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Mycoplasma mycoides subsp. mycoides (LC) infections

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Mycoplasma mycoides subsp. mycoides (LC) infections

Summary

  • Last modified
  • 03 January 2018
  • Datasheet Type(s)
  • Animal Disease
  • Preferred Scientific Name
  • Mycoplasma mycoides subsp. mycoides (LC) infections
  • Overview

  • Mycoplasma mycoides subsp. mycoides large colony (MmmLC) produces a severe disease in goats, but its main significance to researchers has been its close similarity with...

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Pictures

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PictureTitleCaptionCopyright
Goat showing respiratory distress as a result of infection with MmmLC.
TitleSymptoms
CaptionGoat showing respiratory distress as a result of infection with MmmLC.
CopyrightR.A.J. Nicholas
Goat showing respiratory distress as a result of infection with MmmLC.
SymptomsGoat showing respiratory distress as a result of infection with MmmLC.R.A.J. Nicholas
Swollen joints in forelimbs of a sheep caused by MmmLC.
TitleSymptoms
CaptionSwollen joints in forelimbs of a sheep caused by MmmLC.
CopyrightR.A.J. Nicholas
Swollen joints in forelimbs of a sheep caused by MmmLC.
SymptomsSwollen joints in forelimbs of a sheep caused by MmmLC.R.A.J. Nicholas
Keratoconjunctivitis in a sheep caused by MmmLC.
TitleSymptoms
CaptionKeratoconjunctivitis in a sheep caused by MmmLC.
CopyrightR.A.J. Nicholas
Keratoconjunctivitis in a sheep caused by MmmLC.
SymptomsKeratoconjunctivitis in a sheep caused by MmmLC.R.A.J. Nicholas
Abnormal milk (left) from a goat with contagious agalactia caused by MmmLC; Normal milk on the right.
TitleAbnormal milk samples
CaptionAbnormal milk (left) from a goat with contagious agalactia caused by MmmLC; Normal milk on the right.
CopyrightR.A.J. Nicholas
Abnormal milk (left) from a goat with contagious agalactia caused by MmmLC; Normal milk on the right.
Abnormal milk samplesAbnormal milk (left) from a goat with contagious agalactia caused by MmmLC; Normal milk on the right.R.A.J. Nicholas
Lung from pneumonic goat showing enlarged interlobular septa caused by MmmLC.
TitleLung pathology
CaptionLung from pneumonic goat showing enlarged interlobular septa caused by MmmLC.
CopyrightR.A.J. Nicholas
Lung from pneumonic goat showing enlarged interlobular septa caused by MmmLC.
Lung pathologyLung from pneumonic goat showing enlarged interlobular septa caused by MmmLC.R.A.J. Nicholas

Identity

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Preferred Scientific Name

  • Mycoplasma mycoides subsp. mycoides (LC) infections

International Common Names

  • English: caprine pleuropneumonia; contagious agalactia; granular vulvovaginitis of goats and sheep; MmmLC arthritis; MmmLC balanoposthitis in sheep; MmmLC keratoconjunctivitis; MmmLC mastitis; MmmLC pleuropneumonia; MmmLC septicaemia; MmmLC vulvovaginitis in sheep; mycoplasma mycoides infection in sheep - exotic; mycoplasmal balanoposthitis and vulvovaginitis in sheep

Overview

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Mycoplasma mycoides subsp. mycoides large colony (MmmLC) produces a severe disease in goats, but its main significance to researchers has been its close similarity with the small colony type, M. mycoides subsp. mycoides SC (MmmSC), the cause of one of the most serious diseases in cattle; contagious bovine pleuropneumonia (CBPP). It was originally thought that strains of M. mycoides subsp. mycoides isolated from goats produced large colonies in vitro, whereas cattle strains gave small colonies; as a result Cottew and Yeats (1978) used this feature to distinguish the two mycoplasmas. Later, however, Valdiviesio and Rosendal (1982) found this to be unreliable as both small and large could be recovered from goats infected with MmmLC. Although serologically related, recent evidence shows that the two types are clearly distiguishable. However, it is the relationship between MmmLC and M. mycoides subsp. capri which is more contentious and has led many to consider the two to be identical, particularly on the basis of 16S rRNA sequencing which reveals 99.9% similarity (Pettersson et al., 1996).

MmmLC is one of 4 mycoplasmas described by the Offices des International Epizooties as a cause of contagious agalactia (a list B disease) together with M. agalactiae, M. capricolum subsp. capricolum and M. putrefaciens; it is also a major cause of pleuropneumonia in goats. The following table shows how MmmLC compares clinically with other mycoplasmas of small ruminants.

