title: Evaluation of GeneXpert MTB/RIF for diagnosis of tuberculous meningitis.
abstract: Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Microbiological confirmation is rare, and treatment is often delayed, increasing mortality and morbidity. The GeneXpert MTB/RIF test was evaluated in a large cohort of patients with suspected tuberculous meningitis. Three hundred seventy-nine patients presenting with suspected tuberculous meningitis to the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, between 17 April 2011 and 31 December 2012 were included in the study. Cerebrospinal fluid samples were tested by Ziehl-Neelsen smear, mycobacterial growth indicator tube (MGIT) culture, and Xpert MTB/RIF. Rifampin (RIF) resistance results by Xpert were confirmed by an MTBDR-Plus line probe assay and all positive cultures were tested by phenotypic MGIT drug susceptibility testing. Overall, 182/379 included patients (48.0%) were diagnosed with tuberculous meningitis. Sensitivities of Xpert, smear, and MGIT culture among patients diagnosed with TBM were 59.3% (108/182 [95% confidence interval {CI}, 51.8 to 66.5%]), 78.6% (143/182 [95% CI, 71.9 to 84.3%]) and 66.5% (121/182 [95% CI, 59.1 to 73.3%]), respectively. There was one false-positive Xpert MTB/RIF test (99.5% specificity). Four cases of RIF resistance (4/109; 3.7%) were identified by Xpert, of which 3 were confirmed to be multidrug-resistant (MDR) TBM and one was culture negative. Xpert MTB/RIF is a rapid and specific test for the diagnosis of tuberculous meningitis. The addition of a vortexing step to sample processing increased sensitivity for confirmed TBM by 20% (P = 0.04). Meticulous examination of a smear from a large volume of cerebrospinal fluid (CSF) remains the most sensitive technique but is not practical in most laboratories. The Xpert MTB/RIF represents a significant advance in the early diagnosis of this devastating condition.
authors.affiliation: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.
authors.forename: Nguyen Thi Quynh
authors.initials: NT
authors.lastname: Nhu
authors.forename: Dorothee
authors.initials: D
authors.lastname: Heemskerk
authors.forename: Do Dang Anh
authors.initials: do DA
authors.lastname: Thu
authors.forename: Tran Thi Hong
authors.initials: TT
authors.lastname: Chau
authors.forename: Nguyen Thi Hoang
authors.initials: NT
authors.lastname: Mai
authors.forename: Ho Dang Trung
authors.initials: HD
authors.lastname: Nghia
authors.forename: Pham Phu
authors.initials: PP
authors.lastname: Loc
authors.forename: Dang Thi Minh
authors.initials: DT
authors.lastname: Ha
authors.forename: Laura
authors.initials: L
authors.lastname: Merson
authors.forename: Tran Thi Van
authors.initials: TT
authors.lastname: Thinh
authors.forename: Jeremy
authors.initials: J
authors.lastname: Day
authors.forename: Nguyen van Vinh
authors.initials: Nv
authors.lastname: Chau
authors.forename: Marcel
authors.initials: M
authors.lastname: Wolbers
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
authors.forename: Maxine
authors.initials: M
authors.lastname: Caws
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000494:pharmacology*; D002555:Cerebrospinal Fluid / Q000382:microbiology; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000302:isolation & purification*; D012293:Rifampin / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D014390:Tuberculosis, Meningeal / Q000175:diagnosis*; D014744:Vietnam; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D012293:Rifampin