False Negative Serum Cryptococcal Antigen Lateral Flow Assay Test in a Patient with Disseminated Cryptococcal Disease

2019 ◽  
Author(s):  
P. Soni ◽  
S. Sharma ◽  
A. Ghatak ◽  
R.K.S. Patti ◽  
C. Seneviratne ◽  
...  
Keyword(s):  
False Negative ◽  
Lateral Flow ◽  
Lateral Flow Assay ◽  
Cryptococcal Antigen ◽  
Cryptococcal Disease

scholarly journals Evaluation of a Cryptococcal Antigen Lateral Flow Assay and Cryptococcal Antigen Positivity at a Large Public Hospital in Atlanta, Georgia

2021 ◽  
Author(s):  
Kristin R V Harrington ◽  
Yun F (Wayne) Wang ◽  
Paulina A Rebolledo ◽  
Zhiyong Liu ◽  
Qianting Yang ◽  
...  
Keyword(s):  
Public Hospital ◽  
Clinical Care ◽  
Latex Agglutination ◽  
Lateral Flow ◽  
Lateral Flow Assay ◽  
Clinical Implications ◽  
Cryptococcal Antigen ◽  
Cryptococcal Disease ◽  
Percent Positivity ◽  
The U.S

Abstract Background Cryptococcus neoformans is a major cause of morbidity and mortality among HIV-infected persons worldwide, and there is scarce recent data on cryptococcal antigen (CrAg) positivity in the U.S. We sought to determine the frequency of cryptococcal disease and compare the performance of a CrAg lateral flow assay (LFA) versus latex agglutination (LA) test. Methods All patients from Grady Health System in Atlanta who had a serum or cerebrospinal fluid (CSF) sample sent for CrAg testing as part of clinical care from November 2017 – July 2018 were included. Percent positivity and test agreement were calculated. Results Among 467 patients, 557 diagnostic tests were performed; 413 on serum and 144 on CSF. Mean age was 44 years, most were male (69%) and had HIV (79%). Twenty-four (6.4%, CI95% = 4.1, 9.4) patients were serum CrAg positive, and eight (5.8%, CI95% = 2.6, 11.2) individuals tested positive for CSF CrAg. While overall agreement between the LA and LFA was substantial to high for CSF (κ= 0.71, CI95% = 0.51, 0.91) and serum (κ= 0.93, CI95% = 0.86, 1.00), respectively, there were important discrepancies. Five patients had false-positive CSF LA tests which affected clinical care, and four patients had discordant serum tests. Conclusions We found a moderately high proportion of cryptococcal disease and important discrepancies between the LA test and LFA. Clinical implications of these findings include accurate detection of serum CrAg and averting unnecessary treatment of meningitis with costly medications associated with high rates of adverse events.

scholarly journals Performance of the Lateral Flow Assay and the Latex Agglutination Serum Cryptococcal Antigen Test in Cryptococcal Disease in Patients with and without HIV

2020 ◽  
Vol 58 (11) ◽  
Author(s):  
Matthew A. Hevey ◽  
Ige A. George ◽  
Adriana M. Rauseo ◽  
Lindsey Larson ◽  
William Powderly ◽  
...  
Keyword(s):  
Pulmonary Disease ◽  
Real Life ◽  
Latex Agglutination ◽  
Lateral Flow ◽  
Lateral Flow Assay ◽  
People Living With Hiv ◽  
Cryptococcal Antigen ◽  
Cryptococcal Disease ◽  
Disseminated Disease ◽  
Hiv Negative

ABSTRACT Cryptococcal epidemiology is shifting toward HIV-negative populations who have diverse presentations. Cryptococcal antigen (CrAg) testing is also changing, with development of the lateral flow assay (LFA) having reported increased sensitivity and specificity, but with minimal knowledge in the HIV-negative population. In this study, we evaluate the real-life performance of CrAg testing in patients with cryptococcal disease. We conducted a retrospective review of patients with cryptococcosis from 2002 to 2019 at Barnes-Jewish Hospital. Latex agglutination (LA) was used exclusively until April 2016, at which point LFA was used exclusively. Demographics, presentations, and testing outcomes were evaluated. Serum CrAg testing was completed in 227 patients with cryptococcosis. Of 141 HIV-negative patients, 107 had LA testing and 34 had LFA testing. In patients with disseminated disease, serum CrAg sensitivity by LA was 78.1% compared to 82.6% for LFA. In patients with localized pulmonary disease, serum CrAg sensitivity was 23.5% compared to 90.9% for LFA. Of 86 people living with HIV (PLWH), 76 had LA testing, and 10 had LFA testing. Serum CrAg sensitivity for LA was 94.7% compared to 100% for LFA in patients with disseminated disease. We noted a significant improvement in sensitivity from LA testing to LFA testing, predominantly in those with localized pulmonary disease. However, both LFA and LA appear to be less sensitive in HIV-negative patients than previously described in PLWH.

