Routine Diagnosis of Tuberculous Meningitis with MODS Assay

Background: Tuberculous meningitis (TBM) is a devastating condition. The rapid instigation of appropriate chemotherapy is vital to reduce morbidity and mortality. However rapid diagnosis remains elusive; smear microscopy has extremely low sensitivity on cerebrospinal fluid (CSF) in most laboratories and PCR requires expertise with advanced infrastructure and has sensitivity of only around 60% under optimal conditions. Neither technique allows for the microbiological isolation of M. tuberculosis and subsequent drug susceptibility testing. We report here on the routine use of the microscopic observation drug susceptibility assay (MODS) format for diagnosis of TBM in our hospital. Methods: Four hundred and ten consecutive CSF samples collected from 277 patients clinically suspected of TBM presented at the Hospital for Tropical Diseases, HCMC, between December 2006 and October 2007 were tested by Ziehl-Neelsen (ZN) smear, MODS, Mycobacterium growth indicator tube (MGIT) and Lowenstein-Jensen (LJ) culture. One hundred and sixty-eight samples were from patients already on TB therapy for >1day and 32 samples were excluded due to untraceable patient records. Two hundred and forty-two samples from 226 newly presenting patients included in. 49.6% (n = 112/226) of patients were deemed to have TBM by clinical diagnostic and microbiological criteria (excluding MODS). Results: Sensitivity by patient against clinical gold standard for ZN smear, MODS, MGIT and LJ were 26.3%, 55.9%, 66.9% and 58.5%, respectively. Specificity of all microbiological techniques was 100%. Positive and negative predictive values for MODS were 100% and 71.3%, respectively for HIV infected patients and 100% and 69.8% for HIV negative patients. The median time to positive was 7 days, significantly faster than MGIT at 16 days and LJ at 31 days. Conclusions: We have shown MODS to be a sensitive, rapid technique for the diagnosis of TBM in routine use.