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    Reporting of suspect cases offoot-and-mouth-disease during the 2001

    epidemic in the UK, and the herd sensitivityand herd specificity of clinical diagnosis

    Melissa McLaws a,1, Carl Ribble a,*, Craig Stephen b,Bruce McNab c, Pablo Romero Barrios a,1

    aDepartment of Population Medicine, University of Guelph, Guelph, Ont. N1G 2W1, Canadab Centre for Coastal Health, 900 5th Street, Nanaimo, BC V9R 5S5, Canada

    c Office of the Chief Veterinarian for Ontario, Ontario Ministry of Agriculture, Food and Rural Affairs,

    1 Stone Rd., W., Guelph, Ont. N1G 4Y2, Canada

    Received 25 August 2005; received in revised form 17 July 2006; accepted 17 September 2006

    Abstract

    We described the clinical diagnostic process utilized during the 2001 epidemic of foot-and-

    mouth-disease in the United Kingdom (UK), and considered it as a series of diagnostic tests. Premises

    were classified according to these diagnostic-test results and actual disease status, determined by the

    reference test, which in this case was one or more internationally accepted laboratory tests. The herd-

    level sensitivity (HSe) and herd-level specificity (HSp) of the clinical diagnostic process were

    calculated directly, relative to these internationally accepted reference tests. In this process, the first

    diagnostic test was routine monitoring, which resulted in the identification of suspect cases based

    solely on the clinical observations of farmers or veterinarians. 6762 suspect cases were identified, andthe test had a HSe of 97.6% (95% C.I.: 96.7, 98.3) and a HSp of 95.2% (95% C.I.: 95.0, 95.3). Suspect

    cases were then subject to the second diagnostic test, termed declaration, which consisted of a

    review of a description of the clinical signs by government veterinarians. Premises that tested positive

    became clinical cases. The HSe of this test was 97.1% (95% C.I.: 96.2, 97.9), and the HSp was

    www.elsevier.com/locate/prevetmed

    Preventive Veterinary Medicine 78 (2007) 1223

    * Corresponding author at: Faculty of Veterinary Medicine, University of Calgary, HS G 380, 3330 Hospital

    Drive NW, Calgary, Alta. T2N 4N1, Canada. Tel.: +1 403 220 4008; fax: +1 403 210 3919.

    E-mail address: [email protected] (C. Ribble).1 Present address: Alberta Agriculture, Food and Rural Development, O.S. Longman Building, 6909 116 St,

    Edmonton, Alta. T6H 4P2, Canada.

    0167-5877/$ see front matter # 2006 Elsevier B.V. All rights reserved.

    doi:10.1016/j.prevetmed.2006.09.001

    mailto:[email protected]://dx.doi.org/10.1016/j.prevetmed.2006.09.001http://dx.doi.org/10.1016/j.prevetmed.2006.09.001mailto:[email protected]
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    90.9% (95% C.I.: 90.1, 91.6). During the epidemic, these tests were combined and applied in series,

    with an overall HSe of 94.7% (95% C.I.: 93.5, 95.7) and an overall HSp of 99.6% (95% C.I.: 99.5,

    99.6). We also examined the effect of a policy shift that prohibited delaying the diagnosis pending

    laboratory testing where the animals exhibited equivocal clinical signs.# 2006 Elsevier B.V. All rights reserved.

    Keywords: Foot-and-mouth-disease; Clinical diagnosis; Clinical epidemiology; Disease surveillance; Herd

    sensitivity; Herd specificity

    1. Introduction

    Foot-and-mouth-disease (FMD) is an extremely contagious viral disease that can affect

    cloven-footed mammals. Most developed countries are officially considered free of the

    disease, a status that is very desirable for trade purposes. On 20 February 2001, however, the

    UK confirmed that FMD had been identified in an abattoir in England. This was the beginning

    ofalargeepidemicthatresultedin2026premises(plusfourinNorthernIreland)beingdeclared

    infected and the loss of the UKs FMD-free without vaccination status for 11 months, until

    restored by the World Organisation for Animal Health (OIE) on 22 January 2002.

