Sampling Frames
Appropriate sampling frames have been identified for each organism. In order to determine transmission characteristics and rates, consecutive samples from potential donors and all identified recipients in an area of transmission are being collected together with appropriate clinical details (potential risk factors for acquisition of pathogen, development of disease and infectiousness), basic demographics and time/space information (including date of hospital admission, date of last hospital admission, dates and times of all ward movements since admission).
Sequencing Platforms
We have access to a range of whole genome sequencing platforms including Illumina Solexa Genome Analyzer II sequencing system, Illumina MiSeq personal sequencing system, and the Roche 454 Genome Sequencer FLX next generation sequencers. All of the pathogens are being sequenced using next generation sequencing.
Further, the translation of sequence-based typing from whole genome sequencing into clinical practice via interrogation of databases by individual practitioners will be a major behaviour change much anticipated by the NHS clinical record system. This is an opportunity to study and optimise approaches for successful adoption of new technologies.
Bioinformatics and databases
The four exemplar organisms provide a representative range of challenges for the development of a coherent unified informatics platform that could be extended to infectious disease caused by any organism. This includes linked databases for management of large sequence and epidemiological datasets, software tools for general and specific bioinformatic and modelling needs, and a web platform to provide access for clinicians and scientists to upload local data, and view national data and local analyses and predictions. These activities are under considerable development, synergising with ongoing projects at the HPA, and Oxford University.
One goal is to develop web-accessible informatics tools which are attractive and easy-to-use, enabling local practitioners to direct their routine infection control practice efficiently; but which are based on a platform that is flexible enough to add further types of data, scaleable for implementation across UK NHS service, and modular, to allow changes that can enable generalisation across the whole range of infection surveillance.
Association studies
The samples accumulated by the consortium will be a UK representative resource providing a unique research opportunity for years to come, direct for association studies assessing the impact of host and microbial factors on pathogenesis. Organism-specific sampling frames will also be developed for association studies, and both isolates and samples of host DNA as well as clinical data will be archived specifically for human and pathogen association studies throughout the project for S. aureus, C. difficile and Norovirus following the appropriate ethical approval.
