Evaluation of host Hsp(s) as potential biomarkers for the diagnosis of tuberculous meningitis

• We evaluated diagnostic potential of host Hsps in tuberculous meningitis.
• We included Fungal meningitis (n = 04) group in the manuscript as suggested by reviewer.
• We propose that host Hsp 70 and Hsp 90 have potential in the diagnosis of TBM disease.
• Combined use of all Hsps is also beneficial in diagnosis of TBM.

ObjectivesDiagnosis of tuberculosis meningitis (TBM) remains challenging in tuberculosis (TB) endemic countries. The need for TB biomarkers arises, in part, from the difficulty of accurately diagnosing TBM with the available methods.Patients and methodsTo explore the potential of host Hsps (Hsp 25, Hsp 60, Hsp 70 and Hsp 90) as an alternative marker in TBM diagnosis, we evaluated cerebrospinal fluid (CSF) sample of TBM (n = 49), Pyogenic Meningitis (PM) (n = 20), Viral Meningitis (VM) (n = 09), Fungal Meningitis (FM) (n = 04) and non infectious control (n = 79) patients using indirect ELISA.ResultsOut of four Hsps, Hsp 70 and Hsp 90 yields 89% & 88% sensitivity and 82% & 89% specificity, respectively. The positive (PPV) and negative (NPV) predictive values yielded in TBM group for Hsp 70 was 86.27% (73.74–94.27) and 93.51% (85.48–97.83), respectively. For Hsp 90 the obtained PPV was 89.36% (76.88–96.41) and NPV was 91.36% (82.99–96.44). In 86% of TBM patients all the four Hsps were found to be positive and none of the patient was found to be negative for all Hsps in the same group.ConclusionsThe data presented in the study indicate that host Hsp 70 and Hsp 90 shows good sensitivity and specificity and have potential in the diagnosis of TBM disease. The combined use of all Hsps (Hsp 25, Hsp 60, Hsp 70 and Hsp 90) effectively distinguishes patients with TBM from other disease controls.