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

Author:

Sutherland Jayne S1,van der Spuy Gian2,Gindeh Awa1,Thuong Nguyen Thuy Thuong34,Namuganga AnnRitah5,Owolabi Olumuyiwa1,Mayanja-Kizza Harriet5,Nsereko Mary5,Thwaites Guy34,Winter Jill6,Dockrell Hazel M7,Scriba Thomas J8,Geluk Annemieke9,Corstjens Paul10,Stanley Kim2,Richardson Tracy2,Shaw Jane A2,Smith Bronwyn2,Malherbe Stephanus T2,Walzl Gerhard2,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,

Affiliation:

1. Vaccines and Immunity Theme, Medical Research Council (MRC) Unit, The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, The Gambia

2. Department of Science and Technology National Research Foundation (DST-NRF) Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

3. Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam

4. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK

5. Makerere University, Kampala, Uganda

6. Catalysis Foundation, Berkeley, California, USA

7. London School of Hygiene and Tropical Medicine, London, United Kingdom

8. South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, South Africa

9. Department of Infectious Diseases, Leiden University Medical Center, The Netherlands

10. Department of Cell and Chemical Biology, Leiden University Medical Center, The Netherlands

Abstract

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.

Funder

EDCTP

NIH

Bill & Melinda Gates Foundation

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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