TY - JOUR
T1 - Symptomatic Cryptococcal Antigenemia Presenting as Early Cryptococcal Meningitis with Negative Cerebral Spinal Fluid Analysis
AU - For the Adjunctive Sertraline for Treatment of HIV-associated Cryptococcal Meningitis Team
AU - Ssebambulidde, Kenneth
AU - Bangdiwala, Ananta S.
AU - Kwizera, Richard
AU - Kandole, Tadeo Kiiza
AU - Tugume, Lillian
AU - Kiggundu, Reuben
AU - Mpoza, Edward
AU - Nuwagira, Edwin
AU - Williams, Darlisha A.
AU - Lofgren, Sarah M.
AU - Abassi, Mahsa
AU - Musubire, Abdu K.
AU - Cresswell, Fiona V.
AU - Rhein, Joshua
AU - Muzoora, Conrad
AU - Hullsiek, Kathy Huppler
AU - Boulware, David R.
AU - Meya, David B.
N1 - Publisher Copyright:
© 2018 The Author(s) 2018.
PY - 2019/6
Y1 - 2019/6
N2 - Background: Individuals with cryptococcal antigenemia are at high risk of developing cryptococcal meningitis if untreated. The progression and timing from asymptomatic infection to cryptococcal meningitis is unclear. We describe a subpopulation of individuals with neurologic symptomatic cryptococcal antigenemia but negative cerebral spinal fluid (CSF) studies. Methods: We evaluated 1201 human immunodeficiency virus-seropositive individuals hospitalized with suspected meningitis in Kampala and Mbarara, Uganda. Baseline characteristics and clinical outcomes of participants with neurologic-symptomatic cryptococcal antigenemia and negative CSF cryptococcal antigen (CrAg) were compared to participants with confirmed CSF CrAg+ cryptococcal meningitis. Additional CSF testing included microscopy, fungal culture, bacterial culture, tuberculosis culture, multiplex FilmArray polymerase chain reaction (PCR; Biofire), and Xpert MTB/Rif. Results: We found 56% (671/1201) of participants had confirmed CSF CrAg+ cryptococcal meningitis and 4% (54/1201) had neurologic symptomatic cryptococcal antigenemia with negative CSF CrAg. Of those with negative CSF CrAg, 9% (5/54) had Cryptococcus isolated on CSF culture (n = 3) or PCR (n = 2) and 11% (6/54) had confirmed tuberculous meningitis. CSF CrAg-negative patients had lower proportions with CSF pleocytosis (16% vs 26% with ≥5 white cells/μL) and CSF opening pressure >200 mmH2O (16% vs 71%) compared with CSF CrAg-positive patients. No cases of bacterial or viral meningitis were detected by CSF PCR or culture. In-hospital mortality was similar between symptomatic cryptococcal antigenemia (32%) and cryptococcal meningitis (31%; P =. 91). Conclusions: Cryptococcal antigenemia with meningitis symptoms was the third most common meningitis etiology. We postulate this is early cryptococcal meningoencephalitis. Fluconazole monotherapy was suboptimal despite Cryptococcus-negative CSF. Further studies are warranted to understand the clinical course and optimal management of this distinct entity.
AB - Background: Individuals with cryptococcal antigenemia are at high risk of developing cryptococcal meningitis if untreated. The progression and timing from asymptomatic infection to cryptococcal meningitis is unclear. We describe a subpopulation of individuals with neurologic symptomatic cryptococcal antigenemia but negative cerebral spinal fluid (CSF) studies. Methods: We evaluated 1201 human immunodeficiency virus-seropositive individuals hospitalized with suspected meningitis in Kampala and Mbarara, Uganda. Baseline characteristics and clinical outcomes of participants with neurologic-symptomatic cryptococcal antigenemia and negative CSF cryptococcal antigen (CrAg) were compared to participants with confirmed CSF CrAg+ cryptococcal meningitis. Additional CSF testing included microscopy, fungal culture, bacterial culture, tuberculosis culture, multiplex FilmArray polymerase chain reaction (PCR; Biofire), and Xpert MTB/Rif. Results: We found 56% (671/1201) of participants had confirmed CSF CrAg+ cryptococcal meningitis and 4% (54/1201) had neurologic symptomatic cryptococcal antigenemia with negative CSF CrAg. Of those with negative CSF CrAg, 9% (5/54) had Cryptococcus isolated on CSF culture (n = 3) or PCR (n = 2) and 11% (6/54) had confirmed tuberculous meningitis. CSF CrAg-negative patients had lower proportions with CSF pleocytosis (16% vs 26% with ≥5 white cells/μL) and CSF opening pressure >200 mmH2O (16% vs 71%) compared with CSF CrAg-positive patients. No cases of bacterial or viral meningitis were detected by CSF PCR or culture. In-hospital mortality was similar between symptomatic cryptococcal antigenemia (32%) and cryptococcal meningitis (31%; P =. 91). Conclusions: Cryptococcal antigenemia with meningitis symptoms was the third most common meningitis etiology. We postulate this is early cryptococcal meningoencephalitis. Fluconazole monotherapy was suboptimal despite Cryptococcus-negative CSF. Further studies are warranted to understand the clinical course and optimal management of this distinct entity.
KW - HIV
KW - aseptic meningitis
KW - cryptococcal meningitis
KW - diagnosis
KW - fungal antigen
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U2 - 10.1093/cid/ciy817
DO - 10.1093/cid/ciy817
M3 - Article
C2 - 30256903
AN - SCOPUS:85059841299
SN - 1058-4838
VL - 68
SP - 2094
EP - 2098
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 12
M1 - ciy817
ER -