Evidence for the circulation of antimicrobial-resistant strains and genes in nature and especially between humans and animals.

The concern over antibiotic-resistant bacteria producing human infections that are difficult to treat has led to a proliferation of studies in recent years investigating resistance in livestock, food products, the environment and people, as well as in the mechanisms of transfer of the genetic elements of resistance between bacteria, and the routes, or risk pathways, by which the spread of resistance might occur. The possibility of transfer of resistant genetic elements between bacteria in mixed populations adds many additional and complex potential routes of spread. There is now considerable evidence that transfer of antimicrobial resistance from food-producing animals to humans directly via the food chain is a likely route of spread. The application of animal wastes to farmland and subsequent leaching into watercourses has also been shown to lead to many potential, but less well-documented, pathways for spread. Often, however, where contamination of water sources, processed foods, and other environmental sites is concerned, specific routes of circulation are unclear and may well involve human sources of contamination. Examination of water sources in particular may be difficult due to dilution and their natural flow. Also, as meat is comparatively easy to examine, and is frequently suspected of being a source of spread, there is some bias in favour of studying this vehicle. Such complexities mean that, with the evidence currently available, it is not possible to prioritise the importance of potential risk pathways and circulation routes.

The effect of climate change on the occurrence and prevalence of livestock diseases in Great Britain: a review.

There is strong evidence to suggest that climate change has, and will continue to affect the occurrence, distribution and prevalence of livestock diseases in Great Britain (GB). This paper reviews how climate change could affect livestock diseases in GB. Factors influenced by climate change and that could affect livestock diseases include the molecular biology of the pathogen itself; vectors (if any); farming practice and land use; zoological and environmental factors; and the establishment of new microenvironments and microclimates. The interaction of these factors is an important consideration in forecasting how livestock diseases may be affected. Risk assessments should focus on looking for combinations of factors that may be directly affected by climate change, or that may be indirectly affected through changes in human activity, such as land use (e.g. deforestation), transport and movement of animals, intensity of livestock farming and habitat change. A risk assessment framework is proposed, based on modules that accommodate these factors. This framework could be used to screen for the emergence of unexpected disease events.

Risk modelling for vaccination: a risk assessment perspective.

Any risk assessment involves a number of steps. First, the risk manager, in close liaison with the risk assessor, should identify the question of interest. Then, the hazards associated with each risk question should be identified. Only then can the risks themselves be assessed. Several questions may reasonably be asked about the risk associated with avian influenza vaccines and their use. Some apply to any vaccine, while others are specific to avian influenza. Risks may occur during manufacture and during use. Some concern the vaccines themselves, while others address the effect of failure on disease control. The hazards associated with each risk question are then identified. These may be technical errors in design, development or production, such as contamination or failure to inactivate appropriately. They may relate to the biological properties of the pathogens themselves displayed during manufacture or use, for example, reversion to virulence, shedding or not being the right strain for the subsequent challenge. Following a consideration of risks and hazards, the information needed and an outline of the steps necessary to assess the risk is summarized, for an illustrative risk question using, as an example, the risks associated with the use of vaccines in the field. A brief consideration of the differences between qualitative and quantitative risk assessments is also included, and the potential effects of uncertainty and variability on the results are discussed.

Two-way learning.

I have been a mentor for many years and believe it is a role all nurses should take on, as mentoring is a two-way process - we also learn from students.

Quantitative risk assessment case study: smuggled meats as disease vectors.

Outbreaks of foot and mouth disease (FMD), African swine fever (ASF), classical swine fever (CSF) and swine vesicular disease (SVD) can cause significant economic and social costs and severe trade limitations. A number of commodities may be contaminated with these hazards, including meat and meat products derived from infected animals. Great Britain (GB) enforces a number of regulations to prevent the importation of such pathogens. However, the illegal importation of meat provides a route by which controls may be circumvented and pathogens imported. This paper discusses a series of risk assessments examining the disease risk to the GB livestock population of FMD, CSF, ASF and SVD from the illegal importation of any meat product from any region in the world. This paper describes the development of a quantitative risk assessment model designed to identify the major contributors to this risk, and discusses the challenges posed when undertaking such complex risk assessments.

A simple approach to improving sensitivity in a one-step monoclonal antibody-based ELISA for human IIbIIIa using multiple conjugates.

This paper describes an approach which can be used to increase both the speed and the sensitivity of a monoclonal antibody (MAb) based ELISA for human IIbIIIa by using a mixture of enzyme labeled MAbs (conjugates) and a one step incubation format (where analyte and conjugates were incubated simultaneously for 2 h in the MAb coated well). A simple competitive blocking method is described for mapping the relative epitopes of five monoclonal antibodies (MAbs) with minimum preparation of enzyme conjugate. This method permits the selection of three MAbs which recognize distinctly different epitopes, and are suitable for use in a one step ELISA format. Compared to the regular two step ELISA using two MAbs, this simple modification improves the assay sensitivity by three-fold and decreases the incubation time by 75%, while maintaining a high level of precision (2-15%). The assay is very specific and can accurately measure both recombinant and native IIbIIIa.

