Influence of Strongyloides stercoralis Coinfection on the Presentation, Pathogenesis, and Outcome of Tuberculous Meningitis.

Joseph Donovan ORCID logo ; Trinh Thi Bich Tram ; Nguyen Hoan Phu ; Nguyen Thi Thu Hiep ; Vu Thi Thu Van ; Dang Thi Hong Mui ; Nguyen Thi Han Ny ; Ho Dang Trung Nghia ; Nguyen Ho Hong Hanh ; Le Van Tan ; +2 more... Nguyen Thuy Thuong Thuong ; Guy E Thwaites ; (2022) Influence of Strongyloides stercoralis Coinfection on the Presentation, Pathogenesis, and Outcome of Tuberculous Meningitis. The Journal of infectious diseases, 225 (9). pp. 1653-1662. ISSN 0022-1899 DOI: 10.1093/infdis/jiaa672
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BACKGROUND: Helminth infections may modulate the inflammatory response to Mycobacterium tuberculosis and influence disease presentation and outcome. Strongyloides stercoralis is common among populations with high tuberculosis prevalence. Our aim was to determine whether S. stercoralis coinfection influenced clinical presentation, cerebrospinal fluid (CSF) inflammation, and outcome from tuberculous meningitis (TBM). METHODS: From June 2017 to December 2019, 668 Vietnamese adults with TBM, enrolled in the ACT HIV or LAST ACT trials (NCT03092817 and NCT03100786), underwent pretreatment S. stercoralis testing by serology, stool microscopy, and/or stool polymerase chain reaction. Comparisons of pretreatment TBM severity, CSF inflammation (including cytokines), and 3-month clinical end points were performed in groups with or without active S. stercoralis infection. RESULTS: Overall, 9.4% participants (63 of 668) tested positive for S. stercoralis. Active S. stercoralis infection was significantly associated with reduced pretreatment CSF neutrophil counts (median [interquartile range], 3/μL [0-25/μL] vs 14 /μL [1-83/μL]; P = .04), and with reduced CSF interferon ɣ, interleukin 2, and tumor necrosis factor α concentrations (11.4 vs 56.0 pg/mL [P = .01], 33.1 vs 54.5 pg/mL [P = .03], and 4.5 vs 11.9 pg/mL [P = .02], respectively), compared with uninfected participants. Neurological complications by 3 months were significantly reduced in participants with active S. stercoralis infection compared with uninfected participants (3.8% [1 of 26] vs 30.0% [33 of 110], respectively; P = .01). CONCLUSIONS: S. stercoralis coinfection may modulate the intracerebral inflammatory response to M. tuberculosis and improve TBM clinical outcomes.

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