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Contenido archivado el 2022-12-23

Brucellosis in Animals and Man

Objetivo

A. BACKGROUND

Brucellosis is a serious disease caused by bacteria of the genus Brucella that currently contains six species. The disease affects all species of farm animals although is most important when it affects ruminants. The preferred host of B. abortus is cattle and the preferred hosts of B. melitensis are sheep and goats. Other species affect preferentially pigs (B. suis) and sheep (B. ovis). In all farm animal species the predominant symptom is abortion, with consequent loss of offspring and milk yield. In males orchitis and epididymitis occurs with a resulting loss in fertility. Brucellosis is characterised by slowly developing and spreading outbreaks. There is often a long incubation period that hinders epidemiological tracing. The epidemiological unit is the flock/village/mountainside under those systems where animals from different herds are mixed.

The disease is readily transmitted to man, either following professional contact with infected animals or following the ingestion of contaminated dairy products. If transmission is via the latter route, large outbreaks in the general population can occur. Brucella belongs to hazard group 3 as it is very readily acquired in the laboratory. The organism must be handled using Category III facilities although professional exposure of veterinary and other personnel in the field is unavoidable. No vaccine is available for human prophylaxis. The disease in man is severe and long lasting usually requiring hospitalisation and treatment for many weeks. Permanent, disabling sequelae occur if the disease is left untreated. A surprising range of symptoms is reported to characterise the disease in man. However, fever, malaise, night sweats and joint and muscle pain are the most common on presentation. Neurological, osteoarticular, genitourinary, and cardiovascular signs and symptoms are often observed as the disease progresses. In some countries, the incidence may locally exceed 70 cases per 100 000 population. In the most severely affected Europe, the incidence rate in man is high. For example, official returns from Greece report over 30 cases per 100 000 and rising in some Nomos (administrative areas) but they estimate that these official notifications only represent only 8% of the actual level.

Some northern Member States have successfully eradicated B. abortus infection from cattle following many years of vaccination and culling and there is a need to protect this investment by preventing the re-introduction via imported animals. Those Member States affected by B. melitensis infection are, to varying degrees, experiencing much greater difficulty in eradicating or even controlling the disease. In Greece, the premature cessation of vaccination in 1991 has resulted in a dramatic increase in the prevalence of brucellosis leading to a tripling of the incidence in man. Transmission of Brucella from person to person is very rare and therefore virtually all human cases originate from infected animals. The successful control or eradication of brucellosis in farm animals always results in a parallel reduction or elimination of the disease in man.

Within the European Union the control and eradication of brucellosis is governed by European and national law. In particular, Council Directive 64/432/EC (as amended by Directive 97/12/EC) governs brucellosis with regard to intra-community trade in bovine animals and swine as does Directive 91/68EC for sheep and goats. Member States carrying out eradication programmes receive balancing Community assistance towards eradication and the amount budgeted for 1998 was ECU 28 million. Despite this high level of funding, many Member States are making very slow, if any, progress towards the eradication of brucellosis in sheep and goats and none has yet achieved it.

Brucellosis appears on List B of the Office International des Epizooties (OIE) and testing is almost universally required for international trade purposes. This has become of even greater importance since the Sanitary and Phytosanitary (SPS) agreement was established under GATT. The OIE is the reference organisation set up under GATT "to set guidelines and standards for health regulations applicable to international trade in animals". The continued presence of brucellosis throughout the COST countries, the slow progress towards its eradication and the imperfect harmonisation of tests and strategies are a serious hindrance to free trade.

Brucellosis has a truly pan-European nature both in terms of its epidemiology, human health risks and its impact on trade. Its greatest impact is in the southernmost Member States but research is also carried out in the northern Member States. At present, although there are a number of teams collaborating with each other, this is often on an ad hoc, piece-meal and informal basis. Although International Brucellosis Reference Centres exist (OIE, FAO/WHO) they are unfunded and therefore have a limited impact. For these reasons, COST funding is an efficient means of linking research teams across Europe and facilitating the dissemination of information to the legislators and to the field. Due to its complexity, brucellosis requires a multidisciplinary approach that can only be achieved by combining scientific, medical and veterinary expertise and resources from different Member States.

