Bed rest, the mountains and the seashore were some of the early remedies for tuberculosis. It was only in 1944 to1952 that effective chemotherapeutic agents for "consumption" became available. From the microorganism Streptomyces griseus came the antituberculosis agent streptomycin, and almost simultaneously came para-amino salicylic acid (PAS). Both agents were effective in treating tuberculosis, but soon enough, it became apparent that drug resistance developed with single agent therapy. Combination therapy was necessary to avoid treatment failure. In 1951-52, isonicotinic acid hydrazide (INH) was discovered, which soon became the mainstay of antituberculosis drug regimens.
Triple therapy involving INH, streptomycin and PAS was the standard treatment for tuberculosis for several years and despite the advent of other drugs, this regimen was widely employed. However the long duration (18-24 months) of therapy, among other factors, resulted in poor patient compliance. A better understanding of the metabolic properties of the tuberculosis bacilli, and several trials undertaken involving various regimens, led to short course chemotherapy, which made it possible to treat tuberculosis in just 6 months. Short course chemotherapeutic drug regimens usually involve rifampicin, INH and pyrazinamide with ethambutol or streptomycin for the first 2 months, followed by rifampicin and INH for the next 4 months. This regimen continues to be in use today. However, multidrug-resistant (MDR) strains are now a major threat to controlling the disease. The spread of acquired immune deficiency syndrome (AIDS) is contributing to the spread of multidrug-resistant tuberculosis (MDR-TB). Furthermore, anti-TB programmes are often poorly managed, threatening to make tuberculosis incurable.
So great is the threat that in 1993, the World Health Organization (WHO) declared tuberculosis a global emergency. Tuberculosis kills 2 million people each year. It is estimated that between 2000 and 2020, 35 million people could die from tuberculosis. Left untreated, a person with active tuberculosis infects between 10 and 15 people every year. The only vaccine available against tuberculosis is the BCG vaccine, whose efficacy has varied in different parts of the world and has had a negligible effect on the epidemiology of the disease.
India accounts for about 30% of the world’s tuberculosis patients. 14 million cases of tuberculosis are prevalent in this country, with 2 million new cases every year. Nearly 500,000 people die of tuberculosis in India every year, corresponding to 1 death per minute. The seriousness of the problem is compounded by the spread of MDR-TB and poor surveillance. However, in recent years, the World Health Organization's DOTS (Directly Observed Treatment, Short-course) strategy has shown significant benefits in the treatment of tuberculosis. Directly observed treatment (DOT) involves watching patients taking their medications, to ensure that the drugs are taken appropriately. Isoniazid, rifampicin, pyrazinamide, streptomycin and ethambutol are the commonly used agents. DOTS involves case detection by sputum smear microscopy among symptomatic patients, standardised treatment for 6-8 months with directly observed therapy (DOT) for at least the initial two months, a standardized reporting system, and requires an uninterrupted supply of antituberculosis drugs.
India’s Revised National Tuberculosis Control Programme (RNTCP) launched in 1997 is based on the use of DOTS, and ambitiously plans to cover half the country by 2002 -- the second largest programme of its kind in the world, after China. The RNTCP and DOTS may be our last chance to control the emerging epidemic of tuberculosis in India. Incidentally, we have not seen a major new antituberculosis drug in decades, and in any case, new agents may be too expensive for widespread use in developing countries. It will therefore require the commitment of all concerned to make the most of what we have and get it right this time.
26th January 2001.
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This article appeared in Pharma Business, February 9, 2001.
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