Vaccine 17 (1999) 17601766

Vital elements for the successful control of foot-and-mouth disease by vaccination

A.J.M. Garland *
`Collingwood', Dawney Hill, Pirbright, Surrey GU24 0JB, UK

Abstract The ecient control of foot-and-mouth disease (FMD) by immunisation depends not only on the appropriate choice of vaccine in terms of innocuity, potency and strain composition, but also on a series of inter-related zoo-sanitary factors which are equally important. These include: national, centralised planning (including contingency planning) and control; vaccination and revaccination policy; the availability of epizootiological intelligence based on adequate diagnostic capability and ongoing immunological surveillance; the logistics of supply with its components of storage, transport and distribution; proper vaccine application; cleaning and disinfection of premises, vehicles and personnel; identication of individual animals; control of animal movement; recording; ongoing economic outcome and benet analyses; training and retraining of professional and technical sta; public relations and especially the commitment of the agricultural community. These elements are reviewed in this paper. # 1999 Elsevier Science Ltd. All rights reserved.

1. Introduction In the 70 years which have elapsed since the rst publications appeared on vaccination against foot-andmouth disease (FMD) [1], major advances have been made in virtually all aspects of our understanding of the virus, the disease and the methods for its control. Studies in areas including: the molecular biology of the virus; the pathogenesis of the disease; the excretion, dissemination and persistence of the virus; the epidemiology of the disease; the immune response; the genetic and antigenic relationships between strains of virus and the reliable production of safe and potent vaccines [2] have all provided information which has been applied in increasingly eective approaches to the control of FMD. Nevertheless, and despite spectacular success in many countries where the disease was formerly endemic, large areas of the globe continue to suer the depredations of FMD. The reasons for these failures are complex, but insucient attention to basic elements of planning and resource in the prosecution of control schemes can be critically important.
* Tel.: +44-1483-473-476; fax: +44-1483-480-023. 0264-410X/99/$19.00 # 1999 Elsevier Science Ltd. All rights reserved. PII: S 0 2 6 4 - 4 1 0 X ( 9 8 ) 0 0 4 4 3 - 5

2. Centralised planning and control While control schemes for FMD may be aimed initially at the local reduction of infection, of disease severity and of disease incidence and prevalence, the ultimate aim should be the total eradication of the disease. In endemic areas the approach taken will vary according to local circumstances. However, the ultimate goal is inevitably attained in stages. Thus the disease and measures for its control progress from endemicity at the initiation of mass vaccination, moving through increasing control of sporadic outbreaks, to the status of `freedom from disease with vaccination' and nally to the status of `freedom from disease without vaccination', a progression known as `the OIE pathway' [3]. Each of these stages has associated criteria, as described in the International Animal Health Code of the Oce des Epizooties (OIE) [4], and each has international trading implications for live animals and animal products. It is important to recognise that vaccination is only one of several zoo-sanitary measures which are essential for the control of FMD and that vaccination alone cannot be relied upon for a successful outcome. The

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disease has extreme communicability and the modalities for its dissemination are very numerous. Some modes, such as airborne spread, are virtually impossible to prevent. Moreover, the duration of immunity following inactivated FMD vaccination is short relative to that of many other vaccines (particularly live vaccines) and it is unlikely that immunity can be continuously maintained at a protective level in all individuals within the national herd and/or ock. For these and other reasons the strategy should include mass revaccination biannually or even triannually, depending on the characteristics of the vaccine employed, and possibly special reinforcement of vaccination in strategic areas (e.g. barrier vaccination in vulnerable border areas) and ring vaccination around foci of disease. Additional zoo-sanitary measures are also essential. These include: . Control of legal and illegal animal movement within the country. . Prohibition of the import of susceptible animals and certain animal products from areas with a high risk of FMD infection. . Application of risk assessment and risk management for the importation of susceptible animals and animal products from areas with an acceptable risk of FMD infection. . Appropriate pre-testing of susceptible animals for FMD prior to import and the application of quarantine measures. . Control of foci by restricting the movement of animals and animal products from the infected area and by the disinfection/safe destruction of infected and potentially infected materials. . Application of a slaughter policy for infected and susceptible, in-contact animals, as justied by the overall epizootiological situation. Eective mass vaccination depends to a great extent on co-ordinated, centralised planning, organisation and control. This responsibility is usually vested in the National Veterinary Service. The department concerned must be adequately staed in terms of numbers of experienced, knowledgeable personnel and be provided with the necessary physical and nancial resources. The areas of expertise which, ideally, should be available to the central authority include: . Epidemiology (with specialised knowledge of FMD). . Animal health legislation. . Veterinary/agricultural economics (including cost/ benet analysis). . Risk analysis (assessment and management). . Logistics. . Information technology.

