Diagnosing TB in a flash

September 2, 20100 comments

Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis has affected mankind for several centuries, and still continues to be a leading cause of morbidity and mortality. According to an estimate by WHO, more than 2 billion people, equal to one-third of the world’s population are infected with TB bacilli and 9.4 million new TB cases were reported in 2008. India is the highest TB burden country accounting for one fifth of the global incidence. Global annual incidence estimate is 9.4 million cases out of which it is estimated that 1.98 million cases are from India. India is 17th among 22 high burden countries in terms of TB incidence rate [WHO global TB report 2009].

TB is one of the leading causes of mortality in India, killing two persons every three minutes, nearly 1000 every day [WHO global TB report 2009] and being the most common HIV-related opportunistic infection in India and caring for patients with both diseases is a major public health challenge. The WHO report states that people who are co-infected with both TB and HIV are 20 to 40 times more likely to develop active TB than people not infected with HIV living in the same country. Moreover, TB infection in HIV patients has different clinical presentations and manifestations, hence becoming a diagnostic challenge. Drug resistant TB is widespread and found in all the countries surveyed. Multidrug-resistant TB (MDR-TB) is caused by Mycobacteria that are resistant to the most effective anti-TB drugs, isoniazid and rifampicin. MDR-TB results from either primary infection or may develop in the course of patient’s treatment. WHO estimates 440,000 MDR-TB cases and 150,000 deaths in 2008 worldwide and the highest absolute numbers of MDR-TB cases are in China and India, accounting for 50% of the world’s burden [WHO Report 2010]. 

Since Koch’s discovery of tubercle bacilli in 1882, microscopic detection of acid fast bacilli (AFB) remains the cornerstone of TB diagnosis. While having the advantages of being inexpensive, relatively rapid to perform and specific in most settings, the sensitivity of sputum microscopy in HIV infection is reportedly low, ranging from 34 to 80% . A study on the usefulness of single sputum smear AFB microscopy in diagnosing TB among HIV infected patients from South India revealed a sensitivity of 53% . To be considered smear positive, AFB microscopy requires the sputum specimen to contain about 105 mycobacteria per mL thereby giving false negative results and since TB transmission occurs before the level of bacilli reaches 104 per mL and that, during this period the patient continues to transmit the bacilli, the diagnostic value of AFB smear microscopy is eroded. The influence of atypical mycobacterial infections in reducing the sensitivity of AFB smear microscopy has also been reported .

In this scenario, culture of mycobacteria on selective media remains the most sensitive method for detecting M.tuberculosis in clinical specimens and allows subsequent strain characterization and drug sensitivity tests. Conventional mycobacterial culture for the diagnosis of TB is time consuming and proceeding further to anti-TB drug susceptibility testing adds up to the cost and further delay in getting results.  A rapid and reliable method for detecting TB and MDR-TB is the need of the hour for timely diagnosis and clinical management of TB and to address this inequity,  wherein the access to rapid automated tests to detect TB are limited to the countries with high burden of TB.

In a recent study reported in the New England Journal of Medicine (NEJM), team of scientists under Dr.Catherina C. Boehmer have evaluated a  new automated test that detects TB infections and the presence of an antibiotic-resistant TB strain that can cut down days to weeks off the time it normally  takes to identify new infections. The study involved specimens from 1730 patients from various countries with high TB disease burden like Peru, South Africa and India.
  The PCR based new test, developed by Cepheid Inc. of Sunnyvale requires placing the clinical specimen in a small cartridge inserted into an automated processor called GeneXpert. The test makes many copies of any bacterial DNA in the specimen for analysis and also amplifies the DNA for the gene that confers resistance to the antibiotic rifampin (RIF).

The samples tested were also subjected to conventional analysis parallelly for comparison and based on the analyses, the new test accurately identified 98% of all confirmed smear-positive TB cases and 72% of those that were negative in the smear test.  The test also accurately identified 98% of those samples resistant to rifampin. The study claims that, with limited training, this new test can be performed by technicians and  could prove highly valuable in developing and developed countires. The WHO is expected to announce by the end of this month whether or not to recommend use of the new test.The need for verifying the tests in resource limited settings and the expensive nature of test and infrastructure required are the current limitations of the new test to be addressed.

Related Posts:
1. XDR-TB & HIV - The Deadly Duo
2. MODS 
Keywords: TB diagnostics, TB diagnosis, PCR, Catharina C. Boehme, et al.(2010) Rapid Molecular Detection of Tuberculosis and Rifampin Resistance. September 1, 2010 (10.1056/NEJMoa0907847
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