Chronic Meningitis Investigated via Metagenomic Next-Generation Sequencing

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Michael R. Wilson, MD, MAS; Brian D. O’Donovan, MS; Jeffrey M. Gelfand, MD, MA; et al

JAMA Neurol. April 16, 2018

COMMENT: The authors present a study of metagenomics NGS (mNGS) where they compare detected organisms in cerebrospinal fluid (CSF) samples of patients of noninfectious neuroimflammatory disorders with organisms detected in CSF samples of chronic and subclinical meningitis and organisms detected in control samples (water and reagent controls). 

One of the main objectives of the study is the development of a statistical framework that could help distinguishing the organisms responsible for the infection from the organisms coming from environmental contamination. Distinguishing organisms really present in the CSF samples from those coming from contamination sources is particularly important in the diagnosis of subacute or chronic meningitis as there are several causes that might lead to the illness and the treatment is defined based on the actual cause of it.

The authors remark the importance of the use of water, reagents control and cohort control to be able to detect the real infective cause (in any) of the subclinical and chronic meningitis. These controls are critical for the algorithms the authors describe in the article to distinguish the organisms from the CSF samples which really come from such samples to the organisms which come from environmental contamination.

The combination of the use of such controls, the mNGS sequencing approach and the developed stasticial framework allowed the identification of the cause of 6 meningitis cases: Taenia solium in 2 participants, HIV-1 in one participant , and 4 fungi (Cryptococcus neoformans, Aspergillus oryzae, Histoplasma capsulatum, and Candida dubliniensis)


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Marina Manrique