Published in PLOS One on 2026-06-26, this study is presented as an attributed evidence briefing. The excerpts below are the original researchers’ words, reproduced under their Creative Commons Attribution licence. Health Signal has selected the abstract and, where needed, opening background paragraphs; the complete methods, results, limitations and references remain in the linked paper.
Original authors: Joshua Kitimbo, Esther Buregyeya, Geofrey Mutole, John Paul Ibanda, Joseph Tumwine, Noah Kiwanuka, Thomas Buyinza, Mohamed Hamed Shehata
Source: PLOS One • DOI 10.1371/journal.pone.0340951
Read the complete primary study ↗ · Creative Commons Attribution licence
From the researchers
Abstract
Cryptococcal meningitis remains a leading cause of HIV-related mortality in sub-Saharan Africa despite expanded antiretroviral therapy coverage. Evidence on the burden of disease and inpatient mortality among people living with HIV (PLHIV) in routine care settings in Uganda remains limited. This study assessed the proportion of cryptococcal meningitis among HIV-related admissions and examined clinical factors associated with inpatient mortality.
We conducted a retrospective cohort study of adult PLHIV admitted with cryptococcal meningitis between 1st/01/2017–31st/12/2022 at a national referral hospital in Uganda. Diagnosis was based on cerebrospinal fluid cryptococcal antigen or India ink positivity. Data were abstracted from medical records and analysed using descriptive statistics and multivariable logistic regression to identify factors associated with inpatient mortality. Specific antifungal treatment regimens were not consistently documented and could not be analysed.
Of 3,042 HIV-related admissions, cryptococcal meningitis accounted for 21.4% (650/3,042). Medical records for 634 patients were analysed, among whom 39.3% (249/634) died during hospitalization. Factors independently associated with higher odds of inpatient mortality included convulsions, headache, vomiting, cryptococcal meningitis–associated immune reconstitution inflammatory syndrome, concurrent opportunistic infections, chronic kidney disease, anaemia, and severe immunosuppression (low CD4 cell count). Longer duration of hospitalization (≥7 days) and symptom duration of one to two weeks before admission were associated with lower odds of mortality.
Cryptococcal meningitis continues to account for a substantial proportion of HIV-related hospital admissions and inpatient deaths in Uganda. Mortality is associated with identifiable clinical and health-system factors, underscoring the need for early diagnosis, risk stratification, and optimized inpatient management for PLHIV with cryptococcal meningitis in resource-limited settings.
Introduction
Cryptococcal meningitis (CM) is a life-threatening opportunistic fungal infection of the central nervous system that occurs predominantly among people living with HIV (PLHIV) with advanced immunosuppression. It is caused mainly by Cryptococcus neoformans and less frequently by Cryptococcus gattii, with infection typically acquired through inhalation of environmental spores followed by hematogenous dissemination to the brain, resulting in severe meningoencephalitis [1]. Without timely diagnosis and effective antifungal treatment, cryptococcal meningitis is associated with rapid clinical deterioration, neurological complications, and high short-term mortality [2,3].
Despite substantial progress in HIV care and expanded access to antiretroviral therapy (ART), cryptococcal meningitis remains a major cause of HIV-related morbidity and mortality globally, with the greatest burden concentrated in sub-Saharan Africa (SSA) [4]. Of the estimated 38.4 million PLHIV worldwide, more than two-thirds reside in SSA [5], where late HIV diagnosis, advanced disease at presentation, and limited access to optimal management of opportunistic infections persist [6]. Cryptococcal meningitis accounts for over 70% of cryptococcal disease among HIV-infected individuals and is responsible for approximately 20% of HIV-related deaths globally, highlighting its continued contribution to preventable mortality [7,8].
Reading this evidence
Use the full paper to check the study design, participant selection, comparator and outcome definitions before drawing a practical conclusion. An association does not by itself show cause and effect. A reported performance measure needs its denominator and uncertainty. A finding from a particular facility, sample or time period should retain that scope when it is discussed elsewhere.
This briefing makes the source accessible within the wider research & evidence desk. It does not assess an individual patient or certify a product. When considering relevance to another health system, examine the original authors’ account of context and limitations, then seek local implementation evidence. The related reporting below provides other studies to read alongside this one; it is a topic connection, rather than a claim that their results are directly comparable.
© 2026 Joshua Kitimbo, Esther Buregyeya, Geofrey Mutole, John Paul Ibanda, Joseph Tumwine, Noah Kiwanuka, Thomas Buyinza, Mohamed Hamed Shehata. Excerpts reproduced under CC BY. Selection, formatting and contextual notes by Health Signal. The researchers are the authors of the source study, not members of Health Signal’s staff.
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- Evidence brief: Empiric tuberculosis treatment and 12-month mortality among sputum GeneXpert-negative adults living with HIV in Uganda in the era of widespread antiretroviral therapy: A prospective cohort study
- Evidence brief: Change in plasma cryptococcal antigen titers in Uganda among outpatients with advanced HIV disease from 2017 to 2022 with rollout of national cryptococcal screening
- Evidence brief: Spectrum and immunovirological determinants of tumours among people living with HIV in Uganda: A retrospective cross sectional study from a specialised HIV centre, 2017–2026
