Prevalence, correlates, and outcomes of cryptococcal antigen positivity among patients with AIDS, United States, 1986-2012.

BACKGROUND: Cryptococcal meningitis (CM) is one of the most common causes of AIDS-related mortality worldwide, accounting for 33%-63% of all cases of adult meningitis in sub-Saharan Africa and >500 000 deaths annually. In sub-Saharan Africa, the World Health Organization recommends routinely screening AIDS patients with a CD4 count ≤100 cells/µL for cryptococcal infection. In the United States, there are no recommendations for routine screening. We aimed to determine the prevalence of cryptococcal infection and outcomes of those infected among people living with advanced AIDS in the United States, to inform updates in the prevention and management of CM. METHODS: Using stored sera from participants in the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study from 1986 to 2012, we screened 1872 specimens with CD4 T-cell counts ≤100 cells/µL for cryptococcal antigen (CrAg) using the CrAg lateral flow assay. RESULTS: The overall prevalence of CrAg positivity within the study population was 2.9% (95% confidence interval, .2%-3.8%). Results from multivariable analysis revealed that a previous diagnosis with CM and a CD4 count ≤50 cells/µL were significantly associated with CrAg positivity. Participants who were CrAg positive had significantly shorter survival (2.8 years) than those who were CrAg negative (3.8 years; P = .03). CONCLUSIONS: The prevalence of cryptococcal infection among advanced AIDS patients in the United States was high and above the published cost-effectiveness threshold for routine screening. We recommend routine CrAg screening among human immunodeficiency virus-infected patients with a CD4 count ≤100 cells/µL to detect and treat early infection.

Large-scale evaluation of the immuno-mycologics lateral flow and enzyme-linked immunoassays for detection of cryptococcal antigen in serum and cerebrospinal fluid.

Cryptococcosis is a systemic infection caused by the pathogenic yeasts Cryptococcus neoformans and C. gattii. Detection of cryptococcal capsular antigen (CrAg) in serum and cerebrospinal fluid (CSF) plays an important diagnostic role. We prospectively compared the new Immuno-Mycologics Inc. (IMMY) lateral flow assay (LFA) and enzyme immunoassay (EIA) to our current CrAg test (Premier EIA; Meridian Bioscience Inc.). Discordant samples were retested with the latex-Cryptococcus antigen test (IMMY) and using serotype-specific monoclonal antibodies (MAbs). A total of 589 serum and 411 CSF specimens were tested in parallel. Qualitative agreement across assays was 97.7%. In all, 56 (41 serum and 15 CSF) samples were positive and 921 (527 serum and 394 CSF) samples were negative by all three assays. The 23 discrepant specimens were all Meridian EIA negative. Of 23 discordant specimens, 20 (87.0%) were positive by both the IMMY LFA and EIA, 2 were LFA positive only, and 1 was EIA positive only. Eleven discrepant specimens had adequate volume for latex agglutination (LA) testing; 8 were LA positive, and 3 were LA negative. LA-negative samples (2 CSF samples and 1 serum) had low IMMY LFA/EIA titers (≤1:10). Serotype-specific MAb analysis of the LA-positive samples suggested that these specimens contained CrAg epitopes similar to those of serotype C strains. In conclusion, the IMMY assays showed excellent overall concordance with the Meridian EIA. Assay performance differences were related to issues of analytic sensitivity and possible serotype bias. Incomplete access to patient-level data combined with low specimen volumes limited our ability to fully resolve discrepant results.

Performance characteristics of a polyclonal enzyme immunoassay for the quantitation of Histoplasma antigen in human urine samples.

An antigen detection assay was prepared with rabbit anti- Histoplasma antibodies to detect and quantitate Histoplasma capsulatum antigen in urine samples. By using a 4-parameter curve fit, the assay calibration ranges from 2 to 1,000 enzyme immunoassay (EIA) units. We compared results for 99 urine samples with those of a reference laboratory, half of which tested positive or equivocal by that reference laboratory. Performance characteristics were further defined by studying the assay linearity, precision, percentage of positive agreement, and percentage of negative agreement. An acceptable correlation with the reference laboratory (R2=0.7174) was obtained with results ranging from less than 2 (negative samples) to 132 EIA units by the new method. Compared with the reference laboratory, the percentage of agreement for positive samples, excluding equivocal samples, was 92% and for negative samples was 98%. Crossreactivity occurred with culture filtrates of Paracoccidioides brasiliensis, Coccidioides immitis, and Blastomyces dermatiditis. No cross-reactivity was observed with Candida albicans or Aspergillus fumigatus culture filtrates. The current EIA for the detection and quantitation of H capsulatum antigen in urine specimens is a valid assay that agrees well with results from an established reference laboratory.