Last Tuesday was World TB Day and in order to improve our understandings of this complex disease, and to get a better picture of what’s being done to combat it, we attended three separate events which marked the day. All of them were intending to highlight the problems faced by those attempting to confront what is already a plague of drug-resistant disease. Two of them were in London - one of these a research conference at University College London [UCL] and the other a gathering convened by the All Party Parliamentary Group (AGGP) on TB at the Houses of Parliament. The third was an international teleconference convened by Partners in Health (PIH) from Boston, USA.
When considered all together, they offer a sobering picture of what is almost certainly already in the pipeline.
The title of the UCL conference was unambiguous: “What do we need to know to reach, treat and cure everyone with TB?” One answer, at least as far as MDR-TB is concerned, didn’t come from the UCL conference at all but came from the teleconference in a throw-away comment made by Dr Salmaan Keshavjee (one of PIH’s experts). He simply said that, “MDR-TB requires you to have a health system”, and of course in too many instances countries that are now under very serious threat from this disease have none worth shining a candle at.
So in these eight words he effectively summed up the challenge that faces public health personnel anywhere where TB is rife because the truth is that the tools to fight this drug-resistant disease simply don’t exist where they’re needed. And even where they do exist, the treatment of DR-TB (according to Dr Carole Mitnick, the other PIH expert in the teleconference) is simply too “crushing for health systems” – and that’s even the case where there are better health infrastructures.
So is this mismatch between problem and resource why so many governments, health ministries and health agencies seem to be so willing to pretend that this problem still doesn’t exist at any scale – colluding with the WHO’s words that “no evidence exists” that rates of MDR-TB are rising. Because of course it surely doesn’t exist if you don’t go looking for it!
Such an evasive viewpoint is to some extent understandable if you simply don’t have the tools or resources to fight the disease, although just as surely it’s not remotely an ethically acceptable one.
So exactly what tools are required? Well, quite typically of TB, answering even this straightforward question isn’t that simple. Last Tuesday’s central debate at UCL was entitled simply “Tools vs Social Determinants” – asking which is now more important for bringing down the rates of TB, new drugs and diagnostics or social change. The consensus reached was surprising because it came down so clearly in favour of social change. It was surprising because most of those attending the conference were researchers, people currently earnestly devoted to finding new and improved tools that might help fight this disease (both drugs and diagnostics). As such they might be expected to be more excited by the possibilities arising from the fruits of their efforts – new tools, in other words, rather than more nebulous social determinants. Clearly their hopes must be being polluted by the difficulties of the challenge that confronts them.
So what exactly is meant by these “social determinants”? It certainly includes reducing poverty. It also means clearing slums. It means improving conditions in certain critical workplaces which are known to promote TB. It also means reducing the chasms of inequality that exist, even in middle- and high-income countries. So broadly speaking, the majority of about two hundred TB researchers at the UCL conference last week in London believe that these sorts of social changes, not new drugs or new diagnostics, represent the better hope of containing the disease in the 21st century.
Pretty much the same story got told in Westminster later the same day by an economist who had been involved in the development of a projection of the future impact of antimicrobial (DR) disease in the next 35 years. A graph which she displayed (see below) tellingly illustrated why the lessons of history show us unequivocally why the consensus of the researchers is almost certainly correct. In fact this graph had already been reflected by similar graphs shown earlier in the day at UCL, and what they all show is that death rates from TB were sky high in the middle of the 19th century, and that wherever industrialisation took place they dropped massively over the next century until 1950 when the first TB drugs (listed on the graph) began to be widely used. Many factors allowed this to happen: improved nutrition (according to some the biggest factor of all); better living and working conditions (arising from the social legislation which began to be enacted in the 1890s); the introduction of the BCG vaccine (which is actually not that effective, and in any case was not used everywhere); pasteurisation of milk (bovine TB was contributing as much as a tenth of the epidemic); and X-Rays and radiography (that allowed signs of disease to be spotted much earlier and therefore cases to be far better managed).
In fact by 1950 the death rate from TB in the UK was less than a quarter of what it had been a hundred years before and half of what it was in 1900 - and it was at thisparticular point in the decline that the drugs finally arrived. Effectively this was at exactly the right time, especially because their arrival also happened to coincide withunprecedented socio-economic hikes in the same industrialised countries. This is why rates of TB finally plummeted in what are now called the ‘high-income countries’ –because the drugs arrived at just the right time, and then because there was a finalmassive effort employed to go out and look for every single remaining case of the disease. This also included those 90% of cases who were only latently infected but whose disease might pop out some time later.
As a result of this, by 1970 this ancient disease which had been ravaging Europe and North America a century before (causing between one-in-four and one-in-seven deaths)had effectively disappeared –an astonishing achievement. But when the focus was then switched to similarly dealing with the disease in lower-income countries there was unfortunately nowhere near the same amount of concerted effort made. More importantly when the drugs were introduced into these countries the existing levels of infectious disease in these countries were that much higher than they had been in those higher-income ones where they had been so successfully introduced 20 years previously. In these less developed countries, in other words, these drugs should never have been expected to make the same difference on their own – and they didn’t.
