Test Improves Diagnosis of Tuberculous Meningitis in HIV Patients

Tuberculous meningitis (TBM) is a serious and often fatal illness that is difficult to diagnose particularly in resource-poor areas and is especially common in individuals infected with the human immunodeficiency virus (HIV).

A newly available DNA test that can be used in these resource-poor settings and is generally used to detect Mycobacterium tuberculosis (TB), the causative organism, in sputum, and to detect TB DNA in cerebrospinal fluid, has been evaluated for TBM.


Microbiologists at the University of KwaZulu-Natal (Durban, South Africa) performed an evaluation study in 204 South African patients with a meningeal-like illness, of whom 87% were HIV-infected. In this cohort, using a gold standard of positive culture or traditional polymerase chain reaction (PCR) to determine who truly had TBM, 59 individuals had definite TBM, 64 had probable TBM, and 81 did not have TBM. These patients were recruited from hospitals in South Africa between January 2008 and December 2011.

The newly available test was the Xpert MTB/RIF (Cepheid; Sunnyvale, CA, USA) which is an integrated automated sample-processing and real-time PCR platform developed to simultaneously detect M. tuberculosis and rifampicin resistance in a single-use-cartridge hands-free step. The sensitivity of Xpert MTB/RIF was significantly better than that of smear microscopy (62% versus 12%) and significantly better than that of clinical signs (CS) (62% versus 30%) The sensitivity of the Xpert MTB/RIF was higher when centrifuged versus uncentrifuged samples were used (82% versus 47%). The test did not perform as well in the few individuals who were not HIV-infected.

The Xpert MTB/RIF test correctly identified more positive cases than the other tests used to diagnose TB meningitis, within 24 hours of first seeing a patient. However, the test accuracy was more robust when the cerebrospinal fluid sample was centrifuged to achieve the best results. This means additional apparatus would be required, resulting in higher cost and requiring more training. The scientists concluded that this test could still be useful in settings where resources are limited.

The authors concluded that Xpert MTB/RIF might be a good rule-in test for the diagnosis of TBM in HIV-infected individuals from a tuberculosis-endemic setting, particularly when a centrifuged CSF pellet is used. Further studies are required to confirm these findings in different settings. The study was published on October 22, 2013, in the journal Public Library of Science Medicine.

Related Links:
University of KwaZulu-Natal
Cepheid