there is no scientific evidencethat they are effective Although the efficacy of antiviral therapies is also debatable there is someevidence of benefit from a combination of interferon- and- in patients with detectable enterovirusRNA in their lymphocytes (Chia 2005)

There may be benefits from stimulating immune function in horses with chronic fatigue syndromeespecially because of the likely role of viral infection Immunostimulants used in horses range fromrelatively crude bacterial extracts to the endogenous immunomodulators interferon- andgranulocytecolony stimulating factor as well as the anthelmintic levamisole and several plantextracts (Lunn and Rush 2004)

Extracts of Propionibacterium acnes and mycobacterial cell walls are sold in other veterinarymarkets (EqStim and Equimune IV respectively) and are licensed for the treatment of acute andchronic respiratory conditions caused by viruses and bacteria Immunostimulation has beendemonstrated in controlled clinical studies of both products In addition to respiratory diseasessuccess in the treatment of endometritis osteomyelitis papillomatosis abdominal abscessationfistulous withers and by intralesional injection sarcoid tumours has been reported (Rush andLunn 2004)

There are some anecdotal reports of EqStim being used in horses with chronic fatigue syndromeon the internet but these are owner rather than veterinarian described

Oral administration of interferon- has been shown to reduce pulmonary inflammation in horseswith chronic inflammatory airway disease (Rush Moore et al 1996) High parenteral doses ofinterferon-aacute have been used to treat horses with West Nile virus and direct antiviral activity hasbeen documented in vitro (Rush and Lunn 2004) I have used oral interferon at a once-daily dose

5 15

of 22 IUkg bodyweight in horses with both acute respiratory viruses and chronic fatigue syndromewith variable results

Granulocyte-colony stimulating factor has been used in horses for the treatment of neutropeniaresulting from sepsis (Zinkl et al 1994) endotoxaemia (Sullivan et al 1993) and drug-inducedmyeloid hypoplasia (Toribio et al 1998) There is no evidence of any effect on the lymphocyte orcell-mediated immunity or reports of its use in viral conditions

Levamisole has been shown to repair immune defences in humans and a number of animalspecies (Sajid et al 2006) Although controlled studies of the immunostimulatory potential oflevamisole have not been reported it is widely used as an immune stimulant by horse trainers inNorth America and it is seen as an important element of therapy for equine protozoal myelitis

The internet is awash with so-called natural immune stimulants for horses ndash with a Google searchreturning 171000 results ndash but there is practically no scientific support for their use Productsinclude essentials oils curcumin ginger garlic Ginkgo biloba ginseng Capsicum Boswellia andgrape seed There is however some evidence for the efficacy of acemannan and extracts of Echinacea

Acemannan is extracted from the pulp of the ldquomeatyrdquo leaves of aloe vera plants and is a potentanti-viral agent that also has the ability to enhance the immune system particularly the function oflymphocytes It is used for the treatment of certain viral diseases and cancers of dogs and catsand has a US licence for the treatment of fibrosarcomas

A number of anecdotal reports exist over the use of acemannan in horses either by intravenousinjection or oral administration of aloe vera gels and drinks

Clinical efficacy in the treatment of equine respiratory disease has been reported as has successin treating sarcoids when the acemannan is injected directly into the tumour (Rush and Flaminio2000) An experience with aloe vera in the treatment of equine chronic fatigue syndrome ishighlighted in the accompanying case history

Extracts of the plant Echinacea angustifolia are widely reported to be immune stimulants and thereis some scientific support for an immunostimulatory effect in horses In a controlled study Echinacea was found to boost peripheral lymphocyte counts increase the phagocytic ability ofisolated neutrophils and stimulate neutrophil migration from peripheral circulation into the tissues(OrsquoNeill et al 1992) Supplementation also increased the size and concentration of peripheral redblood cells the concentration of haemoglobin and packed cell volume

Case history

Vinnie was a 12-year-old gelding eventing at intermediate level that went off his food developed a

6 15

serous nasal discharge and dry cough and had a fever in January 2007

Blood samples showed a markedly reduced white blood cell count an almost total depletion oflymphocytes and low haematocrit (Table 2) Initial treatment with trimethoprim- sulphonamideantibiotics and a clenbuterol-based syrup improved Vinniersquos respiratory condition Subsequentendoscopic examination with a tracheal wash revealed no significant abnormalities White bloodcell and lymphocyte counts increased with a fourweek period of rest so Vinnie returned to work

