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.

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.

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.

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.

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.

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.

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.

Vertical ovalness of glaucomatous cupping.

Slit-lamp examination and stereoscopic fundus photography were found to be helpful in differentiating between physiological and glaucomatous cupping of the disc. Vertical ovalness of any cup in the disc should raise the suspicion of glaucoma, and the magnitude of the vertical cup: disc ratio is of particular significance.

Incidence of optic disc haemorrhages in chronic simple glaucoma and ocular hypertension.

1829 photographs of optic discs taken during routine examination and follow-up of 320 glaucoma patients and 169 cases of ocular hypertension were examined for the presence of haemorrhages on the disc. As expected, the observed incidence of disc haemorrhages rose with increase in the number of occasions on which the patient was photographed. It was concluded that at least one-third of glaucoma patients show a disc haemorrhage at one time or another. Disc haemorrhages were seen more often in patients with established glaucoma than in those with ocular hypertension. In patients with chronic simple glaucoma eyes with full fields and low cup: disc ratios showed haemorrhages less often than eyes with field defects and more advanced damage to the optic disc, but apart from this there was no marked tendency for haemorrhages to occur at a particular stage of the disease. Haemorrhages were more frequent in low-tension than in chronic simple glaucoma, but this was probably only part of a more general variation which was revealed when eyes were graded according to the maximum pressures ever recorded, there being a very significant trend in which more haemorrhages were found in eyes with lower than with higher intraocular pressures over the range from 10 to 60 mmHg.

Quantitative relationship between cupping of the optic disc and visual field loss in chronic simple glaucoma.

The extent of cupping was measured from optic disc photographs of 300 patients with ocular hypertension and suspected or established chronic simple glaucoma, and their visual fields were recorded. The incidence of field defects increased as the vertical cup:disc ratio increased, a value of 0-70 for this ratio being a particularly useful guide to the presence or absence of field loss. There was a significant correlation between the extent of cupping and the size of the visual field. The vertical cup:disc ratio was the most useful quantitative index of cupping.

Colour vision in patients with chronic simple glaucoma and ocular hypertension.

Normal subjects and patients with chronic simple glaucoma and ocular hypertension were examined with the Farnsworth-Munsell 100 hue test. Two groups of glaucoma patients were studied, one group having field defects in both eyes and the other being 'unilateral' in the sense that one eye had a full visual field. The stage of the disease was assessed by the amount of field loss or by the amount of optic disc damage as expressed by the vertical cup:disc ratio. Hue discrimination in eyes with glaucomatous field defects was worse than in eyes of normal subjects, but there was no clear indication of one range of colours being more affected than another. In glaucoma patients with field defects in both eyes the difference in error scores between the 2 eyes was greater than in normal subjects. There was a significant correlation between the degree of impairment of hue discrimination, expressed as the error score, and the amount of glaucomatous field loss. There was also a significant correlation between error score and the amount of glaucomatous damage to the optic disc, expressed by the vertical cup:disc ratio. Findings in a group of patients with ocular hypertension suggested that some of these were cases of incipient glaucoma.

Association between optic disc haemorrhages in glaucoma and abnormal glucose tolerance.

Data concerning the results of glucose tolerance tests and levels of intraocular pressure were analysed for 120 patients with primary open-angle glaucoma, many of whom had been under observation for a period of four to five years. The patients consisted of two groups: in 62 patients a disc haemorrhage had been recorded at some time during the observation period, and in 58 no haemorrhages had been seen. Patients with disc haemorrhages had a higher incidence of abnormal glucose tolerance or frank diabetes and lower intraocular pressures than those without haemorrhages.

The incorporation and distribution of 3H oleic acid in the isolated perfused guinea-pig heart: a biochemical and EM autoradiographic study.

The incorporation of 3H oleic acid into tissue lipids of guinea pig heart was studied after 15, 30, 60 or 120 sec perfusion using EM autoradiography with 'hypothetical grain' analysis and lipid analysis by thin-layer chromatography. Radioactivity in triacylglycerol and phospholipid increased and in free fatty acid decreased with time. This corresponded to an increase in radioactivity associated with lipid droplets in the autoradiographs. High levels of radioactivity were found associated with the mitochondria after only 15 sec. The movement of fatty acids is interpreted in terms of transport mechanisms, concentration gradients and bound and unbound molecules.

Air sampling of pigs infected with foot-and-mouth disease virus: comparison of Litton and cyclone samplers.

The air in looseboxes containing groups of pigs in the acute stage of foot-and-mouth disease was sampled simultaneously with two air-sampling devices: a large volume sampler (Litton) and a cyclone sampler. Although the cyclone sampler was slightly less efficient at trapping airborne virus it was easier to operate. When pigs were sampled individually within a 610 litre cabinet using the cyclone sampler, the mean recovery of virus over a 24 hour period was log10 8 X 6 TCID50 per animal. This figure is four times higher than the maximum amount estimated in previous studies in which groups of pigs held in looseboxes were sampled with a Litton apparatus.

Transport of fatty acids in the heart.

Fatty acids are taken up by the myocardium in the unesterified form, either directly from the unbound pool of free fatty acids in the plasma or following release from plasma triglycerides by lipoprotein lipase. They pass extremely rapidly into the cardiac cells, where their distribution is determined by a number of physical and biochemical factors. For the intracellular spaces these factors are essentially physical and depend on gradients of concentration of unbound fatty acids and on the concentration and affinity of protein binding sites. In the cytoplasm of the myocardial cell, myoglobin seems to play a specific carrier role. Passage of fatty acids across cell membranes depends on their chemical forms and, largely, on the degree of solubility of these forms in the lipid layer of the membranes. In addition, there may be specific transport systems, such as is mediated by carnitine in the inner mitochondrial membrane. Finally, the mass movement on fatty acids through the cells depends on the rate at which they are removed by oxidation or esterification. Under normal conditions, these various factors lead to a rapid movement of fatty acids into the mitochondria where they are oxidised and a more gradual esterification into complex lipids.

Long distance transport of foot-and-mouth disease virus over the sea.

The conditions required for the transport of foot-and-mouth disease (FMD) virus in the atmosphere over long distances and in sufficient concentrations to cause infection in exposed animals are described. Using these factors a series of 23 outbreaks of FMD in Europe, where the original outbreaks were separated from later outbreaks by sea passage, have been investigated. The findings obtained support the hypothesis that under certain conditions the airborne transmission of FMD over a long sea passage is possible.

Analysis of a series of outbreaks of Aujeszky's disease in Yorkshire in 1981-82: the possibility of airborne disease spread.

A series of outbreaks of Aujeszky's disease occurred in Yorkshire during 1981-82. These were investigated from epidemiological and meteorological viewpoints to determine if airborne disease spread could have occurred between any of the premises. The results suggest that seven out of the 11 outbreaks investigated could have resulted from airborne virus.

Use of prediction models to forecast and analyse airborne spread during the foot-and-mouth disease outbreaks in Brittany, Jersey and the Isle of Wight in 1981.

Between March 4 and 26, 1981 the French veterinary authorities reported a series of 14 outbreaks of disease due to type O foot-and-mouth (FMD) virus, 13 in Brittany and one in Normandy. The United Kingdom reported FMD type O in Jersey on March 19 and in the Isle of Wight on March 22. The field and laboratory investigations on the farm in the Isle of Wight are outlined. The way in which short and long range numerical models were used to forecast the airborne spread of FMD from Brittany to the UK and then to assess the risk of further airborne spread within the UK is described.