Determinants of Mortality in a Combined Cohort of 501 Patients With HIV-Associated Cryptococcal Meningitis: Implications for Improving Outcomes
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BACKGROUND: Cryptococcal meningitis (CM) is a leading cause of death in individuals infected with human immunodeficiency virus (HIV). Identifying factors associated with mortality informs strategies to improve outcomes. METHODS: Five hundred one patients with HIV-associated CM were followed prospectively for 10 weeks during trials in Thailand, Uganda, Malawi, and South Africa. South African patients (n = 266) were followed for 1 year. Similar inclusion/exclusion criteria were applied at all sites. Logistic regression identified baseline variables independently associated with mortality. RESULTS: Mortality was 17% at 2 weeks and 34% at 10 weeks. Altered mental status (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.7-5.9), high cerebrospinal fluid (CSF) fungal burden (OR, 1.4 per log10 colony-forming units/mL increase; 95% CI, 1.0-1.8), older age (>50 years; OR, 3.9; 95% CI, 1.4-11.1), high peripheral white blood cell count (>10 × 10(9) cells/L; OR, 8.7; 95% CI, 2.5-30.2), fluconazole-based induction treatment, and slow clearance of CSF infection were independently associated with 2-week mortality. Low body weight, anemia (hemoglobin <7.5 g/dL), and low CSF opening pressure were independently associated with mortality at 10 weeks in addition to altered mental status, high fungal burden, high peripheral white cell count, and older age. In those followed for 1 year, overall mortality was 41%. Immune reconstitution inflammatory syndrome occurred in 13% of patients and was associated with 2-week CSF fungal burden (P = .007), but not with time to initiation of antiretroviral therapy (ART). CONCLUSIONS: CSF fungal burden, altered mental status, and rate of clearance of infection predict acute mortality in HIV-associated CM. The results suggest that earlier diagnosis, more rapidly fungicidal amphotericin-based regimens, and prompt immune reconstitution with ART are priorities for improving outcomes.
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A strong IFNγ response is indicative of a good prognosis in patients with cryptococcosis.
“A strong IFNγ response is indicative of a good prognosis in patients with cryptococcosis123,124.”
From Treatment strategies for cryptococcal infection: challenges, advances and future outlook (2021) · cites this paper as [123]
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Noninvasive Testing and Surrogate Markers in Invasive Fungal Diseases
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Self-citationCryptococcal Antigen Screening and Early Antifungal Treatment to Prevent Cryptococcal Meningitis
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Detection of High Cerebrospinal Fluid Levels of (1→3)-β-d-Glucan in Cryptococcal Meningitis
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Diagnosis and management of cryptococcal meningitis in HIV-infected adults
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Genomic Variation across a Clinical Cryptococcus Population Linked to Disease Outcome
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Fungal CNS Infections in Africa: The Neuroimmunology of Cryptococcal Meningitis
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Implementation and Operational Research
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Self-citationEmerging concepts in HIV-associated cryptococcal meningitis
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Self-citationNoninvasive intracranial pressure monitoring for HIV-associated cryptococcal meningitis
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Innate host defenses against Cryptococcus neoformans
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- Authors
- Jarvis, J. N., Bicanic, T., Loyse, A., Namarika, D., Jackson, A., Nussbaum, J. C., Longley, N., Muzoora, C., Phulusa, J., Taseera, K., Kanyembe, C., Wilson, D., Hosseinipour, M. C., Brouwer, A. E., Limmathurotsakul, D., White, N., van der Horst, C., Wood, R., Meintjes, G., Bradley, J., Jaffar, S., & Harrison, T.
- Affiliations
- University of Cape Town (ZA)
- St George's, University of London (GB)
- University of California, San Francisco (US)
- Mbarara University of Science and Technology (UG)
- Edendale Hospital (ZA)
- Radboud University Medical Center (NL)
- Mahidol University (TH)
- London School of Hygiene & Tropical Medicine (GB)
- Corresponding author
- Jarvis, Joseph N.
- ORCID
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-12-06
- Volume
- 58
- Issue
- 5
- Pages
- 736-745
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- PMC
- PMC3922213
- OpenAlex
- W2101195119
- Cited by
- 367
- References
- 30
- Citations by year
- 2026: 19 · 2025: 22 · 2024: 30 · 2023: 22 · 2022: 24 · 2021: 28 · 2020: 31 · 2019: 39 · 2018: 39 · 2017: 37 · 2016: 28 · 2015: 29 · 2014: 19
- FWCI
- 18.28
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Clinical Infectious Diseases (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- St George's Online Research Archive (St George's University of London) (acceptedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- Greater South Information System
- Funders
- Wellcome Trust (84323)
- National Institute for Health and Care Research (CL-2012-20-001)
- Medical Research Council (MR/K012126/1)
- National Institute of Allergy and Infectious Diseases (P30AI045008, P30AI050410)
- Fogarty International Center (D43TW001039)
- Topics
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Keywords
- cryptococcal meningitis, HIV, mortality determinants, altered mental status, immune reconstitution inflammatory syndrome, amphotericin B, fluconazole, antiretroviral therapy, anemia, CSF opening pressure, age, white blood cell count
- MeSH terms
- Adult, Africa, Mental Disorders, Cerebrospinal Fluid, Female, Humans, Longitudinal Studies, Male, Prospective Studies, Risk Factors, Thailand, Colony Count, Microbial, Cohort Studies, HIV Infections, Meningitis, Cryptococcal, AIDS-Related Opportunistic Infections
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