Mycoplasma Bovis - available
Control ToolsDiagnostics availabilitySome commercial ELISA tests are available. GAP: BioX produce ELISA kits for antigen and antibody detection. The sensitivity and specificity of these and other kits is not known, but questionable. Some commercial ELISA tests are available. None. Not included in the OIE Manual of Diagnostic Tests and Vaccines for Terrestrial animals. Potential exists with the need to identify whether Mycoplasma bovis is a primary or secondary causal agent associated with production problems. GAPS: Considerable potential for the development of more specific and sensitive tests, ideally rapid with the possibility of pen-side application. Multiplexed testing for different organisms and activity associated with disease could be developed. None, but would be helpful if effective vaccines are developed. Should be linked to the vaccine development. Comments NA Vaccines availabilityCommercially available vaccines are licensed in the USA. These are Bacterin type vaccines with a number licensed for prevention of respiratory disease and others for the prevention of mastitis. GAPS:
No commercial vaccines exist for Mycoplasma bovis. None. None. Not applicable. High provided demand and price are satisfactory. Use of genetically modified vaccines might be problematic in some countries. The field trials may need specific regulation regarding the release of GMOs into the environment. Feasible. Could be used to protect farms in regions or zones provided that the vaccinated animals do not excrete the organism. Genomic analysis and anticipated expansion to various species differing in clinical properties will aid the identification of species consensus target genes. While there are several research groups worldwide that have both interest and expertise to work on vaccine development, it has been impossible to get proper funding for this topic in the past decade. The apparent disregard by funding organisations of mycoplasma-associated diseases is not due to insufficient evidence showing the economic importance, but rather a consequence of the generally low profile of these pathogens in the decision-making bodies. GAPS: need to develop and market vaccines. They should be safe and effective against all clinical signs, at all stages of animal production, against all M. bovis variations, stable, ideally single shot, provide long-term effective protective immunity and be usable in all countries. DIVA would be beneficial. Pharmaceutical availabilityThere is a poor response to treatments especially in cases of chronic respiratory disease or mastitis. The US Food and Drug administration have approved the only antibiotic for the treatment of bovine respiratory disease linked to Mycoplasma bovis. This is DRAXXIN (tulathromycin) an injectable solution produced by Pfizer Animal Health. A range of other antibiotics are used against Mycoplasma bovis infection but high levels of resistance are seen with a number of the antibiotics. GAPS: Lack of an understanding of the epidemiology of the disease at the herd level hampers the development of therapeutic preventive measures. Currently the most widely used preventive measure is chemotherapy but test and slaughter is a crude and less economical strategy to control this disease. Effective anti-mycoplasma drugs. High potential for an effective anti mycoplasma drug but there could be constraints in relation to potential resistance if the antibiotic is applied widely. None foreseen. Commercially feasible but would depend on the market, price and demand. Genomic analysis and anticipated expansion to various species differing in clinical properties will aid the identification of species consensus target genes. Identification of the drug exporter ABC transporters in the M. bovis PG45 genome. Such proteins may be involved in the export of antibiotics and they are potential targets for development of new antimicrobial agents. GAPS: Effective antibiotic treatment regimes need investigating, especially with the widespread occurrence of resistance. Development of new or alternative antibiotics is required. Consideration could be given to assessing the effectiveness of medicinal plants. New developments for diagnostic tests
GAPS:
In general the development of tests is much faster and less expensive than developing vaccines. From development through validation to commercial availability will be time consuming and can take years. The development and validation of new tests is time consuming and labour intensive which is costly. Costs cannot be specified as they will depend on the nature of the test and the cost of producing reagents and supplying reading or processing machines if necessary. Once validated there will need to be a commercial company willing to market the test.
