Mycobacteriosis in Horses (Equis) | Vetlexicon
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Mycobacteriosis

ISSN 2398-2977


Introduction

  • Cause:Mycobacteriumspp   Mycobacterium spp  are the agents of equine mycobacteriosis.
  • Mycobacteriosis in horses is extremely rare, but when encountered, cases are most often caused byM. aviumsubspeciesavium(agent of avian tuberculosis). Rarely the agents of human tuberculosis (Mycobacterium tuberculosis) or bovine tuberculosis (Mycobacterium bovis) are the cause.
  • Signs: the clinical signs of equine mycobacteriosis depend on the organ(s) infected. Equine mycobacteriosis most commonly affects the intestinal or respiratory tracts, but cases of abortion, guttural pouch infection, arthritis and ocular infection, often associated with disseminated infection, have been reported.
  • Diagnosis: usually at necropsy. The organism is identified by culture and histopathology.
  • Treatment: treatment of systemic mycobacteriosis in horses is rarely attempted because of the cost and poor prognosis.
  • Prognosis: the prognosis is grave; most cases are diagnosed post mortem.

Presenting signs

  • The first clinical sign of mycobacteriosis in horses is often chronic loss of body condition.
  • Appetite is unchanged.

Acute presentation

  • Equine mycobacteriosis is usually a chronic disease, but may present acutely, eg in cases of abortion.

Geographic incidence

  • Worldwide in various species.
  • Mycobacterium tuberculosisandM. bovishave been known to be present since antiquity.
  • The incidence of tuberculosis in people is increasing in many countries due to developing drug resistance, migration and co-infection with human immunodeficiency infection.
  • The incidence of bovine tuberculosis in cattle and wildlife is also increasing, notably in the UK.
  • The incidence of equine mycobacteriosis caused byM. tuberculosisorM. bovisis very low in countries with a national programs of control or eradication of the disease in other species.

Age predisposition

  • The disease in horses is very rare; there is no known age predisposition, although cases are more common in horses 6 years of age or younger.
  • Immature individuals, if infected, may develop more severe lesions than adults.

Breed/Species predisposition

  • There is no known breed predisposition in horses.

Public health considerations

  • Mycobacterium bovis, is an important zoonotic organism.
  • Mycobacterium tuberculosismay be involved in reverse zoonoses, transmission from humans to animals.
  • Tuberculosis (M. tuberculosis) in humans is the leading infectious cause of death of humans in developing countries.
  • Mycobacterium aviumsubsp.aviumis generally not considered to be a zoonotic agent.

Cost considerations

  • If treatment of equine mycobacteriosis were attempted, the long course of expensive antibiotics would be prohibitively costly.

Special risks

  • Because of the potential zoonotic risk, horses infected withM. tuberculosisorM. bovisare rarely or never treated.

Pathogenesis

Etiology

  • Bacteria of the genusMycobacterium, family Mycobacteriaceae are the agents of equine mycobacteriosis   Mycobacterium spp  .
  • Mycobacteriumare closely related to the generaCorynebacterium,NocardiaandRhodococcus.
  • MycobacteriumtuberculosisandM. bovisare strict pathogens.
  • Mycobacterium aviumsubspeciesaviumis an environmental organism that causes opportunistic infections. 
  • M. aviumsubsp.aviumis theMycobacteriumspecies most often associated with granulomatous lesions in horses.
  • M. aviumsubsp.paratuberculosiscauses Johnes disease in ruminants but has not been reported in horses.
  • OtherMycobacteriumspp ('atypical mycobacteria') may occasionally cause granulomatous or pyogranulomatous infections in horses.

Predisposing factors

General
  • The horse is relatively resistant to infection withMycobacteriumspecies, including the agents of human and bovine tuberculosis.

Specific

  • Direct or indirect contact with livestock or wildlife shedding the bacteria.
  • Sporadic contact from environmental sources in the case ofM. aviumsubspaviumand other environmental mycobacterial species.

