Role of IS6110-Targeted PCR, Culture, Biochemical, Clinical, and Immunological Criteria for Diagnosis of Tuberculous Meningitis

Abstract

An open prospective clinical, microbiological, and molecular analysis of a national molecular diagnostic service for tuberculous meningitis (TBM) using an in-house IS6110-targeted PCR for molecular “Fastrack” diagnosis was carried out. Between April 1997 and June 1998. Consecutive cerebrospinal fluid (CSF) samples from 131 patients were assessed. Against a culture on the same sample, PCR had a sensitivity of 75% and a specificity of 94%. Of samples from patients classified as definite or probable TBM cases based on clinical criteria, 81% had raised CSF protein levels and 73% had a lymphocytosis, although 57% of all submitted samples showed a raised lymphocyte count. While only 46% had a CSF glucose level below the normal range, the CSF glucose level was significantly lower (P = 0.0281) than in cases of meningitis of other etiologies. Levels of tumor necrosis factor alpha were also found to be significantly raised in definite or probable TBM cases (P = 0.028), while adenosine deaminase levels were not. The study showed IS6110-targeted PCR to be a rapid, sensitive, and specific test in routine use for the diagnosis of TBM.

Diagnosis of tuberculous meningitis: clinical and laboratory parameters

“…The results of PCR studies in the CSF have shown a 94-100% specificity but sensitivities ranging from 75% to 100%. [19][20][21][22] Variations in the PCR methodologies have been attempted to improve the sensitivity and specificity of the test. Primers targeting regions other than the insertional sequence IS6110 have been used.…”

Tuberculous meningoencephalitis in HIV-seronegative patients: variety of clinical presentation and impact on diagnostics and treatment

“…Moreover, PCR studies are heterogeneous concerning sample preparation and target sequence amplification and therefore not comparable. Reported sensitivities for the diagnosis of TBM ranged from 32% to 100% with specificities ranging from 89% to 100% (12–16). The CSF PCR for TBM is rapid and therefore of value when clinical suspicion is high, but results have to be interpreted in context with clinical and other laboratory findings and treatment should not be withheld on the basis of a negative PCR result.…”

Molecular genetic methods for diagnosis and antibiotic resistance detection of mycobacteria from clinical specimens

“…This MTBC‐specific insertion sequence is commonly used as a target in NAATs for detecting MTBC. The IS 6110 (IS 986 ) segments that have frequently been used include the 123‐bp (78–83, 95), 158‐bp (84), 181‐bp (85, 86), 200‐bp (87), 215‐bp (88), 245‐bp (89), 263‐bp (90, 93), 325‐bp (91) and 541‐bp (16, 92) fragment. Both single‐ and nested‐PCR systems have been used, and detection was done by simple agarose electrophoresis, autoradiograms or hybridisation assays.…”