The effect of therapeutic lumbar punctures on acute mortality from cryptococcal meningitis.

Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

Volume: 59

Issue: 11

Year of Publication: 2015

Affiliated Institutions:  Department of Medicine, Medical School. Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis. Department of Medicine, Medical School Infectious Diseases Institute, Makerere University, Kampala. Infectious Diseases Institute, Makerere University, Kampala. Internal Medicine, Faculty of Medicine, Mbarara University of Science and Technology, Uganda. Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town, South Africa. 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; Department of Medicine, Medical School Infectious Diseases Institute, Makerere University, Kampala School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda.

Abstract summary 

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.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.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.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 & Co-authors:  Rolfes Melissa A MA Hullsiek Kathy Huppler KH Rhein Joshua J Nabeta Henry W HW Taseera Kabanda K Schutz Charlotte C Musubire Abdu A Rajasingham Radha R Williams Darlisha A DA Thienemann Friedrich F Muzoora Conrad C Meintjes Graeme G Meya David B DB Boulware David R DR

Study Outcome 

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Statistics
Citations :  Brouwer AE, Rajanuwong A, Chierakul W, et al. Combination antifungal therapies for HIV-associated cryptococcal meningitis: A randomised trial. Lancet. 2004;363:1764–7.
Authors :  14
Identifiers
Doi : 10.1093/cid/ciu596
SSN : 1537-6591
Study Population
Male,Female
Mesh Terms
AIDS-Related Opportunistic Infections
Other Terms
HIV;cryptococcal meningitis;epidemiology;mortality;therapeutic lumbar punctures
Study Design
Randomized Control Trial,Case Control Trial,Cross Sectional Study
Study Approach
Country of Study
Uganda
Publication Country
United States