Seeing politicians getting behind TB...

Last week at the ‘TB2016’ Conference in Durban, the official launch of an African TB Caucus was hailed as “a renewed political commitment” to ending TB in Africa. Let's hope that it is one.

Political representatives from twenty African countries had gathered to launch a formal network of parliamentarians from the entire African continent - politicians who are now saying that they are dedicated to leading the fight against tuberculosis. It should be cautiously noted that twenty countries in Africa add up to less than half of the countries in the region, which surely must leave some concern, but the same thing’s been happening recently global regions as well, each caucus representing a regional effort to launch parliamentary networks specifically dedicated to ‘upping the anti’ on TB, particularly to raise the disease higher up the list of priorities for Ministers of Health across every regions, and to generally build pressure for action on TB through parliamentary routes.

Parliamentarian Abera Buno Adula from Kenya signing the statement of commitment.

It all sounds really good, but we only too well know what politicians can be like, don’t we? (They’ll pretty much sign up to anything if it gives them a soundbite in the media and a few votes..)

Well, the day before the African Caucus was launched, the Stop TB Partnership and MSF (who were also in Durban) co-launched their Step Up for TB Campaign, demanding that countries do something more than focus their attentions on this neglected pandemic at TB conferences – that they must specifically ensure that their TB Policies are updated to align with current WHO global guidelines and that they must do so “within the next 500 days”. They have several good reasons to be more than insistent as we’ll see below.

One reason (which they didn’t mention in the report) is that three years ago another group of African politicians (this time the Health Ministers from the eight Southern African Development Zone countries - a region with the highest regional rates of TB anywhere in the world by a country mile) signed what they called the “Swaziland Statement” – on this occasion pledging to catch up on TB targets in the “following thousand days” – targets which had been most appallingly missed in the previous two thousand having been set as part of the Global Targets for TB set in 2006.

2013 through till 2016 … hmmm. This interval of time pretty much amounts to that thousand days which makes that pledge sound a litttle hollow today because there's far too little still to show for it. And now we’re seeing another pledge for the next 500 days? And what then? Should we simply expect another pledge, or another statement of intent?

Perhaps this sounds unfair, but we’re far from sure that it is. Last November the Stop TB Partnership and MSF (those same co-authors of the ‘Step Up for TB’ campaign) published the results of the first ever survey reviewing the true status of countries’ adoptions of the WHO's TB policies and guidelines. They published them in their ‘Out of Step’ Report, a document which surveyed the situation in 24 strategically important countries, all with big TB problems. Fifteen of the 24, for instance are on the WHO’s list of 22 so-called TB High Burden Countries (HBCs), and 13 of them are on the WHO’s other list of 27 so-called High Burden MDR-TB Countries (HBMDRTBCs). (All of them except one are on one or other of these lists, and six were on both lists). In other words all of these are key countries in the battle against TB.

In the report they took a look at how well these countries’ had adopted WHO policies and guidelines – basically assessing how they’re all doing in terms of responding to the WHO’s 1993 rallying cry that TB is a life and death global emergency, and also looking at how they were addressing the growth and threat of MDR-TB. These countries, we must stress, form the bulk of those which have had the most international focus directed on their epidemics (both by the global authorities and by international donors). As such it would be reasonable to expect that they’d be pretty up to date in their compliances with WHO recommendations and policies – as up to date, in fact, as any countries in the world.

Unfortunately the report shows that it’s not like that at all. Here’s one quote from the report as an for example:

“No country has [yet] registered the full set of DR-TB medicines recommended by the WHO guidelines.”

The truth is that a national TB program needs a bunch of different drugs to properly respond to a TB epidemic. One group of drugs (Group 1) are effective for treating drug-susceptible disease (which is thankfully still the bulk of the pandemic), and then four more groups can eaxh come into play when the disease becomes resistant (usually a drug is selected from at least three groups to maximise chance of cure). Here’s the list of the groups of drugs:

Group 1: pyrazinamide, ethambutol, rifabutin, isoniazid, rifampicin, rifapentin

Group 2: kanamycin, amikacin, capreomycin, streptomycin

Group 3: levofloxacin, moxifloxacin, ofloxacin

Group 4: para–aminosalicylic acid, cycloserine, terizidone, ethionamide, prothionamide

Group 5: bedaquiline, delamanid, clofazimine, linezolid, amoxicillin/clavulanate,

thioacetazone, imipenem/cilastatin, high-dose isoniazid, clarithromycin.

Notwithstanding this registering of the drugs (or lack of it), it also transpires that only three of the 24 countries actually had all the medicines in these five groups even in their National Essential Medicine List (EML) and so would comply with the Global WHO Model List of Essential Medicines. In fact five of the countries didn’t even have one single complete group of any of these anti-MDR-TB drugs (i.e. in groups 2-5) in their EML.

So let’s tell this the way it is (and the way we think it should have been told at the UN when another bunch of politicians signed up to the wonderful sustainable development goals) or at the World Heath Assembly (when another bunch still merrily and unanimously endorsed the Plan to End TB by 2035 when they must of known it was a dream): no country, let alone any region of our world, is going to defeat this disease pharmaceutically by 2030 if they don’t have the necessary drugs to do so in their drug cabinets.

The reality, at least according to this report, is that none of these special countries has all the drugs they need registered for use, and only three have all of them on their EML. Of the remaining countries, a shameful five of the 24 had only one complete group of anti-TB drugs on their national EML – the other four groups were incomplete. A further four countries had just two complete groups, and five countries had only three complete groups. And truly shockingly, five countries (India, Nigeria, Kyrgyzstan, Kenya and Zimbabwe) didn’t have a single complete group of any of the MDR-TB drugs on their EML – with the first three of these hanging out there in the WHO’s HBMDR-TBC list (with India being one of them with the dubious honour of being home to the most MDR-TB cases in the world).