Forty-five years on and these same drugs and diagnostics are still being used to find and treat the disease. What this majority of TB researchers appear to have fully understood in London last week is that, without some similar beneficial cascade of ‘social determinants’ to those listed above, there really is little chance of getting on top of TB today even if new drugs and diagnostics are developed. There’s a very compelling explanation for why this is so – it’s because a dose of TB doesn’t confer any long term immunity in recovered patients. So if there’s enough TB circulating in their environment, there’s a very depressing chance that they will go down with the disease for a second time, and a not-very-merry-go-round of challenging lengthy treatment will be needed all over again – or(far worse) a strain of drug-resistant disease will emerge out of the shadow of the first.
In perplexing contrast to the above, the two organisations which are most experienced infacing up to the challenges of MDR-TB are both, in different ways, hanging their hopes on new drugs and diagnostics. One is MSF, and the other PIH. In fact both Keshavjeeand Mitnick, the two experts who anchored the PIH teleconference, were in complete agreement not just that “we do have the tools” but also that they will work if they are implemented properly. PIH’s clinical experiences in Haiti, Peru and Russia unequivocallytell them that they can achieve really telling success rates if the existing treatment for MDR-TB (which they make no bones about is still extremely difficult to endure and requires substantial technical resource) is well managed along with comprehensivepsycho-social, financial and nutritional support and ‘patient accompaniment’ (a therapeutic concept which lies at the heart of PIH’s dynamic approach).
The problem, of course, remains the massive imbalance between scale of problem and the available resource available to confront it. This situation is exacerbated because the populations that are most at risk of TB are those who are also the most “invisible to the halls of power” (in Mitnick’s words) – in other words they are the world’s poor. And this situation won’t improve, she reckons, as long as all policies continue to be developed around “a paradigm of limited resources”.
The policies so far developed by the WHO hardly give cause for anything but furtherconcern. In the 1970s its expert committee on TB advised not to treat latent infections in poor countries (as is done as a matter of course in higher-income countries) – effectively allowing an immense reservoir of inevitable disease to remain untouched and to feed the infectious pandemic. Then twenty years later in the 1990’s, after it became clear to everybody that TB had re-emerged as an immense global problem big enough to warrant an unprecedented announcement of a ‘Global Emergency’, the WHO homed in on a one-fits-all-solution which it called DOTS (directly observed treatment short-course)as being the best response to the problem. The sad fact, however, was that this was never going to able to deal with drug-resistant disease, a phenomenon which already existed and which has been slowly growing ever since.
Whilst the WHO still bask in the glory of their DOTS policy, Keshavjee rather sadly summed DOTS up last tuesday as “a great first step but a terrible long-term strategy”. The reality is that the WHO’s response looks to be continuously at least one stage out of step with the realtime development of the disease.
There was a WHO representative at UCL who could have further enlightened us on all of this, but what he offered was not that edifying. His short presentation centred on the WHO’s new ‘Post-2015’ Global Plan – the new strategy to supposedly ‘end’ TB. It contains massively ambitious targets which he developed in an irritatingly and stultifying fashion. In fact his style of presentation seemed intent on ensuring that he deliberately overran his allotted time span and therefore avoid any uncomfortable questions – and questions about this Global Plan are surely warranted because bafflingly not a single one of its new targets addresses drug-resistant tuberculosis. In the event just one short question was allowed before he whisked himself away. He was immediately (and perhaps not accidentally) followed by Professor Eskild Petersen, the editor-in-chief of the International Journal of Infectious Diseases, who promptly summarised his own opinion that TB today is “too big a problem to be left in the hands of physiscians alone” – and, as if this weren’t enough, told us in plain terms that he doesn’t believe that the WHO plan will work.
So exactly who is going to get to grips with this problem now if physicians can’t do it and the international agency designated to deal with global pandemics doesn’t want to? PIH believes that it can be done with a more collaborative, flexible and dynamic approach. They’re intending to take this to Chennai in India later this year where they will treat 3,000 patients over three years. But the reality is that there will probably be well over two hundred times as many MDR- and XDR-TB cases out there this year alone, and the number is growing year on year. Carole Mitnick played it safe last Tuesday by reporting that only about 10% of MDR-TB cases get treated – but Paul Farmer (another PIH expert who can be more vocal) has said that it’s less than 1% - and only half of these are treated successfully. The bottom line is that the vast majority of DR cases never see treatment.
