title: The effect of therapeutic lumbar punctures on acute mortality from cryptococcal meningitis.
abstract: BACKGROUND
  Cryptococcal meningitis is the most common cause of adult meningitis in sub-Saharan Africa. Raised intracranial pressure (ICP) is common in cryptococcosis. Prior studies suggest elevated ICP is associated with mortality, and guidelines recommend frequent lumbar punctures (LPs) to control ICP. However, the magnitude of the impact of LPs on cryptococcal-related mortality is unknown.
  
  
  METHODS
  In sum, 248 individuals with human immunodeficiency virus (HIV)-associated cryptococcal meningitis, screened for the Cryptococcal Optimal ART Timing (COAT) trial in Uganda and South Africa, were observed. Individuals received an LP to diagnose meningitis, and subsequent therapeutic LPs were recommended for elevated ICP (>250 mmH2O) or new symptoms. We compared survival, through 11 days, between individuals receiving at least 1 therapeutic LP with individuals not receiving therapeutic LPs. The COAT trial randomized subjects at 7-11 days; thus, follow-up stopped at time of death, randomization, or 11 days.
  
  
  RESULTS
  Seventy-five (30%) individuals had at least 1 therapeutic LP. Individuals receiving therapeutic LPs had higher cerebrospinal fluid (CSF) opening pressures, higher CSF fungal burdens, and were more likely to have altered mental status at baseline than those with no therapeutic LPs. Thirty-one deaths (18%) occurred among 173 individuals without a therapeutic LP and 5 deaths (7%) among 75 with at least 1 therapeutic LP. The adjusted relative risk of mortality was 0.31 (95% confidence interval: .12-.82). The association was observed regardless of opening pressure at baseline.
  
  
  CONCLUSIONS
  Therapeutic LPs were associated with a 69% relative improvement in survival, regardless of initial intracranial pressure. The role of therapeutic LPs should be reevaluated.
authors: Department of Medicine, Medical School.
authors: Melissa A
authors: MA
authors: Rolfes
authors: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis.
authors: Kathy Huppler
authors: KH
authors: Hullsiek
authors: Department of Medicine, Medical School Infectious Diseases Institute, Makerere University, Kampala.
authors: Joshua
authors: J
authors: Rhein
authors: Infectious Diseases Institute, Makerere University, Kampala.
authors: Henry W
authors: HW
authors: Nabeta
authors: Internal Medicine, Faculty of Medicine, Mbarara University of Science and Technology, Uganda.
authors: Kabanda
authors: K
authors: Taseera
authors: Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town, South Africa.
authors: Charlotte
authors: C
authors: Schutz
authors: Infectious Diseases Institute, Makerere University, Kampala.
authors: Abdu
authors: A
authors: Musubire
authors: Department of Medicine, Medical School Infectious Diseases Institute, Makerere University, Kampala.
authors: Radha
authors: R
authors: Rajasingham
authors: Department of Medicine, Medical School Infectious Diseases Institute, Makerere University, Kampala.
authors: Darlisha A
authors: DA
authors: Williams
authors: Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town, South Africa.
authors: Friedrich
authors: F
authors: Thienemann
authors: Internal Medicine, Faculty of Medicine, Mbarara University of Science and Technology, Uganda.
authors: Conrad
authors: C
authors: Muzoora
authors: Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town, South Africa Department of Medicine, Imperial College London, United Kingdom;
authors: Graeme
authors: G
authors: Meintjes
authors: Department of Medicine, Medical School Infectious Diseases Institute, Makerere University, Kampala School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda.
authors: David B
authors: DB
authors: Meya
authors: Department of Medicine, Medical School.
authors: David R
authors: DR
authors: Boulware
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D017088:AIDS-Related Opportunistic Infections / Q000382:microbiology / Q000401:mortality; D015331:Cohort Studies; D019586:Intracranial Hypertension / Q000382:microbiology / Q000601:surgery; D016919:Meningitis, Cryptococcal / Q000401:mortality / Q000601:surgery / Q000821:virology; D013129:Spinal Puncture
keywords: HIV; cryptococcal meningitis; epidemiology; mortality; therapeutic lumbar punctures