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Multidrug resistant tuberculosis: risk factors and the application of innovative techniques for the rapid identification of resistances

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Rapid identification of multi-drug resistant tuberculosis

Tuberculosis (TB) until recently was considered of passing historical significance, a horrible ghost from the pre-antibiotic era. Unfortunately, the disease not only has ceased to decline but highly virulent multi-drug resistant strains of the responsible bacterium are being reported. Given that TB often occurs in patients already infected with the Human Immunodeficiency Virus (HIV) the sharp rise in research on TB is self-evident. A collaboration of biology laboratories offers a novel method, a diagnostic kit, for the immediate detection of drug resistant bacteria.

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In the mid 1980s it was realised that tuberculosis was actually increasing in many developed countries. One third of the word's population is estimated to be infected with the mycobacterium tuberculosis. Once infected, most people remain healthy and only at a later time may become sick. The latent infection does not spread this disease, only in its later, active stages does this occur. In addition, tuberculosis can nowadays be an indication of HIV infection, since many HIV infected patients develop this specific disease long before any other of the so-called opportunistic infections. Current antibiotic therapies based on drugs like isoniazid, streptomycin and ethambutanol effectively reduce infection and usually a patient recovers and is considered non-infectious after a treatment on average of four weeks in duration. Even so the bright picture is immediately darkened from incidents where the responsible bacteria have undergone multiple gene mutations and became multi-drug resistant. The Multi-Drug Resistant tuberculosis (MDR-TB) not only produced fatal diseases among patients with HIV, but is also highly infectious, since it has been reported that at least 19 healthcare workers have become infected with MDR-TB. Early diagnosis of the presence of drug resistant mutations is essential for the treatment of the disease. Such diagnostic detection required until now the culture of the bacteria and the subsequent identification of specific mutations that are known to be drug resistant. The slow growth of the tubercle bacillus impedes and delays substantially the diagnostic detection. To remedy this and contribute substantially in the fight against this disease, a collaboration of medical and microbiological laboratories belonging to European Universities and well-established research institutes has developed a routine diagnostic setting to detect resistance-specific mutations within two working days instead of two weeks, which is currently the time required. The detection technique requires a Polymerase Chain Reaction (PCR) machine and a simple (mini-gel) electrophoresis chamber. Isoniazid resistance can be diagnosed within 48 hours without the need to cultivate mycobacteria, i.e. without the need for special licence or any sophisticated equipment. Moreover, the technique can be assembled and marketed in the form of a diagnostic kit, facilitating further its much-needed introduction to the market.

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