Blood-based host biomarker diagnostics in active case finding for pulmonary tuberculosis: A diagnostic case-control study.

BACKGROUND

There is a need to identify scalable tuberculosis screening strategies among high burden populations. The WHO has identified a non-sputum-based triage test as a development priority.

METHODS

We performed a diagnostic case-control study of point-of-care C-reactive protein (CRP) and Prototype-Xpert-MTB-Host-Response (Xpert-MTB-HR) assays in the context of a mass screening program for tuberculosis in two prisons in Brazil. All incarcerated individuals irrespective of symptoms were screened by sputum Xpert MTB/RIF and sputum culture. Among consecutive, Xpert MTB/RIF or culture-confirmed cases and Xpert MTB/RIF and culture-negative controls, CRP was quantified in serum by a point-of-care assay (iChroma-II) and a 3-gene expression score was quantified from whole blood using the Xpert-MTB-HR cartridge. We evaluated receiver operating characteristic area under the curve (AUC) and assessed specificity at 90% sensitivity and sensitivity at 70% specificity, consistent with WHO target product profile (TPP) benchmarks.

FINDINGS

Two hundred controls (no TB) and 100 culture- or Xpert MTB/RIF-positive tuberculosis cases were included. Half of tuberculosis cases and 11% of controls reported any tuberculosis symptoms. AUC for CRP was 0·79 (95% CI: 0·73-0·84) and for Xpert-MTB-HR was 0·84 (95% CI: 0·79-0·89). At 90% sensitivity, Xpert-MTB-HR had significantly higher specificity (53·0%, 95% CI: 45·0-69·0%) than CRP (28·1%, 95% CI: 20·2-41·8%) (

INTERPRETATION

For active case finding in this high tuberculosis-burden setting, CRP and Xpert-MTB-HR did not meet TPP benchmarks for a triage test. However, Xpert-MTB-HR was highly sensitive in detecting individuals with medium or high sputum bacillary burden.

FUNDING

National Institutes of Health (R01 AI130058 and R01 AI149620) and Brazilian National Council for Scientific and Technological Development (CNPq-404182/2019-4).

Informations de copyright

© 2021 The Author(s).

Déclaration de conflit d'intérêts

JRA received grants from the U.S. National Institutes of Health to support this research. PK is a co-inventor on a 3-gene TB score pending patent owned by Stanford University, which has been licensed for commercialization. PK is a consultant with Cepheid. DHP, ES, and DG are employed by Cepheid. Xpert-MTB-HR cartridges were provided by Cepheid. Cepheid had no role in selection of participants, assay performance and interpretation, or data analysis, and did not have access to the study results until all analyses were completed.