Mycoplasma bovis infections

International Common Names

• English: bovine mycoplasma conjunctivitis; bovine mycoplasmal arthritis; bovine mycoplasmal conjunctivitis; bovine mycoplasmal polyarthritis; calf pneumonia; endemic pneumonia in calves; enzootic calf pneumonia; infectious bovine keratoconjunctivitis, moraxella bovis, pinkeye; keratoconjunctivitis; mastitis; mycoplasma abortion in cattle; Mycoplasma bovis arthritis; Mycoplasma bovis infertility; Mycoplasma bovis keratoconjunctivitis; Mycoplasma bovis pneumonia; mycoplasma bovis pneumonia, arthritis, tenosynovitis, in calves and cows; Mycoplasma bovis reproductive disease; Mycoplasma bovis tenosynovitis; mycoplasmal abortion in cattle; mycoplasmal mastitis in cattle; otitis media, externa, interna, middle and inner ear infections; pink eye; pinkeye

Arguably the most important mycoplasma of animals because of the range of diseases and economic losses it causes, M. bovis was first isolated in 1961 from a case of severe mastitis in cattle in the USA. It then appears to have spread via animal movements to many countries, Israel (1964), Spain (1967), Australia (1970), France (1974), Britain (1975), Czechoslovakia (1975), Germany (1977), Denmark (1981), Switzerland (1983), Morocco (1988), South Korea (1989), Brazil (1989), Northern Ireland (1993), Republic of Ireland  (1994), Chile (2000), South Africa (2005), the Czech Republic (2007) and China (2008) (Nicholas, 2011). Most European countries are thought to be affected and M. bovis has been reported in Africa and Asia.

Its prevalence is almost certainly under reported, as Pasteurella (Mannheimia), and Haemophilus (Histophilus) species are invariably isolated from calf pneumonia and are easier to detect. In arthritis and mastitis where M. bovis is a primary and uncomplicated cause, it is often overlooked as few laboratories routinely monitor for mycoplasmas. However, unlike these 'conventional' bacteria, the occurrence of M. bovis in a herd is always linked to cases of disease, in particular mastitis, arthritis and/or pneumonia (Pfützner and Sachse, 1996). M. bovis has also been linked to endometritis, salpingitis, oophoritis, abortion and seminovesiculitis which have all been reproduced experimentally (Ruhnke, 1994). Otitis media and meningitis resulting in neurological signs and permanent head tilt has also been reported (Gosselin et al., 2012) and reproduced experimentally (Maunsell et al., 2012). An unusual case of toxic epidermal necrolysis was associated with M. bovis in calves (Senturk et al., 2012).  

While M. bovis infections have always been difficult to treat, there is now considerable evidence that many strains are resistant to chemotherapy (Ayling et al., 2000; Gerchman et al., 2009).

The genome of M. bovis type strain is 1,003,404 base pairs and has a G+C content of 29.3% (Wise et al., 2011); whereas the Hubei-1 isolate was slightly smaller at 953,114 base pairs (Li et al., 2011).

Pulmonary lesions in naturally infected calves comprise exudative bronchopneumonia and extensive foci of coagulative necrosis surrounded by inflammatory cells. In studies involving experimental infections of gnotobiotic calves with M. bovis, significant pneumonia was induced involving up to 30% of the lung surface and was of sufficient severity to cause clinical respiratory disease in some calves (Thomas et al., 1986). Distinctive areas of coagulative necrosis were prominent within the lesions. More chronic infections are often associated with a chronic lymphocytic ‘cuffing’ pneumonia where there is marked hyperplasia of peribronchial lymphoid tissue causing stenosis of airway lumina and compression and collapse of adjacent pulmonary pyrenchyma. M. bovis antigen is mainly detected at the periphery of the areas of coagulative necrosis, in necrotic exudates and in close association with infiltrating macrophages and neutrophils (Rodríguez et al., 1996). More recently chronic caseonecrotic bronchopneumonia with multiple dry and crumbly foci of caseous necrosis, which resembles bovine tuberculosis, has been recognised in the USA and Europe (Nicholas, 2011).

