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World TB Day 2014 - and Einstein and keeping it simple

To make a good theory, Einstein is said to have taught that “everything should be kept as simple as possible, but no simpler.” So exactly how does this relate to World TB?

Well, as far as combatting the disease worldwide is concerned, the strategy so far has been pretty much as per the first part of Einstein’s assertion – to keep things as simple as possible. This involved the adoption and roll-out of DOTS in the 1990s in response to the unprecedented declaration of a global TB health crisis by the WHO in 1993.

So twenty-one years later, and the overall rates of disease have started coming down in the last few years (estimated to be by 2% a year), and (very definitely) more victims of this disease have had access to better treatment. The WHO credit DOTS with these achievements, and even hail them as being “impressive”, but frankly, given the bigger picture, it’s a claim that’s worthy of challenge – but not because the turn-around has been so slow (because no-one should pretend that trends in TB can be changed quickly), it's because of what is almost certainly going on beneath the surface of the pandemic in relation to drug-resistant disease.

The WHO is far from blind to these things – the people there well recognise that drug-resistance is putting the whole enterprise in jeopardy – but it’s far from evident that they’re doing anything remotely "impressive" to confront the problem. In fact, there’s good reason to suspect that there’s been a certain amount of burying of heads on the topic.. but whether it’s been a burying of heads in the sand or in the hands is the real issue. Perhaps it’s been both, because TB is not that ‘simple’ a disease to fight, and drug-resistant TB is less simple still.

The WHO currently is reporting that: “Progress towards global targets for reductions in TB cases and deaths in recent years has been impressive: TB mortality has fallen over 45% worldwide since 1990, and incidence is declining. New TB tools such as rapid diagnostics are helping transform response to the disease and new life-saving drugs are being introduced.

In truth it’s impossible to agree with this summary.

  • Progress towards meeting global targets hasn't really been that impressive, but when it comes to the targets set for DR-TB it’s been downright appalling.

  • The targets for TB mortality rates casually ignore TB deaths among people with known HIV infections – and in any case TB mortality is probably underestimated anyway.

  • Incidence rates are certainly now declining, but it’s been identified by the WHO itself that, if the decline stays at the current rate, we may only see the eradication of TB as a health threat at around the end of the century.

  • New drugs may be on the horizon, but it’s uncertain how they will be used.

  • And these new diagnostics are long overdue and extremely welcome, but can the response to what they will almost certainly uncover be appropriately mobilised? Currently, this looks unlikely.

But what these sound bites consistently choose to ignore in their summaries is the situation with DR-TB itself – that’s both MDR-TB, XDR-TB - and also strains that are more resistant still. TB in its drug-susceptible form can still be said to be ‘curable’, but when the disease becomes drug-resistant it is a very different ball game.

And this is where the problem of ‘as simple as possible’ may come back to haunt us, because the WHO is still hamstrung by its policy of DOTS being the necessary one-size-fits-all solution to a problem that is endemic in the very environments that have least resource with which to respond to it. DOTS simply doesn't cut the mustard with DR-TB, but the WHO simply has too much invested in DOTS (both politically and financially) so is unable to respond to DR-TB as it should be doing.

Einstein supposedly said to “keep it simple”.. but he also said “but no simpler..” So is this the problem? Has DOTS been one step too far in the simplicity stakes.

Unfortunately, it almost certainly has been. While drug-susceptible ‘normal’ TB can be contained and controlled by DOTS with rudimentary resources, DR-TB can’t be. It needs a response that is far more robust and rigorous, and which is also, unfortunately, far more expensive. Second line drugs for DR-TB cost 200 times what standard drugs for DOTS cost. The infrastructure required to administer them is still light-years away in those countries with most drug-resistant disease - whether or not this resistance has yet been measured or properly assessed.

There is a chilling logic to the development of drug-resistant TB: drug-resistance is caused by the mismanagement of drugs to treat TB; MDR-TB is caused by mismanagement of DOTS; and XDR-TB is caused by mismanagement of DOTS-Plus (or the second line drugs). So (quite simply) if a country has a significant TB problem today but has been using TB drugs for twenty years or more it should be expected also to have a dangerous level of MDR-TB unless proven otherwise.

