Inflammatory biomarkers of asymptomatic and symptomatic tuberculosis
- Denis Awany
- Dominique T. Ariefdien
- Simon C. Mendelsohn
- Virginie Rozot
- Humphrey Mulenga
- Sarah Nyangu
- Michele Tameris
- Tumelo Moloantoa
- Austin Katona
- Fernanda Maruri
- Firdows Noor
- Ravindre Panchia
- Khuthadzo Hlongwane
- Kim Stanley
- Yuri F. van der Heijden
- Katie Hadley
- Andrew- Fiore Gartland
- Craig Innes
- William Brumskine
- Keertan Dheda
- Shameem Jaumdally
- Tahlia Perumal
- Neil Martinson
- Al Leslie
- Bernard Fourie
- Andriëtte Hiemstra
- Stephanus T. Malherbe
- Gerhard Walzl
- Kogieleum Naidoo
- Gavin Churchyard
- Novel N. Chegou
- Timothy R. Sterling
- Mark Hatherill
- Thomas J. Scriba
- Pattamukkil Abraham
- Thakiera Allie
- Cynthia Baard
- Zainab Baig
- John Belisle
- Nicole Bilek
- Gerard Cangelosi
- Ace Carstens
- Kevyna Chetty
- Yolundi Cloete
- Marwou de Kock
- Gareta Dickman
- Charity Dire
- Karen Dobos
- Stephany Norah Duda
- Mzwandile Erasmus
2026-07-25
A large proportion of individuals with tuberculosis (TB) are asymptomatic. The biological and inflammatory underpinnings of asymptomatic TB are unknown and may differ from symptomatic TB. We characterise blood transcriptomic and proteomic profiles in South African community screening vs. health facility-based triage cohorts. Asymptomatic TB shares core transcriptomic and proteomic features with symptomatic TB, including upregulation of innate, interferon and inflammatory pathways and downregulation of T and B cell pathways. Integration of transcriptomic and proteomic data from asymptomatic TB individuals identifies two distinct sub-clusters characterized by higher or lower bacterial burden, blood IFN-γ responses, BMI, and chest radiographic abnormalities, suggesting different disease severity. We identify a new blood transcriptomic signature of asymptomatic TB. However, diagnostic performance of transcriptomic and proteomic markers is weaker for asymptomatic TB than symptomatic TB, suggesting that policy development for community-based, asymptomatic TB screening should not adopt biomarkers developed for symptomatic TB triage without further optimization.