    Contingency plans to control an epidemic of FMD were in place in the UK prior to the

    2001 outbreak. The plans were sufficient to cope with up to 10 simultaneous infected

    premises (outbreaks), which was the scale of epidemics experienced in Europe in the

    previous three decades. However, the 2001 epidemic was much larger than anticipated, and

    rapidly surpassed the scope of these contingency plans (Scudamore and Harris, 2002).Rapid detection of infection is critical to the control of a contagious pathogen such as

    the FMD virus. The strategy in place prior to the epidemic called for laboratory testing of

    the first case of suspected FMD; thereafter, premises could be declared infected on the basis

    of clinical signs alone. On premises where the clinical picture was equivocal, the plans

    stipulated that diagnosis should await laboratory verification, which can take up to 5 days

    (Anderson, 2002). The need for rapid diagnosis during this epidemic led to a policy shift to

    declaration of FMD based solely on clinical findings after 22 March 2001. Slaughter on

    suspicion of FMD was used for equivocal cases (Anderson, 2002).

    In this paper, we explored the effectiveness of the system used to detect and diagnose

    cases of FMD during the 2001 outbreak in the UK by calculating the herd-level sensitivity(HSe) and herd-level specificity (HSp) of the component tests of the clinical diagnostic

    process. To investigate the effect of permitting laboratory testing prior to diagnosis, we

    compared the diagnostic test parameters before and after the policy changed on 22 March

    2001. We also considered the implications and usefulness of this analysis to the

    management of future epidemics.

    2. Materials and methods

    2.1. The diagnostic process during the course of the epidemic

    Premises, as opposed to individual animals, are usually the unit of analysis in FMD

    investigations because the virus is so highly contagious. Premises that contained FMD-

    M. McLaws et al. / Preventive Veterinary Medicine 78 (2007) 1223 13

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    susceptible livestock in Great Britain in 2001 can be divided into four categories regarding

    their FMD status: (1) disease never suspected, (2) suspect case, (3) clinical case, and (4)

    laboratory-verified case. The latter three categories could be considered the result of a

    positive diagnostic test (Fig. 1). We avoid the commonly used terms infected premisesand confirmation of disease in this paper because they led to confusion when describing

    the true implication of the different diagnostic steps.

    The first diagnostic test was routine monitoring (RM) of FMD-susceptible stock,

    performed by farmers, veterinarians and others that checked stock for clinical signs of

    FMD. Under the Foot-And-Mouth-Disease Order of 1983, FMD is a notifiable disease in

    the UK and all suspect cases must be reported to the national veterinary authorities

    (DEFRA, 2002).

    In response to every report of suspected FMD during the 2001 epidemic, the premises

    was visited by a government veterinarian from the nearest Local Disease Control Centre. If

    the report had originated from a government veterinarian, the same veterinarian continued

    the investigation. Regardless of the degree of suspicion of the attending veterinarian, the

    clinical and epidemiological findings were relayed by telephone to a veterinarian at the

    National Disease Control Centre in London. The veterinarian in London recorded the

    findings on a standard form and then consulted with one of three senior veterinarians. On

    the basis of the contents of the telephone report, the senior veterinarian decided whether or

    not to declare the suspect premises a clinical case; there was no official case definition

    (Wilesmith, personal communication). All suspect cases were subject to this second

    diagnostic test, which we refer to as declaration in the remainder of the paper.

    M. McLaws et al. / Preventive Veterinary Medicine 78 (2007) 122314

    Fig. 1. Outline of the diagnostic process used to detect cases of FMD on the basis of clinical signs during the

    epidemic in the UK in 2001.

