The Indian Factor (part 2) and prevalence surveys...

We think that we’ve already made the point in these blogs that moving the goal posts (or indeed not moving them depending on how the picture is being rigged), using moving benchmarks neat-sounding soundbites or exploiting small print in reports is making TB data very difficult indeed for either the TB stakeholder, the  harried journalist (or even the expert at TB Alliance or MSF) - in fact for any of us for that matter to understand. It’s certainly hard to properly evaluate.

So how much of this data that we’re presented with is yet really that solid? All we feel qualified to say on the matter is that the better the national or regional prevalence survey, the more solid must be the resultant estimate. Unfortunately it’s sometimes been the case that such better surveillance reveals more disease than was hitherto believed to exist (this certainly hasn’t always been the case – though of the 18 countries that were identified in the 2016 Global Report as having had prevalence surveys conducted only one, Gambia, reported significantly less than was previously estimated and five reported significantly more, Lao, Indonesia, Tanzania and Ghana[1]). It has to be noted, however, that on occasion it’s revealed not just more disease, but an awful lot more of it. But while such a revelation might be terrible it surely does add much needed solidity to our understandings of the state of tuberculosis today and what’s really needed to defeat it.

China in 2011

Six years ago. the 2011 Report offered evidence of how the global burden of disease could be re-estimated downwards in terms of both incidence and death rates, and not upwards. This  followed new data gleaned from “consultations” with a number of countries during the previous year, mainly data from China (though it didn’t in this instance include a national prevalence survey). The dramatic reductions in TB cases and deaths which China reported that year were still taken very seriously in Geneva, however, something which had a positive impact on the whole global picture simply because of the proportionate size of China’s population. As a consequence the 2011 Report was able to retrospectively conclude that the number of incident cases had actually been falling since 2006 (rather than still rising slowly as was believed to be the case up until that year). So the graphs were redrawn, something which must have given cause for a sigh of relief in Geneva because this included the estimate of the annual number of deaths which was revised downwards as well. (It had been 1.7 million in the previous Report and dropped to 1.45 million which incidentally is actually the lowest it’s ever been reported to have been to date).

Pakistan

A prevalence survey conducted in 2011 revealed a prevalence:notification ratio of 3:1 though oddly this wasn’t interpreted as meaning that the estimated prevalence or incidence rates needed much adjustment.

Nigeria

Unfortunately another report soon really upset the numbers however. This was a national prevalence survey which was conducted in Nigeria in 2012. It was a survey that tested random individuals at carefully selected locations across the country and then analysed the results to extrapolate the estimated national prevalence rate.  What was concluded was that the total number of Nigerian TB cases (by being identified as being sputum positive) was five times higher than the number of cases that were being notified in Nigeria that year. That was pretty terrifying but actually it was worse because about half of all cases that had been notified into the Nigerian TB program that year weren’t even sputum positive anyway (but had been diagnosed based on symptoms or X-rays). In other words, directly comparing the number of cases that were found sputum positive against confirmed sputum positive cases who’d been notified to the TB program suggested that it was even possible that there was as much as ten times more sputum positive TB in the country in 2012 than was being notified and treated that same year – and of course sputum positive cases can generally be expected to be infectious. 

Of course, there inevitably had to be an awful lot more TB deaths as well, and this couldn’t possibly have only applied in isolation to 2012 either: it logically must been happening in the years before then as well. Furthermore it could hardly be denied that such an immense under-estimation of disease (one that had been being made by so-called ‘experts’) might also be typical of other countries in the same region as well.

Adjustments had to me made to the Nigerian estimates as a result: in the next Report its prevalence rate was ramped up by 100%, incidence rate by 200%, and the death rate by 400% with these rates in turn having a consequential impact on both regional and global numbers. The case detection rate, meanwhile, was reduced to less than a third of what it had been, to a quite appalling 15% (the goal for 2010 is 90%). Were these all fair adjustments to have made? The answer is that we don’t know and never will.

Indonesia

Something more dramatic was revealed more recently in Indonesia where another prevalence survey also reported far more TB than had been hitherto estimated. The burden of TB in Indonesia was found to be “much higher than previously thought” resulting in an upward incidence rate revision of 403/100,000 (instead of 188/100,000) adding an extra half a million new cases to the 2015 Global Report and seeing a collapse of the Indonesian case detection rate from 72% to a quite terrible 32%. Once again, the expert opinion had got things terrifyingly wrong. And like Nigeria and China, Indonesia is a very populous country, so anomalies here also inevitably had impact on global estimates.

