The potential contribution of the polymerase chain reaction to the diagnosis of tuberculous meningitis
L. N. Nguyen, L. F. Kox, L. D. Pham, S. Kuijper and A. H. Kolk
Pham Ngoc Thach Tuberculosis and Lung Disease Center, Ho Chi Minh City, Vietnam.
OBJECTIVE: To examine diagnostic utility of polymerase chain reaction (PCR)
on cerebrospinal fluid (CSF) in tuberculous meningitis (TBM). DESIGN:
Comparison study. SETTING: Referral center for tuberculosis diagnosis and
treatment in Ho Chi Minh City, Vietnam, and research laboratory in
Amsterdam, the Netherlands. PATIENTS: One hundred thirty-six consecutive
patients, aged 4 months to 85 years, with features compatible with TBM seen
during a 12-month period. MEASUREMENTS: Clinical examination; cytology;
Gram, india ink, and Ziehl-Neelsen staining; culture of CSF for bacteria,
mycobacteria, fungi, and viruses; and CSF chloride, protein, and glucose.
All these tests were performed in Vietnam. The PCR on CSF was performed in
the Netherlands. RESULTS: Patients were managed in Vietnam without
knowledge of PCR results. Based on clinical grounds and the results of
initial CSF microscopy, antituberculous treatment was given to 104
patients, 66 of whom had evidence of extraneural tuberculosis. Among the 39
patients with confirmed TBM (ie, positive Ziehl-Neelsen staining or culture
or PCR results for Mycobacterium tuberculosis), PCR detected 32 patients
(82%), 1 case was proven positive through microscopy and 17 (44%) had
positive culture results. There were no false-positive PCR results. In 99
patients with a final diagnosis of confirmed or probable TBM (ie, clinical
features of TBM and response to antituberculous treatment), PCR had a
sensitivity of 32%; culture, 17% and microscopy, 1%. CONCLUSIONS: Many
patients who respond to treatment for TBM do not have M tuberculosis in the
CSF identifiable by microscopy, PCR, or culture. Polymerase chain reaction
on CSF is the best method for the laboratory diagnosis of TBM. Polymerase
chain reaction is especially useful for the early diagnosis of TBM in those
without active extraneural tuberculosis.
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