Destructive tension: mathematics versus experience--the progress and control of the 2001 foot and mouth disease epidemic in Great Britain.

The 2001 foot and mouth disease epidemic in Great Britain was characterised by control using both traditional and novel methods, some resulting from conclusions of mathematical models. Seven days before the implementation of the novel controversial automatic pre-emptive culling of all susceptible livestock on premises adjacent to infected premises (the 'contiguous cull'), the spread of infection had already been controlled by a combination of the traditional stamping out policy with a national movement ban on livestock. A second controversial novel policy requiring the slaughter of sheep within 3 km of premises on which disease had been confirmed (the 3-km cull) also commenced after the peak of infection spread, was untargeted and took several weeks to complete; serosurveillance of culled sheep detected infection in only one flock, suggesting that cryptic infection of sheep was not propagating the epidemic. Extensive post-epidemic serological surveillance of sheep found only a small number of seropositive animals in a very few flocks, suggesting that foot and mouth disease may self-limit in extensive sheep populations. The epidemic was finally brought to an end following the introduction of enhanced agricultural movement restrictions and biosecurity measures. A welfare culling scheme of unaffected animals was required to support the prolonged national livestock movement ban. The models that supported the contiguous culling policy were severely flawed, being based on data from dissimilar epidemics; used inaccurate background population data, and contained highly improbable biological assumptions about the temporal and quantitative parameters of infection and virus emission in infected herds and flocks.

De-boned beef - an example of a commodity for which specific standards could be developed to ensure an appropriate level of protection for international trade.

De-boned beef from which lymph nodes and risk material associated with bovine spongiform encephalopathy have been removed, is a product which can be produced for safe international trade irrespective of whether the locality of production is recognized as free from so-called transboundary diseases or not. Further processing of such beef provides an additional safety factor. However, this approach requires specific control measures being in place, supported by appropriate auditing and certification procedures. This document presents the arguments supporting this concept and details how safety in respect of both animal diseases and human food safety can be achieved using an integrated hazard analysis and critical control points approach.

Certification for regional and international trade in livestock commodities: the need to balance credibility and enterprise.

The current system for the certification of internationally traded animal commodities can act as a barrier to developing countries accessing high-value international markets. In this Viewpoint article, Gavin Thomson and colleagues discuss the situation as it stands and identify inconsistencies with respect to the certification process. They suggest ways to address the lack of capacity for credible certification in some developing countries that will encourage market access for livestock commodities. They emphasise the role of mechanisms other than demonstrating that an area of production is free from a range of animal diseases, arguing that this could be of significant benefit to developing regions and countries, but that a reliable and independent system of certification based on international standards is essential.

Validation of a foot-and-mouth disease antibody screening solid-phase competition ELISA (SPCE).

This paper describes the validation of a solid-phase competition enzyme-linked immunosorbent assay (SPCE) for the serological detection of antibody to serotype O foot-and-mouth disease (FMD) in sheep, cattle and pigs. The specificity of the SPCE was calculated from the results of testing known negative sera from sheep, cattle and pigs (n=3030, 1418 and 1495, respectively). The mean percentage inhibition (PI) for known negative sheep, cattle and pig sera were 19.3, 24.1 and 20.8%, respectively. The specificity of the SPCE at a cut-off point (COP) of 60 PI was 99.50% for sheep sera, 99.44% for cattle sera and 100% for pig sera. The analytical sensitivity of the SPCE was examined by testing sera from sheep, cattle and pigs. Based on the testing of serial bleeds from experimentally infected animals, seroconversion at the 60 PI COP occurred between 4 and 9 days post-infection or -exposure, similar to that observed using the virus neutralisation test (VNT) with a COP of 1/45. When applied to 267 sheep and 143 pig samples, that were obtained in Great Britain (GB) during the 2001 FMD UK outbreak, the SPCE identified more positive samples than did the VNT. Estimates of the accuracy, repeatability and reproducibility of the SPCE were verified during the large-scale serosurveillance necessitated by the 2001 outbreak. Results from field and experimental sera showed that when compared against the VNT, the sensitivity of the SPCE was less affected by the choice of virus strain used in the test. Using the O(1) UKG 2001 FMD virus in the VNT with samples representative of the uninfected GB sheep population, the test specificity was 100% at a COP of 1/45.