. Training and education. In an ideal situation the headquarters team should have access to the following data and resources: . Species, numbers and locations of susceptible livestock (cattle, bualo, sheep, goats, pigs). . Systems of animal management and marketing employed. . Routes of animal movement both legal and illegal (cross border trade movements, movement for breeding, fattening, slaughter, transhumance, etc.). . Location of particularly valuable livestock (articial insemination stations, pedigree herds/ocks, etc.). . Availability/non-availability of aids to animal management for vaccination (cattle races, crushes, etc.). . Availability of climatic data (rainy seasons, drought periods, etc.). . Disposition and condition of vaccination equipment. . Location and condition of cold stores, cool boxes, gel packs and temperature monitors. . Availability and condition of protective clothing (overalls, rubber boots, possibly waterproof clothing and gloves). . Availability of disinfectants and disinfection equipment (nail and boot brushes, pressurised spraying equipment). . Availability and condition of transport. . Availability and competence of manpower (veterinarians, animal assistants, vaccinators, administrative sta). . Availability of a system of identication and registration of individual animals. . Availability of recording systems (manual and/or computerised). . Availability of suitable vaccine (correct antigenic composition, correct formulation, safety data and potency data in compliance with international standards, adequate remaining shelf-life). . Availability of written Standing Operating Procedures (SOPs) for all aspects of vaccination (vaccination, revaccination, ring vaccination, etc.). . Availability of written contingency plans. . Existence of appropriate national legislation dening the responsibilities and powers of the Ministry of Agriculture/Veterinary Department for all aspects of the control of FMD, including, for example, legislation on the enforcement of compulsory vaccination; the collection of fees as appropriate; and any penalties for non-compliance. . Access to current research information relevant to the control of FMD. This checklist summarises the principal data and equipment to be assembled and/or considered in planning for mass vaccination. The manuals for the control

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of rinderpest published by the Food and Agriculture Organisation also provide useful guidance [5] although the vaccine in this case is a live attenuated preparation. Additional useful information is available in textbook form [68] and in international legislation such as European Union Directives and Guidelines. A further important option to be considered is that of the possibility of combining elements of disease control schemes, for example, by vaccinating against FMD, rinderpest and sheep and goat pox simultaneously. Some items listed above are desirable rather than essential. Local conditions make some aspects more important than others and successful campaigns have been mounted in the absence of some of these elements. A notable example might be the absence of a national system for the identication and registration of individual animals. Some elements are concerned with measures other than vaccination per se (e.g. disinfection between farms and/or in the event of discovering clinical FMD) and many have application beyond the specic control of FMD in the general elds of hygiene, animal health, animal production and disease control. The importance of written plans, contingency plans and SOPs is emphasised, as is the need for a calendar for the routine critical review of these documents at least annually [69]. These provide a formal structure for the campaign, aid consistency of approach and are very valuable aids in training and education. A further requirement is that of carrying out simulation exercises annually or more frequently as necessary. These are used in training and also to test out the practical aspects of theoretical methodology and procedures. Documentation should be revised appropriately in the light of the results of such simulations. Other desirable functions of the headquarters sta are in the performance of cost benet and risk benet analyses, providing the basis for decisions on the adoption of various options and strategies for the control of FMD, and other diseases, and in monitoring the progress of the programmes during implementation [1013]. Having dened the overall campaign strategy the detailed plans for implementation are drawn up. The plans should include timetables for the assembly of materials and equipment and for successive rounds of vaccination and revaccination at specic locations. Allowance must be made for the immunisation of successive generations of new-born animals and for interference in their vaccinal response due to maternal immunity. The time taken to achieve coverage is also an important aspect, since the more rapidly an area can be vaccinated, the sooner will levels of herd immunity be established capable of minimising the amount of virus circulating in the environment.

