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

Background The monocyte-to-lymphocyte ratio has been advocated as a biomarker in tuberculosis. Our objective was to evaluate its clinical role in diagnosis, prognosis and treatment outcome. Methods Complete blood counts from an unselected population aged 16 to 65 years defined normal values of the ratio and associations with other indices. Blood counts, inflammatory markers and clinical parameters were measured in patients with and those screened for tuberculosis. We examined the ratio for its associations with these variables and for diagnosis, screening, prediction of poor prognosis and response to treatment. Results. In the unselected population, monocyte-to-lymphocyte ratios were higher in males than females and correlated with neutrophil counts (Spearman’s rho=0.48, P<0.00001, n=14,573). In 356 patients notified with tuberculosis, ratios were higher in males (high monocyte counts), especially in smear-positive pulmonary tuberculosis (S+PTB), lung cavitation and raised inflammatory markers. The sensitivities for confirmed tuberculosis were 42% (males) and 32% (females), with specificities of 70% and 71% respectively. Using sex-specific cut-offs in 629 adults screened for tuberculosis and with a positive tuberculin skin test or interferon-gamma release assay, diagnostic sensitivities for active tuberculosis were better in males (25%; all and contacts of a S+PTB index, respectively) than females (14-17%) with specificities of 89-96%. Positive likelihood ratios were better with upper limits alone but were still poor (6.64 when screening for tuberculosis, with an area under the curve of 0.688). Ratios did not predict death or response to treatment. Ratios were especially higher in males than female ratios in the 16-45 years age group. Conclusions Severe tuberculosis and male sex associated with high monocyte-to-lymphocyte ratios. The ratio performed poorly as a clinical aid. (269 words) ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial The study was an audit ### Funding Statement This work was supported by the Homerton University Hospital Research and Development Office/North Thames Clinical Research Network (NIHR 4177; TSB 0.5 wte salary), but all other authors received no specific funding for this work. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Blood Tests in Tuberculosis III was approved by the East London and City Health Authority Research Ethics Committee (P/03/285), registered under the number NIHR 4177. The UK PREDICT TB procedures and protocol were approved by the Brent NHS Research Ethics Committee (10/H7017/14). Both gave access to the data for full blood counts, which were used in this study. Waivers for the full blood count data were given for those who were screened for participation in these studies. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Anonymised data is available in the data supplements.