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Mycoplasma bovis
Summary
Introduction
1. This note provides a brief summary of the Disease and Product analysis prepared by a
DISCONTOOLS group of experts on Mycoplasma bovis (M.bovis). They reviewed the current
knowledge on the disease, considered the existing disease control tools, identified current gaps in
the availability and quality of the control tools and finally determined the research necessary to
develop new or improved tools. Full details are available on the web site at
http://www.discontools.eu/ and can be downloaded by selecting Disease Database, then the
specific disease and highlighting the variables of interest. This is completed by selecting “create a
report” which can then be downloaded as either a PDF or Excel spread sheet.
Disease profile
2. M.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. The organism is
considered to be one of the more pathogenic species of Mycoplasma and is an important
pathogen of cattle. The diseases caused by M. bovis can be very variable and include mastitis,
pneumonia, arthritis and genital disorders which can occur in cattle of all ages. Infected 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. Other species may become infected, or be
carriers with cases having 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.
Risk
3. There is no evidence for human disease caused by M. bovis but a few cases have been
reported in immuno-compromised patients. M.bovis 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. The 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. Ingestion of contaminated milk
is a major source for calves. It is suspected that stress of cattle through climatic changes,
overcrowding, introduction of new animals, and translocation might trigger an outbreak.
.
Diagnostics
4. Diagnosis is by the isolation and identification of M. bovis from bulk milk tank or from cows
with clinical mastitis using the PCR and the DGGE (denaturing gradient gel electrophoresis) to
differentiate the strains of mycoplasma. Intermittent shedding of organisms and the inhibitors
present in milk may reduce the effectiveness of current tests. Other molecular based tests such
as LAMP, R-T PCR and Micro-array are beginning to be reported but are not in routine use.
5. Many different antibody tests are in use including indirect ELISA, indirect haemagglutination
etc. Other tests being developed include Latex agglutination tests, lateral flow devices,
resonance devices, etc. No pen-side tests are currently available. Some commercial ELISA kits
are available for antigen and antibody detection but the sensitivity and specificity of these kits is
not known. Methods for diagnosis should include antibiotic sensitivity testing and determining
antibiotic resistance in real time.
6. The availability of the full genome sequence of M. bovis type strain PG45 as well as
accumulated data regarding the presence of variable antigens and multiple repeat sequences
may allow the design of molecular typing schemes for M. bovis disease surveillance. Molecular
tests for use in epidemiological investigations have been developed to differentiate isolates, but
a universal “typing scheme” has not been developed nor
can “types” be related to
pathogenicity/clinical signs. There is 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 also be developed.
Vaccines.
7. Commercially 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. No commercial vaccines are licensed for M. bovis in Europe. Autogenous vaccines are
produced by several companies for use solely in the USA but data about their effectiveness is
sparse. Some success has been reported using a saponised autogenous vaccine on a few farms
in the UK. The contribution of the immune response to the development of chronic lesions
indicates caution in the use of vaccines as there is the possibility that some 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 in stimulating a protective immune response. The mechanism
of disease development needs to be understood to develop safe and effective vaccines for
worldwide use.
8. Vaccines need developing and marketing and which in the ideal world would be i) safe, ii)
effective against all clinical signs, iii) usable at all stages of animal production, iv) active against
all M. bovis variations, v) stable, vi) ideally single shot, vii) provide long-term effective protective
immunity and viii) be usable in all countries. DIVA would be beneficial
Pharmaceuticals
9. M. bovis as with other organisms in the group lacks a cell wall, which means the organism is
resistant to some commonly, used antibiotic therapies which can also be expensive and
ineffective. There 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
(DRAXXIN (tulathromycin) for the treatment of bovine respiratory disease linked to M.bovis.
Several countries have reported antibiotic resistance by M.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. As a consequence
effective antibiotic treatment regimens need further investigation.
Knowledge
10. Increased knowledge on ability of M. bovis to invade host is needed as is an understanding
of the transmission within the host, predilection for specific sites, intermittent shedding and
differences in resulting clinical signs all of which are still not known. The role of some defined
virulence factors such as the variable surface proteins in disease is still to be ascertained.
Possible differences in route of infection, infectious dose, host susceptibility, age, breed etc also
requires investigation. The mechanism of disease development needs to be understood to
develop safe and effective vaccines for worldwide use.
11. The role of variable surface proteins is not currently understood. The recent publication of one
genome of the M. bovis type strain (GenBank accession no. CP002188) showed the enormous
potential variation that the organism has. More genome sequences of isolates from hosts with
different clinical signs could increase knowledge of the organism’s mechanisms for survival and its
evasion of the host defence mechanisms. The identification of protective antigens through
genomic, bioinformatics, proteomic, immunological and biological approaches is also important to
enable the development of vaccine candidates.
Conclusions
12. There is a worldwide problem disease caused by M.bovis has a significant economic impact
on cattle rearing. It is a major constraint on intensive production affecting intensive beef
production particularly in feed lots and milk production in high yielding herds. The following
factors summarises the problems: i) No effective vaccines available, ii) Insidious infection not
always easily diagnosed, iii) Difficult to eliminate from a herd, iv) Difficult to assess the cause of
the bovine respiratory disease complex when a number of other pathogens are also involved and
finally v) Development of antibiotic resistance to many of the antibiotics currently in use.
13. 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.