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Infectious Diseases: Foot-and-Mouth Disease

R S Schrijver, Veteffect Veterinary and Public Health, Bilthoven, The Netherlands

W Vosloo, Australian Animal Health Laboratory, Geelong, VIC, Australia

ª 2011 Elsevier Ltd. All rights reserved.

This article is a revision of the previous edition article by

R. S. Schrijver, Volume 2, pp 797–804,ª 2002, Elsevier Ltd.

Introduction

Foot-and-mouth disease (FMD) is one of the most impor-tant infectious diseases that can affect cattle. This is due tothe severe economic consequences of outbreaks, causedboth by the direct losses in animal productivity and by theindirect losses associated with the high costs of controlmeasures coupled to trade restrictions that usually result

from outbreaks. Several characteristics of FMD contri-bute to this: the disease is highly contagious; it affects awide range of artiodactyls; and the virus is relativelystable in the environment and can easily be transmitted,including via airborne spreads under specific conditions.In addition, seven serotypes of FMD virus (FMDV) exist,which confer little or no cross-protection, and many var-iants occur within each serotype. For this reason, vaccinescontaining specific strains are required to protect againstantigenically different isolates of FMDV.

Since the cessation of vaccination against FMDV atthe end of 1991 in the European Union, it was estimated

from cost–benefit studies that mass vaccination cam-paigns were costlier than the estimated expenditure tocontrol occasional outbreaks. Added to this, there is thelonger waiting period necessary to regain the FMD-freestatus when using vaccines. Also, several FMD outbreakshave been associated with improperly inactivated vac-cines, or by escape of the virus from the vaccine plants.The decision to cease all vaccination has led to a fullysusceptible population of cloven hoofed animals wherethe disease can rapidly spread resulting in unprecedentedeconomical and social damage. This was amply demon-strated when an outbreak of FMD occurred in 2001,

starting in the United Kingdom, with limited spread toFrance and the Netherlands. More than 2000 FMD caseswere confirmed in the United Kingdom, and more than3.7 million animals were slaughtered. Vaccination wasapplied only in the Netherlands, followed by stampingout of vaccinated animals leading to 26 confirmed casesand 265 000 animals slaughtered. This has initiated aninternational debate on the role of vaccination in theFMD control policy in the European Union (EU).

FMDV is still endemic in many countries, which limitstrade in live animals or animal products with FMDV-free

countries. Illegal trade and the widespread occurrence of FMD in many parts of the world is a constant threat tofree areas, justifying regular consideration, review, andupdate of surveillance programs and contingency plans,and creation of awareness among those working withsusceptible animals in free countries. In endemic areas,it is essential to monitor the possible emergence of newviruses that may differ antigenically from existing vaccine

strains with potential failure of protection against thedisease in the face of an outbreak.

There is a trade incentive not to use vaccination anddespite the developments in serological assays to distin-guish between vaccinated and infected animals, countriesfree of the disease are often reluctant to accept liveanimals and their products from areas where vaccinesare used. It is expected that the number of FMDV-freecountries will gradually increase.

This article reviews the epidemiology, economy, andcontrol of FMD, with special emphasis on ruminants.

Epidemiology

The Causative Virus and Its Characteristics

FMD is caused by a positive-sense, single-stranded RNAvirus. The genome consists of approximately 8500nucleotide bases, and encodes one large polyprotein.This polyprotein is posttranslationally cleaved by viral-encoded proteases into structural and nonstructural (NS)proteins. The virus has an icosahedral symmetry and iscomposed of 60 copies of each of the four structural

proteins 1A (VP4), 1B (VP2), 1C (VP3), and 1D (VP1).Four structural proteins form a protomer, and five proto-mers form a pentamer (with a sedimentation coefficient of 12 S). Twelve pentamers assemble into one virion (with asedimentation coefficient of 146 S). The NS proteins areL (leader protease), 2A, 2B, 2C, 3A, 3B (associated to the5’-end of the viral RNA), 3C (protease), and 3D (RNA-dependent RNA polymerase). The function of eachprotein is not known, but the proteases are associatedwith the processing of the viral polyprotein intofunctional proteins and also mediate the host cell’s

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cap-dependent mRNA translation shutoff and interferewith the innate immune response.