Pathophysiology

  • The organism gains access to the body, usually via the respiratory tract or digestive tract, and avoids initial killing by host phagocytes. 
  • The lesions produced are in part due to the cell-mediated immune response, which is generated after the infection has established. 
  • Acquired resistance depends on cell-mediated responses. 
  • Antibodies are not protective.
  • The virulence of the organism is due to the lipids of the cell wall, which protect the bacilli from phagocytosis. 
  • Mycobacteria can grow inside phagosomes and phagolysosomes.
  • Initially, the organism proliferates and lymphatic spread may occur at this stage. Acute or subacute inflammation occurs with polymorphonuclear infiltration. 
  • After delayed hypersensitivity develops, granulomatous inflammation supervenes and the macrophages become elongated and are concentrically arranged to form a granuloma. 
  • Outside these epithelioid cells a fibrous layer builds up and caseous necrosis occurs at the center of the lesion. In horses the granulomatous lesions caused byM. aviumsubsp.aviumonly rarely develop caseous necrosis. 
  • Liquefaction of caseous lesions may occur and a cavity develops in which further proliferation of the organism takes place. 
  • Further spread may occur via the erosion of bronchi or viscera to new areas or via the bloodstream. 
  • Mycobacteria are able to persist in a dormant (latent) state in the host.

Equine cases

  • Horses are rarely affected by mycobacterial species.
  • Horses are most often infected byM. aviumsubsp.aviumand rarely byM. bovisorM. tuberculosis
  • Usually infected via the gastrointestinal or respiratory tract; primary lesions occur in the pharynx, intestine or lungs. 
  • Secondary lesions occur in the liver, spleen and serous membranes.
  • Cutaneous forms, arthritis/synovitis, abortion, guttural pouch infection    Guttural pouch: mycosis  and ocular lesions have also been reported.

Timecourse

  • The disease is chronic.

Epidemiology

  • Most cases of equine mycobacteriosis are isolated and sporadic.
  • Agents of human and bovine tuberculosis are generally transmitted by infected individuals or animals: the definitive hosts are humans forM. tuberculosis, and cattle and wildlife reservoirs such as badgers, possums and deer forM. bovis.M. aviumsubsp.aviumcauses avian tuberculosis in a variety of avian species but is also found in the environment. Infections in animals withM. aviumsubsp.aviumare not necessarily associated with a specific animal host as the source of infection. 
  • Other mycobacteria are generally saprophytic, but some are commensals in various animal species.
  • Infection in horses is usually contracted from contaminated feed or water.
  • By aerosols or fomites - mainly from respiratory discharges from infected animals.

Diagnosis

Presenting problems

  • Depends on the location of infection.
  • Abortion, lameness or ocular signs may be present. 
  • The usual presenting problem is non-specific weight loss.

Client history

  • The history is likely to be non-specific (weight loss with normal appetite) unless localized infection is present.

Clinical signs

  • The first clinical sign of equine mycobacteriosis is often chronic loss of body condition with unchanged appetite.
  • Animals with respiratory tract infection typically do not show respiratory signs.
  • Signs referable to the location of infection, eg joints, eyes, or occasionally abortion, may be seen.

Diagnostic investigation

  • Live animal: aspirate, lymph node, biopsy tissue, urine, feces. 
  • Skin testing (tuberculin test) is not used in horses.
  • Dead animal: tissue from lesion or a selection of lymph nodes.

Strict safety precautions are required if a diagnosis of equine mycobacteriosis is suspected, especially ifM. tuberculosisorM. bovismight be involved. All samples must be handled in a safety cabinet in appropriate biocontainment facilities. Effective mycobacteriocidal disinfectants must be used and all contaminated material must be autoclaved before disposal.

