Dataset Information

Prospective multicentre head-to-head validation of host blood transcriptomic biomarkers for pulmonary tuberculosis by real-time PCR.

ABSTRACT:

Background

Sensitive point-of-care screening tests are urgently needed to identify individuals at highest risk of tuberculosis. We prospectively tested performance of host-blood transcriptomic tuberculosis signatures.

Methods

Adults without suspicion of tuberculosis were recruited from five endemic South African communities. Eight parsimonious host-blood transcriptomic tuberculosis signatures were measured by microfluidic RT-qPCR at enrolment. Upper respiratory swab specimens were tested with a multiplex bacterial-viral RT-qPCR panel in a subset of participants. Diagnostic and prognostic performance for microbiologically confirmed prevalent and incident pulmonary tuberculosis was tested in all participants at baseline and during active surveillance through 15 months follow-up, respectively.

Results

Among 20,207 HIV-uninfected and 963 HIV-infected adults screened; 2923 and 861 were enroled. There were 61 HIV-uninfected (weighted prevalence 1.1%) and 10 HIV-infected (prevalence 1.2%) tuberculosis cases at baseline. Parsimonious signature diagnostic performance was superior among symptomatic (AUCs 0.85-0.98) as compared to asymptomatic (AUCs 0.61-0.78) HIV-uninfected participants. Thereafter, 24 HIV-uninfected and 9 HIV-infected participants progressed to incident tuberculosis (1.1 and 1.0 per 100 person-years, respectively). Among HIV-uninfected individuals, prognostic performance for incident tuberculosis occurring within 6-12 months was higher relative to 15 months. 1000 HIV-uninfected participants were tested for respiratory microorganisms and 413 HIV-infected for HIV plasma viral load; 7/8 signature scores were higher (p < 0.05) in participants with viral respiratory infections or detectable HIV viraemia than those without.

Conclusions

Several parsimonious tuberculosis transcriptomic signatures met triage test targets among symptomatic participants, and incipient test targets within 6 months. However, the signatures were upregulated with viral infection and offered poor specificity for diagnosing sub-clinical tuberculosis.

SUBMITTER: Mendelsohn SC

PROVIDER: S-EPMC8954216 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Prospective multicentre head-to-head validation of host blood transcriptomic biomarkers for pulmonary tuberculosis by real-time PCR.

Mendelsohn Simon C SC Mbandi Stanley Kimbung SK Fiore-Gartland Andrew A Penn-Nicholson Adam A Musvosvi Munyaradzi M Mulenga Humphrey H Fisher Michelle M Hadley Katie K Erasmus Mzwandile M Nombida Onke O Tameris Michèle M Walzl Gerhard G Naidoo Kogieleum K Churchyard Gavin G Hatherill Mark M Scriba Thomas J TJ

Communications medicine 20220310 1

<h4>Background</h4>Sensitive point-of-care screening tests are urgently needed to identify individuals at highest risk of tuberculosis. We prospectively tested performance of host-blood transcriptomic tuberculosis signatures.<h4>Methods</h4>Adults without suspicion of tuberculosis were recruited from five endemic South African communities. Eight parsimonious host-blood transcriptomic tuberculosis signatures were measured by microfluidic RT-qPCR at enrolment. Upper respiratory swab specimens were ...[more]

PMID: 35342900

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Dataset Information

Prospective multicentre head-to-head validation of host blood transcriptomic biomarkers for pulmonary tuberculosis by real-time PCR.

Background

Methods

Results

Conclusions

Publications

Prospective multicentre head-to-head validation of host blood transcriptomic biomarkers for pulmonary tuberculosis by real-time PCR.

Similar Datasets

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