Table 2.
Comparative accuracy for detection of tuberculosis and rifampicin resistance
|
Tuberculosis detection* |
Detection of rifampicin resistance† |
||||||
|---|---|---|---|---|---|---|---|
| Sensitivity: all culture-positive (95% CI; n/N) | Sensitivity: smear-negative (95% CI; n/N) | Sensitivity: HIV-negative (95% CI; n/N)‡ | Sensitivity: HIV-positive (95% CI; n/N)‡ | Specificity (95% CI; n/N) | Sensitivity (95% CI; n/N) | Specificity (95% CI; n/N) | |
| Xpert | 83%(79 to 86; 383/462) | 46%(37 to 55; 63/137)§ | 90%(84 to 94; 143/159) | 77%(68 to 84; 88/155) | 98%(97 to 99; 960/977) | 95%(91 to 98; 167/175) | 98%(96 to 99; 369/376) |
| Xpert Ultra | 88%(85 to 91; 408/462) | 63%(54 to 71; 86/137)§ | 91%(86 to 95; 145/159) | 90% (83 to 95; 103/115) | 96%(94 to 97; 934/977) | 95%(91 to 98; 166/175) | 98%(97 to 99; 370/376) |
| Difference (Xpert Ultra minus Xpert) | 5·4% (3·3 to 8·0; 25/162) | 17% (10 to 24; 23/137) | 1·3% (−1·8 to 4·9; 2/159) | 13% (6·4 to 21; 15/115) | −2·7% (−3·9 to −1·7; 36/977) | −0·6% (−3·2 to 1·6; 1/175) | 0·3% (−0·7 to 1·5; 1/376) |
| Non-inferiority margin | Not predefined | −7% | Not predefined | Not predefined | Not predefined | −3% | −3% |
Results are based on initial testing of the first sample with Xpert MTB/RIF and Xpert MTB/RIF Ultra (Xpert Ultra) assays. Uninterpretable results (contaminated cultures or non-determinate Xpert or Ultra results) were excluded from the analysis. Culture contamination averaged 4·3–7·8%, depending on sample and culture type. Non-determinate results (invalid, error, no result) are reported in the main text. Sensitivities of Xpert and Xpert Ultra for detection of smear-positive tuberculosis (n=323) were 99% (95% CI 97–100) and 99% (97–100).
Accuracy for tuberculosis detection was estimated in study participants in the case detection group. Patients with unknown HIV-infection status are excluded from analyses stratified by HIV status but included in all other analyses.
Accuracy for detection of rifampicin resistance was estimated in all study participants with available drug susceptibility test results and valid rifampicin resistance results for both Xpert and Xpert Ultra.
Data on HIV-infection status were not available for 188 culture-positive and 336 culture-negative study participants. Sensitivity of Xpert and Xpert Ultra in study participants with missing HIV status was 81% and 85%, respectively. Note that the estimate for pooled sensitivity of Xpert Ultra irrespective of HIV status does not fall between the estimates for HIV-infected and HIV-uninfected individuals.
Accuracy estimates are based on the reference standard as defined in the Methods section (using four cultures to define tuberculosis); using a less stringent reference standard with only one liquid and one solid culture (both from sputum sample 2), which is similar to the reference standard used in 21 of 22 studies included in the most recent Cochrane systematic review of the Xpert assay,4 resulted in Xpert sensitivity for smear-negative tuberculosis of 73% (Cochrane review pooled estimate 67%) and Xpert Ultra sensitivity of 84% (appendix p 5).