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@article{Boloko:2026:10.1016/j.jinf.2026.106828,
author = {Boloko, L and Schutz, C and Ward, A and Wilkinson, RJ and Jacob, ST and Meintjes, G and Barr, DA},
doi = {10.1016/j.jinf.2026.106828},
journal = {J Infect},
title = {Mycobacterium tuberculosis pathogen load and associated inflammatory responses define infection severity in HIV-associated TB and interact with age to predict mortality.},
url = {http://dx.doi.org/10.1016/j.jinf.2026.106828},
year = {2026}
}
TY - JOUR
AB - BACKGROUND: Sepsis pathobiology is shaped by both pathogen load and host characteristics, yet pathogen load is rarely measurable in clinical cohorts. Severe HIV-associated tuberculosis (TB), a leading cause of critical illness in Africa, provides a unique model in which Mycobacterium tuberculosis bacilli load can be quantified. We investigated how pathogen load and age influence sepsis pathophysiology and mortality in this high-risk population. METHODS: We conducted a prospective cohort study of adults admitted with severe HIV-associated TB. Systemic bacillary load was estimated from multiple routinely collected TB diagnostics. Blood-based sepsis markers were summarised using principal components analysis, and pathophysiological processes were evaluated using directed acyclic graphs and regression modelling. FINDINGS: Among 519 patients with microbiologically confirmed TB, 75 (14.5%) died by day 28. Two major axes of host response were identified: PC1, capturing IL-6, CRP, and procalcitonin; and PC2, reflecting venous lactate, aspartate aminotransferase, and cytopenias. Both strongly correlated with bacilli load (PC1 r=0.46; PC2 r=0.43; both p<0.001) but not with age. Mortality independently associated with infection severity - whether defined by bacilli load (aOR 2.1, 95%CI 1.6-2.9) or by inflammatory axes (PC1 aOR 2.3, 95%CI 1.7-3.1; PC2 aOR 1.9, 95%CI 1.5-2.5) - and with age (aOR 1.84, 95%CI 1.4-2.4). Absolute mortality risk therefore reflected an interaction between pathogen load and age. Hyperlactataemia, metabolic acidosis, kidney dysfunction, and temperature were all correlated with bacilli load, inflammation and mortality (all p<0.001). Older patients showed less respiratory compensation for metabolic acidosis, higher blood glucose at a given lactate level, and attenuated fever response at a given bacilli load. INTERPRETATION: Pathogen load and associated inflammatory responses define infection severity in HIV-associated TB and interact with age to pre
AU - Boloko,L
AU - Schutz,C
AU - Ward,A
AU - Wilkinson,RJ
AU - Jacob,ST
AU - Meintjes,G
AU - Barr,DA
DO - 10.1016/j.jinf.2026.106828
PY - 2026///
TI - Mycobacterium tuberculosis pathogen load and associated inflammatory responses define infection severity in HIV-associated TB and interact with age to predict mortality.
T2 - J Infect
UR - http://dx.doi.org/10.1016/j.jinf.2026.106828
UR - https://www.ncbi.nlm.nih.gov/pubmed/42570730
ER -