Tuberculosis – Still A Scourge

Two Indians die of TB every three minutes. Why are 330,000 Indians dying from a disease that is completely curable?

Part 1 of a three-part essay on Tuberculosis. The Doctor.

There was a time when our heroes died of tuberculosis.

Midway through the melodrama the doctor would bite on his pipe and disclose hesitantly to the main lead that yes, what he feared was true: it is tuberculosis. That was the cameraman’s cue to spring into action with his array of slo-mo and zoom-ins, later copied to great effect by saas-bahu serials. Meanwhile, post the dua–dawa sermon, the hero would slump on the nearest available chair and stare blankly at the doctor, his whole life flashing before him. The rest of the film would deal with the catastrophic consequences this ancient disease – sometimes called “wasting” or “consumption” – would have on the protagonist’s race against time to settle his ailing parents, marry his sisters and pay the home loan.

Then, somewhere in the decade following Independence, after the introduction of Streptomycin, tuberculosis became curable and the ever-bankable cancer replaced it as Bollywood’s death of choice.

Strange it is, then, that every year 330,000 of us who go and watch films, still die of tuberculosis. For them it remains incurable. Why?

Yes, yes, yes, there are government reports and brochures and advisories and statistics – and I have referenced a few below – but to a man about to die of tuberculosis they are as useful as those budget papers that arrive by the crateful at Parliament every year before the Finance minister’s budget speech. We’ve all seen the photographs: half a dozen men unloading boxes like they unload gunnysacks at Azadpur mandi. Why do they arrive at all, these papers, what purpose do they serve – who reads them? The answer is that no one reads them. Their sole purpose is to convince us of the FM’s drudgery in drafting the year’s budget.

In Cuba, as in Switzerland and the US, no one died of tuberculosis in 2011. India’s tuberculosis death rate per 100,000 population, though, is higher than Rwanda, Sudan, Uganda, Yemen, Sri Lanka, Nepal, China, and Algeria. Hunh, Superpower, saala!

Two Indians die of tuberculosis every three minutes – that’s two deaths in the time it takes for Maggi noodles to go supple and slippery.

Enough! Sixty-five years after Independence, I do not want our elected leaders to slap the snooze down and pretend those wasted lives and spent minutes were just part of a statistic. I don’t want to read those tuberculosis “budget papers” which explain in excruciating boffin-babble what is tuberculosis, what is DOTS, what is RNTCP, what are the millennium development goals, what is the target for 2014. That’s right – 65 years after Independence I do not want 330,000 of my countrymen to die from a disease that is completely curable.

No more shoulder-shrugging, I want answers. I want someone to explain to me in simple language what exactly is going wrong, just like how the Finance minister squeezes out a para or two from that mountain of babu-babble so his colleagues in the Lok Sabha can thump desks.

Granted, we aren’t Switzerland or America, but I want someone to explain to me why a tropical country like Sri Lanka – as dusty and bug-cushioned as ours, and one almost ruined by internal strife and a civil war that lasted 30 years – has a TB death incidence rate that is one-fifth of ours.

Poverty is an excuse. State apathy isn’t. But who will answer the door? I know one man.

Away from all the 10 minutes of desk thumpings and 15 minutes of fame, sits a doctor who understands tuberculosis like very few in the world do. He has dedicated his life to it. Dawn to dusk, most days, he can be found in his chamber at the Hinduja Hospital in Mumbai. He treats patients, conducts research, and is an awe-inspiring speaker. This last trait doesn’t go down well with the establishment – not many like facing up to the truth. Tough. Beat it – he isn’t a paid doctor.

The first time I heard Zarir Udwadia speak on tuberculosis I was stunned. It was as though the good Dr Rioux (of Camus’ Plague) was among us, confronting the audience with stark reality, narrating gut-wrenching case studies, listing the countless problems, throwing up scientific and non-scientific solutions…I left the auditorium feeling optimistic, thinking that those who matter will pay heed, will gulp spit at the Maggi noodle death rate and do something, will wake up.

Well, they didn’t.