In severe cases of mastitis, one or more quarters are tense and swollen but neither hot nor painful and on section consists of yellow greenish tissue with a purulent exudate replacing milk secretion. Affected animals usually show no signs of illness although mild respiratory symptoms and slight malaise may be seen; this absence of systemic disease is also an indication of mycoplasma mastitis.

M. bovis-induced arthritis usually affects the dithrodal joints which are grossly swollen and hot to the touch. At necropsy, the synovial capsule is turbid and thickened and a viscous opaque synovial fluid is present in excessive amounts. This is associated with distension of the tendon sheaths. Large fibrin deposits on the membranes and within the joints, sometimes forming large pads, are also seen (Stipkovits et al., 2001).

It has been reported that Mycoplasma species including M. bovis have the ability to form biofilms (McAuliffe et al., 2006). Whether the formation of biofilms has a role in the pathology of the disease is not known, however it is likely to provide the organism with some protection against the hosts immune response and antibiotic treatments, it will also facilitate longer survival in the environment than previously thought.

A clinical study of endemic pneumonia caused predominantly by M. bovis showed that nearly half of dairy calves were shedding mycoplasma at 5 days of age and by 4 weeks this reached over 90% (Stipkovits et al., 2000). Clinical disease in calves, including up to 10% mortality as a result of severe serofibrinous pneumonia, is maximal at 10-15 days. Surviving calves show very poor weight gain and remain retarded; other signs included fever, depression, hyperpnoea, dysnpnoea, nasal discharge, mild to continuous coughing and loss of appetite. While Pasteurella multocida is often isolated, the rate does not always increase over time. In the UK, calf pneumonia usually begins in November and peaks around January before declining, but deaths continue to occur in some herds in the spring at pasture representing relapses because of unresolved lung lesions (Nicholas et al., 2001a).

In M. bovis-induced mastitis, clinical signs vary from subclinical to very severe and from acute to chronic. Usually with overt disease, there is a sharp reduction in milk production, swelling and firmness of the mammary glands; the condition is usually refractory to antibiotics (Ross, 1993). In an infected herd, mastitis usually affects more than 20% of cows independently of the stage of lactation with even dry cows developing the disease. The main symptoms include a great alteration in milk consistency (watery to purulent), a rapid decrease of milk yields down to a few millilitres within 3-5 days, and quick spread of the infection from one udder quarter to the others leading to agalactia. The overall number of cells in the milk increases dramatically and after a further few weeks the affected quarters become atrophic. M. bovis mastitis is characterised by the failure of cows to recover from the disease during the continuing lactation period and from the often complete lack of response to antibiotic treatment. On recovery, milk production rarely resumes normal output.

Arthritis associated with M. bovis infection may be a sequel to either the respiratory or mastitic form of the disease (Pfützner, 1990). There is lameness, swelling of joints, slight elevation of temperature, failure of antibiotic treatment, and if severe, reduced consumption of feed and debilitation. This condition often arises within 2-3 weeks of housing and also following transportation of calves over long distances. The initial signs are reluctance to stand and a stiff gait. Many cases are mild and the animal usually recovers; in more severe cases, lameness becomes more pronounced within 1-4 days and the animal is reluctant to stand. The affected limb is either stiff or held stiffly at the affected joint. If the animal is walking, the limb may be dragged or thrown outwards to minimise articular action.

Genital disease caused by M. bovis is indistinguishable from common fertility disorders and is normally found in only a small number of individuals (Pfützner and Sachse, 1996).

M. bovis is not ubiquitous, but is widespread within the bovine population of enzootically infected areas. Infected, but clinically healthy calves and young cattle, shed the mycoplasma via the respiratory tract, thereby acting as the reservoir of infection (Pfützner, 1990). The appearance of M. bovis on some farms has been associated with increased severity of respiratory disease and increased mortality (Nicholas, 1997).

The infection is usually brought in to M. bovis-free herds by clinically healthy calves or young cattle shedding the mycoplasma and once established in a multi-age site is very difficult to eradicate. Cattle get infected via the teat canal, the respiratory tract and genital tract; artificial insemination with infected semen is another common route (Pfützner, 1990).