The pathogenesis and diagnosis of foot-and-mouth disease.

The pathogenesis of foot-and-mouth disease (FMD) is reviewed, taking account of knowledge gained from field and experimental studies and embracing investigations at the level of the virus, the cell, the organ, the whole animal and the herd or flock. The review also addresses the immune response and the carrier state in FMD. Progress made in understanding the pathogenesis of the disease is highlighted in relation to developments in diagnosis and methods of control.

Clinical and laboratory investigations of five outbreaks of foot-and-mouth disease during the 2001 epidemic in the United Kingdom.

Clinical and laboratory investigations of five outbreaks of foot-and-mouth disease (FMD) were made during the early stages of the 2001 epidemic in the UK. The first outbreak, confirmed on February 20, was at an abattoir in Essex which specialised in the processing of culled sows and boars. On February 23, the disease was confirmed at a pig farm in Northumberland which held cull sows and boars fed on waste food; the findings indicated that it was the first of the five premises to be infected. The disease had probably been present since early February, and it was the most likely origin of the epidemic. The other premises investigated were a waste food-fed cull sow/boar pig unit in Essex, approximately 30 km from the abattoir, which was probably infected at the same time or before the abattoir, a sheep and cattle farm approximately 6 km from the Northumberland pig farm, which was probably infected by airborne virus from it in the period immediately before February 13, and a sheep and cattle farm in Devon which had clinical disease from February 20 and was probably infected by sheep transported from Northumberland on February 13 which arrived on February 15.

Airborne transmission of foot-and-mouth disease virus from Burnside Farm, Heddon-on-the-Wall, Northumberland, during the 2001 epidemic in the United Kingdom.

The results of a detailed assessment of the atmospheric conditions when foot-and-mouth disease (FMD) virus was released from Burnside Farm, Heddon-on-the-Wall, Northumberland at the start of the 2001 epidemic in the UK are consistent with the hypothesis that the disease was spread to seven of the 12 farms in the immediate vicinity of the source by airborne virus, and airborne infection could not be ruled out for three other premises; the remaining two premises were unlikely to have been infected by airborne virus. The distances involved ranged from less than 1 km up to 9 km. One of the farms which was most probably infected by airborne virus from Burnside Farm was Prestwick Hall Farm, which is believed to have been key to the rapid spread of the disease throughout the country. In contrast, the results of detailed atmospheric modelling, based on a combination of clinical evidence from the field and laboratory experiments have shown that by assuming a relationship between the 24-hour average virus concentrations and subsequent infection, threshold infection levels were seldom reached at the farms close to Burnside Farm. However, significant short-term fluctuations in the concentration of virus can occur, and short-lived high concentrations may have increased the probability of infection and explain this discrepancy.

Investigation of the possible spread of foot-and-mouth disease virus by the burning of animal carcases on open pyres.

An atmospheric dispersion model was used to predict the airborne spread and concentrations of foot-and-mouth disease virus within the plumes generated by 11 pyres built to burn infected carcases during the epidemic of 2001 in the UK. On the basis of assumptions about the quantity of virus emitted during the three hours after the pyres were built and the threshold concentration of virus required to cause an infection in cattle, it was concluded that none of the disease breakdowns which occurred under the plumes was due to the spread of virus from the pyres.

Quantities of infectious virus and viral RNA recovered from sheep and cattle experimentally infected with foot-and-mouth disease virus O UK 2001.

