RAMYA KANNAN

The challenge this World Tuberculosis Day, which falls on March 24, is to spread the awareness that sticking to the prescribed drug regimen is the only way to beat this dreaded disease…

The entire course of first line DOTS treatment lasts between six and nine months, costs about Rs. 2000. with the second line drugs, the course runs for two years and costs about Rs. 2 lakh.

Depending on the way it is handled, Mycobacterium tuberculosis can actually be a gentle monster or a savage killer. While conforming to prescribed drug regimens can gently persuade the monster to leave, forsaking the dosage is tantamount to invoking its entire and wholesome wrath.

That then is the challenge this World Tuberculosis Day. With the threat of drug-resistant strains of TB now a certain reality, how does the nation ensure that it can prevent the danse macabre of the Mycobacterium tuberculosis? While drugs are integral, spreading awareness about the need to stick to drug regimens and continue with the full course of the treatment is surely the road to take.

Drug-resistant strains

The World Health Organisation defines Multi-Drug Resistant TB (MDR-TB) as resistance to at least two of the first line drugs used: rifampicin and isoniazid. It is, by and large, caused when patients default on treatment, though it is also known to be caused by spontaneous mutation of the bacteria as well. The world is also concerned now about XDR-TB or eXtensively Drug Resistant TB, a subset of MDR-TB also resistant to fluoroquinolones and one of the three injectibles, Kanamycin, Capreomycin and Amikacin. XDR-TB has been noted as an emerging health threat, especially in countries like India, with a high prevalence of HIV.

Tuberculosis Control India, the wing of the Union Ministry of Health that implements the Revised National Tuberculosis Control Programme (RNTCP), indicates that MDR-TB levels in the country are about three per cent in new cases and 12-17 per cent in re-treatment cases. A 2004 WHO Global TB Control Study in India notched MDR-TB at 4.1 percent of the total estimated number of cases of new and previously treated TB cases.

TBC points out that low percentage figures are not a source of comfort. In India it translates into large absolute numbers. L.S. Chauhan, Deputy Director General (TB), Central TB Division, in a paper in the Indian Journal of Tuberculosis, 2008, “Drug Resistant TB-RNTCP Response”, says WHO estimates that there are over 4,00,000 cases of MDR-TB every year across the world, with estimated deaths of over 1,00,000. China, India and the Russian Federation contribute to a majority of this case burden, with India itself contributing 80,000 cases every year.

DOTS Plus

He also goes on to diagnose the problem: “This is mainly due to under-investment in basic TB control, poor management of anti-TB drugs and transmission of drug-resistant strains. MDR-TB is more difficult and costly to treat than drug susceptible TB, but recent work has shown that it is feasible and cost-efective even in settings of very limited resource.”

Poorly-treated patients can develop drug resistance and potentially incurable forms of TB. Though drug resistant tuberculosis has frequently been encountered in India and its presence has been known virtually from the time anti-tubercular drugs were introduced, it was only recently that the government launched a programme to take on the challenge of MDR-TB. DOTS Plus was the answer. DOTS Plus would ride on the achievement of its predecessor DOTS, that is being used nationwide to treat TB.

According to TBC, the diagnosis and treatment of MDR-TB cases are complex, and therefore RNTCP has developed national guidelines based on the WHO guidelines. As per the DOTS Plus strategy the diagnosis of MDR-TB will be made at the Intermediate Reference Laboratories (IRLs) accredited to perform culture and Drug Sensitivity Testing (DST).

After diagnosis, the treatment of MDR-TB patients is assigned to certain DOTS Plus sites, established in tertiary care centres (like Medical Colleges and speciality hospitals). Hopefully, there will be at least one in each State. The Cat IV regimen of treatment, prescribed for MDR-TB will be given daily, under Directly Observed Treatment at the centre during a short period of in-patient care. Follow-up action will be initiated to deliver the drugs through DOTS again, making it available through DOTS providers directly to the patient.

At the end of 2008, the DOTS Plus services were available in seven States: Gujarat, Maharashtra, Andhra Pradesh, Haryana Delhi, Kerala and West Bengal. Tamil Nadu joined this group in January 2009, after the IRL was set up at the Tuberculosis Research Centre late last year. According to TBC, the plan is to make DOTS Plus services available in all States by 2010.

Why patients default

Most experts believe that in India, the problem of drug resistance arises when patients stop taking the treatment prescribed to them. Dr. Chauhan says, in his article, “Contrary to popular belief I would like to say that many failures are due to failure to take treatment and not failure of treatment per se.”

