June 8th 2014

The WHO's new 'Post-2015 Plan to create a World that is free of Tuberculosis'

Part 1 - A Critical Analysis

Article 1 of the WHO’s constitution states that that the objective given to it by its members includes the attainment by all peoples of the highest possible level of health. Article 20 even adds that it can actually direct its members to “take action” relative to the acceptance of any convention adopted by the World Health Assembly in pursuit of such a goal. The WHO has also been granted extensive international law-making or normative powers, powers which were intended to enable its noble aims. The record suggests, however, that these powers are never really used, even in the face of a global crisis with millions at risk. Certainly this has certainly been the case so far with TB, with a global emergency having been formally declared back in 1993 and with a pandemic still in full flow.

On the 19th May the World Health Assembly approved a new resolution to accept and adopt a new post-2015 strategy to fight this ancient disease. This resolution was unanimously endorsed by all of those member governments who make up the Assembly. What this means is that the governments of the world have now committed to a new and ambitious strategy to end TB as a global pandemic (they intend that it should be reduced to a global average of less than 10 new tuberculosis cases per 100,000 population each year) by 2035. This would still mean over three-quarters of a million new cases each year, but given the ‘story so far’ it is an astonishing ambition and would be a momentous achievement if it is achieved. As things stand today, in fact, it would seem to be an impossible one, so it certainly deserves some further consideration.

The World Health Assembly (WHA) effectively determines the policies of the World Health Organization (WHO). The Assembly meets annually in Geneva and is attended by ministerial delegations from all of the WHO Member States. Normally it focuses on a specific health agenda on each occasion, one which will have been previously worked on by its Executive Board. In this particular instance the proposed resolution has been being painstakingly developed by experts within the WHO itself over several years, as well as by a high level panel established by the Secretary General of the UN which submitted its own report to the WHO with recommendations for the new plan.

It should be noted that this is not the first time that the Assembly has passed a resolution in relation to TB. In May 2005 the World Health Assembly passed a resolution relating to the Sustainable Financing for TB Prevention and Control. Within this resolution it encouraged all of its member states “to ensure that all tuberculosis patients have access to the universal standard of care.” In other words, the decision-making body of the WHO was unequivocally intending that all patients as of 2005 should be having access to diagnosis and treatment by second line drugs if they were dug-resistant since this was the universal standard of care. This resolution is still a goal that is far  too far from  being met ten years later despite having been repeated since. It is in fact even repeated once again in the new Plan. In 2005 the Assembly also specifically requested that the Director-General of the WHO “implement and strengthen strategies for the effective control of, and management of persons with, drug-resistant TB”. Once again, this can hardly be claimed to have been achieved since the drug-resistant component of the pandemic remains so comprehensively uncontrolled, is still rising and threatens the whole enterprise of reducing the global prevalence of the disease.

At face value it may sound like the WHA itself has effective powers of direction over the implementation of strategies by the WHO, but given this single example from 2005 it can be seen that there is a chasm of reality between a resolution made in the comfort of a convention centre in Geneva and what is then taking place at the coal face of the disease. Almost everything that is TB-related remains a challenge in fact, something which may help explain why, nearly ten years down the line, such little progress has been made in implementing this fundamentally important directive.

The new Plan, however, is intended to be built on three main pillars. We will need to look at each of these in more detail shortly, but first we can take a look at the goals of the Plan itself.

The principle targets for 2035 are as follows:

1.      A 95% reduction in annual tuberculosis deaths (compared with a 2015 baseline of 1.3 million)

2.      A 90% reduction in tuberculosis incidence rate (to less than 10 tuberculosis cases per 100,000 population)

3.      No affected families facing catastrophic costs due to tuberculosis.

There are milestones identified that are expected to be being met along the way (for 2020 and 2025): at these points progress will be assessed and, if necessary, the targets will be adjusted. This has happened before. To anyone unfamiliar with the current pandemic and who is also unfamiliar with the multi-factorial complexities of this disease, these goals may not seem so extraordinarily ambitious given that the world is giving itself a full twenty years in which to achieve them, but one very important aspect of this disease needs to be properly understood – with TB everything tends to happen very slowly, even down to the rate that the bacilli replicate. Twenty years is a very short timescale indeed for tuberculosis.

A very brief review of these first two goals in the light of the achievements of the last twenty-five years may help to illustrate this.

