The microbiological diagnosis of tuberculous meningitis: results of Haydarpasa-1 study

Erdem H., Ozturk-Engin D., ELALDI N., Gulsun S., Sengoz G., Crisan A., ...More

CLINICAL MICROBIOLOGY AND INFECTION, vol.20, no.10, 2014 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 20 Issue: 10
  • Publication Date: 2014
  • Doi Number: 10.1111/1469-0691.12478
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Keywords: culture, diagnosis, meningitis, PCR, tuberculosis, ACID AMPLIFICATION TESTS, ADENOSINE-DEAMINASE, CEREBROSPINAL-FLUID, CSF
  • Dokuz Eylül University Affiliated: No


We aimed to provide data on the diagnosis of tuberculous meningitis (TBM) in this largest case series ever reported. The Haydarpasa-1 study involved patients with microbiologically confirmed TBM in Albania, Croatia, Denmark, Egypt, France, Hungary, Iraq, Italy, Macedonia, Romania, Serbia, Slovenia, Syria and Turkey between 2000 and 2012. A positive culture, PCR or Ehrlich-Ziehl-Neelsen staining (EZNs) from the cerebrospinal fluid (CSF) was mandatory for inclusion of meningitis patients. A total of 506 TBM patients were included. The sensitivities of the tests were as follows: interferon- release assay (Quantiferon TB gold in tube) 90.2%, automated culture systems (ACS) 81.8%, Lowenstein Jensen medium (L-J) 72.7%, adenosine deaminase (ADA) 29.9% and EZNs 27.3%. CSF-ACS was superior to CSF L-J culture and CSF-PCR (p<0.05 for both). Accordingly, CSF L-J culture was superior to CSF-PCR (p<0.05). Combination of L-J and ACS was superior to using these tests alone (p<0.05). There were poor and inverse agreements between EZNs and L-J culture (=-0.189); ACS and L-J culture (=-0.172) (p<0.05 for both). Fair and inverse agreement was detected for CSF-ADA and CSF-PCR (=-0.299, p<0.05). Diagnostic accuracy of TBM was increased when both ACS and L-J cultures were used together. Non-culture tests contributed to TBM diagnosis to a degree. However, due to the delays in the diagnosis with any of the cultures, combined use of non-culture tests appears to contribute early diagnosis. Hence, the diagnostic approach to TBM should be individualized according to the technical capacities of medical institutions particularly in those with poor resources.