Scientists have discovered a new blood test to diagnose human tuberculosis (TB) and identify the patients most at risk.
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 seven times higher than in the least deprived.
The research, carried out at the National Institute for Health Research Leicester Biomedical Research Centre and the University of Nottingham's School of Biosciences, used a new blood test called Actiphage to look for the presence of Mycobacterium tuberculosis (MTB).
The study*, published today in the medical journal Clinical Infectious Diseases, 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 new blood test was used to test all of the patients twice, 12 months apart.
Actiphage tested positive in 73% of people that we subsequently diagnosed with TB - for an experimental study 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.
Intriguingly, two of the three participants with latent TB infection who tested positive with Actiphage went on to develop the disease more than six months later, suggesting the test may have a predictive role in identifying people with the infection at risk of developing the disease.
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. Our observations provide new insights into how human TB develops and support recent evidence of the existence of a transitional state of TB infection 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, both as a mainstream blood test to diagnose TB and as a test used in screening programmes to help us identify and treat people with latent infection.
"As a blood test, it is particularly suitable for patients unable to produce sputum, including children, and may help support diagnosis in underserved groups that struggle to access freely available healthcare resources.”
The new Actiphage test has been developed by the University of Nottingham in conjunction with the UK's Royal Veterinary College and commercialised by PBD Biotech 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.
Study co-author Dr Catherine Rees, associate professor in microbiology at the University of Nottingham and chief scientific officer at PBD Biotech, said: "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. 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.
"The new Actiphage blood 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.”
*Verma R, Swift BMC, Handley-Hartill W, et al. A novel high sensitivity bacteriophage-based assay identifies low level M. tuberculosis bacteraemia in immunocompetent patients with active and incipient TB. Clinical Infectious Diseases, ciz548, https://doi.org/10.1093/cid/ciz548