Aerosol transmission of foot-and-mouth disease virus Asia-1 under experimental conditions.

Foot-and-mouth disease virus (FMDV) control measures rely on understanding of virus transmission mechanisms. Direct contact between naïve and infected animals or spread by contaminated fomites is prevented by quarantines and rigorous decontamination procedures during outbreaks. Transmission of FMDV by aerosol may not be prevented by these control measures and this route of transmission may allow infection of animals at distance from the infection source. Understanding the potential for aerosol spread of specific FMDV strains is important for informing control strategies in an outbreak. Here, the potential for transmission of an FMDV Asia 1 strain between pigs and cattle by indirect aerosol exposure was evaluated in an experimental setting. Four naïve calves were exposed to aerosols emitted from three infected pigs in an adjacent room for a 10h period. Direct contact between pigs and cattle and fomite transfer between rooms was prevented. Viral titres in aerosols emitted by the infected pigs were measured to estimate the dose that calves were exposed to. One of the calves developed clinical signs of FMD, whilst there was serological evidence for spread to cattle by aerosol transmission in the remaining three calves. This highlights the possibility that this FMDV Asia 1 strain could be spread by aerosol transmission given appropriate environmental conditions should an outbreak occur in pigs. Our estimates suggest the exposure dose required for aerosol transmission was higher than has been previously quantified for other serotypes, implying that aerosols are less likely to play a significant role in transmission and spread of this FMDV strain.

Investigating incursions of bluetongue virus using a model of long-distance Culicoides biting midge dispersal.

Bluetongue virus (BTV) is an economically important pathogen of ruminants that is the aetiological agent of the haemorrhagic disease bluetongue. Bluetongue virus is biologically transmitted by Culicoides biting midges (Diptera: Ceratopogonidae), and long-range dispersal of infected vector species contributes substantially to the rapid spread of the virus. The range of semi-passive flights of infected Culicoides on prevailing winds has been inferred to reach several hundred kilometres in a single night over water bodies. In this study, an atmospheric dispersion model was parameterized to simulate Culicoides flight activity based on dedicated entomological data sets collected in the UK. Five outbreaks of BTV in Europe were used to evaluate the model for use as an early warning tool and for retrospective analyses of BTV incursions. In each case, the generated predictions were consistent with epidemiological observations confirming its reliability for use in disease outbreak management. Furthermore, the model aided policy makers to predict, contain and eradicate BTV outbreaks in the UK during 2007 and 2008.

Comparison of pre-emptive and reactive strategies to control an incursion of bluetongue virus serotype 1 to Great Britain by vaccination.

Bluetongue (BT) is a disease of ruminants caused by bluetongue virus (BTV), which is spread between its hosts by Culicoides midges. Vaccination is the most effective way to protect susceptible animals against BTV and was used reactively to control the recent northern European outbreak. To assess the consequences of using vaccination pre-emptively we used a stochastic, spatially explicit model to compare reactive and pre-emptive vaccination strategies against an incursion of BTV serotype 1 (BTV-1) into Great Britain. Both pre-emptive and reactive vaccination significantly reduced the number of affected farms and limited host morbidity and mortality. In addition, vaccinating prior to the introduction of disease reduced the probability of an outbreak occurring. Of the strategies simulated, widespread reactive vaccination resulted in the lowest levels of morbidity. The predicted effects of vaccination were found to be sensitive to vaccine efficacy but not to the choice of transmission kernel.

Atmospheric dispersion models and their use in the assessment of disease transmission.

Atmospheric dispersion models can be used to assess the likely airborne spread of both plant and animal diseases. These models, often initially developed for other purposes, can be adapted and used to study past outbreaks of disease as well as operationally to provide advice to those responsible for containing or eradicating disease in the event of a specific emergency. The models can be run over short periods of time where emissions and infection periods can be accurately determined or in situations requiring a statistical approach perhaps covering many weeks or even months. They can also be embedded within other simulation models, i.e. models which seekto represent a wider variety of disease transmission mechanisms. Whilst atmospheric dispersion models have been used successfully in a number of instances, they have the potential for wider application in the future. To achieve maximum success in these ventures, close collaboration between the modellers and scientists from the appropriate range of disciplines is required.

