1687. Differences in immunologic factors among those presenting with altered mental status in cryptococcal meningitis
Session: Poster Abstract Session: HIV: Other Opportunistic Infections in HIV
Saturday, October 10, 2015
Room: Poster Hall
Background: Altered mental status is a common presentation in HIV-associated cryptococcal meningitis and such persons have worse survival. Underlying causes of altered mental status are unknown.

Methods: We assessed risk factors for altered mental status, defined by a Glasgow Coma Scale (GCS) score <15, among participants with cryptococcal meningitis who were screened for two clinical trials in Uganda and South Africa from 2010 to 2014. We examined the relationship between demographics, 19 CSF cytokines/chemokines, and antiretroviral medications and mental status.

Results: 326 participants were consented, of whom 97 (30%) had altered mental status and 229 (70%) had normal mental status (GCS=15).  Those with altered mental status had similar CD4, viral loads, and CSF fungal burdens. Median CSF cryptococcal antigen titers were slightly higher in persons with normal mental status (P=0.03). Persons with altered mental status had higher CSF opening pressures (330 mm vs. 284 mm H2O, P=0.016) as well as higher concentrations of interleukin (IL)-10 (P=0.03) and macrophage inflammatory protein-1 alpha (MIP1a; P=0.003) compared to persons with normal mental status. Median levels of monocyte chemoattractant protein-1 (MCP-1) were lower among those with altered mental status (P=0.013). Receiving antiretroviral medicines at presentation was not associated with GCS score.

Conclusion: A significant proportion of patients with cryptococcal meningitis presented with altered mental status. Those with altered mental status had higher intracranial pressure at baseline but a similar fungal burden to those without altered mental status. Altered mental status was also associated with 1) higher levels of IL-10, an anti-inflammatory cytokine which down regulates Th1 signaling, which is important in controlling Cryptococcus; 2) higher MIP1a, a granulocyte-recruiting chemokine (non-protective); and 3) lower MCP1, a chemokine which recruits monocytes and memory T cells. Altered mental status may be associated with the host’s immune response to infection, rather than to the burden of cryptococcal infection.

Sarah Lofgren, MD1, Kathy Huppler Hullsiek, PhD2, Bozena Morawski, MPH1, Henry Nabeta, MBChB3, Reuben Kiggundu, MBChB3, Kabanda Taseera, MBChB MSc4, Abdu Musubire, MMed3, Charlotte Schutz, MPH5, Mahsa Abassi, DO1, Nathan Bahr, MD MA1, Lillian Tugume, MBChB3, Conrad Muzoora, MMed4, Darlisha Williams, MPH1,3, Melissa Rolfes, PhD MPH1, Graeme Meintjes, MBChB, FCP, MRCP, DipHIVMan, PhD5,6, Joshua Rhein, MD1,3, David Meya, MMed1,3,7 and David Boulware, MD, MPH1, (1)Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, (2)Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, (3)Infectious Disease Institute, Makerere University, Kampala, Uganda, (4)Mbarara University of Science and Technology, Mbarara, Uganda, (5)Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa, (6)Department of Medicine, Imperial College London, London, England, (7)Department of Medicine, Faculty of Health Sciences, Makerere University, Kampala, Uganda

Disclosures:

S. Lofgren, None

K. H. Hullsiek, None

B. Morawski, None

H. Nabeta, None

R. Kiggundu, None

K. Taseera, None

A. Musubire, None

C. Schutz, None

M. Abassi, None

N. Bahr, None

L. Tugume, None

C. Muzoora, None

D. Williams, None

M. Rolfes, None

G. Meintjes, None

J. Rhein, None

D. Meya, None

D. Boulware, None

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