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MYCOPLASMOSIS OF RUMINANTS

Objective

A. GENERAL BACKGROUND

Mycoplasmoses are infectious diseases due to mycoplasmas, fastidious bacteria-like organisms, some of them being highly pathogenic, contagious and causing severe herd infections particularly in ruminants. In particular, contagious bovine pleuropneumonia (CBPP), contagious caprine pleuropneumonia (CCPP) and contagious agalactia of small and large ruminants, caused by different Mycoplasma species, are considered to constitute a particular threat and need to be controlled by specific diagnostic and epidemiological approaches. In addition, it is recognized that the quality of diagnostic methods for the detection of the diseases is insufficient and causes severe problems. During the 62nd General Assembly of the Office International des Epizooties (OIE) held in Paris on 16-20 May 1994, the socio-economic impact of mycoplasmal infections in bovine, ovine and caprine species was considered to be of very great importance worldwide. Therefore, the OIE recommended giving high priority to the research on contagious bovine, ovine and caprine mycoplasmoses with the aim of developing new, efficient and reliable diagnostic procedures (OIE Resolution XI, 1994).

These contagious mycoplasmoses are already known to be present in Europe. Contagious agalactia in small ruminants has been endemic for many years in Mediterranean countries and in Switzerland. Reports from different countries on agalactia and bronchopneumonia in cattle, due to Mycoplasma bovis, point out the emergence of the problem in Europe. Contagious bovine pleuropneumonia (CBPP), endemic in Africa and Asia, was present in France until 1984 and has been recorded in Portugal since 1983, in Spain since 1989 and in Italy since 1990. The prevalence of contagious caprine pleuropneumonia (CCPP) is more obscure. Its occurrence has been reported in a few African and Middle East countries and also from Turkey.

The presence of such mycoplasmoses is known to be of great economic importance for the affected countries. In view of the insufficient diagnostic methods available, the introduction of a single market in Europe has considerably enhanced the risk of spreading such diseases in Europe. Consequently, the spread of diseases could give rise to high costs for eradication, and would thus considerably weaken the agronomical competitiveness of Europe.

New technological developments for diagnostic tools depend on solid knowledge of the biology of the infectious agents. However, due to the great technical and scientific difficulties encountered with this group of organisms and also due to the small number of specialized laboratories, fundamental scientific data on bovine, ovine and caprine mycoplasmas are very poor.

Scientific activity on highly contagious mycoplasmoses is basically focused on European countries, since North American countries, in particular USA, which generally provide considerable contributions in the field of molecular pathogenicity of infectious diseases are free of most of these infections and do not carry out research in this field. This remains therefore an important task and challenge for Europe.

Relatively few laboratories in Europe are at present active in the research on mycoplasmas. Their research areas range from experimental infections to analysis of variability of immunogenic proteins, development of immunoassays, DNA sequence analysis of 16SrRNA genes, development of PCR methods and biochemical purification of structural membrane proteins. A few other institutions carry out applied tasks such as pathology, diagnostics, epidemiology and surveillance. Although current research contributes to a better understanding of this group of mycoplasmas, definite progress can only be reached by intensive collaboration between the respective research groups and institutions making applied efforts with the exchange of information, the coordination of research projects and the standardization and evaluation of diagnostic procedures. Currently there are no international coordination programmes in this field.

The proposed action is innovative, interdisciplinary of very great importance for the whole European continent. Its benefits can easily be shared among all European countries, and the standard procedures drawn up as well as the introduction of new, more efficient methodologies will help tremendously to facilitate the control of the disease and thus avoid the spread of the diseases. The veterinary services will obtain efficient tools for the surveillance of the disease, particularly in international animal exchanges and trade. Therefore, this Action is highly suitable to be incorporated in the framework of COST.

B. OBJECTIVES OF THE ACTION

The main objective of the Action is to reduce the considerable socio-economic effects in Europe due to several forms of ruminants' mycoplasmoses, to ensure animal welfare, and to strengthen European status in international agronomical exchange by:

- Promoting and coordinating research activity (biochemistry, genetics, immunology, molecular mechanisms of pathogenicity) of ruminants' mycoplasmoses.

- Developing efficient diagnostic tools.

- Gaining much needed information on basic research of animal mycoplasmas.

- Transferring technology between countries and thus enhancing the competitiveness of European scientific activity.

- Developing diagnostic tests which can be commercialized.

- Obtaining a better insight in the epidemiological situation in different countries.

- Recommending basic approaches for the development of efficient vaccines.

C. SCIENTIFIC CONTENT OF THE ACTION

Taking into account the complexity of the topics involved, the task will be achieved by several working groups which should convene in different workshops. Within these working groups, researchers with a common interest will form common research teams. Furthermore, the exchange of qualified researchers between laboratories will be encouraged.

