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Reference: Naranbhai, V, Kim, S, Fletcher, H et al., (2014). The association between the ratio of monocytes:lymphocytes at age 3 months and risk of tuberculosis (TB) in the first two years of life. BMC Medicine, 12 (1), Article no. 120.Citable link to this page:

 

The association between the ratio of monocytes:lymphocytes at age 3 months and risk of tuberculosis (TB) in the first two years of life

Abstract: BACKGROUND: Recent transcriptomic studies revived a hypothesis suggested by historical studies in rabbits that the ratio of peripheral blood monocytes to lymphocytes (ML) is associated with risk of tuberculosis (TB) disease. Recent data confirmed the hypothesis in cattle and in adults infected with HIV. METHODS: We tested this hypothesis in 1,336 infants (540 HIV-infected, 796 HIV-exposed, uninfected (HEU)) prospectively followed in a randomized controlled trial of isoniazid prophylaxis in Southern Africa, the IMPAACT P1041 study. We modeled the relationship between ML ratio at enrollment (91 to 120 days after birth) and TB disease or death in HIV-infected children and latent Mycobacterium tuberculosis (MTB) infection, TB disease or death in HEU children within 96 weeks (with 12 week window) of randomization. Infants were followed-up prospectively and routinely assessed for MTB exposure and outcomes. Cox proportional hazards models allowing for non-linear associations were used; in all cases linear models were the most parsimonious. RESULTS: Increasing ML ratio at baseline was significantly associated with TB disease/death within two years (adjusted hazard ratio (HR) 1.17 per unit increase in ML ratio; 95% confidence interval (CI) 1.01 to 1.34; P = 0.03). Neither monocyte count nor lymphocyte counts alone were associated with TB disease. The association was not statistically dissimilar between HIV infected and HEU children. Baseline ML ratio was associated with composite endpoints of TB disease and death and/or TB infection. It was strongest when restricted to probable and definite TB disease (HR 1.50; 95% CI 1.19 to 1.89; P = 0.006). Therefore, per 0.1 unit increase in the ML ratio at three to four months of age, the hazard of probable or definite TB disease before two years was increased by roughly 4% (95% CI 1.7% to 6.6%). CONCLUSION: Elevated ML ratio at three- to four-months old is associated with increased hazards of TB disease before two years among children in Southern Africa. While significant, the modest effect size suggests that the ML ratio plays a modest role in predicting TB disease-free survival; its utility may, therefore, be limited to combination with existing tools to stratify TB risk, or to inform underlying pathophysiologic determinants of TB disease.

Peer Review status:Peer ReviewedPublication status:PublishedVersion:Publisher's version Funder: National Institute of Allergy and Infectious Diseases   Funder: National Institute of Child Health and Human Development   Funder: National Institute of Mental Health   Funder: Harvard School of Public Health   Funder: Bristol-Myers Squibb   Notes:Copyright 2014 Naranbhai et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Bibliographic Details

Publisher: BioMed Central Ltd.

Publisher Website: http://www.biomedcentral.com/

Journal: BMC Medicinesee more from them

Publication Website: http://www.biomedcentral.com/bmcmed/

Volume: 12

Issue: 1

Extent: Article no. 120

Issue Date: 2014

pages:Article no. 120Identifiers

Urn: uuid:51218965-4375-40cb-a2de-ffdc3b8c42a2

Source identifier: 480833

Eissn: 1741-7015

Doi: https://doi.org/10.1186/s12916-014-0120-7

Issn: 1741-7015 Item Description

Type: Journal article;

Language: eng

Version: Publisher's versionKeywords: tuberculosis HIV combination antiretroviral therapy monocytes lymphocytes ML ratio Tiny URL: pubs:480833

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Author: Naranbhai, V - institutionUniversity of Oxford Oxford, MSD, Clinical Medicine, WTC Human Genetics fundingRhodes Trust - - - Kim,

Source: https://ora.ox.ac.uk/objects/uuid:51218965-4375-40cb-a2de-ffdc3b8c42a2



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