India has the highest burden of tuberculosis patients among all the countries in the world. The implementation of DOTS (Directly Observed Short Course Chemotherapy) programme for diagnosis and treatment of tuberculosis in the first decade of the 21st century has been a reasonable success. This has allowed us to focus further on additional problems that may have existed earlier and new ones which have emerged. These new problems can be envisaged to reach proportions that threaten the success of the programme itself.
The relatively small numbers of patients (<10 per cent) which had recurrent tuberculosis (repeated diagnosis > one year after being ‘cured’), persistent tuberculosis (not cured after completion of therapy) and illness due to drug resistant tuberculosis have existed but obtain prominence now with extensions of earlier problems of drug resistance scaling new heights in the number of drugs that have now become ineffective and the spread of these organisms to cause first time illness is a matter of concern.
The most alarming concern from a public health point of view is the spread of illness caused by drug resistant organisms. Tuberculosis is an illness caused by live micro-organisms, which are transmissible from person to person. It is inevitable that drug resistant bacteria will also spread causing new infections, which are difficult to treat with the drugs that are available presently. Although it is a long-term view, it is definitely possible that at some stage – without undertaking measures to halt its spread – the majority of treatable, susceptible tuberculosis will be replaced totally or near totally by resistant, difficult to treat illness. When we couple this with the lack of our present ability to predict those who are susceptible to tuberculosis and the lack of an effective vaccine, it makes the situation scary.
A large proportion of microbes in a population (>99 per cent) are initially susceptible to the drugs that are available – these drugs would have been tested earlier for its ability to control the microbe. The drug regimens are tuned to deliver the amount required to control the growth of the microbe at the site of infection and the period required to clear the body of any persistent forms. Moreover, combinations of drugs are included in the regimen to ensure complete kill as microbes, which are resistant to one drug would be susceptible to another. This balance is finely tuned to effect cure by years of scientific evidence-based methods and debated widely by experts before becoming public policy.
The programmes start with a rosy picture of successful outcomes if the protocols are adhered to. The significance then shifts to the “if”. When there is a breach of protocol, the disease behaves in a bizarre manner and gives rise to complications. Individual preference of the patient and the treating physician (which are not factored into programmatic recommendations) become unpredictable without monitoring and the complications unmanageable. Irregular adherence to treatment and modifications in the dosage, timing and combinations of the drugs are the main culprits.
The DOTS programme controls this by direct observation of the therapy being administered controlling the drugs used. However, there is an admitted failure in enrollment of upto 40 – 50 per cent of the patients with tuberculosis who do not get registered under the DOTS programme and take treatment of various regimes which may be deviant from the accepted regimen and are not of proven efficacy. There is anecdotal evidence of this practice under the care of physicians unregistered and untrained under the DOTS programme.
Inadequately treated infections invariably ends up with a population of bugs either tolerant and finally resistant to the concentration and combinations of drugs used and we see a transition from drug sensitive to drug resistant infection over time – alternatively a person is infected with resistant microbes from the outset. The frequently used terms MDR – Multi-drug-resistant – is when the microbes is resistant to INAH and Rifampicin, the two most powerful drugs in the first line of treatment.
XDR – Extensively drug-resistant is a term used when organisms are resistant to the key drugs in the second line of treatment as well – ethionamide / ofloxacin and kanamycin / capreomycin. The treatment of patients with XDR tuberculosis is difficult with the need of advanced drug susceptibility studies and a choice of drugs which is limited. When these studies show that the microbe is resistant not just to the key drugs in the first and second line of treatment but to all the supplementary drugs used in the regimens – this is termed TDR – Totally drug-resistant or XXDR – this terminology is yet to be accepted and validated globally. Treatment of TDR strains will follow similar strategies as for XDR and will potentially include experimental compounds.
The origin and perpetuation of drug resistance thus grows and could lead to disastrous outcomes. The strategy at this point would include:
1. Compulsory notification and treatment of all patients diagnosed with tuberculosis (like other epidemic diseases)
2. Policy and implementation of steps to treat drug resistant cases – this begins by diagnosing those who have drug resistant TB which is now available in very few centres across the country.
Although multiple factors exist to influence the above measures – it would be the first and most critical steps to take towards controlling the epidemic.