Evaluating vaccination strategies to control foot-and-mouth disease: a country comparison study.

Vaccination is increasingly being recognised as a potential tool to supplement 'stamping out' for controlling foot-and-mouth disease (FMD) outbreaks in non-endemic countries. Infectious disease simulation models provide the opportunity to determine how vaccination might be used in the face of an FMD outbreak. Previously, consistent relative benefits of specific vaccination strategies across different FMD simulation modelling platforms have been demonstrated, using a UK FMD outbreak scenario. We extended this work to assess the relative effectiveness of selected vaccination strategies in five countries: Australia, New Zealand, the USA, the UK and Canada. A comparable, but not identical, FMD outbreak scenario was developed for each country with initial seeding of Pan Asia type O FMD virus into an area with a relatively high density of livestock farms. A series of vaccination strategies (in addition to stamping out (SO)) were selected to evaluate key areas of interest from a disease response perspective, including timing of vaccination, species considerations (e.g. vaccination of only those farms with cattle), risk area vaccination and resources available for vaccination. The study found that vaccination used with SO was effective in reducing epidemic size and duration in a severe outbreak situation. Early vaccination and unconstrained resources for vaccination consistently outperformed other strategies. Vaccination of only those farms with cattle produced comparable results, with some countries demonstrating that this could be as effective as all species vaccination. Restriction of vaccination to higher risk areas was less effective than other strategies. This study demonstrates consistency in the relative effectiveness of selected vaccination strategies under different outbreak start up conditions conditional on the assumption that each of the simulation models provide a realistic estimation of FMD virus spread. Preferred outbreak management approaches must however balance the principles identified in this study, working to clearly defined outbreak management objectives, while having a good understanding of logistic requirements and the socio-economic implications of different control measures.

Comparison of alternatives to passive surveillance to detect foot and mouth disease incursions in Victoria, Australia.

This study aimed to evaluate strategies to enhance the early detection of foot and mouth disease incursions in Australia. Two strategies were considered. First, improving the performance of the current passive surveillance system. Second, supplementing the current passive system with active surveillance strategies based on testing animals at saleyards or through bulk milk testing of dairy herds. Simulation modelling estimated the impact of producer education and awareness by either increasing the daily probability that a farmer will report the presence of diseased animals or by reducing the proportion of the herd showing clinical signs required to trigger a disease report. Both increasing the probability of reporting and reducing the proportion of animals showing clinical signs resulted in incremental decreases in the time to detection, the size and the duration of the outbreak. A gold standard system in which all producers reported the presence of disease once 10% of the herd showed clinical signs reduced the median time to detection of the outbreak from 20 to 15days, the duration of the subsequent outbreak from 53 to 42days and the number of infected farms from 46 to 32. Bulk milk testing reduced the median time to detection by two days and the number of infected farms by six but had no impact on the duration of the outbreak. Screening of animals at saleyards provided no improvement over the current passive surveillance system alone while having significant resource issues. It is concluded that the most effective way to achieve early detection of incursions of foot and mouth disease into Victoria, Australia is to invest in improving producer reporting.

Evaluating vaccination strategies to control foot-and-mouth disease: a model comparison study.

Simulation models can offer valuable insights into the effectiveness of different control strategies and act as important decision support tools when comparing and evaluating outbreak scenarios and control strategies. An international modelling study was performed to compare a range of vaccination strategies in the control of foot-and-mouth disease (FMD). Modelling groups from five countries (Australia, New Zealand, USA, UK, The Netherlands) participated in the study. Vaccination is increasingly being recognized as a potentially important tool in the control of FMD, although there is considerable uncertainty as to how and when it should be used. We sought to compare model outputs and assess the effectiveness of different vaccination strategies in the control of FMD. Using a standardized outbreak scenario based on data from an FMD exercise in the UK in 2010, the study showed general agreement between respective models in terms of the effectiveness of vaccination. Under the scenario assumptions, all models demonstrated that vaccination with 'stamping-out' of infected premises led to a significant reduction in predicted epidemic size and duration compared to the 'stamping-out' strategy alone. For all models there were advantages in vaccinating cattle-only rather than all species, using 3-km vaccination rings immediately around infected premises, and starting vaccination earlier in the control programme. This study has shown that certain vaccination strategies are robust even to substantial differences in model configurations. This result should increase end-user confidence in conclusions drawn from model outputs. These results can be used to support and develop effective policies for FMD control.

