European research action on protozoal reproduction losses in farm ruminants (COST)

April 2, 2002

Brussels, 29 March 2002

European Cooperation in the field of Scientific and Technical Research - COST - Secretariat.
Memorandum of Understanding for the implementation of a concerted European research action designated as COST Action 854 "Protozoal reproduction losses in farm ruminants." Brussels, March 2002 (document COST 229/02). Full text

Delegations will find attached hereto the text of the abovementioned Memorandum, signed in Brussels on 6 March 2002 by Greece and Spain, on 11 March 2002 by Poland and on 19 March 2002 by Belgium and the Netherlands.

The Signatories to this Memorandum of Understanding, declaring their common intention to participate in the concerted Action referred to above and described in the Technical Annex to the Memorandum, have reached the following understanding:

1. The Action will be carried out in accordance with the provisions of document COST 400/01 "Rules and Procedures for Implementing COST Actions", the contents of which are fully known by the Signatories.

2. The main objective of the Action is to develop strategies to control reproductive diseases caused by protozoa in farm ruminants.

3. The economic dimension of the activities carried out under the Action has been estimated, on the basis of information available during the planning of the Action, at Euro 25 million in 2001 prices.

4. The Memorandum of Understanding will take effect on being signed by at least five Signatories.

5. The Memorandum of Understanding will remain in force for a period of four years, unless the duration of the Action is modified according to the provisions of Chapter 6 of the document referred to in Point 1 above.

TECHNICAL ANNEX

"Protozoal reproduction losses in farm ruminants" COST 854

A. BACKGROUND

Infectious organisms can cause significant losses in farm ruminant production as a result of abortion, embryonic damage or maternal infertility. The two principal agents causing protozoal abortion in ruminants are Neospora caninum in cattle and Toxoplasma gondii in sheep and goats. Both pathogens are closely related. Tritrichomonas foetus is a serious cause of cattle infertility.

Furthermore, parasites of the genus Sarcocystis are widely distributed and may inflict infections affecting the reproductive tract of ruminants, which also may result in abortion.

Abortion in ruminants may pose a very considerable public health risk as many of the pathogens that cause disease in ruminants may pose a significant danger to humans. Thus rapid, accurate diagnosis is vital in order to be able to assess the degree of risk caused by potential ruminant abortifacients with zoonotic potential such as T. gondii, Chlamydophila abortus (Chlamydia psittaci), Coxiella burnetii, Listeria monocytogenes, Salmonella spp., Campylobacter spp. and Brucella spp.. While N. caninum and Sarcocystis spp. are not currently considered to be zoonotic, rapid accurate diagnostic methods for protozoal causes are essential to rule in or out more dangerous pathogens, to allow meaningful risk assessments.

Neospora caninum is an important cause of infectious abortion and stillbirth in cattle world-wide.

Infection is common and may frequently be passed from mother to calf (vertical transmission) with no signs of disease. Disease occurs when the parasite multiplies in the developing calf and its placenta and causes sufficient damage to trigger abortion or stillbirth. Preliminary research suggests that infection of the foetus early in gestation is more likely to be fatal to the conceptus than infection later in gestation. However, it also appears that infection is more likely to be transmitted in late rather than early pregnancy. Thus, the majority of infections are not fatal and in this way inapparent infections are maintained in a herd. Vertical transmission is the major route of transmission, but it is likely that oocysts of N. caninum, produced by dogs and excreted in their faeces, may also infect cattle if they ingest contaminated food or water (horizontal transmission).

Control of bovine neosporosis is difficult. Pharmaceutical preparations are known that will kill Neospora, but their use to control infection/disease in cattle have not been sufficiently evaluated yet, and no effective vaccine is currently available. Control measures therefore rely on applying certain management strategies, which are only partially satisfactory. Current knowledge suggests, that Neospora does not cause disease in human beings.

