title: Outcomes of cryptococcal meningitis in Uganda before and after the availability of highly active antiretroviral therapy.
abstract: BACKGROUND
  Cryptococcal meningitis (CM) is the proximate cause of death in 20%-30% of persons with acquired immunodeficiency syndrome in Africa.
  
  
  METHODS
  Two prospective, observational cohorts enrolled human immunodeficiency virus (HIV)-infected, antiretroviral-naive persons with CM in Kampala, Uganda. The first cohort was enrolled in 2001-2002 (n = 92), prior to the availability of highly active antiretroviral therapy (HAART), and the second was enrolled in 2006-2007 (n = 44), when HAART was available.
  
  
  RESULTS
  Ugandans presented with prolonged CM symptoms (median duration, 14 days; interquartile range, 7-21 days). The 14-day survival rates were 49% in 2001-2002 and 80% in 2006 (P < .001). HAART was started 35 +/- 13 days after CM diagnosis and does not explain the improved 14-day survival rate in 2006. In 2006-2007, the survival rate continued to decrease after hospitalization, with only 55% surviving to initiate HAART as an outpatient. Probable cryptococcal-related immune reconstitution inflammatory syndrome occurred in 42% of patients, with 4 deaths. At 6 months after CM diagnosis, 18 persons (41%) were alive and receiving HAART in 2007. The median cerebral spinal fluid (CSF) opening pressure was 330 mm H(2)O; 81% of patients had elevated pressure (>200 mm H(2)O). Only 5 patients consented to therapeutic lumbar puncture. There was a trend for higher mortality for pressures >250 mm H(2)O (odds ratio [OR], 2.1; 95% confidence interval [CI], 0.9-5.2; P = .09). Initial CSF WBC counts of <5 cells/mL were associated with failure of CSF sterilization (OR, 17.3; 95% CI, 3.1-94.3; P < .001), and protein levels <35 mg/dL were associated with higher mortality (OR, 2.0; 95% CI, 1.2-3.3; P = .007).
  
  
  CONCLUSIONS
  Significant CM-associated mortality persists, despite the administration of amphotericin B and HIV therapy, because of the high mortality rate before receipt of HAART and because of immune reconstitution inflammatory syndrome-related complications after HAART initiation. Approaches to increase acceptance of therapeutic lumbar punctures are needed.
authors.affiliation: Infectious Disease Institute, Makerere University, Kampala Uganda.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kambugu
authors.forename: David B
authors.initials: DB
authors.lastname: Meya
authors.forename: Joshua
authors.initials: J
authors.lastname: Rhein
authors.forename: Meagan
authors.initials: M
authors.lastname: O'Brien
authors.forename: Edward N
authors.initials: EN
authors.lastname: Janoff
authors.forename: Allan R
authors.initials: AR
authors.lastname: Ronald
authors.forename: Moses R
authors.initials: MR
authors.lastname: Kamya
authors.forename: Harriet
authors.initials: H
authors.lastname: Mayanja-Kizza
authors.forename: Merle A
authors.initials: MA
authors.lastname: Sande
authors.forename: Paul R
authors.initials: PR
authors.lastname: Bohjanen
authors.forename: David R
authors.initials: DR
authors.lastname: Boulware
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D000666:Amphotericin B / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D006760:Hospitalization; D006801:Humans; D016919:Meningitis, Cryptococcal / Q000453:epidemiology / Q000276:immunology / Q000503:physiopathology*; D011446:Prospective Studies; D016896:Treatment Outcome; D014454:Uganda / Q000453:epidemiology
chemical_list: D000666:Amphotericin B