Integrated ultrasonic biosensing for point-of-care diagnostics

Lead Research Organisation: University of Glasgow
Department Name: School of Engineering

Abstract

Context Nearly 260 million people are infected with schistosomiasis with >90% of infections found in sub-Saharan Africa. There is a need to develop new highly sensitive diagnostic methods that enable to monitor treatment outcomes, with the specific aims of (i) preventing re-emergence of infections following local treatment; and (ii) reducing resistance by ensuring effective and appropriate treatment.
Aims: We will develop a new low-cost, rapid (<30 min), point-of-care, highly sensitive stool-based test which the ability to detect S. mansoni (eggs), and Schistosoma hybrids using a paper based (low cost) DNA assay based upon isothermal amplification (e.g. LAMP). The device will separate the eggs, lyse the sample and detect species specific DNA. We aim to obtain initial proof-of-concept data of the performance of the device in the field in Uganda on patients' samples. To our knowledge, this will be the first instance of these low cost methods for looking at stool based samples and has the future potential applications in a range of other helminth infections.

The schistosoma live in the hepatic portal vein and shed cells into the blood. In parallel with the stool test, we will therefore also develop a blood based assay, where DNA will be detected from a fingerpick of blood. The assay will again be configured as a low cost, paper based assay and will be developed as a duplex, enabling both malaria and bliharzia (schistosomiasis) to be detected at the same time. This will guide appropriate treatment for febrile patients

Through enabling low-cost, point-of-care genomic diagnostics, the project aligns specifically with EPSRC's Healthcare Technology theme, including optimising treatment by monitoring efficacy, developing capabilities in priority research areas such as Engineering and Sensors. This research is based on fundamental developments in SAW made in EPSRC-funded activity (Cooper fellowship, Proxomics project).

Benefits: This project is aligned with the Health priority of the Global Challenge Fund, which aims 'to tackle diseases, strengthen health systems and reach the worlds' most vulnerable'. Inded, according to the latest WHO estimates, at least 258 million people have required treatment for Schistosomiasis in 2014, with 61.6 million people reported to be treated. 90% of those requiring treatment live in Africa. In children, Schistosomiasis causes anaemia, stunted growth and reduced ability to learn. Treatment usually reverses these effects, but its efficacy need to be monitored to establish cure and adapt therapy. If untreated, chronic disease affects people's ability to work and can result in death. The disease burden has been estimated to account for 4.5 million DALYs (disability affected life years).

Mass drug administration of praziquantel has been delivered through National Control Programmes in Uganda for over a decade. Hotspots of infection have been detected, where prevalence, intensity and associated morbidity are now higher than they were at baseline. Emergence of praziquantel resistance through over-use or in appropriate use is seen as a major threat. Field based diagnosis, with local communities, is key to ensure that appropriate administration of the drug is carried out until treatment is complete, without over exposure.

Collaborators. Dr. Edridah Muheki Tukahebwe, Ministry of Health, Uganda; Track record in research: Dr Poppy Lamberton (MVLS) will help with field studies and has a long established collaboration with Dr Tukahebwe.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509668/1 01/10/2016 30/09/2021
1804615 Studentship EP/N509668/1 03/10/2016 29/10/2020 Alice Catherine Garrett
 
Description I have further developed and tested our paper platform for point-of-care molecular diagnostics in the field in low-resource settings. The platform has been used to diagnose Malaria from a finger prick of blood in rural settings in Uganda (https://www.pnas.org/content/early/2019/02/12/1812296116.full )
Additionally, detection of Schistosome parasite eggs in stool, in order to diagnose Bilharzia (intestinal Schistosomiasis), using this platform has been trialled in the field in Uganda. However, due to additional complications that arose whilst working with small volumes of stool, more work needs to be conducted on sample extraction in order to improve sensitivity of the technique.
In our 3 field trials conducted over the last 18 months, we have seen a high prevalence of both schistosomiasis and malaria within rural communities in Uganda, in areas where health monitoring does not reveal such burden (due to the difficulties associated with field-based diagnostics, which our work is aiming to alleviate). Working closely with the Vector Control Division (Ugandan Ministry of Health), it was made clear that a diagnostic device that could diagnose both diseases simultaneously would be extremely beneficial to both disease surveillance and wider diagnostics and control activities. However, in order to merge malaria and Bilharzia testing on a single platform, we must move away from the traditional method of diagnosing Bilharzia from stool. Further work must now be conducted on developing additional molecular tools, to detect Bilharzia from a blood sample.
Exploitation Route In February 2019, I trained Dr. Bosco Kalule, a veterinary researcher from Makerere University in Uganda on the use of the platform. His interest lie with using the platform to diagnose and detect Brucellosis and leptospirosis in cattle and farm animals in remote areas. This in future could enable to explore transmission pathways of these zoonotic diseases and thus devise interventions to curb their highly detrimental impact in communities.
Sectors Agriculture, Food and Drink,Education,Healthcare

URL https://www.gla.ac.uk/research/beacons/futurelife/diagnostics/
 
Description Jon Cooper (PI) has undertaken a number of public engagement activities with my support, ranging from international conferences and seminars to paper origami classes in rural Uganda, a new approach to teaching about diseases and transmission (https://twitter.com/joncoopervp/status/1101909885489504257) After a short trip to the northern region of Uganda, we experienced first-hand what a difference community education and involvement can have on minimising cases Schistosomiasis. Through education and awareness of the diseases and its symptoms in a once endemic area, the headmaster of the primary school within the small village had been able to minimise cases of schistosomiasis. When children showed signs of the disease, the school headmaster would inform the district health authority, prompting testing and treatment of the community. This highlights the impact that awareness and education plays on community lead progress towards detection, diagnosis and treatment. However, the headmaster and the community in general, lack devices and capabilities to detect the disease before symptoms occur. When we arrived in Apac in 2018, we carried out testing in 2 local schools and found a high prevalence of both malaria and schistosomiasis, which was not known. This prompted the local authorities (under the auspices of the Ministry of Health) to treat the whole community for these diseases. This highlights the need for our research but also resulted in the community being treated and thus burden free. During our most recent field trip (February 2019), we visited a district in which the community and even district health coordinator, did not believe Bilharzia existed. During our trial, we found over 80% prevalence in children aged 6-13. Our results have been sent to the Vector Control Division in Uganda, this data will be shared with the district health officials, to both initiate the necessary interventions (mass treatment and net distributions for example), as well as raise awareness to the issue and prompt a larger scale district survey and treatment. I have presented our work at a number of primary and secondary schools around Glasgow, having the opportunity to educate a much larger and diverse community about neglected tropical diseases and the challenges of diagnosis has been fantastic. Each session has returned highly positive feedback and enthusiasm from both students and teachers. Additional to this, I am a member of the Ingenious Circuits Team. Together with engineers from the university of Glasgow and Edinburgh, we produced new teaching tools to promote biomedical engineering in Scottish schools (https://ingeniouscircuits.weebly.com/). We took inspiration from this project by focusing on the use of sound (covered in the school curriculum) to diagnose parasitic disease. When demonstrating in schools we presented our current research and the potential impact for the communities we work in. Although most of the children had heard of Malaria, it was the first time they had learnt about other neglected parasitic diseases and the impact they have on communities around the world. I believe that being able to provide this background and our research made the activity much more engaging.
First Year Of Impact 2018
Sector Communities and Social Services/Policy,Education,Healthcare
Impact Types Societal,Policy & public services