Reanalysis of the start of the UK 1967 to 1968 foot-and-mouth disease epidemic to calculate airborne transmission probabilities.

The aims of this study were to statistically reassess the likelihood that windborne spread of foot-and-mouth disease (FMD) virus (FMDV) occurred at the start of the UK 1967 to 1968 FMD epidemic at Oswestry, Shropshire, and to derive dose-response probability of infection curves for farms exposed to airborne FMDV. To enable this, data on all farms present in 1967 in the parishes near Oswestry were assembled. Cases were infected premises whose date of appearance of first clinical signs was within 14 days of the depopulation of the index farm. Logistic regression was used to evaluate the association between infection status and distance and direction from the index farm. The UK Met Office's NAME atmospheric dispersion model (ADM) was used to generate plumes for each day that FMDV was excreted from the index farm based on actual historical weather records from October 1967. Daily airborne FMDV exposure rates for all farms in the study area were calculated using a geographical information system. Probit analyses were used to calculate dose-response probability of infection curves to FMDV, using relative exposure rates on case and control farms. Both the logistic regression and probit analyses gave strong statistical support to the hypothesis that airborne spread occurred. There was some evidence that incubation period was inversely proportional to the exposure rate.

Possible means of introduction of bluetongue virus serotype 8 (BTV-8) to Sweden in August 2008: comparison of results from two models for atmospheric transport of the Culicoides vector.

In September 2008, bluetongue virus serotype 8 (BTV-8) infection was detected for the first time in Sweden, in a dairy herd on the west coast. Two different previously published operational atmospheric dispersion models indicate that midges from infected regions in Europe are likely to have reached Sweden by atmospheric transport during an estimated infection window. Both models indicated that the likely dates for the incursion of midges were overnight on August 6 to 7 and August 14 to 15; however, the less constrained model indicated a number of additional possible dates. The distribution of infected herds detected by active surveillance coincides with the regions that were indicated by the models to have been reached by midges from regions in Denmark and Germany with infected herds. It is likely that several points of introduction of infected midges occurred, possibly on different occasions. No alternative routes for introduction of the infection to Sweden were identified, supporting the theory that BTV-8 was introduced by infected midges carried by the wind.

Short-lived carriage of foot-and-mouth disease virus in human nasal cavities after exposure to infected animals.

A quarantine period for potentially contaminated personnel can be used to reduce the risk of transfer of foot-and-mouth disease virus (FMDV) from infected to susceptible premises. This is set at 72 hours in the UK, on the basis of results from laboratory studies and field observations. Previous analysis of FMDV carriage within human nasal cavities has relied upon virus isolation by culture in susceptible cells. This study, involving 51 people, evaluated a PCR method, which detected viral genomic material within 35 nasal swabs taken from personnel after up to eight hours exposure to infected animals. Only one of 23 people who was PCR-positive immediately after exposure to FMDV-infected animals remained positive the following day, indicating a low risk of prolonged carriage of virus in the nasal cavities.

Why were there no outbreaks of bluetongue in the UK during 2008?

With bluetongue rampant on the main European Continent in 2008, why were there no outbreaks reported in the UK? The essential criteria for introduction of the disease by carriage of infected midges on the wind have been assessed for 2006, 2007 and 2008, and it is concluded that temperatures were favourable for virus replication and midge activity and that suitable winds were present on a considerable number of occasions. A major difference between 2007, when virus was introduced to the UK, and 2008 was the extensive vaccination programme implemented by the UK Government in 2008, with the support of the farming community. Vaccination reduced the numbers of susceptible animals, making it difficult for a focus of disease to become established. The authors believe that if bluetongue re-establishes itself on the near Continent in 2009, it will be of critical importance that UK livestock are fully protected by vaccination against the disease.

Evidence for transplacental and contact transmission of bluetongue virus in cattle.

