Can an infectious disease that is only successfully treated in 48% of cases not be on the rise?

That’s exactly what the WHO has been proposing. And that 48% success rate only relates to the cases that are treated: according to the WHO's own estimates those who see treatment are probably as few as 10% of all of the disease's victims (and they may well be even less). The idea that such a disease isn't on the rise surely defies both the laws of logic and the laws of epidemiology.

We’re talking about MDR-TB (and also  XDR-TB) here, the two most dangerously lethal parts of today’s TB pandemic. The WHO is insistent that the percentage of MDR-TB within the TB pandemic “has not changed compared with recent years” - they’ve been saying so in both of their last annual Global Reports on TB.  We certainly don’t have access to their raw data, nor do we pretend to have a shadow of their collective epidemiological expertise, but we’re sorry… their position just doesn’t make any sense at all. If we’re wrong we’ll be happy to stand corrected (and even be shamed for our presumptive ignorance), but it looks to us like there are millions of people currently out there being put at risk for dubious reasons that may be largely political.

So here’s why we think their statement is wrong.

The WHO report that the wider TB pandemic is now reducing at a rate of a little under 2% a year. The reason that this tide has turned is largely because ‘normal’ drug-susceptible TB (DS-TB) is generally successfully treated by the standard approved TB drugs (DOTS). The current published success rates suggest that success is achieved in 86% of cases.

In contrast they report that MDR-TB is only successfully treated in 48% of those cases who ever see treatment - and XDR-TB in a terrible 18%. It’s important to recognise that we now have three quite distinct parts to the pandemic – one of which can be reliably cured by DOTS in most cases (DS-TB), one that can be cured (though not by DOTS) only half of the time (MDR-TB), and one that is only getting cured in one in every fifth case (XDR-TB). It’s not difficult to see why the WHO’s position is so illogical: all of the annual 2% global reduction in disease has to be being made in the ‘normal’ part of the pandemic where 86% are being cured, whilst it has to be impossible that any progress at all can be being made with the drug-resistant parts given that their treatment success rates are so wayward. Here's a rough outline of the situation including the WHO's own estimated rates of case finding which makes the situation even worse:-

DS-TB  -  66% of global patients found and treated, with 86% of these cured => c.2% reduction in disease.

MDR-TB - at most 10% of global patients found and treated with 48% of these cured => ?% increase in disease

XDR-TB - ?% of global patients found and treated with 18% of these cured => ?% increase in disease.

(It's quite possible to argue that both types of DR disease may be increasing at close to 10% a year).

But there’s other evidence of the WHO’s flawed position, and this is visible in their own published data (or lack of it). On page 56 of their last Global Tuberculosis Report there’s a section entitled “Recent trends in MDR-TB: a new analysis”. It was this analysis that formed the grounds for their conclusion that the percentage of new cases that are MDR hasn’t been changing., and it used the available surveillance surveillance data from 1994 right through to 2013.  

To establish a trend, of course, you need to have at least two pieces of data separated by an appropriate period of time - but you can really only draw conclusions with any real confidence if you have several data points rather than just two. This is the normal way of establishing a trend – and it follows that if you don’t have sufficient data points you can’t express confidence in any trend that emerges.

So how many countries were able to offer what would be considered a really decent amount of data to the analysis – i.e. more than sixteen data points? According to the map on page 56 (see below)  it looks like there were 11. Unfortunately only two of these (Latvia and Estonia) have any recognised TB problem, so the remaining nine really can’t count for much in any global analysis of a trend.

Meanwhile, right at the other end of the scale how many countries offered no data at all?

At least 40 it seems. That may seem bad enough, but of real significance is that four of these are in the WHO’s special list of 22 ‘High Burden Countries’ (HBCs). They also happen to be amongst the ten most populous countries in the world as well, so on both these accounts they could be expected to have made a very big difference indeed to the trends. (In order of populations these countries were India, Indonesia, Brazil and Russia). To make matters worse, three of them are not just in that list of HBCs, they’re also already recognised by the WHO as having an MDR-TB problem by being on the WHO’s other list of 27 High Burden MDR-TB Countries (HBMDR-TBCs).