That first new goal relating to reducing TB deaths has involved a fundamental shift of emphasis from the previous goal that was set for 2015. This previous goal had been to halve the rate of deaths (i.e. the numbers of deaths per 100,000 population) from a baseline set from the estimated rate for 1990. This new goal, meanwhile ,looks to reduce the absolute numbers of deaths.

Currently it is being promoted that this previous goal may be being met by next year – but this is a disingenuous projection: this is because the deaths that are being counted for this purpose do not include any TB deaths that occur each year in people also diagnosed with HIV/AIDS – and there are around half a million of them annually. If these deaths are included the fact is that this target will definitely not be being met next year; in fact it will be being missed by a significant margin. What is even more disconcerting is that, in terms of those ‘absolute numbers’ of TB deaths (which is how this new target will be measured), the current annual death total is actually not very different today to what it was being estimated to be back in 1990. The records show that deaths consistently rose for most years after 1990, and (according to the WHO’s own figures from its 2012 annual report) has only recently begun to fall in terms of absolute numbers at all. Because of the simultaneous growth of the global population, however, those 'rates per 100,000 population' were proportionately calculated to be reducing in the second half of this 25 year period even at the same time that those absolute numbers were still rising. So, when viewed in this way, this 95% numerical reduction in TB deaths looks to be a very ambitious target indeed.

The second new target, a 90% reduction in incidence rates of disease, presents a similar anomaly. Globally these rates also rose after 1990, just as the deaths did, peaking around 2006 following which they began to decline. This decline, however, is only very slow (though it has been enough to meet the ludicrously unambitious Millennium Development Goal for TB of “halting and beginning to reverse the incidence of tuberculosis by 2015”). Today, twenty years into a global emergency, these rates are only reducing at a meagre 2% each year. To give an idea of how meagre a decline this is, if it were to stay the same the new target now set for 2035 won’t actually be met until the year 2180.

There is nothing wrong, of course, with setting ambitious targets, but it should now be being realised that some serious game-changing is going to be needed if these new targets are to be taken seriously (as they certainly should be). The Plan itself offers some carefully considered ideas as to what these will need to be, and we will review a few of them shortly. But, the Plan in places also reveals what might be viewed as sufficient aberrations from reality to suggest that  the entire endeavour should be treated with circumspection.

It states, for instance, that the current WHO-coordinated global efforts to control tuberculosis (as led by its member states and as supported by their technical and financial partners) have produced “remarkable results”. The idea that the recent story of TB control has achieved anything that might be described as “remarkable” is, by any account, an appalling misrepresentation of the facts. TB remains the number two global infectious killer disease (and is quite possibly in fact still the number one infectious killer that it always was given the accepted dearth of vital registration surveillance systems required to monitor it). Drug-resistant strains of the disease have meanwhile been allowed to slip the net because of such an inert response to them and they now probably pose the biggest public health challenge of our age. The claim that the WHO-coordinated efforts had created such “remarkable results” was even justified within the text of the Resolution - by quoting the Millennium Development Goal “to have halted and begun to reverse the incidence of tuberculosis” by 2015. This goal has certainly been achieved, but it has hardly been “remarkable” given that it has been redundant for nearly ten years having been superseded by goals which the WHO’s StopTB Partnership itself set instead of it. These subsequent goals include a couple which will have been met by next year, some which haven’t yet been met and some which haven’t been nearly met.

So exactly how are these new targets going to be achieved? As already mentioned, the Plan identifies three pillars for its foundational structure: one is of “integrated patient-centred care and prevention”; the second is of “bold policies and supportive systems”, and the third is of “intensified research and innovation”.

Each of these pillars themselves are individually composed of what might be best envisaged as individual component steel reinforcement rods, some of which are identified as being absolutely essential for success. The Plan identifies this in the language that is used to define them. It’s worth looking at a few of them, and (where this language is identifiable in the paragraphs which follow) the relevant words will be accentuated in bold type to make them easier to spot.

One of them is that, understandably, the rate of reduction in incidence of disease will need to increase –from 2% to 10% per year. This increase is judged to be “ambitious yet feasible”. It is projected as being feasible, however, based on the fastest national level rates of reduction of TB disease ever documented. These are identified within the Resolution as being those “which occurred in the context of universal access to health care and rapid socioeconomic development in Western Europe and North America during the second half of the past century”. This has to relegate this goal to being one that is incredibly optimistic if it to be projected on to the regions of the world most affected by TB today. Whilst the whole world in the second half of the twentieth century was recovering from the devastations of a world war, Western Europe and North America in particular were enjoying a prolonged period of huge economic growth and unparalleled general affluence. Incidence rates of TB certainly certainly did dramatically decline in these regions as is being suggested, but this decline did not just come out of the air. It did so following a century of slower decline that had already reduced the disease to levels at which it could be attacked by the new drugs as well as by concerted campaigns of active case finding looking for cases of early disease.