Assessing the risk of Nipah virus establishment in Australian flying-foxes.

Nipah virus (NiV) is a recently emerged zoonotic virus that causes severe disease in humans. The reservoir hosts for NiV, bats of the genus Pteropus (known as flying-foxes) are found across the Asia-Pacific including Australia. While NiV has not been detected in Australia, evidence for NiV infection has been found in flying-foxes in some of Australia's closest neighbours. A qualitative risk assessment was undertaken to assess the risk of NiV establishing in Australian flying-foxes through flying-fox movements from nearby regions. Events surrounding the emergence of new diseases are typically uncertain and in this study an expert opinion workshop was used to address gaps in knowledge. Given the difficulties in combining expert opinion, five different combination methods were analysed to assess their influence on the risk outcome. Under the baseline scenario where the median was used to combine opinions, the risk was estimated to be very low. However, this risk increased when the mean and linear opinion pooling combination methods were used. This assessment highlights the effects that different methods for combining expert opinion have on final risk estimates and the caution needed when interpreting these outcomes given the high degree of uncertainty in expert opinion. This work has provided a flexible model framework for assessing the risk of NiV establishment in Australian flying-foxes through bat movements which can be updated when new data become available.

Options for managing animal welfare on intensive pig farms confined by movement restrictions during an outbreak of foot and mouth disease.

An outbreak of foot and mouth disease in Australia would trigger a major disease control and eradication program that would include restriction of movement of live animals within defined disease control zones. Experiences from outbreaks in other countries show that restrictions that limit the ability to turn off stock can lead to animal welfare compromise on intensively managed farms that are not infected with the disease. Intensive pig farms are considered to be at high risk of developing welfare problems during a control program due to the imposed movement restrictions and limited space available to house growing pigs. This study was designed to investigate strategies that could be used to mitigate animal welfare problems on intensive pig farms during a simulated outbreak of foot and mouth disease in a livestock dense region of Australia. Three strategies for managing farms affected by animal welfare problems were assessed, including on-farm culling of grower and finisher pigs, on-farm culling of finisher pigs only, and permit-based movement of finisher pigs to slaughter at abattoir. Under traditional approaches of giving infected premises (IP) priority over culling of farms with welfare problems (WP), delays of up to 25 days were experienced prior to culling of WPs. Deployment of vaccination did little to reduce the delay to culling of WPs. These delays were sensitive to resources available for control, with reduced resources increasing the time until welfare problems were addressed. Assigning equal priority to all farms requiring culling regardless of status as IP or WP and culling each as they arose reduced the delay to culling of WPs to no more than 4 days without large increases in either the duration or the size of the outbreaks observed.

How do resources influence control measures during a simulated outbreak of foot and mouth disease in Australia?

An outbreak of foot and mouth disease (FMD) could seriously impact Australia's livestock sector and economy. As an FMD-free country, an outbreak would trigger a major disease control and eradication program that would include the culling of infected and at risk animals ('stamping out'), movement restrictions and zoo-sanitary measures. Additional control measures may also include pre-emptive culling or vaccination. However, it is unclear what disease strategy would be most effective under Australian conditions and different resource levels. Using a stochastic simulation model that describes FMD transmission between farms in a livestock dense region of Australia, our results suggest that using current estimates of human resource capacity for surveillance, infected premises operations and vaccination, outbreaks were effectively controlled under a stamping out strategy. However, under more constrained resource allocations, ring vaccination was more likely to achieve eradication faster than stamping out or pre-emptive culling strategies.

Descriptive overview of the 2011 epidemic of arboviral disease in horses in Australia.