Working Groups

The activity of each group will be managed by a coordinator assisted by a substitute. Members of the group will be the different national experts participating in the Action. Additional experts on specific topics may also participate in the activities of the group. Three different working groups are proposed:

Working Group 1 (Research)

The main activity of this group will be the coordination of the on-going research in different participating laboratories and the stimulation of new scientific approaches. Within the mycoplasmas to be studied priority will be given to members of the "mycoides cluster", Mycoplasma agalactiae and Mycoplasma bovis. The fields of research are:

Genetics: molecular phylogeny, genetic variation, gene structures, gene maps, gene cloning and expression, molecular biology.

Biochemistry and Physiology: Immunogenicity and variability of surface proteins, surface carbohydrates, metabolites and toxic factors.

Immunology and Pathogenesis: Humoral and cell mediated immune response, immunological mediators, mitogen activity, auto-immunity, pathology, pathogen-host interactions.

All research fields are highly interactive and have to be discussed in the presence of all the scientific specialists.

Working Group 2 (Diagnostics)

This Working Group will develop, evaluate and coordinate the use of diagnostic procedures for field applications. This activity will be closely connected with new knowledge issued from Working Group 1 (Research).
The main objectives are:

Evaluation of currently used diagnostic procedures.

Elaboration of standardized protocols for diagnostic techniques.

Evaluation of new techniques in vitro.

Exchange of standardized material, in particular antigens and sera.

Multicentric comparative analyses.

Organization of collections of strains and immunoreagents and establishment of data banks.

Working Group 3 (Field Applications)

This Working Group will evaluate the practicability of the different diagnostic procedures in field situations. This activity is strongly dependent on the activity of the Working Group 2 (Diagnostics) and should consequently be coordinated. The objectives of this group are:

Evaluation and validation of different diagnostic procedures including new developments concerning the detection and identification of the infectious agents and their immunological responses in defined animal populations, with documented epidemiological and pathological data.

Drawing up protocols and recommendations for an efficient field diagnosis of contagious mycoplasmoses with emphasis on the reliability of the diagnostic tests (specificity, sensitivity, cutoff values, predictive values) and their proper use in control programmes.

Development of schemes for collection and analysis of epidemiological data (electronic data exchange).

Organization of training courses for peripheral laboratories involved in the diagnosis of mycoplasmoses.

D. TIMETABLE

The duration of the Action is planned for 5 years. An evaluation of the progress will be made after the second and fourth year. Annual reports will be presented to the COST Secretariat. We consider a phase 1 (1-2 years), during which Working Group I (Research) and Working Group 2 (Diagnostics) will start to work in parallel (see diagram). During phase 2 (2-3 years) the Working Group 1 (Research) will still continue its activity, but the Working Group 2 (Diagnostics) will successively integrate its activity into Working Group 3 (Field Applications).

collage diagram

E. ORGANIZATION, MANAGEMENT AND RESPONSIBILITIES

The organization and coordination of the Action will be ensured by the Management Committee, assisted by the COST Secretariat. The Management Committee will consist of at least one representative of the signatory countries. The first task of the Committee will be to designate its president and the coordinators of the three working groups and to define the strategy and the programmes for each working group. During the course of the Action, the Management Committee will regularly supervise and coordinate the different activities and prepare annual and final reports. The Management Committee will meet annually. If a Technical Committee is designated, yearly meetings with the management committee will be planned.

Each Working Group will have a coordinator whose responsibilities are to follow the progress of the programmes, to make a short report of each meeting and to assure the information of the management committee. Coordinators are members of the Management Committee. The coordinators will be assisted by a substitute who represents the coordinator in case of absence. The coordinators will furthermore propose to the Management Committee the organization of work-shops and training courses. Each Working Group will organize its own working schedule to fulfil the proposed objectives, and nominates scientific leaders for handling specific topics.

The Working Group will organize one workshop of 2-3 days annually in different participating countries. The workshops and training courses will be organized by the coordinator and members of the working group, in collaboration with the COST Secretariat, upon approval of the management committee. Proceedings of the workshops and manuals of training courses will be published in collaboration with the COST Secretariat. The coordinator will assist scientists in their demands for exchange visits between different laboratories.

The Management Committee will define the modalities of publication of common work within the Action. Reports from each working group are submitted by their coordinator to the Management Committee for approval.

All recommendations for standardization of diagnostic procedures and validation of new techniques elaborated by the working groups will be coordinated by the Management Committee and will be available to interested national, European and international institutions, in particular to the Office International des Epizooties (OIE) for information of Veterinary services.

The Management Committee will regularly inform the OIE on the progress of the activity in the working groups 2 and 3 (Diagnostics and Field Applications) via the coordinators of these groups.

The Management Committee will assist in diffusing the common results of the Action in international congresses.

Special attention will be paid to the manner of transferring new technologies, elaborated by common efforts within the COST Action, to industry and to the possibilities of exploitation. Basically, newly drawn up standard procedures within the common COST efforts should be public domain.