FMDV has no envelope and is moderately resistant inthe environment. A relatively high humidity of more than60%, a pH of 7.2–7.6, and low temperatures are theenvironmental factors that favor long-term survival of the virus. The virus is unstable at pH below 6 or above9, and is inactivated at temperatures above 56 C.Consequently, FMDV is rapidly inactivated by citricacid and by bases such as caustic soda. FMDV isolatesmay differ in their resistance to heat inactivation, the typeA strains being relatively more resistant. When the virusis associated with proteins, such as in milk or other dairyproducts where the virus is incorporated into the casein(CN) micelles and fat droplets, or present in organicmaterial, such as slurry, the inactivation is greatlyreduced, and more severe conditions or the use of deter-gents is necessary for complete inactivation. In skeletalmuscles, reduction of pH to a value below 6 due to lactic

acid formation leads to the inactivation of FMDV post-mortem, but this requires that the meat be stored forabout 48h at 4 C after slaughter. In lymph nodes andbone marrow, virus may survive for months.

Seven serotypes of FMDV have been identified (O, A,C, Asia-1, and the South African serotypes (SAT) 1, 2,and 3), of which serotype C is most likely extinct. Theseserotypes differ in their geographic distribution as sum-marized in Table 1. However, certain isolates appearfrom time to time and spread rapidly over vast areas. Forexample, the serotype O virus that caused the outbreakin Europe in 2001, the so-called Pan-Asia O virus, has

replaced many other viruses in the Middle East and Asia.It was first identified in northern India in 1990 andspread westward into Saudi Arabia in 1994, throughoutthe Near East and into Europe (Turkish Thrace,Bulgaria, and Greece) in 1996. In addition, the A-Iran05-strain has similarly become the predominant strain inwestern Asia, the Middle East, and Turkey. The SATstrains are restricted to sub-Saharan Africa, althoughincidental outbreaks have occurred in the Middle East(see Table 1).

Within each serotype, considerable genetic and anti-genic variation occurs, notably within the three SATserotypes and serotype A, which can explain the insuffi-cient cross-protection by vaccines when the vaccine strainand the circulating viruses differ significantly from eachother. This variation is due to the high rate of mutation,well known to occur with single-stranded RNA viruses.Within serotypes, differences in infectivity, virulence, andpathogenicity occur. Although generally one strain willinfect ruminants as well as pigs, particular viruses belong-ing to serotype O have shown species adaptation, such asthe O Taiwan isolate that infected pigs but not cattle in the1997 outbreak in Taiwan. Molecular epidemiology, basedon sequencing data from a genomic region encoding theVP1 protein, has contributed significantly to the classifica-tion of FMDVs. It has been shown that FMDV showsmarked variation in time and between regions within ser-otypes. FMDVs are therefore also classified into separategenotypes or ‘topotypes’, reflecting the occurrence of a

genotype within a given geographic region. The SATserotypes show significantly more variation than theother serotypes, probably due to the involvement of thewildlife host and long-term carrier status. It has beenshown that genetic and antigenic variants are generatedduring long-term persistence in African buffalo (Syncerus caffer ). Serotype A also demonstrates marked variation, butAsia-1 seems to be the most conserved serotype (Figure 1).Such variations have an impact on vaccine strain develop-ment (see section ‘Control Measures’).

Hosts and Epidemiological Features

All cloven hoofed animals are susceptible to FMDVinfection, and over 70 species have been found to beinfected. Infected animals start excreting the virus inexcreta and secreta during the incubation period beforethe onset of visible clinical signs. Milk may containinfectious virus up to 4 days before the onset of clinicalsigns. All excretions and secretions contain infectiousvirus and consequently may be a source of infection forother animals until the onset of neutralizing antibodies,

Table 1 Serotypes of foot-and-mouth disease and their geographic distribution

FMDV serotypes Geographic distribution

A (Ardennes) South America, southeastern Europe, Africa, Southeast Asia, the Middle East

O ( Oise) South America, southeastern Europe a, Africa, Southeast Asia, the Middle East

C b South America, Africa, Asia

Asia-1 The Middle East, the Far East, Southeast Asia

SAT-1 (South African Territories) Sub-Saharan Africa

SAT-2 Sub-Saharan Africa

SAT-3 Sub-Saharan Africa

a2001 outbreak in Europe caused by the Pan-Asia serotype O strain. The outbreak started in pigs, and later on was predominantly

found in cattle, sheep, and goats. bPossibly extinct.

