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BackgroundRecent evidence highlights human cytomegalovirus (HCMV) and immune activation as risk factors for tuberculosis disease. It is not known whether other herpesviruses are also implicated, nor whether a dose-response relationship exists between tuberculosis risk and herpes coinfection.MethodsThis nested case-control study used stored serum samples from 25 persons with tuberculosis up to 10 years before tuberculosis diagnosis and between 3 and 6 matched controls without tuberculosis from a rural Ugandan cohort. Samples were investigated for Epstein-Barr virus, herpes simplex virus, and HCMV-specific immunoglobulin G (IgG), serum markers of inflammation, and mycobacterial antibody levels.ResultsHumoral response to HCMV, but not Epstein-Barr or herpes simplex virus, was associated with increased risk of active tuberculosis disease up to 10 years before diagnosis. Individuals with medium HCMV IgG were 2.8 times more likely to have tuberculosis (P = .055), and those with high HCMV IgG 3.4 times more likely to have tuberculosis (P = .007). Mycobacterial antibody levels were not associated with differences in odds of tuberculosis disease. Interferon-induced protein 10 was independently associated with increased odds of tuberculosis (odds ratio, 4.2; P = .009).ConclusionsThese data provide evidence of a dose response between magnitude of HCMV IgG with risk of tuberculosis disease. An inflammatory environment, characterized by serum interferon-induced protein 10 and interleukin 1α, is independently associated with increased risk of tuberculosis disease.

Original publication

DOI

10.1093/infdis/jiz581

Type

Journal article

Journal

The Journal of infectious diseases

Publication Date

03/2020

Volume

221

Pages

1127 - 1134

Addresses

London School of Hygiene & Tropical Medicine, Faculty of Infectious and Tropical Diseases, London, United Kingdom.

Keywords

Humans, Mycobacterium tuberculosis, Cytomegalovirus, Tuberculosis, Cytomegalovirus Infections, Antibodies, Viral, Case-Control Studies, Adolescent, Adult, Middle Aged, Child, Child, Preschool, Rural Population, Uganda, Female, Male, Chemokine CXCL10, Young Adult