Simon Gubbins

Assessing the risk of bluetongue to UK livestock: uncertainty and sensitivity analyses of a temperature-dependent model for the basic reproduction number

Since 1998 bluetongue virus (BTV), which causes bluetongue, a non-contagious, insect-borne infectious disease of ruminants, has expanded northwards in Europe in an unprecedented series of incursions, suggesting that there is a risk to the large and valuable British livestock industry. The basic reproduction number, R0, provides a powerful tool with which to assess the level of risk posed by a disease. In this paper, we compute R0 for BTV in a population comprising two host species, cattle and sheep. Estimates for each parameter which influences R0 were obtained from the published literature, using those applicable to the UK situation wherever possible. Moreover, explicit temperature dependence was included for those parameters for which it had been quantified. Uncertainty and sensitivity analyses based on Latin hypercube sampling and partial rank correlation coefficients identified temperature, the probability of transmission from host to vector and the vector to host ratio as being most important in determining the magnitude of R0. The importance of temperature reflects the fact that it influences many processes involved in the transmission of BTV and, in particular, the biting rate, the extrinsic incubation period and the vector mortality rate.

Bovine Plasmacytoid Dendritic Cells Are the Major Source of Type I Interferon in Response to Foot-and-Mouth Disease Virus In Vitro and In Vivo

ABSTRACT Type I interferons (alpha/beta interferons [IFN-α/β]) are the main innate cytokines that are able to induce a cellular antiviral state, thereby limiting viral replication and disease pathology. Plasmacytoid dendritic cells (pDCs) play a crucial role in the control of viral infections, especially in response to viruses that have evolved mechanisms to block the type I IFN signal transduction pathway. Using density gradient separation and cell sorting, we have highly enriched a population of bovine cells capable of producing high levels of biologically active type I IFN. These cells represented less than 0.1% of the total lymphocyte population in blood, pseudoafferent lymph, and lymph nodes. Phenotypic analysis identified these cells as bovine pDCs (CD3− CD14− CD21− CD11c− NK− TCRδ− CD4+ MHC II+ CD45RB+ CD172a+ CD32+). High levels of type I IFN were generated by these cells in vitro in response to Toll-like receptor 9 (TLR-9) agonist CpG and foot-and-mouth disease virus (FMDV) immune complexes. In contrast, immune complexes formed with UV-inactivated FMDV or FMDV empty capsids failed to elicit a type I IFN response. Depletion of CD4 cells in vivo resulted in levels of type I IFN in serum early during FMDV infection that were significantly lower than those for control animals. In conclusion, pDCs interacting with immune-complexed virus are the major source of type I interferon production during acute FMDV infection in cattle.

Quantitative assessment of the probability of bluetongue virus overwintering by horizontal transmission: application to Germany

Even though bluetongue virus (BTV) transmission is apparently interrupted during winter, bluetongue outbreaks often reappear in the next season (overwintering). Several mechanisms for BTV overwintering have been proposed, but to date, their relative importance remain unclear. In order to assess the probability of BTV overwintering by persistence in adult vectors, ruminants (through prolonged viraemia) or a combination of both, a quantitative risk assessment model was developed. Furthermore, the model allowed the role played by the residual number of vectors present during winter to be examined, and the effect of a proportion of Culicoides living inside buildings (endophilic behaviour) to be explored. The model was then applied to a real scenario: overwintering in Germany between 2006 and 2007. The results showed that the limited number of vectors active during winter seemed to allow the transmission of BTV during this period, and that while transmission was favoured by the endophilic behaviour of some Culicoides, its effect was limited. Even though transmission was possible, the likelihood of BTV overwintering by the mechanisms studied seemed too low to explain the observed re-emergence of the disease. Therefore, other overwintering mechanisms not considered in the model are likely to have played a significant role in BTV overwintering in Germany between 2006 and 2007.

Assessing the consequences of an incursion of a vector-borne disease: I. Identifying feasible incursion scenarios for bluetongue in Scotland

Following the arrival of bluetongue virus serotype 8 (BTV-8) in southeast England in September 2007, the Scottish Government commissioned research to assess the economic consequences of a BTV-8 incursion to Scotland. Here we present the first component of the assessment, which entailed identifying feasible incursion scenarios for the virus. Our analyses focused on three routes of introduction: wind-borne dispersal of infected vectors, import of infected animals and northwards spread of BTV from affected areas in GB. These analyses were further refined by considering the spatial and temporal variation in the probability of onward transmission from an initial incursion.

Prevalence of sheep infected with classical scrapie in Great Britain: integrating multiple sources of surveillance data for 2002

Estimates for the prevalence of sheep infected with classical scrapie are essential for assessing the efficacy of control strategies that have been implemented in Great Britain (GB). Here a back-calculation approach was used to estimate the prevalence in the GB national flock by integrating data on reported cases and the results of abattoir and fallen stock surveys for 2002. Prevalence estimates ranged from 0.33 to 2.06%, depending on the estimates used for the frequencies of prion protein (PrP) genotypes in the national flock and the stage of incubation at which the diagnostic tests used are able to detect infected animals. The risk of infection was found to be higher than that of clinical disease, especially in those PrP genotypes that have a later age at onset of clinical disease. Moreover, results suggest that a high proportion (more than 55%) of infected animals surviving to disease onset die on farm before clinical signs become apparent, which helps account for the high observed prevalence in the fallen stock compared with the abattoir survey. The analyses indicated that attention needs to be given to identifying the stage of incubation at which diagnostic tests are able to detect infected animals and obtaining better demographic data for the GB national flock.

Cattle remain immunocompetent during the acute phase of foot-and-mouth disease virus infection

Infection of cattle with foot-and-mouth disease virus (FMDV) results in the development of long-term protective antibody responses. In contrast, inactivated antigen vaccines fail to induce long-term protective immunity. Differences between susceptible species have also been observed during infection with FMDV, with cattle often developing persistent infections whilst pigs develop more severe symptoms and excrete higher levels of virus. This study examined the early immune response to FMDV in naïve cattle after in-contact challenge. Cattle exposed to FMDV were found to be viraemic and produced neutralising antibody, consistent with previous reports. In contrast to previous studies in pigs these cattle did not develop leucopenia, and the proliferative responses of peripheral blood mononuclear cells to either mitogen or third party antigen were not suppressed. Low levels of type 1 interferon and IL-10 were detected in the circulation. Taken together, these results suggest that there was no generalised immunosuppression during the acute phase of FMDV infection in cattle.

Demographic characteristics of scrapie-affected holdings identified by active and passive surveillance schemes in Great Britain: 2002–2005

Several surveillance techniques have been used to quantify the prevalence of both classical and atypical scrapie in British sheep, namely the recording of clinical suspects (RC) and the testing of animals slaughtered at abattoir (AS) or reported as fallen stock (FS). Any estimate of prevalence based on a particular source is likely to have been affected by demographic differences in the populations sampled. In this study, the demographic characteristics of scrapie-affected holdings detected by each of the surveillance streams (RC, AS, FS) in Great Britain were compared. Analyses of all three streams indicated that the probability of an affected holding being detected by a particular stream differed by geographical area, the number of animals brought onto the holding, the type of scrapie identified (classical vs. atypical) and the year. More detailed analysis of AS and FS suggested that the annual and regional differences between these surveys could be explained by differences in sampling effort.