The profiles of virus production and excretion have been established for sheep experimentally infected with the UK 2001 strain of foot-and-mouth disease (FMD) virus by inoculation and by direct and intensive contact. Virus replicated rapidly in the inoculated sheep, from which a peak infectivity of airborne virus of 10(4.3) TCID(50) per sheep per 24 h was recovered. Around 24 h later, contact-infected sheep excreted airborne virus maximally. Similar amounts of airborne virus were recovered from cattle. The excretion of virus by the sheep under these conditions fell into three phases. First, a highly infectious period of around 7-8 days. Second, a period of 1-3 days soon afterwards when trace amounts of viral RNA were recovered in nasal and rectal swabs. Third, at 4 weeks after exposure, the demonstration, by tests on oesophageal-pharyngeal samples, that 50% of the sheep were carriers. The implications of the results and the variable role that sheep may play in the epidemiology of FMD are discussed.

Natural aerosol transmission of foot-and-mouth disease virus to pigs: minimal infectious dose for strain O1 Lausanne.

Foot-and-mouth disease virus (FMDV) can spread by a variety of mechanisms, including, under certain circumstances, by the wind. Simulation models have been developed to predict the risk of airborne spread of FMDV and have played an important part in decision making during emergencies. The minimal infectious dose of FMDV for different species by inhalation is an important determinant of airborne spread. Whereas the doses for cattle and sheep have been quantified, those for pigs are not known. The objective of the study was to obtain that data in order to enhance the capability of simulation models. Under experimental conditions, forty pigs were exposed individually to naturally generated aerosols of FMDV, strain O1 Lausanne. The results indicated that doses under 100 TCID50 failed to infect pigs but doses of approximately 300 TCID50 caused short-term sub-clinical infection. The calculations suggested that a dose of more than 800 TCID50 is required to cause infection and typical disease.

Further studies to quantify the dose of natural aerosols of foot-and-mouth disease virus for pigs.

Foot-and-mouth disease virus (FMDV) can be spread by a variety of mechanisms, including wind. Simulation models, developed to predict the risk of airborne spread, have played an important part in decision making in some outbreaks. The amount of airborne virus excreted as well as the minimal infectious dose (MID) of FMDV for different species are important determinants of airborne spread. The objective of this study was to obtain data for the O1 Lausanne, O SKR 2000 and O UKG 2001 strains of FMDV to enhance the capability of such models. Pigs were exposed to naturally generated aerosols of the three strains using an experimental design which delivered high doses of the two strains O1 Lausanne and O SKR 2000 over a short period, or of the O UKG 2001 strain over an extended period. The average excretion of the O1 Lausanne strain was 10(6.4) TCID50 per pig per hour. The excretion of the O SKR 2000 strain averaged 10(5.8) and the O UKG 2001 strain 10(6.1) TCID per pig per 24 h. The results show that the previous estimate of 'above' 800 TCID50 as the MID50 for the O1 Lausanne strain is a considerable under-estimate and that the real dose may be as high as 6000 TCID50. A dose of around 650 TCID50 of the O SKR 2000 strain failed to infect any pigs. Thus, the aerosol MID50 for pigs for this isolate is at least 1000 TCID50 and likely to be as high or higher than the O1 Lausanne strain. The exposure of pairs of recipient pigs kept physically separated from donor pigs in a series of rooms to aerosol exposure doses of the O UKG 2001 strain of around 50 TCID50 per min for 24-48 h failed to infect any of eight pigs. Thus, the present experiment confirms our previous findings that pigs, compared to cattle and sheep, are relatively resistant to infection with airborne FMDV.

Predicting the spread of foot and mouth disease by airborne virus.

Foot and mouth disease (FMD) can spread by a variety of mechanisms which, under certain climatic and epidemiological conditions, includes the windborne spread of disease. Recent advances in knowledge of the aerobiological features of FMD are described. The strain of virus and species of infected animal are major determinants of airborne virus emission. Pigs emit most virus, cattle and sheep lesser but similar amounts to each other. Peak excretion of airborne virus by sheep occurs before the clinical phase of disease, whereas with cattle and pigs, it coincides with the development of early clinical disease. The probability of aerogenous infection differs greatly between livestock species. Cattle are the most susceptible, followed by sheep, whereas pigs are very resistant. Computer-based simulation models have been developed to analyse and predict the risk of airborne spread of FMD and have been used successfully during outbreaks to support decision-making. Further research is required to refine and extend the models for operational use.