3. Epizootiological intelligence and diagnosis Comprehensive and up-to-date epizootiological information is a prerequisite for eective disease control. Within a country or region, information on the status of a particular disease can be gathered by veterinarians, in both the private and public sectors, and even earlier and more eectively by an educated livestock community. In the case of FMD the notication procedure is usually reinforced by the designation of the disease in national legislation as being compulsorily notiable on the basis of suspicion of the presence of disease on clinical grounds. The national veterinary service usually has the responsibility for the conrmation of the presence or absence of FMD by means of expert clinical examination, epidemiological investigations and laboratory testing of suspect samples. Such samples are preferably of fresh vesicular lesion material or, in the case of asymptomatic fatalities, of cardiac muscle. However samples may also be of serum, milk or oesophagealpharyngeal uid. The overall speed of obtaining samples of lesion material can be accelerated by the preparation of sample bottles containing glycerol-phosphate buer at pH 7.0 and their advance distribution to veterinary establishments at strategic locations. Samples for antigen or antibody detection and/or assay may be tested by several dierent techniques at various levels of sensitivity. The long established method of complement xation (CF) continues to nd application for the typing of FMD virus in a few laboratories, although enzyme linked immunosorbent assays (ELISAs) of various descriptions have been increasingly used for both antigen and antibody identication and assay [14, 15]. ELISA oers signicant advantages of sensitivity, specicity and objectivity over CF tests and is the preferred, optimal method as prescribed by OIE [4]. Passage of eld samples in susceptible animals or, more commonly, susceptible tissue cultures may also be used to amplify small amounts of infectious virus. Of the other advanced techniques, as yet restricted to a limited number of laboratories, the polymerase chain reaction (PCR) method has the advantage of being able to detect minute amounts of viral RNA, even in the absence of infectious virus. Nucleic acid sequencing of selected portions of the RNA genome allows for the precise characterisation of virus isolates and their comparison with the sequences of reference strains held in data banks. These molecular techniques have particular application in dening the relationship between a current eld isolate and existing eld and vaccine strains of virus and can assist in the identication of the origin of outbreaks [16]. While the characterisation of virus isolates may well be eected in national laboratories and regional FMD

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laboratories, it is also strongly advisable to submit representative samples to the OIE/FAO World Reference Laboratory in order to conrm the diagnosis and to enable the detailed classication of the sample in relation to other existing strains. Samples must be despatched in accordance with established procedures for the preservation of viral infectivity and the maintenance of disease security in transit, including compliance with current international postal regulations [17]. National epizootiological intelligence should be supplemented by the continual exchange of information between neighbouring countries within a region and, most importantly, by the prompt exchange of information with the international authorities including: the OIE in Paris, France; the Food and Agriculture Organisation (FAO) of the United Nations in Rome, Italy and the OIE/FAO World Reference Laboratory at Pirbright in the United Kingdom.

4. Diagnostic laboratory capability Many countries maintain virological laboratories equipped for the diagnosis of FMD and the serological surveillance for both the disease and the immune status of herds and ocks in which vaccination has been applied. Much of this work can today be eected without the necessity to employ live virus by the use of inactivated viruses and non-infectious viral components. This approach is to be commended. However, it is to be noted that where the work involves material which is known, or suspected, to contain infectious virus, such laboratories should be operated under full disease security in compliance with international recommendations [4]. Desirable procedures in this context are adherence to the disease security recommendations formulated by the European Union, Standing Veterinary Committee's Expert Group in FMD disease security and the inspection and approval of the laboratory by this group [18]. Laboratory sta should maintain an awareness that FMD exists as seven immunologically distinct but clinically indistinguishable virus types and that new strains of FMD can and do emerge from time to time. Such antigenic drift was exemplied by the A22 strain which rst appeared in Iran in 1964 and which subsequently spread to be the most common subtype throughout the Near Eastern countries. More recently this phenomenon has again been demonstrated by the emergence and dissemination of a new type A strain, antigenically and genomically distinct from all other known strains of type A virus, which is now prevalent in Turkey.

