Poor long-term outcomes despite improved hospital survival for patients with cryptococcal meningitis in rural, Northern Uganda

PLoS One. 2024 May 21;19(5):e0303805. doi: 10.1371/journal.pone.0303805. eCollection 2024.

Abstract

Background: Cryptococcal meningitis (CM) remains a major cause of death among people living with HIV in rural sub-Saharan Africa. We previously reported that a CM diagnosis and treatment program (CM-DTP) improved hospital survival for CM patients in rural, northern Uganda. This study aimed to evaluate the impact on long-term survival.

Methods: We conducted a retrospective study at Lira Regional Referral Hospital in Uganda evaluating long-term survival (≥1 year) of CM patients diagnosed after CM-DTP initiation (February 2017-September 2021). We compared with a baseline historical group of CM patients before CM-DTP implementation (January 2015-February 2017). Using Cox proportional hazards models, we assessed time-to-death in these groups, adjusting for confounders.

Results: We identified 318 CM patients, 105 in the Historical Group, and 213 in the CM-DTP Group. The Historical Group had a higher 30-day mortality of 78.5% compared to 42.2% in the CM-DTP Group. The overall survival rate for the CM-DTP group at three years was 25.6%. Attendance at follow-up visits (HR:0.13, 95% CI: [0.03-0.53], p <0.001), ART adherence (HR:0.27, 95% CI: [0.10-0.71], p = 0.008), and fluconazole adherence: (HR:0.03, 95% CI: [0.01-0.13], p <0.001), weight >50kg (HR:0.54, 95% CI: [0.35-0.84], p = 0.006), and performance of therapeutic lumbar punctures (HR:0.42, 95% CI: [0.24-0.71], p = 0.001), were associated with lower risk of death. Altered mentation was associated with increased death risk (HR: 1.63, 95% CI: 1.10-2.42, p = 0.016).

Conclusion: Long-term survival of CM patients improved after the initiation of the CM-DTP. Despite this improved survival, long-term outcomes remained sub-optimal, suggesting that further work is needed to enhance long-term survival.

MeSH terms

  • Adult
  • Antifungal Agents / therapeutic use
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy
  • HIV Infections / mortality
  • Humans
  • Male
  • Meningitis, Cryptococcal* / drug therapy
  • Meningitis, Cryptococcal* / mortality
  • Middle Aged
  • Proportional Hazards Models
  • Retrospective Studies
  • Rural Population*
  • Survival Rate
  • Treatment Outcome
  • Uganda / epidemiology

Grants and funding

R.B; was supported by NIH grant R21TW012439, the Fulbright U.S. Scholars Program, the University of Minnesota Medical School, and the University of Rochester Medical Center. A.L.; was supported through the Robert Wood Johnson Foundation Future of Nursing Scholars Fellowship; GO Health Travel Fellowship, University of Washington Department of Global Health; Boeing International Fellowship, University of Washington Graduate School; Hester McClaws Dissertation Fellowship; Fulbright Student Fellowship; NIH Fogarty Global Health Fellowship grant D43TW009345; NIH training grant T32AI055433; and NIH grant R21TW012439. M.O.; was supported by the Fulbright Foreign Scholars Program, the University of Rochester Department of Public Health Sciences, and NIH grant R21TW012439. The funding supported study design, implementation, data collection, analyses, and publication.