Evidence map›Paper›PMID 36303432›Full record

ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2023

Recurrence of Symptoms Following Cryptococcal Meningitis: Characterizing a Diagnostic Conundrum With Multiple Etiologies.

Nathan C Bahr, Caleb P Skipper, Kathy Huppler-Hullsiek, Kenneth Ssebambulidde, Bozena M Morawski, Nicole W Engen, Edwin Nuwagira, Carson M Quinn, Prashanth S Ramachandran, Emily E Evans and 7 more

Registry-linked trialOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01802385 (Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.6field-weighted citation impact, top 17% of its field
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.

NCT01802385 phase3completednot on this map

Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis

TypeinterventionalSponsorUniversity of MinnesotaRan2015 to 2017Enrolled460ConditionsCryptococcal Meningitis, Fungal MeningitisArmsSertraline
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 10 citations in OpenAlex.

  1. Oral Lipid Nanocrystal Amphotericin B for Cryptococcal Meningitis: A Randomized Clinical Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023
    Trial
  2. Article
  3. Observational
  4. Review
  5. Article
  6. Review
  7. Cryptococcal meningitis.Nature reviews. Disease primers · 2023
    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

17 authors at 7 institutions in 2 countries.

Nathan C BahrDivision of Infectious Diseases, Department of Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.ORCID 0000-0002-9431-8938
Caleb P SkipperDivision of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
Kathy Huppler-HullsiekDivision of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
Kenneth SsebambuliddeInfectious Diseases Institute, Makerere University, Kampala, Uganda.
Bozena M MorawskiCancer Data Registry of Idaho, Idaho Hospital Association, Boise, Idaho, USA.
Nicole W EngenDivision of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
Edwin NuwagiraDepartment of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda.
Carson M QuinnDepartment of Neurology, Harvard Medical School, Boston, Massachusetts, USA.
Prashanth S RamachandranWeill Institute of Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
Emily E EvansDepartment of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Sarah M LofgrenDivision of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
Mahsa AbassiDivision of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
Conrad MuzooraDepartment of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda.
Michael R WilsonWeill Institute of Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
David B MeyaInfectious Diseases Institute, Makerere University, Kampala, Uganda.
Joshua RheinDivision of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
David R BoulwareDivision of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
University of Minnesota · USInfectious Diseases Institute · UGMbarara University of Science and Technology · UGUniversity of California, San Francisco · USHarvard University · USUniversity of Kansas Medical Center · USUniversity of Pittsburgh · US

Funding

University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UL1TR002494 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R, WEISDORF, DANIEL J · 2018 to 2022
$34.9M
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
Institutional Career Development CoreKL2TR002492 · NCATS · UNIVERSITY OF MINNESOTA · PI INGBAR, DAVID H · 2018 to 2022
$6.3M
Infectious Disease Training in Clinical InvestigationT32AI055433 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI David R Boulware · 2003 to 2026
$6.1M
Redefining Tuberculosis Meningitis with Metagenomics and Host TransciptomicsR01AI145437 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WILSON, MICHAEL R · 2019 to 2023
$3.5M
Targeting Neuropathogenesis of Altered Mental Status to Improve Survival in Cryptococcal MeningitisK23NS122601 · NINDS · UNIVERSITY OF MINNESOTA · PI ABASSI, MAHSA · 2021 to 2025
$1.1M
Novel Diagnostic Development for TB Meningitis and HistoplasmosisK23NS110470 · NINDS · UNIVERSITY OF MINNESOTA · PI BAHR, NATHAN · 2019 to 2023
$1.0M
Neuroinflammation and Modulating Factors in Depression and HIVK23MH121220 · NIMH · UNIVERSITY OF MINNESOTA · PI LOFGREN, SARAH · 2019 to 2022
$795k
Improving Outcomes of HIV-Associated Cryptococcosis in Resource-Limited SettingsK01TW010268 · FIC · UNIVERSITY OF MINNESOTA · PI RHEIN, JOSHUA R · 2016 to 2020
$703k
FIC NIH HHS D43 TW009345FIC NIH HHS K01 TW010268NCATS NIH HHS KL2 TR002492NCATS NIH HHS UL1 TR002494NCI NIH HHS HHSN261201800006INIAID NIH HHS R01 AI145437NIAID NIH HHS T32 AI055433NIMH NIH HHS K23 MH121220NINDS NIH HHS K23 NS110470NINDS NIH HHS K23 NS122601NINDS NIH HHS R01 NS086312
6 · The paper itself

Abstract

backgroundCryptococcal meningitis is a common cause of AIDS-related mortality. Although symptom recurrence after initial treatment is common, the etiology is often difficult to decipher. We sought to summarize characteristics, etiologies, and outcomes among persons with second-episode symptomatic recurrence.

methodsWe prospectively enrolled Ugandans with cryptococcal meningitis and obtained patient characteristics, antiretroviral therapy (ART) and cryptococcosis histories, clinical outcomes, and cerebrospinal fluid (CSF) analysis results. We independently adjudicated cases of second-episode meningitis to categorize patients as (1) microbiological relapse, (2) paradoxical immune reconstitution inflammatory syndrome (IRIS), (3) persistent elevated intracranial pressure (ICP) only, or (4) persistent symptoms only, along with controls of primary cryptococcal meningitis. We compared groups with chi-square or Kruskal-Wallis tests as appropriate.

results724 participants were included (n = 607 primary episode, 81 relapse, 28 paradoxical IRIS, 2 persistently elevated ICP, 6 persistent symptoms). Participants with culture-positive relapse had lower CD4 (25 cells/μL; IQR: 9-76) and lower CSF white blood cell (WBC; 4 cells/μL; IQR: 4-85) counts than paradoxical IRIS (CD4: 78 cells/μL; IQR: 47-142; WBC: 45 cells/μL; IQR: 8-128). Among those with CSF WBC <5 cells/μL, 86% (43/50) had relapse. Among those with CD4 counts <50 cells/μL, 91% (39/43) had relapse. Eighteen-week mortality (from current symptom onset) was 47% among first episodes of cryptococcal meningitis, 31% in culture-positive relapses, and 14% in paradoxical IRIS.

conclusionsPoor immune reconstitution was noted more often in relapse than IRIS as evidenced by lower CSF WBC and blood CD4 counts. These easily obtained laboratory values should prompt initiation of antifungal treatment while awaiting culture results. CLINICAL TRIALS REGISTRATION: NCT01802385.

Indexed as

AIDS-Related Opportunistic InfectionsHIV InfectionsMeningitis, CryptococcalAntifungal AgentsHumansRecurrenceAntifungal Agentscryptococcal meningitiscryptococcosisimmune reconstitution inflammatory syndromemeningitisrelapse

Identifiers

PMID36303432
PMCPMC10226736
OpenAlexW4307720426

What OpenQuestion holds

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Registered trials

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 OpenQuestion graph.