Neither of these initiatives is remotely possible in regions where the disease is now out of control.

Today’s new drugs (and there are two) will not be able to be rolled out in anything like the scale in which the first two new drugs were rolled out in the 1950s and 60s – both because of lack of resource, and because of a very proper fear of promoting new resistances if they are in any way mismanaged. Furthermore the DOTS strategy that is so well established as the cornerstone of the general strategy (and which is not intended to be altered) does not rely on active case finding at all as occurred in the Europe and America – realities of resource and rates of disease dictate that it has no choice but to rely on passive case finding, i.e. on waiting for the patients to come for treatment. Active case finding in any high incident country remains impossible because of the scale of the task given the level of active infectious disease in the environment – it is really only physically possible when the rates of disease are already reduced to a manageable level.

The plan also depends upon tuberculosis care and prevention continuing to benefit from what the Plan describes as “general economic growth”. This itself is hardly something than can be relied upon given so many global uncertainties, but it is also a statement that is in any case rendered questionable in exactly one of the disease’s most dangerous hotspots. South Africa is a country which is most definitely currently benefiting from economic growth – it is after all one of the five growing BRICS economies. Its growth, however, is also at risk of being crippled by its enormous TB epidemic which is itself bedevilled further by its more recent growth of MDR- and XDR-TB. Incidence rates of TB in the country are the second highest in the world (at 1,000/100,000 - or 100 times higher than the 2035 incidence target) and these rates still show no sign of reducing, with experts now also stating that drug-resistance is out of control in the country.

There are many factors that impact on these national numbers – too many to be touched on here, but the one relating to budgets and funding is as relevant as any because it reflects directly on one of the steel reinforcement for the first pillar. The global budgets for the 2035 targets are still in development (most of them will be irrelevant in any case to South Africa given that it funds most of its national TB programme itself). The worry is, however, that they will prove to be both wayward and worthless if they do not pay good heed to the South African experiences in relation to DR-TB because the Plan dictates that the new budgets should adequately allow for the cost of “providing universal access to services for drug-resistant tuberculosis”. Universal access to treatment is a major reinforcing rod in the first of the three pillars. In fact “universal health coverage” is well defined in the Plan: it is “the situation where all people are able to use the quality health services that they need and do not suffer financial hardship paying for them”, and it adds that this provision is “fundamental” for effective tuberculosis care and prevention.

It also quite correctly states that providing this “will require a rapid scale up of laboratory services and programmatic management”. Based on the experience of the last few years with the so-called ‘high burden countries’ which are said to comprise 80% of the global burden of disease still struggling with their diagnostic resources this will be a massive task: the levels of vital diagnostic provision in these countries remains bafflingly below the global average.  It will also require a roll-out of second line drugs which is something that has proved impossible to implement anywhere at scale in the last twenty years.

Providing both diagnostics and drugs for DR-TB also come at considerable cost, but despite this both are being currently attempted in South Africa. Whilst notified cases of drug-resistant TB comprised just 2.2% of South Africa’s total TB case burden, the management of the DR-TB epidemic in 2011 consumed around 32% of its total national TB budget. (And it should be noted that the true rate of untreated drug-resistant disease is much higher than this percentage of notified cases). Drug-resistant TB is proportionately that much more costly to treat than the straightforward drug-susceptible variety. The nearest that the Plan comes to addressing this financial anomaly is in vaguely stating that “funding requirements are likely to increase in the immediate post-2015 period”. This is surely an understatement. These funding requirements will actually have to increase very substantially indeed if the goal of universal access is to be met – and we should remind ourselves that this is goal not a new one, addressed as it was by that other resolution passed by the Assembly back in 2005.