When I heard Dr Udwadia next – after a gap of seven years – he began his lecture thus: “For two weeks in January 2012, India coughed and the rest of the world paid attention”, and on his first slide was a quote: The growing TB epidemic is no longer an emergency only for those who care about health, but also for those who care about justice.

Talk about a “you had me at hello” moment for a scientific audience. The rest of the lecture dealt with the drug-resistant nightmare that confronts us and its systemic decade-long neglect by our Revised National Tuberculosis Control Program (RNTCP). In this lecture he also disclosed his recent finding, and as is the norm he gave it an acronym: TDR. Sounds as harmless as MTR or SUV, doesn’t it. You couldn’t be more wrong.

Many patients who come to him have expended their life savings already in search for a cure. Some of them will not live longer than six months for multiplying slowly in the crevices of their bodies they have a strain of tuberculosis that is drug-resistant, rendering the frontline anti-TB drugs – and there are principally four: Isoniazid, Rifampicin, Ethambutol, and Pyrazinamide – useless, as useless as Isabgol is against HIV.

But how resistant? Well, there are grades, and genetic techniques can pin-point the degree of resistance of a particular strain towards a particular drug. There is MDR (multiple drug-resistant) and XDR (Extensively drug-resistant).

And then there is this: TDR. Totally drug-resistant. Totally.

“What was your very first reaction when you discovered TDR?” I ask Dr Udwadia.

“Working at my TB OPD for two decades I thought I’d become inured to patients with bad resistance profiles. I’ve witnessed the relentless amplification of resistance firsthand, from MDR in the 90s to XDR around 2006. But when a patient walked in with resistance to all 12 of the first- and second-line drugs available to treat TB, it was startling. And when we had a further three cases in quick succession it would have been churlish not to put them together in the form of a report. This we did in the form of a short article [referenced below]. The article appeared in the Christmas issue of Clinical & Infectious Diseases and I thought it would die a natural death in the post-Christmas torpor. But it was seized by the medical and lay press, took on a life of its own, and in the words of my daughter ‘went viral’.”

Went viral it certainly did. For a week TDR was Gangnam. The government, however, refused to believe Dr Udwadia. They said it wasn’t TDR but rather XXDR. In a Madam Speakeresque fashion they asked everyone to “calm down, calm down”, traumatised as they were by that one word: Totally.

Quite right. XXDR is so much better for the Indian psyche than TDR. These bards know: a rose by any other name doesn’t smell as sweet.

And so we wait for doubleX-DR to become tripleX-DR and then we wait some more until tripleX-DR sheds most of its letters and is left with only TDR. How many lives would we have lost by then? How many packets of noodles served?

“There is more to tuberculosis than the mycobacterium”, says Udwadia. “It’s a disease steeped in history and politics. The government response swung from hostile denial and aggression to passive acceptance…Yes, it doesn’t get much worse than TDR, and the government position was: ‘We have a great TB program in place and drug resistance is not an Indian problem’. Perhaps it was an ostrich-in-the-sand approach they were loathe to change. Fences have now been mended, though, and the article has been the catalyst for many changes in TB policy.”

One certainly hopes so, but going by previous record…

“What went wrong with DOTS?” I ask him.

DOTS, short for Directly Observed Treatment, short-course, was a WHO suggested policy that our government decided to take up in the 1990s. It meant monitoring each one of the millions of TB patients by a health worker and making them pop anti-TB drugs under “direct observation”. The course kicked off once the patient showed TB in the sputum – in other words, sputum-negative TB patients were not put on DOTS. It worked for a while, like most new things do in our country, from flyovers to NREGA – and it’s not that the lacs of health workers or thousands of TB centres were at fault. The problem, as always, lies in implementation. 90% of us are not fools, but we are 90%ers alright. It’s always that last stretch, that last connecting road, that last canal – that last 10%…

Udwadia is forthright. “About 10 brave studies have questioned the premise of DOTS and the extra supervision it entails, and found that there is no difference in terms of outcome in supervised versus non-supervised groups. A Cochrane review [an international scientific think-tank and network] also found no justification in DOTS. Whilst I agree that Indian DOTS is one of the great Indian public health successes, I wonder if we have only converted one form of TB (sensitive) to another (resistant). The intermittent nature of the therapy, the six-month treatment regimen for all patients, and the humiliating Cat 2 Rx [category II re-treatment cases under RNTCP] that we seem so fond of – all have the potential of amplifying resistance. DOTS has to become more inclusive, less rigid, and more flexible if it is to succeed. And of course, the huge pool of MDR patients must be reached out to and treated. At present only 1% of MDR patients receive DOTS-Plus drugs.”