B. OBJECTIVES AND BENEFITS

The main objective of the Action is to improve the efficiency of control and eradication of brucellosis from animals in Europe thereby facilitating international trade and improving public health.

This will be achieved by several secondary objectives. Firstly a better understanding of the epidemiology of brucellosis, including the role of wildlife, the epidemiological link between animals, food and man and the effects on public health will facilitate development of improved control and eradication strategies. Secondly, by gaining a greater understanding of the immune response of the animal and human hosts and the molecular biology of Brucella, more sensitive and specific diagnostic tests can be developed. Thirdly, the study of pathogenesis and the identification of the main virulence factors and the understanding of mechanisms leading to a protective immune response will, by giving insight into the processes involved, lead to opportunities for the development of improved vaccines or vaccination strategies. Lastly, any new tests, vaccines or control strategies will require standardisation and legislative amendment before they can be used in the context firstly of the European Union and also more widely.

C. SCIENTIFIC PROGRAMME

Different Working Groups (WG) will be established to focus on selected topics. Regular meetings and exchanges will be held in each WG that will be managed by a coordinator. Where appropriate, the collaboration among WG and of external experts will be encouraged.

Working group 1. Epidemiology

The aim of this group will be to increase knowledge of the epidemiology of brucellosis in farm animals and its link with disease in man in the COST countries and define the role played by wildlife, including its impact on public health, in the maintenance of disease. The work will be coordinated with that on Molecular Biology and Vaccine Development by WG 3.

The main objectives of this WG will be:

(a) To define standard protocols to gain objective data on the prevalence of animal brucellosis in various species under several epidemiological conditions throughout Europe.

(b) To gain a greater understanding of the means of spread within or between herds or flocks and the possible role played by wildlife in the epidemiology of infection in cattle, small ruminants and pigs.

(c) To assess the relative effectiveness of various control strategies.

(d) To gain greater understanding of the epidemiology of human brucellosis.

(e) To evaluate protocols of antibiotic treatment in man.

The expected benefits will be improved control and eradication strategies in animal hosts.

Leading contributors to this working group are expected to be Drs. J. Blasco and R. Diaz, Spain, Dr. B. Garin, France, Dr. J. Godfroid, Belgium, Dr. Minas, Greece, Dr. Naninni, Italy, Dr. Henighan, Ireland, Dr. Staak, Germany, Dr. Maria Correia de Sa, Portugal.

Working group 2. Immunology and Diagnosis in Brucellosis

The aim of this group will be to increase knowledge of the immunology of the response to Brucella infection and vaccination in domestic animals leading to the development of improved diagnostic tests. The work will be coordinated with that of WG 1 and WG 3.

The main objectives of this WG will be:

(a) To gain greater understanding of the immune responses of domestic animals following infection and vaccination, including the evaluation of the responses at Ig class and subclass level against purified antigens.

(b) To develop diagnostic tests with improved sensitivity and specificity including tests for the improved discrimination of vaccinates, with emphasis in the brucellosis of small ruminants.

(c) To evaluate the incidence of cross-reactions with taxonomically related bacteria that may act as animal pathogens.

The expected benefits will be improved diagnostic tests and efficiency in eradication programmes.

Leading contributors to this working group are expected to be Dr. Godfroid, Belgium, Drs. Favero and Dornand, France, Drs. R. Dias and Moriyon, Spain.

Working group 3. Molecular Biology of Brucella: Application to Taxonomy, Pathogenesis and Vaccine Development

The aim of this group will be to improve the understanding of the Molecular Biology of the genus Brucella to facilitate Molecular Epidemiology, to improve the understanding of the major virulence factors involved in the pathogenicity of the bacteria, and to improve the development of new vaccine candidates.

