The microbiological diagnosis of tuberculous meningitis of Haydarpasa-1 study

Abstract

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-γ release assay (Quantiferon TB gold in tube) 90.2%, automated culture systems (ACS) 81.8%, Löwenstein 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 (κ = -0.189); ACS and L-J culture (κ = -0.172) (p <0.05 for both). Fair and inverse agreement was detected for CSF-ADA and CSF-PCR (κ = -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.

Other Foci of Infections in Community Acquired Central Nervous System Infections

“…ID-IRI has produced bulk of information on pneumococcal meningitis [4], brucellar meningitis [5], tuberculous meningitis [6,7], and herpetic meningoencephalitis [8]. Among these CNS infection studies [5][6][7][8] are the largest case series ever reported in the literature. The strength of these studies was that all patients included were confirmed microbiologically and patients with presumptive diagnoses were excluded.…”

Clinical Reasoning: A 57-year-old man with unilateral anosmia, papilledema, and meningismus

“…6 Suspicion for tuberculous meningitis is increased when there is evidence of exposure (a positive PPD or interferon-g release assay), and in this setting additional testing such as CSF mycobacterial PCR or adenosine deaminase testing may be indicated. 7 Findings on chest CT may suggest cancer, sarcoidosis, histoplasmosis, or tuberculosis. Our patient had normal CT chest, abdomen, and pelvis.…”

A case of tuberculous meningitis

“…13 The sensitivities in another large case series were 27% for staining with Ziehl-Neelsen and 82% for automated liquid culture systems. 14 Nucleic acid amplification tests can provide a rapid diagnosis and detect dead bacteria (after treatment initiation) with a sensitivity reported between 57% and 94% for CSF samples. 14,15 As seen in this case, real time PCR can be positive with smear negative CSF samples.…”

“…14 Nucleic acid amplification tests can provide a rapid diagnosis and detect dead bacteria (after treatment initiation) with a sensitivity reported between 57% and 94% for CSF samples. 14,15 As seen in this case, real time PCR can be positive with smear negative CSF samples. Therefore, a combination of rapid tests with confirmatory culture from multiple samples is required to obtain a definitive diagnosis.…”