Diagnostic Accuracy of the Cepheid 3-gene Host Response Fingerstick Blood Test in a Prospective, Multi-site Study: Interim Results

• Published in: Clinical infectious diseases Vol. 74; no. 12; pp. 2136 - 2141
• Main Authors: Sutherland, Jayne S, van der Spuy, Gian, Gindeh, Awa, Thuong, Nguyen Thuy Thuong, Namuganga, AnnRitah, Owolabi, Olumuyiwa, Mayanja-Kizza, Harriet, Nsereko, Mary, Thwaites, Guy, Winter, Jill, Dockrell, Hazel M, Scriba, Thomas J, Geluk, Annemieke, Corstjens, Paul, Stanley, Kim, Richardson, Tracy, Shaw, Jane A, Smith, Bronwyn, Malherbe, Stephanus T, Walzl, Gerhard
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 06.07.2022
• Subjects: Adult; Hematologic Tests; HIV Infections - diagnosis; Humans; Major and Commentaries; Mycobacterium tuberculosis - genetics; Prospective Studies; Sensitivity and Specificity; Tuberculosis - diagnosis; Cepheid 3-gene host-response prototype; diagnostics; triage test; fingerstick blood; tuberculosis
• DOI: 10.1093/cid/ciab839
• ISSN: 1058-4838; 1537-6591

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. This study is the first prospective evaluation of the Cepheid MTB-HR test using fingerstick blood in a multi-site cohort. Interim results indicate the test reaches the WHO TPP for a TB Triage test regardless of geographical location and HIV status.