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False negative polymerase chain reaction on cerebrospinal fluid samples in tuberculous meningitis
  1. Department of Microbiology, The General Infirmary at Leeds, Great George Street, Leeds LS1 3EX, UK
  1. Dr D M Gascoyne-Binzi, Department of Microbiology, The General Infirmary at Leeds, Great George Street, Leeds LS1 3EX, UK.

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There have been few studies in the literature concerned solely with the use of the polymerase chain reaction (PCR) to identifyMycobacterium tuberculosis DNA directly from CSF.1-4 These studies suggest that in some cases, PCR may be more sensitive than culture; however, in the largest study, performed by Nguyen et al,3specimens from seven patients who were culture positive forM tuberculosis were not positive by PCR. The study did report on 22 culture negative, PCR positive patients, suggesting that PCR can be more sensitive than culture. Studies comparing PCR with culture of M tuberculosisusing other clinical specimens, particularly respiratory specimens, have reported that PCR may be less sensitive than culture for the detection of M tuberculosis 5-9and that the low sensitivity correlated with low colony counts on culture.5 Dalovisio et al 6 also reported that multiple specimens may be required to improve the sensitivity of the test in some patients. In the two cases described above, colonies were seen after incubation for 12 and 8 weeks on LJ slopes, suggesting a low inoculum.

The PCR has been reported to detect the equivalent of 1–10 mycobacteria in in vitro testing. However, lower sensitivity is found with clinical specimens.5 6 The low sensitivity of PCR may be the result of inhibitors of PCR present in the reaction, poor lysis of mycobacteria, and the uneven distribution of mycobacteria in clinical specimens.5 6