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usually between 3 and 5 days after infection, when adecrease in virus excretion relates to a concomitant risein antibody titers.

The most common way of virus transmission is bydirect animal contact. Other indirect sources of transmis-sion are contaminated transport vehicles, humans, and,under very specific climatic conditions, air. Transmissionby ingestion of infected milk or meat or even throughabrasions on the skin is possible, but occurs less frequently.Cattle are highly susceptible to FMDV and can be infectedby inhalation of the virus, by contact, by ingestion of thevirus, and by contaminated semen. The incubation periodis generally shorter when the infectious dose is higher, butalso depends on the strain of the virus, the susceptibilityand breed of the host, and the route of infection. Forinstance, after (artificial) intradermolingual inoculation of virus in the course of FMD vaccine control experiments,animals may show clinical signs as soon as 1 day afterinoculation, whereas clinical signs may appear only after10–14 days with aerosol infection. Consequently, the incu-bation period may vary, but generally lasts 2–14 days.Cattle are most susceptible to infection by the respiratorytract (10–25 TCID50 [tissue culture infectious doses]),

whereas for infection by the oral route at least 10 000 timesas much virus is required. Because cattle have a largeinspiratory volume, they are highly susceptible to airborneinfection. There are significant differences in virus excre-tion and susceptibility among domestic livestock. Cattleexcrete a maximum of 120000 TCID50 a day, whereaspigs can excrete up to 400 million TCID50 a day, andpigs need more viruses than needed by cattle to becomeclinically infected by the respiratory route.

Milk can be infectious for about 7–9 days, starting upto 4 days before the onset of clinical signs, and could be a

source of transmission when infected milk is fed to pigletsor calves. In one study, virus could be observed in milk23 days postinfection while viremia lasted only 4–6 days.However, the infectious dose may not be sufficient toinfect other animals via ingestion. Aerosolized infectedmilk generated during bulk handling procedures couldalso be a source of infection and, since the minimuminfectious dose by the respiratory route is lower as com-pared to the oral route for both cattle and pigs, may evenbe a more important source. However, studies of recentoutbreaks have shown that transmission of FMDV bymilk or dairy products occurs relatively rarely.

The duration of virus excretion depends on the host andvaries between different secreta and excreta. The highestamounts of virus occur in lesion material such as vesicularfluid and epithelium from the vesicles, and in saliva. Incattle milk, virus titers can reach up to log10 10

5–6 TCID50.Importantly, pigs excrete up to 3000 times more infectiousvirus in the air than cattle.

Sheep and goats show less severe clinical signs, andthis, often subclinical infection, makes them a threat fortransmission of FMDV in many regions of the world.Cattle and pigs mostly show overt signs of infection,

which are easy to identify.A particular phenomenon is the occurrence of carrier

animals post-FMDV infection in the absence of circulat-ing virus and the presence of neutralizing antibodies. Ananimal is considered a carrier when the virus can beintermittently recovered from the esophago-pharyngealfluid more than 28 days after infection. In a small propor-tion of animals, FMDV can be recovered from thesethroat scrapings up to 3.5 years in cattle and up to9 months in sheep after infection. It is estimated that50–70% of the cattle may become carriers soon after an

Figure 1 Several international organizations such as the OIE and Food and Agriculture Organisation (FAO) together with the WRL for

FMDhave divided FMDworldwide into virus pools as a first step in globalcontrol. Each pool contains similar serotypesand topotypesto

assist with decisions regarding vaccines that could be used in controlling infection. The map represents a rough estimation of the

geographic distribution and the serotypes included in each pool. Artwork by Frank Filippi.

