Abstract
BackgroundThe World Health Organization (WHO) has endorsed the next-generation Xpert MTB/RIF Ultra (Ultra) cartridge, and Uganda is currently transitioning from the older generation Xpert MTB/RIF (Xpert) cartridge to Ultra as the initial diagnostic test for pulmonary tuberculosis (TB). We assessed the diagnostic accuracy of Ultra for pulmonary TB among adults in Kampala, Uganda.MethodsWe sampled adults referred for Xpert testing at two hospitals and a health center over a 12-month period. We enrolled adults with positive Xpert and a random 1:1 sample with negative Xpert results. Expectorated sputum was collected for Ultra, and for solid and liquid culture testing for Xpert-negative patients. We measured sensitivity and specificity of Ultra overall and by HIV status, prior history of TB, and hospitalization, in reference to Xpert and culture results. We also assessed how classification of results in the new “trace” category affects Ultra accuracy.ResultsAmong 698 participants included, 211 (30%) were HIV-positive and 336 (48%) had TB. The sensitivity of Ultra was 90.5% (95% CI 86.8–93.4) and specificity was 98.1% (95% CI 96.1–99.2). There were no significant differences in sensitivity and specificity by HIV status, prior history of TB or hospitalization. Xpert and Ultra results were concordant in 670 (96%) participants, with Ultra having a small reduction in specificity (difference 1.9, 95% CI 0.2 to 3.6, p=0.01). When “trace” results were considered positive for all patients, sensitivity increased by 2.1% (95% CI 0.3 to 3.9, p=0.01) without a significant reduction in specificity (− 0.8, 95% CI − 0.3 to 2.0, p=0.08).ConclusionsAfter 1 year of implementation, Ultra had similar performance to Xpert. Considering “trace” results to be positive in all patients increased case detection without significant loss of specificity. Longitudinal studies are needed to compare the benefit of greater diagnoses to the cost of overtreatment.
Highlights
The World Health Organization (WHO) has endorsed the next-generation Xpert M. tuberculosis (MTB)/RIF Xpert MTB/RIF Ultra (Ultra) (Ultra) cartridge, and Uganda is currently transitioning from the older generation Xpert MTB/RIF (Xpert) cartridge to Ultra as the initial diagnostic test for pulmonary tuberculosis (TB)
The next-generation cartridge, Xpert MTB/ RIF Ultra (Ultra), includes two multi-copy amplification targets, a larger DNA reaction chamber, and fully nested nucleic acid amplification to lower the limit of detection from 113 colony forming units/mL to 16 cfu/ml, which is similar to growth detection [2]
Most participants were identified in the outpatient setting (n=620, 89%), and the median Karnofsky score was 80 (IQR 70–90)
Summary
The World Health Organization (WHO) has endorsed the next-generation Xpert MTB/RIF Ultra (Ultra) cartridge, and Uganda is currently transitioning from the older generation Xpert MTB/RIF (Xpert) cartridge to Ultra as the initial diagnostic test for pulmonary tuberculosis (TB). Nucleic acid amplification testing (NAAT) is recommended by the World Health Organization (WHO) as an initial test for pulmonary TB. The next-generation cartridge, Xpert MTB/ RIF Ultra (Ultra), includes two multi-copy amplification targets, a larger DNA reaction chamber, and fully nested nucleic acid amplification to lower the limit of detection from 113 colony forming units (cfu)/mL to 16 cfu/ml, which is similar to growth detection [2]. Based on a multicenter assessment demonstrating increased sensitivity [3], the WHO recommended that Ultra replace Xpert as the initial diagnostic test [4]. While the hope is that the lower limit of detection will increase case detection of patients with less advanced disease, there is concern for reduced specificity and increased false-positive results, among the category of “trace” results or in patients with past tuberculosis history [6]
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