Kenya

On March 24th this year (World TB Day) the Kenyan government released the results of their own national prevalence survey that they'd done on TB across the country. The survey reported a prevalence rate of 558/100,000 whilst the most recent reported official estimate was 266/100,000 (as had been published in the 2015 Global Report) - i.e. almost half what the survey found. This suggests that there's pretty much twice as much TB as previously reckoned to be out there in Kenya. (For reasons that we can’t really fathom and we may blog on in due course, the Global Reports now no longer include estimates of prevalence. This seems to us to be a shortcoming which should be being questioned since it will make future prevalence studies very difficult to assess against official incidence estimates.)  Whatever, this survey also meant that the country’s case detection rate had to be slashed by a quarter meaning that there must be a lot more untreated infectious TB out there in the country each year.

 

…and India (where a national prevalence survey has never been done but is being carried out this year..

As we’ve blogged before, in this latest report it’s been India which is finally beginning to come under the microscope. As with Nigeria and Indonesia, because of new data (a regional prevalence survey in the state of Gujerat) the number of cases of TB for the country has been revised significantly upwards, which in turn has meant that the number of deaths have had to be revised upwards as well. In many ways India is far less typical of the other countries in the same region than perhaps Nigeria or Tanzania may be, but the proportion of TB cases in India was already so huge in terms of the total global burden that the numbers of regional and global new cases (as well as the number of estimated global deaths) have been consequentially significantly hiked in this latest Report as well. It’s realised, for instance, that at least an extra million cases are being missed from being properly treated – and it looks like they must also almost all be in India. The same applies for the extra annual 300,000 deaths that have retrospectively materialised – hence that telling statement in the most recent Report that “the TB epidemic is larger than previously estimated” while at the same time it’s still paradoxically claimed that the slow downward trends in reductions in both TB deaths and disease are “much the same as previous”.

As we identified in Part 1 of this blog on India, in this most recent Report the numbers for India have been hiked following “accumulating evidence that previous estimates were too low”. As we discussed in Part 1 as well, it looks highly likely that this picture is going to get worse after India completes its first national TB prevalence survey in 2018.

In fact the picture that is finally emerging (which is really of no surprise to many) is that TB control in India is in real trouble. Not only are the numbers looking to be dramatically higher than was being reported, but rates of DR-TB are frightening as well – something that is easily explained by the way that drugs are prescribed in the country. The bottom line is that India, without any doubt at all, needs to get its act together in terms of TB control.

Well just three months ago in February the Government of India announced what it’s going to do about this: quite simply it plans to eliminate TB in the country by 2025 – a quite astonishing announcement that was made as part of the country’s Union Budget address.[2]

We immediately wondered how on earth India’s government could really conceive this to be any sort of possibility because what they’re essentially saying is that they intend to beat the rest of the world in this endeavour by a decade (and the global targets are already ambitious enough!). Well we soon came across an interesting article in the BMJ which spelled out some rather basic suggestions as to what they need to do at least to set the wheels in motion.[3]   

Here are some of the article’s main suggestions. (We very seriously suggest that you don’t have anything in your mouth as you review them because you may well find yourself choking in disbelief):

1. India needs to give priority to and begin investing in health.

2. The budget for India's Revised National TB Control Program (RNTCP) … needs to see an increase.

3. India must start to seriously tackle key determinants of TB, especially poverty, undernutrition and tobacco smoking.

4. India must address the major gaps that have already been identified in the TB cascade of care in the public system. 

 In other words it’s the blindingly bloody obvious that’s needed even to begin to kick off this campaign - the same blindingly bloody obvious that’s been lacking for decades. But even more beyond belief is some of the background for this dire situation that the finance minister reckons can be resolved in just seven years (which is a blink of an eye in the world of TB).

Up until January 23rd this year the recommended way of treating TB in India was to give the patients doses of their TB drugs three times each week. So what about that ‘D’ in DOTS (the WHO approved regimen that’s been the backbone of the global response to TB for twenty years)? That ‘D’ doesn’t stand for ‘daily’ but it does stand for directly observed which is meant to occur on a daily basis... Oddly that didn’t seem to matter to the Indian TB program until January this year because it was going to cost more and India’s national spend on the health of its citizens has been so frighteningly low.

There’s a very good reason, of course, for that daily directly observed dosing (which is why it’s so extraordinary that international pressure hadn’t been effectively applied before this to the Indian TB programme to get into line with the rest of the world): it’s to ensure that the patients take their drugs in a way that stands the most chance of eradicating the pathogen by putting consistent pressure on it, and most particularly that doesn’t allow it regular windows of reduced pressure in which to develop resistance. Unfortunately there’s every probability that the Indian three-day-a-week regimen has been doing exactly this – allowing the bacteria windows of opportunity to survive the assaults against them – and that it’s been doing so on a truly colossal scale.