This idea has been being ignored in these same last twenty years in favour of explaining away DR-TB where and when it was found by other means.. with the result that MDR-TB was allowed to slip the net in its early days when it could have been far more easily contained. As a result the world is now playing catch-up, not even knowing where the worst drug-resistance is because the resources to identify it are still not in place or available where they should be. We’re probably at least ten years behind the disease, possibly more.

Meanwhile, XDR-TB has been developing slowly within the shadows of the world's first drug-resistant pandemic. XDR-TB can be expected to appear wherever DOTS-Plus has been mismanaged or when second line TB drugs have been used and misued, but what’s really baffling is that the rates of XDR-TB, in as much as they are identifiable, seem now to be rising faster than MDR-TB. In fact the WHO seems to remain reluctant to comprehensively admit that rates of MDR-TB are rising at all – saying twice in their last report that the rates in 2012 were “essentially unchanged”, something which goes against simple common sense and which may well be epidemiologically impossible.

If drug-susceptible TB is being contained and controlled whilst drug-resistant TB isn’t, then there simply has to be more infectious drug-resistant TB growing in the global community year-on-year. The WHO reckons that 33% of the total epidemic gets missed, whilst we are missing 75% of the resistant epidemic is (which itself is probably a gross underestimation). If their conservative figures are right, though, then more than twice the proportion of drug-resisters are continuously out there infecting other people than are those with simpler and cheaper-to-treat bog-standard TB. And this proportion can only get worse unless the resources to contain BOTH types of disease are brought into line.

Even this is oversimplifying things, however, since there are so many other factors at play with this disease - but it’s difficult not to conclude that the writing’s now well and truly on the wall.. that the drug-resistant genie is out of the bottle and won’t be put back in there by that simple one-size-fits all DOTS as was originally hoped.

XDR-TB, meanwhile, requires a more complex and expensive response even than MDR-TB, and there is good reason to fear that the WHO is currently doing the same thing with XDR-TB that it did with MDR-TB in the 1990s – underestimating its dangers and letting it slip the net when the problem is small – because it looks like almost all of the resource with which the WHO is tooling up to fight DR-TB relates to MDR-TB and won’t work with XDR-TB (and there’s far too little even of this).

So what is to be expected in the next twenty years? Well, unless both policy and resourcing changes dramatically we can expect the following: rates of ‘normal’ TB will continue to fall, probably at a cumulatively faster rate; meanwhile rates of MDR-TB will rise, and the proportional burdens of disease will begin to shift faster still, more and more in favour of drug-resistant TB; meanwhile XDR-TB (and more resistant strains) will also continue to rise, but only in any significantly startling way if treatments for MDR-TB continue to be mismanaged, as they surely must have been already.

TB does everything in slow waves, so we’re not facing the Black Death here, but what we are facing is something that is extremely serious. First off, unlike a disease like the plague, TB is, for many reasons, particularly selective in terms of those it picks off. Basically it feeds off the poor.. and so, while rates may well rise across the world, it’s impossible that things in, say Europe, the US or Japan will return to what they were in the early part of the twentieth century, whatever the lazy media may want to suggest in their scare stories. Living and working conditions have simply improved too much, as has nutrition and general affluence, to allow this to happen. But things will get worse and worse where they’re bad enough already. The disease will begin feasting on the poor and there will be less and less that can be done about it.

It may even be that, by 2035, the proportion of ‘normal’ TB to MDR-TB will not be 20:1, as it is said to be today, but will be close to 1:1. The world needs to be making a choice today as to whether or not it is going to do something about this. As of World TB Day 2014 it hasn’t even begun to make that choice. In fact it’s not even started to properly think about it because there is still so little wider awareness of the problem. But it surely should do, or millions of the world's most vulnerable people are going to die of untreatable disease and the historians of the future are going to be very hard on us for having neglected them - and quite rightfully so.

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