OBJECTIVE: To provide an overview and descriptive analysis of the 2011 arboviral disease epidemic in horses that involved three important Australian mosquito-borne viruses: Murray Valley encephalitis virus, West Nile virus (Kunjin strain) and Ross River virus. METHODS: Data from states affected between January and June 2011 were collated and comprised reports of horses showing signs of neuromuscular disease and the associated laboratory findings. A summary of the data is presented, together with a spatiotemporal analysis of cases and preliminary assessment of rainfall patterns and case distribution. RESULTS: A total of 982 cases of equine arboviral disease were reported across Australia between January and June 2011. The majority of cases were reported from south-east Australia and included horses that developed neurological signs consistent with encephalitis. It was the largest epidemic of equine arboviral disease in Australia's history. Two likely causes for this unprecedented epidemic were the unusual weather events that preceded the epidemic and the emergence of a new strain of Kunjin virus. CONCLUSIONS: The epidemic highlights to horse owners and policy makers the potential for future outbreaks of arboviral diseases and the need for vigilance. It also highlights the complex interactions among hosts, vectors and climatic conditions that are required for such an outbreak to occur.

Trans-silencing by P elements inserted in subtelomeric heterochromatin involves the Drosophila Polycomb group gene, Enhancer of zeste.

Drosophila P-element transposition is regulated by a maternally inherited state known as P cytotype. An important aspect of P cytotype is transcriptional repression of the P-element promoter. P cytotype can also repress non-P-element promoters within P-element ends, suggesting that P cytotype repression might involve chromatin-based transcriptional silencing. To learn more about the role of chromatin in P cytotype repression, we have been studying the P strain Lk-P(1A). This strain contains two full-length P elements inserted in the heterochromatic telomere-associated sequences (TAS elements) at cytological location 1A. Mutations in the Polycomb group gene (Pc-G gene), Enhancer of zeste (E(z)), whose protein product binds at 1A, resulted in a loss of Lk-P(1A) cytotype control. E(z) mutations also affected the trans-silencing of heterologous promoters between P-element termini by P-element transgenes inserted in the TAS repeats. These data suggest that pairing interactions between P elements, resulting in exchange of chromatin structures, may be a mechanism for controlling the expression and activity of P elements.

P-element repressor autoregulation involves germ-line transcriptional repression and reduction of third intron splicing.

P cytotype is a regulatory state, characteristic of Drosophila P-strain females, in which P-element transposition is repressed. P cytotype is established maternally in the germ line but is also dependent on the presence of P elements in the zygote. One aspect of P cytotype involves transcriptional repression of the P-element promoter. Here, we show that transcriptional repression by P cytotype in the female germ line occurs by a general promoter-independent mechanism with heterologous promoters carried in P-element vectors. P-cytotype transcriptional repression results in low levels of pre-mRNA and a reduction in splicing of the P-element third intron (IVS3)-containing mRNA, thus causing an increase in the proportion of 66-kD repressor mRNA. Increased retention of IVS3 in P cytotype would result in an autoregulatory loop of 66-kD repressor production. This combination of germ-line transcriptional repression and splicing control provides a mechanism to maintain repression during the maternal inheritance of P cytotype. These findings suggest that transcriptional repression may play an additional role in the regulation of gene expression, namely allowing alteration of pre-mRNA splicing patterns.

The conserved pre-mRNA splicing factor U2AF from Drosophila: requirement for viability.

The large subunit of the human pre-messenger RNA splicing factor U2 small nuclear ribonucleoprotein auxiliary factor (hU2AF65) is required for spliceosome assembly in vitro. A complementary DNA clone encoding the large subunit of Drosophila U2AF (dU2AF50) has been isolated. The dU2AF50 protein is closely related to its mammalian counterpart and contains three carboxyl-terminal ribonucleoprotein consensus sequence RNA binding domains and an amino-terminal arginine- and serine-rich (R/S) domain. Recombinant dU2AF50 protein complements mammalian splicing extracts depleted of U2AF activity. Germline transformation of Drosophila with the dU2AF50 complementary DNA rescues a lethal mutation, establishing that the dU2AF50 gene is essential for viability. R/S domains have been found in numerous metazoan splicing factors, but their function is unknown. The mutation in Drosophila U2AF will allow in vivo analysis of a conserved R/S domain-containing general splicing factor.