A statement that is well borne out on the field. E. Subburam, State TB Officer, Tamil Nadu, says, “There are four main reasons why patients stop medication, leading to drug resistance. In our country, the primary reason is migration. Persons with alcohol and drug dependency are the second largest group of defaulters. Patients also stop treatment when after a month or two, the symptoms subside. In some cases, violent side-effects put the patient off the treatment.”

This is something that worries A. Devi, senior treatment supervisor, at the DOTS Centre in Saidapet, one of the 10 zones of the Chennai Corporation. Her biggest problem has been, and continues to be, patients who do not turn up for treatment and have moved home. “People have to move suddenly, either for work or other reasons. We only wish they would leave a forwarding address, so that these people do not fall out of the DOTS network. If they let us know, it is possible to get the DOTS Centre closest to their new place of work or residence to start the treatment.”

Tamil Nadu is trying to tackle this key issue of migration now. Studies are on in six districts to study the patterns of migration and how they affect TB treatment. Also, inter-State meetings with border States have been called for in order to have better co-ordination and to keep tabs on patients with TB migrating across borders, V.K. Subburaj, Principal Secretary, Health, Government of Tamil Nadu, informs.

But migration is not the only problem for F. Deenadayabari, field worker of REACH, a Chennai-based NGO working over the past decade to spread awareness about TB. Drug and alcohol dependencies are big concerns too. While Deena, as she is known, has a reputation to tenaciously hunt down defaulters and get them back on the programme, she confesses that with persons with chemical dependency, she can hardly make any headway. Be it at a rural DOTS centre or in urban centres such as the DOTS centre in CSI Rainy Hospital, North Chennai, or the Saidapet Corporation health centre, or at the Government Hospital for Thoracic Medicine, that plays a key role in detecting and treating HIV-TB co-infections in Tamil Nadu, enforcing drug regimens among such people continues to be a problem.

Dr.G. Ranjana, Medical Officer, Tamil Nadu State TB Cell, is part of the committee co-ordinating the MDR-TB drug programme of the State. She says the message has to go out to people taking anti-TB drugs that the adverse drug reactions can be addressed. “There can be giddiness, vomiting and gastritis for patients, with different degrees of severity. Vomiting is more common.”

That seems to be precisely what is bothering Santhanam, a theatre projection operator in Chennai, who was diagnosed sputum positive a couple of weeks ago. Vomiting, he says, is making him feel ill, worse than before. On her field visit, Dr. Ranjana tells him rather menacingly, hoping the message would go home, “Never ever stop your drugs. Come to us, we can sort out the side effects. After a month, they may even disappear. If you stop now, you will get a terrible disease that is difficult to treat and you may end up infecting your children too.” Vijaykumar nods weakly, offering that he has been regular so far.

On the other side of the spectrum is Jeena, 48, a State government employee living in North Chennai. Diagnosed in August 2002 with spine TB, Jeena was prone for the first month of her treatment. “It was terrible. My stomach was bloated and for the first week I was vomiting and retching constantly. I guess I could have stopped then. But not once did that thought enter my head. I had been clearly told that to live I had to take the drugs. I have two sons to look after, I badly needed to live,” she says. To her, the constancy of her DOTS provider S. Kirubavalli, a friend and neighbour, helped her get through those awful days.

Stigma, however, continues to be an issue that comes in the way of effective treatment. Ratnam, a driver with the State-run transport corporation, works odd hours and therefore is unable to come to the DOTS centre to take his drugs. When his local DOTS centre offered to place the drugs in the bus terminus and appoint an employee there to give him the drugs, he refused. He did not want anyone to know he had TB, least of all his colleagues. So he dropped out, even as his treatment supervisor tried to find other ways of reaching the drugs to him.

There exists in place a really stringent means of ensuring compliance, says K. Nalini of REACH. Even during the testing phase, three samples of sputum have to be collected, two of them by the patient as he wakes up in the morning and one at the hospital. Field workers go to the residence of the patient to ensure that the two samples are collected. When on DOTS, during the Intensive Phase, of two months and the Continuous phase that follows, this scrutiny is kept up. Wherever there is a default, the retrieval programme is launched instantly to get the patient back on track.

If patients default initially or when the first category of TB drugs fail to work, there is still the option of treating him or her with CAT II, under the DOTS regimen itself. Defaulting again is what will put the patient at great risk of multi-drug resistance.

At the Government Hospital for Thoracic Medicine, now a designated DOTS Plus centre, two patients have just been discharged after being treated as in-patients for the second-line drug therapy. Kannan, 64, is the third patient, hospitalised after tests revealed him positive for MDR-TN. Though Kannan denies that he had ever missed drug treatment, it is difficult to confirm since he is far removed from his home village in Cheyyar. He has been told repeatedly by doctors that he needs to take the drugs and injections every day this time. Once he is ready to go home, the drugs will be routed to the local DOTS Centre closest to his home, where he will be required to go to take the drugs everyday.