Toxoplasma gondii is an important zoonotic infection as well as being a major cause of abortion in sheep and goats. The majority of cases of human toxoplasmosis follow the consumption of uncooked or lightly cooked meat (sheep, goat, pig, cattle, deer). There is also an added risk from drinking unpasteurised goats milk as well as from the ingestion of fruit and vegetables contaminated with soil containing Toxoplasma oocysts. Control is very difficult as it depends on preventing a primary infection in a pregnant sheep or goat. While certain management procedures may reduce the risk, elimination is not possible. A live commercial vaccine ­ for use in sheep - is sold in some EU member states. Use of a vaccine sufficiently effective to protect against abortion in sheep and goats would be considered very likely to reduce, if not prevent, the development of tissue cysts in muscle. This would make the meat (and milk) very much safer for human consumption. However, this is a neglected area of research.

Tritrichomonas foetus, a venereally transmitted bovine infection, is an important cause of pregnancy loss and abortion in naturally bred cattle throughout the world. Trichomonosis has been a list B disease by OIE classification for many years and is therefore the subject of animals disease control in several countries. Since the introduction of artificial insemination the economic importance of this disease has decreased, but there is evidence of a re-emergence in extensive husbandry in some European states. As T. foetus may have spread inapparently also among other livestock animals such as pigs, a basic reconsideration of the epidemiological situation in Europe and the classification of virulence and pathogenicity among Tritrichomonas isolates is strongly required.

To limit the impact of protozoal reproduction failure in farm ruminants, research into the biochemistry, biology and genetics of these protozoa is urgently required to answer questions relevant for diagnosis and control. This, combined with a practical understanding of the immune responses of sheep, goats and cattle to these organisms will provide some understanding of important differences in the pathogenesis of the infections. For instance, such studies may be able to answer the question why do sheep not abort more than once with T. gondii, while cattle may pass N. caninum infection to their offspring in subsequent pregnancies, sometimes with no clinical effect and sometimes with fatal effect. Diagnosis of protozoal abortifacients is not always easy and the diagnostic criteria may vary from lab to lab. Standard procedures and parameters need to be set between labs and different countries so that epidemiological data can be improved and consolidated.

The knowledge of risk factors for infection needs to be increased (e.g. presence of dogs or cats, which may shed infectious Neospora or Toxoplasma oocysts in their faeces, lactogenic infection, seasonality, factors causing recrudescence in bovine neosporosis, a-symptomatic carriers of T. foetus within or outside the ruminant host range etc). On the basis of a quantitative assessment of the consequences of protozoal reproduction failure it will be possible to establish models for the estimation of the economic losses and to perform cost-benefit analyses for potential control programmes. In this way management procedures to reduce the impact of disease can be developed. The ultimate goal is to enable the development of control measures including vaccine strategies for these diseases.

With a move to more extensive systems of agriculture the risk of protozoal abortion in ruminants would remain and perhaps attain greater significance. In the case of toxoplasmosis in sheep and goats, infection is picked up from contaminated grass, hay and water as well as from concentrated loose feed. It occurs just as commonly in extensive as in intensive farming systems. With bovine neosporosis evidence is accumulating to indicate, that the incidence of abortion is exacerbated by stress. In some situations this may occur with more intensive farming methods (such as the feedlot systems encountered in California), while in other cases stress may occur in extensive systems of agriculture due to severe environmental conditions, such as caused by extremes of weather. Cases of fatal sarcocystiosis occur more frequently when extensively reared animals are moved to grassland nearer the farm or to locations visited by people, due to contamination of the ground by dog and cat faeces.

Despite considerable scientific efforts currently being undertaken in several European countries with these infections, no formal framework exists at the European level to permit an ongoing, structured discussion process in this rapidly evolving field. COST provides an excellent basis for such a co-operation, particularly because it allows the inclusion of groups from countries outside the European Union. This has been demonstrated for the particular aspect of vaccines against animal coccidioses in COST 820, where a Working Group on sarcocystiosis, toxoplasmosis and neosporosis existed.

Relationship to the activities of COST 820 and relevant conclusions

While COST 820 ("Vaccines against Animal Coccidioses") originally focused on parasites of the genus Eimeria and Cryptosporidium (mainly parasites of poultry, ruminants, pigs and rabbits), the so-called cyst-forming coccidia (Toxoplasma gondii, Sarcocystis spp., Neospora caninum) gained considerable attention during the course of the Action, which was mainly due to the fact, that N. caninum had emerged as one of the most frequently diagnosed causes of abortion in cattle....

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