(Plenary) From Gene to Device: The Route to Diagnostics in Low Resource Countries

Abstract

Infectious diseases remain a major cause of morbidity and mortality in the low income countries. Patients present with fever, which is difficult to diagnose without specialist laboratory tests. This results in presumptive diagnosis and treatment, which may be incorrect. Without tools to identify infection, antibiotic administration is an attractive generic treatment. The situation is similar for non-communicable diseases. Thus, instead of having accurate diagnosis, patients are more often managed based on probability and clinical judgment. The healthcare economics therefore make antibiotic administration an attractive generic treatment, but now antibiotic resistance is so serious that in some regions half the patients with pneumonia do not respond to the first-line antibiotics. There have been numerous attempts to propose low cost diagnostics for LMICs, but when they are produced in high income countries they remain at high cost when taken in the local context. The required biological reagents for a diagnostic is often be the largest proportion of its total cost (eg >80% in the Philippines for a polymerase in a nucleic acid test, and similar price to US/ Europe, despite the average household income being 80-90% lower). We have revisited the ‘unaffordable’ diagnostics and created a novel design that can be manufactured locally, with only basic infrastructure. We have used synthetic biology to design a protein fusion for nucleic acid amplification, that incorporates locally resourced materials and is targeted to easy local production in resource poor areas.By taking a ‘gene to diagnostic’ approach, a rational design will be discussed for a diagnostic platform that uses a multifunctional fusion enzyme for point-of-care diagnostics. The platform is demonstrated in nucleic acid tests for leptospirosis, dengue and malaria and a device for sarcosine determination in urine presented (as a marker of early-stage prostate cancer). We have the first step towards providing low cost diagnostics in resource poor areas, which could deliver a sustained improvement in healthcare, while also developing the local economy.