The Veterinary Journal

The Veterinary Journal 167 (2004) 167174 www.elsevier.com/locate/tvjl

A generic spreadsheet model of a disease epidemic with application to the rst 100 days of the 2001 outbreak of foot-and-mouth disease in the UK
I. Ap Dewi *, B. Molina-Flores, G. Edwards-Jones
School of Agricultural and Forest Sciences, University of Wales Bangor, Gwynedd, LL57 2UW, UK Accepted 31 July 2003

Abstract A generic, stochastic spreadsheet model was developed to calculate the number of cases within the rst 100 days of a propagating epidemic and with the ability to incorporate generic control measures. Foot-and-mouth disease (FMD) epidemics were simulated with a range of assumptions about the number of cases incubating the disease on day 1 and the eciency of control measures. Particularly severe epidemics resulted from scenarios with low eciency of control measures and high numbers incubating. Control measures that prevented 0.8 of cases from resulting in new cases were able to reduce substantially the cumulative number of cases. The results of various scenarios using the model were compared to the number of cases of FMD in the rst 100 days of the 2001 outbreak in the UK, with specic reference to cases in Cumbria and Anglesey. Potential practical and educational applications of the model are discussed. 2003 Elsevier Ltd. All rights reserved.
Keywords: Epidemic; Disease; Modelling; Foot-and-mouth; Spreadsheet

1. Introduction There are several approaches to modelling the outbreak of a transmissible disease. These include deterministic models where the outputs are a function of the input variables and stochastic models that include the probability of an event occurring. The use of random numbers leads to models incorporating Monte-Carlo techniques. Such techniques are applied specically in the case of disease spread in Reed-Frost models that incorporate the probability of eective contact between susceptible and infectious animals (Hammersley and Handscombe, 1964; Hoppensteadt and Peskin, 1992; Hurd et al., 1993; Kalos and Whitlock, 1986; Takizawa et al., 1977). State-transition models divide the population into several categories and model movement of animals from one category to another, e.g., from susceptible to infectious, including estimates of births and

Corresponding author. Fax: +44-1248-354997. E-mail address: afs047@bangor.ac.uk (I. Ap Dewi).

deaths in the case of diseases having long incubation periods (Matthews et al., 1999; Miller, 1978; Thruseld, 1986; Woolhouse et al., 1998). The choice of modelling strategy depends on the characteristics of the disease and on the purpose of the model. Models provide valuable information that assist in the understanding of the problem; they allow scenarios of disease spread to be compared and the evaluation of control strategies (Horst et al., 1999; Maragon et al., 1994; Woolhouse and Donaldson, 2001). With regard to foot-and-mouth disease (FMD), many models have been described (Donaldson et al., 1982; Donaldson, 1988). Several forecast the airborne spread of FMD incorporating information on climatic variables such as wind speed and relative humidity (Cannon and Garner, 1999; Casal et al., 1997; Gloster et al., 1981; Maragon et al., 1994; Moutou and Durand, 1994; Rumney, 1986). Hugh-Jones (1976) developed a spatial model that related spread of FMD to the transport of milk. Others have incorporated economic evaluations of control strategies (Dijkhuizen, 1989; Ferguson et al., 2001; Garner and Lack, 1995). Sanson

1090-0233/$ - see front matter 2003 Elsevier Ltd. All rights reserved. doi:10.1016/S1090-0233(03)00149-7

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et al. (1991) described a decision support system for managing FMD that incorporated various modelling techniques including a geographical information system. Most of these models rely on detailed input data with the associated disadvantage that their application is both expensive and time consuming. In the context of policy development and evaluation there are advantages associated with models that demand only limited input data and that are easy to use (Brnnum-Hansen, 1999). Computer spreadsheets provide a exible modelling environment that can be used to evaluate a range of physical and nancial scenarios (Chiew, 1995; Collins and Morgan, 1992; Cornell et al., 2001; Pfeier et al., 1997; Wahlstrom et al., 1998). We have developed a generic, stochastic spreadsheet model that, with a minimum of input data, provides a rapid estimate of disease outbreak size and a platform for evaluating the impact of disease control measures. The use of the spreadsheet is demonstrated here by simulating FMD outbreaks and comparing the results to the number of cases of FMD within the rst 100 days of the 2001 FMD outbreaks in Cumbria and Anglesey.

