i-sense: EPSRC IRC in Agile Early Warning Sensing Systems for Infectious Diseases and Antimicrobial Resistance

In 2017 the need for disruptive sensing systems to detect and limit infectious outbreaks has taken centre stage - Zika virus and Ebola add to the threat of pandemic influenza, HIV and antimicrobial resistance, for which the world remains unprepared. Infections are a global problem and our response must therefore be global in nature. The House of Commons Ebola report recognised the 'heroic' work of scientists, researchers and agencies but highlighted that 'the UK response - like the international response - was undermined by systemic delay' and 'we must take the opportunity now to ensure that the UK is not caught unprepared when the next disease emergency strikes. Lives can be lost for every day of delay.'

The i-sense2 EPSRC IRC aims to engineer a new generation of agile and globally impactful early warning sensing systems for infectious diseases and antimicrobial resistance. We are harnessing the power of mobile phones, biomedical engineering, nanotechnology, genomics and big data to detect outbreaks much earlier than ever before. Next Steps funding is pivotal to; maximising the impact of our current IRC research programme, retaining key staff and delivering a step change in our capabilities to respond to emerging infections and antimicrobial resistance. This will in-turn leverage over £10M in translational 'test bed' infrastructure, new laboratories, academic positions, studentships and industry partnerships to help ensure our sustainability as a National Centre of Excellence.

We will build on our pioneering work within our current i-sense IRC which focused on three infectious diseases - influenza, HIV and C. difficile. The step change we now propose is to engineer more 'agile' systems that are rapidly adaptable to different diseases, antimicrobial resistant strains and different countries. Recognising the need to develop new systems through an understanding of context, i-sense2 brings together multiple disciplines, Public Health England, the Africa Health Research Institute, the Royal College of General Practitioners Research Surveillance Centre, the NIHR UCLH Biomedical Research Centre, and industry to:

1. Harness deep learning of millions of symptoms reported online (e.g. social media, searches) to track outbreaks, potentially before people visit their doctors and in resource-limited settings;
2. Build smartphone connected diagnostic tests to support front-line health-workers and self-testing. We will develop low-cost biobarcode paper microfluidic tests and handheld sequencing technologies to detect the earliest biomarkers of infection and drug-resistance, and securely send results to online infectious disease clinics;
3. Create state-of-the-art visualisation tools to link patients to treatment and map disease 'hot spots' by fusing mHealth, genomic, clinical and epidemiological data;
4. Invest in the careers of our talented researchers to become future leaders;
5. Grow a National Centre of Excellence supported by a plurality of funding.

Our disease focus will expand to influenza-like-illnesses, sexually transmitted infections and resistant-bacteria, as exemplars of acute, chronic and emerging infections. We will build population-level 'test beds' in the UK and South Africa, to pilot our technologies and then bid for next stage translational funding for clinical trials and product development. Future 'IRC Next Steps Plus Awards' will explore new research directions e.g. sensing systems for Ebola and Zika virus.

i-sense2 has the potential to bring major human and economic benefits to millions of people worldwide. Patients will benefit from receiving faster access to potentially life-saving treatment. Populations will benefit from reduced disease transmission, health systems will benefit from rapid diagnostics, and patient self-management. Industry will benefit from skilled people and new commercial opportunities. Public health will benefit from more timely interventions and pandemic preparedness.

The i-sense2 EPSRC IRC will combine cutting-edge UK research with world-leading partners to bring significant benefits to patients, the public, the NHS, Public Health England, the Africa Health Research Institute, industry, government, policy makers and regulators:

i. Patient benefit - The major beneficiaries will ultimately be patients who will benefit from rapid and reliable diagnosis of infection, and fast access to effective life-saving treatments with reduced morbidity or mortality, and improvements in quality of life.

ii. Public good - The public will benefit since early detection and diagnosis tends to curb the spread of infectious diseases, preserving the effectiveness of antimicrobials for future generations.

iii. NHS and global healthcare systems - will benefit from improved service delivery and sustainable models of community care. Widening access to testing for infectious diseases and AMR in community settings will enable more patients be tested and will increase the likelihood of identifying patients at an early acute stage where the risk of onwards transmission is high. Currently, unacceptably high numbers infections are undiagnosed or diagnosed at a late stage. Early diagnosis will enable more prompt treatment (improving health outcomes) and prevent onwards transmission. This could potentially reduce the economic cost of infectious diseases on the NHS and global healthcare system - for example, reducing hundreds of thousands of flu-related NHS GP appointments each winter, and reducing treatment costs (South Africa spends $1B per annum on HIV antiretroviral treatments). Moreover, the O'Neill Report suggests that rapid tests and better diseases surveillance, together with new antimicrobial treatments, could help to avert the estimated 10 million annual deaths related to AMR infections by 2050.

iv. Public-health benefits - include new tools to harness of millions of symptoms reported online, smartphone connected diagnostic self-tests, whole genome sequencing and data visualisation tools could transform the "active" real-time surveillance of infectious diseases and antimicrobial resistance, even for patients who do not attend clinics or from geographical regions outside the remit of conventional surveillance systems. Public Health England, the Africa Health Research Institute and global public health bodies, will benefit from the proposed early-warning sensing systems, enabling them to make more rapid, evidence-based clinical interventions and monitor the effect of these strategies in real-time

v. Commercial benefits - Beyond trained personnel, the potential commercial benefits to the UK and South Africa accrue through better population testing, prevention and care, and new employment opportunities in the emerging flourishing digital economy sector. Through our first workshop, planned at the end of year 1, we will reach out to industry and SMEs, including diagnostic test manufacturers, mobile network providers, handset manufacturers, app developers, policy makers and regulators to communicate developments in our understanding of the needs and technology developments to meet them and this will seed new collaborations, particularly with the digital, molecular and sequencing companies. The UK is at the forefront of the digital economy and 5G communication, and is well placed to grow commercial opportunities in this space. The work of i-sense2 will have commercial value and we will actively seek to exploit IP in conjunction with the partner institution Technology Transfer Offices - indeed spin outs and wealth creation for the UK will, in itself, form a major deliverable for i-sense2.

vi. Government, Policy Makers, Regulators and the media will benefit from balanced information about the facilitators and barriers to adoption and implementation of new products and practices, with the goal of responsible research innovation and lowering barriers to market entry for test developers and adoption.