Comparative characteristics of some mycoplasmas of small ruminants including M. mycoides subsp. mycoides LC


MycoplasmaHostPrimary site of isolation (other)Disease*Pathogenicity
M. m. mycoides LCGoat (sheep, cattle)Respiratory tract (udder, joints)Plp, M, A, CModerate
M. m. capriGoat (sheep)Respiratory tract (joints)Plp, A, CModerate
M. c. capricolumGoat, sheepJoints/Respiratory tract (udder)Plp, M, AHigh
M. c. capripneumoniaeGoat (sheep)LungsCCPPHigh
M. ovipneumoniaeSheep, goatRespiratory tractPneumoniaLow
M. conjunctivaeSheep and goatsEyesKCModerate
M. agalactiaeSheep and goatsUdder (joints, eyes)M, A, KC, PHigh
M. putrefaciensGoats (sheep)Udder (joints)M, AModerate
M. argininiUbiquitousRespiratory tractNoneLow/non pathogenic

*Plp- pleuropneumonia

P- pneumonia

M- mastitis

A-arthritis

C-conjunctivitis

KC-keratoconjunctivitis

CCPP- contagious caprine pleuropneumonia

Host Animals

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Animal nameContextLife stageSystem
Bos taurus (cattle)Domesticated hostCattle & Buffaloes: All Stages
Capra hircus (goats)Domesticated hostSheep & Goats: All Stages
Ovis aries (sheep)Domesticated hostSheep & Goats: All Stages|Sheep & Goats/Lamb|Sheep & Goats/Gimmer|Sheep & Goats/Mature female

Hosts/Species Affected

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MmmLC has been isolated mainly from goats, and occasionally from sheep with balanoposthitis and vulvovaginitis (Trichard et al., 1993). There have been a few reports from cattle; Perreau (1979) isolated MmmLC from one of four cases of pericarditis, pleurisy and bronchopneumonia in calves in France and Kapoor et al. (1989) detected MmmLC in aborted bovine foetuses. More recently MmmLC has been detected in healthy cattle during the CBPP eradication campaigns in Portugal and Italy where it was reported to cause serological cross reactions with MmmSC (Machado et al., 2000). Perrin et al. (1994) isolated MmmLC from captive wild goats in Switzerland.

Antibody responses to MmmLC were detected in 5-15% of Peruvian camelids including alpacas and llamas by passive haemagglutination tests (Hung et al., 1991) but no mycoplasmas have been isolated to date (Nicholas, 1998). Alpacas, llamas and vicunas suffer pneumonia, pleuritis and polyarthritis so it is not unlikely that mycoplasmas are causative agents.

Systems Affected

Top of page blood and circulatory system diseases of small ruminants
mammary gland diseases of small ruminants
multisystemic diseases of small ruminants
reproductive diseases of small ruminants
respiratory diseases of large ruminants
respiratory diseases of small ruminants

Distribution

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MmmLC has one of the widest geographic distribution of ruminant mycoplasmas, being found in all continents where small ruminants are kept and wherever contagious agalactia and caprine pleuropneumonia are reported; however, the lack of diagnostic facilities for mycoplasma diseases in many countries means that infections are usually under-reported.

Distribution Table

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The distribution in this summary table is based on all the information available. When several references are cited, they may give conflicting information on the status. Further details may be available for individual references in the Distribution Table Details section which can be selected by going to Generate Report.

Pathology

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The close similarity of MmmLC and M. m. capri often leads to misidentification and reports of pleuropneumonia caused by M. m. capri must be treated with caution. Those caused by MmmLC are characterised by lungs which are enlarged and firm with hepatisation of cardiac and diaphragmatic lobes and marked pleural effusion and fibrinous pleuritis. There is extensive pulmonary oedema and interlobular septa are usually distended and pale. Histopathologically there is little to distinguish the two mycoplasmas. Arterial and arteriolar vasculitis with necrosis of vessel wall and thrombi are common.

Severe repiratory signs and high mortality were the most significant findings in one goat herd with pleuropneumonia caused by MmmLC in Spain (Rodriguez et al., 1995). The adults presented mainly with respiratory disease and/or mastitis whereas the young animals died showing arthritis and/or keratoconjunctivitis. The most significant lesions were found in the thoracic cavity. Macroscopically, a focal extensive fibrinonecrotic pleuropneumonia was seen and histopathological analysis confirmed a fribrinopurulent and necrotic pleuropneumonia with areas of acute pyogenicbronchopneumonia and fibrinous pericarditis associated with a mucopurulent mastitis and/or a fibrinopurulent arthritis.