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outbreak with a sharp decrease over time. The Africanbuffalo is the natural reservoir of FMDV in sub-SaharanAfrica, and can probably harbor FMDV lifelong. There isno firm evidence yet that pigs can become carriers,although it has recently been described that viral RNAwas detected in sera from infected pigs several monthsafter infection; this finding still needs to be confirmed.Importantly, vaccinated animals can also become carriers.However, because the amount of virus in carrier animalsis relatively low and seems to be confined to the light zoneof the germinal centers in cattle, the risk of virus trans-mission by carriers is low as compared to that during theacute phase of infection. The occurrence of carrier ani-mals is of special concern in eradication programs.

FMD is not a zoonosis and seroconversion has beendetected only in a few individuals with high exposure tothe virus.

Clinical Signs in Various DomesticSpecies

Clinical signs in dairy cattle usually start with fever,depression, a reduced appetite, and in lactating animalsa sudden drop in milk yield that could be significant.Disease can range from a subclinical infection to overtclinical signs. Affected animals salivate, and vesicle for-mation can be observed in the mouth and on the dorsalsurface of the tongue. Vesicles may also appear on theteats and the udder, but are usually smaller than thevesicles in the mouth, and could result in mastitis andbecome infected with bacteria (Figures 2–4). Cattle maybecome lame due to vesicles appearing in the interdigitalspace and coronary bands. Feet lesions usually take longerto heal, and bacterial infection often aggravates the

symptoms. Based on the appearance of lesions in themouth, experienced clinicians can estimate the age of the lesions to help determine the start of the infectionand backward tracing during more widespread outbreaks.Young animals such as calves and piglets may suddenlydie as a result of an acute myocarditis, called tiger heartdisease based on the striped appearance of the heartmuscle, and this may be the only clinical sign. Mortalityin adult animals is usually low, but morbidity may reach100%. The differential diagnosis is indicated in Table 2.

Sheep and goats differ from cattle in that their clinicalsigns are much less apparent. Lameness is usually the

most predominant clinical sign, but in a sheep flock onlya small number of animals may show clinical signs.Lactating animals may show a sudden drop in milkyield, with pyrexia.

Pigs become recumbent, huddle together, and arereluctant to move. When forced to move, they mayshow lameness. In adult sows, FMD could go unnoticed,and in young piglets mortality may be the only sign of infection. Vesicles in the mouth and on the nose, and onthe feet and the elbows may be pronounced when theanimals are kept on hard surfaces, while vesicles may alsoform on the teats of lactating sows. Vesicles will easilyrupture. The lesions in pigs are indistinguishable fromswine vesicular disease, caused by the closely relatedswine vesicular disease virus.

Laboratory Diagnosis of Foot-and-MouthDisease

The World Organisation for Animal Health (OIE) hasissued a manual with standards for diagnostic tests andvaccines, which provides detailed descriptions of tests for

Figure 2 Infected cattle salivate due to the presence of lesions

in the mouth. Salivation can be pronounced. Photo courtesy

Peter Geertsma.

Figure 3 Feet lesions occur in the interdigital space and take

longer to heal than lesions in the mouth. Photo courtesy Peter

Geertsma.


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the purpose of international trade. In a number of coun-tries where the disease is exotic, high-security FMDVlaboratories maintained under biosecurity level 3 stan-dards have been constructed, which are especiallyequipped to handle samples suspected of carryingFMDV without the risk of further disseminating the dis-ease. In most countries where FMD does not occur, it is anotifiable disease included in the legislation and onlygovernment veterinarians or accredited personnel areallowed to collect and submit diagnostic samples. Greatcare should be taken to ensure that these people do notspread the infection between farms. If a high-security

laboratory is not regionally available, samples can besubmitted to the OIE World Reference Laboratory(WRL) for FMDV in Pirbright, UK.

The virus can be identified by virus isolation, anenzyme-linked immunosorbent assay (ELISA) that detectsthe viral antigen, or reverse transcription-polymerasechain reaction (RT-PCR). Virus isolation on specific celllines or primary cells is very sensitive but requires a fewdays before the final result is available. This delay could becrucial when dealing with such a highly infectious disease.The antigen ELISA provides results much more rapidly

(within a few hours) and can distinguish between thevarious serotypes. RT-PCR is a highly sensitive assaythat similarly can deliver results within hours, and tests todistinguish between the serotypes are available. In addi-tion, the RT-PCR products obtained from the structuralgene regions can be sequenced and used to determine themolecular epidemiology of FMDV isolates and to establishthe relationship with other viruses and possibly trace theorigin of an outbreak. Should vaccination be a controloption, knowledge about the serotype is essential.