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    The procedure described above was followed throughout the epidemic, except for 2

    weeks in April when the veterinarians answering the telephone in London were given

    authority to declare premises clinical cases of FMD without consulting a senior

    veterinarian (Wilesmith, personal communication). Prior to 22 March 2001, the diagnosisof FMD could be delayed pending laboratory verification for suspect cases when the

    clinical signs were ambiguous. After 22 March 2001, it was not permitted to await

    laboratory results. Regardless of the eventual laboratory results, all clinical cases of disease

    were subject to infection-control measures: all FMD-susceptible livestock on these

    premises were killed, as were those on contiguous premises and premises judged to be at

    increased risk of FMD through links with a clinical case, such as common workers.

    Approximately 85% of clinical cases had samples submitted for laboratory verification,

    the third test. The decision as to whether or not samples should be submitted was based

    primarily on available laboratory capacity at the time. Internationally agreed laboratory

    procedures, as described in the OIE Manual of Standards for Diagnostic Tests and Vaccines

    (Kitching et al., 2000), were used during the epidemic (Royal Society of London, 2002;

    DEFRA, 2002). An antigen-detection enzyme-linked immunosorbent assay (ELISA) was

    immediately performed, which takes about 3 h to complete. Samples negative to the

    ELISA were subjected to the more sensitive virus-isolation test, which can take up to 4 days

    to complete (Royal Society of London, 2002). A case was deemed laboratory-positive if

    either the ELISA or the virus-isolation test was positive, and laboratory-negative only if

    both tests yielded negative results.

    Some laboratory-confirmed cases were identified by the discovery of antibodies to FMD

    virus in blood submitted as part of routine procedures. Cases detected in this mannerrepresented the failure of RM to detect FMD, because the clinical phase of disease had

    passed without any suspicion being reported. Because clinical signs are much more obvious

    in cattle than small ruminants, only the latter were subject to routine serological testing.

    A full description of the protocol for identifying premises subjected to serological

    testing may be found in the report submitted to the OIE following the outbreak (DEFRA,

    2002). Briefly, all premises with sheep and/or goats within a 3-km radius around each

    outbreak were tested prior to the lifting of restrictions. A random sample of premises within

    a 310-km radius around each outbreak were tested, using a protocol able to detect a 2%

    prevalence of seropositive flocks of sheep and/or goats with 95% confidence. On each of

    the selected premises, the serological sampling was designed to detect a 5% prevalence ofseropositive sheep and/or goats with 95% confidence in each management group of small

    ruminants. Additional sero-surveillance to ensure freedom from FMD was conducted in

    counties with many cases of FMD, such that >95% of flocks in these counties were tested.

    Furthermore, throughout the UK, sheep and goats had blood taken for serological testing:

    (1) during pre-emptive culls of animals at high risk for FMD, (2) in conjunction with

    various epidemiological investigations conducted in areas considered to be at high risk of

    containing infected animals, and in areas where the FMD status of animals was unknown,

    and (3) as part of pre-movement inspection protocols.

    The competitive solid-phase ELISA (csp ELISA) test was the serological-screening test;

    blood samples giving an inconclusive result were resolved by the virus-neutralisation test(VNT) (DEFRA, 2002). The decision to designate a premises as infected with FMD or not on

    the basis of the serological-test results depended on the number of seropositive animals, the

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    location of the premises, any epidemiological links to other FMD cases, and if FMD virus

    was isolated from a sample of esophagealpharyngeal fluid at the time of slaughter.

    2.2. Herd-sensitivity and herd-specificity calculations

    Because a true gold standard is rarely available (Dohoo et al., 2003; pp. 9394),

    sensitivity and specificity are usually estimated in relation to an accepted reference test.

    Therefore, when referring to the results of the reference test, the terms reference-positive

    and reference-negative are preferable to true-positive and true-negative or disease-

    positive and disease-negative, and are used in this paper.

    The entire population susceptible to FMD present in Great Britain at the time of the

    epidemic was used in the calculations. No single reference test was used in our

    calculations. Rather, the reference state of premises (reference-positive or reference-

    negative) was inferred from the reported laboratory results, as determined by one or more

    of several internationally accepted OIE-prescribed tests: virus isolation, an antigen-

    detecting ELISA, an antibody-detecting ELISA, and virus neutralisation.

