Mycobacterium tuberculosis cough aerosol culture status associates with host characteristics and inflammatory profiles
Open Access
- 1 September 2024
- journal article
- research article
- Published by Springer Nature in Nature Communications
- Vol. 15 (1) , 1-15
Abstract
Interrupting transmission events is critical to tuberculosis control. Cough-generated aerosol cultures predict tuberculosis transmission better than microbiological or clinical markers. We hypothesize that highly infectious individuals with pulmonary tuberculosis (positive for cough aerosol cultures) have elevated inflammatory markers and unique transcriptional profiles compared to less infectious individuals. We performed a prospective, longitudinal study using cough aerosol sampling system. We enrolled 142 participants with treatment-naïve pulmonary tuberculosis in Kenya and assessed the association of clinical, microbiologic, and immunologic characteristics with Mycobacterium tuberculosis aerosolization and transmission in 129 household members. Contacts of the forty-three aerosol culture-positive participants (30%) are more likely to have a positive interferon-gamma release assay (85% vs 53%, P = 0.006) and higher median IFNγ level (P < 0.001, 4.28 IU/ml (1.77-5.91) vs. 0.71 (0.01-3.56)) compared to aerosol culture-negative individuals. We find that higher bacillary burden, younger age, larger mean upper arm circumference, and host inflammatory profiles, including elevated serum C-reactive protein and lower plasma TNF levels, associate with positive cough aerosol cultures. Notably, we find pre-treatment whole blood transcriptional profiles associate with aerosol culture status, independent of bacillary load. These findings suggest that tuberculosis infectiousness is associated with epidemiologic characteristics and inflammatory signatures and that these features may identify highly infectious persons.Keywords
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Funding Information
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (5R01AI150815, UH2AI152621, TW011817-01, 5R01AI150815, TW011817-01, TW011817-01, TW011817-01, 5R01AI150815, TW011817-01)
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases
- U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (UL1 TR002319)
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases
- University of Washington/Fred Hutch Center for AIDS Research
This publication has 75 references indexed in Scilit:
- CD4+ T cells regulate sickness-induced anorexia and fat wasting during a chronic parasitic infectionCell Reports, 2023
- Tutorial on directed acyclic graphsJournal of Clinical Epidemiology, 2022
- Changes in body mass index and mid-upper arm circumference in relation to all-cause mortality in older adultsClinical Nutrition, 2018
- Cyclopropane Modification of Trehalose Dimycolate Drives Granuloma Angiogenesis and Mycobacterial Growth through Vegf SignalingCell Host & Microbe, 2018
- Fixed and random effects models: making an informed choiceQuality & Quantity, 2018
- Turning off the tap: stopping tuberculosis transmission through active case-finding and prompt effective treatmentThe Lancet, 2015
- Perspectives on host adaptation in response to Mycobacterium tuberculosis: Modulation of inflammationSeminars in Immunology, 2014
- Associations Between Changes in Anthropometric Measures and Mortality in Old Age: A Role for Mid-Upper Arm Circumference?Journal of the American Medical Directors Association, 2013
- Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics supportJournal of Biomedical Informatics, 2009
- Index for rating diagnostic testsCancer, 1950