The gold standard antibody test for detecting antibo-dies is the virus neutralization test, which relies on live

cell culture and virus, but is not conducive for high-throughput testing. ELISAs such as the solid phase com-petition ELISA have been developed and are widely useddue to their ease and the fact that no live cells or live virusis needed. All these assays measure antibodies to thestructural proteins of the virus. Some NS proteins aresufficiently immunogenic to allow antibody detectionafter infection, but are not detectable in modern purifiedFMD vaccines and rarely induce antibody formation afterone or more vaccinations. In addition, NS proteins arerelatively conserved among the serotypes, and one test

Table 2 Differential diagnosis of foot-and-mouth disease

Cattle Sheep Pigs

Infectious bovine rhinotracheitis Contagious ecthyma (orf) Swine vesicular diseaseBovine viral diarrhea Blue tongue Vesicular exanthema of pigs

Malignant catarrhal fever Foot rot

Stomatitis papulosa

Rinderpest

Vesicular stomatitis

Calf diphtheria

Pseudocowpox

Bovine herpes mammillitis

Foul in the foot and foot rot

Lumpy skin disease

Orf (contagious pustular dermatitis)

Figure 4 Lesions occur on the gums (a) and on the tongue (b) of infected animals. Photo courtesy Peter Geertsma.


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can therefore be used regardless of the serotype, in con-trast to the other serological assays where reagents have tobe serotype-specific. This allowed the development of differentiating ELISAs and immunoblot assays based onNS proteins, and especially 3ABC-specific antibodydetection, to distinguish infected animals from vaccinatedanimals. The current tests are not sufficiently sensitive todetect single infected animals and can be used only on aherd basis. In addition, there is evidence that the NSproteins of the SAT-type viruses differ to such an extentfrom the other serotypes that commercial assays may notbe sufficiently sensitive to use when those serotypesoccur. It is expected that these tests will increasingly beused in eradication and control programs of FMDV.

Although assays for detecting antibodies to FMDV andviral genomic material detection using RT-PCR in cattleand sheep milk have been described, these are not widelyused in surveillance and control programs. However, ithas been indicated that especially the sensitive RT-PCR

could detect one infected animal in a herd when testingpooled milk.

A particular problem in FMDV control is the occur-rence of many antigenically different variants. Thisrequires that reagents for both virus and antibody testsbe regularly updated to ensure that they are suitable todetect antibodies against the circulating serotypes andthat they are able to detect newly emerging FMDVisolates.

Diagnosis of carrier animals is challenging as theseanimals are seropositive to the structural proteins andvirus, and viral RNA can only be intermittently detectedin the esophago-pharyngeal fluid and cellular material,collected with a probang cup especially designed for thispurpose. However, these animals may be negative forantibodies to the NS proteins and would therefore not bedetected as having been infected. Newer assays looking forsecretory IgA may in future assist to detect carrier animals.

Economy

Outbreaks of FMD in free areas are usually associatedwith significant economic losses. Direct losses are due tomortality and decreased production. Lactating animals

could lose production in one or more quarters perma-nently. Indirect losses are due to trade restrictions onanimals and animal products and the costs of controlmeasures such as stamping out, compensation of farmers,vaccination, cleaning, and disinfection, as well as of move-ment control. When large numbers of animals aredestroyed, loss of high-performing animals and difficul-ties in repopulation may also account for severe economicdamage. In addition, reduced draft power may lead tofood insecurity if fields cannot be plowed during thegrowth season in developing countries. Endemic FMD

usually precludes countries from exporting animals andanimal products and could further impact the alreadystrained economies.