FMD virus types historically absent from a region may occasionally migrate, as seen with South Africa Type 1 (SAT 1) which moved rapidly through the Middle East and as far north as Turkey and Greece in 1962. Similarly Type Asia 1 penetrated into Turkey in 1973. Yet again, existing diseases or completely novel diseases which resemble FMD clinically may appear and/or reappear, such as vesicular stomatitis, vesicular exanthema of pigs and swine vesicular disease, the latter appearing in Italy and elsewhere from 1966 onwards. Laboratories should therefore have the capability for dierential diagnosis. The practice of some laboratories to test suspect samples of FMD virus only for types and strains of FMD which are known to be prevalent in that region must be recognised as carrying at least a potential risk. Apart from diagnosis such laboratories can undertake serological surveillance. Studies of this type should have clearly dened objectives, such as the investigation of antibody levels in the national herds and ocks after vaccination and revaccination or of the presence of sub-clinical FMD, as may be encountered particularly in sheep and goats. The surveys should have a sound statistical basis and should include an element of sequential sampling of specied herds, ocks and individuals. In future FMD laboratories are also likely to have the valuable capability to dierentiate between antibodies induced by vaccination and infection, using assays for non-structural proteins of FMD virus [19]. A further recommendation is that FMD laboratories should be accredited in terms of human and physical resources and technical capability in compliance with international norms (e.g. OIE Guidelines for Laboratory Quality Evaluation [20] and OIE Guidelines for Laboratory Prociency testing) [21]. Moreover the tests employed should be calibrated and performed in compliance with international standards wherever possible [4]. Participation in the ongoing exercises for the standardisation of tests as organised under the auspices of OIE/FAO is valuable in this context [22]. 5. Selection of FMD vaccine There are currently a number of commercially manufactured vaccines available of diering strain composition, antigenic content, adjuvant formulation and cost [2]. All are produced using inactivated antigens. Vaccine is available as fully formulated and tested product or, more usually in emergency situations, it can be freshly formulated from concentrated, inactivated antigen(s) stored at low temperature in vaccine banks maintained by commercial manufacturers or by national and international authorities [23].

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In selecting the appropriate vaccine or vaccines a number of factors must be taken into account. The rst is that the antigenic composition of the vaccine, mono- or polyvalent, should give immunity against the virus strain(s) known to be prevalent in the region or those considered most likely to be introduced. The second is that the vaccine should have been satisfactorily tested for innocuity and potency according to international standards as detailed in national or international pharmacopoeias, e.g. as in the European Pharmacopoeia [24] and/or the recommendations of the OIE [4]. In terms of potency the present pharmacopoeial requirement is that the vaccine should have been shown to contain at least three 50% protective doses (PD50) per vaccine dose volume. However, many of today's commercially available vaccines contain greatly in excess of 3 PD50 per dose and the Research Group of the European Commission for the Control of FMD has recently recommended that vaccines should contain a minimum of 6 PD50 per dose for routine prophylaxis and 10 PD50 per dose for emergency use. There is evidence that the higher the antigenic content of a vaccine, and thus usually the potency, then the wider the spectrum of antigenic cover that will be engendered and the longer the duration of immunity which will persist [23]. Experimental vaccines have been reported formulated with very high levels of antigen giving PD50 values in the order of 100 PD50 per dose and protection lasting for at least one year [25]. However, the cost of vaccine is also related to the level of incorporation of antigen and a balance has to be struck between vaccine potency, vaccine cost and available funds. The third factor is that of the vaccine adjuvant. The most common adjuvants are aluminium hydroxide plus saponin in aqueous (AS) vaccines and oils and emulsiers in various oil emulsion (OE) vaccines. Broadly speaking, and depending on the individual vaccine, OE vaccines are claimed to engender longer lasting immunity than AS vaccines following primary vaccination and so require less frequent boosting. AS vaccines are suitable for the immunisation of ruminants but give very poor responses in pigs, whereas OE vaccines provide immunity in both ruminants and pigs. Maternal immunity can interfere with the ecacy of the response to AS vaccines, whereas OE vaccines are signicantly less eected in this way. OE vaccines are more costly than AS vaccines and concerns have been expressed over the association of OE vaccines with persistent carcass reactions. Once again a balance must be struck between the various characteristics of the available vaccines in selecting the most appropriate formulation. The fourth factor is that of the stability of the vaccine and the question of its expiry date. Most FMD

