1. Global Health Diagnostics – Science or Fiction? 4 th IAS Conference on HIV Pathogenesis, Treatment and Prevention 22-25 July 2007 - Sydney, Australia Dr Penny Wilson Diagnostic Specialist, UK

2. The Golden Age of Diagnostics Diagnostics now a central and integral part of disease management. Driven by the human genome project, trends towards personalised medicine and economics. Contribute to:- –Diagnosis, prognosis and predisposition –Treatment selection –Drug monitoring –Assessing treatment efficacy, adverse side effects and drug resistance

3. Diagnostic Technologies (1) Trends are towards: –Miniaturisation (including POC devices), greater sensitivity, increased speed, decreased cost –Multiplexing/microarrays –Possible to sequence the human genome overnight by 2020 ? –Improved bioinformatic capabilities considered the rate limiting step by informatics companies

4. Diagnostic Technologies (2) Trends are towards: –Novel biomarkers Including non-invasive markers (eg VOCs) –Improved ICT capabilities at reduced cost –Development of technologies by companies outside the classical Diagnostic arena –Industry-wide trend towards interoperability Intellectual property, ROI and securing market share have inhibited this

5. Mobile Phone companies move to e-health Fitness and Lifestyle Preventative Healthcare Professional Diagnosis and Therapy Cambridge University and the MRC are developing a device to detect cancer and infectious diseases The technology utilises thin film transistors

6. Do these technological advances benefit the developing world or increase the North: South divide? Technologies are too costly for the developing world Designed for use by trained professionals in modern laboratories Third and fourth generation devices may be more cost effective (10 – 20 yrs) Devices for self-testing may offer robust solutions (lateral flow)

7. Commitment to disease futures “sustained action and coherent, multi-national cooperation to fully mobilize new and existing technical, medical and financial resources in the fight against infectious diseases” G8 Summit 2002 “improved international surveillance…intensification of scientific research … fulfilment of prior G8 commitments on the major infectious diseases” G8 Summit 2006

8. Global Activity Global Health The World Bank WHO The Bill & Melinda Gates Foundation The UK Foresight Programme (2006) OECD (2003) Institutes of Medicine, NAS studies (1992-2007) FIND Diagnostics

9. Malaria rapid diagnostics manufacturers: 1992 Becton Dickinson

10. Malaria rapid diagnostics manufacturers: 2002

11. Components of a Classical Diagnostic (pathogen detection/host response) Biomarker Sample type (and preparation) Technology for biomarker detection System for reporting presence of biomarker Infrastructure for delivering appropriate response THESE COMPONENTS ARE UNIVERSAL

12. Test characteristics include Sensitivity Specificity Time to first result Through- put Requirement for electricity, reagents (including clean water) and auxiliary equipment Level of training required to run test COST

14. Infrastructural Levels Lab InfrastructureHealthcare setting (personnel) None Community or home (pharmacist, family member, healthcare worker) Minimal Health clinics in Africa /rural clinics in Latin America & Asia (nurse) Moderate to Advanced Hospitals in Africa/urban clinics in Latin America & Asia (nurses, technicians, physicians)

15. Infrastructural Levels (2) 123 Electricity and clean water XUnreliableDependable Personnel No trained Minimal trained Trained Lab spaceX Minimal or none Dedicated Cold storageXOccasionallyAvailable RT controlXRarelySometimes

16. Infrastructural Levels (3) 123 VenipunctureImpossibleUnlikelyRoutine Sputum processing ImpossibleDifficult Acceptable (not children) Acceptable time to result < 1 hour< I hour Clinic < 1h Hospital – not critical Physician oversight None Routine

17. The Ideal Diagnostic - ASSURED Affordable Sensitive Specific User-friendly Rapid and Robust Equipment -free Delivered to those who need it. Developed by WHO

19. H207

20. Quantum leaps will benefit the developing world

21. Impact of improved HIV test in infants

22. Foresight Infectious Diseases: preparing for the future OFFICE OF SCIENCE AND INNOVATION Foresight “Creates challenging visions of the future to inform effective strategies now.” Infectious Disease Project: Key Question: How can we use science and technology to improve our capability for detecting, identifying and monitoring infectious diseases in order to improve control? Ultimate goal: To detect all known and unknown infectious diseases, of plants animals and humans, in ~ 30 years.

