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Cutting to the chase – how a folded piece of paper is saving lives

Cutting to the chase – how a folded piece of paper is saving lives

Around the world, many hundreds of millions of people are infected by parasitic diseases such as malaria and schistosomiasis. Many more millions of people are affected by the impact of these diseases with profound consequences in terms of education of children and economic sustainability of communities.

Early, accurate diagnosis is paramount for effective treatment, so we thought it was time that Bioscience Today shone a light on work ongoing to develop accessible, affordable tests for parasitic diseases.

We spoke to Professor Jonathan Cooper about a University of Glasgow-led project which is putting tests for parasitic diseases within easy reach of under-served communities in low and middle income countries. What may surprise you, is the material being harnessed to achieve this goal.

Jonathan holds the Wolfson Chair of Bioengineering and is Vice Principal of International Knowledge Exchange, with a long track record of translatable research. Working with Dr Julien Reboud, who has been central to many of the innovations, this latest project, depends on a material you may more readily associate with a craft project rather than the cutting edge of science – a folded piece of paper.

Yet it is just what the doctor ordered, for Jon’s team has designed a paper-based DNA diagnostic tests for a range of infectious diseases in humans and animals, which when combined with mobile phone-based imaging technology, provides rapid, very low cost point-of-care testing in remote locations – that enable informed decisions to be made around treatment.

“Microbial detection has often depended upon having infrastructure in place – whether to support the growth of bacteria in a lab for its subsequent detection or for genetic analysis. Recent efforts, however, have focused on enabling DNA analysis to happen at point of need settings, so patients can be treated quickly.

“Our project is taking DNA testing into communities – even where there is very little infrastructure, with no power or running water. Using the principles of paper-folding, we’ve developed very low-cost DNA-based tests that analyse the species of the micro-organism infecting patients. From just a finger-prick sample of blood, deposited on a piece of paper, we can inform the appropriate treatments for these infectious diseases.

“The tests are low-cost and user-friendly – enabling health workers to test entire communities that are at risk and live in remote areas, and the tests are easily and safely disposed of by burning. Perhaps most importantly, we have employed very accessible production techniques; using commercially available printing technologies to develop devices that would be easy to produce in countries where the disease elimination initiatives are taking place.

“After initial development in the UK, we tested our devices in the Mayuge District, on the banks of Lake Victoria, working with healthcare workers from Uganda’s Ministry of Health. The design of the device means that testing can be performed by a non-expert – using folding of the paper in a manner similar to origami to bring the sample and the reagents together and provide an answer.

“Importantly, we integrated the sample preparation into a easily-read device – akin to a conventional pregnancy test – so that untrained staff could easily read the result – with the appearance of coloured lines indicating the outcome.”

It is at this point that we ask Jonathan about schistosomiasis, a parasitic disease of which there is far less awareness than malaria. “It is one of the neglected diseases,” explains Jonathan, “as it is not widely recognised in terms of mortality, yet its impact is far-reaching in communities. New evidence is showing it may be involved in many co-morbitidies. For example, it most recently has been implicated in deaths associated with liver failure, especially in patients with hepatitis.

“Schistosomiasis is caused by a parasitic worm that lives in water, which infects humans and then lives in the vein surrounding the liver. The worms produce eggs continuously, which return to the lake, either through urine or faeces, where the offspring hatch and infect snails – going on to infect more humans.

“Many hundreds of millions of people are infected worldwide and the disease affects many hundreds of millions more, as it is physically debilitating, eroding the livelihoods of families and disrupting children’s education in schools. It also kills many, especially if patients have complicating diseases.”

The projects all began in a small way. “We were working in a laboratory with colleagues in Africa on a project with little funding,” explains Jonathan, “but all of that changed earlier this year when the project received £1.5m in funding.”

The Glasgow-led project was one of 15 projects to be awarded a share of £16m in funding from the Engineering and Physical Sciences Research Council (EPSRC) and the National Institute of Health Research (NIHR), all of which aim to tackle international health challenges.

The funding is part of the Global Challenges Research Fund (GCRF), a £1.5 billion government fund to support cutting-edge technology and methods that address challenges faced by low and middle income countries.

“The aim of which,” explains Jonathan, “is to support projects that change outcomes in low and middle income countries in producing healthcare and economic benefits. In our particular project, we aim to reduce the impact of these parasitic diseases on those affected: diseases which prevent children from going to school and adults from going to work, and hence have a huge impact on the community.”

The GCRF harnesses the strengths of the UK’s research base to support excellent, multidisciplinary research that addresses complex global development challenges. Funding for the project is part of the GCRF’s focus on the development of affordable, robust, reliable and portable imaging and diagnostics tools that can be used to diagnose and monitor both infectious and non-communicable diseases.

The project brings together the expertise of the University’s School of Engineering, Institute of Health and Wellbeing, and Institute of Biodiversity, Animal Health and Comparative Medicine, with Epigem Ltd, FIND, Omega Diagnostics (UK), the Gloag Foundation, The Ministry of Health in Uganda and the University of California Los Angeles. The Royal Academy of Engineering has also had a large role to play in the project, as Jonathan is quick to acknowledge.

Health Technology Assessment (HTA) methods are being used to identify, measure, and value the health and broader environmental and societal impacts resulting from the improved diagnosis and targeted treatment for both diseases. The team in Glasgow has demonstrated that the “origami” sensors can not only detect infectious diseases with the same sensitivities as the gold-standard laboratory methods, such as those using PCR amplification, but that the tests can be performed in under-served communities, where there are no power-supplies or infrastructure.

The tests have also been used to detect multiple infections simultaneously, providing healthcare teams with a new tool to carry out disease surveillance. It is now possible to visit a rural village and test and treat for two or more diseases that are co-endemic, or to monitor the decline in rates of infections as part of an elimination programme

What began as a small project in the Mayuge District of Uganda, is also starting to be used across more of Sub-Saharan countries including Tanzania as well as in parts of Asia, including China and India. The diagnostic devices are now also being adapted to diagnose other veterinary diseases, including those which infect livestock and which transfer disease from cattle to humans.

Moving forward, the hope is that at least some of those many hundreds of millions of people infected by parasitic diseases will benefit from informed, appropriate and rapid treatment, when they need it most – even where healthcare facilities are few and far between – in fact, especially when that is the case.

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