2. Materials and methods 2.1. Model inputs and generated output The model estimates the number of cases per day during the rst 100 days of a propagating epidemic as classied by Thruseld (1986) where a primary case infects susceptible individuals leading to secondary cases. The model was developed using the Microsoft Excel spreadsheet software and consists of four worksheets. The rst provides an area for data input and includes tabular and graphical summaries of the results. The other worksheets are used to perform calculations and to store results from consecutive iterations of the model. The model estimates the number of cases per day over a 100 day period. The spreadsheet incorporates macros (Visual Basic modules) that allow the user to perform either a single iteration of the model or to perform 1000 iterations and store the results of each run. The single iteration allows the user to obtain an approximate estimate of the number of cases and is generally used to test that input parameters and outputs are within the bounds of the model. Where 1000 iterations are performed the average number of cases per day is calculated. Cases may be interpreted as being individual subjects or groups of subjects. The spreadsheets output includes two graphs showing the number of cases per day and the cumulative number of cases. Both graphs display 95% condence intervals for the number of cases over time. Summary statistics include the minimum and maximum number of

cases per day, the mean number of cases per day and the mean incubation period. The model requires the following input data: Initial number of cases. The initial number of cases discovered on day 1 of the epidemic. Number of cases incubating. The number of cases incubating the disease on day 1 and that will therefore exhibit symptoms of the disease after day 1. Incubation period. The incubation period specied as a range of likely minimum (I1 ) and maximum (I2 ) time period (days) from infection to having detectable symptoms. The spreadsheet has limits of one and 30 days for the minimum and maximum incubation period, respectively. Infections per case. The minimum and maximum number of infections that are likely to result from a single case of the disease. This is conceptually equivalent to R, the basic reproduction rate or number (Matthews et al., 1999; Woolhouse and Donaldson, 2001) which can range from 0 with no dened upper limit. The initial value specied is modied during the simulation depending on the Infection scenario (dened later) chosen and by assumptions regarding the eectiveness of control strategies. Infections are not attributed specically to a particular factor and may be the result of airborne transmission, contact or movement. Infection scenario. The spreadsheet oers three scenarios regarding the number of infections per case of the disease. In scenarios 1, 2 and 3 the number of infections per case is assumed to be the minimum specied value, the maximum specied value or a random number between the minimum and maximum value, respectively. k. This is a scaling factor that can be between 1 and 2. It inuences the distribution of infectious cases within the incubation period, i.e., when within the incubation period animals will display detectable symptoms. When k is 1 there is no scaling of the distribution, and there is a tendency, as evidenced by the mean incubation period, for there to be more cases earlier, rather than later in the incubation period. A k value of 2, which is used for all simulations in this paper, will result is a more uniform distribution of cases within the incubation period. The eect of k in mathematical terms is described later. Introduction of control measures. Control measures have to be interpreted in the context of specic diseases. In the case of FMD they would include measures such as movement restriction but also failures in measures, e.g., associated with transmission after detection due to delay in culling (Woolhouse and Donaldson, 2001). The spreadsheet allows the modelling of two consecutive control strategies, primary and secondary and the day when each of these is introduced can be specied. The primary and secondary control measures are modelled consecutively. If the day when primary measures are introduced is specied, then on and from that day the model uses the eciency (as dened below) of the

