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Meta-Analysis
. 2021 Apr 8;72(7):1268-1278.
doi: 10.1093/cid/ciaa1243.

Cryptococcal Antigen in Serum and Cerebrospinal Fluid for Detecting Cryptococcal Meningitis in Adults Living With Human Immunodeficiency Virus: Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies

Elvis Temfack  1   2 , Jean Joel Bigna Rim  3 , Rene Spijker  4 , Angela Loyse  5   6   7 , Tom Chiller  8 , Peter G Pappas  9 , John Perfect  10 , Tania C Sorell  11 , Thomas S Harrison  5   6   7 , Jérémie F Cohen  12   13 , Olivier Lortholary  1   14
Affiliations
Meta-Analysis

Cryptococcal Antigen in Serum and Cerebrospinal Fluid for Detecting Cryptococcal Meningitis in Adults Living With Human Immunodeficiency Virus: Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies

Elvis Temfack et al. Clin Infect Dis. .

Abstract

Cryptococcal antigen (CrAg) detection could direct the timely initiation of antifungal therapy. We searched MEDLINE and Embase for studies where CrAg detection in serum/cerebrospinal fluid (CSF) and CSF fungal culture were done on adults living with human immunodeficiency virus (HIV) who had suspected cryptococcal meningitis (CM). With Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2), we evaluated the risk of bias in 11 included studies with 3600 participants, and used a random-effects meta-analysis to obtain summary sensitivity and specificity of serum and CSF CrAg, as well as agreement between CSF CrAg and CSF culture. Summary sensitivity and specificity of serum CrAg were 99.7% (97.4-100) and 94.1% (88.3-98.1), respectively, and summary sensitivity and specificity of CSF CrAg were 98.8% (96.2-99.6) and 99.3% (96.7-99.9), respectively. Agreement between CSF CrAg and CSF culture was 98% (97-99). In adults living with HIV who have CM symptoms, serum CrAg negativity may rule out CM, while positivity should prompt induction antifungal therapy if lumbar puncture is not feasible. In a first episode of CM, CSF CrAg positivity is diagnostic.

Keywords: antigen; cryptococcus; diagnosis; lateral flow assay; latex agglutination.

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Figures

Figure 1.
Figure 1.
Flow diagram of the study selection process. Abbreviation: CM, cryptococcal meningitis.
Figure 2.
Figure 2.
Prevalence of CrAg positivity in (A) serum and (B) CSF in adults living with HIV who have central nervous system symptoms. Abbreviations: CI, confidence interval; CrAg, cryptococcal antigen; CSF, cerebrospinal fluid; HIV, human immunodeficiency virus.
Figure 3.
Figure 3.
Prevalence of confirmed CM in adults living with HIV who have central nervous system symptoms. Abbreviations: CI, confidence interval; CM, cryptococcal meningitis; HIV, human immunodeficiency virus.
Figure 4.
Figure 4.
Forest plots of serum (8 cohorts) and CSF (16 cohorts) CrAg sensitivity and specificity for CM diagnosis in adults living with HIV who have central nervous system symptoms. Abbreviations: CI, confidence interval; CM, cryptococcal meningitis; CrAg, cryptococcal antigen; CSF, cerebrospinal fluid; HIV, human immunodeficiency virus; TP, True positive; FP, False positive; FN, False negative; TN, True negative..
Figure 5.
Figure 5.
Direct head-to-head comparisons of serum and CSF CrAg performed in the same patients (7 cohorts). Circles and diamonds represent serum and CSF CrAg, respectively. The curved lines represent the summary Receiver Operating Characteristics (ROC) curves of sensitivity and specificity. Abbreviations: CrAg, cryptococcal antigen; CSF, cerebrospinal fluid.
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