期刊
CLINICAL INFECTIOUS DISEASES
卷 56, 期 3, 页码 450-460出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/cid/cis899
关键词
meningitis; tuberculosis; neutrophils; pathogenesis
资金
- Carnegie Corporation Training Award
- Discovery Foundation Academic Fellowship Award
- Perinatal HIV Research Unit
- US Agency for International Development
- President's Emergency Plan for AIDS Relief
- Wellcome Trust [WT 097254, 081667, 084323, 088316]
- Fogarty International Center South Africa TB/AIDS Training Award [NIH/FIC U2R TW007373-01A1, U2R TW007370-01A1]
- European Union [SANTE/2005/105-061-102]
- Medical Research Council [U.1175.02.002.00014.01]
- MRC [MC_U117588499] Funding Source: UKRI
- Medical Research Council [MC_U117588499] Funding Source: researchfish
Background. Tuberculosis immune reconstitution inflammatory syndrome (IRIS) is a common cause of deterioration in human immunodeficiency virus (HIV)-infected patients receiving tuberculosis treatment after starting antiretroviral therapy (ART). Potentially life-threatening neurological involvement occurs frequently and has been suggested as a reason to defer ART. Methods. We conducted a prospective study of HIV-infected, ART-naive patients with tuberculous meningitis (TBM). At presentation, patients started tuberculosis treatment and prednisone; ART was initiated 2 weeks later. Clinical and laboratory findings were compared between patients who developed TBM-IRIS (TBM-IRIS patients) and those who did not (non-TBM-IRIS patients). A logistic regression model was developed to predict TBM-IRIS. Results. Forty-seven percent (16/34) of TBM patients developed TBM-IRIS, which manifested with severe features of inflammation. At TBM diagnosis, TBM-IRIS patients had higher cerebrospinal fluid (CSF) neutrophil counts compared with non-TBM-IRIS patients (median, 50 vs 3 cells x 10(6)/L, P = .02). Mycobacterium tuberculosis was cultured from CSF of 15 TBM-IRIS patients (94%) compared with 6 non-TBM-IRIS patients (33%) at time of TBM diagnosis; relative risk of developing TBM-IRIS if CSF was Mycobacterium tuberculosis culture positive = 9.3 (95% confidence interval [CI], 1.4-62.2). The combination of high CSF tumor necrosis factor (TNF)-alpha and low interferon (IFN)-gamma at TBM diagnosis predicted TBM-IRIS (area under the curve = 0.91 [95% CI, .53-.99]). Conclusions. TBM-IRIS is a frequent, severe complication of ART in HIV-associated TBM and is characterized by high CSF neutrophil counts and Mycobacterium tuberculosis culture positivity at TBM presentation. The combination of CSF IFN-gamma and TNF-alpha concentrations may predict TBM-IRIS and thereby be a means to individualize patients to early or deferred ART.
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