Of course a single data point is as much use as no data point at all if you’re looking to establish a trend, so how many countries offered the analysis just a single data point?

Again at least 40. This time two of them are in both the list of 22 HBC’s and among the ten most populous countries of the world (Nigeria and Bangladesh); and both of these countries are also in the WHO’s list of 27 HBMDR-TBCs. Furthermore of the remaining countries with single data points eight appear in a list of the ten countries with the highest estimated TB incidence rates in the world - in other words they are countries where drug-resistant TB should be expected to be a real likelihood if not a given.

So let’s summarise this: at least five of the 27 countries listed by the WHO as having MDR-TB epidemics failed to offer any useful data to the analysis and also happen to be among the most populous countries in the world; furthermore eight of the ten countries with the worst estimated rates of TB in the world failed to offer any useful data.

The introductory summary to this ‘new analysis’ casually states that the data used to develop these trends were available from “16 of the 36 high TB and/or MDR-TB burden countries” almost as if this was inconsequential. What this means is that (20 years into a global emergency) over 50% of those countries that are believed by the WHO to be most at risk from MDR-TB have yet to provide even two data points for analysis.

So exactly what is going on here? Well clearly there’s a desperate dearth of surveillance data but exactly whose responsibility this deficiency is isn’t identified. For sure it has to be largely the responsibility of the governments of the countries themselves as part of their social contracts with their citizens. But this responsibility is shared with the WHO itself. In fact the WHO accepts this is a shared responsibility with the prime responsibility normally resting on the shoulders of the governments themselves, but wherever resources are known to be particularly poor these responsibilities have to be weighted heavily in the direction of Geneva. The WHO meanwhile has to accept full responsibility for collecting the data from the countries themselves and representing it appropriately. Whoever you care to blame, one thing is certain – something is very seriously wrong here.

In any case what sort of “new analysis” allows such questionable conclusions to be drawn - ones that will be used to inform global policies in the coming decades but which are based on such appallingly poor data? Let’s call a spade a spade – it’s a very unreliable one.

So does it look like there any reasons why the WHO appears so shy of applying either simple logic, precautionary principles, or even good epidemiological practice to what’s shaping up to be a lethal pandemic? We think that there may be, though we don’t see them as being very edifying.

In 1993 the WHO declared an unprecedented global emergency in relation to tuberculosis. By then the disease had effectively slipped form the consciousness of the wealthier nations but had still been festering away in the poorer ones. What was seen to be changing was that this old disease was suddenly re-energised with a vengeance because of HIV. The response from the WHO was a carefully considered one-size-fits-all treatment strategy called DOTS. It was first implemented in the mid-90s and has been being rolled out ever since. If you look at almost any recent WHO press release on TB you’ll find that they are still inclined to hail DOTS as a “success story”, suggesting that it may have saved as many as 35 million lives in the past 20 years. It may well have, and if so it should surely be given credit, but has it really proved to have been a success story? Well not if drug-resistance is now on the rise, because right from the start there were experts who were shaking their heads and saying, “But what about drug-resistant TB? DOTS won’t cure it…”. And certainly not if drug-resistance is getting beyond control.

DR-TB isn’t new. It first popped up as resistance to a single drug (the very first one that was discovered) in the 1940s. Things develop slowly with tuberculosis, though. It wasn’t until the mid-1980s that multi drug-resistant TB began to be recognised assignificant public health threat, with the first cases of XDR-TB appearing soon after. The hopewith DOTS, however, was that it would slowly still see off the drug-susceptible bulk of the pandemic while the diminutive drug-resistant component wouldn’t be robust enough to maintain itself. In hindsight it seems like a bit of a naïve idea but it seemed a good one at the time if only because DOTS was seen as the only affordable and implementable option that could possibly be managed where resources were deficient (in other words where TB likes to make its home).