Three months later the owner became concerned that Vinnie was not able to cope with hiscompetition programme and was tiring easily He performed badly in the cross-country phases ofseveral events with an unusual number of jumping penalties and a couple of retirements

Further blood tests at the end of May revealed a lowering of the white blood cell and lymphocytecounts although he was now no longer anaemic These parameters remained low despitetreatment with a dietary copper supplement levamisole and interferon- over the ensuing twomonths Vinnie was then turned away to grass for three months with no ridden exercise

Prolonged rest did not improve the blood picture with the white blood cell count in particularremaining low and this did not improve with further rest over the winter months In spring 2008 theowner came across an article on the usefulness of acemannan in post-viral lethargy syndromesand Vinnie was started on a six-week treatment with aloe vera gel

The owner noticed a significant improvement in Vinniersquos demeanour and general condition andblood samples taken towards the end of the treatment period in June 2008 showed substantialimprovements in white blood cell and lymphocyte counts ndash which had more than doubled during thecourse of treatment ndash and haematocrit This was accompanied by a marked transformation in hiswork with him being much more responsive not tiring and making fewer jumping errors Vinniereturned to competitive activities soon after

Conclusion

Vinniersquos story is typical of many horses with equine chronic fatigue syndrome and serves toillustrate the frustration that it can cause owners particularly of competition horses

Symptoms can persist for a long period of time ndash in Vinniersquos instance considerably longer than 12months ndash and treatment including prolonged rest and potential immunostimulants can beineffective However the six-week course of aloe vera gel cost pound180 and was backed by a 60-daymoney-back guarantee from the local distributor which promised a full refund if there was noimprovement

References

7 15

Baker R and Shaw E J (2007) Diagnosis and management of chronic fatigue syndrome ormyalgic encephalomyelitis (or encephalopathy) summary of NICE guidance BMJ 335446-448Chia J K (2005) The role of enterovirus in chronic fatigue syndrome J Clin Pathol Nov 58(11) 1126-1132 Hampil B et al (1965) Preparation of antiserum to enteroviruses inlarge animals J Immunol 95 895-908Hampil B and Melnick J L (1968) WHO collaborative studies on enterovirus referenceantisera second report Bull World Health Organ 38 577-593Lunn D P and Rush B R (2004) Immunomodulation in horses principles and mechanismsIn Proceedings of 50th Annual Convention of the American Association of EquinePractitioners Denver P14811204OrsquoNeill W McKee S and Clarke A F (2002) Immunological and haematinic consequencesof feeding a standardized Echinacea (Echinacea angustifolia) extract to healthy horses Equine Vet J 34 222-227Plummer G (1963) An equine respiratory enterovirus some biological and physicalproperties Archives of Virology 12(5) 694-700Ricketts SW et al (1992) Equine fatigue syndrome The Veterinary Record 131 58-59Rush B R and Flaminio M J (2000) Immunomodulation in horses Vet Clin North Am Pract 16 183-197Rush B R and Lunn D P (2004) Immunomodulation in horses indications and preparationsProceedings of 50th Annual Convention of the American Association of EquinePractitioners Denver P14811204Rush Moore B R et al (1996) Changes in airway inflammatory cell populations instandardbred racehorses after interferon-alpha administration Vet Immunol Immunopathol 49 347-358Sajid M S et al (2006) Immunomodulatory effect of various anti-parasitics a review Parasitology 132 301-313Sasagawa A Miyamura K and Kono R (1982) Enterovirus type-70 neutralising IgM inanimal sera Jpn J Med Sci Biol 35 63-73Sullivan K E et al (1993) Effects of perioperative G-CSF on horses with ascending colonicischaemia Vet Surg 22 343-350Tarello W (2001) Chronic fatigue syndrome in horses diagnosis and treatment of fourcases Comparative Immunology Microbiology and Infectious Diseases 24 57-70Toribio R E et al (1998) Congenital defects in newborn foals of mares treated for equineprotozoal myeloencephalitis during pregnancy J Am Vet Med Assoc 212 697-701Urasawa S et al (1987) Comparison of naturally occurring poliovirusreactiveimmunoglobulins in bovine and equine sera Jpn J Med Sci Biol 40(2) 61-74thehorsedoctor (2008) www thehorsedoctorblogspotcom200808chronic-fatiguesyndrome- in-horseshtmlZinkl J G et al (1994) Haematological bone marrow and clinical chemical changes inneonatal foals given canine recombinant granulocytecolony stimulating factor Equine Vet J 26 313-318

