DNA Fragments detection in the Blood: New Diagnostic Test for TB

Myobacteria were the first bacterial infections to be discovered in humans, and they continue to cause serious illnesses till date. Robert Koch described the bacterium that causes tuberculosis in 1882. Since then, a vast number of mycobacterial species that cause pulmonary and extrapulmonary infections in humans and wildlife have been reported. Two primary pathogenic organisms, Mycobacterium tuberculosis and Mycobacterium leprae, are known to cause tuberculosis (TB) and leprosy in humans, respectively.

TB is a contagious infection that primarily affects the lungs but can also affect the brain and spine. Like a cold or the flu, bacteria can spread through the air.

Tuberculosis (TB) is still one of the most devastating infectious diseases on the universe. TB claims the lives of about 4100 people per day, and nearly 28,000 individuals become infected with this curable and preventable disease. Since the year 2000, global efforts to eliminate tuberculosis have reportedly saved 66 million lives. The COVID-19 epidemic, on the other hand, has pushed back years of progress in the fight against tuberculosis. For the first time in more than a decade, tuberculosis deaths increased in 2020.According to the World Health Organization, 10 million people will get tuberculosis (TB) by 2020, with 1.5 million deaths.

Despite extensive investigation, we still require a simple, rapid, sensitive, and specific test to discriminate most or all individuals with active tuberculosis from those with inactive lesions, past immunization, or other diseases, or even those who are totally healthy.

Traditional techniques such as Ziehl-Neelsen (ZN) staining, fluorochrome staining, sputum culture, gastric lavage, and other non-traditional approaches are still being used physicians. Although the tuberculin test has been used to diagnose tuberculosis for more than 85 years, its interpretation is challenging due to false-positive results caused by nontuberculous mycobacteria sensitization. Attempts to produce clinically relevant tuberculosis serodiagnosis kits have failed repeatedly.

Sputum, a thick form of mucus from the lungs, is used in most tuberculosis testing. However, collecting sputum from individuals suspected of having tuberculosis, especially infants, can be problematic. In immunocompromised HIV patients and others whose illness has spread beyond the lungs to other parts of the body, TB can be more difficult to identify. Patients with extrapulmonary infections may have few bacteria in their sputum, resulting in false negatives with current diagnostic methods.

Two important public health strategies that can be performed to address the tuberculosis pandemic are timely and accurate identification (screening) of persons infected with M. tuberculosis and rapid laboratory confirmation of tuberculosis. To prevent the spread of Mycobacterium tuberculosis, prompt identification and treatment are crucial.

In this scenario, researcher from Tulane University School of Medicine have developed a new extremely sensitive TB blood test that examines for DNA fragments of the bacteria that causes the deadly disease, Mycobacterium tuberculosis. This test has the potential to not only offer reliable diagnosis findings but also to anticipate disease progression and monitor treatment, making it a game-changer for tuberculosis diagnosis.

The study examined at a CRISPR-based technique for detecting cell-free DNA from live bacteria. The screening target is introduced into the bloodstream and removed quickly, allowing for a real-time picture of active infection and results in a short period of two hours.

CRISPR-mediated detection of circulating Mtb-cfDNA has shown promise in enhancing the detection of paediatric tuberculosis and HIV-associated tuberculosis, as well as the possibility for early diagnosis and rapid monitoring of tuberculosis treatment responses, according to the findings. Finally, these data provide strong preliminary support for the efficacy of serum Mtb-cfDNA analysis in non-sputum tuberculosis diagnosis as well as a potential secondary application for monitoring of tuberculosis medication.

This assay has the ability to not only offer appropriate diagnosis results, but also to predict illness progression and monitor treatment, enables physicians to intervene early in treatment and decrease the chance of mortality.

Millions of people living in resource-limited settings with a high TB burden would benefit from a highly accurate, rapid blood test, according to Zhen Huang. Hunag and his colleagues were also delighted that the level of Mycobacterium tuberculosis cell-free DNA in HIV-infected children began to decline within a month of treatment, and that most of the children’s blood was cleared of bacteria DNA fragments after treatment, suggesting that CRISPR-TB has the potential to monitor treatment and will enable physicians to better treat worldwide TB infections.


Huang Z, LaCourse SM, Kay AW, et al. CRISPR detection of circulating cell-free Mycobacterium tuberculosis DNA in adults and children, including children with HIV: a molecular diagnostics study. The Lancet Microbe. 2022. doi: 10.1016/S2666-5247(22)00087-8.

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