GAPS: Most technologies are available to develop the required new diagnostics, however the main issue is investment in the small number of workgroups working on these fastidious and specialist organism. Limited investment in none-zoonotic and endemic diseases has restricted development of new improved diagnostics. Improved diagnostic tests required either to be developed or evaluated and implemented:
Would need effective mechanisms to determine freedom from infection with Mycoplasma bovis using a mixture of culture, PCR and serology. New developments for vaccines
GAPS: Vaccine development is required. Some success has been reported using a saponised autogenous vaccine in the UK. EMIDA project will examine this vaccine more widely. Some other vaccine development has resulted in exacerbation of disease. Other concerns relate to the variability of the surface proteins expressed by M. bovis and the possible requirement to use multiple strains in a vaccine. Adjuvant selection could be critical is stimulating a protective immune response. Depending on when a candidate vaccine could be identified the timescale will be 5-10 years. This will involve development, clinical trials and licensing. Potential vaccines need to be identified and subjected to initial trials and depending on the outcome will depend the time to commercial availability. Expensive with the need to develop and undertake all the relevant tests to provide data to enable the product to be authorised. Field trial will be difficult as will evaluating the results.
GAPS: Improved understanding of the disease pathogenicity and infectious routes along with a good understanding of the host’s immunological response would provide a sound basis for antigen and adjuvant selection. In addition a good reproducible model for disease is also essential, especially as the infection can result in varied clinical signs such as calf pneumonia, arthritis, mastitis, etc. Evaluation of potential vaccines against these clinical signs will be required. New developments for pharmaceuticalsGAPS:
Time to develop would depend on the product and the trials necessary to validate the efficacy and safety. Commercial production would then take further time. 5 to 10 years seems a realistic timeframe. Expensive but difficult to assess as it will depend on the product and the trials necessary to validate and license.
GAPS: Rapid and improved minimum inhibition concentration and mycoplasmacidal tests need developing and standardising. Breakpoint values need to be determined to relate in vitro tests to in vivo situations. These tests should take into account the possible impact of biofilm formation. The development of resistance and mechanisms of resistance will also need investigating. Disease detailsDescription and characteristics.Mycoplasma bovis is a member of the genus Mycoplasma and Family Mycoplasmataceae within the Class Mollicutes. Mycoplasma bovis was first detected as a cause of bovine mastitis in the USA in the 1960s and has since been detected in most countries worldwide with only a few exceptions. Mycoplasma bovis is considered to be one of the more pathogenic species of Mycoplasma and is an important pathogen of cattle. GAPS:
Mycoplasma bovis can survive outside the host in the environment especially if protected from sunlight. At lower temperatures it can survive for days or weeks in water, manure etc. GAPS: Mycoplasmas lack a cell wall that should make them susceptible to environmental pressures, however they do survive for long periods, with one report (Justice-Allen et al., 2010) indicating survival in bedding sand for 8 months. Recent research has partly explained extended survival through the presence of biofilms, however further work is required. Species involvedInfected cattle can become asymptomatic carriers and may shed the organism through nasal discharges or in milk for months to years without showing clinical signs. It is the most frequent Mycoplasma pathogen linked to pneumonia, mastitis, and arthritis in cattle. GAPS: Other species may become infected, or be carriers – cases have been reported in sheep, goats, buffaloes, deer and chickens. Diagnosis in sheep and goats is complicated by genetic homology of M. bovis with Mycoplasma agalactiae. No evidence for human disease with Mycoplasma bovis. GAP: A few cases have been reported in immunocompromised patients (Pitcher and Nicholas, 2005). None. Cattle. Description of infection & disease in natural hostsHighly contagious. Easily transmitted often by the aerosols. Not applicable. The diseases caused by Mycoplasma. bovis can be very variable. These include mastitis, pneumonia, arthritis and genital disorders which can occur in cattle of all ages. The organism has been associated with polyarthritis in feedlot cattle and otitis media in young calves. Subclinical, clinical or chronic mastitis may be caused by Mycoplasma bovis. Mastitis can be severe with one or all quarters being affected with a serous or purulent exudate. Cows may not show any systemic signs in spite of the udder