Tuberculosis (TB) has been around in the human society since time immemorial. From Egyptian mummies to Indian Ayurveda, ample evidence testifies to the formidable presence of tuberculosis as an ancient companion of human race.

In today's world, TB has put on the mantle of a renewed menace and added a new meaning to the consorted global health initiative. One may add to it the dreadful combination of the lack of a powerful vaccine against TB. exquisite susceptibility of HIVpositive individuals to TB. and the emergence of MDR-TB (multiple drug resistant Mycobacterium tuberculosis). Further, the persistent nature of the tubercle bacilli adds to the complexity, by remaining dormant deep within the host tissue and organs to evade multi drug therapy.

Since the early days of introduction of chemotherapy, drug resistant TB has been reported. Soon after the discovery of streptomycin in 1944 by Schatz and Walksman and the introduction of the drug to treat TB. resistance to this drug became apparent. Subsequently, para amino salicylic acid (PAS) and isoniazid were introduced to the TB treatment regimen. The landmark controlled clinical trial conducted by British Medical Research Council (BMRC) during this period however, reported the emergence of drug resistant M. tuberculosis strains. As a result. BMRC developed methods for measuring resistance to antituberculosis drugs and introduced therapy combinations to prevent emergence of drug resistance1.

Interestingly enough, following the discovery of streptomycin and subsequently of isoniazid, PAS, ethambutol and finally rifamycin in rapid succession, the global attitude was that of a conqueror. TB surveillance and research were virtually put on the back burner by the managers of public health and the funding agencies. The outbreak of MDR-TB in the New York City in early 19902 rang the alarm bell and what was perceived as the social and economic burden of the developing nations turned out to be a global emergency.

While emergence of resistance to antimicrobials is a natural biological occurrence, emergence of MDR-TB is generally considered as man made. Wild isolates of M. tuberculosis that were never exposed to antituberculosis drugs were certainly not clinically resistant.

The emergence of drug resistant M.tuberculosis has been associated with a variety of factors such as, the lack of a standardized therapeutic regimen, inadequate resources, poor programme implementation, frequent and prolonged shortage of drugs, substandard quality of drugs and finally, non-compliance of the patients. To understand the impact of such factors on the tuberculosis control programme, a number of studies were conducted in various parts of the world. Snider et aP in a case control study demonstrated that contacts of patients with drug resistance and drug susceptible incident cases of TB had an equal prevalence of positive tuberculin skin test results; suggesting that infectivity was not diminished by drug resistance. In another study in California, Burgos et al4 used elaborate mathematical model to analyse the data generated over a nine year period. They concluded that drug resistant strains (isoniazid resistant and MDR-TB) were not likely to produce new, incident drug resistant TB cases. Mathematical modeling suggested that MDR-TB may remain a locally severe problem rather than a global one5. Finally, two sequential global surveys showed that the prevalence of drug resistant TB was influenced by the quality of TB control programme and by local epidemiologic circumstances67. In other words, indicator or marker for spread of MDR-TB may be programme and community dependent. It thus becomes imperative on the part of the programme managers to find a marker for community spread of MDR-TB that would be best suited for the country. In this context and to the context of the ongoing revised national TB control programme (RNTCP) in India, the article by Gupta et al9 appearing in this issue may be a significant step in that direction. The authors have analyzed the drug susceptibility profile of 380 M. tuberculosis isolates to the first line antituberculosis drugs, namely, isoniazid (INH), ethambutol (EMB), and rifampicin (RIF). The analysis showed a recognizable association of ethambutol resistance with isoniazid resistance whereas ethambutol resistance was weakly linked to multi drug resistance. Overall, 85 per cent of the ethambutol resistant isolates were resistant to isoniazid also. Further, at the highest ethambutol concentration tested, only a fraction of 28.75 per cent isoniazid resistant isolates was ethambutol resistant. The authors suggested that the simultaneous occurrence of isoniazid resistance in a large fraction of ethambutol resistant isolates can be partly explained on the basis of local epidemiological factors of overuse or misuse of ethambutol and isoniazid in India. Quoting from reports published from elsewhere, the authors mentioned that a similar trend was observed in Philippines also. The present paper, in addition, raises another important issue regarding antituberculosis drug susceptibility assays. Although WHO has formulated guidelines and protocols, still some debates are on to identify the best methods and optimum drug concentrations for the first line drug susceptibility testing, particularly, ethambutol. High level EMB resistance is a multistep process. The first step resistance results from overexpression of the EMB proteins (MIC >10 µg/ ml)8. A further decrease in susceptibility requires a mutation in a conserved region of EmbE or additional changes in expression levels (MIC >20 µg/ml). The choice of critical drug concentration for testing of EMB susceptibility in vitro is still a matter under consideration. The suggestion by the authors that susceptibility assay for EMB using 6 μg/ml can be adopted in a diagnostic microbiology laboratory is promising. However, it would need further evaluation by testing a larger number of M. tuberculosis isolates.