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A new approach towards antibiotic resistant tuberculosis

Tuberculosis (TB) is a bacterial infection caused by the organism, Mycobacterium tuberculosis, and it’s deadly. Not only that, due to the problems with determining the appropriate antibiotic, multiresistant tuberculosis has the potential to become a worldwide epidemic, negating all medical achievements of the last several decades. The good news: a new approach to finding antibiotic-resistant TB could dramatically improve treatment options.

TB Facts

In humans, the bacillus (rod-shaped bacterium) thrives in environments where the oxygen tension is relatively high, such as the rounded upper part of the lungs, the renal parenchyma, and the growing ends of bones. Infection may lead to lung necrosis and cavitation. An person with untreated pulmonary tuberculosis is infectious, and may transmit the organism to those with whom he is in close contact.

Tuberculosis: Scourge of the 19th and 20th Century

A century ago, tuberculosis was more terrifying than cancer is today. Over the nineteenth and twentieth centuries, a billion people died from  TB – more than the world population in 1800. During the 1950s, the disease was interdicted using newly developed antibiotics. European sanatoria were closed and converted into hotels. Today the industrialized world does not comprehend  the gruesome nature of consumptive disease. The treatment was so successful that the World Health Organization (WHO) in 1960 decided to eradicate tuberculosis once and for all. It almost worked.

Persistent Resistant Tuberculosis

Mycobacterium tuberculosis is persistent, demanding treatment with several antibiotics simultaneously for months, which is impossible in developing countries. Erratic or halted treatments led to growing numbers of bacilli which were resistant to several antibiotics. In the early 1980s, the death toll stagnated, then rose inexorably. The arrival of AIDS during the 1980s caused grave concern, because infection with AIDS made the patient  more susceptible to TB.

TB Treatment in 2012

Today, there is a growing incidence of multi-resistant tuberculosis, withstanding the best antibiotics, which is only treatable with costly toxic drugs, which patients in developing countries cannot afford. According to WHO, of the 5 million or so multiresistant cases during the last decade, only one percent had access to treatment. In 1991, for example, a tuberculosis outbreak in New York was resistant to 11 antibiotics, and cases have also been reported where every antibiotic was ineffective. Thankfully, these omniresistant bacilli perished with their hosts before they could spread.

In 2012, 1 in 30 of new TB cases worldwide were multiresistant, with some incidents of 1 in 3. Patients relapsed after a first treatment, with on average, 1 in 5 being multiresistant, with peaks up to 65%. The highest numbers were registered in the former Soviet Union.

Resistant cases, which do not react to normal treatments, need to be recognized as early as possible, and immediately treated with effective second-line antibiotics. The laboratory tests to identify resistant TB bugs are cumbersome – the WHO estimates that in 2009 only 11% of multiresistant cases were actually discovered.

Tuberculosis bacilli resistant to major antibiotics are a serious threat to world health, but now, scientists of the Antwerp Institute of Tropical Medicine have redeveloped a forgotten technique which detects resistant tuberculosis in circumstances where this was not previously feasible.

The Test for Multiresistant TB

Checking smears under the microscope remains the recommended technique for TB screening, but it cannot differentiate between living and dead bacilli, so the bacilli found may be the cadavers of a successful treatment, or resistant survivors. If the numbers don’t fall after multiple tests, then the bacilli is identified as a resistant strain, with the patient remaining contagious.

High-tech PCR technology immediately ascertains whether the bacillus is from a resistant strain, but in practice and certainly in resource-limited countries this is unfeasible. It also is impossible to cultivate every sample and then bombard it with every possible antibiotic to survey which ones still work for that individual patient.

Dr. Armand Van Deun and colleagues therefore gave a new application to a forgotten technique: vital staining with fluorescein diacetate (FDA). It only stains living TB bacilli, so doctors can  immediately see those bacilli that are escaping treatment. The scientists improved the detection of the luminous bacilli by replacing the classical fluorescence microscope with its LED counterpart. Together with colleagues in Bangladesh, they tested the approach in the field for four years in a study made possible by a grant from the Damien Foundation.

Their approach appears to be much more efficient for poor countries. If, after treatment, the FDA-test were negative, in 95% of cases more elaborate tests didn’t find active bacilli in the patient’s sputum either. If the test were positive, the patient was identified as the carrier of a resistant bacillus.

A Simple, Less Costly, Fluorescein Test Allows for Correct Second Line Treatment of TB

This simple test allows the detection of a high number of resistant TB bacilli that otherwise would not have been discovered. The scientists report in the International Journal of Tuberculosis and Lung Disease that three times more patients could directly switch to the correct second-line treatment without losing time on a regimen ineffective against their resistant bacilli. This rediscovered technique can cut in half the number of cases where doctors start a retreatment, because it ascertains that the bacilli detected by the classical microscopy in fact are dead ones, which do not require further treatment.

The result? A more efficient treatment system, fewer deaths, and less spread of the disease. If this test is used consistently, it could be the turning point in the fight against TB around the world.

References

Van Deun, A., Maug, A. K. J., Hossain, A., Gumusboga, M., de Jong, B. C. Fluorescein diacetate vital staining allows earlier diagnosis of rifampicin-resistant tuberculosis. (2012). International Journal of Tuberculosis and Lung Disease. Accessed September 5, 2012.

United States Center for Disease Control and Prevention.  Report on Tuberculosis. (2012). Accessed September 5, 2012.

World Health Organization. Report on Tuberculosis. (2012). Accessed September 5, 2012.

Decoded Science

http://decodedscience.com

http://decodedscience.com/antibiotic-resistant-tuberculosis-tb-treatment/16814

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By Michael Manning

Published: Sept. 7, 2012, 6:42 p.m.

Last updated: Sept. 7, 2012, 6:49 p.m.

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