A morphological study of radiation nephropathy in the pig.

Both kidneys of mature pigs received a single dose of 9.8 Gy 60Co gamma rays. Pigs were killed between 2 and 24 weeks after irradiation and the kidneys examined histologically. Glomerular and tubular changes were observed within 2 weeks of irradiation. Neutrophils and other leukocytes were seen within glomerular capillary loops; mesangial matrix and cell number increased. A progressive increase in thickening of the basement membrane and a decrease in capillary lumina were then noted. Basement membrane duplication occurred within 12 weeks. By 24 weeks these lesions had increased in severity, sclerotic endstage glomeruli, predominantly subcapsular or juxtamedullary, being evident. Tubular lesions initially consisted of focal areas of tubular atrophy in the juxtamedullary region. By 6 weeks subcapsular foci of tubular degeneration, regeneration, and necrosis were found; these appeared to resolve 12 weeks after irradiation. At later times the severity of the tubular lesions varied between pigs, with some exhibiting interstitial fibrosis involving a complete band of subcapsular tissue, while others showed relatively mild changes. There was no apparent change in the vasculature. These findings indicate that (a) there is no one target or dose-limiting cell, and (b) the vasculature does not play a primary role in the development of radiation nephropathy.

Animal growth promoters: to ban or not to ban? A risk assessment approach.

The use of antibiotics for animal growth promotion has been controversial because of the potential transfer of antibiotic resistance from animals to humans. Such transfer could have severe public health implications in that treatment failures could result. We have followed a risk assessment approach to evaluate policy options for the streptogramin-class of antibiotics: virginiamycin, an animal growth promoter, and quinupristin/dalfopristin, a antibiotic used in humans. Under the assumption that resistance transfer is possible, models project a wide range of outcomes depending mainly on the basic reproductive number (R(0)) that determines the potential for person-to-person transmission. Counter-intuitively, the benefits of a ban on virginiamycin were highest for intermediate values of R(0), and lower for extremely high or low values of R(0).

A quantitative risk assessment for the importation of brucellosis-infected breeding cattle into Great Britain from selected European countries.

Great Britain (GB) has been "Officially Brucellosis Free" (OBF) since 1991; because this disease has both public-health and international-trade implications, it is in the country's interest to maintain this freedom. A quantitative risk-assessment model was developed to determine the annual risk of importing brucellosis-infected breeding cattle into GB from Northern Ireland and the Republic of Ireland. (These countries exported the largest number of cattle into GB and were not brucellosis free during the development of the assessment in 2000.) We predicted that we can expect to import brucellosis from Northern Ireland every 2.63 years (1.89, 4.17) and from the Republic of Ireland, every 3.23 years (2.13, 5.88). The estimates of risk are sensitive to the assumed proportion of animals missed during routine surveillance that originate from OBF herds and the uncertainty associated with the surveillance test sensitivities. As a result of the assessment, the Department for Environment, Food and Rural Affairs (Defra) introduced post-calving testing for all cattle imported into British herds.

A simulation model of brucellosis spread in British cattle under several testing regimes.

Brucellosis is a widespread, economically devastating and highly infectious zoonosis. In cattle, infection predominantly is caused by Brucella abortus, and is usually detected in pregnant females through abortions. Great Britain (GB) has been declared free from brucellosis (officially brucellosis free (OBF)) since 1993 and as such is required by European Union (EU) regulations to test > or =20% of both beef and dairy cattle >24 months old routinely. Currently, however, GB serologically tests more cattle than required and the issue of reducing the level of testing has come under consideration. We developed a simulation model to determine the rate of spread of brucellosis under a variety of testing regimes. For dairy herds, we found that reducing the level of testing would have a major effect on the rate of spread of infection, should it be imported. For beef herds, reducing the level of testing would have much less effect. We also found that abortion notification is a very-important additional means of surveillance. As a result of our predictions, policy-makers decided not to reduce the level of testing and actively to promote abortion notification.

Efficacy of an inactivated feline calicivirus (FCV) vaccine against challenge with United Kingdom field strains and its interaction with the FCV carrier state.

The efficacy of an inactivated vaccine derived from feline calicivirus (FCV) strain FS2 was assessed against challenge with three UK field strains of FCV. The mean clinical score, calculated on the number of signs recorded per day over 21 days after challenge, was lower for vaccinated cats when compared to unvaccinated animals though the difference was not statistically significant. All cats excreted FCV throughout the three weeks following challenge and there was no difference in the number of days of virus shedding during this period between vaccinated and unvaccinated animals. The development of FCV serum neutralising antibody titres following vaccination and challenge was recorded. In the second part of the study the ability of vaccinated and challenged cats to become FCV carriers and then infect susceptible in-contact animals was demonstrated.

European brown hare syndrome in England.

