(Plenary) From Gene to Device: The Route to Diagnostics in Low Resource Countries
Authors: Hall Lisa , Seevaratnam Dushanth , Henderson Cassi , Daly Ronan , Ansah Felix , Awandare Gordon 
Published: July 2021

Infectious diseases remain a major cause of morbidity and mortality in the low income countries.
Patients present with fever and non-specific symptoms,

which are 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. Chronic non-communicable disease is also under monitored in low income countries (LICs). For example, in a study in Mozambique only 6% of facilities could carry out a blood glucose analysis and personal monitoring is not generally available.

Thus, instead of having accurate diagnosis, patients are more often managed based on probability and clinical judgment. The healthcare economics can 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 low and middle income countries (LMICs), but a barrier to low-cost diagnostics, especially in LICs, arises through purchases from the west, without Purchasing Power Parity. When diagnostics are produced in high income countries they remain at high cost when taken in the local affordability context. The required biological reagents for a diagnostic are often the largest proportion of its total cost (eg >80% in the Philippines for a polymerase in a nucleic acid test, and a similar price to US/ Europe, despite the average household income being 80-90% lower).

We have revisited the ‘unaffordable’ diagnostics and created a design with reagents that can be manufactured locally, with only basic infrastructure. For example, we have used synthetic biology to design a polymerase fusion for nucleic acid amplification, that incorporates locally resourced materials and is targeted to easy local production in resource poor areas.

We will report on a ‘gene to diagnostic’ approach with a multifunctional fusion enzyme as the central reagent in point-of-care diagnostics. The components of the fusion are a functional assay protein reagent, a visualising unit and an in-built immobilisation peptide. This reduces downstream isolation steps and eliminates expensive coupling chemicals for integration in a diagnostic. In-built production monitoring and QA for the analytical reagent product is shown with the visualising protein.

The platform is demonstrated in nucleic acid tests for leptospirosis and malaria as well as a device for sarcosine determination in urine (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. Data from a clinical trial of a nucleic acid amplification test, designed for malaria screening in Africa will be presented and the first reports of the latter nucleic acid test which is beginning trials in Ghana for Covid-19.