    Each agricultural holding (including livestock markets, abattoirs, and farms) in the UK

    is assigned a unique identifier, termed a county-parish-holding (CPH) number. For

    suspect cases that were notdeclared clinical cases, the date of report and the CPH number

    were obtained from the Department for Environment, Food and Rural Affairs Disease

    Control System. This database was created during the outbreak to manage the epidemic.

    For each clinical case, the CPH number, date of report, origin of report (to determine

    whether the case was discovered by sero-surveillance or as a clinical case) and laboratoryresults were obtained from the database developed by the epidemiology team at the

    National Disease Control Centre during the outbreak. Both of these databases have been

    described previously (Gibbens et al., 2001).

    The herd sensitivity and herd specificity of RM and declaration were estimated directly

    (Tables 1 and 2). We assumed that clinical cases from which samples were notsubmitted to

    the laboratory had the same distribution of laboratory results as the laboratory-tested

    premises. In other words, because (over the course of the epidemic) 76% of laboratory-

    tested clinical cases were laboratory-positive, we assumed that 76% of laboratory-untested

    M. McLaws et al. / Preventive Veterinary Medicine 78 (2007) 122316

    Table 1

    Classification of premises for estimation of herd sensitivity and herd specificity of routine-monitoring test for

    FMD during the 2001 epidemic in the UK

    Reference-positive Reference-negative

    Test-positive (reports of

    suspected FMD)

    Lab-positive clinical cases +76%

    of lab-untested clinical cases plus

    false-negative declaration testsa

    True-negative declaration

    tests plus lab-negative clinical

    cases +24% of lab-untested

    clinical cases

    Test-negative (premises never

    reporting suspected FMD)

    Cases identified by serological

    testing

    All premises with susceptible

    stock in Great Britain on which

    FMD was never suspected oridentified

    a See text for detail.

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    clinical cases were laboratory-positive and the remaining untested clinical cases were

    laboratory-negative.

    Suspected FMD was reported more than once on some premises; each report

    represented a positive routine-monitoring test. A premises may consist of either a single

    land parcel or several non-confluent land parcels owned by the same person; we considered

    that premises reported suspect disease more than once if the CPH number was repeated in

    the data. Some premises on which suspected FMD was reported more than once eventually

    became clinical cases. If FMD was actually present on these premises at the time of the

    initial report(s) of suspicion, then the first report(s) had been incorrectly declared FMD-free. Such reports were true-positive routine-monitoring tests and false-negative

    declaration tests. We assumed that FMD was present at the first report(s) if the final result

    was laboratory-positive (plus 76% of untested clinical cases that fit the criteria), and if the

    difference in time between the declaration test-negative and test-positive reports minus the

    age of oldest lesion was 3. This gave liberal allowance for the inaccuracy inherent in

    estimating the age of lesions (Gibbens et al., 2001). If there were multiple declaration test-

    negative reports associated with a premises, only those that fit the above criteria were

    considered false-negatives.

    2.3. HSe and HSp of routine monitoring

    The routine-monitoring test was positive if disease was suspected and reported to the

    authorities. The test was negative if disease was either never suspected and therefore not

    reported, or suspected but not reported; it was not possible to distinguish between these two

    possibilities. We assumed that all FMD-susceptible stock in Great Britain had RM to some

    extent, during milking, feeding, or inspection by veterinary patrols. We classified premises

    into a 2 2 table with respect to their RM and reference-test status (Table 1). The total

    number of premises in Great Britain with susceptible stock was estimated by subtracting

    the number of premises in N. Ireland with susceptible stock in 2001 (N= 26,287)

    (Department of Agriculture and Rural Development Northern Ireland, 2004) from the totalnumber of such premises in the UK (N= 134,600) (European Commission, 2003). Because

    it is theoretically possible that some FMD cases remained undetected by the sero-