Diagnosis

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Clinical signs and pathological changes associated with MmmLC, if any are present, are not characteristic. It is very important to distinguish between infections caused by MmmLC/M. m. capri and those caused M. c. capripneumoniae, the cause of classical contagious pleuropneumonia (CCPP) which is not present in Europe. The key features in CCPP infections are its highly infectious nature, the lack of distention of the interlobular septa in the lungs, and restriction to the lungs. Laboratory diagnosis must always be performed to determine the true cause of disease (Nicholas and Baker, 1998).

Samples of choice from living animals include: nasal swabs and secretions; milk from mastitic does or from apparently healthy does where there is a high rate of mortality/morbidity in kids; joint fluid from arthritic cases; eye swabs from cases of ocular disease; blood for antibody detection from affected and non-affected animals; and ear swabs. Samples from dead animals should include lung tissue (at the interface between diseased and healthy tissue) and pleural/pericardial fluid. Samples should be dispatched quickly to a diagnostic laboratory in a moist and cool condition. MmmLC is readily recoverable from internal organs, joints and milk, and grows well in most media producing large colonies (1-2 mm) in 2-3 days.

Biochemical tests can give some guidance to the identification of the causative mycoplasma (see table below), but confirmation is definitively achieved by growth inhibition, fluorescent antibody or metabolic inhibition tests using hyperimmunne specific rabbit antiserum (Poveda and Nicholas, 1998).

Major biochemical differences between mycoplasmas of small ruminants


MycoplasmaGlucose fermentationArginine hydrolysisPhosphatase activityFilm and spotsCasein digestionTetrazolium reduction Aerobic / Anaerobic
M. mycoides LC+---++ +
M. m. capri+---++ +
M. c. capricolum+++-++ +
M. c. capripneumoniae+---+nk* nk
M. ovipneumoniae+----Varies +
M. conjunctivae+----- +
M. agalactiae--++-+ +
M. putrefaciens+-++-Varies +
M. arginini-+---- +

*nk- not known

Rodriguez et al. (1996a) reported a monoclonal antibody-based sandwich ELISA which could detect as little as 105 CFU/ml of both M. mycoides biotypes within two hours. Sensitivity could be improved significantly by incubating samples for 48 hours. This test could not distinguish between the SC and LC types but coupled with pathological and serological information from affected animals, the test could prove very useful.

Polymerase chain reaction tests (PCR) are now also available to provide highly specific diagnoses in hours on cultured mycoplasmas or clinical material. Bashiruddin et al. (1994) reported a set of primers, based on CAP-21 sequences, capable of amplifying DNA from all members of the M. mycoides cluster; MmmLC could be differentiated from MmmSC but not from M. m. capri by digestion with a restriction enzyme Asn1. Using the same gene fragment, Hotzel et al. (1994) reported PCR tests differentiating Mmm LC from M. m. m.capri.

Serological detection of antibodies to MmmLC is not widely performed. Those that have been reported include complement fixation and indirect haemagglutination tests (Lefevre et al., 1987). In-house ELISAs have been produced which can distinguish MmmLC from M. agalactiae (Levisohn et al., 1991). In the UK, a country which is currently free of contagious agalactia, immunoblotting tests are used on all ELISA-positive sera; to date no positive results have been confirmed (Nicholas, 1998).

An immunohistochemical method of detecting MmmLC antigens using monoclonal antibodies on paraffin sections of caprine lungs was described by Rodriguez et al. (1996b). This technique detected antigens in the cell debris around necrotic areas and in macrophages, neutrophils and epithelial cells in lungs from both natural and experimental infections.

