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James Greenan-Barrett @jgreenanbarrett.bsky.social · 1d

Thanks to @rishigupta.bsky.social @mnoursad.bsky.social @tomscriba.bsky.social

James Greenan-Barrett @jgreenanbarrett.bsky.social · 1d

7/7
In summary:
1. Single-gene transcripts are just as good as multi-gene signatures - this may aid translation by simplifying assays & encouraging commercial competition
2. They show promise to stratify therapy, either alone in high-burden settings or in combination w/ IGRA in low-burden settings

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James Greenan-Barrett @jgreenanbarrett.bsky.social · 1d

6/7
We performed decision curve analysis to evaluate the clinical utility of biomarker-stratified therapy
- High-burden settings: RNA biomarker > IGRA
- Low-burden settings: IGRA > RNA biomarker, but combining both tests was superior if aiming to treat <50 people to prevent 1 case

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James Greenan-Barrett @jgreenanbarrett.bsky.social · 1d

5/7
Importantly, the performance of single-gene transcripts was consistent across high- and low-burden settings

In comparison, IGRA performance was heterogenous (v poor specificity in high-burden settings, as expected)

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James Greenan-Barrett @jgreenanbarrett.bsky.social · 1d

4/7
Performance was similar for asymptomatic prevalent and incident disease up to 12 months, but dropped after 12 months from sampling to disease

Shown here for BATF2, the best performing single-gene:

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James Greenan-Barrett @jgreenanbarrett.bsky.social · 1d

3/7
We performed an IPD-MA of >6500 samples from 7 cohorts across high- and low-burden settings, and compared 80 single-genes vs 8 multi-gene signatures

5 single-genes were equivalent to the best-performing multi-gene signature to detect subclinical TB over a 12 month interval

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James Greenan-Barrett @jgreenanbarrett.bsky.social · 1d

2/7
Previously, we showed that several of these multi-gene signatures perform equivalently, are co-correlated and have common upstream IFN & TNF signalling pathways

So multiple genes might not offer orthogonal value, and simplification of signatures may accelerate translation...

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James Greenan-Barrett @jgreenanbarrett.bsky.social · 1d

1/7
Detecting and treating subclinical TB is essential to prevent progression to clinical disease and reduce transmission

Several multi-gene RNA signatures have been discovered with promising accuracy to detect clinical TB or predict progression to disease

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James Greenan-Barrett @jgreenanbarrett.bsky.social · 1d

Check out our new paper in @lancetmicrobe.bsky.social

In this IPD-MA we show that single-gene transcripts are equivalent to multi-gene signatures to Dx subclinical TB

They perform consistently across settings + show potential clinical utility to stratify therapy

#IDsky #TBsky

bit.ly/47jU7GN

Single-gene transcripts for subclinical tuberculosis: an individual participant data meta-analysis

Single-gene transcripts are equivalent to multi-gene signatures for detection of subclinical tuberculosis, with consistent performance across settings. Single-gene transcripts show potential clinical ...

bit.ly

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James Greenan-Barrett @jgreenanbarrett.bsky.social · Aug 14

Agreed, my key takeaway is dalbavancin is non-inferior to SOC for clinical efficacy. So a good option especially if issues with compliance/IV access/self-discharge etc

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Reposted by James Greenan-Barrett

Daniel Grint @danieljgrint.bsky.social · Jun 13

Optimising the use of currently available treatments through treatment stratification could reduce treatment duration by 2-months for the majority. TB treatment stratification strategies should be prospectively trialled in a phase III RCT.
#TBSky

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Reposted by James Greenan-Barrett

Mahdad Noursadeghi @mnoursad.bsky.social · Mar 27

We’re hiring! Looking for a laboratory post-doc fellow to help us disentangle protective and pathogenic T cells in TB, so we can stratify disease-risk after infection, and develop more effective vaccines. Interdisciplinary science in the heart of London. What's not to like? More here: bit.ly/4iIEiwu

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James Greenan-Barrett @jgreenanbarrett.bsky.social · Jan 17

📌

Reposted by James Greenan-Barrett

Hannah Rickman @hannahrickman.bsky.social · Jan 10

New preprint (with all pre-print caveats!) tinyurl.com/589ffhu4 on Mtb infection risk by sex & age.
Men are at higher risk of #tuberculosis v women- but unclear how much driven by higher infection vs progression to disease. We meta-analysed Mtb immunoreactivity surveys to find out more🧵 #tbsky

Sex Differences in the Risk of Mycobacterium Tuberculosis Infection: A Systematic Review and Meta-Analysis of Population-Based Immunoreactivity Surveys

Background: Tuberculosis (TB) killed 1·25 million people globally in 2023. Men have a 1·7-fold higher TB incidence than women, but it is not known to what exten

papers.ssrn.com

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James Greenan-Barrett @jgreenanbarrett.bsky.social · Jan 5

Nice case, thanks for sharing!