    M. McLaws et al. / Preventive Veterinary Medicine 78 (2007) 1223 17

    Table 2

    Classification of premises for estimation of herd sensitivity and herd specificity of declaration of FMD at the

    National Disease Control Centre during the 2001 epidemic in the UK

    Reference-positive Reference-negativeTest-positive (declared

    clinical cases)

    Lab-positive clinical cases identified

    by routine monitoring +76%a of

    lab-untested clinical cases

    Lab-negative clinical cases +24%a

    of lab-untested clinical cases

    Test-negative (declared

    disease-free)

    Reports of suspect disease

    wrongly declared disease-freebPremises that reported suspect

    disease that were correctly

    declared free of diseaseb

    a Of premises that reported suspect FMD prior to March 22nd, 82% of lab-tested premises tested positive,

    compared to 74% of lab-tested premises that reported on or after March 22nd. The weighted overall average was

    76%. HSe and HSp calculations for these sub-groups were adjusted accordingly.b

    See text for details.

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    surveillance program, we repeated the calculations increasing the number of cases detected

    by sero-surveillance from 39 to 129. This is the number of cases that would be expected if

    the number of undetected cases was proportional to the number of untested premises. This

    is an extreme example, because the concentration of FMD cases varied widely by regionwith the most highly infected areas subjected to very extensive sero-surveillance.

    2.4. HSe and HSp of declaration

    Routine monitoring was a screening test; only premises positive to this test were subject

    to the second diagnostic test of declaration. Performing HSe and HSp calculations on this

    population is valid because this is the only population to which this test would ever be

    applied. FMD cases identified by routine sero-surveillance were not included in the

    evaluation of the declaration test, because suspect clinical disease had never been reported

    on these premises. Premises were considered declaration test positive if they were deemed

    a clinical case by the National Disease Control Centre in London. Those authorities

    referred to these cases as infected premises. Premises were otherwise considered

    declaration test negative. The classification of premises used to evaluate the declaration

    test is shown in Table 2.

    Because the policy of laboratory testing on premises where stock had equivocal clinical

    signs changed after 22 March 2001, we calculated the HSe and HSp of declaration (HSeDecand HSpDec) considering: (1) only reports prior to 22 March, (2) only reports after 22

    March, and (3) all reports. The assumed proportions of laboratory-untested clinical cases

    considered laboratory-positive and laboratory-negative were adjusted to reflect the actualproportions of the laboratory-test results in each time period.

    2.5. HSe and HSp of the clinical diagnostic process

    The routine-monitoring and declaration tests were interpreted in series. Overall,

    premises were considered test-positive only if they tested positive to both tests (i.e. were

    declared a clinical case following a report of suspected FMD). Premises were considered

    test-negative if either test had a negative result. HSe and HSp of the clinical diagnostic

    process were calculated with premises classified as follows: (1) test-positive and reference-

    positive: all laboratory-positive clinical cases (including 76% of laboratory-untestedclinical cases) detected by RM; (2) test-positive but reference-negative: clinical cases that

    were laboratory-negative (including 24% of laboratory-untested clinical cases); (3) test-

    negative but reference-positive: FMD cases detected by results of serological tests plus

    suspect cases wrongly declared FMD-free; and (4) test-negative and reference-negative: all

    premises with FMD-susceptible stock in Great Britain on which FMD was never suspected

    plus suspect cases correctly declared FMD-free.

    3. Results

    There were 6762 reports of suspected clinical FMD filed in Great Britain in 2001, on

    6182 different premises (Fig. 2). A total of 2026 premises became FMD cases. RM initially

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    detected all but 39 of these cases. The remaining 39 cases were identified subsequent to thediscovery of antibodies to FMD virus in blood from sheep or goats submitted as part of

    routine-sampling procedures.

