Diagnostics
Mycobacterium tuberculosis in their blood were those that were most likely to progress to active cases of TB, even if they had no other clinical signs of infection.”
Embark on the journey towards acceptance
Actiphage is still in development when it comes to human diseases, and the team will need to complete additional trials before they can move towards commercialisation. However, it is already being used to detect Johne’s disease – a serious wasting condition in cattle.
When a phage attacks a bacterium, it injects its DNA. The bacterium then makes more phages that are released when the bacterium burst.
difficult to break open using the normal sorts of methods that we use to extract DNA from cells.” With the Actiphage test, the phage will infect any mycobacteria that are present in a sample. The phage then copies itself, before producing enzymes that break open the cells – a process known as cell lysis. Once that happens, the DNA is released and a PCR test is used to detect which type of mycobacteria has been infected. “In effect, we are using the phage as a novel way to break open these cells efficiently, so we are able to use standard PCR to detect their DNA,” says Rees.
“It seems scientists have always been quite sceptical about new ideas, and sometimes it has felt like pushing water uphill trying to get phage-based diagnostics off the ground.” Dr Cath Rees
20
The number of years it took for PCR-based tests to become widely accepted and routinely used as a diagnostic method.
Dr Cath Rees 24
The key to diagnosis Ultimately, Actiphage could be used to diagnose human TB by detecting mycobacteria from blood samples. It could even identify latent (asymptomatic) infections, which current diagnostics often miss. This means the infection could be treated at an early stage before it starts to cause obvious symptoms.
“People who have been exposed to TB may produce a detectable immune response, but very few go on to develop active disease,” says Rees. “What we have found, using Actiphage, is that patients that had detectable levels of
“This is on a very small scale, but we are moving towards the point where we can sell the tests to veterinary diagnostic labs so that the tests are more widely available,” says Rees. Through their work on Actiphage, the researchers have been emboldened to ask new questions about TB itself. This may help not just with diagnostics, but also with the development of new treatments or control strategies. “There are lots of new areas of fundamental research where we hope Actiphage will be useful for the wider scientific community,” says Rees. With regard to phage-based diagnostics more generally, Rees believes they are slowly but surely moving towards the scientific mainstream. She cites JBS Haldane’s Four Stages of Acceptance for Scientific Ideas, which starts with stage 1 – ‘this is worthless nonsense’, and moves towards stage 4 – ‘I always said so!’. Currently, she believes phage-based diagnostics are somewhere between stage 2 and 3 (‘this is an interesting, but perverse, point of view’ and ‘this is true, but quite unimportant’). After all, it took about 20 years for PCR-based tests to become widely accepted and routinely used as a diagnostic method – so why wouldn’t phage tests follow the same trajectory?
“It seems scientists have always been quite sceptical about new ideas, and sometimes it has felt like pushing water uphill trying to get phage-based diagnostics off the ground,” she says. “Hopefully within the next 20 years, phage-based diagnostics will have become well established, not only for detecting mycobacteria but also for detecting other types of bacteria that are difficult to detect by traditional methods.” Although it is still very much early days for this line of enquiry, and it is likely to take years before phage-based diagnostics are considered mainstream, there is justifiable excitement among the pioneers in the field – and rightly so. “It is thought the vast majority of phages remain undescribed by science,” says Edwards. “This incredible biological resource remains mainly untapped.”
Practical Patient Care /
www.practical-patient-care.com
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