scholarly journals Clinical Significance of Low Serum Cryptococcal Antigen Titers by Lateral Flow Assay in Immunocompromised Patients: a Retrospective Case-Control Study

2019 ◽  
Vol 58 (2) ◽  
Author(s):  
Erin Dizon ◽  
Wonjae Seo ◽  
Susan M. Butler-Wu ◽  
Rosemary C. She
Keyword(s):  
Clinical Significance ◽  
Fungal Infections ◽  
High Titer ◽  
Lateral Flow ◽  
Lateral Flow Assay ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Cryptococcal Antigen ◽  
Cryptococcal Disease ◽  
Low Serum

ABSTRACT Cryptococcus species are associated with invasive fungal infections in immunosuppressed individuals. The clinical significance of low-titer cryptococcal antigen (CrAg) by lateral flow assay is frequently uncertain. We investigated the correlation of low CrAg titers with disease in an immunocompromised patient population. Patients with first-time positive CrAg results with low serum titers (≤1:10) at two medical centers (Los Angeles, CA) from April 2014 to July 2018 were included. Age-matched controls with high (≥1:20) and negative titers were selected. We extracted medical records for pertinent clinical, radiologic, and laboratory data for cryptococcal disease. From 2,196 serum samples submitted for CrAg testing, 96 cases were included (32 each in low-titer, high-titer, and negative-titer groups). One or more immunocompromising condition was identified in 95% of patients, including HIV infection (45%), solid organ transplant (26%), and cirrhosis (22%). Pulmonary cryptococcosis was diagnosed in 9 (28%) low-titer and 8 (25%) high-titer patients (P = 1.00). Disseminated cryptococcosis occurred in 7 (22%) low-titer and 15 (47%) high-titers cases (P = 0.064). Titers ≤1:10 more frequently represented isolated antigenemia in HIV-positive than non-HIV, immunocompromised patients (P < 0.001). Follow-up testing in patients with ≤1:5 titers (n = 21) showed persistently low titers in 6 of 12 instances and increased titers in 2 cases. Twenty-seven patients with low CrAg titers were treated with antifungal therapy and 22 (81%) responded well clinically. Low-serum CrAg titers (≤1:10) correlated with cryptococcal disease in a substantial proportion of non-HIV immunocompromised patients and should prompt careful clinical workup for cryptococcal infection.

scholarly journals False-negative result of serum cryptococcal antigen lateral flow assay in an HIV-infected patient with culture-proven cryptococcaemia

2019 ◽  
Vol 26 ◽  
pp. 64-66 ◽  
Author(s):  
Moara Alves Santa Bárbara Borges ◽  
João Alves de Araújo Filho ◽  
Renata de Bastos Ascenço Soares ◽  
José Ernesto Vidal ◽  
Marília Dalva Turchi
Keyword(s):  
Infected Patient ◽  
False Negative ◽  
Lateral Flow ◽  
Lateral Flow Assay ◽  
False Negative Result ◽  
Cryptococcal Antigen

scholarly journals 253. Evaluation of a Cryptococcal Antigen Lateral Flow Assay and the Burden of Cryptococcal Disease: A Cohort Study at Grady Memorial Hospital in Atlanta, Georgia

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S141-S142 ◽  
Author(s):  
Kristin Harrington ◽  
Yun Wang ◽  
Paulina Rebolledo ◽  
Zhiyong Liu ◽  
Qianting Yang ◽  
...  
Keyword(s):  
The United States ◽  
Latex Agglutination ◽  
Lateral Flow ◽  
Lateral Flow Assay ◽  
High Rate ◽  
Memorial Hospital ◽  
Cryptococcal Antigen ◽  
India Ink ◽  
Cryptococcal Disease ◽  
Positive Serum

