Performance of 2 Finger-Stick Blood Tests to Triage Adults With Symptoms of Pulmonary Tuberculosis: A Prospective Multisite Diagnostic Accuracy Study
Jayne S. Sutherland, Gian D van der Spuy, Jane A Shaw, Tracy Richardson, Elisa M Tjon Kon Fat, Awa Gindeh, Olumuyiwa Owolabi, Nguyễn Thụy Thương Thương, Le Hong Van, Van Hoang Nguyen, Dang Thi Thanh Thao, Harriet Mayanja-Kizza, Mary Nsereko, AnnRitah Namuganga, Sophie Nalukwago, John Belisle, Emmanuel Moreau, Adam Penn‐Nicholson, Guy Thwaites, Jill Winter, Hazel M Dockrell, Thomas J. Scriba, Kim Stanley, Bronwyn Smith, Novel N. Chegou, Stephanus T. Malherbe, Annemieke Geluk, Paul L. A. M. Corstjens, Gerhard Walzl, Jayne S. Sutherland, Olumuyiwa Owolabi, Amie Secka, Bintou Njai, Abdou K. Sillah, Georgetta K. Daffeh, Awa Gindeh, Amadou Barry, Momodou Rashid, Joseph Mendy, Binta Sarr, Abi-Janet Riley, Alhaji Jobe, Monica Davies, Kairaba Kanyi, Momodou W. Jallow, Salieu Barry, Ousainou Cham, Gerhard Walzl, Stephanus T. Malherbe, Bronwyn Smith, Gian D van der Spuy, Kim Stanley, Jane A Shaw, Alicia Chetram, Tracy Richardson, Bernadine Fransman, Isaac Johnson, Marika Finn, Andriëtte Hiemstra, Novel N. Chegou, Helena Kuivaniemi, Gerard Tromp, Susanne Tönsing, Elizma Smit, Balie Carstens, Harriet Mayanja‐Kizza, Mary Nsereko, AnnRitah Namuganga, Sophie Nalukwago, Joseph Akol, Saidah Menya, Veronica Kizza, Yusuf Kironde, Deborah Banturaki, Immaculate Nahereza, Simon Okiror, Immaculate Kemigisha, Paul Mutumba, Henry Ojiambo, Lilian Murungi, Joan Nassuna, Gladys Mpalanyi, Michael Odie, Guy Thwaites, Nguyễn Thụy Thương Thương, Van Le, Son Vo Thanh, Hau Nguyen Thi, Ha Vu Thi Ngoc, Ngoc Le Hong, John Belisle, Karen M. Dobos, Hazel M Dockrell, Thomas J. Scriba, Mark Hatherill, Kate Hadley, Justin Shenje, Stanley Kimbung, Humphrey Mulenga, Rachel Oelofse
Abstract
BACKGROUND: Non-sputum-based, point-of-care triage tests for pulmonary tuberculosis could enhance tuberculosis diagnostic programs. We assessed the diagnostic accuracy of 2 finger-stick blood tests: the Cepheid 3 gene host-response cartridge (Xpert-HR), which measures 3 host messenger RNA transcripts, and the 3-host protein multibiomarker test (MBT). METHODS: We performed a prospective diagnostic accuracy study of consecutive participants with symptoms compatible with pulmonary tuberculosis in The Gambia, South Africa, Uganda, and Vietnam. A composite reference standard for active pulmonary tuberculosis incorporated chest radiography, symptom resolution, and sputum microbiological test results. A training-test set approach was used to evaluate test cutoff specificities at 90% sensitivity. RESULTS: Between 1 November 2020 and 1 May 2023, we screened 1262 participants aged 12-70 years with cough lasting >2 weeks and another symptom suggestive of tuberculosis. Of those who were classifiable by reference tests, 1154 participants had evaluable Xpert-HR results and 961 had evaluable MBT results. Xpert-HR had an area under the receiver operating characteristic (AUROC) curve of 0.92 at a cutoff of -1.275 or below, with a sensitivity of 92.8%, specificity of 62.5%, positive predictive value of 47.9%, and negative predictive value of 95.9%. The MBT had an AUROC of 0.91 at a cutoff of ≥0.42, with a sensitivity of 91.4%, specificity of 73.2%, positive predictive value of 52.0%, and negative predictive value of 96.4%. CONCLUSIONS: Our results show that both Xpert-HR and the MBT are promising non-sputum-based point-of-care tests. The MBT met the World Health Organization target product profile for a triage test, which suggests it should be further developed.