Cargando…

Sterile Cerebrospinal Fluid Culture at Cryptococcal Meningitis Diagnosis Is Associated with High Mortality

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-p...

Descripción completa

Detalles Bibliográficos
Autores principales: Skipper, Caleb P, Hullsiek, Katherine Huppler, Stadelman, Anna, Williams, Darlisha A, Ssebambulidde, Kenneth, Okafor, Elizabeth, Tugume, Lillian, Nuwagira, Edwin, Akampurira, Andrew, Musubire, Abdu K, Abassi, Mahsa, Muzoora, Conrad, Rhein, Joshua, Boulware, David R, Meya, David B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9866844/
https://www.ncbi.nlm.nih.gov/pubmed/36675867
http://dx.doi.org/10.3390/jof9010046
_version_ 1784876192793362432
author Skipper, Caleb P
Hullsiek, Katherine Huppler
Stadelman, Anna
Williams, Darlisha A
Ssebambulidde, Kenneth
Okafor, Elizabeth
Tugume, Lillian
Nuwagira, Edwin
Akampurira, Andrew
Musubire, Abdu K
Abassi, Mahsa
Muzoora, Conrad
Rhein, Joshua
Boulware, David R
Meya, David B
author_facet Skipper, Caleb P
Hullsiek, Katherine Huppler
Stadelman, Anna
Williams, Darlisha A
Ssebambulidde, Kenneth
Okafor, Elizabeth
Tugume, Lillian
Nuwagira, Edwin
Akampurira, Andrew
Musubire, Abdu K
Abassi, Mahsa
Muzoora, Conrad
Rhein, Joshua
Boulware, David R
Meya, David B
author_sort Skipper, Caleb P
collection PubMed
description 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 CrAg-positive 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.
format Online
Article
Text
id pubmed-9866844
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-98668442023-01-22 Sterile Cerebrospinal Fluid Culture at Cryptococcal Meningitis Diagnosis Is Associated with High Mortality Skipper, Caleb P Hullsiek, Katherine Huppler Stadelman, Anna Williams, Darlisha A Ssebambulidde, Kenneth Okafor, Elizabeth Tugume, Lillian Nuwagira, Edwin Akampurira, Andrew Musubire, Abdu K Abassi, Mahsa Muzoora, Conrad Rhein, Joshua Boulware, David R Meya, David B J Fungi (Basel) Article 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 CrAg-positive 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. MDPI 2022-12-28 /pmc/articles/PMC9866844/ /pubmed/36675867 http://dx.doi.org/10.3390/jof9010046 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Skipper, Caleb P
Hullsiek, Katherine Huppler
Stadelman, Anna
Williams, Darlisha A
Ssebambulidde, Kenneth
Okafor, Elizabeth
Tugume, Lillian
Nuwagira, Edwin
Akampurira, Andrew
Musubire, Abdu K
Abassi, Mahsa
Muzoora, Conrad
Rhein, Joshua
Boulware, David R
Meya, David B
Sterile Cerebrospinal Fluid Culture at Cryptococcal Meningitis Diagnosis Is Associated with High Mortality
title Sterile Cerebrospinal Fluid Culture at Cryptococcal Meningitis Diagnosis Is Associated with High Mortality
title_full Sterile Cerebrospinal Fluid Culture at Cryptococcal Meningitis Diagnosis Is Associated with High Mortality
title_fullStr Sterile Cerebrospinal Fluid Culture at Cryptococcal Meningitis Diagnosis Is Associated with High Mortality
title_full_unstemmed Sterile Cerebrospinal Fluid Culture at Cryptococcal Meningitis Diagnosis Is Associated with High Mortality
title_short Sterile Cerebrospinal Fluid Culture at Cryptococcal Meningitis Diagnosis Is Associated with High Mortality
title_sort sterile cerebrospinal fluid culture at cryptococcal meningitis diagnosis is associated with high mortality
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9866844/
https://www.ncbi.nlm.nih.gov/pubmed/36675867
http://dx.doi.org/10.3390/jof9010046
work_keys_str_mv AT skippercalebp sterilecerebrospinalfluidcultureatcryptococcalmeningitisdiagnosisisassociatedwithhighmortality
AT hullsiekkatherinehuppler sterilecerebrospinalfluidcultureatcryptococcalmeningitisdiagnosisisassociatedwithhighmortality
AT stadelmananna sterilecerebrospinalfluidcultureatcryptococcalmeningitisdiagnosisisassociatedwithhighmortality
AT williamsdarlishaa sterilecerebrospinalfluidcultureatcryptococcalmeningitisdiagnosisisassociatedwithhighmortality
AT ssebambuliddekenneth sterilecerebrospinalfluidcultureatcryptococcalmeningitisdiagnosisisassociatedwithhighmortality
AT okaforelizabeth sterilecerebrospinalfluidcultureatcryptococcalmeningitisdiagnosisisassociatedwithhighmortality
AT tugumelillian sterilecerebrospinalfluidcultureatcryptococcalmeningitisdiagnosisisassociatedwithhighmortality
AT nuwagiraedwin sterilecerebrospinalfluidcultureatcryptococcalmeningitisdiagnosisisassociatedwithhighmortality
AT akampuriraandrew sterilecerebrospinalfluidcultureatcryptococcalmeningitisdiagnosisisassociatedwithhighmortality
AT musubireabduk sterilecerebrospinalfluidcultureatcryptococcalmeningitisdiagnosisisassociatedwithhighmortality
AT abassimahsa sterilecerebrospinalfluidcultureatcryptococcalmeningitisdiagnosisisassociatedwithhighmortality
AT muzooraconrad sterilecerebrospinalfluidcultureatcryptococcalmeningitisdiagnosisisassociatedwithhighmortality
AT rheinjoshua sterilecerebrospinalfluidcultureatcryptococcalmeningitisdiagnosisisassociatedwithhighmortality
AT boulwaredavidr sterilecerebrospinalfluidcultureatcryptococcalmeningitisdiagnosisisassociatedwithhighmortality
AT meyadavidb sterilecerebrospinalfluidcultureatcryptococcalmeningitisdiagnosisisassociatedwithhighmortality