Diagnostic Accuracy of the Cepheid 3-gene Host Response Fingerstick Blood Test in a Prospective, Multi-site Study: Interim Results
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 ,   TrENDx-TB Consortium, Sutherland Jayne , Owolabi Olumuyiwa , Secka Amie , Daffeh Georgetta , Gindeh Awa , Mendy Joseph , Sarr Binta , Riley Abi-Janet , Jobe Alhaji , Davies Monica , Kanyi Kairaba , Jallow Momodou , Barry Salieu , Cham Ousainou , Nkereuwem Esin , Walzl Gerhard , Malherbe Stephanus , Smith Bronwyn , van der Spuy Gian , Stanley Kim , Shaw Jane , Chetram Alicia , Richardson Tracy , Finn Marika , Hiemstra Andriette , Chegou Novel , Kuivaniemi Helena , Tromp Gerard , Tonsing Susanne , Smit Elizma , Carstens Balie , Mayanja-Kizza Harriet , Nsereko Mary , Namuganga AnnRitah , Nalukwago Sophie , Akol Joseph , Lamunu Dorcas , Ordie Michael , Thwaites Guy , Nguyen Thuong , Le Van , Vo Thanh Son , Thi Hau Nguyen , Thi Ngoc Ha Vu , Le Hong Ngoc , Belisle John , Dobos Karen , Dockrell Hazel , Scriba Thomas , Hatherill Mark , Hadley Kate , Shenje Justin , Kimbung Stanley , Mulenga Humphrey , Oelofse Rachel , Bilek Nicole , van Rooyen Elma , Mabwe Simba , Corstjens Paul , Geluk Annemieke , Kon Fat Elisa Tjon , Pierneef Louise , van Hooij Anouk , Winter Jill , Ruhwald Morten , Moreau Emmanuel , Penn-Nicholson Adam , Schacht Claudia , Büech Julia , Streitz Malte 
Published: September 2021

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.