Confirmation of diagnosis

Discriminatory diagnostic features

  • Ziehl-Neelsen   Staining techniques: Ziehl-Neelson stain  (acid-fast) staining reveal slender red-staining rods, some beaded against a blue/green background.
  • Non-specific fluorochrome, eg auramine or rhodamine, stained slides are examined using a fluorescent microscope.
  • Failure to detect mycobacteria on direct smear does not preclude a diagnosis of equine mycobacteriosis.
  • Specimens must be treated before culture media are inoculated. This involves selective decontamination, liquefaction of mucus and concentration by centrifugation. 
  • Mycobacteriumspp can be grown on complex organic media such as solid slants of Lowenstein-Jensen incorporating malachite green to inhibit contaminants or on Stonebrinks media. 
  • M. tuberculosisforms 'rough buff and tough' eugonic colonies on glycerol containing media.
  • Most pathogenic species grow slowly; culture requires 15-28 days.
  • Biochemical tests: to distinguish species, eg tests for niacin production, pyrazinamidase, urease and nitrate reduction. 
  • Polymerase chain reaction, DNA hybridization or DNA sequencing may be used in diagnosis.

Definitive diagnostic features

  • Mycobacterial species can be distinguished by biochemical reactions or by using DNA/DNA hybridization, ribosomal RNA probes, species specific polymerase chain reaction assays or polymerase chain reaction assays with generic mycobacterial primers and DNA sequencing.
  • Mycobacteria can be differentiated from related species, egRhodococcus  Rhodococcus equi  , on the basis of mycolic acid synthesis, phenotypic testing or by molecular-based assays.
  • Spoligotyping is used to investigate the molecular epidemiology of mycobacterial strains, especiallyM. tuberculosisandM. bovisstrains. It is based on polymorphism of the direct repeat region of the bacterial genome; the spacer sequences between the repeats are used as genetic markers.
  • Serotyping and insertion sequence restriction fragment length polymorphism (IS-RFLP) analysis are methods used to differentiate strains ofM. aviumsubsp.avium.

Gross autopsy findings

  • Most equine cases are diagnosed at necropsy. 
  • The lesions appear tumor-like on gross inspection.
  • Lesions are often found in the mesenteric lymph nodes, liver and lung.
  • Granulomatous lesions in horses rarely exhibit caseation or calcification.

Histopathology findings

  • Acid-fast bacilli are present in lesions but may be in low numbers.
  • Non-caseating granulomas, often containing degenerate neutrophils, cellular debris and multinucleated giant cells.
  • Few lymphocytes are present.
  • The lesions are not usually firmly encapsulated, but there is proliferation of fibroblasts.

Differential diagnosis

  • Identification of the species of mycobacteria involved   Mycobacterium spp  may elucidate the epidemiology of the case.
  • Differentiate from other causes of granulomatous disease, egRhodococcus equi  Rhodococcus equi  ,Corynebacteriumspp andNocardia, on the basis of bacteriology and molecular testing.

Treatment

Initial symptomatic treatment

  • Treatment for tuberculosis in domestic animals is rarely attempted because of cost, ongoing eradication programs or, in some cases, the potential zoonotic risk.
  • Treatment attempts for other myobacterial infections often result in failure.
  • Treatment has been successfully attempted in non-human primate colonies.
  • Treatment of bovine tuberculosis in animals is illegal or strongly discoraged in countries with eradication programs.

Standard treatment

  • Drugs used to treat mycobacterial infections must be able to penetrate into macrophages.
  • First-line drugs for tuberculosis therapy are isoniazid, pyrazinamide, ethambutol and rifampicin   Rifampicin  .
  • Newer drugs like chalithromycin and azithromycin may be useful in some cases of mycobacterial infections in conjunction with other drugs, eg rifampicin   Rifampicin  .
  • Second-line drugs include streptomycin   Streptomycin  , against which resistance is now common, rifapentine, kanamycin   Kanamycin  /amikacin   Amikacin  , capreomycin and fluoroquinolones   Therapeutics: nitrofurans / nitroimidazoles / quinolones  .
  • Combinations of drugs are usually used, because resistance often develops under a single-drug regime. 
  • Long-term therapy is required to effect a cure and eliminate the organism (9-24 months). 
  • Short or incomplete courses of therapy are an important cause of the development of resistantM. tuberculosis
  • Prophylactic treatment with isoniazid may be considered for pets exposed to human or bovine tuberculosis agents.

