Wednesday, 10 July 2019
A new blood test for tuberculosis (TB) developed by researchers at the Universities of Nottingham and Leicester has shown the potential for a new blood test to not only diagnose human tuberculosis (TB) but also detect those at most risk of developing the disease.
The research, carried out at the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre (BRC) and the University of Nottingham’s School of Biosciences, used new blood test called Actiphage to look for the presence of the bacteria that cause TB (Mycobacterium tuberculosis; MTB). The study involved 66 participants in four groups: those with active pulmonary TB, those with latent TB, a control group of patients referred for suspected TB but found not to have the disease, and a control group of healthy individuals. The findings of this new trial were published in Clinical Infectious Diseases.
Despite recent reductions, England still has one of the highest rates of TB in Western Europe . While TB cases have been declining overall in the UK, the rate of TB in some of the most deprived areas remains more than 7 times higher than in the least deprived. TB is a serious bacterial infection, which can be life threatening if not properly treated with antibiotics. Pulmonary TB of the lungs or throat is contagious, but TB can affect any part of the body.
The new blood test was used to test all of the patients twice, 12 months apart. Actiphage tested positive in 73% of people that were subsequently diagnosed with TB – this was a much higher level than expected. None of the participants in the control groups tested positive with Actiphage and none of the patients with latent TB who tested negative with Actiphage went on to develop active TB. Intriguinly, two of the three participants with latent TB infection who tested positive with Actiphage went on to develop the disease more that six months later, suggesting the test may have a predictive role in identifying people with the infection risk of developing the disease.
Actiphage® has been developed by the University of Nottingham in conjunction with the UK’s Royal Veterinary College and commercialised by PBD Biotech Ltd for major diseases in livestock, primarily as a blood or milk test for bovine TB and Johne’s disease. This is the first time the blood test has been trialled in humans.
From animal to human
The research team behind the new test was led by Dr Cath Rees, an expert in microbiology in the School of Biosciences and Dr Ben Swift (now at the Royal Veterinary College),
In 2016 they developed a new test to detect Mycobacteria in the blood and milk of cattle in just six hours, allowing affected animals to be identified quickly to allow effective disease management.
Unlike many common bacterial infections, detection of the bacteria that cause TB is limited by the fact that Mycobacterium tuberculosis (MTB) is very slow growing, making traditional culture methods inefficient. More rapid molecular tests that detect MTB DNA are limited due to its tough cell wall that makes DNA extraction difficult. The new test uses specific bacteriophage that infects live MTB and breaks open the cells to release DNA. The whole testing process can be completed in as little 6 hours.
Actiphage® is a novel blood test for mycobacteria that was developed to identify mycobacterial infections in farmed animals, helping farmers to control these difficult diseases. The data from our initial study in humans suggest that following infection, MTB is circulating in the blood at levels that were previously undetectable, and that the immune system may be failing to effectively contain the bacteria within the lungs. While we are cautious about generalising from a small sample size, we are optimistic that these initial findings indicate that Actiphage® can be used as a tool to help us better understand the dynamics of the infection in humans. This new test offers the potential to target those at risk of TB and allow treatment to start early. This is a very exciting development that invites further study.
New insights
Senior author of the paper, Dr Pranabashis Haldar, Clinical Senior Lecturer at the University of Leicester and Consultant in Respiratory Medicine at Leicester’s Hospitals, said:“TB is the leading cause of death from an infectious disease. It most commonly affects the lungs and from this site is transmitted to others by coughing and sneezing. As there is a lack of diagnostic tools for people unable to bring up sputum, diagnosis is delayed, increasing the likelihood that the disease is spread.”
Around a quarter of the world’s population carry the infection. In the vast majority, this is in the form of latent TB, which does not affect their health, but carries a risk of progressing to the active form of TB in around ten per cent of those infected. The mechanism for this is poorly understood.
Dr Haldar continued: “Our observations provide new insights into how human TB develops and support recent evidence of the existence of a transitional state of human TB called incipient TB that does not produce symptoms but carries a high risk of progressing to active TB. There is potential for Actiphage® to be developed into a mainstream diagnostic and be used in screening programmes to help us identify and treat this patient group.
Furthermore, as a blood test, it is particularly suitable for patients unable to produce sputum, in children, and in underserved groups that struggle to access freely available healthcare resources.”
The paper, ‘A novel high-sensitivity bacteriophage-based assay identified low M. tuberculosis bacteraemia in immunocompetent patients with active and incipient TB’, can be accessed at Clinical Infectious Diseases academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciz548/5522421?
Story credits
More information is available from Dr Cath Rees, University of Nottingham, School of Biosciences. Cath.rees@nottingham.ac.uk
Notes to editors:
About the University of Nottingham
Ranked 32 in Europe and 16th in the UK by the QS World University Rankings: Europe 2024, the University of Nottingham is a founding member of the Russell Group of research-intensive universities. Studying at the University of Nottingham is a life-changing experience, and we pride ourselves on unlocking the potential of our students. We have a pioneering spirit, expressed in the vision of our founder Sir Jesse Boot, which has seen us lead the way in establishing campuses in China and Malaysia - part of a globally connected network of education, research and industrial engagement.
Nottingham was crowned Sports University of the Year by The Times and Sunday Times Good University Guide 2024 – the third time it has been given the honour since 2018 – and by the Daily Mail University Guide 2024.
The university is among the best universities in the UK for the strength of our research, positioned seventh for research power in the UK according to REF 2021. The birthplace of discoveries such as MRI and ibuprofen, our innovations transform lives and tackle global problems such as sustainable food supplies, ending modern slavery, developing greener transport, and reducing reliance on fossil fuels.
The university is a major employer and industry partner - locally and globally - and our graduates are the second most targeted by the UK's top employers, according to The Graduate Market in 2022 report by High Fliers Research.
We lead the Universities for Nottingham initiative, in partnership with Nottingham Trent University, a pioneering collaboration between the city’s two world-class institutions to improve levels of prosperity, opportunity, sustainability, health and wellbeing for residents in the city and region we are proud to call home.
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