List of Symptoms/Signs

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SignLife StagesType
Digestive Signs / Anorexia, loss or decreased appetite, not nursing, off feed Sign
Digestive Signs / Diarrhoea Sign
General Signs / Fever, pyrexia, hyperthermia Sheep & Goats:Lamb Sign
General Signs / Forelimb lameness, stiffness, limping fore leg Sheep & Goats:Lamb Sign
General Signs / Forelimb swelling, mass in fore leg joint and / or non-joint area Sign
General Signs / Generalized lameness or stiffness, limping Sheep & Goats:Lamb Sign
General Signs / Haemorrhage of any body part or clotting failure, bleeding Sign
General Signs / Hindlimb lameness, stiffness, limping hind leg Sign
General Signs / Hindlimb swelling, mass in hind leg joint and / or non-joint area Sign
General Signs / Lack of growth or weight gain, retarded, stunted growth Sheep & Goats:Lamb Sign
General Signs / Mammary gland swelling, mass, hypertrophy udder, gynecomastia Sign
General Signs / Reluctant to move, refusal to move Sheep & Goats:Lamb Sign
General Signs / Sudden death, found dead Cattle & Buffaloes:Calf Sign
General Signs / Swelling mass penis, prepuce, testes, scrotum Sign
General Signs / Swelling mass, vulva, clitoris Sign
General Signs / Underweight, poor condition, thin, emaciated, unthriftiness, ill thrift Sign
General Signs / Weight loss Sheep & Goats:Lamb Sign
Nervous Signs / Dullness, depression, lethargy, depressed, lethargic, listless Sign
Nervous Signs / Dullness, depression, lethargy, depressed, lethargic, listless Sign
Ophthalmology Signs / Blindness Sheep & Goats:All Stages Sign
Ophthalmology Signs / Corneal edema, opacity Sheep & Goats:All Stages Sign
Ophthalmology Signs / Decreased or absent menace response but not blind Sheep & Goats:All Stages Sign
Pain / Discomfort Signs / Forelimb pain, front leg Sheep & Goats:Lamb Sign
Pain / Discomfort Signs / Hindlimb pain, hind leg Sheep & Goats:Lamb Sign
Pain / Discomfort Signs / Pain mammary gland, udder Sign
Pain / Discomfort Signs / Pain, penis Sign
Pain / Discomfort Signs / Pain, prepuce Sign
Pain / Discomfort Signs / Pain, vulva, vagina Sign
Reproductive Signs / Abortion or weak newborns, stillbirth Sheep & Goats:Mature female Sign
Reproductive Signs / Agalactia, decreased, absent milk production Sign
Reproductive Signs / Heat on palpation penis Sign
Reproductive Signs / Lack of libido or erection Sign
Reproductive Signs / Mastitis, abnormal milk Sign
Reproductive Signs / Necrosis, vagina, vulva Sign
Reproductive Signs / Papule, pustule, vesicle, ulcer penis or prepuce Sign
Reproductive Signs / Purulent discharge, penis or prepuce Sign
Reproductive Signs / Purulent discharge, vulvar, vaginal Sign
Reproductive Signs / Purulent discharge, vulvar, vaginal Sign
Reproductive Signs / Vaginal or cervical ulcers, vesicles, erosions, tears, papules, pustules Sign
Reproductive Signs / Vulval ulcers, vesicles, erosions, tears, cuts, pustules, papules Sign
Reproductive Signs / Vulval ulcers, vesicles, erosions, tears, cuts, pustules, papules Sign
Reproductive Signs / Warm mammary gland, hot, heat, udder Sign
Respiratory Signs / Coughing, coughs Sheep & Goats:All Stages Sign
Respiratory Signs / Dyspnea, difficult, open mouth breathing, grunt, gasping Sheep & Goats:All Stages Sign
Respiratory Signs / Increased respiratory rate, polypnea, tachypnea, hyperpnea Sheep & Goats:All Stages Sign
Skin / Integumentary Signs / Skin crusts, scabs Sign
Skin / Integumentary Signs / Skin ulcer, erosion, excoriation Sign
Urinary Signs / Haematuria, blood in urine Sign
Urinary Signs / Increased frequency of urination, pollakiuria Sign
Urinary Signs / Red or brown urine, pink Sign

Disease Course

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Experimental infections with MmmLC readily reproduce severe pathogenic effects in kids including fever, anorexia, acute pain, swollen joints, recumbancy and dyspnoea often with death as a result of septicaemia (Nayak and Bhowmik, 1991). Goats and sheep inoculated experimentally by the respiratory or intravenous route frequently developed lung lesions whereas the subcutaneous or intramuscular route results in a massive cellulitis at the site of inoculation accompanied by a marked febrile response. Infection via the teat canal invariably leads to mastitis (DaMassa et al., 1983). Whether caprine strains of MmmLC can cause disease in calves is uncertain; in some experiments, caprine strains of MmmLC caused significant clinical signs in calves including arthritis (Rosendal, 1981) and pleuropneumonia (Ojo et al., 1980); in another other study, calves in contact with infected goats or inoculated directly did not lead to clinical disease (Rosendal, 1983).

The most common clinical findings in adult goats with natural infections are fever, mastitis, pleuropneumonia, polyarthritis and occasionally abortion; in kids, arthritis, septicaemia and, occasionally, meningitis and abortion. Keratoconjunctivitis may be also be seen in both. Kids are most frequently and more severely affected than adults but mastitis may affect 25-30% of does. The most severe outbreaks occur amongst kids after the onset of the kidding season. Arthritis, more common in kids, always occurs as a result of septicaemia frequently involving multiple joints and accompanied by generalised malaise and fever. It rarely occurs in isolation and usually follows mastitis, abortion, agalactia, pneumonia and keratoconjunctivitis. In extreme cases septicaemic goats may die without manifestation of localised signs, which may be the result of galactan production produced by MmmLC (Smith and Sherman, 1994).