    Samples were submitted to the Institute for Animal Health (Pirbright Laboratory) for

    laboratory confirmation of disease from 85% of clinical cases. Of all samples submitted

    from clinical cases, 76% tested positive for the FMD virus. Seventy premises had a

    negative declaration test but became clinical cases of FMD shortly afterwards, at which

    time the age of FMD lesions indicated that the first declaration test had been falsely

    negative. Samples were submitted for laboratory analysis from 55 of these 70 clinical

    cases; 34 were found to be laboratory positive and 21 laboratory negative. We assumed

    76% (11) of the untested cases were reference-test positive, and thus used a value of 45false-negative declaration tests in the calculations. No single premises had more than one

    false-negative declaration test.

    Prior to 22 March 2001, 87% of premises declared infected had samples submitted for

    laboratory confirmation. Eighty-two percent of these samples were laboratory positive.

    With the available data, it was not possible to distinguish between suspect cases that had

    been declared FMD cases on the basis of the laboratory results, and those that had samples

    submitted subsequent to being declared clinical cases.

    After 22 March 2001, when the policy changed to prohibit laboratory testing prior to

    declaration, samples were submitted to the laboratory from 84% of clinical cases, and 74%

    of these were positive. The difference in the proportion of laboratory-positive samplesbefore and after the change in policy was statistically significant (Chi-square = 9.77,

    d.f. = 1, p = 0.002).

    M. McLaws et al. / Preventive Veterinary Medicine 78 (2007) 1223 19

    Fig. 2. Breakdown of the FMD status of premises in Great Britain during the 2001 epidemic.aThese occurred on premises that had a negative declaration test but became a clinical case of FMD shortly

    afterwards, at which time the age of FMD lesions indicated that the first declaration test had been falsely negative.

    These premises, and associated laboratory testing, are also included within the 1987 clinical cases.

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    The HSe and HSp of routine monitoring, declaration and the overall clinical diagnostic

    process (i.e. RM and declaration tests applied in series) are presented in Table 3.

    Increasing the number of cases detected by sero-surveillance from 39 to 129 decreased

    the HSeRM to 92.35% (95% CI: 90.98 and 93.57%) and had no significant effect on

    the HSpRM.

    4. Discussion

    Our results suggest that the HSe and HSp of clinical diagnosis of FMD during the 2001

    epidemic in the UK were high, relative to internationally accepted reference tests. Thisindicates that, after identifying the first case in an epidemic, determination of FMD status

    based on clinical signs alone can be a fairly accurate diagnostic test. No other studies of this

    kind concerning FMD have been performed to our knowledge.

    For any surveillance program that relies heavily on farmers for detection of cases, the

    reporting of suspected disease must be actively encouraged. This might be accomplished

    by programs designed to increase awareness about the disease (e.g. media campaigns,

    veterinary visits), and also by ensuring that fair compensation is provided for infected

    stock. Both of these tactics were employed during the 2001 FMD epidemic. Another

    approach is to provide a financial incentive for all reported suspect cases (Doherr and

    Audige, 2001).Although the HSe of RM (the screening test used during this epidemic) was very high,

    39 premises were detected on the basis of seroconversion rather than clinical signs.

    Because cattle were not subject to testing as part of the sero-surveillance program, sheep or

    goats were the species affected on all of these 39 premises. Because clinical disease in

    sheep is often subtle and transient, the stock on these premises might not have exhibited

    obvious clinical signs; indeed, some might not have manifested any symptoms at all. In this

    situation, an effective awareness campaign should emphasize the inter-species variation so

    that all farmers are aware of the need for extra vigilance with small ruminants. It might be

    worthwhile to offer additional compensation for the labour that this vigilance requires.

    During this epidemic, some farmers co-grazed a few cattle with large flocks of smallruminants, on the basis that the cattle would act as sentinels for FMD infection. The

    effectiveness of this strategy during an epidemic is worthy of further investigation.

