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SEVAMED EDITORIAL

Science & Commerce of the TB Diagnostics – The tiny microbe laughs

The story of Tuberculosis is an interesting saga of Mycobacterium tubercle bacillus fighting all the way from ancient times to modern times, for survival and in the process becoming stronger and laughing away at the mismanagement of human effort. According to WHO, India accounts for one-fifth of the global TB problem with about 8 lakhs of new infectious cases each year, resulting in two deaths per three minutes.

HIV infection increased the incidence and severity of active TB and in particular increase in extra pulmonary tuberculosis cases. Emergence of multidrug resistance TB (MDR-TB) and extensively drug resistance TB (XDR-TB) is causing concern in eradicating the disease, highlighting the importance of tools namely diagnostics, vaccines and drugs for control of tuberculosis.

            Tuberculosis, as a protean disease is believed to have been present in humans for thousands of years. Skeletal remains of prehistoric humans (4000 BC) and spines of Egyptian mummies (3000 – 2400 BC) with tubercular decay show presence of tuberculosis. During ancient times and in the past two centuries, the diagnosis of TB was purely clinical that too in the late phase with bad prognosis. However Hermann Brehmer, a Silesian botany student suffering from TB was advised by his doctor to seek out a healthier climate. He went to Himalayas and returned cured. In 1854, he presented his doctoral dissertation titled ‘TB is a curable disease’ giving introduction to the ‘Sanitorium cure’ with fresh air and good nutrition (http://www.caaglop.com/robbenisland-blog/health/tb/).

            In 1882 Dr. Robert Koch isolated Mycobacterium tubercle bacilli responsible for TB. A century later, in 1993 WHO declared TB a global emergency, the first such declaration by the organization.

            WHO had supported maintenance of banks of recombinant TB antigens and monoclonal antibodies for tubercular antigens under TB research programme as soon as high techniques such as Hybridoma and recombinant technology arrived on the scene. Perkins had explored a cocktail of recombinant antigens and wrote Editorial – Admitting defeat in International Journal of Tuberculosis and Lung Disease (2006). Matthys et al (2009) commented ‘not so smart’ on the global targets for TB control, adopted by World Health Assembly, which are to cure 85% of the newly detected smear positive TB cases and to detect 70% of the estimated incidence of sputum smear positive TB cases. The sensitivity of sputum smear microscopy has been observed to be 45% requiring >10000 bacilli per ml of sputum and further not useful in extra pulmonary tuberculosis and paediatric tuberculosis. Rapid automated liquid culture systems reduce the time required but expensive, requiring expertise and infrastructure. WHO funded research projects on rapid techniques did not yield encouraging results. Over the past decade, the involvement of agencies such as stop TB Partnership’s New Diagnostics working group, WHO, TDR, FIND (Foundation for Innovative New Diagnostics), GLI (the Global Laboratory Initiative), several industry partners, non governmental agencies has led to resurgence of interest in the development of new diagnostics. However breakthrough on development of simple, rapid and cost effective diagnostic kit for mass use is still evading the health administrators for successful TB control. In spite of considerable effort and good science, TB diagnosis has been a challenging problem. I wonder why potential Nobel laureates do not touch these health problems of immense interest to public health. The tiny bug is laughing the way TB diagnosis problem is tackled by our scientists and research granting agencies in developed and developing countries and the people getting exploited by commercially interested industries and for the extra margin by some doctors and laboratories. Our research granting agencies and scientists are happy with ‘Me too’ catching syndrome with new word jargon, using high technology and sophisticated and costly gadgets which become obsolete in 3-5 years in spite of having plenty of clinical material at our door steps. Crores of rupees have been spent by our research agencies without a Task Force approach. Vision 2020 document on TB is gathering dust. We may announce lofty ideals but without rigorous monitoring and taking corrective steps, no significant outcome will be realized. TB diagnostic research in India is reviewed by Haldar et al (2011) recently in Tuberculosis journal with some progress in hospital patient evaluation studies which needs support and further evaluation.

            Seeing the vacuum in availability of reliable diagnostic kits and the eagerness of the doctors to have rapid tests, the industries and laboratories exploited the situation by releasing the kits without proper evaluation. This resulted in supply of 60 test kits in rapid format and 13 kits based on ELISA (Singh & Katoch, 2011).  Out of these 24 kits are from China and 15 from USA. How US companies with rigorous standards have become party to this exploitation? The question arises how they were allowed to be imported? Why the imported kits are not evaluated by Drug Controller General of India or research funding agencies, like it is done in Brazil? This will open pandora’s box for other infectious disease rapid diagnostic kits.

            WHO in its first – ever negative policy recommendation called on governments to immediately ban commercial tests to detect PTB and EPTB. In the diagnosis not only we come across pathogen, immune status of infected host but we also face the clinician’s judgment of the case adding complexity to diagnosis (Harinath, 2010). Immunodiagnostic test is an indirect test and can not be gold standard in substituting sputum smear / culture. But the latter suffers with sensitivity or delay and not convenient to the patient attending a tertiary care hospital. Evaluation in hospital setting and feedback by the clinician on the usefulness of the test in supporting clinical diagnosis and monitoring in suspected PTB,  EPTB, Paediatric TB and smear negative tuberculosis cases will be helpful. Otherwise we may face unnecessary empirical drug trials under ‘Response to Therapy’, leading to drug toxicity in man and increased resistance of the micro organism.

 

March 26, 2012                                                                    Prof. B.C. Harinath 

References:

  • Perkins MD, Small PM. Admitting defeat. Int J Tuberc Lung Dis. 2006;10:31-8.  
  • Matthys et al. Universal tuberculosis control targets: not so smart. Int J Tuberc Lung Dis. 2009;13:923-4.
  • Singh S, Katoch VM. Commercial serological tests for the diagnosis of active tuberculosis in India: Time for introspection. Indian J Med Res. 2011;134: 583-587.  
  • Haldar et al. Improved Laboratory Diagnosis of Tuberculosis – The Indian Experience. Tuberculosis. 2011;91:414-426.
  • Harinath BC. Immunodiagnostics for Tuberculosis – Problems and progress. Indian J Tuberc. 2010;57:123-127.

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