Background: Individuals with cryptococcal antigenemia are at high risk for developing cryptococca... more Background: Individuals with cryptococcal antigenemia are at high risk for developing cryptococcal meningitis (CM) if left untreated. It is unknown if meningitis precedes the detection of cryptococcal antigen (CrAg) in cerebrospinal fluid (CSF). We present a sub-population of individuals with symptomatic cryptococcal antigenemia, but negative CSF CrAg. Methods: We evaluated serum and CSF CrAg among 1,236 HIV-seropositive individuals presenting with suspected meningitis in Kampala and Mbarara, Uganda between August 2013 and May 2017. Baseline characteristics and clinical outcomes of individuals with symptomatic cryptococcal antigenemia with negative CSF CrAg were compared to individuals with confirmed CM. Results: We found 45% (559/1,236) of individuals screened had CM and 4% (54/1,236) had symptomatic cryptococcal antigenemia with negative CSF CrAg. Of those presenting with negative CSF CrAg, 6% (3/54) subsequently grew Cryptococcus on CSF culture. Of those without evidence of cryptococcal meningitis by CSF CrAg or culture, 12% (6/51) had confirmed tuberculous meningitis (TBM). The median CD4 count was higher for individuals with negative CSF CrAg compared to those with CM (p=0.15). Headache was a less common symptom for individuals with negative CSF CrAg compared to those with CM (82% vs 97%; p<0.01). Individuals with a negative CSF CrAg presented more frequently with normal CSF WBC (p<0.01) and had lower opening pressure [median 118 (95% CI 90-150) vs 265 (180-390)mmH2O; p<0.01]. There were no cases of bacterial meningitis on CSF PCR or culture, and most with symptomatic CrAg antigenemia had no other known meningitis etiology. Among those with recorded in-hospital outcome, mortality was similar between those with symptomatic antigenemia with negative CSF CrAg and those with CM (33% vs 32%; p=0.85). Conclusions: Symptomatic cryptococcal antigenemia with a negative CSF CrAg is a relatively common presentation. It is unclear whether this represents early cryptococcal meningitis. We observed similar high in-hospital mortality in individuals with CrAg antigenemia regardless of CSF CrAg positivity. Further studies to better understand the clinical course and management of this subset of individuals are warranted. Abstract Etiology of Symptomatic CrAg antigenemia
Background: Individuals with cryptococcal antigenemia are at high risk for developing cryptococca... more Background: Individuals with cryptococcal antigenemia are at high risk for developing cryptococcal meningitis (CM) if left untreated. It is unknown if meningitis precedes the detection of cryptococcal antigen (CrAg) in cerebrospinal fluid (CSF). We present a sub-population of individuals with symptomatic cryptococcal antigenemia, but negative CSF CrAg. Methods: We evaluated serum and CSF CrAg among 1,236 HIV-seropositive individuals presenting with suspected meningitis in Kampala and Mbarara, Uganda between August 2013 and May 2017. Baseline characteristics and clinical outcomes of individuals with symptomatic cryptococcal antigenemia with negative CSF CrAg were compared to individuals with confirmed CM. Results: We found 45% (559/1,236) of individuals screened had CM and 4% (54/1,236) had symptomatic cryptococcal antigenemia with negative CSF CrAg. Of those presenting with negative CSF CrAg, 6% (3/54) subsequently grew Cryptococcus on CSF culture. Of those without evidence of cryptococcal meningitis by CSF CrAg or culture, 12% (6/51) had confirmed tuberculous meningitis (TBM). The median CD4 count was higher for individuals with negative CSF CrAg compared to those with CM (p=0.15). Headache was a less common symptom for individuals with negative CSF CrAg compared to those with CM (82% vs 97%; p<0.01). Individuals with a negative CSF CrAg presented more frequently with normal CSF WBC (p<0.01) and had lower opening pressure [median 118 (95% CI 90-150) vs 265 (180-390)mmH2O; p<0.01]. There were no cases of bacterial meningitis on CSF PCR or culture, and most with symptomatic CrAg antigenemia had no other known meningitis etiology. Among those with recorded in-hospital outcome, mortality was similar between those with symptomatic antigenemia with negative CSF CrAg and those with CM (33% vs 32%; p=0.85). Conclusions: Symptomatic cryptococcal antigenemia with a negative CSF CrAg is a relatively common presentation. It is unclear whether this represents early cryptococcal meningitis. We observed similar high in-hospital mortality in individuals with CrAg antigenemia regardless of CSF CrAg positivity. Further studies to better understand the clinical course and management of this subset of individuals are warranted. Abstract Etiology of Symptomatic CrAg antigenemia
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Conference Presentations by Edward Mpoza