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primary measures in its calculations. If the day when secondary measures are introduced is specied, then on and from that day the model uses the eciency (as dened below) of the secondary measures. Eciency of control measures. The eciency of both the primary and secondary control measures can be entered as a proportion of infections prevented. 2.2. Model computing strategy The spreadsheet uses the input data to calculate the number of cases per day over a 100-day period. The number of cases on a particular day after day 1 is a function of the number of infections in preceding days and of the distribution of those infections within the incubation period. The number of infections resulting from the number of cases each day is a function of the number of cases and of the number of infections per case, the latter being related to the infections scenario selected. Cases incubating the disease on day 1 are distributed (i.e, as cases with detectable symptoms) from day 2 to day I2 , where I2 is the maximum incubation period. They are distributed using a random number function subject to the constraints described later. The model calculates the number of cases using a matrix (X) with 100 rows and 30 columns. The rows represent days (d) from 1 to 100. The columns represent days (n) from 1 to 30 (i.e., the maximum incubation period allowed by the model is 130 days). Each element in the matrix (xdn ) calculates the number of detectable cases that will result on day d n from those animals infected on day d. A specic element (xDN ) of the matrix denotes the number of detectable cases resulting on day D N from cases detactable on day D, where D and N are row D and column N of the marix, respectively. The values of n are constrained by the Incubation period. Thus, a disease with Incubation period I1 to I2 days would have corresponding values of n so that cases of the disease would only be detectable between n I1 and n I2 . The number of cases on a particular day (D) is calculated as the sum of the elements of X on the upward sloping diagonal from xD1 . From d 1 to d I2 the number of cases also includes cases incubating the disease on day 1. The number of infections (Id ) that will result from the cases is calculated as: Id Cases day d 1 efficiency of control measures Infections per case; where eciency of control measures and Infections per case are as dened previously. The distribution of cases between n I1 and n I2 inclusive utilises a random number function which

generates the number of cases in xdn . The model constrains the random number of cases within certain bounds to avoid mathematically possible, but epidemiologically improbable, distributions of cases. The number of cases in xdn will be zero if n < I1 or n > I2 ; these represent cases where element xdn is outside the dened incubation period for the disease. xdn will be zero if the number incubating (Id ) is zero. The number of cases in xdn will also be zero if all the number incubating (Id ) have been allocated, that is, if
N 1 X nI1

xDn Id :

If N I2 then the number incubating in xDn will be however many of Id remain unallocated, that is: xDI2 Id
I2 1 X nI1

xDn :

In all other cases xdn will be a random number chosen from a uniform distribution between two values, RN1 and RN2 as shown below. " # PN 1 1 Id nI1 xDn RN1 INT ; k I2 I1 1 # PN 1 Id nI1 xDn RN2 INT k ; I2 N 1 where INT is an excel function that rounds down to the nearest integer. Note. if RN1 < 0 then a value of zero is assumed and if RN2 < 1 then a value of 1 is assumed. 2.3. General assumptions Because of the intention to apply the model to the 2001 FMD outbreak, initial assumptions were based on publications that preceded this epidemic. It was assumed that there was one case detected on day 1. It is sensible to include cases where the disease is incubating because Sellers and Forman (1973) suggested that the virus was present seven days before the rst outbreak of FMD in Hampshire in 1967. The number of cases incubating the disease on day 1 was varied as described later but the ranges adopted were based on a consideration of the number of cases during the rst seven days of the 1967 FMD epidemic, where there were 12 and 23 cases by days 6 and 7, respectively (DEFRA, 2001). It is likely that many of these cases were the result of infection before day 1 given the incubation period of FMD. It was assumed that cases were whole ocks/herds as in Miller (1978) and that the incubation period could range from 2 to 14 days (Donaldson et al., 1982; Kitching, 1997) and that each case could result in between 0 and 5 infections with the actual number of infections within this range being random (Scenario 3). A number "

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of infections within this range has been supported by several reports (Casal et al., 1997; Donaldson et al., 1982; Maragon et al., 1994; Sanson et al., 1993; Sellers and Forman, 1973). 2.4. Analysis 1: eects of eciency of control measures and number incubating Analysis 1 examined the eect of eciency of control measures and number incubating the disease on day 1. It was assumed that control measures were applied from day 2. Eciencies of control measures were assumed to be 0.0, 0.25, 0.50, 0.75 and 1.0. The number of cases incubating FMD was assumed to be 0, 10, 20, 30, 40 and 50. This gave 30 possible combinations (scenarios) which were each run 1000 times. The eects of number incubating and eciency on the number of cases at the beginning of the epidemic were determined by analysing the number of cumulative cases for days 120 in a general linear model that included initial number and eciency as linear covariates and also the interaction between initial number and eciency. The analysis used the data from each individual iteration. 2.5. Analysis 2: eects of eciency of control measures and timing of secondary control measures Analysis 2 examined the eect of the eciency of control measures and of the timing of secondary control measures. It was assumed that primary control measures were introduced on day 2 with eciencies of 0.2, 0.4, 0.6 or 0.8. Secondary control measures were introduced on days 14, 21 or 28 with eciencies of 0.2, 0.4, 0.6, or 0.8 at each day. This gave 4 3 4 48 possible combinations (scenarios) which were each run 1000 times. However, some of these combinations are identical, i.e., where the eciency of primary and secondary control measures was identical the timing of the secondary measures is irrelevant. Without repeated runs of identical scenarios, there were 40 possible scenarios. 2.6. Application to the 2001 FMD epidemic in the UK The model was applied to the 2001 FMD epidemic in the UK for two areas, Cumbria and Anglesey, and in two stages. First, the actual number of cases from days 114 was compared to the results of selected scenarios from Analysis 1. The scenarios chosen were those that were most similar to the actual results, determined by comparing root mean square error (RMSE) as dened by Van Delden et al. (2001). Second, the model was run with various eciencies of secondary control measures (applied at day 15) but with actual number of cases/day inserted into the model for days 114. With these values inserted, the model becomes independent of number incubating, which was