Monitoring

  • If treatment were to be attempted, it would be important to complete the full course of therapy.

Prevention

Control

  • Avoid exposure to sources of infection. 
  • Control ofM. bovisis based on tuberculin testing and slaughter of cattle, often in conjunction with control of the infection in wildlife reservoirs.

Prophylaxis

  • Vaccine strategies (BCG) are used for human tuberculosis in many countries but have not yet been satisfactorily developed for use in other species.
  • The use of such vaccines would necessitate the development of tests to discriminate between infected animals and those that have merely been vaccinated (DIVA strategy).

Group eradication

  • Because of the sporadic nature of the disease in horses, this is rarely appropriate.
  • Eradication is the focus of many control programs for bovine tuberculosis.

Outcomes

Prognosis

  • Grave.
  • Treatment of equine mycobacteriosis is rarely attempted; most cases are diagnosed at post mortem examination.

Expected response to treatment

  • Treatment of equine mycobacteriosis is rarely attempted.

Reasons for treatment failure

  • Antimicrobial resistance.
  • Difficulty in achieving drug concentrations at affected sites.
  • Lack of recognition of mycobacterial diseases until late in the course of infection.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Keck N, Dutruel H, Smyej F, Nodet M & Boschiroli M L (2010) Tuberculosis due to Mycobacterium bovis in a Camargue horse. Vet Rec 166 (16), 499-500 PubMed.
  • Hewes C A, Schneider R K, Baszler T V & Oaks J L (2005) Septic arthritis and granulomatous synovitis caused by infection with Mycobacterium avium complex in a horse. JAVMA 226 (12), 2035-2038 PubMed.
  • Monreal L, Segura D, Segales J, Garrido J M & Prades M (2001) Diagnosis of Mycobacterium bovis infection in a mare. Vet Rec 149 (23), 712-714 PubMed
  • Booth T M & Wattret A (2000) Stifle abscess in a pony associated with Mycobacterium smegmatisVet Rec 147 (16), 452-454 PubMed
  • Leifsson P S, Olsen S N & Larsen S (1997) Ocular tuberculosis in a horse. Vet Rec 141 (25), 651-654 PubMed
  • Thorel M F, Huchzermeyer H, Weiss R & Fontaine J J (1997) Mycobacterium avium infections in animals. Literature review. Vet Res 28 (5), 439-447 PubMed
  • Hart C A, Becking N J & Duerden B I (1996) Tuberculosis into the next century. J Med Microbiol 44, 1-34 PubMed
  • Helie P & Higgins R (1996) Mycobacterium avium complex abortion in a mare. J Vet Diagn Invest (2), 257-258 PubMed.
  • Gunnes G, Nord K, Vatn S & Saxegaard F (1995) A case of generalized avian tuberculosis in a horse. Vet Rec 136 (22), 565-566 PubMed
  • Cline J M, Schlafer D W, Callihan D R et al (1991) Abortion and granulomatous colitis due to Mycobacterium avium complex infection in a horse. Vet Pathol 28 (1), 89-91 PubMed.
  • Flores J M, Sanchez J & Casta M (1991) Avian tuberculosis dermatitis in a young horse. Vet Rec 128 (17), 407-408 PubMed.

Other sources of information

  • Manning E J B & Collins M T (2001) Mycobacterial Infections in Domestic and Wild Animals. Rev Sci Tech 20 (1), 331. ISBN: 929044519X.
  • Biberstein E L (1990) Mycobacterium species: The Agents of Animal Tuberculosis. In: Review of Veterinary Microbiology. Eds: Biberstein E L & Zee Y C. Boston: Blackwell Scientific. pp 202-212. ISBN: 0865420858.