8 15

treatment but simply recur once this has finished is suggestive of the immune suppression that ischaracterised by chronic fatigue in some horses

Treatment

Treatment for equine chronic fatigue syndrome is largely empirical and typically comprises aprolonged period of rest Dietary supplementation with vitamins and minerals is often suggested tocorrect any anaemia as well as in an effort to support immune function NSAIDs may be used torelieve any musculoskeletal pain

No ldquomagicrdquo therapies are available for humans with chronic fatigue syndrome and a range oftreatments are employed to manage an individualrsquos symptoms These include a well-balanceddiet graded exercise and pacing programmes and cognitive behavioural therapy (Baker andShaw 2007)

Complementary treatments such as relaxation therapy acupuncture homoeopathy special dietsor mineral supplements are also often recommended even though there is no scientific evidencethat they are effective Although the efficacy of antiviral therapies is also debatable there is someevidence of benefit from a combination of interferon- and- in patients with detectable enterovirusRNA in their lymphocytes (Chia 2005)

There may be benefits from stimulating immune function in horses with chronic fatigue syndromeespecially because of the likely role of viral infection Immunostimulants used in horses range fromrelatively crude bacterial extracts to the endogenous immunomodulators interferon- andgranulocytecolony stimulating factor as well as the anthelmintic levamisole and several plantextracts (Lunn and Rush 2004)

Extracts of Propionibacterium acnes and mycobacterial cell walls are sold in other veterinarymarkets (EqStim and Equimune IV respectively) and are licensed for the treatment of acute andchronic respiratory conditions caused by viruses and bacteria Immunostimulation has beendemonstrated in controlled clinical studies of both products In addition to respiratory diseasessuccess in the treatment of endometritis osteomyelitis papillomatosis abdominal abscessationfistulous withers and by intralesional injection sarcoid tumours has been reported (Rush andLunn 2004)

There are some anecdotal reports of EqStim being used in horses with chronic fatigue syndromeon the internet but these are owner rather than veterinarian described

Oral administration of interferon- has been shown to reduce pulmonary inflammation in horseswith chronic inflammatory airway disease (Rush Moore et al 1996) High parenteral doses ofinterferon-aacute have been used to treat horses with West Nile virus and direct antiviral activity hasbeen documented in vitro (Rush and Lunn 2004) I have used oral interferon at a once-daily dose

5 15

of 22 IUkg bodyweight in horses with both acute respiratory viruses and chronic fatigue syndromewith variable results

Granulocyte-colony stimulating factor has been used in horses for the treatment of neutropeniaresulting from sepsis (Zinkl et al 1994) endotoxaemia (Sullivan et al 1993) and drug-inducedmyeloid hypoplasia (Toribio et al 1998) There is no evidence of any effect on the lymphocyte orcell-mediated immunity or reports of its use in viral conditions

Levamisole has been shown to repair immune defences in humans and a number of animalspecies (Sajid et al 2006) Although controlled studies of the immunostimulatory potential oflevamisole have not been reported it is widely used as an immune stimulant by horse trainers inNorth America and it is seen as an important element of therapy for equine protozoal myelitis

The internet is awash with so-called natural immune stimulants for horses ndash with a Google searchreturning 171000 results ndash but there is practically no scientific support for their use Productsinclude essentials oils curcumin ginger garlic Ginkgo biloba ginseng Capsicum Boswellia andgrape seed There is however some evidence for the efficacy of acemannan and extracts of Echinacea

Acemannan is extracted from the pulp of the ldquomeatyrdquo leaves of aloe vera plants and is a potentanti-viral agent that also has the ability to enhance the immune system particularly the function oflymphocytes It is used for the treatment of certain viral diseases and cancers of dogs and catsand has a US licence for the treatment of fibrosarcomas

A number of anecdotal reports exist over the use of acemannan in horses either by intravenousinjection or oral administration of aloe vera gels and drinks

Clinical efficacy in the treatment of equine respiratory disease has been reported as has successin treating sarcoids when the acemannan is injected directly into the tumour (Rush and Flaminio2000) An experience with aloe vera in the treatment of equine chronic fatigue syndrome ishighlighted in the accompanying case history