Prevention is key

Mr. Subburaj stresses that the need of the hour is to prevent MDR-TB. Treating MDR-TB is like crying over spilt milk. The entire course of first line DOTS treatment, lasting between six and nine months, costs about Rs. 2000. The drugs have to be taken thrice a week. Compare that with the second line drugs, the entire course of which runs for a period of two years and costs about Rs. 2 lakh. Plus, more drugs have to be taken daily. “Commonsense will tell us that it is better to prevent MDR-TB. We need to step up awareness, case detection and IEC activities.”

There has, no doubt, been a dip in enthusiasm concerning dissemination activities surrounding DOTS treatment, Dr. P.R. Narayanan, former director, Tuberculosis Research Centre, says, “DOTS started with a bang. There was a blitz in the media also. Facts about TB and DOTS treatment were being disseminated widely. Now, that has reached a kind of stagnation.” Also, there are a lot of vacancies in TB control posts in many States, affecting the programme adversely.

The ramifications of this are far-reaching. “The result is that the new entrants, including the field staff and DOTS providers, are not getting the same kind of training. The sincerity and doggedness this requires is not quite touching them. As a result, the entire programme, case detection and cure rate suffers.” The international Stop TB Partnership also advocates that communities can stop TB by sharing information on how to prevent it. Awareness generation is also said to have a major role to play in reducing stigma and therefore, discrimination.

Experts have also called for widespread use of the DOTS programme in the private sector that has largely remained aloof, preferring to recommend anti-tuberculosis drugs outside the structured system. Referred to as AKT4, these drugs have to be paid for, taken every day and the patients have no supervision, nothing to confirm if the drugs have indeed been taken. The Indian government’s consensus document on handling drug-resistant TB pointed out that all healthcare providers managing TB patients need to be linked to RNTCP. “The proportion of TB patients being treated outside the DOTS strategy needs to be minimised.”

As Dr. Chauhan summed up in his article, “At this point of time in the history of tuberculosis in our country, we are at cross roads. There is apparently only one path that appears to be the most appropriate. The path of preventing the emergence of drug resistance by according the highest priority to the implementation of quality DOTS services.”

The names of some of the patients have been changed to protect their identity.

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Classic case of defaulting

Kandan, 55, from Mylapore in the heart of Chennai, is probably a classic defaulter. He is admitted to the Government Institute of Thoracic Medicine and awaits confirmatory tests for MDR-TB.

Six years ago, when he was found to be sputum positive, his TB was very much in the realm of an easy cure. All he had to do was to take the drugs from the DOTS centre within walking distance of home.

Simple enough, one would think. Not so for Kandan. After a month or so of taking the CAT I drugs under DOTS, his cough disappeared, he began to put on weight. He was also lazy to go to the nearby DOTS Centre. He thought he was cured and stopped taking the pills.

For three months he refused to take another drug, despite efforts by the field workers at the local DOTS centre to convince him. “I have to work with wastes, so I’m used to taking alcohol. Under the influence of liquor I would obstinately refuse treatment.”

When he stopped CAT I drugs and became resistant, he was put on CAT II drugs. Repeatedly he defaulted. Now, when he finally has a clue that he has pushed it too far, Kandan says he is ready to take the drugs regularly this time. He wants the doctors to figure out a way of getting the drugs to him at office so he will not default because of reasons of being unable to go to the Centre to get the pills.

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Crusader for a cause

If all DOTS providers were as sincere as S. Kirubavalli, then it is likely that there would be no defaulters at all.

A resident of New Washermanpet in Chennai, Kirubavalli first got into the DOTS programme when her friend was diagnosed with spine TB. “She was so badly off, I was determined to help her get back on her feet again,” Kirubavalli says. Three days a week she would go to her friend’s place and wait until the drugs had been taken. “I did not miss a single day, as I was afraid she would not get well if I did.” The patient she tended to was cured in nine months.

Since then, Kirubavalli has taken care of many more patients referred to her by the DOTS Centre at CSI Rainy Hospital. She is now a pro and has a timetable for the different patients she has to see to every week. Even when she has to be out of town, she makes sure that the drugs are delivered to the patient and taken without fail.

The first person to hear when she has shifted her residence is the DOTS centre, “So that they can allot patients closer to my area. Though I am willing to go anywhere to help patients with TB, I have found that it is more practical to take care of patients closer home.”