The influence of Strongyloides stercoralis co-infection on the presentation, pathogenesis and outcome of tuberculous meningitis

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Helminth infections may modulate the inflammatory response to Mycobacterium tuberculosis and influence disease presentation and outcome. Strongyloides stercoralis is common amongst populations with high tuberculosis prevalence. Our aim was to determine if S. stercoralis co-infection influenced clinical presentation, cerebrospinal fluid (CSF) inflammation, and outcome from tuberculous meningitis (TBM).</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>From June 2017 to December 2019, 668 Vietnamese adults with TBM, enrolled in the ACT HIV or LAST ACT trials (NCT03092817; NCT03100786), underwent pre-treatment S. stercoralis testing by serology, stool microscopy, and/or stool PCR. Comparisons of pre-treatment TBM severity, CSF inflammation (including cytokines), and 3-month clinical endpoints were performed in active S. stercoralis infected and uninfected groups.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Overall, 9.4% (63/668) participants tested positive for S. stercoralis. Active S. stercoralis infection was significantly associated with reduced pre-treatment CSF neutrophils (3 cells/mm 3[0-25] vs. 14 (cells/mm 3[1-83], p=0.04), and with reduced CSF IFN-ɣ, IL-2, and TNF-α concentrations (11.4 vs. 56.0pg/mL p=0.01; 33.1 vs. 54.5pg/mL p=0.03; 4.5 vs. 11.9pg/mL p=0.02, respectively), compared with uninfected participants. Neurological complications by 3 months were significantly reduced in active S. stercoralis infection vs. uninfected participants (3.8%[1/26] vs. 30.0%[33/110], respectively, p=0.01).</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>S. stercoralis co-infection may modulate the intracerebral inflammatory response to M. tuberculosis and improve TBM clinical outcomes.</jats:p> </jats:sec>