Indian J Med Res 120, October 2004, pp 205-206 Editorial Tuberculosis research in India Tuberculosis is the second most common cause Diagnosis of tuberculosis in its various forms of death from infectious disease at the global level, continues to a major problem challenging the clinicians being second only to HIV/AIDS. Most deaths occur and the basic scientist alike. From the public health in developing countries, and affect the young in point of view, diagnosis by simple sputum microscopy productive years of their life. Effective combination is enough to bring under control the transmission of chemotherapy for tuberculosis has been available for disease in the community. Earlier stages of pulmonary almost half a century, but it has done little to reduce tuberculosis with pauci-bacillary disease, and most the disease burden in low-income countries including forms of extra-pulmonary tuberculosis still requires India. The prevalence, incidence and annual risk of sound clinical judgment in the absence of satisfactory infection continue to be the same as they were at the gold standards. The same is true for the diagnosis of time of the baseline National Survey fifty years ago. childhood tuberculosis. Widely available and The number of patients with active disease has frequently used serological tests for the diagnosis of continued to increase in proportion to the growth of active tuberculosis using antibody detection with the population in India. commercially available kits have not been validated in the Indian context. PCR-based diagnostic tests It is in recognition of this important public health hold considerable promise but lack of strict quality problem that the Indian Council of Medical Research control, limited availability and high cost are major decided to publish this special issue of the Indian issues. This topic has been discussed in this issue Journal of Medical Research on tuberculosis with summarizing the Indian experience. Several advances contributions from eminent epidemiologists, public have been made in the diagnosis of latent tuberculosis health specialists, microbiologists, clinicians and basic using enzyme linked immunospot to measure T-cell scientists. It is to be expected that many of them are responses to early secretory antigens. Although its drawn from the Tuberculosis Research Center, value in areas of high prevalence lies in exclusion of Chennai, of the ICMR, an Institution which has made the diagnosis with a negative test result, the test major contribution on various aspects of tuberculosis appears to have higher sensitivity and specificity as in India. Indeed, it is this institution which recognized compared to traditional tuberculin skin test. the importance of supervised and directly observed High prevalence of (multi) drug resistant chemotherapy for tuberculosis in achieving high cure tuberculosis in certain subject groups and regions has rates. This now forms one of the basic tenets of the been a subject of major concern for public health DOTS (directly observed therapy, short course) administrators as well as clinicians. Almost one third advocated by the World Health Organization. of the patients with past history of having been treated Chapters on clinical aspects of tuberculosis have been for tuberculosis have been reported to have multi- contributed by authors from the all India Institute of drug resistant organisms when they present with Medical Sciences, New Delhi, a center recognized sputum positive disease. There is a trend for increase for academic excellence. Other authors are eminent in multi-drug resistant tuberculosis even amongst scientists and public health workers with major original patients who have never received anti-tuberculosis contributions in their respective areas. An attempt agents in the past. There are concerns regarding the has been made to cover several areas of current adequacy of standard regimen recommended for interest, and to avoid duplication of recently published category II patients which includes chronic cases as material on the same topic. well. Tuberculosis specialists from academic centers 205 206 INDIAN J MED RES, OCTOBER 2004 have advocated wider availability of culture and drug- infection amongst these patients with moderate to susceptibility testing facilities in different parts of the advanced immunosuppression. HIV positivity country for the management of multi-drug resistant amongst patients with tuberculosis attending tuberculosis. It is clear that it would not be cost- tuberculosis centers is considerable higher than in the effective at the present time to advocate DOTS plus general population. As the pool of people living with under the revised national program, but it is also clear HIV/AIDS expands in India, the prevalence and that the necessary infra-structure for reference incidence of tuberculosis is expected to increase. laboratories and trained personnel needs to be created Current reports do not suggest higher prevalence of at several academic institutions in the country for the drug-resistant tuberculosis amongst HIV infected management of patients referred from the existing individuals in India, but this scene may change with program. changing transmission dynamics and environmental factors. There are several issues which need to be Considerable progress has been made in considered for reducing the impact of HIV epidemic speciation and rapid identification of drug resistant on the epidemiology of tuberculosis. These include organisms using molecular tools. Notable in this chemoprophylaxis for patients with latent infection, regard is the identification of mutations in rpoB gene and strategies for chemotherapy of dually infected which are associated with drug-resistant phenotype. individuals. Indian along with other low-income There is possibility of undertaking this investigation countries is preparing for three by five movement directly on the sputum samples rather than cultures although several questions remain unanswered. They which take several weeks. Unfortunately these relate to financial and management issues, as well as investigations are unlikely to be widely available in concerns regarding emergence of drug resistant strains the field and would be undertaken only in the reference of HIV. Public health planners and administrators laboratories. Nevertheless, they hold great promise have the enormous responsibility of choosing as they would supplement the results of conventional appropriate and feasible strategies for controlling drug susceptibility testing. Specific contributions of tuberculosis in the wake of HIV epidemic. the Indian scientists along with others have been discussed in this issue. Review articles in this issue of the Journal take There has been debate as to how much of newly stock of the currently available information on diagnosed active tuberculosis in adults is the tuberculosis in India. Important lacunae in knowledge consequence of new infection or reactivation of have been highlighted emphasizing the need for future infection from the past. Restriction length research in several areas including diagnosis, polymorphism analysis is helpful in recognizing chemotherapy, molecular epidemiology, operational ongoing transmission in the community. Only limited research and vaccine development. I am sure the data is available from India on this subject which readers would find the information as useful as I did. has been presented in this issue of the Journal. Much more information, however, needs to be generated regarding transmission dynamics in overcrowded J.N. Pande slums, public utilities and large hospitals with Sitaram Bhartia Institute of Science and Research inadequate infection control measures. B-16 Qutab Institutional Area The HIV epidemic is yet to reach its peak in India. New Delhi 110016, India Tuberculosis is the most frequent opportunistic e-mail:[email protected] Review Article Indian J Med Res 120, October 2004, pp 207-212 Genomics of Mycobacterium tuberculosis: Old threats & new trends Niyaz Ahmed & Seyed E. Hasnain Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India Received July 22, 2003 Tuberculosis (TB) has been declared as a global health emergency by the World Health Organization (WHO). This has been mainly due to the emergence of multiple drug resistant strains and the synergy between tubercle bacilli and the human immunodeficiency virus (HIV). Genomic analysis of strains for outbreak investigations is in vogue for about a decade now. However, information available from whole genome sequencing efforts and comparative genomics of laboratory and field strains is likely to revolutionize efforts towards understanding molecular pathogenesis and dissemination dynamics of this dreaded disease. Genomic information is also going to fuel discovery projects where new targets will be identified and explored towards a new drug for TB. Besides this, efforts of information technologists, chemists, population biologists, freelance workers, media persons, non-governmental organizations and administrators to needed to handle the problem of tuberculosis to prevent it from becoming a pandemic. Key words Genomics - Mycobacterium tuberculosis - multidrug resistant strains Mycobacterium tuberculosis is reputed to have the Problem of multi drug resistant tuberculosis highest annual global mortality among all of the (MDR-TB) pathogens1. The rise in tuberculosis (TB) incidence over the last two decades is partly due to TB deaths One of the classical threats of the tuberculosis in HIV-infected