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Mortality in Severe HIV-TB Associates with Innate Immune Activation and Dysfunction of Monocytes.

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Janssen, Saskia, Schutz, Charlotte, Ward, Amy, Nemes, Elisa, Wilkinson, Katalin A, Scriven, James, Huson, Mischa A, Aben, Nanne, Maartens, Gary, Burton, Rosie, Wilkinson, Robert J, Grobusch, Martin P, Van der Poll, Tom and Meintjes, Graeme (2017) 'Mortality in Severe HIV-TB Associates with Innate Immune Activation and Dysfunction of Monocytes.'. Clinical Infectious Diseases, Vol 65, Issue 1, pp. 73-82.

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Abstract

Case fatality rates among hospitalised patients diagnosed with HIV-associated tuberculosis remain high, and tuberculosis mycobacteremia is common. We aimed to define the nature of innate immune responses associated with 12-week mortality in this population. This prospective cohort study was conducted at Khayelitsha Hospital, Cape Town, South Africa. Hospitalised HIV-infected tuberculosis patients with CD4 counts <350 cells/µL were included; tuberculosis blood cultures were performed in all. Ambulatory HIV-infected patients without active tuberculosis were recruited as controls. Whole blood was stimulated with E. coli derived lipopolysaccharide, heat-killed S. pneumoniae and M. tuberculosis. Biomarkers of inflammation and sepsis, intracellular (flow cytometry) and secreted cytokines (Luminex) were assessed for associations with 12-week mortality using Cox-proportional hazard models. Secondly, we investigated associations of these immune markers with tuberculosis mycobacteremia. Sixty patients were included (median CD4 count 53 cells/µL (interquartile range 22-132)), sixteen (27%) died after a median of 12 (interquartile range 0-24) days. Thirty-one (52%) grew M. tuberculosis on blood culture. Mortality was associated with higher concentrations of procalcitonin, activation of the innate immune system (% CD16+CD14+ monocytes, interleukin-6, tumour necrosis factor-ɑ and colony stimulating factor 3), and anti-inflammatory markers (increased interleukin-1RA and lower monocyte and neutrophil responses to bacterial stimuli). Tuberculosis mycobacteremia was not associated with mortality, nor with biomarkers of sepsis. Twelve-week mortality was associated with greater pro- and anti-inflammatory alterations of the innate immune system, similar to those reported in severe bacterial sepsis.

Item Type: Article
Subjects: QW Microbiology and Immunology > Immunity by Type > QW 541 Natural immunity. Immunogenetics
WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections
WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General)
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1093/cid/cix254
SWORD Depositor: JISC Pubrouter
Depositing User: JISC Pubrouter
Date Deposited: 28 Apr 2017 13:56
Last Modified: 15 Jun 2018 14:47
URI: https://archive.lstmed.ac.uk/id/eprint/7024

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