As time has proved, unfortunately, DOTS (unsurprisingly) can’t cure MDR-TB because this type of TB is by definition resistant to the two most powerful drugs in the DOTS therapy. Worse still, drug-resistant TB seems to be pretty much as infectious as ordinary TB. Moreover it’s now widely accepted that if you carry on haplessly treating MDR disease with standard DOTS drugs you run the risk of further stoking the resistance – in other words that favoured one-size-fits-all response can actually make things worse. (Though this possibility was originally pointed out in the 1990s as well.)

Dr Salmaan Keshavjee, a global expert on TB, calls DOTS “a great first step but a terrible long-term strategy”. It was certainly never going to work as a way of eradicating TB as a global threat, although it was always going to help bring down the rates of disease by reducing the bulk of drug-susceptible ‘normal’ tuberculosis. Meanwhile DOTS never offered any answer at all in the longer term because it was always going to let the drug-resistant part of the pandemic off the hook. It’s this implicit deficiency in the global strategy, we suspect, that’s the reason that the WHO is so intent on underplaying – and even actually knowingly disguising – the trends of the MDR pandemic that surely now exist by offering a ‘new analysis’ that is so patently and dangerously dodgy. If the organisation were to acknowledge as logic dictates that the percentage of new cases that are MDR must be on the rise, they would also have to accept that DOTS (their fundamental strategy) is failing and is even stoking the most dangerous part of the pandemic.

The WHO can at least still congratulate itself for having turned the tide of the wider pandemic and can still credit DOTS with this. Actually it does so quite often, by identifying that the Millennium Development Goal set for TB (of halting and reversing the overall tide of disease) was reached several years before 2015, its target date. In doing so, however, they casually ignore the fact that their own Stop TB Partnership replaced this target in 2005 with more appropriate ones, most of which have been missed, and also set a bunch of targets for DR-TB which have been missed quite catastrophically.

There’s an institutional pattern that reveals itself here – to look for success where it can be identified, talk it up a bit and then give the credit to DOTS before burying heads and hoping. And of course since the disease is coming down – slowly admittedly, but it still is coming down so - it looks like things are indeed moving in the right direction and all we’ve got to do is to do DOTS more effectively and it will come down faster.

The current target being promoted by both the WHO and the Stop TB Partnership is to “bend the curve” of the downward sloping graph of disease reduction, forcing it into a steeper downward trajectory and thus “end” the pandemic by 2035. The danger is that if we only focus on the single curve of the whole pandemic and ignore and fail to measure the secondary component curves of drug-resistant disease within it we will easily fool ourselves (or those with the political power to do something about this disaster) into thinking that the war is being won, and fail to notice that the curves of MDR- and XDR-TB are heading upwards in the opposite direction until way too late.

There is even some very good evidence of a rising trend of DR disease within the WHO’s recent Reports where every year an extra few countries are recorded as having diagnosed at least one case of lethal XDR-TB. In fact this number has as good as doubled in the same period (2004-2012) that the WHO reckons that no trend has emerged. XDR-TB doesn't just come out of nowhere. It most probably emerges from a local epidemic of MDR-TB.

So we know that these two particular curves can’t be bending downwards at all.  

Whether it likes it or not the WHO has no choice now but to properly separate the pandemic out into its more manageable and less manageable parts – to split it into three (because XDR-TB is clinically distinct disease to MDR-TB) and then set separate targets, budgets and strategies for each.

It seems so obvious, but one thing seems to be getting in the way and that’s this baffling institutional resistance to the idea that the drug-resistant proportion of the pandemic must be changing – and that by 2035 it might even be the principle part of the pandemic (paradoxically probably helped there by DOTS). But DR disease looks to be the cause of the majority of deaths in the wider pandemic before this.

There should be a new Global Report published in late October. So the big question is: how will the WHO choose to assess the trend of MDR-TB this year?