Extracts of the plant Echinacea angustifolia are widely reported to be immune stimulants and thereis some scientific support for an immunostimulatory effect in horses In a controlled study Echinacea was found to boost peripheral lymphocyte counts increase the phagocytic ability ofisolated neutrophils and stimulate neutrophil migration from peripheral circulation into the tissues(OrsquoNeill et al 1992) Supplementation also increased the size and concentration of peripheral redblood cells the concentration of haemoglobin and packed cell volume

Case history

Vinnie was a 12-year-old gelding eventing at intermediate level that went off his food developed a

6 15

serous nasal discharge and dry cough and had a fever in January 2007

Blood samples showed a markedly reduced white blood cell count an almost total depletion oflymphocytes and low haematocrit (Table 2) Initial treatment with trimethoprim- sulphonamideantibiotics and a clenbuterol-based syrup improved Vinniersquos respiratory condition Subsequentendoscopic examination with a tracheal wash revealed no significant abnormalities White bloodcell and lymphocyte counts increased with a fourweek period of rest so Vinnie returned to work

Three months later the owner became concerned that Vinnie was not able to cope with hiscompetition programme and was tiring easily He performed badly in the cross-country phases ofseveral events with an unusual number of jumping penalties and a couple of retirements

Further blood tests at the end of May revealed a lowering of the white blood cell and lymphocytecounts although he was now no longer anaemic These parameters remained low despitetreatment with a dietary copper supplement levamisole and interferon- over the ensuing twomonths Vinnie was then turned away to grass for three months with no ridden exercise

Prolonged rest did not improve the blood picture with the white blood cell count in particularremaining low and this did not improve with further rest over the winter months In spring 2008 theowner came across an article on the usefulness of acemannan in post-viral lethargy syndromesand Vinnie was started on a six-week treatment with aloe vera gel

The owner noticed a significant improvement in Vinniersquos demeanour and general condition andblood samples taken towards the end of the treatment period in June 2008 showed substantialimprovements in white blood cell and lymphocyte counts ndash which had more than doubled during thecourse of treatment ndash and haematocrit This was accompanied by a marked transformation in hiswork with him being much more responsive not tiring and making fewer jumping errors Vinniereturned to competitive activities soon after

Conclusion

Vinniersquos story is typical of many horses with equine chronic fatigue syndrome and serves toillustrate the frustration that it can cause owners particularly of competition horses

Symptoms can persist for a long period of time ndash in Vinniersquos instance considerably longer than 12months ndash and treatment including prolonged rest and potential immunostimulants can beineffective However the six-week course of aloe vera gel cost pound180 and was backed by a 60-daymoney-back guarantee from the local distributor which promised a full refund if there was noimprovement

References

7 15

Baker R and Shaw E J (2007) Diagnosis and management of chronic fatigue syndrome ormyalgic encephalomyelitis (or encephalopathy) summary of NICE guidance BMJ 335446-448Chia J K (2005) The role of enterovirus in chronic fatigue syndrome J Clin Pathol Nov 58(11) 1126-1132 Hampil B et al (1965) Preparation of antiserum to enteroviruses inlarge animals J Immunol 95 895-908Hampil B and Melnick J L (1968) WHO collaborative studies on enterovirus referenceantisera second report Bull World Health Organ 38 577-593Lunn D P and Rush B R (2004) Immunomodulation in horses principles and mechanismsIn Proceedings of 50th Annual Convention of the American Association of EquinePractitioners Denver P14811204OrsquoNeill W McKee S and Clarke A F (2002) Immunological and haematinic consequencesof feeding a standardized Echinacea (Echinacea angustifolia) extract to healthy horses Equine Vet J 34 222-227Plummer G (1963) An equine respiratory enterovirus some biological and physicalproperties Archives of Virology 12(5) 694-700Ricketts SW et al (1992) Equine fatigue syndrome The Veterinary Record 131 58-59Rush B R and Flaminio M J (2000) Immunomodulation in horses Vet Clin North Am Pract 16 183-197Rush B R and Lunn D P (2004) Immunomodulation in horses indications and preparationsProceedings of 50th Annual Convention of the American Association of EquinePractitioners Denver P14811204Rush Moore B R et al (1996) Changes in airway inflammatory cell populations instandardbred racehorses after interferon-alpha administration Vet Immunol Immunopathol 49 347-358Sajid M S et al (2006) Immunomodulatory effect of various anti-parasitics a review Parasitology 132 301-313Sasagawa A Miyamura K and Kono R (1982) Enterovirus type-70 neutralising IgM inanimal sera Jpn J Med Sci Biol 35 63-73Sullivan K E et al (1993) Effects of perioperative G-CSF on horses with ascending colonicischaemia Vet Surg 22 343-350Tarello W (2001) Chronic fatigue syndrome in horses diagnosis and treatment of fourcases Comparative Immunology Microbiology and Infectious Diseases 24 57-70Toribio R E et al (1998) Congenital defects in newborn foals of mares treated for equineprotozoal myeloencephalitis during pregnancy J Am Vet Med Assoc 212 697-701Urasawa S et al (1987) Comparison of naturally occurring poliovirusreactiveimmunoglobulins in bovine and equine sera Jpn J Med Sci Biol 40(2) 61-74thehorsedoctor (2008) www thehorsedoctorblogspotcom200808chronic-fatiguesyndrome- in-horseshtmlZinkl J G et al (1994) Haematological bone marrow and clinical chemical changes inneonatal foals given canine recombinant granulocytecolony stimulating factor Equine Vet J 26 313-318