Epidemiology

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MmmLC is invariably introduced into a disease-free farm/region via asymptomatic or subclinically afftected carrier goats. After an incubation period of 2-28 days, it spreads to kids predominantly via the milking process, with high numbers of mycoplasmas being shed in the milk. Adults become infected through contaminated milking machinery or milkers’ hands, with mycoplasma ascending the teat canal; other routes such as direct contact and aerosol may also be important. Stress caused by changes in husbandry, nutrition and climate is seen as a major factor in outbreaks in adults. Rosendal et al. (1979) reported maintenance of infection in a herd for over 10 years with only occasional clinical cases of Mycoplasma arthritis in young animals, these almost certainly precipitated by an outbreak of coccidiosis, and by de-horning and castration.

In most countries in Europe, M. agalactiae is the primary cause of contagious agalactia, followed by MmmLC (Loria et al., 1999); in the Canary Islands, the seroprevalence of these two mycoplasmas in affected herds during the early 1990s was 23% and 16%, respectively (Real et al., 1994). In mainland Spain, M. agalactiae was found to account for 83% of isolates from goats affected by contagious agalactia while MmmLC accounted for 7% (Gil et al., 1997). While MmmLC is found less frequently, the disease it causes is usually far more severe than that caused by M.agalactiae, with mortality reaching 25% in adults and 90% in kids. In the goat milking regions of western France, over 50% of mycoplasma isolates from bulk milk tanks have been found to be MmmLC; 27% were M. putrefaciens and only 6% were M. agalactiae (Mercier et al., 2001). MmmLC is also the most frequently reported caprine mycoplasma infection in the USA, particularly in the eastern and coastal states (Smith and Sherman, 1994).

MmmLC, as with other mycoplasmas of small ruminants, has been found in the ear canals, often associated with ear mites (DaMassa et al., 1991) or with fleas (Nayak and Bhowmik, 1990). Both mites and fleas are likely vectors and reservoirs of infection.

Impact: Economic

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Economic losses caused by decreased production, diagnosis and treatment costs can be very high in severe outbreaks, particularly in intensively commercial goat dairy operations. Unfortunately, little mycoplasma diagnosis is carried out in countries where the mycoplasma-induced diseases are most prevalent. In one outbreak in the Canary Islands, 150 of 700 goats died of respiratory disease caused by a combination of MmmLC and M. m. capri (Rodriguez et al., 1996a).

Disease Treatment

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As with most mycoplasma diseases, those caused by MmmLC do not respond well to chemotherapy in particular in cases of mastitis. Although clinical improvements may be seen, the mycoplasma may remain viable in the goats. Infected but apparently healthy does may continue to produce milk containing large numbers of mycoplasmas causing problems in vulnerable kids. In such circumstances pasteurisation of milk may help to control outbreaks; in one case morbidity and mortality was reduced from 90% to less than 5% when only mycoplasma-free milk was fed to kids (DaMassa et al., 1983). Tylosin and oxytetracycline have both been reported to be effective against pneumonia but all animals in a herd must be treated including apparently healthy goats. For arthritis, a combination of spectinomycin and lincomycin given intramuscularly for 3 days generates some recovery in sheep and goats (Smith and Sherman, 1994).

Prevention and Control

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No vaccines are currently available for MmmLC; the disease is thought not be sufficiently widespread in Europe. In Greece, Turkey and the Middle East, clinical disease is more prevalent, but differential diagnosis is not routinely performed. Most disease-free herds become infected following the introduction of a carrier animal, so knowledge of the health status of the herd of origin is essential; serious consideration should also be given to maintaining any bought-in animals in quarantine until serological testing has been carried out (see Diagnosis). Stress such as that triggered by movement or parturition should be minimised. Where mastitis is present, affected animals should be milked last and machines/hands should be disinfected. Where the situation warrants, culling of clinically affected animals should also be considered.

The possible involvement of ear mites and fleas in transmission suggest that use of insecticides such as ivermectin may be worth considering.

References

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Machado M; Ferreira H; Brandao E, 2000. Restriction endonuclease pattern of large colony biotype from bovine and caprine with particular reference to methylation of GATC sequence. In: Bergonier D, Berthelot X, Frey J, eds. Mycoplasmas of ruminants:pathogenicity, diagnostics, epidemiology and molecular genetics. Brussels: European Commission, Vol. 4 186-189.

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