The monocyte-to-lymphocyte ratio: Sex-specific differences in the tuberculosis disease spectrum, diagnostic indices and defining normal ranges

Abstract

Background The monocyte-to-lymphocyte ratio (MLR) has been advocated as a biomarker in tuberculosis. Our objective was to evaluate its clinical value and associations. Methods Blood 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. Results Multivariate 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. Conclusions Severe 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.