Evidence map›Paper›PMID 30596708›Full record

Trial reportPloS one2018

Blood neutrophil counts in HIV-infected patients with cryptococcal meningitis: Association with mortality.

Abdu Kisekka Musubire, David B Meya, Joshua Rhein, Graeme Meintjes, Paul R Bohjanen, Edwin Nuwagira, Conrad Muzoora, David R Boulware, Kathy Huppler Hullsiek, COAT and ASTRO trial teams

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 15% 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.

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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

  1. Pooled it
  2. Predictors of Treatment Failure in Children With HIV Starting First-line Antiretroviral Therapy in the ODYSSEY Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026
    Trial
  3. Fungal Infections in Disorders of Inborn Errors of Immunity.Clinical reviews in allergy & immunology · 2026
    Review
  4. Review
  5. The hypervirulent Type-1/Type-17 phenotype ofInfection and immunity · 2025
    Article
  6. Article
  7. Review
  8. Molecular Diagnostics ofDiseases (Basel, Switzerland) · 2024
    Review
  9. Innate Pulmonary Phagocytes and Their Interactions with PathogenicJournal of fungi (Basel, Switzerland) · 2023
    Review
  10. Importance of Clinical Isolates inJournal of fungi (Basel, Switzerland) · 2023
    Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Mechanisms of fungal dissemination.Cellular and molecular life sciences : CMLS · 2021
    Review
  17. Review
  18. Cerebrospinal Fluid Early Fungicidal Activity as a Surrogate Endpoint for Cryptococcal Meningitis Survival in Clinical Trials.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020
    Article
  19. Article
  20. Article
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

10 authors at 5 institutions in 3 countries.

Abdu Kisekka MusubireInfectious Disease Institute, College of Health Sciences, Makerere University, Kampala, Uganda.ORCID 0000-0003-2410-5344
David B MeyaInfectious Disease Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
Joshua RheinInfectious Disease Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
Graeme MeintjesCentre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University Cape Town, Cape Town, South Africa.
Paul R BohjanenDivision of Infectious Diseases & International Medicine, Dept. of Medicine, University of Minnesota, Minnesota, Minneapolis, United States of America.
Edwin NuwagiraDepartment of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda.
Conrad MuzooraDepartment of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda.
David R BoulwareDivision of Infectious Diseases & International Medicine, Dept. of Medicine, University of Minnesota, Minnesota, Minneapolis, United States of America.
Kathy Huppler HullsiekDivision of Biostatistics, School of Public Health, University of Minnesota, Minnesota, Minneapolis, United States of America.
COAT and ASTRO trial teams
University of Minnesota · USMbarara University of Science and Technology · UGMakerere University · UGMulago Hospital · UGWellcome Centre for Infectious Diseases Research in Africa · ZA

Funding

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
Trial for the Optimal Timing of HIV Therapy after Cryptococcal MeningitisU01AI089244 · NIAID · UNIVERSITY OF MINNESOTA · PI BOULWARE, DAVID R · 2010 to 2014
$7.6M
Infectious Disease Training in Clinical InvestigationT32AI055433 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI David R Boulware · 2003 to 2026
$6.1M
Northern/Pacific Universities Global Health Research Training ConsortiumR25TW009345 · FIC · UNIVERSITY OF WASHINGTON · PI KOLARS, JOSEPH C., NERURKAR, VIVEK RAMCHANDRA · 2012 to 2016
$5.9M
Epidemiology, Immunopathogenesis, and Outcomes of Non-traumatic Spinal Cord Injury in UgandaK43TW010718 · FIC · INFECTIOUS DISEASES INSTITUTE · PI MUSUBIRE, ABDU KISEKKA · 2017 to 2021
$514k
FIC NIH HHS K43 TW010718FIC NIH HHS R25 TW009345Medical Research Council MR/M007413/1NIAID NIH HHS T32 AI055433NIAID NIH HHS U01 AI089244NINDS NIH HHS R01 NS086312Wellcome TrustWellcome Trust 098316
6 · The paper itself

Abstract

backgroundThe mortality from cryptococcal meningitis remains high, despite the availability of antiretroviral therapy (ART) and amphotericin-based fungal regimens. The role of neutrophils in cryptococcosis is controversial. Our objective was to examine the association between blood neutrophil counts and outcomes in terms of mortality, the incidence of bacterial infections (including Mycobacterium tuberculosis) and hospitalization among HIV-infected patients presenting with cryptococcal meningitis.

methodsWe used data from participants from the Cryptococcal Optimal ART Timing (COAT) trial (2010-2012; Uganda and South Africa) and the Adjunctive Sertraline for Treatment of Cryptococcal Meningitis (ASTRO-CM) trial (2013-2017; Uganda). We estimated 30-day mortality risk with Cox proportional hazards models by baseline neutrophil counts (a) on a continuous scale and (b) with indicators for both relatively high (> 3,500 cells/mm3) and low (≤ 1,000 cells/mm3) counts. Follow-up neutrophil counts from the COAT trial were used to examine the time-dependent association of neutrophil counts with 12-month mortality and rehospitalization.

results801 participants had an absolute neutrophil value at meningitis diagnosis. The median baseline absolute neutrophil count was 2100 cells/mm3 (IQR, 1400 to 3300 cells/mm3). Baseline neutrophil count was positively associated with 30-day mortality (adjusted hazard ratio = 1.09, 95%CI, 1.04-1.13, per 1000 cells/mm3 increase; p<0.001). Baseline absolute neutrophil counts ≤ 1000 cells/mm3 did not have increased risk of 30-day mortality compared to those with baseline neutrophils of 1001-3500 cells/mm3; however, baseline >3500 cells/mm3 had significantly increased risk, with an adjusted hazard ratio of 1.85(95%CI, 1.40-2.44; p<0.001). Among the COAT participants with follow-up neutrophil data, there was a strong association between time-updated neutrophil count and 12-month mortality (adjusted hazard ratio = 1.16, 95% CI 1.09-1.24; p<0.001.

conclusionHigher blood neutrophil counts in HIV-infected patients with cryptococcal meningitis were associated with mortality. Neutrophils role requires further investigation as to whether this may be a mediator directly contributing to mortality or merely a marker of underlying pathologies that increase mortality risk.

Indexed as

NeutrophilsAdultAnti-HIV AgentsCoinfectionFemaleHIV InfectionsHumansLeukocyte CountMaleMeningitis, CryptococcalPatient ReadmissionPrognosisSouth AfricaSurvival AnalysisTime FactorsUgandaAnti-HIV Agents

Identifiers

PMID30596708
PMCPMC6312212
OpenAlexW2907378598

What OpenQuestion holds

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LicenceCC BY
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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 OpenQuestion graph.