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

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.

Delays in Cryptococcal Meningitis Diagnosis and Care: A Mixed Methods Study in Rural Uganda.

Background: Cryptococcal meningitis (CM) remains a major cause of mortality for HIV-infected persons in sub-Saharan Africa, despite widespread access to antiretroviral therapy. Delays in CM diagnosis and treatment contribute to high mortality, with patients often arriving "too late" for treatment to be effective. Little is known about patient-related delays and their experiences with CM. Objectives: This study seeks to identify the factors related to delays in diagnosis and care among patients with cryptococcal meningitis. Methods: A convergent mixed-methods approach was used to understand delays related to diagnosis and treatment of CM among patients admitted to Lira Regional Referral Hospital in rural northern Uganda. We collected data from February to March 2020 using surveys followed by semi-structured interviews from 20 CM patients who survived hospitalization and 20 family members of deceased patients during February 2017-November 2019. Interviews were audio-recorded, transcribed, and thematically coded for analysis. Findings: Delays to CM care were related to 1) self-medication, 2) lack of CM education, 3) seeking treatment multiple times at health centers with 4) missed/misdiagnosis, and 5) cultural factors. Among patients who died, 70% sought care ≥3 times, while those who survived, 35% of sought care ≥3 times before CM diagnosis. Only 10% of patients and 40% of family members knew what caused CM, indicating a lack of knowledge. Conclusions: Patients sought medical care for CM symptoms, but several factors contributed to CM diagnosis and care delays. Many of these factors relate to a lack of CM education and knowledge among patients and providers. A CM awareness campaign for the general public, targeted education for HIV patients, and continuing medical education for healthcare providers can decrease delays and improve outcomes.