Diagnostic Accuracy of the Cepheid 3-gene Host Response Fingerstick Blood Test in a Prospective, Multi-site Study: Interim Results
Jayne S. Sutherland, Gian van der Spuy, Awa Gindeh, Nguyễn Thụy Thương Thương, AnnRitah Namuganga, Olumuyiwa Owolabi, Harriet Mayanja‐Kizza, Mary Nsereko, Guy Thwaites, Jill Winter, Hazel M. Dockrell, Thomas J. Scriba, Annemieke Geluk, Paul L. A. M. Corstjens, Kim Stanley, Tracy Richardson, Jane Shaw, Bronwyn Smith, Stephanus T. Malherbe, Gerhard Walzl, Jayne S. Sutherland, Olumuyiwa Owolabi, Amie Secka, Georgetta K. Daffeh, Awa Gindeh, Joseph Mendy, Binta Sarr, Abi-Janet Riley, Alhaji Jobe, Monica Davies, Kairaba Kanyi, Momodou W. Jallow, Salieu Barry, Ousainou Cham, Esin Nkereuwem, Gerhard Walzl, Stephanus T. Malherbe, Bronwyn Smith, Gian van der Spuy, Kim Stanley, Jane Shaw, Alicia Chetram, Tracy Richardson, 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, Dorcas Lamunu, Michael Ordie, Guy Thwaites, Thuong Nguyen, Van Le, Son Vo Thanh, Hau Nguyen Thi, Ha Vu Thi Ngoc, Ngoc Le Hong, John T. Belisle, Karen M. Dobos, Hazel M. Dockrell, Thomas J. Scriba, Mark Hatherill, Kate Hadley, Justin Shenje, Stanley Kimbung, Humphrey Mulenga, Rachel Oelofse, Nicole Bilek, Elma van Rooyen, Simba Mabwe, Paul L. A. M. Corstjens, Annemieke Geluk, Elisa M. Tjon Kon Fat, Louise Pierneef, Anouk van Hooij, Jill Winter, Morten Rühwald, Emmanuel Moreau, Adam Penn‐Nicholson, Claudia Schacht, J. Buech, Malte Streitz
Abstract
BACKGROUND: The development of a fast and accurate, non-sputum-based point-of-care triage test for tuberculosis (TB) would have a major impact on combating the TB burden worldwide. A new fingerstick blood test has been developed by Cepheid (the Xpert MTB Host Response [MTB-HR] prototype), which generates a "TB score" based on messenger RNA (mRNA) expression of 3 genes. Here we describe the first prospective findings of the MTB-HR prototype. METHODS: Fingerstick blood from adults presenting with symptoms compatible with TB in South Africa, The Gambia, Uganda, and Vietnam was analyzed using the Cepheid GeneXpert MTB-HR prototype. Accuracy of the Xpert MTB-HR cartridge was determined in relation to GeneXpert Ultra results and a composite microbiological score (GeneXpert Ultra and liquid culture) with patients classified as having TB or other respiratory diseases (ORD). RESULTS: When data from all sites (n = 75 TB, 120 ORD) were analyzed, the TB score discriminated between TB and ORD with an area under the curve (AUC) of 0.94 (95% confidence interval [CI], .91-.97), sensitivity of 87% (95% CI, 77-93%) and specificity of 94% (88-97%). When sensitivity was set at 90% for a triage test, specificity was 86% (95% CI, 75-97%). These results were not influenced by human immunodeficiency virus (HIV) status or geographical location. When evaluated against a composite microbiological score (n = 80 TB, 111 ORD), the TB score was able to discriminate between TB and ORD with an AUC of 0.88 (95% CI, .83-.94), 80% sensitivity (95% CI, 76-85%) and 94% specificity (95% CI, 91-96%). CONCLUSIONS: Our interim data indicate the Cepheid MTB-HR cartridge reaches the minimal target product profile for a point of care triage test for TB using fingerstick blood, regardless of geographic area or HIV infection status.