F. ECONOMIC DIMENSION OF THE ACTION

The economic dimension of the action is estimated on the basis of current activities of the interested groups. The estimation includes manpower and national and international research grants already available or expected to be available in the near future for the work planned.

In each of the 11 participating countries, 3-5 persons are expected to devote their work to projects relating to this COST Action.

The total economic impact includes:

Scientist: 18 persons x ECU 60 000 ECU 1 080 000
Technicians: 15 persons x ECU 40 000 ECU 600 000
PhD Students: 15 persons x ECU 25 000 ECU 375 000
Total Personnel per year ECU 2 055 000

TOTAL Personnel in 5 years 5 x ECU 2 055 000 ECU 10 275 000
TOTAL Investment 5 years ECU 1 600 000
TOTAL Running costs 5 years ECU 1 900 000
Coordination costs (COST) 5 years ECU 300 000
TOTAL economic dimension ECU 14 075 000.

Current status
The COST Action 826 has 5 active international Working Groups

Working group 1 : "Research, Molecular Genetics"
Genetic basis for the differentiation and identification of the mycoides group of Mycoplasma species.
Development of PCR methodology for identification and diagnosis of pathogenic mycoplasmas in ruminants.
Identification of molecular tools for subtyping and epidemiology of pathogenic mycoplasmas in ruminants.
Basic research in molecular biology on virulence attributes and immunogenic factors of pathogenic mycoplasmas in ruminants.

Working group 2 : "Structures and functions"
Biochemical and physiological aspects
Surface proteins, carbohydrates, metabolites
Variable antigens and their role in serology
Immunological aspects and pathogenesis

Working group 3 : "Diagnostics"
Diagnostic and epidemiological aspects
Strain collections, isolation techniques, identification techniques
Realisation of new diagnostic techniques and methods

Working group 4 : "Field studies Mycoplasma agalactiae/bovis"
Analysis of M. agalactiae and M. bovis infections
Epidemiological studies on M. agalactiae and M. bovis infections
Impact of M. agalactiae and M. bovis infections on animal health and livestock production
Studies for the evaluation and validation of diagnostic methods including new methods for the diagnosis of diseases caused by M. agalactiae and M. bovis
Drawing up protocols and recommendations for efficient field diagnosis of contagious mycoplasmoses with emphasis on the reliability of the diagnostic test
Drawing up control programmes for the proper use of diagnostic methods

Working group 5 : "Field studies on mycoplasmas of the mycoides group"
Analysis of infections with mycoplasmas of the mycoides group
Epidemiological studies on M. agalactiae and M. bovis infections
Impact of infections by mycoplasmas of the mycoides group on animal health and livestock production
Studies for the evaluation and validation of new diagnostic methods for the diagnosis of diseases caused by mycoplasmas of the mycoides group
Drawing up protocols and recommendations for an efficient field diagnosis of contagious mycoplasmoses with emphasis on the reliability of the diagnostic test
Drawing up control programmes for the proper use of the diagnostic methods

In order to initiate this Action and to favour scientific exchange and contacts between all persons involved working in laboratory, field and regulations, a Workshop "Mycoplasmas of ruminants : pathogenicity, diagnostics, epidemiology and molecular genetics" was held at the Aristotle University in Thessaloniki Greece from 24 to 26April 1996. This brought together from 15 different European countries 70 researchers and veterinarians working in the different areas on mycoplasmas affecting ruminants. Its main objective was to give an overview on the current work done in the field of ruminants' mycoplasmoses, to intensify discussion among COST participants and to benefit from related scientific expertise in order to develop improved concepts in scientific research, diagnosis and prevention of mycoplasmal diseases of ruminants. This workshop achieved its function as an ideal start of the scientific activities of COST Action 826. It launched a series of actions to be taken up by the different working groups. Meanwhile, intensive work was started on genetic methods for strain identification, on the establishment of a data base, accessible to all members of this COST Action, for a European strain collection, and on standardisation of biologicals used for diagnosis and research in mycoplasmas from ruminants.
An important novel result on contagious bovine pleuropneumonia (CBPP), which directly resulted from the contacts of this COST Action, is the finding that the mycoplasma strains which cause this severe disease in Europe are clearly distinct from those isolated in Africa. This gives clear evidence, that the epidemiological situations of the two continents are different, and that the new outbreaks of CBPP in Europe since 1980 are not due to a re-import of the disease from Africa. The new European outbreaks must be of other origin, most probably froman as yet undefined reservoir, possibly sheep and goats [see : Cheng et al, (1995). Insertion element IS1296 in Mycoplasma mycoides subsp. mycoides small colony type identifies a European clonal line distinct from African and Australian strains. Microbiology vol. 141, p 3221-3228].
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Coordinator

CEC

Address

Rue De La Loi 200
1049 Brussels

Belgium

Administrative Contact

(Ms.)

Project information

Grant agreement ID: 826

  • Start date

    5 July 1995

  • End date

    4 July 2000

Funded under:

IC-COST

Coordinated by:

CEC

Belgium