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

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.

Keywords: Cepheid 3-gene host-response prototype; diagnostics; fingerstick blood; triage test; tuberculosis.

Figure 1.

Xpert MTB-HR prototype test analysis in TB and ORD patients detected by GeneXpert Ultra. (A) DUSP3, (B) GBP5, (C) KLF2, (D) TB score. Data were analyzed using Mann-Whitney U test. Bars indicate 10–90% percentile, line indicates median, and dots indicate outliers. Ct value derived from the GeneXpert machine. Abbreviations: Ct, cycle threshold; DUSP3, dual specificity phosphatase 3; GBP5, guanylate binding protein 5; KLF2, Krüppel-like factor 2; MTB-HR, MTB-Host Response; ORD, other respiratory disease; TB, tuberculosis.

Figure 2.

Xpert MTB-HR prototype analysis of all participants combined against Xpert Ultra. A, ROC curve for TB score all participants (black line) and participants who do not have HIV only (green line). B, ROC curve for GBP5 all participants (black line) and participants who do not have HIV only (green line). C, All participants evaluated against a composite microbiological score for TB score. D, All participants evaluated against a composite microbiological score for GBP5. Abbreviations: AUC, area under the curve; GBP5, guanylate binding protein 5; HIV, human immunodeficiency virus; MTB-HR, MTB-Host Response; ROC, receiver operator characteristic; TB, tuberculosis.

Figure 3.

Evaluation at individual sites against Xpert Ultra. ROC curves are shown for Gambia (black line), South Africa (green line), Uganda (red line), and Vietnam (blue line). Abbreviations: AUC, area under the curve; CI, confidence interval; ROC, receiver operator characteristic.