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James Greenan-Barrett @jgreenanbarrett.bsky.social · Jan 5

“…despite the recent introduction of BPaL/M, resistance to these new antituberculosis drugs has already developed in at least 27 countries across four continents. Furthermore, a quarter of these cases involved patient-to-patient transmission”

Worrying stuff

Gabriele Pollara @gpollara.bsky.social · Jan 5

⚠️ Bit of an alarm bell to MDR-TB regimen BPaL/M - resistance to constituent antibiotics developing and transmission of such strains already occurring
#TBSky #IDSky @nejm.org

www.nejm.org/doi/10.1056/...

Transmission as a Key Driver of Resistance to the New Tuberculosis Drugs | NEJM

Whole-genome sequencing was used to show that resistance to newer antituberculosis drugs is present in at least 27 countries and that up to a quarter of this resistance may be due to person-to-...

www.nejm.org

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James Greenan-Barrett @jgreenanbarrett.bsky.social · Jan 3

Exactly, we analyse tests like they act in isolation but (most) clinicians interpret them with Bayesian inference.

There’s no such thing as a bad test, just a bad user!

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James Greenan-Barrett @jgreenanbarrett.bsky.social · Dec 24

📌

Reposted by James Greenan-Barrett

Tom Scriba @tomscriba.bsky.social · Dec 13

Interested in the immunopathology of human tuberculosis? Here is our latest review:
www.science.org/doi/10.1126/...

Immunopathology in human tuberculosis

The balance between protective and pathological immune responses shapes progression of Mycobacterium tuberculosis infection.

www.science.org

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James Greenan-Barrett @jgreenanbarrett.bsky.social · Dec 10

Agreed. But I think the median of 10 days probably reflects the stormy course and source control challenges in sick ICU patients rather than guidelines

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James Greenan-Barrett @jgreenanbarrett.bsky.social · Dec 10

The population were patients with sepsis in ICU (50% had septic shock) so I think 10 days is probably reflective of practice in ICU.

Though the estimate for effect size (-0.88 days duration) from PCT is not practice changing…

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Reposted by James Greenan-Barrett

Antibiotic Steward 🅱️C🆔🅿️🌟 @absteward.bsky.social · Nov 21

🆕️⚡️⚡️Selected TB blood RNA signatures& CRP do not provide biomarkers of microbiological clearance to support TB treatment cessation at 8 weeks
CRP achieved marginal albeit statistically significant discrimination/AUROC 0.69(95%CI 0.52–0.87) #idsky #medsky #tbsky
publications.ersnet.org/content/erj/...

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Reposted by James Greenan-Barrett

Mahdad Noursadeghi @mnoursad.bsky.social · Nov 30

First wave ISGs (eg MX1) induced rapidly, correlate with VL & infectivity - potential biomarker to stratify patients who'll benefit from antivirals?

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James Greenan-Barrett @jgreenanbarrett.bsky.social · Dec 1

Check out our paper on RNA biomarkers in COVID-19

MX1 expression occurred early in infection before PCR detection…potential role to stratify treatment

#IDSky

Mahdad Noursadeghi @mnoursad.bsky.social · Nov 30

Also out now.. after peer review, our analysis of blood transcriptional biomarkers of acute respiratory viral infection leveraging the SARS-CoV-2 human challenge model: www.nature.com/articles/s41...

SARS-CoV-2 human challenge reveals biomarkers that discriminate early and late phases of respiratory viral infections - Nature Communications

It’s not always clear whether blood biomarkers are differentially expressed in the time course of viral infections. In this SARS-CoV-2 human challenge study, the authors identify distinct single-gene ...

www.nature.com

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James Greenan-Barrett @jgreenanbarrett.bsky.social · Nov 28

Those NNTs are convincing (34 for all cause mortality, 48 for infection-related mortality)!