Once and for all.

It seems that, once again, some people are a little confused about the difference between latent TB (LTBI) and active TB. The recent announcement that WHO has endorsed the Xpert MTB/RIF fast diagnostic for active TB appears to have created some (unwarranted) nervousness amongst CST investors.

Let's see if we can clearly put this to rest once and for all.

We can look at this from a couple of perspectives, the technical distinction; and the operational impact of improved Active TB diagnosis. We will discover that improved Active TB diagnostics are actually a positive for Cellestis.

Active Vs Latent.

Whilst active and latent Tb are both the results of the same bacterium, they exist in quite different states. Active Tb is, well ... active, it is destroying human tissue and has an ultimate outcome, if untreated, of death of the patient. Fortunately, the human immune system is incredibly capable and in the majority of cases is able to effectively fight the Tb bacterium. Unfortunately, the Tb bacterium has a defence mechanism which, in my simple layman terms, is implemented by building a shell around itself to protect itself from destruction by the immune system. The result of this is a stand off - the Tb bacterium is contained and inactive, protected by its shell while the immune system patrols. In this state the Tb is termed latent and is essentially harmless. Of course if the immune system becomes compromised (age, HIV, some medical interventions) then the latent Tb will "break out" and become active. It is clearly important, then, to diagnose and treat latent Tb to avoid that future possibility.

Now, here is a really important differentiation for our consideration. When Tb is active it can be found in various bodily fluids. All of the specific diagnostics (including the Xpert MTB/RIF) for active Tb look for traces of the actual Tb bacterium. However, when Tb is latent it is hidden and cannot be found in bodily fluids at all. Latent Tb cannot be diagnosed by looking for the bacterium itself. Therefore, the only way to "find" latent Tb is to look for some other indication that it is in the body. This is what all diagnostics for latent Tb do - they look to the immune system to notify them that they are currently waging a war with some Tb.

Whilst the above is clearly a very imprecise description of the situation it does allow us to understand that no amount of tweaking will ever make a diagnostic for Active Tb diagnose Latent Tb. They are totally different diagnostic methods.

So, next time somebody announces a new test for Tb (and it happens frequently), check to see if it is a diagnostic for Active Tb. In fact, I can pretty much save you the effort - there are no records of anybody having a diagnostic for latent Tb in development other than the three existing diagnostics - TST (skin test), T-Spot (IGRA by Oxford Immunotech) and QuantiFERON (IGRA by Cellestis).

Now,

The Operational Impact.

Firstly, putting aside our own desires, we should always be pleased to hear of any progress in the fight against Tb. After all, it kills around two million people each year.

However, as it turns out, better diagnostics and treatments for Active Tb are actually of benefit to Cellestis. In low incidence countries (ie the developed world) the diagnosis and treatment of latent Tb is a worthwhile and viable exercise. Unfortunately, in less developed countries, where Active Tb is rife, the first attack on Tb has to be the diagnosis and treatment of Active Tb (Incidentally, the treatment is not expensive). In these situations, the vast majority of resources must be used in this fight. It will only be once effective control programs for active Tb are in place that resources can be turned to dealing with the reservoir of latent Tb.

We should therefore give three cheers every time we hear of a new diagnostic or treatment for Active Tb.