GeneXpert MTB/Rif to Diagnose Tuberculous Meningitis: Perhaps the First Test but not the Last

Abstract

Tuberculous meningitis (TBM) is the most severe form of tuberculous with substantial mortality. In May 2015, 54 researchers from 10 countries met in Da Lat, Vietnam, to discuss advances in TBM. Among the attendees were researchers involved in pivotal studies on the use of Xpert MTB/Rif for TBM diagnosis. Attendees discussed the 2014 World Health Organization strong recommendation favoring the use of Xpert "in preference to conventional microscopy and culture as the initial diagnostic test for cerebrospinal fluid (CSF) if the sample volume is low or if additional specimens cannot be obtained to make a quick diagnosis." Attendees were concerned that the limitations of Xpert testing for TBM are not emphasized. Clear guidance is needed for the investigational pathway for TBM, including recommendations on the diagnostic package of investigations, which does not stop with Xpert testing. Second, emphasis on the large CSF volumes (ideally 8-10 mL) needed for Xpert testing is required. Guidelines should also emphasize that TBM is a medical emergency and early treatment reduces mortality.

Keywords: diagnosis; guideline; meningitis; perspective; tuberculous.

Figure 1.

Suggested algorithm for diagnosis of Subacute Meningitis in population with high human immunodeficiency virus (HIV) and tuberculous (TB) prevalence. The algorithm is the suggested method of the authors and is meant as guidance. The circumstances of any individual clinical situation may render deviation from this algorithm preferable, and expert physician opinion remains vital. The figure describes our preferred method for investigating meningitis suspects with symptoms for >5 days in settings with moderate to high endemic levels of TB and HIV. *If possible use a manometer in these cases as well; however, if cost is a limitation a manometer is of most use in those suspected to have cryptococcal meningitis and so could be omitted in cases not suspected to have cryptococcal meningitis. ^†In areas of high utility (eg, southeast Asia), acid-fast bacillus (AFB) microscopy should be included if laboratory technicians have adequate time to perform a thorough investigation. However, the AFB microscopy should be omitted in other settings where sensitivity is much lower. ^‡Tests to exclude other causes for neurologic syndromes should be performed as clinically indicated and available (eg, cerebrospinal fluid [CSF] syphilis serology, viral polymerase chain reaction testing, cytology, anti-N-methyl D-aspartate [NMDA] receptor antibodies). Consider brain imaging (computerized tomography/magnetic resonance imaging) as available for focal neurologic deficit(s) and/or to aid in tuberculous meningitis diagnosis.