Evidence map›Paper›PMID 39207255›Full record

ArticleThe Journal of infectious diseases2025

Cerebrospinal Fluid Cytokines and Chemokines Involved in Cytotoxic Cell Function and Risk of Acute 14-Day Mortality in Persons with Advanced HIV and Cryptococcal Meningitis.

Elizabeth C Okafor, Liliane Mukaremera, Kathy H Hullsiek, Nicole Engen, Lillian Tugume, Kenneth Ssebambulidde, Abdu K Musubire, Edwin Nuwagira, Edward Mpoza, Darlisha A Williams and 5 more

Abstract read
In one paragraph

Article in The Journal of infectious diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Foxp3Research square · 2025
    Article
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Elizabeth C OkaforDepartment of Medicine, University of Minnesota School of Medicine.ORCID 0000-0003-1495-4596
Liliane MukaremeraDepartment of Medicine, University of Minnesota School of Medicine.
Kathy H HullsiekDivision of Biostatistics and Health Data Science, University of Minnesota, Minneapolis.
Nicole EngenDivision of Biostatistics and Health Data Science, University of Minnesota, Minneapolis.ORCID 0000-0003-1118-4194
Lillian TugumeInfectious Diseases Institute, Makerere University, Kampala.
Kenneth SsebambuliddeInfectious Diseases Institute, Makerere University, Kampala.ORCID 0000-0002-8125-0698
Abdu K MusubireDepartment of Medicine, University of Minnesota School of Medicine.
Edwin NuwagiraDepartment of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda.
Edward MpozaInfectious Diseases Institute, Makerere University, Kampala.
Darlisha A WilliamsDepartment of Medicine, University of Minnesota School of Medicine.
Conrad MuzooraDepartment of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda.
Joshua RheinDepartment of Medicine, University of Minnesota School of Medicine.
David B MeyaDepartment of Medicine, University of Minnesota School of Medicine.
Kirsten NielsenDepartment of Medicine, University of Minnesota School of Medicine.
David R BoulwareDepartment of Medicine, University of Minnesota School of Medicine.

Funding

NPGH LEADERs YR12: OBSSR (Greenberg, Ngwafong Mukere) & NIBIB (Lee)D43TW009345 · FIC · UNIVERSITY OF WASHINGTON · PI Dibyadyuti Datta, Chandy C. John · 2017 to 2026
$15.2M
Improving Diagnostics and Neurocognitive Outcomes in HIV/AIDS-related MeningitisR01NS086312 · NINDS · UNIVERSITY OF MINNESOTA · PI David R Boulware, David Bisagaya Meya · 2013 to 2026
$8.3M
Infectious Disease Training in Clinical InvestigationT32AI055433 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI David R Boulware · 2003 to 2026
$6.1M
Genomic Research Capacity Building for Cryptococcosis Translational StudiesR01NS118538 · NINDS · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI Joel Bazira, David Bisagaya Meya · 2020 to 2026
$3.4M
Continuum of Immune Responses to Cryptococcus neoformansR01AI176922 · NIAID · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI Kirsten Nielsen · 2023 to 2026
$3.0M
Encochleated Oral Amphotericin for Cryptococcal Meningitis TrialR01NS110519 · NINDS · UNIVERSITY OF MINNESOTA · PI BOULWARE, DAVID R, MEYA, DAVID BISAGAYA · 2019 to 2022
$2.6M
Multi-morbidity in Uganda Research Capacity Initiative (MURCI) at Mbarara University of Science and TechnologyD43TW011632 · FIC · MBARARA UNIVERSITY/SCIENCE/ TECHNOLOGY · PI BAJUNIRWE, FRANCIS · 2020 to 2024
$1.2M
Improving Outcomes of HIV-Associated Cryptococcosis in Resource-Limited SettingsK01TW010268 · FIC · UNIVERSITY OF MINNESOTA · PI RHEIN, JOSHUA R · 2016 to 2020
$703k
Improving Diagnostic Strategies for Post-Tuberculosis Lung Disease in Ugandan Primary Healthcare SettingsK43TW012781 · FIC · MBARARA UNIVERSITY/SCIENCE/ TECHNOLOGY · PI Edwin Nuwagira · 2024 to 2026
$327k
Doris Duke International Clinical Research Fellows ProgramFIC NIH HHS D43 TW009345FIC NIH HHS D43 TW011632FIC NIH HHS K01 TW010268FIC NIH HHS K43 TW012781National Institute of Allergy and Infectious Diseases F31AI62230NIAID NIH HHS R01 AI176922NIAID NIH HHS T32 AI055433NINDS NIH HHS R01 NS086312NINDS NIH HHS R01NS086312NINDS NIH HHS R01 NS110519NINDS NIH HHS R01 NS118538the Fogarty International Center K01TW010268United Kingdom Medical Research CouncilUniversity of Minnesota Medical School and by theWellcome TrustWellcome Trust MR/M007413/1
6 · The paper itself

Abstract

backgroundThe role of the immune response in acute mortality of cryptococcal meningitis remains unclear.

methodsCerebrospinal fluid (CSF) from 337 Ugandans with first-episode cryptococcal meningitis was collected. CSF cytokines and chemokines were quantified and compared by 14-day survival, stratification by quartiles, and logistical regression to determine association with acute mortality.

resultsEighty-four (24.9%) participants died by day 14. Persons who survived to day 14 had higher levels of proinflammatory macrophage inflammatory protein (MIP)-3β and interferon (IFN)-β and cytotoxicity-associated granzyme B and inteferon gamma-induced protein (IP)-10 compared to those who died (P < .05 for each). Logistic regression analysis revealed that per 2-fold increase in proinflammatory interleukin (IL)-6, IL-1α, MIP-1β, MIP-3β, and IFN-β and cytotoxicity-associated IL-12, tumor necrosis factor-α, granzyme-B, and IP-10 CSF concentrations, the risk of acute 14-day mortality decreased. Similar biomarkers were implicated when stratified by quartiles and further identified that lower concentrations of anti-inflammatory IL-10 and IL-13 were associated with 14-day mortality (P < .05 for each).

conclusionsProinflammatory and cytotoxicity-associated cytokine and chemokine responses in the CSF decrease the risk of acute 14-day mortality. These data suggest that a cytotoxic immune environment in the CSF could potentially improve acute survival. Further research on cytotoxic cells is crucial to improve understanding of innate and adaptive immune responses in cryptococcal meningitis.

Indexed as

ChemokinesCytokinesHIV InfectionsMeningitis, CryptococcalAdultBiomarkersFemaleGranzymesHumansMaleMiddle AgedYoung AdultBiomarkersChemokinesCytokinesGranzymescerebrospinal fluidcryptococcal meningitiscytokinescytotoxic cellsinflammation

Identifiers

PMID39207255
PMCPMC11841645

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.