arbitrarily set to zero. It was assumed that the eciency of primary control measures was 0.25 and 1.0 for Cumbria and Anglesey, respectively, based on the results of the day 114 comparisons which identied the most likely eciency of control measures. One thousand iterations of the model were completed for each scenario. In both analyses the actual and estimated number of cases were plotted against time and dierences were assessed visually.

3. Results 3.1. Analysis 1: eects of eciency of control measures and number incubating All simulations had one case on day 1 and no new cases appeared on day 2. There was no eect of eciency on count on days 3 or 4 (P > 0:50) but a significant eect of eciency was detectable (P < 0:01) on day 5. However, eect of eciency on day 5 was small in magnitude with a decrease in number of cases of 0.98 between eciency 0 and 1. Number incubating had a signicant eect on the cumulative number of cases in days 3, 4 and 5. The number incubating and eciency had signicant eects on the number of cumulative cases (P < 0:001) from day 6 to 20 with number of cases increasing as the number incubating increased, and as the eciency of control measures decreased. Across all efciencies, as number incubating increased from 0 to 50 the number of cases increased by 13, 35, 69 and 3317 at days 5, 10, 15 and 50, respectively. A signicant interaction (P < 0:01) between number incubating and eciency was detected from day 5 onwards. The interaction was the result of a much greater eect of number incubating as eciency decreased. For example, at day 50 and eciency 0, the dierence in number of cases between number incubating of 0 and 50 was 13,828 whilst at eciency 1 the dierence was 45. The eects of number incubating and eciency on counts on day 5, 10, 15 and 50 are shown in Fig. 1. There is a marked contrast between Figs. 1a and d. In Fig. 1a there is a notable eect of number incubating but little eect of eciency. In Fig. 1d there is a marked eect of both number incubating and eciency with particularly high numbers of cases where number incubating was high and eciency was low. 3.2. Analysis 2: eects of eciency of control measures and timing of secondary control measures The eects of eciency of primary and secondary control measures and timing of the secondary control measures are shown in Table 1. Overall, decreasing the eciency of primary control measures from 0.8 to 0.2 increased the number of cases. The maximum number of

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(a) Day 5

(c) Day 15

15 10 Cases 5 0 0 Efficiency (%) 25 50 75 0 100 10 20 50 Number incubating

Cases

100 80 60 40 20

30 40

0 0 Efficiency (%) 25 50 75 0 100 10 20 30

40 50 Number incubating

(b) Day 10
50 40 30 Cases 20 10 0 25 50 75 Efficiency (%) 0 0 100 10 20 30 40 50 Number incubating

(d) Day 50

14000 12000 10000 Cases 8000 6000 4000 2000 0 0 25 50 75 Efficiency (%) 0 100 10 20

30 40

50 Number incubating

Fig. 1. Eects of eciency of control measures and number incubating on the number of cumulative cases on day (a) 5, (b) 10, (c) 15 and (d) 50.

