Real-time Polymerase Chain Reaction for Mycobacterium tuberculosis Meningitis is More Sensitive in Patients with HIV Co-Infection.

BACKGROUND: Tuberculous meningitis (TbM) is the most severe complication of extra pulmonary tuberculosis (Tb). There is a higher frequency of positive cerebrospinal fluid (CSF) cultures for Mycobacterium tuberculosis (MTb) in samples from human immunodeficiency virus (HIV) co-infected patients than in those from HIV-negative patients. We hypothesized that real time PCR assays for MTb (MTb qPCR) using CSF would be more sensitive in HIV co-infected patients owing to a greater MTb burden. The present study aimed to verify the diagnostic performance of MTb qPCR in CSF of TbM patients who either were co-infected with HIV or were HIVnegative. METHODS: A total of 334 consecutive participants with suspected TbM were divided into two groups: HIV co-infected and HIV-negative; each group was categorized into definite TbM, probable TbM, possible TbM, and TbM-negative subgroups based on clinical, laboratory and imaging data. We evaluated the diagnostic characteristics of MTb qPCR analysis to detect TbM in CSF by comparing the results to those obtained for definite TbM (i.e., positive MTb culture) and/or probable TbM in CSF, as gold standard. RESULTS: The sensitivity of MTb qPCR in the definite and probable subgroups of the HIV coinfected participants (n = 14) was 35.7%, with a specificity of 93.8%, negative predictive value (NPV) of 94.4%, and negative clinical utility index (CUI-) of 0.89. Results of the HIV-negative group (n = 7) showed lower sensitivity (14.3%) and similar specificity, NPV, and CUI-. CONCLUSION: The findings confirmed our hypothesis, despite the low sensitivity. MTb qPCR may significantly contribute to diagnosis when associated with clinical criteria and complementary examinations.

TB meningitis in HIV-positive patients in Europe and Argentina: clinical outcome and factors associated with mortality.

OBJECTIVES: The study aimed at describing characteristics and outcome of tuberculous meningitis (TBM) in HIV-positive patients and comparing these parameters with those of extrapulmonary TB (TBEP) and pulmonary TB (TBP). METHODS: Kaplan-Meier estimation and Poisson regression models were used to assess the mortality following TB diagnosis and to evaluate potential prognostic factors for the 3 groups of TB patients separately. RESULTS: A total of 100 patients with TBM, 601 with TBEP, and 371 TBP were included. Patients with TBM had lower CD4 cell counts and only 17.0% received antiretroviral therapy (ART) at TB diagnosis. The cumulative probability of death at 12 months following TB was 51.2% for TBM (95% CI 41.4-61.6%), 12.3% for TBP (8.9-15.7%), and 19.4% for TBEP (16.1-22.6) (P<0.0001; log-rank test). For TBM, factors associated with a poorer prognosis were not being on ART (adjusted incidence rate ratio (aIRR) 4.00 (1.72-9.09), a prior AIDS diagnosis (aIRR=4.82 (2.61-8.92)), and receiving care in Eastern Europe (aIRR=5.41 (2.58-11.34))). CONCLUSIONS: TBM among HIV-positive patients was associated with a high mortality rate, especially for patients from Eastern Europe and patients with advanced HIV-infection, which urgently calls for public health interventions to improve both TB and HIV aspects of patient management.