Abstract
Background
Cryptococcal meningitis is a common cause of AIDS-related mortality. Although symptom recurrence after initial treatment is common, the etiology is often difficult to decipher. We sought to summarize characteristics, etiologies and outcomes among persons with second-episode symptomatic recurrence.
Methods
We prospectively enrolled Ugandans with cryptococcal meningitis and obtained patient characteristics, ART and cryptococcosis histories, clinical outcomes, and CSF analysis results. We independently adjudicated cases of second-episode meningitis to categorize patients as 1: microbiological relapse, 2: paradoxical Immune Reconstitution Inflammatory Syndrome (IRIS), 3: persistent elevated intracranial pressure (ICP) only, or 4: persistent symptoms only; along with controls of primary cryptococcal meningitis. We compared groups with chi-square or Kruskal Wallis tests as appropriate.
Results
724 participants wer e included (n = 607 primary episode, n = 81 relapse, n = 28 paradoxical IRIS, n = 2 persistently elevated ICP, n = 6 persistent symptoms). Participants with culture-positive relapse had lower CD4 (25 cells/mcL, IQR 9-76) and lower CSF WBC (4 cells/mcL, IQR 4-85) counts than paradoxical IRIS (CD4 78 cells/mcL, IQR 47-142 and WBC 45 cells/mcL, IQR 8-128). Among those with CSF WBC <5 cells/mcL, 86% (43/50) had relapse. Among those with CD4 counts < 50 cells/mcL, 91% (39/43) had relapse. 18-week mortality (from current symptom onset) was 47% among first episodes of cryptococcal meningitis, 31% in culture-positive relapses, and 14% in paradoxical IRIS.
Conclusions
Poor immune reconstitution was noted more often in relapse compared to IRIS as evidenced by lower CSF WBC counts and blood CD4 counts. These easily obtained lab values should prompt initiation of antifungal treatment while awaiting culture results.
