PMID- 23097584
OWN - NLM
STAT- MEDLINE
DCOM- 20130620
LR  - 20220419
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Print)
IS  - 1058-4838 (Linking)
VI  - 56
IP  - 3
DP  - 2013 Feb
TI  - Frequency, severity, and prediction of tuberculous meningitis immune 
      reconstitution inflammatory syndrome.
PG  - 450-60
LID - 10.1093/cid/cis899 [doi]
AB  - 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 x10(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.
FAU - Marais, Suzaan
AU  - Marais S
AD  - Clinical Infectious Diseases Research Initiative, Institute of Infectious 
      Diseases and Molecular Medicine, University of Cape Town, South Africa. 
      marais.suzaan@gmail.com
FAU - Meintjes, Graeme
AU  - Meintjes G
FAU - Pepper, Dominique J
AU  - Pepper DJ
FAU - Dodd, Lori E
AU  - Dodd LE
FAU - Schutz, Charlotte
AU  - Schutz C
FAU - Ismail, Zahiera
AU  - Ismail Z
FAU - Wilkinson, Katalin A
AU  - Wilkinson KA
FAU - Wilkinson, Robert J
AU  - Wilkinson RJ
LA  - eng
GR  - U2R TW007370/TW/FIC NIH HHS/United States
GR  - U2R TW007370-01A1/TW/FIC NIH HHS/United States
GR  - U.1175.02.002.00014.01/MRC_/Medical Research Council/United Kingdom
GR  - 088316/Wellcome Trust/United Kingdom
GR  - PEPFAR/PEPFAR/United States
GR  - ImNIH/Intramural NIH HHS/United States
GR  - MC_U117588499/MRC_/Medical Research Council/United Kingdom
GR  - U2R TW007373/TW/FIC NIH HHS/United States
GR  - U2R TW007373-01A1/TW/FIC NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121024
PL  - United States
TA  - Clin Infect Dis
JT  - Clinical infectious diseases : an official publication of the Infectious Diseases 
      Society of America
JID - 9203213
RN  - 0 (Anti-Retroviral Agents)
RN  - 0 (Antitubercular Agents)
SB  - IM
MH  - Adult
MH  - Anti-Retroviral Agents/*therapeutic use
MH  - Antitubercular Agents/*therapeutic use
MH  - Cerebrospinal Fluid/microbiology
MH  - Female
MH  - HIV Infections/*complications/drug therapy
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome/cerebrospinal fluid/drug 
      therapy/*etiology
MH  - Logistic Models
MH  - Male
MH  - Mycobacterium tuberculosis/isolation & purification
MH  - Prospective Studies
MH  - Risk Factors
MH  - Severity of Illness Index
MH  - South Africa
MH  - Tuberculosis, Meningeal/cerebrospinal fluid/drug therapy/*etiology
PMC - PMC3540040
EDAT- 2012/10/26 06:00
MHDA- 2013/06/21 06:00
PMCR- 2012/10/24
CRDT- 2012/10/26 06:00
PHST- 2012/10/26 06:00 [entrez]
PHST- 2012/10/26 06:00 [pubmed]
PHST- 2013/06/21 06:00 [medline]
PHST- 2012/10/24 00:00 [pmc-release]
AID - cis899 [pii]
AID - 10.1093/cid/cis899 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2013 Feb;56(3):450-60. doi: 10.1093/cid/cis899. Epub 2012 Oct 
      24.