vaccines claim a shelf life of 12 to 24 months post-testing. Ideally the vaccine should be obtained from the manufacturer with the longest possible remaining shelf life, or at least with sucient remaining shelf life to allow adequate time for the use of the vaccine in the eld prior to its expiry. The fth factor is the availability of the chosen vaccine formulation in sucient quantity to enable the completion of the planned vaccination campaign(s). Calculations of the number of doses of vaccine required should take into account both vaccination and revaccination and allow for a certain amount of wastage, for example when part used vaccine bottles are discarded according to good practice at the end of a day's work and/or between farms. Allowance must also be made for possible supplementary, ring vaccination in emergency situations. 6. The cold chain FMD vaccines must be maintained under refrigeration for the optimal retention of antigenic potency, usually at 4 2 28C. The antigen loses immunogenic activity progressively as the storage temperature increases above these levels [26]. In addition freezing and thawing of FMD vaccines damages their integrity and can also cause the breakage of both aluminium hydroxide gels and oil emulsions, decreasing and possibly destroying the immunogenicity of the vaccines. The eciency of the cold chain is therefore a critical factor for optimal vaccine storage. The cold chain includes all the refrigerated storage of the vaccine from the time of manufacture, through vehicular and air transport, warehousing and distribution, to the point of inoculation into the animal. Shipments of vaccine should be in thermally insulated containers, possibly with gel packs and accompanied with validated temperature monitoring and/or recording equipment. Domestic refrigerators and walk-in cold rooms should be tted with temperature recorders which are calibrated against international standards and regularly revalidated. Cool boxes used to transport vaccine should be tested to determine the time for which they are capable of maintaining vaccine at the recommended storage temperature under conditions which simulate the most extreme environmental temperatures likely to be encountered in the eld. Portable refrigeration equipment should be subjected to regular maintenance and routinely tested prior to use. 7. Training and education Veterinarians, animal technicians and vaccinators should be educated, trained and tested to appropriate

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levels in good vaccination practice, good hygienic practice, disease control and legislation. Plans, contingency plans and SOPs are valuable aids in this area. Topics to be covered may include: . The disease and its eects. . The care of vaccine and vaccination equipment, including the sterilisation of syringes and needles. . Vaccine application (site(s) of inoculation, dose rates for dierent species). . Cleaning and disinfection of persons, protective clothing, equipment and vehicles. . Recording. . Animal handling. . Animal identication. . Taking and treatment of samples. . Means of managing any outbreaks of FMD (or other diseases) which they may encounter. A most important aspect is the appreciation by such sta of the role which they can inadvertently play in the spread of FMD and other communicable diseases between farms. Supplementary training may include such topics as the collection and recording of fees and rst aid. Training records should be kept and refresher courses organised.

Vaccine discarded at the expiry of its validity, or for any other reason, should be safely destroyed, securely disposed of and its fate recorded. 9. Public relations The commitment of the farming community to schemes of animal disease control can greatly facilitate success. Conversely, the lack of their commitment renders the task much more dicult. This is particularly evident when there is an element of cost to the farmer. For these reasons it is important to use all available means to publicise control measures for FMD and to explain the rationale, the legal requirements, the timetable and the benets which are expected to accrue from their implementation. Media which can be utilised for these purposes include: leaets, newspapers, magazines, trade journals, radio and television. Meetings can also be arranged with associations, organisations and clubs connected with agriculture, and particularly with livestock, such as Farmers Unions, Collectives, Co-operatives, Breed Associations, etc. Use can also be made of veterinary schools, agricultural colleges and extension services for these purposes. The public awareness campaign should be planned in advance and should also allow for the messages to be reinforced periodically, ideally with bulletins describing the ongoing success of the control scheme. 10. Conclusions Despite the complexity of FMD in terms of the multiplicity of types and strains, the wide host range and the highly contagious nature of the disease, vaccination campaigns combined with other zoo-sanitary control measures have been attended with notable success in many parts of the world. A conspicuous example is found in continental Europe where mass compulsory vaccination together with the control of the movement of live animals and of animal products, sometimes combined with the slaughter and destruction of infected animals, reduced the incidence of the disease from being endemic throughout much of the twentieth century to the point at which vaccination was could be totally discontinued in 1990/1991. Similarly, in South America, decades of endemic FMD are now coming under control following renewed vaccination campaigns in many countries utilising OE vaccines. Thus Chile and Uruguay have attained the status of freedom without vaccination, while Paraguay, Argentina and the southern states of Brazil have reported no outbreaks for several years and have applied to OIE for recognition of the status of freedom with vaccination. These examples demonstrate what

