Fujifilm SILVAMP TB LAM assay on cerebrospinal fluid for the detection of tuberculous meningitis in HIV-infected adults.

BACKGROUND Tuberculous meningitis (TBM) has a high fatality rate with inadequate diagnostic tests being a major contributor. The rollout of Xpert MTB/Rif and Xpert MTB/Rif Ultra (Xpert Ultra) have improved time-to-diagnosis with sensitivities similar to culture, yet test availability and sensitivity are inadequate. The TB lipoarabinomannan lateral flow assay (AlereLAM) offers ease of use, but its low sensitivity in cerebrospinal fluid (CSF) limits clinical utility for TBM. The Fujifilm SILVAMP TB LAM (FujiLAM) assay has excellent sensitivity in urine, but performance on cerebrospinal fluid is uncertain. METHODS We conducted a prospective cohort study at Kiruddu National Referral Hospital in Kampala, Uganda enrolling patients suspected to have TB meningitis. CSF was tested using AlereLAM, Xpert Ultra, culture, and FujiLAM. Results were compared to two reference standards: probable and definite TBM, or definite TBM alone by the uniform TBM case definition. RESULTS Of 101 patients enrolled (95/101 HIV-positive), 34 had definite TBM and 24 had probable TBM. FujiLAM sensitivity on CSF was 52% (30/58) for definite or probable TBM, compared to 55% (32/58) for Xpert Ultra. AlereLAM had lower sensitivity than FujiLAM in the subgroup of patients tested with both assays (14%, 4/28 vs. 50%,14/28; p<0.01). FujiLAM specificity was 98% (42/43) for patients without probable or definite TBM. CONCLUSIONS FujiLAM showed higher sensitivity than AlereLAM, with sensitivity potentially approaching that of Xpert Ultra. FujiLAM could improve time-to-treatment-initiation, especially in settings where the more technical Xpert Ultra system might not be feasible. Large confirmatory studies are needed.