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Indian Journal of Medical Microbiology, Vol. 29, No. 1, January-March, 2011, pp. 2-3 Guest Editorial Diagnostics for tuberculosis: Time to usher in a new era C Rodrigues Department of Microbiology, P D Hinduja National Hospital & MRC, Mahim, Mumbai, India Correspondence Address: C Rodrigues, Department of Microbiology, P D Hinduja National Hospital & MRC, Mahim, Mumbai, India, dr_crodrigues@hindujahospital.com Date of Submission: 22-Dec-2010 Code Number: mb11002 PMID: 21304186 DOI: 10.4103/0255-0857.76515 Ultimately, treating and controlling disease is about availability of timely and accurate diagnostics. In countries with a high burden of infectious disease, the weakness of a diagnostic armamentarium is well documented. Aptly exemplified in tuberculosis (TB), spiralling empiricism in the practice of infectious disease has insidiously evolved to what it is today, possibly because of our inability to provide a diagnosis fast enough. The failure to interrupt transmission fuels the global epidemic so that every year there are more new cases of TB than in the previous year. [1] The lack of accessible diagnostic tools is the stumbling block preventing TB control worldwide. Lack of recognition of laboratory importance in TB control has not been a matter of affordability, but an underestimation of its importance. Every day, we seem to lose more ground to a disease that infects someone every second and kills four in 60 seconds. One hundred and twenty-five years after discovering the TB bacillus, it is a travesty that we still have antiquated diagnostics, and in parts of our world, delayed diagnosis is the rule and not the exception. Because of the low sensitivity of conventional testing and inadequate access, patients remain undiagnosed for 3-6 months. The vicious cycle of morbidity, loss of work, transmission within the community only serves to compound the problem. Global control of TB is hampered by slow insensitive methods, particularly for detection of drug resistant TB. Accurate biomarkers to predict exposure, latency, infection and fresh, chronic, relapse or resistant disease, though described, are not yet available for diagnosis. [2] Laboratory strengthening is challenged by inadequate infrastructure, inadequate resources, weak health systems and slow technology transfer. Sputum smear microscopy remains the standard diagnostic test but is woefully inadequate in HIV, children and in drug resistant TB. Yet, in India, TB testing is a very large market and a substantial percentage of TB patients use the private sector. Despite strong evidence-based medicine that commercial serology (antibody) tests for TB are imprecise and provide inconsistent estimates of sensitivity and specificity, [3] it is estimated that 1.5 million TB serological tests are done in India every year at a conservative expenditure estimated at US$ 15 million. As there is no compelling evidence that serological tests actually aid in the diagnosis of TB, the Strategic and Technical Advisory Group for TB (STAG-TB), WHO, supports a negative policy recommendation discouraging the use of commercial serological tests. [4] Similarly, commercial Interferon Gamma Release Assays (IGRAs) that are useful in the detection of latent TB do not play a role in diagnosis of active TB. What are the Tests That Should Replace These Recommendations that reduce the recommended number of sputum specimens submitted for smear microscopy from three to two (without compromising the incremental yield) help to initiate faster treatment. "Front loaded microscopy" ensures that sputum smears results are collected the same day. Significant organisational and programmatic changes will be required to optimise the advantages of a same-day diagnosis. Also, optimising microscopy with acid fast fluorochrome dyes has become easier with low cost, ultra bright light emitting diodes (LEDs). At our centre, we found that fluorescent microscopy reduces the burden on lab staff and can potentially improve the sensitivity of smear microscopy with an increase in speed of detection. [5] We have found liquid cultures enable an improvement in turnaround time with increased isolation as well. [6],[7] "Dedicated decontamination" serves to decrease contamination and additionally prevent cross contamination in high turnover labs. [8] Drug susceptibility testing results can also be hastened using liquid cultures. The WHO endorsed liquid cultures along with rapid speciation in 2007 and the use of Line probe assays (LPA) in 2008. LED and selected non-commercial drug susceptibility methods were also addressed in 2009. The new kid on the block, Xpert MTB/RIF test, provides sensitive detection of TB and rifampicin resistance in less than 2 hours. [9] This technology has been endorsed by the WHO in December 2010, essentially in high MDR TB settings and high HIV prevalence settings. WHO will provide guidance to national TB programmes on the actual integration of this technology into existing practices and provide a robust protocol to guide phased implementation over the next 12 months. Any new point-of-care diagnostic test for TB should be designed to meet minimal specifications satisfying the most urgent medical needs in resource constrained settings. There are several versions of mycobacterial lipoarabinomannan (LAM) antigen detection in urine in development, including in-tube enzyme-linked immunosorbent assay (ELISA) and dipstick methods. Urinary antigen detection may be of particular value in diagnosing TB in HIV co-infected patients. There is potential for further development and simplification resulting in a lateral flow test that could significantly increase case finding, if combined with smear microscopy and /or culture in high HIV prevalent areas. The performance of the lateral flow test is expected to be submitted in May 2013 to the WHO STAG-TB for recommendation. Till recently, lack of innovation was the biggest limitation in TB control. However, with funding of over US$ 1 billion per year on TB diagnostics and increasing interest, the diagnostic pipeline for TB is making slow but incremental progress. Global TB diagnostics is expanding and availability of several newer tools is being scaled up, driven to a large extent by both drug resistance and HIV TB co-infection. Recent developments indicate that there are at least 20 new technologies in various stages of development and evaluation. The Indian in vitro diagnostic market needs to step into diagnostics for TB. We need to get beyond scepticism and investment returns in the short run. Lastly, assessing the evidence base for translation of newer tests into a policy that ultimately has epidemiological and public health impact entails engagement of all key stakeholders including scientists, industry, policymakers, regulators, funders and civil activists. [10] References
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