8 15

of 22 IUkg bodyweight in horses with both acute respiratory viruses and chronic fatigue syndromewith variable results

Granulocyte-colony stimulating factor has been used in horses for the treatment of neutropeniaresulting from sepsis (Zinkl et al 1994) endotoxaemia (Sullivan et al 1993) and drug-inducedmyeloid hypoplasia (Toribio et al 1998) There is no evidence of any effect on the lymphocyte orcell-mediated immunity or reports of its use in viral conditions

Levamisole has been shown to repair immune defences in humans and a number of animalspecies (Sajid et al 2006) Although controlled studies of the immunostimulatory potential oflevamisole have not been reported it is widely used as an immune stimulant by horse trainers inNorth America and it is seen as an important element of therapy for equine protozoal myelitis

The internet is awash with so-called natural immune stimulants for horses ndash with a Google searchreturning 171000 results ndash but there is practically no scientific support for their use Productsinclude essentials oils curcumin ginger garlic Ginkgo biloba ginseng Capsicum Boswellia andgrape seed There is however some evidence for the efficacy of acemannan and extracts of Echinacea

Acemannan is extracted from the pulp of the ldquomeatyrdquo leaves of aloe vera plants and is a potentanti-viral agent that also has the ability to enhance the immune system particularly the function oflymphocytes It is used for the treatment of certain viral diseases and cancers of dogs and catsand has a US licence for the treatment of fibrosarcomas

A number of anecdotal reports exist over the use of acemannan in horses either by intravenousinjection or oral administration of aloe vera gels and drinks

Clinical efficacy in the treatment of equine respiratory disease has been reported as has successin treating sarcoids when the acemannan is injected directly into the tumour (Rush and Flaminio2000) An experience with aloe vera in the treatment of equine chronic fatigue syndrome ishighlighted in the accompanying case history

Extracts of the plant Echinacea angustifolia are widely reported to be immune stimulants and thereis some scientific support for an immunostimulatory effect in horses In a controlled study Echinacea was found to boost peripheral lymphocyte counts increase the phagocytic ability ofisolated neutrophils and stimulate neutrophil migration from peripheral circulation into the tissues(OrsquoNeill et al 1992) Supplementation also increased the size and concentration of peripheral redblood cells the concentration of haemoglobin and packed cell volume

Case history

Vinnie was a 12-year-old gelding eventing at intermediate level that went off his food developed a

6 15

serous nasal discharge and dry cough and had a fever in January 2007

Blood samples showed a markedly reduced white blood cell count an almost total depletion oflymphocytes and low haematocrit (Table 2) Initial treatment with trimethoprim- sulphonamideantibiotics and a clenbuterol-based syrup improved Vinniersquos respiratory condition Subsequentendoscopic examination with a tracheal wash revealed no significant abnormalities White bloodcell and lymphocyte counts increased with a fourweek period of rest so Vinnie returned to work