During FMD outbreaks that affect the dairy indus-try, milk from infected areas will be excluded fromconsumption or production of milk products, unless ithas been treated appropriately to inactivate FMDV. Inthe European Union, directives have been adopted formilk and dairy products (85/511/EU and 92/46/EU)that contain prescribed treatments for these products.FMDV present in milk and dairy products is particu-larly resistant to inactivation, and even in vitro assessment of the absence of infectious FMDV doesnot exclude that cattle may become infected afterinoculation. Despite this potential risk, the risk of transmission of FMDV by infected milk and dairy pro-ducts under natural conditions and after treatmentssuch as pasteurization may be considered low, becauselarge amounts of FMDV-containing milk must be

ingested by susceptible animals to establish an infectiondue to the high infectious dose needed to establishinfection via the oral route. Production processes con-taining specific heat treatment, or pasteurizationfollowed by acid treatment, decrease the risk of FMDV transmission to practically zero, provided theprocess is properly implemented. Thus, the highest riskof FMDV-containing milk will most likely be the directfeeding of the milk to susceptible animals, or spilling oraerosol formation during handling of the milk so thatthe disease can be transmitted by contact or by aero-solized virus.

The costs of outbreaks vary greatly depending onthe species affected, density of the animal population,production systems, and trade implications, and no gen-eral estimate can be given. Widespread outbreaks inpreviously free regions or countries could easily lead todamages of several hundreds of millions of dollars. Forinstance, direct economic losses due to the 1997 outbreakin Taipei, Taiwan, were estimated at US$400 million,with indirect losses estimated at US$3650 million.During the 2001 FMD outbreaks in Europe, theEuropean Commission authorized E400 million of advance payments to member states to reimburse com-pensation paid to farmers for animals slaughtered.

Advances of E355 million were allocated to the UnitedKingdom, E39 million to the Netherlands, E3.3 million toFrance, and E2.7 million to Ireland.

Costs of controlling the disease in areas where vacci-nation is routinely used or where infected zones occur canalso be significant. In southern Africa, a number of coun-tries use game fences and limited vaccination of livestockat risk to prevent contact and disease transmissionbetween infected buffaloes and domestic animals. Strictmovement control of animals and products prevents theinfection from reaching the disease-free zones. All these


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measures are costly, but a study performed in Zimbabweindicated that the benefits from having access to exportmarkets in the European Union outweighed the signifi-cant costs for control.

Control Measures

Control measures generally differ between endemic andfree areas. Whereas free areas may take significant actionto eradicate the disease should it be accidentally intro-duced, endemic countries may rely on limited vaccinationand movement control to protect certain areas, zones, orindustries. In many endemic countries, no actions aretaken to control the disease as other priorities competewith the limited funding.

For effective control of FMDV, the number of farms orherds infected by one newly infected farm or herd (thereproduction ratio, R ) must be significantly below 1 after

implementation of control measures to assist with eradi-cation. However, under natural conditions, the basicreproduction ratio (R 0) for FMDV is significantly higherthan 1, based on observations that major outbreaks usuallyfollow single introductions of FMDV in susceptible popu-lations. The spread of infection depends on variousparameters, such as population size and contacts betweenfarms. In addition, little is known about the impact of herdsize, contact structure, and control measures such as vac-cination on the transmission of FMDV, and consequentlyon the R value. Evidently, control measures must beimposed aiming to reduce the R value, but these mayvary for different regions where dissimilarities exist inanimal population densities, production systems, andavailability and suitability of vaccines and destructionplants.

To assist in defining control measures that are effec-tive in reducing transmission, a thorough risk assessmentfor transmission of FMDV in the animal population at riskduring an outbreak must be performed. The time betweenintroduction of the virus and its identification, theso-called high-risk period (HRP), must be as short aspossible. A long HRP allows the virus to spread and infectmultiple farms, which significantly increases the magni-tude of the outbreak and the necessary control measures.

Therefore, in FMDV-free regions, an adequate surveil-lance system must be operational, aimed at reducing theHRP. This again requires risk assessments, aimed at iden-tification, quantification, and subsequent reduction of riskfactors. For the Netherlands, it has been estimated that70% of the potential contagious animal disease introduc-tion could be attributed to import of infected animals orcontaminated transport vehicles, based on conjoint ana-lysis of expert opinions. Studies of recent outbreaks ineastern European countries and Italy strongly suggest thatanimal movements – sometimes illegal – transport

vehicles, and infected animal products have caused sev-eral outbreaks. Control measures must be targeted atmitigating these risk factors. Contingency plans are fre-quently legally required, but these must be regularlyupdated and practiced.