infection Mycoplasma bovis is a primary cause of calf pneumonia typically in a non specific respiratory disease that does not respond to antibiotics. In pneumonia it is nearly always associated with a range of other pathogens where it may have a synergistic role. As a consequence Mycoplasma. bovis may be overlooked as the causal agent due to the presence of the more familiar pathogens. GAP: A few isolates have been made from the brain, one of these cases was associated with a large spheroidal fibrinous lesion in the heart. Variable depending on the age of animals, the clinical and pathological effects of infection. Difficult to define due to difficulty in diagnosis and in assessing the time of infection. Experimentally incubation may be a few days for mastitis and from 7 day for pneumonia. Field cases of pneumonia are probably much longer and influenced by the co-infectants present. GAP: In one herd outbreak of mycoplasma mastitis the incubation period was estimated to be 13.6 days (Punyapornwithaya et al., 2011). But strain and herd management differences likely impact the length of the incubation period making this a relatively unknown factor in the control of the disease. Variable depending on the clinical disease, age of animals and other infections. Can be high in the case of pneumonia and arthritis. Infected cattle can shed the organism for months to years. GAP: Role of the asymptomatic carrier in a herd outbreak is largely unknown. Mycoplasma bovis can probably invade tissues and enter the bloodstream to spread to other tissues. GAPS:
Zoonotic potentialNo evidence of transmission to humans. GAP: A few cases have been reported in immunocompromised patients (Pitcher and Nicholas, 2005). Not applicable. GAP: Immunocompromised people with close contact with infected cattle or their products (infected milk or faeces). Not applicable. GAP: Immunocompromised people with close contact with infected cattle or their products (infected milk or faeces). Not applicable. GAP: Respiratory disease, bronchopneumonia. Rare. Impact on animal welfare and biodiversitySerious impact on the welfare of cattle through the disease it causes. No information although a case of infection in buffalo in the USA caused a high mortality. GAPS: Some farmed species of bison, buffalo and deer have been affected, but spread into wildlife or their potential as hosts has not been investigated. Farmed bison have experienced acute outbreaks with high mortality in adults, and it is not known if this represents high susceptibility of this species or naive status of the herds. Probably low risk for cervids and antelope family of species. Culling infected carrier animals especially those with mastitis may be the only method of reducing the infection levels on a farm. Geographical distribution and spreadMycoplasma bovis was first identified in the USA in 1961 and is now considered to be present worldwide. It is the most important Mycoplasma pathogen in cattle in the USA. Can spread very rapidly once introduced into a herd. Spread to new herds is usually due to the movement of asymptomatic carriers being purchased and introduced into a clear herd. GAP: Suspect that stress of cattle (climatic changes, overcrowding, introduction of new animals, and translocation) might trigger an outbreak. None. GAPS: Calf pneumonia is undoubtedly higher during colder seasons with M. bovis pneumonia appearing to account for approximatively 20-30% of infections. Temperature fluctuations are more likely to be a key factor in disease and not just exposure to the cold. Poor housing conditions are probably an important contribution to pneumonia in winter conditions. In seasons of reduced pneumonia M. bovis may account for a higher percentage of pneumonic cases. Rapid. GAP: Instances of few seropositive animals within large sero-negative herds requires additional study on epidemiology of transmission. High association with movement of clinically normal infected animals. No. No. No apart form the impact of adverse weather on the animals. GAP: Link to sudden changes of weather. No. Route of TransmissionThe primary routes of infection can vary depending on the problem in the infected herd but are usually close contact through direct nose to nose transmission via aerosols and/or by the ingestion of infected milk. Milking parlour hygiene for mastitis. GAP: Arthritis is not necessarily a final result of a bacteraemia, pneumonia and mastitis can result from primary mastitis and pneumonia respectively. Ingestion of contaminated milk is a major source for calves. Movement of infected animals into clean herds or vice-versa. Detection and Immune response to infectionHumoral response. GAP: Immune response contributes to the lesion development, at least at chronic stage. Serological tests for the presence of antibodies. Main means of prevention, detection and controlMycoplasmas can be introduced in a herd by subclinical infected carriers. Once established in the herd, the infection is difficult to control. Limited methods available for control. Control