Three months later the owner became concerned that Vinnie was not able to cope with hiscompetition programme and was tiring easily He performed badly in the cross-country phases ofseveral events with an unusual number of jumping penalties and a couple of retirements

Further blood tests at the end of May revealed a lowering of the white blood cell and lymphocytecounts although he was now no longer anaemic These parameters remained low despitetreatment with a dietary copper supplement levamisole and interferon- over the ensuing twomonths Vinnie was then turned away to grass for three months with no ridden exercise

Prolonged rest did not improve the blood picture with the white blood cell count in particularremaining low and this did not improve with further rest over the winter months In spring 2008 theowner came across an article on the usefulness of acemannan in post-viral lethargy syndromesand Vinnie was started on a six-week treatment with aloe vera gel

The owner noticed a significant improvement in Vinniersquos demeanour and general condition andblood samples taken towards the end of the treatment period in June 2008 showed substantialimprovements in white blood cell and lymphocyte counts ndash which had more than doubled during thecourse of treatment ndash and haematocrit This was accompanied by a marked transformation in hiswork with him being much more responsive not tiring and making fewer jumping errors Vinniereturned to competitive activities soon after

Conclusion

Vinniersquos story is typical of many horses with equine chronic fatigue syndrome and serves toillustrate the frustration that it can cause owners particularly of competition horses

Symptoms can persist for a long period of time ndash in Vinniersquos instance considerably longer than 12months ndash and treatment including prolonged rest and potential immunostimulants can beineffective However the six-week course of aloe vera gel cost pound180 and was backed by a 60-daymoney-back guarantee from the local distributor which promised a full refund if there was noimprovement

References

7 15

Baker R and Shaw E J (2007) Diagnosis and management of chronic fatigue syndrome ormyalgic encephalomyelitis (or encephalopathy) summary of NICE guidance BMJ 335446-448Chia J K (2005) The role of enterovirus in chronic fatigue syndrome J Clin Pathol Nov 58(11) 1126-1132 Hampil B et al (1965) Preparation of antiserum to enteroviruses inlarge animals J Immunol 95 895-908Hampil B and Melnick J L (1968) WHO collaborative studies on enterovirus referenceantisera second report Bull World Health Organ 38 577-593Lunn D P and Rush B R (2004) Immunomodulation in horses principles and mechanismsIn Proceedings of 50th Annual Convention of the American Association of EquinePractitioners Denver P14811204OrsquoNeill W McKee S and Clarke A F (2002) Immunological and haematinic consequencesof feeding a standardized Echinacea (Echinacea angustifolia) extract to healthy horses Equine Vet J 34 222-227Plummer G (1963) An equine respiratory enterovirus some biological and physicalproperties Archives of Virology 12(5) 694-700Ricketts SW et al (1992) Equine fatigue syndrome The Veterinary Record 131 58-59Rush B R and Flaminio M J (2000) Immunomodulation in horses Vet Clin North Am Pract 16 183-197Rush B R and Lunn D P (2004) Immunomodulation in horses indications and preparationsProceedings of 50th Annual Convention of the American Association of EquinePractitioners Denver P14811204Rush Moore B R et al (1996) Changes in airway inflammatory cell populations instandardbred racehorses after interferon-alpha administration Vet Immunol Immunopathol 49 347-358Sajid M S et al (2006) Immunomodulatory effect of various anti-parasitics a review Parasitology 132 301-313Sasagawa A Miyamura K and Kono R (1982) Enterovirus type-70 neutralising IgM inanimal sera Jpn J Med Sci Biol 35 63-73Sullivan K E et al (1993) Effects of perioperative G-CSF on horses with ascending colonicischaemia Vet Surg 22 343-350Tarello W (2001) Chronic fatigue syndrome in horses diagnosis and treatment of fourcases Comparative Immunology Microbiology and Infectious Diseases 24 57-70Toribio R E et al (1998) Congenital defects in newborn foals of mares treated for equineprotozoal myeloencephalitis during pregnancy J Am Vet Med Assoc 212 697-701Urasawa S et al (1987) Comparison of naturally occurring poliovirusreactiveimmunoglobulins in bovine and equine sera Jpn J Med Sci Biol 40(2) 61-74thehorsedoctor (2008) www thehorsedoctorblogspotcom200808chronic-fatiguesyndrome- in-horseshtmlZinkl J G et al (1994) Haematological bone marrow and clinical chemical changes inneonatal foals given canine recombinant granulocytecolony stimulating factor Equine Vet J 26 313-318