The main objectives of this WG will be:

(a) To gain a greater understanding of the genome structure and genome organisation of the genus, and to evaluate the taxonomical implications.

(b) To develop PCR and related tests that will enable strain differentiation thus facilitating Molecular Epidemiology.

(c) To study and characterise the main virulence factors of Brucella, and their genetic and structural background.

(d) To use such characterisation to develop new generation vaccines, and test vaccine candidates initially in small animal models and ultimately in the target species.

The expected benefits will be the characterisation of tests suitable for Molecular Epidemiology and a more rational taxonomy, and the development of new vaccines and vaccination strategies of improved efficacy.

Leading contributors to this working group are expected to be Drs. Verger, O'Callaghan, Liautard, France, Prof. Lettesson, Belgium, Dr. Bakker, Netherlands, Drs. Lopez-Goni and Garcia-Lobo, Spain.

Working group 4: Standardisation, harmonisation and legislation

The aim of this group will be to facilitate the introduction throughout Europe of tests, vaccines and strategies developed by this project. The group will coordinate with the other WGs.

The main objectives of this WG will be:

(a) To formulate standard protocols for new tests, vaccines and strategies developed by other WGs.

(b) To establish an EU Community Reference Laboratory

(c) To make recommendations to legislators on necessary changes to legislation.

The expected benefits will be the widespread availability of standardised tests, vaccines and strategies, coordinated by a Community Reference Laboratory.

Leading contributors to this working group are expected to be Drs. Sander and Moynagh, European Commission, Dr. Reichard, OIE, Dr. Benkirane, FAO, Dr. Garin-Bastuji, France

D. ORGANISATION AND TIMETABLE

The organisation and coordination of the COST Action will be assumed by a Management Committee (MC) composed of a maximum of two members of each participating country. The MC will be established during a meeting in Brussels organised by the COST Secretariat. The first task of the MC will be the appointment of chairmen and deputies of the MC and the various WGs and formulating the remit of each WG.

The role of the MC during the action will be:

- To manage the Action through the WGs.
- To write the final and annual reports.
- To make publishing decisions regarding work performed during the Action.
- To finalise recommendations to the Commission, OIE and other international authorities.
- To agree short term exchange and training visits between laboratories.

The role of the WGs will be:

- To coordinate and plan the work.
- To write a report after each annual meeting.
- To transmit information to the MC.
- To propose exchange and training visits of researchers and technicians to the MC.

In each WG, workshops (2-3 days) will be organised at least annually in one of the participating countries and the proceedings will be published. Scientific exchanges will be considered during these meetings and transmitted to the MC by the coordinator. The MC will hold an annual management-evaluation meeting. The MC will produce and maintain an Action Web Site and issue Press Releases for the dissemination of information about the Action.

The duration of the COST Action will be five years. Two extended international meetings will be organised, one in the middle and one at the end of the Action. These could be combined with other international brucellosis meetings. External experts from outside COST member states will be invited to participate in several meetings. Following each international meeting, full proceedings will be published.

E. ECONOMIC DIMENSION

As this proposal is in the early stages, only a limited number of countries have been informally approached to participate. Nevertheless, I estimate that in excess of 15 COST countries will wish to participate. I also envisage that several international bodies and industrial companies will be interested in the Action.

The national costs per annum currently expended have been estimated from data provided by researchers who have expressed an interest in participating in the Action.

Country
Researchers
1Budget (Euro)
Belgium
7
728 000
Denmark
4
432 000
France
19
1 702 000
Germany
4
380 000
Greece
4
340 000
Ireland
4
410 000
Italy
4
340 000
Netherlands
4
520 000
Portugal
4
350 000
Spain
16
173 000
United Kingdom
7
870 000
Total national costs
80
6 245 000.

Convocatoria de propuestas

Data not available

Régimen de financiación

Data not available

Coordinador

N/A
Aportación de la UE
Sin datos
Dirección


Reino Unido

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Coste total
Sin datos