Scholarly Works - Cambridge Infectious Diseases Consortium

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    Final CIDC Report to Defra
    (2010-11-30) Wood, James
    The Cambridge Infectious Diseases Consortium (CIDC) was established to provide a multi-institutional, world class quality environment for infectious disease research addressing important questions and for the recruitment and training of high quality veterinarians into careers in infectious disease research. The programme has been a demonstrable success in achieving these overall aims. The institutions that have played a key role in the consortium include the Department of Veterinary Medicine, the Department of Zoology and The Department of Pathology in the University of Cambridge, The Wellcome Trust Sanger Institute (WTSI), The Animal Health Trust, The Veterinary Laboratories Agency (VLA), The Institute of Animal Health (IAH), The Institute of Zoology (London: IOZ) and the University of Pretoria. In terms of research infrastructure, the programme has successfully consolidated or established research and education collaborations with all of the participating institutions, including VLA, IAH, IOZ, WTSI and AHT. Since the inception of CIDC, additional collaborative research funds have supported collaborative projects in infectious disease dynamics with all of these institutions. Subject areas have included bovine Tuberculosis, Bluetongue serotype-8 vaccination, bat rabies and other viral infections and swine and equine influenza. On the education and training front, the programme has successfully: a) introduced 23 veterinarians into research programmes (far more than the 14 initially planned for at the application stage); a further 2 veterinarians have been funded on other, external funds and 3 of the current fellowship have gained their own personal Fellowship funding from the Wellcome Trust and are now completing their PhDs within CIDC. Of the 22, 11 have successfully completed PhD or other programmes. These fellows have been placed in research programmes in 4 University of Cambridge departments, VLA, IAH, AHT, IOZ and Sanger (WTSI). Diseases studied have included Foot and Mouth Disease, avian influenza, swine and equine influenza, henipaviruses and rabies like viruses in bats, bovine Tuberculosis (problem herds) and Tuberculosis in wild living mammals (meerkats). Without specific additional funding, this programme will be difficult to sustain, although some aspects of it have been taken up by the Wellcome Trust. However, importantly, the programme has demonstrated very clearly that we can provide veterinarians with no prior research experience with an excellent training environment which can prepare them to be independent, internationally competitive research scientists. The success of the programme is demonstrated clearly by the positions that these graduate students have gone on to; 10 of these 11 are in fully funded postdoctoral positions, including within Defra funded programmes in VLA and IAH and on a number of Wellcome Trust programmes. A further 11 are still on time to complete. b) established a training programme for practicing veterinarians in clinical research methods and trained a large number (67) through this course. This is a far greater number than initially envisaged. The course is now a registered with the RCVS and a financial structure for its sustainability has been identified. c) established an infectious disease dynamics (DDU) / epidemiology unit in Cambridge University with links into several other departments which is now undertaking high quality infectious disease research in animals. The interactions of DDU members across the consortium has resulted in a substantial change in the nature of the science that others have been undertaking. Individuals in DDU have gained their own personal funds. A key infectious disease modelling course developed during the 5 years of the CIDC funding has now been taken up and run as a highly successful Wellcome Trust Advanced Course. The outputs from scientist have been published in highest ranking journals, including in the last 2 years in Science, PLoS Biology and Journal of the Royal Society Interface, as well as in many leading discipline specific journals such as Journal of Virology, Proceedings of Royal Society (B), Equine veterinary Journal, International Journal of Biostatistics and Vaccine. d) provided an excellent environment for post-doctoral training in infectious disease dynamics, with 2 of the post-docs working in CIDC programmes having gained their own Fellowship funding as a result (with further scientists being attracted in from the outside). Within the environment in Cambridge, this personal funding provides a key mechanism for sustaining the programme. e) established a new 3rd year undergraduate honours course, the Dynamics of Infectious Diseases (DID) course, focused on the dynamics of animal and zoonotic infections. Significant proportions (>25%) of all Cambridge veterinary students have been selecting this voluntary course, as well as a proportion of natural scientists and medical students. The course is now being sustained with support from the University. We have also provided high quality training in transboundary disease control, particularly for clinical veterinary students in their 5th year. Research The directly funded research programme in Mammalian Influenza A dynamics was the subject of a sub-contract with The Animal Health Trust in Newmarket. The programme has met all milestones and achieved all objectives in the funded programme of research in the quantitative dynamics of mammalian (swine and equine) influenza. In particular, we have: - successfully undertaken long chain influenza transmission studies in both pigs and horses with viruses adapted for transmission in the two respective species. Studies in both species were undertaken in both immunologically naïve animals, as well as in animals that had partial immunity derived from traditional vaccination approaches. These studies were designed to test the hypothesis that rates of within and between host adaptation, or mutation rates of the adapted viruses are higher in animals which have prior immunity which therefore drives selection, particularly at transmission. - with additional funding from the Wellcome Trust, including individual fellowships, successfully developed a sequencing pipeline at WTSI for deep sequencing analysis of the viral genetic diversity found within individual hosts. We have studied samples from pigs and horses infected in experiments by the natural respiratory contact transmission route and have also started to use the approach to study naturally occurring epidemics in both vaccinated (Newmarket) and naïve (Australian) hosts. The results have demonstrated that a) there is considerable diversity of viruses within natural hosts b) a considerable proportion of this diversity transmits, at least between immunologically naïve hosts and c) transmission chains longer than those practically achievable experimentally in large animals are often needed for changes at the consensus level to occur. This work has formed the basis for important aspects of the Combating Swine Influenza (COSI) awards. We have also studied adaptation of an avian virus in swine tissues including natural, air interface, pig tracheal explants. - demonstrated, using cutting edge antigenic cartographic methods, the key antigenic determinants in equine H3N8 influenza and how this virus has evolved over 40 years. It has also quantified issues of original antigenic sin following equine influenza vaccination which have broad applicability to the study of repeated dosing with multivalent vaccinal products. The programme has exceeded all commitments made through high quality delivery and generation of additional funding based on the core support from Defra and Hefce. It has has met all milestones agreed at the outset. Importantly, the highly successful fellowship programme has addressed the key objective of the Veterinary Training and Research Initiative (VTRI) in successfully demonstrating the potential for introducing large numbers of veterinarians into high quality research careers.