An on-the-spot, low-cost diagnostic test for leptospirosis (Weil's disease), a bacterial infection recognised as a neglected disease by the World Health Organization, could save lives in developing countries where there is little or no access to medical pathology laboratories and specialist technicians.

Our target is to develop a diagnostic test requiring a blood sample from a finger prick at a cost of less than $0.50 per test.

Lisa Hall

Each year an estimated 1.03 million people around the world, many of them in poor countries, contract leptospirosis, with 58,900 of these infections resulting in death. Better known as Weil’s disease, leptospirosis is spread by animals such as rats and transmitted to humans when they come into contact with food, water or soil that is contaminated by infected animal urine. The infection can be successfully treated if diagnosed early. Untreated, the disease can lead to death.

Diagnosis of leptospirosis presents problems: the infection shares symptoms with other diseases, including dengue, malaria and viral hepatitis. The only way to confirm the illness is to take a blood sample and run specialised diagnostic tests. This process can be time-consuming and expensive.

Now, a global collaboration between Cambridge University and University of Ghana researchers in biotechnology, pathology and manufacturing is bringing a cheap diagnostic test a step closer.

The global project was made possible through the Royal Society’s Global Challenge Research Fund, which enables outstanding UK research leaders to develop international collaborations with the best leading researchers from around the world, to work on some of the global challenges and problems facing developing countries.

Lead researchers Professor Elizabeth (Lisa) Hall (Head of the Cambridge Analytical Biotechnology Group) and Dr Gordon Awandare (Director of the West African Centre for Cell Biology of Infectious Pathogens) are also working with engineers such as Dr Ronan Daly (IfM, Department of Engineering) to manufacture a single instrument, similar to the home pregnancy test, which will deliver accurate and rapid point-of-care diagnosis.

“Health practitioners need a simple test that enables them to detect the difference between bacterial and viral infections – such as leptospirosis and dengue – because they require very different treatments,” says Professor Hall.

“Our target is to develop a diagnostic test requiring a blood sample from a finger prick at a cost of less than $0.50 per test. The test has the potential to transform the way we diagnose and treat the one million people who contract leptospirosis every year.”

One of the most expensive components of the test for leptospirosis is the enzyme used to amplify the pathogen’s genetic material (DNA/RNA) to high enough levels to be detected.

“Specialist skills and refrigeration are required in traditional manufacturing of the enzyme,” says Professor Hall. “To overcome these barriers to local production, we’ve developed a technique that allows for direct purification of the enzyme from cell culture and packages it ready for use.”

The team is also developing a novel technique to extract the pathogen’s DNA/RNA directly from the blood sample. “Both the DNA/RNA extraction system and the enzyme will be contained on a diagnostic card that can be manufactured locally – and ultimately from local materials,” says Professor Hall.

International cooperation has been crucial in the development of the test (see panel below). The Cambridge scientists are also working with Universiti Putra Malaysia – and would welcome new partners, both in the UK and overseas.

“We hope to deliver a sustained improvement in healthcare while also developing local economies. Local fabrication will drive sustainable local enterprise and help improve technological education,” says Dr Daly. “Leptospirosis has been recognised as a neglected disease by the World Health Organization and there is scope for taking a similar approach for developing point-of-care diagnostic tests for other treatable infectious diseases.

“They include food and waterborne diseases (bacterial diarrhoea, enteric fever, hepatitis A), vector-borne diseases (malaria, dengue, chikungunya and Zika), zoonotic diseases (leptospirosis, rabies) respiratory infections (influenza-like illnesses, pneumonia, tuberculosis) and HIV infection. These patients present with fever and a wide range of non-specific symptoms, which are difficult to diagnose without specialist laboratory tests. These may be expensive and/or unavailable, resulting in presumptive diagnosis and empirical treatment, which may be unnecessary, incorrect or potentially even harmful.”

The various elements of the test are currently being developed in the lab, with the first protoype expected to be produced in 2018.

Research partnership

Project leaders: Professor Lisa Hall (Department of Chemical Engineering and Biotechnology, University of Cambridge), Professor Gordon Awandare (West African Centre for Cell Biology of Infectious Pathogens) and Dr Ronan Daly (IfM, Department of Engineering, University of Cambridge)

Project members: Cassi Henderson, Dushanth Seevaratnam, Dr Hui Yee Chee

Partners: West African Centre for Cell Biology of Infectious Pathogens (WACCBIP); Faculty of Medicine and Health Sciences, Universiti Putra Malaysia

Funding: Royal Society International Collaboration Awards for Research Professors, IC160089 (Hall/Awandare): UPM Sabbatical award (Chee); Gates Cambridge Scholarship (Henderson)

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