title: Frequency, severity, and prediction of tuberculous meningitis immune reconstitution inflammatory syndrome.
abstract: 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 ×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)-α and low interferon (IFN)-γ 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-γ and TNF-α concentrations may predict TBM-IRIS and thereby be a means to individualize patients to early or deferred ART.
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, South Africa. marais.suzaan@gmail.com
authors.forename: Suzaan
authors.initials: S
authors.lastname: Marais
authors.forename: Graeme
authors.initials: G
authors.lastname: Meintjes
authors.forename: Dominique J
authors.initials: DJ
authors.lastname: Pepper
authors.forename: Lori E
authors.initials: LE
authors.lastname: Dodd
authors.forename: Charlotte
authors.initials: C
authors.lastname: Schutz
authors.forename: Zahiera
authors.initials: Z
authors.lastname: Ismail
authors.forename: Katalin A
authors.initials: KA
authors.lastname: Wilkinson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000627:therapeutic use*; D002555:Cerebrospinal Fluid / Q000382:microbiology; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000209:etiology*; D016015:Logistic Models; D008297:Male; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D013019:South Africa; D014390:Tuberculosis, Meningeal / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000209:etiology*
chemical_list: D044966:Anti-Retroviral Agents; D000995:Antitubercular Agents