In the many lectures that I have attended of Udwadia, half the slides discuss new treatments, some of them revolutionary. Like a man possessed he scours the scientific literature for even a faint whiff of hope. Something, anything, will do. His lab constantly strikes collaborations with researchers worldwide. There are experimental treatments involving psychotropic drugs, inhaled Nitric Oxide and new molecules or analogues of old ones that are still under phase II trials. Drug-resistant TB for him is cancer by a different name.

“We have thrown every possible salvage drug in a desperate attempt to treat each patient”, says Udwadia. “We have come a full circle, back to the sanatoria days, and are operating on large numbers, too. The new drugs, Bedaquiline and Delamanid offer hope. One of our TDR patients was the first Indian patient to start on Bedaquiline and I was delighted he sputum-converted [i.e. responded to treatment]. But a single new drug is doomed to failure and we need new regimens, which are a decade away.”

Udwadia goes further: “Each case of drug-resistant TB, whether MDR or XDR or TDR, we now know is as “fit to transmit” as the drug-sensitive strain, and if left untreated will infect ten or so contacts a year. Without sounding alarmist we have the makings of an epidemic on our hands as these strains do spread in our very crowded communities.”

What about a vaccine, I ask him. “How far are we from an anti-TB vaccine?”

“The recent Oxford vaccine study [with Antigen85A] was a disappointment. I am involved with another large African vaccine trial but again we are decades away from an available new vaccine.”

All doom and gloom, it must be said. But one has to start somewhere. Of course, it’s not that all is lost – just that it’s time to wake up, think out-of-the-box, and spend billions – of our money not WHO’s.

“We spend millions of dollars on an obsolete test like TB serology and we have barely a handful of labs capable of diagnosing MDR TB, so we are woefully lacking here as well. Having said that, the new GeneXpert test [for diagnosing tuberculosis] is a potential game-changer. This new test must be embraced by the program, be widely rolled out across the country, and be the basis on which MDR treatment is commenced. That needs additional funding and political will, neither of which we have in large supply.

Udwadia ends with a sobering thought. “How many people are aware that this ancient scourge still kills 2 Indians every 3 minutes? A grim statistic that underlines the failure of the RNTCP. The scandalous quality of the average private doctor’s prescriptions also needs to be seized on. There is also the fact that there are still no government controls on who prescribes second-line TB drugs. Education of not just the public but also the medical profession is needed.”

He is right. There are no magic solutions to this scourge, and to think about eradicating it within a decade is worse than a nightmare – it’s a daydream. It requires a collective effort from doctors, from scientists, and – strange as it may seem – from journalists.

In part II of this series I’ll discuss tuberculosis from the perspective of a journalist – someone who wrote one of the most definitive articles on TB to have come out of India in recent times.

The author is currently attending a conference on Public Health & Journalism, Who’s There? Yes (WTY), on the sidelines of the World

Health Assembly, where Tuberculosis and non-communicable diseases are part of the discussion.

Bibliography:

http://www.nejm.org/doi/full/10.1056/NEJMoa1112433

http://www.nature.com/nature/journal/v405/n6789/full/405962a0.html

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(13)70030-6/abstract

http://online.wsj.com/article/SB10001424127887323320404578213421059138236.html

http://www.who.int/tb/en/

http://www.cepheid.com/systems-and-software/genexpert-system

http://articles.timesofindia.indiatimes.com/2012-01-19/india/30642784_1_mdr-tdr-tb-killer-tb

http://aac.asm.org/content/49/3/1209.long

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2822329/