This paper presents evidence that a field strain of bluetongue virus serotype 8 (BTV-8) was transmitted transplacentally and that it was also spread by a direct contact route. Twenty pregnant heifers were imported from the Netherlands into Northern Ireland during the midge-free season. Tests before and after the animals were imported showed that eight of them had antibodies to bluetongue virus, but no viral RNA was detected in any of them by reverse transcriptase-PCR (RT-PCR). Two of the seropositive heifers gave birth to three calves that showed evidence of bluetongue virus infection (RT-PCR-positive), and one of the calves was viraemic. Two further viraemic animals (one newly calved Dutch heifer, and one milking cow originally from Scotland) were also found to have been infected with BTV-8 and evidence is presented that these two animals may have been infected by direct contact, possibly through the ingestion of placentas infected with BTV-8.

Clinical and laboratory investigations of the outbreaks of foot-and-mouth disease in southern England in 2007.

A case of foot-and-mouth disease (fmd) on a cattle farm in Normandy, Surrey, was confirmed on Friday August 3, 2007, the first case in the uk since 2001. The infection was detected nearby on a second farm on August 6. On September 12, fmd was confirmed on a farm approximately 20 km from Normandy in Egham, and this was followed by cases on five more farms in that area in the next three weeks. The majority of the infected farms consisted of multiple beef cattle holdings in semi-urban areas. In total, 1578 animals were culled on the infected farms, and fmd virus infection was confirmed in 278 of them by the detection of viral antigen, genome or antibodies to the virus, or by clinical signs. This paper describes the findings from animal inspections on the infected farms, including the estimated ages of the fmd lesions and the numbers of animals infected. It also summarises the test results from samples taken for investigation, including the detection of preclinically viraemic animals by using real-time reverse transcriptase-pcr.

Emergency vaccination of sheep against foot-and-mouth disease: significance and detection of subsequent sub-clinical infection.

This study has quantified the level of foot-and-mouth disease virus (FMDV) replication and shedding in vaccinated sheep and correlated this to the severity of clinical signs, the induction of antibodies against FMDV non-structural proteins (NSPs) and the transmission of virus to in-contact vaccinated sentinel sheep. To mimic an emergency vaccination regime in the field, sheep were vaccinated with O(1) Manisa vaccine and 4 or 10 days later were indirectly challenged with aerosols from O(1) UKG FMDV infected pigs. Vaccinated and control unvaccinated sheep were monitored for a minimum of 39 days post-challenge. The vaccinated sheep became sub-clinically infected, with reduced virus replication and excretion compared to unvaccinated and clinically infected sheep. Seroconversion to NSP was weak and transient in sheep in which virus replication was of low level and short duration. Virus transmission from vaccinated sub-clinically infected sheep to introduced vaccinated sentinels was not sufficient to cause NSP seroconversion or significant virus shedding. 10% of 10 days and 20% of 4 days vaccinated sheep were virus carriers at greater than 28 days post-challenge compared to 37.5% in the unvaccinated and clinically infected sheep. These results suggest that the low levels of virus replication likely if an effective vaccine is administered at least 4 days prior to challenge exposure are unlikely to result in the spread of infection even under intensive management conditions. Although it may be difficult to detect this infection by serosurveillance, the significance of missing it is likely to be low and the main value of such testing will be to detect undisclosed clinical infection resulting from lack of observation or from exposure to virus before or very soon after vaccination or from vaccine failure due to maladministration or inappropriate strain selection.

Bluetongue in the United Kingdom and northern Europe in 2007 and key issues for 2008.

As predicted, bluetongue arrived in the UK in 2007. Here, John Gloster and colleagues investigate the meteorological parameters that allowed this incursion into the UK and discuss key issues related to the disease's possible re-establishment in 2008.

Reduction of foot-and-mouth disease (FMD) virus load in nasal excretions, saliva and exhaled air of vaccinated pigs following direct contact challenge.