of other pathogens by vaccination to reduce the impact of Mycoplasma bovis as a secondary infection. When Mycoplasma bovis is the primary pathogen it can be difficult to control. Preventing the introduction into the herd by sourcing replacement stock from know free herds, management factors by avoiding mixing cattle of different ages especially calves and culling positive animals. Reducing co-mingling stress can reduce clinical presentations, both for mastitis or respiratory disease. Isolation and identification of Mycoplasma bovis from bulk milk tank or from cows with clinical mastitis. Use of PCR and the DGGE (denaturing gradient gel electrophoresis) to differentiate the strains of mycoplasma. Serology using paired sera collected at 10-14 day intervals to detect rising antibody titres. Many different tests have been used including indirect ELISA, indirect haemagglutination etc... GAPS: Intermittent shedding of organisms and the inhibitors present in milk may reduce the effectiveness of current tests. Other tests such as LAMP, R-T PCR and Micro-array are beginning to be reported but are not in routine use. No pen-side tests are available. A number of commercial vaccines exist prepared from a limited number of strains. GAP: Autogenous vaccines are produced by several companies for use solely in the USA. Data about their effectiveness is sparse. Autogenous vaccine is prepared in the UK. Mycoplasma bovis as with other organisms in the group lacks a cell wall, which means the organism is resistant to some commonly used antibiotics. In general Mycoplasma bovis is resistant to antibiotic therapy which can also be expensive and ineffective. Draxxin has recently been approved in the USA for treatment but can be very costly. GAPS: Several countries have reported antibiotic resistance by Mycoplasma bovis to many antibiotics, including macrolides, tetracyclines, lincosamides, aminocyclitols and fluoroquinolones. Some mechanisms of resistance have been determined as similar to other bacterial species, however some mechanisms have not yet been discovered and require further investigation. Efflux mechanisms are one possible area for investigation. Limited effect, but a closed herd policy preventing the introduction of M. bovis into a herd is important along with general measures to reduce the levels of infection in the environment. Avoid mixing calves of different age groups. Some recommend distancing dairy farms from calf fattening units. No specific controls in place to control movements. GAP: NZ/Israel impose additional testing on exporting countries. Limited availability. Serosurveillance and disease surveys can be undertaken. GAPS: The true incidence of M. bovis is not really known, available information appears to be based on passive surveillance information. A serological survey and abattoir survey could give more information about its true prevalence. The real economic cost of the disease has not been determined – a survey to include all cost factors that includes mortality, veterinary costs, treatment, milk loss, added housing/feed costs through lack of weight gain etc would provide useful evidence. This is an organism which has spread widely since it was first identified. Successful measures to control the infection have been very limited. Culling and antibiotic treatments are used to reduce the impact of disease. The prevalence of mycoplasma disease has been reported to be increasing with a significant positive correlation with increasing herd size. GAPS: While it is clear the disease has spread by international trade and opening of EU single market, detection is also the result of increased awareness. Expensive. Culling can be devastating and the use of antibiotics is expensive. GAPS: Reports indicate that early recognition of disease and prolonged therapy is required and consideration should be given of metaphylaxic treatment of whole groups. Disease information from the OIENo. No. None. None. Socio-economic impactNot applicable. Not applicable. High with an impact on weight gain, carcase value and mortality as part of the bovine respiratory disease complex. Reduced milk production as a result of clinical and sub clinical mastitis. Overall increased mortality due to a range of clinical conditions. Sterility and abortions may also result from infection. The cost associated with Mycoplasma bovis infection is borne by the private sector. These are related to the treatment, premature culling, mortality and the need to purchase of replacement animals. Causes disruption to production. Trade implicationsNo restrictions on movements. GAP: No official restrictions on movement within EU, however some countries importing cattle are increasingly aware of the risks of importing infected cattle and are requesting cattle are tested and shown to be free of Mycoplasma bovis. No restrictions on movements. No restrictions on movements. Main perceived obstacles for effective prevention and control
Main perceived facilitators for effective prevention and controlEffective vaccines. GAPS:
|
