Outpatient Cryptococcal Antigen Screening Is Associated With Favorable Baseline Characteristics and Improved Survival in Persons With Cryptococcal Meningitis in Uganda

Anna E. Levin, Ananta S. Bangdiwala, Elizabeth Nalintya, Enock Kagimu, John Kasibante, Morris K. Rutakingirwa, Edward Mpoza, Samuel Jjunju, Edwin Nuwagira, Rose Naluyima, Paul Kirumira, Cody Hou, Kenneth Ssebambulidde, Abdu K. Musubire, Darlisha A. Williams, Mahsa Abassi, Conrad Muzoora, Katherine H. Hullsiek, Radha Rajasingham, David B. MeyaDavid R. Boulware, Caleb P. Skipper

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Background: It is unknown whether persons with symptomatic cryptococcal meningitis detected during routine blood cryptococcal antigen (CrAg) screening have better survival than persons presenting with overt meningitis. Methods: We prospectively enrolled Ugandans with HIV and cryptocococcal meningitis from December 2018 to December 2021. Participants were treated with amphotericin-based combination therapy. We compared outcomes between persons who were CrAg screened then referred to hospital with those presenting directly to the hospital with symptomatic meningitis. Results: Among 489 participants with cryptococcal meningitis, 40% (194/489) received blood CrAg screening and were referred to hospital (median time to referral 2 days; interquartile range [IQR], 1-6). CrAg-screened persons referred to hospital had lower 14-day mortality than non-CrAg-screened persons who presented directly to hospital with symptomatic meningitis (12% vs 21%; hazard ratio,. 51; 95% confidence interval,. 32-.83; P =. 006). Fewer CrAg-screened participants had altered mental status versus non-CrAg-screened participants (29% vs 41%; P =. 03). CrAg-screened persons had lower quantitative cerebrospinal fluid (CSF) culture burden (median [IQR], 4570 [11-100 000] vs 26 900 [182-324 000] CFU/mL; P =. 01) and lower CSF opening pressures (median [IQR], 190 [120-270] vs 225 [140-340] mmH2O; P =. 004) compared with non-CrAg-screened persons. Conclusions: Survival from cryptococcal meningitis was higher in persons with prior CrAg screening than those without CrAg screening. Altered mental status was the most potent predictor for mortality in a multivariate model. We suggest that CrAg screening detects cryptococcal meningitis at an earlier stage, as evidenced by a favorable baseline risk profile and notably fewer persons with altered mental status.

Original languageEnglish (US)
Pages (from-to)E759-E765
JournalClinical Infectious Diseases
Issue number3
StatePublished - Feb 1 2023

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health's National Center for Advancing Translational Sciences (KL2TR002492, UL1TR002494), National Institute of Neurologic Disorders and Stroke (R01NS086312, K23NS122601), the Fogarty International Center (K01TW010268, K43TW010718, D43TW009345), and the National Institute of Allergy and Infectious Diseases (K23AI138851, T32AI055433, U01AI125003).

Publisher Copyright:
© 2022 The Author(s). Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved.


  • AIDS
  • advanced HIV disease
  • cryptococcal antigenemia
  • cryptococcal meningitis


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