THE POTENTIAL CONTRIBUTION OF THE POLYMERASE CHAIN-REACTION TO THE DIAGNOSIS OF TUBERCULOUS MENINGITIS

Objective: To examine diagnostic utility of polymerase chain reaction (PCR) on cerebrospinal fluid (CSF) in tuberculous meningitis (TBM). De sign: Comparison study. Setting: Referral center for tuberculosis diag nosis and treatment in Ho Chi Minh City, Vietnam, and research laborat ory in Amsterdam, the Netherlands. Patients: One hundred thirty-six co nsecutive patients, aged 4 months to 85 years, with features compatibl e with TBM seen during a 12-month period. Measurements: Clinical exami nation; cytology; Gram, india ink, and Ziehl-Neelsen staining; culture of CSF for bacteria, mycobacteria, fungi, and viruses; and CSF chlori de, protein, and glucose. All these tests were performed in Vietnam. T he PCR on CSF was performed in the Netherlands. Results: Patients were managed in Vietnam without knowledge of PCR results. Based on clinica l grounds and the results of initial CSF microscopy, antituberculous t reatment was given to 104 patients, 66 of whom had; evidence of extran eural tuberculosis. Among the 39 patients with confirmed TBM (ie, posi tive Ziehl-Neelsen staining or culture or PCR results for Mycobacteriu m tuberculosis), PCR detected 32 patients (82%), 1 case was proven pos itive through microscopy and 17 (44%) had positive culture results. Th ere were no false-positive PCR results. In 99 patients with a final di agnosis 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 resp ond to treatment for TBM do not have M tuberculosis in the CSF identif iable by microscopy, PCR, or culture. Polymerase chain reaction on CSF is the best method for the laboratory diagnosis of TBM. Polymerase ch ain reaction is especially useful for the early diagnosis of TBM in th ose without active extraneural tuberculosis.