8 15

serous nasal discharge and dry cough and had a fever in January 2007

Blood samples showed a markedly reduced white blood cell count an almost total depletion oflymphocytes and low haematocrit (Table 2) Initial treatment with trimethoprim- sulphonamideantibiotics and a clenbuterol-based syrup improved Vinniersquos respiratory condition Subsequentendoscopic examination with a tracheal wash revealed no significant abnormalities White bloodcell and lymphocyte counts increased with a fourweek period of rest so Vinnie returned to work

Three months later the owner became concerned that Vinnie was not able to cope with hiscompetition programme and was tiring easily He performed badly in the cross-country phases ofseveral events with an unusual number of jumping penalties and a couple of retirements

Further blood tests at the end of May revealed a lowering of the white blood cell and lymphocytecounts although he was now no longer anaemic These parameters remained low despitetreatment with a dietary copper supplement levamisole and interferon- over the ensuing twomonths Vinnie was then turned away to grass for three months with no ridden exercise

Prolonged rest did not improve the blood picture with the white blood cell count in particularremaining low and this did not improve with further rest over the winter months In spring 2008 theowner came across an article on the usefulness of acemannan in post-viral lethargy syndromesand Vinnie was started on a six-week treatment with aloe vera gel

The owner noticed a significant improvement in Vinniersquos demeanour and general condition andblood samples taken towards the end of the treatment period in June 2008 showed substantialimprovements in white blood cell and lymphocyte counts ndash which had more than doubled during thecourse of treatment ndash and haematocrit This was accompanied by a marked transformation in hiswork with him being much more responsive not tiring and making fewer jumping errors Vinniereturned to competitive activities soon after

Conclusion

Vinniersquos story is typical of many horses with equine chronic fatigue syndrome and serves toillustrate the frustration that it can cause owners particularly of competition horses

Symptoms can persist for a long period of time ndash in Vinniersquos instance considerably longer than 12months ndash and treatment including prolonged rest and potential immunostimulants can beineffective However the six-week course of aloe vera gel cost pound180 and was backed by a 60-daymoney-back guarantee from the local distributor which promised a full refund if there was noimprovement

References

7 15

Baker R and Shaw E J (2007) Diagnosis and management of chronic fatigue syndrome ormyalgic encephalomyelitis (or encephalopathy) summary of NICE guidance BMJ 335446-448Chia J K (2005) The role of enterovirus in chronic fatigue syndrome J Clin Pathol Nov 58(11) 1126-1132 Hampil B et al (1965) Preparation of antiserum to enteroviruses inlarge animals J Immunol 95 895-908Hampil B and Melnick J L (1968) WHO collaborative studies on enterovirus referenceantisera second report Bull World Health Organ 38 577-593Lunn D P and Rush B R (2004) Immunomodulation in horses principles and mechanismsIn Proceedings of 50th Annual Convention of the American Association of EquinePractitioners Denver P14811204OrsquoNeill W McKee S and Clarke A F (2002) Immunological and haematinic consequencesof feeding a standardized Echinacea (Echinacea angustifolia) extract to healthy horses Equine Vet J 34 222-227Plummer G (1963) An equine respiratory enterovirus some biological and physicalproperties Archives of Virology 12(5) 694-700Ricketts SW et al (1992) Equine fatigue syndrome The Veterinary Record 131 58-59Rush B R and Flaminio M J (2000) Immunomodulation in horses Vet Clin North Am Pract 16 183-197Rush B R and Lunn D P (2004) Immunomodulation in horses indications and preparationsProceedings of 50th Annual Convention of the American Association of EquinePractitioners Denver P14811204Rush Moore B R et al (1996) Changes in airway inflammatory cell populations instandardbred racehorses after interferon-alpha administration Vet Immunol Immunopathol 49 347-358Sajid M S et al (2006) Immunomodulatory effect of various anti-parasitics a review Parasitology 132 301-313Sasagawa A Miyamura K and Kono R (1982) Enterovirus type-70 neutralising IgM inanimal sera Jpn J Med Sci Biol 35 63-73Sullivan K E et al (1993) Effects of perioperative G-CSF on horses with ascending colonicischaemia Vet Surg 22 343-350Tarello W (2001) Chronic fatigue syndrome in horses diagnosis and treatment of fourcases Comparative Immunology Microbiology and Infectious Diseases 24 57-70Toribio R E et al (1998) Congenital defects in newborn foals of mares treated for equineprotozoal myeloencephalitis during pregnancy J Am Vet Med Assoc 212 697-701Urasawa S et al (1987) Comparison of naturally occurring poliovirusreactiveimmunoglobulins in bovine and equine sera Jpn J Med Sci Biol 40(2) 61-74thehorsedoctor (2008) www thehorsedoctorblogspotcom200808chronic-fatiguesyndrome- in-horseshtmlZinkl J G et al (1994) Haematological bone marrow and clinical chemical changes inneonatal foals given canine recombinant granulocytecolony stimulating factor Equine Vet J 26 313-318

