Rapid and Simultaneous Tuberculosis and Antibiotic Susceptibility Testing for the Diagnosis of Pulmonary Tuberculosis and Rifampicin Resistance: A Review of Diagnostic Accuracy [Internet]

Excerpt

Tuberculosis (TB) is one of the top 10 causes of death, worldwide. Worldwide 10 million people developed TB in 2017, (i.e.,133 cases per 100,000).^– However, only 6.4 million cases were reported to WHO, indicating that 36% of cases were undiagnosed or not reported. According to a 2017 estimate, the rate of active TB in Canada was 4.9 per 100,000 population. The rate was highest among Canadian-born Indigenous Peoples (21.5 per 100,000 population).

TB is caused by the bacterium, Mycobacterium tuberculosis. It is a communicable disease and can spread from person to person through air (such as when a person with TB coughs).^, TB mainly affects the lungs (pulmonary tuberculosis [PTB]) but can also affect other organs and is referred to as extrapulmonary TB (such as TB meningitis, and TB lymph nodes). TB is a curable disease, if diagnosed early and treated.

The conventional diagnostic approach for individuals with presumptive pulmonary TB includes smear microscopy, followed by the culture-based method to confirm the diagnosis and for drug susceptibility testing. The culture-based method is considered the gold standard. However, it takes two to six weeks to get the culture results and an additional three or more weeks for conventional multi drug resistance testing. Hence there is potential for treatment being delayed if waiting for confirmatory culture results. Also, if treatment is started based on less reliable test results there is potential for initiation of treatment that was necessary. Treatment options for TB include medications such as isoniazide, rifampicin, ethambutol and pyrazinamide. Drug resistant TB continues to be a public health concern. Globally in 2019, close to half a million people developed rifampicin-resistant TB, and 78% of them had multidrug-resistant TB Considering these issues there is a need for a test that is rapid and can simultaneously diagnose TB and antibiotic resistance.

The Xpert MTB/RIF assay is a relatively new test that is rapid (takes less than two hours) and can simultaneously detect Mycobacterium tuberculosis and rifampicin resistance. It is a nucleic acid amplification test that requires a disposable cartridge and the GeneXpert Instrument system. Sputum sample collected from the patient suspected of TB, is mixed with a reagent that is provided with the assay, and then the cartridge containing the mixture is placed in the GeneXpert Instrument. From this point onwards the process is fully automated. Technical training to run the test is minimal. Subsquently, to enhance the performance of Xpert MTB/RIF assay, the Xpert MTB/RIF Ultra (Xpert Ultra) assay was developed. Xpert Ultra assay uses a newly developed cartridge and an updated software with the same instrument.

This report is an upgrade from a CADTH report (Summary of Abstracts) published in June 2020. The aim of this current report is to review the evidence regarding the rapid and simultaneous tuberculosis and antibiotic susceptibility testing for PTB and rifampicin resistance. This report will be followed by a second report on the cost-effectiveness rapid and simultaneous tuberculosis and antibiotic susceptibility testing for the diagnosis of pulmonary tuberculosis and rifampicin resistance. Additionally, these reports are components of a larger CADTH Condition Level Review on tuberculosis. A condition level review is an assessment that incorporates all aspects of a condition, from prevention, detection, treatment, and management. For more information on CADTH’s Condition Level Review of tuberculosis, please visit the project page (https://www.cadth.ca/tuberculosis).