In a study of calves in the Netherlands, Laak et al. (1992a, 1992b) found M. bovis in 20% of pneumonic lungs from fattening herds but not in dairy herds and in only 3% of healthy calves. Following its introduction into Ireland in 1994, M. bovis has been consistently isolated from 13-23% of pneumonic lungs (Byrne et al., 2001). In Britain, about 20-25% of pneumonic herds contain antibodies to M. bovis (Nicholas et al., 2001). In France, serological screening for M. bovis in suckling beef cattle in seven counties revealed that over 80% of herds contained at least one infected animal although the number of seropositive cattle was generally low (15%) (Le Grand et al., 2001). The low ELISA titres obtained in the study suggested a less active infection process within the adult population. In Poland, Bednarek et al. (2012) found nearly 81% of 361 herds had positive M. bovis titres.

M. bovis is an important pathogen of cattle causing disease with significant detrimental impacts on animal welfare and the farming economy (Nicholas and Ayling, 2003). The real economic cost of the disease has not been determined; a detailed analysis of all cost factors such as mortality, veterinary costs, treatment, milk loss, added housing/feed costs through lack of weight gain would yield a more complete appreciation of the full economic burden. There are no official restrictions on animal movement within the European Union; however, some countries importing cattle are increasingly aware of the risks of importing infected cattle and are requesting that cattle are tested and shown to be free of M. bovis (Calcutt et al., 2018).

In the UK, it is estimated that up to 1.9 million cattle are affected annually by respiratory disease, with a consequent loss in performance of £54 million to the cattle industry (Reeve-Johnson, 1999). Furthermore, approximately 157,000 calves die annually as a result of pneumonia and related illnesses, which would have a potential market value of £99 million. Across Europe with approximately 84.5 million cattle in 1995 this translated as total losses of 576 million ECU. It is likely that M. bovis is responsible for at least a quarter to a third of these losses, although this is certainly an underestimate as few countries report mycoplasma diseases (Nicholas et al., 2000). In the USA, losses caused by M. bovis as a result of loss of weight gain and carcass value have been estimated at $32 million per year (Rosengarten and Citti, 1999).

The losses due to bovine mastitis caused by M. bovis may be higher than that for respiratory disease. In the USA losses have been estimated at $108 million per year with infection rates of up to 70% of a herd (Rosengarten and Citti, 1999). A survey of bulk milk tank samples in New York State over 9 years reported that about 2.3% contained M. bovis; similar results have been reported in Iowa where culling rates of infected cows of 30-70% are not uncommon. In eastern Canada, 52% of dairy herds are affected with M. bovis mastitis resulting in culling rates of close to 33% and average milk production losses of 6.4 kg per cow each day (Rosengarten and Citti, 1999).

No data are available for losses due to M. bovis arthritis or reproductive disease.

Pfützner (1990) stated that diseases due to M. bovis were resistant to any therapy. In spite of this, antibiotics are widely used to reduce secondary bacterial infections, but often they are ineffective for the treatment of the core mycoplasma infections. Many in vitro studies have compared the susceptibility of M. bovis to a range of antibiotics (see Table). While it is clear that antibiotics which are ineffective in vitro are unlikely to be effective in vivo, those with strong activities in vitro will not necessarily perform well in the field for reasons which are unclear (Ayling et al., 2000). Recent evidence suggests that M. bovis strains are becoming resistant to antibiotics traditionally used for treatment of mycoplasma infections; in particular oxytetracyclines, tilmicosin and spectinomycin (Nicholas et al., 2000). Some in vitro resistance to the fluoroquinolones has also been reported (Gerchman et al., 2009). Some of the new triamalides are licensed for use in treating mycoplasma respiratory disease in cattle, and are reported to be effective in the field, but in vitro test results are not always consistent with that finding (Godinho et al., 2005).    

Some success against M. bovis pneumonia and arthritis in calves was reported by Stipkovits et al. (2001) using valnemulin added to the milk from 4 days of age for 3 weeks. Animals in the treated group had fewer clinical signs and reduced clinical scores though the number of animals with nasal discharge was similar. In spite of the continuous chemotherapy, animals required a considerable number of individual treatments.

Effectiveness of antibiotics against field strains of M. bovis (minimum inhibitory concentrations µg/ml*)

=or<1 µg/ml = mycoplasmas susceptible

2-4 µg/ml = show intermediate susceptibility

>8 µg/ml = mycoplasmas resistant

(Laak et al., 1992a, 1992b)