Table 1 Eects of eciency of primary (Ep ) and secondary (Es ) control measures and timing of Es on the maximum cumulative count (day at which maximum occurs) Ep Timing of Es (day) 14 21 28 0.4 14 21 28 0.6 14 21 28 0.8 14 21 28 138,848 (100) 109,985 (100) 78,888 (100) 75,541 (100) 39,795 (100) 18,399 (99) 37,651 (100) 8,067 (87) 1,611 (69) 211,674 (100) Es 0. 2 0.4 8,996 (100) 11,531 (100) 15,627 (100) 0.6 561 (100) 853 (100) 1,451 (100) 406 (98) 520 (99) 673 (100) 0.8 137 (49) 253 (62) 460 (76) 106 (44) 156 (54) 240 (65) 67 (36) 86 (43) 108 (51)

0.2

5,445 (100)

3,143 (100) 2,228 (100) 1,523 (100) 1,673 (96) 549 (84) 176 (46)

272 (95)

144 (85) 76 (59) 52 (39)

39 (27)

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cases also increased as the eciency of secondary control measures decreased but with much greater increase between 0.4 and 0.2 than between 0.8 and 0.4. The eect of eciency of secondary control measures was greater at the lower eciency of primary control measures. In most scenarios the number of cases continued to rise until day 100. Only where eciency of control measures was at 0.8 did the number of cases stop rising before 100 days. With eciencies of 0.8, there was a close association between the day at which secondary control measures were introduced and the day at which the maximum number of cases was reached. Delaying the start of secondary control measures delayed the day at which the maximum number of cases was reached by a comparable number of days. Scenarios above the diagonal in Table 1 represent situations where secondary control measures are better than primary control measures. In these scenarios the maximum number of cases increased as the timing of the secondary control measures was delayed. Conversely, scenarios below the diagonal represent situations where secondary control measures are less eective that the primary control measures. In these scenarios the maximum numbers of case decreased as the introduction of secondary measures was delayed. 3.3. Evaluation by reference to the 2001 FMD epidemic in the UK Fig. 2 shows the number of simulated cases from day 1 to 14 of an FMD epidemic. The three scenarios chosen for comparison with the actual data for Cumbria and Anglesey were those that had the lowest RMSE. For Cumbria the three scenarios were 20:0.0, 30:0.0 and 30:0.25 (Number incubating: Eciency of primary control measures) with RMSE of 2.61, 2.62 and 2.60, respectively (RMSE ranged from 2.60 to 4.90 across all simulations). For Anglesey the three scenarios were
80 70 60 50
Cases

0:0.50, 0:0.75 and 0:1.00 with RMSE of 0.92, 0.77 and 0.69, respectively (RMSE ranged from 0.69 to 8.19 across all simulations). The simulated data most similar to the actual data for Cumbria are approximately exponential. The simulated data for Anglesey appear almost linear. The actual data for Cumbria is also exponential, following closely the simulated data (30:0.25) particularly from day 9 to 14. The results imply that there were a large number of cases incubating the disease on day 1 and that the eciency of primary control measures were no better than 0.25. The actual data for Anglesey remained lower than the three simulations in days 19 but the cumulative count at days 1014 was similar to the simulated data (0:1.0). These results imply that there were no animals incubating the disease on day 1 and that the eciency of primary control measures were high. Figs. 3 and 4, for Anglesey and Cumbria, respectively, show the actual number of cases from day 1 to 100, and simulated number of cases from day 15 to 100, using the actual number of cases per day from day 1 to 14 in the model. For Anglesey (Fig. 3), the number of cases remained comparatively low with no new cases after day 27. The increase in the number of cases from day 15 to 27 is larger for the actual data than for any of the simulations. However, the eectiveness of control measures is reected in the fact that the simulations with eciencies of secondary control measures of 0.75 and 1.0 are comparable in number (within 10 cases) and shape (no major increase in numbers after day 27), if not identical, to the actual data. For Cumbria (Fig. 4) the actual data is similar to the simulations having the lowest eciency of control measures (0.0 and 0.25) from day 15 to 35. Thereafter, there was generally a decrease in the number of cases per day with the actual data following a sigmoidal curve, more similar in shape to the

Cumbria 20 : 0.00 30 : 0.00 30 : 0.25 0 : 0.50 0 : 0.75 0 : 1.00 Anglesey

40 30 20 10 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Time (days)

Fig. 2. Estimated and actual (Anglesey and Cumbria) number of cases of FMD on day 114 with estimates based on number incubating 050 and eciency of primary control measures of 0.5.

