Pre-treatment cerebrospinal fluid bacterial load correlates with inflammatory response and predicts neurological events during tuberculous meningitis treatment.

Thuong, Nguyen T T, Vinh, Dao N, Hai, Hoang T, Thu, Do D A, Nhat, Le T H, Heemskerk, Dorothee, Bang, Nguyen D, Caws, Maxine ORCID: https://orcid.org/0000-0002-9109-350X, Mai, Nguyen T H and Thwaites, Guy E (2019) 'Pre-treatment cerebrospinal fluid bacterial load correlates with inflammatory response and predicts neurological events during tuberculous meningitis treatment.'. Journal of Infectious Disease, Vol 2019, Issue 6, pp. 986-995.

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Abstract

Background
Mycobacterium tuberculosis (Mtb) bacillary load in the brain of those with tuberculous meningitis (TBM) may reflect the host ability to control the pathogen and determine disease severity and treatment outcomes.

Methods
We measured pre-treatment cerebrospinal fluid (CSF) Mtb bacterial load by GeneXpert in 692 adults with TBM. We sought to understand the relationship between CSF bacterial load and inflammation, and their respective impact on disease severity and treatment outcomes.

Results
Ten-fold higher Mtb load was associated with increased disease severity (Odds Ratio=1.59, p=0.001 for grade 1 versus grade 3), and increased CSF neutrophils (r=0.364, p<0.0001) and cytokine concentrations (r=0.438, p<0.0001). High Mtb load predicted new neurological events after starting treatment (Multinomial logistic regression, p=0.005), but not death. Death was previously associated with attenuated inflammatory response at the start of treatment, with reduced cytokine concentrations compared to survivors. In contrast, patients with high pre-treatment CSF bacterial loads, cytokines, and neutrophils were more likely to subsequently suffer neurological events.

Conclusions
Pre-treatment GeneXpert-derived Mtb load may be a useful predictor of neurological complications occurring during TBM treatment. Therapeutic strategies aimed at reducing neurological complications and deaths from TBM may need reassessment, given the evidence for their divergent pathogenesis.

Item Type:	Article
Subjects:	QY Clinical Pathology > Diagnostic Tests > QY 250 Immunodiagnostic tests WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General) WF Respiratory System > Tuberculosis > WF 310 Therapy WL Nervous System > WL 200 Meninges. Blood-brain barrier
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1093/infdis/jiy588
Depositing User:	Stacy Murtagh
Date Deposited:	22 Oct 2018 08:57
Last Modified:	21 Jun 2019 14:44
URI:	https://archive.lstmed.ac.uk/id/eprint/9491

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