8. Logistics of supply and distribution Ideally vaccine will be ordered with the maximum remaining shelf life and in quantities appropriate to a given phase of the vaccination campaign. The aim should be to attain at least 80% and preferably 100% vaccine coverage of susceptible livestock. Lesser levels of coverage and the use of vaccines of poor potency are likely to be associated with inecient control and, importantly, with the selection of antigenic mutants in partially immune animal populations. It is to be recognised, however, that decisions have sometimes been made to vaccinate only certain species, such as cattle, bualo and pigs and to ignore small ruminants, usually on the grounds of cost. This approach may well carry the risk of perpetuating the disease. Vaccine should be removed from the central cold stores only in sucient quantity for the day's work and the movement and utilisation of vaccine will be recorded in respect of the date, the number of bottles and doses removed, the location at which they were used, the numbers of doses utilised according to species and the number of doses discarded. Standard record forms should be used which also allow for supplementary notes (e.g. on the number of young stock which may need to be re-vaccinated and when).

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A.J.M. Garland / Vaccine 17 (1999) 17601766 [15] Hamblin C, Barnett ITR, Hedger RS. A new ELISA for the detection of antibodies against foot and mouth disease virus. J. Infect. Dis. 1986;93:11521. [16] Locher F, Suryanarayana VVS, Tratschin JD. Rapid detection and characterisation of foot-and-mouth disease virus by restriction enzyme and nucleotide sequence analysis of PCR products. J. Clin. Microbiol. 1995;33:4404. [17] Kitching RP, Donaldson AI. Collection and transportation of specimens for vesicular virus investigation. Rev. Sci. Tech. O. Int. Epiz. 1987;6:26372. [18] Anon. Minimum standards for laboratories working with footand-mouth disease virus in-vivo and in-vitro. EEC Document AGA:EUFMD/93/2. 1993. [19] Mackay DKJ. The diagnostic potential of assays measuring antibody to the non-structural proteins of foot-and-mouth disease to dierentiate infection from vaccination. Report of a session of the Research Group of the Standing Technical Committee of the European Commission for the Control of Foot-and-Mouth Disease, Poiana-Brasov, Romania, 2327 September 1997, Appendix 7. Rome, Italy: Food and Agriculture Organisation of the United Nations, 1997. p. 4551. [20] De Clercq K. Oce International des Epizooties guidelines for laboratory quality evaluation and prociency testing as a basis for the implementation of a quality assurance programme in national foot-and-mouth disease laboratories. Report of a session of the Research Group of the Standing Technical Committee of the European Commission for the Control of FMD, Ma'ale Hachmisha, Israel. Rome, Italy: The Food and Agriculture Organisation of the United Nations, 1996. p. 208 18. [21] Anon. Standards for laboratory quality evaluation. Report of the Meeting of the Oce International des Epizooties Standards Commission, 1922 September, 1995. Document 64 SG/12/ CS2A. Paris: OIE, 1995. [22] Mackay DKJ. Standardisation of foot-and-mouth disease diagnosis. Report on Phase XIV of the Oce International des Epizooties/Food and Agriculture Organisation of the United Nations, International Standardisation Programme. Session of the Research Group of the Standing Technical Committee of the European Commission for the Control of Foot-and-Mouth Disease, Ma'ale Hachmisha, Israel. Rome, Italy: the Food and Agriculture Organisation of the United Nations, 1996. [23] Garland AJM. The availability of foot-and-mouth disease vaccine for emergency vaccination in Europe. Report of the 32nd Session of the European Commission for the Control of Footand-Mouth Disease, Appendix 8. Rome, Italy, 1997. p. 89111. [24] European Pharmacopoeia. 3rd ed. Saint Rune, France: Maissoneuve, 1997. [25] Dudnikov AI, Mikhalishin VV, Gusev AA, Ulupov NA, Mamkov NS, Polyakov ON, Lezova TN. Immunological properties of inactivated foot-and-mouth disease vaccine of new generation. Report of the Research Group of the Standing Technical Committee of the European Commission for the Control of Foot-and-Mouth Disease, Vienna, Austria, 1922 September 1994, Appendix 18. 1994. p. 989. [26] Doel TR, Baccarini PJ. Thermal stability of foot-and-mouth disease virus. Arch. Virol. 1981;70:2132.

can be achieved when all the elements of control are successfully combined, including the use of vaccination campaigns which have been carefully planned, adequately resourced and eectively administered. Acknowledgement I thank Dr. A.I. Donaldson for his critical review of the manuscript. References
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