Abstract Background While Cryptococcus neoformans is a major cause of morbidity and mortality among HIV-infected persons worldwide, there is scarce recent data on disease prevalence in the United States, including in Southeastern states, where HIV rates are high. We sought to determine the prevalence of cryptococcal disease and compare the performance of a cryptococcal antigen (CrAg) lateral flow assay (LFA) vs. latex agglutination (LA) test. Methods All patients from Grady Memorial Hospital in Atlanta, Georgia who had a serum or cerebrospinal fluid (CSF) sample sent for CrAg LA testing as part of routine management from November 2017 to July 2018 were included. The LFA was performed on all samples by research staff; results were not available to clinicians. Rates of disease and agreement between the LA test and LFA were calculated. Results Among 467 patients, 570 LA tests were performed; 417 on serum and 153 on CSF (87 patients with multiple tests performed). Mean age was 44 years, and most were male (n = 322, 69%). Most patients had HIV (n = 371, 79%); median CD4 count was 73 cells/mm3 and 77% were not receiving ART. Among HIV-infected individuals, testing was performed equally in the inpatient and outpatient setting. Cryptococcal testing was done in 53 persons without apparent risk factors. Thirty-three (7%) patients had a positive serum or CSF test. Five (1%) patients had both a positive serum and CSF LA test and LFA. While the overall agreement between the LA test and LFA was substantial to high for CSF (κ = 0.71) and serum (κ = 0.93), respectively, there were important discrepancies. Four patients with a negative serum LA test had a positive serum LFA. Five patients had false-positive CSF LA tests, determined by negative CSF LFA testing, India ink, and CSF and fungal cultures. All were treated with amphotericin and flucytosine with one patient experiencing a severe anaphylactic reaction to amphotericin. Conclusion We found a moderately high rate of cryptococcal disease and important discrepancies between the LA test and LFA. The LFA appeared to be more sensitive for cryptococcemia and more specific for meningitis. Clinical implications of these findings include earlier detection and treatment of cryptococcemia, and averting unnecessary treatment of meningitis with costly medications associated with high rates of adverse events. Disclosures All authors: No reported disclosures.

scholarly journals Evaluation of a Novel Semiquantitative Cryptococcal Antigen Lateral Flow Assay in Patients with Advanced HIV Disease

2020 ◽  
Vol 58 (9) ◽  
Author(s):  
Joseph N. Jarvis ◽  
Mark W. Tenforde ◽  
Kwana Lechiile ◽  
Thandi Milton ◽  
Amber Boose ◽  
...  
Keyword(s):  
High Sensitivity ◽  
Lateral Flow ◽  
Lateral Flow Assay ◽  
Hiv Positive ◽  
Plasma Samples ◽  
Prognostic Information ◽  
Cryptococcal Antigen ◽  
Cryptococcal Disease ◽  
Sequential Samples ◽  
Advanced Hiv Disease

ABSTRACT Higher cryptococcal antigen (CrAg) titers are strongly associated with mortality risk in individuals with HIV-associated cryptococcal disease. Rapid tests to quantify CrAg levels may provide important prognostic information and enable treatment stratification. We performed a laboratory-based validation of the IMMY semiquantitative cryptococcal antigen (CrAgSQ) lateral flow assay (LFA) against the current gold standard CrAg tests. We assessed the diagnostic accuracy of the CrAgSQ in HIV-positive individuals undergoing CrAg screening, determined the relationship between CrAgSQ scores and dilutional CrAg titers, assessed interrater reliability, and determined the clinical correlates of CrAgSQ scores. A total of 872 plasma samples were tested using both the CrAgSQ LFA and the conventional IMMY CrAg LFA, of which 692 were sequential samples from HIV-positive individuals undergoing CrAg screening and an additional 180 were known CrAg-positive plasma samples archived from prior studies. Interrater agreement in CrAgSQ reading was excellent (98.17% agreement, Cohen’s kappa 0.962, P < 0.001). Using the IMMY CrAg LFA as a reference standard, CrAgSQ was 93.0% sensitive (95% confidence interval [CI] 80.9% to 98.5%) and 93.8% specific (95% CI, 91.7% to 95.6%). After reclassification of discordant results using CrAg enzyme immunoassay testing, the sensitivity was 98.1% (95% CI, 90.1% to 100%) and specificity 95.8% (95% CI, 93.9% to 97.2%). The median CrAg titers for semiquantitative score categories (1+ to 4+) were 1:10 (interquartile range [IQR], 1:5 to 1:20) in the CrAgSQ 1+ category, 1:40 (IQR, 1:20 to 1:80) in the CrAgSQ 2+ category, 1:640 (IQR, 1:160 to 1:2,560) in the CrAgSQ 3+ category, and 1:5,120 (IQR, 1:2,560 to 1:30,720) in the CrAgSQ 4+ category. Increasing CrAgSQ scores were strongly associated with 10-week mortality. The IMMY CrAgSQ test had high sensitivity and specificity compared to the results for the IMMY CrAg LFA and provided CrAg scores that were associated with both conventional CrAg titers and clinical outcomes.

scholarly journals Diagnostic Accuracy of the Biosynex CryptoPS Cryptococcal Antigen Semiquantitative Lateral Flow Assay in Patients with Advanced HIV Disease

