Impact of prior cryptococcal antigen screening on in-hospital mortality in cryptococcal meningitis or fungaemia among HIV-seropositive individuals in South Africa: a cross-sectional observational study

Objectives: We investigated whether patients with cryptococcal meningitis (CM) or fungaemia detected through South Africa's laboratory cryptococcal antigen (CrAg) screening programme had better outcomes than those presenting directly to the hospital. Methods: We compared 14-day in-hospital case-fatality ratios of HIV-seropositive individuals with CD4 counts below 100 cells/μL and laboratory-confirmed CM/fungaemia from 2017–2021, with or without evidence of a positive blood CrAg test within 14 days prior to diagnosis. We evaluated whether the impact of prior CrAg screening on mortality varied according to the study period (pre–COVID-19: before March 2020 vs. COVID-19: after March 2020). Results: Overall, 24.5% (830/3390) of patients had a prior positive CrAg test within 14 days of diagnosis. CrAg-screened patients were less likely to have an altered mental status at baseline than non-CrAg-screened patients (38.1% [296/776] vs. 42.6% [1010/2372], p = 0.03), and had a lower crude 14-day case-fatality ratio (24.7% [205/830] vs. 28.3% [724/2560]; OR, 0.83 [95% CI, 0.69–0.99]; p = 0.045). Previous CrAg screening was associated with a greater reduction in the crude 14-day mortality during the COVID-19 period (OR, 0.64 [0.47–0.87]; p = 0.005) compared with before (OR, 0.95 [0.76–1.19]; p = 0.68). After adjustment, previous CrAg screening within 14 days was associated with increased survival only during the COVID-19 period (adjusted OR, 0.70 [0.51–0.96]; p = 0.03). Discussion: Previous CrAg screening was associated with a survival benefit in patients hospitalized with CM/fungaemia during the COVID-19 period, with fewer patients having an altered mental status at baseline, suggesting that these patients may have been diagnosed with cryptococcosis earlier.