Abstract
BackgroundThe monocyte-to-lymphocyte ratio (MLR) has been advocated as a biomarker in tuberculosis. Our objective was to evaluate its clinical value and associations.MethodsBlood counts, inflammatory markers and clinical parameters were measured in patients with and those screened for tuberculosis. Complete blood counts (CBCs) from a multi-ethnic population aged 16 to 65 years were evaluated; a sub-group with normal hematological indices was used to define the range of MLRs.ResultsMultivariate analysis in proven tuberculosis (n = 264) indicated MLR associated with low serum albumin, high white cell counts and a positive culture; values were higher in sputum smear-positive pulmonary tuberculosis (S+PTB). Analysis in S+PTB (n = 296) showed higher MLRs in males and those with high neutrophil counts, low serum albumin and high C-reactive protein. The diagnostic value of MLRs was assessed by comparing notified patients with TB (n = 264) with denotified cases (n = 50), active case-finding in non-contacts (TB n = 111 and LTBI n = 373) and contacts of S+PTB (n = 149) with S+PTB found at screening (n = 75). Sensitivities and specificities ranged from 58.0–62.5% and 50.0–70.0% respectively for optimal cut-off values, defined by ROC curves. In CBCs obtained over one month, ratios correlated with neutrophil counts (ρ = 0.48, P<0.00001, n = 14,573; MLR = 0.45 at 8–8.9 x 109/L) and were higher in males than females (P<0.0001). The MLR range (mean ± 2SD) in those with normal hematological indices (n = 3921: females 0.122–0.474; males 0.136–0.505) paralleled LTBI MLRs. Ratios did not predict death (n = 29) nor response to treatment (n = 178 S+PTB with follow-up CBCs). Ratios were higher in males than female in the 16–45 years age group, where immune differences due to sex hormones are likely greatest.ConclusionsSevere tuberculosis and male sex associated with high MLRs; the same variables likely affect the performance of other biomarkers. The ratio performed poorly as a clinical aid.
Highlights
Tuberculosis (TB) was declared a global health emergency by the World Health Organization in April 1993 and remains a leading cause of death and disease [1]
Multivariate analysis in proven tuberculosis (n = 264) indicated monocyte-to-lymphocyte ratio (MLR) associated with low serum albumin, high white cell counts and a positive culture; values were higher in sputum smear-positive pulmonary tuberculosis (S+PTB)
The diagnostic value of MLRs was assessed by comparing notified patients with TB (n = 264) with denotified cases (n = 50), active case-finding in non-contacts (TB n = 111 and latent tuberculosis infection (LTBI) n = 373) and contacts of S+PTB (n = 149) with S+PTB found at screening (n = 75)
Summary
Tuberculosis (TB) was declared a global health emergency by the World Health Organization in April 1993 and remains a leading cause of death and disease [1]. Many non-specific biomarkers have been proposed to identify those with a positive IGRA who will develop active TB [4], those with sub-clinical disease (i.e. those without symptoms often with a normal chest x-ray without raised inflammatory markers) [5], those likely to die from TB [6], those whose genotype might suggest a protective response to Mycobacterium tuberculosis [7] and transcriptomic measures of risk, diagnosis and treatment response [8]. Identified in TB patients, a rabbit model suggested that both high and low MLRs might be markers for TB progression [11]. The monocyte-to-lymphocyte ratio (MLR) has been advocated as a biomarker in tuberculosis. Our objective was to evaluate its clinical value and associations
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