2020 ◽  
Vol 59 (1) ◽  
pp. e02307-20
Author(s):  
Mark W. Tenforde ◽  
Timothée Boyer-Chammard ◽  
Charles Muthoga ◽  
Leabaneng Tawe ◽  
Thandi Milton ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Predictive Value ◽  
High Titer ◽  
False Negative ◽  
Lateral Flow ◽  
Lateral Flow Assay ◽  
Hiv Disease ◽  
Cd4 Cell Count ◽  
Cryptococcal Antigen ◽  
Advanced Hiv Disease

ABSTRACTHigh cryptococcal antigen (CrAg) titers in blood are associated with subclinical meningitis and mortality in CrAg-positive individuals with advanced HIV disease (AHD). We evaluated a novel semiquantitative lateral flow assay (LFA), CryptoPS, that may be able to identify individuals with high CrAg titers in a cohort of AHD patients undergoing CrAg screening. In a prospective cohort of patients with AHD (CD4 cell count, ≤200/μl) receiving CD4 count testing, whole blood was tested for CrAg by CryptoPS and the IMMY LFA; the two assays were conducted by two different operators, each blind to the results of the other assay. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CryptoPS were assessed against the IMMY LFA as a reference. CryptoPS low-titer (T1 band) and high-titer (T2 band) results were compared with IMMY LFA titers obtained through serial dilution. A total of 916 specimens were tested. The sensitivity of the CryptoPS assay was 61.0% (25/41) (95% confidence interval [95% CI], 44.5 to 75.8%), its specificity was 96.6% (845/875) (95% CI, 95.1 to 97.7%), its PPV was 45.5% (95% CI, 32.0 to 59.4%), and its NPV was 98.1% (95% CI, 97.0 to 98.9%). All (16/16) CryptoPS false-negative results were obtained for samples with IMMY titers of ≤1:160. Of 29 patients (30 specimens) who tested positive by CryptoPS but negative by the IMMY LFA, none developed cryptococcal meningitis over 3 months of follow-up without fluconazole. Median CrAg titers were 1:20 (interquartile range [IQR], 0 to 1:160) in CryptoPS T1-positive samples and 1:2,560 (IQR, 1:1,280 to 1:10,240) in T2-positive samples. We conclude that the diagnostic accuracy of the CryptoPS assay was suboptimal in the context of CrAg screening, with poor sensitivity at low CrAg titers. However, the CryptoPS assay reliably detected individuals with high titers, which are associated with poor outcomes.

scholarly journals PEMERIKSAAN CRYPTOCOCCAL ANTIGEN ANTARA METODE SISTEM AGLUTINASI LATEKS ANTIGEN KRIPTOKOKUS DAN LATERAL FLOW ASSAY DI PASIEN AIDS (Cryptococcal Antigen of Acquired Immune Deficiency Syndrome with Lateral Flow Assay and Cryptococcus Antigen Latex Agglutination System)

2018 ◽  
Vol 21 (1) ◽  
pp. 45
Author(s):  
Artiti Aditya ◽  
Indrati AR ◽  
Ganiem AR
Keyword(s):  
Immune Deficiency ◽  
Immune Deficiency Syndrome ◽  
Acquired Immune Deficiency Syndrome ◽  
Deficiency Syndrome ◽  
Latex Agglutination ◽  
Lateral Flow ◽  
Lateral Flow Assay ◽  
Positive Probability ◽  
Cryptococcal Antigen ◽  
Acquired Immune Deficiency

Cryptococcosis is the fourth most common opportunistic infection among Acquired Immune Deficiency Syndrome (AIDS) patients.About 100% mortality has been reported within two weeks in patient with cryptococcal meningitis but without specific treatment. Theaim of the study was to compare Cryptococcal antigen (CrAg) detection between Cryptococcus Antigen Latex Agglutination System(CALAS) and Lateral Flow Assay (LFA) among AIDS patients. This research was designed as comparative analytic with cross sectionalstudy on 56 serum derived from AIDS patient who visited Teratai Clinic before ARV therapy initiation and who had never been diagnosedas Cryptococcal meningitis. Each sample was tested for CrAg with CALAS and LFA according to the manufacturer instructions. Thisstudy was conducted in the Clinical Pathology Laboratory at Dr. Hasan Sadikin Hospital/Centre Research Unit (CRU) Medical Faculty,Padjajaran University between December 2012March2013. The statistical analysis was done using Chi square test. The result showed thatthere was no significant difference between CALAS and LFA method with p=0.596 (p>0.05), the positive probability of CrAg detectionusing LFA was 0.75 times compared to the CALAS method. For the CrAg detection in the AIDS patients there was no significant differencebetween CALAS and LFA and the positive probability of CrAg for LFA was detected about 0.75 times compared to the CALAS method.

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