A Andama1,2, D Jaganath3,4,5, R Crowder3,4, L Asege6, M Nakaye6, D Katumba6, J Mukwatamundu6, S Mwebe6, C F Semitala7,6, W Worodria7,8, M Joloba9, S Mohanty10, A Somoskovi11, A Cattamanchi3,4,12,13. 1. Department of Internal Medicine, Makerere University College of Health Sciences, Ground Floor Pathology Building, Room A4, Kampala, Uganda. andama.alf@gmail.com. 2. Infectious Diseases Research Collaboration, Kampala, Uganda. andama.alf@gmail.com. 3. Department of Medicine, Division of Pulmonary & Critical Care Medicine, University of California San Francisco, San Francisco, California, USA. 4. Center for Tuberculosis, University of California San Francisco, San Francisco, California, USA. 5. Department of Pediatrics, Division of Pediatric Infectious Diseases, University of California San Francisco, San Francisco, California, USA. 6. Infectious Diseases Research Collaboration, Kampala, Uganda. 7. Department of Internal Medicine, Makerere University College of Health Sciences, Ground Floor Pathology Building, Room A4, Kampala, Uganda. 8. Mulago National Referral Hospital, Kampala, Uganda. 9. Department of Medical Microbiology, Makerere University College of Health Sciences, Kampala, Uganda. 10. Department of Chemical Engineering, Department of Materials Science Engineering, University of Utah, Salt Lake City, USA. 11. Global Good Intellectual Ventures Laboratory, Seattle, USA. 12. Center for Vulnerable Populations, Department of Medicine, University of California San Francisco, San Francisco, USA. 13. Curry International Tuberculosis Center, University of California San Francisco, San Francisco, USA.
Abstract
BACKGROUND: 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). We assessed the diagnostic accuracy of Ultra for pulmonary TB among adults in Kampala, Uganda. METHODS: We 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. RESULTS: Among 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). CONCLUSIONS: After 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.
BACKGROUND: 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). We assessed the diagnostic accuracy of Ultra for pulmonary TB among adults in Kampala, Uganda. METHODS: We 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. RESULTS: Among 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). CONCLUSIONS: After 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.
Authors: David J Horne; Mikashmi Kohli; Jerry S Zifodya; Ian Schiller; Nandini Dendukuri; Deanna Tollefson; Samuel G Schumacher; Eleanor A Ochodo; Madhukar Pai; Karen R Steingart Journal: Cochrane Database Syst Rev Date: 2019-06-07
Authors: Hridesh Mishra; Byron W P Reeve; Zaida Palmer; Judy Caldwell; Tania Dolby; Charissa C Naidoo; Jennifer G Jackson; Samuel G Schumacher; Claudia M Denkinger; Andreas H Diacon; Paul D van Helden; Florian M Marx; Robin M Warren; Grant Theron Journal: Lancet Respir Med Date: 2020-02-14 Impact factor: 30.700
Authors: Jérémie F Cohen; Daniël A Korevaar; Douglas G Altman; David E Bruns; Constantine A Gatsonis; Lotty Hooft; Les Irwig; Deborah Levine; Johannes B Reitsma; Henrica C W de Vet; Patrick M M Bossuyt Journal: BMJ Open Date: 2016-11-14 Impact factor: 2.692
Authors: Soumitesh Chakravorty; Ann Marie Simmons; Mazhgan Rowneki; Heta Parmar; Yuan Cao; Jamie Ryan; Padmapriya P Banada; Srinidhi Deshpande; Shubhada Shenai; Alexander Gall; Jennifer Glass; Barry Krieswirth; Samuel G Schumacher; Pamela Nabeta; Nestani Tukvadze; Camilla Rodrigues; Alena Skrahina; Elisa Tagliani; Daniela M Cirillo; Amy Davidow; Claudia M Denkinger; David Persing; Robert Kwiatkowski; Martin Jones; David Alland Journal: mBio Date: 2017-08-29 Impact factor: 7.867