‘The time has come to move TB to centre stage’ – but what’s happening in India?

The UN has only ever previously called summits on health issues for three reasons: HIV, Ebola, and widespread chronic diseases (which essentially means diabetes). This week has been the fourth, with the UN hosting a panel discussion and making a resolution regarding the growing global threat from AMR or anti-microbial resistance – or the disquieting ability of microbes to morph and mutate to make themselves immune to assaults by the drugs meticulously developed to kill them.

Within the resolution itself there is an important reference to tuberculosis: “Within the broader context of AMR, resistance to antibiotics which are not like other medicines, including medicines for the treatment of tuberculosis, is the greatest and most urgent global risk that requires increased attention and coherence at the international, regional, and national levels.”

So far so good, because anti-miocrobial resistance (with MDR- and XDR-TB very much acting as its vanguard) unquestionably poses a major health risk worldwide. We have already recorded our concerns, however, that this threat is still being dangerously numerically underestimated, but whilst Dr David Nabarro, the UN Special Advisor on the 2030 Agenda for Sustainable Development,might well not agree with some of our calculations, we certainly would agree with his own observation that “Multi-drug resistant TB needs to be high on the global antimicrobial resistance agenda as we discuss these issues at the upcoming United Nations high-level meeting.”

We’d go further, though, and line up behind South African Health Minister and Chair of the Stop TB Partnership Aaron Motsoaledi who has proclaimed that, “The time has come to move TB to the centre of the stage”. He reckons that this week’s summit should be seen as only a first step towards doing this: “A United Nations High-Level Meeting devoted [entirely] to TB in 2017 is an important way to do this and to reframe TB from simply a technical health problem, to a global development challenge requiring a whole of society response.”

The true enormity of this challenge (as well as its urgency), however, has been highlighted by two separate papers which have been recently published in the Lancet. Both concern the management of TB in India, a country estimated to have as much as one quarter of the global burden of the disease, as well as what is reckoned by many experts to be MDR- and XDR-TB problems that are already well out of control.

(photo by James Nachtwey)

(photo by James Nachtwey)

The first study[1], led by Nim Pathy of Imperial College London and funded by the Gates Foundation, fundamentally challenges the estimate of tuberculosis in the country, calculating that the total number of patients receiving TB treatment in India in 2014 wasn’t 2.2 million (as per the most recent WHO Report), but was much more probably at least 3.6 million. Put another way, the WHO estimated that 800,000 cases of TB were missed by the Indian National TB programme (RNTCP) in 2014 (which is surely bad enough), but this study puts this missing number at 2.2 million (i.e. a case detection rate of just 44% instead of an officially suggested 74%). And this number doesn't include those who just weren't treated at all. If this study is right then this in turn adds up to more than two million infectious cases who weren’t properly treated in 2014, many of whom will have remained infectious, and a proportion of whom will inevitably have become drug-resistant because of partially completed treatment. (This is no fantasy – the study calculated that the average length of time of the treatments which were conducted in the private sector was only four months’ duration – two months short of the WHO requirement.) It surely suggests a TB programme that is dramatically failing the nation.

Compute the study’s conclusions into the global numbers and it doesn’t make for very cheery reading at all for those tasked with bringing the numbers down either. Current global ‘new case’ estimates of TB incidence run at 9.6 million a year; if this current study is correct in its conclusions, then the global incident rate is actually running at 11 million (globally a 15% hike at a stroke). Meanwhile according to the WHO the current global estimate of missed cases runs at 3.6 million – but this study’s estimate hikes this number up to over 4.4 million (or at least four out of every ten TB cases worldwide). Meanwhile God alone knows what this might be doing to the annual death toll…

The team reached their conclusions by analysing the nationwide sale of anti-tuberculosis drugs which occurred nationally across the private sector in India in the course of 2014 (sales which legally have to be recorded and reported, which amounted to almost 18 million patient months of treatment). They then allowed a generous deduction for TB drugs which would have been probably mis-prescribed to patients who wouldn’t have had TB at all (they cut these reported numbers by half), and then coupled this number up with the number of known notified treatments made by the national TB programme (RNTCP) to come up with a grand total of estimated incident cases of TB – amounting to 3.6 million instead of 2.2 million.

It’s tempting to point the finger at India’s huge informal health sector as being responsible for what is such a truly immense consumption of tuberculosis drugs (half of which, or 9 million patient months’ worth, is believed by the study team to be straightforward misuse which of course itself will increase rates of anti-microbial resistance). The second study, however, (which we’ll come to in a minute) shows quite clearly that anti-tuberculosis drugs are actually very rarely dispensed by the sector’s other operatives – by its pharmacists, informal health providers, and practitioners of alternative medical systems. In fact it’s fully qualified, allopathic doctors who are the primary source of these anti-tuberculosis drug sales, and should surely thus be the immediate and well overdue target of far more proactive engagement to ensure better antimicrobial stewardship if this week’s UN resolution stands a prayer of adding up to anything.

