@jgreenanbarrett
NIHR Academic Clinical Fellow in Infectious Diseases | Specialist Registrar in Infectious Diseases & General Internal Medicine | UCL Respiratory & LSHTM | Interested in TB biomarkers, disease states & natural history
Interesting point! I did look at higher QFN thresholds but the gains in spec were balanced by losses in sens so PPV stayed at 4%. Only combining both tests got PPV up to 7%.
My understanding is that direct measures of IFN are less dynamic and have a higher limit of detection, esp if unstimulated
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
Thanks to @rishigupta.bsky.social @mnoursad.bsky.social @tomscriba.bsky.social
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
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
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)
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:
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
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...
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
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
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
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
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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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
Nice case, thanks for sharing!
“…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
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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Interested in the immunopathology of human tuberculosis? Here is our latest review:
www.science.org/doi/10.1126/...
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
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…
🆕️⚡️⚡️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/...
First wave ISGs (eg MX1) induced rapidly, correlate with VL & infectivity - potential biomarker to stratify patients who'll benefit from antivirals?
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
Those NNTs are convincing (34 for all cause mortality, 48 for infection-related mortality)!
Please can you add @rishigupta.bsky.social and @mnoursad.bsky.social
Additional benefit of using CXR as a screening test is that it could triage sputum non-producers to more intensive investigations e.g. induced sputum, extended follow-up?
Great detective work 🕵🏻♂️