8 15

Baker R and Shaw E J (2007) Diagnosis and management of chronic fatigue syndrome ormyalgic encephalomyelitis (or encephalopathy) summary of NICE guidance BMJ 335446-448Chia J K (2005) The role of enterovirus in chronic fatigue syndrome J Clin Pathol Nov 58(11) 1126-1132 Hampil B et al (1965) Preparation of antiserum to enteroviruses inlarge animals J Immunol 95 895-908Hampil B and Melnick J L (1968) WHO collaborative studies on enterovirus referenceantisera second report Bull World Health Organ 38 577-593Lunn D P and Rush B R (2004) Immunomodulation in horses principles and mechanismsIn Proceedings of 50th Annual Convention of the American Association of EquinePractitioners Denver P14811204OrsquoNeill W McKee S and Clarke A F (2002) Immunological and haematinic consequencesof feeding a standardized Echinacea (Echinacea angustifolia) extract to healthy horses Equine Vet J 34 222-227Plummer G (1963) An equine respiratory enterovirus some biological and physicalproperties Archives of Virology 12(5) 694-700Ricketts SW et al (1992) Equine fatigue syndrome The Veterinary Record 131 58-59Rush B R and Flaminio M J (2000) Immunomodulation in horses Vet Clin North Am Pract 16 183-197Rush B R and Lunn D P (2004) Immunomodulation in horses indications and preparationsProceedings of 50th Annual Convention of the American Association of EquinePractitioners Denver P14811204Rush Moore B R et al (1996) Changes in airway inflammatory cell populations instandardbred racehorses after interferon-alpha administration Vet Immunol Immunopathol 49 347-358Sajid M S et al (2006) Immunomodulatory effect of various anti-parasitics a review Parasitology 132 301-313Sasagawa A Miyamura K and Kono R (1982) Enterovirus type-70 neutralising IgM inanimal sera Jpn J Med Sci Biol 35 63-73Sullivan K E et al (1993) Effects of perioperative G-CSF on horses with ascending colonicischaemia Vet Surg 22 343-350Tarello W (2001) Chronic fatigue syndrome in horses diagnosis and treatment of fourcases Comparative Immunology Microbiology and Infectious Diseases 24 57-70Toribio R E et al (1998) Congenital defects in newborn foals of mares treated for equineprotozoal myeloencephalitis during pregnancy J Am Vet Med Assoc 212 697-701Urasawa S et al (1987) Comparison of naturally occurring poliovirusreactiveimmunoglobulins in bovine and equine sera Jpn J Med Sci Biol 40(2) 61-74thehorsedoctor (2008) www thehorsedoctorblogspotcom200808chronic-fatiguesyndrome- in-horseshtmlZinkl J G et al (1994) Haematological bone marrow and clinical chemical changes inneonatal foals given canine recombinant granulocytecolony stimulating factor Equine Vet J 26 313-318

8 15

Acemannan is extracted from the pulp of the ldquomeatyrdquo leaves of Aloe vera plants and is a potentanti-viral agent that also has the ability to enhance the immune system particularly the function oflymphocytes

9 15

10 15

11 15

11 15

Vinnie a 12-year-old gelding before (left) and after treatment with aloe vera gel

12 15

13 15

13 15

Vinnie a 12-year-old gelding before (left) and after treatment with aloe vera gel

TABLE 1 Causes of lymphopaenia in horses

14 15

TABLE 2 White blood cell lymphocyte and haematocrit parameters in Vinnie over the course ofhis illness and treatment

Powered by TCPDF (wwwtcpdforg)

15 15