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Automated Measurement of Cryptococcal Species Polysaccharide Capsule and Cell Body
Published on: January 11, 2018
Symptomatic Cryptococcal Antigenemia Presenting as Early Cryptococcal Meningitis With Negative Cerebral Spinal Fluid
Kenneth Ssebambulidde1, Ananta S Bangdiwala2, Richard Kwizera1
1Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
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/microL) 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.
Clinical Trials Registration:
NCT01802385.
Insights
Cryptococcal antigenemia with neurological symptoms but negative CSF CrAg is a distinct entity, potentially early meningoencephalitis. In-hospital mortality was similar to cryptococcal meningitis, suggesting a need for revised treatment strategies.
Area of Science:
- Infectious Diseases
- Neurology
- Clinical Microbiology
Background:
- Cryptococcal antigenemia poses a high risk for cryptococcal meningitis.
- The progression from asymptomatic infection to meningitis is not well understood.
- This study identifies a subpopulation with neurological symptoms and antigenemia but negative cerebrospinal fluid (CSF) studies.
Purpose of the Study:
- To characterize individuals with neurological symptoms and cryptococcal antigenemia but negative CSF cryptococcal antigen (CrAg) tests.
- To compare their clinical outcomes with those of confirmed cryptococcal meningitis.
- To investigate potential early meningoencephalitis in this population.
Main Methods:
- Evaluated 1201 HIV-seropositive individuals hospitalized with suspected meningitis in Uganda.
- Compared baseline characteristics and outcomes of patients with neurologic-symptomatic antigenemia and negative CSF CrAg to those with confirmed CSF CrAg+ meningitis.
- Performed extensive CSF testing, including microscopy, fungal/bacterial/tuberculosis cultures, and PCR (FilmArray, Xpert MTB/Rif).
Main Results:
- 4% (54/1201) had neurologic symptomatic antigenemia with negative CSF CrAg; 9% had Cryptococcus cultured or detected by PCR.
- 11% of CSF CrAg-negative patients had confirmed tuberculous meningitis.
- CSF CrAg-negative patients showed lower rates of pleocytosis and elevated opening pressure compared to CrAg-positive patients; in-hospital mortality was similar (32% vs 31%).
Conclusions:
- Neurologic symptomatic cryptococcal antigenemia with negative CSF CrAg was the third most common meningitis etiology, possibly representing early meningoencephalitis.
- Fluconazole monotherapy was suboptimal in this group, even with negative CSF.
- Further research is needed to define the clinical course and optimal management of this condition.
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