But back to January 23rd for a moment: this was the day that the Indian Supreme Court directed that the nine months long regimen of giving patients three dosages of their drugs a week should ‘as far as possible’ be replaced with daily doses.[4] The case that was being adjudged in the Court that day had been filed by TB specialist Dr Raman Kakkar who had called the three-times-a-week protocol both ‘unscientific’ and ‘improper’, saying that it was only there to cut costs. Furthermore he stated that it both promoted relapses and generated drug-resistance in the patients’ bacteria, doing so by quoting numbers that were truly frightening – India’s TB patients have a quite terrifying 10% relapse rate as against a 3% global rate.

Well a few weeks ago the Indian Health Minister J.P.Nadda weighed in behind the governement’s Finance Minister announcing that India has formulated a “national strategic plan” with a special focus on stamping out the disease at “grass-root levels”.[5] “We have implemented daily drug regimen for treating tuberculosis (TB) in five states”, he said “and by the year end it will be rolled out in the entire country.”  Wow! That adds up to daily DOTS, the program that’s been the cornerstone of global TB policy for decades. Talk about ramping things up at grass roots levels…

But there’s actually worse still in the existing pipeline because when those 10% of Indian patients relapse the vast majority (if treated further at all) are put on the infamous Category II treatment. This is a regimen that really should have been internationally banned by now because it’s widely accepted that it has the potential to promote further drug-resistance by only introducing one new drug (streptomycin) into what’s already a failing regimen (when at least two should be added). That’s bad enough but in India the‘strepto’ is only administered three times a week as well (it has to be injected) when it should also be being administered daily – which means (wait for it..) that these multitude of relapsed patients get only 24 doses when elsewhere in the world (i.e. wherever Category II is still unfortunately being administered) they get 60 of them.

Is it surprising that India has so many relapsed cases, and furthermore is it surprising that it has so much drug-resistance emerging? The answer of course is ‘no’.

Arun Jaitley, the Indian finance minister, may have grandly proclaimed how TB was going to be eliminated in India by 2025 in his February budget speech, but he didn’t exactly explain how this was going to happen and Health Minister Nadda’s optimistic announcement doesn’t get anywhere near explaining it either. There have been strong hints that the health budget will be hiked, but one analysis of the country’s health budget has shown that most of the increase isn’t even going to be spent on India’s principle health priorities (many of which are facing funding cuts).[6] In fact allowing for purchasing power parity it even seems possible that the funds available for TB control may end up being even lower than they are currently just when they need to be dramatically increased.

Let’s put this in perspective for a minute: Indian government expenditure on healthcare has been among the lowest in the word (at 1.4% of GDP).  It’s now being said that this percentage is going to be hiked up to 2.5%. Time will tell if this happens – but it’s worth bearing in mind that high-income countries spend as much as 15% of GDP on healthcare. Even amongst similar BRICS economies, India’s spending is poor. According to World Bank data, in 2013 India spent 1.3% of its GDP [7]on the public health sector; by contrast, Brazil spent 4.7%, China 3.1%, and South Africa 4.3%.

So what is going to happen to TB control in India – the country that probably has one in three of the world’s TB cases within its borders and has such a dysfunctional TB program that needs massive re-organisation? Well something truly massive needs to change or it’s going to be more of the same with more and more drug-resistance thrown in to make it all a whole heap worse and millions more will die from a disease which is still (when it's not drug-resistant) cheap to treat and curable.

We’re sure some citizens of this great nation will disagree with our analysis and might even feel offended on behalf of its democracy given that we’re choosing to be so critical of the nation’s elected leaders, but as playwright Lillian Hellman once said: “Since when do you have to agree with people to defend them from injustice?”.

[1] http://www.who.int/tb/advisory_bodies/impact_measurement_taskforce/meetings/tf6_p06_prevalence_surveys_2009_2015.pdf

[2] Kumar S. Winners and losers in India's science budget. Science 2017.http://www.sciencemag.org/news/2017/02/winners-and-losers-india-s-science-budget)

[3] http://gh.bmj.com/content/2/2/e000326#ref-1

[4] http://indianexpress.com/article/india/sc-asks-govt-to-provide-daily-drug-doses-to-tb-patients-4488068/

[5] http://www.financialexpress.com/india-news/india-aims-to-eliminate-tuberculosis-by-2025-union-health-minister-j-p-nadda/677048/

[6] http://www.indiaspend.com/cover-story/rs-10290-cr-boost-for-health-hides-funding-cuts-for-key-programmes-33876

[7] The World Bank (2013). World Development Index Online Database, The World Bank, Washington, DC, USA. http://data.worldbank.org/indicator/SH.XPD.PUBL.ZS