All together now

WORLD TB DAY


Tuberculosis (TB) is one of the oldest diseases known to mankind—fragments of the spinal column from Egyptian mummies from 2400 B.C. show definite pathological signs of tubercular decay. It has taken a heavy toll on mankind both in terms of lives and development. For ages, it was difficult to diagnose and treat TB. Scientists have made enormous efforts in diagnosing and treating the disease. When drugs for treatment of tuberculosis were not available, the only way to treat it was to put patients on a healthy lifestyle (fresh air, nutritional support, avoidance of physical and mental strain, prolonged bed rest, artificial pneumothorax and thoracoplasty) and hope for the patient’s recovery, aided by his/her immune system. With the introduction of drugs to treat tuberculosis, it was realized very early that for its successful treatment and to prevent drug resistance, it is necessary to put patients on multi-drug therapy.



With the advent of chemotherapy with anti-TB drugs, drug resistance was reported very early. After the discovery of streptomycin, it was noted that case fatality from TB was significantly reduced. A the same time, however, it was also observed that while patients’ condition improved over the first few months, subsequently it deteriorated and in many cases this was due to drug resistance.



Single drug resistance is found in almost countries treating tuberculosis with anti-TB drugs. However, multi/poly drug resistance (resistance to more than one drug) is the real cause for concern. MDR-TB is defined as resistance to Isoniazid and Rifampicin, with or without resistance to other first-line drugs (FLD). MDR-TB is being increasingly reported these days. WHO estimated that there were about 6, 50,000 cases of MDR-TB that occurred world-wide in 2010.



In 2006, the first reports of extensively drug-resistant tuberculosis (XDR-TB), an even more severe form of drug resistant TB, began to appear. XDR-TB is defined as resistance to at least Isoniazid and Rifampicin, to any of the fluoroquinolones and to any of the three second-line injectables (Amikacin, Capreomycin, and Kanamycin). Within a year of the first reports of XDR-TB, isolated cases were reported in Europe that had resistance to all first-line anti-TB drugs (FLD) and second-line anti-TB drugs (SLD) that were tested. In 2009, a group of 15 patients in Iran was reported that were resistant to all anti-TB drugs tested. The terms “extremely drug resistant” (“XXDR-TB”) and “totally drug-resistant TB” (“TDR-TB”) were given by the respective authors reporting this group of patients. Recently, four patients from India with “totally drug resistant” tuberculosis (“TDR-TB”) were found, with subsequent media reports suggesting further eight such cases.



The term “totally drug resistant” has not been clearly defined for tuberculosis, while the concept of “total drug resistance” is easily understood in general terms. New drugs are under development, and their effectiveness against these “totally drug resistant” strains has not yet been proved. For these reasons, the term “totally drug resistant” tuberculosis is not yet recognized by the WHO. For now, these cases are defined as extensively drug resistant tuberculosis (XDR-TB).




The discovery of patients with MDR or XDR-TB emphasizes the importance of ensuring that all care for tuberculosis, whether in the public or private sector, must conform to international standards in order to prevent the emergence of drug resistance. Almost all countries must, in addition, ensure appropriate diagnosis and treatment of cases of MDR-TB. National regulations for quality and dispensing of anti-TB drugs, particularly of the second-line drugs, need to be strictly enforced. To achieve this, most countries require simultaneous scale-up of the diagnostic and treatment services for drug-resistant TB.



It is pertinent to mention that drug resistance is not synonymous with failure of treatment. A patient may fail to respond to treatment because of non-compliance, which could be due to economic constraints, distance from health center, adverse drug reactions and social stigma.



Resistant strains of tuberculosis bacteria (Mycobacterium tuberculosis) are man-made; they develop when the medications used to treat the disease are not used or managed correctly.



The reports on TDR-TB are worrisome because it is a clear sign that TB is not being correctly diagnosed and managed. If TDR-TB continues to spread, TB will become incurable again and patients will have to rely on their immune system, rather than on medical intervention—a scenario last seen a century ago.



Tuberculosis is a highly contagious lung infection that kills about 1.5 million people worldwide each year, according to the World Health Organization (WHO), so the development of a totally untreatable form of the disease would be a cause for alarm. In all probability, "extensively drug-resistant" or XDR-TB will remain the highest level of tuberculosis threat. For one thing, current laboratory tests for determining drug-resistant TB are not reliable enough to rule out all TB drugs conclusively, particularly three of the six classes of second-line drugs. "The tests aren´t highly reproducible," says Peter Cegielski, head of the US Centers for Disease Control and Prevention´s drug-resistant TB program. "You can even get different results from the same patient specimen."



There are also new tuberculosis drugs on the horizon, including two that will perhaps be available to patients in the next few years, making the timing of adding a "totally drug-resistant" TB category impractical. That doesn´t mean, however, that it is impossible for an untreatable form of TB to exist. It also does not mean that public health workers can rest easy.



The new, soon-to-be-released TB drugs have been specifically developed to address drug-resistant strains, but experts warn that without proper disease management, patients will become resistant to the new treatments before they can do much good. Hence, there is a need to be alert and ensure proper management of drug sensitive TB cases. The theme for this year’s World TB Day (March 24)—‘Stop TB in my life time’ has been very appropriately coined. We need to completely eradicate this disease and make our future generations safe. Let us all pledge on World TB Day, 2012 to work towards the elimination of this deadly disease.


The authors are doctors and TB experts at the SAARC TB & HIV/AIDS Centre, Bhaktapur

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