title: Improved diagnosis of childhood tuberculous meningitis using more than one nucleic acid amplification test.
abstract: BACKGROUND
  Early treatment is critical to reducing tuberculous meningitis (TBM) related morbidity and mortality. Diagnosis based on cerebrospinal fluid (CSF) culture is impractical due to slow turnaround times, while microscopy has poor sensitivity. Enhanced detection methods are essential to guide early treatment initiation, especially in vulnerable young children.
  
  
  METHODS
  We assessed the diagnostic accuracy of the GenoType(®) MTBDRplus and Xpert(®) MTB/RIF assays on CSF collected from paediatric meningitis suspects prospectively enrolled at Tygerberg Hospital, Cape Town, South Africa. Fluorescent auramine-O microscopy, liquid culture for Mycobacterium tuberculosis, GenoType and Xpert assays were performed on all CSF samples.
  
  
  RESULTS
  Of 101 meningitis suspects, 55 were diagnosed with TBM and 46 served as non-TBM controls. Using a pre-defined TBM case definition as reference standard, sensitivities and specificities were 4% and 100% for fluorescent microscopy, 22% and 100% for culture, 33% and 98% for GenoType, 26% and 100% for Xpert, 22% and 100% for microscopy and culture combined and 49% and 98% for GenoType and Xpert combined. Culture, GenoType and Xpert combined performed best, with 56% sensitivity and 98% specificity.
  
  
  CONCLUSIONS
  Although commercial nucleic-acid amplification tests performed on CSF revealed incrementally improved diagnostic accuracy, providing rapid microbiological confirmation, they cannot serve as a rule-out test.
authors.affiliation: Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: R S
authors.initials: RS
authors.lastname: Solomons
authors.affiliation: Department of Paediatric Infectious Diseases and Immunology, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands.
authors.forename: D H
authors.initials: DH
authors.lastname: Visser
authors.affiliation: Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: S O
authors.initials: SO
authors.lastname: Friedrich
authors.affiliation: Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: A H
authors.initials: AH
authors.lastname: Diacon
authors.affiliation: Division of Medical Microbiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: K G P
authors.initials: KG
authors.lastname: Hoek
authors.affiliation: Marie Bashir Institute for Infectious Diseases and Biosecurity Institute, The Children's Hospital at Westmead, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: B J
authors.initials: BJ
authors.lastname: Marais
authors.affiliation: Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: J F
authors.initials: JF
authors.lastname: Schoeman
authors.affiliation: Department of Paediatric Infectious Diseases and Immunology, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: van Furth
mesh_terms: D002675:Child, Preschool; D005260:Female; D060005:Genotyping Techniques; D015658:HIV Infections / Q000382:microbiology; D006801:Humans; D007223:Infant; D008297:Male; D009017:Morbidity; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000302:isolation & purification*; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D013019:South Africa / Q000453:epidemiology; D014374:Tuberculin Test; D014390:Tuberculosis, Meningeal / Q000175:diagnosis* / Q000453:epidemiology*