Fig. 3. Estimated (day 15100) and actual number of cases of FMD on Anglesey (day 1100) with estimates based on several eciencies of secondary control measures. Footnote: 0.75 and 1.00 have identical results on this scale.

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Fig. 4. Estimated (day 15100) and actual number of cases of FMD in Cumbria (day 1100) with estimates based on several eciencies of secondary control measures.

simulations having the highest eciency of control measures (0.75 and 1.0). The results suggest that control measures were less eective in days 1535 than in the later stages when greater control was achieved.

4. Discussion Analysis 1 demonstrated the use of the model for a range of assumptions regarding eciency of primary control measures and number incubating on day 1. Analysis of the data showed that the cumulative number of cases early in the epidemic (days 3, 4 and 5) was affected by number incubating but with only a small eect of eciency. Analysis 1 also showed that number incubating and eciency had large eects on eventual count at day 50, with particularly severe epidemics resulting from scenarios with low eciency and high numbers incubating. Analysis 2 demonstrated the eect of secondary measures showing that their eciency had a large impact on the number of cases. Timing of secondary measures inuenced the day at which the maximum number of cases occurred. Application of the model to the 2001 outbreak of FMD in two regions of the UK illustrated how the model could be used to explore the numbers likely to be incubating the disease and the eciency of the control measures. For Cumbria, it is reasonable to assume that the number incubating the disease on day 1 was high (20 30) given the close association between the results for scenarios with these numbers and the actual data. In contrast, the number incubating the disease in Anglesey was most likely to be very small. The results (Fig. 2) suggest that in day 114 the eciency of primary control measures was low in Cumbria and high in Anglesey,

resulting in a rapid increase in the number of cases in the former and small changes in the latter. Application of the model to days 1100 (Figs. 3 and 4) shows that spread of the disease was controlled well in Anglesey, but more rapid control was potentially possible in Cumbria had secondary control measures been more eective. In Cumbria eciency of control measures of 0.75 and 1.00 from day 15 onwards should have resulted in less than 300 and 150 cases, respectively, at day 100 compared to the actual count which exceeded 700. The model estimates the number of cases in a disease epidemic from days 1 to 100. Its main advantage is that it can provide a rapid appraisal without the need for detailed input data. Its disadvantage is that it cannot incorporate specic data that might inuence spread within an area, for example climatic factors or knowledge of animal movement. In relation to state-transition models, of the four states dened by Miller (1978) three are in the model, the number susceptible is assumed to be limitless, the number infectious is calculated specically, and it is assumed that diagnosed animals are removed. Removal of infected animals, as in culling dangerous in-contact animals, is not explicitly included in the model but is implied by the eciency of control measures and infection scenario chosen. Immune animals are not considered explicitly by the model. In the case of FMD the model would assume that animals do not remain beyond initial infection which is in-line with most control strategies for FMD that rely on slaughter of animals. Evaluation of the model in the context of a FMD outbreak illustrates the way in which the model can be used to evaluate alternative control measures. The results suggest that initial control measures introduced (mainly movement restrictions) were eective in Anglesey but had less impact on number of cases within the rst 15 days in Cumbria. This is probably the consequence of the spread of the disease to several areas before it was detected, and consequently the high number incubating the disease on day 1. The number of infections was potentially very high due to airborne infection (Kitching, 1997) and through contact (Nielen et al., 1996; Sanson et al., 1993). Continuation of the epidemic in Cumbria probably reects relatively poor eciency of secondary control measures. A variety of control strategies for FMD have been described including stamping-out, culling of dangerous contact animals, slaughter and vaccination (Garner and Lack, 1995; Woolhouse and Donaldson, 2001). Although the model can evaluate alternative control strategies it does not provide a means to determine how these strategies can be achieved. It is suggested that the model could be used in combination with alternative, disease-specic, models as a tool for rapid prediction of disease outbreak and as a method of evaluating the consequences of employing control measures. The

