Xpert® MTB/RIF assay for extrapulmonary tuberculosis and rifampicin resistance

27 Aug 2018

Why is improving the diagnosis of extrapulmonary tuberculosis important?

Tuberculosis (TB) is the world’s leading infectious cause of death. It mainly affects the lungs (pulmonary TB) but may occur in other body parts than the lungs (extrapulmonary TB). In most people, TB can be cured if the disease is diagnosed and properly treated. One problem involved in treating TB is that the bacteria become resistant to antibiotics. Not recognizing TB early (false‐negative result) may result in delayed diagnosis and treatment and increased illness and death. An incorrect TB diagnosis (false‐positive result) may result in increased anxiety and unnecessary treatment.

What is the aim of this review?

To find out how accurate Xpert® MTB/RIF (Xpert) is for diagnosing extrapulmonary TB and drug resistance. We included eight forms of extrapulmonary TB: tuberculous meningitis and pleural, lymph node, bone or joint, genitourinary, peritoneal, pericardial, and disseminated TB.

What was studied in this review?

Xpert is a relatively new, automated, rapid test that detects TB and rifampicin resistance at the same time. Rifampicin is an important drug for treating people with TB. Another Cochrane Review showed that Xpert is accurate for diagnosing pulmonary TB. The current review assessed Xpert accuracy for detecting eight forms of extrapulmonary TB, as well as the different specimens that may be collected for diagnosis, for instance, cerebrospinal fluid, pleural fluid, and urine. Xpert results were measured against culture results (benchmark).

What are the main results reported in this review?

We included 66 studies that evaluated 16,213 specimens for extrapulmonary TB and rifampicin resistance. Only one study evaluated the newest test version, Xpert Ultra (Ultra), for tuberculous meningitis.

In urine and bone or joint fluid and tissue, Xpert was sensitive (more than 80%), that is, registered positive in people who actually had TB. In cerebrospinal fluid, pleural fluid, urine, and peritoneal fluid, Xpert was highly specific (98% or more), that is, did not register positive in people who were actually negative.

For a population of 1000 people:

• where 100 have TB meningitis on culture, 89 would be Xpert‐positive: of these, 18 (20%) would not have TB; and 911 would be Xpert‐negative: of these, 29 (3%) would have TB.

• where 150 have pleural TB on culture, 83 would be Xpert‐positive: of these, seven (8%) would not have TB ; and 917 would be Xpert‐negative: of these, 74 (8%) would have TB.

• where 70 have genitourinary TB on culture, 70 would be Xpert‐positive: of these, 12 (17%) would not have TB; and 930 would be Xpert‐negative: of these, 12 (1%) would have TB.

• where 120 have rifampicin‐resistant TB, 125 would be positive for rifampicin‐resistant TB: of these, 11 (9%) would not have rifampicin resistance; and 875 would be negative for rifampicin‐resistant TB: of these, 6 (1%) would have rifampicin resistance.

How confident are we in the review's results?

The diagnosis of extrapulmonary TB was made by assessing patients with culture, generally considered to be the best reference standard. However, it appears that culture did not work well as a reference test for lymph node TB.

Who do the review's results apply to?

People presumed to have extrapulmonary TB. Most studies included only inpatients at tertiary care centres or did not report the clinical setting. Therefore, we could not say how the test would work in primary care.

What are the implications of this review?

Xpert may be helpful in diagnosing extrapulmonary TB. The ability of Xpert to detect TB varies when different specimens are used, while Xpert rarely yields a positive result for people without TB (defined by culture). Xpert is accurate for diagnosing rifampicin resistance. In patients thought to have TB meningitis, which is considered a medical emergency, providers should use clinical judgment and should not rely solely on an Xpert result when deciding to withhold treatment, as is common practice when culture results are negative.

How up‐to‐date is this review?

The review authors searched for studies published up to 7 August 2017.