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

10/
2nd by Hanif Esmail:
- >½ of undiagnosed sputum +ve cases are asympt
- Unlike symptom-based screening, symptom-agnostic screening is effective
- Screening can be done on scale - 10% of the entire USA pop was screened in 1950s
- Treatment outcomes are affected by symptoms and sputum status

9/
Two excellent talks on asymptomatic TB
1st by Frank Cobelens:
- “Subclinical” meaning varies between studies
- Rates of infection of contacts not affected by +/- symptoms
- Asymp TB may have longer duration due to lower mortality and lower probability of diagnosis --> overall higher prevalence

7/
Preliminary results from TRUNCATE biomarker analysis by @mnoursad.bsky.social
- In both the truncated and SOC arms, RNA expression had not normalised by Wk8 but resolution continued after Wk8 despite no Abx in intervention arm- is this post-Rx immune clearance of bacteria?
cont...

6/
Estimations of scaling up RATIONS (Finn McQuaid)
- Lower TB disease mainly from reduced disease in contacts
- Lower deaths mainly from reduced deaths in pts
- If scaled up across India could result in up to 1.4m fewer cases
- Cost effective ($149/DALY) even before considering non TB disease

5/
Insights from the H56 vaccine trial by @tomscriba.bsky.social
- RCT of H56 vaccine given after 6 months HRZE for PTB
- Vaccine was safe and immunogenic but did not protect against TB recurrence - and may have increased the risk of TB relapse (not powered to look for this) but not re-infection

4/
...cont
- However Helen Cox showed digital steths have good sens (79.2%) but poor spec (51%) for Dx of PTB

Some thought needed about their use case - specificity limits diagnostic use but could be used as triage test or for severity assessment (but needs comparison against clinical endpoints)

2/
Implications of a trace Xpert Ultra (Joowhan Sung)
- 129 pts with trace Ultra were thoroughly investigated at baseline + followed up for 2 yrs
- ½ of pts diagnosed w/ prevalent or incident TB
- Incident TB strongly associated w/ abnormal CXR but NOT symptoms - supports symptom-agnostic testing