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I. Ap Dewi et al. / The Veterinary Journal 167 (2004) 167174 Hugh-Jones, M.E., 1976. A simulation spatial model of the spread of foot-and-mouth disease through the primary movement of milk. Journal of Hygiene 77, 19. Hurd, H.S., Kaneene, J.B., Lloyd, J.W., 1993. A stochastic distributeddelay model of disease processed in dynamic populations. Preventative Veterinary Medicine 16, 2129. Kalos, M.H., Whitlock, P.A., 1986. Monte-Carlo Methods. Vol. 1: basics. Wiley, New York. pp 15. Kitching, P., 1997. Notiable viral diseases and spongiform encephalopathies of cattle, sheep and goats. In Practice 19, 5156, 5963. Maragon, S., Facchia, E., Moutou, F., Massirio, I., Vincenzi, G., Davies, G., 1994. The 1993 foot-and-mouth disease epidemic: epidemiological features of the four outbreaks identied in Verona province (Veneto region). Veterinary Record 135, 5357. Matthews, L., Woolhouse, M.E.J., Hunter, N., 1999. The basic reproduction number for Scrapie. Proceedings of the Royal Society London B 266, 10851090. Miller, W.M., 1978. A state-transition model of epidemic foot-andmouth disease. In: P.R. Ellis, A.P.M. Shaw, A.J. Stephens (Ed.), New Techniques in Veterinary Epidemiology and Economics, Department of Agriculture, University of Reading. Moutou, F., Durand, B., 1994. Modelling the spread of foot-andmouth disease virus. Veterinary Research 25, 279285. Nielen, M., Jalving, A.W., Horst, H.S., Dijkhuizen, A.A., Maurice, H., Schut, B.H., Van Wuijckhuise, L.A., De Jong, M.F., 1996. Quantication of contacts between Dutch farms to assess the potential risk of foot-and-mouth disease spread. Preventative Veterinary Medicine 28, 143158. Pfeier, D.U., Williamson, N.B., Thorbton, R.N., 1997. A simple spreadsheet simulation model of the economic eects of Neospora caninum abortions in dairy cattle in New Zealand. Epidemiologie et Sante Animale No. 3132, 10.12.110.12.3. Rumney, R.P., 1986. Meteorological inuences on the spread of footand-mouth disease. Journal of Applied Bacteriology 61 (Suppl. 15), 105114. Sanson, R.L., Liberona, H., Morris, R.S., 1991. The use of a geographical information system in the management of a footand-mouth disease epidemic. Preventative Veterinary Medicine 11, 309313. Sanson, R.L., Struthers, G., King, P., Weston, J.F., Morris, R.S., 1993. The potential extent of transmission of foot-and-mouth disease: a study of the movement of animals and materials in Southland, New Zealand. New Zealand Veterinary Journal 41, 2128. Sellers, R.F., Forman, A.J., 1973. The Hampshire epidemic of foot-and-mouth disease, 1967. Journal of Hygiene 71, 1534. Takizawa, T., Ito, T., Kosuge, M., 1977. Prototype of simulation models for epizootics in domestic animals. National Institute of Animal Health Quarterly Japan 17, 171178. Thruseld, M., 1986. Veterinary Epidemiology. Butterworths, London. pp 9293, 187198. Van Delden, A., Krop, M.J., Haverkort, A.J., 2001. Modelling temperature- and radiation-driven leaf area expansion in the contrasting crops potato and wheat. Field Crops Research 72, 119142. Wahlstrom, H., Englund, L., Carpenter, T., Emanuelson, U., Engvall, A., Vagsholm, I., 1998. A Reed-Frost model of the spread of tuberculosis within seven Swedish extensive farmed fallow deer herds. Preventative Veterinary Medicine 35, 181193. Woolhouse, M., Donaldson, A.I., 2001. Managing foot-and-mouth. Nature 410, 515516. Woolhouse, M.E.J., Stringer, S.M., Matthews, L., Hunter, N., Anderson, R.M., 1998. Epidemiology and control of Scrapie within a sheep ock. Proceedings of The Royal Society London B 265, 12051210.

model can also be used as an educational tool, allowing rapid investigation of a range of scenarios.

Acknowledgements The authors are grateful for Mikey Wests assistance with aspects of programming. They also acknowledge the valuable comments made by Chris Bishop and Louise Matthews on early versions of the model and draft paper.

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