The Plan admits that the “capacity to diagnose drug-resistant tuberculosis is limited in most places where it is sorely needed.” In fact almost everything that is needed to contain the disease in any of its forms is in too short supply where it is most needed - this is one of the most troublesome pervasive paradoxes of the pandemic. The Plan also recognises that, “only a fraction of the estimated cases of multidrug-resistant tuberculosis receive a laboratory test to confirm their disease.” No-one would argue with this either, but it also states that an “adequate capacity to diagnose all cases of drug-resistant tuberculosis is essential to make further progress in global tuberculosis care and control”.  So we have here another steel reinforcing rod for the first pillar. Every member of the Assembly who knows anything about this disease must have been wondering exactly how such an “essential” part of the plan is going to be achieved and how it is going to be paid for. They certainly should have been doing so because the Plan which they approved also correctly recognises that “in most low- and middle-income countries, the currently available resources are inadequate or sufficient only for modestly ambitious plans”. Drug susceptibility testing is not a one-size-fits-all process.: it involves not just testing for resistance to first line drugs for MDR-TB  but also testing for second line drugs for XDR-TB. The capacity for testing for the former is still deficient even in high burden countries where the need is recognised to be greatest, but testing for the latter is almost non-existent in most countries where the disease is now appearing. 

The current gaps in funding the global strategic response to the pandemic are estimated to be around US$ 2 billion per year for programme implementation and around US$ 1.3 billion per year for research. These shortfalls, however, are only computed for the current plan which only addresses the pandemic up until 2015 with far more limited ambitions than the new Plan has. Attempting to resource what will be needed in order to manage the new post-2015 Plan is unquestionably going to reveal shortfalls of a quite different magnitude, and the Plan itself offers no real explanations as to how these further funding gaps are going to addressed beyond vaguely accepting that they are “likely”.

Meanwhile, the world is also short of nearly 4 million health workers. The unfortunate fact is that many of the more acute shortages of human resource also happen to occur where TB burdens are the highest, and this is hardly coincidental. Limited health resources promote unmanageable TB epidemics and this is one of the reasons that it is generally accepted in the world of TB epidemiology that no treatment at all is better than a poorly managed one. This factor of limited human resource must have been creating unexpressed discomfort in the minds of some of the ministerial representatives of those member states as they were unanimously endorsing the new Plan. Surely they must have been wondering how on earth the implementation of this Plan might be properly managed back on their home turfs. In fact the Plan is actually quite explicit on how this should happen: “National governments have to provide the overall stewardship to keep tuberculosis elimination high on the development agenda through political commitment, investments and oversight, while making rapid progress towards universal health coverage and social protection.” This must be as big a challenge as any. Certainly the recent story of the disease in South Africa (where almost all funding for its programme is ‘in-house’ and where the disease is most definitely high on the agenda, but where it is also out of control) is hardly encouraging in this respect. South Africa is a middle-income country: but it is especially the lower-income ones which remain the most vulnerable to this disease.

The Plan is not exactly enlightening on how such a challenge might be overcome. It suggests that “coordinated efforts” will be required to mobilize the additional resources required to fund such ambitious national strategic plans, ones which will include “a progressive increase in domestic funding”. Can such significant increases be achieved in a low-income country if a middle-income one like South Africa can’t effectively manage it?

But the Plan counts on something even more ambitious still, this time as a reinforcing rod for its second pillar. It unequivocally states that “effective tuberculosis prevention will require actions resulting in poverty reduction, improved nutrition, and better living and working conditions”. It lists other requirements as well, but what is worth realising is that it was exactly these particular factors which accounted for those early historical reductions of disease in Europe and North America – the ones that finally allowed for those subsequent rapid reductions in incidence in the second half of the twentieth century. And it is, of course, those subsequent rapid reductions of disease that the aspirations of this Plan are being modelled upon. These same preliminary factors, however (reduced poverty, improved nutrition, and better living conditions) had not happened overnight. They had actually been incrementally falling into place in these regions over an entire century between 1870 and 1970. For this new Plan to succeed, however, they appear to be being required to develop in as little as a decade.

No-one can argue that these are valid and timely ideas, not just because they lie at the core of the continuing pandemic which feeds of the poor and the malnourished, but also because they remain a stain on our collective humanity. But can such immense wider strategies be so rapidly mobilised as is apparently being imagined? The accountability for addressing this part of the Plan, at least as far as its expert authors are concerned, “will rest not only with health ministries, but also other ministries including finance, labour, social welfare, housing, mining and agriculture”. In fact it goes further still: “Eliciting actions from across diverse ministries will require commitment and stewardship from the highest levels of government.” As such, the Plan is beginning to look to be one that might effectively change the emphases on which our world is currently being managed. It is going to depend on the normative interventions of the G8, the UN and the World Bank as well.