Important elements of control measures are stampingout of infected herds, movement control, and vaccination.The disease should be controlled in pigs first, becausethey excrete by far the maximum amounts of the virus,followed by cattle. Should the decision be to slaughterout, special emphasis must be given to the hygiene pro-cedures involved in killing, removal, and destruction of animals, as the virus may easily be spread during theseprocedures. Therefore, disinfection must immediatelyfollow killing of the animals to prevent virus escape byventilation, people, or secretions. Movement controlshould prevent the spread of FMDV by infected animals,their products, transport vehicles, or people. In Europe, aprotection zone directly around an outbreak and an outer

surveillance zone are established after an FMDV out-break, according to the EU directives (EU directive85/511). Border inspection posts or buffer zones mayalso be useful, depending on the geographic situation. Insome African countries, fences are used to separateFMDV-carrying buffaloes from disease-free cattle.

Vaccination is an important part of FMDV control.Vaccines against FMDV are still manufactured accordingto classical methods where large volumes are cultured onbaby hamster kidney cells in suspension followed byinactivation using aziridines, purification, and concentra-tion. For ruminants, both aluminum-adjuvanted vaccinesand oil emulsion vaccines are available, while only oilemulsion vaccines are suitable for pigs. During emergen-cies in free zones and countries, high-potency vaccinesare administered that should provide a rapid immuneresponse. In contrast, during routine vaccination, pay-loads are generally lower and the duration of immunityis important. The duration of immunity is short-lived andthe aluminum-based adjuvants need to be administeredevery 4–6 months while annual vaccination should sufficewhen using oil-adjuvanted vaccines. Vaccine strainsshould be chosen based on the serotype and its protectivecapacity against the virus causing the outbreak. The latteris determined in cross-neutralization assays, where the R

value is an indication of the antigenic relationshipbetween a virus and a vaccine strain. In general, it isaccepted that R values of 0.4–1.0 indicate a sufficientrelationship that would confer protection. The geneticrelationships between viruses need to be used with care,as changes in critical regions of the gene encoding thestructural proteins that make the virus capsid could leadto significant antigenic differences.

Although it is known that some highly potent vaccinesare able to prevent transmission under experimental con-ditions, little is known of the rate by which transmission is


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prevented by emergency vaccination in an outbreak indensely populated areas. Most vaccine studies are basedon prevention of clinical disease, in agreement with theEuropean Pharmacopoeia and OIE Manual of DiagnosticTests and Vaccines, which prescribes PD50 challenge infec-tion experiments in the natural host. Because the periodbefore a country can obtain disease freedom from the OIE is

extended if vaccination is used in previously free zones, thedecision to start with vaccination may be postponed untilother measures have failed to stop the outbreak.

Due to the inadequacies of the current vaccines, sev-eral attempts have been made to improve the vaccineusing recombinant technologies. However, these are notyet commercially available and will most probably be tooexpensive for routine applications.

Surveillance of FMDV is aimed at reducing theHRP (high-risk period). Because FMDV has a shortincubation period and normally causes overt disease,it will easily be recognized in cattle. Thus, if regular

clinical inspection is guaranteed, serological surveil-lance for FMDV does not seem cost-effective in theface of an outbreak. However, most countries have theirown emergency plans that describe the actions needed.Awareness among farmers and veterinary practitionersis critical for a quick identification of FDMV. If clinicalinspection of animals cannot be performed regularly,serological surveys may be necessary to identify con-valescent or carrier animals, such as in regions wherelittle or no veterinary control is in place.

To aid in the decision process for control of FMDV,management support systems have been developed, andthese may prove useful in the decision-making process in

the emergency situation of an outbreak.For online references, see Table 3, which contains a

set of relevant websites.

See also: Contaminants of Milk and Dairy Products:

Environmental Contaminants. Hazard Analysis and

Critical Control Points: HACCP Total Quality

Management and Dairy Herd Health. Husbandry of Dairy

Animals: Goat: Health Management; Sheep: Health

Management. Office of International Epizooties:

Mission, Organization and Animal Health Code. Policy

Schemes and Trade in Dairy Products: Trade in Milk

and Dairy Products, International Standards: World Trade

Organization. Risk Analysis.