Unfortunately, this first study’s numerical conclusions are almost certainly an underestimate anyway, because there are also several types of TB patient that this data didn’t capture at all. There are those who must indeed be receiving treatment for tuberculosis in the more informal health-care sector (of whom there are bound to be many); there are those who for many reasons don’t ever contact the health-care system at all (the number of whom is certain to be substantial); and there are also those who receive very risky treatment for multidrug-resistant tuberculosis in the private sector (a number which is known to be growing and which is surely the most frightening of all since it’s already been well recognised that these are the worst served and can easily stoke community rates of untreatable XDR-TB). Taken together, these factors would suggest that the true burden of tuberculosis in India is probably even greater than what is suggested in this paper.

What’s of additional concern is surely this, though– why on earth are TB patients resorting in such droves to the private sector of India’s health system and paying for this dubious privilege when TB drugs are free at point of care in this country? Can the public sector really be so appallingly bad? India’s RNTCP, after all, is fully committed to providing free high-quality tuberculosis care to patients in the private sector as well as the public one. (See: Sachdeva et al. New vision for Revised National Tuberculosis Control Programme(RNTCP): universal access—“Reaching the Un-reached”. Indian Journal of Medical Research 2012; 135: 690–94).

If a 6-month course of first-line TB drugs costs US$20, this first Lancet paper implies (quite incredibly) that nearly US$60 million was spent in out-of-pocket expenditure on first-line tuberculosis drugs by Indian TB patients (forget consultation charges) – by a patient group that is already well-recognised to be the most vulnerable to this disease because of their poor economic status.

Something has clearly been going drastically wrong with India’s TB programme and it’s been going on for years right under the global authorities’ noses.

Well, so far we’re pointing our finger towards India’s doctors, many of whom seem happy to ignore WHO recommendations and take money that they shouldn’t do from their patients. So what about this great nation’s pharmacists – how do they hold up to scrutiny in this respect?

This question is a valid one because many tuberculosis patients in India seek both medical advice and drugs from their nearest pharmacies, understandably so because of ease of access and the chance of avoiding the doctors’ consultation charges by doing so.  Unfortunately, it looks like this sector of health care is also sorrily suspect as regards of promoting AMR, though for other reasons. Certainly this is the case as far as the second paper is concerned.

This second study[2], conducted by a team led by Srinath Satyanarayana (of McGill University, Canada), mobilised a group of standardized patients (otherwise called ‘simulated’ or ‘mystery patients’) to reveal how pharmacies in three Indian cities respond to members of the public who might present to them either with TB symptoms or with clinical TB diagnoses, and thus determine whether or not these pharmacies are contributing to the inappropriate use of antibiotics.

These 1200 ‘mystery patients’ presented themselves in 622 pharmacies in Mumbai, Chennai and Pathna in 2014-15. They split into two categories, either reporting symptoms which should immediately have alerted the dispensing pharmacist that the person in front of them had a high probability of having active TB, or alternatively presenting them with evidence of bacteriological confirmation of TB diagnosis (in other words leaving no doubt at all about it). In either case, if the pharmacist responded properly, the mystery patient should have been directed immediately to an appropriate TB DOTS centre without dispensing either antibiotics or steroids.

Unfortunately the team recorded ‘ideal management’ of these patients (defined by the team as a referral at least to a ‘health care provider’ and without a prescription of either antibiotics or steroids in the process) in only 80 (or 13%) of the 599 cases who presented with ‘TB-probable’ symptoms.  That’s a terrifyingly low number. The pharmacists did better with the patients who came in with confirmation of diagnosis, but even this only occurred in 372 (or just 62%) of the 601 cases who presented with indisputable bacteriological evidence of disease.

Most astonishingly of all, in only three instances of all 1200 pharmacy presentations was the standardised patient referred specifically to an official ‘directly observed treatment, short-course’ (DOTS) centre as opposed to a health care provider – as should have been optimally (and reasonably) expected to be the case if procedures were being properly followed.

We’ve noted already that many patients resort to pharmacists in order to avoid doctors’ consultation costs. It seems, however, that India’s pharmacists show little sensitivity to this economic vulnerability, being as they are quite happy to inappropriately sell these patients drugs (albeit not TB drugs, but still other antibiotics or steroids) that not only will probably do these patients no good, but might also stoke the national AMR problem at the same time. It’s no wonder, perhaps, that India has the highest total national consumption of antibiotics: it may well be because it makes such financial sense to the nation’s pharmacists. What we now ask is whether the nation’s pharmacists will still try to keep it that way in the light of the UN resolution.

We also sadly note that, of the total referrals that were made, 60% were to doctors in the private sector where the patient would most certainly have to pay at least for their consultation. This begs the logical question as to whether informal financial arrangements might exist between pharmacists and private physicians which might induce such unnecessary referrals.

So three further questions need asking.

The first is this rather blunt one: does the Indian pharmacy industry in these cities give a flying fig about the people it serves? The second is more fundamental: does it have any real clue about how TB cases, either probable or definite, should be being handled?

The third is the biggest one of all: is the Indian Health Ministry going to do something about all of this?

Meanwhile, if you are a person who prays, it looks like every TB patient in India is in need of your active and immediate help.

[1] The number of privately treated tuberculosis cases in India: an estimation from drug sales data

http://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(16)30259-6.pdf

[2] Use of standardised patients to assess antibiotic dispensing for tuberculosis by pharmacies in urban India: a cross-sectional study

http://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(16)30215-8.pdf