    M. McLaws et al. / Preventive Veterinary Medicine 78 (2007) 122320

    Table 3

    Herd sensitivity and herd specificity of routine monitoring, declaration and the entire clinical diagnostic process

    during the 2001 epidemic of FMD in the UK

    Sensitivity (95% CI)a

    Specificity (95% CI)a

    Routine monitoring 97.6 (96.7, 98.3) 95.2 (95.0, 95.3)

    Declaration

    Overall 97.1 (96.2, 97.9) 90.9 (90.1, 91.6)

    Suspicion reported prior to 22 March 2001 97.3 (95.1, 98.6) 93.6 (92.2, 94.9)

    Suspicion reported on or after 22 March 2001 97.1 (95.9, 98.0) 89.9 (88.9, 90.8)

    Clinical diagnostic process (both tests interpreted in series) 94.7 (93.5, 95.8) 99.6 (99.5, 99.6)

    a The confidence intervals are exact based on the binomial distribution.

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    Both the HSe and HSp of declaration were important. Less-than-perfect HSeDec resulted

    in the delayed removal of infected animals, which potentially allowed further spread of

    disease. Less than 100% HSpDec resulted in the destruction of healthy animals, with

    important economic and social consequences.The discussion between the veterinarians in the field and at the National Disease Control

    Centre was an important component of the declaration test during this epidemic. In this

    type of situation, excellent communication between the two parties is needed to achieve an

    accurate diagnosis from a remote location. Communication might be improved with the

    use of digital cameras, which would enable the remote veterinarian, or possibly an FMD

    expert, to view the lesions. To ensure that diagnostic errors are not repeated, both the

    veterinarian in the field and at headquarters should be informed of the laboratory results of

    cases with which they have been involved.

    Developing and using a formal case definition might also improve the HSe and HSp of

    the declaration test; this is worthy of further research. However, the need for a final

    diagnosis based on clinical signs might soon be eliminated by the development of pen-

    side diagnostic tests for FMD, which could be used as alternative to the declaration

    test to provide rapid diagnosis. According to a recent review, such tests have been

    developed but have not yet been adequately validated for use in the field ( Alexandersen

    et al., 2003).

    During this epidemic, the HSpDec dropped after it was prohibited to delay clinical

    diagnosis pending laboratory results on premises where stock had equivocal clinical signs.

    This suggests that the veterinarians making the diagnosis at headquarters responded to the

    change in policy by labelling some questionable cases infected, rather than using theslaughter-on-suspicion provision or risk declaring them FMD-free. The risk of false-

    positive diagnosis (as determined by the reference test) was approximately 6% prior to 22

    March 2001, and 10% after 22 March 2001. Further analysis is required to compare the

    benefits gained by increasing the speed of diagnosis (faster implementation of control

    measures that eliminate the spread of infection from FMD cases) to the losses that resulted

    from increased risk of false-positive diagnosis of FMD. The change in policy did not

    appear to affect the risk of false-negative diagnosis.

    The sensitivity and specificity of the reference laboratory tests for FMD used during the

    UK epidemic are reported to be very good under ideal conditions (Alexandersen et al.,

    2003). However, to our knowledge, the precise values for these tests have not beenpublished. Under field conditions, false-negative reference-test results might have resulted

    from inappropriate sampling (non-acute disease, poor specimen quality) or improper

    handling of the sample (contamination with disinfectant, delayed testing). This would

    effectively decrease the sensitivity of the laboratory test.

    It was necessary to make assumptions in this study. Firstly, we assumed that all premises

    containing cases of FMD in the UK in 2001 were identified, and that the remaining

    premises were truly free from FMD. This assumption is supported by the extensive sero-

    surveillance campaign carried out to prove national freedom from FMD (DEFRA, 2002).

    However, it is theoretically possible that a few, subtle dead-end cases were missed.

    These would have relatively little effect on the calculated HSeRM and essentially none onthe HSpRM. Secondly, we assumed that the submission of laboratory samples (i.e.

    submitted: yes or no) was not related to the true FMD status of the animal.

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    We might have overestimated the number of false-negative declaration tests. If the

    number of these cases were indeed overestimated, all of the HSe and HSp parameters

    would also be overestimated, except for the HSeDec, which would be underestimated.