MSF say the same thing as PIH but do so in slightly differently terms. Instead of focusing on the concept of treatment “accompaniment” as PIH do, they focus on “decentralisation”. Not long ago the only way that treatment of MDR-TB was considered possible was in hospitals. Given that demand has so massively exceeded any available supply of hospital beds, MSF have taken the bull by the horns and taken the fight directly to the townships and slums, into local clinics where they implement treatment in the heart of the community. This decentralised approach seems the only practical response possible but it still only sees around half of enrolled patients successfully completing their treatment. Despite this, in 2011 the idea was officially adopted by the South African Ministry of Health, and last year the country’s Health Minister Aaron Motsoaledi (who also happens to be President of the Stop TB Partnership) committed his country to a massive decentralisation programme aiming for 2,500 decentralised sites. To date, however (4 years after the decentralised policy was first endorsed) only around 70 sites exist, suggesting a lot more talk than action.
In any case MSF implore that “Each year we are diagnosing more patients with DR-TB, but the current treatments aren’t good enough to make a dent in the epidemic” and they hang a lot of their hope in new drugs – a lot more, it would seem, than the researchers did last week in London.
Two new drugs did appear two years ago, but a similar story to what MSF calls “Ready, Steady, Slow Down” revealed itself behind their approval. MSF reported last week that: “In the intervening two years, companies and researchers have received awards, accolades and reams of media coverage for introducing two new drugs to tackle TB, but meanwhile patients are largely stuck facing the same dismal outcomes they have for decades…to date, fewer than 1,000 people worldwide have been able to access the two new TB drugs…just a fraction of those who desperately need them.”
These sorts of anomalous numbers seem to take us right to the heart of the matter, and were also addressed to some degree last Tuesday by Yael Selfin, the KPMG economist presenting at the AGGP ‘World TB Day’ meeting at Westminster. Her team was tasked last year with the job of assessing the economic threat posed by DR disease. They didn’t just deal with the dollars, however – they took a tilt at assessing the human cost as well,concluding that there could be a staggering 76 million cumulative deaths from MDR-TB by 2050. They worked this from an estimated 40% rise in the rate of MDR-TB cases (which is far from extreme) – and predicted that this rise alone will result in deaths from TB (which are already running at an estimated 1.5 million and maybe more) rising by a further 2.6 million or 175%. In other words, death rates from TB look to be the worst recorded since the start of the 20th century. Ms Selfin seemed pretty clear that she saw it as the responsibility of politicians to address this problem (so essentially she was agreeing with Professor Petersen that it’s beyond the capacity of doctors alone to turn the tide). She was also to a large degree agreeing with Carole Mitnick (that populations who are being decimated by this disease remain invisible to halls of power) when pointing out that governments are still intent on to ignoring these sorts of numbers of human tragedy, but will readily focus on the same problem if they come to appreciate the consequential economic loss that might result from them. The USA, she reported, will likely suffer economic losses of £67.23 (£67.23 (£67.23 (£67.23 (US$100)))) billionfrom MDR-TB by 2050 – and India (one of the middle-income powerhouses for the ongoing tenuous global recovery) will suffer economic losses of £2.02 (£2.02 (£2.02 (£2.02 (US$3)))) trillion (along with over 18 million accumulated deaths from MDR-TB). The gross cost to the world economy in the next 35 years from MDR-TB will amount to US£11.23 (£11.23 (£11.23 (£11.23 ($16.7)))) trillion – or about the same as the gross economic product of the whole of Europe for a year. If these sorts of economic projections don’t wake politicians up to the problem, what else will? (And these economists should certainnly be congratulated on having enough faith in their figures to make the sorts of projections that epidemiologists have been so reluctant to do).
TB activism, sadly, has a poor history of success and civil society has also been very poor at engaging politicians around TB. Last year, however, there was a potentially important new initiative, the so-called ‘Global TB Caucus’. At last year’s World Lung Health Conference in Barcelona this Causcus issued a Declaration which is intended to provide civil society with a tool to pressurise politicians anywhere and everywhere
At least this now gives us a tool that each of us can use, because the Declaration requires that we each write directly to our democratic representatives over the coming months. The idea is to build up a global political movement. No-one should pretend that this is going to be an easy task but there is now a way of getting started. Of course it’s still astonishing that an initiative like this should be being started so late in the day, but at least it’s finally happening. Building a global political framework to drive action on TB is going to take time and and a lot of persistence, with the Declaration intended at least to be a tool to help achieve this.
But will our elected politicians just end up doing the same as those appointed to look after the health and welfare of the world’s most vulnerable, by paying some lip service and then burying their heads in the sand pretending the problem doesn’t exist or that somehow it will miraculously go away on someone else’s watch? (It should be noted that only one of the three members of the APPG, Nick Herbert, saw fit to attend the World TB Day meeting – suggesting that the others, Virendra Sharma and Andrew George, may have been more focused on seeing themselves returned in the forthcoming UK general elections than on showing up on the big day in the year for what is possibly the biggest public health challenge currently facing mankind.)
And will the circus of specialist TB conferences continue at the same time as the numbers of corpses grow? Only time is going to tell – and time is most certainly not on the side of those most at risk of this terrible morphing disease, but at least we now have an opportunity to make our stand on the matter.