23. Foresight Infectious Diseases: preparing for the future OFFICE OF SCIENCE AND INNOVATION User Challenges UC1: Novel information technology for the capture, analysis and modelling of data for the early detection of infectious disease events. UC2: Early detection and characterisation of new or newly resistant/virulent pathogens using genomics and post genomics. UC3: Taking technology for identification and characterisation of infectious diseases to individuals by designing smart swabs, hand-held or portable devices that analyse fluids. UC4: High throughput screening for infectious diseases of people, animals and plants using surrogate, non-invasive markers (e.g. electromagnetic radiation, volatiles), for example in airports, containers and livestock markets.

24. User Challenge Roadmaps – basic template Now5 Near1025-3020 Systems Applications Technologies Drivers and trends Time (Years)

25. UC3 Roadmap (section) Applications Technologies “Time” Standard platforms agreed Wild animal surveillance defines zoonotic hot- spots. Lab informs design of screening test Animal biomarkers for pathogens Detection of pre- symptomatic disease and host susceptibility Novel sequencing/detection technologies Devices for increasing numbers of known diseases available. Trend from stand- alone to ICT integrated devices and from professional to non-skilled users Smart objects Trend from PCR to robust simple amplification technologies and systems capable of functioning in extreme environmental conditions Devices for novel human diseases ICT type systems mature enabling full integration of POC devices with global networks Devices for all known pathogens available. Output fully integrated into international networks maximising data utility etc Immune signatures of animal infectious diseases emerging Immune signatures of human infectious diseases emerging Systems

26. Roadmap for using handheld/portable devices for the detection, identification and monitoring of infectious diseases in plants, animals and humans (Fig. 1) Growing market in personal healthcare, driven by devices for management of chronic diseases, general wellbeing and lifestyle Nanotechnologies, microfluidics, MEMS, developed for other markets allow reduction in sensor size and improved capabilities Decreasing size and cost of GC-MS - driven by space flight, environmental and homeland security Drivers and trends Systems Applications Technologies Animal DIM mainly by symptoms, not biomarkers NowNear1025-3020 Standard platforms agreed Wild animal surveillance defines zoonotic hot-spots. Lab informs design of screening test Animal biomarkers for pathogens Detection of pre- symptomatic disease and host susceptibility Novel sequencing/detection technologies Devices for increasing numbers of known diseases available. Trend from stand-alone to ICT integrated devices and from professional to non-skilled users Smart objects POC devices for non-ID applications eg. SMBG and pregnancy tests Mobile telephony and pervasive computing allow more rapid networking and greater local data and processing power Trend from PCR to robust simple amplification technologies and systems capable of functioning in extreme environmental conditions Cheaper microfluidic based biosensor technologies for nucleic acid and protein determination POC technologies available for DIM but limited POC devices emerge for professional use Mobile phones measure pulse, blood pressure etc Devices for novel human diseases ICT type systems mature enabling full integration of POC devices with global networks Devices for all known pathogens available. Output fully integrated into international networks maximising data utility etc Immune signatures of human infectious diseases emerging Immune signatures of animal infectious diseases emerging Devices linked to networks Stand-alone devices POC devices KEY

27. Culture and governance issuesSSAChinaUK Governance International+++++ Regional/supra-national groupings+++ National++ +++ Local/provisional+++++ Ability to implement measures through legal or coercive measures ++++++ DIM interaction with control mechanisms++++++ Investment in science and technology++++++ Data-sharing culture++++++ Socialaspects Religious and societal beliefs/concerns+++ + limited influence +++ prominent influence Greater importance In 10 – 25 yrs

28. In Conclusion The concept of Global Health Diagnostics is deeply embedded in science and is certainly not fiction Diagnostic tools will provide only part of the solution, their impact will depend on the disease management infrastructure into which they are deployed, including the availability of appropriate therapies.