TB or not TB? That is the question.

These treatments are all we have to tackle TB once someone has become diseased due to the lack of an effective vaccine.  As a consequence, the control and elimination of TB is highly dependent on rapid diagnosis. According to the WHO, 1.6 million people died from TB in 2021, many of which will have been due to late or missed diagnosis preventing prompt treatment. Professor Keertan Dheda jointly from the University of Cape Town and The London School of Hygiene and Tropical Medicine.

Keertan - As has already been outlined, the diagnosis of TB is a huge problem. 4 million roughly of the 11 million newly ill people with TB every year, or roughly one in three patients with active TB, remain undiagnosed or undetected. And this is a startling statistic. And there are three key reasons why the diagnosis of TB is problematic or, put in another way, the weak links in the chain are threefold. Firstly, the public health or casefinding strategy for reasons of affordability is inappropriate. And by this I mean patients are expected to self report when they have symptoms. And we call this passive case finding. And this is in contradistinction to active case finding where healthcare workers or diagnostics are taken out of the laboratories and healthcare facilities into the community. However, with the passive case finding strategy, in a way the horse has already bolted because considerable TB transmission would've occurred before the diagnosis is made. These are individuals who would be spreading the bacilli. The second weak link in the chain, or key reason why diagnosis is problematic, is the inability to collect sputum samples. We already heard Sebastian talk about cavities, but not all TB patients produce sputum. And so getting a sample in about a third of patients is a problem. And this is because TB is either outside the lung, we call it exopthalmy TB, and second that somebody may not be producing sputum as such. And then thirdly, suboptimal diagnostic tools. And he alluded to smear microscopy where one looks down the microscope to identify the bug in, for example, a sputum sample, but that only detects about 50% of TB. We have DNA based tests, but these only pick up roughly about 80% of tb. And one can also grow the bug in the lab, but this takes many, many weeks and is also quite expensive.

James - So the problems are extensive and numerous. What are the most promising avenues to sorting this problem out? How do we get people diagnosed more quickly so they can get the treatment they need?

Keertan - Well, I think, again, going back to the three points I mentioned, the first thing is that we need to take diagnostics out into the community. And we've been doing research where we've developed a model where we take these DNA based diagnostic tests. These are portable diagnostic tests, and we take this in a mini mobile clinic. And, um, it's manned by two healthcare workers. And so we go out into the community to diagnose cases on site, we call that point of care diagnosis. We also do other research where we've developed or are developing, through the research teams at the University of Cape Town and the London School Sputum, Independent tests. And one of the tests we are working on is a protein based test. We discovered this using a mass spectroscopy approach. We can use, for example, a simple lateral flow assay using urine, for example, to rapidly screen for somebody in the community that has TB. The important point there is that one can rapidly identify individuals who might have TB and so target them for diagnosis and treatment. And we've also been doing work where we've developed a more sensitive tool called ERISA TB for a specific type of TB called exopthalmy tb. I had spoke about that early on. That's TB outside the lungs. And this is being scaled up through a spinoff company at the University of Cape Town. And we, for example, have managed to improve the diagnostic rate of extra pulmonary TB from about 30% using conventional tools to about 90%, which makes diagnosis much more accurate and efficient. So these are some of the examples of how one can make a more efficient and rapid diagnosis of TB.

James - Keertan, I'm afraid that's where we'll have to leave it. It sounds very promising. That's Keertan Dheda from the University of Cape Town.