Further Reading

Cox SJ and Barnett PV (2009) Experimental evaluation of foot-and-

mouth disease vaccines for emergency use in ruminants and pigs:

A review. Veterinary Research 40(3): 13. Epub 2008 December 2.

Donaldson AI (1997) Risks of spreading foot andmouth disease through

milk and dairy products. Revue Scientifique et Technique

16(1): 117–124.

Grubman MJ and Baxt B (2004) Foot-and-mouth disease. Clinical

Microbiology Reviews 17(2): 465–493.

Kitching RP (1998) A recent history of foot-and-mouth disease. Journal

of Comparative Pathology 118: 89–108.

Knowles NJ, Samuel AR, Davies PR, Kitching RP, and Donaldson AI

(2001) Outbreak of foot-and-mouth disease virus serotype O in the UK

caused by a pandemic strain. The Veterinary Record 148: 258–260.

Parida S (2009) Vaccination against foot-and-mouth disease virus:

Strategies and effectiveness. Expert Review of Vaccines

8(3): 347–365.

Paton DJ, Valarcher JF, Bergmann I, et al. (2005) Selection of foot and

mouth disease vaccine strains – a review. Revue Scientifique et

Technique 24(3): 981–993.

Rueckert R (1996) Picornaviridae: The viruses and their replication.

In: Fields BN, Knipe DM, and Howley PM (eds.) Fields Virology , 3rd

edn., pp. 609–654. Philadelphia, PA: Lippincott-Raven.

Rweyemamu MM and Leforban Y (1999) Foot-and-mouth disease and

international development. Advances in Virus Research 53: 111–126.

Rweyemamu M, Roeder P, Mackay D, et al. (2008) Epidemiological

patterns of foot-and-mouth disease worldwide. Transboundary and

Emerging Diseases 55(1): 57–72.

Ryan E, Mackay D, and Donaldson A (2008) Foot-and-mouth disease

virus concentrations in products of animal origin. Transboundary and

Emerging Diseases 55(2): 89–98.

OIE (2008) Foot and mouth disease. The Manual of Diagnostic Tests and Vaccines for Terrestrial Animals, Ch. 2.1.5. http://www.oie.int/

eng/normes/mmanual/2008/pdf/2.01.05_FMD.pdf

OIE (2009) Foot and mouth disease. Terrestrial Animal Health Code,

Ch. 8.5. http://www.oie.int/eng/normes/mcode/en_chapitre_1.8.5.htm

Thomson GR and Bastos ADS (2004) Foot-and-mouth disease.

In: Coetzer JAW and Tustin RC (eds.) Infectious Diseases of

Livestock , pp. 1324–1365. Cape Town, South Africa: Oxford

University Press.

Tomasula PM and Konstance RP (2004) The survival of foot-and-mouth

disease virus in raw and pasteurized milk and milk products. Journal

of Dairy Science 87(4): 1115–1121.

Table 3 Websites for further information on foot-and-mouth disease

Website URL

OIE www.oie.int

FAO www.fao.org

World Reference Laboratory for FMDV www.iah.bbsrc.ac.uk

European Union legislation europa.eu.int/eur-lex

European commission for the control of FMDV www.fao.org/ag/againinfo/commissions/en/enfmd/enfmd.htmlPan American Foot-and-Mouth Disease Center (PANAFTOSA) www.panaftosa.org.br

Picornavirus home page www.iah.bbsrc.ac.uk/virus/Picornaviridae/index.html

http://www.oie.int/eng/normes/mmanual/2008/pdf/2.01.05_FMD.pdfhttp://www.oie.int/eng/normes/mmanual/2008/pdf/2.01.05_FMD.pdfhttp://www.oie.int/eng/normes/mmanual/2008/pdf/2.01.05_FMD.pdfhttp://www.oie.int/eng/normes/mcode/en_chapitre_1.8.5.htmhttp://www.oie.int/eng/normes/mcode/en_chapitre_1.8.5.htmhttp://www.oie.int/eng/normes/mcode/en_chapitre_1.8.5.htmhttp://www.oie.int/eng/normes/mmanual/2008/pdf/2.01.05_FMD.pdfhttp://www.oie.int/eng/normes/mmanual/2008/pdf/2.01.05_FMD.pdf

Documents

AFTOSA[1]