Monocyte-to-Lymphocyte Ratio Is Associated With Tuberculosis Disease and Declines With Anti-TB Treatment in HIV-Infected Children

• Type of Material: Article
• Authors: Rewa K. Choudhary, Emory University; Kristin Wall, Emory University; Irene Njuguna, Kenyatta National Hospital; Patricia B. Pavlinac, University of Washington; Sylvia M. LaCourse, University of Washington; Vincent Otieno, University of Nairobi; John Gatimu, University of Nairobi; Joshua Stern, University of Washington; Elizabeth Maleche-Obimbo, University of Nairobi; Dalton Wamalwa, University of Nairobi; Grace John-Stewart, University of Washington; Lisa Cranmer, Emory University
• Language: English
• Date: 2019-02-01
• Publisher: LIPPINCOTT WILLIAMS & WILKINS
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 Wolters Kluwer Health, Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1097/QAI.0000000000001893
• Title of Journal or Parent Work: JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
• Volume: 80
• Issue: 2
• Start Page: 174
• End Page: 181
• Grant/Funding Information: This work was supported by the National Institute of Child Health and Human Development (NICHD), National Institute of Allergy and Infectious Diseases (NIAID), Fogarty International Center, and National Center For Advancing Translational Sciences at the National Institutes of Health (NIH) (R01 HD023412 and K24 HD054314–06 to GJS, D43TW009783 to IN, T32 AI007140 to PBP, K12 HD000850 to LMC, K23 AI 120793–01 to SML, and UL1TR000423 for REDCap), University of Washington Center for AIDS Research (P30 AI027757), UW Global Center for Integrated Heath of Women, Adolescents and Children (Global WACh), the Pediatric Scientist Development Program (PSDP) through grants from the American Pediatric Society and American Academy of Pediatrics (LMC), and the Infectious Diseases Society of America Medical Scholars Program (RKC). Portions of these data were presented at the 48th Union World Conference on Lung Health in Guadalajara, Mexico on October 12, 2017.
• Keywords: tuberculosis; PERIPHERAL-BLOOD; URINE LIPOARABINOMANNAN; children; MYCOBACTERIUM-TUBERCULOSIS; RISK; SPECIMENS; biomarkers; Infectious Diseases; STOOL; PULMONARY TUBERCULOSIS; lymphocytes; monocytes; Immunology; Science & Technology; RAPID DIAGNOSIS; XPERT MTB/RIF; HIV; INTRATHORACIC TUBERCULOSIS; Life Sciences & Biomedicine
• Research Categories: Biology, Genetics; Health Sciences, Medicine and Surgery; Health Sciences, Immunology; Biology, Virology

Abstract

Background:The blood monocyte-to-lymphocyte ratio (MLR) is associated with active tuberculosis (TB) in adults but has not been evaluated as a TB diagnostic biomarker in HIV-infected children in whom respiratory sampling is difficult.Setting:In a cohort of HIV-infected hospitalized Kenyan children initiating antiretroviral therapy, absolute monocyte and lymphocyte counts were determined at enrollment and 4, 12, and 24 weeks thereafter.Methods:Children were classified as confirmed, unconfirmed, or unlikely pulmonary TB. Receiver operating characteristic curves of MLR cutoff values were generated to distinguish children with confirmed TB from those with unconfirmed and unlikely TB. General estimating equations were used to estimate change in the MLR over time by TB status.Results:Of 160 children with median age 23 months, 13 (8.1%) had confirmed TB and 67 (41.9%) had unconfirmed TB. The median MLR among children with confirmed TB {0.407 [interquartile range (IQR) 0.378-0.675]} was higher than the MLR in children with unconfirmed [0.207 (IQR 0.148-0.348), P < 0.01] or unlikely [0.212 (IQR 0.138-0.391), P = 0.01] TB. The MLR above 0.378 identified children with confirmed TB with 77% sensitivity, 78% specificity, 24% positive predictive value, and 97% negative predictive value. After TB treatment, the median MLR declined in children with confirmed TB and levels were similar to children with unlikely TB after 12 weeks.Conclusions:The blood MLR distinguished HIV-infected children with confirmed TB from those with unlikely TB and declined with TB treatment. The MLR may be a useful diagnostic tool for TB in settings where respiratory-based microbiologic confirmation is inaccessible.