The livers from 50 brown hares (Lepus europaeus) were examined by electron microscopy for calicivirus-like particles typical of the virus of European brown hare syndrome (EBHS). The virus was visible in 23 of the livers which included four taken from hares which died in 1982 and 1985 and which had been stored at -20 degrees C. The clinical histories, post mortem and other findings associated with these 23 hares were similar to those described in cases of European brown hare syndrome in other European countries. The findings were compared with those associated with viral haemorrhagic disease (VHD) of rabbits which, although it did not occur in the United Kingdom until 1992, is also caused by a calicivirus believed to be related to EBHS virus. The finding of the virus in hares which died from the disease in 1982 is the earliest recorded isolation of the organism and predates the description of VHD virus and VHD in China in 1984. A retrospective review of post mortem reports revealed cases of disease between 1976 and 1977 which may have been due to EBHS and it is considered that the disease has occurred sporadically in England for several years. The results from suspected and confirmed cases of EBHS in England between 1976 and 1990 are reported and the epidemiology and emergence of the disease is considered.

Estimating the risk of importation of foot-and-mouth disease into Europe.

The opinions of a number of recognised world experts on foot-and-mouth disease (FMD) were sought in order to answer key questions relating to the importation of the disease into European countries from countries outside Europe. In addition, their opinions were sought on where in Europe a primary outbreak of FMD was most likely to occur and the number of outbreaks likely to occur within European countries in the next five years. The Balkans group of countries was considered to be the most likely group within Europe to have a primary outbreak of FMD and also most likely to have the highest number of primary outbreaks. Turkey was considered to be the country outside Europe which was most likely to be the source of an outbreak within Europe as a whole, and the illegal importation of livestock was considered to be the most likely route of introduction of FMD into Europe. Results specific to the Islands group of countries, which included the UK and Ireland, suggested that this group was likely to have a mean of one primary outbreak of FMD in the five years from September 2000, and that the importation of foodstuffs by people entering those countries from Turkey was the most likely source of an outbreak.

Natural scrapie in goats: case histories and clinical signs.

The case histories of the 20 goats affected with natural scrapie which have been examined since 1975 at the Central Veterinary Laboratory, Weybridge, are reviewed. Their ages ranged from two to seven years (median three years, four months) and 85 per cent of them were between two and four years old. The most common clinical signs were hyperaesthesia, ataxia and pruritus. The histories indicated that scrapie can occur in goats which have not been in contact with sheep.

Quantitative estimates of the risk of new outbreaks of foot-and-mouth disease as a result of burning pyres.

The risk of dispersing foot-and-mouth disease virus into the atmosphere, and spreading it to susceptible holdings as a result of burning large numbers of carcases together on open pyres, has been estimated for six selected pyres burned during the 2001 outbreak in the UK. The probability of an animal or holding becoming infected was dependent on the estimated level of exposure to the virus predicted from the concentrations of virus calculated by the Met Office, Bracknell. In general, the probability of infection per animal and per holding decreased as their distance from the pyre increased. In the case of two of the pyres, a holding under the pyre plumes became infected on a date consistent with when the pyre was lit. However, by calculating their estimated probability of infection from the pyres it was concluded that it was unlikely that in either case the pyre was the source of infection.

First isolation of a rabies-related virus from a Daubenton's bat in the United Kingdom.

On May 30, 1996, a sick Daubenton's bat (Myotis daubentonii) was recovered from the cellar of a public house in Newhaven, East Sussex. Its condition deteriorated rapidly, and it was euthanased and examined. Positive results, establishing the presence of a rabies or rabies-related virus in its brain, were obtained from the fluorescent antibody test, the rabies tissue culture isolation test, and a hemi-nested reverse-transcription PCR. The complete sequence of the nucleoprotein gene was determined and a phylogenetic analysis, based on the 470 nucleotide bases of the amino terminus of the nucleoprotein, established the genotype of the virus as European bat lyssavirus 2. Bat rabies had not previously been recorded in the UK but does occur in mainland Europe. A study of the back-trajectories of the wind on May 29 and 30, established that the infected bat possibly came from near the Franco-Swiss border.

Assessment of farm-level biosecurity measures after an outbreak of avian influenza in the United Kingdom.

During Avian Influenza outbreaks in England, the 'AI Order' states that a poultry keeper may be required to keep domestic birds separate from wild birds. This study aimed to assess a) how effectively this was done and b) the negative impact this had for bird owners and animal welfare during the November 2007 Highly Pathogenic Avian Influenza (HPAI) outbreak in Suffolk, UK. A voluntary questionnaire was posted to holdings (n=296) that were within 10 km of an infected premises; these holdings were required to separate domestic and wild birds where possible. Holdings were identified during outbreak investigations conducted by the authorities. Holdings of all sizes were included. A sample of holdings received a follow-up visit or telephone call to validate the questionnaire (n=29). From the 38% of eligible holdings that responded, 13% (95% CI 7-22%) left their birds outdoors throughout the outbreak. If game birds were excluded, 9% (CI 4-17%) of holdings did not house their birds. Major cost and welfare problems were rare; however, there were exceptions. Enforced housing was often relaxed before a minor welfare problem deteriorated. Contact between wild and domestic birds was greatly reduced during the outbreak, resulting in a reduced probability of HPAI transmission via wild birds for most, but not all, holdings.