Added Value of Xpert MTB/RIF Ultra for Diagnosis of Pulmonary Tuberculosis in a Low-Prevalence Setting

Abstract

Xpert MTB/RIF (Xpert) for direct molecular detection of Mycobacterium tuberculosis and rifampin resistance from clinical specimens has dramatically improved the diagnosis of tuberculosis (TB). Xpert MTB/RIF Ultra (Ultra) is proposed as a substitute of Xpert with increased sensitivity and improved rifampin resistance detection.

The rapid molecular test Xpert MTB/RIF ultra: towards improved tuberculosis diagnosis and rifampicin resistance detection

“…These data did not show any difference in sensitivity between Ultra and Xpert for smear-positive specimens but a higher sensitivity of Ultra for smear-negative specimens. Similar results were obtained in a study conducted in a region of low tuberculosis prevalence; sensitivities of Ultra and Xpert were 95.7% and 82.9%, respectively, when considering all culture-positive specimens, 100% for both tests when considering smear-positiveeculture-positive specimens, and 91.8% and 66.7% when considering smear-negativeeculture-positive specimens [16]. This suggests an increased sensitivity for Ultra, especially for paucibacillary specimens.…”

“…Similarly, a correlation is also observed between the semi-quantitative result of Ultra and smear microscopy. Thus, Ultra might also help to rapidly identify the most infectious patients (those with Ultra-positive medium and high) as well as the less infectious patients, those with ultra-negative [12,16]. Studies making a direct link between the DNA load and the transmission potential are still missing.…”

“…This is more likely to occur with ultrasensitive tests, explaining their slightly decreased specificity. In addition, decreased specificity due to a patient's previous history of tuberculosis is more likely to occur in the setting of medium to high tuberculosis prevalence when compared to region of low tuberculosis burden [16,25]. Ultra provides an additional category called 'trace' that does not exist with Xpert, which corresponds to specimens positive for the PCR targeting the multicopy genes IS6110 and IS1810 and negative for the PCR targeting the single copy gene rpoB.…”

“…A 'trace' result represents the detection of a very low quantity of M. tuberculosis DNA. Clinical information of patients with Ultra 'trace' results helps to distinguish (a) ongoing active paucibacillary tuberculosis from (b) detection of dead bacilli from previous infections [16].…”

Xpert MTB/RIF ultra for rapid diagnosis of extrapulmonary tuberculosis in a high-income low-tuberculosis prevalence setting

“…The increased sensitivity of Ultra is achieved by incorporation of two new PCR assays targeting the multicopy genes IS6110 and IS1081 for the diagnosis of TB, a larger DNA reaction chamber and transformation from hemi-nested to fully nested PCR reactions 7 . A number of studies report increased sensitivity of Ultra compared to Xpert in smear negative PTB [9][10][11][12][13][14][15][16] , and several studies also show promising results for diagnosing EPTB 11,14,15,[17][18][19][20][21][22][23][24][25] . However, most of the studies that investigate Ultra for diagnosing EPTB have been conducted in low-resource settings with high TB incidence.…”