Abstract
Tuberculosis remains a leading cause of death globally despite curative treatment, partly due to the difficulty of identifying patients who will not respond to therapy. Simple host biomarkers that correlate with response to drug treatment would facilitate improvement in outcomes and the evaluation of novel therapies. In a prospective longitudinal cohort study, we evaluated neutrophil count and phenotype at baseline, as well as during TB treatment in 79 patients [50 (63%) HIV-positive] with microbiologically confirmed drug susceptible TB undergoing standard treatment. At time of diagnosis, blood neutrophils were highly expanded and surface expression of the neutrophil marker CD15 greatly reduced compared to controls. Both measures changed rapidly with the commencement of drug treatment and returned to levels seen in healthy control by treatment completion. Additionally, at the time of diagnosis, high neutrophil count, and low CD15 expression was associated with higher sputum bacterial load and more severe lung damage on chest x-ray, two clinically relevant markers of disease severity. Furthermore, CD15 expression level at diagnosis was associated with TB culture conversion after 2 months of therapy (OR: 0.14, 95% CI: 0.02, 0.89), a standard measure of early TB treatment success. Importantly, our data was not significantly impacted by HIV co-infection. These data suggest that blood neutrophil metrics could potentially be exploited to develop a simple and rapid test to help determine TB disease severity, monitor drug treatment response, and identify subjects at diagnosis who may respond poorly to treatment.
Highlights
Though global tuberculosis (TB) disease incidence is falling at a rate of 1.5–2% per year, it remains one of the leading causes of death from a single infectious agent, and much greater declines in incidence are required to meet global TB targets [1]
We examined the association between bacterial load, chest X-ray (CXR) score, neutrophil count, and CD15 with TB treatment outcome, defined according to the World Health Organization (WHO) definitions
In this study we investigated changes in the frequency and phenotype of blood neutrophils associated with active TB at diagnosis and patient response to standard TB drug therapy
Summary
Though global tuberculosis (TB) disease incidence is falling at a rate of 1.5–2% per year, it remains one of the leading causes of death from a single infectious agent, and much greater declines in incidence are required to meet global TB targets [1]. Host immune responses are potential biomarkers for predicting response to anti-TB treatment [5, 6] as the current approach of evaluating culture conversion at 2 months has proved poorly predictive of cure [7,8,9]. These biomarkers are measured in blood or urine, which makes them an attractive option for groups that are inherently difficult to diagnose and monitor with conventional sputum samples, such as children, pregnant women, and people living with HIV [10,11,12]
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