In future, a policy of "vaccinate-to-live" may be included in the repertoire of foot-and-mouth disease (FMD) control measures and in support of this approach, we have investigated the hypothesis that vaccine-induced reduction in virus replication and excretion from pigs can be correlated to the severity of clinical signs of FMD by measuring excretion of virus in natural secretions and aerosols. The other aims of this study were to verify the existence of sub-clinical infection in vaccinated pigs, to evaluate the correlation between this and seroconversion to foot-and-mouth disease virus (FMDV) non-structural protein antibodies and to re-examine the occurrence of FMDV persistence in the oro-pharynx of pigs. Therefore, pigs were vaccinated (O1 Manisa) and challenged (O1 UKG) in a manner calculated to produce a broad range of clinical outcomes and were monitored for a minimum of another 33 days post-challenge. Eighty-one percent of the early (10 days vaccinated) challenged pigs and 25% of the late (29 days vaccinated) challenged pigs were clinically infected and all other vaccinated pigs were sub-clinically infected. Although vaccination could not provide complete clinical or virological protection, it reduced the severity of the disease, virus excretion and production of non-structural FMDV antibodies in vaccinated and subsequently infected pigs. As hypothesised, vaccine-induced reduction of virus replication and excretion was found to be correlated to the severity of clinical disease. RNA copies, but no live virus was detected from the pharyngeal and soft palate tissues of a minority of vaccinated and infected pigs beyond the acute stage of the infection.

Will bluetongue come on the wind to the United Kingdom in 2007?

In 2006, over 2000 cases of bluetongue were recorded in northern Europe. The disease, which has been more typically associated with Mediterranean areas, is believed to have become established hundreds of kilometres to the north of its traditional area, probably as a consequence of the hottest summer/autumn period since records began. In this special article, John Gloster and colleagues describe the meteorological conditions surrounding the 2006 outbreak, and investigate the possibility of bluetongue virus (BTV) spreading on the wind to the UK in 2007. For this to happen there would need to be a source of windborne virus, together with a susceptible population of ruminants in the vicinity of the coast. Evidence from outbreaks in the Mediterranean Basin suggests that long-distance transport of BTV-infected vectors has already occurred, at least in that region. The overall likelihood of this occurring in northern Europe depends critically on whether the virus overwinters on the near continent; this will not be known until around May 2007. The 2006 outbreak has highlighted the importance of understanding the impact of climate change on animal disease.

Re-assessing the likelihood of airborne spread of foot-and-mouth disease at the start of the 1967-1968 UK foot-and-mouth disease epidemic.

The likelihood of airborne spread of foot-and-mouth disease at the start of the 1967-1968 epidemic is re-assessed in the light of current understanding of airborne disease spread. The findings strongly confirm those made at the time that airborne virus was the most likely cause of the rapid early development of the disease out to 60 km from the source. This conclusion is reached following a detailed epidemiological, meteorological and modelling study using original records and current modelling techniques. The role played by 'lee waves' as the mechanism for the spread is investigated. It is thought that they played little part in influencing the development of the epidemic. A number of lessons learned from the work are drawn, identifying the need for further research on the quantity and characteristics of airborne virus. The results are also used to illustrate what advice would have been available to disease controllers if the outbreak had occurred in 2004.

The 2001 epidemic of foot-and-mouth disease in the United Kingdom: epidemiological and meteorological case studies.

The possibility of the airborne spread of foot-and-mouth disease during the 2001 epidemic in the uk has been investigated in three epidemiological case studies. On the basis of evidence from field investigations, and a simple meteorological analysis, it is concluded that the spread of disease was consistent with the airborne transport of virus. The distances ranged from less than 1 km to 16 km; six of the farms were over 6 km from the source and involved the passage of virus over the sea combined with meteorological conditions which strongly favoured airborne disease transmission. The results of detailed atmospheric modelling demonstrated that airborne virus could have challenged livestock on all the farms studied. However, with one exception the 24-hour average daily concentrations of the virus were significantly below the experimentally estimated threshold for infection. A detailed model intercomparison established that, under stable atmospheric conditions, peak concentrations of virus up to two orders of magnitude higher might have been experienced for short periods, owing to fluctuations within the plume of virus, and model limitations. This finding would significantly reduce the apparent discrepancy between the experimentally estimated threshold for infection and the modelling results.