    However, even if the actual number of false-negative declaration tests were 50% lower thanthe number used in the analysis, this would result in changes of

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    Acknowledgements

    We gratefully acknowledge the assistance of Graeme Cooke with data collection. We

    thank John Wilesmith for his comments on the manuscript. The Ontario Veterinary CollegeDVM/PhD Fellowship and a grant from the Department for Environment, Food and Rural

    Affairs (UK) provided funding for this project. The latter also supplied the data used in the

    analysis.

    References

    Alexandersen, S., Zhang, Z., Donaldson, A.I., Garland, A.J.M., 2003. The pathogenesis and diagnosis of foot-and-

    mouth disease. J. Comp. Pathol. 129, 136.

    Anderson, I., 2002. Foot and mouth disease 2001: lessons to be learned inquiry report http://213.121.214.218/fmd/documents/index.htm.

    DEFRA, 2002. Foot and mouth disease in the United Kingdom 2001: Report to the OIE. Part 1. Great Britain.

    Doherr, M.G., Audige, L., 2001. Monitoring and surveillance for rare health-related events: a review from the

    veterinary perspective. Phil. Trans. R. Soc. Lond. B 356, 10971106.

    Dohoo, I., Martin, W., Stryhn, H., 2003. Veterinary Epidemiologic Research. AVC Inc., Charlottetown, P.E.I,

    p. 706.

    European Commission, 2003. Farm structure - 1999/2000 survey. http://epp.eurostat.cec.eu.int/cache/ITY_

    OFFPUB/KS-52-03-756-3A/EN/KS-52-03-756-3A-EN.PDF.

    Gibbens, J.C., Sharpe, C.E., Wilesmith, J.W., Mansley, L.M., Michalopoulou, E., Ryan, J.B.M., Hudson, M., 2001.

    Descriptive epidemiology of the 2001 foot-and-mouth disease epidemic in Great Britain: the first five months.

    Vet. Rec. 149, 729742.

    Kitching, R.P., Barnett, P.V., Donaldson, A.I., Mackay, D.K.J., 2000. Foot and mouth disease.In: Manual ofStandards for Diagnostic Tests and Vaccines. fourth ed. OIE, Paris.

    McLaws, M., Ribble, C., Martin, S.W., Stephen, C., 2006. Factors associated with the clinical diagnosis of foot and

    mouth disease during the 2001 epidemic in the UK. Prev. Vet. Med. 77, 6581.

    Royal Society of London, 2002. Infectious Diseases in Livestock. Royal Society, London http://www.royalsoc.

    ac.uk/inquiry/index.html .

    Scudamore, J.M., Harris, D.M., 2002. Control of foot and mouth disease: lessons from the experience of the

    outbreak in Great Britain in 2001. Rev. Sci. Tech. 21, 699710.

    M. McLaws et al. / Preventive Veterinary Medicine 78 (2007) 1223 23

    http://213.121.214.218/fmd/documents/index.htmhttp://213.121.214.218/fmd/documents/index.htmhttp://epp.eurostat.cec.eu.int/cache/ITY_OFFPUB/KS-52-03-756-3A/EN/KS-52-03-756-3A-EN.PDFhttp://epp.eurostat.cec.eu.int/cache/ITY_OFFPUB/KS-52-03-756-3A/EN/KS-52-03-756-3A-EN.PDFhttp://www.royalsoc.ac.uk/inquiry/index.htmlhttp://www.royalsoc.ac.uk/inquiry/index.htmlhttp://www.royalsoc.ac.uk/inquiry/index.htmlhttp://www.royalsoc.ac.uk/inquiry/index.htmlhttp://epp.eurostat.cec.eu.int/cache/ITY_OFFPUB/KS-52-03-756-3A/EN/KS-52-03-756-3A-EN.PDFhttp://epp.eurostat.cec.eu.int/cache/ITY_OFFPUB/KS-52-03-756-3A/EN/KS-52-03-756-3A-EN.PDFhttp://213.121.214.218/fmd/documents/index.htmhttp://213.121.214.218/fmd/documents/index.htm