Utility of genexpert in evaluating patients with suspected Tuberculous Meningitis at Moi Teaching and Referral Hospital, Eldoret Kenya

Abstract

Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis (TB) that is almost 100% fatal if not treated and case fatality rates remain high (15-40%) despite effective treatment. Early diagnosis and treatment can lead to reduction in morbidity and mortality caused by this disease. Liquid culture techniques, including the mycobacterial growth indicator tube (MGIT) has been the gold standard test for detecting Mycobacterium tuberculosis (MTB) in cerebrospinal fluid (CSF). CSF culture has a sensitivity of up to 77% but the clinical value is limited due to the long duration required to get results: 1 to 4 weeks. GeneXpert is a molecular real time polymerase chain reaction (PCR) test that is rapid and can give results for TB and rifampicin resistance in 2 hours. It has been approved by the World Health Organization for the diagnosis of pulmonary TB but there is paucity of data on its use in CSF. Objective: The aim of this study was to compare the yields of GeneXpert and MGIT culture on CSF samples from patients presenting with suspected tuberculous meningitis. Methods: This was a cross sectional study. Patients aged 18 years and above with suspected tuberculous meningitis based on a clinical entry criteria were recruited from the adult medical wards, Moi Teaching and Referral Hospital (MTRH) between December 2013 and July 2014. Recruited patients with no contraindications to lumbar puncture were consecutively enrolled after giving an informed consent until the desired sample size was obtained. They underwent a physical examination followed by a lumbar puncture. The CSF was analyzed for MTB using GeneXpert and MGIT culture. Part of the CSF was sent to MTRH laboratory for routine tests. Results: 101 patients with suspected TBM were enrolled in the study. Of the 93 evaluable patients, 57 (61%) were female, median age was 36 years (27-46) and HIV positivity was 77 (83%). Using a consensus case definition, 10 (11%) had definite TBM, 27 (29%) had probable TBM, 49 (52%) had possible TBM and 7 (8%) had no TBM. 10 patients had a positive MGIT culture result while 8 patients had a positive GeneXpert test. The yield of GeneXpert compared to MGIT culture was 8/93 (0.086) vs 10/93 (0.1075) 95% C.I p=0.06199. The sensitivity and specificity of GeneXpert as compared to MGIT liquid culture was 80% and 100% respectively. One case of rifampicin resistance (1/8; 12.5%) was identified. Findings associated with a positive GeneXpert result include elevated proteins 233 (116.5-342.2) vs 77.0 (26.8-143.0) p=0.003, low glucose 1.5 (1.0-2.1) vs 2.6 (1.8-3.6) p=0.015 and high diagnostic score 11(10-11) vs 8 (7-11) p=0.024. Conclusion: There was no statistical significant difference between the yield of GeneXpert and MGIT liquid culture in CSF samples of patients presenting with suspected TBM. The prevalence of Rifampicin resistance was 12.5% among patients with a positive GeneXpert test. Patients with high CSF protein count, low CSF glucose and a high diagnostic score were more likely to have a positive GeneXpert result. Recommendations: GeneXpert should be used as the initial diagnostic test in place of MGIT liquid culture in patients with suspected tuberculous meningitis.