Combined Tests Improve Tuberculous Meningitis Diagnosis

At present, there is no established laboratory test to diagnose early tuberculous meningitis and cerebrospinal fluid (CSF) culture sensitivity is low in developing countries and it usually takes several weeks to obtain results with this method.

Tuberculous meningitis (TBM), the most severe form of tuberculosis (TB), accounts for 5% to 10% of extrapulmonary TB and 0.5% of systemic TB worldwide. Those who have contracted this disease have a mortality rate of 20% to 41% in developed countries and 44% to 69% in developing countries.


Scientists at Huashan Hospital Fudan University (Shanghai, China) studied a total of 30 patients who were suspected of having TBM, of whom six were clinically diagnosed as having TBM and 24 as probably harboring the disease. These patients included 24 men and six women, aged between 18 and 79 years, with a mean age of 45 years. The diagnostic criteria for TBM were positive acid-fast (AFS) results or positive CSF culture results for Mycobacterium tuberculosis.

After the first admission of each study participant from the TBM and control patient to the hospital, a 1-mL CSF specimen from each via lumbar puncture was collected. The team also collected cerebrospinal fluid from 10 patients in the TBM group on initial visit and at four weeks, to observe changes. A total of 30 individuals with TBM and 39 control individuals without TBM participated in this study. IFN-γ-secreting T cells were detected by ELISPOT, an enzyme-linked immunospot (T-SPOT.TB, Oxford Immunotec International, Abingdon, UK), and cerebrospinal fluid interferon-γ (cIFN-γ) was detected by enzyme-linked immunosorbent assay (ELISA).

The sensitivity and specificity of peripheral-blood T-SPOT.TB testing in the diagnosis of TBM were 70% and 87%, respectively. The area under the receiver operating characteristic (ROC) curve of cIFN-γ (greater than 81.36 pg/mL) for TBM diagnosis was 0.819, and the corresponding sensitivity and specificity were 83% and 85%, respectively. When T-SPOT.TB and cIFN-γ results were positive, the specificity and positive predictive value of TBM diagnosis reached 100%. The consistency is poor between peripheral-blood T-SPOT.TB and cIFN-methods probably due to the factors that could result in false-negative and false-positive results. However, this finding may partially confirm that the combination of these approaches can improve the efficiency of diagnosis of TBM.

The authors concluded that cIFN-γ testing is a rapid, economical, and highly sensitive approach to the diagnosis of TBM. Dynamic observation of cIFN-γ is important for monitoring patients with TBM, a condition that responds well to treatment. Peripheral blood T-SPOT.TB testing for TBM diagnosis is also important. The combination of peripheral blood T-SPOT.TB and cIFN-γ detection can improve overall sensitivity and specificity in the diagnosis of TBM. The study was published on January 4, 2016 in the journal Laboratory Medicine.

Related Links:
Huashan Hospital Fudan University 
Oxford Immunotec International