Such aspirations should definitely not be dismissed out of hand. Any attempt at implementing them really does need to be founded on realities, however. In another part of the Plan it is a little less certain that its authors recognise what such realities are. A further steel re-inforcing rod, this one for the third pillar relates to the development of new vaccines given that the existing vaccine for TB is probably the least reliable widely-used vaccine in modern medicine. Certainly, everyone recognises that a more effective new vaccine is needed. The fundamental problem, however, is that developing one is far from straightforward: vaccinating against a disease which, even without mutation, confers no significant degree of lasting immunity in those infects is an enormous challenge. But the Plan now raises the stakes for this challenge further still. It states that “a post-exposure vaccine that prevents the disease in latently infected individuals will be essential to eliminating tuberculosis in the foreseeable future.” While the Plan’s authors might have been seeing this type of vaccine as being essential, many experts might equally consider it to be a practical impossibility. A post-exposure vaccine that can stop a recent instant infection like rabies or tetanus developing is one thing, but a vaccine that might hope to prevent re-activation of latent tuberculosis long after an initial cumulatively acquired infection must be viewed by most as a pipedream. The Plan, however, insists that this dream is realised in the next ten years. If this happens it will constitute perhaps the most dramatic medical achievement of our age.

There also seems to be one important component target that is missing: there are no percentage target reductions relating to drug-resistant strains of disease. Since the wider drug-susceptible pandemic is now reducing whilst the drug-resistant components are doing the opposite, making no attempt to monitor them as a principle part of the new Plan seems to ignore something rather important. This is not least because the achievements so far in respect of managing drug-resistant TB have been the least remarkable of all. Pretty much all of the targets relating to DR-TB that have so far been set are currently on course not just to be missed but to be missed by miles.

What follows is a table of some of the targets for MDR-TB for 2015 which were established in 2011  along with their baselines from 2009 and their current situations as made available from the pages of the 2013 Global Report. It certainly does not make for very encouraging reading. Some targets show little or no progress; only one seems remotely close to being met; and one (the rate of successful treatment for MDR-TB) even shows a significant reversal from the baseline target:

2009

(baseline)

2012

(2013 report)

2015

(Target)

% of previously treated TB patients tested for MDR-TB

7%

9%

100%

% of new TB patients tested for MDR-TB

7%

5%

20%

Number of countries among the 22 HBCs and 27 high MDR-TB burden countries with ≥1 culture laboratory per 5 million population

18-21

19

36

Number of confirmed cases of MDR-TB enrolled on treatment according to international guidelines

11,000

77,321

270,000

% treatment success rate among confirmed cases of MDR-TB

60%

48%

75%

% of national reference laboratories implementing a quality management system according to international standards

<5%

No data

>50%

% of confirmed cases of MDR-TB enrolled on treatment according to international guidelines

36%

92% of notifications

100%

Global, regional and national targets have been and still are the main tools for getting to grips with any pandemic. What has been repetitively identified is that certain selected targets which were set for 2015 are going to be hit (albeit that one of them will be ignoring deaths amongst the HIV co-infected). It is also being promoted that some will only be near-missed. What rarely gets mentioned, however, is the number of targets that are almost certain to be not just missed, but catastrophically missed, and most of these relate to drug-resistant disease.

The existing plan for 2015 was itself revised in 2010, midway during its programme period, in order to accommodate some of the emerging complexities. The original target for 2015, for instance, to reduce the rates of MDR-TB by 74%, was massively reduced to simply “reduce the global burden of drug-resistant TB”. In the event, even this won’t be achieved. So will this new Plan have to be similarly drastically revised midway? As things stand, almost certainly it will..

Meanwhile, who should be taking responsibility for the implementation of the Plan and for its success or failure? On this there is little clarity. The WHO certainly takes responsibility for developing the Plan, as well as for providing the requisite technical advice for its implementation and for collating the numbers. It also takes on the challenge of stimulating the massive research initiatives which are now needed. The governments themselves, however, have taken on the responsibility of adopting the Plan and so have the responsibility of its implementation – something which certainly is right and proper given their designated responsibilities to the welfare of their peoples. Whether the governments of some of those counties most affected by the pandemic can actually do much at all to ramp up their efforts, however, remains very much the biggest billion dollar question of all.

Part 2 of this analysis take a look at some actions that could be developed to help kick start a proper response to this immense challenge that has been set for2035.