| Background:Tuberculous meningitis(TBM) is the most severe form of extrapulmonary tuberculosis and causes substantial mortality and morbidity in adults and children. Early diagnosis and treatment are key to determining the prognosis. The current laboratory tests have not met clinical demands. Gene Xpert MTB/RIF(Xpert MTB/RIF or Xpert), a newly developed rapid and sensitive method, has been approved by WHO for the diagnosis of pulmonary and extrapulmonary tuberculosis in adults and children. However, its diagnostic value for TBM is not entirely clear and lacks of systemetic research in China. This study aimed to evaluate the diagnostic performance of Xpert MTB/RIF for TBM and provide new clues for the diagnosis and treatment of the disease. Methods:This was a prospective, single center clinical study. A total of 264 consecutive patients with suspected meningitis admitted to Xijing Hospital from August 2013 to October 2015 were recruited. Cerebrospinal fluid(CSF) samples were collected from each of 218 subjects enrolled in the study and 1ml CSF was conducted the Xpert MTB/RIF assay, Ziehl-Neelsen(ZN) staining, MGIT960 liquid culture respectively and peripheral blood T-SPOT.TB was also detected. And the enrolled patients were grouped according to the 2010 South African expert consensus. When compared with MGIT960 liquid culture and clinical score > 5 points as reference standards respectively, we evaluated the diagnostic performance of these above assays, including sensitivity, specificity, positive predictive value(PPV), negative predictive value(NPV), Youden Index and the Kappa value. Results:Among the enrolled 218 HIV-uninfected cases, 42 cases were diagnosed with definite TBM, 28 cases were classified as probable TBM, 51 cases were classified as possible TBM, and 97 cases were classified as non-TBM.1 ml uncentrifuged CSF from 218 samples were tested using Xpert MTB/RIF and a total of 48 samples were positive(one CSF sample was false positive). 35 of 42 culture-confirmed cases were Xpert-positive(83.3%). In probable and possible TBM patients, 7(25%) and 5(9.8%) were reported positive by Xpert MTB/RIF. MTB detection grades reported by Xpert MTB/RIF were mostly low or very low(97.9%, 47/48). A significant positive correlation was found between Xpert MTB/RIF cycle threshold(CT) values and MGIT960 time to positive culture(γ = 0.751, P < 0.001). Rifampicin(RIF) resistance was detected in 2 cases by Xpert MTB/RIF, one was confirmed by drug susceptibility test, the other was non-TBM. Xpert testing for RIF resistance showed “indeterminate” results in 2 cases, and both were classified as possible TBM.When tested against clinical score > 5 points as a reference standard, the sensitivity of Xpert MTB/RIF was comparable to that of MGIT960 liquid culture(38.8% vs 34.7%, P = 0.505), significantly better than that of ZN staining(38.8% vs 12.4%, P < 0.001), and lower than that of T-SPOT.TB(38.8% vs 66.9%, P < 0.001). The specificities of Xpert MTB/RIF, MGIT960 culture, and ZN staining were higher than that of T-SPOT.TB(99.0%, 100.0%, 99.0% vs 79.4%; P < 0.001). When Xpert MTB/RIF was coupled with T-SPOT.TB to conduct a parallel test, the sensitivity was better than the individual Xpert MTB/RIF tests(69.4% vs 38.8%,P < 0.001), but its specificity was only 78.4%(76/97). When tested against MGIT960 culture as a reference standard, no significant difference was found between the sensitivity of Xpert MTB/RIF and T-SPOT.TB(83.3% vs 92.9%, P = 0.313). The sensitivity of the combined parallel test was 97.6%(41/42). And Youden Index(YI) of Xpert MTB/RIF was highest among these assays(YI=0.84). The Kappa value of Xpert MTB/RIF and MGIT960 liquid culture was 0.858. Conclusion:Xpert MTB/RIF exhibited a good “rule in” value for the diagnosis of TBM, and showed sensitivity comparable with that of MGIT 960 culture. Given the comparable sensitivity to culture, Xpert MTB/RIF has the advantage of preferred method being able to provide rapid diagnosis of TBM, thus saving valuable time in initiating prompt treatment. |
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