And then this gets worse.

Only “half of the countries surveyed” says the report, “have guidelines in place to allow the initiation of DR-TB treatment at district level” – in other words in these countries MDR-TB treatment will only be administered to MDR patients at their major city centres.

And we still hope to see TB ended by 2030?

At least there's been some good news appearing in the media in the last couple of years on TB - on the ‘much needed and long overdue new TB drug’ front. Bedaquiline received accelerated approval from the US Food and Drug Administration in 2012, and then delamanid received approval from the European Medicines Agency and Japan’s Pharmaceuticals Medical Devices Agency in 2014 - the first new TB drugs appearing in the last fifty years. So how are these two new drugs being received out there in these critical countries where TB and MDR-TB is entrenched? Are patients seeing them as they should be (and as they certainly would be in high-income countries)? Well, according to the report only eleven of them even have national guidelines in place on the use of the first one (bedaquiline approved in 2012) – and only four had national guidance on delamanid. That’s some enthusiastic response in the countries where patients most need them…

The report looked at this same thing another way as well. They surveyed each country in accordance with four different criteria for their capacity to address MDR-TB: whether they had a national policy on bedaquiline, and whether they had a policy on delaminid (as discussed immediately above); but also whether they had an essential medicines list which included drug groups 2-5; and finally whether they had either new or repurposed drugs available for compassionate use. Four of the 24 countries failed on all four counts (two of these being HBMDR-TBCs); seven of the 24 failed on three of the four criteria (four of whom were HBMDR-TBCs). And only one country out of all 24 met all of them – so let’s name it because they deserve an accolade: it was Belarus.

Okay, we hear you say - so here they are banging on about MDR-TB. But it’s only a small proportion of the pandemic, after all, and the WHO say it isn't really rising: surely the rest of the disease must be being handled better…?

Well (leaving aside what the true state of the MDR pandemic may really be) the report took a look at DOTS – the very cornerstone of the WHO global TB strategy (‘Daily Observed Treatment Short Course’). As part of this policy the WHO, the report explains, recommends daily dosing “wherever feasible”.

Bizarrely, though, India and China still recommend intermittent therapy for DS-TB instead of daily therapy (with these two countries alone accounting for almost 40% of the estimated global burden of TB). In fact, six of the 24 countries surveyed reported still using intermittent treatment. In other words a quarter of these countries with global focus directed on their well-recognised epidemics for nearly two decades don’t see fit even to properly implement DOTS.

And what about the standard Group 1 drugs themselves? Well, since 2010 the WHO guidelines have recommended so-called “fixed-dose combinations” (FDCs) of these for the optimal treatment of drug-susceptible TB. In the 'Out of Step' report, however, three countries (India [again!], the Russian Federation and Ukraine) were reported as not using FDCs as their preferred formulations in their national guidelines. Why on earth are any HBCs still using FDCs let alone any others?

Since 2010 the WHO have also not recommended the empirical use of the ‘Category II’ regimen for re-treatment TB cases. (Category II adds streptomycin as a single additional agent to a standard four-drug Group 1 combo when it’s seen to be failing). We should add that in our humble opinion this practice shouldn’t just not be recommended – it should be immediately globally banned because it’s long been accepted that adding a single drug to a failing multi-drug regimen for TB likely amplifies drug-resistance. Whatever the case, the report records that only “ten [of the 24] countries are in line with WHO guidance” on this aspect. Dear God – fourteen of 24 critical countries still use a regimen that is known to potentially stoke drug-resistance?

It’s looking pretty bad, isn’t it? Actually the report itself could even be accused of understating how bad it is, cautiously qualifying that Category II has been shown to have “poor outcomes” in countries with high background rates of MDR-TB. For “poor outcomes”, we’d say it would be more accurate to have said ‘more dead patients along with more avoidable untreatable infectious airborne disease’.

In fact this looks even worse when we read in the report that Category II is still recommended by both India and China (these countries together having 40% of the total estimated burden of TB - or about four million new cases each year) and both also with recognised existing high burdens of MDR-TB (Well - surprise, surprise…).

Any reader of these blogs will be aware that we are more prone to direct the focus of our concerns at the WHO in Geneva. This blog’s a little different in this respect: whilst we think it’s still quite reasonable, in the light of the report, to suggest that WHO’s officers on the ground might have been making a lot more effort to influence policies and implementation of TB treatment in these key countries, we find ourselves focusing our admonishments at health ministers of these countries and at the managers of their national TB programs. Twenty-two years into a Global Emergency there can be NO excuses at all for what’s still going on out there. This is still a shameful response to an ongoing public health disaster.

So if parliamentarians are now seeing it as a good thing to be seen to be getting stuck into this issue, then we say “Well and good, and not a moment too soon!”.. but we'll take this back if it all ends up changing too little too late. Not if we see another deadline being set behind another deadline, and another pledge made as if an earlier one had never been made. There's a mountain to climb here. It can be climbed for sure but it needs real political will and resource. Dr Joanne Carter nailed it last week when she explained how TB “has climbed the list of major killers”. She said that it’s simply “because it is at the bottom of the list of political priorities". She’s Executive Director of RESULTS and Vice-Chair of the Stop TB Partnership Board, and she should know.

So please, politicians to step on up in your caucuses - but make sure that we see you staying standing for the duration - staying there for TB till we see this disease properly defeated. The whole world’s need to start watching.