dc.contributor.author | Skipper, Caleb P | |
dc.contributor.author | Hullsiek, Katherine Huppler | |
dc.contributor.author | Stadelman, Anna | |
dc.contributor.author | Williams, Darlisha A | |
dc.contributor.author | Ssebambulidde, Kenneth | |
dc.contributor.author | Okafor, Elizabeth | |
dc.contributor.author | Muzoora, Conrad | |
dc.date.accessioned | 2023-01-12T11:46:12Z | |
dc.date.available | 2023-01-12T11:46:12Z | |
dc.date.issued | 2023 | |
dc.identifier.citation | Skipper, C. P., Hullsiek, K. H., Stadelman, A., Williams, D. A., Ssebambulidde, K., Okafor, E., ... & Meya, D. B. (2023). Sterile Cerebrospinal Fluid Culture at Cryptococcal Meningitis Diagnosis Is Associated with High Mortality. Journal of Fungi, 9(1), 46. | en_US |
dc.identifier.uri | http://ir.must.ac.ug/xmlui/handle/123456789/2698 | |
dc.description.abstract | Cryptococcus is the leading cause of AIDS-related meningitis in sub-Saharan Africa. The clinical implications of a sterile cerebrospinal fluid (CSF) culture among individuals diagnosed with cryptococcal meningitis using CSF cryptococcal antigen (CrAg) are unclear. We prospectively enrolled 765 HIV-positive Ugandans with first-episode cryptococcal meningitis from November 2010 to May 2017. All persons were treated with amphotericin-based induction therapy. We grouped participants by tertile of baseline CSF quantitative Cryptococcus culture burden and compared clinical characteristics, CSF immune profiles, and 18-week mortality. We found 55 (7%) CSF CrAgpositive participants with sterile CSF cultures. Compared to the non-sterile groups, participants with sterile CSF cultures had higher CD4 counts, lower CSF opening pressures, and were more frequently receiving ART. By 18 weeks, 47% [26/55] died in the sterile culture group versus 35% [83/235] in the low culture tertile, 46% [107/234] in the middle tertile, and 56% [135/241] in the high tertile (p < 0.001). The sterile group had higher levels of CSF interferon-gamma (IFN-γ), IFN-α, interleukin (IL)-6, IL-17, G-CSF, GM-CSF, and chemokine CXCL2 compared with non-sterile groups. Despite persons with sterile CSF cultures having higher CD4 counts, lower CSF opening pressures, and CSF cytokine profiles associated with better Cryptococcus control (e.g., IFN-γ predominant), mortality was similar to those with higher fungal burdens. This unexpected finding challenges the traditional paradigm that increasing CSF fungal burdens are associated with increased mortality but is consistent with a damage-response framework model | en_US |
dc.description.sponsorship | National Institutes of Health’s National Center for Advancing Translational Sciences | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Journal of Fungi | en_US |
dc.subject | Cryptococcus | en_US |
dc.subject | HIV | en_US |
dc.subject | AIDS | en_US |
dc.subject | Cryptococcal meningitis | en_US |
dc.title | Sterile Cerebrospinal Fluid Culture at Cryptococcal Meningitis Diagnosis Is Associated with High Mortality | en_US |
dc.type | Article | en_US |